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MAY 2015 NEUROSCIENCE NEWSLETTER Georg-August-Universität Göttingen ∙ International Max Planck Research School

The , ... CONTENT … the 15th Anniversary, and the three new institutes Editorial ...... 1 The CNS myelination process...... 3 Molecular espionage...... 7 Welcome to the 4th Neuro-Newsletter fact that neuroscientists at all levels, The devloping neocortex...... 11 published by the Göttingen Inter- from senior scientists to junior group A SIP of Ninein...... 14 national Master/PhD/MD-PhD Pro- leaders and PhD students, competed Master’s class 2014/15...... 18 gram and International Max Planck successfully for national and interna- PhD projects started in 2014...... 19 Research School (IMPRS) for Neuro- tional awards, reflects the competitive The Doctors of 2014...... 20 sciences. research efforts of one of the largest Alumnus: Aaron Wong...... 21 research communities in the field in Alumna: Jayeeta Basu...... 22 First of all, congratulations to Stefan . The Neuroscience Program Alumna: Pooja Rao...... 26 Hell who was awarded the Nobel Prize is pleased to contribute to the success Alumnus: Benjamin Wilhelm...... 28 for Chemistry in 2014 (together with and growth of the neurosciences on Creutzfeldt Award...... 30 , William E. Moerner). The the Göttingen Campus for more than a Honors and Awards…...... 30 Neuroscience program is delighted to decade now. Joining the program from 2013...... 31 again have a Nobel laureate among Left the program since 2013...... 32 its members, after Erwin Neher, Nobel Founded in the year 2000 as one of the Neurizons 2015...... 33 laureate in Physiology or Medicine in first international schools in the field in Joint Retreat with MDC...... 34 1991 and founding member of the IM- Germany, the Neuroscience Program ELECTRAIN courses...... 35 PRS for Neurosciences, retired. celebrates its 15th Anniversary in May Info Booth at SFN...... 35 2015. The alumni day 3rd DAAD Summer School...... 36 activities, which are EU Neuroscience Campus Network...... 37 organized together Live the Weizmann Cooperation...... 37 with the Molecular 15th Anniversary and Intl. Alumni Day...... 39 Biology Program / IMPRS, take place during the week- end directly after the overview on relevant disciplines in NEURIZONS sympo- the neurosciences, the content and sium. This arrange- focus have continuously been adjus- ment will hopefully ted to the most actual research topics. again allow many Namely the area of biophysics relevant MSc/PhD alumni to for quantitative approaches in the life come to Göttingen for sciences and the introduction to novel a scientific meeting imaging techniques important for cli- and subsequent alum- nically-related research on neurode- Gregor Eichele, Stefan Hell, Martin Stratmann, , ni get-together to re- generation have been integrated into Erwin Neher (from right to left) new the connections the teaching canon. between the graduates In addition to the glamour of the Nobel and the local scientific community. These adjustments in teaching reflect Prize it is noteworthy that other pro- the dynamic changes in research and gram members have been conferred While the program keeps its tradition go along with the construction of two prestigious research prizes as well to offer a full year intensive MSc cur- new research buildings accommoda- (see section ‘Honors & Awards’). The riculum providing a comprehensive ting three new institutes directly re- Neurosciencein Göttingen…

lated to the neurosciences on the Göt- institutes focusing on high-resolution novel early diagnostic tools. The U- tingen Campus. imaging on the molecular and cel- shaped building architecture with over lular level in 2016. The ‘twin’ facility 200 rooms on 5 floors allows for ef- The new Imaging Center of the Ger- currently still under construction will ficient joint use of common facilities man Primate Centre (DPZ) and an ad- house two research institutes located and research equipment. ditional ‘multifunctional’ building with close to the university clinics. The Bio- a lecture hall and space for offices and structural Imaging of Neurodegenera- These new institutes extend the basis laboratories have been opened in April tion (BIN) institute will be operated by for competitive research and the for- 2015. Financed by the Leibniz Society the UMG; the Göttingen section of the mation of networks and new forms of and the State of Lower Saxony the DPZ German Center for Neurodegenera- co-operation between scientists in the imaging center will operate two mag- tion (DZNE) will be supported by the future allowing the development of netic resonance tomography scanners Helmholtz Society. Concentrating on novel fields and further growth of the for use in primates and small labora- high resolution imaging and the inves- neurosciences in Göttingen. Nonethe- tory animals in direct vicinity of a mo- tigation of mechanisms of neurode- less, given the worldwide increasing dern animal care facility. generative diseases, the two new insti- number and quality of research and tutes will enable a close cooperation teaching facilities in the neuroscien- The University Medical Center Göt- between basic researchers and clinical ces, it will remain a challenge to attract tingen (UMG) plans to open two new scientists towards the development of sufficient numbers of young talented scholars and scientists to the Göttingen Campus.

Gregor Eichele Speaker of the Max Planck Research School

Detlev Schild Speaker of the MSc/PhD/MD-PhD Program

Sandra Drube Administrative Coordinator of the Program

Michael Hörner Scientific Coordinator

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Publisher: Coordination Office of the international MSc/PhD/MD-PhD Neuroscience Program Design and page layout: LifeTechMedia (Martin Nolte, Eva-Maria Twehues) and Neuroscience Coordination Office (Sandra Drube, Michael Hörner)

The views expressed in this newsletter by the authors of articles are not necessarily those of the Neuroscience program. All reasonable measures have been taken to ensure that the material contained in this newsletter is correct. However, the Neuroscience program gives no warranty and accepts no responsibility for the accuracy or the completeness of the material.

2 NEUROSCIENCE Science Spotlight2015 One step closer... towards the understanding of the CNS myelination process by Nicolas Snaidero

Central nervous system myelin is a axon. More than 60 years after the during its formation. Some of these multilayered membrane sheath ge- seminal discovery demonstrating that shortcomings were reconciled in the nerated by oligodendrocytes for rapid myelin is made by axon-associated gli- “yo-yo” model (Knobler et al., 1974, impulse propagation. However, the al cells, and not by the axon itself, the Pedraza et al., 2009). In the latter case, underlying mechanisms of myelin molecular mechanisms by which the myelin growth begins with a single wrapping have remained unclear. U- myelin sheath is wrapped around the glial process that, after making axonal sing an integrative approach of live axon are still largely unknown. Seve- contact, spirally encircles the future in- imaging, electron microscopy, and ral key questions remain unanswered, ternode, followed by the lateral growth genetics, we show that new myelin such as what is the morphology of a of the individual membrane layers. membranes are incorporated adjacent growing myelin sheath? Where is the More recent models, like the “liquid to the axon at the innermost tongue. Si- synthesized material added during my- croissant” and the “Ofiomosaic mo- multaneously, newly formed layers ex- elination? How does the myelin sheath del”, based on light microscopy imag- tend laterally, ultimately leading to the reach such an organized state of com- ing implied a growth from the outer formation of a set of closely apposed paction? Is there a way for the material surface of the myelin sheath and the paranodal loops. An elaborated system to go through the compacted myelin involvement of the axon membrane of cytoplasmic channels within the to ensure the growth and the axo-glia rotation as an active force driving the growing myelin sheath enables mem- communication? myelination (Sobottka et al., 2011, Io- brane trafficking to the leading edge. annidou et al., 2012). However, due Most of these channels close during The investigation of the myelination to the physical limitations of imaging development but can be reopened process is directly correlated with the such processes, it has not been pos- in adults by experimentally raising capacity to visualise the morphology sible to experimentally support any of phosphatidylinositol-(3,4,5)-triphos- of such a complex structure. Several these models of myelin wrapping. phate levels, which reinitiates myelin technical challenges are on the way to growth. In addition, we could better investigate the myelin biogenesis due In order to investigate the myelin bio- our understanding of the mechanisms to the physical limitations of visual- genesis, a critical step was to under- responsible for the intra and extracel- izing membrane dynamics at the na- stand the exact morphology of the lular compaction of this highly ordered nometre scale and the duration of the myelin sheath at various time points structure. Our model can explain as- wrapping process (few days in vivo). As during its development. To achieve this, sembly of the myelin as a multilayered a consequence of these imaging limita- we prepared mouse CNS tissue using structure, abnormal myelin outfold- tions there is no unified theory of my- the high pressure freezing technique ings in neurological disease, and plas- elination and several myelin models for electron microscopy described to ticity of myelin biogenesis observed presenting different modality of mem- give preservation close to native state throughout adult life. brane wrapping were proposed. (Mobius et al., 2010). To cover a large volume of tissue and, at the same time, In the nervous system of vertebrates According to the “carpet crawler” mo- being able to reach a very high resolu- axons are ensheathed with myelin, del, the oligodendrocyte forms a pro- tion we used serial block face imaging which is one of the most remarkable cess that broadens and extends along of high pressure frozen optic nerve and complex transformations of a the entire axonal segment (the future by scanning electron microscopy. By plasma membrane achieved by a sin- internode) before it makes one turn combining volume microscopy with gle cell. In the CNS, one single oligo- and moves underneath the growing conventional TEM of high pressure dendrocyte can produce up to 50 my- sheet (Bunge et al., 1961). However, at frozen optic nerve and live imaging elin sheaths of around 200 µm length. least in the CNS, several morphologi- of myelin biogenesis in zebrafish, we Each sheath is composed by a tightly cal features of myelin are incompatible could reconstruct the 3D organization compacted spiral of a membrane that with this model, such as an uneven my- and follow the changes of the myelin is wrapped several times around the elin thickness along the myelin sheath sheath during its growth, allowing us

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to propose a new model of CNS myeli- they align and form paranodal loops. are regulated by PI(3,4,5)P3 levels. In- nation. We suggest that myelin grows In addition to the detailed morpho- deed, even in adult mice the network by two coordinated motions: (1) wrap- logy of the growing sheath, using viral of cytoplasmic channels could be re- ping of the leading edge at the inner reporter approach combined with im- opened prior to the myelin thickening tongue around the axon in a triangle- mune electron microscopy we could in response to an increase of PI(3,4,5) like shape, underneath the previously identify that the newly synthesised P3 levels specifically in oligodendro- deposited membrane; together with (2) material was inserted into the grow- cytes (Goebbels et al., 2012). Fig 1. the lateral extension of myelin mem- ing myelin sheath at the inner tongue brane layers toward the nodal regions. (Snaidero et al., 2014a, Fig 1). Conjointly with the morphological In this model, the lateral cytoplasmic analysis of the myelination we could domains of each myelin layer are al- It has also become apparent that my- gain a better understanding of the cy- ways in contact with the axonal sur- elin is a dynamically active structure toplasmic compaction of the myelin face and move in a continuous helical that can provide metabolic support to sheath mediated by MBP, as well as the manner toward the future node, where associated axons. However, it remains mechanisms that are responsible for completely un- the close interactions between myelin clear how mol- membranes at their external surfaces. ecules reach the Indeed, valuable insides were gained innermost myelin on the role of MBP in extruding pro- layer, i.e., passing teins with large cytoplasmic domains through a mul- from the compacted areas (Aggarwal tilamellar stack et al 2011), as well as on the molecu- of membranes. lar basis that drive myelin membrane Based on the pre- assembly by a phase transition of the servation of the MBP into a cohesive protein mesh- sample by high work. (Aggarwal et al 2013). In addi- pressure freezing tion, we could observe that, while the we could iden- growth occurs at the inner tongue, the tify an elaborated compaction of the intracellular do- system of cyto- main of the myelin sheath by MBP pro- plasmic channels gresses from the outer layers towards within compacted the inner tongue, spatially separating myelin that pro- these two processes (Snaidero et al., vides shortcuts for 2014a). Furthermore, when consider- the transport of ing the compaction of the extracellular membrane to the leaflets of the myelin sheath, the loss of growth zone at electrostatic cell surface repulsion me- the inner tongue diated by oligosaccharides of the glico- in the developing calix together with transmembrane Fig. 1a: Morphology of the growing myelin sheath in the CNS. Wrapped myelin sheath. We tetra span (PLP) homo-interaction were and unrolled views of the growing myelin showing the geometry of the could show that shown to mediate the extracellular ad- sheath and the direction of growth (blue arrow heads). The cytoplasmic most channels ap- hesion (Bakhti et al 2013a, Bakhti et al channels are connecting the cell body with the inner tongue where the pear transiently in 2013b). newly synthesised material is added. The wrapped view illustrates that development at the lateral cytoplasmic rich areas of the sheath are in constant contact the most intense Taken together, we have used an in- with the axon, forming a coiled structure towards the both ends of the phase of mem- depth integrated approach of advanced segment. brane growth and imaging at the light and electron mi-

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croscopic level, as well as molecular that allow membrane trafficking toward nisms of intracellular compaction by tools, to dissect the morphogenesis the growing tip (at the inner tongue), MBP and extracellular week adhesions and stabilization of myelin membrane our observations led to a model where that would allow the membrane gli- wrapping. Combined with the disco- the inner layer of the myelin sheath ding during myelin formation and my- very of the previously unknown myelin would advance beneath the already elin remodelling (Bakhti et al 2013b). growth zone and identification of tran- present layers (Snaidero et al., 2014a). This model not only fills a gap in our sient cytoplasmic channels in myelin In addition, we described the mecha- understanding of myelin biogenesis

Fig. 2: Compaction of the myelin sheath from the extracellular and intracellular leaflets. The formation of the intraperiod line (IPL) is thought to be mediated by the removal of the glycocalyx components along with the PLP expression of the membrane. On the cytosolic surface, upon interaction with the membrane, the MBP protein is undergoing a conformational change that allows self-assembly. Resulting protein meshwork extrudes bulky cytoplasmic proteins, which results in the formation of the major dense line (MDL). The formation of the IPL is happening prior to the MDL which, in its turn, occurs starting from the more superficial layers of the myelin sheath towards the inner tongue. Scale bar: 100nm Picture adapted from Bakhti et al., 2013 (License Number: 3474830244857)

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in brain development, but also sheds Nicolas SNAIDERO did his doctoral in light on myelin pathology in various Mikael Simon’s department, Max Planck Institute for neurological disorders (Snaidero et al., Experimental Medicine, Centre for Biochemistry and 2014b). Molecular Cell Biology. His doctoral thesis and oral defense were rated ‘summa cum laude’ by a team of internal and external reviewers. He defended his PhD thesis in July 2013. He will be awarded the Otto- Creutzfeldt PhD Award in 2015.

