Brain, Vol. 122, No. 8, 1599-1600,
August 1999
© 1999 Oxford University Press
Book Reviews |
GLIAL CELLS: THEIR ROLE IN BEHAVIOUR.
By Peter R. Laming, Eva Sykova, Andreas Reichenbach, Glenn I. Hatton and Herbert Bauer. 1998. Pp. 424. Cambridge: Cambridge University Press. Price £95.00. ISBN 0-521-57368-8..
Addenbrookes's Hospital, Cambridge, UK
The 20th century was long and dark for friends of glia; already dismissed by Virchow as `glue', Sherrington then Cajal nailed the coffin lid shut with their nervous theories. All manner of insult followed—`scaffolding', `supporting cells', `their principle function is to fill the space between the nerves'—glia invariably cast in every kind of non-role. But all the time, recalcitrant gnostics kept the secret flame alight, a small band of scientists watching glia. After all, what do neurons, `the generators of spiking messages' do? Sedentary, solid, unchanging, they discharge. Fizz and vesicles.
But glia can behave: Wilder Penfield was amongst the first to tell us (despite sadly later defecting to both electricity and surgery). In the early 1920s, he visited Madrid to work with Del Rio Hortega, discoverer of both oligodendroglia and microglia, and Cajal. Penfield (with William Cone) observed and described in exquisite detail the morphological changes characterizing the metamorphosis of resting microglia to activated phagocytes (reported in Brain in 1924). A decade later, Dorothy Russell, working in the histopathology laboratories of St Bartholomew's and The London Hospitals with Canti (who sadly died before their findings were published) fastened a cine camera to a microscope, kept resected brain tumour cells (given to her by the then Mr Hugh Cairns) alive in a Petri dish and recorded the behaviour of cultured transformed glial cells. She showed the cine film to an audience of neuropathologists in New York in December, 1935. Wilder Penfield was in the audience; they already knew each other well, Russell having worked with him for a year in 1929 when she paid an extended visit to the Montreal Neurological Institute whilst holding a Rockefeller Fellowship. Penfield loved the film; watching it `was a very thrilling experience' (all very sobering for those of us still struggling to perfect the conditions for time lapse video microscopy of glial cell cultures). These and related techniques have allowed the observation of oligodendrocytes extending processes to make tentative contact with axons, then ensheathing and myelinating; microglia scavenging and phagocytosing; progenitors migrating; astrocytes stimulating precursor proliferation. Morphological change, motility, myelination, mitosis, all manner of behaviour is here.
So glia can, as it were, behave themselves, but can they inform, dictate or generate behaviour of the organism? No question, of course, to glial die-hards, resolute in maintaining that the function of neurons is simply to fill space between and support glia; we need no convincing. Others might go so far as to accept a key role for glia in behaviour in so far as `in the absence of their activity, axonal function and hence behaviour would be unreliable or disturbed'. But is there more than this? In Glial Cells: Their Role in Behaviour these questions are comprehensively addressed.
Ideas concerning how glia influence neuronal behaviour have evolved. Exploration of their supporting role emphasized their importance in controlling the extracellular milieu of neurons, itself of course an important determinant of neuronal activity. Glial induction and regulation of the blood–brain barrier is of similar relevance. An increasing appreciation of the intimate anatomical relationship between astrocyte processes and neurons implied a higher order of functional intercourse—and then came electricity. First oligodendrocytes and astrocytes both were found to express a range of ion channels. Then, excitingly, Cornell-Bell and colleagues reported in 1990 that astrocytes (examined in vitro, like all good studies) were capable of propagating signals in the form of calcium waves. Three years later, the neuron's electrical monopoly was finally broken when Nedergard showed that electrical signals could be propagated from astrocytes to neurons.
The evolution of the glial–neuronal functional relationship is more literally explored in an excellent, semi-introductory chapter by Betty Roots and Peter Laming. After a timely reminder that `in encephalopod molluscs, brain size was a minor constraint' we follow the increasing number and differentiation of astrocytes and their increasing intimacy with axons, with vertebrate phylogeny. Working by way of annelids and arthropods, we see that teleosts are the first species to have well developed (if slightly Schwann-like) oligodendrocytes.
Development often mirrors phylogeny, but this is not the line taken by Schwabb in his chapter concerning glial roles in development and plasticity. The importance of astrocytes in guiding neuronal migration, and of oligodendrocytes in influencing neuronal outgrowth and regeneration, is discussed, as are the roles of glia in the differentiation of neuronal phenotypes and in neuronal survival. Again, in exploring and expanding their supporting functions, the passive importance of glia in neuronal behaviour is illustrated.
