8 th International Ph. D. Symposium Berlin Brain Days 2011 Berlin

/ program, curricula vitae,program, curricula and abstracts Brain Days 2011 /dec. 7 – 9

Program & Abstract Abstracts Curricula The Berlin Brain Days 2011 are jointly organized schedule of the open­ of the six vitae of of the sym­ ing lecture by keynote the keynote by six Berlin-based neuroscience Ph. D. programs posium Christian lectures speakers Lüscher

LANGUAGES OF Abstracts Abstracts Information EMOTION of all Ph.D. of all pre­ on the orga­ conference sented Ph.D. nizing Ph.D. talks posters programs

BERLIN SCHOOL OF MIND AND BRAIN

www.neuroscience-berlin.de/bbd/ Max Delbrück Center for Molecular Medicine Berlin­Buch NATURKUNDE- MUSEUM

Langenbeck-Virchow-Haus, Luisenstraße 58/59, 10117 Berlin

Imprint

Editor Annette Winkelmann Design and Typesetting Sebastian Lehnert, www.deskism.com Original Design Holger Gerhardt Typefaces Adobe Caslon Pro and FF Meta Pro Editorial deadline 18 November 2011 Printing house Flyeralarm, Würzburg Copies 200

Max Delbrück Center for Molecular Medicine Berlin-Buch Conference Center MDC.C ( labeled 83 on the map ), lecture hall “Axon” Robert-Rössle-Straße 10, 13125 Berlin Contents

Program and Schedule 4

Opening Lecture Christian Lüscher 7

Session 1 Frank Bradke 10 Session 2 Luiz Pessoa 15 Session 3 Adrienne Fairhall 21 Session 4 Kalanit Grill-Spector 27 Session 5 Hermona Soreq 33 Session 6 Hans Markowitsch 39

Posters 45 P 1 – P12 Medical Neurosciences 47 P13 – P19 Learning and Memory 59 P20 – P25 Mind and Brain 66 P26 – P31 Molecular Neurobiology 72 P32 – P36 Computational Neuroscience 78 P37 – P39 Languages of Emotion 83 P40 – P57 External 86

Graduate Programs 104

Appendix 111 Index of Speakers and Poster Presenters 112 Public Transport 120 Orientation 121 2

Welcome to the Berlin Brain Days 2011

The Berlin Brain Days are an activity of­ doctoral students across several independent Berlin institu- tions. Initiated in 2005 by faculty and students in “Medical Neurosciences” (a graduate school at the Charité Medical School), it has ­subsequently grown year-by-year as the neuro­scientific esearchr and training environment has rapidly developed within the city. The growth in the number and variety of new doctoral programs within Berlin is really quite remarkable. In 2005, the DFG research ­training group on “Cellular Mechanisms of Learning and Memory” was established. In 2006, as part of the Excellence Initiative for German universities, the “Berlin School of Mind and Brain” was found- ed to foster interdisciplinary research across the mind and brain sciences. The School joined the Berlin Brain Days program planning soon after and has since been tasked with the scientific program coordination. The doctoral program “Computa- tional Neuroscience” of the Bernstein Center­ for Computational Neuroscience, now merged with the DFG research training group “Sensory Com- putation in Neural Systems”, has also been active in the Berlin Brain Days organizing team since late 2007. The Helmholtz InternationalResear­ ch School “Molecular Neurobiology”, established in 2007, has been a long-standing member program of the organizing group. A second and third ac- quisition of the Excellence Initiative resulted in the establishment of two Clusters of Excellence, “NeuroCur­ e” and “Languages of Emotion”, both with additional funding for doctoral students. They too join the meeting with posters and talks. 3

We very successfully joined our forces for the first time four years ago, and the ­Berlin Brain Days 2011 again are a common ­activity of all these programs. Students and ­faculty alike are highly motivated to learn about the ­research of neighboring programs, and the ­Berlin Brain Days have become an important ­forum for information exchange in the city. Berlin has a good tradition in ­fostering activi- ties in the neurosciences: the ­Berlin Neuro­ science Forum has been organized e­ very other year since 1997 and is a ­common ­activity of the Berlin universities and Berlin-­based collabora- tive research centers and groups (Sonder­forschungs­ bereiche, Forscher­gruppen, Graduierten­kollegs, etc.). It ­regularly attr­ acts 200 neuroscientists to a small resort ­outside of ­Berlin, Liebenwalde. The next ­meeting of the Berlin Neuroscience Forum will take place 5 – 6 July 2012. It is in our best interest that we meet regular- ly and continue to develop Berlin as a hotspot for research across the neurosciences. With this in mind, I am convinced that we will have a very interactive and successful meeting that will result in new collaborations within the Berlin neuro- science research community.

Helmut Kettenmann, Conference Chair 4

Wednesday, 7 December 2011 Langenbeck-Virchow-Haus | Luisenstraße 58 / 59 | 10117 Berlin

Opening session 18.00 Helmut Kettenmann > Opening Address Stephan Sigrist > Introduction Christian Lüscher “Addiction, the dark side of learning” Annette Grüters-Kieslich (Dean, Charité – Universitäts­ medizin Berlin) Klaus Obermayer (Graduate Programs, Bernstein Center for Computational Neuroscience) > Award of master’s diplomas and doctoral certificates 20.00 Cheese & Wine Reception (Humboldt Graduate School, Luisenstraße 56, Festsaal, 2nd floor, 10117 Berlin) 5

Thursday, 8 December 2011 Max Delbrück Center for Molecular Medicine Berlin-Buch | Conference Center MDC.C, lecture hall “Axon”, Robert-Rössle-Straße 10 | 13125 Berlin

Session 1 | Molecular Neuroscience 09.30 Gary Lewin > Introduction Frank Bradke “Cytoskeletal mechanisms of axonal growth and regeneration” 10.30 D amir Omerbasic, Kristin Stock > Ph. D. talks 11.15 Coffee break

Session 2 | Languages of Emotion 11.45 Hauke R. Heekeren > Introduction Luiz Pessoa “On the relationship between emotion and ­cognition” 12.45 Christoph Korn, Soyoung Park, Timo Stein > Ph. D. talks 13.30 Lunch ( + coffee ) & Poster presentations ( even numbers )

Session 3 | Computational Neuroscience 15.00 Susanne Schreiber > Introduction Adrienne Fairhall 16.00 Jorge Jaramillo, Anne Porbadnigk, Vinzenz Schönfelder > Ph. D. talks 6

Friday, 9 December 2011 Max Delbrück Center for Molecular Medicine Berlin-Buch | Conference Center MDC.C, lecture hall “Axon”, Robert-Rössle-Straße 10 | 13125 Berlin

Session 4 | Mind & Brain 09.30 Philipp Sterzer > Introduction Kalanit Grill-Spector “Re-thinking the functional organization of human high-level visual cortex 10.30 Fatma Imamoglu, Karin Ludwig, Fernando Ramirez > Ph. D. talks 11.15 Coffee break

Session 5 | Medical Neurosciences 11.45 Andreas Meisel > Introduction Hermona Soreq “Micro-RNAs in the interface between ­inflammation and neurodegeneration” 12.45 Odilo Engel, Michael Kintscher, Katyayni Vinnakota > Ph. D. talks 13.30 Lunch ( + coffee ) & Poster presentations ( odd numbers )

Session 6 | Learning & Memory 15.00 Jörg Geiger > Introduction Hans Markowitsch “Memory and brain: neuropsychology, ­neurology, and psychiatry” 16.00 Gürsel Çalışkan, Jakob Gutzmann, Chia-Ling Chang > Ph. D. talks 16.45 Improv Comedy ( while evaluation for “Best Talk” and “Best Poster” goes on ) 17.15 Award of “Best Talk” and “Best Poster” 20.00 BBD Party Bar Babette, Karl-Marx-Allee 36, 10178 Berlin www.barbabette.com 7

OPENING LECTURE

Wednesday, 7 December 2011

18.00 Christian Lüscher Addiction, the dark side of learning

Opening Helmut Kettenmann Address Max Delbrück Center for Molecular Medicine Berlin-Buch

Chair Stephan Sigrist Institute of Biology, Freie Universität Berlin 8 Opening Lecture : Christian Lüscher

Christian Lüscher

Dept. of Basic Neurosciences, Medical Faculty, University of Geneva, Switzerland mail [email protected] web www.addictionscience.unige.ch

Current Positions

Full Professor at the Dept. of Basic Neurosciences (NeuFo), Medical Faculty, University of Geneva Attending at the Neurological Clinic (Médecin associé), Department of Clinical Neurosciences, Geneva University Hospital, Switzerland

Professional Activities

2010 Visiting Scholar, Stanford University, Palo Alto, CA 2003 – 2009 Associate Professor at the NeuFo department, University of Geneva 1999 – 2007 Attending in neurology (Chef de Clinique), University of Geneva 1999 – 2003 SCORE A recipient (Assistant professor) at the Dept. of Physiology & Pharmacology, Unige 1996 – 1999 Visiting postdoctoral fellow, Dept. of Cellular & Molecular Pharmacology, University of California San Francisco (R. A. Nicoll) 1995 / 96 Postdoc, Institute of Physiology, University of Berne (H.-R. Lüscher) 1994 / 95 Intern, Neurology, HUG, Geneva (Th. Landis) 1994 Postdoc, Institute of Physiology, Univ. of Berne (E. Niggli) 1993 / 94 Intern, Neurology, Inselspital, Berne (C. W. Hess) Opening Lecture : Christian Lüscher 9

Christian Lüscher

Addiction, the dark side of learning

Dept. of Basic Neurosciences, Medical Faculty, University of Geneva, Switzerland

We will discuss the hypothesis that addiction is a form of pathological learning ­driven by the excessive increase of dopamine in the reward circuit ultimately leading to the loss of behavioral control. This process, while systematically engaged after exposure to drugs, only leads to compulsion in persons with increased vulnerability. The early hallmarks of this process are are various forms of drug-evoked synaptic plasticity. 10

SESSION 1

Thursday, 8 December 2011

09.30 Frank Bradke Cytoskeletal mechanisms of axonal growth and regeneration

10.30 Damir Omerbasic Kristin Stock › Ph. D. talks

Introduction Gary Lewin Max Delbrück Center for Molecular Medicine Berlin-Buch

Chair Jan Walcher Max Delbrück Center for Molecular Medicine Berlin-Buch Session 1 : Frank Bradke 11

Frank Bradke

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Ludwig-Erhard-Allee 2 53175 Bonn mail [email protected]

2011 – present Head of a Senior Research Group at the DZNE 2009 Habilitation in Neurobiology 2003 – 2011 Head of an Independent Junior Research Group, Max-Planck-Institute of Neurobiology, Martinsried 2000 – 2002 Postdoc at University of California, San Francisco & Stanford University 1999 Ph.D. in Biology, The European Molecular Biology Laboratory, Heidelberg 1989 – 1995 Studies of Biochemistry, Anatomy and Developmental Biology in Berlin (FU) and London (UCL) 12 Session 1 : Frank Bradke

Frank Bradke

Cytoskeletal mechanisms of axonal growth and regeneration

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn

Neurons are the cellular basis of the circuits of our nervous system that allow us to sense the environment, control our muscles and, sometimes, even to think. In these circuits, neurons fulfill very different functions at different part of the cells, including signal reception, integration and propagation. This is possible because neurons have a high degree of asymmetry ( or polarity ). We want to understand how neurons develop their polarity. How do neurons generate an axon? While this is an interesting question by itself, answers will also allow us to reactivate the polarity program under pathological conditions, such as a spi- nal injury, to induce axon regeneration. Session 1 : Frank Bradke 13

Damir Omerbasic,1, 2 A. Sivasubramaniam,1 E. St J. Smith,1 and G. R. Lewin 1

Ablation of heat-gated TRPV1-currents by single amino-acid ­exchanges

1 Department of Neuroscience, Max Delbrück Center for Molecular Medicine ­Berlin-Buch; 2 Helmholtz International Research School Molecular Neurobiology

The capsaicin receptor TRPV1 is expressed by sensory neurons, which innervate the skin and it has been postulated to be involved in the detection of heat as a noxious stimulus. Additionally, TRPV1 is fundamental for thermal hyperalgesia associated with inflammation. Although, much is known about TRPV1 activa- tion and modulation, it is still not fully understood how such a diverse range of physical and chemical stimuli can activate one ion channel. Here we describe single amino acid mutations of TRPV1 that affect channel activation. Specifical- ly, we have characterized novel mutations, which render the channel either fully non-functional, or selectively insensitive to only one of the modalities. Two resi- dues were identified in the N-terminal domain, a region of TRPV1 that is in- volved in binding to multiple ligands and plays a role in channel sensitivity. Our first TRPV1 mutation leads to the complete inactivation of the channel making it insensitive to capsaicin, low pH, voltage and temperature activation. In con- trast, a further TRPV1 mutation resulted in a channel that can be activated ( ­although weakly ) by capsaicin, low pH and voltage. However, temperature acti- vation of this mutant channel was completely abolished, even when challenged with temperatures greater than 55 ° C. Both point mutations did not affect traf- ficking of TRPV1 to the plasma membrane, indicating that other mechanisms are responsible for the lack of channel activation. Temperature activation of TRPV1 is far less characterized than other TRPV1 activators, such as capsaicin, and thus this study expands our knowledge of understanding the differential activation of polymodal channels. 14 Session 1 : Frank Bradke

Kristin Stock,1, * J. Kumar,1, * M. Synowitz,1, 2 V. Matyash,1 L. Cristino,4 V. Di Marzo,3 H. Kettenmann,1, * and R. Glass 1, *

Neural precursor cells induce glioma cell-death via stimulation of TRPV1

1 Cellular Neuroscience, Max Delbrück Center for Molecular Medicine Berlin-Buch; 2 Department of Neurosurgery, Charité – Universitätsmedizin Berlin; 3 Endocanna­ binoid Research Group, Institute of Biomolecular Chemistry, Pozzuoli (NA), Italy; 4 Institute of Cybernetics, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy * contributed equally

Neural precursor cells ( NPCs ) with somatic mutations likely are the source for primary brain tumors like glioblastomas. In extension to this concept, we have previously shown that physiological NPCs also mediate paracrine tumor sup- pressive effects against glioblastomas. Here, we studied the molecular nature of the anti-tumorigenic factors that are released from NPCs. We found that NPCs release endovanilloids which can stimulate the vanilloid receptor ( TRPV1 ) on cultured NPCs and glioblastoma cells and thereby mediate specific physiologi- cal or tumor-suppressive effects. Cultured NPCs and glioma cells express functional vanilloid receptors and their activation by endogenous and synthetic TRPV1 agonists triggers calcium transients. In normal NPCs, TRPV1 knockout resulted in an increased prolifer- ation as compared to wild type controls. In glioma cells, but not in NPCs, the application of vanilloids results in cell death mediated by TRPV1. The adminis- tration of the synthetic vanilloid Arvanil to ex vivo organotypic brain slices in- oculated with glioma cells decreased tumor expansion. Furthermore, application of Arvanil mediated a significant improvement of survival in an in vivo glioma mouse model. Overall, our data imply that NPCs utilize vanilloids as endogenous paracrine tumor suppressors which could be clinically exploited as a new strategy for brain tumor therapy. Our data also indicate that signal transduction via TRPV1 has a profound impact on NPC proliferation in vitro and that direct or systemic endo­ vanilloid signaling impacts adult neurogenesis in vivo. 15

SESSION 2

Thursday, 8 December 2011

11.45 Luiz Pessoa On the relationship between emotion and cognition

12.45 Christoph Korn Soyoung Park Timo Stein › Ph. D. talks

Introduction Hauke Heekeren Cluster of Excellence Languages of Emotion Freie Universität Berlin

Chair Dorit Kliemann International Graduate School Languages of Emotion 16 Session 2 : Luiz Pessoa

Luiz Pessoa

Department of Psychology University of Maryland, College Park, USA web http://emotioncognition.org

Luiz Pessoa is Full Professor at the Department of Psychology, University of Maryland, College Park. He received a Ph.D. in computational neuroscience from Boston University ( 1996 ) and post-doctoral training at the National Institute of Mental Health ( 1999 – 2003 ). His research focuses on understanding cognitive – emotional interactions by employing behavioural and neuroimaging methods, such as functional magnetic resonance imaging ( f MRI ) and, more recently, EEG and MEG. His current research addresses how top-down factors such as attention and executive control are involved in the processing of emotion-laden stimuli. Also he is interested in developing quantitative methods to link trial-by-trial fluctuations in physiological responses ( e. g., f MRI ) and changes in behaviour ( e. g., successful vs. unsuccessful task performance ). Luiz Pessoa has published more than 85 journal articles, chapters, and full-length conference papers. Session 2 : Luiz Pessoa 17

Luiz Pessoa

On the relationship between emotion and cognition

Department of Psychology, University of Maryland, USA

The current view of brain organization supports the notion that there is a con- siderable degree of functional specialization and that many regions can be con- ceptualized as either ‘affective’ or ‘cognitive’. Popular examples are the amygdala in the domain of emotion and the lateral prefrontal cortex in the case of cogni- tion. This prevalent view is problematic for a number of reasons. It will be argued that complex cognitive – emotional behaviors have their basis in networks of brain areas, none of which should be conceptualized as specifically affective or cognitive. Central to cognitive – emotional interactions are brain areas with a high degree of connectivity called hubs ( e. g., amygdala ), which are critical for regulating the flow and integration of information between regions. To illustrate cognitive-emotional processing, I will discuss a series of studies that have inves- tigated interactions between emotion and perception ( including studies showing that emotional perception is not automatic ) and, more recently, between emo- tion and executive function. 18 Session 2 : Luiz Pessoa

Christoph W. Korn,1, 2 K. Prehn,3 H. Walter,2, 4 and H. R. Heekeren 1, 2, 3

Positively biased processing of social feedback

1 Department of Education and Psychology, Freie Universität Berlin; 2 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin; 3 Cluster of Excellence Languages of Emotion, Freie Universität Berlin; 4 Department of Psychiatry, Division of Mind & Brain Research, Charité – Universitätsmedizin Berlin

Humans process self-related feedback in a positively biased way, i. e. they tend to accept desirable social feedback such as praise uncritically while they receive undesirable social feedback such as blame with mistrust. Here, we investigated the behavioural and neural mechanisms of biased social feedback processing in the general framework of reinforcement learning. Briefly, five participants got to know each other and rated each other on 80 trait adjectives ( e. g. modest, arrogant ). On the next day in the scanner, each participant first rated herself and then saw how the others had rated her. To assess how this feedback changed self-perception, participants rated themselves a second time. To compare the neural processing of self- and other related feed- back each participant also received feedback for one of the other four players. Our results support the idea of a biased updating mechanism. When feed- back was more desirable than expected, participants consequently changed their second ratings towards this desirable feedback. However, for undesirable feed- back participants did not change their ratings to the same degree. Medio-­ prefrontal cortex ( MPFC ) activity, which is typically involved in processing ­self- and other-referential information, differed between receiving self- and ­other-related feedback. Importantly, MPFC activity also correlated with the difference between participants’ own rating and the feedback they received. Consistent with the role of the striatum in learning about reward and value, stri- atal activity in our task correlated with the overall positivity of the others’ rating. By investigating social feedback processing from the viewpoint of reinforce- ment learning, we report evidence for biased information processing in MPFC and striatum. Session 2 : Luiz Pessoa 19

Soyoung Q Park,1, 2 T. Kahnt,2, 3 D. Talmi,4 J. Rieskamp,5 R. J. Dolan,4 and H. R. Heekeren 1, 2

Adaptive coding of reward prediction errors in human brain

1 Department of Education and Psychology, Freie Universität Berlin; 2 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin; 3 Bernstein Center for Compu­ tational Neuroscience, Berlin; 4 Wellcome Trust Centre for Neuroimaging, Univer­ sity College London, United Kingdom; 5 University of Basel, Department of Psy- chology, Basel, Switzerland

Rewards we encounter in daily life vary in its size from a piece of chocolate to the lottery. To efficiently represent all the possible rewards in the world with its limited coding range, dopaminergic midbrain neurons dynamically adapt their coding range to momentarily available rewards. These neurons enhance their firing rate for the better outcome than expected and reduce a worse than expect- ed, independent of absolute reward magnitude. Although this adaptive coding is well documented in animals, it is unclear how this rescaling is implemented in humans. Here, we used human functional magnet resonance imaging ( fMRI ) in combination with a reward prediction task that involved different reward contexts. We present that reward prediction errors in the human striatum are expressed according to an adaptive coding scheme. Strikingly, we show that an adaptive coding is gated by changes in effective connectivity between the ­striatum and other reward sensitive regions, namely the midbrain and medial prefrontal cortex. Our results provide powerful evidence of how human striatal prediction errors are rescaled by a context-dependent alteration in inter-regional connectivity within the brain reward system. 20 Session 2 : Luiz Pessoa

Timo Stein,1, 2 K. Seymour1, M. N. Hebart,2, 3 and P. Sterzer 1, 2, 3

Rapid fear processing relies on high spatial frequencies

1 Department of Psychiatry, CCM, Charité – Universitätsmedizin Berlin; 2 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin; 3 Bernstein Center for Computational Neuroscience, ­Berlin

Threatening emotional stimuli, such as fearful faces, are equipped with an inher- ent processing advantage. It is commonly assumed that this fear advantage in- volves a subcortical pathway from the superior colliculus and the pulvinar to the amygdala that bypasses visual cortex. Although direct anatomical evidence for this ‘low road’ is lacking, the known tuning properties of neurons in this puta- tive low road allow testing its functional role in mediating the fear advantage. While neurons in the superior colliculus are tuned to low spatial frequencies, neurons in the ventral visual cortical pathway receive mainly high spatial fre- quency information. In a series of psychophysical experiments we used binocu- lar rivalry suppression and sandwich masking to test which spatial frequency bands would contribute to the detection advantage of fearful over neutral faces. Contrary to the purported role of a subcortical low road, we consistently found the fear advantage to rely on high spatial frequencies. This suggests a critical role of high spatial frequency information from the eyes and the mouth that differentiate fearful and neutral faces and that is represented by cortical visual areas. Consistent with this view, an additional fMRI study revealed distinct pat- terns of brain activity in visual cortex for fearful and neutral faces when present- ed in high spatial frequencies, but not for low spatial frequency faces. These findings strongly challenge a functional role of a putative low road in mediating the fear advantage, thereby casting doubt on the existence of a direct feedforward connection between the pulvinar and the amygdala in the primate visual system. 21

SESSION 3

Thursday, 8 December 2011

15.00 Adrienne Fairhall

16.00 Jorge Jaramillo Anne Porbadnigk Vinzenz Schönfelder › Ph. D. talks

Introduction Susanne Schreiber Theoretical Biology, Humboldt-Universität zu Berlin

