GABA IN THE MAMMALIAN SUPRACHIASMATIC NUCLEUS AND ITS ROLE IN DIURNALRHYTHMICITY

Mammals manifest circadian behaviour timed by an endogenous clock in t he hypothalamic suprachiasmatic nucleus (SCN)(1). Considerable progres s has been made in identifying the molecular basis of the circadian cl ock(2,3), but the mechanisms by which it is translated into cyclic fir ing activity, high during the day and low at night, are still poorly u nderstood. GABA (gamma-aminobutyric acid), a common inhibitory neurotr ansmitter in the central nervous system, is particularly densely distr ibuted within the SCN, where it is located in the majority of neuronal somata(4,5) and synaptic terminals(6,7). Using an in vitro brain-slic e technique, we have now studied the effect of bath-applied GABA on ad ult SCN neurons at various times of the day. We find that GABA acts as an inhibitory neurotransmitter at night, decreasing the firing freque ncy; but during the day GABA acts as an excitatory neurotransmitter, i ncreasing the firing frequency. We show that this dual effect, which i s mediated by GABA(A) receptors, may be attributed to an oscillation i n intracellular chloride concentration. A likely explanation is that t he amplitude of the oscillation in firing rate, displayed by individua l neurons, is amplified by the dual effect of GABA in the SCN's GABAer gic network.