Institute of Neuronal Cell Biology Technical University München Biedersteiner Str. 29 80802 München

Institute of Clinical Neuroimmunology Ludwig-Maximilians University Munich Marchioninistr. 17 81373 München

References 1. Aggarwal, S., Snaidero, N., Pahler, G., Frey, S., Sanchez, P., Zweckstetter, M., Janshoff, A., Schneider, A., Weil, M.T., Schaap, I.A., et al. (2013). Myelin membrane assembly is driven by a phase transition of myelin basic proteins into a cohesive protein meshwork. PLoS Biol 11, e1001577. 2. Aggarwal, S., Yurlova, L., Snaidero, N., Reetz, C., Frey, S., Zimmermann, J., Pahler, G., Janshoff, A., Friedrichs, J., Muller, D.J., et al. (2011). A size barrier limits protein diffusion at the cell surface to generate lipid-rich myelin-membrane sheets. Dev Cell 21, 445-456. 3. Bakhti, M., Aggarwal, S., Simons, M. (2013). Myelin architecture: zippering membranes tightly 4. together. Cell Mol Life Sci. 71(7):1265-77. 5. Bakhti, M., Snaidero, N., Schneider, D., Aggarwal, S., Mobius, W., Janshoff, A., Eckhardt, M., Nave, K.A., and Simons, M. (2013). Loss of electrostatic cell-surface repulsion mediates myelin membrane adhesion and compaction in the central nervous system. Proc Natl Acad Sci U S A 110, 3143-3148. 6. Goebbels, S., Oltrogge, J.H., Wolfer, S., Wieser, G.L., Nientiedt, T., Pieper, A., Ruhwedel, T., Groszer, M., Sereda, M.W., and Nave, K.A. (2012). Genetic disruption of Pten in a novel mouse model of tomaculous neuropathy. EMBO Mol Med 4, 486-499. 7. Knobler, R.L., Stempak, J.G., and Laurencin, M. (1974). Oligodendroglial ensheathment of axons during myelination in the developing rat central nervous system. A serial section electron microscopical study. J Ultrastruct Res 49, 34-49. 8. Ioannidou, K., Anderson, K.I., Strachan, D., Edgar, J.M., and Barnett, S.C. (2012). Time-lapse imaging of the dynamics of CNS glial-axonal interactions in vitro and ex vivo. PLoS One 7, e30775. 9. Pedraza, L., Huang, J.K., and Colman, D. (2009). Disposition of axonal caspr with respect to glial cell membranes: Implications for the process of myelination. J Neurosci Res 87, 3480-3491. 10. Snaidero N, Moebius W, Czopka T, Hekking L., Mathisen C, Verkleij D, Goebbels S, Edgar J, Merkler D,Lyons D, Nave K, Simons M. (2014). Myelin Membrane Wrapping of CNS Axons by PI(3,4,5)P3- Dependent Polarized Growth at the Inner Tongue. Cell. 156, 277-90 11. Snaidero N, Simons M. (2014). Myelin at a Glance. J Cell Sci. 127, 2999-3004. 12. Sobottka, B., Ziegler, U., Kaech, A., Becher, B., and Goebels, N. (2011). CNS live imaging reveals a new mechanism of myelination: the liquid croissant model. Glia 59, 1841-1849.

6 NEUROSCIENCE Science Spotlight2015 Molecular espionage: revealing the identity of endocytosed organelles by Natalia H. Revelo

Membrane trafficking is of capital im- cal hallmarks have led to identification 1A). Moreover, due to the typical small portance in the function of eukaryotic of different organelle types. size of trafficking organelles, imaging cells. The simultaneous study of the should be performed under high- morphology and molecular composi- Membrane trafficking processes were resolution microscopy (nanoscopy). tion of trafficking organelles was not initially studied with electron micros- During my PhD project we devel- possible due to the lack of a suitable copy (2–4). Later on, with the devel- oped such an endocytosis probe and and efficient technique. To overcome opment of immunostaining proce- named it mCLING (membrane-binding this difficulty, we developed a mem- dures based on metallic or fluorescent fluorophore-Cysteine-Lysine-Palmitoyl brane-binding fluorescent marker markers (5–7), it was now possible to Group)(Figure 1B). It is composed of a compatible with immunostaining. identify the molecular players of these hydrophobic tail that allows binding to Using this tool we could reveal endo- processes. Moreover, with the increa- membranes; a peptide containing sev- cytotic structures and their molecular sing use of fluorescence microscopy, en lysine molecules that provide amine identity in a multitude of biological fluorescent lipid-soluble molecules groups for aldehyde fixation; and final- preparations. were developed to label membranes ly, a fluorescent molecule (Atto647N) in living cells and follow physiologi- suitable for stimulated emission deple- The main characteristic of eukariotic cal processes like endocytosis and tion (STED) nanoscopy (11). cells is the compartmentalization and organellar trafficking (8). The combi- separation of the different cellular pro- nation of two of these approaches led We found that mCLING is not toxic for cesses into membrane-bound struc- to photo-oxidation, a technique that the cells at the concentration required tures. This leap forward in evolution converts an endocytosed fluorescent for its imaging. It is readily taken up meant an easier “administration” of marker into an electron-dense precipi- by the cells once it reaches the plasma the cellular resources and isolation of tate, making endocytosed organelles membrane and, in contrast to other specific biochemical processes, con- visible for electron microscopy (EM) endocytosis markers, it is not washed tributing to cell complexity and spe- (9). Despite these advances, one im- off the cell surface, due to its strong cialization. The outer surface of the portant question has remained difficult binding to membranes. Co-incuba- cell, the plasma membrane, consti- to solve: can one track an endocytosed tions with mCLING and fluorescently tutes not only a barrier between the organelle and simultaneously establish labeled ligands for surface receptors cell and its environment but also an its molecular identity? One possibility like epidermal growth factor (EGF), exchange platform. It internalizes nu- would be to combine photo-oxidation transferrin or low-density lipoprotein trients necessary for the cell function and immuno-EM (10). However, this (LDL), showed colocalization of both or receptors molecules for their recy- approach has several disadvantages: signals in endocytosed organelles, in- cling (endocytosis), and secretes syn- laborious sample preparation and ex- dicating that mCLING is successfully thesis products, like chemical signals tensive imaging time resulting in low endocytosed and that it can label dif- (exocytosis). These basic functions are throughput; difficult data interpretation ferent trafficking pathways. supported by a highly active trafficking due to typical low labeling density of network, which constantly exchanges immuno-EM; parallel labeling of sev- In biological preparations, aldehyde cargo molecules and solutes between eral proteins limited by the use of dif- fixatives mainly crosslink with amine the plasma membrane and the diffe- ferent sizes of metallic particles. groups found in proteins, thereby stop- rent membranous compartments (for ping cellular processes and preserv- review see 1). The fusion and fission To solve this problem one would re- ing the subcellular structure. Several events required for such traffic are or- quire an endocytosis marker that, endocytosis markers have been modi- chestrated by a plethora of proteins, once internalized, could be chemi- fied with one amine group to render some of which preferentially residing cally fixed (e.g. with aldehyde fixa- them fixable. We evaluated the fix- in or returning back to a specific type of tives), in order to allow subsequent ability of amine-modified versions of compartment. This molecular behavior immunolabeling of typical organellar molecules from the FM family, a group and the identification of morphologi- markers or proteins of interest (Figure of styryl dyes widely used to monitor

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membrane uptake and recycling (12). first study focused on understanding in high rates of release (14, 15). Two We found that after fixation these mol- synaptic vesicle recycling in the audi- models of synaptic vesicle recycling in ecules were lost from the originally la- tory inner hair cells (IHCs), responsi- IHCs have been proposed: 1) vesicles beled membranes, reflected in fluores- ble for sound encoding in mammals. recycle at the base of the cell, in pro- cence intensity reduction and/or mo- In conventional chemical synapses, ximity to the synaptic ribbons (16–18). bilization of the dye molecules into like those in the central nervous sys- 2) Vesicles are endocytosed at the cell other compartments. After permeabi- tem or at the neuromuscular junctions, top, then fused with organelles residing lization, a detergent-based procedure neurotransmitter-filled synaptic vesi- at the cell upper level, like the Golgi that extracts lipids from membranes cles are exocytosed upon the arrival apparatus, and from there regenerated to allow antibody penetration during of an electrical stimulus and then in- and sent towards the cell base (19–21). immunostaining, the fixable FM dyes ternalized back via endocytosis (see were largely lost, indicating that one (13)). This process of vesicle recycling In order to test these models, we ap- amine group is not sufficient to keep is isolated into the presynaptic bouton, plied mCLING to IHCs at resting con- these molecules in place. In contrast, separated from other membrane traf- ditions (low K+) expecting to label only mCLING remained attached to the ficking processes required for normal constitutive traffic, and at stimulating plasma membrane and endocytosed cell function, referred here as constitu- conditions (high K+) to label both con- organelles after fixation and permea- tive trafficking (e.g. receptor internali- stitutive and synaptic traffic. STED ima- bilization, confirming its fixability and zation, nutrient uptake, or membrane ging on mCLING-labeled organelles suitability for immunostaining proce- traffic between the organelles involved showed that constitutive traffic is abun- dures (Figure 1C). in protein synthesis). However, IHCs dant in these cells, it occurs mainly at are polarized cells that do not have the cell top and nuclear levels, and it We then used mCLING to answer long- synaptic boutons, developing instead involves tubulocisternal structures as standing biological questions. Our vesicle release sites directly at the cell recycling intermediates. Conversely, soma, concentra- synaptic vesicle recycling takes place ted at the cell base. at the cell base. These results are in This implies that agreement with a previous morpholo- synaptic vesicle gical study we performed using elec- recycling shares tron microscopy (22). Combining the same cyto- mCLING and immunostaining against plasmic volume the synaptic ribbon we found that im- as the constitutive portant processes of membrane remo- pathways, ma- deling take place in the vicinity of this king it difficult to structure. Depending on the stimula- assign trafficking tion strength (i.e. K+ concentration) syn- routes to an endo- aptic vesicles will be directly retrieved cytosed organelle. from the plasma membrane, or rather Additionally, IHCs from membrane invaginations and cis- Fig. 1 A: Experimental workflow to reveal the molecular identity of present special- terns formed in response to abundant trafficking organelles. Living cells are incubated with the marker for ized active zones, vesicle release (bulk endocytosis). its uptake (red), then fixed and immunostained for organellar marker topped with a pro- proteins. Samples can then be imaged in conventional or high-resolution teinaceous struc- To confirm the previous results we microscopy. B. Molecular structure of mCLING compared with a smaller ture called synap- combined mCLING labeling with non-fixable membrane-binding probe. C. mCLING labeling after fixation tic ribbon, which immunostaining against synaptic is comparable to that in living cells. In contrast, conventional fixable tethers and con- vesicle markers (VGLUT3, Rab3) or membrane-binding dyes (AM 1-43 and FM 4-64FX) are largely lost from centrates synaptic proteins belonging to the constitu- membranes after fixation, ending up in mitochondria-like structures. vesicles, resulting tive trafficking pathways (GM130,

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Syntaxin 6, Syntaxin 16, Vti1a). The vesicular markers colocalized only with the organelles recycled at the cell base (Figure 2A). On the contrary, the constitutive markers colocalized mainly with the structures at the top and nuclear cell levels. Furthermore, the tubulocisternal structures strongly colocalized with Syntaxin 6 and 16, suggesting that these could be recy- cling endosomes (Figure 2B). From Fig. 2 A-B: Two-color STED imaging of mCLING-labeled endocytosed organelles (red), combined these results we concluded that IHCs with immunostaining against a synaptic vesicle marker (A. VGLUT3, green) or against a constitutive functionally and spatially separate endosomal marker (B. Syntaxin 16, green) at three different cellular levels. C. Model of membrane synaptic vesicle recycling from consti- trafficking in IHCs. Constitutive membrane trafficking and synaptic vesicle recycling are functionally tutive membrane trafficking pathways and spatially separated, the former taking place at the top and nuclear levels of the cell and the latter (Figure 2C). at the base of the cell. SR, synaptic ribbon.

We then addressed a highly debated dye used in these cells. We could not only suitable for studying mem- question: are there differences in mo- also label the membrane of Escheri- brane traffic in cultured cells and lecular composition between actively chia coli cells and image them at microorganisms, but also in com- and spontaneously released synaptic high-resolution microscopy finding plex tissues. Another application vesicles? (23–25). For this we incu- heterogeneous labeling patterns. of mCLING, not presented here, is bated cultured hippocampal neurons its application at low temperature with mCLING during electrical stimu- Conclusions and Perspectives leading to endocytosis inhibition. lation (active release) or inhibition Our study shows that mCLING is the The result is a surface labeling that with tetrodotoxin (spontaneous re- first fluorescent probe that allows can be used to distinguish the im- lease). Subsequently, these were im- morphological and molecular cha- munostained proteins sitting on the munostained for synaptic vesicle or racterization of subdiffraction-sized plasma membrane, from those loca- endosomal markers. Two-color STED endocytotic organelles. mCLING is ted inside the cell. imaging showed that spontaneously released vesicles have higher levels of endosomal proteins and lower levels Natalia REVELO NUNCIRA did her doc- of synaptic vesicle proteins. This indi- toral thesis in Silvio Rizzoli’s group, STED microscopy cates that the two groups of vesicles of synaptic function group, European Neuroscience are different in composition, with the Institute Göttingen (ENI-G). Her doctoral thesis and oral spontaneously released ones more re- defense were rated ‘summa cum laude’ by a team of lated to constitutive recycling. internal and external reviewers. She will be awarded the Otto-Creutzfeldt PhD Award in 2015. She defended Finally, we tested mCLING in other her PhD thesis in June 2014. preparations. We could label synap- tic vesicle recycling in the Drosophila Dept. Neuro- and Sensory Physiology neuromuscular junction. We imaged University Medical Center labeled, endocytosed organelles in Humboldtallee 23 live, fixed or immunostained yeast 37073 Göttingen cells (Saccharomyces cerevisiae), outperforming FM4-64, the standard

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The versatility of mCLING is further will also be complemented by the de- from camelids, ~13 kDa) and apta- broadened by the possibility of re- velopment of novel protein labeling mers (DNA or RNA oligonucleotides, placing the fluorophore according tools that are smaller and therefore ~15 kDa) (see for example 26). to the investigator’s needs or the re- more efficient than antibodies (~150 quirements of a particular microsco- kDa) at binding to epitope regions. py technique. The success of mCLING Examples are nanobodies (obtained

