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Thalamic oscillations and signaling
Neuroscience Vol. 41, No. 213, pp. 841-843, 1991 Printed in Great Britain
Pergamon Press plc IBRO
BOOK REVIEWS
OseiIIatlom and Sllg. M. STEtU4DE,E. G. JONESand R. R. LLIN~~S.John Wiley, New York. (1990) 430 pp. $115. Thalamle
The discovery of brain waves by Caton (1870) failed to capture the attention of neurophysiologists until Adrian and Matthews validated Berger’s rediscovery over 60 years ago. Since then the study of spontaneous and evoked electrocortical potentials has contributed greatly to the understanding of thalamocortical functional relations, as well as to the role of brain sternthalamic interactions in modifying states of vigilance and the neural substrate of cortical electrogenesis. Central to these issues is the special role of the thalamus in the generation of electrocortical synchronization and desynchronization and modulation of transmission of afferent and efferent signals in cortical synaptic organizations. It follows that the understanding of neocortical neuronal processing systems requires adequate knowledge of the basic morphophysioloical substrate for thalamic transactions. Thalamic Oscillations and Signaling is a unique exposition of the major problems concerning the role of the thalamus and thalamocortical circuitry in a wide variety of electrocortical and behavioral activities. Its genesis can be traced to two conferences held at the Neuroscience Institute and the authors’ personal interests. While the book is not meant to be an encyclopedic volume, according to the authors, it will clearly serve the purpose until one comes along. Those unfamiliar with thalamic studies prior to the 1970s will be rewarded with a critical and comprehensive review in Part I of the issues concerning thalamocortical synchronization, particularly spindle rhythmicity. While the authors correctly point out the difficulties encountered by early thalamologists in securing adequate intracellular data in uiuo, they are generous in their appraisal of the contributions of these workers in identifying the role of prolonged inhibitory activities, postinhibitory rebound and in characterizing synaptic sequences in many thalamic nuclei in spontaneous and evoked thalamocortical synchronization activities. They are also appropriately critical of the extent to which theoretical formulations of thalamic synchronization failed to appreciate available morphological data, particularly in respect to the organization of thalamic relay nuclei. This section also provides a useful review and discussion of concepts of thalamocortical augmentation, recruitment and spontaneous spindle waves, and the hoary notions concerning non-specific and diffuse thalamic projection systems. Part II deals in considerable depth with the nuclear organization of the thalamus, the differential thalamic projections on the telencephalon, types of thalamic inputs, special features of the reticular thalamic nucleus and the intrinsic circuitry in the thalamus and cortex including a survey of putative transmitter and receptor systems. The authors hasten to note that recognition of the role of GABA as the major transmitter agent in the dorsal thalamus does not readily permit conclusions as to the overall significance of GABA in general thalamic functions. The same might be said for studies that implicate a modifying or “enabling” role of noradrenergic, serotonergic or cholinergic inputs on thalamic activities. The use of the term “nonspecific” (p. 55) to describe these affercnt systems illustrates the tendency of recurrent appeal to vagaries in lieu of data. Attention is drawn to studies of the past decade that have confirmed a major role of the reticular nucleus in
the morphological substrate of thalamic synchronization. Collaterals of thalamocortical and related corticothalamic fibers terminate in particular sectors of the reticular nucleus whose neurons appear to produce GABA. In turn, reticular neurons project upon related dorsal thalamic nuclei with the possible exception of the anterior nuclear group. The authors emphasize that any recurrent inhibitory effects on thalamic relay neurons are likely to be mediated by circuits through the reticular nucleus rather than recummt collaterals, as proposed by earlier thalamologists. Considering the importance of inhibitory mechanisms in the control of thalamocortical activities, definition of the morphological substrate for intrathalamic internuclear inhibition is no little accomplishment. However, the authors also point out that despite remarkable advances in morphotechnologies, many questions concerning thalamocortical corticothalamic, intracortical and nonspecific inputs and circuitry remain unanswered. A bounty of superb problems is defined for many a budding neuroscientist to devour. Detailed electrophysiological studies on the fundamental membrane processes underlying oscillatory behavior of