《医学生理学 Medical Physiology》参考教材资料（PDF电子书籍）Neuroscience in Medicine, Third edition, 2008

NEUROSCIENCE IN MEDICINE THIRD EDITION Edited b P. MICHAEL CONN Oregon National Primate Research Center Oregon Health and Science University Beaverton, OR, USA EE Humana press

NEUROSCIENCE IN MEDICINE THIRD EDITION Edited by P. MICHAEL CONN Oregon National Primate Research Center Oregon Health and Science University Beaverton, OR, USA

PREFACE When the first edition of this book was prepared, we I am pleased to continue the tradition of presenting ere midway into the " Decade of the Brain"the "Clinical Correlations"for select chapters and that 1990s. The passage of time has allowed the promise Dr. Greg Cooper has taken over primary respon of this field to become the reality of progress. Research bility for this task. Because of their popularity in neuroscience and remarkable technology have now Dr. Cooper has expanded the number of these nade material contributions to human well-being Another feature of this edition is the addition of an As in the first two editions, the challenge remained Interactive Atlas, which is provided on a CD to define the"core material"in a rapidly expanding In late 2006, as preparations were being made for field. I have continued to restrict peripheral areas(cell initiation of this revision, we learned of the loss of function and biosynthesis, for example) in order to David V. Smith, Ph. D, who succumbed to a brain focus on emerging and important areas that would tumor at the age of 63. Dr. Smith was the Simon r not be found in a more generalist text Bruesch Professor and Chair of the Department of The book has benefited by supportive contributors Anatomy Neurobiology and the Director of the who were carefully selected because they are both excel- Neuroscience Institute at the University of Tennessee lent teachers and academic leaders. That they chose to Health Science Center(UTHSC)and a contributor to contribute the time and energy needed for this project is the earlier editions of this book. We miss his presence a strong endorsement of their commitment to this dis- in the current revision. cipline and to this project. A substantial number of the Finally, I thank the staff at Springer for guiding me authors have been participating since the first edition. through this process P. Michael Conn Portland, Oregon

PREFACE When the first edition of this book was prepared, we were midway into the ‘‘Decade of the Brain’’—the 1990s. The passage of time has allowed the promise of this field to become the reality of progress. Research in neuroscience and remarkable technology have now made material contributions to human well-being. As in the first two editions, the challenge remained to define the ‘‘core material’’ in a rapidly expanding field. I have continued to restrict peripheral areas (cell function and biosynthesis, for example) in order to focus on emerging and important areas that would not be found in a more generalist text. The book has benefited by supportive contributors who were carefully selected because they are both excel￾lent teachers and academic leaders. That they chose to contribute the time and energy needed for this project is a strong endorsement of their commitment to this dis￾cipline and to this project. A substantial number of the authors have been participating since the first edition. I am pleased to continue the tradition of presenting ‘‘Clinical Correlations’’ for select chapters and that Dr. Greg Cooper has taken over primary responsi￾bility for this task. Because of their popularity, Dr. Cooper has expanded the number of these. Another feature of this edition is the addition of an Interactive Atlas, which is provided on a CD. In late 2006, as preparations were being made for initiation of this revision, we learned of the loss of David V. Smith, Ph.D., who succumbed to a brain tumor at the age of 63. Dr. Smith was the Simon R. Bruesch Professor and Chair of the Department of Anatomy & Neurobiology and the Director of the Neuroscience Institute at the University of Tennessee Health Science Center (UTHSC) and a contributor to the earlier editions of this book. We miss his presence in the current revision. Finally, I thank the staff at Springer for guiding me through this process. P. Michael Conn Portland, Oregon v

CONTENTS Contributors List of color plates Cytology and Organization of Cell Types: Light and Electron Microscopy Rochelle S Cohen and Donald w. pfaff 2. Anatomy of the Spinal Cord and Brain Bruce w. newton Ion Channels, Transporters, and Electrical Signaling 53 Stanko S. Stojilkovic CLINICAL CORRELATION: DEMYELINATING DISORDERS Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky Synaptic Transmission Henrique von Gersdorff Presynaptic and Postsynaptic Receptors l11 Robert D. grubbs Neuroembryology and Neurogenesis G. Jean Harry and Christina T. Teng CLINICAL CORRELATION: DISORDERS OF NEURONAL MIGRATION .........144 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky The vasculature of the human brain 147 Suresh C. Patel, Rajan Jain and Simone Wagner CLINICAL CORRELATION: STROKE 167 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky Choroid Plexus-Cerebrospinal Fluid Circulatory Dynamics: Impact on Brain Growth, Metabolism, and Repair 173 Conrad E Johanson Organization of the Spinal Cord Marion Murray CLINICAL CORRELATION: DISORDERS OF THE SPINAL CORD 216 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky The Cerebellum Charles r. goodlett The Brain Stem and Cranial Nerves 247 Harold H. Traurig CLINICAL CORRELATION: DISORDERS OF THE AUTONOMIC NERVOUS SYSTEM 270 Gregory Cooper Gerald Eichhorn and Robert Rodnitzky The brain stem reticular formation 273 Harold H. Traurig The Trigeminal System 287 Harold H. Traurig

