Sex-specific effect of the circadian clock gene Per1 in the retrosplenial cortex for context fear memory formation
Restricted (Penn State Only)
- Author:
- Lo, Chenyu
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Janine Kwapis, Thesis Supervisor
Bernhard Luscher, Thesis Honors Advisor - Keywords:
- Circadian rhythms
Memory
RSC
Gene expression - Abstract:
- Circadian rhythms are essential for organisms to regulate various biological processes, including long-term memory formation, across the day/night cycle. Various psychiatric disorders, including PTSD, are characterized by the dysfunction in both memory and circadian rhythmicity, suggesting a common molecular player underlying the multiple aspects of these disorders. We previously identified the circadian gene Period1 (Per1) to play a local role in hippocampal memory formation, in addition to its well-documented pacemaker function in the suprachiasmatic nucleus. It is unclear, however, whether Per1 underlies a general mechanism of memory formation in structures outside the hippocampus. Here, we decided to assess the role of Per1 in the retrosplenial cortex (RSC) due to its reciprocal connections to the prefrontal cortex, hippocampus, and thalamus and its known integrative role in context fear memory. We specifically tested whether Per1 within the RSC contributes to context fear memory formation, when both Per1 expression and fear memory formation peak. First, we showed that Per1 is increased in the RSC 60 min after fear learning. Next, we used the HSV-CRISPRi and CRISPRa systems to reduce or increase Per1 transcription specifically within the RSC before context fear conditioning. We found that Per1 knockdown in the RSC interfered with memory formation in both male and female mice. Lastly, we observed that Per1 overexpression in the RSC only impaired fear memory formation in male, but not female mice. Together, these findings suggest that proper Per1 expression in the RSC is critically important and can modulate contextual fear memory bidirectionally, thereby exerting local circadian control over memory formation. Our work further suggests that optimal Per1 levels in the RSC may be crucial for memory formation and that these levels may differ across male and female mice.