thalamic neurons are presented in Part III. Following upon the successes of one of the authors (R.R.L.) in studies of inferior olive neurons in slice and isolated brain preparations, attention is focused on the virtues (and limitations) of in oitro techniques in defining thalamic neuronal membrane properties. Thalamic neurons are found to exhibit relatively uniform properties including electroresponsiveness in two modes: relay-type or phasic burst-type, both modes being intrinsic to thalamic cells and controlled by membrane potential. Data supporting the existence of a variety of voltage-dependent Na+, Caz+ and K+ conductances of somatic and dendritic origin are elegantly displayed and appropriately referenced. Differences between reticular and other thalamic neurons are noted particularly in regard to the presence of small (partial) spikes possibly of dendritic origin as well as two distinct all-or-none low-threshold calcium responses in reticular cells. A brief discussion of theoretical models relating to thalamic cell oscillations leads to the conclusion that “thalamic neurons belong to a class of neurons having tonic conductances organ&d so as to facilitate intrinsic voltage oscillatory properties” (p. 135). The authors remind us, however, “that in the context of thalamic function, synaptic bombardment will clearly alter the rather simple sequence of conductances illustrated here.” So much for reconciliation. The last section (Part IV) comprises more than half of the book. In many respects it provides the greatest challenge to the reader for focused attention since it attempts to integrate a vast literature on methodological aspects of studies on vigilance, the cellular basis of synchronized spindle oscillations during sleep, the synaptic processes related to thalamic and cortical transfer of information during activated states and a brief review on brainstem control of thalamic operations. These complex subjects are presented in detail (with 122 illustrations), most representing published or unpublished work of one of the authors (MS.). In effect, Part IV constitutes a primer on thalamocortical electrophysiology. Its completeness is underscored by the inclusion of ontogenetic investigations which have been lamentably few in number. Perhaps more might have been said about membrane processes in event-related potentials, set-related neurons and the neural mechanism of selective attention for these are
841
842
Book Reviews
subjects undergoing intense scrutiny by an increasingly large number of neuroscientists. Several themes dominate this book. Foremost is the pursuit of the morphophysiological substrate of prolonged rhythmically recurring inhibition set into operation during thalamic neuronal synchronization. Another is concerned with attenuation of this inhibition occasioned by brainstem reticular activation. Both underly transitions in global brain function associated with altered states of vigilance. The essential importance of these processes for normal and
aberrant brain functions requires no further comment. Neuroscientists engaged in similar or related studies will encounter a wealth of information here, and, not infrequently, an insight or two. Others never privileged to study the mammalian forebrain because of bias towards “simple network systems” in (much) lower forms may experience an epiphany in the revelation that even the most complex higher nervous system functions can be explicable in terms of robust morphophysiological data. D. P. PUKPUKA
Tbalsmic Oactitioes and Signaling.M. STERMDE, E.G. JONESand R. R. LLINAS. John Wiley, New York. (1990)
the thalamus stands out here. In contrast to other systems of the brain, a large proportion of thaIamic afferents utilize the inhibitory neurotransmitter GABA. In the third and fourth parts, we learn about the importance of hyperpolarization in thalamic oscillation and the reader might expect that these two thoughts (i.e. inhibitory inputs and the induced hyperpolarization) will be discussed in a systems context at a later point. To my regret, however, virtually no discussion is devoted to the role and importance of the major source of extrinsic inhibition, the extrapyramidal system, in the oscillatory behavior of the thalamus. The discovery of the low-threshold calcium spike by the authors, discussed in detail in Part 3, triggered a paradigm shift in thalamic research. Suddenly, everything fell into place. Population synchrony can be induced and maintained not only by extensive axon collaterals, but also by inhibition. Textbooks must be rewritten! In this section we learn about the nature of “preparedness” of the thalamocortical cells to deal with inhibition. The rest of the book beautifully illustrates that the low-threshold calcium spike is not a peculiar phenomenoninteresting only for membrane biophysicists-but rather is of cardinal importance for the population oscillation of neuronal aggregates. It is here the reader finds examples