CONTENTS 2 Preface . . . . . ................................................................ v 2 Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi 2 List of Color Plates . . . ...................................................... xiii 1. Cytology and Organization of Cell Types: Light and Electron Microscopy ............... 1 Rochelle S. Cohen and Donald W. Pfaff 2. Anatomy of the Spinal Cord and Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Bruce W. Newton 3. Ion Channels, Transporters, and Electrical Signaling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Stanko S. Stojilkovic CLINICAL CORRELATION: DEMYELINATING DISORDERS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky 4. Synaptic Transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 Henrique von Gersdorff 5. Presynaptic and Postsynaptic Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 Robert D. Grubbs 6. Neuroembryology and Neurogenesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 G. Jean Harry and Christina T. Teng CLINICAL CORRELATION: DISORDERS OF NEURONAL MIGRATION . . . . . . . . . . . . . . . . . . . . . . . . 144 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky 7. The Vasculature of the Human Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 Suresh C. Patel, Rajan Jain and Simone Wagner CLINICAL CORRELATION: STROKE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky 8. Choroid Plexus–Cerebrospinal Fluid Circulatory Dynamics: Impact on Brain Growth, Metabolism, and Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 Conrad E. Johanson 9. Organization of the Spinal Cord . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 Marion Murray CLINICAL CORRELATION: DISORDERS OF THE SPINAL CORD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky 10. The Cerebellum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221 Charles R. Goodlett 11. The Brain Stem and Cranial Nerves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247 Harold H. Traurig CLINICAL CORRELATION: DISORDERS OF THE AUTONOMIC NERVOUS SYSTEM . . . . . . . . . . . . . . . . 270 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky 12. The Brain Stem Reticular Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 Harold H. Traurig 13. The Trigeminal System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 Harold H. Traurig vii

Contents The Hypothalamus Marc E. Freeman, David R Grattan and Thomas A Houpt The Cerebral Cortex 359 Michael W. Miller and Brent A. Vogt CLINICAL CORRELATION: DEMENTIA AND ABNORMALITIES OF COGNITION Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky The Limbic s 379 Thomas van Groen, Inga Kadish Lawrence Ver Hoef and J. Michael Wyss CLINICAL CORRELATION: DISORDERS OF THE LIMBIC SYSTEM Lawrence Ver Hoef, Inga Kadish, Gregory Cooper and Thomas van Groen The Basal Ganglia Irene Martinez-Torres, Stephen Tisch, and Patricia Limousin CLINICAL CORRELATION: DISORDERS OF THE BASAL GANGLIA 415 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky The Thalamus 19 Roland smith Spinal Mechanisms for Control of Muscle Length and Force 443 Charles/. Heckman and William Z Rymer Chemical Messenger Systems 479 Robert d. grubbs CLINICAL CORRELATION: PARKINSON'S DISEASE 508 Gregory Cooper, Gerald Eichhorn and Robert L. rodnitzky 21. Pain 513 Mary M. Heinricher CLINICAL CORRELATION: PHYSICAL TRAUMA TO NERVES 526 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky CLINICAL CORRELATION PERIPHERAL NEUROPATHY 528 Gregory Cooper Gerald Eichhorn and Robert L. Rodnitzky 531 /. Fielding Hejtmancik, Edmond j. Fitz Gibbon and Rafael C. Caruso CLINICAL CORRELATION: DISORDERS OF OCULAR MOTILITY 572 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky Audition 575 Tom C.T. Yin The Vestibular Syster A. Tucker Gleason The Gustatory System 601 Steven). St. John and John D. Boughter /r. The Olfactory System 6l1 Michael T Shipley, Matthew Ennis and Adam C. Puche Sleep, Dreams, and States of Consciousness Robert w. McCarle CLINICAL CORRELATION: DISORDERS OF SLEEP Gregory Cooper and Gerald Eichhorn

14. The Hypothalamus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301 Marc E. Freeman, David R. Grattan and Thomas A. Houpt 15. The Cerebral Cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359 Michael W. Miller and Brent A. Vogt CLINICAL CORRELATION: DEMENTIA AND ABNORMALITIES OF COGNITION . . . . . . . . . . . . . . . . . . 377 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky 16. The Limbic System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379 Thomas van Groen, Inga Kadish, Lawrence Ver Hoef and J. Michael Wyss CLINICAL CORRELATION: DISORDERS OF THE LIMBIC SYSTEM . . . . . . . . . . . . . . . . . . . . . . . . . . . 397 Lawrence Ver Hoef, Inga Kadish, Gregory Cooper and Thomas van Groen 17. The Basal Ganglia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401 Irene Martinez-Torres, Stephen Tisch, and Patricia Limousin CLINICAL CORRELATION: DISORDERS OF THE BASAL GANGLIA. . . . . . . . . . . . . . . . . . . . . . . . . . . 415 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky 18. The Thalamus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419 Yoland Smith 19. Spinal Mechanisms for Control of Muscle Length and Force . . . . . . . . . . . . . . . . . . . . . . . 443 Charles J. Heckman and William Z. Rymer 20. Chemical Messenger Systems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479 Robert D. Grubbs CLINICAL CORRELATION: PARKINSON’S DISEASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 508 Gregory Cooper, Gerald Eichhorn and Robert L. Rodnitzky 21. Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 513 Mary M. Heinricher CLINICAL CORRELATION: PHYSICAL TRAUMA TO NERVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 526 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky CLINICAL CORRELATION: PERIPHERAL NEUROPATHY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 528 Gregory Cooper, Gerald Eichhorn and Robert L. Rodnitzky 22. Vision . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 531 J. Fielding Hejtmancik, Edmond J. FitzGibbon and Rafael C. Caruso CLINICAL CORRELATION: DISORDERS OF OCULAR MOTILITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . 572 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky 23. Audition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 575 Tom C.T. Yin 24. The Vestibular System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 591 A. Tucker Gleason 25. The Gustatory System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601 Steven J. St. John and John D. Boughter Jr. 26. The Olfactory System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 611 Michael T. Shipley, Matthew Ennis and Adam C. Puche 27. Sleep, Dreams, and States of Consciousness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 623 Robert W. McCarley CLINICAL CORRELATION: DISORDERS OF SLEEP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647 Gregory Cooper and Gerald Eichhorn viii Contents