References 1. J. S. Bonifacino, B. S. Glick, The mechanisms of vesicle budding and fusion. Cell. 116, 153–66 (2004). 2. D. W. Fawcett, Surface Specializations of Absorbing Cells. J. Histochem. Cytochem. 13, 75–91 (1965). 3. J. E. Heuser, T. S. Reese, Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction. J. Cell Biol. 57, 315–44 (1973). 4. R. G. Anderson, M. S. Brown, J. L. Goldstein, Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts. Cell. 10, 351–64 (1977). 5. J. Marrack, Nature of Antibodies. Nature. 133, 292–93 (1934). 6. A. H. Coons, H. J. Creech, R. N. Jones, Immunological properties of an antibody containing a fluorescent group. Proc. Soc. Exp. Biol. Med. 47, 200–202 (1941). 7. W. Faulk, G. Taylor, An immunocolloidal method for the electron microscope. Immunochemistry. 8, 1081–1083 (1971). 8. M. G. Honig, R. I. Hume, Fluorescent carbocyanine dyes allow living neurons of identified origin to be studied in long-term cultures. J. Cell Biol. 103, 171–87 (1986). 9. J. H. Sandell, R. H. Masland, Photoconversion of some fluorescent markers to a diaminobenzidine product. J. Histochem. Cytochem. 36, 555–559 (1988). 10. M. Malatesta, C. Zancanaro, M. Costanzo, B. Cisterna, C. Pellicciari, Simultaneous ultrastructural analysis of fluorochrome-photoconverted diaminobenzidine and gold immunolabelling in cultured cells. Eur. J. Histochem. 57:e26, 168–171 (2013). 11. N. H. Revelo et al., A new probe for super-resolution imaging of membranes elucidates trafficking pathways. J. Cell Biol. 205, 591–606 (2014). 12. W. J. Betz, F. Mao, G. S. Bewick, Activity-dependent fluorescent staining and destaining of living vertebrate motor nerve terminals. J. Neurosci. 12, 363–75 (1992). 13. T. C. Südhof, The synaptic vesicle cycle. Annu. Rev. Neurosci. 27, 509–47 (2004). 14. G. Zanazzi, G. Matthews, The molecular architecture of ribbon presynaptic terminals. Mol. Neurobiol. 39, 130–48 (2009). 15. G. Matthews, P. Fuchs, The diverse roles of ribbon synapses in sensory neurotransmission. Nat. Rev. Neurosci. 11, 812–22 (2010). 16. J. H. Siegel, W. E. Brownell, Synaptic and Golgi membrane recycling in cochlear hair cells. J. Neurocytol. 15, 311–328 (1986). 17. J. Neef et al., Modes and regulation of endocytic membrane retrieval in mouse auditory hair cells. J. Neurosci. 34, 705–16 (2014). 18. D. Lenzi, J. Crum, M. H. Ellisman, W. M. Roberts, Depolarization Redistributes Synaptic Membrane and Creates a Gradient of Vesicles on the Synaptic Body at a Ribbon Synapse. Neuron. 36, 649–659 (2002). 19. J. Meyer, a F. Mack, a W. Gummer, Pronounced infracuticular endocytosis in mammalian outer hair cells. Hear. Res. 161, 10–22 (2001). 20. C. B. Griesinger, C. D. Richards, J. F. Ashmore, FM1-43 reveals membrane recycling in adult inner hair cells of the mammalian cochlea. J. Neurosci. 22, 3939–52 (2002). 21. C. B. Griesinger, C. D. Richards, J. F. Ashmore, Fast vesicle replenishment allows indefatigable signalling at the first auditory synapse. Nature. 435, 212–5 (2005). 22. D. Kamin, N. H. Revelo, S. O. Rizzoli, FM Dye Photo-Oxidation as a Tool for Monitoring Membrane Recycling in Inner Hair Cells. PLoS One. 9, e88353 (2014). 23. T. W. Groemer, J. Klingauf, Synaptic vesicles recycling spontaneously and during activity belong to the same vesicle pool. Nat. Neurosci. 10, 145–7 (2007). 24. B. G. Wilhelm, T. W. Groemer, S. O. Rizzoli, The same synaptic vesicles drive active and spontaneous release. Nat. Neurosci. 13, 1454–6 (2010). 25. Y. Sara, T. Virmani, F. Deák, X. Liu, E. T. Kavalali, An isolated pool of vesicles recycles at rest and drives spontaneous neurotransmission. Neuron. 45, 563–73 (2005). 26. F. Opazo et al., Aptamers as potential tools for super-resolution microscopy. Nat. Methods. 9, 938–9 (2012).

10 NEUROSCIENCE Science Spotlight2015 Understanding progenitor fate switch... in the developing neocortex by Srinivas Parthasarathy

The mammalian neocortex is compo- neurons to occupy their final position to the types of cells they can produce. sed of six layers of neurons, which are in the cortex, thus giving rise to the ‘in- Individual cortical progenitors cul- responsible for our highest cognitive side first-outside last’ cortex (Angevine tured in vitro can faithfully recapitulate abilities. This extremely heteroge- and Sidman, 1961; Rakic, 1974). The the entire sequence of corticogenesis neous population of neurons is born various layers of the cortex show a (Shen et al., 2006). This suggests that sequentially from a small pool of re- high degree of heterogeneity with successive fate restriction is hardwired latively homogenous progenitor cells. respect to their functions. This cor- into a progenitor cell. Transplantation Cortical neurons are produced in an relates to the fact that these neurons experiments showed that when young- inside first-outside last manner, where- also show great variation with respect er cortical progenitors are transplanted by deeper layer neurons are generated to their molecular and morphological into an older brain, they adapt to pro- before upper layer neurons. After their characteristics (Fishell and Hanashima, ducing neurons appropriate to their birth in the ventricular zone these neurons migrate and occupy their fi- nal position in the developing corti- cal plate. Understanding how cortical progenitors sequentially undergo fate restriction to produce these diverse classes of pyramidal neurons has al- ways attracted great interest. Here, I summarize our latest findings which highlight how previously generated populations of neurons signal back to the progenitors instructing them to change their cell fate, thereby forming a cortical feedback loop. We then in- vestigated how cortical progenitors respond to these feedback cues, there- by finally leading to a fate switch. Fig. 1: Model depicting the two possible modes of Ntf3 mediated signaling. Receptors located along the radial glial process or on the cell body could sense Ntf3 released by postmitotic neurons. Introduction Such a signaling initiates the generation of basal progenitors, which in turn could lead to the Within the neocortex hundreds of dif- expansion of UL neurons ferent cell subtypes are arranged into specific neuronal networks that are 2008). However, such diverse groups new environment (Desai and McCon- engaged in receiving, processing and of neurons are born from a relatively nell, 2000). This would suggest that responding to complex stimuli. The homogenous progenitor population. environmental cues also dictate the neocortex consists of two major neu- Thus, how progenitors undergo suc- ability of a progenitor to produce one ronal subtypes- excitatory projection cessive fate restriction to generate the neuronal subtype over another. How- neurons and inhibitory interneurons. entire repertoire of cortical neurons, ever, consistent with the progressive While interneurons are born in the has invited detailed study and research fate restriction theory, older progeni- ganglionic eminence, cortical projec- over the last two decades. tors when transplanted into an younger tion neurons arise from progenitors environment, do not adapt and con- lining the dorsal aspects of the lateral Similar to all progenitor populations, tinue to produce late born upper layer ventricles. These progenitors give rise cortical progenitors too loose their neuron (Desai and McConnell, 2000). to the different cortical layers sequen- multi-potency over time. As develop- Thus, collectively it is well established tially. During this process, later born ment progresses, cortical progenitors that while cortical progenitors undergo neurons must migrate past earlier born become more restricted with respect self-programmed fate restriction, en-

NEUROSCIENCE 11 Science2015 Spotlight

vironmental cues influence this pro- comitant premature start of upper layer Using a variety of gain and loss-of- cess to a large extent. Work from our neurogenesis. Subsequently, neuro- function experiments we demonstrated lab suggested that cortical postmitotic genesis ended prematurely giving way that Ntf3 indeed functions as a cortical neurons signal back to the progenitors to gliogenesis (Seuntjens et al., 2009). feedback signal (Figure1, Parthasarathy thereby forming a negative feedback The deletion of a postmitotic specific et al., 2014). Over-expression of Ntf3 loop (Seuntjens et al., 2009). We pro- transcription factor leading to changes specifically in cortical postmitotic neu- posed that neurons within each corti- in progenitor fate switch lead us to rons, led to a premature shift from deep cal layer signal back to the progenitors, hypothesize about a possible cortical layer to upper layer neurogenesis, repli- instructing them to change their fate feedback mechanism. cating the Sip1 phenotype. We further and start producing the next layer of showed that Sip1 directly controls Ntf3 neurons. This would ensure that neu- To identify molecules that were possibly expression by binding to the Ntf3 en- rons of a particular kind are not over- involved in this signaling between post- hancer region (Seuntjens et al., 2009; mitotic neurons Parthasarathy et al., 2014). and progenitors, we performed While from these studies we gained a microarray ana- better understanding of how postmi- lysis to compare totic neurons influence the fate of corti- gene expression cal progenitors, we had little idea about profiles between how progenitors sense these feedback wildtype and signals and respond to them. We star- Sip1 mutant cor- ted by studying the localization of the tices. We then known Ntf3 receptor- TrkC, using in situ narrowed our hybridization. Much to our surprise, we search to genes did not find any expression of the re- Fig. 2: Effect of miR-34c on its targets under physiological conditions and encoding for se- ceptor in cortical progenitors. This led upon insults with increased expression of miR-34c leading to inhibition of creted proteins, us to study the expression of the alter- target expression. as these would nate splice variants of TrkC, which lack be the most suit- the intracellular autocatalytic kinase produced, thereby laying the founda- able for carrying out a feedback function. domain. These Non-catalytic isoforms tion for the generation of the different (NC-TrkC) also have a distinct 3’ UTR, layers at the right time and in the right Amongst many candidates, we studied suggesting differential post-transcrip- amount. the role of the neurotrophin- Ntf3, and tional control. Using riboprobes spe- its roles as a Sip1 downstream effector cifically targeting the truncated isoform, First insights into the mechanism un- molecule that contributes to feedback we observed that NC-TrkC was indeed derlying cortical feedback signaling signaling (Seuntjens et al., 2009; Par- expressed in the ventricular zone of the came from the analysis of a knock- thasarathy et al., 2014). Neurotrophins developing cortex. However, the most out mouse of the transcription factor are a class of small-secreted molecules interesting feature about the expression Sip1 (Seuntjens et al., 2009). Sip1 is that have profound influence on a large pattern of NC-TrkC was that it mirrored expressed exclusively in postmitotic variety of neuronal functions. Each of the generation of deep layer neurons. neurons of the cortex. Deleting Sip1 the family members binds to a specific NC-TrkC expression was highest within within cortical neurons had a profound Tropomyocin related kinase (Trk) re- cortical progenitors when they were effect on the timing of neurogenesis. In ceptor with maximum affinity and with producing deep layer neurons and de- the Sip1 mutant, the entire process of one or more of the other receptors to creased sharply as they started produc- neurogenesis was temporally shifted a lesser account. (Cordon-Cardo et al., ing upper layer neurons. such that the production of deep layer 1991; Klein et al., 1991; Lamballe et neurons stopped earlier with a con- al., 1991). This drove us to study the role of NC-

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TrkC in fate determination of cortical prevents it from being trafficked to the NC-TrkC to that which is present within neuron identity. We used gain and loss- plasma membrane, thereby retaining the secretory pathway. This novel and of-function experiments in vivo to study it within the secretory pathway, mostly non-classical interaction between two its role. These experiments showed that within the Golgi apparatus (Figure 2). membrane proteins away from the NC-TrkC over-expressing progenitors While we have still not answered how plasma membrane opens up exciting favored the production of deep layer Ntf3 affects this interaction, we specu- new insights into signaling within corti- neurons, while those in which NC-TrkC late that it disrupts the interaction by cal radial glial progenitors that controls was down regulated were inclined to- changing the ratio of plasma membrane neuronal fate determination. wards producing upper layer neurons.

However, we still did not understand Srinivas PARTHASARATHY did his doctoral how NC-TrkC signals within cortical thesis in Victor Tarabykin’s group, Max Planck Institute progenitors, since it lacks a kinase do- for Experimental Medicine Göttingen. During his docto- main. In a completely serendipitous ral thesis he moved to the Institute of Cell Biology and experiment, we observed that NC-TrkC Neurobiology, University Medicine Charité Berlin. His physically interacts with the BMP class doctoral thesis and oral defense were rated ‘summa I receptor- BmprIA. We showed that cum laude’ by a team of internal and external review- the interaction between these receptors ers. He defended his PhD thesis in June 2014. is important and necessary for cortical fate determination. We further went on Charité-Universitätsmedizin Berlin to show that these receptors interact Anatomy, Inst itute of Cell Biology and Neurobiology intracellularly and not on the plasma Charitéplatz 1 Charité CrossOver membrane. We have identified that the 10117 Berlin interaction of BmprIA with NC-TrkC

References 1. Angevine, J. B., Jr. and Sidman, R. L. (1961) ‘Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse’, Nature 192: 766-8. 2. Cordon-Cardo, C., Tapley, P., Jing, S. Q., Nanduri, V., O’Rourke, E., Lamballe, F., Kovary, K., Klein, R., Jones, K. R., Reichardt, L. F. et al. (1991) ‘The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3’, Cell 66(1): 173-83. 3. Desai, A. R. and McConnell, S. K. (2000) ‘Progressive restriction in fate potential by neural progenitors during cerebral cortical development’, Development 127(13): 2863-72. 4. Fishell, G. and Hanashima, C. (2008) ‘Pyramidal neurons grow up and change their mind’, Neuron 57(3): 333-8. 5. Klein, R., Nanduri, V., Jing, S. A., Lamballe, F., Tapley, P., Bryant, S., Cordon-Cardo, C., Jones, K. R., Reichardt, L. F. and Barbacid, M. (1991) ‘The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3’, Cell 66(2): 395-403. 6. Lamballe, F., Klein, R. and Barbacid, M. (1991) ‘trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3’, Cell 66(5): 967-79. 7. Parthasarathy, S., Srivatsa, S., Nityanandam, A. and Tarabykin, V. (2014) ‘Ntf3 acts downstream of Sip1 in cortical postmitotic neurons to control progenitor cell fate through feedback signaling’, Development 141(17): 3324-30. 8. Rakic, P. (1974) ‘Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition’, Science 183(4123): 425-7. 9. Seuntjens, E., Nityanandam, A., Miquelajauregui, A., Debruyn, J., Stryjewska, A., Goebbels, S., Nave, K. A., Huylebroeck, D. and Tarabykin, V. (2009) ‘Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors’, Nat Neurosci 12(11): 1373-80. 10. Shen, Q., Wang, Y., Dimos, J. T., Fasano, C. A., Phoenix, T. N., Lemischka, I. R., Ivanova, N. B., Stifani, S., Morrisey, E. E. and Temple, S. (2006) ‘The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells’, Nat Neurosci 9(6): 743-51.

