DOCSLIB.ORG

Neural Architecture Underlying Thirst Regulation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Neural Architecture Underlying Thirst Regulation Neural architecture underlying thirst regulation Thesis by Vineet Augustine In Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy CALIFORNIA INSTITUTE OF TECHNOLOGY Pasadena, California 2019 (Defended 13th February 2019) ii 2019 Vineet Augustine ORCID: 0000-0003-4431-1663 iii ACKNOWLEDGEMENTS The successful completion of any project requires many hands, and this is a PhD. I have numerous people to thank without whose help this would not have been possible. I would like to express my heartfelt gratitude to my advisor, Prof. Yuki Oka, for giving me the opportunity to work in his lab. His enthusiasm for science and the ability to work hard is infectious. More importantly, the freedom which he gave me allowed me to explore areas that in the end turned out to be very rewarding. Being his first graduate student, I got the invaluable opportunity to learn the ropes of setting up a new lab- buying equipment, setting up protocols, and most importantly hiring new members. This is one of the most valuable things I have learned and will forever be grateful. I could not have asked for a more productive graduate school experience. I would like to thank my thesis committee members, Prof. Thanos Siapas, Prof. David Anderson, and Prof. Viviana Gradinaru, for their invaluable input that forced me to go back to the drawing board and think. They were always available to answer my queries and provide advice. I hope to stay in touch and keep on learning from them. A special word of thanks to my program chairs, Profs. Siapas and Pietro Perona, for having faith in me and being supportive throughout. Without their guidance and support, this thesis would not have seen the light of the day. A special shoutout to Prof. K VijayRaghavan who is probably the busiest person in Indian science, but has always made time for me. His humility and passion is something I wish I could emulate. My high school teacher, Madam Sandipa Bhattacharjee, deserves a special mention. It was because of her help that I got through my graduate applications in the first place and has been a constant source of encouragement throughout. I would like to thank other lab members: Sangjun, Brittany, Kutal, Haruka, Takako, Yuan, Bo, and Allan, for being co-travelers along this journey. Though small, the Oka Lab has a very conducive environment for carrying out science and it is largely because of the lab members. Prof. Ralph Adolphs has been one of my greatest inspirations to pursue neuroscience. Since the time I was an undergraduate researcher in his lab till now, he has been there always. He is the reason why I got into Caltech. No words can express the gratitude I feel. One of the greatest gifts that I have received from Caltech are a bunch of friends whom I cherish dearly and will maintain for a lifetime. My cohort: Janis, Ryan, Gabi, Juri, and Mason. We lived together, danced on pool-tables, had crazy parties, did homework, egged each other on, and are now a family. My brothers from different mothers, Sangjun and Dhruv, were my pillars of support at Caltech. To literally ensuring I would have food every day to doing experiments together, from disappearing from lab all together midweek for roadtrips to waiting for hours at the emergency room, we did it all. Their company is what I will miss the most. Thanks folks! iv Pursuing a PhD is a long journey, where failure abounds much more than success. And during these times I always had my safe haven to go back to. My godfather, Prof. Charles Greene, who picked up a small town boy and instilled in him the belief that he can do well, supported him at every stage and gave him the most sage advice ever. This thesis will be incomplete without his mention. Thank you Chuck! Chilly and Chris aunty, Sinobi and Soniya chechi for having their doors always open, for paying a bunch of my fees and for sending me home-cooked food from across the country. Alice and Elizabeth aunty, Joy achan for their support in spirit. Abhishek and Supriya for all the road-trips across the US. Prateek, Lenin, Ved, Sweta, Ajaay, Prakash and Prem for all the fun conversations. Thank you! Lastly, but most