Essential Neuroscience T H I R D E D I T I O N SSiieeggeell__33ee__FFMM..iinndddd ii 33//77//1144 33::4444 AAMM SSiieeggeell__33ee__FFMM..iinndddd iiii 33//77//1144 33::4444 AAMM Essential Neuroscience T H I R D E D I T I O N Allan Siegel, PhD Professor Emeritus Department of Neurology and Neurosciences Department of Psychiatry University of Medicine and Dentistry of New Jersey New Jersey Medical School Newark, New Jersey Hreday N. Sapru, PhD Professor Department of Neurological Surgery Department of Neurology and Neurosciences Department of Pharmacology and Physiology University of Medicine and Dentistry of New Jersey New Jersey Medical School Newark, New Jersey Case Histories written by Heidi E. Siegel, MD SSiieeggeell__33ee__FFMM..iinndddd iiiiii 33//77//1144 33::4455 AAMM Acquisitions Editor : Crystal Taylor Product Development Editor : Lauren Pecarich Production Project Manager: David Saltzberg Marketing Manager : Joy Fisher Williams Manufacturing Manager : Margie Orzech-Zeranko Design Coordinator : Holly Reid McLaughlin Art Director: Jennifer Clements Compositor : Absolute Service, Inc. Third Edition Copyright © 2015 Lippincott Williams & Wilkins, a Wolters Kluwer business. 351 West Camden Street Two Commerce Square, 2001 Market Street Baltimore, MD 21201 Philadelphia, PA 19103 Printed in China All rights reserved. This book is protected by copyright. No part of this book may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their offi cial duties as U.S. government employees are not covered by the above-mentioned copyright. To request permission, please contact Lippincott Williams & Wilkins at Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103, via email at permissions@ lww.com, or via website at lww.com (products and services). Library of Congress Cataloging-in-Publication Data Siegel, Allan, 1939- author. Essential neuroscience / Allan Siegel, Hreday N. Sapru ; case histories written by Heidi E. Siegel.—Third edition. p. ; cm. Includes index. ISBN 978-1-4511-8968-1 (paperback) I. Sapru, Hreday N., author. II. Siegel, Heidi. III. Title. [DNLM: 1. Nervous System Physiological Phenomena. 2. Mental Disorders—physiopathology. 3. Nervous System—- anatomy & histology. 4. Nervous System Diseases. WL 102] RC343.6 612.8—dc23 2014003977 DISCLAIMER Care has been taken to confi rm the accuracy of the information present and to describe generally accepted practices. H owever, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from a pplication of the information in this book and make no warranty, expressed or implied, with respect to the currency, c ompleteness, or accuracy of the contents of the publication. Application of this information in a particular situation r emains the professional responsibility of the practitioner; the clinical treatments described and recommended may not be considered absolute and universal recommendations. T he authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with the current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant fl ow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug. S ome drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings. It is the responsibility of the health care provider to ascertain the FDA status of each drug or device planned for use in their clinical practice. T o purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320 . International customers should call ( 301) 223-2300 . Visit Lippincott Williams & Wilkins on the Internet: http://www.lww.com. Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6:00 pm, EST. 9 8 7 6 5 4 3 2 1 SSiieeggeell__33ee__FFMM..iinndddd iivv 33//77//1144 33::4455 AAMM D e d i c a t i o n This book is dedicated to our wives, Carla Siegel, of blessed memory, and Millie Sapru. “We have learned much from our teachers and from our colleagues more than from our teachers, but from our students, more than from them all.” SSiieeggeell__33ee__FFMM..iinndddd vv 33//2200//1144 11::1133 AAMM Preface A most effective. Consistent with this approach, the book s we noted in the fi rst edition of this text, there has begins with analysis of the single neuron, which then been a dramatic explosion of information in the fi eld of expands to how neurons communicate with each other. neuroscience over the last few decades. This explosion of Following d iscussion of the anatomy of the spinal cord and information has presented a great challenge to those of us brain, the text continues with a detailed study of the sen- who teach neuroscience in terms of synthesizing a coherent sory, motor, and integrative systems. This approach was approach in which the diverse topics encompassed by neu- deemed helpful by both students and faculty. Moreover, the roscience can be taught in a lucid and effective manner. We building-blocks approach improved student performance met this challenge by designing Essential Neuroscience , a on National Board and Neuroscience Shelf examinations. book that considers all of the basic neuroscience topics to The book comprises 28 chapters and a glossary. allow the students to focus on the essential concepts and Chapters 1 through 3 (“Overview of the Central Nervous facts intrinsic to any given topic without overwhelming System,” “Development of the Nervous System,” and them with distracting or confusing extraneous information. “Meninges and Cerebrospinal Fluid”) provide a back- Consistent with this approach, each chapter begins with ground for understanding the structural organization of the Learning Objectives followed by a discussion of the sub- brain and spinal cord. These chapters provide a basis for ject matter in a succinct yet informative manner. To pres ent a more in-depth analysis of nervous system functions and the material in an