Hippocampal Per1 contributes to time-of-day effects on memory consolidation
Research Poster Health & Life Sciences 2025 Graduate ExhibitionPresentation by Megan Von Abo
Exhibition Number 181
Abstract
Many biological processes are affected by the circadian system, including memory. Behavioral paradigms, such as the dorsal hippocampus (DH)-dependent Object Location Memory (OLM), show oscillating memory performance across the diurnal cycle, specifically better memory during the day than at night. Here, we used OLM to investigate a potential molecular mechanism underlying this time-of-day memory effect. First, we determined which phase of memory is impacted by the time of day. We assessed acquisition by testing short-term memory and found normal short-term memory performance in the mice. We then assess retrieval by training mice at the peak (ZT5/12p) and trough (ZT17/12a) of memory performance and testing them 36 hours later. Mice trained during the day retained memory at night, whereas night-trained mice exhibited poor retrieval regardless of test time. These experiments suggest nighttime deficits stem from impaired consolidation, not acquisition or retrieval. Since memory consolidation is transcription-dependent, we performed RNA-seq on DH tissue to identify learning-induced gene changes over the diurnal cycle. Notably, the circadian gene Period1 (Per1) was upregulated in response to learning during the day but not night, mirroring memory performance. To determine if hippocampal Per1 contributes to memory across the day/night cycle, we knocked down Per1 using CRISPR interference (CRISPRi) in the DH before ZT5 training, which impaired learning. In conclusion, diurnal oscillations in memory consolidation may be regulated in part by hippocampal Per1 expression. Future work will determine if different transcript variants of Per1 specifically contribute to learning and memory or the circadian system.
Importance
Before this study, recent work had suggested that clock genes function within memory-relevant brain regions to exert local diurnal control over memory, however, it was unclear which clock genes regulate memory and which phase of memory (acquisition, consolidation, or retrieval) is impacted by the time of day. By deducing the involvement of Per1 in regulating memory during consolidation, we are able to expand our understanding of Per1’s roles in various parts of the brain. Since Per1 plays a major role in both the circadian rhythm and memory and since both of these systems show deficits in aged-populations, investigating how to control Per1’s impact in these realms can be beneficial in discovering potential methods to prolong the healthy aging process.