PRINCIPLE,S
`OF NEI-]RAL
`SCIE,NCE
`
`Fifth Edition
`
`Edited by
`
`ERIC R. KANDEL
`JAME,S H. SCH\TARTZ
`THOMAS M. JESSELL
`STEVEN A. SIE,GELBAUM
`
`A. J. HUDSPETH
`
`Art Editor
`Sarah Mack
`
`ffi
`
`Medical
`
`New York Chicago San Francisco Lisbon London Madrid Medco City
`Milan New Delhi San Juan Seoul Singapore Sydney Toronto
`
`ANTECIP EXHIBIT 2002
`Grunenthal GmbH v. Antecip Bioventures II LLC
`PGR2019-00028
`
`Page 1
`
`

`

`Principles of Neural Science, Fifth Edition
`Copyright @ 2013byThe McGraw-Hill Companies, Inc' Ail rights reserved' Printed in the united
`States of Amerl.a. n*c"pt us permitted undei the United Statei Copyright Act o11976, no part of
`this publicatior, *uy Uu *friar.ea or distributed in any form o1 by any means, or stored in a data
`bure or retrieval ,yrtu-, without the prior written permission of the publisher'
`previous editions copyright o 2000 by McGraw-Hill Companies; @ 1991' by Appleton & Lange'
`67 89 LWI 20 19 1'8
`
`ISBN 978-0-07 -139011.-8
`MHID 0-07-139011.-1.
`
`This book was set in Palatino by Cenveo Publisher Services'
`The editors were Anne Sydor and Harriet Lebowitz'
`The production supervisor was John Williams'
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`The illustrators were Precision Graphics'
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`Library of Congress Cataloging-in-Publication Data
`principles of neural science / edited by Eric R. Kandel ... let a1.] ; art editof, sarah Mack' - 5th ed
`p. L760; cm.
`Includes bibliographical references and index'
`ISBN 978-0-02'1}sif'-a (hard cover : alk' paper)
`I. Kandel, Eric R.
`[DNLM: 1. Central Nervous System-physiology'
`3. Nervous System Diseases. 4. Neuropsychology'
`LC classification not assigned
`6123-dc23
`
`2. Mental Processes-PhYsiologY.
`wL300l
`
`2012023071.
`
`cover image:This image is a lithograph by E Schima from a drawing by sigmund Freud of the
`spinal ganglion of the lr;;;t Peiromyzon. Before he discovered the unconscious, Freud had
`a promising career as a neural scientist. The cover thus recognizes that, a century after Freud's
`discovery, progress in the study of cognition has reemphasized the importance of unconscious
`mental processes for peiception and Jction. (Reproduced, with permission, from Sigmund Freud'
`;;UU"i Spinuiganglien und Ruckenmark der Petromyzon j' Sitzungsberichte der Mathematisch-
`Naturwissenschaftlichen classe der Kaiserlichen Akademie derwissenschaften, LXXV|ll Band l'
`Abtheilung, 1878, copyright NewYork Academy of Medicine )
`
`Page 2
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`

`

`47
`
`The Autonomic Motor System
`and the Hypothalamus
`
`The Autonomic Motor System Mediates Homeostasis
`The Autonomic System Contains Visceral Motor Neurons
`That Are Organized into Ganglia
`Preganglionic Neurons Are Localized in Three Regions
`Along the Brain Stem and Spinal Cord
`Sympathetic Ganglia Project to Many Targets
`Throughout the Body
`Parasympathetic Ganglia Innervate Single Organs
`The Enteric Ganglia Regulate the Gastrointestinal Traci
`Both the Pre- and Postsynaptic Neurons of the Autonomic
`Motor System Use Co-Tiansmission at Their Synaptic
`Connections
`Autonomic Behavior Is the Product of Cooperation Between
`All Three Autonomic Divisions
`Autonomic and Endocrine Functions Are Coordinated by a
`Central Autonornic Network Centered in the Hypothalamus
`The Hypothalamus Integrates Autonomic, Endocrine, and
`Behavioral Responses
`Magnocellular Neuroendocrine Neurons Controi the
`Pituitary Gland Directiy
`Parviceliular Neuroendocrine Neurons Control the
`Pituitary Gland Indirectly
`An Overall View
`
`T A /unN wE ARE FRTGHTENED ouR HEARr races,
`
`y v ffi l:TllT3.n':S";':il'#1,:l?:f,:;
`
`our palms become sweaty, and we may want to run.
`These bodily changes accompanying fear are medi-
`ated by the autonomic motor system, which controls
`
`heart muscle, smooth muscle, and exocrine
`The autonomic motor system is controlled
`neuronal network that includes the h
`As we shall learn in this and the next two
`the hypothalamus regulates the autonomic
`as to recruit appropriate physiological
`specific emotions and to coordinate these
`and emotional responses with other aspects
`ior to insure constancy of the internal
`(homeostasis). The hypothalamus
`maintenance of homeostasis by acting on
`systems: the autonomic motor system, the
`system, and an ill-defined neural system
`with motivation.
`The autonomic motor system is distinct
`somatic motor system, which controis
`Nevertheless, to produce behaviors the
`and autonomic motor systems must work
`\Atrhereas neurons in the somatic motor
`
`body temperature, and controls eatitrg,
`sexual behavior.
`Although the autonomic motor svstern
`involuntary, the behaviors controlled
`integrated with voluntary movements
`
`Page 3
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`