importantly, my parents, Rosamma and Augustine, Julie and Joy, and my brother, Ashly, for being the main reason for where I am today. Their love, kindness, and support are my greatest blessings. And finally, a big thank you to my wife, Janet, who gave up everything she had - friends, family, career - to join me in a different country along this journey. She is my biggest cheerleader and my greatest strength. Words are inadequate a vessel to express what I feel for her. This thesis is for them. v ABSTRACT An important aspect of thirst is its quick quenching. When thirsty, you drink a glass of water for a few seconds; the water travels from the mouth to the stomach and you are satiated. The water has not yet been absorbed into the blood, so the brain needs to have mechanisms to signal stopping of drinking. It cannot simply depend on the body, as the body takes a good 15 - 30 minutes to even start absorption. In this dissertation, I describe dynamic thirst circuits that integrate the homeostatic- instinctive requirement for fluids, the consequent drinking behavior, and reward processing to maintain internal water balance. In Chapter 1, I show how neural populations in the lamina terminalis, a forebrain structure, form a hierarchical circuit architecture to regulate thirst. Among them, excitatory neurons in the median preoptic nucleus (MnPO) are essential for the integration of signals from the thirst-driving neurons of the subfornical organ (SFO). Thirst-driving neurons in the SFO receive temporarily distinct preabsorptive inhibition by drinking action and gastrointestinal osmolality sensing. A distinct inhibitory circuit, involving MnPO GABAergic neurons that express glucagon-like peptide 1 receptor (GLP1R), is activated immediately upon drinking and monosynaptically inhibits SFO thirst neurons. These responses are induced by the ingestion of fluids but not solids, and are time-locked to the onset and offset of drinking. Furthermore, loss-of-function manipulations of these neurons lead to a polydipsic, overdrinking phenotype. These neurons therefore facilitate rapid satiety of thirst by monitoring real-time fluid ingestion. In Chapters 2 and 3, I talk about how thirst triggers a strong motivational state that drives animals toward drinking behavior. The consequent fluid intake provides both satiation and pleasure of drinking to animals. However, how these two factors are processed and represented by the brain remains poorly understood. Here I will use in vivo optical recording, genetics, and intragastric infusion approaches to dissect thirst satiation circuits and their contribution to reward signals. Thirst-driving neurons in the subfornical organ (SFO) receive multiple temporally-distinct satiation signals prior to the homeostatic vi recovery: oropharyngeal stimuli induced by drinking action and gastrointestinal sensing of osmolality changes. In chapter 1, I have shown that drinking action is represented by inhibitory neurons in the median preoptic nucleus (MnPO). Here, I demonstrate that gut osmolality signals are mediated by specific GABAergic neurons in the SFO. These neurons were selectively activated by hypo-osmotic stimuli in the gut independent of drinking action. Optogenetic gain- and loss-of-function of this inhibitory population suppressed and increased water intake in thirsty animals, respectively. These results indicate that oropharyngeal- and gastrointestinal-driven satiation signals are transmitted to thirst neurons through different neural pathways. Furthermore, I investigated the contribution of thirst satiation signals to the reward circuit using a genetically-encoded ultrafast dopamine (DA) sensor. Interestingly, oral ingestion but not gut osmolality changes triggered robust DA release. Importantly, chemogenetic activation of thirst-quenching neurons did not induce DA release in water-deprived animals. Together, this dissected genetically-defined thirst satiation circuits, the activity of which are functionally separable from reward-related brain activity. Taken together, these finding provide answers to some longstanding questions in the neural control of fluid intake, and appetite in general. vii PUBLISHED CONTENT AND CONTRIBUTIONS Augustine, V. et al. (2018). “Hierarchical neural architecture underlying thirst