INHIBITORY SYNAPTIC PLASTICITY IN THE SUPRACHIASMATIC NUCLEUS (SCN) ENTRAINS PHOTOPERIOD-DEPENDENT BEHAVIOR

Seasonal changes in daylight duration require flexible adjustments in circadian timing. The suprachiasmatic nucleus (SCN) integrates photoperiodic information through vasoactive intestinal peptide (VIP) neurons, with GABAergic signaling coordinating network activity. We investigated how inhibitory signaling is tuned through GABA_A receptor subunits α1 and α2 to enable photoperiodic adaptation. Immunofluorescence mapping across four photoperiods (12L:12D, 6L:18D, 18L:6D, constant darkness) revealed that α1 expression is photoperiod-regulated while α2 remains stable, creating dynamic α2/α1 ratios peaking at 1.7 during 18L:6D at lights-off transitions. Behavioral experiments using conditional deletions in VIP neurons or pan-SCN (Syt10) populations across over 150 mice revealed distinct roles during entrainment to 6L:18D and 18L:6D. In 12L:12D baseline, VIP-specific α2 deletion shifted the second activity peak while α1 deletion increased dark-phase activity. Pan-SCN α1 deletion eliminated bimodal patterns while α2 deletion increased overall activity. During photoperiod transitions, VIP-specific α2 deletion accelerated entrainment by 2.3 days in 6L:18D, while α1 deletion produced photoperiod-specific offset delays only in 18L:6D. Pan-SCN manipulations primarily affected activity amplitude with photoperiod-specific patterns. Ex vivo calcium imaging in organotypic slice cultures showed that α1-mediated inhibition regulates oscillation amplitude while α2-mediated inhibition regulates phase synchrony, providing cellular mechanisms for the behavioral phenotypes. These findings demonstrate that different types of GABAergic inhibition tune distinct network properties to enable seasonal flexibility. Ongoing in vivo calcium imaging during photoperiod transitions will link these cellular mechanisms to real-time network dynamics, revealing how inhibitory plasticity coordinates seasonal behavioral adaptation.