NEUROSCIENCE 13 Science2015 Spotlight A SIP of Ninein... for the formation of neocortical projections by Swathi Srivatsa

Neuronal connections in the neocor- paramount importance for the regu- derstanding brain function (Innocenti tex that relay and integrate informa- lar functioning of the brain (Innocenti & Price, 2005). tion form the basis of our higher cog- & Price, 2005). nitive abilities. Transcription factors In this research report I would like play an important role in controlling It is extremely interesting to note to focus on some of the work that I the trajectory of neuronal projec- that the axons of necortical neurons conducted during my PhD to better tions. Sip1 is an important transcrip- follow extremely organized and ste- understand the molecular programs tion factor that regulates many diffe- reotypical pathways to reach their involved in the formation of these rent aspects of CNS development. In target. Due to this, axons of neurons stereotypical neocortical connec- this study, using a series of in vitro projecting towards a similar target tions. I have focused on a transcrip- and in vivo experiments performed in fasciculate together to give rise to tion factor called Sip1 (Smad inter- mice, we have shown that, Sip1 plays thick axonal bundles or white mat- acting protein 1) and have studied its an important role in the development ter tracts. Within the mammalian role in the formation of neocortical of neocortical projections. First, the brain there are two types of tracts axonal pathways within the mouse alteration in cortical axonal tracts origina-ting from the neocortex, the brain. Sip1 exhibits a very interesting was examined in case of the Sip1 commissural projections and the cor- pattern of expression within the brain mouse mutant followed by a detailed ticofugal connections. The commis- being expressed selectively in the analysis of the cell autonomous re- sural connections connect the two postmitotic neurons of the neocortex quirement of Sip1 within pyramidal hemispheres of the brain. These in- (Miquelajauregui et al., 2007; Se- neurons. Next, the effector molecule clude the corpus callosum (CC) that untjens et al., 2009). Examining the downstream of Sip1 was identified connects the two neocortical hemi- Sip1 mutant mouse brains through and its mechanism of action was also spheres and the anterior commissure histological techniques and tract trac- uncovered. (AC) that connects the two piriform ing using dye injections revealed that cortices (Aboitiz & Montiel, 2003; multiple axonal tracts were disrupted Our brain acts as the central proces- Fame, MacDonald, & Macklis, 2011; in the absence of Sip1. While com- sing unit of our entire being, helping Robin, 2006; Schüz & Preißl, 1996). missural connections such as the CC in orchestrating, controlling and co- The corticofugal projections on the and AC were absent in the Sip1 mu- ordinating a myriad of complex tasks other hand, are formed by axons that tant, cortico fugal connections such with seeming ease. Where different leave the neocortex and project to as the projections forming the CST regions in the brain are specialized various sub-cortical structures. These were also not formed. Interestingly, to perform different roles, the neo- include the corticothalamic tract (CT) similar to the phenotype in mice, cortex, which is the biggest and the and the corticospinal tract (CST) (Ar- haploinsufficiency of the human SIP1 most recently evolved structure in onoff et al., 2010; Fame et al., 2011; gene has been found to cause a neu- the brain, is responsible for all our Kennedy & Dehay, 1993; Molnár et rological disorder called the Mowat- higher cognitive functions, which al., 2007). Apart from these projec- Wilson syndrome (MWS) which apart include sensing our environment, tions that arise from within the neo- from being associated with severe generating motor output, language, cortex, the thalamocortical axons mental retardation, motor deficits, thinking, creativity, problem solving (TC) project from the thalamus into epilepsy and craniofacial abnormali- and imagination (Geschwind & Ra- the neocortex and the hippocampal ties is frequently accompanied by the kic, 2013). This is made possible by commissure (HC) interconnect the agenesis of the CC, thus further link- the billions of neocortical neurons two hippocampi. Since all of these ing the function and importance of and their connections to different cortical projections act as conduits Sip1 in the correct establishment of regions within the neocortex as well for the passage of information to and neocortical projections (D R Mowat, as with other parts of the central ner- from the cerebral cortex, understan- M J Wilson, 2003; Garavelli & Main- vous system. Thus the correct forma- ding how these connections are es- ardi, 2007; Moal et al., 2007; Wilson tion of these neuronal circuits is of tablished forms an integral part of un- et al., 2003).

14 NEUROSCIENCE Science Spotlight2015

As a first step in understanding the jections we used a technique called tion to establish a system where Sip1 cell autonomous contribution of Sip1 in utero electroporation together with could be deleted in a mosaic manner. in the formation of neocortical pro- Cre and lox p mediated gene dele- This meant that we could study the behavior of the axons of these Sip1 negative neurons within a native, un- altered wild type brain. We observed that in the absence of Sip1, rate of axonal extension was severely retar- ded. While by embryonic day E18.5 (a day before birth of the pups) wild type axons have already crossed the midline forming the CC, Sip1 defi- cient neurons are unable to extend their axons through the callosal white matter tract (Fig 1A, C). Additionally, Sip1 negative axons also show a delay in the formation of ipsilateral axonal branches. While wild type pyramidal neurons that occupy the upper lay- ers of the neocortex extend axonal branches to connect with deeper layer neurons, commencing four days after birth (P4), the Sip1 deficient upper layer neurons are unable to form such branches even 7 days after birth (P7) (Fig 1B, D).

In order to characterize the underly- ing mechanism involved in Sip1 medi- ated axonal extension and branching we performed microarray screening to identify probable target molecules that might be acting downstream of Sip1 in mediating these above men- tioned effects. We zeroed in on a mo- lecule called ninein because it was ex- pressed in the developing neo-cortex, it showed a four-fold down regulation in the Sip1 mutant and the protein has been previously shown to be associ- ated with microtubules, which being Fig. 1 (A): In the mouse brain, wild type callosal axons are able to cross the midline by E18.5 while the building blocks of the cytoske- Sip1 deficient axons are unable to do so. Reintroduction of ninein expression in these Sip1 deficient leton are directly linked to axonal neurons restores CC formation. (B) Interstitial branches by upper layer neurons on deeper layer growth and branching. To validate if neurons are abolished on deletion of Sip1. The branching is also restored on ninein re-expression. ninein is indeed acting downstream (C, D) Quantification of the CC and interstitial branching indicating the extent of rescue. of Sip1 and is a direct target, we per-

NEUROSCIENCE 15 Science2015 Spotlight

formed chromatin immunoprecipita- We then introduce the expression of acting downstream of Sip1 to control tion assay and luciferase assays which ninein in the Sip1 negative neocor- axonal growth rate or branching, then went to show that Sip1 binds directly tical neurons and followed the rate re-expressing it in theses Sip1 deficient to the enhancer region of the ninein of extension and branching of their neurons would rescue the effect and gene and acts as a transcriptional ac- axons. The rationale behind this ex- restore wild type conditions. In fact, tivator. periment was that if ninein is indeed the experiment showed that these Sip1 deficient neurons with ninein expres- sion were capable of crossing the mid- line by E18.5 forming the CC as well as forming interstitial branches (Fig1).

We have, there after tried and uncov- ered the mechanism with which the molecule ninein might be exerting its influence over axon extension. We observed that when neuronal microtubules are challenged with a microtubule depolymerizing agent, in the presence of ninein they are much more resistant to breakdown. Additionally in the absence of Sip1 and hence ninein, the rate of growth of microtubules is diminished, which can be brought back to normal levels on reintroducing ninein. These ex- Fig. 2 (A): Transcriptional factor Sip1 is expressed in all postmitotic neocortical neurons and activates periments indicate that ninein is an the expression of downstream molecule ninein. (B) Ninein binds axonal and dendritic microtubules important protein that helps stabilize (C) Within the cytoskeleton ninein confers microtubule stability and controls microtubule dynamics microtubules and maintain a set rate thus influencing axonal growth rate and branching. of microtubule growth, which aid in axonal extension and branch forma- tion. Swathi SRIVATSA did her doctoral thesis in Vic- tor Tarabykin’s group, Max Planck Institute for Experi- In conclusion this work illuminates mental Medicine Göttingen. During her doctoral thesis how molecular programs are intri- she moved to the Institute of Cell Biology and Neurobi- cately fine-tuned in the brain to con- ology, University Medicine Charité Berlin. Her doctoral trol specific aspects of circuit forma- thesis and oral defense were rated ‘summa cum laude’ tion and hence in the larger picture, by a team of internal and external reviewers. She de- CNS function. It helps to directly link fended her PhD thesis in June 2014. transcriptional activity of Sip1 to sub cellular movements and modifica- Charité-Universitätsmedizin Berlin tions (Fig2). It could further help in Anatomy, Inst itute of Cell Biology and Neurobiology understanding the molecular under- Charitéplatz 1 Charité CrossOver pinnings of the MWS, the human dis- 10117 Berlin order associated with SIP1. This work has been published in the journal Neuron - 2015.

16 NEUROSCIENCE Science Spotlight2015

References 1. Aboitiz, F., & Montiel, J. (2003). One hundred million years of interhemispheric communication: the history of the corpus callosum. Brazilian Journal of Medical and Biological Research = Revista Brasileira de Pesquisas Médicas E Biológicas / Sociedade Brasileira de Biofísica ... [et Al.], 36(4), 409–20. 2. Aronoff, R., Matyas, F., Mateo, C., Ciron, C., Schneider, B., & Petersen, C. C. H. (2010). Long-range connectivity of mouse primary somatosensory barrel cortex. The European Journal of Neuroscience, 31(12), 2221–33. doi:10.1111/j.1460-9568.2010.07264.x 3. D R Mowat, M J Wilson, M. G. (2003). Mowat-Wilson syndrome, (Table 1), 305–311. 4. Fame, R. M., MacDonald, J. L., & Macklis, J. D. (2011). Development, specification, and diversity of callosal projection neurons. Trends in Neurosciences, 34(1), 41–50. doi:10.1016/j.tins.2010.10.002 5. Garavelli, L., & Mainardi, P. C. (2007). Mowat-Wilson syndrome. Orphanet Journal of Rare Diseases, 2, 42. doi:10.1186/1750-1172-2-42 6. Geschwind, D. H., & Rakic, P. (2013). Perspective Cortical Evolution : Judge the Brain by Its Cover. Neuron, 633–647. 7. Innocenti, G. M., & Price, D. J. (2005). Exuberance in the development of cortical networks. Nature Reviews. Neuroscience, 6(12), 955–65. doi:10.1038/nrn1790 8. Kennedy, H., & Dehay, C. (1993). Cortical specification of mice and men. Cerebral Cortex (New York, N.Y. : 1991), 3(3), 171–86. 9. Miquelajauregui, A., Van de Putte, T., Polyakov, A., Nityanandam, A., Boppana, S., Seuntjens, E., … Tarabykin, V. (2007). Smad-interacting protein-1 (Zfhx1b) acts upstream of Wnt signaling in the mouse hippocampus and controls its formation. Proceedings of the …, 104(31), 12919–12924. 10. Moal, F. D., Wilson, M., Mowat, D., Collot, N., Niel, F., & Ã, M. G. (2007). ZFHX1B Mutations in Patients With Mowat- Wilson Syndrome, 28(4), 313–321. doi:10.1002/humu 11. Molnár, Z., Hoerder-Suabedissen, A., Wang, W. Z., DeProto, J., Davies, K., Lee, S., … Cheung, A. F. P. (2007). Genes involved in the formation of the earliest cortical circuits. Novartis Foundation Symposium, 288, 212–24; discussion 224–9, 276–81. 12. Robin, M. (2006). The Corpus Callosum as an Evolutionary Innovation. JOURNAL OF EXPERIMENTAL ZOOLOGY, 17(August 2005), 8–17. doi:10.1002/jez.b 13. Schüz, A., & Preiβl, H. (1996). Basic Connectivity of the Cerebral Cortex and some Considerations on the Corpus Callosum. Neuroscience & Biobehavioral Reviews, 20(4), 567–570. doi:10.1016/0149-7634(95)00069-0 14. Seuntjens, E., Nityanandam, A., Miquelajauregui, A., Debruyn, J., Stryjewska, A., Goebbels, S., … Tarabykin, V. (2009). Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors. Nature Neuroscience, 12(11), 1373–80. doi:10.1038/nn.2409 15. Wilson, M., Mowat, D., Dastot-Le Moal, F., Cacheux, V., Kääriäinen, H., Cass, D., … Goossens, M. (2003). Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B. American Journal of Medical Genetics. Part A, 119A(3), 257–65. doi:10.1002/ajmg.a.20053 16. Srivatsa, S., Parthasarathy, S., Molnár, Z., Tarabykin, V. (2015) Sip1 Downstream Effector ninein Controls Neocortical Axonal Growth, Ipsilateral Branching, and Microtubule Growth and Stability. Neuron. 85(5), 998-1012. doi: 10.1016/j.neuron.2015.01.018.

NEUROSCIENCE 17 StudentsCurrent Master’s class 2014/15

Reham Abdelaziz Egypt, BSc from Yi An Liao Taiwan, MD from National Lenka Vaculčiaková Slovakia, BSc German University in Cairo, Egypt Yang-Ming University, Taiwan from Charles University in Prague, Czech Republic Martina Arends Germany, BSc from Noam Nitzan Israel, BSc from Hum- Carl Ossietzky University Oldenburg, boldt University Berlin, Germany Dennis Vollweiter Germany, BSc from Germany Georg August University Göttingen, Myrto Panopoulou Greece, BSc from Germany Mar Bosch Queralt Spain, BSc from National and Kapodistrian University Autonomous University of Barcelona, of Athens, Greece Kanishka Waghmare India, BTech Spain from the Indian Institute of Technology M Sadman Sakib Bangladesh, BSc Madras, India Lucas Caldi Gomes Brazil, BSc from from University of Dhaka, Bangladesh State University of Maringá, Brazil Rebecca Wallrafen Germany, BSc from Erik Schäffner Germany, BSc from Radboud University Nijmegen, The Leonard Frederik Engels Germany, BSc University of Würzburg, Germany Netherlands from University of Cologne, Germany Sinem Meleknur Sertel Turkey, BSc Lukas Weiss Italy, BSc from University Madhura Ketkar India, BTech from from Bilkent University, Turkey of Cologne, Germany the National Institute of Technology Warangal, India Jiyun Shin Republic of Korea, BSc from Rashad Yusifov Azerbaijan, BSc from Seoul National University, South Korea McGill University Montreal, Canada Albert Lehr Germany, BSc from Rhei- nische Friedrich-Wilhelms-Universität Bonn, Germany

Applications 2014/15

In the year 2014, the Neuroscience program received 324 applications from 57 countries.

