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Glutamate: Transmitter in the central nervous system
1038
Book Reviews
ebral, rational and deductive and the right hemisphere as non-verbal, intuitive and imaginative. They set out ‘to sur-
vey the current state of knowledge’ and ‘to point out the gaps which still exist’. The first aim is met, as far as splitbrain studies are concerned. The second aim has less to recommend it in that the major gaps are self evident, namely, that we have not yet found a satisfactory model to describe the functional asymmetry of the hemispheres. and as the authors themselves remark, we need ‘to assess more carefully the contribution of brain-stem structures and commissures to perception, emotion and other aspects of human behaviour’. The early chapters provide a good summary not only of split-brain research but also of related experimental studies of some functional asymmetries in the normal brain. A very short chapter on physiological and radiological correlates can only skim the surface of this subject and does not refer to recent developments such as the positron scanner and nuclear magnetic resonance. The chapters on hand preference and gender differences are not comprehensive: some substantial work in the field is not cited and it is simply not true to state that ‘the most general predictions of Annett’s model (of the distribution of hand preference) await testing’. Annett’s predictions show a remarkably close fit to published data on large population samples: it is not clear how well they accord with clinical material. A reference to the lateralisation of language in congenitally deaf persons is simplistic: the work of Battisford, Lane and others has demonstrated that visual field
differences (with their implications of contralateral ‘dominance’) may vary for the native deaf signer whether the sign is static or moving.
according
to
In general, very little attention is paid to the mam stream of clinical research that preceded split brain studies by several decades and has continued to yield an important corpus of data regarding cerebral organisation. The apraxias observed in association with left hemisphere lesions and the material-specific memory deficits seen after unilateral temporal-lobe lesions have been given scant place. Ingenious and impressive as the work with splitbrain patients has been, it can hardly serve as the sole or even primary basis for studying brain and behaviour relationships, in that the sample is small and most of the patients brain-damaged from an early age. An appendix to the book, described as a brief review of functional neuroanatomy and clinical disorders, can hardly do justice to the subject matter in fifteen pages. The book, in fact, has a narrow brief, constrained by the limited clinical and experimental material that it addresses. Within these confines, it is clear, agreeable to read and often stimulating. It would make a good undergraduate manual, to be used in conjunction with more comprehensive neuropsychology texts of the kind recently produced by Heilman & Valenstein, Walsh and Kolb & Whishaw.
F. NEWCOMBE
Glutamate: Transmitter in the Central Nervous System. P. J. ROBERTS,J. STORM-MATHISEN & G. A. R. JOHNSFW (Eds). John Wiley, Chichester, New York. 226 pp. f16.50. This is a most timely publication, for interest in acidic amino acids as possible transmitter substances has now reached the stage when a single volume devoted to studies on glutamate is necessary not so much for the specialist but for most other neuroscientists. The present book is nearly ideal as an introduction to, and a review of, current knowledge in the field. No substance can ever be accepted as a neurotransmitter until there is pharmacological evidence that the postsynaptic response to stimulation of the nerve is antagonised by a drug that also antagonises the action of the substance when it is applied. The first chapter (Watkins) shows that we still have a long way to go before this can safely be concluded for L-glutamate or L-aspartate. However, the author describes the evidence that there may be as many as three different receptors for excitatory amino acids: there is a degree of specificity not only for antagonists but also for agonists. This is clearly a most important discovery and will hopefully lead to the development of even more specific agonists and antagonists, some of which could well be useful clinically. Further pharmacological studies, this time on the binding of glutamate and aspartate to membrane fractions from the brain, are described by Roberts. The conclusions that can be drawn at present are few since it is not at all clear that the binding sites are receptors. If glutamate can be released from surfaces of the brain upon specific stimulation, then it becomes a stronger candidate for a transmitter. The problem is that many amino
acids are released from tissue spontaneously. An excclknt survey of the literature and discussion of the technical problems is given in the chapter by AbdulGhani et al. which concludes with a most uacful tabk in which in uioo studies on the evoked release. of several amino acids are compared. The evidence for the release of glutamate is good; what remains to be established is that the rekase occurs from nerve endings and not from glial cells. The hippocampus is the part of the brain where the evidence for a transmitter role for glutamate is fairly convincing and several chapters deal with this area. The sensitivity of hippocampal pyramidal neurons to glutamate applied by iontophoreais in tissue sliecs is strikingly illustrated by And-: the highest sensitivity was found only at certain parts of the dcndritic tree. How one would like to combine this electrophysiological ‘mapping’ with morphological analysis of the same material! The uptake of glutamate by high and low atfmity systems (Johnston) is an important biochemical contribution since it not only may be a clue to the ph~kqieal inactivrtion of the transmitter but provides a vabmble tool whateby radi&bcRd glutamate (or the tnctf&rolically inert D-aSpattatC.) can be taken up and studied by autor&iiogr@&. The appBiepti~n of the latter approach to the hippoaopu hasbaenpartitularly fruitful and is very nicaly reviewed by StormMatRisen. The use of hypoth&4 rppin anelyaia of eketron microscopic a4stor&agraa3a baa C0nvi&i&y shown that axons accumulate ‘H after exposure of the daatate area to C3H]glutamate. The uptake measured biochemi-