of the perfect harmony between the ionic properties of individual neurons and population behavior of thalamic cell aggregates. The four scholarly chapters of Part 4 deal with rhythmic thalamocortical patterns and their relationship with behavior, oscillatory and non-oscillatory modes of the thalamus during sleep and brainstem control of thalamus. Finally, there is a 50-page bibliography, spanning from the classical works of Bremer to papers published-or in press-in the late 1980s. Inevitably, some specialists will find parts in the book with which they are leas than entirely happy. Let me pick the title Thalamic oscillations and sianallina first. I believe that signalling and oscillating modes-are not dichotomous but orthogonal. I fully accept and support the view that the thalamus has two diametrically opposite functional states and I subscribe to the notion that both states are extremely important for normal physiological functions. However, the antithesis of oscillation is non-oscillation and these terms should refer to the experimentally monitored (independent) variables. We simply state our experimental observations with these descriptive terms. On the other hand, the “signailing” mode refers to an inferred function (the dependent variable) and its antithesis therefore should be another functional entity, i.e. the dependent variable of the oscillatory behavior. But what physiological mechanism is behind the oscillatory pattern, the only collective behavior of thalamic neurons? Yes, we have learnt that it correlates with sleep, but are we much closer to its function from this information alone? To my disappointment I found that only two pages were devoted to the possible significance of thalamocortical oscillations. My second point of criticism is that the authors paradoxically deny the key importance of the thalamus in the occipital alpha rhythm and toss the problem of rhythm generation back to the neocortex. If the occipital cortex is
430 pp. S115. According to handbook knowledge the thalamus is a large structure intercalated between the ascending sensory pathways and the neocortex. Its morphological specialty is that the individual nuclei and the neurons therein have very few collaterals to their neighbors. A structure with such features is a gold-mine for the anatomist but has been an embarrassment for the function-oriented scientist for many years. “Thalamic neurons passively transmit (or relay) incoming information” was the best hypothesis. How the individual nuclei of thalamus communicate with one another and how they play a concert without a conductor have remained a mystery until very recently. The authors of Thalamic Oscillations and Sianaliinn have spared no effort in unveiling this secret and putting their-thoughts into a brilliant volume. The book is a coherent and lucid account of the paradigms and major preparations currently used in investigating the structural-functional bases of information processing and transfer in the thalamus from the ionic mechanisms of individual cells to the system level. If any one word can characterize this text it is “thoughtful”. The authors have thought deeply about many fundamental issues in the field and expressed these thoughts clearly. Without hesitation I claim that the rapid advancement of the authors’ understanding of the basic mechanisms of the thalamus is a result of a perfect marriage between in vitro and in oiuo physiology. Perhaps no other part of the brain benefitted so eloquently from such a combined approach. The power and limitations of the in vitro and in vivo experiments are well understood here and compliment each other. The reward is a meaningful fusion of knowledge about the biophysical properties of thalamic cells and the network behavior of thalamic circuitry in the intact animal. The 430-page volume consists of four major parts: historical background, intrinsic circuitry and afferents of the thalamus, physiological cellular mechanism, and behavioral correlates of the collective neuronal activity. Being a newcomer to thalamic research, I most enjoyed the historical part. These pages belong to a genre of scientific tell-it-as-it-was, applauding and criticizing the major players of the game from a historical perspective. While the young generation can learn about the de facto discoveries from research papers, it is only the historical perspective that teaches them how major discoveries are ma& and how opinions of authoritative figures can suppress the evolution of new thought in a very direct way. In addition, what emerges clearly from this historical review is that no matter how hard we try to solve a problem with conventional tools and intuition, often only new methods are capable of turning the nature of scientific arguments. We should be thankful to the authors for sharing with us this fascinating story of neuroscience. The second part is a thorough account of thalamic connectivity, transmitters, receptors and afferents. Although not particularly emphasized, a unique anatomical feature of
