Circadian Gene Per1 Drives Local Regulation of Hippocampal Memory Consolidation

open_access
Open Access
Author:
Von Abo, Megan
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Janine Kwapis, Thesis Supervisor
Scott E. Lindner, Thesis Honors Advisor
Keywords:
circadian rhythms
memory consolidation
Per1
dorsal hippocampus
RNA-seq
CRISPR interference
object location memory
RT-qPCR
Abstract:
Circadian rhythms shape numerous physiological processes across the 24 hour cycle, including learning and memory. Although behavioral studies have demonstrated diurnal oscillations in memory performance due to changes in the consolidation phase of memory, the molecular mechanisms underlying these diurnal oscillations remain unclear. Here, we used unbiased RNA-seq to identify genes differentially expressed across the day/night cycle following learning. We found the circadian clock gene Per1 was selectively upregulated during peak memory periods. After that, we used RT-qPCR validation to confirm that learning-induced Per1 expression mirrors the oscillation in behavioral performance. Finally, we locally knockdown of Per1 in the dorsal hippocampus using HSV-mediated CRISPR interference, resulting in an impairment of long-term memory formation and established a causal role for Per1 in consolidation. These results reveal that beyond its canonical role in the suprachiasmatic nucleus, Per1 functions locally in the hippocampus to gate transcriptional processes critical for memory, highlighting how circadian timing can shape cognitive outcomes.