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New Concepts in Cerebellar Neurobiology(Neurology and Neurobiology, Vol. 22)
prised of different types of neurons. This covers the generation of rhythmic motor activity in the well-studied crustacean stomatogastric ganglion and the structure, function and modulation of neurons in central visual pathways and in the cerebral cortex. This theme is expanded in the fourth section, which describes many of the best models for synaptic plasticity and learning. These include the Aplysia sensory neurons, hippocampus, cerebellum and red nucleus. The chapter by Kandel et al. starts with an interesting account of how views of the nature of synaptic transmission have changed in the last fifty years. The section terminates with a contribution from Changeux and Heidmann, which includes a model of short-term regulation of synaptic efficacy based on allosteric interactions in the acetylcholine receptor and also sets the stage for the final section on theoretical models.
The last section deals with mathematical models both of individual neurons and neural networks. Although such work is both stimulating and fun to carry out, it is clear, on comparing this section with the remainder of the book, that we have a long way to go before neural modelling reaches a stage at which it can work routinely in parallel with experimental work, as is the case in other disciplines. In summary, the book describes a wealth of synaptic mechanisms that have come to light in the last 20 years, and indicates that many more are likely to be unearthed. This is not a book for the beginning student. Many of the chapters presuppose a great deal of background knowledge of their respective fields. Nevertheless, the more advanced student or practising neurobiologist will find it a useful review of the direction of research in the different subdisciplines featured in the book.
informative reviews of the different topics covered by this volume. Is it possible to understand the edited by James S. King, Alan R. Liss, cerebellum? It seems, at first sight 1987. £66.00 (xi + 435 pages) ISBN that, as in nuclear physics before 0 8451 2724 1 the discovery of quarks, the As can be infered from its pro- beautiful simplicity of the strucvocative title, this book sounds ture superbly analysed by Eccles, like the first attempt to give a Ito and SzentagotaT 20 years ago comprehensive view of the pre- (The Cerebellum as a Neuronal sent status of our knowledge on Machine, Springer-Verlag) has the cerebellum since the remark- now progressively given rise to a able monograph of Masao Ito in monster of heterogeneity and 1984 (The Cerebellum and Neural complexity waiting for some kind Control, Raven Press). The book is of unifying theory. based on a symposium of the same For instance, we now know name held in 1985 at the annual from the review of King eta/. that meeUng of the Cajal Club in Toronto, cerebellar afferents probably also and covers many different aspects include enkephalinergic fibers, of recent research in cerebellar some having a distribution similar neurobiology. These include che- to those of monoaminergic fibers mical heterogeneity of cortical and the others resembling climbneurons, variations in local cir- ing fibers. Similarly, the papers by cuits, anatomical organization of Bishop et a/. and Voogd e t a / . afferent and efferent connec- clearly emphasize the heterotions, as well as developmental geneity of Purkinje cells, not only and physiological properties of in their biochemical markers, but also in the spatial arrangement of the cerebellar network. Not unexpectedly, the contri- their recurrent axon collaterals, butions deal primarily with the depending on their location in work of their respective authors, cortical zones organized in sagitbut to be fair, most have attemp- tal strips or in a mosaic of patches. The complexity of the structure ted to place their own data in a broader context, so that most of is also stressed by the detailed the 14 papers are up-to-date and reviews of anatomical and func-
tional organization of cerebellar afferents and efferents in the second part of the book, where one soon realizes that the already complicated parasagittal zonation of the cerebellar cortex (well documented by Voogd et aL) on anatomical and biochemical grounds can be further fractionated into a mosaic of subzones when considering the functional representation of the periphery via mossy and climbing fibers, as elegantly shown by Welder and by Lee Robertson. This also holds for the cerebropontocerebellar connections reviewed by Brodal, showing that every Iobule of the cerebellar cortex always receives inputs from several cortical areas, even though one can clearly dominate the others. Besides the functional properties of the cerebellar network mentioned above, the physiological contributions to the book mainly concern the processing of information during sensorymotor transactions and during locomotion, as well as the role of climbing fibers afferents in cerebellar information processing. In particular, Anderson et al. emphasize the possible role of these afferents as error detectors during locomotion (but see also
actions of specific neurotransmitter systems. Several of these chapters deal with the role of corelease of multiple neurotransmitters and some hint at the occurrence of autoreceptors for peptides co-released with classical transmitters. In particular, without over-indulging in speculation, the chapter by H6kfelt flirts with several exciting ideas about how co-released peptides, acting at autoreceptors, may selectively change synaptic flow in repetitively stimulated pathways. The contribution by Hemmings eta/. gives a review of the power of neurotransmitter-lin ked second messengers to produce profound changes in the properties of postsynaptic cells, and, using the phosphoprotein DARPP-32 as an example, shows how the response to second messengers may be differentially regulated in different neurons. The third section deals with the complexity of networks com-
New Concepts in Cerebellar Neurobiology (Neurology and Neurobiology,Vol. 22)