Pergamon Press plc IBRO
BOOK REVIEWS
OseiIIatlom and Sllg. M. STEtU4DE,E. G. JONESand R. R. LLIN~~S.John Wiley, New York. (1990) 430 pp. $115. Thalamle
The discovery of brain waves by Caton (1870) failed to capture the attention of neurophysiologists until Adrian and Matthews validated Berger’s rediscovery over 60 years ago. Since then the study of spontaneous and evoked electrocortical potentials has contributed greatly to the understanding of thalamocortical functional relations, as well as to the role of brain sternthalamic interactions in modifying states of vigilance and the neural substrate of cortical electrogenesis. Central to these issues is the special role of the thalamus in the generation of electrocortical synchronization and desynchronization and modulation of transmission of afferent and efferent signals in cortical synaptic organizations. It follows that the understanding of neocortical neuronal processing systems requires adequate knowledge of the basic morphophysioloical substrate for thalamic transactions. Thalamic Oscillations and Signaling is a unique exposition of the major problems concerning the role of the thalamus and thalamocortical circuitry in a wide variety of electrocortical and behavioral activities. Its genesis can be traced to two conferences held at the Neuroscience Institute and the authors’ personal interests. While the book is not meant to be an encyclopedic volume, according to the authors, it will clearly serve the purpose until one comes along. Those unfamiliar with thalamic studies prior to the 1970s will be rewarded with a critical and comprehensive review in Part I of the issues concerning thalamocortical synchronization, particularly spindle rhythmicity. While the authors correctly point out the difficulties encountered by early thalamologists in securing adequate intracellular data in uiuo, they are generous in their appraisal of the contributions of these workers in identifying the role of prolonged inhibitory activities, postinhibitory rebound and in characterizing synaptic sequences in many thalamic nuclei in spontaneous and evoked thalamocortical synchronization activities. They are also appropriately critical of the extent to which theoretical formulations of thalamic synchronization failed to appreciate available morphological data, particularly in respect to the organization of thalamic relay nuclei. This section also provides a useful review and discussion of concepts of thalamocortical augmentation, recruitment and spontaneous spindle waves, and the hoary notions concerning non-specific and diffuse thalamic projection systems. Part II deals in considerable depth with the nuclear organization of the thalamus, the differential thalamic projections on the telencephalon, types of thalamic inputs, special features of the reticular thalamic nucleus and the intrinsic circuitry in the thalamus and cortex including a survey of putative transmitter and receptor systems. The authors hasten to note that recognition of the role of GABA as the major transmitter agent in the dorsal thalamus does not readily permit conclusions as to the overall significance of GABA in general thalamic functions. The same might be said for studies that implicate a modifying or “enabling” role of noradrenergic, serotonergic or cholinergic inputs on thalamic activities. The use of the term “nonspecific” (p. 55) to describe these affercnt systems illustrates the tendency of recurrent appeal to vagaries in lieu of data. Attention is drawn to studies of the past decade that have confirmed a major role of the reticular nucleus in
the morphological substrate of thalamic synchronization. Collaterals of thalamocortical and related corticothalamic fibers terminate in particular sectors of the reticular nucleus whose neurons appear to produce GABA. In turn, reticular neurons project upon related dorsal thalamic nuclei with the possible exception of the anterior nuclear group. The authors emphasize that any recurrent inhibitory effects on thalamic relay neurons are likely to be mediated by circuits through the reticular nucleus rather than recummt collaterals, as proposed by earlier thalamologists. Considering the importance of inhibitory mechanisms in the control of thalamocortical activities, definition of the morphological substrate for intrathalamic internuclear inhibition is no little accomplishment. However, the authors also point out that despite remarkable advances in morphotechnologies, many questions concerning thalamocortical corticothalamic, intracortical and nonspecific inputs and circuitry remain unanswered. A bounty of superb problems is defined for many a budding neuroscientist to devour. Detailed electrophysiological studies on the fundamental membrane processes underlying oscillatory behavior of thalamic neurons are presented in Part III. Following upon the successes of one of