Contents Higher brain Functions 651 Rache Casas and danie/ tranel CLINICAL CORRELATION: THE APHASIAS AND OTHER DISORDERS OF LANGUAGE 667 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky Neuroimmunology: An Overview 671 Michael D. Lump Nervous System-Immune System Interactions 677 Sonia L. Carlson Watson and Dwight M. Nance CLINICAL CORRELATION: MYASTHENIA GRAVIS Gregory Cooper Gerald Eichhorn and robert Rodnitzky 31 Degeneration, Regeneration, and Plasticity in the Nervous System 691 Paul/. Reier and Michael A Lane CLINICAL CORRELATION: CONGENITAL CHROMOSOMAL AND GENETIC ABNORMALITIES 728 nd gerald Eiche The Biology of Drug Addiction 731 Scott. Russo and Colleen A. McClung 33. The Neuropathology of Disease 749 Bruce w. ne and robert E mrak Index 775

28. Higher Brain Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 651 Rachel Casas and Daniel Tranel CLINICAL CORRELATION: THE APHASIAS AND OTHER DISORDERS OF LANGUAGE . . . . . . . . . . . . . 667 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky 29. Neuroimmunology: An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 671 Michael D. Lumpkin 30. Nervous System–Immune System Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 677 Sonia L. Carlson Watson and Dwight M. Nance CLINICAL CORRELATION: MYASTHENIA GRAVIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 688 Gregory Cooper, Gerald Eichhorn and Robert Rodnitzky 31. Degeneration, Regeneration, and Plasticity in the Nervous System . . . . . . . . . . . . . . . . . . . 691 Paul J. Reier and Michael A. Lane CLINICAL CORRELATION: CONGENITAL CHROMOSOMAL AND GENETIC ABNORMALITIES . . . . . . . . 728 Gregory Cooper and Gerald Eichhorn 32. The Biology of Drug Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 731 Scott J. Russo and Colleen A. McClung 33. The Neuropathology of Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 749 Bruce W. Newton and Robert E. Mrak 2 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 775 Contents ix

CONTRIBUTORS JOHN D. BOUGHTER JR, PhD. Department of Anatomy& G. JEAN HARRY, PhD. Neurotoxicology Group, Neurobiology, University of Tennessee Health Laboratory of Neurobiology, National Institute of Sciences Center, Memphis, TN, USA Environmental Health Sciences National Institutes SONIA L CARLSON WATSON, PhD. Rochester, MN, USA of Health, Department of Health and Human RAFAEL C. CARUSO. MD PhD.OGVFB National Services, Research Triangle Park, NC, US.A Institutes of Health, Bethesda, MD, US.A CHARLES J. HECKMAN, PhD. Department of Physiol RACHEL CASAS, BA. Department of Psychology, ogy, Feinberg School of Medicine, Northwestern University of lowa Hospitals and Clinics, Iowa City, University, Chicago, IL, USA IA. USA MARY M. HEINRICHER, PhD. Department of Neurolo- ROCHELLE S COHEN, PhD. Department of Anatomy gical Surgery, Oregon Health Science University, nd Cell Biology, University of Illinois at Chicago, Portland, OR, USA Chicago, IL, USA J. FIELDING HEJTMANCIK, MD, PhD. National Eye GREGORY COOPER. MD PhD. Sanders-Brown Center Institute, National Institutes of Health, Bethesda on Aging, The University of Kentucky, Lexington, MD, USA KY, USA; Baptist Neurology Center, Lexington, LAWRENCE VER HOEF, MD. Department of Cell Biol- KY USA gy, The University of Alabama at Birmingh GERALD EICHHORN, MD. The Lexington Clinic, Birmingham, AL, USA Lexington, KY, USA THOMAS A HOUPT, PhD.Department of Biological MATTHEW ENNIS, PhD. Department of Anatomy& Science, Florida State University, Tallahassee, FL Neurobiology, University of Tennessee Health USA Science Center, Memphis, TN, USA RAJAN JAIN, MD. Henry Ford Hospital, Department of EDMOND J. FITZ GIBBON, MD. National Eye Institute, Radiology, Detroit, MI, USA National Institutes of Health, Bethesda, MD, USA CONRAD E JOHANSON, PhD. Program in Neurosur MARC E. FREEMAN, PhD. Department of Biological gery, Department of Clinical Neurosciences, Warren Science, Florida State University, Tallahassee, FL, Alpert Medical School, Brown University, Pro dence RL USA HENRIQUE VON GERSDORFF, PhD.Oregon Health STEVEN J. ST JOHN, PhD. Department of psychology, Science University, The Vollum Institute, Portland, Rollins College, Winter Park, FL, USA OR USA INGA KADISH, PhD. Department of Cell Biology A. TUCKER GLEASON, PhD. Department of Otolaryn- The University of Alabama at Birmingham gology-Head Neck Surgery, University of virgi Birmingham, AL, USA nia. Charlottesville VA USA MICHAEL A LANE, PhD. Department of Neuroscience, CHARLES R GOoDLETT, PhD.Department of University of florida College of Medicine and Psychology and Program in Medical Neuroscience, McKnight Brain Institute, Gainesville, FL, USA Indiana University-Purdue University Indianapolis, PATRICIA LIMOUSIN, MD, PhD. Unit of Functional Indianapolis, IN, USA Neurosurgery, Institute of Neurology, University DAVID R. GRATTAN, PhD. University of otago College, London, United Kingdom Medical School, Department of Anatomy and MICHAEL D LUMPKIN, PhD. Department of physiol- Structural Biology, Dunedin, New Zealand ogy and Biophysics, Georgetown University Medical THOMAS VAN GROEN, PhD. Department of Cell Biol- School, Washington, DC, USA ogy, The University of Alabama at Birmingham IRENE MARTINEZ-TORRES, MD. Unit of Functional Birmingham, AL, US.A Neurosurgery, Institute of Neurology, University ROBERT D. GRUBBS, PhD. Department of Pharmaco/- College, London, United Kingdo ogy, School of Medicine, University of Washington, ROBERT W. MCCARLEY, MD. Professor and Chair, Seattle, WA, USA; Department of pharmacology Department of psychiatry, and Director, N and Toxicology, Boonshoft School of medicine roscience laboratory, Harvard Medical School Wright State University, Dayton, OH, USA Department of Psychiatry, Associate Director

