The Thalamus
Second Edition

The only book of its kind for 20 years, this comprehensive and extensive review, with massive photographic documentation of the structure, connections, physiology, chemistry, development, and comparative anatomy of the mammalian thalamus, with special chapters on the human thalamus and its pathology, and on thalamic evolution, features the author's own historical perspective. As leader in the field, Edward G. Jones has been able to show how knowledge of the thalamus has developed with the introduction of new technologies and ideas. The author's photographic skills are exhibited in brilliant preparations of thalamic structure in a wide range of common and uncommon species. The second edition of The Thalamus can be viewed both as an up-to-date scientific review of virtually all aspects of forebrain function and as a work of immense neuroscientific scholarship. Essential for neuroanatomists, neurophysiologists, molecular neurobiologists, developmental neurobiologists, and clinicians, its deep historical perspective will be of value to historians of science.

Edward G. Jones is Director of The Center for Neuroscience and Distinguished Professor of Psychiatry, University of California, Davis. He is a past president of the Society for Neuroscience.

The Thalamus

Second Edition

Volume I, Volume II

Edward G. Jones
Center for Neuroscience, University of California, Davis, USA

CAMBRIDGE UNIVERSITY PRESS
Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo

Cambridge University Press
The Edinburgh Building, Cambridge CB2 2RU, UK

Published in the United States of America by Cambridge University Press, New York

www.cambridge.org
Information on this title: www.cambridge.org/9780521858816

© E. G. Jones 2007

This publication is in copyright. Subject to statutory exception
and to the provisions of relevant collective licensing agreements,
no reproduction of any part may take place without
the written permission of Cambridge University Press.

First published 2007

Printed in the United Kingdom at the University Press, Cambridge

A catalog record for this publication is available from the British Library

ISBN-13 978-0-521-85881-6 hardback
ISBN-10 0-521-85881-X hardback

Cambridge University Press has no responsibility for the persistence or accuracy of
URLs for external or third-party internet websites referred to in this publication, and
does not guarantee that any content on such websites is, or will remain, accurate
or appropriate.

For Sue, Pippa and Chris

And now

For Michael, Susanna and Emilie

Hic rudis et castris. . . . . ,
Qui tetigit thalamos praeda novella tuos,
Te solam norit, . . .

Ovid, Ars Amatoria 3, 559–661

Contents

PREFACE TO THE THALAMUS, FIRST EDITION

It is now more than fifty years since Sir Wilfrid Le Gros Clark (1932a) published his Arris and Gale lectures on the structure and connections of the thalamus. This authoritative overview came at a time when thalamic studies were passing from a descriptive to an experimental phase and, in his review, Le Gros Clark was able to cover virtually every aspect of the organization and development and much of the comparative anatomy of the thalamus then known.

It is also approaching a half-century since A. Earl Walker (1938a) wrote The Primate Thalamus, which was strongly experimental, but with many clinical insights, and which he described as “an attempt to elucidate the role of the thalamus in sensation.” The intervening years have seen published a few reports of conferences on aspects of thalamic organization and function but no monographs comparable to those of Le Gros Clark or Walker. Perhaps this is understandable when one considers, not so much the enormity of the new data that have been added, but rather the emphasis upon individual thalamic nuclei as components of separate functional systems, not all of them sensory. It is probably also true to say that studies in the commoner experimental animals such as the rat, cat, and monkey have been so productive in their own right that there was little interest in making an across-species synthesis. Studies of the human thalamus virtually ceased with the introduction of L-DOPA and the decline of interest in stereotaxic thalamotomy. Overall, too, looms the lateral geniculate nucleus, from which such an enormous body of fascinating new information continues to come that virtually all other thalamic nuclei fall in its shadow. It is interesting to reflect that Walker virtually ignored the lateral geniculate nucleus, seeing it as presenting “few new problems that need to be solved.” In a sense perhaps he was right: the problems are old ones but the solutions keep advancing! Unlike in Walker’s book, therefore, the lateral geniculate nucleus poses the threat of domination of the present work.