the authors (R.R.L.) in studies of inferior olive neurons in slice and isolated brain preparations, attention is focused on the virtues (and limitations) of in oitro techniques in defining thalamic neuronal membrane properties. Thalamic neurons are found to exhibit relatively uniform properties including electroresponsiveness in two modes: relay-type or phasic burst-type, both modes being intrinsic to thalamic cells and controlled by membrane potential. Data supporting the existence of a variety of voltage-dependent Na+, Caz+ and K+ conductances of somatic and dendritic origin are elegantly displayed and appropriately referenced. Differences between reticular and other thalamic neurons are noted particularly in regard to the presence of small (partial) spikes possibly of dendritic origin as well as two distinct all-or-none low-threshold calcium responses in reticular cells. A brief discussion of theoretical models relating to thalamic cell oscillations leads to the conclusion that “thalamic neurons belong to a class of neurons having tonic conductances organ&d so as to facilitate intrinsic voltage oscillatory properties” (p. 135). The authors remind us, however, “that in the context of thalamic function, synaptic bombardment will clearly alter the rather simple sequence of conductances illustrated here.” So much for reconciliation. The last section (Part IV) comprises more than half of the book. In many respects it provides the greatest challenge to the reader for focused attention since it attempts to integrate a vast literature on methodological aspects of studies on vigilance, the cellular basis of synchronized spindle oscillations during sleep, the synaptic processes related to thalamic and cortical transfer of information during activated states and a brief review on brainstem control of thalamic operations. These complex subjects are presented in detail (with 122 illustrations), most representing published or unpublished work of one of the authors (MS.). In effect, Part IV constitutes a primer on thalamocortical electrophysiology. Its completeness is underscored by the inclusion of ontogenetic investigations which have been lamentably few in number. Perhaps more might have been said about membrane processes in event-related potentials, set-related neurons and the neural mechanism of selective attention for these are
841
842
Book Reviews
subjects undergoing intense scrutiny by an increasingly large number of neuroscientists. Several themes dominate this book. Foremost is the pursuit of the morphophysiological substrate of prolonged rhythmically recurring inhibition set into operation during thalamic neuronal synchronization. Another is concerned with attenuation of this inhibition occasioned by brainstem reticular activation. Both underly transitions in global brain function associated with altered states of vigilance. The essential importance of these processes for normal and
aberrant brain functions requires no further comment. Neuroscientists engaged in similar or related studies will encounter a wealth of information here, and, not infrequently, an insight or two. Others never privileged to study the mammalian forebrain because of bias towards “simple network systems” in (much) lower forms may experience an epiphany in the revelation that even the most complex higher nervous system functions can be explicable in terms of robust morphophysiological data. D. P. PUKPUKA
Tbalsmic Oactitioes and Signaling.M. STERMDE, E.G. JONESand R. R. LLINAS. John Wiley, New York. (1990)
the thalamus stands out here. In contrast to other systems of the brain, a large proportion of thaIamic afferents utilize the inhibitory neurotransmitter GABA. In the third and fourth parts, we learn about the importance of hyperpolarization in thalamic oscillation and the reader might expect that these two thoughts (i.e. inhibitory inputs and the induced hyperpolarization) will be discussed in a systems context at a later point. To my regret, however, virtually no discussion is devoted to the role and importance of the major source of extrinsic inhibition, the extrapyramidal system, in the oscillatory behavior of the thalamus. The discovery of the low-threshold calcium spike by the authors, discussed in detail in Part 3, triggered a paradigm shift in thalamic research. Suddenly, everything fell into place. Population synchrony can be induced and maintained not only by extensive axon collaterals, but also by inhibition. Textbooks must be rewritten! In this section we learn about the nature of “preparedness” of the thalamocortical cells to deal with inhibition. The rest of the book beautifully illustrates that the low-threshold calcium spike is not a peculiar phenomenoninteresting only for membrane biophysicists-but rather is of cardinal importance for the population oscillation of neuronal aggregates. It is here the reader finds examples of the perfect harmony between the ionic properties of individual neurons and