Circadian Modulation of GABA Function in the Rat Suprachiasmatic Nucleus: Excitatory Effects During the Night Phase

Abstract

Gramicidin-perforated patch-clamp recordings were made from slices of the suprachiasmatic nucleus (SCN) of adult rats to characterize the role of gamma-amino butyric acid (GABA) in the circadian timing system. During the day, activation of GABA(A) receptors hyperpolarized the membrane of SCN neurons. During the night, however, activation of GABA(A) receptors either hyperpolarized or depolarized the membrane. These night-restricted depolarizations in a large subset of SCN neurons were capable of triggering spikes and thus appeared to be excitatory. The GABA(A) reversal potentials of SCN neurons revealed a significant day-night difference with more depolarized GABA(A) reversal potentials during the night than during the day. The emergence of depolarizing GABA(A)-mediated responses in a subset of SCN neurons at night can be ascribed to a depolarizing shift in GABA(A) reversal potential. The GABA(A) receptor antagonist bicuculline (12.5 microM) increased the spontaneous firing rate of all SCN neurons during the day, indicating that spontaneous GABA(A)-mediated inputs inhibited the SCN neurons during this period. The effect of bicuculline (12.5 microM) on the spontaneous firing rate of SCN neurons during the night was heterogeneous due to the mixture of depolarizing and hyperpolarizing GABA(A)-mediated inputs during this period. We conclude that GABA uniformly acts as an inhibitory transmitter during the day but excites a large subset of SCN neurons at night. This day-night modulation of GABAergic neurotransmission provides the SCN with a time-dependent gating mechanism that may counteract propagation of excitatory signals throughout the biological clock at day but promotes it at night.