Germany 41 other Western Europe 36 Eastern Europe 19 North America 10 In the year 2015, the Neuroscience North America 17 Central/South America 13 program received 363 applications Central/South America 19 North Africa 19 from 59 countries. North Africa 28 Central/South Africa 24 Central/South Africa 42 Asia / Near East 53 Germany 35 Asia / Near East 55 Central Asia / Far East 107 other Western Europe 33 Central Asia / Far East 100 Australia 2 Eastern Europe 32 Australia 2

18 NEUROSCIENCE StudentsNew PhD projects started in 2014

Tamer Abdelaal Diego Giraldo Sánchez Sharlen Moore Corona The role of glial cell dif- Linking senses: rhodop- Role of oligodendrocytes ferentiation phenotypes in sin’s role in mechanore- in supporting demyelinating diseases of ception axonal metabolic the PNS and CNS Martin Göpfert, demands during cognitive Michael Sereda, André Fiala, processes Klaus-Armin Nave, Manuela Schmidt Klaus-Armin Nave, Wolfgang Brück Mikael Simons, Swen Hülsmann

Erika Avendaño Guzmán Sindhuja Gowrisankaran Pratibha Narayanan Evaluating the function The significance of rab- Characterization of pro- of cytotoxic leukocytes in connectin3 - endophilinA tein complexes involved CNS autoimmunity interaction for synaptic in mechanosensation in Wolfgang Brück, vesicle recycling vertebrates Klaus-Armin Nave, Ira Milosevic, Manuela Schmidt, Alexander Flügel Reinhard Jahn, Luis Pardo, Nils Brose Martin Göpfert

Chi Chen Florentin Masurat Neural Correlates of Ca- Control of sleep through tegorization Behavior in sleep-active neurons Auditory System Henrik Bringmann, Robert Gütig, Ralf Heinrich, Tim Gollisch, Nils Brose Alexander Gail

NEUROSCIENCE 19 StudentsGraduated The Doctors of 2014

Dorota Badowska Srinivas Parthasarathy Nicolas Snaidero Schizophrenia Risk Factor Molecular Control of Mechanisms underlying Tcf4 and Gene x Environ- Pyramidal Neuron Fate the CNS myelination: A ment Interaction in Mice Determination in the molecular and morpho- Moritz Rossner, Developing Neocortex logical analysis of the Hannelore Ehrenreich, Victor Tarabykin, wrapping process André Fischer Judith Stegmüller, Mikael Simons, Till Marquardt Uwe-Karsten Hanisch, Holger Stark

Wan Ilma Dewiputri Pooja Rao Swathi Srivatsa An Exploration of Real- Coding and Non-Coding Transcriptional control time Functional Magnetic RNA in Age-Associated of the establishment of Resonance Imaging Neu- Memory Impairment and neocortical projections in rofeedback in Cognition Alzheimer’s Disease the mammalian telen- Jens Frahm, André Fischer, cephalon Stefan Treue, Wolfgang Fischle, Victor Tarabykin, Michael Waldmann Judith Stegmüller Judith Stegmüller, André Fischer

Hung-En Hsia Natalia Revelo Nuncira Diana Urrego-Blanco Roles of HECT-Tpye A novel membrane- Dynamics of Kv10.1 Ubiquitin E3 Ligases of binding probe for the expression through the the Nedd4 and WWP morphological and mo- cell cycle of cancer and Subfamilies in Neuronal lecular characterization of non-cancer cells Development synaptic vesicle recycling Luis Pardo, Nils Brose, pathways Tobias Moser, Judith Stegmüller, Silvio Rizzoli, Detlev Schild Andreas Wodarz Mikael Simons, Tobias Moser

20 NEUROSCIENCE AlumniRegional Fitting into new shoe in the Netherlands by Aaron Wong

When I went to Germany seven years retina, and people are still studying Switching to a small group means I ago, I did not have the slightest clue how it works. need to be more proactive in seeking where I would end up next. Two ye- out help. It is not uncommon to find ars ago when I defended my thesis, I Being in a new environment is not long-forgotten equipment which no- was still wondering whether I would easy, especially as a postdoc. Getting body knows how to use. It also me- still continue with science or not. my own funding via fellowship was ans I have to handle slightly more on What I did know, after staying several exciting, while the experience and the administrative and bureaucra- years in the dry Göttingen, is that I results from my PhD certainly helped tic side. That is something that I am was hoping to be closer to water in the next position. That part did come true, as I am now at the largest port in Europe.

Surely, Rotterdam is a much bigger city than the little town of Göttin- gen. Not that you will bump into a colleague every Saturday at the city center, and who needs to be out on Saturday anyway? I have finally got rid of the “stock-up-for-Sunday-or- you-will-starve” curse. What is more, everybody speaks English! What a re- lief after failed attempts in trying to get by with German with an accent.

Science goes on, and the tree of wis- dom grows on. (Yes, mine has not jumped out of the window yet, which allegedly happened to some others.) After learning about the develop- ment of cochlear hair cells, I deci- a lot, not to mention the help from slowly learning. On the upside, I am ded to leave the auditory periphery successful predecessors from the always excited to learn new things and venture deeper into the auditory program. Before starting out, I often that I do not know, and also amazed midbrain. Now at the Erasmus MC, heard that becoming a postdoc im- at how things I learnt from my PhD I try to decipher how and which be- plies the magical switch of expecta- helped me in unexpected ways. The haviorally relevant parameters are tion in which you are now supposed ample opportunities for supervising extracted by the inferior colliculus. to know everything. Interestingly, I lab rotation and master students in I still remember how one professor found myself trapped into an even Göttingen definitely helped me build in Göttingen questioned “what is stranger dichotomy between that and confidence in taking up my own stu- the point of studying brainstem nu- the label of a “fresh student”. As I was dents now. Know-how in things such clei in the auditory system? They are pampered and instructed in histolo- as image analyses, programming and like the retina, just scattered within gy by experienced technician, a PI micro-dissection do come in handy the brainstem.” I couldn’t answer at in the department asked, “You are a for in vivo imaging. I must also thank the time, but I think it is precisely the postdoc, right? Why are you taking a my oral examiners in the IMPRS ma- reason it allures me. Decades of re- course?” I guess that captures the my- ster program for brutally slaughtering search on the much more accessible sterious sandwich status of a postdoc. me, and thus motivated me in lear-

NEUROSCIENCE 21 AlumniRegional

ning all the basic principles behind techniques I am using. Aaron WONG did his doctoral thesis on calcium signaling during exocytosis in hair cells in Tobias Mo- Continuing my scientific journey ser’s group, Dept. of Otorhynolaryngology, University in the new, hopefully not wooden, Medical Center Göttingen. He was awarded a doctoral schoen has so far been challenging scholarship by the Croucher Foundation in Hong Kong yet exciting. Let us see where it will and a Georg-Christoph-Lichtenberg Scholarship in bring me next. 2010. He defended his PhD thesis in May 2013. He was awarded a Marie Sklodowska-Curie individual Fellowship in 2015 to pursue his studies as a postdoc- toral fellow in Rotterdam.

Department of Neuroscience (Prof. J. Gerard G. Borst) Synaptic transmission in the auditory brainstem and midbrain Erasmus MC Wytemaweg 80, NL-3015 CN Rotterdam P.O.Box 2040, NL-3000 CA Rotterdam

My pathway to independence: from being mentored as a student in Göttingen to mentoring students in New York by Jayeeta Basu

I have recently started my own labo- I grew up in Calcutta, India and went search School, Göttingen booth. This ratory and independent research pro- to Presidency College, one of the is what got me started on the path of gram at the Neuroscience Institute at country’s oldest institutions of western becoming a neuroscientist. I applied to New York University School of Medi- education, to earn my bachelor’s de- the Neuroscience MSc/PhD program cine. The journey to get here has been gree in Physiology (B.Sc. Hon.’s). A in Göttingen and was invited to sit for truly exhilarating. And it all began whole year of our BSc curriculum was the admission test in New Delhi. The when I set foot in a small but grand dedicated to neurophysiology and bio- date of the test fell during my college and historic university town nestled physics and this is where I developed BSc written final exams and the IMPRS in the heart of Germany, twelve years my fascination for neuroscience, speci- program was surprisingly accommo- ago on a rainy mid-September after- fically synaptic physiology. While I was dating to send the test to the Goethe noon. Göttingen, the city of Gänselie- away on a college field trip in central Institute in Calcutta, so I could take sel, boasting of the largest number of India, where we were studying the an- the test in their library, without hinde- Nobel laureates amongst all European thropometric and cardiovascular phy- ring my exam schedule. Things moved cities and home to the 281 year old siology of coal miners and a native tri- fast after that, with the call for an in Georg August University, several Max bal hill population, the German DAAD person interview to Göttingen in May Planck Institutes and last but not the education fair was held in Calcutta. 2002. My first trip abroad fell right in least Cron & Lanz confectionary was My mother offered to go and sample the middle of the university practical also my home for two of my most for- the offerings of this fair and chanced final exams. This time, our Physiology mative years as a neuroscientist. upon the International Max Planck Re- head of the department, Dr. Chandan

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Mitra came to my rescue. He appealed my rotations. We had the benefit to Mathematicians and heavily to the University of Calcutta and shif- choose from a wide array of top-notch populated the department and it was a ted our college’s entire practical block labs that employed path-breaking ap- unique experience catching a glimpse to two weeks later so I could go to Ger- proaches in Neuroscience. My first of their world. many and interview for the program. I rotation was at the European Neuros- do remember distinctly the interviews cience Institute with Dr. Fred Wouters. Learning patch clamp electrophysio- at the Deutsche Primatum Zentrum We were exploring how phosphoryla- logy during my third lab rotation with (DPZ) in Nord Kampus and the neuro- tion of the Alzheimer’s protein Tau im- Dr. Rosenmund at the Max Planck In- physiology department in Humboldtal- pacts tangle formation using molecu- stitute for Biophysical Chemistry was lee with Profs. Fuchs, Richter, Schild, lar biology and fluorescence recovery a technological revelation for me. The Missler and Moser, being housed in after photobleaching (FRAP) imaging. department of Membrane Biophysics the Studentenwerk youth hostel, my It was fun working in Fred’s group and headed by Prof. Erwin Neher was the first meal at a German Mensa – one of getting to know the other graduate stu- birth-place of this technique and it is many hundreds in the future. And of dents, post-docs and group leaders in with utmost pride that I can claim that course the sheer joy of being admitted the ENI community. The second rota- lineage. Christian literally taught me to the program! tion was in Prof. Jens Frahm’s lab up with his own hands how to record in- the hill at the Max Planck Institute for tracellular currents by patch clamping Neurowissenschaft: The neuroscience Biophysical Chemistry. It was a shared the hippocampal neurons. He would graduate program in Göttingen was rotation with two of my classmates Ben initially perform the experiments with and continues to be excellent. Unlike Cooper and Katharina Anton-Erxleben; me. This left a strong impression on most European and UK based MSc/ we had several theoretical lectures me through the years and I value this PhD programs it is modeled on US gra- on fMRI within the rotation and then as being an important part of training duate program featuring coursework, served as each other’s subjects in the my own graduate students. During this lab rotations and qualifying exams. MRI scanner. It was quite fascinating rotation, I characterized the Ca2+ de- My tryst with formal coursework and to get these high-resolution functional pendence of vesicular release probabi- hands on training in neuroscience be- images of BOLD activity in our visual lity and how pre-synaptic protein Rab3 gan with our theoretical and practical cortices during stimulus presentations. regulates short-term plasticity. We classes spread across the Max Planck published this work as part of a Rab3 Institute for Experimental Medicine, knockout mouse study in collaborati- Klinikum, University Medical Center, on with Dr. Thomas Südhof (Schlüter, DPZ, Zoology department and even Basu et al. 2006, Journal of Neurosci- the Max Planck for Fluid Dynamics. ence). I spent the next four years in the A small class size, with intensive lec- Rosenmund lab first in Göttingen fol- tures by experts in the field, exposure lowed by Baylor College of Medicine, to workshops, seminars, presentations Houston studying the molecular me- and tutorials comprised just the right chanism of neurotransmitter release in ingredients to form a rock-solid foun- mouse hippocampal cultured neurons. dation in Neuroscience. This is the un- derpinning upon which my career as In 2003, soon after I started my PhD a neuroscience researcher and faculty thesis project at the Max Planck Insti- was built upon. tute (MPI) for Biophysical Chemistry, my primary advisor Dr. Rosenmund I came in to the Neuroscience pro- moved his lab from Germany to Bay- gram with a broadminded research fo- lor College of Medicine in Houston, cus and tried to get a flavor for diverse Texas. I stayed on in Dr. Erwin Neher’s techniques and research topics during With Prof. Erwin Neher and Dr. Ira Milosevic research group at the MPI to finish a

NEUROSCIENCE 23 AlumniRegional

Master’s degree from the Max Planck graduate program and my credits got I realized that moving forward, I wan- Neuroscience program. My MSc thesis transferred over. As Dr. Rosenmund’s ted to rigorously dissect and manipu- research at MPI-BPC examined bio- first graduate student at BCM, I worked late activity in neural circuits to study physical methods to quantify vesicu- very closely with him and learnt a great how changes in information flow re- lar release kinetics and explore how deal from him, from building an elec- sulted in the formation of long-term synaptic vesicles overcome the energy trophysiology setup, to developing new memories and learning behavior. I barrier for fusion and release neuro- assays for quantifying synaptic release, was convinced to pursue such a re- transmitter spontaneously or sucrose to writing our first scientific paper to- search goal, I could not be limited by induced and Ca2+evoked stimulation. gether. My PhD research on synaptic techniques and had to go where the Being in Prof. Neher’s department and vesicle priming and short-term plasti- science took me. I decided to follow interacting with him and the other city was highly collaborative and inter- these objectives at Columbia Univer- groups was a privilege and great lear- disciplinary combining electrophysio- sity, under the mentorship of Dr. Ste- ning experience. The weekly group logy, genetics and fluorescent imaging. ven Siegelbaum, whose research I had meetings, the invigorating scientific It culminated in two first- and one co- been closely following since 2006, discussions, journal clubs were some author research papers. My first study when I had first hosted him as a semi- of the highlights of my time there. One performed in close collaboration with nar speaker at BCM. thing I remember from Prof. Neher is Dr. Jose Rizo Rey’s lab at UT South- the amount of attention to detail he western, Dallas, identified the minimal Since the 1950s, the hippocampus has dedicated to looking at our electrophy- functional domain of the presynaptic been extensively studied as the seat siological traces and the stress he laid protein Munc13 for its essential role of learning and episodic memory, our on doing the right and meticulous con- in synaptic vesicle fusion (Basu et al. knowledge of people places, objects trol experiments. These aspects of my 2005, Nature Structural and Molecular and events. However intact connec- training have shaped how I have been Biology). Next using a biophysical me- tions with the entorhinal cortex, an conducting my own research since. thod we had devised during my MSc adjacent area that acts as a hub for to quantify the rate of synaptic vesicle routing information about the outside release in Munc13 knock in mutant world, are crucial for these functions mice, I uncovered a regulatory role of and for spatial navigation. During my Munc13 in vesicular release kinetics post-doctoral research with Dr. Siegel- (Basu et al. 2007, Journal of Neurosci- baum at Columbia University, I wor- ence). Finally, I performed a structure- ked on how precisely timed activity of function based mapping study of the glutamatergic and GABAergic inputs Munc13 N-terminus using several loss from the entorhinal cortex to CA1 neu- and gain of function point and deleti- rons, the principle output source of the on mutations. I identified an inhibitory hippocampus can enhance informati- region in Munc13 that gates vesicular on flow within the circuit through an release efficacy through its interaction input timing-dependent plasticity. In With Drs. Ben Cooper, Zaved A. Khan and with the active zone protein Rab Inter- the Siegelbaum lab, I have learnt, esta- Fernando Rodriguez at the Gänseliesel, acting Molecule (RIM). A Cold Spring blished and implemented several avant Göttingen Harbor Laboratory imaging course garde approaches in neuroscience, during my PhD, in 2006, opened my including electrophysiology coupled In 2004, I enrolled in the Neuroscience eyes to all the innovative technologies with high-resolution two-photon Ca2+ Graduate program at Baylor College of for quantitative fluorescent microscopy imaging, optogenetics and pharma- Medicine (BCM), and started my PhD of cells and molecules. Using these in- cogenetics and behavioral analysis. thesis in Dr. Rosenmund’s lab. All my sights, I designed a novel FRET based One of my most exhilarating accom- curricular coursework from Göttin- Munc13 biosensor probe to detect ac- plishments as a patch clamp electro- gen were at par with that of the BCM tivity-dependent presynaptic plasticity. physiologist is performing long-term

