Neuroscience in the 21st Century

Donald W. Pfaff Editor

Neuroscience in the 21st Century

From Basic to Clinical

With 1059 Figures and 71 Tables Editor Donald W. Pfaff Laboratory of Neurobiology and Behavior The Rockefeller University New York, NY, USA

ISBN 978-1-4614-1996-9 ISBN 978-1-4614-1997-6 (eBook) DOI 10.1007/978-1-4614-1997-6 ISBN 978-1-4614-1998-3 (print and electronic bundle) Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2012945545

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Springer is part of Springer ScienceþBusiness Media (www.springer.com) Preface

The primary purpose of this project has been to produce a comprehensive, elec- tronic introduction to current-day neuroscience in a didactic form useful for upper- level premedical students, entering medical students, and graduate students in a wide variety of countries. The Supervisory Editors and the authors, in their international distribution, reflect our intention to recognize the growing interest in neuroscience and expertise in neuroscientific research across the world.

Neuroscience Addresses Medical and Public Health Problems Worldwide

Neuroscience research provides basic discoveries about how the works and about how the brain controls behavior. These discoveries are then applied for the good of humankind. Neuroscience, broadly defined, also offers pivotal components of both medical education and the delivery of medical services. For example, depression and schizophrenia – once viewed as purely “behavioral” problems – are now candidates for neurochemical/neuropharmacological treatments. Degener- ative conditions such as neurosyphilis, HIV-associated dementia, and Alzheimer’s can now be delayed by science-based treatments. Coma and persistent vegetative state are approached by manipulating brain mechanisms responsible for arousal. Indeed, as neuroscience explores the etiology of disease – the complex interplay between biological, psychological, and sociocultural factors – it is increasingly valuable in understanding an array of diseases. A recent report by the Surgeon General, in the United States, cites several such diseases: schizophrenia, bipolar disorder, early onset depression, autism, attention deficit/hyperactivity disorder, anorexia nervosa, substance abuse disorders, and panic disorder, among many others. The Surgeon General states that in the USA, the 1-year prevalence rate for mental illness is about 21%. The figure was derived by synthesizing two major studies indicating that within a 1-year period this percentage of the adult popu- lation has a diagnosable mental disorder based on “reliable, established criteria.” Based on 2010 census figures, this means that over 45 million individuals are affected. Moreover, the Surgeon General indicates that almost half these individ- uals – 9% of US adults – experience some significant functional impairment.

v vi Preface

A subpopulation of 5.4% of adults have a “serious” mental illness that interferes with some area of social functioning. Most distressingly, none of these huge figures even included the approximately 20% of children and adolescents estimated to have mental disorders with at least mild functional impairment, or the 5–9% who suffer “serious emotional distur- bance.” Adults aged 55 years and older are another subpopulation. Though not as extensively documented, the Surgeon General cites figures indicating that almost 20% have some diagnosable mental disorder during a 1-year period and that almost 4% have a serious mental illness. Various reports from the World Health Organization (WHO) demonstrate that mental health problems in the USA are mirrored in other countries, often in an extreme form because there is less help available. Here are some of the findings: • Mental, neurological, and behavioral disorders are common to all countries and cause immense suffering. People with these disorders are often subjected to social isolation, poor quality of life, and increased mortality. These disorders are the cause of staggering economic and social costs. That is, because mental disorders often strike early, their total economic cost to society is almost as large as all other illnesses combined. • Hundreds of millions of people worldwide are affected by mental, behavioral, neurological, and substance abuse disorders. For example, estimates made by WHO in 2002 showed that 154 million people globally suffer from depression and 25 million people from schizophrenia; 91 million people are affected by alcohol abuse disorders and 15 million by drug abuse disorders. A recently published WHO report shows that 50 million people suffer from epilepsy and 24 million from Alzheimer and other dementias. • In addition to the above figures, many other disorders affect the nervous system or produce neurological sequelae. Projections based on a WHO study show that worldwide in 2005, 326 million people suffered from migraine, 61 million from cerebrovascular diseases, and 18 million from nervous system infections or neurological sequelae of infections. The number of people with neurological sequelae of nutritional disorders and neuropathies (352 million) and neurolog- ical sequelae secondary to injuries (170 million) also add substantially to the above burden. Uncounted are the large number of people who suffer from chronic pain. • About 877,000 people die every year by committing suicide. In at least two thirds of these cases, a treatable mental illness is deemed to be causal. • One in four patients visiting a health service has at least one mental, neurolog- ical, or behavioral disorder, but most of these disorders are neither diagnosed nor treated. • Mental illnesses affect and are affected by chronic conditions such as cancer, heart, and cardiovascular diseases; diabetes, and HIV/AIDS. Untreated, they bring about unhealthy behavior, noncompliance with prescribed medical regi- mens, diminished immune functioning, and poor prognosis. Some common disorders, such as lung cancer, are the consequences of mental disorders (in this case, nicotine addiction). Preface vii

• Cost-effective treatments exist for most disorders and, if correctly applied, could enable most of those affected to become functioning members of society. • Barriers to effective treatment of mental illness and substance abuse disorders include lack of recognition of the seriousness of mental illness and lack of understanding about the benefits of services. Policy makers, insurance compa- nies, health and labor policies, and the public at large – all discriminate between physical and mental problems. • Most middle- and low-income countries devote less than 1% of their health expenditure to mental health. There are as many as 200 times more psychiatric workers in high- as opposed to low-income countries. Consequently, mental and behavioral health policies, legislation, community care facilities, and treatments for people with mental illness are not given the priority they deserve. • War and other disasters have a major influence on mental health and psychoso- cial well-being. Rates of mental health disorder tend to double after emergencies.

Further Reading In addition to our text, we recommend the following. For material on the molecular events that occasion the development of primitive cells into , we recommend the writings by Ali Hemmati-Brivanlou; for information regarding the genetic guidance of neuronal developmental processes, we recommend to consult papers by Marc Tessier-Lavigne and by Sarah Guthrie. Also, see Part VIII in the Kandel text referenced below, chapters by Thomas Jessell and Joshua Sanes, and the several chapters on CNS development in the Squire text, mentioned below. For comprehensive coverage of the visceral motor system, students can consult the Purves text, referenced above, Chapter 21. For more coverage of mechanisms of reward, please consult the Squire et al text, Chapter 43. For systematic coverage of attention, please see the Squire text, referenced above, Chapter 48. For a treatment of the mechanisms underlying language, please consult the Kandel text, Chapter 60, and the Purves text, Chapter 27. Treatments of addictive disorders in other texts include Chapter 49 in the Kandel text, referenced above, and Chapter 42 in the Squire et al text.