CONTRIBUTORS JOHN D. BOUGHTER JR., PhD Department of Anatomy & Neurobiology, University of Tennessee Health Sciences Center, Memphis, TN, USA SONIA L. CARLSON WATSON, PhD Rochester, MN, USA RAFAEL C. CARUSO, MD, PhD OGVFB, National Institutes of Health, Bethesda, MD, USA RACHEL CASAS, BA Department of Psychology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA ROCHELLE S. COHEN, PhD Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA GREGORY COOPER, MD, PhD Sanders-Brown Center on Aging, The University of Kentucky, Lexington, KY, USA; Baptist Neurology Center, Lexington, KY, USA GERALD EICHHORN, MD The Lexington Clinic, Lexington, KY, USA MATTHEW ENNIS, PhD Department of Anatomy & Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA EDMOND J. FITZGIBBON, MD National Eye Institute, National Institutes of Health, Bethesda, MD, USA MARC E. FREEMAN, PhD Department of Biological Science, Florida State University, Tallahassee, FL, USA HENRIQUE VON GERSDORFF, PhD Oregon Health & Science University, The Vollum Institute, Portland, OR, USA A. TUCKER GLEASON, PhD Department of Otolaryn￾gology–Head & Neck Surgery, University of Virgi￾nia, Charlottesville, VA, USA CHARLES R. GOODLETT, PhD Department of Psychology and Program in Medical Neuroscience, Indiana University–Purdue University Indianapolis, Indianapolis, IN, USA DAVID R. GRATTAN, PhD University of Otago Medical School, Department of Anatomy and Structural Biology, Dunedin, New Zealand THOMAS VAN GROEN, PhD Department of Cell Biol￾ogy, The University of Alabama at Birmingham, Birmingham, AL, USA ROBERT D. GRUBBS, PhD Department of Pharmacol￾ogy, School of Medicine, University of Washington, Seattle, WA, USA; Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA G. JEAN HARRY, PhD Neurotoxicology Group, Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA CHARLES J. HECKMAN, PhD Department of Physiol￾ogy, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA MARY M. HEINRICHER, PhD Department of Neurolo￾gical Surgery, Oregon Health & Science University, Portland, OR, USA J. FIELDING HEJTMANCIK, MD, PhD National Eye Institute, National Institutes of Health, Bethesda, MD, USA LAWRENCE VER HOEF, MD Department of Cell Biol￾ogy, The University of Alabama at Birmingham, Birmingham, AL, USA THOMAS A. HOUPT, PhD Department of Biological Science, Florida State University, Tallahassee, FL, USA RAJAN JAIN, MD Henry Ford Hospital, Department of Radiology, Detroit, MI, USA CONRAD E. JOHANSON, PhD Program in Neurosur￾gery, Department of Clinical Neurosciences, Warren Alpert Medical School, Brown University, Provi￾dence, RI, USA STEVEN J. ST. JOHN, PhD Department of Psychology, Rollins College, Winter Park, FL, USA INGA KADISH, PhD Department of Cell Biology, The University of Alabama at Birmingham, Birmingham, AL, USA MICHAEL A. LANE, PhD Department of Neuroscience, University of Florida College of Medicine and McKnight Brain Institute, Gainesville, FL, USA PATRICIA LIMOUSIN, MD, PhD Unit of Functional Neurosurgery, Institute of Neurology, University College, London, United Kingdom MICHAEL D. LUMPKIN, PhD Department of Physiol￾ogy and Biophysics, Georgetown University Medical School, Washington, DC, USA IRENE MARTINEZ-TORRES, MD Unit of Functional Neurosurgery, Institute of Neurology, University College, London, United Kingdom ROBERT W. MCCARLEY, MD Professor and Chair, Department of Psychiatry, and Director, Neu￾roscience Laboratory, Harvard Medical School Department of Psychiatry, Associate Director xi