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intracellular recordings from extremely postdocs, two technicians and I. I hope put some of these ideas to the test ex- thin sub-micron dendritic processes of to transfer the good experiences I have perimentally based on the ability to mouse CA1 pyramidal neurons (Basu had in being mentored as a graduate electrically and optically monitor acti- et al., Neuron, 2013; Kupferman, Basu and post doc to my own mentees. The vity in acute brain slices and in brains et al., Cell, 2014; Basu et al., accepted idea is to be a close-knit, highly col- of head-fixed awake behaving mice. Science, 2015). Using somatic and laborative group, where all of us work dendritic recordings with functional together towards a common over- The hippocampus receives informati- mapping approaches, I identified two arching research goal: How does the on about space and contexts from the kinds of GABAergic circuits that are brain encode and recall memories and entorhinal cortex. Once processed, important for dynamically regulating produce adaptive behaviors based on the hippocampus feeds back the in- excitation in the hippocampus. The past experience? formation to the entorhinal cortex. Is first is a local microcircuit that is ac- the hippocampal feedback relevant for tivated by excitatory inputs to provide We have chosen to address this through maintaining the native firing proper- the major feed-forward inhibition to studying how hippocampal memory ties of entorhinal cortex neurons? To CA1 pyramidal neurons (Basu et al., information may shape the processing address this we are first characterizing 2013, Neuron). Modulation of soma- and perception of sensory information the much elusive connectivity of inputs tic inhibition from these interneurons in the cortex. Spatial navigation is a cri- that feedback from the hippocampus is required to increase the magnitude tical brain func- of long-term plasticity in CA1 pyra- tion that requires midal neuron soma. The second is a neural circuits to ‘disinhibitory’ GABAergic long-range form a represen- projection circuit from the entorhinal tation of the envi- cortex to the hippocampus (Basu et al. ronment. Both the 2015 accepted Science). These inputs hippocampus and suppress local hippocampal dendritic entorhinal cortex feed-forward inhibition at a precise have cells that time interval, thereby disinhibiting show increased CA1 pyramidal neuron excitation. This firing at distinct disinhibition triggers dendritic spikes locations in space and long-term plasticity. Furthermore, during explorato- in vivo two-photon imaging in awake ry behavior. The behaving mice, showed that contextu- discovery of these al sensory stimuli trigger Ca2+ activity “nerve cells in the in these long-range GABAergic pro- brain that enable With my classmates Dr. Fernando Rodriguez and Dr. Dragana Jancic at jection inputs from entorhinal cortex a sense of place rajesh and my wedding in Calcutta. to CA1. Finally pharmacologenetic si- and navigation” lencing of the activity of these inputs was recently recognized with the No- to the entorhinal cortex. We are using during contextual fear learning impairs bel Prize in Physiology and Medicine functional mapping approaches where the precision of encoding contextual (2014). There has been great theoreti- we can genetically target the hippo- information. cal interest in the field to understand campus to entorhinal cortex pathway how the properties (fields, firing rates, and probe using electrical recordings The past three months have been thril- patterns) of these cells are shaped. For which neurons in the entorhinal cor- ling in populating and setting up my example, modeling suggests that the tex receive the hippocampal inputs. own laboratory at New York University. distinct firing patterns in entorhinal We will further investigate how these We are a growing group, soon to be of cortex require inputs from hippocam- hippocampal inputs can influence cel- six members – a graduate student, two pus. My laboratory is in a position to lular activity and flow of sensory infor-

NEUROSCIENCE 25 AlumniRegional

mation in the entorhinal cortex. Our ternational students into the German etiquette of never using a knife while research will fuel our understanding way of life, learning the language and eating potatoes, of always being dot of how the mammalian brain builds a sharing each other’s cultures through on time punctual for a dinner invitati- map of the environment. organized events. I learnt German in on but how it is acceptable to be late high school back in Calcutta, which at a casual party. We also visited her Gesellschaft, Gemeinschaft, Freund- did give me a head start conversing place in the countryside to learn how schaft: A major part of my positive with my Mitbewohner in Rosenbach- to make Zwiebelkuchen. I remember experience in Göttingen comes from weg. As a member of Sabine Ihlenfeld’s organizing the first poetry night with the people interactions – the effort the German language class at Uni Göt- my classmates Dragana and Primoz in program put in to integrating us in- tingen, I learnt the correct German the library of MPI-EM. These culture nights introduced by the program were a huge success and I cherish those Jayeeta BASU did her Master’s thesis in Christian memories dearly. The interactions at Rosenmund’s group at the Max Planck Institute for class or lab as well as outside socially Biophysical Chemistry. She started her PhD thesis in with my fellow classmates lead to se- April 2004 in the Rosenmund group in Göttingen and veral life-long friendships, bound by a moved with the lab to the Baylor College of Medicine common thread – being proud alumni where she graduated in 2007. of the IMPRS Göttingen. Twelve years since the time we met I still see some Jayeeta Basu, PhD, Assistant Professor, at least once a year, we have shared NYU Neuroscience Institute, many a special occasions in life – in- Department of Neuroscience and Physiology, cluding my grand Indian wedding in New York University School of Medicine Calcutta in 2007 to thanksgiving at our place in New York in 2014.

Beyond Academia - Making the transition by Pooja Rao

In January 2014, I graduated from the Long before I graduated, I realized that science outside academia. While I was Neuroscience program and moved I preferred reading, writing, and thin- surprised to see that plenty of scientific from Göttingen to The Netherlands. king about research to working at the research takes place outside universi- At the same time, I took my first steps bench. I was also keen to work more ties and research institutes, this also away from academia towards a ca- closely with human clinical research, meant that there was a world of inter- reer in the industry. After doing a brief and to learn about its commercial side. esting career opportunities in pharma- postdoc stint at a biotech company in While working on my PhD at the ENI, it ceutical companies, biotech, publish- Leiden, I currently work at Excerpta often seemed as if the main goal of re- ing and many other industries. Further, Medica, a medical communications search was publishing papers, and that there are several non-research jobs that consultancy in Amsterdam. In my role the science world was largely domi- fit very well with the skills one acquires as medical publications manager, I nated by professors, universities and during a PhD. work with pharmaceutical companies research institutes. I later learned that to help communicate their clinical re- this is far from true, especially for clini- While I was looking for positions in the search. cal studies, and that there is plenty of industry, I had the opportunity to learn

26 NEUROSCIENCE AlumniRegional

which of these skills I could take with city they live in is not the same city they searches, data analysis, writing and edi- me. I found that analyzing data criti- work in. It’s quite common to take the ting. I spend a lot of time in meetings cally, visualizing it and presenting my train to work every day and I commute with clients and colleagues. My pro- work, were perhaps the most transfer- from The Hague to Amsterdam daily, jects tend to be shorter, lasting weeks to able skills from my time in the Fischer using the time to read or to catch up months, and have clearly defined goals lab at the ENI. By the time I had de- on work. and tight deadlines. The pace of work fended my PhD thesis, I had made so can be quite hectic and since clients many different kinds of presentations in For my first job as a ‘postdoc in the in- are based across the globe, there are the form of lab seminars, journal clubs dustry’ I worked at a small biotech com- tele- and web-conferences on a daily and retreats that it had become second pany that specializes in next-generation basis. I find it satisfying and motivat- nature to me to use data to build a story sequencing. In addition to my own bio- ing to have concrete time-bound goals and to present it in a concise, engag- informatics research projects, my role and to achieve them. My work usually ing manner. Equally handy were the was to analyze genome and transcrip- spans a broad overview of a therapeu- numerous tips on writing, presentation, tome data for clients - mostly scientists tic area or disease rather than a being and communication that I had picked doing clinical and preclinical research. a dive deep into a molecule, pathway up from GGNB soft skill courses. Fi- Working with university scientists from or synapse. This means that I’m always nally, the large number of alumni that within a commercial organization gives learning new things. One of the most the IMPRS has accumulated around the you a unique perspective on the simi- interesting parts of my job is keeping world, and who have chosen various larities and differences between the on top of new therapies as they pass career paths was also a helpful source two and on the motivations that drive through clinical trials and are brought of information. I was able to locate an academic research versus those that into practice. ex-Neuro in most jobs that I was con- drive commercial R&D. Working at a sidering, and pleasantly surprised by small company also meant that I got to All in all, I enjoy my new job tremen- how willing they were to help out, see many sides of the business, doing a dously, but it’s too soon to say what the share their experience or give advice. bit of project management, setting up future will bring. I learned a lot dur- new research collaborations and even ing my years in Göttingen, and a lot helping out with sales and marketing. more in the time since I graduated and moved out of academia, but I am sure Soon, I decided to move into a job that there are many more new experi- where I could write about research ences to come. It’s been an interesting rather than do it myself. The focus of my journey so far and I look forward to see- current work is performing literature ing what lies ahead.

Pooja RAO did her doctoral thesis in André Moving away from Göttingen, I was Fischer’s group at the European Neuroscience Institute keen to find another equally multicul- in Göttingen. She was awarded a stipend of the Euro- tural place to live in, and preferably a pean Neuroscience Campus Network and defended larger city. I found both of these in The her PhD thesis in October 2013. Hague in The Netherlands. Even after the relatively international environment Excerpta Medica Amsterdam of the IMPRS, I am amazed by how di- Apollo Building verse and multilingual my new city is. Herikerbergweg 17 Since the country is so small, commut- 1101 CN Amsterdam ing to work is a way of life in Holland. Netherlands For most of my colleagues, like me, the

NEUROSCIENCE 27 AlumniOutside Academia So – why did you do this…? by Benjamin Wilhelm

This is by far the question I have heard We had planned the trip for at least Cambodian ruins, Thai beaches, Indo- most in the past year and a half and in two years and hence were thoroughly nesian dive sites and the friendliness the following paragraphs I will try to excited when we finally got going. We of the people in Myanmar. During this illustrate why… started our trip with three months in time we also hopped over to India for Africa where we climbed Mt. Kiliman- two weeks to attend the wedding of But let me start from the beginning: jaro and did an overlanding tour from our good friends Mrinalini and Rau- I have done my entire university stu- Uganda all the way down to South nak (and saw a lot of familiar faces…). dies in Göttingen. Starting with my Africa via Kenya, Tanzania, Zanzi- Our next flight brought us to New undergrads in Biology and transferring bar, Malawi, Zambia, Zimbabwe, Zealand. Here we hired a camper and to the Neuroscience program for my Botswana and Namibia. If we had to cruised both the north and the south is- land. From beautiful beaches to snow- capped mountains, from an incredible wildlife to warm hearted Kiwi’s – NZ really has it all! After such an amazing time it was of course difficult to move on but we still had one gem on our list: Mexico! Mexico spoiled us with pristine beaches, whales, baby turtles, ancient ruins and fabulous food and it was certainly a worthy highlight to end the trip.

Upon returning from the big trip I de- cided to finally leave science for good and to start as a business consultant. After such a long time “on the road” it was of course quite a change retur- ning to Germany in Mai 2014, but we were also ready to start the next ad- venture: new city and job. We moved to Hamburg where I started with Master’s and PhD. For the latter I was pick our personal highlights it would McKinsey in July. When you start at lucky enough to join the lab of Silvio probably be the Balloon-Safari over McKinsey without a business back- Rizzoli at the ENI. To be frank, I think the Masai Mara in Kenya (seeing mil- ground the firm provides you with a I had quite an unusual PhD as I was lions of animals migrating) and hiking crash course (mini MBA) on econom- spoiled with a great supervisor, a very to the Mountain Gorillas in the forests ics and business administration. Al- promising and straight forward project of Uganda – simply breathtaking! Our though the mini MBA provides you and awesome colleagues in the lab. next stop was Moscow where we got with thorough business knowledge I am very grateful for this because I on the Trans-Mongolian train to take I was still quite nervous when I got know that not many of my peers can us East. Two stops (Lake Baikal and staffed on my first project – how could actually tick all these boxes. When Ulaanbaatar) and countless hours in I possibly add value? But believe it or I graduated in April 2013 I decided the train later we arrived in Beijing. not after a few days into the project I to take an early sabbatical to travel After a few more weeks in China we was amazed how much one can actu- around the world for almost an entire moved on to South East Asia were ally do. Being critical and asking the year together with my wife before de- we spend the next 4 months explo- right questions, dissecting a problem ciding what to do next. ring Vietnamese food, Laotian jungles, to get to its core and finding creative

28 NEUROSCIENCE OutsideAlumni Academia

solutions to solve it are essential skills and I had learned all of this in the past years in Göttingen. Equipped with this it is secondary how much knowledge you have about economics – this will come with time and actually much faster than one would think. So how do I feel after the first 6 months? I have been challenged more than ever be- fore and the “learning curve” has most likely only been steeper in the first couple of years of my life. Is it stress- ful? I’d call it intense! Do I like it? Yes, it is exactly what I was looking for!

