GABA involvement in the circadian regulation of sleep

Abstract

γ-aminobutyric acid (GABA) plays a fundamental role in the circadian regulation of behavior and physiology. GABA and its receptors are found in most, if not all, cells of the suprachiasmatic nucleus (SCN), the location of the putative master circadian pacemaker. Furthermore, nearly every cell in the SCN receives GABAergic input. Thus, GABA is anatomically positioned to play a major role in regulating the circadian clock. The available data indicate firstly that GABA release in the SCN is required for nonphotic stimuli to phase shift the clock during the day, when the circadian clock is not reset by light. Secondly, the acute release of GABA in the SCN potentially inhibits the phase-shifting effects of light exposure at night, and these effects are likely mediated at least in part by extrasynaptic GABAA receptors. Thirdly, several lines of recent evidence suggest that the sustained release of GABA in the SCN may mediate the ability of light to phase shift the clock. In summary, although much remains to be learned about GABA function in the SCN, existing data indicate that GABA activity in the SCN can profoundly influence circadian phase and the ability of phase shifting stimuli such as light to reset the clock.