regulation”. In: Nature 555, pp. 204-209. doi: 10.1038/nature25488. V.A. conceived the research program, designed and carried out experiments, analyzed data and wrote the paper. Augustine, V. et al. (2018). “Peripheral and Central Nutrient Sensing Underlying Appetite Regulation”. In: Trends in Neurosciences 41, pp. 526–539. doi: 10.1016/j.tins.2018.05.003 V.A. conceived the manuscript outline, designed and made figures, and wrote the review. Augustine, V. et al. (2019). “Temporally-and spatially-distinct thirst satiation signals”. In: Neuron. doi:10.1016/ j.neuron.2019.04.039 V.A. conceived the research program, designed and carried out experiments, analyzed data and wrote the paper. Lee, S., Augustine, V. et al. (2019). “Chemosensory modulation of neural circuits for sodium appetite”. In: Nature 41, pp. 93–97. doi: 10.1038/s41586-019-1053-2. V.A. designed and carried out experiments and analyzed data Ichiki, T., Augustine, V. et al. (2019). “Neural populations for maintaining body fluid balance”. In: Current Opinion of Neurobiology 57, pp. 134–140. doi: 10.1016/j.conb.2019.01.014 V.A. conceived the manuscript
Load more

Recommended publications
  • Resting State Connectivity of the Human Habenula at Ultra-High Field
    Author’s Accepted Manuscript Resting State Connectivity of the Human Habenula at Ultra-High Field Salvatore Torrisi, Camilla L. Nord, Nicholas L. Balderston, Jonathan P. Roiser, Christian Grillon, Monique Ernst www.elsevier.com PII: S1053-8119(16)30587-0 DOI: http://dx.doi.org/10.1016/j.neuroimage.2016.10.034 Reference: YNIMG13531 To appear in: NeuroImage Received date: 26 August 2016 Accepted date: 20 October 2016 Cite this article as: Salvatore Torrisi, Camilla L. Nord, Nicholas L. Balderston, Jonathan P. Roiser, Christian Grillon and Monique Ernst, Resting State Connectivity of the Human Habenula at Ultra-High Field, NeuroImage, http://dx.doi.org/10.1016/j.neuroimage.2016.10.034 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 Resting State Connectivity of the Human Habenula at Ultra-High Field Salvatore Torrisi1, Camilla L. Nord2, Nicholas L. Balderston1, Jonathan P. Roiser2, Christian Grillon1, Monique Ernst1 Affiliations 1 Section on the Neurobiology of Fear and Anxiety, National Institute of Mental Health, Bethesda, MD 2 Neuroscience and Cognitive Neuropsychiatry group, University of College, London, UK Abstract The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders.
    [Show full text]
  • Lesions in the Bed Nucleus of the Stria Terminalis Disrupt
    Neuroscience 128 (2004) 7–14 LESIONS IN THE BED NUCLEUS OF THE STRIA TERMINALIS DISRUPT CORTICOSTERONE AND FREEZING RESPONSES ELICITED BY A CONTEXTUAL BUT NOT BY A SPECIFIC CUE-CONDITIONED FEAR STIMULUS G. M. SULLIVAN,a* J. APERGIS,b D. E. A. BUSH,b Activation of the hypothalamic–pituitary–adrenal (HPA) L. R. JOHNSON,b M. HOUb AND J. E. LEDOUXb axis, including release of glucocorticoids, is a central com- aDepartment of Psychiatry, Columbia University College of Physicians ponent of the adaptive response to real or anticipated and Surgeons, 1051 Riverside Drive, Unit #41, New York, NY 10032, aversive physical or psychological challenge. Surprisingly USA little is known about the neural circuits by which environ- bCenter for Neural Science, New York University, 4 Washington Place, mental stimuli come to elicit HPA responses. Fear condi- New York, NY 10003, USA tioning, a behavioral model of emotional stress, is poten- tially useful for exploring this issue since the neural path- Abstract —The bed nucleus of the stria terminalis (BNST) is ways by which stimuli initiate fear behaviors and believed to be a critical relay between the central nucleus of associated autonomic responses have been characterized the amygdala (CE) and the paraventricular nucleus of the in detail (LeDoux, 2000; Davis and Whalen, 2001; Maren, hypothalamus in the control of hypothalamic–pituitary– 2001). adrenal (HPA) responses elicited by conditioned fear stimuli. Through fear conditioning an organism learns that a If correct, lesions of CE or BNST should block expression of simple sensory stimulus (a cue), or more complex environ- HPA responses elicited by either a specific conditioned fear mental representation (a context), predicts imminent ad- cue or a conditioned context.