Early support for the ideas underlying this project came through letters expressing clear understanding and encouragement from the Society for Neurosci- ence (the President, and the Chair of the Education Committee), the Federation of European Neuroscience Societies (FENS), the Japanese Neuroscience Society, the Indian Academy of Neuroscience, from UNESCO, from the International Brain Research Organization (IBRO, whose regional offices will assist with dissemina- tion of the text), from the Director of the Earth Institute, Jeffrey D. Sachs (Professor of Sustainable Development, Columbia University), from the American expert on education Professor Howard Gardner (Harvard University), and from the Chinese Academy of Sciences (three Members are among our Editors). viii Preface

Insofar as professors in developing countries want to use this text as part of their efforts to launch neuroscience programs, they might want to see the Appendix by Richard Brown (Dalhousie University, Canada), a paper that gives tips about developing such programs. In addition, a few authors have supplied videos to let students in developing countries know how these authors became interested in neuroscience and to give an idea of what their laboratories look like. Finally, I consider this large volume to comprise a “feeder text” for other, more detailed treatments such as those edited by Eric Kandel et al. (“Principles of Neural Science, 5th edition, McGraw-Hill), Larry Squire et al. (“Fundamental Neurosci- ence”, 3rd edition, Elsevier), and Dale Purves et al. (“Neuroscience”, 4th edition, Sinauer). At spots in the current text where I feel bereft, I have referred to specific chapters in one or more of these texts in order to make up for the deficit. I gratefully acknowledge financial support from the Nour, Moos, and New York NeuroScience Foundations and from Pfizer, Inc. All authors and editors agreed to do their work without compensation. This entire project benefitted from the wise counsel and foresight of the Neuroscience editor at Springer, Ann Avouris. With a high level of skill, Ann has encouraged and guided this project from its inception to its completion. Special thanks to the International Brain Research Organization (Pierre Magistretti, Secretary-General) for assisting the free interna- tional distribution of this text, in electronic form, to universities in developing countries.

New York, NY Donald W. Pfaff About this Book

Biophysics The capacity of the to absorb and use information from the physical sciences is increasing every year, with the techniques of the physical sciences adding to the rigor and depth of current neuroscientific work. In some of the chapters below, we have had to pick examples from complex fields, as the numbers of topics (e.g. potassium channels) are too large to cover individually. Our authors are experts. For example, Roger Papke has described unique properties of certain nicotinic acetylcholine receptors and Ramon Latorre, based in Chile, is also a member of the US National Academy of Sciences.

Development Molecular and genetic approaches are most easily applied to development of the nervous system. We expect this area of neuroscience to continue to grow explosively.

Cell Biology of Neurons and Glia Two of the most unique features of the central nervous system are the arrangement of neuronal processes in space (neuroanatomy) and the presence of electrically excitable cells (biophysics). Rather than trying to subsume an entire text of neuro- , we have emphasized those aspects of neuroanatomy which essentially comprise subjects in the field of cell biology. Among our authors, Anthony Brown is an axonal transport expert, Roberto Araya has demonstrated that dendritic spines can act as electrical compartments, and Helmut Kettenmann has taken leadership positions in European Neuroscience. Rae Silver and her team discovered mast cells in the brain, while Robert Dantzer is a leading scholar in psychoneuroimmunology.

Sensory Systems (Neuroanatomy and ) Two modalities of sensory signaling are given extra attention here: vision, because of its plentiful and strong history of work, and pain, because of its prevalence in clinical settings. Pain is treated here as a ‘basic neuroscience’ subject, but clearly is also important for the clinical topics below. Ji-Sheng Han, Chinese Academy of Sciences, is a world renowned expert in the regulation of pain. Christine Petit, is Professor, College de France and Institut Pasteur, French Academy of Sciences, and

ix x About this Book is a world leader in sensory disorders and hearing molecular physiology and pathophysiology, having won the 2006 Louis-Jeantet Prize for Medicine. Katherine Cullen is William Dawson Chair in Neurophysiology, McGill University, and an Associate Editor for the Journal of Neurophysiology. And a world leader in taste physiology, Linda Bartoshuk, is a member of the US National Academy of Sciences and past-president of the Association for Chemo- reception Sciences and of the Association for Psychological Science.

Motor Control Starting with the work of the great, Nobel Prize winning physiologist Sir Charles Sherrington, the nervous system’s control over muscle contraction has provided the most fundamental analyses of CNS function. The cerebellum and basal ganglia are so important that they are treated at two different levels. Among our authors, Robert Burke and Elzbieta Jankowska have world-wide reputations for their superb contributions to the neurophysiology of motor control.

Neurophysiology of Other, Specific CNS Regions and Networks Among the topics that fall outside straightforward sensory and motor functions, we have included the following. Among our authors, Larry Swanson is widely recog- nized as a foremost neuroanatomist, Ruud Buijs has done the most to put forebrain nerve cell biology in the context of whole-body physiological requirements, while Morten Kringelbach is a widely admired forebrain neuroanatomist. Greg Funk has contributed to our understanding of glutamatergic signaling for central respiratory control and is the Triennial Gold Medal. Recipient, Physiological Society of New Zealand for outstanding contributions to physiological research.

Neurochemistry, Neuropharmacology There is an amazing variety of chemical reactions specific to the nervous system that are crucial for regulating CNS performance. The aim in the following chapters is to (a) state some general principles; and (b) give specific examples (e.g. the hypothalamic nonapeptides and opioid peptides). Lakshmi Devi and Lloyd Fricker cover the basic topics in a systematic and didactic fashion, appropriate for medical students and graduate students. The expert in brain energy supplies, Pierre Magistretti, has become Secretary-General of the International Brain Research Organization (IBRO).

Neuroendocrinology Several chapters will cover the brain’s control over pituitary and, in turn, effects on brain and behavior. Marc Freeman’s long and strong career on hypothalamic control of the pituitary is widely admired. Cheryl Sisk has made multiple discoveries in the timing of hormone effects on the brain during develop- ment, while Joel Elmquist is a world leader in the analysis of the brain’s regulation of feeding. About this Book xi

Regulation of Natural Behaviors Far from covering all the natural behaviors that might be considered, we have included only a few, large domains of behavioral states that have received intense study with respect to their mechanisms. Gert Holstege (Groningen) has made breakthrough discoveries about brain activity during emotional excitement, while Ron de Kloet (Leiden) and Marian Joels (Utrecht) are world leaders in neurochem- ical mechanisms related to stress. Ralph Adolphs has combined sophisticated neuroanatomy with discriminating experimental design in the analysis of how the amygdala regulates social behaviors in humans.

Cognitive Neuroscience Studies of cognitive functions and learned behaviors involve the types of mecha- nisms covered above and, in addition, involve regulated changes in CNS perfor- mance according to the environment and schedules of reinforcement. Richard Morris is perhaps the best known contributor to methodologies for studying learn- ing,notably the “Morris Water Maze”, while Paul Luiten and his team have shown progressive deterioration of brain microvessels during aging.

Computational Neuroscience Neural information is encoded in the timing of neuronal activity across a network. Computational neuroscience attempts to decode this information. William Lytton is the author of an authoritative text on the subject, a rapidly emerging area that joins neuroscience with computer science.

