Temporal Variation and Region- and Sex-Specific Expression of GABA_A Receptor Subunits in the Mouse Suprachiasmatic...

GABAergic neurotransmission plays a central role in regulating the mammalian circadian clock. However, the precise contribution of GABA type A receptor (GABA_AR) subunits to timekeeping within the suprachiasmatic nucleus (SCN) remains incompletely defined. Here, we investigated the spatiotemporal expression patterns of four GABA_AR subunits (α1, α5, β3, and γ2) in the SCN of male and female C57BL/6 mice. Our aim was to determine whether these subunits exhibit circadian, regional, and sex-specific variation under entrained (LD12:12) and free-running (DD) conditions. Fluorescence immunohistochemistry revealed the expression of all four subunits in the SCN, with several displaying rhythmic profiles. The α1 subunit peaked during the day in both sexes and was preferentially expressed in the shell region. The α5 subunit also varied across time but lacked strong regional specificity. Temporal variation in β3 and γ2 expression was observed in males but not females, indicating potential sex-dependent regulation. Notably, the γ2 subunit showed a dynamic shift in regional distribution over the circadian cycle, with higher shell expression during the day and core enrichment at night. Under DD conditions, rhythmic expression of the α1 and γ2 subunits persisted, suggesting endogenous control independent of external light cues. However, overall amplitude and regional specificity were reduced in the absence of light. These findings demonstrate that GABA_AR subunit expression within the SCN is regulated by circadian phase, SCN subregion, and biological sex. This study provides new insight into the molecular architecture of the SCN and supports the hypothesis that subunit-specific GABAergic signalling contributes to the temporal organisation of the circadian clock. Further investigation into the functional significance of these subunit patterns will help clarify their roles in SCN synchrony, photic entrainment, and sex-specific circadian regulation.