TINS, Vol. 11, No. 5, 1988
F. Crepel Labora~'rede Neuro/~'ologieet Neuropharrnacologie, Bat.440, UniversitE ParisJ;ud,91405 Orsay,France.
239
Ito's monograph), whereas Ebner and Bloedel propose that the inferior olive (i.e. the source of climbing fibers) functions as a central clock that times and controls the output of the cerebellum by a short-term modulation of the transactions through the mossy fiber system. As the reader will certainly realize, the unifying theory that links together these observations is still based on the notion of microzones in the cerebellar cortex (Oscarson, 1980), or, more precisely, units consisting of these microzones, the subset of olivary neurons projecting to them, and the subset of their target cerebellar nuclei neurons. Such units might use the multiple representation of the body found in the cerebellum for different purposes
depending on their output toward premotor sites or toward higher centers of motor control. However, as Welker says in his paper, further elaboration along this line has a good chance of remaining mainly metaphorical, given the present limitations of our knowledge! Finally, three reviews in this book deserve further comment. First, Haines and Dietrich describe in great detail reciprocal and direct connections between the cerebellum and the hypothalamus, which is of major importance for understanding of the otherwise well established clinical observations of the role of the cerebellum in visceral function and various behaviors. Second, early stages in the development of cerebellar afferents and in the
formation of synaptic junctions have been particularly well analysed by Carol Mason and by Landis and Wenstein, respectively. Both these anatomical and ultrastructural studies stress the existence of transient connections during development and the presence of recognition sites prior to proper synaptogenesis, which may underlie the formation of highly specific connections through a trial and error process of transient multiple innervation. Even though the new concepts alluded to in the title are scattered throughout more than 400 pages, I do believe that this book is worth a read for neuroscientists who want an up-to-date overview of current research in cerebellar neurobiology.
Phosphoproteins in Neuronal Function (Progress in Brain Research, Vol. 69)
grown enormously, and the discovery that certain products of this metabolism act as second messengers and may activate other protein kinases has given enormous impetus to neurochemistry. Coupled to evidence that protein kinases may regulate ion channels, the linkage between neuronal function and brain biochemistry is on a considerably firmer basis today. It is therefore not surprising that many articles in this volume address these new developments. The first section is devoted to polyphosphoinositide metabolism and although there is some overlap between the contents of the six articles, they are a useful collection of reviews with an emphasis on the nervous system. The pace of research in this area is exemplified by a 1986 update added to the article by Eichberg and Berti-Mattera. Here, among other results, they describe the discovery of the novel inositol tetrakisphosphate, yet today in 1988 a second messenger role for this metabolite is likely and two other tetrakisphosphate isomers have been discovered! Regulation of ion channels by phosphorylation is reviewed in five articles and provides a useful collection of papers. There is discussion of the role of cyclic AMP, calcium-dependent and independent protein kinases and their putative interaction in situ in relation to change in neuronal excita-
bility and possibly in associative learning. There is obvious overlap in this section with several articles that appear under a section entitled plasticity. I feel we can expect in the future that considerable definition of specific sites of phosphorylation on receptor proteins will provide a major impetus in this area. With the recent cloning and sequencing of several neurotransmitter receptors, work on the I]-adrenoceptor at least is beginning to define sites of phosphorylation associated with agonist-induced desensitization. It is perhaps another indication of the pace in this field that such studies are not described in this book. For many years now several groups have suggested that information storage may be associated with post-translational modification of synaptic proteins. Although I always considered such claims to be highly speculative, our recent dramatically improved understanding of the mechanisms and substrates of protein phosphorylation in the central nervous system may allow more confident claims in the future. I believe that this volume should be available through the library shelves to neuroscientists in general. The specialist may wait for a pause in the rapid developments in this area before buying a state-of-the-art review.
edited by W. H. Gispen and A. Routtenberg, Elsevier, 1986. $131.00/ Dfl.295.00 (xi + 394 pages) ISBN 0 444 80781 0 S. R. Nahorski
Departmentof Pharmacologyand Therapeutics, Universityof Leicester,Leicester LE17RH,UK.
