Preface

The discovery that the development of the nervous system involves the loss of a considerable number of apparently healthy nerve cells in many structures has provided one of the deepest insights into mechanisms underlying the maintenance of nerve cells and the development of the neuronal organization. *OJ* It seems that developing nerve cells become transiently dependent for their survival and differentiation on certain influences provided by their environment.7*‘0*‘2 The influence of target-derived trophic factors, of which Nerve Growth Factor is the most celebrated, has attracted special attention and has been the subject of many reviews and multi-author books (e.g. Refs 13 and 20). In addition, it is believed that both glial cells*l and afferent nerve fibres* also exert trophic influences on nerve cells. The effect of afferents appears to be usually mediated through neurotransmitters and involves the active responsiveness of the postsynaptic cell. Both transmitters and bioelectric activity have been implicated, each in their own right, as trophic influences within the developing brain (e.g. Refs 1, 3, 6, 10 and 11). This Special Issue explores the influence of a particular group of transmitters on the survival and maturation of nerve cells and on the use-dependent organization of neuronal networks during development. The focus here is on excitatory amino acids, such as glutamate (the first nine papers), and inhibitory amino acids, such as gamma-aminobutyrate (GABA) (the following four papers), while taurine is also considered, although it is still controversial whether it fulfills the criteria to be accepted as a transmitter. Glutamate and GABA are probably the most abundant neurotransmitters in the vertebrate central nervous system. GABA has already been suspected for some time in exerting trophic effects in the nervous system (see chapters in Ref. 17). The trophic influence of excitatory amino acid transmitters on the developing brain is, however, just emerging and this Special Issue is the first attempt to present a collection of directly relevant original contributions. In contrast to the very recent recognition of the trophic effects exerted by glutamate and its analogues, the potential toxicity of these excitatory amino acids has been well appreciated over many years (e.g. Refs 9,18 and 19): the view that, besides possible roles in certain disorders involving neurodegeneration, neurotoxicity may also play an important part in shaping developing neuronal networks in the brain is, nevertheless, fairly new (e.g. Ref. 14). Excitatory amino acids appear to exert their trophic effects, along with their influence on synaptic plasticity during development, as a result of the association of their receptors with transduction systems: activation of these leads to unique interactions between events in the transduction cascade and certain developmentally determined processes in the differentiating ce11.2 Such transient effects also seem to characterize the effect of GABA.“j Thus, depending on the maturational stage of the cell, the activation of the same transduction systems can trigger biochemical reactions other than those involved in information processing, which these systems primarily subserve in the fully differentiated cell. The economy of such an arrangement may be considerable in terms of the sparing of genetic information. Finally, in this Special Issue we also present papers which extend recent information5*‘” about the integration of signals hitherto considered in isolation (e.g. Refs 4 and 21) by demonstrating the effect of multiple inputs and of interactions between transmitters and more conventional trophic factors, in determining the survival and maturation of developing nerve cells.