Developmental Disorders While not aiming to be a complete neurology text, it is important to provide some ideas about the applications of modern neurobiology to clinical syndromes of great importance. Three criteria influenced our choices of topics: (i.) that the disorder has some estimable degree of prevalence; (ii.) that it relates to an interesting area of neuroscience; and (iii.) that we can cover it better than in other texts. As mentioned above, genetic modifications that cause brain pathol- ogies are most sensitively detected in the cases of developmental disorders. Among our authors, Merlin Butler’s work led to the discovery of genomic imprinting as the cause of Prader-Willi syndrome. Catherine Barthe´le´my has an international reputation for her work as a clinician dealing with children having autism spectrum disorders.

Systems Disorders Damage or dysfunction of networks in the brain can have severe consequences on behavior. We include some prevalent forms of system disorders. Among our authors, Michal Schwartz has made discoveries concerning the role of immune cells in ameliorating effects of spinal cord damage; while Steven Laureys and his team have made startling observations about brain activity in vegetative state patients. xii About this Book

Pain Four topics on pain are included in the basic neuroscience section, above. Three essentially important clinical subjects are treated here. John Brust has, literally, “written the book” on headache, while Richard Bodnar has made career-long contributions on the neurophysiology and neurochemistry of pain suppression.

Neuroimmune Disorders Some neural/immune interactions have disastrous consequences. Socrates Tzartos has determined the pathogenic role of autoantibodies against the main immuno- genic region of the acetylcholine receptor in myasthenia gravis.

Addictive Disorders Addictions pose tremendous threats to public health and can impact entire commu- nities. Addiction to heroin is discussed above, in the chapter on opioid peptides.

Degenerative Diseases Progressive deterioration of the nervous system can impair many systems concur- rently. These diseases are distinct from developmental disorders and infectious diseases. Kay Double has contributed novel insights into the vulnerability of the degenerating neurons in Parkinson’s disease while John Finberg is a co-inventor of the Parkinson medication rasagiline. Aldrin Molero and Mark Mehler’s demonstra- tion of Huntington’s-related alterations in the development of striatal cells suggest novel mechanistic links between development and aging in the brain.

Gender Identity Sexual differentiation of the human brain is treated here in both its basic neuroen- docrine (above) and its clinical aspects. Dick Swaab’s team in has led world in analyzing of hormone dependent and gender depen- dent neuroanatomical and histochemical features of the human brain.

Psychiatric Disorders The World Health Organization charts the large number of people disabled by various psychiatric disorders. These disorders are, in some cases, closely linked to the basic science chapters involving regulation of natural behavior. Helen Mayberg and her team have made a startling rate of progress in linking human anterior cortex neuronal activity to depression. Andreas Meyer-Lindenberg, working both at NIH in Betheda, Maryland and in Germany, has made breakthroughs in identifying brain mechanisms of risk factors for schizophrenia. Editor-in-Chief

Donald W. Pfaff Professor and Head of Laboratory, Neurobiology and Behavior The Rockefeller University 1230 York Avenue New York, NY 10065 USA

Managing Editors

Eugene Martin The Rockefeller University

Eben Pariser The Rockefeller University

xiii

Supervisory Editors

Andrea Ballabio Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy Francisco Bezanilla Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA Pierre Chambon Institute for Genetics and Cellular and Molecular Biology in Strasbourg, Illkirch, Strasbourg, France B. N. Dhawan Indian National Science Academy, Lucknow, India Richard Faull School of Medical Sciences, University of Auckland, Auckland, New Zealand Eberhard Fuchs Medical School, University of Goettingen, Gottingen,€ Germany Detlev Ganten Department of Pharmacology, University of Heidelberg, Heidelberg, Germany Jisheng Han Department of Neurobiology, Director of the Neuroscience Institute, Peking University, , Tomas Hokfelt Department of Neuroscience, Karolinska Institutet, , Sweden Nancy Ip Hong Kong University, Kowloon, Hong Kong, China Tadashi Isa National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan Reinhard Jahn Department of Neurobiology, Max-Planck Institute for Biophysical Chemistry, Goettingen, Germany E. Barry Keverne Department of Animal Behaviour, University of Cambridge, Cambridge, UK Stephen Laureys Medical School, University of Liege, Lie`ge, Belgium Andrew Lumsden MRC Centre for Developmental Neurobiology, King’s College London, London, England

xv xvi Supervisory Editors

Michel Le Moal 3INSERM, U862, Neurocentre Magendie Neurogenesis and Physiopathology Group, Bordeaux, France Andreas Meyer-Lindenberg Professor of Psychiatry and Psychotherapy, Central Institute of Mental Health, J5, University of Heidelberg, Mannheim, Germany Till Roenneberg Department of Medical Psychology, Institute of Medical Psychology, Ludwig-Maximilians-University, , Germany Yasuo Sakuma Professor and Chair of Physiology, Nippon Medical School, Bunkyo, Tokyo, Japan Mriganka Sur Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA Dick F. Swaab Professor of Neurobiology, Institute for Neuroscience, Amsterdam, Netherlands Ryosuke Takahashi Department of Neurology, School of Medicine, University of Kyoto, Sakyo-ku, Kyoto, Japan Xiong-Li Yang Institute of Neurobiology, Fudan University, Shanghai, China Contents

Volume 1

Section 1 Basic Neuroscience ...... 1

Part 1 Biophysics ...... 3

1 Water, Ions, Membranes, Pumps, and Transporters ...... 5 Roger L. Papke 2 Voltage-Gated Ion Channels ...... 29 Lori Isom, Gustavo Patino, Luis Lopez-Santiago, and Yukun Yuan 3 Ionotropic Glutamate Receptors ...... 59 Rolf Sprengel 4 Signal Transduction–Dependent Channels ...... 81 Ramon Latorre, Carlos Gonza´lez, and Patricio Rojas 5 Membrane Potentials ...... 109 Stewart Hendry

Part 2 Development ...... 135

6 Stem Cells: Neural Stem Cells in Cerebral Cortex Development ...... 137 Felipe Mora-Bermu´dez, Miguel Turrero Garcı´a, and Wieland B. Huttner 7 Adult Neurogenesis ...... 161 Gerd Kempermann 8 Dendrites: A Key Structural Element of Neurons ...... 179 Astrid Rollenhagen and Joachim H. R. Lubke€

Part 3 Cell Biology of Neurons and Glia ...... 219

9 Dendritic Function ...... 221 Roberto Araya

xvii xviii Contents

10 Axonal Transport ...... 255 Anthony Brown 11 Cell Biology of the Synapse ...... 309 Rochelle S. Cohen 12 Molecular Regulation of Synaptic Release ...... 351 Reinhard Jahn and Janina Boyken 13 The Postsynaptic Density ...... 403 Rochelle S. Cohen 14 Gap Junctions, Electric Synapses ...... 439 Rolf Dermietzel and David C. Spray 15 Glial Cells ...... 475 Helmut Kettenmann and Alex Verkhratsky 16 Immune System Cells ...... 507 Katherine Nautiyal 17 Psychoneuroimmune Phenomena: Neuroimmune Interactions . . . 527 Robert Dantzer and Keith W. Kelley