Book Reviews tally and autoradiographically was reduced by axotomy in the preformant path. Cotman and Nadler describe their own complementary studies which strongly suggest that glutamate may be the transmitter of the perforant path fibres from the entorhinal cortex to the dentate gyrus. The latter authors suggest that aspartate and/or glutamate may be the transmitter of the Schaffer collaterals of pyramidal cell axons that pass commissurally, but that neither substance is a transmitter of hippocampal mossy fibres. The final chapter by Fonnum and Mathe-Sorenssen is a review of the evidence for glutamate as a transmitter in other parts of the nervous system as well as the hippocampus; this is perhaps a little too brief, although it does point one to the relevant literature. The book includes a substantial chapter that is not specifically about glutamate as a transmitter: it deals with kainic acid, an analogue of glutamate that has powerful excitatory actions on many neurons. Kainic acid is the active principal of an antithelmintic seaweed that grows in
1039
the East China Sea, but for neuroscientists it has become a most valuable agent for destroying neuronal cell bodies in the brain while sparing axons of passage. The McGeers provide an excellent and critical review of the latter use of kainic acid that should be compulsory reading for all those who use it. It is most refreshing to read a book that arose out of a symposium which does not contain a mixture of previously published and unpublished results presented in a way that only the specialist can follow. (Publishers would do the scientific community a service if they refused to print books of the latter type.) The chapters in the present book are all written as surveys or reviews of the field and so the book will serve for some time as a vaiuable source; it can be strongly recommended to students and all those who wish to find out what is the current status of L-glutamate as a transmitter. A. D.
SMITH
Book Reviews
ebral, rational and deductive and the right hemisphere as non-verbal, intuitive and imaginative. They set out ‘to sur-
vey the current state of knowledge’ and ‘to point out the gaps which still exist’. The first aim is met, as far as splitbrain studies are concerned. The second aim has less to recommend it in that the major gaps are self evident, namely, that we have not yet found a satisfactory model to describe the functional asymmetry of the hemispheres. and as the authors themselves remark, we need ‘to assess more carefully the contribution of brain-stem structures and commissures to perception, emotion and other aspects of human behaviour’. The early chapters provide a good summary not only of split-brain research but also of related experimental studies of some functional asymmetries in the normal brain. A very short chapter on physiological and radiological correlates can only skim the surface of this subject and does not refer to recent developments such as the positron scanner and nuclear magnetic resonance. The chapters on hand preference and gender differences are not comprehensive: some substantial work in the field is not cited and it is simply not true to state that ‘the most general predictions of Annett’s model (of the distribution of hand preference) await testing’. Annett’s predictions show a remarkably close fit to published data on large population samples: it is not clear how well they accord with clinical material. A reference to the lateralisation of language in congenitally deaf persons is simplistic: the work of Battisford, Lane and others has demonstrated that visual field
differences (with their implications of contralateral ‘dominance’) may vary for the native deaf signer whether the sign is static or moving.
according
to
In general, very little attention is paid to the mam stream of clinical research that preceded split brain studies by several decades and has continued to yield an important corpus of data regarding cerebral organisation. The apraxias observed in association with left hemisphere lesions and the material-specific memory deficits seen after unilateral temporal-lobe lesions have been given scant place. Ingenious and impressive as the work with splitbrain patients has been, it can hardly serve as the sole or even primary basis for studying brain and behaviour relationships, in that the sample is small and most of the patients brain-damaged from an early age. An appendix to the book, described as a brief review of functional neuroanatomy and clinical disorders, can hardly do justice to the subject matter in fifteen pages. The book, in fact, has a narrow brief, constrained by the limited clinical and experimental material that it addresses. Within these confines, it is clear, agreeable to read and often stimulating. It would make a good undergraduate manual, to be used in conjunction with more comprehensive neuropsychology texts of the kind recently produced by Heilman & Valenstein, Walsh and Kolb & Whishaw.
