Table Of ContentFrom Neuron to Brain
FIFTH EDITION
From
Neuron
t o Brain
FIFTH EDITION
John G. Nicholls
International School for Advanced Studies, Trieste, Italy
A. Robert Martin
Emeritus, University of Colorado School of Medicine
Paul A. Fuchs
The Johns Hopkins University School of Medicine
David A. Brown
University College London
Mathew E. Diamond
International School for Advanced Studies, Trieste, Italy
David A. Weisblat
University of California, Berkeley
Sinauer Associates, Inc. • Publishers
Sunderland, Massachusetts • USA
ABOUT THE COVER
Computer artwork of a human brain © Pasieka/Science Photo
Library/Fotosearch. Neurons (background) are from the
Third Edition cover, designed by Laszlo Meszoly.
From Neuron to Brain, Fifth Edition
Copyright © 2012 by Sinauer Associates, Inc.
All rights reserved. This book may not be reproduced in
whole or in part without permission.
Address inquiries and orders to
Sinauer Associates, Inc.
23 Plumtree Road
Sunderland, MA 01375 U.S.A.
FAX: 413-549-1118
E-mail: [email protected]
Internet: www.sinauer.com
Library of Congress Cataloging-in-Publication Data
From neuron to brain / John G. Nicholls ... [et al.]. -- 5th ed.
p. cm.
Includes bibliographical references and index.
ISBN 978-0-87893-609-0
1. Neurophysiology. 2. Brain. 3. Neurons. I. Nicholls, John G.
QP355.2.K83 2012
612.8--dc23
2011037528
8 7 6 5 4 3 2 1 Printed in U.S.A.
This book is dedicated to the memory of our friend
and colleague, Steve Kuffler.
In a career that spanned 40 years, Stephen Kuffler made experiments on funda-
mental problems and laid paths for future research to follow. A feature of his work
is the way in which the right problem was tackled using the right preparation.
Examples are his studies on denervation, stretch receptors, efferent control, in-
hibition, GABA and peptides as transmitters, integration in the retina, glial cells,
and the analysis of synaptic transmission. What gave papers by Stephen Kuffler a
special quality were the clarity, the beautiful figures, and the underlying excitement.
Moreover, he himself had done every experiment he described. Stephen Kuffler’s
work exemplified and introduced a multidisciplinary approach to the study of
the nervous system. At Harvard he created the first department of neurobiology,
in which he brought together people from different disciplines who developed
new ways of thinking. Those who knew him remember a unique combination of
tolerance, firmness, kindness, and good sense with enduring humor. He was the
J. F. Enders University Professor at Harvard, and was associated with the Marine
Biological Laboratory at Woods Hole. Among his many honors was his election
as a foreign member of the Royal Society.
Preface to the Fifth Edition
When the First Edition of our book appeared in 1976, its pref- date. In addition there are two obvious, major changes from the
ace stated that our aim was “…to describe how nerve cells go last edition. First, as in the original text by Kuffler and Nicholls,
about their business of transmitting signals, how the signals are a discussion of the visual system now comes in the first part of
put together, and how out of this integration higher functions the book, with the same intent. Placing this information at the
emerge. This book is directed to the reader who is curious about beginning of the book highlights its importance and immediately
the workings of the nervous system but does not necessarily have gives the reader a glimpse of the whole functioning “brain” that
a specialized background in biological sciences. We illustrate the comprises part of our title. Experience shows that a beginning
main points by selected examples…”. student who wants to know how the brain works is often drawn
This new, Fifth Edition has been written with the same aim in to the subject (as were the authors of this book) by fascination
mind but in a very different context. When the First Edition appeared with higher functions. Thanks to the elegance of work done on
there were hardly any books, and only a few journals devoted to the the retina and visual cortex, it is possible to show the clear link
nervous system. The extraordinary advances in molecular biology, between the properties of nerve cells and our visual perception.
genetics, and immunology had not yet been applied to the study of Moreover, this information can evoke curiosity about succeeding
nerve cells or the brain, and the internet was not available for searching chapters, which deal with the cellular, biophysical, and molecular
the literature. The explosion in knowledge since 1976 means that properties of nerve cells.
even though we still want to produce a readable narrative, the topics A second major change is in the number of authors. From
that have to be addressed and the number of pages have increased. two, then three and four, we have now grown to six authors. In
Inevitably, descriptions of certain older experiments have had to be the last years the amount of new information that is produced
jettisoned, even though they still seem beautiful. Nevertheless, our and the number of new techniques that must be described have
approach continues to be to follow ideas from their conception to grown faster than ever. As a result, the choices that have to be
the latest developments. To this end, in this edition we have retained made about what to include or leave out are so sophisticated that
descriptions of classical experiments as well as the newest findings. it would be a full-time task beyond the capabilities of two or three
In this way we hope to present key lines of research of interest for neuroscientists (especially if they still wished to continue their
practicing research workers and teachers of neurobiology, as well research and get grants). Nevertheless, as in the past, we have
as for readers who are not familiar with the field. aimed to maintain a consistent, continuous, narrative style. As in
For the Fifth Edition, new chapters have been added, others the past, we hope to make the whole book appear to the reader
have been completely rewritten and all have been brought up to as if it were the work of a single author.