population behavior of thalamic cell aggregates. The four scholarly chapters of Part 4 deal with rhythmic thalamocortical patterns and their relationship with behavior, oscillatory and non-oscillatory modes of the thalamus during sleep and brainstem control of thalamus. Finally, there is a 50-page bibliography, spanning from the classical works of Bremer to papers published-or in press-in the late 1980s. Inevitably, some specialists will find parts in the book with which they are leas than entirely happy. Let me pick the title Thalamic oscillations and sianallina first. I believe that signalling and oscillating modes-are not dichotomous but orthogonal. I fully accept and support the view that the thalamus has two diametrically opposite functional states and I subscribe to the notion that both states are extremely important for normal physiological functions. However, the antithesis of oscillation is non-oscillation and these terms should refer to the experimentally monitored (independent) variables. We simply state our experimental observations with these descriptive terms. On the other hand, the “signailing” mode refers to an inferred function (the dependent variable) and its antithesis therefore should be another functional entity, i.e. the dependent variable of the oscillatory behavior. But what physiological mechanism is behind the oscillatory pattern, the only collective behavior of thalamic neurons? Yes, we have learnt that it correlates with sleep, but are we much closer to its function from this information alone? To my disappointment I found that only two pages were devoted to the possible significance of thalamocortical oscillations. My second point of criticism is that the authors paradoxically deny the key importance of the thalamus in the occipital alpha rhythm and toss the problem of rhythm generation back to the neocortex. If the occipital cortex is
430 pp. S115. According to handbook knowledge the thalamus is a large structure intercalated between the ascending sensory pathways and the neocortex. Its morphological specialty is that the individual nuclei and the neurons therein have very few collaterals to their neighbors. A structure with such features is a gold-mine for the anatomist but has been an embarrassment for the function-oriented scientist for many years. “Thalamic neurons passively transmit (or relay) incoming information” was the best hypothesis. How the individual nuclei of thalamus communicate with one another and how they play a concert without a conductor have remained a mystery until very recently. The authors of Thalamic Oscillations and Sianaliinn have spared no effort in unveiling this secret and putting their-thoughts into a brilliant volume. The book is a coherent and lucid account of the paradigms and major preparations currently used in investigating the structural-functional bases of information processing and transfer in the thalamus from the ionic mechanisms of individual cells to the system level. If any one word can characterize this text it is “thoughtful”. The authors have thought deeply about many fundamental issues in the field and expressed these thoughts clearly. Without hesitation I claim that the rapid advancement of the authors’ understanding of the basic mechanisms of the thalamus is a result of a perfect marriage between in vitro and in oiuo physiology. Perhaps no other part of the brain benefitted so eloquently from such a combined approach. The power and limitations of the in vitro and in vivo experiments are well understood here and compliment each other. The reward is a meaningful fusion of knowledge about the biophysical properties of thalamic cells and the network behavior of thalamic circuitry in the intact animal. The 430-page volume consists of four major parts: historical background, intrinsic circuitry and afferents of the thalamus, physiological cellular mechanism, and behavioral correlates of the collective neuronal activity. Being a newcomer to thalamic research, I most enjoyed the historical part. These pages belong to a genre of scientific tell-it-as-it-was, applauding and criticizing the major players of the game from a historical perspective. While the young generation can learn about the de facto discoveries from research papers, it is only the historical perspective that teaches them how major discoveries are ma& and how opinions of authoritative figures can suppress the evolution of new thought in a very direct way. In addition, what emerges clearly from this historical review is that no matter how hard we try to solve a problem with conventional tools and intuition, often only new methods are capable of turning the nature of scientific arguments. We should be thankful to the authors for sharing with us this fascinating story of neuroscience. The second part is a thorough account of thalamic connectivity, transmitters, receptors and afferents. Although not particularly emphasized, a unique anatomical feature of