Chair Jan Clemens Bernstein Center for Computational Neuroscience 22 Session 3 : Adrienne Fairhall

Adrienne Fairhall

Assistant Professor Department of Physiology and Biophysics University of Washington, USA mail [email protected]

Adrienne Fairhall is interested in the computational principles underlying information processing in the nervous system. One can think about spiking neurons as computational elements that perform a transformation on their inputs to produce a discrete spiking output. She is interested in general methods for building reduced models for this neural computation in terms of extracting relevant features from a complex input. The methods she is exploring start both from experimental data and from biophysical descriptions of neural dynamics. She and her group aim to relate the functional models determined from spiking data directly with the underlying channel dynamics. The brain is a highly adaptive organism, assimilating and adjusting to changes in the environment on a multiplicity of temporal and spatial scales. Thus, the neural code of several systems has been shown to be adaptive with respect to changes in the statistical distribution of the inputs. In her work she is seeking to elucidate how such adaptation may be beneficial for neural information processing, and to explore potential mechanisms underlying adaptation to statistics at the level of single neuron computation. Session 3 : Adrienne F 23airhall

Adrienne Fairhall

Title to be announced 24 Session 3 : Adrienne Fairhall

Jorge Jaramillo,1, 2 R. Schmidt,1, 2 R. Kempter1, 2 and D. Schmitz2, 3

Hippocampal coding and the inheritance of phase precession

1 Institute for Theoretical Biology, Humboldt-Universität zu Berlin; 2 Bernstein Center for Computational Neuroscience, Berlin; 3 Neuroscience Research Center, Charité – Universitätsmedizin Berlin

Hippocampal pyramidal cells in rodents encode information by their phase of firing relative to the local theta rhythm. The phase decreases monotonically dur- ing the traversal of the cell's place field and hence correlates with the position of the animal. This phenomenon, better known as “phase precession”, is a promi- nent example of phase coding in the hippocampus and is thought to underlie processes of memory formation. An open question is the origin of phase preces- sion, particularly whether it is generated independently in different subregions of the hippocampus or whether it is inherited by feedforward propagation. Through computational modeling, we investigated the possibility of the CA1 region inheriting phase precession from the CA3 region, and we explored the implications this possibility has for coding in the CA3 – CA1 combined system. Taking into account the firing rate of CA3 place cells and the parameters char- acterizing excitatory postsynaptic potentials in CA1, we were able to predict the time course of the CA1 membrane potential and calculate its analytical form as a function of the model parameters. The simulated membrane potential trace was consistent with data from intracellular recordings from awake behaving mice. A signal-to-noise ratio analysis constrained the parameters of the model and predicted a lower bound for the number of active CA3 neurons providing input to a single CA1 place cell. The inheritance of phase precession in the hippo­ campus suggests that the CA3 – CA1 combined system could work as a single computational unit. Session 3 : Adrienne Fairhall 25

Anne K. Porbadnigk,1, 2, 3 J. -N. Antons,2, 4 M. S. Treder,1 B. Blankertz,1, 2 R. Schleicher,2, 4 S. Möller,2, 4 K. -R. Müller,1, 2 and G. Curio 2, 5

Towards EEG-based assessment of audio quality using machine learning

1 Berlin Institute of Technology, Machine Learning Laboratory; 2 Bernstein Focus: Neurotechnology, Berlin; 3 International Graduate Program Computational ­Neuroscience, Berlin; 4 Quality and Usability Lab, Telekom Laboratories, Berlin; 5 Department of Neurology and Clinical Neurophysiology, Charité – Universitäts- medizin Berlin

The quality of audio signals has a significant impact on the joy of use when ­operating a device such as a phone. Typically, signal quality is assessed by means of users' subjective ratings. As shown recently for MEG ( Miettinen, 2010 ), ­neurophysiological data can be used to complement these, providing an objective and non-intrusive measure, while at the same time giving deeper insights into the cortical mechanisms of quality processing. Additionally, this approach might allow quantifying nuances too subtle for being reflected on the behavioral level. In particular, it has the potential to reveal neural differences in quality process- ing below the threshold of conscious perception that might lead to growing dis­ satisfaction of a user over time. Here, we present steps towards investigating the neural correlates of ( non- ) conscious processing of audio quality based on EEG recordings, employing methods typically used in the context of Brain-Computer Interfacing ( e. g., Dornhege, 2007 ). For a first study on phonemes disturbed by different levels of signal-correlated noise, neural correlates could be identified that allowed to quantify the level of disturbance ( early auditory and late cognitive components ). Based on these, linear classifiers were able to single out trials at the threshold of perception, where loss of quality was seemingly processed on a non-conscious level. Recently, this paradigm could be transferred successfully to full words ­degraded by realistic broadcast limitations. These results support the potential of EEG analysis combined with machine learning not only to complement con- ventional methods of audio quality assessment, but also to extend their sensitiv- ity to sub-threshold stimuli. 26 Session 3 : Adrienne Fairhall

Vinzenz H. Schönfelder,1, 2 I. Fründ,1, 2. and F. A Wichmann 3, 4

Peering into the Black Box – using sparse feature selection to identify critical stimulus properties in audition

1 Department for Modelling of Cognitive Processes, Technische Universität Berlin; 2 Bernstein Center for Computational Neuroscience, Berlin; 3 Neural Information Processing Group, Eberhard-Karls-Universität Tübingen; 4 Bernstein Center for Computational Neuroscience, Tübingen

In order to understand and predict human behaviour in perceptual tasks, we need to learn which stimulus features are critical to the observer's decisions. As a particular instance of this general question, we investigated a classical task in auditory psychophysics, Tone-in-Noise detection. Understanding the percep- tual mechanisms behind this task is of general interest to our basic understand- ing of auditory processing. A number of sound features have been proposed that human listeners use to detect a pure tone masked by noise. So far, however, no conclusive answer has been given as to which features are critical to explain be- haviour on a trial-by-trial level. We collected a large data set for Tone-in-Noise detection with six naive listeners. Relying on sparse feature selection algorithms developed in machine learning we fit an observer model that combines a set of sound features as well as the history of previous responses. Listeners could hardly be discriminated in terms of psychometric performance averaged across trials. Nevertheless, we observed substantial differences as regards the features that explain single-trial response behaviour. For all observers, only a mixture of multiple sound features – including energy, spectral fine structure and enve- lope spectrum – could account for individual decisions. In addition, for three listeners, responses in previous trials played a significant role for the current decision. Contrasting trials with slow and fast reaction times, differences in ­feature weighting were also found within individuals. In conclusion, only a mix- ture of different stimulus features combined with the history of previous re- sponses was generally sufficient to explain trial-by-trial behaviour of individual listeners in the present task. 27

SESSION 4

Friday, 9 December 2011

09.30 Kalanit Grill-Spector Re-thinking the functional organization of human high-level visual cortex

10.30 Fatma Imamoglu Karin Ludwig Fernando Ramirez › Ph. D. talks

Introduction Philipp Sterzer Charité – Universitätsmedizin Berlin

Chair Martin Hebart Bernstein Center for Computational Neuroscience & Berlin School of Mind and Brain 28 Session 4 : Kalanit Grill-Spector

Kalanit Grill-Spector

Associate Professor Vision & Perception Neuroscience Lab Department of Psychology and Neuroscience Institute Stanford University, California, USA mail [email protected] web http://vpnl.stanford.edu/kalanit.htm

Research Summary Kalanit Grill-Spector’s research utilizes functional imaging ( f MRI ), computa- tional techniques and behavioral methods to investigate visual recognition and high-level visual processes. For humans, visual recognition is a natural, effortless skill that occurs within a few hundreds of milliseconds, yet, it is one of the least understood aspects of visual perception. She and her group investigates the un- derlying representations and cortical mechanisms that subserve recognition, and the relation between these neural processes, and our visual perception of the world. They are interested to learn how these neural representations come about, how they change with experience and development and what are the basic com- putations that are implemented in the brain that enable visual perception.

Education Ben-Gurion University, Israel, Electrical Engineering & Computer Science, B. Sc., 1990

Research Topics Computational approaches, developmental approaches, neuroscience approaches, perception, plasticity and change, psychopathology and risk, vision science Session 4 : Kalanit Grill-Spector 29

Kalanit Grill-Spector

Re-thinking the functional organization of human high-level ­visual cortex

Department of Psychology and Neuroscience Institute, Stanford University, USA

The visual system contains systematic representations of the visual field in a series of retinotopic maps, as well as specialized regions for processing certain stimuli such as objects, body parts, faces, words, and places. The prevailing view is that separate organization principles produce these seemingly different functional maps. Contrary to this view, research from my lab using higher resolution fMRI shows common organization principles throughout early and high-level visual cortex where functional regions have consistent anatomical locations and pre- served spatial relationships to neighboring regions. I will expand on three basic organization principles of high-level visual cortex revealed by our measurements: 1 ) consistency in the anatomical location of functional regions, 2 ) preserved ­spatial relationship among functional regions as well as retinotopic maps, and 3 ) a topographic organization of face- and limb-selective regions in adjacent and alternating clusters. Employing these principles enables the first framework for consistent parcellation of high-level visual regions, which can also be applied to other sensory and nonsensory cortical systems. I will highlight the implica- tions of this structure in comparing functional brain organization between typi- cal and atypical populations and conclude with a new model of high-level visual cortex consisting of ventral, lateral, and dorsal components. 30 Session 4 : Kalanit Grill-Spector

Fatma Imamoglu,1 T. Kahnt,1 C. Koch,2, 3 and J. -D. Haynes 1, 4

Changes in effective connectivity support conscious object ­recognition

1 Bernstein Center for Computational Neuroscience, Berlin; 2 California Institute of Technology, Pasadena, CA, USA; 3 Allen Institute for Brain Sciences, Seattle, WA, USA; 4 Cluster of Excellence Neurocure, Charité – Universitätsmedizin Berlin

Which brain mechanisms mediate conscious perception of physically constant but perceptually changing visual stimuli? It has previously been shown that high-level sensory and prefrontal brain regions integrate visual signals over time with brain activity peaking at the time of observer’s conscious perception. However, the possible role of changes in connectivity between early visual and higher-order frontal regions has only rarely been studied. Here, we used f MRI and connectivity analyses, together with 120 custom-generated two-tone, Mooney images to directly assess whether conscious recognition of an object is accompanied by a dynamical change in the functional coupling between early visual and prefrontal areas. We compared two different perceptual conditions ( seen vs. not seen ) in the presence of the same physical stimulus in 19 naïve sub- jects using two different response modalities. We find that connectivity between the early visual cortex and the dorsolateral prefrontal cortex ( DLPFC ) increases when objects are consciously perceived. This interaction was independent of the response modality that we used to report conscious perception. Furthermore, ­using Granger causality analysis, we provide evidence for an increase in the ­directed influence of early visual cortex on DLPFC when subjects recognized the objects consciously. These findings are in line with predictions about the involvement of prefrontal cortex in conscious perception made by Crick and Koch as well as the Global Workspace Theory ( GWT ). We suggest that frontal and visual brain regions are part of a functional network that supports conscious object recognition by changes in connectivity. Session 4 : Kalanit Grill-Spector 31

Karin T. Ludwig,1, 2 A. Pastukhov,1 and J. Braun 1

Persistent priming by challenging visual perceptions

1 Cognitive Biology, Otto-von-Guericke-Universität Magdeburg; 2 Visual Perception Laboratory, Department of Psychiatry, Charité – Universitätsmedizin Berlin

Both low-contrast visual signals and ambiguous stimuli can influence subsequent perception in the form of a priming effect (Tanaka & Sagi, 1998; Pearson & Brascamp, 2008 ). These effects share some critical properties. They build up rela- tively quickly ( below one second ), decay slowly ( in the order of dozens of sec- onds ) and are specific to retinal position. Most importantly, both effects are ­facilitative: in the first case detection is enhanced, in the latter case ambiguity is resolved in favour of the formerly dominant percept. In this study their interconnection was examined by testing the effect of ­ambiguous primes on contrast detection tasks and that of low-contrast primes on ambiguous vision. As ambiguous primes failed to exhibit an effect on low- contrast probes and vice versa, we conclude that it is unlikely that they share a neural substrate. Priming strength was, however, found to correlate with the level of ambigu- ity as it does with contrast. Just like lower contrast results in a stronger priming effect (as reported by Tanaka and Sagi in 1998 ), we found that higher ambiguity produced more facilitation. This suggests, together with the known similarities, the following processing principle: when the build-up of visual perception is challenging because the visual input is weak ( e. g., of low contrast ) or ambiguous, more processing re- sources seem to be recruited, which leads to the generation of a facilitative priming effect. 32 Session 4 : Kalanit Grill-Spector

Fernando Ramírez,1, 2, 3, 4 R. M. Cichy,1, 3 C. Allefeld,1, 3 and J. -D. Haynes 1, 2, 3

Category selective encoding of orientation in the fusiform face area

1 Bernstein Center for Computational Neuroscience, Berlin; 2 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin; 3 Cluster of Excellence Neurocure, Charité – Universitätsmedizin Berlin; 4 Institute of Psychology, Humboldt-Univer- sität zu Berlin

The fusiform face area is a region of the human ventral visual pathway that ex- hibits a stronger response to faces than objects. The role of this region for face perception is not well understood and its face selectivity has been debated. Fur- thermore, it is unclear which properties of visual stimuli are systematically re- flected in the patterns of activation of this region. Prior research suggested that FFA might encode orientation. Here we directly explored the encoding of ori- entation using a combination of functional magnetic resonance imaging ( f MRI ) multivoxel pattern analysis ( MVPA ) and representational dissimilarity analysis ( RDA ). We presented subjects with synthetic images of faces and cars that were rotated in depth and displayed either above or below fixation. We explored ori- entation-related information available in fine-grained activity patterns in FFA, lateral occipital ( LO ) and early visual cortex ( EVC ). Distributed signals from FFA allowed above-chance classification of orientation within category only for faces. This finding generalized to faces presented in different retinotopic posi- tions. In contrast, classification in EVC and LO resulted in comparable, above- chance classification of face and car orientation information, but only when trained and tested on corresponding retinotopic positions. Classification accura- cies across position were substantially decreased for both categories in LO, while not different from chance in EVC. Modeling results suggest a translation tolerant code of face-angle information in FFA that represents frontal views more robustly. We conclude that category-selective effects of stimulus orienta- tion are reflected in the fine grained patterns of activation in FFA, and that the structure of these patterns is tolerant to translation. 33

SESSION 5

Friday, 9 December 2011

11.45 Hermona Soreq Micro-RNAs in the interface between inflammation and neurodegeneration

12.45 Odilo Engel Michael Kintscher Katyayni Vinnakota › Ph. D. talks

Introduction Andreas Meisel Charité – Universitätsmedizin Berlin

Chair Katarzyna Winek International Graduate Program Medical Neurosciences 34 Session 5 : Hermona Soreq

Hermona Soreq

The Edmond and Lily Safra Center for Brain Sciences and The Life Sciences Institute The Hebrew University of Jerusalem (HUJI), Israel mail [email protected]

Education and Positions

2009 – 2011 Coordinator of the Heidelberg – Jerusalem University’s Academic Exchange Program 2005 – 2008 Elected Dean, Faculty of Mathematics and Natural Sciences, HUJI 2005 – 2012 Non-Resident Research Professor, The Bio-Design Institute, Arizona State University 2002 – 2005 Vice Dean for R & D, Faculty of Science, HUJI 2000 – 2005 Head, The Roland Centre for Neurodegenerative Diseases, HUJI 1995 – 1999 Head, The Alexander Silberman Institute of Life Sciences, HUJI 1992 – 1995 Head, Department of Biological Chemistry, HUJI 1989 – ongoing Professor of Molecular Biology, Dept. of Biological Chemistry, HUJI

Honors and Awards (selection)

2010 Visiting scholar ( July – September), Berlin School of Mind and Brain, Humboldt-Universität zu Berlin 2009 The Lise Meitner ward,A Alexander von Humboldt Foundation 2007 Doctor of Philosophy honoris causa in Medicine, Friedrich Alexander University Erlangen-Nuremberg Doctor of Philosophy honoris causa in Science, Beer-Sheva University of the Negev, Israel 2005 Landau Prize for Biomedical Research 2001 Honorary Professorship, The Maimonides University, Buenos Aires Session 5 : Hermon 35a Soreq

Hermona Soreq

Micro-RNAs in the interface between inflammation and neurodegeneration

The Edmond and Lily Safra Center for Brain Sciences and The Life Sciences Institute, The Hebrew University of Jerusalem, Israel

Alzheimer’s disease (AD) notably involves failed synaptic functioning, neuro­ inflammation and premature death of cholinergic neurons, but the underlying mechanism(s) and possible inter-relationships between these phenomena are yet incompletely understood. Using a high throughput exon microarray screen- ing, we discovered alternative splicing impairments and corresponding decreas- es in the exon exclusion regulators, heteronuclear ribonucleoprotein particles (hnRNPs) in the entorhinal cortex from AD patients compared to non-dement- ed controls. This was accompanied by increased micro-RNA (miR)-211 which co-targets three different hnRNP mRNAs; and lentiviral-mediated knockdown of these hnRNPs caused synapse loss in cultured neurons and learning and memory impairments in brain-injected mice. Furthermore, in vivo destruction of cholinergic neurons but not APP or TAU mutations reduced brain hnRNP levels, the inflammation regulating and acetylcholinesterase (AChE)-targeted miR-132 was drastically reduced in the AD entorhinal cortex and manipulating­ one of these miRs caused inverse changes in the other. Together, our findings­ suggest that in AD, cholinergic signaling failure causes miR-211 incr­ eases and miR-132 decreases. MiR-211 excess mediates hnRNP depletion, lea­ ding to syn- apse loss; and miR-132 decreases cause AChE elevation and impair cholinergic­ signaling yet further, which exacerbates hnRNPs loss and enhances neuro­­ inflammation. Approaching the complex interactions between simultaneously acting miRs may open new venues for therapeutic interference with neuro­ degeneration processes. 36 Session 5 : Hermona Soreq

Odilo Engel,1 A. C. da Costa Goncalves,3 S. Shenhar-Tsefarty,4 M. Thielke,1 H. Soreq,4 C. Meisel,2 and A. Meisel 1

Parasympathetic activity dampens peripheral immune responses after stroke

1 Department for Experimental Neurology, Charité – Universitätsmedizin Berlin; Institute for Medical Immunology, Charité – Universitätsmedizin Berlin; 3 Max-­ Delbrück-Centrum für Molekulare Medizin Berlin-Buch; 4 Department of Biological Chemistry, The Silberman Institute of Life Sciences, and the Interdisciplinary ­Center for Neural Computation, The Hebrew University of Jerusalem, Israel

Infection is the most important complication after ischaemic stroke, caused by a profound immunodepression following the ischaemic event. As the nervous and the immune system maintain an intense bidirectional communication, this immune-depression is caused by anti-inflammatory signals from the damaged CNS via the Sympathetic nervous system and the Hypothalamus-Pituitary-­ Adrenal axis. ( Prass et al. 2003 ) Recently it became evident that the parasympathetic nervous system plays an important role in brain immune communication. In response to locally re- leased acetylcholine, activated macrophages swiftly decrease the production of proinflammator­ y cytokines. ( Tracey 2002 ) We hypothesize that after stroke an activation of the parasympathetic nervous system could be the initial step in the immunodepression after stroke. Particular importance arises from the fact, that this pathway regulates with the innate immunity the “first line of defence” being crucial for the integrity of immunological barriers. Using telemetry mice showed a specific change in parasympathetic heart ­rate variability after stroke, proving an increased parasympathetic tone. Discon- necting vagal communication led to lower bacterial burden and infection after experimental stroke. Here we also described different cell types which are re- sponsible for the parasympathetic role in post stroke immunodepression. Additionally to direct signals from the vagus nerve, also the expression of the cleaving enzyme Achetylcholinesterase is changed in a tissue-specific kinetic. Session 5 : Hermon 37a Soreq

Michael Kintscher, F. Johenning, D. Schmitz, * and J. Breustedt *

RIM1α controls short-term plasticity by setting release probability

Neuroscience Research Center, Charité – Universitätsmedizin Berlin * equally contributing

Changes in the strength of synaptic transmission are activity dependent and can occur on short- or long-term time scales. Whereas long-term changes are due to a persistent alteration of presynaptic proteins and / or insertion of postsynap- tic receptors, short-term plasticity is mostly determined by the composition and organisation of the presynaptic release machinery at the active zone. One of the central proteins in this complex is the Rab interacting molecule ( RIM ). It has been shown to bind to multiple proteins of the active zone, such as Munc-13, RIM-BP, Ca2+-channels and Rab3. Therefore RIM plays a pivotal role in mech- anisms of presynaptic release and plasticity. Recent studies have provided a detailed analysis of the function of multi­ domain RIM isoforms at the active zone of the presynapse. The removal of all RIM1 / 2 isoforms led to a reduced tethering of Ca2+-channels to the active zone, less docked vesicles and a smaller readily releasable pool. Here we examine the role of the prototypic RIM isoform, RIM1α, in short- term plasticity. The deletion of this protein in mice leads to an increased short- term plasticity at hippocampal Schaffer collateral – CA1 synapses and cerebellar parallel fiber – Purkinje cell synapses. By using electrophysiological means and pharmacology we show that the basal synaptic transmission is deceased at both synapses. This is accompanied by a reduction of the glutamate transient in the synaptic cleft. Performance of mean-variance analysis revealed that this reduction can be explained by a lower release probability, whereas the quantal content is unchanged. Further analysis using 2-photon laser scanning microscopy revealed a reduced Ca2+-influx at ­single boutons ( presynaptic release sites ) in granule cell ascending axons. 38 Session 5 : Hermona Soreq

Katyayni Vinnakota,1 S. Lehmann,2 K. Rosenberger,2 S. Lehnardt,2 D. Markovic,1, 3 S. Wolf,1 R. Glass,4 and H. Kettenmann 1

TLR signaling modulates MT1-MMP expression in glioma-­ associated microglia and contributes to glioma growth

1 Max Delbrück Center for Molecular Medicine Berlin-Buch; 2 Centre for Anatomy, Institute of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin; 3 Helios Klinikum Berlin-Buch; 4 Klinikum der Ludwig-Maximilians-Universität München, Klinik für Neurochirurgie, Neurochirurgische Forschung, München