In a GGNB class on writing for the public I have learned that at the end of an article it is good practice to close the narrative loop and get back to where you started. In this sense: why have I done it? Well for the world trip – I just had the feeling I needed an in- me a unique opportunity to challenge whole (I spent 8 years there!). But as I spirational and mental break before I me in ways science could not. Look- said it was time to move on, to learn would start the next phase of my life ing back I would lie if I’d say that I did and see something new and even in and I most certainly got what I was not miss my old friends, my supervi- rough times I have not yet regretted it looking for! For the second part – I sor and the lab, the coordination team and am still enjoying the new adven- joined McKinsey because they offer and the ENI as well as Göttingen as a ture.

Benjamin WILHELM did his doctoral thesis in Silvio Rizzoli’s department, STED-Microscopy of Synap- tic Functions, European Neuroscience Institute Göt- tingen (ENI-G). He was awarded a GGNB Excellence stipend in 2010 and a Boehringer Ingelheim Foundation stipend in 2011. He graduated in March 2013.

McKinsey & Company, Inc. Am Sandtorkai 77 20457 Hamburg Germany

NEUROSCIENCE 29 HonorsAwards & Creutzfeldt Award

Honors and Awards Creutzfeldt PhD Prize Dr. Ioanna BETHANI (2011) Goethe-Universität Frankfurt Students The Creutzfeldt PhD Prize is awarded Institute of Cell Biology and for the best PhD thesis in memoriam Neuroscience Cluster of Excellence The following doctoral students of Prof. Dr. Otto Detlev Creutzfeldt, Molecular and Cellular Neuroscience have been awarded a GGNB founding director of the department of Macromolecular Complexes (CEF) Excellence Stipend: Neurobiology at the Max Planck Insti- Max-von-Laue-Str. 9, Tanvi Butola (2013), tute for Biophysical Chemistry in Göt- 60438 Frankfurt am Main Ricardo Merino (2013), tingen. The prize has been awarded Florentin Masurat (2014), since 2007 to PhD graduates of the Dr. Stephan JUNEK (2011) Julio Santos Viotti (2014) Neuroscience program based on ex- Max Planck Institute for Brain cellent achievements during the PhD Research and the grading of the written disserta- Neural Systems and Coding Group Junior Group Leaders tion and the oral defense. In 2011 for Deutschordenstraße 46 the first time 2 winners were selected 60528 Frankfurt am Main Henrik Bringmann: for the Creutzfeldt Prize. Traditionally, ERC Starting Grant the award ceremony is part of the of- Sadim JAWHAR, Ph.D. (2013) Marion Silies: ficial opening of the NEURIZONS Biomedical Research Institute Emmy Noether independent junior Symposium and will take place on 26 Doha, Qatar research group funding, Schilling May 2015 in the presence of Gregor Prize of the German Neuroscience Eichele (Dean of the IMPRS for Neuro- Dr. David OWALD (2013) Society (NWG) sciences), Denise van Rossum (Sarto- Center for Neural Circuits rius stedim AG) and Mary Creutzfeldt, and Behavior who will present the book ‘Cortex Ce- Oxford University, Faculty rebri’ written by her late husband Otto United Kingdom Creutzfeldt to the awardees. The award Stefan Hell: also includes a gift of 500,-€ which is Dr. Natalia REVELO NUNCIRA (2015) Nobelprize for Chemistry, sponsored by the Göttingen company Dept. Neuro- and Sensory Physiology Sartorius stedim biotech AG, which University Medical Center Reinhard Jahn: has generously supported the Neuro- Humboldtallee 23 Heinrich-Wieland-Prize science program since its foundation. 37073 Göttingen Tobias Moser: Dr. Irina DUDANOVA (2007) Nicolas SNAIDERO, Ph.D. (2015) Silvio Rizzoli: Max Planck Institute of Neurobiology Institute of Neuronal Cell Biology ERC Consolidator Grant Department of Molecular Technical University München Mikael Simons: Neurobiology Biedersteiner Str. 29 Alzheimer Research Award Am Klopferspitz 18 80802 München D-82152 Martinsried Institute of Clinical Neuroimmunology Dr. Henry LÜTCKE (2009) Ludwig-Maximilians University Brain Research Institute Munich University of Zurich Marchioninistr. 17 Winterthurerstrasse 190 81373 München 8057 Zurich, Switzerland

30 NEUROSCIENCE FacultyNew Joining the program from 2013

Tim Gollisch Her group aims to understand how to manipulate sleep towards functional was appointed Professor neural networks receive, analyze and sleep studies. for Sensory Processing in extract visual information from the en- Further information: http://www.uni- the Retina, School of Me- vironment to guide adaptive behavior. goettingen.de/en/138623.html dicine, University of Göt- By studying motion detection in the tingen in 2010. He joined visual system of fruit flies using cell Jeong Seop Rhee the Neuroscience program in 2013 biological and genetic approaches is a research group leader and is engaged in teaching in the MSc in combination with physiology and at the Max Planck Institute curriculum (Sensory and Motor Sys- quantitative behavioral analysis, she of Experimental Medicine, tems lectures) and hosts MSc and PhD aims to identify mechanisms by which Göttingen since 2006. He candidates from the program and from nervous systems integrate molecular, studies synaptic signa- GGNB. The focus of his work is the cellular and circuit characteristics to ling between nerve cells to elucidate function of the various neuron types compute behaviorally relevant outputs. the molecular mechanisms that un- in the retina and to better understand Further information: http://www.eni. derlie synaptic plasticity at synapses neural computation in the retina. On gwdg.de/index.php?id=356&L=1%27a in the central nervous system. Various this basis, he also studies dysfunctions techniques including mouse genetics, of the retinal circuitry. Henrik Bringmann molecular biological and morphologi- He uses various techniques of recor- has been appointed as a cal methods, and patch clamp electro- ding the activity of neurons in the Max Planck research group physiological analyses of autaptic cul- retina including multi-electrode array leader at the Max Planck tured neurons, organotyptic brain slice recordings, whole-cell patch-clamp Institute for Biophysical cultures, acute brain slices, or acutely recordings, and fluorescence imaging Chemistry, Dept. of Sleep isolated neurons are used to identify and combines the experiments with and Waking in 2009. He joined the the molecular mechanisms underlying statistical analyses and mathematical Neuroscience program in 2013 and in- individual synaptic vesicle recycling mo-deling. troduces invertebrate models in the MSc steps. Further information: http://www.uni- curriculum ever since. He also hosts Further information: http://www.uni- goettingen.de/en/201928.html PhD program candidates from GGNB. goettingen.de/en/122329.html He investigates the function and regula- Marion Silies tion of sleep by studying different model holds a group leader organisms, especially in the larva of the (Emmy Noether Group) nematode Caenorhabditis elegans, and position at the European in mice using behavioral assays, gene- Neuroscience Institute, tics and functional imaging. Recently Göttingen since 2014. In his group identified a single sleep- the MSc part of the neuroscience pro- inducing neuron in C. elegans that is gram and in GGNB she is engaged homologous to mammalian sleep neu- in training activities introducing the rons. This provides a starting point to genetics and quantitative behavioral understand the regulation of sleep and analysis in fruit flies.

NEUROSCIENCE 31 FacultyLeaving Left the program since 2013

Uwe-Karsten Hanisch Moritz Rossner Andreas Wodarz Very sadly, the program came to Göttingen as a was appointed Head of the has to announce that Uwe- group leader at the Max Department of Stem Cell Karsten Hanisch unexpec- Planck Institute for Experi- Biology at the University tedly passed away on 18. mental Medicine in 2003. of Göttingen in 2004. From April 2015. The Medical The group’s research inte- 2005 until 2013 he was a Faculty of the University of Göttingen rest is directed towards the generation member of the Neuroscience program. and the University of Leipzig, where and analysis of transgenic mouse mu- His research activities focus on diffe- he was recently appointed as Professor tants in order to understand individual rent aspects of the asymmetric division for Dynamics of Brain Function at the gene functions in the adult brain. Dr. of neural stem cells. He was appointed prestigious Paul-Flechsig-Institute for Rossner has been a member of the full professorship at the University of Brain Research, have expressed deep Neuroscience (IMPRS) and the CMPB Cologne, Faculty of Medicine, Institute sorrow. He leaves behind his wife and program (Molecular Physiology of the of Anatomy, head of the Dept. Micro- 2 children with who is the compas- Brain). In 2014 he accepted a position scopic Anatomy and Molecular Cell sion of his colleagues, co-workers and at the Ludwig Maximilians University Biology. friends. in Munich Clinics, and became full Further information: http://www. professor at the Dept. Molecular Neu- anatomie.uni-koeln.de/404.html Uwe Karsten Hanisch, born May 6, robiology and Behavioral Biology of 1961 in Lützen, studied biochemistry Psychiatric Disorders. in Leipzig and did his doctoral thesis Further information: http://www. in 1990 at the Paul-Flechsig-Institute, klinikum.uni-muenchen.de/Klinik-und- the very same institute he returned to Poliklinik-fuer-Psychiatrie-und-Psycho- as professor and designated director therapie/de/mitarbeiter/rossner.html 25 years later. As a postdoctoral fel- low he worked at McGill University in Montreal/Canada and at the Max Del- Current Faculty Members brück Centre for Molecular Medicine Matthias Bähr Ralf Heinrich Manuela Schmidt in Berlin. He took over a professorship Thomas Bayer Stefan Hell Michael Sereda at the University of Applied Sciences Henrik Bringmann Michael Hörner Marion Silies in Senftenberg in 2002 and accepted Nils Brose Swen Hülsmann Mikael Simons an appointment as Professor for Ex- Wolfgang Brück Reinhard Jahn Jochen Staiger perimental Neurobiology, Institute for Camin Dean Hubertus Jarry Judith Stegmüller Neuropathology at the University of Thomas Dresbach Siegrid Löwel Anastassia Stoykova Göttingen in 2004. Prof. Hanisch’s ma- Hannelore Ehrenreich Till Marquardt Walter Stühmer jor research interests focussed on the Gregor Eichele Ira Milosevic Stefan Treue expression and functions of cytokines André Fiala Tobias Moser Fred Wolf in the CNS and the role of plasma fac- André Fischer Klaus-Armin Nave Fred Wouters tors as endogenous signals for micro- Alexander Flügel Luis Pardo glial cells. He joined the Neuroscience Jens Frahm Walter Paulus program in 2010. Tim Friede Jeong Seop Rhee For details regarding the Theo Geisel Michael Rickmann research of all faculty Tim Gollisch Silvio Rizzoli members, please see www.gpneuro.uni- Martin Göpfert Detlev Schild goettingen.de/content/c_ Robert Gütig Oliver Schlüter faculty.php

32 NEUROSCIENCE CampusEvents Neurizons 2015 – notes of an orchestrated brain

This May, the city of science Göttin- gen comes alive to host its 6th biennial neuroscience conference – Neurizons 2015. Neurizons is the flagship neu- roscience conference organized by the students of the International Max Planck Research School (IMPRS) Göt- tingen. The conference is to be held from the 26th to the 29th of May this year, at the Max Planck Institute for Biophy- sical Chemistry, Am Fassberg, Göttin- gen. Keeping with tradition, this year’s conference boasts an exciting line- up of speakers, including the Brain prize winner, Dr. György Buzsáki, who will deliver the keynote speech. The speakers will delve on a range of topics including synaptic physiology, sensory and motor systems, develop- mental neuroscience, translational neuroscience, systems neuroscience and cognition, in five sessions spread over three days.

As a student organized conference, Neurizons recognizes and caters to the needs and interests of the student com- munity. The conference is set to begin with a series of workshops on critical research methods and a career fair which includes talks from the repre- sentatives of Sartorius AG, McKinsey and Company Inc., and Georg-August University Göttingen. In addition to the quintessential poster sessions, Neuri- zons 2015 also provides a platform for students to present their work through “Young Investigator Talks”, short talks The issue is addressed with pub crawls ture on super-resolved fluorescence nestled in between the five sessions. and guided city tours to ensure inter- microscopy from Göttingen’s very Strong emphasis is laid on personal action in enriched environments. The own Nobel laureate Prof. Stefan Hell. communication, with “Coach Me”, final day of the conference, 29 May With renowned experts orchestrating a one-on-one mentoring session with 2015 also marks the 15th Anniversary this symphony, a strong platform to guest speakers. of the International Max Planck Re- interact and forge connections, inters- search Schools for Neurosciences and persed with fun and frolic, Neurizons As neuroscientists, the organizers rea- Molecular Biology. The celebration 2015-notes of an orchestrated brain, lize the importance of social behavior. features the scientific keynote lec- promises to enthrall.

NEUROSCIENCE 33 CampusEvents Joint Retreat with Max-Delbrück-Center... Helmholtz International Research School Molecular Neurobiology by Dennis Nestvogel

Brain: the final frontier. These are the licious barbecue, a session of “Power- with the role of rhodopsins 1 and 6 in voyages of the IMPRS for Neuroscien- Point-Karaoke” and stimulating con- thermoreception and proprioception. ces. Its mission: to explore strange neu- versations on the lakeshore. ral networks, to seek out mechanisms Sven Truckenbrodt from the laborato- that contribute to brain function and The next day was particularly dedi- ry of Silvio Rizzoli (UMG, Göttingen) behavior, to boldly go where no man cated to scientific exchange. Eugenia was the first speaker of the session on has gone before.* Chiappe (Champlimaud Foundation, “Synaptic Research”, on the third and Lisbon) opened the first session on last day of the retreat. He gave a very On that note and in the spirit of the “Sensory and Motor Neuroscience” entertaining and thought-provoking 25 years of the fall of the Berlin wall, with an inspiring talk on linking mo- talk on the molecular architecture and students from the MSc/PhD/MD-PhD tion-vision to walking in flies and was organization of chemical synapses and Program and IMPRS for Neurosciences followed by two student talks. After a was followed by three student talks. in Göttingen and the Helmholtz Inter- short coffee break, Yang Dan (Univer- The prize for the best student talk of national Research School Molecular sity of California at Berkeley) presented the retreat was awarded to Mohammed Neurobiology Max-Delbrück-Center some of her latest research in the field Khani, whose talk was on chromatic for Molecular Medicine in Berlin-Buch of vision and gave some valuable ca- signal integration in the mouse retina. gathered together in September 2014 reer advice to the graduate students. After some concluding remarks by the for a joint retreat in Lychen, Branden- She was followed by three more stu- student organizers and a refreshing burg. dent talks, before lunch was served. lunch, the participants traveled back to The final session of the day on “Neu- Berlin or Göttingen, respectively. Well-equipped with poster boxes, ral Development” was opened by snacks and an omnipresent motiva- Till Marquardt (ENI, Göttingen), who Overall, the joint-retreat offered a great tion to discuss science, the IMPRS stu- shared some of his newest insights on opportunity for the students of the dents together with their office team, the development of motor neurons IMPRS to discuss science with experts, engaged into a lengthy bus ride from with the participants and ended with as well as with graduate students that Göttingen to Lychen on the first day of three student talks. In the evening, all are at a similar stage in their career the retreat. Possible doubts or discon- of the participants gathered together and to make new friends – within and tents with regards to the length of the for a poster session. The topics pre- across the programs. bus ride immediately vanished upon sented on the posters ranged from the arrival at the beautiful venue that was structural analysis of single ion chan- *Modified after the title sequence of carefully chosen by the coordinator of nels to complex behavior of flies and Star Trek and with apologies to James the Helmholtz International Research mice. The prize for the best poster went Tiberius Kirk, Captain of the USS En- School. The first day ended with a de- to Diego Giraldo, whose poster dealt terprise

