Reversing an epigenetic mechanism that limits memory flexibility in old age
Aging is accompanied by cognitive decline, including drastic impairments in memory formation and updating. Very little is understood about age-related impairments in memory updating, as most laboratory paradigms focus on initial memory formation. Using their own novel updating task, Objects in Updated Locations (OUL), Dr. Kwapis' lab recently discovered that the repressive histone deacetylase HDAC3 plays a crucial role in memory updating. Here, they will test the hypothesis that dysregulation of HDAC3 in the aging brain disrupts memory co-allocation, the transcription-dependent process of storing linked memories in overlapping neuronal populations. Using a combination of activity-dependent neuronal tagging, chemogenetic inhibition, and behavior, they will determine how updating and co-allocation change with age, how blocking HDAC3 affects these processes and whether artificially encouraging co-allocation improves updating in old mice. Broadly, this work will identify basic biological mechanisms that contribute to age-related impairments in memory updating, a critically understudied aspect of the aging process.