Membrane type 1 metalloprotease ( MT1-MMP ) expressed by microglia activates the pro-MMP2 released by glioma cells and thus promotes glioma invasion. Deletion of the Toll-like Receptor ( TLR ) adaptor molecule MyD88 led to a concomitant decrease in microglial MT1-MMP expression and glioma growth, indicating a possible role of TLRs in microglia-mediated glioma pathology ( Markovic, D. et al., 2009 ). When microglia cells from Bl / 6 wild-type ( WT ) mice were stimulated for 3h and 6h with specific ligands for TLR1 / 2, TLR3, TLR4, TLR5, TLR6 / 2 and TLR7 / 8 to analyze MT1-MMP expression, the TLR1 / 2 ligand Pam3CSK4 induced nearly 3-fold upregulation of MT1-MMP at 6 h as quantified yb RT-PCR analysis while the other TLR agonists had little or no effect. Knocking-out the TLR2 gene locus decreased MT1-MMP expres- sion in microglia stimulated with glioma conditioned medium ( GCM ) for 3 h and 6 h as seen by qRT-PCR analysis. To examine if microglial TLR2 mediates glioma expansion ex vivo, eGFP-GL261 glioma cells were injected into organo- typic brain slices ( OBS ) from Bl / 6 WT and TLR2 knock-out ( KO ) mice and tumor growth was monitored after 5 days. Loss of TLR2 reduced tumor expan- sion to nearly 40 % of tumor size as compared to WT controls. Further deple- tion of microglia with clodronate reduced tumor size not only in OBS from WT mice ( Markovic, D. et al, 2005 ), but also decreased glioma expansion in the OBS from TLR2 KO mice. Changes in glioma size and MT1-MMP expression were evaluated in Bl / 6 WT and TLR2, 4 and 9 KO mice 2 weeks after tumor inocu- lation in vivo. A significant decrease in microglial MT1-MMP expression and reduction in tumor size were observed in TLR2 KO mice compared to WT controls. No significant differences were noted in TLR4 and 9 KO mice. These results substantiate the role of microglial TLR2- MT1-MMP signalling in glio- ma progression. 39

SESSION 6

Friday, 9 December 2011

15.00 Hans Markowitsch Memory and Brain: Neuropsychology, Neurology, and Psychiatry

16.00 Gürsel Çalışkan Jakob Gutzmann Chia-Ling Chang › Ph. D. talks

Introduction Jörg Geiger Institute of Neurophysiology, Charité − Universitätsmedizin Berlin

Chair Stephanie Wegener Neuroscience Research Center, Charité – Universitätsmedizin Berlin 40 Session 6 : Hans Markowitsch

Hans Markowitsch

Physiological Psychology University of Bielefeld, Bielefeld mail [email protected] web www.uni-bielefeld.de/psychologie/personen/ ae14/markowitsch.html

Hans Markowitsch is professor of physiological psychology at Bielefeld ­University. He was co-director of the Center for Advanced Study (ZiF) of the University of Bielefeld. He studied psychology and biology at the University of Constance. He had professorships for biopsychology and physiological ­psychology at the Universities of Constance, Bochum, and Bielefeld and was offered chairs of psychology and neuroscience at Australian and Canadian ­Universities. Hans Markowitsch has several co-operations with scientists from universities and Max Planck Institutes in Germany and North America. His research concentrates on the neural and psychic bases of memory and memory disorders. He is author, co-author or editor of more than two dozen books and has written more than 600 scientific articles and book chapters. Session 6 : Hans Markowitsch 41

Hans J. Markowitsch

Memory and brain: neuropsychology, neurology, and psychiatry

Physiological Psychology, University of Bielefeld

Memory is described as a multifaceted phenomenon, dividable into time and content-based systems. It is proposed that the content-based systems develop and build-up on each other during ontogeny and phylogeny. The lowest two systems are considered motor- ( procedural memory ) and sensory-related ( prim- ing ) and as being processed unconsciously, the other three as being processed consciously ( perceptual memory, semantic memory, episodic-autobiographical memory [ EAM ] ). The EAM-system is seen as requiring the synchronous ac- tion of cognition and emotion; it is proposed that it exists only in human beings and as requiring autonoetic consciousness. Damage to focal brain regions and networks is considered to lead to impairments in encoding, storing, or retrieving one or several of these memory systems, as will be outlined on the basis of data from neurological patients. It will furthermore be shown that stress- and psychic trauma-related forms of dissociative or psychogenic amnesia not only lead to severe and lasting forms of ( mostly retrograde ) amnesia, but also to changes in brain structure and neural metabolism. It is concluded that there is an intensive interchange between brain development and memory, as well as between the social and biological environment and brain function.

Literature Markowitsch, H. J. & Staniloiu, A. ( in press ). Amnesia. Lancet 42 Session 6 : Hans Markowitsch

A. Albrecht,1, * Gürsel Çalışkan,2, * M. Oitzl,3 U. Heinemann,2 and O. Stork 1

Long-lasting increase in plasma corticosterone associated with changes in anxiety behavior and hippocampal gamma oscillations following fear memory reconsolidation

1 Institute of Biology, Otto-von-Guericke-Universität Magdeburg; 2 Institute for Neurophysiology, Charité − Universitätsmedizin Berlin; 3 Faculty of Science, Leiden/Amsterdam Center for Drug Research, Medical Pharmacology, Gorlaeus ­Laboratories, Leiden, The Netherlands

Reconsolidation of fear memory provides a starting point for developing thera- peutic strategies against anxiety disorders. Although comprehensive work is done concerning molecular events induced by reconsolidation, the long-term consequences are less well understood. We now evaluated, in mice, long-term effects of reconsolidation of auditory cued fear memory on anxiety-like behavior, on HPA-activity and responsiveness as well as on network activity in a key ­region for mediating anxiety-like behavior, the ventral hippocampus. We found that reconsolidation of fear memory resulted in reduced anxiety-like behavior; accompanied by increased basal CORT plasma levels and increased freezing towards the conditioned background context four weeks later. We could also demonstrate that, while a circadian rhythm in basal CORT plasma levels was still established circadian differences in anxiety-like behavior were inverted after reconsolidation. Since individual differences in HPA- responsiveness are also observed in anxiety patients and intermingle with circadian effects in CORT plasma levels, a re-analyzed of our data with respect to high vs. low basal activ- ity of the HPA- axis revealed a correlation between increased basal CORT ­plasma levels and reduced anxiety-like behavior. Oscillatory activity at the gam- ma frequency range in ventral hippocampal slices induced by 100 nM kainate was diminished in power and correlation four weeks after fear conditioning and its reconsolidation. These effects could be rescued by CORT. Together, reconsoli- dation of fear memory elicits long-term alterations in HPA-axis basal activity and responsiveness that may have protective effects against exaggerated anxiety in a subset of individuals. Session 6 : Hans Markowitsch 43

Jakob Gutzmann, G. Hermey and D. Kuhl

Characterization of novel Arc/Arg3.1 interaction partners

Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), Universitätsklinikum ­Hamburg-Eppendorf

The immediate early gene Arg3.1 is highly and transiently expressed after ­neuronal activity and its mRNA is actively transported into dendrites and spines of neurons with a recent history of activity. Experiments with Arg3.1 knockout mice demonstrate that Arg3.1 is crucial for the consolidation of ­long-term memories in a variety of behavioural paradigms. Dynamin2 and Endophilin3 have been described as interaction partners of the Arg3.1 protein, implicating Arg3.1 in trafficking processes of postsynaptic vesicles that contain AMPA type glutamate receptors. Yet these interactions cannot fully explain the observed phenotype of Arg3.1 knockout mice. By Split-Ubiquitin Yeast 2 Hybrid analysis we identified two novel inter­ action partners of Arg3.1, TMP1 and TMP2. Both are so far uncharacterized multiple pass transmembrane proteins that can be implicated in vesicle traffick- ing based on sequence homology. By expression of tagged versions of TMP1 and TMP2 in different cell types we demonstrate that both proteins are local- ized to the endoplasmatic reticulum ( ER ), and we show that both proteins are found in the ER of neurons including branches of the ER in distal tips of den- drites. Topology analysis reveals that the N-termini of both proteins face the cytoplasm and potentially convey the interaction with Arg3.1. Genomic analysis and semi quantitative RT-PCR establishes that TMP2 is alternatively spliced resulting in mRNAs with different 3’-UTRs but encoding identical proteins. One of these transcripts is induced by neuronal activity in cultured hippocampal neurons. Taken together, our results indicate that Arg3.1 partakes in the activity regulated dendritic secretory pathway. Further experiments will be performed to clarify the precise role of TMP1 and TMP2 in the dendritic ER. 44 Session 6 : Hans Markowitsch

Chia-Ling Chang,1, 2, 4 and C. Rosenmund 1, 3, 4

Identify the targets that are involved in regulating synapse ­formation by MeCP2

1 Neuroscience Research Centre, Charité – Universitätsmedizin Berlin; 2 Graduate Program Medical Neuroscience, Charité – Universitätsmedizin Berlin; 3 Cluster of Excellence Neurocure, Charité – Universitätsmedizin Berlin; 4 Baylor College of Med- icine, Depts of Neuroscience and Molecular and Human Genetics, Houston, TX, USA

Loss of function mutations in the X-linked gene encoding the transcriptional repressor, methyl-CpG binding protein 2 (MeCP2), results in Rett syndrome. MeCp2 expression in central nervous system is associated with synapse matura- tion. Based on our studies it was shown that neurons loss of MeCp2 results in re- duced excitatory synaptic strength and doubling of MeCP2 results in enhanced synaptic strength. The change of synaptic strength is due to the corresponding synapse number. However, which molecules are involved in synapse formation still need to be elucidated. In this study, we first want to focus on whether pre- or the post- synaptic site is responsible for the MeCP2 regulating synapse formation. To achieve this aim, we used a two-cell circuitry that composed a wildtype (WT) and a MeCP2 mutant (either knockout [KO] or double [Tg1] of MeCP2 protein) neuron to separate the pre and the post contribution on synapse formation. After 13 to 16 days in vitro, we recorded both neurons simultaneously by paired recording. Both neurons were labeled with different membrane dye to let us visibly identify the genotype before performing electrophysiology. We analyzed the compound EPSC charge (summation of WT to WT and KO to WT or summation of KO to KO and WT to KO), compound RRP (sucrose size onto WT and onto KO neuron) and compound miniature EPSC (mEPSC) frequency (onto WT or onto KO). In WT-KO pairs, we hypothesized that if it is postsynaptic effect, we expect to find that the compound RRP and the compound mEPSC frequency of WT is larger than KO compound RRP. However, if it is presynaptic effect, we expect to find the total EPSC charge (the summation of autaptic and heterosynaptic EPSC) from WT neuron is larger than KO neuron. There was no difference in compound RRP size between WT and KO neuron as well as mEPSC frequency. The total EPSC charge of WT was larger than KO however the compound EPSC of WT and KO was comparable. Together, these results indicate that molecules located in presynaptic site might play a major role in MeCP2 regulated synapse formation. Session 6 : Hans Markowitsch 45

POSTERS

Thursday, 8 December 2011

13.30 – 15.00 even numbers

Friday, 9 December 2011

13.30 – 15.00 odd numbers

Foyer of the Conference Center MDC.C 46

POSTERS

P 1 – P12 Medical Neurosciences 47 P13 – P19 Learning and Memory 59 P20 – P25 Mind and Brain 66 P26 – P31 Molecular Neurobiology 72 P32 – P36 Computational Neuroscience 78 P37 – P39 Languages of Emotion 83 P40 – P57 External 86 International Graduate Program Medical Neurosciences 47

Anna L. Dätwyler,1, C.2 Hoffmann,1 M. Endres,1 and C. Harms 1

The roles of Uracil-DNA glycosylase 1 and 2 in endogenous P1 ­neuroprotection and DNA repair

1 Center for Stroke Research and Klinik für Neurologie, Charité − Universitäts­ medizin Berlin; 2 International Graduate Program Medical Neurosciences

Uracil-DNA glycosylase ( UNG ) is part of the base excision repair complex ( BER ) which repairs a broad variety of oxidative lesions in nuclear and mito- chondrial DNA. Ung- / - mice develop increased lesion volumes after middle ­cerebral artery occlusion ( Endres et al., 2004 ). Furthermore, ung- / - neurons show a mitochondrial phenotype pointing to a dysfunction linked to the mito- chondrial splice variant UNG1 ( Kronenberg et al., 2011 ). Thus, we tested the neuroprotective impact of UNG1 after ischemic-like stress ie. oxygen-glucose deprivation ( OGD ). First, we analyzed the splice variant specific dynamics on RNA and protein level at baseline and after OGD. Second, we applied a neuronal specific loss-of-function approach in which we used lentiviral delivery of UNG1- and UNG1 / 2 microRNAs to block neuronal translation of both splice variants. Viability of the cortical neuronal cell cultures was unaffected by UNG1- and UNG1 / 2 silencing unless they were stressed by OGD. In cultures subjected to 30 min of OGD, control as well as UNG1 / 2 microRNA transduced cultures were unaffected, but survival of UNG1 transduced neurons dropped to approximately 75 %. Both 45 and 60 min were still tolerated by control micro­ RNA transduced cultures, but survival dropped to ca 60 % and 50 % for UNG1 knock down and to ca 80 % and 60 % for UNG1 / 2 knock down, respectively. Damaging OGD lead to less than 50 % surviving neurons in control microRNA cultures, less than 1 % in UNG1 microRNA cultures and to approximately 55 % in UNG1 / 2 microRNA cultures. We conclude that mitochondrial UNG1 induc- tion is an endogenous neuroprotective stress response of the BER complex in mitochondria and we could further show a role of UNG2 with a negative im- pact on neuronal survival if UNG1 expression is knocked. 48 International Graduate Program Medical Neurosciences

Lina Issa,1, 2, N.3 Kraemer,1, G.2 Stoltenburg,1 O. Ninnemann,1 C. Rickert,4 and A. M. Kaindl 1, 2

P2 Cdk5rap2 in murine and human brain development

1 Institute of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin; 2 Pediatric Neurology, Charité – Universitätsmedizin Berlin; 3 International ­Graduate Program Medical Neurosciences; 4 Neuropathology and Paidopathology, Vivantes, Berlin

Primary autosomal recessive microcephaly ( MCPH ), also historically known as microcephalia vera, is an isolated developmental brain disorder specifically target- ing the cerebral cortex. A recessive mutation in the Cyclin dependent kinase 5 regulatory subunit-associated protein 2 gene CDK5RAP2 was discovered in 2005 to cause MCPH type 3. The highly conserved CDK5RAP2 protein plays a role in various cellular functions such as centrosome function, spindle formation / dynamics, kinetochore attachment to spindles, DNA repair, spindle checkpoint control and apoptosis and thereby contributes to the human MCPH phenotype. Still the exact pathomechanisms underlying the human MCPH phenotype are not known. Here we describe the temporal and spatial Cdk5rap2 protein local- ization in the murine and human cortex. International Graduate Program Medical Neurosciences 49

Lyudmyla Kovalenko,1, C.2 J. Ploner,3 and F. Ostendorf 2, 3

The role of thalamus-mediated corollary discharge P3 in perisaccadic localization

1 International Graduate Program Medical Neurosciences; 2 Berlin School of Mind and Brain; 3 Department of Neurology, Charité – Universitätsmedizin Berlin

As we explore the visual scene, the image on the retina changes continuously. Despite the frequent interruptions such as head and eye movements, we main- tain a stable visual percept of the world. This phenomenon is called perceptual stability. In reality, visual perception is not continuous, but rather consists of a succession of discrete retinal images. These images are the fixations that occur in between quick and frequent eye movements called saccades. While the sac- cade itself presents a massive disturbance to visual stability, it usually passes un- noticed. Should a comparable shift of the visual image occur without our having made a voluntary saccade, we would interpret this movement as an external change in the visual scene. It is believed that we are able to distinguish between these perceptual scenarios because voluntary eye movements are coupled to a signal that acts as an internal reference, allowing the brain to discriminate ­between sensory input from the external world and the reafference from self- generated movements. This internal signal is called corollary discharge ( CD ) and represents a copy of the motor command sent to sensory centers of the brain, where it relays information about the impending movement. Such feed- back from motor centers to sensory brain areas is thought to be an important mechanism for maintaining perceptual stability. Faulty processing of CD has been associated with a perturbed sense of space constancy and misattribution of one’s motor agency. Studies in patients with focal thalamic lesions have ­identified the medial thalamus as a key structure for relaying CD. The follow- ing study will closer investigate CD alterations in patients with focal thalamic lesions using a perisaccadic localization paradigm. 50 International Graduate Program Medical Neurosciences

Inês Laginha, M. Kopp, B. Brommer, N. Gatzemeier, and J. M. Schwab

P4 Spinal cord injury-induced immune depression syndrome ( SCI-IDS ) – role of NK- and T-cells function in the development of the syndrome

Department of Experimental Neurology, Charité – Universitätsmedizin Berlin

The nervous and the immune systems interact in a bidirectional way. The ner- vous system “hardwires” the immune relevant organs and the immune system relays information to the CNS through cognate receptors. This interplay between these both “megasystems” becomes evident in case of lesions in the nervous system such as stroke, traumatic brain injury as well as spinal cord injury ( SCI ). Following such an insult, a downregulation of the immune system has been observed. This phenomenon is called CNS Injury-­ Induced Immune Depression Syndrome ( CIDS ) ( Meisel 2005 ). In the context of SCI, this fluctuating deficit was shown for the first time at a cellular level by Rieger et al. affecting monocytes, dendritic cells, T- and B-lymphocytes sub- populations during the first week after SCI. Indeed infections are the main cause of death in the post-acute phase after SCI suggesting that an immunologi- cal deficit persists beyond the first week after the injury. Previous studies demonstrated that CIDS affects a broad range of immune functions, including reduced peripheral blood lymphocyte counts, impaired phagocytic activity of granulocytes, reduced mitogen-induced cytokine produc- tion, and impaired activity of T- and natural killer ( NK )-cells. The latter were shown to have decreased function manifested by their reduced cytolytic capacity in the chronic phase after SCI and reduced IFN-γ production after stroke ( Prass et al., 2003 ). These deficits might play a major role in the persisting im- mune depression, as NK cells are key players in the front-line defense against viral and bacterial infection. In this study we analyse the fluctuations of NK (CD161+ CD3– ) and T cells ( CD3+ ) along time in the experimental model of SCI as well as their capacity to produce IFN-γ by FACS and ELISA readout systems. International Graduate Program Medical Neurosciences 51

Ezequiel G. Lapilover,1 I. Weissberg,2 U. Heinemann,1 and A. Friedman 1

Altered hippocampal network plasticity in a model P5 of blood-brain barrier dysfunction

1 Institute of Neurophysiology, Charité – Universitätsmedizin Berlin; 2 Department of Physiology and Neurobiology, Ben-Gurion University of the Negev, Israel

Blood-brain barrier is a structural and functional barrier characterizing blood vessels within the central nervous system and is essential for normal brain ­functions. Dysfunction of the BBB has been shown in all common neurological disorders, including stroke, traumatic brain injury, tumors or epilepsy ( Abbott 2006; Schlosberg et al. 2010 ). Clinical studies showed co-localization of abnormal brain activity with BBB dysfunction, suggesting that brain exposure to serum components leads to neuronal dysfunction ( Tomkins 2008; Ivens 2009 ). Studies in experimental animals showed that exposure to the most abundant serum pro- tein, albumin, is sufficient to induce a long-lasting hypersynchronous neuronal network activity through tansforming growth factor beta signaling in astrocytes ( Friedman 2009; Weissberg 2011 ). However, the effect of serum albumin on ­synaptic integration and plasticity are not known. The main goal of the present study was to examine the effect of serum albumin on homo- and heterosynaptic long term plasticity in the hippocampus exposed to albumin. 52 International Graduate Program Medical Neurosciences

Ekaterina-Maria Lyras,1 Nefeli Slavi,1 and S. Mergler 2

P6 Calcium regulation in human conjunctival epithelial cells: a putative role of thermosensitive transient receptor potential channels

1 International Graduate Program Medical Neurosciences, Charité – Universitäts- medizin Berlin; 2 Biomedical Research Centre, Department of Ophthalmology, Charité – Universitätsmedizin Berlin

Transient receptor potential ( TRP ) channels are a superfamily of non-selective cation channels expressed on the membranes of number of different cell types. They are polymodally activated and can elicit various downstream effects on the cells they reside on. The existence and function of heat and osmosensitive TRP channels has previously been shown in the human corneal endothelium and ­epithelium. Dysregulation of either of these two cell layers is a causative of dry eye syndrome ( DES ) and the modulation of TRP channels has been implicated in having therapeutic effects. Further investigations need to be undertaken, however, in order to support these findings. The expression and role of TRPs in human conjunctival epithelial cells ( HCjEC ) is largely unknown. Our research project focuses on the characterization of calcium regulation by putative TRPV1, TRPM8 and / or TRPA1 in human HCjEC. We used fura-2 calcium imaging and planar patch-clamp techniques on cell cultures corresponding to this tissue in order to monitor the electrophysiological responses of cells to activators and blockers of these channels. The TRPV1 agonist capsaicin (CAP ) induced calcium transients and non-selective currents, an effect that was blocked when cells were preincubated with the TRPV1 selective antagonist capsazepine ( CPZ ). Cold stimulation and the agonist icilin were additionally applied to the cells to activate cold sensitive TRPM8 and TRPA1 channels. Icilin-induced Ca2+ transients were suppressed when the general TRP blocker lanthanum chloride ( La3+ ) was applied in the cells. Our data demonstrate the expression of thermo- sensitive receptors HCjEC and their complex role in regulating [ Ca2+ ] I and temperature sensing. International Graduate Program Medical Neurosciences 53

Thomas Pelz,1 S. Kurtenbach,2 S. Märschenz,3 and E. M. Neuhaus 1

GPRC5 receptors – from evolution to physiological functions P7

1 Neuroscience Research Center, Charité – Universitätsmedizin Berlin; 2 Depart- ment of Cell Physiology, Ruhr-Universität Bochum; 3 Department of Experimental Neurology, Charité – Universitätsmedizin Berlin

For the four members of the receptor group 5 within the family C of G protein- coupled receptors ( GPCR ), termed GPRC5A-D, to date neither interacting cytosolic or membrane proteins nor GPRC5-activating ligands have been iden- tified. GPRC5 receptors lack a large extracellular domain that contains both a ligand-binding site and a site for protein oligomerization in the other family C GPCRs, which makes it difficult to predict receptor-binding interactors. It has been shown that GPRC5 transcription is regulated by retinoic acid ( RA ) in vitro, which is crucially involved in the development and maintenance of organ- isms, especially the nervous system. In our recent publication we could show that GPRC5B is also regulated by RA in vivo. Furthermore we performed large-scale sequence analyses which revealed that GPRC5 receptor expression is exclusive for vertebrates. Among species the receptors show a highly conserved expression pattern in tissues, e. g. GPRC5B in the brain. Considering this and the very specific localization of the receptor in distinct regions of the brain involved in neurogenesis, it is tempting to anticipate implications on vertebrate development and / or physiologically relevant neuronal processes. Our approach to discover protein interactors involved the split ubiquitin system, which provides a large-scale assay where protein interaction with inte- gral and membrane-associated proteins can be analyzed. Thereby we could ­determine a set of potential interactors of murine GPRC5B. To verify these ­results we perform BRET assays with selected hits, all of the GPRC5 receptors and other putatively interacting proteins. To gain some knowledge about the functions of GPRC5B we performed expression analyses in in vivo and in vitro stroke models. 54 International Graduate Program Medical Neurosciences

Muhammad Liaquat Raza, I. Papageorgiou, K. Lehmann, and U. Heinemann

P8 sK-channel agonists: new hope for pharmacoresistant epilepsies?