In attempting to survey virtually all past and most existing knowledge on the mammalian thalamus (and much of that on the nonmammalian thalamus as well), I have been mindful of Sir Charles Bell’s (1811) comment: “I have found some of my friends so mistaken in their conception of the object of the demonstrations which I have delivered in my lectures, that I wish to vindicate myself at all hazards. They would have it that I am in search of the soul; but I wish only to investigate the structure of the brain . . .” To the last part of his comment, I would add function as well as structure, for I am also cognizant of William Rushton’s (1977) dictum: “The great chapters on minute anatomy – those deserts of detail without a living functional watercourse, only a mirage from unverified speculation – are nearly unreadable.” Although my book has, justifiably, a strong anatomical content, it surveys the physiology and, where relevant, the clinical pathology of the thalamus as well. I have tried to bring together what I see as principles of mammalian thalamic organization, function, and development, drawing examples from whatever nucleus and species seemed relevant. These principles, or information that seems best suited to lead to new principles, are surveyed in Chapters 3– 6. The individual nuclei or constellations of related nuclei are given separate treatment in Chapters 7– 16. In these chapters, the basic format is as follows: structure including species variations, followed by terminology, connections, and functional characteristics. The reader should be able to find in these chapters reference to and often a detailed consideration of most mammalian thalami. However, in order to provide a kind of anatomical baseline, brief descriptions and ample photographs of sections through the thalami of six representative mammalian species are provided in Chapter 2. Given the current comparative anatomical climate, I would not dare attempt a synthesis of the nonmammalian thalamus with that of the mammal; therefore, a survey of the thalamus in nonmammals appears separately in Chapter 17. Despite my timidity and some past skepticism, having reviewed the nonmammalian literature, I cannot help but feel that the nonmammalian thalamus may hold some principles in common with that of the mammal after all.

My approach in virtually all the chapters has been a strongly historical one, coupled with a certain degree of didacticism, leading up to what I see as some of the currently exciting issues in thalamic research. This historical emphasis, which starts with a 2000-year perspective in Chapter 1, seemed necessary in all chapters in view of the long period that had elapsed since publication of the works of Le Gros Clark and Walker. But I am also conscious that some of the truly seminal works on thalamic anatomy by European workers of the half-century prior to Le Gros Clark and Walker are virtually lost to view nowadays. The same can probably even be said of the works of several more recent scientists, despite their contributions to fundamental knowledge. I hope that the major contributors are now given the credit they deserve, and the reader who wishes to know who named what and in which species ought to be able to find it in these pages. The didactic element also stems in part from the long period without a comprehensive treatment of the thalamus. However, it also arises from a desire to formulate principles unconstrained by accounts of individual thalamic nuclei or species and to provide a baseline of knowledge for a student or for a neuroscientist entering the area from another discipline. I trust that the reviews of new information will speak for themselves.

This work has occupied me for more time than I care to admit, and I am particularly grateful to my fellows and students, whose forbearance has given me the opportunity to complete it: Stewart Hendry, Chen-Tung Yen, Blair Clark, Michael Conley, Javier DeFelipe, May Kay Floeter, and David Schreyer kept the laboratory going as I became more and more preoccupied and saved me from many potential solecisms in the text. The photography is largely my own, with much assistance from Margaret Bates, but it could not have reached its standard if it had not been for the consistently high quality of the histological material provided by Bertha McClure. The experimental material prepared by Ms. McClure in my laboratory has been generated by the group of colleagues mentioned above as well as by past collaborators and students, who include Randi Leavitt, Maxwell Cowan, Harold Burton, John Krettek, Larry Swanson, Thomas Thach, Nancy Berman, Steven Wise, Joe Dan Coulter, Jean Graham, David Friedman, James Fleshman, Karen Valentino, David Tracey, Robert Porter, Chisato Asanuma, Lorraine Yurkewicz, and Todd Rainey.

Over the last 12 years, my experimental work has been supported by Research Grants NS-10526 and NS-15070, and by various training grants from the National Institutes of Health, United States Public Health Service, and briefly at Washington University by the McDonnell Center for Studies of Higher Brain Function and the George H. and Ethel Ronzoni Bishop Bequest. Many colleagues have kindly provided brains of uncommon animals to be sectioned or other materials. For their help I am most grateful, and I have acknowledged their contributions at appropriate places in the text. My greatest debt of thanks is to Margo Gross who, with equanimity, typed, retyped, and typed yet again, while simultaneously dealing with all the secretarial demands of a busy laboratory.