    [Show full text]
  • The Connexions of the Amygdala
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.28.2.137 on 1 April 1965. Downloaded from J. Neurol. Neurosurg. Psychiat., 1965, 28, 137 The connexions of the amygdala W. M. COWAN, G. RAISMAN, AND T. P. S. POWELL From the Department of Human Anatomy, University of Oxford The amygdaloid nuclei have been the subject of con- to what is known of the efferent connexions of the siderable interest in recent years and have been amygdala. studied with a variety of experimental techniques (cf. Gloor, 1960). From the anatomical point of view MATERIAL AND METHODS attention has been paid mainly to the efferent connexions of these nuclei (Adey and Meyer, 1952; The brains of 26 rats in which a variety of stereotactic or Lammers and Lohman, 1957; Hall, 1960; Nauta, surgical lesions had been placed in the diencephalon and and it is now that there basal forebrain areas were used in this study. Following 1961), generally accepted survival periods of five to seven days the animals were are two main efferent pathways from the amygdala, perfused with 10 % formol-saline and after further the well-known stria terminalis and a more diffuse fixation the brains were either embedded in paraffin wax ventral pathway, a component of the longitudinal or sectioned on a freezing microtome. All the brains were association bundle of the amygdala. It has not cut in the coronal plane, and from each a regularly spaced generally been recognized, however, that in studying series was stained, the paraffin sections according to the Protected by copyright. the efferent connexions of the amygdala it is essential original Nauta and Gygax (1951) technique and the frozen first to exclude a contribution to these pathways sections with the conventional Nauta (1957) method.
    [Show full text]
  • Functional Heterogeneity in the Bed Nucleus of the Stria Terminalis
    8038 • The Journal of Neuroscience, August 3, 2016 • 36(31):8038–8049 Dual Perspectives Dual Perspectives Companion Paper: Contributions of the Central Extended Amygdala to Fear and Anxiety, by Alexander J. Shackman and Andrew S. Fox Functional Heterogeneity in the Bed Nucleus of the Stria Terminalis Nur Zeynep Gungor and Denis Pare´ Center for Molecular and Behavioral Neuroscience, Rutgers State University, Newark, New Jersey 07102 Early work stressed the differing involvement of the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST) in the genesis of fear versus anxiety, respectively. In 2009, Walker, Miles, and Davis proposed a model of amygdala-BNST interactions to explain these functional differences. This model became extremely influential and now guides a new wave of studies on the role of BNST in humans. Here, we consider evidence for and against this model, in the process highlighting central principles of BNST organization. This analysis leads us to conclude that BNST’s influence is not limited to the generation of anxiety-like responses to diffuse threats, but that it also shapes the impact of discrete threatening stimuli. It is likely that BNST-CeA interactions are involved in modulating responses to such threats. In addition, whereas current views emphasize the contributions of the anterolateral BNST region in anxiety, accumulating data indicate that the anteromedial and anteroventral regions also play a critical role. The presence of multiple functional subregions within the small volume of BNST raises significant technical obstacles for functional imaging studies in humans. Key words: amygdala; anxiety; BNST; fear Introduction et al., 2003; Xu et al., 2012), and alarm pheromones (Breitfeld In 2009, Walker et al.
    [Show full text]
  • White Matter Tracts - Brain A143 (1)
    WHITE MATTER TRACTS - BRAIN A143 (1) White Matter Tracts Last updated: August 8, 2020 CORTICOSPINAL TRACT .......................................................................................................................... 1 ANATOMY .............................................................................................................................................. 1 FUNCTION ............................................................................................................................................. 1 UNCINATE FASCICULUS ........................................................................................................................... 1 ANATOMY .............................................................................................................................................. 1 DTI PROTOCOL ...................................................................................................................................... 4 FUNCTION .............................................................................................................................................. 4 DEVELOPMENT ....................................................................................................................................... 4 CLINICAL SIGNIFICANCE ........................................................................................................................ 4 ARTICLES ..............................................................................................................................................