Contributors Mental health services, VA Boston Healthcare WILLIAm Z RYmER. MD phd. Rehabilitation Institute System, Brockton, MA. US.A of chicago, Chicago, IL, USA CoLLEeN A. MCCLUNG. PhD. UT Southwestern MICHAEL T SHIPLEY, PhD. Department of Anatomy Medical Center, Department of Psychiatry and Neurobiology, University of Maryland, Program Center for Basic Neuroscience, Dallas, TX, USA in Neuroscience. Baltimore MD. USA MICHAEL W. MILLER, PhD. Department of Neul- YOLAND SMITH PhD. Yerkes National Primate roscience and Physiology, State University of New Research Center and Department of Neurology, York-Upstate Medical University, Syracuse, NY, Emory University, Atlanta, GA, USA STANKO S. STOJILKOVIC. PhD. Section on Cellular ROBERT E MRAK, MD, PhD. Department of Pathol- Signaling, National Institute of Child Health and ogy, University of Toledo Health Sciences Campus, Human Development, National Institutes of Health Toledo, OH USA Bethesda md. usa MARION MURRAY, PhD. Drexel University College STEPHEN TISCH, MD, PhD. Unit of Functional Neuro of Medicine, Department of Neurobiology and surgery, Institute of Neurology, University College Anatomy, Philadelphia, PA, USA London, United Kingdom DWIGHT M. NANCE, PhD. Susan Samueli Center for HAROLD H. TRAURIG, PhD. Department of Anatomy Integrative Medicine, University of California and Neurobiology, University of Kentucky College Irvine, Orange, CA, USA of Medicine, Lexington, KY, USA BRUCE W. NEWTON, PhD. Department of Neurobiology CHRISTINA T. TENG, PhD. Gene Regulation Section and Developmental Sciences, University of Arkansas Laboratory of Reproductive and Developmental for Medical Sciences, Little Rock, AR, US Health Sciences, National Institutes of hello Toxicology, National Institute of Environmen SURESH C. PATEL, MD. Henry Ford Hospital, A Department of Radiology, Detroit, MI, USA Department of Health and Human Services DONALD W. PFAFF, PhD.Professor of Neurobiology Research Triangle Park, NC, USA and Behavior, The Rockefeller University, New DANIEL TRANEL, PhD. Department of Neurology, York. NY USA University of lowa Hospitals and Clinics, lowa City ADAM C. PUCHE, PhD. Department of Anatomy IA. USA Neurobiology, University of Maryland, Program in BRENT A VOGT, PhD. Department of Neuroscience Neuroscience. Baltimore MD. USa and Physiology, State University of New York PAUL J REIER, PhD. Department of Neuroscience Upstate Medical University, Syracuse, NY, USA University of florida College of Medicine and SIMONE WAGNER, MD. Department of Neurology, McKnight Brain Institute, Gainesville, FL, USA University of Heidelberg, Heidelberg, Germany ROBERT RODNITZKY, MD. Department Head of J. MICHAEL WYSS, PhD. Department of Cell Biolo Neurology, University of lowa Hospitals and The University of Alabama at Birmingham Clinics, lowa City, IA, USA Birmingham, AL, USA ScotT J. RUSSO. PhD. UT Southwestern medical TOM C.T. YIN, PhD. Department of physiology Center, Department of Psychiatry and Center for Neuroscience Training Program, University of Basic Neuroscience. Dallas TX. USA Wisconsin-Madison. Madison WL USA

Mental Health Services, VA Boston Healthcare System, Brockton, MA, USA COLLEEN A. MCCLUNG, PhD UT Southwestern Medical Center, Department of Psychiatry and Center for Basic Neuroscience, Dallas, TX, USA MICHAEL W. MILLER, PhD Department of Neu￾roscience and Physiology, State University of New York–Upstate Medical University, Syracuse, NY, USA ROBERT E. MRAK, MD, PhD Department of Pathol￾ogy, University of Toledo Health Sciences Campus, Toledo, OH, USA MARION MURRAY, PhD Drexel University College of Medicine, Department of Neurobiology and Anatomy, Philadelphia, PA, USA DWIGHT M. NANCE, PhD Susan Samueli Center for Integrative Medicine, University of California, Irvine, Orange, CA, USA BRUCE W. NEWTON, PhD Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA SURESH C. PATEL, MD Henry Ford Hospital, Department of Radiology, Detroit, MI, USA DONALD W. PFAFF, PhD Professor of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA ADAM C. PUCHE, PhD Department of Anatomy & Neurobiology, University of Maryland, Program in Neuroscience, Baltimore, MD, USA PAUL J. REIER, PhD Department of Neuroscience, University of Florida College of Medicine and McKnight Brain Institute, Gainesville, FL, USA ROBERT RODNITZKY, MD Department Head of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA SCOTT J. RUSSO, PhD UT Southwestern Medical Center, Department of Psychiatry and Center for Basic Neuroscience, Dallas, TX, USA WILLIAM Z. RYMER, MD, PhD Rehabilitation Institute of Chicago, Chicago, IL, USA MICHAEL T. SHIPLEY, PhD Department of Anatomy & Neurobiology, University of Maryland, Program in Neuroscience, Baltimore, MD, USA YOLAND SMITH, PhD Yerkes National Primate Research Center and Department of Neurology, Emory University, Atlanta, GA, USA STANKO S. STOJILKOVIC, PhD Section on Cellular Signaling, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA STEPHEN TISCH, MD, PhD Unit of Functional Neuro￾surgery, Institute of Neurology, University College, London, United Kingdom HAROLD H. TRAURIG, PhD Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY, USA CHRISTINA T. TENG, PhD Gene Regulation Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA DANIEL TRANEL, PhD Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA BRENT A. VOGT, PhD Department of Neuroscience and Physiology, State University of New York– Upstate Medical University, Syracuse, NY, USA SIMONE WAGNER, MD Department of Neurology, University of Heidelberg, Heidelberg, Germany J. MICHAEL WYSS, PhD Department of Cell Biology, The University of Alabama at Birmingham, Birmingham, AL, USA TOM C.T. YIN, PhD Department of Physiology, Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA xii Contributors