34 NEUROSCIENCE CampusEvents ELECTRAIN courses... at the European Neuroscience Institute supported by FENS

participants, who take the course to- ology, with lectures in the morning and gether with local doctoral students. In hands-on lab work in the afternoons. 2015 again 2 participants from Florida The ELECTRAIN course concept was Atlantic University in Jupiter join the awarded by the Federation of Europe- The ELECTRAIN courses in electrophy- course in the ENI. This brings again life an Neuroscience Societies (FENS) fol- siology are held in the ENI teaching labs to the partnership with the Florida cam- lowing calls for neuroscience training since 2009. Started as one of the trai- pus, which also hosts the Max Planck courses launched by FENS since 2013. ning initiatives of the Graduate School Florida Institute, the only MPI in the US. The GGNB course was selected for GGNB the course is meant to train local FENS funding in 2014 and 2015. ELEC- PhD students and postdocs in advanced This extended methods course provides TRAIN will, thus, again host 3 FENS par- electrophysiological techniques. Mean- both theoretical and practical know- ticipants, who receive financial support while, ELECTRAIN also attracts external ledge and skills of modern electrophysi- to cover their living and travel costs. Info Booth at SFN ‘Neuroscience in Germany’

The Society for Neuro- www.nncn.de/de) and the organization commercial exhibition area directly science Annual Meet- ‘Research in Germany’ (http://www. at the main poster passage. More than ing 2014 was held 15.- research-in-germany.org/en; Alexander 550 visitors discussed in detail with the 19. November 2014 in Washington DC. von Humboldt Foundation, the Ger- representatives of the different research man Academic Exchange Service, the organizations research and funding Based on the experience of the existing German Research Foundation). The opportunities in Germany. The main network of international graduate pro- common booth ‘Neuroscience in Ger- advantage turned out to be the fact that grams in the neurosciences in Germa- many’ was also supported by the local visitors with very different specific in- ny ‚Neuro Schools Germany‘ compri- office of the German Research Founda- terests could directly be guided to the sing the universities in Berlin, Bochum, tion in Washington. suitable partners of teaching programs, Bonn, Göttingen, Magdeburg, Mainz, research institutions or funding agen- München and Tübingen (http://www. This booth provided comprehensive cies at the very same booth. neuroschools-germany.com) thoughts information on the German research to join forces with other German in- landscape, training options, funding stitutions in the field of neuroscientific opportunities, and open positions in research have finally been realized in the neurosciences at German research fall 2014 in Washington. The idea was institutions. Compared to similar mar- to create a common landmark Ger- keting efforts in previous years with all man platform at the Society for Neuro- partners running their own booths se- science meeting including the Excel- parately, the joint booth attracted sig- lence Clusters in the neurosciences, nificantly more meeting participants. the national Bernstein network (http:// The joint financial support by the After successfully establishing the above mentioned ‘Neuroscience in Germany’ booth the partners allowed organizing team has already started to set up one of to plan a similar joint outreach stand the largest booth at the next Society for Neuroscience areas in the non- Meeting in Chicago in fall 2015.

NEUROSCIENCE 35 CampusEvents 3rd DAAD Summer School... at Universiti Sains at Kota Bharu, Malaysia

Neuroscience is one of the most inter- gust University, Göttingen, which was nationally oriented fields of scientific instrumental for the continued support research. Based on existing research by the DAAD. Following the success cooperation and recognizing the im- and proven concept of the 1st and 2nd portance of research-orientated trai- DAAD summer schools, the FEP course ning, neuroscientists from Germany 2015 was again selected for DAAD in cooperation with colleagues at the funding. The course is meant to expose Department of Neurosciences of the the participants to state-of-the-art theo- School of Medical Sciences and the retical and practical coursework intro- Universiti Sains Malaysia (USM) de- ducing relevant techniques with a focus veloped plans for a joint international on science-oriented neurophysiology. summer school. Following the experi- For the first time, also the USM main ence of international training courses campus is part of the DAAD summer established in the European Neuro- school and scientists at Penang actively science Institute in Göttingen (ENI-G), conduct one module of the FEP course. the 1st DAAD (German Academic Ex- All DAAD-USM summer school orga- change Service) summer school in the nizers are part of international study/ field of the neurosciences was orga- research programs and, thus, believe nized at the Kota Bharu campus in in international exchange in teaching 2009. This summer school has been and science. In this respect, the DAAD- the nucleus for establishing an interdis- USM summer school series also marks ciplinary training laboratory for excel- our efforts to recruit excellent scholars lent MSc and PhD students, integrating worldwide. The organizers of the DAAD scholars from medical school and the Summer School are convinced that the natural sciences and related fields. The now established DAAD-USM summer 2nd DAAD summer school ‘Fundamen- school provides the basis for a continu- tals of Electrophysiology’ (‘FEP Course’) ous and sustainable training scheme was conducted in 2012. making use of the neuroscience training laboratory at USM. In fact, based on the and will be useful for further joint activi- Meanwhile a formal cooperation treaty training activities numerous scientific ties between neuroscientists in Malay- was signed by USM and the Georg Au- co-operations were successfully started sia and Germany in the future.

36 NEUROSCIENCE CampusEvents European Neuroscience Campus Network New Proposal submitted

ports the further development of joint ence Program per year. They are trained EU research/teaching partnerships, in- in at least two home institutes of the cluding the ENC Network. ENC Network and have the option to enroll in existing and established PhD In conjunction with the establish- courses in each of the participating The ENC-Network is the organization ment of the European Neuroscience home institutes after successful gradu- that hosts both the Erasmus Mundus Campus training network for doctoral ation from the MSc program. Master Course (EMMC) and the Eras- candidates the European Master Neu- mus Mundus Joint (EMJD) roscience program ‘NEURASMUS’ has A new proposal to further develop and program, in addition to two ITN (Brain- been launched in 2010 with the aim to extend the joint MSc training scheme Train and SymBad). The ENC-Network extend exchange and training oppor- called ‘NEUROMUNDUS’ has been (ENC: http://www.enc-network.eu) tunities also for MSc students. Since submitted to the EU authorities in Feb- was founded in 2009 with EU funding 2011 three to five NEURASMUS MSc ruary 2015 and will be decided upon granted in 2010 (doctoral positions, students join the Göttingen Neurosci- by fall 2015. overhead of 1.3 Mio €/year).

The Consortium Agreement stated that ENC doctoral students in Göttingen will be integrated into GGNB. In addi- tion, ENC partners are asked to imple- ment joint/double degree regulations for ENC doctoral students. GGNB sup-

Live the Weizmann Cooperation External Master Thesis project at the Weizmann Institute of Science in Israel by Alexander Dieter

-year after I made this decision I am fi הזתה תא בותכל יתטלחהו סקלא ימש ,ןלהא -nally working here. Actually the deci ,תובוחר ,עדמל ןמציו ןוכמב ינש רותל ילש Ahlan, shmi Alex v’hechlat’ti sion has been made long before. Not .לארשי likhtov et hateza sheli l’tor sheni bim- for Israel and not for the WIS, but for khon Vaitzman l’mada’, Rechovot, spending time of my studies abroad. Yisrael. During my bachelor studies I have al- al classmates, who combine continu- ready stayed in laboratories of differ- ing their graduate education in Göt- Hey, my name is Alex Dieter, I am ent countries and always profited from tingen, with the adventure of coming currently a MSc student of the Neuro- these times, both in a personal and a to a new country and experiencing a science Program, class of 2013. I de- professional way. When I started my different culture. When I then heard cided to write my Master’s thesis at the Master’s degree at the IMPRS for Neu- about the collaboration between the Weizmann Institute of Science (WIS), roscience in Göttingen I was a bit jea- IMPRS in Göttingen and the Feinberg Rehovot, Israel. More or less half a lous of many of my mostly internation- Graduate School at the WIS for the first

NEUROSCIENCE 37 CampusEvents

time, I immediately started thinking netics and patch-clamp recordings I style. Rehovot itself is famous for the about ways to do my master studies at contribute to a project that deals with science that is done here and for its the Weizmann Institute. the balance between excitation and in- flowering orange industry. Apart from hibition in the mouse barrel cortex. By this it is a relaxed and quiet city. During The WIS, as one of the leading research optogenetic inactivation (using either the week it is really nice to stay here, institutions in Israel, has an excellent archaerhodopsin or halorhodopsin, there are a lot of pubs and restaurants reputation worldwide and provides on two light activated ion pumps that en- where one can meet both local and in- the one hand a solid base for interdis- able hyperpolarization of transfected ternational people, mainly connected ciplinary research by uniting scientists neurons) of excitatory cortical neurons via the WIS. The international people I dissect thalamic feedforward- from I meet here are a more than welcome intra-cortical feedback-inhibition. The company for traveling, since a lot of proportions of feedforward- vs feed- Israelis in my age are already settled back inputs can then be quantified by and often have family. Compared to patching inhibitory neurons in the cor- Europe, people are married and have tex and compare their firing behavior children much earlier. On the week- during the somatosensory response ends, however, I try to ‘escape’ from (feedforward and feedback contribu- the life in Rehovot and either go to Tel tions) vs the somatosensory response Aviv, which one can reach in 30 mi- while shining laser on the cortex (i.e. nutes by train from Rehovot, or to ex- inhibiting excitatory cortical neurons, plore other parts of Israel. Tel Aviv is a leaving just feedforward-inhibition). highly diverse city, which offers ancient The establishment of the model system as well as colorful alternative districts as well as the scientific findings subse- and a modern, business-governed city quently then get confirmed with extra- center, just to mention a few. cellular multi-unit recordings and with histology. During the establishment of Israel as a whole is even more diverse, from a wide variety of fields but on the our model system I found differences which I experience as a country with other hand focuses the research by its in cytotoxicity caused by archae- and a lot of contrasts on many levels. Most specialization on natural and compu- halorhodopsin, which lead to exten- ter sciences. This unique feature finally sive cell death in the cortex. Now that convinced me to join a lab at the WIS these problems are settled and we have instead of looking for laboratories in a working model system, I recorded other places of the world. Thanks to the the first (quite promising) data to an- support of the IMPRS and established swer the original questions. Overall, I collaborations between laboratories am working with diverse techniques in Göttingen and Rehovot, it was re- which I will hopefully be able to use obvious of course Arab vs. Israeli cul- ally easy to get in contact with people during my PhD in Göttingen. ture, but also religious vs. secular life, at the WIS and to find the right lab for the ubiquitous rich vs. poor, war vs. the work of my master thesis, which Even though the lab-life is quite busy, peace and apart from this, in a more turned out to be the one of Professor there is of course always time to grab pleasant way, beachside vs. deserts Ilan Lampl. In this lab I experience a some of the delicious Hummus (a local and a huge number of important an- lot of contact with all postdocs and specialty made from chickpeas) in the cient sites vs. multifarious modern ci- the PI himself on a daily basis in order cafeteria with my colleagues! Apart of ties. Due to a lot of diversity in a rela- to review recent results, solve techni- the lab-work, there is, of course, also tively small area, Israel is the perfect cal problems and discuss new ideas. time left to discover the country and location for everyone who wants to Using stereotactic injections, optoge- experience the Israeli culture and life- experience something different in daily

38 NEUROSCIENCE CampusEvents

life. The Dead Sea, the ancient fortress have to say that even though Israel my stay and I am convinced that the Masada, the diving paradise Eilat, the was not the first country coming to my stimulating atmosphere I am experi- Golan Heights and of course Jerusalem mind when it comes to study abroad I encing over here will again benefit me are just a few highlights that I would have no regrets about the decision of in both personal and professional as- like to mention here. In conclusion I coming here. I enjoy every minute of pects of my life.

15th Anniversary... and International Alumni Day

From 29 to 31 May 2015 the Neu- pate in guided tours on the Göttingen Jochen Maas (Sanofi, General Manager roscience program and International campus. These site visits include the R&D Germany, Head R&D Germany), Max Planck Research School (IMPRS) university’s collections such as the cast Tamara Darsow, PhD (Vice President, together with its partner program and collection of antique sculptures or the Research Programs, American Diabe- IMPRS Molecular Biology will celebra- art collection or an introduction into tes Association, Washington DC) and te their 15th Anniversary in Göttingen. the work of the Center for Retrospec- Prof. Jan Philipp Reemtsma (Professor Many alumni from both programs have tive Digitization Göttingen. On the of German literature, founder and di- already confirmed that they will join North Campus, site visits are offered rector of the Hamburg Institute for So- the activities organized for this week- to the new Max Planck Institute for cial Research, sponsor and promoter of end to celebrate with the local students Solar Systems Research, to the Laser- the Max Planck Foundation). The talks and faculty. Laboratorium Göttingen, which close- are followed by a podium discussion ly collaborate with industry partners in with additional invited guests. The celebrations will start in the Uni- the area of application-orientated laser versity Aula with a scientific keynote research, and to the Microscopy Lab of On Sunday, the 15th Anniversary cele- lecture by Stefan Hell, Nobel Prize lau- Stefan Hell at the MPI for Biophysical brations and alumni meeting end with reate in Chemistry 2014. Subsequently, Chemistry. a hike to the nearby Plesse Castle for the president of the University of Göt- a farewell brunch in the castle’s inner tingen, Ulrike Beisiegel, will officially The day continues with the Alumni courtyard. open the 15th Anniversary celebrations Career Forum, intended to promote to which all current and formers mem- the interaction of alumni among each bers, colleagues and friends of both other across the different generations graduate programs have been invited. and disciplines. This forum also gives our current students the opportunity The celebrations mark the end of the to meet the graduates of former years NEURIZONS week (www.neurizons. and benefit from their experience. One uni-goettingen.de; 26-29 May 2015), key element of the International Alum- which gives the alumni the opportuni- ni Day is a series of ‘Vision Talks’, for ty to combine their return to Göttingen which distinguished guest speakers with a scientific meeting, organized by will outline their personal view on the PhD students of the Neuroscience current and expected future develop- program. Saturday is reserved for the ments in their field with reference to International Alumni Day. In the mor- the professional perspectives for alum- ning, all alumni are invited to partici- ni. The three talks will be given by Prof.

NEUROSCIENCE 39 Neurofaces

2000 – 2015