PREFACE TO THE THALAMUS, SECOND EDITION

When The Thalamus was published in 1985, I could confidently assert that it was the first work of its type for nearly 50 years. Despite the lengthy time that had elapsed since the publication of its forerunners, it was still possible to survey at reasonable length the status of knowledge of the thalamus as it stood at the time of publication. However, as I was penning the concluding chapter, I realized that studies of the thalamus were about to undergo a sea change that would not only be more highly productive but which would also place the thalamus more than ever before at the forefront of much of modern neuroscience.

The discovery by Llinás and Jahnsen (1982; Jahnsen and Llinás, 1984) of the low-threshold calcium current in thalamic neurons and of what it meant for relay cell function was as much a revolution in studies of the thalamus as Nissl’s first description of the thalamic nuclei and their connectivity. Soon to be followed by the evidence of its role in thalamic function in vivo at the hands of Steriade and co-workers (Deschênes et al., 1984; Roy et al., 1984), the discovery of the T current was to spawn a large number of important investigations on subjects as seemingly disparate as the intrinsic biophysical properties of thalamic neurons, the interactions between neurotransmitters and their receptors in thalamic neurons, and the large-scale operations of the thalamocortical network in states of sleep and wakefulness. The first two were perhaps natural extensions of the widespread studies of neuronal function in many parts of the brain that had been made possible by the introduction of the in vitro slice preparation and by advances in the fields of neuropharmacology and molecular biology. However, the third represented a remarkable revivification of the field of state-dependent activities of the forebrain that had been kept alive in only a few laboratories, notably that of Steriade, since its heyday in the 1940s and 1950s. Bringing all these themes together in the hands of many workers has given rise to a new view of the thalamus. It is one that transcends the view of the thalamus as a relay for sensory information that was based upon the early anatomical studies and upon studies of the stimulus–response properties of single neurons, although it by no means diminishes the relay function as one of the most important of thalamic states. The principal focus is now, however, on assemblies of thalamic neurons, rather than on individual neurons, and on how the synchronous activity of these assemblies in low- and high-frequency oscillations correlates with sleep, arousal, attentive wakefulness, perception, higher cognitive function, and disorders such as epilepsy – something that a friend has popularized under the rubric of “states of vigilance.”

This second edition of The Thalamus revisits the thalamus and has much new ground to cover as a consequence of the outpouring of new information, an outpouring that has further burgeoned by the addition of new findings on the early development of the thalamus, also a result of the molecular revolution. It still follows the format of its predecessor and although a careful reader may discern in places echoes of the earlier work, it is a completely new book. The chapters on synaptic organization and function and on the intrinsic properties of thalamic cells in particular have been expanded enormously and the chapters on the chemistry and development of the thalamus, for which there was very little information 20 years ago, are among the largest. Data pertaining to each nuclear group and its connections have been brought up to date and occasionally reinterpreted. Photographs of the architecture of the thalamus from the commoner experimental mammals have been expanded and those from many new species, including rare ones such as the two monotremes, have been added. There is also a specific chapter devoted to the human thalamus – something that was omitted from the first The Thalamus because of space constraints. Finally, the chapter on comparative anatomy has been broadened by the introduction of some evolutionary considerations that now seem reasonable in view of the discovery of many common patterns of gene expression in developing mammals and non-mammals.

