Amino acid transmitters in the mammalian central nervous system

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130 D.R. CURTIS and G. A. R. JOHNSTOY : vermis it seems probable that all inhibitory Purkinje, basket, stellate and Golgi cells within the mammalian cerebellum operate by releasing GABA as an inhibitory transmitter. 4.3. Rhinencephalon 4.3.1. Excitation Little is known regarding excitant amino acid transmitters, apart from many observations of excitation of neurones by L-glutamate (STEVANIS, 1964; HERZ and GOGOLAK, 1965; HERZ and NACIMIENTO, 1965; STRAUGHAN and LEGGE, 1965; LEGGE, RANDI~ and STRAUG~AN, 1966; BISCOE and STRAUGHAN, 1966; STEIYER and RtJF, 1967). One noteworthy feature is the ease with which seizure-like activity can be triggered (Bxsco~ and STRAUGHAN, 1966; STEFANIS, 1969) by exciting relatively few neurones within the hippocampal cortex. A study of the sensitivity of neurones in hippocampal slices (Guinea pig, cat: DtJDAR, 1972) suggests that there are glutamate receptors on both cell bodies and dendrites. The latter presumably are associated with axodendritic synapses, but this type of experiment, both in vitro and in vivo, requires correlation with the distribution of enzymes involved in glutamate metabolism such as aspartate aminotransferase (BORRE and GENESER-JENSEN, 1972). 4.3.2. Inhibition GABA is present in the hippocampus (Rabbit: 2.4 lamole/g. Rat: 3.6. Guinea pig: 2.7. Baboon: 2.8, O~ADA, NITSCH-HASSLER, KIM, BAK, and HASSLER, 1971), and although detailed studies have not been reported of the distribution of depressant amino acids within various regions of the rhinencephalon, several investigations have been concerned with the distributions of GAD and GABA-T. In contrast to low activity in the fimbria, high levels of GAD occur in the molecular and pyramidal layers of area CA1, and in the molecular and granular layers of the area dentata (Rat: STORM-MATHISEN and FONNUM, 1971, 1972; see also ALBERS and BRADY, 1959). Futhermore surgical interruption of afferent pathways to these areas did not reduce GAD levels in either CA1 or area dentata (STORM- MATH1SEN, 1972), suggesting that the enzyme is associated with cells intrinsic to the hippocampal cortex. A high proportion of the GAD from homogenized hippocampal tissue can be recovered in the synaptosomal fraction, the particles being denser than those containing choline acetyltransferase (FONNUM, 1972). All of these results are consistent with the presence of GAD in the bodies of inhibitory basket cells and their axosomatic terminals upon hippocampal pyramidal cells (SToRN-MATmSEN and FONNtJM, 1971 ; STORM-MATHISEN, 1972; FONNtJN, 1972). Supporting neurochemical evidence is provided by the presence of GABA-T in the hippocampal cortex (SALVADOR and ALBERS, 1959) which in the mouse surrounds pyramidal cell bodies (VAN GELDER, 1965b), and the similar distribution of radio-label when slices of hippocampal tissue are incubated with [3H]-GABA
Amino Acid Transmitters in the Mammalian Central Nervous System 131 in the presence of amino-oxyacetic acid (Rat: HOKFELT and LJUNGDAHL, 1971 b). Electrophoretically administered GABA depresses the firing of neurones in the many regions of the cat rhinencephaton which have been examined--CA1, CA2, CA3 (STEEANIS, 1964; BISCOE and STRAUGHAN, 1966; CURTIS et al., 1971b): dentate gyrus (STEFANIS, 1964): septum (HERz and GOGOLAK, 1965): amygdala (STRAUGHAN and LEGGE, 1965): pyriform cortex (LEGGE, RANDI~, and STRAUGnAN, 1966); and similar results have been observed in the rat (STEINER and RUE, 1967). Although GABA was a more effective depressant of the firing of pyramidal cells than either glycine or fl-alanine (CURTIS et al., 197 lb), hyperpolarization by GABA has yet to be demonstrated. However, bicuculline blocks the inhibition of pyramidal cells by GABA (and by fl-alanine, CURTIS et al., 1971b) and reduces the prolonged synaptic inhibition (ANDERSEN, ECCLES, and LOYNING, 1964) of these neurones which follows excitation of basket cells (CURTIS, FELIX, and MCLENNAN, 1970C). This synaptic inhibition is not affected by strychnine (ANDERSEN et al., 1963), an alkaloid which appeared to have little selectivity as an amino acid antagonist in this region (CURTISet al., 1971b). The effects of systemic or topical convulsants on hippocampal responses are complex (BAKER, KRATKY and BENEDICT, 1965; GESSI, RABINI, and VOLTA, 1967). 4.4. Retina Although a number of amino acids are present in the vertebrate retina, together with relevant enzymes and transport processes (LOLLEr, 1969), the precise nature of the neurones synthesising and releasing particular amino acids has yet to be determined. The organization and structure of the vertebrate retina has been reviewed recently by DOWLING (1970). The high levels of both GABA and GAD in the ganglion cell layer of the rabbit were considered to reflect technical difficulties in the physical separation of retinal layers rather than an association of the amino acid with excitatory neurones (KuRIYAMA, SISKEN, HABEN and ROBERTS, 1968). The distribution of the enzyme and amino acid in the frog retina led to the suggestion that amacrine, and probably also horizontal, cells may synthesise GABA (GRAHAM, 1972). Glutamate is evenly distributed between the receptor, bipolar and ganglion cell layers of the frog retina, and the levels are not significantly different in retinae adapted to light or to darkness. In contrast GABA levels in both bipolar and ganglion cell layers are decreased in dark adapted frog retina (GRAHAM, BAXTER, and LOLLEY, 1970). Similarly, in the goldfish, light stimulation enhances the synthesis of GABA from glutamate (LAM, 1972). Retinal tissue takes up amino acids, both in vivo and in vitro, and use has been made of radiolabelled compounds to determine both the kinetics of the processes (GABA-Rat: GOODCHILD and NEAL, 1973: high affinity, STARR and VOADEN, 1972a; NEAL and STARR, 1973. Glycine-Rabbit: high affinity, BRUUN and EHINGER, 1972. Taurine-Rat: low affinity, STARR and VOADEN, 1972 b ; Chicken: PASANTES-MORALES, KLETHI, URBAN, and MANDEL, 1972. Glutamate-Rat: high affinity, NEAL and WHITE, 1971) and sites of amino acid accumulation.
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