O030 GABAA Receptor Expression in the Suprachiasmatic Nucleus under Different Light Conditions

Abstract

Abstract Our research group has made inroads investigating the phase shifting effects of general anaesthesia (GA) on the circadian clock. Most clinical anaesthetics function by potentiating the effect of GABA on the GABA type A receptor (GABAARs). While the precise role of GABA in the suprachiasmatic nucleus (SCN) is still not fully understood, it has been implicated in circadian functions including photic entrainment and clock coupling. However, we have discovered that the expression of GABAARs in the central circadian clock remains poorly understood. To address this gap in knowledge, we examined the expression of GABAAR subunits α1, α5, β3, and γ2 in male (n = 80) and female (n = 82) C57Bl/6 mice under light-dark (LD) and constant darkness (DD) conditions (male, n = 95). Analysis of GABAAR subunit expression in the SCN was quantified by immunohistochemical analysis. Additionally, we investigated the time-dependent effects of isoflurane GA and light on GABAAR subunit expression in the SCN (male, n = 60). Our findings revealed rhythmic expression of GABAAR subunits in the mouse SCN under LD conditions which differed by sex, suggesting environmental light conditions may regulate GABAAR expression in the circadian clock in a sex-specific manner. In the SCN, γ2 subunit expression was increased following light and GA treatment compared to light-alone, while α1 subunit expression was increased at times of large behavioural phase delays. We conclude that the expression of GABAAR’s in the SCN is phase-dependent and may contribute to the time-dependent relationship between light and GA on the clock.