Institute of Neurophysiology, Charité – Universitätsmedizin Berlin

Pharmacoresistance in epilepsy is among the bothersome effects for patient suf- fering from it, nearly 30 % patients are non-responsive to antiepileptic drugs. To address this issue we tested sK-channel agonist using pharmacosensitive and pharmacoresistant organotypic hippocampal slices cultures ( OHSCs ). Further we have test effects of sK-channel agonist on human tissue which is surgically removed from pharmacoresistant epileptic patients. Slice cultures were prepared from 7 – 8 days old rat pups and field potential recordings were performed from 7 – 14 days after incubation. For induction of seizure-like events ( SLEs ) in slice culture s, we have used 4-AP ( 100 µM ) & zero magnesium ACSF. In human tissue protocol of high K+ ( 8 mM ) + bicu- culline ( 50 µM ) & 4-AP ( 100 µM ) is followed to induce epileptiform activities. Results showed anticonvulsant actions of CyPPa, interestingly 4-AP induced SLEs in both pharmacosensitive and pharmacoresistant OHSCs were blocked by CyPPa at 100µM in 100 % slices ( n = 8 ). Whereas, zero magnesium induced SLEs are blocked in 88 % ( n = 7 ) and 74 % ( n = 6 ) of pharmacosensitive and pharma­coresistant OHSCs respectively. Similarly, CyPPa at same dose blocked SLE induced by 4-AP in all human tissues ( n = 4 ). K+ ( 8 mM ) + bicuculline ( 50 µM ) induced SLEs are blocked in 3 out of 5 slices used in this study. CyPPa at 20 µM blocked SLEs in 100 % pharmacosensitive slices ( n = 6 ) whereas, same dose of CyPPa was ineffective against SLEs induced by 4-AP in pharmacoresistant OHSCs ( n=6 ). In zero magnesium model, 20 µM dose failed to block SLEs in both pharmacosensitive and pharmacoresistant OHSCs ( n = 6 ). Our findings suggests CyPPa has potential to block both pharmacosensi- tive & pharmacoresistant type of seizures. Therefore it may serve as future anti­ epileptic drug after further characterization. International Graduate Program Medical Neurosciences 55

Christine Römer,1 O. Engel,1 C. Meisel,2 and A. Meisel 1

The role for stroke-induced immunodepression (SIDS) P9 in development of autoreactive immune responses after MCAo

1 Department for Experimental Neurology, Charité – Universitätsmedizin Berlin; 2 Department for Medical Immunology, Charité – Universitätsmedizin Berlin

Stroke-induced immunodepression ( SIDS ) renders an organism susceptible to infections and worsens neurological outcome. Here, we studied if and how SIDS inhibits the development of autoreactive immune responses after stroke. Female 2d2 transgenic mice carrying a T cell receptor for myelin oligoden- drocyte glycoprotein ( mMOG35-55 ) were subjected to a 60-minute middle cere- bral artery occlusion ( MCAo ). Sympathetic nervous system ( SNS ) mediated SIDS was blocked by administration of propranolol ( 30 mg / kg 0 h, 4 h and 8 h after MCAo ) and hypothalamic-pituitary-adrenal ( HPA ) axis mediated SIDS by mifepristone ( 20 mg / kg 24 h, 5 h and 0 h before MCAo ). Stroke volumes were measured with MRI technique 24 hours after MCAo induction. Autoreactive potential of brain infiltrating T cells was evaluated on an Elispot assay. We found a significant reduction in edema-corrected infarct volumes in mice where immunodepression was blocked ( p < 0.001 ). Elispot assay revealed that the secretion of IFN-gamma cytokine but also IL-4 production from T cells following stimulation with MOG35-55 peptide was higher in mice treated with propranolol and mifepristone despite the infarct volume was initially smaller compared to controls. Our results suggest that SIDS mediated by SNS and HPA inhibit the devel- opment of autoreactive immune response after stroke. However, more experi- ments are necessary to confirm this finding. 56 International Graduate Program Medical Neurosciences

Steffen B. Schulz,1, 2 Z. J. Klaft,1 A. Mike,3 U. Heinemann,1, 2 and Z. Gerevich 1

P10 Typical and atypical antipsychotics modulate hippocampal gamma oscillations

1 Institute of Neurophysiology, Charité – Universitätsmedizin Berlin; 2 Cluster of ­Excellence Neurocure, Charité – Universitätsmedizin Berlin; 3 Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary

Cortical oscillations in the gamma band ( 30 – 80 Hz ) have been implicated in a range of higher order brain functions such as sensory processing, working memory and attention. In addition, gamma oscillations are supposed to mediate the synchronization and functional coordination of distant cortical areas to ­enable or simplify information transfer. An increasing number of studies demonstrate that gamma oscillations are re- duced in schizophrenia patients. Schizophrenia is characterized by disturbances in many of higher brain functions known to be linked to gamma oscillations. This leads to the conception that disruption of gamma band network activity may underlie the pathophysiology of the disease. Both typical and atypical antipsychotic drugs have a highly complex pharmacol- ogy with considerable affinity for a variety of receptors (e. g. 5-HT, dopamine and adrenoceptors ). Therefore the aim of the present study was to investigate the effects of antipsychotic drugs on in vitro gamma oscillations. The oscillations were induced in rat hippocampal slices by bath application of acetylcholine mimicking cholinergic input from the septum. These cholinergic oscillations share many characteristics with in vivo intrahippocampal gamma oscillations making them an appropriate in vitro model for this network activity. 5 out of 8 tested drugs effected gamma oscillations by altering the peak power, peak frequency and / or bandwidth ( at 50 % of max. peak power ). Drugs classified into the same group ( atypical / weak typical / strong typical antipsychotics ) showed similar effects. In addition, for each of 15 different receptors, we correlated these changes against the pKi values of the corresponding drug and could thus estimate the contribution of each receptor to the changes in gamma oscillation. International Graduate Program Medical Neurosciences 57

Sophie Schweizer, A. Meisel, and S. Märschenz

Histone methylation in cerebral ischemia and neuroprotection P11

Department for Experimental Neurology, Charité – Universitätsmedizin Berlin

Significant changes in gene expression occur in the pathology of cerebral ­ischemia. A panoply of both neuroprotective and deleterious genes are differ­ entially regulated during brain injury maturation. Findings from our group show that manipulation of either DNA methylation or histone acetylation can induce a state that resembles endogenous tissue preservation and results in ­limitation of damage in case of stroke ( Endres et al. 2001, Meisel et al. 2006 ). For instance, pre-treatment with histone deacetylase inhibitor Trichostatin A protects mice from ischemic brain injury ( Yildirim et al. 2008 ). The involve- ment of histone methylation in cerebral ischemia remains to be elucidated. We explore the role of histone de- / methylating enzymes in ischemic injury and tolerance. As an in vitro model of ischemia we use oxygen-glucose depriva- tion ( OGD ). The demethylase LSD1 is not known to be directly regulated in response to hypoxia unlike several Jumonji demethylases. Yet, we were able to demonstrate that pharmacological blockade of LSD1 with Phenelzine, a mono- amine oxidase inhibitor, leads to a strong neuroprotective effect upon OGD in rat cortical neurons. The increase of global H3K4me2 levels following pre- treatment with Phenelzine indiciates the involvement of LSD1 in neuroprotec- tion. With RNAi and overexpression experiments we want to characterize ­cerebroprotective mechanisms of action and targets of LSD1. 58 International Graduate Program Medical Neurosciences

Katarzyna Winek,1 O. Engel,1 A. Meisel,1 P. W. Dabrowski,2 A. Radonic,2 A. Nitsche,2 A. Rex,1 and U. Dirnagl 1

P12 The impact of focal cerebral ischemia on the composition of murine intestinal microbiota

1 Department of Experimental Neurology, Charité – Universitätsmedizin Berlin; 2 Robert Koch Institute, Berlin

The intestine is inhabited by the community of commensal bacteria that con- tains more cells than the body. This microflora is dominated by strict anaerobic species, difficult to culture in standard laboratory conditions what made studying gut microbiota difficult until the development of DNA-sequencing methods. Today we can make use of these techniques to assess the role of the gut micro- biome in health and disease ( ‘metagenomics’ ). In recent years the gut micro­ biome and the brain-gut-microbiota communication axis have received growing attention. Interestingly, it was found that gut microflora may be involved in the pathogenesis and course of the central nervous system diseases. In our experi- ments we aim to assess the composition of the intestinal flora before and after stroke – one of the most common diseases of CNS. In order to do that, 12 mice were subjected to either Middle Cerebral Artery Occlusion ( MCAO ), a well- characterized animal model of ischemic stroke, or to sham operation. Fecal samples from each mouse were taken one day before and 48 hours after the sur- gical procedure. DNA was extracted from the samples and amplified using spe- cific primer sets targeting V1 – V3 and V6 – V8 hypervariable regions of 16S rRNA. As the last step 454 pyrosequencing was performed to comprehensively charac- terize the microbial gut community. We observed dramatic changes in the com- position of the intestinal flora before and after surgical procedures. However, the differences between MCAO and sham animals were only moderate. Our results indicate a strong influence of stress on the microbiota community. Changes in the gut flora after stroke and their possible role still demand further investigations, and a functional role of microbiome changes for stroke outcome needs to be established. GRK 1123 Cellular Mechanisms of Learning and Memory 59

Dorothea Deuschel,1, 2 P. Fidzinski,1, M.2 Heidenreich,1, 2 and T. J. Jentsch 1, 2

Electrophysiological characterization of the KCNQ3 P13 potassium channel subunit in mouse brain

1 FMP – Leibniz Institut für molekulare Pharmakologie; 2 Max-Delbrück-Centrum für Molkulare Medizin Berlin-Buch

KCNQ genes encode five Kv 7 potassium channel subunits that form either ­homotetrameric or heterotetrameric voltage-gated potassium channels. Four of these subunits ( K v 7.2 – K v 7.5 ) are expressed in the nervous system. KCNQ2 and KCNQ 3 heteromers are the principle molecular components that under- lie the M-current, an important regulator of neuronal excitability. In humans, ­mutations in the KCNQ 2 and KCNQ 3 potassium channel genes are associat- ed with benign familial neonatal convulsions ( BFNC ), an inherited epilepsy syndrome. Using a knockout mouse-model we have studied the contribution of the KCNQ 3 channel subunit to the electrophysiological properties of CA 1 pyrami- dal cells in the hippocampus. We show that in KCNQ 3 knockout mice the ­M-current is reduced. Likewise, subthreshold theta resonance at depolarized potentials is abolished. However, we could not find a difference in neuronal ­excitability: neither in action potential frequency nor in the resting membrane potential. A direct comparison of resonance properties between different KCNQ ho- momers and heteromers was performed in a heterologous expression system. Cells expressing KCNQ3 heteromers showed stronger membrane resonance than cells expressing KCNQ3 homomers, suggesting that KCNQ heteromers are the major contributors to theta resonance in neuronal cells. 60 GRK 1123 Cellular Mechanisms of Learning and Memory

K. Liu,*, M.2 Siebert,*, S.2 Mertel,*, 1 Elena Knoche,*, S.2 Wegener,*, 2 C. Wichmann,2 T. Matkovic,1 K. Muhammad,1 H. Depner,1 C. Mettke,1 J. Bückers,3 S. Hell,3 M. Müller,4 G. Davis,4 D. Schmitz,2, # and S. Sigrist 1, 2, # P14 * contributed equally, # correspondence shared

RIM binding protein is a core component of the active zone ­cytomatrix and essential for neurotransmitter release

1 Institute for Biology / Genetics, Freie Universität Berlin; 2 Cluster of Excellence Neurocure, Charité – Universitätsmedizin Berlin; 3 Department of Nanobio­ photonics, Max Planck Institute for Biophysical Chemistry, Göttingen; 4 Depart- ment of Biochemistry and Biophysics, University of California San Francisco, USA

Synaptic transmission is enabled by the fusion of synaptic vesicles ( SVs ) at pre- synaptic active zone ( AZ ) membranes. The concerted action of the core fusion machinery ensures SV fusion, while the AZ-associated protein scaffolds ( cyto- matrices ) are considered to play a modulatory role in this process. Here, we show that Drosophila RIM binding protein ( DRBP ), a component of the AZ cytomatrix, is not only crucial for the integrity of this protein scaffold, but also essential for evoked neurotransmitter release. Using stimulated emission deple- tion and electron microscopy, we show that DRBP tightly surrounds the central Ca2+ channel field at the base of the AZ cytomatrix. This cytomatrix is defective in drbp mutants, and synaptic responses to single action potentials are severely reduced. Specifically, Ca2+ channel clustering and Ca2+ influx are impaired, and synaptic release probability is decreased. This is reflected by an impressive short- term facilitation in drbp mutants. Based on this data, we propose that the highly conserved RBP proteins are prime effectors of the AZ cytomatrix, where they link SVs, Ca2+ channels and the SV fusion machinery. GRK 1123 Cellular Mechanisms of Learning and Memory 61

Filip Liebsch,1, 2 D. Kaden,1 L. M. Munter,1 and G. Multhaup 1, 2, 3

BACE and copper in Alzheimer’s Disease ( AD ) – P15 possible roles in learning and memory

1 Freie Universität Berlin, Institut für Chemie und Biochemie; 2 GRK 1123 Cellular Mechanisms of Learning and Memory; 3 Freie Universität Berlin, Cluster of Excel- lence Neurocure

The central event in the formation of Abeta is the initial proteolysis of APP by BACE1 followed by cleavages exerted by the gamma-secretase. Disturbances in the copper homeostasis have been observed in the brain of Alzheimer’s dis- ease patients which could be linked on the molecular level to an altered APP- processing influenced by copper. Although it is known that both APP and BACE1 bind copper and BACE1 interacts with the copper chaperone of SOD1, i. e., CCS, it has remained unclear, what role BACE1 plays in copper homeosta- sis in health and disease. Based on our biochemical studies we postulate that BACE1 might be involved in cellular copper transport. We use two model systems to examine a possible copper transport function of BACE1. Experiments including overexpression or knockdown of BACE1 in embryonic mouse cell lines which are depleted for Ctr1, a membrane protein responsible for high affinity copper uptake, will pro- vide an answer to the question if BACE1 is involved in cellular copper import. In order to address this question in vivo we have generated different D. melano­ gaster fly strains with a knockout of the copper transporter 1B ( Ctr1B ) and co- expression of different BACE1 forms. By appropriate crossings of stocks among themselves, it will be possible to figure out whether BACE1 exerts a direct or indirect function in cellular copper transport in the presence or absence of a low-copper-background in D. melanogaster. Further studies will aim at behavioral testing of these flies to characterize the neuromodulating effect of copper at glutamatergic synapses and to finally understand the role of copper and BACE1 at the synapse in concert with APP. 62 GRK 1123 Cellular Mechanisms of Learning and Memory

Kristina Lippmann,1 J. Nichtweiß,1 A. Reichert,1 G. Bar-Klein,2 U. Heinemann,1 and A. Friedman 1, 2

P16 Altered synaptic plasticity in the hippocampus following vascular injury and blood-brain barrier dysfunction

1 Institute of Neurophysiology, Charité – Universitätsmedizin Berlin; 2 Department of Physiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba,­ Israel

Recent studies have elucidated a key role for dysfunction of the blood-brain barrier ( BBB ) in the pathogenesis of neuronal dysfunction, epileptogenesis and delayed neurodegeneration within the neocortical network. Since the hippo- campus – a brain area involved in high cognitive functions – is sensitive to vas- cular insults we investigated electrophysiological alterations ex vivo following BBB injury using the photosensitive agent Rose-bengal ( RB ). The sensorimotor cortex of rats was exposed to 15 min halogen light following i.v. injection of RB. Using Evans blue injections, we confirmed BBB dysfunction within the hippo- campus from 12 h to 1 week following treatment with no acute cell death. Losar- tan might be a potential treatment to attenuate BBB breakdown and conse- quences. Ex vivo electrophysiological recordings were obtained from the CA1 region of the hippocampal slice using routine procedures. Recordings showed increased likelihood of spontaneous high frequency paroxysmal activity, lower threshold for spreading depolarization and reduced long-term potentiation upon tetanic stimulation. Our findings suggest significant hippocampal dys- function in the presence of peri-ischemic vascular injury and new understand- ings of the sequence of events underlying cognitive dysfunction in vascular pathologies.­ GRK 1123 Cellular Mechanisms of Learning and Memory 63

Magnus C. Mayer,1, 2 D. Kaden,1 L. M. Munter,1 M. Schaefer,4 and G. Multhaup 1, 2, 3

Physiological function of APP family proteins: Zinc-dependent P17 oligomerization of APLP1

1 Freie Universität Berlin, Institut für Chemie und Biochemie; 2 GRK 1123 Cellular Mechanisms of Learning and Memory; 3 Freie Universität Berlin, Cluster of Excel- lence Neurocure; 4 Universität Leipzig, Rudolf-Boehm-Institut für Pharmakologie und Toxikologie

The amyloid precursor protein ( APP ) involved in Alzheimer’s disease is part of a larger protein family that includes the amyloid precursor like proteins APLP1 and APLP2. These proteins are highly conserved and mice studies re- vealed a strong functional redundancy among the three proteins ( Heber et al., 2000 ). The physiological functions of the APP protein family still remain ­questionable although putative functions in metal ion transport, cell – cell or cell – matrix contact formation were suggested. Interestingly, application of zinc ions to APLP1 expressing HEK293 cells or primary hippocampal neurons forces APLP1 into protein clusters at the ­plasma membrane of living cells within a few seconds. Further analysis of dele- tion mutants showed that this effect is not mediated by the conserved zinc bind- ing site in the E1 domain ( Bush et al., 1994 ). We identified a yet un-described zinc binding site in the E2 domain of APLP1 and could show that zinc has an influence on structure and oligomeric state of the E2 domain in vitro. Further analysis will concentrate on the exact binding mode of zinc and the functional relevance of zinc-mediated oligomerization of APP family protein in neurons. 64 GRK 1123 Cellular Mechanisms of Learning and Memory

Eric T. Reifenstein,1, 2 M. B. Stemmler,2, 3. A. V M. Herz,2, 3 S. Schreiber 1, 2

P18 Entorhinal phase precession revisited – single-run analysis of in-vivo grid cell data

1 Institute for Theoretical Biology, Humboldt-University zu Berlin; 2 Bernstein Center for Computational Neuroscience, Berlin; 3 Department II, Biology, Division of Neuro- biology, Ludwig-Maximilians-University, Munich

When a rat explores its environment, grid cells in the medial entorhinal cortex show increased activity at specific locations that constitute a regular hexagonal grid. As the rat enters and progresses through one of these “grid fields” on a lin- ear track, spikes occur at successively earlier phases in the LFP’s theta rhythm. This phenomenon is called phase precession. For rats foraging in two-dimen- sional environments, however, phase precession has not yet been quantified. ­Unlike on the linear track, a rat does not repeat the same path over and over again in an open arena; pooling different runs to assess phase precession be- comes fraught with difficulty. Instead, we analyze grid-cell spike trains recorded by Sargolini et al., 2006 on a run-by-run basis, and do the same also for linear track data ( by Hafting et al., 2008 ). Surprisingly, even on the linear track, phase precession during single runs is stronger than the average phase precession in the pooled data. We show that a grid cell spike’s theta phase allows one to esti- mate the animal’s position on a linear track to within about 10 % of the size of a typical grid field. Also in 2D – despite low firing rates and theta cycle skip- ping – phase precession can be observed in both, pooled data and single runs. GRK 1123 Cellular Mechanisms of Learning and Memory 65

Stephanie Wegener,1 A. V. Stempel,1 M. J. Schmeisser,2 A. Kuebler,2 T. M. Boeckers,2 and D. Schmitz 1

ProSAP/Shank-dependent orchestration of glutamate receptor P19 composition in a model of pathophysiologic spine maturation

1 Neurowissenschaftliches Forschungszentrum, Charité − Universitätsmedizin Berlin; 2 Institut für Anatomie und Zellbiologie, Universität Ulm

ProSAPs / Shanks are large multidomain proteins that organize the protein ­scaffold of the postsynaptic density (PSD ) in a laminar fashion ( Baron et al. 2006 ). Functional studies suggest that ProSAPs / Shanks serve crucial functions in synaptogenesis, synaptic plasticity, and the regulation of dendritic spine ­morphology ( Boeckers et al. 2002 ). Mutations in the human ProSAP2 / Shank3 and ProSAP1 / Shank2 genes have been directly linked to patients diagnosed with autism and / or intellectual disability ( reviewed in Grabrucker et al. 2011 ). We have recently characterized ProSAP1 / Shank2-deficient ( Shank2 KO ) mice. These animals develop fewer dendritic spines and have increased protein levels of ProSAP2 / Shank3 and the NMDA receptor subunit GluN1 in the PSD. At the physiological level, basal synaptic transmission is reduced and their synaptic glutamate receptor composition is shifted towards NMDARs. Behav- iourally, Shank2 Kos are hyperactive, anxious and show abnormalities in social interactions and vocalisation ( data not shown ). As neuropsychiatric diseases are increasingly understood as synaptopathies, we now aim for a detailed investigation into the role of ProSAP1 / Shank2 in synaptic glutamate receptor composition as a hall mark of dendritic spine matu- ration. We plan to use two-photon ( 2P ) glutamate uncaging on single dendritic spines to characterize and correlate glutamate receptor composition, morphol- ogy, and plasticity of individual Shank2 KO synapses. 66 Berlin School of Mind and Brain

Isabelle Bareither,1, A.3 Villringer,1, N.3 and N. Busch 1, 2

P20 Supraliminal and subliminal visual stimuli evoke divergent ­responses in alpha-oscillatory power

1 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin; 2 Institut für Medizinische Psychologie, Charité − Universitätsmedizin Berlin; 3 Max-Planck-­ Institut für Kognitions- und Neurowissenschaften, Leipzig

The sensory systems of human beings are continuously confronted with a wide range of stimuli. Although stimuli of low intensity, also known as subliminal stimuli, may escape conscious perception, they can evoke brain responses. This has been shown within the somatosensory system by Libet ( 1967 ) and Ray et al. ( 1999 ) recording subdurally as well as Blankenburg et al. ( 2003 ) using func- tional Magnetic Resonance Imaging. The purpose of our study was to investigate brain activity in response to sub- liminal and supraliminal visual stimuli by means of Electroencephalography ( EEG ). In phase 1 of the experiment, we estimated each participant’s visual sen- sitivity threshold. In phase 2, we recorded EEG responses for subliminal and supraliminal stimuli. After the EEG recording, in phase 3 of the experiment, we repeated the threshold estimation in order to verify that visual thresholds had not changed during EEG acquisition. Our key-result indicates that supraliminal and subliminal visual stimuli evoke divergent responses in alpha-band oscillatory power: while supraliminal stimuli elicit an increase in lower-frequency band power as well as a decrease in alpha- band power, subliminal visual stimuli evoke an increase in alpha-band power. This increase alpha-band power in response to subliminal visual stimuli might reflect gating or inhibition mechanisms of potentially distracting information. Berlin School of Mind and Brain 67

Sophie Herbst,1 A. Homayoun Javadi,2 and N. Busch 1, 3

How long depends on how fast – a broad range of flicker P21 ­frequencies influence duration judgments

1 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin; 2 Technische Universität Dresden; 3 Institut für Medizinische Psychologie, Charité − Universitäts- medizin Berlin

The duration of a dynamic stimulus is perceived as longer than the duration of a static stimulus ( Brown 1995 ), and the extent of overestimation depends on the stimulus' temporal frequency ( Kanai et al. 2006 ). It is yet unclear which compo- nents of the underlying perceptual processes cause this subjective time-dilation. We assessed duration judgments of flickering stimuli using on a broad range of frequencies, below and above the flicker fusion threshold (the highest frequen- cy still consciously perceived as flickering ). We stimulated participants’ visual field with flickering light ( ranging from 8 to 166 Hz ) using LEDs mounted in a custom-built binocular flicker-goggle while recording EEG from 64 electrodes. In phase I of the experiment, we recorded steady state visual evoked potentials ( SSVEP ) and behaviorally assessed subjects’ subjective flicker fusion threshold. We found a range of flicker frequencies ( 45 – 70 Hz ) that were subjectively per- ceived as static, but still evoked SSVEP responses over occipital cortex. In phase II we measured the subjective duration judgment of the same flickering stimuli by asking subjects to compare the durations of test stimuli flickering at frequen- cies from 4 – 166 Hz to a standard stimulus that was flickering at 166 Hz ( there- fore perceived as static ). Stimuli that were consciously perceived as flickering were judged longer than the quasi-static reference stimulus. Importantly, over­ estimation of the stimulus’ duration was still found – albeit less pronounced – for flicker frequencies that were not consciously perceived as flickering. No over­ estimation was found for frequencies above 70 Hz. In conclusion, our findings show that dynamics of the stimulus influence perceived duration, even if those dynamics are not perceived consciously.

