The Role of HDAC3 in Memory Updating via the Objects in Updated Locations (OUL) Task
Open Access
- Author:
- Wright, Destiny
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Janine Kwapis, Thesis Supervisor
Stephen Wade Schaeffer, Thesis Honors Advisor - Keywords:
- memory updating
aging
mice
memory reconsolidation
HDAC3
hippocampus
age-related cognitive decline
memory impairments
epigenetic mechanisms - Abstract:
- Recent work provides evidence that epigenetic mechanisms play a vital role in memory formation. One epigenetic mechanism in particular, the repressive histone deacetylase HDAC3, operates in the hippocampus as a key negative regulator of memory; HDAC3 disruption or deletion transforms subthreshold learning into stable long-term memory. In older brains, HDAC3 contributes to age-related memory decline; HDAC3 deletion ameliorates age-related hippocampal memory impairments. Presently, it remains unclear whether HDAC3 induces age- related impairments in memory updating—the process through which an existing memory is updated with new information. The goal of this experiment was to determine the impact of HDAC3 on memory updating in young and old mice. To test this, we injected a pharmacological HDAC3 inhibitor, RGFP966, immediately after a hippocampal memory update in the Objects in Updated Location (OUL) paradigm in young (3-m.o.) and old (18-m.o.) mice. In old mice, HDAC3 blockage ameliorated age-related memory updating impairments, so that these mice now expressed intact memory for the update and memory for the original information at test time. In young mice, however, which already show robust memory updating, blocking HDAC3 after the update session led to disruption of the original memory, so that only memory for the update was robustly expressed at test. These results demonstrate that HDAC3 contributes to age-related impairments in hippocampus memory updating. Further, our work indicates that the original memory and the updated information appear to compete for expression, with HDAC3 helping to regulate which memory dominates at test.