Volume 2

Part 4 Sensory Systems (Neuroanatomy and Physiology) ...... 555

18 Retina: Neuroanatomy and Physiology ...... 557 Andreas Reichenbach and Andreas Bringmann 19 The Superior Colliculus and Visual Thalamus ...... 629 Barry E. Stein, Terrence R. Stanford, Dwayne W. Godwin, and John G. McHaffie 20 Cortical Processing of Visual Signals ...... 655 Caitlin Williams Kiley and W. Martin Usrey 21 Audition: Hearing and Deafness ...... 675 Christine Petit, Aziz El-Amraoui, and Paul Avan 22 Somatosensation: End Organs for Tactile Sensation ...... 743 Nieves Martı´n-Alguacil, Ignacio de Gaspar, Justine M. Schober, and Donald W. Pfaff 23 Taste ...... 781 Linda M. Bartoshuk and Derek J. Snyder 24 Olfaction ...... 815 Julie Bakker Contents xix

25 Visuomotor Integration ...... 839 Kathleen E. Cullen 26 Vestibular Inputs: The Vestibular System ...... 883 Jay M. Goldberg 27 Kinesthetic Inputs ...... 931 Janet L. Taylor 28 Pain ...... 965 Jun Chen, Ji-Sheng Han, Zhi-Qi Zhao, Feng Wei, Jen-Chuen Hsieh, Lan Bao, Andrew CN Chen, Yi Dai, Bi-Fa Fan, Jian-Guo Gu, Shuang-Lin Hao, San-Jue Hu, Yong-Hua Ji, Yong-Jie Li, Yun-Qing Li, Qing Lin, Xian-Guo Liu, Yan-Qing Liu, Yan Lu, Fei Luo, Chao Ma, Yun-Hai Qiu, Zhi-Ren Rao, Lin Shi, Bai-Chuang Shyu, Xue-Jun Song, Jing-Shi Tang, Yuan-Xiang Tao, You Wan, Jia-Shuang Wang, Ke-Wei Wang, Yun Wang, Guang-Yin Xu, Tian-Le Xu, Hao-Jun You, Long-Chuan Yu, Sheng-Yuan Yu, Da-Ying Zhang, De-Ren Zhang, Jun-Ming Zhang, Xu Zhang, Yu-Qiu Zhang, and Min Zhuo

Part 5 Motor Control ...... 1025

29 Spinal Motoneurons ...... 1027 Robert Burke 30 Spinal Interneurons ...... 1063 Elzbieta Jankowska 31 Systems Descending from the Brainstem: Basic Principles ...... 1101 R. Chris Miall 32 Systems Descending from the Brainstem: Functional Recovery Following Damage ...... 1115 Tadashi Isa 33 Basal Ganglia: Basic Principles ...... 1127 R. Chris Miall 34 Dystonia ...... 1143 Atsushi Nambu 35 Cerebellum: Anatomy and Function ...... 1149 R. Chris Miall 36 The Cerebellum: Eye Movements ...... 1169 Mario Prsa and Peter Thier 37 Cortical Motor Control ...... 1187 R. Chris Miall xx Contents

38 Locomotion: Circuits and Physiology ...... 1209 Ole Kiehn and Kimberly Dougherty 39 Posture ...... 1237 R. Chris Miall

Volume 3

Part 6 Neurophysiology of Other, Specific CNS Regions and Networks ...... 1253

40 Basic Principles of Nervous System Organization ...... 1255 Larry W. Swanson 41 Frontal Cortex ...... 1289 Helen Barbas 42 Limbic Forebrain: The Functional Neuroanatomy of Emotion and Hedonic Processing ...... 1335 Morten L. Kringelbach 43 ...... 1365 Andries Kalsbeek and Eric Fliers 44 Autonomic Nervous Systems ...... 1407 Ruud Buijs 45 Respiration ...... 1423 John J. Greer and Gregory D. Funk 46 Spinal Reflexes ...... 1463 Elzbieta Jankowska

Part 7 Neurochemistry, Neuropharmacology ...... 1485

47 Transmitters and Peptides: Basic Principles ...... 1487 Lakshmi A. Devi and Lloyd D. Fricker 48 Transmitter and Peptide Receptors: Basic Principles ...... 1505 Lakshmi A. Devi and Lloyd D. Fricker 49 Opioid Peptides ...... 1525 Ryszard Przewlocki 50 Trophic Factors: Neurotrophic Factors ...... 1555 Eero Castre´n 51 Brain Energy Metabolism ...... 1591 Pierre J. Magistretti and Igor Allaman 52 Blood Brain Barrier ...... 1621 Rebecca Leshan, Teresa Milner, and Donald W. Pfaff Contents xxi

Part 8 Neuroendocrinology ...... 1631

53 Brain Control Over Pituitary Gland Hormones ...... 1633 Arturo E. Gonzalez-Iglesias and Marc E. Freeman 54 Hormone Effects on Behavior ...... 1683 Yoav Litvin and Donald W. Pfaff 55 Critical Periods During Development: Hormonal Influences on Neurobehavioral Transitions Across the Life Span ...... 1715 Cheryl Sisk, Joseph S. Lonstein, and Andrea C. Gore 56 Mechanisms of Homeostatically Regulated Behaviors ...... 1753 Joel K. Elmquist, Jeffrey M. Zigman, and Clifford B. Saper 57 Mechanisms of Behaviors Related to Reproduction ...... 1783 Yasuo Sakuma 58 Seasonal Rhythms in Behavior ...... 1795 Zachary M. Weil and Randy J. Nelson

Volume 4

Part 9 Regulation of Natural Behaviors ...... 1811

59 Circadian Physiology ...... 1813 Horst-Werner Korf and Charlotte von Gall 60 The Suprachiasmatic Nucleus and the Circadian Timekeeping System of the Body ...... 1847 Rae Silver and Megan Rainbow 61 Sleep Regulation and Insomnia ...... 1889 Eus van Someren and Raymond Cluydts 62 Genomic Imprinting and Brain Function ...... 1917 Anthony R. Isles 63 Epigenetic Mechanisms: DNA Methylation and Histone Protein Modification ...... 1939 Khatuna Gagnidze and Donald W. Pfaff 64 Stress Research: Past, Present, and Future ...... 1979 E. R. (Ron) de Kloet and Marian Joe¨ls 65 Fear ...... 2009 Gregory J. Quirk 66 Aggression ...... 2027 Jaap Koolhaas xxii Contents

67 Emotions Studied by Imaging of the Human Brain: The Somatic and Emotional Motor Systems ...... 2045 Gert Holstege and Hieu K. Huynh 68 Parental Behavior ...... 2069 Gabriela Gonza´lez-Mariscal and Angel I. Melo 69 Sexual Behavior ...... 2101 Joseph J. Normandin, Donald W. Pfaff, and Anne Z. Murphy 70 Social Behavior ...... 2115 Ralph Adolphs and Michael Spezio