LIST OF COLOR PLATES Color plates follow p 378 Color Plate 1 An electron micrograph of a CNS synapse. This example of a synaptic bouton-type synapse is located in the"molecular layer"of rat cerebellum. a single en passant bouton of the parallel fibers synapses onto a single Purkinje cell spine. Note the multiple synaptic vesicles in the presynaptic bouton terminal. Several vesicles seem to be linked by thin filaments in the cytoplasm. On average, the vesicles have a diameter of about 40 nm. One synaptic vesicle is clearly docked to the presynaptic membrane. Note also the narrow synaptic cleft, which contains a "fuzzyset of electron-dense material (this probably includes cell adhesion proteins that span the cleft). The opposing postsynaptic membrane in the postsynaptic spine has an electron-dense postsynaptic density(PSD), where glutamate receptors and modulatory proteins are located. A thin glial process wraps itself around the synaptic cleft and postsynaptic spine and also partially around the presynaptic bouton-type terminal(Electron micrograph courtesy of Constantino Sotelo, Instituto de Neurociencias de Alicante, Spain) Color Plate 2 A schematic diagram showing the sequence of events that leads to Wallerian(anterograde) degeneration. The normal cytology of a peripheral nerve is shown as a point of reference (expanded inset A). After axonal injury, the proximal stumps retract from the site of injury forming distinctive"retraction bulbs"(expanded inset B). Meanwhile, the distal portion of injured axons degenerate, but all other elements of the peripheral nerve remain intact (expanded inset C). Thereafter, Schwann cells begin to proliferate, and blood-borne macro- phages infiltrate the degenerating nerve stump and assist Schwann cells with phagocytosis of axonal and myelin debris(expanded inset B). Schwann cells then become arranged in columns known as the"bands of Bunger"within common basal laminae(expanded inset C). Such Schwann cell units provide a cellular pathway along which regenerating axons extend distal to the site of injury(see also Fig. 10) Color Plate 3(A)A three-dimensional rendition of early axonal regeneration after peripheral-nerve damage Growth cones(e.g, boxed profile) are seen extending into the lesion gap(blue profiles repre- senting connective tissue elements), and some make contact with Schwann cells(red profiles)in the distal stump ( Drawing kindly provided by Dr Susan E. Mackinnon, Washington Uni- versity School of Medicine and Barnes-Jewish Hospital. )(B) An axonal growth cone of an embryonic chick sensory neuron is shown. The growth cone is doubly stained with an antibody against tubulin (green), which labels microtubules, and rhodamine-phalloidin to label actin filaments red. The bundle of axonal microtubules(green)splays apart in the growth cone, and individual microtubules extend forward to interact with actin filament bundles and network These interactions between actin filaments and microtubules are important in determinin directions of axonal growth and branching(see text). A small axonal sprout has formed at the lower left margin of the growth cone( Figure generously provided by Paul C. Letourneau Ph. D, University of Minnesota