    [Show full text]
  • Basic Organization of Projections from the Oval and Fusiform Nuclei of the Bed Nuclei of the Stria Terminalis in Adult Rat Brain
    THE JOURNAL OF COMPARATIVE NEUROLOGY 436:430–455 (2001) Basic Organization of Projections From the Oval and Fusiform Nuclei of the Bed Nuclei of the Stria Terminalis in Adult Rat Brain HONG-WEI DONG,1,2 GORICA D. PETROVICH,3 ALAN G. WATTS,1 AND LARRY W. SWANSON1* 1Neuroscience Program and Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-2520 2Institute of Neuroscience, The Fourth Military Medical University, Xi’an, Shannxi 710032, China 3Department of Psychology, Johns Hopkins University, Baltimore, Maryland 21218 ABSTRACT The organization of axonal projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis (BST) was characterized with the Phaseolus vulgaris-leucoagglutinin (PHAL) anterograde tracing method in adult male rats. Within the BST, the oval nucleus (BSTov) projects very densely to the fusiform nucleus (BSTfu) and also innervates the caudal anterolateral area, anterodorsal area, rhomboid nucleus, and subcommissural zone. Outside the BST, its heaviest inputs are to the caudal substantia innominata and adjacent central amygdalar nucleus, retrorubral area, and lateral parabrachial nucleus. It generates moderate inputs to the caudal nucleus accumbens, parasubthalamic nucleus, and medial and ventrolateral divisions of the periaqueductal gray, and it sends a light input to the anterior parvicellular part of the hypothalamic paraventricular nucleus and nucleus of the solitary tract. The BSTfu displays a much more complex projection pattern. Within the BST, it densely innervates the anterodorsal area, dorsomedial nucleus, and caudal anterolateral area, and it moderately innervates the BSTov, subcommissural zone, and rhomboid nucleus. Outside the BST, the BSTfu provides dense inputs to the nucleus accumbens, caudal substantia innominata and central amygdalar nucleus, thalamic paraventricular nucleus, hypothalamic paraventricular and periventricular nuclei, hypothalamic dorsomedial nucleus, perifornical lateral hypothalamic area, and lateral tegmental nucleus.
    [Show full text]
  • Memory Loss from a Subcortical White Matter Infarct
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.51.6.866 on 1 June 1988. Downloaded from Journal of Neurology, Neurosurgery, and Psychiatry 1988;51:866-869 Short report Memory loss from a subcortical white matter infarct CAROL A KOOISTRA, KENNETH M HEILMAN From the Department ofNeurology, College ofMedicine, University ofFlorida, and the Research Service, Veterans Administration Medical Center, Gainesville, FL, USA SUMMARY Clinical disorders of memory are believed to occur from the dysfunction of either the mesial temporal lobe, the mesial thalamus, or the basal forebrain. Fibre tract damage at the level of the fornix has only inconsistently produced amnesia. A patient is reported who suffered a cerebro- vascular accident involving the posterior limb of the left internal capsule that resulted in a persistent and severe disorder of verbal memory. The inferior extent of the lesion effectively disconnected the mesial thalamus from the amygdala and the frontal cortex by disrupting the ventral amygdalofugal and thalamic-frontal pathways as they course through the diencephalon. This case demonstrates that an isolated lesion may cause memory loss without involvement of traditional structures associated with memory and may explain memory disturbances in other white matter disease such as multiple sclerosis and lacunar state. Protected by copyright. Memory loss is currently believed to reflect grey day of his illness the patient was transferred to Shands matter damage of either the mesial temporal lobe,' -4 Teaching Hospital at the University of Florida for further the mesial or the basal forebrain.'0 l evaluation. thalamus,5-9 Examination at that time showed the patient to be awake, Cerebrovascular accidents resulting in memory dys- alert, attentive and fully oriented.