The second edition of The Thalamus is not an encyclopedic work. While much factual information can be obtained from it, it is by no means all-inclusive and occasionally material has been reduced or even omitted in the interests of preserving a flow of ideas. Like its predecessor, this edition is strongly historical. This is not an approach that is fashionable today in an era in which the more favored vehicles of scientific publication encourage superficiality, and if authors look back at all it is only to the sources of their own dogmata. However, rather than being seen as a latter day Gibbon sitting “. . . musing amidst the ruins of the Capitol while the barefoot fryars were singing Vespers in the temple of Jupiter, . . .”¹ I would prefer to be seen as having provided a tour d’horizon that presents the current state of knowledge about most aspects of the thalamus and looks in depth at the way in which this knowledge has been built up over the centuries. When the original The Thalamus was published, a colleague, now deceased, remarked that “everyone will use it and nobody will reference it”. While it is true that The Thalamus has served, unacknowledged, as a source of an opening sentence in many an introduction or as a source of a reference to an earlier author such as Cajal in its original form, it has in fact proven to be one of the most quoted neuroscience books. Admittedly, it has more often than not been quoted simply as a generic reference to the thalamus, or as a straw man against which to wield a whip (“. . . (Jones, 1985). However, . . .”), but sometimes it has been quoted as if an author had actually studied some part of it. With in excess of 7500 references and a strong expression of an individual point of view, the second edition of The Thalamus will hopefully prove of equal usefulness.

One feature of the original The Thalamus that has been expanded is the high-quality photographic material that displays the cyto-, myelo-, and chemoarchitecture of the thalami of most of the commonly used experimental mammals, as well as of a number of less-well-known species, including the monotremes, which can be used to illustrate unique features of the thalamus. To these have been added extensive series of preparations illustrating patterns of gene expression in the adult and developing thalamus, and photomicrographs and electron micrographs showing the morphology, fine structure, and finer chemical anatomy of thalamic neurons. I have also sought to include many figures from physiological and neuropharmacological studies that are the most illustrative of the functional attributes of thalamic neurons, either as representatives of the thalamus and the thalamocortical network as a whole or as elements peculiar to individual nuclei. These figures are a combination of the most recent and the most historical.

As in the original The Thalamus, all the photographs and artwork are my own, with much help from Kristyna Lensky, Adeoluwa Idowu, and Matthew Countryman. The high quality of the histological material that has made the photographs possible is a tribute to the superior technical abilities of a succession of excellent assistants who over the last 20 years have included Kim Anh Nguyen, Christopher Nguyen SJ, Amy Vu, Hao Truong, Bich-Van Tran, Clyde King Ⅲ, Xiaohan Fan, Malalai Yusufzai, and especially Phong Nguyen. In the same period, I have benefited enormously from the privilege of working with a succession of students, postdoctoral fellows, and other associates, all of whom have left their marks on some aspect of this work. They include David Schreyer, Carol Hunt, Stewart Hendry, Javier DeFelipe, Marco Molinari, Harris Schwark, Christopher Honda, Tatsuo Hirai, Aric Agmon, Lee Yang, Richard Warren, Xao-Bo Liu, George Huntley, Deanna Benson, Isabel Scarisbrick, Timothy Woods, Tsutomo Hashikawa, Hisayuki Ojima, Yasuo Kawaguchi, Yoshiyuki Kubota, Patricia Morino-Wannier, Estrella Rausell, Fengyi Liang, Jufang He, Elisabetta Dell’Anna, Mariella Leggio, Schahram Akbarian, Molly Huntsman, Damien Longson, Carol Longson, Alberto Muñoz, Gregory Popken, Liming Zhang, Margherita Molnar, Peyman Golshani, Sonia Bolea, Shawn Hayes, James Stone, Prabhakara Choudary, Alessandro Graziano, and Karl Murray. To several of these and to my colleagues Drs. Kenneth Britten, Leo Chalupa, Gregg Recanzone, and Martin Usrey, I am indebted for reading and commenting on many aspects of the manuscript. I also owe a considerable debt of gratitude to Evan McMillan for managing the reference database and to Amy Maliska and Kathleen Keeter for general assistance of all kinds. Thanks, too, to Cambridge University Press and especially Jane Ward, without whom this would have been a lesser book.

The work of my laboratory in the years over which this work was being written has been supported by research grants numbers NS21377, NS22317, NS30101, NS39094, EY07193, MH/DA52154, MH54844, and MH60398 from the National Institutes of Health, United States Public Health Service, by grants from the W. M. Keck Foundation, the National Alliance for Research in Schizophrenia and Depression, the Pritzker Family Philanthropic Fund, the Frontier Research Program, and the University of California, Davis. For this support I am deeply grateful.