F. NEWCOMBE
Glutamate: Transmitter in the Central Nervous System. P. J. ROBERTS,J. STORM-MATHISEN & G. A. R. JOHNSFW (Eds). John Wiley, Chichester, New York. 226 pp. f16.50. This is a most timely publication, for interest in acidic amino acids as possible transmitter substances has now reached the stage when a single volume devoted to studies on glutamate is necessary not so much for the specialist but for most other neuroscientists. The present book is nearly ideal as an introduction to, and a review of, current knowledge in the field. No substance can ever be accepted as a neurotransmitter until there is pharmacological evidence that the postsynaptic response to stimulation of the nerve is antagonised by a drug that also antagonises the action of the substance when it is applied. The first chapter (Watkins) shows that we still have a long way to go before this can safely be concluded for L-glutamate or L-aspartate. However, the author describes the evidence that there may be as many as three different receptors for excitatory amino acids: there is a degree of specificity not only for antagonists but also for agonists. This is clearly a most important discovery and will hopefully lead to the development of even more specific agonists and antagonists, some of which could well be useful clinically. Further pharmacological studies, this time on the binding of glutamate and aspartate to membrane fractions from the brain, are described by Roberts. The conclusions that can be drawn at present are few since it is not at all clear that the binding sites are receptors. If glutamate can be released from surfaces of the brain upon specific stimulation, then it becomes a stronger candidate for a transmitter. The problem is that many amino
acids are released from tissue spontaneously. An excclknt survey of the literature and discussion of the technical problems is given in the chapter by AbdulGhani et al. which concludes with a most uacful tabk in which in uioo studies on the evoked release. of several amino acids are compared. The evidence for the release of glutamate is good; what remains to be established is that the rekase occurs from nerve endings and not from glial cells. The hippocampus is the part of the brain where the evidence for a transmitter role for glutamate is fairly convincing and several chapters deal with this area. The sensitivity of hippocampal pyramidal neurons to glutamate applied by iontophoreais in tissue sliecs is strikingly illustrated by And-: the highest sensitivity was found only at certain parts of the dcndritic tree. How one would like to combine this electrophysiological ‘mapping’ with morphological analysis of the same material! The uptake of glutamate by high and low atfmity systems (Johnston) is an important biochemical contribution since it not only may be a clue to the ph~kqieal inactivrtion of the transmitter but provides a vabmble tool whateby radi&bcRd glutamate (or the tnctf&rolically inert D-aSpattatC.) can be taken up and studied by autor&iiogr@&. The appBiepti~n of the latter approach to the hippoaopu hasbaenpartitularly fruitful and is very nicaly reviewed by StormMatRisen. The use of hypoth&4 rppin anelyaia of eketron microscopic a4stor&agraa3a baa C0nvi&i&y shown that axons accumulate ‘H after exposure of the daatate area to C3H]glutamate. The uptake measured biochemi-
Book Reviews tally and autoradiographically was reduced by axotomy in the preformant path. Cotman and Nadler describe their own complementary studies which strongly suggest that glutamate may be the transmitter of the perforant path fibres from the entorhinal cortex to the dentate gyrus. The latter authors suggest that aspartate and/or glutamate may be the transmitter of the Schaffer collaterals of pyramidal cell axons that pass commissurally, but that neither substance is a transmitter of hippocampal mossy fibres. The final chapter by Fonnum and Mathe-Sorenssen is a review of the evidence for glutamate as a transmitter in other parts of the nervous system as well as the hippocampus; this is perhaps a little too brief, although it does point one to the relevant literature. The book includes a substantial chapter that is not specifically about glutamate as a transmitter: it deals with kainic acid, an analogue of glutamate that has powerful excitatory actions on many neurons. Kainic acid is the active principal of an antithelmintic seaweed that grows in
1039
the East China Sea, but for neuroscientists it has become a most valuable agent for destroying neuronal cell bodies in the brain while sparing axons of passage. The McGeers provide an excellent and critical review of the latter use of kainic acid that should be compulsory reading for all those who use it. It is most refreshing to read a book that arose out of a symposium which does not contain a mixture of previously published and unpublished results presented in a way that only the specialist can follow. (Publishers would do the scientific community a service if they refused to print books of the latter type.) The chapters in the present book are all written as surveys or reviews of the field and so the book will serve for some time as a vaiuable source; it can be strongly recommended to students and all those who wish to find out what is the current status of L-glutamate as a transmitter. A. D.
SMITH