CIRCADIAN DISRUPTION IMPAIRS HIPPOCAMPAL SPATIAL MEMORY THROUGH DEGRADED ENCODING STABILITY AND ALTERED OFFLINE PROCESSING

Circadian rhythms modulate hippocampal activity and memory consolidation, yet how circadian disruption affects consolidation at the circuit level remains unclear. We performed longitudinal calcium imaging in the hippocampus of twelve male Thy1-GCaMP6f mice performing a spatial foraging task under either stable light–dark cycles (controls) or a repeated 3-hour daily phase advance (T21) for seven days, followed by a return to stable lighting (circadian-shifted). During initial encoding, both groups accurately represented spatial positions, and population-level decoding remained robust. However, across days, circadian-shifted animals showed reduced place cell stability and higher decoding error. At retention tests 7 and 23 days later, circadian-shifted mice showed reduced spatial information and a higher sparsity index (lower spatial selectivity), despite largely intact spatial maps, indicating a gradual degradation of spatial representation. To test whether this degradation was related to altered offline processing, we analyzed place-cell coactivity during active behaviour and rest periods before and after running. In controls, similarity between run activity and subsequent rest increased across days, while pre-to-post rest similarity remained moderate, consistent with experience-dependent reactivation. In circadian-shifted mice, pre-to-post rest similarity remained significantly higher relative to run-to-post rest similarity, indicating that rest dynamics were more internally stable and less tightly coupled to recent spatial experience. This pattern emerged during training, persisted transiently after the disruption ended, and gradually normalized at later retention time points. Together, these results demonstrate coordinated changes in place-cell stability during behaviour and offline network organization that may underlie the progressive degradation of spatial memory following circadian rhythm disruption.