LIST OF COLOR PLATES Color plates follow p. 378. Color Plate 1 An electron micrograph of a CNS synapse. This example of a synaptic bouton-type synapse is located in the ‘‘molecular layer’’ of rat cerebellum. A single en passant bouton of the parallel fibers synapses onto a single Purkinje cell spine. Note the multiple synaptic vesicles in the presynaptic bouton terminal. Several vesicles seem to be linked by thin filaments in the cytoplasm. On average, the vesicles have a diameter of about 40 nm. One synaptic vesicle is clearly docked to the presynaptic membrane. Note also the narrow synaptic cleft, which contains a ‘‘fuzzy’’ set of electron-dense material (this probably includes cell adhesion proteins that span the cleft). The opposing postsynaptic membrane in the postsynaptic spine has an electron-dense postsynaptic density (PSD), where glutamate receptors and modulatory proteins are located. A thin glial process wraps itself around the synaptic cleft and postsynaptic spine and also partially around the presynaptic bouton-type terminal. (Electron micrograph courtesy of Constantino Sotelo, Instituto de Neurociencias de Alicante, Spain). Color Plate 2 A schematic diagram showing the sequence of events that leads to Wallerian (anterograde) degeneration. The normal cytology of a peripheral nerve is shown as a point of reference (expanded inset A). After axonal injury, the proximal stumps retract from the site of injury forming distinctive ‘‘retraction bulbs’’ (expanded inset B). Meanwhile, the distal portion of injured axons degenerate, but all other elements of the peripheral nerve remain intact (expanded inset C). Thereafter, Schwann cells begin to proliferate, and blood-borne macro￾phages infiltrate the degenerating nerve stump and assist Schwann cells with phagocytosis of axonal and myelin debris (expanded inset B). Schwann cells then become arranged in columns known as the ‘‘bands of Bunger’’ within common basal laminae (expanded inset C). Such Schwann cell units provide a cellular pathway along which regenerating axons extend distal to the site of injury (see also Fig. 10). Color Plate 3 (A) A three-dimensional rendition of early axonal regeneration after peripheral-nerve damage. Growth cones (e.g., boxed profile) are seen extending into the lesion gap (blue profiles repre￾senting connective tissue elements), and some make contact with Schwann cells (red profiles) in the distal stump. (Drawing kindly provided by Dr. Susan E. Mackinnon, Washington Uni￾versity School of Medicine and Barnes-Jewish Hospital.) (B) An axonal growth cone of an embryonic chick sensory neuron is shown. The growth cone is doubly stained with an antibody against tubulin (green), which labels microtubules, and rhodamine-phalloidin to label actin filaments red. The bundle of axonal microtubules (green) splays apart in the growth cone, and individual microtubules extend forward to interact with actin filament bundles and networks. These interactions between actin filaments and microtubules are important in determining directions of axonal growth and branching (see text). A small axonal sprout has formed at the lower left margin of the growth cone. (Figure generously provided by Paul C. Letourneau, Ph.D., University of Minnesota.) xiii

Cytology and Organization of Cell Types Light and Electron Microscopy Rochelle s cohen and donald w. pfaff CoNTENTS NEURONAL RESPONSE TO A CHANGING ENVIRONMENT MECHANISMS OF NEURONAL FUNCTION CYTOSKELETON DETERMINATION OF NEURONAL FORM NEURONAL SYNAPSES GLIAL CELLS SELECTED READING 1. NEURONAL RESPONSE TO A CHANGING changes in the internal milieu, may have to travel long ENVIRONMENT distances through the bloodstream to reach their tar- Although neurons are cells that conform to funda- gets. This voyage takes time-seconds, hours, oreven dered slow- mental cellular and molecular principles, they are acting agents, although evidence is differentiated from other cells in ways that reflect effects of hormones, such as for the steroid hormones their unique ability to receive, integrate, store, and estrogen and corticosterone. Because hormones are send information Signals received from the internal diluted in the bloodstream, they must be very potent and external environment are processed by neurons, and act at low concentrations to be effective. These resulting in the generation of a response that can be properties are sufficient for endocrine functions neces- communicated to other neurons or tissues. In this sary to keep the organism in a homeostatic state, but way, the organism can successfully adapt to rapidly more immediate challenges require a rapid coupling of changing events, ensuring its survivaL. stimulus and response and a faster rate of communica All organisms possess stimulus-response systems tion among relevant cells. Rapid communication is that permit them to sense environmental fluctuations. achieved exquisitely by the neuron, whose form and In bacteria, for example, intracellular regulatory mole- function are designed to meet such demand cules couple the stimulus to the proper response Mul- The rapidity with which neurons can conduct signals ticellularorganisms must communicate information to (i.e, time is measured in less than I ms) is primarily a other cells, some of which may be local, but others are function of certain basic features common to all neu- positioned some distance away. Communication may rons: polarization of their form, unique associations be accomplished by the release of chemical messengers with their neighboring neurons, and special properties that bind to specific compler itary proteins called of their plasma membranes. Information is conveyed receptors, located on the surface of other cells. For within and between neurons in the form of electrical local communication, diffusion can deliver the mes- and chemical signals, respective\'. functional circuits Neurons are orga senger to the receptive surface. Messengers such as nized into complex networks, or hormones, secreted by endocrine cells in response to which translate these signals into the myriad responses that constitute an organism's behavioral repertoire From: Neuroscience in Medicine, Edited by: P. M. Conn Neural circuits develop in a predictable manner. e Humana Press. Totowa NJ 2008 achieving organizational specificity at functional sites

