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

Jun 1, 2023Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

The gene Per1 may control daily rhythms in memory storage in the hippocampus

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Mice exhibit better long-term memory performance during the day compared to night, with improved memory consolidation identified as the key factor.

Memory performance is influenced by the time of day, showing a significant difference between day and night.
The enhanced memory during the day is specifically linked to memory consolidation, not acquisition or retrieval.
The circadian clock gene Period1 (Per1) is identified as a critical mechanism supporting this diurnal variation in memory consolidation.
Learning-induced oscillations of Per1 correlate with changes in memory performance within the hippocampus.
Local reduction of Per1 levels in the dorsal hippocampus impairs spatial memory without disrupting circadian rhythms or sleep.

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The circadian system influences many different biological processes, including memory performance. While the suprachiasmatic nucleus (SCN) functions as the brain's central pacemaker, downstream "satellite clocks" may also regulate local functions based on the time of day. Within the dorsal hippocampus (DH), for example, local molecular oscillations 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 24 h 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 learning-induced Per1 oscillates in tandem with memory performance in the hippocampus. We then show that local knockdown of Per1 within the DH impairs spatial memory without affecting either the circadian rhythm or sleep behavior. Thus, Per1 may independently function within the DH to regulate memory in addition to its known role in regulating the circadian system within the SCN. Per1 may therefore exert local diurnal control over memory consolidation within the DH.

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

Abstract

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