Gabaa receptor-mediated neurotransmission in the suprachiasmatic nucleus

GABAergic neurotransmission is a fundamental component of the suprachiasmatic nucleus (SCN) neural network, and virtually all SCN neurons communicate using GABA as a neurotransmitter. GABAergic neurotransmission plays a critical role in light-induced phase shifts, synchronization of the dorsal and ventral SCN, and, although controversial, synchronization of the circadian phase of individual SCN neurons. The circadian clock regulates the strength of GABAa receptor- mediated neurotransmission although the signaling mechanisms mediating this regulation are not known. GABA released from axon terminals acts on synaptic GABAA receptors producing postsynaptic currents that have a rapid onset and offset and desensitize in the continued presence of GABA. In the SCN, the postsynaptic GABAA receptor-mediated currents may be excitatory or inhibitory depending on the time of day. Once released GABA is removed from the synaptic cleft by specific sodium-chloride-dependent transporters (GAT). Some GABA can diffuse out of the synaptic cleft and act on extrasynaptic GABAa receptors. These extrasynaptic GABAa receptors have high affinity for GABA and show little or no desensitization. They mediate a –tonic— GABAa current that could modulate the input-output characteristics of individual SCN neurons. While significant scientific questions remain about the roles of GABAergic neurotransmission in the circadian timing signals, recent findings have yielded important advances in our understanding of GABAergic neurotransmission in the SCN.