integrated fashion, Clinical Consider- clinical disorders. ations are included as are discussions of the physiological Having provided the student with a basic understanding aspects. At the end of each chapter, a Chapter Summary of the gross anatomy and general functions of the brain Table is provided that highlights the most important facts and spinal cord, the book then introduces a series of topics and concepts of the chapter and allows for review of the designed to provide an understanding of the basic elements material in a simple, effi cient manner. A Clinical Case is of the nervous system and the role they play in neuronal also presented, which is followed by a Chapter Test con- communication. These topics are discussed in Chapters sisting of questions that can also be used effectively for 4 through 7 (“Histology of the Nervous System,” “Elec- USMLE preparation. trophysiology of Neurons,” “Synaptic Transmission,” and Recent developments in neuroscience have also been “Neurotransmitters”). The basic physiological processes incorporated in the text. For example, over the past two presented in these chapters prepare the student for fur- decades, there have been signifi cant advances in our under- ther understanding of the diverse functions of the nervous standing of the molecular bases of development. Accord- system in the subsequent sections. Chapters 8 through 12 ingly, a section has been added in Chapter 2, “Development (“The Spinal Cord,” “Brainstem I: The Medulla,” “Brain- of the Nervous System,” which summarizes the key aspects stem II: Pons and Cerebellum,” “Brainstem III: The Mid- of these developmental mechanisms. In addition, in recent brain,” and “The Forebrain”) enable the student to examine years, great strides have been made in the identifi cation of the organization of the central nervous system in a system- neurotransmitter malfunction in several diseases. There- atic way. After learning about the key structures and func- fore, a detailed chapter has been included on neurotrans- tions at each level of the neuraxis of the central nervous mitters and implications of their malfunctions in mental system, the student will begin to develop an understanding disorders. Similarly, genetic abnormalities involved in cer- of why damage to a given structure produces a particu- tain diseases (e.g., cystic fi brosis, schizophrenia, Hunting- lar constellation of defi cits. Because of the importance of ton’s chorea) have been briefl y discussed. Malfunctions Chapter 13, “The Cranial Nerves,” and the extent to which of the immune system in certain diseases (e.g., Lambert- this material is tested on USMLE examinations, each cra- Eaton syndrome, multiple sclerosis, myasthenia gravis) nial nerve is presented separately in terms of its structural have also been discussed where applicable. and functional properties as well as the defi cits associated The genesis of this textbook evolved over the past with its dysfunction. 30 years, as a result of our efforts in teaching neurosci- A t this point in the study of the nervous system, the stu- ence to medical and graduate students in ways that would dent has developed a basic knowledge of the anatomical make learning the subject matter simple yet meaningful. organization of the central nervous system and its physiol- After testing a variety of approaches, a building-blocks ogy and neurochemistry. Consequently, the student is now approach in the presentation of the subject matter proved ready to study the sensory, motor, and integrative systems vi SSiieeggeell__33ee__FFMM..iinndddd vvii 33//77//1144 33::4455 AAMM Preface vii that require the knowledge accumulated thus far. The science that were highlighted in bold in each chapter and next section of the book includes Chapters 14 through 17 explained in an e xtensive glossary at the end of the book, (“Somatosensory System,” “Visual System,” “Auditory which was doubled in the second edition and expanded in and Vestibular Systems,” and “Olfaction and Taste”) and the third edition. discusses anatomical and physiological properties of sen- Also, as a result of the positive feedback we received sory systems. in the changes made in the second edition, we have main- T he next section of the text turns to the study of motor tained these changes in the third edition with respect to systems and includes Chapters 18 to 20, “The Upper Motor Chapter Summary Tables at the end of each chapter. These Neurons,” “The Basal Ganglia,” and “The Cerebellum.” tables not only helped students review chapters, which These chapters examine, in an integrated manner, the ana- were just studied, but also served as valuable, high-yield tomical, physiological, and neurochemical bases for nor- tools for study and review at examination time. Moreover, mal movement and movement disorders associated with in addition to these changes, 150 questions, answers, and the cerebral cortex, basal ganglia, cerebellum, brainstem, explanations of the correct and incorrect choices will be and spinal cord. accessible on the Internet to all students who purchased The fi nal section of the text (Chapters 21 to 28) concerns the textbook. a variety of functions of the nervous system characterized In the third edition, we have maintained, enhanced, by higher levels of complexity. Chapters 21 to 24, “The and expanded wherever appropriate the full-color illustra- Autonomic Nervous System,” “The Reticular Formation,” tions, which have been universally praised in the second “The Hypothalamus,” and “The Limbic System,” include edition and which we believe are even better in the third analyses of visceral processes, sleep, and wakefulness. edition. In addition, 140 questions covering all chapters, In addition, an analysis