The clock gene Per1 expression may exert diurnal control over hippocampal memory consolidation

Abstract

The circadian system influences many different biological processes, including memory performance. While the suprachiasmatic nucleus (SCN) functions as the brains central pacemaker, satellite clocks have also been identified in other brain regions, such as the memory-relevant dorsal hippocampus. Although it is unclear how these satellite clocks contribute to brain function, one possibility is that they may serve to exert diurnal control over local processes. Within the hippocampus, for example, the local clock may contribute to time-of-day effects on memory. Here, we used the hippocampus-dependent Object Location Memory task to determine how memory is regulated across the day/night cycle in mice. First, we systematically determined which phase of memory (acquisition, consolidation, or retrieval) is modulated across the 24h day. We found that mice show better long-term memory performance during the day than at night, an effect that was specifically attributed to diurnal changes in memory consolidation, as neither memory acquisition nor memory retrieval fluctuated across the day/night cycle. Using RNA-sequencing we identified the circadian clock gene Period1 (Per1) as a key mechanism capable of supporting this diurnal fluctuation in memory consolidation, as Per1 oscillates in tandem with memory performance. We then show that local knockdown of Per1 within the dorsal hippocampus has no effect on either the circadian rhythm or sleep behavior, although previous work has shown this manipulation impairs memory. Thus, Per1 may independently function within the dorsal hippocampus to regulate memory in addition to its known role in regulating the circadian rhythm within the SCN. Per1 may therefore exert local diurnal control over memory consolidation within the dorsal hippocampus.