1 Cytology and Organization of Cell Types: Light and Electron Microscopy Rochelle S. Cohen and Donald W. Pfaff CONTENTS NEURONAL RESPONSE TO A CHANGING ENVIRONMENT MECHANISMS OF NEURONAL FUNCTION CYTOSKELETON DETERMINATION OF NEURONAL FORM NEURONAL SYNAPSES GLIAL CELLS SELECTED READING 1. NEURONAL RESPONSE TO A CHANGING ENVIRONMENT Although neurons are cells that conform to funda￾mental cellular and molecular principles, they are differentiated from other cells in ways that reflect their unique ability to receive, integrate, store, and send information. Signals received from the internal and external environment are processed by neurons, resulting in the generation of a response that can be communicated to other neurons or tissues. In this way, the organism can successfully adapt to rapidly changing events, ensuring its survival. All organisms possess stimulus-response systems that permit them to sense environmental fluctuations. In bacteria, for example, intracellular regulatory mole￾cules couple the stimulus to the proper response. Mul￾ticellular organisms must communicate information to other cells, some of which may be local, but others are positioned some distance away. Communication may be accomplished by the release of chemical messengers that bind to specific complementary proteins called receptors, located on the surface of other cells. For local communication, diffusion can deliver the mes￾senger to the receptive surface. Messengers such as hormones, secreted by endocrine cells in response to changes in the internal milieu, may have to travel long distances through the bloodstream to reach their tar￾gets. This voyage takes time—seconds, hours, or even days—and hormones are, in general, considered slow￾acting agents, although evidence is emerging for rapid effects of hormones, such as for the steroid hormones estrogen and corticosterone. Because hormones are diluted in the bloodstream, they must be very potent and act at low concentrations to be effective. These properties are sufficient for endocrine functions neces￾sary to keep the organism in a homeostatic state, but more immediate challenges require a rapid coupling of stimulus and response and a faster rate of communica￾tion among relevant cells. Rapid communication is achieved exquisitely by the neuron, whose form and function are designed to meet such demands. The rapidity with which neurons can conduct signals (i.e., time is measured in less than 1 ms) is primarily a function of certain basic features common to all neu￾rons: polarization of their form, unique associations with their neighboring neurons, and special properties of their plasma membranes. Information is conveyed within and between neurons in the form of electrical and chemical signals, respectively. Neurons are orga￾nized into complex networks, or functional circuits, which translate these signals into the myriad responses that constitute an organism’s behavioral repertoire. Neural circuits develop in a predictable manner, achieving organizational specificity at functional sites From: Neuroscience in Medicine, Edited by: P. M. Conn Humana Press, Totowa, NJ 2008 1

2 Cohen and pfaff of contact called synapses. At the synapses, neurons neurons and their processes and appear to provide transmit signals with a great degree of fidelity, allowing them with mechanical and metabolic support. Others some behaviors, particularly those necessary for survi- are arranged along specific neuronal processes so as val, to be stereotyped. Neurons also possess a remark to increase the rate of conduction of electrical signals able ability to modify the way messages are received, Glia are considered later in this chapter. We first processed, and transmitted and may exert profound focus on the neuron, which is the fundamental struc- changes in behavioral patterns. This special property tural and functional unit of the nervous system is called plasticity and depends on the molecular and structural properties of the neuron 1.1. Synapses Are the Sites of Directed In addition to forming specific contacts with other Communication Between Neurons nerve cells, neurons exist in relation to a group of cells The polarization of neuronal shape permits its func collectively known as glia. Some glial cells envelop tioning within a simple or complex circuit. Like other Perikarya Dendrites Axon Perikaryon Axon Axon 2 Single process Fig. 1. Polarization of the neuronal form. Nerve cells conduct impulses in a directed manner, although the position of axons and dendrites relative to the cell body and to each other may vary. (A) The multipolar neuron is the most prevalent type and shows extensive branching of the dendrites that emanate from the cell body. The axons emerge from the opposite end. (B)Bipolar neurons have sensory functions and transmit information received by dendrites along two processes that emerge from the cell body. (C) Pseudounipolar neurons are found in the dorsal root ganglion. These neurons are bipolar during early development Later, the two processes fuse to form a stalk, which subsequently bifurcates into two axons. The action potentials are conducted from sensory nerve endings in skin and muscle to the spinal cord. The action potential usually bypasses the cell body, but in conditions such as a prolapsed vertebral disk, in which the dorsal nerve roots are put under pressure, the cell bodies may lso generate impulses. (D) Unipolar neurons are found in invertebrates. Axons arise from the dendrites, which emerge from the cell body

of contact called synapses. At the synapses, neurons transmit signals with a great degree of fidelity, allowing some behaviors, particularly those necessary for survi￾val, to be stereotyped. Neurons also possess a remark￾able ability to modify the way messages are received, processed, and transmitted and may exert profound changes in behavioral patterns. This special property is called plasticity and depends on the molecular and structural properties of the neuron. In addition to forming specific contacts with other nerve cells, neurons exist in relation to a group of cells collectively known as glia. Some glial cells envelop neurons and their processes and appear to provide them with mechanical and metabolic support. Others are arranged along specific neuronal processes so as to increase the rate of conduction of electrical signals. Glia are considered later in this chapter. We first focus on the neuron, which is the fundamental struc￾tural and functional unit of the nervous system. 1.1. Synapses Are the Sites of Directed Communication Between Neurons The polarization of neuronal shape permits its func￾tioning within a simple or complex circuit. Like other Fig. 1. Polarization of the neuronal form. Nerve cells conduct impulses in a directed manner, although the position of axons and dendrites relative to the cell body and to each other may vary. (A) The multipolar neuron is the most prevalent type and shows extensive branching of the dendrites that emanate from the cell body. The axons emerge from the opposite end. (B) Bipolar neurons have sensory functions and transmit information received by dendrites along two processes that emerge from the cell body. (C) Pseudounipolar neurons are found in the dorsal root ganglion. These neurons are bipolar during early development. Later, the two processes fuse to form a stalk, which subsequently bifurcates into two axons. The action potentials are conducted from sensory nerve endings in skin and muscle to the spinal cord. The action potential usually bypasses the cell body, but in conditions such as a prolapsed vertebral disk, in which the dorsal nerve roots are put under pressure, the cell bodies may also generate impulses. (D) Unipolar neurons are found in invertebrates. Axons arise from the dendrites, which emerge from the cell body. 2 Cohen and Pfaff