Part 10 Cognitive Neuroscience ...... 2145

71 Elementary CNS Arousal ...... 2147 Eugene M. Martin and Donald W. Pfaff 72 Neurobiology of Learning and Memory ...... 2173 Richard Morris 73 Cognitive Functions as Revealed by Imaging of the Human Brain ...... 2213 Rene San Martin and Scott A. Huettel 74 Aging of the Brain ...... 2239 Paul Luiten, Csaba Nyakas, Ulrich Eisel, and Eddy van der Zee

Part 11 Computational Neuroscience ...... 2273

75 Computational Neuroscience of Synapses and Neurons ...... 2275 William W. Lytton and Cliff C. Kerr 76 Computational Neuroscience of Neuronal Networks ...... 2301 Samuel A. Neymotin, AnnMary Mathew, Cliff C. Kerr, and William W. Lytton 77 Biological Modeling ...... 2333 George Reeke

Volume 5

Section 2 Clinical Neuroscience ...... 2355

Part 12 Developmental Disorders ...... 2357

78 Prader-Willi and Angelman Syndromes ...... 2359 Merlin G. Butler Contents xxiii

79 Fragile X–Associated Disorders ...... 2391 Jacky Au and Randi Hagerman 80 Fetal Alcohol Syndrome ...... 2411 Piyadasa Kodituwakku and E. Louise Kodituwakku 81 Autism ...... 2431 Catherine Barthe´le´my and Fre´de´rique Bonnet-Brilhault 82 Anorexia Nervosa and Bulimia ...... 2445 Tom Hildebrandt

Part 13 Systems Disorders ...... 2471

83 Sleep Disorders ...... 2473 Michael Thorpy and Chi George Zhao 84 Traumatic Brain Damage ...... 2499 Steven Laureys 85 Spinal Cord Damage ...... 2529 Michal Schwartz 86 Ischemic Stroke: Basic Pathophysiology and Clinical Implication ...... 2543 Philipp Mergenthaler, Ulrich Dirnagl, and Alexander Kunz

Part 14 Pain ...... 2565

87 Non-migrainous Headache ...... 2567 John C. M. Brust 88 Migraine ...... 2581 Peter J. Goadsby 89 Central Mechanisms of Pain Suppression ...... 2595 Richard Bodnar and Mary M. Heinricher

Part 15 Neuroimmune Disorders ...... 2621

90 ...... 2623 Samuel K. Ludwin, Jack Antel, and Douglas L. Arnold 91 Myasthenia Gravis ...... 2667 Konstantinos Lazaridis and Socrates Tzartos

92 Infections of the Nervous System ...... 2701 Krister Kristensson, Martin Rottenberg, and Marina Bentivoglio xxiv Contents

Part 16 Addictive Disorders ...... 2729

93 Psychostimulants and Addiction ...... 2731 Luigi Pulvirenti, Michel Le Moal, and George F. Koob

94 Neurobiology of Alcohol Addiction ...... 2745 Rainer Spanagel, Mathias Zink, and Wolfgang H. Sommer

95 Internet Addiction ...... 2775 Daniel T. L. Shek, Rachel C. F. Sun, and Lu Yu

96 Abuse of Performance-Enhancing Drugs ...... 2813 Tom Hildebrandt

97 Food Addiction ...... 2833 Serge H. Ahmed, Nicole M. Avena, Kent C. Berridge, Ashley N. Gearhardt, and Karine Guillem

Part 17 Degenerative Diseases ...... 2859

98 Motor Disease: Amyotrophic Lateral Sclerosis ...... 2861 P. Nigel Leigh, Jemeen Sreedharan, and Lokesh Wijesekera

99 Parkinson’s Disease ...... 2903 Kay Double and John Finberg

100 Huntington’s Disease ...... 2923 Aldrin Molero and Mark F. Mehler

101 Problems During Aging (Alzheimer’s and Others) ...... 2953 Thomas A. Bayer, Sadim Jawhar, Jessica L. Wittnam, and Oliver Wirths

Part 18 Gender Identity ...... 2971

102 Sexual Differentiation of the Human Brain in Relation to Gender-Identity, , and Neuropsychiatric Disorders ...... 2973 Dick Swaab and Ai-Min Bao

Part 19 Psychiatric Disorders ...... 2999

103 Depressive Disorders ...... 3001 Charles F. Gillespie and Helen S. Mayberg

104 The Neurobiology of Bipolar Disorder ...... 3017 Andrea Levinson and Trevor Young Contents xxv

105 Schizophrenia ...... 3037 Andreas Meyer-Lindenberg Appendix: Seven Steps to Setting Up a Neuroscience Program in a Developing Country ...... 3059 Richard E. Brown Index ...... 3087

List of Contributors

Ralph Adolphs Division of Humanities and Social Science, California Institute of Technology, Pasadena, CA, USA Serge H. Ahmed Institut des Maladies Neurode´ge´ne´ratives, University Bordeaux- Segalen Centre National de la Recherche Scientifique, Bordeaux, CNRS-UMR 529, France Igor Allaman Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fe´de´rale de Lausanne (EPFL), Lausanne, Switzerland Jack Antel Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada Roberto Araya Faculty of Medicine/Department of Physiology, University of Montreal, Montreal, QC, Canada Douglas L. Arnold Montreal Neurological Institute and Hospital, McGill Univer- sity, Montreal, QC, Canada Jacky Au Department of Pediatrics, University of California-Davis Medical Cen- ter M.I.N.D.-Institute, Sacramento, CA, USA Paul Avan Faculte´ de Me´decine, Universite´ d’Auvergne, Biophysique Neurosen- sorielle INSERM UMR 1107, Clermont-Ferrand, France Nicole M. Avena Department of Psychiatry, University of Florida College of Medicine, McKnight Brain Institute, Gainesville, FL, USA Julie Bakker University of Lie`ge, Lie`ge, Belgium Ai-Min Bao Department of Neurobiology, School of Medi- cine, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang, , China Lan Bao State Key Laboratory of Cell Biology Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China Helen Barbas Department of Health Sciences, Boston University, Boston, MA, USA