– Br own, S.W., 1995. Time, change, and motion: the effects of stimulus move- ment on temporal perception. Perception & Psychophysics, 57 ( 1 ), 105. – K anai, R. & Watanabe, M., 2006. Visual onset expands subjective time. Per- ception & Psychophysics, 68 ( 7 ), 1113 − 23. 68 Berlin School of Mind and Brain

Saskia Köhler,1, E.2 Hasselmann,1 T. Wüstenberg,1 A. Heinz,1 and N. Y. Seiferth 1

P22 Brain structure changes in males with pathological gambling symptoms

1 Klinik für Psychiatrie und Psychotherapie, Charité – Universitätsmedizin Berlin, CCM; 2 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin

Pathological gambling is a psychiatric disorder, which is characterized by ­persistent and recurrent maladaptive gambling behavior. Recent neuroimaging studies on pathological gambling report functional changes in several brain ­areas. Our study investigated whether there are also changes in the brain struc- ture. Using magnetic resonance imaging ( MRI ), we examined male subjects, who were engaged in machine gambling or betting, and showed pathological gambling symptoms. We performed voxel-based morphometry ( VBM ), a ­method, which identifies local volumetric changes in the acquired MRI data. In ­comparison to healthy control subjects, pathological gambler showed higher local gray matter volumes in the striatum and prefrontal cortex. Both brain ­areas are part of a network, which mediates the behavioral bias toward either the pursuit of immediate rewards or the accomplishment of long-term goals. The observed structural changes might contribute to an imbalance in this ­network, which in turn might account for the development and maintenance of the compulsive and uncontrollable gambling behavior. The question wheth- er these changes are a disposition or a consequence of the aforementioned ­disorder has still to be clarified. Berlin School of Mind and Brain 69

Sophie Lebrecht,1, 6 M. Bar,2 D. L. Sheinberg,3 and M. J. Tarr 4, 5

Micro-valence: Nominally neutral objects have affective valence P23

1 Department of Cognitive, Linguistic, & Psychological Science, Brown University, Providence, RI, USA; 2 Department of Psychiatry, Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA; 3 Department of Neuroscience, Brown University, Providence, RI, USA; 4 Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA, USA; 5 Department of Psychology, Carnegie Mellon University, Pittsburgh, PA, USA; 6 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin

While some visual objects prompt strong affective responses (e. g., guns and ice cream), most objects are thought to be affectively neutral. Previously, we report- ed evidence for the existence of “micro-valences” (Lebrecht & Tarr, 2010): that nominally neutral objects actually possess subtle valences that we hypothesize form an integral part of object perception. In the current experiment we used f MRI to investigate: a) the extent to which micro-valences are coded within the extended visual object recognition network (Bar, 2007); b) how micro-valences are neurally instantiated with respect to valence strength and direction. Using slow event-related f MRI, participants viewed an object picture for 500ms and evaluated the object’s “pleasantness” on each trial. Participants were shown 120 everyday, nominally neutral objects (e. g., teapots and clocks) and 120 strongly valenced objects (e. g., gold and a skull). Two results stand out. First, somewhat consistent with previous findings, lateral regions of PFC and regions of medial OFC are selective to a positive versus negative comparison for strongly valenced objects. Second, and intriguingly, almost all participants show selectivity for micro-valence objects, comparing positive to negative, in a region adjacent to the region for strongly valenced objects. We posit that intrinsic to visual object perception, object valence – for the majority of objects – is evaluated in PFC. This valence metric forms one of many associated object properties that can influence subsequent perceptual and non-perceptual object-related processing. 70 Berlin School of Mind and Brain

Philip Rausch,1, 2, 3 M. Bayer,1, 2 J. S. Morris,4 M. Krifka,3, 5 and W. Sommer 2

P24 Linking wavelet-based functional mixed models with psycho­physiology and R

1 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin; 2 Department of Psychology, Humboldt-Universität zu Berlin; 3 Department of German Language and Linguistics, Humboldt-Universität zu Berlin; 4 Department of Biostatistics, University of Texas MD Anderson Cancer Center; 5 Centre for General Linguistics (ZAS), Berlin

Mixed effect modelling of scalar behavioural responses like reaction times is becoming a new analysis standard in psychology ( Baayen et al., 2008 ). In psy- chophysiology, however, many data come in the form of curves, such as event- related potentials ( ERPs ) derived from the EEG, or peripheral measures like pupil size or muscle activity over time. Applying standard statistical analyses to such functional data implies treatment of curves as point-like data, involving feature extraction and aggregation within arbitrary time windows. This leads to a loss of information and neglects the inherent temporal dynamics of function- al data. The wavelet-based functional mixed model ( WFMM ) of Morris and ­Carroll ( 2006 ) combines the advantages of functional data analysis ( Ramsay & ­Silverman, 1997 ), mixed models and Bayesian data analysis ( Kruschke, 2010 ): It allows flexible statistical modelling of curve data by specifying multiple fixed effects of any kind ( factorial or continuous covariates ) and accounts for correla- tions among curves induced by multilevel and sequential experimental designs via the inclusion of random effects. The WFMM yields posterior samples for model parameters in functional form, allowing to track credible intervals, effect sizes and dynamics over time. We apply the WFMM to different kinds of psy- chophysiological data, such as ERPs ( Davidson, 2009 ) and pupillary responses acquired in language processing experiments and discuss the benefits of this approach to psychophysiological data analysis. We further present a set of func- tions written in R ( R Development Core Team, 2011 ) that serves as a user- friendly R / WFMM-interface, providing functions for running the WFMM via simple model formulas, flexibly summarising the model posteriors as tables or graphics and more. Berlin School of Mind and Brain 71

Georgina Torbet,1 and D. Bolton 2

A phenomenological perspective on schizophrenia: P25 disunity of self and disorientation in time

1 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin; 2 King’s College London, United Kingdom

The phenomenological method is utilized in analysing descriptions of experi- ences given by people with schizophrenia. Schizophrenia is characterised as a disorder of self, and the particular features of hyperreflexivity (excessive self- awareness ) and loss of ipseity ( lack of “mineness” of experiences ) are considered. The disunity of self is considered in terms of its relation to temporal experience, and the link between self and time is explicated. It is proposed that disorienta- tion within time could lead to a loss of meaning and continuity. Thus the diverse and various symptoms of schizophrenia can be accounted for by postulating a high level dysfunction in selfhood and temporality. 72 Helmholtz International Research School Molecular Neurobiology

Anja L. Dorrn,1, 2 and J. F. A. Poulet 1, 2

P26 Two-photon targeted recordings from interneurons of mouse ­forepaw primary somatosensory cortex

1 Max Delbrück Center for Molecular Medicine Berlin-Buch; 2 Cluster of Excellence Neurocure, Neuroscience Research Center, Charité – Universitätsmedizin Berlin

While auditory, visual and whisker barrel cortex have been highly studied, there are very few studies on forepaw S1. We use the primary somatosensory cortex ( S1 ) representation of the mouse forepaw as a model system to investigate cir- cuit and synaptic mechanisms of sensory perception. We used intrinsic optical imaging to localize forepaw S1 and then made two-photon targeted recordings from the anaesthetized GAD67-GFP mouse to record the synaptic input and spiking output of layer 2 / 3 excitatory and inhibitory neurons and investigate their role in processing of tactile stimuli. We conclude that ( i ) the mouse fore- paw S1 is an accessible model system to study neural circuits involved in sensory perception of tactile stimuli and ( ii ) that inhibitory neurons show a diversity of firing rates during spontaneous and sensory evoked activity. In a second step we now ask how synaptically connected neurons process sensory input. Therefore we perform simultaneous whole-cell recordings from either two interneurons or one interneuron and one pyramidal cell. We can then test for possible connections and investigate the impact of brain state on synaptic integration and how connected neurons process sensory input. Helmholtz International Research School Molecular Neurobiology 73

Min-Chi Ku, Rainer Glass, and Helmut Kettenmann

Interaction of glioma cells with intrinsic brain cells P27

Max Delbrück Center for Molecular Medicine Berlin-Buch

Gliomas, like other solid tumors, are not a homogenous cellular mass, but con- tain many parenchymal cells, which have substantial impact on tumor progression. In the present study, we investigated soluble factors and related receptors by which glioma cells communicate with resident brain cells. We have demonstrated previously that glioma cells attract neural progenitor cells ( NPCs ) and micro­ glial cells into its surround or into the tumor core. We now established a proto- col to encapsulate glioma cells into a hollow fiber (HF ) which allows the passage of diffusible molecules, but not cells. With this model we can study the impact of released factors from glioma cells and exclude effects mediated by cell-cell contacts. The GL261 mouse glioma line survived in HF and expanded for at least 2 weeks after cell encapsulation as studied with metabolic and histological assays. When implanted into mouse brain, HF attracted NPCs, microglial cells but not NG2 glial cells. Astrocytes surrounding the HF up-regulated GFAP immunoreactivity. As controls, we implanted HF loaded with fibroblasts in the contra lateral hemisphere which did not attract NPCs or microglia or trigger an increase in astrogliosis. When we implanted HF encapsulated with mouse primary microglial cells, no microgliosis and astrogliosis occurred. Furthermore, human glioma cells can also be encapsulated in HF and were similarly effective in attracting microglial cells or increasing astrogliosis in mouse brain. Taken together, the HF approach confirmed that glioma cells can communicate with intrinsic brain cells via soluble factors. 74 Helmholtz International Research School Molecular Neurobiology

Valentina Mosienko,1 B. Bert,2 D. Beis,1 H. Fink,2 M. Bader,1 and N. Alenina 1

P28 Decreased anxiety, increased aggression and depression-like ­behavior in mice lacking brain serotonin

1 Max Delbrück Center for Molecular Medicine Berlin-Buch; 2 Institute of Pharma- cology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin

Biosynthesis of serotonin is limited on the first step by two distinct tryptophan hydroxylase enzymes, TPH2 and TPH1. Recently, mice lacking central sero- tonin ( Tph2- / -, Tph2-deficient mice ) were generated in our lab. Surprisingly, these mice can be born and survive until adulthood. Tph2- / - mice show sup- pressed respiration, altered body temperature control and decreased blood pres- sure and heart rate during night time. Additionally, when calculated from the locomotor activity data, sleep time was extended during the day in Tph2- / - mice. Using Tph2-deficient mice as a model with disrupted brain serotonin we assess the role of the serotonergic system in the regulation of complex behavior. Tph2-deficient mice displayed behavior associated with less anxiety as indicated by increased entry and time spent in the open arms in an elevated plus maze test, and by fewer amounts of buried marbles in the marble burying test, as well as by decreased latency to reach the food pellet in the novelty suppressed feed- ing task. In the forced-swim test Tph2-deficient mice showed depressive-like behavior demonstrated as shorter latency to immobility and increased immobil- ity time in comparison to wild type. Furthermore, central serotonin ablation in mice led to highly increased aggressive behavior not only among male mice but also in females and pups. Interestingly, heterozygous Tph2+ / - mice with 10 % reduction in brain serotonin did not show significant differences to the wild animals in the tested behavior paradigms for aggressiveness, depression- or anxiety-like behavior. These data demonstrate that serotonin plays important role in anxiety, ­aggressiveness and depression-like behavior. Helmholtz International Research School Molecular Neurobiology 75

Karina Oberheide,1 S. Weinert,1, 2 T. Stauber1, 2 and T. J. Jentsch 1, 2

NHE8: regulator of organellar pH? P29

1 Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch; 2 Leibniz Institut für Molekulare Pharmakologie, Berlin

The pH of cellular organelles is different from that of the cytosol. Organelles of the secretory and endocytic pathway have a weak acidic pH ranging from 6.7 in the Golgi to 4.5 in lysosomes. It was shown that the defined pH and ion com- position of these organelles is important for their specific function including post-translational modification, protein sorting and uptake, degradation or recy- cling of molecules. Acidification of endosomes and lysosomes is primarily performed by the V- ATPase. As a membrane potential is generated by proton pumping of the V- ATPase, a parallel shunting pathway is needed for efficient acidification. Chlo- ride was thought to be the main counter ion compensating the proton current. In recent work our group could show that the ClC-5 Cl- / H+-exchanger is ­important for endosomal acidification. Lysosomal acidification is not abolished in the absence of chloride or the lysosomal Cl- / H+-exchanger ClC-7, but can interestingly be supported by cations. A Na+-efflux from lysosomes can probably compensate the H+-ATPase currents. Members of the Na+ / H+-exchanger ( NHE ) family are thought to perform Na+-transport on cellular compart- ments and thus contribute to the establishment of the specific organellar pH and ion composition. A recent study proposed an important role of the Na+ / H+-exchanger NHE8 in the endosomal / lysosomal ion homeostasis and function. Additionally to its location on endosomes, this member has been ­described to reside in mid to trans-Golgi compartments and the brush border membrane of renal proximal tubules where it might be involved in acid secretion across the brush border membrane. By disrupting the NHE8 gene in mice we will investigate the role of NHE8 in the proximal tubule and in maintaining ­organellar pH and ion homeostasis. 76 Helmholtz International Research School Molecular Neurobiology

Julia Parnis,1 C. Nolte,1 V. Matiash,1 H. Kettenmann,1 and I. Sekler 2

P30 Mitochondrial Na+/Ca2+ exchanger NCLX: connecting ­mitochondria, calcium and physiology in astrocytes

1 Max Delbrück Center for Molecular Medicine Berlin-Buch; 2 Ben Gurion University, Beer-Sheva, Israel

Mitochondria do not only provide cell with energy, but are also a major compo- nent for Ca2+ signaling. Powered by the steep mitochondrial membrane potential, Ca2+ permeates into the mitochondria by the activity of the uniporter and is pumped out by a mitochondrial Na+ / Ca2+ exchanger. Thus mitochondrial Ca2+ shuttling shapes the temporal pattern of Ca2+ signaling in many cell types. De- spite the major role of Ca2+ signaling for astrocytes and well-documented role played by the endoplasmic reticulum and plasma membrane domains, the role of the mitochondria is still poorly understood. We have recently identified a candidate for the mitochondrial Na+ / Ca2+ exchanger termed NCLX. Here we asked if NCLX is the key component responsible for the mitochondrial Ca2+ efflux in astrocytes and examined its role in astrocyte Ca2+ signaling. Immunoblot analysis of organelle-enriched fractions from primary cultured astrocytes showed mitochondrial location of NCLX. Using pericam-based ­mitochondrial Ca2+ imaging and NCLX inhibition either by siRNA targeting NCLX gene or by the pharmacological blocker CGP37157, we demonstrated that NCLX is responsible for mitochondrial Ca2+ extrusion. Suppression of NCLX function by both approaches significantly altered astrocyte Ca2+ homeo- stasis. The rate of Ca2+ entry via Store-Operated channels was decreased and ATP-evoked Ca2+ responses were increased compared with cells treated with control non-targeted siRNA. Finally, we found that NCLX silencing triggered an increase in the propaga- tion of mechanically evoked Ca2+ waves. Thus our results indicate that the mito- chondrial exchanger plays an important role in shaping the metabotropic and ionotropic Ca2+ signaling and in shaping the spatiotemporal pattern of Ca2+ waves’ propagation in astrocytes. Helmholtz International Research School Molecular Neurobiology 77

Sebastian Schütze,1, 2, 3 and T. J. Jentsch 1, 2

Role of KCNQ channels in pain and somatosensation P31

1 Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch; 2 Leibniz Institut für Molekulare Pharmakologie, Berlin 3 Freie Universität Berlin

M-current mediating KCNQ channels play an important role for the electrical properties of a cell. They serve as an intrinsic voltage clamp mechanism by stabi- lizing the neuron’s membrane resting potential and preventing overexcitability. Thus, mutations in KCNQ2 and -3 subunits have been associated with a gener- alized form of epilepsy called benign familial neonatal convulsions ( BFNC ). KCNQ channels have further been described to be present in the somatosenso- ry system where they have been associated with nociception. Recently, KCNQ 4 was shown to be expressed by rapidly-adapting low-threshold Aβ-fibers inner- vating Meissner’s corpuscles and lanceolate endings around hair follicles. How- ever, nothing is known about the precise localization of other neuronal KCNQ subunits in the somatosensory system. To investigate the role of KCNQ2, -3, and -5 in mechanosensation and pain, different KCNQ mouse models are tested by electrophysiological skin-nerve preparation technique and by behavioural studies. Preliminary immunhistochemical and in-situ hybridization data show KCNQ2 and -3 expression at nodes of Ranvier of middle sized neurons. Only few colocalization could be observed with Nav1.8, a tetrodotoxin resistant volt- age gated sodium channel, which is mainly expressed in nociceptors. Thus, these first data speak for KCNQ2 and -3 being most likely in D hair and / or AM Aδ-fibers. 78 International Graduate Program Computational Neuroscience

Nikolay Chenkov,1, 2 R. Schmidt,1, 2 and R. Kempter 1, 2

P32 Modelling the distal reward problem

1 Institute for Theoretical Biology, Humboldt-Universität zu Berlin; 2 Bernstein Center for Computational Neuroscience, Berlin

In his classical experiment, Ivan Pavlov rang a bell ( conditioned stimulus, CS ) each time before giving a meat powder ( unconditioned stimulus, US ) to his dogs. He found that the dogs were able to learn the association between bell and food even when there was a delay between both stimuli. Today this phe- nomenon is well known as the distal reward problem. Here, we propose a bio- logically plausible hippocampal network model that can map the long time scales of the real world to the relatively short time scales at which neurons and induction of plasticity operate. To bridge the temporal gap on the time scale of seconds between two stimuli, we use a phenomenological model of semilunar granule cells ( SGCs ) ( Larimer and Strowbridge, 2010 ), neurons located in the inner molecular layer of the den- tate gyrus. SGCs are persistently depolarized for a few seconds following a single transient input and hence, could act as a short-term memory. We assume that SGCs project to the CA3 area of the hippocampus via mossy fibre synapses ( Gundl­finger et al., 2007 ). Moreover, in the presence of a hippocampal theta rhythm ( 6 – 12 Hz ), the mossy fibre facilitation may drive the post-synaptic CA3 pyramidal neurons to undergo phase precession ( Thurley et al., 2008 ). Thus, the time elapsed since a stimulus onset can be coded into the firing phase of the CA3 cells. Let us assume that two stimuli ( CS and US ) that are sparsely coded in the SGC layer are presented with a time delay of a few seconds. This delay is mapped to the firing phase difference of the corresponding postsynaptic CA3 neurons. The inherited persistent firing rate and evoked phase precession in the CA3 cells lead to multiple repetitions of the CS-then-US episode but on a smaller time scale than the actually experienced episode. Because of the small firing phase difference, we can apply spike-timing-dependent plasticity ( STDP ) as a learning rule to the synapses in the CA3 area. In this way the synaptic connections be- tween the CA3 pyramidal neurons are modified according to the sequence and the temporal delay of the stimuli, allowing for single-trial associative learning. International Graduate Program Computational Neuroscience 79

Tiziano D’Albis,1, 2 J. Jaramillo,1, 2 and R. Kempter 1, 2

Inheritance of place fields in the hippocampus P33 through Hebbian learning

1 Institute for Theoretical Biology, Humboldt-Universität zu Berlin; 2 Bernstein Center for Computational Neuroscience, Berlin