    [Show full text]
  • Mapping the Populations of Neurotensin Neurons in the Male Mouse Brain T Laura E
    Neuropeptides 76 (2019) 101930 Contents lists available at ScienceDirect Neuropeptides journal homepage: www.elsevier.com/locate/npep Mapping the populations of neurotensin neurons in the male mouse brain T Laura E. Schroeder, Ryan Furdock, Cristina Rivera Quiles, Gizem Kurt, Patricia Perez-Bonilla, ⁎ Angela Garcia, Crystal Colon-Ortiz, Juliette Brown, Raluca Bugescu, Gina M. Leinninger Department of Physiology, Michigan State University, East Lansing, MI 48114, United States ARTICLE INFO ABSTRACT Keywords: Neurotensin (Nts) is a neuropeptide implicated in the regulation of many facets of physiology, including car- Lateral hypothalamus diovascular tone, pain processing, ingestive behaviors, locomotor drive, sleep, addiction and social behaviors. Parabrachial nucleus Yet, there is incomplete understanding about how the various populations of Nts neurons distributed throughout Periaqueductal gray the brain mediate such physiology. This knowledge gap largely stemmed from the inability to simultaneously Central amygdala identify Nts cell bodies and manipulate them in vivo. One means of overcoming this obstacle is to study NtsCre Thalamus mice crossed onto a Cre-inducible green fluorescent reporter line (NtsCre;GFP mice), as these mice permit both Nucleus accumbens Preoptic area visualization and in vivo modulation of specific populations of Nts neurons (using Cre-inducible viral and genetic tools) to reveal their function. Here we provide a comprehensive characterization of the distribution and relative Abbreviation: 12 N, Hypoglossal nucleus;
    [Show full text]
  • Neuropeptide Regulation of Signaling and Behavior in the BNST
    Mol. Cells 2015; 38(1): 1-13 http://dx.doi.org/10.14348/molcells.2015.2261 Molecules and Cells http://molcells.org Established in 1990G Neuropeptide Regulation of Signaling and Behavior in the BNST Thomas L. Kash*, Kristen E. Pleil, Catherine A. Marcinkiewcz, Emily G. Lowery-Gionta, Nicole Crowley, Christopher Mazzone, Jonathan Sugam, J. Andrew Hardaway, and Zoe A. McElligott Recent technical developments have transformed how neu- aversion related behaviors, however there is also evidence that roscientists can probe brain function. What was once it can regulate appetitive responses. Numerous pharmacologi- thought to be difficult and perhaps impossible, stimulating a cal studies targeting different peptide systems as well as single set of long range inputs among many, is now relative- monoaminergic systems have found that the BNST plays a key ly straight-forward using optogenetic approaches. This has role in anxiety. For example, the Davis group has found that provided an avalanche of data demonstrating causal roles CRF in the BNST can potently enhance anxiety (Walker et al., for circuits in a variety of behaviors. However, despite the 2009b) and the Hammack group has found that PACAP signal- critical role that neuropeptide signaling plays in the regula- ing can alter stress responses (Kocho-Schellenberg et al., tion of behavior and physiology of the brain, there have 2014; Lezak et al., 2014a; 2014b). In support of this, recent been remarkably few studies demonstrating how peptide findings from several groups using optogenetic approaches release is causally linked to behaviors. This is likely due to have shown the BNST plays a role in anxiety (Jennings et al., both the different time scale by which peptides act on and 2013a; Kim et al., 2013), however these manuscripts also the modulatory nature of their actions.
    [Show full text]
  • No Slide Title
    Laboratory 11: Cartoons Chiyeko Tsuchitani, Ph.D. NOTE: These illustrations are NOT to be reproduced in the public domain For the visually challenged, cartoons that may help you remember some hypothalamic nuclei and limbic structures. You can study the figures and the review questions in Lab 11 of the Laboratory Guide to learn the connections and functions of these structures.. PS #26 For PS24: Two Cows 1. What is the cow at the left eating? 2. What is hanging off the chin of the cow at the left ? 3. What is forming the chin of the cow at the left? 4. What is hanging over the nose of the cow at the left? 5. What is forming the dark nose of the cow at the right? 6. What is forming the chin of the cow at the right? 7. What is forming the hollow “bump” on the forehead of the cow at the right? 8. Is the thalamus present in this picture? 9. Can you locate the supraoptic and suprachiasmatic nuclei? For PS24: Two Cows 1. The anterior commissure 2. The optic chiasm 3. The preoptic nucleus of the hypothalamus 4. The column of the fornix 5. The postcommissural fornix 6. The anterior nucleus of the hypothalamus 7. The terminal vein 8. The thalamus is not present in this picture. 9. The supraoptic nucleus is above the optic tract (right) and suprachiasmatic nucleus is above the optic chiasm. PS #25 For PS25: Armadillo 1. The nose of the armadillo is what structure? 2. What hypothalamic nucleus forms the snout (above the nose) ? 3.