xxvii xxviii List of Contributors

Catherine Barthe´le´my Center of Child and Adolescent Psychiatry, University Hospital, Universite´ Franc¸ois Rabelais de Tours, UMR Inserm U930, 37044 Tours cedex 9, France Linda M. Bartoshuk Community Dentistry and Behavioral Sciences, University of Florida, Gainesville, FL, USA Thomas A. Bayer Division of Molecular Psychiatry, Department for Psychiatry, University Medicine Goettingen, Gottingen,€ Germany Marina Bentivoglio Department of Neurological, Neuropsychological, Morpho- logical and Motor Sciences, University of Verona, Verona, Italy Kent C. Berridge Department of Psychology, University of Michigan, Ann Arbor, MI, USA Richard Bodnar Department of Psychology and Neuropsychology, Queens College City University of New York, Flushing, NY, USA Fre´de´rique Bonnet-Brilhault Center of Child and Adolescent Psychiatry, Uni- versity Hospital, Universite´ Franc¸ois Rabelais de Tours, UMR Inserm U930, 37044 Tours cedex 9, France Janina Boyken Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Gottingen,€ Germany Andreas Bringmann Department of Ophthalmology and Eye Hospital, Univer- sity of Leipzig, Leipzig, Germany Anthony Brown Department of Neuroscience, The Ohio State University, Colum- bus, OH, USA John C. M. Brust Department of Neurology, Columbia University College of Physicians & Surgeons, New York, NY, USA Ruud Buijs Instituto de Investigaciones Biomedicas, Universidad Nacional Auto´noma de Me´xico, Mexico, DF, Mexico Robert Burke The Laboratory of Neural Control, NINDS National Institutes of Health, El Prado, NM, USA Merlin G. Butler Psychiatry and Behavioral Sciences, The University of Kansas Medical Center, Kansas City, KS, USA Eero Castre´n Neuroscience Center, University of Helsinki, Helsinki, Finland Jun Chen Institute for Biomedical Sciences of Pain (IBSP), Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China Andrew CN Chen Department of Neurobiology, Capital Medical University, China Raymond Cluydts Vrije Universiteit Brussel, Brussels, Belgium List of Contributors xxix

Rochelle S. Cohen Department of Anatomy and Cell Biology (MC 512), Univer- sity of Illinois at Chicago College of Medicine, Chicago, IL, USA Kathleen E. Cullen Department of Physiology, McGill University, Montreal, QC, Canada Yi Dai Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Japan Robert Dantzer Division of Internal Medicine, Department of Symptom Research, MD Anderson Cancer Center, Houston, TX, USA Rolf Dermietzel Department of Neuroanatomy and Molecular Brain Research, Ruhr-University Bochum Universit€atsstr. 150, Bochum, Germany Lakshmi A. Devi Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA Ulrich Dirnagl Department of Experimental Neurology, Department of Neurol- ogy, Center for Stroke Research Berlin Charite´ Universit€atsmedizin Berlin, Berlin, Germany Kay Double Neuroscience Research Australia and the University of New South Wales, Sydney, NSW, Australia Kimberly Dougherty Department of Neuroscience, The Karolinska Institute, Stockholm, Sweden Ulrich Eisel Department of Molecular Neurobiology, University of Groningen, Groningen, The Netherlands Aziz El-Amraoui Unite´ de Ge´ne´tique et Physiologie de l’Audition, Institut Pas- teur, Inserm UMRS587, UPMC, Paris, Cedex 15, France Joel K. Elmquist Division of Hypothalamic Research, University of Texas South- western Medical Center, Dallas, TX, USA Bi-Fa Fan Department of Pain Medicine, China-Japan Friendship Hospital, China John Finberg Department of Molecular Pharmacology, Rappaport Faculty of Medicine, Haifa, Israel Eric Fliers Department of Endocrinology and Metabolism, Academic Medical Center (AMC), , Amsterdam, The Netherlands Marc E. Freeman Department of Biological Science and Program in Neurosci- ence, Florida State University, Tallahassee, FL, USA Lloyd D. Fricker Albert Einstein College of Medicine, Bronx, NY, USA Gregory D. Funk Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada xxx List of Contributors

Khatuna Gagnidze Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA Charlotte von Gall Zentrum fur€ Anatomie und Hirnforschung, Institut fur€ Anatomie II, Universit€atsklinikum Dusseldorf,€ Dusseldorf,€ Germany Ignacio de Gaspar Department of Anatomy and Embryology, Universidad Complutense de Madrid, School of Veterinary Medicine, Madrid, Spain Ashley N. Gearhardt Department of Psychology, Yale University, New Haven, CT, USA Charles F. Gillespie Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA Peter J. Goadsby Headache Group- Neurology, University of California, San Francisco, CA, USA Dwayne W. Godwin Neurobiology and Anatomy, Wake Forest School of Medi- cine, Winston-Salem, NC, USA Jay M. Goldberg Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL, USA Arturo E. Gonzalez-Iglesias Department of Biological Science and Program in Neuroscience, Florida State University, Tallahassee, FL, USA Carlos Gonza´lez Centro Interdisciplinario de Neurociencia de Valparaı´so, Universidad de Valparaı´so Facultad de Ciencias, Valparaı´so, Chile Gabriela Gonza´lez-Mariscal Cinvestav-Universidad Auto´noma de Tlaxcala, Tlaxcala, Tlax, Mexico Andrea C. Gore Pharmacology and Toxicology, University of Texas at Austin, Austin, TX, USA John J. Greer Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada Jian-Guo Gu Department of Anesthesiology, University of Cincinnati, College of Medicine, USA Karine Guillem Universite´ de Bordeaux, Institut des Maladies Neurode´ge´ne´ra- tives, Bordeaux, UMR CNRS 5293, France Randi Hagerman Department of Pediatrics, University of California-Davis Medical Center M.I.N.D.-Institute, Sacramento, CA, USA Ji-Sheng Han Neuroscience Research Institute and Key Laboratory of Neurosci- ence under the auspice of Ministries of Health and Education, Peking University, Beijing, China Shuang-Lin Hao Department of Anesthesiology, University of Miami, USA List of Contributors xxxi

Mary M. Heinricher Department of Neurological Surgery, Oregon Health & Science University, Portland, USA

Stewart Hendry Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USA

Tom Hildebrandt Psychiatry, Mount Sinai School of Medicine, New York, NY, USA

Gert Holstege Center for Uroneurology, University Medical Center Groningen, Groningen, The Netherlands

Jen-Chuen Hsieh Institute of Brain Science, Integrated Brain Research Unit, National Yang-Ming University, Taipei Veterans General Hospital, Taipei, Taiwan

San-Jue Hu Department of Neurobiology and Institute of Neuroscience, PLA, Fourth Military Medical University, China

Scott A. Huettel Center for Cognitive Neuroscience, Duke University, Durham, NC, USA

Wieland B. Huttner Max Planck Institute of Molecular Cell Biology and Genet- ics, Dresden, Germany

Hieu K. Huynh Center for Uroneurology, University Medical Center Groningen, Groningen, The Netherlands

Tadashi Isa Department of Developmental Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan

Anthony R. Isles Medicine/Psychological Medicine & Neurology, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK

Lori Isom Pharmacology, Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA

Reinhard Jahn Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Gottingen,€ Germany

Elzbieta Jankowska Department of Physiology, University of Gothenburg, Insti- tute of Neuroscience and Physiology, Goteborg,€ SE, Sweden

Sadim Jawhar Division of Molecular Psychiatry, Department for Psychiatry, University Medicine Goettingen, Gottingen,€ Germany

Yong-Hua Ji School of Life Sciences, Shanghai University, China

Marian Joe¨ls Department of Neuroscience and Pharmacology, University Medi- cal Center Utrecht Rudolf Magnus Institute of Neuroscience, Utrecht, The Netherlands xxxii List of Contributors