`

`Chapter 47 / The Autonomic Motor System and the Hypothalamus 1057
`
`[nked to emotional arousal, stress, moti-
`defensive reactions. Feelings of fear, anger,
`and sadness have characteristic autonomic
`chapter we first examine the peripheral
`of the autonomic system and then their
`
`by hypothalamic control of the autonomic motor sys-
`tem and the endocrine system. We begin the discussion
`of these mechanisms by considering the peripheral
`components: the autonomic ganglia. The circuits of the
`ganglia connect with the spinal cord and brain stem
`and mediate simple reflexes that are the components
`of more complex behaviors.
`
`autonomic network in the brain stem and
`. We conclude by considering the role of
`and specialized areas of cerebral cortex
`autonomic function with motivation,
`and emotion. The autonomic and hypotha-
`involved in emotion and motivation
`in more detail in the next two chapters
`
`Motor System Mediates
`
`middle of the 19th century Claude Bernard in
`attention to the stability of the body's inter-
`which includes the "fluid that sur-
`and bathes all tissues," during a broad range
`states and external conditions. Bernard
`"The internal environment (Ie milieu interior) is
`condition for a free life." Building on this
`1930s Walter B. Cannon introduced the
`of homeostasis to describe the mechanisms
`within a narrow physiological range the
`composition of the bodily fluids, body
`biood pressure, and other physiological
`
`maintaining blood pressure within a much
`range. In the absence of these normal com-
`blood pressure would increase in
`cardiac output, and the resulting
`rn pressure would rupture blood vessels, per-
`composition, and alter the balance among
`interstitial, and intracellular compart-
`
`The Autonomic System Contains Visceral
`Motor Neurons That Are Organized into
`Ganglia
`
`Unlike the somatic motor system, in which the motor
`neurons are located in the ventral spinal cord and
`brain stem, the cell bodies of autonomic motor neurons
`are found in enlargements of peripheral nerves called
`ganglia.l The autonomic ganglia contain motor neurons
`that innervate the secretory epithelial cells in glands or
`smooth and cardiac muscle.
`Overall, the nervous system has many more auto-
`nomic than somatic motor neurons. In humans the
`entire spinal cord contains only approximately 120,000
`somatic motor nerve cells, whereas the superior cer-
`vical ganglion alone contains approximatety 900,000
`autonomic motor neurons. Although the significance
`of this difference in numbers is uncertain, it may reflect
`the great diversity and complexity of autonomically
`controlled target tissues-the stomach, intestine, blad-
`der, heart, lungs, and vasculature-as compared to
`the relative uniformity of skeletal muscle controlled
`by the somatic motor system. Most autonomic ganglia
`contain far fewer cells. For example, in the lungs and
`gastrointestinal tract of humans there are many micro-
`scopic ganglia, each with only tens to hundreds of neu-
`rons. These differences in number of cells are thought
`to reflect differences in the degree of control and the
`size of peripheral target fields.
`Efforts to understand the principles of organiza-
`tion of autonomic ganglia began in 1880 in England
`with the work of Walter Gaskell and were later con-
`tinued by ]ohn N. Langley. Their pioneering studies
`determined how individual autonomic ganglia are
`functionally regulated by central nerves, and in turn
`how the different ganllia regulate different peripheral
`
`resistance to blood flow.
`behavior, including control of
`arises from neural modulation of the
`properties of organ systems, mediated
`
`tThe peripheral nerves also have sensory ganglia, located on the
`dorsal roots of the spinal cord and on five of the cranial nerves:
`trigeminal (V), facial (VII), vestibulocochlear (VIII), glossopharyn-
`geal (IX), and vagus (X) (see Chapter 45).
`
`Page 4
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