    [Show full text]
  • 12-1020-Nuttin-Hall #42873B.PPT
    Electrical brain stimulation for treatment-refractory OCD from rat work to FDA and CE approval Bart Nuttin, Loes Gabriëls, Kris van Kuyck, Marleen Welkenhuysen, Laura Luyten, Dimiter Prodanov, Paul Cosyns Electrical brain stimulation in OCD K.U. Leuven : Gabriëls, van Kuyck, Welkenhuysen, Van Huffel, Gligorijevi_, Luyten, Prodanov, Ahmed, Van Laere, Dupont, Sunaert, Demeulemeester, Gybels, Tousseyn, Dewil, Vandenbroeck, Brak, Das, Arckens, Nuttin. Universiteit Antwerpen : Cosyns, Neefs, Vankerckhoven, Cluydts, … Karolinska : Meyerson, Linderoth, Andréewitch, Mindus, Rück, … IMEC : Bartic, Eberle, Musa, Borghs, Verstreken, … Brown University : Friehs, Rasmussen, Greenberg, … Cleveland Clinic : Rezai, Malone, … Köln : Sturm, Klosterkötter, … University of Michigan : Curtis, Abelson, … Orlando : Goodman, Okun, Foot, … Amsterdam – Utrecht : Bosch, Schuurman, … Grenoble : Benabid, … Medtronic Inc. : Mullett, Gielen, Rise, Stypulkowski, Langevin, … Disclosure • Medtronic is providing grants for research, education and traveling • Patent : DBS in OCD • Grants : OT, FWO, IWT, SBO No stimulation With stimulation Surgery medio-dorsal nucleus bed nucleus of stria terminalis (BST) of the thalamus (MD) • v nucleus accumbens (NACC) DESIGN ! ! ! ! ! ! NACC BST MD SHAM 0.1, 0.2, 0.3, 0.4, 0.5mA 2, 100Hz + stimulation off Kris van Kuyck et al. Kris van Kuyck et al. Electrical stimulation • Study protocol – Approved by the local hospital ethics committees – In accordance with Helsinki Declaration of 1975 (revision 1983) • Committee for neurosurgery for
    [Show full text]
  • Brain Regions Associated with the Expression and Contextual Regulation of Anxiety in Primates Ned H
    Brain Regions Associated with the Expression and Contextual Regulation of Anxiety in Primates Ned H. Kalin, Steven E. Shelton, Andrew S. Fox, Terrence R. Oakes, and Richard J. Davidson Background: A key to successful adaptation is the ability to regulate emotional responses in relation to changing environmental demands or contexts. Methods: High-resolution PET 18fluoro-deoxyglucose (FDG) scanning in rhesus monkeys was performed during two contexts (alone, and human intruder with no eye contact) during which the duration of anxiety related freezing behavior was assessed. Correlations between individual differences in freezing duration and brain activity were performed for each of the two conditions, as well as for the contextual regulation between the two conditions. Results: In both conditions, activity in the basal forebrain, including the bed nucleus of the stria terminalis and the nucleus accumbens were correlated with individual differences in freezing duration. In contrast, individual differences in the ability to regulate freezing behavior between contexts were correlated with activity in the dorsal anterior cingulate cortex, the thalamus and the dorsal raphe nucleus. Conclusions: These findings demonstrate differences in the neural circuitry mediating the expression compared to the contextual regulation of freezing behavior. These findings are relevant since altered regulatory processes may underlie anxiety disorders. Key Words: Anxiety, freezing, PET, monkey, emotion, regulation into a novel environment. Initially, monkeys display some freez- ing which functions to decrease the chances of detection by a he adaptive expression of emotion relates to the ability to potential predator. Once the monkey establishes that in the ALN regulate emotional responses as environmental or contex- environment there is no real predatorial threat, it locomotes and tual demands change (Kalin and Shelton 1989; Davidson emits coo calls.
    [Show full text]