Light during the rest phase disrupts hippocampal clock function and impairs object recognition memory

Abstract

Light exposure in the circadian rest phase is common during shift work and late-night activity, but its effects on memory remain unclear. Using male C57BL/6J mice, we show 6-day rest-phase light exposure (RPL), which combines mistimed light exposure with enforced wakefulness, impairs long-term object recognition memory but not short-delay spatial memory. Behavioral testing, single-nucleus RNA sequencing, and ex vivo electrophysiology show that RPL alters SCN clock organization and output signaling, reduces hippocampal clock-gene rhythmicity, disrupts phase-dependent synaptic gene expression in dentate gyrus and CA1 neurons, and reduces CA1 long-term potentiation. Maintaining enforced wakefulness without light exposure preserved object recognition memory and CA1 clock-gene expression, showing that mistimed light exposure is required for these effects. Local hippocampal dexamethasone treatment restored day–night differences in hippocampal clock-gene expression and preserved memory under RPL, supporting a role for hippocampal clock-related regulation in memory preservation. Together, these findings show that RPL alters clock-related regulation in the SCN and hippocampus and impairs object recognition memory. We examine how rest-phase light affects circadian regulation and memory in mice. Rest-phase light alters SCN and hippocampal clock regulation and impairs long-term object recognition memory.