The hippocampus plays a key role in the acquisition, consolidation, and retrieval of episodic and semantic memory [ Andersen, 2007 ]. Particularly, the hippo­ campus has been found to be fundamental for spatial memory in rodents since the discovery of place cells, i. e., cells that selectively fire in a specific region of the environment ( the place field of the cell ) [ O’Keefe and Dostrovsky, 1971, Moser et al., 2008 ]. The hippocampus has been anatomically differentiated into several interconnected regions, all of them showing place-selective firing [ O’Keefe and Nadel, 1978 ]. Motivated by the connectivity within the hippocampus, we hypothesize that a place field in a downstream region such as CA1 is inherited from an upstream region such as CA3 through Hebbian learning. We examine this possibility by modeling a population of CA3 place cells that projects to a single CA1 cell with synaptic weights that are initially homo- geneously distributed. Assuming an agent running at constant speed on a circu- lar track, we use spike-timing dependent plasticity ( STDP ) [ Markram et al., 1997, Kempter et al., 1999, Song et al., 2000, Dan and Poo, 2004 ] to simulate the evolution of the CA3- CA1 synaptic connections. The STDP rule leads to sym- metry breaking of the synaptic weights and, as a result, place fields emerge in CA1. Finally we show that a random initialization of the synaptic connections, which may be regarded as random synaptic wiring at the CA3- CA1 projection, is sufficient to explain the spatial distribution of the place fields in CA1. 80 International Graduate Program Computational Neuroscience

Frederic Roemschied,1, 2, 3 M. J. B. Eberhard,1 B. Ronacher,1 and S. Schreiber 1, 2

P34 Single-neuron mechanisms of temperature compensation in the locust auditory system

1 Humboldt-Universität zu Berlin; 2 Bernstein Center for Computational Neuro­ science, Berlin; 3 International Graduate Program Computational Neuroscience

Temperature influences basic neuronal properties such as spike rate, amplitude, and conduction velocity. Here, we investigate temperature effects on signal pro- cessing in the grasshopper acoustic communication system, which is used for partner selection. Song recognition is initialized within a three-layer feed-for- ward network comprising receptor neurons, local and ascending interneurons, respectively. We intracellularly recorded responses of neurons within the locust auditory system ( an electrophysiologically easily accessible grasshopper model system ) at all three processing stages to acoustic noise stimuli at behaviorally relevant temperatures. We computed temperature coefficients of neuronal response prop- erties and confirmed an influence of temperature on spike rate, shape, duration, and latency. However, receptor neuron and ascending interneuron spike rate was surprisingly close to temperature-invariance. Since receptor neurons constitute the bottom layer of the network and there- fore do not receive network input, temperature-invariance presumably is receptor- intrinsic. To understand this effect, we investigated how temperature-invariance of spike rate could be achieved in conductance-based neuronal models with temperature-dependent ion channel dynamics. We propose ionic mechanisms that can lead to temperature invariance of spike rate and therefore represent candidate models for receptor neurons of the grasshopper auditory system. International Graduate Program Computational Neuroscience 81

Owen Mackwood,1, 2 J. Ladenbauer,1, 2 and K. Obermayer 1, 2

Rhythmic network dynamics in a primary visual cortex model P35

1 School of Software Engineering and Theoretical Computer Science, Technische Universität Berlin; 2 Bernstein Center for Computational Neuroscience, Berlin

Rhythmic activity in the primary visual cortex is receiving increased attention due to its hypothesized relevance to cognitive function. To illuminate the nature and origin of these rhythms, we employ a recently developed spiking neural net- work model that captures important features of V1 recordings. Using this model, network operating regimes defined by the ratio of recurrent to feed-forward input strength were previously investigated. Strongest experimental support was found for the regime characterized by balanced excitatory and inhibitory recur- rent inputs which dominate the feedforward input ( Stimberg et al., 2009 ). To permit analysis of long-running network dynamics, we replace the original Hodgkin-Huxley neuron in the model with the two-dimensional Adaptive ­Exponential Integrate-and-Fire ( aEIF ) neuron ( Brette & Gerstner, 2005 ) which can well reproduce the spiking behaviour of cortical neurons ( Jolivet et al., 2008 ). We parameterize the aEIF neuron to accurately predict the response of the Hodgkin-Huxley type V1 neuron to random current injection. With this modi- fied V1 model we verify the network operating regime that best replicates the experimental observations. For different stimuli ( i. e. feed-forward inputs ) we then describe the emergence of oscillatory and asynchronous states by measur- ing network coherence and regularity of neuronal spiking. These simulations are performed for the experimentally supported network operating regime and several other less likely operational regimes, where feed-forward or recurrent input is strongest. 82 International Graduate Program Computational Neuroscience

Maria Pannell, S. Seifert, S. Wolf, and H. Kettenmann

P36 Responses of adult and neonatal microglia in vitro to neuro­ transmitters / hormones after activation with LPS

Max Delbrück Center for Molecular Medicine Berlin-Buch

Microglia are the immune cells of the brain which undergo a process of activa- tion in pathology. Microglia are known to express receptors for various neuro­ transmitters / hormones and recent research in adult murine brain slices has shown that there is a population of microglia that are distinct in their respon- siveness to endothelin, histamine, substance P and serotonin. In this study we compared microglia cultured from neonatal and adult mice. To mimic activation, microglia were treated overnight with 100 ng / ml LPS. Cells were stained with fluo-4 and calcium dependant fluorescence change was analysed after application of neurotransmitters / hormones. 6 % of untreated ­neonatal microglia responded to application of 200nM endothelin compared to 47 % of LPS treated microglia. Similarly, 14 % of untreated adult microglia responded to endothelin application compared to 48 % treated. A significant increase in the response of LPS treated neonatal microglia was not seen after application of histamine, substance P, serotonin, galanin, somatostatin, angio­ tensin II, vasopressin, neurotensin and dopamine. Interestingly, LPS treatment in adult microglia resulted in a significant increase in the number of cells re- sponding to histamine, substance P, serotonin, galanin and angiotensin II. We also ‘activated’ neonatal microglia with interferon-γ by treating cells overnight with 20 U / ml. This led to an increase in the number of cells respond- ing to galanin, somatostatin and angiotensin II. These results indicate that the microglial receptor profile changes depending on the state of activation, and that cultured adult microglial cells better resemble the in situ situation. International Graduate School Languages of Emotion 83

Luna Beck, I. R. Kumschick, M. Eid, and G. Klann-Delius

The relation between language and emotional competence: P37 Is there a general ability factor linking them?

Freie Universität Berlin, Cluster of Excellence Languages of Emotion

Both, language and emotional competence, comprise multiple components, which have until now not yet been studied sufficiently with regard to their ­precise interrelations. In our study we examined relations between multiple components of LC and EC in a sample of 210 school-age children. Five mea- sures represented LC: receptive vocabulary, verbal fluency, literacy, narrative structure, and the narrative use of evaluative devices. Four measures represented EC: expressive emotion vocabulary, declarative emotion knowledge, awareness of mixed emotions, and facial emotion recognition. Results identified strong positive correlations between LC and EC ranging between r = .12 and r = .45. In particular, receptive vocabulary and literacy were closely related to emotion knowledge. A confirmatory factor analysis revealed that there seems to be a common general ability factor having an influence on the different facets of EC and LC. 84 International Graduate School Languages of Emotion

Dorit Kliemann,1, 2 G. Rosenblau,1, 2 H. R. Heekeren,1, 2 and I. Dziobek 2

P38 Recognizing emotions from faces: implicit and explicit processing in brain function and behavior

1 Freie Universität Berlin, Cluster of Excellence Languages of Emotion; 2 Freie Uni- versität Berlin, Department of Education and Psychology

Emotion recognition tasks often employ stimuli that are less rich than our social environment, such as static pictures of faces. Additionally, most tasks only in- clude a limited number of emotions, not covering the variety of emotions neces- sary for effective interactions. Crucially, tasks often ask for an explicit judgment, i. e., to label an emotion. Subtle affective impairments, however, may be more accurately identified and quantified by implicit assessment. We thus designed a new more ecologically valid test measuring emotion recognition explicitly and implicitly in controls and populations impaired in emotion recognition, such as autism spectrum disorders ( ASD ). First, we produced a new set of stimuli comprising emotional face videos with 70 actors. The set of 40 emotions comprises basic but also complex social emo- tions ( e. g., envy ) selected based on valence, arousal and communicative relevance ( Hepach et al., in press ). A representative proportion of the stimuli ( 100 videos ) was validated in an expert validation study ( 10 psychologists, 4 male, age 29.6 ( SD 4.3 ), showing high emotion recognition rates ( mean: 92.6 % ( SD 8.7 ) ) and believability ratings ( mean: 4.4 ( SD .7 ), range 1 – 6 ). The test consists of two in- dependent tasks: the implicit task asks to match the upper part of an emotional face video ( i. e., the eyes ) with the correct lower part ( i. e., nose, mouth ) out of four options. The explicit task asks to pick the correct label for the emotional face out of four options. We also developed f MRI adaptions of both tasks, with a gender discrimination condition ( implicit ) and an emotional label condition ( explicit ). Preliminary f MRI data ( N = 4 ) showed reliable activation of the emo- tional face network ( amygdala; fusiform face area ) mediated by complexity of emotional expression. In a next step, sensitivity for typical and impaired emo- tion recognition in a study comparing controls and ASD will be assessed. In addition, the f MRI versions will be used to inform qualitative and quantitative differences in brain responses to implicit and explicit social stimuli in ASD. International Graduate School Languages of Emotion 85

Gabriela Rosenblau,1, 2 D. Kliemann,1, 2, 3 H. Kappelhoff,1, 2 H. R. Heekeren,1, 2, 3 and Isabel Dziobek 1

Behavioural and neural assessment of implicit and explicit P39 ­social cognition

1 Freie Universität Berlin, Cluster of Excellence Languages of Emotion; 2 Depart- ment of Education and Psychology, Freie Universität Berlin; 3 Max Planck Institute for Human Development, Berlin

Few tasks to date assess social cognition based on naturalistic stimuli. On the behavioural level, those tests often ask participants to label the protagonists’ mental states, thereby representing an explicit cue to apply social cognition ( e. g., Golan et al., 2006 ). Given the lack of naturalistic behavioural tasks and f MRI paradigms for the assessment of implicit and explicit social cognition, we devel- oped two new movie based behavioural tasks that in a second step, will be adapted to the f MRI environment. The behavioural test comprises an implicit and an explicit task: In the implicit task, participants first watch a film scene and are then shown four short film clips ( 4 s ) displaying a protagonist’s poten- tial reactions in response to the preceding social interaction. Participants are requested to pick the clip that represents the correct emotional reaction. In the explicit task, participants first watch a film scene and are then asked to pick one out of four text options that correctly describes the mental state of one pro- tagonist when the film stops. In a validation study ( N = 28; 14 male ) the implicit task yielded a mean item difficulty of .76 ( SD .19 ). In the explicit task, however, participants performed at ceiling ( difficulty: .99 ( SD .02 ) ). The item analysis for the implicit task showed a satisfactory reliability of .71 ( Cronbach’s alpha ). After revising the items for both tasks, with the aim of increasing test difficulty and reliability, we will in- vestigate the tasks’ sensitivity in populations impaired in social cognition, such as autism spectrum conditions ( ASC ). In addition, we have adapted the test for fMRI measurements in order to investigate qualitative and quantitative differ- ences of the Theory of Mind network in ASC. 86 External

Ana I. A. Amaral,1, 2 and D. R. M. Langers 1, 3

P40 Attentional modulation of auditory and visual processing in a 1-back task with distractors

1 Department of Otorhinolaryngology / Head and Neck Surgery, University Medical Center Groningen, Groningen, The Netherlands; 2 Champalimaud Neuroscience Programme at Champalimaud Centre for the Unknown, Lisbon, Portugal; 3 Faculty of Medical Sciences, School of Behavioral and Cognitive Neuroscience, University of Groningen, Groningen, The Netherlands

Attention is essential for efficient goal-directed information processing. Attention enables direction of resources to a specific sensory stimulus, avoiding potential interference from other stimuli. This study investigates the effects of attention on sensory processing during the direction of attentional resources to relevant information while simultaneously ignoring irrelevant stimuli. We studied this relationship using functional magnetic resonance imaging ( fMRI ) in humans during the performance of a 1-back task in either the auditory or visual domain, while distractors were simultaneously presented. fMRI images of blood oxygen- ation level-dependent signals were obtained and behavioral outcomes were re- corded. Standard general linear models ( GLMs ) were applied to identify brain activations in both auditory and visual sensory regions. An exploratory indepen- dent component analysis was used, as a complementary method to the inferen- tial models, in order to measure and characterize responses in intrinsic brain networks. A region of interest analysis was carried out on the basis of selected independent components. We presently report preliminary results from an initial subset of subjects. ­Attention significantly modulated stimulus evoked responses in the primary auditory cortex. Visual cortices showed deactivation for all auditory conditions. Attentional modulation in primary visual cortex was not significant. However, higher visual areas showed increased activation when visual stimuli were attend- ed, for the most difficult conditions. Frontal cortex showed deactivation for all task conditions, suggesting an engagement of the default mode network. These results are consistent with previous studies indicating attention-related modula- tory effects in various sensory modalities. External 87

Sujoy Bera,1 M. Mikhaylova,1 V. Raghuram,2 and M. Kreutz 1

Golgi targeting assay for studying protein-protein interaction P41 in vivo

1 Leibniz Institute for Neurobiology, Magdeburg; 2 Center for Cellular and Molecular Biology, Hyderabad, India

Dynamic protein-protein interactions are a key component of biological regula- tory networks. Physical interactions between proteins are the triggering event for transducing signals within the cell. In this study we have generated a novel in-vivo protein-protein interaction method based on targeting of proteins in specific cellular organelle called ‘Golgi apparatus’. We have generated a vector system containing C-terminal 28 amino acids long sequence, including the transmembranal domain from the Golgi-localized protein Calneuron-2 fused to mCherry fluorescence tag. Over-expression of proteins fused to this system leads to it’s targeting and accumulation in golgi apparatus. One of the proteins of interest is fused to golgi targeting vector and the second protein is fused to GFP-tag. When two proteins are co-expressed in Cos7 cells, based on their ­interaction properties the protein with GFP-tag is either targeted to the golgi apparatus along with it’s binding partner ( Golgi targeting ) or it is diffused throughout the cells / present in other compartment when there is no interaction. We also implemented this system as marker of golgi apparatus and golgi-outpost in cultured primary hippocampal neurons. Compare to in-vitro protein-protein interactions study, which uses bacterially expressed protein and involves the study in isolation of cellular environment, our study provides suitable cellular micro- environment with regard to many competing proteins which occurs within the cell. This system will be applicable as a general method to study in-vivo protein- protein interactions. 88 External

Agnieszka Z. Burzynska,1 C. Preuschhof,2 I. E. Nagel,1, 2 S. -C. Li,1 U. Lindenberger,1 L. Bäckman,1, 3 and H. R. Heekeren 1, 2

P42 Adult age associations between brain structure and function ­during working memory performance

1 Max Planck Institute for Human Development, Berlin; 2 Department of Education and Psychology, Freie Universität Berlin; 3 Aging Research Center, Karolinska ­Institute, Stockholm, Sweden

Working memory ( WM ) relies on a distributed fronto-posterior network ( e. g., Rajah and D’Esposito, 2005 ). People differ in WM span as well as the extent to which the fMRI BOLD signal increases as a function of increasing WM de- mand ( “BOLD responsivity” ). Individual differences in BOLD responsivity predict WM performance ( Nagel et al., 2009, 2011 ), but the structural basis of differences in BOLD responsivity is not yet known. We obtained DTI data ( measure of white matter microstructure ), n-back fMRI data ( BOLD responsivity ), and structural MRI data from 30 younger and 30 older adults. First, we related the microstructure of fronto-parietal connec- tions ( superior longitudinal fasciculi, SLF ) to WM performance and BOLD responsivity in younger adults. Higher SLF integrity was associated with better WM performance and greater BOLD responsivity in the fronto-parietal net- work. In addition, BOLD responsivity statistically mediated the effects of SLF integrity on 3-back performance ( Burzynska et al., 2011 ). Second, given that older adults, on average, show compromised BOLD ­responsivity ( Nagel et al., 2009, 2011 ), we related BOLD responsivity in older adults to white matter integrity and the volume of hyperintense white matter lesions. Preliminary analyses indicate that lower integrity of all main white mat- ter tracts ( but not SLF ) and higher volume of hyperintense lesions are related to lower BOLD responsivity in the PFC and greater changes in BOLD signal at the minimal WM load in multiple regions. These results suggest that task-related adjustments of grey matter activity rely primarily on the properties of network-relevant white matter tracts in younger adults ( Burzynska et al., 2011 ), and on global white matter integrity in older adults. External 89

Rúben Duque Do Vale,1, 2 J. Pinho,1, 2 L. V. Lopes,1, 2 J. A. Ribeiro,1, 2 S. M. Sebastião1, 2 A. De Mendonça,1, 2 and M. J. Diógenes 1, 2

Blockade of NMDA receptors by memantine decreases the P43 ­augmented LTP in old rats hippocampus to “physiologic” values

1 Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon; 2 Neurosciences Unit, Institute of Molecular Medicine, University of Lisbon

Memantine is a drug widely used for the treatment of Alzheimer’s disease ( AD ). It is a partial antagonist of the NMDA receptors, which despite of being essen- tial for the memory and learning processes, may lead to excitotoxity, when over- activated, as seen on AD. Previously, we observed that long-term potentiation ( LTP ) – the neurophysiological basis for learning and memory – is increased in hippocampal slices taken from aged rats and we hypothesized that the cognitive enhancing properties of memantine could be related to its ability to reduce the “dysfunctionally increased” LTP upon ageing. In this study we investigated the effect of memantine on LTP upon ageing. LTP, induced by a weak θ-burst protocol, was evaluated by recording excit- atory postsynaptic potentials in the CA1 area of hippocampal slices taken from male Wistar rats belonging to three age groups. We then compared the LTP magnitude. The effect of memantine was evaluated by comparing the LTP ­magnitude in slices pre-incubated with memantine 1 µM, and in slices in the absence of memantine. When the weak θ-burst was applied to hippocampal slices taken from young adult rats ( 10 – 15 w. o. ), an expectedly small LTP was observed; when it was ­applied to hippocampal slices taken from middle-aged and aged rats ( 36 – 40 and 80 – 90, respectively ), a large LTP was obtained. Memantine ( 1 μM ) inhib- its the large LTP magnitude observed in hippocampal slices from middle-aged and aged, without compromising the LTP magnitude in slices taken from younger rats, so that, in the presence of memantine, LTP magnitude in hippo- campal slices from young and aged rats becomes similar. Since memantine is an NMDA receptor antagonist, our data suggest that “dysfunctional” increased LTP upon ageing is due to NMDA receptors over-activation, as seen on AD. 90 External

Eleonora Franzoni,1 H. Fuchs,2 S. Parthasarathy,1 V. Tarabykin,1 and F. G. Wulczyn 1

P44 miR-128: a pleiotropic regulator of neuronal translation

1 Center for Anatomy, Institute of Cell Biology and Neurobiology, Charité – Univer- sitätsmedizin Berlin; 2 Max Planck Institute for Molecular Genetics, Berlin

microRNAs ( miRNA ) are a large class of non-coding RNAs important for the regulation of the proteome mainly through silencing and / or degradation of mRNA. Over 400 miRNA genes have been annotated, they are expressed and function in all cells as regulators of many cellular processes. Several highly tissue specific miRNAs are known to coordinate cell-specific gene expression pro- grams during development. miR-128 is one of a small group of brain enriched, neuron-specific miRNAs. There is evidence for misregulation of miR-128 in glioma and neuroblastoma as well as other malignancies, but functional characterization of miR-128 in CNS development and function is only beginning. Like the paradigm neuronal miRNA, miR-124, miR-128 is not expressed in radial progenitors but is induced upon neuronal differentiation. Deep sequencing of synaptosomal miRNA re- vealed high levels of miR-128. Consistent with this expression pattern, we have identified and verified several target mRNAs for miR-128 that are subject to direct translational repression. miR-128 target gene interactions are likely to influence development (FoxP2, Reelin ), growth control ( Aff4, Casc3, Phf6 ) and activity ( Adora2a, Adora2b, RpsKa5 ). To better understand miR-128 roles in synaptic plasticity and cortex development we are performing in situ hybridiza- tion and gain- and loss-of-function experiments by in utero electroporation in the mouse cortex. External 91

Paulina Gołaska 1, 2

The extreme male brain theory of autism. Sexual dimorphism P45 and functional asymmetry of the human brain

1 Department of Educational Studies, Adam Mickiewicz University of Poznań, ­Poland; 2 ZERO-FIVE. The Foundation for Infant Mental Health

According to the major part of current research in autism , one can find many results and implications indicating different abnormalities in autistic brain which can lead to well-known developmental disturbances and pathology. ­Fortunately, there are some attempts which are likely to change those deficit- concentrated tendencies. One of the theories modifying attitudes toward autism is the Extreme Male Brain Theory (EMBT ) of Simon Baron-Cohen ( 1999 ). The main idea of this construct is that there are two kinds of specific abilities – empathizing ( E ) and systemizing ( S ) with neural basis in functional asymmetry of man and woman brain which are differentiating and determining their every- day psychosocial functioning ( Baron-Cohen 2005 ). Usually they compound in one of three profiles: E > S ( distinctive for women ), S > E ( distinctive for men ) and B ( balanced ). There are also more uncommon profiles of extreme female ( EE > S ) and extreme male ( SS > E ) brain ( Baron-Cohen 2006 ). As it became clear in many research involving people with ASD, the last one is connected to traits ordinarily seen in autism, like a tendency to create systems, to see world as a mosaic of pieces rather than an indivisible whole and a preference for ana- lyzing perceived objects. In this capture, autistic traits are seen as lying on a con- tinuum and can be treated as virtues determining success in many areas, espe- cially in science ( Baron-Cohen, Wheelwright et al. 2001 ). In this presentation I would like to describe the main findings of up-to-date research on EMBT: neural background, diagnostic tools, potential causes of extreme dimorphism of autistic brain and general conclusions for educational and therapeutic practice. 92 External

Katharina Grauel,1, 2 S. Reddy,3 B. Rost,2 A. Schönherr,2 S. Wegener,2 D. Schmitz,2, 4 S. Sigrist,2, 3, 4 and C. Rosenmund 2, 4

P46 Investigations on the active zone scaffold protein RIM-BP2 in autaptic hippocampal neurons

1 Freie Universität Berlin, Institut für Chemie und Biochemie; 2 Neuroscience Re- search Center, Charité – Universitätsmedizin Berlin; 3 Genetics Institute of Biology, Freie Universität Berlin; 4 Cluster of Excellence Neurocure, Freie Universität Berlin