Diseases of myelin provide an immediate and obvious example of disruption of function and behaviour caused by the absence of glia. In de- (or dys-) myelination with persistent loss of oligodendroglia, axonal function is indeed unreliable or disturbed, and normal behaviour compromised. Stephen Waxman and Jeff Cochius provide an excellent account of the other side of this particular coin, the restoration of function by transplantation of myelinating glia. Waxman and Cochius concentrate on and expand two specific publications from their own group, important studies showing improved conduction in the demyelinated rat spinal cord following transplantation, and upon this framework they build an authoritative review of glial cell transplantation, its biology and therapeutic implications. But this is firstly jumping ahead of ourselves and secondly dwelling on the passive (though crucial) role of glia in behaviour. Can they execute a more active role? Here, most of us would perhaps begin to draw the line, but we would be wrong.
The retina serves as an invaluable microcosm in considering the role of glia behaviour: our understanding of its neuroanatomy and physiology is arguably unsurpassed by that of any other CNS region. Reichenbach and colleagues delve deep into this paradigm, illustrating the principal means by which Müller cells, the single macroglial cell type in the retina, influence neuronal activity. Expressing neurotransmitter receptors and ion channels, they are capable of recognizing a variety of neuronal signals, and responding in a manner best suited to the extant neuronal requirements. They fuel and thus regulate neuronal aerobic carbohydrate metabolism and they control extracellular glutamate and GABA levels, thus possessing two further mechanisms for managing neuronal activity and regulating excitability, synaptic plasticity and extrasynaptic transmission. The next three chapters explore individually, and in more detail, these separate mechanisms of glial control—metabolic regulation, neurotransmitter uptake and glial regulation of the neuronal micro-environment. The roles of these aspects of behaviour are explored within and outside the retina, and in an excellent subsequent chapter Joan Abbott considers how periaxonal glia in both vertebrates and invertebrates influence the electrophysiological anatomy and function of axons.
Apart from transplantation (vide supra) and a rather ectopic though sublimely authoritative chapter on pH regulation by glia (technically rather demanding), much of the remaining half of the book is devoted to the phenomenon of slow potential shifts (SPS), and the role of glia in their generation and propagation, although sadly one has to wait until Laming's own chapter (co-authored with Nicol and Roughan) for an explanation of the phenomenon. However, together with the chapters by Heinemann and Walz, and by Bauer, Birbaumer and Rösler, an outstanding account of SPS emerges.
For the uninitiated, the SPS was first described over a century ago, and it would be difficult to improve on Laming and colleagues' definition—`SPSs are long standing changes in the DC recorded potential of a region of nervous tissue . . .[They] occur in the brains of all vertebrates thus far studied in response to trains of electrical impulses applied . . . or to sensory stimuli . . . In all species, they seem to reflect the biological relevance of a stimulus'. Patterns of behaviour as diverse as motivation, seizures, arousal, anticipation, conditioning, memory retrieval and sensory processing all influence the SPS, which has task-specific topography, and load-responsive amplitude. Whilst from a practical standpoint, (surface) SPS recording in patients has important clinical and even therapeutic implications, possessing a number of advantages over fMRI and PET studies (better temporal resolution and fewer design restrictions), in the current context, the contribution of glia to their generation is clearly and persuasively described.
Further glial roles in behaviour are discussed in the last two chapters. Salm and colleagues describe structural plasticity of astrocytes, detailing the changes in astrocyte–neuron relationships and modulation of synaptic contacts occurring in response to neuron activation in a variety of regions—hypothalamus, hippocampus, visual cortex and cerebellum. Finally, Kim Ng and colleagues assert a `central role for astrocytes in learning and memory formation' (at least in chicks). Picking up themes raised throughout the book, they show that inhibition of astrocyte-specific glutamine synthetase, by blocking the conversion of glutamate (taken up by astrocytes) to non-neuroactive glutamine, abolishes memory formation within minutes. A role for astrocyte specific glycogenolysis—i.e. energy production and control—is also offered.
This is a challenging, but overall, very good book. The individual accounts, as stand alone reviews, are universally of high quality, but for the reader to stand back and assemble a greater picture could have been made a little more straightforward by a slight re-organization of chapter order (as hinted above); division into sub-sections might further have assisted this cause. The editing has ensured a reasonable consistency of style and there is not an excessive amount of repetition. Spellers and typographical errors are remarkably few, a tribute to CUP, though an unfortunate and rather important erroneous substitution of `glutamate' for `glutamine' on page 315 challenges the smooth and comprehending read.
Can it be recommended? I certainly learnt much—but had much to learn in this area. Most certainly any neurological library with remotely academic ambitions would be improved by a copy, and I would warmly encourage gliologists to give it serious consideration. It is a good read.
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