of the structure, functions, and and their answers and explanations, are included as an dysfunctions of the cerebral cortex is provided in Chap- online supplement to this edition. ter 25, “The Thalamus and Cerebral Cortex.” In this third Selected topics have been expanded where appropriate: edition of our text, Chapters 26 and 27, “Blood Supply of the functional relationship, memory, and lateralization of the Central Nervous System” and “Vascular Syndromes,” the hippocampal formation and limbic cortex; limbic re- were placed toward the end of the book because by this lationships of the basal ganglia (especially in reference to point the student has gained a deeper understanding and psychiatric issues); the development of the anterior and appreciation of brainstem syndromes than if that material posterior pituitary; a discussion of prions in relation to had been presented earlier in the text. These two chapters Creutzfeldt-Jakob disease; and others. were placed back-to-back in order to allow the student to M aterial has also been integrated in multiple places more effectively relate the distribution of the blood sup- where it would augment understanding of important con- ply (Chapter 26) to vascular syndromes (Chapter 27), cepts. For example, the functional relationships associ- which constitutes an important review for the student on ated with the cerebral cortex are again referred to vis-à-vis a topic that is heavily tested on USMLE examinations. sensory and motor systems. Extensive cross-referencing The fi nal chapter, “Behavioral and Psychiatric Disorders” among chapters has likewise been incorporated. (Chapter 28), examines disorders such as schizophrenia, A lthough this text was originally primarily designed for depression, anxiety, and obsessive compulsion. These dis- medical students who study neuroscience, it can be used orders have a clear relationship to abnormalities in neural quite effectively by neurology residents and graduate and and neurochemical functions and, thus, refl ect an important undergraduate university students specializing in biologi- component of neuroscience. These topics also receive at- cal sciences. In this latest edition, special topics have been tention on the USMLE. reworked to better accommodate dental students. The tri- Essential Neuroscience proved to be a highly effec- geminal nucleus, for instance, has been divided into its tive tool for students and faculty. The goal of this third components for a more detailed study. edition, therefore, is to perfect the formula with which Essential Neuroscience , third edition, distinguishes it- we had such success. For example, we have added num- self from other texts as the concise, clinically relevant neu- bers of photographs of MRIs throughout the text at key roscience text providing balanced coverage of anatomy, locations in order to support basic and clinical phenom- physiology, biology, and biochemistry. With a full array ena presented in those chapters. In addition, we have ex- of pedagogical features, it helps students gain concep- panded a number of chapters in the book to include new tual mastery of this challenging discipline and, we hope, and important information such as mechanisms relating to foments the urge to continue its exploration. feeding (Chapter 24) and autism (Chapter 28). In addition, we have maintained the improvements made in the second Allan Siegel edition. These include key terms and concepts of neuro- Hreday N. Sapru SSiieeggeell__33ee__FFMM..iinndddd vviiii 33//77//1144 33::4455 AAMM Acknowledgments T New Jersey Medical School, for her critique of Chap- he authors thank Dr. Leo Wolansky, Department of ter 28. The a uthors thank Dr. Masanobu Maeda, MD, Radiology, Rutgers New Jersey Medical School, for PhD, Professor and Chairman, Department of Physiol- generously providing us with the MRIs and CT scans ogy, Wakayama Medical University School of Medi- used in Chapter 27, and Dr. Lewis Baxter, University cine, Japan, for serving as “Translation Director” for of Florida Medical School, Gainesville, for provid- the Japanese edition of this book, which was published ing an MRI of a patient with obsessive-compulsive by Maruzen Co, Ltd, Tokyo, Japan. We also thank Ms. disorder shown in Chapter 28. The authors also thank Anne Rains for her excellent illustrations included in Dr. Barbara Fadem, Department of Psychiatry, Rutgers each of the editions of this book. viii SSiieeggeell__33ee__FFMM..iinndddd vviiiiii 33//77//1144 33::4455 AAMM Contents Preface vi Acknowledgments viii SECTION I Gross Anatomy of the Brain 1 1 Overview of the Central Nervous System 3 2 Development of the Nervous System 18 3 Meninges and Cerebrospinal Fluid 35 SECTION II The Neuron 47 4 Histology of the Nervous System 49 5 Electrophysiology of Neurons 66 6 Synaptic Transmission 84 7 Neurotransmitters 95 SECTION III Organization of the Central Nervous System 127 8 The Spinal Cord 129 9 Brainstem I: The Medulla 158 10 Brainstem II: Pons and Cerebellum 172 11 Brainstem III: The Midbrain 187 12 The Forebrain 197 13 The Cranial Nerves 216 SECTION IV Sensory Systems 247 14 Somatosensory System 249 15 Visual System 264 16 Auditory and Vestibular Systems 287 17 Olfaction and Taste 306 SECTION V Motor Systems 319 18 The Upper Motor Neurons 321 19 The Basal Ganglia 338 20 The Cerebellum 353 SECTION VI Integrative Systems 375 21 The Autonomic Nervous System 377 22 The Reticular Formation 406 23 The Hypothalamus 425 24 The Limbic System 443 25 The Thalamus and Cerebral Cortex 462 26 Blood Supply of the Central Nervous System 490 27 Vascular Syndromes 504 28 Behavioral and Psychiatric Disorders 525 Glossary G-1 Index I-1 ix SSiieeggeell__33ee__FFMM..iinndddd iixx 33//77//1144 33::4455 AAMM