In addition to their interaction with Rab-interacting molecules ( RIMs ) RIM- binding proteins ( RIM-BPs ) have been shown to bind to L-, N- and P / Q-type voltage-gated Ca2+-channels ( Wang et al., 2000; Hibino et al., 2002; Kaeser et al., 2011 ) via conserved Src-homology 3 ( SH3 ) domains. Thus, RIM-binding pro- teins seem to be essential for tethering Ca2+-channels to the active zone in close proximity to the release machinery which is crucial for fast synchronous neuro­ transmitter release. Indeed, there has been evidence that RIM-BPs do play an im- portant role for Ca2+-dependent release ( Hibino et al., 2002; Kaeser et al., 2011 ). The mouse enomeg encodes for three different RIM-BPs (Mittelstaedt et al., 2007 ). All of these contain three conserved SH3 domains and two or three consecutive Fibronectin-III repeats. While RIM-BP3 is virtually absent in the nervous system, RIM-BP 1 and 2 are expressed in most brain structures. We analyze the function of murine RIM-binding protein 2 using whole-cell patch clamp recordings of autaptic hippocampal neurons. This system allows us to analyze evoked and spontaneous release as well as basic synaptic properties such as the readily releasable pool ( RRP ) of neurotransmitter vesicles and the vesicu- lar release probability Pvr. External 93

Karen Henning,1 Brita Vorwerk,2 T. G. Ohm,1 and U. Plöckinger 2

Neuronopathic Morbus Gaucher – characterisation and P47 ­validation of the mouse and cell culture model

1 Institut für Integrative Neuroanatomie, Charité − Universitätsmedizin Berlin; 2 ­Interdisziplinäres Stoffwechsel-Centrum, Charité − Universitätsmedizin Berlin

Gaucher disease ( GD ) is the most common of the lysosomal storage disorders. It is inherited in an autosomal recessive trait and caused by mutations in the gba gene, which codes for the membrane bound enzyme β-glucocerebrosidase ( GCase ). Morbus Gaucher is divided in the following types: Type I ( non-­neuro­ nopathic ), Type II ( acute neuronopathic ) and Type III ( sub-acute ). Type II GD, is an acute neuronopathic form, with severe brain damage. Life expectancy is below 5 years. Reduced GCase activity leads to the accumulation of glucocerebrosides and related compounds within lysosomes, distension of the organelle and subsequent cellular malfunction. Lipid-laden macrophages ( Gaucher cells ) accumulate in the liver, spleen, bone marrow and in type II / III patients also in the brain. In the European population type I GD occurs in 1 : 40,000 newborns while the prevalence of type II and type III GD is below 1 : 100,000 each. Currently there is no treatment option for type II GD ( M. Jmou- daik and A. H. Futerman, 2005 ). A recently developed mouse model, K14 lnl / lnl ( Enquist, I. B. et al. 2006; ­Enquist, I. B. et al. 2007 ) displays the neuronopathic Morbus Gaucher. In our study we characterise and validate the mouse model concentrating on brain and liver. This mouse model is the only one so far surviving at least 14 days after birth due to normal GCase activity in the skin. Due to the fact that this model is very hard to breed and due to the short life expectancy we are working on developing a new slice culture model for brain and liver. Finally our study focuses on developing a gene therapy for Morbus Gaucher Type II, before applying the therapy in the mouse model the slice culture model is used for validation. 94 External

Laura Kaltwasser,1 S. Ries,2 W. Sommer,1 R. Knight,2 R. Willems 2, 3

P48 Independence of valence and reward in emotional word processing

1 Department of Psychology, Humboldt-Universität zu Berlin; 2 Helen Wills Neuro- science Institute, University of California, Berkeley, USA; 3 Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen

Previous electrophysiological work on word processing shows that emotional word content can modify word processing at all stages from pre-lexical encoding and semantic access, up to contextual integration, evaluation, and memory en- coding ( for review Kissler, Assadollahi & Herbert, 2006 ). Similarly, reward ­expectancy has been shown to enhance cognitive processing from the perceptual up to the executive control level ( Pessoa & Engelmann, 2010 ). We investigated whether the anticipation of reward or loss modulates ERP components related to the processing of emotion and semantic meaning in words ( EPN, N400, LPC ). Participants ( n = 24 ) performed a semantic categorization task ( concreteness ­decision ) on positive, negative and neutral words, which were preceded by a cue indicating monetary loss or gain. Reward expectancy modulated ERP in re- sponse to the cue and the P2 in response to the word but did neither interact with valence nor with concreteness. In accordance with previous studies emo- tional words elicited a LPC and concreteness modulated the N400. Furthermore valence and concreteness interacted in the LPC time window. Emotion-related and reward-related effects occur in different time windows, do not interact, and show different topographies (map dissimilarity analysis ). This speaks for an independence of reward expectancy and the processing of emotion as a word- inherent feature. Emotional semantics might be related to automatic reactions that are not prone to be affected by short term information of monetary gain or loss. External 95

Martina Michalikova,1 and R. Kempter 1, 2

Exploring the origin of spikelets in hippocampal CA1 pyramidal P49 neurons

1 Institute for Theoretical Biology, Humboldt-Universität zu Berlin; 2 Bernstein Center for Computational Neuroscience, Berlin

Spikelets are brief spike-like depolarizations of small amplitude. Recently, pro- nounced spikelet activity has been demonstrated in hippocampal CA1 pyramidal neurons in awake behaving animals, strongly influencing the firing output of these cells ( Epsztein et al., 2010, Science ). However, the basic mechanisms under­ lying the generation of spikelets in these neurons are unknown. In general, somatic spikelets can be considered as a reflection of action po- tentials generated in an electrotonically distinct compartment. These remote spikes might occur either in the dendrites or in the axon of the same cell or in another electrotonically coupled neuron. Reviewing the literature unveiled two qualitatively different types of spike- lets. One type exhibits small amplitudes ( < 2 mV ) and slow dynamics and is typically found in local cortical interneurons. Its gap junctional origin has been validated in many independent studies. In contrast, cortical pyramidal neurons display substantially faster spikelets at amplitudes up to 20 mV. In these neurons, axo-axonic coupling has been suggested as a possible mechanism for spikelet generation, but direct evidence is rather scarce. To illuminate possible origins of spikelets, we have analyzed computational models: Somatic coupling results in slow spikelets, similar to those observed in cortical interneurons. In contrast, fast spikelets can be generated by large axial currents from a spike elicited at the axon initial segment within the same neuron. Depending on the state of the soma, these spikelets may trigger a full action potential in the soma. Therefore, currents generated in the axon initial segment can account for the experimentally recorded fast dynamics and large amplitude of spikelets in CA1 pyramidal neurons. 96 External

K. Botsakis,1 Theodora Mourtzi,1 N. Panagopoulos,1 F. Angelatou,2 and N. Matsokis 1

P50 Neuroprotective effect of DHEA-S on substantia nigra and stria- tum of the weaver mouse – a genetic model of Parkinson’s disease

1 Laboratory of Human and Animal Physiology, Department of Biology, University of Patras, Greece; 2 Department of Physiology, School of Medicine, University of Patras, Greece

The weaver mouse (wv / wv ) is a genetic model of Parkinson’s disease which car- ries an autosomic recessive mutation that leads ( between others ) to progressive dopaminergic neurodegeneration in substantia nigra ( S. Nigra ), starting at post- natal day 7 ( P7 ) and reaching 50 % at P21, a fact that makes this animal model ideal for neuroprotection studies. In this study, we administrated the neurosteroid dehydroepiandrosterone sulphate ( DHEA-S ) in wv / wv mice from P1 to P22 ( wv / wv DHEA-S ) and then we measured neuronal survival in S. Nigra. Using western blot analysis and a specific antibody against TH our results: ( 1 ) have confirmed that in the wv / wv mesencephalon ( an area that includes S. Nigra ) there is neurodegeneration of about 50 % at P22, compared to control ( + / + ) mice of the same age, that is reflected to the striatum by a reduce to the tyrosine hydroxylase ( TH ) level about 25 %. ( 2 ) have shown that in wv / wv mes- encephalon, DHEA-S induces an increase in TH level about 27 % compared to wv / wv which had received saline ( wv / wv NaCl ) and that in striatum, DHEA-S has a neuroprotective effect about 18 %, bringing the TH level almost to normal. Using immunohistochemical experiments, with the same TH-specific anti- body we found that DHEA-S had very important neuroprotective effect ( in- crease of the dopaminergic cell survival by 90 % ) in the wv / wv S. Nigra com- pared to wv / wv NaCl mice, which brings the number of the dopaminergic neurons almost to the control levels. Those results suggest that DHEA-S represents a very important neuro­ protective agent for the weaver S. Nigra, leading to almost normal dopaminergic neuron number in S. Nigra. It is also important to notice that the induced neu- ronal survival is reflected to the weaver striatum. Supported by “Karatheodoris” C903 ( ELKE University of Patras ) External 97

Adjmal Nahimi,1 M. Høltzermann,1 A. M. Landau,1 M. Simonsen,1 S. Jakobsen,1 A. K. Olsen Alstrup,1 K. Vang,1 A. Møller,1 G. Wegener,2 A. Gjedde,3 and D. J. Doudet 1

Serotonergic modulation of receptor occupancy in rats treated P51 with L-DOPA after unilateral 6-OHDA-lesioning

1 Department of Nuclear Medicine and PET Centre, Aarhus University Hospitals, ­Aarhus, Denmark; 2 Centre for Psychiatric Research, Aarhus University Hospitals, Aarhus, Denmark; 3 Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark

Introduction: Recent studies suggest that LID, a severe complication of conven- tional L-DOPA therapy of Parkinson’s disease ( PD ), may be caused by dopa- mine ( DA ) release originating in serotonergic neurons. Methods: Rats with unilateral 6-hydroxydopamine ( 6-OHDA ) lesions had micro-PET scans with [ 11C ]raclopride at baseline and after two pharmacological challenges with ­L-DOPA+benserazide with or without 8-OHDPAT co-treatment. Identical challenge regimens were used with the subsequent microdialysis concomitant with ratings of LID severity. Results and conclusion: The baseline increase of [ 11C ]raclopride binding potential ( BPND ) in lesioned striatum was eliminated by the L-DOPA challenge, while the concurrent administration of 8-OHDPAT prevented this L-DOPA induced displacement of [ 11C ]raclopride significantly in lesioned ventral striatum and near significantly in the dorsal striatum. With microdialysis, the L-DOPA challenge raised the extracellular DA in parallel with the emergence of strong LID. Co-treatment with 8-OHDPAT significant- ly attenuated the release of extracellular DA and LID. Our findings suggest that LID in advanced PD could be related to DA originating in serotonergic neurons. 98 External

Pasham Parameshwar Reddy,1 M. Mikhaylova,1 R. Fries,2 K. -W. Koch,2 and M. R. Kreutz 1

P52 Homo- and hetero-dimerization of the neuronal calcium sensor proteins Caldendrin and Recoverin

1 PG Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg; 2 Biochemistry group, Institute of Biology and Environmental Science, Carl von Ossietzky University Oldenburg

Caldendrin and Recoverin are neuronal Ca2+-sensor proteins from the EF- hand super family. They share structural similarity with the ancestor protein Calmodulin but differ in their organization of functional and non-functional EF-hands as well as functional properties. Caldendrin regulates IP3 receptors signaling, L-type calcium channels and is involved in calcium dependent ­control of the nuclear translocation of the synapto-nuclear messenger protein Jacob. The only well described function of Recoverin is it binds and inhibits rhodopsin kinase at high calcium-concentration thereby modulating the life- time of photo-activated rhodopsin in retinal rod cells. In a search for novel binding partners of Recoverin, we employed an affinity column and identified Caldendrin as a possible interaction partner. Immunohystological studies re- vealed that both proteins are co-localized in the retina in a subset of bipolar cells and in the pineal gland. Pull-down and surface plasmon resonance exper­ iments further proved that binding occur in a calcium and myristoylation ­dependent manner. Time-lapse fluorescence confocal microscopy showed re- distribution of Recoverin to the intracellular membranes of COS-7 cells upon Ionomycin stimulation, via induction of Ca2+-myristoyl switch. Interestingly, Caldendrin was co-translocated to the membranes when it was co-expressed with Recoverin in the same cells. Additionally, utilizing different biochemical approaches and experiments in living cells ( pull down assays, co-immuno­ precipitations, analytical gel filtration and FRET study ) we identified calcium independent Caldendrin homo-dimer formation. The physiological signifi- cance of homo- and hetero-dimerization of these molecules warrants further investigation.­ External 99

Andrea Rodríguez,1 D. López,1 C. Sancho,1 L. Millian,1 T. Alburquerque,2 J. Carro,1 and J. G. Meilan 1

Alterations in sensorimotor gating mechanism in Parkinson’s P53 Disease and essential tremor: startle reflex and prepulse ­inhibition

1 INCYL Institute of Neuroscience of Castilla y León Salamanca, Spain; 2 University Hospital of Salamanca, Spain

Essential Tremor ET and Parkinson’s disease PD imply the involvement of locus coeruleus (LC). Alterations of LC cause a decreased level of alertness. The audi- tory startle reflex (ASR) is a tool to measure alertness and PPI – a modulation of ASR-assess mechanisms of sensoriomotor gating. Objectives Asses the ASR and PPI in patients with PD and Essential Tremor and establish correlations between them and voice parameters. Material and Methods We studied 44 subjects: 17 controls, 23 patients with PD and 4 patients with ET. For the ASR test, we used a session with different ISIs. We made analysis of voice parameters with diadococinetic tasks and used neuro- psychological tests, minimental test, UPDRS and neurological assessment of Tremor severity, statistical analysis used univariate analysis of variance with post hoc tests, Pearson correlation, linear regression, using the statistical package SPSS(v15). Results Patients with PD had ASR with lower amplitude and long latency and ET group had ASR with shorter latency and higher amplitude than control group. In prepulse inhibition tests, the greatest inhibition for EP was founded at PPI of 480 milisec, for ET was 240 milisec and for control group was 120 milisec. The three groups had as predictors parameters of ASR amplitude: F0r fun- damental frequency and number of voice periods. In PD group the shimmer of voice as a predictor of PPI 60. PD group showed lower scores in immediate auditory memory and delayed auditory memory than ET and control group. The auditory recognition delayed was founded as a significant predictor of motor impairment in PD Conclusions ASR, PPI and some parameters of voice could be an important tool for early differential diagnosis and monitoring of progression of PD and ET. 100 External

Maria Sekutowicz,1 K. Schmack,1 H. Rössler,1 E. Brandl,2 D. J. Müller,2 and P. Sterzer 1

P54 The influence of dopamine-related gene polymorphisms on perceptual stability

1 Department of Psychiatry, Charité – Universitätsmedizin Berlin, CCM; 2 Neuro­ genetics Section, Centre for Addictions and Mental Health, Toronto, ON, Canada

Bistable perception is the spontaneous alternation between two perceptual states that occurs when sensory information is ambiguous and consistent with two mutually exclusive interpretations. A key feature of bistable perception is high intra-individual stability and high inter-individual variability in perceptual switch rates. Recent twin studies indicated a genetic contribution to this vari- ability. Moreover, slow perceptual switching has been reported in bipolar disor- der ( BD ), a highly heritable condition. Given previous findings from pharma­ cological studies and the association of BD with dopaminergic dysfunction, we hypothesized that dopamine-related candidate genes for BD may modulate switch rates in bistable perception. In an exploratory candidate gene approach we tested the association of two VNTRs within DRD4 and DAT1, both candi- date genes for BD known to alter dopaminergic neurotransmission, with bistable perception in a cohort of 112 healthy human subjects. We found a significant association between slow perceptual switching and the occurrence of the 2 re- peat allele ( 2R ) of the DRD4 VNTR, but no effect for the DAT1 VNTR poly- morphism. Both, the increased incidence of 2R in BD and our result are consis- tent with the previous association of BD with slow perceptual switching. Higher dopamine levels associated with the reduced receptor-inhibition potency medi­ ated by 2R may thus reduce perceptual switching, suggesting that differences in dopaminergic neurotransmission may indeed account for inter-individual vari- ability in perceptual stability. Our data are the first to date to specify the genetic substrate for individual differences in perceptual stability and provide a promis- ing starting point for future research on the connection between dopamine and perception. External 101

Bernard Sonnenschein,1, 2 and L. Schimansky-Geier 1, 2

Limitations of the mean-field approach in describing P55 the synchronization transition in small-world networks

1 Department of Physics, Humboldt-Universität zu Berlin; 2 Bernstein Center for Computational Neuroscience, Berlin

Small-world networks are characterized by two properties: 1. a short average path length between the nodes of the network and at the same time, 2. a high clustering coefficient. Both properties have been observed experimentally in living animals, e. g., in the macaque ape visual cortex and in the cat cortex ( Sporns, Tononi & Edelman, 2000 ) and in networks of correlated human brain activity ( Chialvo, 2004 ). For this reason neural networks are often described by small-world networks ( Kwok, Jurica, Raffone & van Leeuwen, 2007 ). We investigate the onset of synchronization in such ring networks of noisy Kuramoto oscillators by both analytical and numerical means. The analytical part contains the derivation of the critical coupling strength which marks the onset of synchronization ( Sonnenschein & Schimansky-Geier, in prep. ). In this way we present a link between the previous work by Strogatz and Mirollo ( 1991 ) and by Ichinomiya ( 2004 ). Our numerical analysis includes simulations and finite-size scaling analysis. In contrast to previous results ( Hong, Choi & Kim, 2002 ) we come to the conclusion that small-world networks have a mean-field synchronization transi- tion only if the network has enough shortcuts ( Sonnenschein & Schimansky- Geier, in prep. ). This is an important result, because it reflects a valid warning that the popular mean-field approach has to be applied with caution when it comes to complex networks. 102 External

Alexander Soutschek,1, 2 and T. Schubert 1, 2, 3

P56 Dissociable mechanisms of conflict regulation in emotional and nonemotional Stroop tasks

1 Department of Psychology, Ludwig-Maximilians-Universität Munich; 2 Munich Center for Neurosciences – Brain & Mind; 3 Department of Psychology, Humboldt- Universität zu Berlin

Recent neuroimaging studies suggest that the human brain activates dissociable cognitive control networks in response to conflicts arising from nonemotional and emotional distractors. The present study tested the hypothesis that non­ emotional and emotional conflict regulation can be dissociated on a functional level, too. For that purpose, we examined the effects of a working memory and an emotional Go / Nogo task on cognitive control in an emotional and a non- emotional variant of the Stroop paradigm. The data confirmed the hypothesized dissociation: Working memory efforts selectively suppressed conflict regulation in the nonemotional Stroop task, while the demands of an emotional Go / Nogo task impaired only conflict regulation in the emotional Stroop task. We con- clude that these findings support a modular architecture of cognitive control with conflict-specific conflict regulation processes. External 103

Katrin Tomson,1, 2 N. Shibata,1 B. Kuerban,1 M. Komatsu,1 T. Ohnuma,1 and H. Arai 1

Genetic association between SLC6A4 polymorphisms P57 and Alzheimer’s Disease in a Japanese population

1 Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan; 2 Department of Psychology, Estonian Centre of Behavioural and Health Sciences, University of Tartu, Estonia

Association between a polymorphism of the human serotonin transporter gene ( SLC6A4 ) and the risk of developing late-onset Alzheimer disease ( AD ) has been previously reported in Caucasian, as well as Japanese populations ( Li et al., 1997, Oliveira et al., 1998 and Hu et al., 2000 ). While the bi-allelic polymorphism ( 5-HTTLPR ) in the 5’ promoter region of SLC6A4 gene having short ( s ) and long ( l ) alleles has been associated with increased anxiety related temperamen- tal traits and increased risk for depression ( Lesch et al., 1996 ), there are also single nucleotide polymorphisms ( SNPs ) either within the promoter region of the gene ( Nakamura et al., 2000 ) or in the close proximity of it that have been associated with variety of mood disorders including mania spectrum disorders ( Rucci et al., 2009 ) and depression – a known risk factor for AD ( Green et al., 2003 ). The current study aims to investigate whether SNPs of the SLC6A4 gene are associated with AD in the Japanese sample. SNPs genotyped using TaqMan technology were analysed using a case-control study design. The case control dataset consisted of 180 AD patients and 130 age-matched controls. All SNPs were in Hardy-Weinberg equilibrium and except one SNP located the furthers from the 5’ regulatory region, showed very high linkage disequilibrium values suggesting low polymorphic rate in that region. Our study failed to show a sig- nificant association between the SLC6A4 polymorphisms and AD suggesting that these SNPs do not play a major role in the pathogenesis of AD in the Japa- nese sample. 104

GRADUATE PROGRAMS

International Graduate Program Medical Neurosciences

International Master and Doctoral Program Computational Neuroscience

Berlin School of Mind and Brain

GRK 1123 : Cellular Mechanisms of Learning and Memory Consolidation in the Hippocampal Formation

Helmholtz International Research School Molecular Neurobiology

International Graduate School Languages of Emotion 105 NeuroCure Towards a better outcome of neurological disorders

International Graduate Program Medical ­Neurosciences

Program Coordination Prof. Dr. U. Dirnagl, Prof. Dr. U. Heinemann, Prof. Dr. H. Kettenmann, Prof. Dr. A. Kupsch, Dr. B. Salmen, Prof. Dr. D. Schmitz

Both the Cluster of Excellence NeuroCure and the International Graduate Program Medical Neurosciences focus on translational research. The main objective is to bridge the gap between successes at the bench and less than satisfactory treatment at the bedside. In Germany, neuro- logical disorders contribute to more than 35% of the overall disease burden. With an aging population, this number will increase. Thus integrating basic laboratory research and the clinic in terms of faculty, students, research projects, education, and infrastructure is the logical and common core feature of both the cluster and the graduate program. Medical Neurosciences’ rigorous and comprehensive teaching program provides a struc- tured education in basic neuroscience to medical students and trains students of the life sci- ences in medical topics and approaches concerning the central and peripheral nervous system. The educational approach is based on in depth classroom teaching in small groups and care­ fully guided practical training. The program covers the breadth of neuroscience from basic neuro­biology to cognition and neurovascular diseases. Within this spectrum, we encourage students to develop their own research focus and career goals. MSc graduates have the theo- retical background, practical skills and faculty contact necessary for continued research in PhD projects. In the PhD program, these qualifications are further enhanced and combined with rigorous research work ranging from molecule to man. NeuroCure – Towards a better outcome of neurological disorders puts strong emphasis on the pro- motion of gender equality and supporting young scientist. The cluster’s strategy is based on recruiting, retaining, and promoting women in higher education as well as supporting Medical Neurosciences’ students on all levels and by providing Master and Ph.D. fellowships and an educational program.