240
This volume contains a number of contributions from a workshop that took place in Utrecht in September 1985. Although the book was published in late 1986, the extraordinary pace of research in certain areas unfortunately gives a somewhat dated flavour to some of the articles. However, having said that, this volume does bring together a number of important review articles that illustrate the crucial role protein kinases and brain protein phosphorylation have in cell-tocell communication particularly associated with synaptic transmission. It was recognized as long as 15 years ago that dramatic changes in protein phosphorylation accompanied depolarizing stimuli as well as the action of several putative neurotransmitters in cerebral tissues. With the discovery that cyclic AMP can mediate the action of certain transmitters, early emphasis was placed on cyclic AMP-dependent protein kinase and its substrates. In the last five years our understanding of receptors linked to polyphosphoinositide metabolism has
TINS, VoL 11, No. 5, 1988
The last section deals with mathematical models both of individual neurons and neural networks. Although such work is both stimulating and fun to carry out, it is clear, on comparing this section with the remainder of the book, that we have a long way to go before neural modelling reaches a stage at which it can work routinely in parallel with experimental work, as is the case in other disciplines. In summary, the book describes a wealth of synaptic mechanisms that have come to light in the last 20 years, and indicates that many more are likely to be unearthed. This is not a book for the beginning student. Many of the chapters presuppose a great deal of background knowledge of their respective fields. Nevertheless, the more advanced student or practising neurobiologist will find it a useful review of the direction of research in the different subdisciplines featured in the book.
informative reviews of the different topics covered by this volume. Is it possible to understand the edited by James S. King, Alan R. Liss, cerebellum? It seems, at first sight 1987. £66.00 (xi + 435 pages) ISBN that, as in nuclear physics before 0 8451 2724 1 the discovery of quarks, the As can be infered from its pro- beautiful simplicity of the strucvocative title, this book sounds ture superbly analysed by Eccles, like the first attempt to give a Ito and SzentagotaT 20 years ago comprehensive view of the pre- (The Cerebellum as a Neuronal sent status of our knowledge on Machine, Springer-Verlag) has the cerebellum since the remark- now progressively given rise to a able monograph of Masao Ito in monster of heterogeneity and 1984 (The Cerebellum and Neural complexity waiting for some kind Control, Raven Press). The book is of unifying theory. based on a symposium of the same For instance, we now know name held in 1985 at the annual from the review of King eta/. that meeUng of the Cajal Club in Toronto, cerebellar afferents probably also and covers many different aspects include enkephalinergic fibers, of recent research in cerebellar some having a distribution similar neurobiology. These include che- to those of monoaminergic fibers mical heterogeneity of cortical and the others resembling climbneurons, variations in local cir- ing fibers. Similarly, the papers by cuits, anatomical organization of Bishop et a/. and Voogd e t a / . afferent and efferent connec- clearly emphasize the heterotions, as well as developmental geneity of Purkinje cells, not only and physiological properties of in their biochemical markers, but also in the spatial arrangement of the cerebellar network. Not unexpectedly, the contri- their recurrent axon collaterals, butions deal primarily with the depending on their location in work of their respective authors, cortical zones organized in sagitbut to be fair, most have attemp- tal strips or in a mosaic of patches. The complexity of the structure ted to place their own data in a broader context, so that most of is also stressed by the detailed the 14 papers are up-to-date and reviews of anatomical and func-
tional organization of cerebellar afferents and efferents in the second part of the book, where one soon realizes that the already complicated parasagittal zonation of the cerebellar cortex (well documented by Voogd et aL) on anatomical and biochemical grounds can be further fractionated into a mosaic of subzones when considering the functional representation of the periphery via mossy and climbing fibers, as elegantly shown by Welder and by Lee Robertson. This also holds for the cerebropontocerebellar connections reviewed by Brodal, showing that every Iobule of the cerebellar cortex always receives inputs from several cortical areas, even though one can clearly dominate the others. Besides the functional properties of the cerebellar network mentioned above, the physiological contributions to the book mainly concern the processing of information during sensorymotor transactions and during locomotion, as well as the role of climbing fibers afferents in cerebellar information processing. In particular, Anderson et al. emphasize the possible role of these afferents as error detectors during locomotion (but see also
actions of specific neurotransmitter systems. Several of these chapters deal with the role of corelease of multiple neurotransmitters and some hint at the occurrence of autoreceptors for peptides co-released with classical transmitters. In particular, without over-indulging in speculation, the chapter by H6kfelt flirts with several exciting ideas about how co-released peptides, acting at autoreceptors, may selectively change synaptic flow in repetitively stimulated pathways. The contribution by Hemmings eta/. gives a review of the power of neurotransmitter-lin ked second messengers to produce profound changes in the properties of postsynaptic cells, and, using the phosphoprotein DARPP-32 as an example, shows how the response to second messengers may be differentially regulated in different neurons. The third section deals with the complexity of networks com-
New Concepts in Cerebellar Neurobiology (Neurology and Neurobiology,Vol. 22)