John G. Nicholls A. Robert Martin Paul A. Fuchs
David A. Brown Mathew E. Diamond David A. Weisblat
October, 2011
Acknowledgments
We owe special thanks to our friend and colleague, Bruce Wal- and figures, including: K. Briggman, A. Brown, R. Constanzo, J.
lace, who was an author of the Third and Fourth Editions of Fernandez, D. Furness, M. S. Graziano, L. L. Iversen, A. Kaneko,
this book. Although it was not possible for him to collaborate J. Kinnamon, E. Knudsen, S. R. Levinson, A. Mallamaci, U. J.
for this Fifth Edition, material from his previous chapters has McMahan, R. Michaels, K. J. Muller, E. Newman, E. Puzuolo, R.
been used extensively in new chapters that have been rewrit- Reed, S. Roper, M. Ruegg, M. M. Salpeter, P. Shrager, P. Sterling,
ten and brought up to date. His work represents an essential M. Stryker, J. Taranda, R. Vassar, D. A. Wagenaar, and D. Zoccolan.
contribution and we are extremely grateful that we are able to It is a pleasure to thank Andy Sinauer, our publisher and
retain in the text much of his scholarly, clear, and authoritative friend. His remarkable sense of style, keen interest, and sound
expositions of key topics. judgment about the contents, illustrations, and appearance of the
We are grateful to the numerous colleagues who have encour- book have motivated and encouraged us at every stage. We were
aged us and influenced our thinking. We particularly thank Dr. fortunate to have the guidance of Sydney Carroll who was with
Denis Baylor, who read all of the chapters. For reading individual us from the inception of the book and provided valuable input to
chapters we thank Drs. W. Kolbinger, G. Legname, F. F. de Miguel, its design and layout. We are also grateful to Kathaleen Emerson,
K. J. Muller, U. J. McMahan, L. Szczupak, and C. Trueta. Helpful Chelsea Holabird, and Azelie Aquadro who edited our text with
discussions and advice were provided by E. Arabzadeh, S.Bensmaïa, great care and courtesy; Chris Small, Joan Gemme, and Marie
D. H. Jenkinson, W. B. Kristan, Jr., D.-H. Kuo, S. R. Levinson, A. Scavotto, who played major roles in producing this new edition,
Mallamaci, L. Mei, M. Ruegg, W. J. Thompson, and D. Zoccolan. and to artist Elizabeth Morales, who transformed our drawings
We are most grateful to colleagues who provided original plates and graphs into elegant and attractive figures.
From the Preface to the First Edition
Our aim is to describe how nerve cells go about their business and insoluble there lies a simplifying principle that will lead to an
of transmitting signals, how these signals are put together, and unraveling of the events. For example, the human brain consists
how out of this integration higher functions emerge. This book of over 10,000 million cells and many more connections that in
is directed to the reader who is curious about the workings of their detail appear to defy comprehension. Such complexity is
the nervous system but does not necessarily have a specialized at times mistaken for randomness; yet this is not so, and we can
background in biological sciences. We illustrate the main points show that the brain is constructed according to a highly ordered
by selected examples, preferably from work in which we have first- design, made up of relatively simple components. To perform all
hand experience. This approach introduces an obvious personal its functions it uses only a few signals and a stereotyped repeating
bias and certain omissions. pattern of activity. Therefore, a relatively small sampling of nerve
We do not attempt a comprehensive treatment of the ner- cells can sometimes reveal much of the plan of the organization
vous system, complete with references and background material. of connections, as in the visual system.
Rather, we prefer a personal and therefore restricted point of view, We also discuss “open-ended business,” areas that are devel-
presenting some of the advances of the past few decades by fol- oping and whose direction is therefore uncertain. As one might
lowing the thread of development as it has unraveled in the hands expect, the topics cannot at present be fitted into a neat scheme.
of a relatively small number of workers. A survey of the table of We hope, however, that they convey some of the flavor that makes
contents reveals that many essential and fascinating fields have research a series of adventures.
been left out: subjects like the cerebellum, the auditory system, From Neuron to Brain expresses our approach as well as our
eye movements, motor systems, and the corpus callosum, to name aims. We work mostly on the machinery that enables neurons to
a few. Our only excuse is that it seems preferable to provide a function. Students who become interested in the nervous system
coherent picture by selecting a few related topics to illustrate the almost always tell us that their curiosity stems from a desire to
usefulness of a cellular approach. understand perception, consciousness, behavior, or other higher
Throughout, we describe experiments on single cells or analyses functions of the brain. Knowing of our preoccupation with the
of simple assemblies of neurons in a wide range of species. In workings of isolated nerve cells or simple cell systems, they are
several instances the analysis has now reached the molecular level, frequently surprised that we ourselves started with similar motiva-
an advance that enables one to discuss some of the functional tions, and they are even more surprised that we have retained those
properties of nerve and muscle membranes in terms of specific interests. In fact, we believe we are working toward that goal (and
molecules. Fortunately, in the brains of all animals that have been in that respect probably do not differ from most of our colleagues
studied there is apparent a uniformity of principles for neuro- and predecessors). Our book aims to substantiate this claim and,
logical signaling. Therefore, with luck, examples from a lobster we hope, to show that we are pointed in the right direction.
or a leech will have relevance for our own nervous systems. As
Stephen W. Kuffl er John G. Nicholls
physiologists we must pursue that luck, because we are convinced
that behind each problem that appears extraordinarily complex August, 1975