Contact Contact Lutz Steiner, Head of Program Office Dr. Tanja Rohweder Medical Neurosciences NeuroCure Managing Director Charité – Universitätsmedizin Berlin Tel: + 49 30 450 539 701 Charitéplatz 1, 10117 Berlin Fax + 49 30 450 539 970 web www.medical-neurosciences.de web www.neurocure.de mail [email protected] mail [email protected] 106

International Master and Doctoral Program Computational Neuroscience

Spokesperson Prof. Dr. Klaus Obermayer

The Bernstein Center offers a combined International Master and Doctoral Program in Com- putational Neuroscience with the goal of training young scientists that will be competent in both computational and experimental neuroscience and will be able to judge scope and limits of theoretical and empirical approaches. The Master Program, a joint program of Humboldt-Universität zu Berlin and Technische Universität Berlin, is articulated in two years. In the first year, students are provided with ­basic experimental and theoretical techniques. In the second year, they participate in research in laboratories affiliated with the Bernstein Center, facilitating conception and development of their own research project – the foundation of their Master Thesis. The Doctoral Program, funded by the German Research Council through the research Training Group “Sensory Com- putation in Neural Systems”, gathers doctoral students working on interdisciplinary projects jointly overseen by supervisors of complementary expertise. Experimentalists and theoreticians join forces to educate young scientists to exploit the recent advances in machine learning, theo- retical neuroscience, and statistics for modeling brain function, and to develop new theories of computation hand in hand with well-controlled experiments in order to put functional hypo­ theses to test. The doctoral students are required to attend courses on advanced topics, such as methods of machine learning and artificial intelligence in addition to computational and ex- perimental neuroscience, as well as courses on transferable skills such as, for instance, presenta- tion and writing skills, ethical and legal aspects of neuroscience, and good scientific practice. The doctoral candidates are integrated into Berlin's collaborative teaching and research environment and the National Network for Computational Neuroscience. They participate in the organization of scientific meetings and attend conferences in Germany and abroad – an excellent platform to connect to the international neuroscience community.

Contact Dr. Vanessa Casagrande, Teaching Coordinator Bernstein Center for Computational Neuroscience Berlin Humboldt-Universität zu Berlin Philippstraße 13, Haus 6, 10115 Berlin web www.computational-neuroscience-berlin.de mail [email protected] 107

Berlin School of Mind and Brain

Spokespersons Prof. Dr. Michael Pauen and Prof. Dr. Arno Villringer

The Berlin School of Mind and Brain is an international doctoral research school. Founded in 2006 and funded by Germany’s Excellence Initiative, it offers a three-year interdisciplinary program in English in the mind/brain sciences. Research within the School focuses on the interface between the humanities and the neuro­ sciences. Of particular interest are research areas that fall on the borders between the mind sciences (e. g., philosophy, linguistics, behavioral and cognitive science, economics), and the brain sciences (e. g., neurophysiology, computational neuroscience, neurology, and neurobiology). Major topics of research within the program include: ‘conscious and unconscious perception’, ‘decision-making’, ‘language’, ‘brain plasticity and lifespan ontogeny’, ‘mental disorders and brain dysfunction’, and ‘human sociality and the brain’. Important are also the philosophy of mind, research in ethics and neuroscience, and molecular and cellular approaches to cognition. The School has a faculty comprised of nearly 60 distinguished researchers, including five Max Planck directors and four Leibniz Prize winners. Hosted by Humboldt-Universität, the School’s research program involves scientists from the Freie Universität, the Charité, the Technische Universität, the Bernstein Center for Computational Neuroscience, and the Max Planck institutes for Human Development and History of Science (all in Berlin), as well as the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig and the univer- sities of Potsdam and Magdeburg. Each year the School accepts ten to fifteen doctoral candidates into its program. Through- out the three-year program, students attend eight research-related teaching weeks, international lecture series, journal clubs, poster presentations, conferences and workshops. They are obliged to take a number of academic soft-skill courses such as presentation skills, grant-application writing, scientific writing, and are offered dissertation coaching and peer-mentoring.

Contact Dr. Inken Dose, Admission Officer Humboldt-Universität zu Berlin Berlin School of Mind and Brain Luisenstraße 56, Haus 1, 10117 Berlin web www.mind-and-brain.de mail [email protected] 108

GRK 1123 Cellular Mechanisms of Learning and Memory Consolidation in the Hippocampal Formation

Spokespersons Prof. Dr. Uwe Heinemann and Prof. Dr. Dietmar Schmitz

The Graduate School offers the possibility to study cellular mechanisms of learning and ­memory formation as well as memory consolidation. Our understanding of such processes is of outmost interest in biology and medicine as it determines the capability of an organism to adapt to its environment independently of genetically determined behaviors. Consequent- ly, formation of ­explicit memory is one of the most important aspects of human behavior and is the prerequisite of our individuality. Conversely, disturbance of the cellular and mole­ cular processes under­lying learning and memory can result in a variety of neurological and psychiatric disorders. These include devastating diseases such as temporal lobe epilepsy and Alzheimer’s disease. The most intensely studied cellular models of learning and memory are LTP ( long-term ­potentiation ) and LTD ( long-term depression ). Many of the underlying ­ pre- and post-synaptic mechanisms are still far from being understood. While short-term memory depends on covalent modifications of preexisting proteins, enduring memorytr­ aces need to be consolidated and depend on gene transcription. The specific translated proteins contribute to changes in neuronal circuitry that might comprise the generation of sharp wave ripple complexes, the formation of frequency memories and low frequency-induced hetero- synaptic increases in LTP. Moreover, stored information may be replayed in the form of pat- terns of neuronal activity during REM sleep superimposed on theta and gamma rhythms and thereby cause alterations of synaptic coupling outside the hippocampus proper. Each ofçthe 13 tutors of this graduate school will bring to these problems his or her specific exper­ tise. Using physiological, morphological, cell biological, genetic, and behavioral methods, as well as modeling of neuronal network properties, the students in the graduate school will have the opportunity to contribute to this exciting field of the neurosciences within an excel- lent environment for training in modern neurobiological methods.

Contact Barbara Neuhoff, Coordinator GRK 1123 Charité – Universitätsmedizin Berlin Neurowissenschaftliches Forschungszentrum /AG Geiger Charitéplatz 1, 10117 Berlin web www.charite.de/GRK1123 mail [email protected] 109

Helmholtz International Research School “Molecular Neurobiology”

Spokesperson Prof. Dr. Gary Lewin Deputy Spokespersons Prof. Dr. Volker Haucke and Prof. Dr. Fritz Rathjen

The aim of this research school is to provide state-of-the-art training to elucidate the molecu- lar basis of neurobiological processes. Within this context, students admitted to the research school are expected to pursue a research project designed to understand the molecular basis underlying normal function or dysfunction of the nervous system. Our flexible training curric- ulum is composed of a two year lecture series covering basic and advanced concepts of Neuro­ biology, a student journal club, practical courses and PhD-student retreats. In addition, we offer soft skill courses organized by the Helmholtz Association in conjunction with students from other Helmholtz Research Schools encompassing a range of research areas. Our School’s faculty comprises researchers from the Max Delbrück Center for Molecular Medicine, Freie Universität Berlin and Charité – Universitätsmedizin Berlin.

Contact Dr. Jana Droese Coordinator Max Delbrück Center for Molecular Medicine Robert-Rössle-Straße 10, 13125 Berlin web www.mdc-berlin.de/molneuro mail [email protected] 110

International Graduate School “Languages of Emotion”

Cluster Coordinator Univ.-Prof. Dr. Hermann Kappelhoff

The graduate program of the Cluster of Excellence “Languages of Emotion” of Freie Univer- sität Berlin aims at attracting highly qualified, international young scholars and promoting their careers, while at the same time integrating them into the overall research agenda and transdisciplinary work of the cluster. The Graduate school allows for pursuing individual research within the thematic framework of the Cluster, encourages team-work and discussion of findings not only among the group of PhD students, but also in the research projects of the Cluster. In this context, the graduate program “Languages of Emotion” seeks to create an atmosphere of collaboration in an interdisciplinary setting and to lay fruitful grounds for ­future scholars in emotion studies. Since the field of study (“Languages of Emotion”) is neither a separate discipline nor con- fined to a particular department, doctoral degrees are awarded in cooperation with the­ academic departments of the Freie Universität Berlin. Students will be granted a maximum of flexibility to answer the demands of the program. To merge innovative research and academic teaching, the education program of the Cluster “Languages of Emotion” integrates alternative forms and formats of research-oriented teaching, adding to our seminars on methods and theories of emotion studies, which make up the backbone of our teaching activities. Apart from the classes of the Graduate School, our PhD program provides sufficient opportunities for students to participate in courses and activities of the respective disciplines with which they are also affiliated. Complementing our scientific course programs for doctoral researchers, a transfer- able skills training is offered in conjunction with FU Berlin’s Dahlem Research School (DRS). Successful students will obtain both a PhD degree from their respective discipline and a second certificate documenting their education at the Cluster of Excellence and their inter­ disciplinary work on “Languages of Emotion”.

Contact Dr. Markus Edler, Coordinator of Graduate Studies Graduate School “Languages of Emotion” Freie Universität Berlin Habelschwerdter Allee 45, 14195 Berlin web www.languages-of-emotion.de/en/graduate-program.html mail [email protected] 111

APPENDIX

Index of Speakers and Poster Presenters

Notes

How to get to the Max Delbrück Center by public transport 112 Index > Speakers & Poster Presenters

A H Amaral, Ana 86 Henning, Karen 93 Herbst, Sophie 67 B I Bareither, Isabelle 66 Beck, Luna 83 Imamoglu, Fatma 30 Bera, Sujoy 87 Issa, Lina 48 Bradke, Frank 12 Burzynska, Agnieszka 88 J Jaramillo, Jorge 24 C ÇalıŞkan, Gürsel 42 K Chang, Chia-Ling 44 Kaltwasser, Laura 94 Chenkov, Nikolay 78 Kettenmann, Helmut 2 Kintscher, Michael 37 D Kliemann, Dorit 84 D’Albis, Tiziano 79 Knoche, Elena 60 Dätwyler, Anne 47 Köhler, Saskia 68 Deuschel, Dorothea 59 Korn, Christoph 18 Dorrn, Anja 72 Kovalenko, Lyudmyla 49 Duque Do Vale, Rúben 89 Ku, Min-Chi 73

E L Engel, Odilo 36 Laginha, Inês 50 Lapilover, Ezequiel 51 F Lebrecht, Sophie 69 Liebsch, Filip 61 Fairhall, Adrienne 23 Lippmann, Kristina 62 Franzoni, Eleonora 90 Ludwig, Karin 31 Lüscher, Christian 9 G Lyras, Ekaterina-Maria 52 Gołaska, Paulina 91 Grauel, Katharina 92 Grill-Spector, Kalanit 29 Gutzmann, Jakob 43 113

M S Mackwood, Owen 81 Schönfelder, Vinzenz 26 Markowitsch, Hans 41 Schütze, Sebastian 77 Mayer, Magnus 63 Schulz, Steffen 56 Michalikova, Martina 95 Schweizer, Sophie 57 Mosienko, Valentina 74 Sekutowicz, Maria 100 Mourtzi, Theodora 96 Slavi, Nefeli 52 Sonnenschein, Bernard 101 N Soreq, Hermona 35 Soutschek, Alexander 102 Nahimi, Adjmal 97 Stock, Kristin 14 Stein, Timo 20 O Oberheide, Karina 75 T Omerbasic, Damir 13 Tomson, Katrin 103 Torbet, Georgina 71 P Pannell, Maria 82 V Parameshwar Reddy, Pasham 98 Vinnakota, Katyayni 38 Park, Soyoung 19 Vorwerk, Brita 93 Parnis, Julia 76 Pelz, Thomas 53 W Pessoa, Luiz 17 Porbadnigk, Anne 25 Wegener, Stephanie 65 Winek, Katarzyna 58 R Ramírez, Fernando 32 Rausch, Philip 70 Raza, Muhammad Liaquat 54 Reifenstein, Eric 64 Rodríguez, Andrea 99 Römer, Christine 55 Roemschied, Frederic 80 Rosenblau, Gabriela 85 114 For your notes on the Berlin Brain Days 2011 For your notes on the Berlin Brain Days 2011 115 116 For your notes on the Berlin Brain Days 2011 For your notes on the Berlin Brain Days 2011 117 118 For your notes on the Berlin Brain Days 2011 For your notes on the Berlin Brain Days 2011 119 120 How to get to the Max Delbrück Center by public transport

From Bahnhof Friedrichstraße, take S-Bahn line S2 direction Buch / Bernau to S-Bahnhof Berlin-Buch. From there take Bus 351 ( direction Campus Buch; bus stop to the left of the train station ) directly to MDC ( last stop ). ( Travel time : about 40 min. from Friedrichstraße. ) There is also a taxi stand upon exiting the S-Bahn station Berlin-Buch. The MDC is about twenty minutes’ walking distance from the station Berlin-Buch.

S+U Friedrichstr. Bhf (Berlin) > Campus Buch (Berlin)

S+U Friedrichstr. Bhf (Berlin) > Campus Buch (Berlin) g ¨ultigvom 08.12.2011 bis 09.12.2011

g ¨ultigvom 08.12.2011 bis 09.12.2011

Ab Fahrt An Umsteigen Ab Fahrt An Dauer Verkehrstage 08:00 S S2 cd 08:24 S Buch (Berlin) 08:30 Bus 353 bf 08:38 00:38 nicht taglich¨ a 08:10Ab FahrtS S2 cd An08:34 UmsteigenS Buch (Berlin) Ab08:40 FahrtBus 353 bf 08:48An Dauer00:38 Verkehrstagenicht taglich¨ a 08:0008:20 SS S2S2 cdcd 08:2408:44 SS Buch Buch (Berlin) (Berlin) 08:3008:50 BusBus 353353 bfbf 08:3808:58 00:3800:38 nichtnicht taglich t¨aglich¨ a a 08:1008:30 SS S2S2 cdcd 08:3408:54 SS Buch Buch (Berlin) (Berlin) 08:4009:00 BusBus 353353 bfbf 08:4809:08 00:3800:38 nichtnicht taglich t¨aglich¨ a a 08:2008:40 SS S2S2 cdcd 08:4409:04 SS Buch Buch (Berlin) (Berlin) 08:5009:10 BusBus 353353 bfbf 08:5809:18 00:3800:38 nichtnicht taglich t¨aglich¨ a a 08:3008:50 SS S2S2 cdcd 08:5409:14 SS Buch Buch (Berlin) (Berlin) 09:0009:20 BusBus 353353 bfbf 09:0809:28 00:3800:38 nichtnicht taglich t¨aglich¨ a a 08:4009:00 SS S2S2 cdcd 09:0409:24 SS Buch Buch (Berlin) (Berlin) 09:1009:30 BusBus 353353 bfbf 09:1809:38 00:3800:38 nichtnicht taglich t¨aglich¨ a a 08:5009:10 SS S2S2 cdcd 09:1409:34 SS Buch Buch (Berlin) (Berlin) 09:2009:40 BusBus 353353 bfbf 09:2809:48 00:3800:38 nichtnicht taglich t¨aglich¨ a a 09:0009:20 SS S2S2 cdcd 09:2409:44 SS Buch Buch (Berlin) (Berlin) 09:3009:50 BusBus 353353 bfbf 09:3809:58 00:3800:38 nichtnicht taglich t¨aglich¨ a a Campus Buch (Berlin) > S+U Friedrichstr. Bhf (Berlin) 09:1009:30 SS S2S2 cdcd 09:3409:54 SS Buch Buch (Berlin) (Berlin) 09:4010:00 BusBus 353353 bfbf 09:4810:08 00:3800:38 nichtnicht taglich t¨aglich¨ a a 09:20 S S2 cd 09:44 S Buch (Berlin) 09:50 Bus 353 bf 09:58 00:38 nicht taglich¨ a 09:30 S S2 cd 09:54 S Buch (Berlin) 10:00 Bus 353 bf 10:08 00:38 nicht taglich¨ a Index > Campusg ¨ultigvom Buch (Berlin) 08.12.2011S+U bis Friedrichstr. 09.12.2011 Bhf (Berlin) a = 8., 9. Dez Index Campus Buch (Berlin) > S+U Friedrichstr. Bhf (Berlin) a = 8., 9. Dez g ¨ultigvom 08.12.2011 bis 09.12.2011 Ab Fahrt An Umsteigen Ab Fahrt An Dauer Verkehrstage g ¨ultigvom 08.12.2011 bis 09.12.2011 17:18 Bus 353 bf 17:28 S Buch (Berlin) 17:35 S S2 cd 17:58 00:40 nicht taglich¨ a ca 17:38Ab BusFahrt 353 bf 17:48An SUmsteigen Buch (Berlin) 17:55Ab SFahrt S2 cd 18:18An Dauer00:40Verkehrstage nicht taglich¨ a 17:18 Bus 353 cabf 17:28 S Buch (Berlin) 17:35 S S2 cd 17:58 00:40 nicht taglich¨ a 17:59Ab FahrtBus 353 bfca An18:08 Umsteigen S Buch (Berlin) Ab18:15 Fahrt S S2 cd 18:38An Dauer00:39 Verkehrstage nicht taglich¨ a 17:1817:38 BusBus 353353 bfcabf 17:2817:48 SS Buch Buch (Berlin) (Berlin) 17:3517:55 SS S2S2 cdcd 17:5818:18 00:4000:40 nichtnicht taglich¨ taglich¨ a a 18:19 Bus 353ca bfca 18:28 S Buch (Berlin) 18:35 S S2 cd 18:58 00:39 nicht taglich¨ a 17:3817:59 BusBus 353353 bfcabf 17:4818:08 SS Buch Buch (Berlin) (Berlin) 17:5518:15 SS S2S2 cdcd 18:1818:38 00:4000:39 nichtnicht taglich¨ taglich¨ a a 18:39 Bus 353ca bfca 18:48 S Buch (Berlin) 18:55 S S2 cd 19:18 00:39 nicht taglich¨ a 17:5918:19 BusBus 353353 bfcabf 18:0818:28 SS Buch Buch (Berlin) (Berlin) 18:1518:35 SS S2S2 cdcd 18:3818:58 00:3900:39 nichtnicht taglich¨ taglich¨ a a 18:59 Bus 353ca bfca 19:08 S Buch (Berlin) 19:15 S S2 cd 19:38 00:39 nicht taglich¨ a 18:1918:39 BusBus 353353 bfcabf 18:2818:48 SS Buch Buch (Berlin) (Berlin) 18:3518:55 SS S2S2 cdcd 18:5819:18 00:3900:39 nichtnicht taglich¨ taglich¨ a a caca Index18:3918:59 BusBus 353353 bfbf 18:4819:08 SS Buch Buch (Berlin) (Berlin) 18:5519:15 SS S2S2 cdcd 19:1819:38 00:3900:39 nichtnicht taglich¨ taglich¨ a a caca 18:59a =Bus 8., 9. 353 Dez bf 19:08 S Buch (Berlin) 19:15 S S2 cd 19:38 00:39 nicht taglich¨ a LegendeIndex ca Indexcda = = barrierefrei 8., 9. Dez bf = barrierefrei Legendeaca = = 8., ab 9. S DezBuch weiter als Bus 351 bis Klinikum Buch cd = barrierefrei Legendebf = barrierefrei cdca = = barrierefrei ab S Buch weiter als Bus 351 bis Klinikum Buch bf = barrierefrei ca = ab S Buch weiter als Bus 351 bis Klinikum Buch

Alle Angaben ohne Gewahr.¨ Bitte beachten Sie unsere aktuellen Streckeninformationen unter www.BVG.de Noch Fragen ? BVG Call Center. Tel.: 030 19 44 9 E-Mail: [email protected] Allec 2002 Angaben HaCon ohne Ingenieurgesellschaft Gewahr.¨ Bitte beachten mbH Sie / IVU unsere Traffic aktuellen Technologies Streckeninformationen AG. Erstellt am 21.11.11 unter www.BVG.de um 23:54. Noch Fragen ? BVG Call Center. Tel.: 030 19 44 9 E-Mail: [email protected] c 2002 HaCon Ingenieurgesellschaft mbH / IVU Traffic Technologies AG. Erstellt am 21.11.11 um 23:54.

Alle Angaben ohne Gewahr.¨ Bitte beachten Sie unsere aktuellen Streckeninformationen unter www.BVG.de Noch Fragen ? BVG Call Center. Tel.: 030 19 44 9 E-Mail: [email protected] c 2002 HaCon Ingenieurgesellschaft mbH / IVU Traffic Technologies AG. Erstellt am 21.11.11 um 23:54. Alle Angaben ohne Gewahr.¨ Bitte beachten Sie unsere aktuellen Streckeninformationen unter www.BVG.de Noch Fragen ? BVG Call Center. Tel.: 030 19 44 9 E-Mail: [email protected] c 2002 HaCon Ingenieurgesellschaft mbH / IVU Traffic Technologies AG. Erstellt am 21.11.11 um 23:54. Alle Angaben ohne Gewahr.¨ Bitte beachten Sie unsere aktuellen Streckeninformationen unter www.BVG.de Noch Fragen ? BVG Call Center. Tel.: 030 19 44 9 E-Mail: [email protected] c 2002 HaCon Ingenieurgesellschaft mbH / IVU Traffic Technologies AG. Erstellt am 21.11.11 um 23:54. NATURKUNDE- MUSEUM

Langenbeck-Virchow-Haus, Luisenstraße 58/59, 10117 Berlin

Imprint

Editor Annette Winkelmann Design and Typesetting Sebastian Lehnert, www.deskism.com Original Design Holger Gerhardt Typefaces Adobe Caslon Pro and FF Meta Pro Editorial deadline 18 November 2011 Printing house Flyeralarm, Würzburg Copies 200

Max Delbrück Center for Molecular Medicine Berlin-Buch Conference Center MDC.C ( labeled 83 on the map ), lecture hall “Axon” Robert-Rössle-Straße 10, 13125 Berlin 8 th International Ph. D. Symposium Berlin Brain Days 2011 Berlin

/ program, curricula vitae,program, curricula and abstracts Brain Days 2011 /dec. 7 – 9

Program & Abstract Abstracts Curricula The Berlin Brain Days 2011 are jointly organized schedule of the open­ of the six vitae of of the sym­ ing lecture by keynote the keynote by six Berlin-based neuroscience Ph. D. programs posium Christian lectures speakers Lüscher

LANGUAGES OF Abstracts Abstracts Information EMOTION of all Ph.D. of all pre­ on the orga­ conference sented Ph.D. nizing Ph.D. talks posters programs

BERLIN SCHOOL OF MIND AND BRAIN

www.neuroscience-berlin.de/bbd/ Max Delbrück Center for Molecular Medicine Berlin­Buch