Andries Kalsbeek Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam & Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands Keith W. Kelley Pathology, College of Medicine, University of Illinois, 212 ERML, M/C 051, Urbana, IL, USA Gerd Kempermann CRTD – Center for Regenerative Therapies Dresden, Technische Universit€at Dresden and DZNE, German Center for Neurodegenerative Diseases, Dresden, Germany Cliff C. Kerr Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, NY, USA Helmut Kettenmann Max-Delbruck-Center€ for Molecular Medicine, Cellular Neurosciences, Berlin, Germany Ole Kiehn Department of Neuroscience, The Karolinska Institute, Stockholm, Sweden Caitlin Williams Kiley UC Davis College of Biological Sciences, UC Davis Center for Neuroscience, Davis, CA, USA E. R. (Ron) de Kloet Medical Pharmacology, LACDR/LUMC, Leiden Univer- sity, Leiden, RA, The Netherlands E. Louise Kodituwakku Department of Pediatrics, School of Medicine, Univer- sity of New Mexico, Albuquerque, NM, USA Piyadasa Kodituwakku Department of Pediatrics, Center for Development and Disability, The University of New Mexico, Albuquerque, NM, USA George F. Koob Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA Jaap Koolhaas Department of Behavioral Physiology, University of Groningen, Groningen, The Netherlands Horst-Werner Korf Dr. Senckenbergische Anatomie, Institute of Anatomy II, and Dr. Senckenbergisches Chronomedizinisches Institut, Johann Wolfgang Goe- the-University, Frankfurt am Main, Germany Morten L. Kringelbach Department of Psychiatry, The University of Oxford Warneford Hospital, Oxford, UK Krister Kristensson Department of Neuroscience, Karolinska Institutet, Stock- holm, Sweden Alexander Kunz Department of Experimental Neurology, Department of Neurol- ogy, Center for Stroke Research Berlin Charite´ Universit€atsmedizin Berlin, Berlin, Germany List of Contributors xxxiii

Ramon Latorre Centro de Neurociencia, Universidad de Valparaı´so, Valparaiso, Chile Steven Laureys Cyclotron Research Center & Neurology Department, University of Lie`ge Coma Science Group, Lie`ge, Belgium Konstantinos Lazaridis Department of Biochemistry, Hellenic Pasteur Institute, Laboratory of Molecular Neurobiology & Immunology, Athens, Greece P. Nigel Leigh Institute of Psychiatry, King’s College London, London, UK Rebecca Leshan Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA Andrea Levinson Departments of Psychiatry and Pharmacology, Centre for Addiction & Mental Health – Clarke Site, Toronto, ON, Canada Yong-Jie Li Beijing Xuanwu Hospital, Capital Medical University, China Yun-Qing Li Department of Anatomy, Histology and Embryology, Fourth Mili- tary Medical University, China Qing Lin Department of Psychology, College of Science, University of Texas at Arlington, USA Yoav Litvin Laboratory of Neurobiology and Behavior, The Rockefeller Univer- sity, New York, NY, USA Xian-Guo Liu Pain Research Center, Sun Yet-Sen University, China Yan-Qing Liu Department of Pain Medicine, Beijing Tiantan Hospital, Capital Medical University, China Joseph S. Lonstein Department of Psychology & Neuroscience Program, Mich- igan State University, East Lansing, MI, USA Luis Lopez-Santiago Pharmacology, University of Michigan, Ann Arbor, MI, USA Yan Lu Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, China Joachim H. R. Lubke€ Institute for Neuroscience & Medicine INM-2, Research Centre Julich,€ Julich,€ Germany Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH/University Hospital Aachen and JARA Translational Brain Medicine, Aachen, Germany Samuel K. Ludwin Pathology and Molecular Medicine, Queens University, Kingston, ON, Canada Paul Luiten Department of Molecular Neurobiology, University of Groningen, Groningen, The Netherlands xxxiv List of Contributors

Fei Luo Institute of Psychology, Chinese Academy of Sciences, China William W. Lytton Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, NY, USA Chao Ma Department of Anatomy, Histology and Embryology, Peking Union Medical College and Chinese Academy of Medical Sciences, China Pierre J. Magistretti Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fe´de´rale de Lausanne (EPFL), Lau- sanne, Switzerland Department of Psychiatry–CHUV, Center for Psychiatric Neuroscience, Prilly– Lausanne, Switzerland Eugene M. Martin Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA Nieves Martı´n-Alguacil Department of Anatomy and Embryology, Universidad Complutense de Madrid, School of Veterinary Medicine, Madrid, Spain AnnMary Mathew Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, NY, USA Helen S. Mayberg Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA John G. McHaffie Neurobiology and Anatomy, Wake Forest School of Medicine, Winston-Salem, NC, USA Mark F. Mehler Albert Einstein College of Medicine, Rose F. Kennedy Center, Bronx, NY, USA Angel I. Melo Cinvestav-Universidad Auto´noma de Tlaxcala, Tlaxcala, Tlax, Mexico Philipp Mergenthaler Department of Experimental Neurology, Department of Neurology, Center for Stroke Research Berlin Charite´ Universit€atsmedizin Berlin, Berlin, Germany Andreas Meyer-Lindenberg Central Institute of Mental Health, Mannheim, Germany R. Chris Miall Behavioral Brain Sciences, School of Psychology, University of Birmingham, Birmingham, UK Teresa Milner Weill Cornell Medical School, New York, NY, USA Michel Le Moal 3INSERM, U862, Neurocentre Magendie Neurogenesis and Physiopathology Group, Bordeaux, France Aldrin Molero Neurogenetics and Regenerative Neurology, Albert Einstein College of Medicine, Rose F. Kennedy Center, Bronx, NY, USA List of Contributors xxxv

Felipe Mora-Bermu´dez Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany Richard Morris Centre for Cognitive and Neural Systems, Neuroscience, The University of Edinburgh, Edinburgh, UK Anne Z. Murphy Neuroscience Institute, Georgia State University 814 Petit Science Center, Atlanta, GA, USA Atsushi Nambu Division of System Neurophysiology, National Institute for Phys- iological Sciences, Okazaki, Aichi, Japan Katherine Nautiyal Department of Psychology, Columbia University, New York, NY, USA Randy J. Nelson Ohio State University Medical Center, Columbus, OH, USA Samuel A. Neymotin Biomedical Engineering Program, SUNY Downstate / NYU-Poly, Brooklyn, NY, USA Joseph J. Normandin Neuroscience Institute, Georgia State University 814 Petit Science Center, Atlanta, GA, USA Csaba Nyakas Department of Molecular Neurobiology, University of Groningen, Groningen, The Netherlands Roger L. Papke Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA Gustavo Patino Neuroscience Program, Pharmacology, University of Michigan, Ann Arbor, MI, USA Christine Petit De´partement de Neuroscience, Colle`ge de France, Institut Pasteur, Paris, Cedex 15, France Donald W. Pfaff Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA Mario Prsa Brain-Mind Institute, Ecole Polytechnique Fe´de´rale de Lausanne (EPFL), Lausanne, Switzerland Ryszard Przewlocki Department of Molecular Neuropharmacology, Institute of Pharmacology, PAS, Krakow, Poland Department of Neurobiology and Neuropsychology, Jagiellonian University, Krakow, Poland Luigi Pulvirenti Neuroscience School of Advanced Studies San Quirico d’Orcia, Siena, Italy Yun-Hai Qiu Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, China xxxvi List of Contributors