TINS, Vol. 11, No. 5, 1988
F. Crepel Labora~'rede Neuro/~'ologieet Neuropharrnacologie, Bat.440, UniversitE ParisJ;ud,91405 Orsay,France.
239
Ito's monograph), whereas Ebner and Bloedel propose that the inferior olive (i.e. the source of climbing fibers) functions as a central clock that times and controls the output of the cerebellum by a short-term modulation of the transactions through the mossy fiber system. As the reader will certainly realize, the unifying theory that links together these observations is still based on the notion of microzones in the cerebellar cortex (Oscarson, 1980), or, more precisely, units consisting of these microzones, the subset of olivary neurons projecting to them, and the subset of their target cerebellar nuclei neurons. Such units might use the multiple representation of the body found in the cerebellum for different purposes
depending on their output toward premotor sites or toward higher centers of motor control. However, as Welker says in his paper, further elaboration along this line has a good chance of remaining mainly metaphorical, given the present limitations of our knowledge! Finally, three reviews in this book deserve further comment. First, Haines and Dietrich describe in great detail reciprocal and direct connections between the cerebellum and the hypothalamus, which is of major importance for understanding of the otherwise well established clinical observations of the role of the cerebellum in visceral function and various behaviors. Second, early stages in the development of cerebellar afferents and in the
formation of synaptic junctions have been particularly well analysed by Carol Mason and by Landis and Wenstein, respectively. Both these anatomical and ultrastructural studies stress the existence of transient connections during development and the presence of recognition sites prior to proper synaptogenesis, which may underlie the formation of highly specific connections through a trial and error process of transient multiple innervation. Even though the new concepts alluded to in the title are scattered throughout more than 400 pages, I do believe that this book is worth a read for neuroscientists who want an up-to-date overview of current research in cerebellar neurobiology.
Phosphoproteins in Neuronal Function (Progress in Brain Research, Vol. 69)
grown enormously, and the discovery that certain products of this metabolism act as second messengers and may activate other protein kinases has given enormous impetus to neurochemistry. Coupled to evidence that protein kinases may regulate ion channels, the linkage between neuronal function and brain biochemistry is on a considerably firmer basis today. It is therefore not surprising that many articles in this volume address these new developments. The first section is devoted to polyphosphoinositide metabolism and although there is some overlap between the contents of the six articles, they are a useful collection of reviews with an emphasis on the nervous system. The pace of research in this area is exemplified by a 1986 update added to the article by Eichberg and Berti-Mattera. Here, among other results, they describe the discovery of the novel inositol tetrakisphosphate, yet today in 1988 a second messenger role for this metabolite is likely and two other tetrakisphosphate isomers have been discovered! Regulation of ion channels by phosphorylation is reviewed in five articles and provides a useful collection of papers. There is discussion of the role of cyclic AMP, calcium-dependent and independent protein kinases and their putative interaction in situ in relation to change in neuronal excita-
bility and possibly in associative learning. There is obvious overlap in this section with several articles that appear under a section entitled plasticity. I feel we can expect in the future that considerable definition of specific sites of phosphorylation on receptor proteins will provide a major impetus in this area. With the recent cloning and sequencing of several neurotransmitter receptors, work on the I]-adrenoceptor at least is beginning to define sites of phosphorylation associated with agonist-induced desensitization. It is perhaps another indication of the pace in this field that such studies are not described in this book. For many years now several groups have suggested that information storage may be associated with post-translational modification of synaptic proteins. Although I always considered such claims to be highly speculative, our recent dramatically improved understanding of the mechanisms and substrates of protein phosphorylation in the central nervous system may allow more confident claims in the future. I believe that this volume should be available through the library shelves to neuroscientists in general. The specialist may wait for a pause in the rapid developments in this area before buying a state-of-the-art review.
edited by W. H. Gispen and A. Routtenberg, Elsevier, 1986. $131.00/ Dfl.295.00 (xi + 394 pages) ISBN 0 444 80781 0 S. R. Nahorski
Departmentof Pharmacologyand Therapeutics, Universityof Leicester,Leicester LE17RH,UK.
240
This volume contains a number of contributions from a workshop that took place in Utrecht in September 1985. Although the book was published in late 1986, the extraordinary pace of research in certain areas unfortunately gives a somewhat dated flavour to some of the articles. However, having said that, this volume does bring together a number of important review articles that illustrate the crucial role protein kinases and brain protein phosphorylation have in cell-tocell communication particularly associated with synaptic transmission. It was recognized as long as 15 years ago that dramatic changes in protein phosphorylation accompanied depolarizing stimuli as well as the action of several putative neurotransmitters in cerebral tissues. With the discovery that cyclic AMP can mediate the action of certain transmitters, early emphasis was placed on cyclic AMP-dependent protein kinase and its substrates. In the last five years our understanding of receptors linked to polyphosphoinositide metabolism has
TINS, VoL 11, No. 5, 1988