Gregory J. Quirk Departments of Psychiatry and Anatomy & Neurobiology, University of Puerto Rico School of Medicine, San Juan, PR, USA Megan Rainbow Department of Psychology, Columbia University, New York, NY, USA Zhi-Ren Rao Department of Neurobiology and Institute of Neuroscience, PLA, Fourth Military Medical University, China George Reeke Rockefeller University Laboratory of Biological Modeling, New York, NY, USA Andreas Reichenbach Paul-Flechsig-Institut fur€ Hirnforschung, University of Leipzig, Leipzig, Germany Patricio Rojas Departamento de Biologı´a, Facultad de Quı´mica y Biologı´a Universidad de Santiago de Chile, La Serena, Chile Astrid Rollenhagen Institute for Neuroscience & Medicine INM-2, Research Centre Julich,€ Julich,€ Germany Martin Rottenberg Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden Yasuo Sakuma Department of Physiology, Nippon Medical School, Bunkyo, Tokyo, Japan Rene San Martin Center for Cognitive Neuroscience, Duke University, Durham, NC, USA Clifford B. Saper Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA Justine M. Schober Department of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA Michal Schwartz Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel Daniel T. L. Shek Department of Applied Social Sciences, The Hong Kong Polytechnic University, Hong Kong, P. R. China Lin Shi Janssen Pharmaceutical Companies of Johnson & Johnson, Belgium Bai-Chuang Shyu Institute of Biomedical Sciences, Academia Sinica, Taiwan Rae Silver Department of Psychology, The Silver Neurobiology Laboratory, Columbia University, New York, NY, USA Cheryl Sisk Department of Psychology & Neuroscience Program, Michigan State University, East Lansing, MI, USA List of Contributors xxxvii

Derek J. Snyder Community Dentistry and Behavioral Sciences, University of Florida, Gainesville, FL, USA

Eus van Someren Department of Sleep & Cognition, Netherlands Institute for Neuroscience and VU University and Medical Center, Amsterdam, The Netherlands

Wolfgang H. Sommer Institute of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany

Xue-Jun Song Section of Basic Science Research, Parker Research Institute, Parker University, USA

Rainer Spanagel Institute of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany

Michael Spezio Psychology & Neuroscience, Scripps College, Claremont, CA, USA

David C. Spray Department of Neuroscience and the Department of Medicine, Albert Einstein College of Medicine Room 840 Kennedy Center, Bronx, NY, USA

Rolf Sprengel Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Heidelberg, Germany

Jemeen Sreedharan Department of Clinical Neuroscience, King’s College Lon- don, Medical Research Council (MRC) Centre for Neurodegeneration Research and Institute, London, UK

Terrence R. Stanford Neurobiology and Anatomy, Wake Forest School of Med- icine, Winston-Salem, NC, USA

Barry E. Stein Neurobiology and Anatomy, Wake Forest School of Medicine, Winston-Salem, NC, USA

Rachel C. F. Sun Division of Learning, Development and Diversity, Department of Education, Faculty of Education, The University of Hong Kong, Hong Kong, P. R. China

Dick Swaab Netherlands Institute for Neuroscience, Amsterdam, BA, The Netherlands

Larry W. Swanson Biological Sciences, University of Southern California, Los Angeles, CA, USA

Jing-Shi Tang Department of Physiology and Pathophysiology, School of Medicine, Xi’an Jiaotong University, China

Yuan-Xiang Tao Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, USA xxxviii List of Contributors

Janet L. Taylor Neuroscience Research Australia and The University of New South Wales, Randwick, NSW, Australia Peter Thier Brain-Mind Institute, Ecole Polytechnique Fe´de´rale de Lausanne (EPFL), Lausanne, Switzerland Michael Thorpy Department of Neurology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA Miguel Turrero Garcı´a Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany Socrates Tzartos Department of Biochemistry, Hellenic Pasteur Institute, Labo- ratory of Molecular Neurobiology & Immunology, Athens, Greece W. Martin Usrey Neurology – Medicine, UC Davis College of Biological Sci- ences Center for Neuroscience, Davis, CA, USA Alex Verkhratsky Faculty of Life Sciences, University of Manchester, Manches- ter, UK You Wan Neuroscience Research Institute, Peking University, China Ke-Wei Wang Neuroscience Research Institute, Peking University, China Yun Wang Neuroscience Research Institute, Peking University, China Jia-Shuang Wang Department of Pain Medicine, Guangzhou Red Cross Hospital, Jinan University, China Feng Wei Department of Neural and Pain Sciences, Dental School and Program in Neuroscience, University of Maryland, Baltimore, MD, USA Zachary M. Weil Department of Neuroscience, The Ohio State University, Columbus, OH, USA Lokesh Wijesekera Department of Clinical Neuroscience, MRC Centre for Neurodegeneration Research, King’s College London, London, UK Oliver Wirths Division of Molecular Psychiatry, Department for Psychiatry, University Medicine Goettingen, Gottingen,€ Germany Jessica L. Wittnam Division of Molecular Psychiatry, Department for Psychiatry, University Medicine Goettingen, Gottingen,€ Germany Guang-Yin Xu Department of Neurobiology and Psychology, Institute of Neuro- science, Soochow University, China Tian-Le Xu School of Medicine, Shanghai Jiaotong University, China Hao-Jun You Department of Physiology and Pathophysiology, School of Medi- cine, Xi’an Jiaotong University, China List of Contributors xxxix

Trevor Young Departments of Psychiatry and Pharmacology, Centre for Addic- tion & Mental Health – Clarke Site, Toronto, ON, Canada Lu Yu Department of Applied Social Sciences, The Hong Kong Polytechnic University, Hong Kong, P. R. China Yukun Yuan Pharmacology, University of Michigan, Ann Arbor, MI, USA Sheng-Yuan Yu Department of Neurology, General Hospital PLA, China Long-Chuan Yu School of Life Sciences, Peking University, China Eddy van der Zee Department of Molecular Neurobiology, University of Groningen, Groningen, The Netherlands Jun-Ming Zhang Department of Anesthesiology, University of Cincinnati, College of Medicine, USA Da-Ying Zhang Department of Pain Medicine, Nanchang University, China De-Ren Zhang Department of Pain Medicine, Sixth Shenzhen Renmin Hospital, China Yu-Qiu Zhang Institute of Brain Science, Fudan University, China Xu Zhang Institute of Neuroscience, Chinese Academy of Sciences, China Chi George Zhao Department of Neurology, Montefiore Medical Center, Sleep Wake Disorders Center, Bronx, NY, USA Zhi-Qi Zhao Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China Min Zhuo Department of Physiology, Faculty of Medicine, University of Toronto, Canada Jeffrey M. Zigman Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX, USA Mathias Zink Department of Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany