The ability to learn, consolidate and retrieve information is critical for everyday survival and this ability begins to decline with normal aging and is severely exacerbated by Alzheimer’s Disease (AD). In this seminar, I discuss aspects of my past, current, and future research using exercise as an approach to unlocking a novel understanding of the molecular and epigenetic mechanisms that drive memory formation by utilizing specific exercise parameters that enhance cognitive benefits. I show that a ‘molecular memory window’ exists for maintaining the cognitive benefits of exercise through sedentary periods in females and males. An unbiased examination of this ‘window’ reveals a key molecular mechanism by which exercise enhances synaptic plasticity and drives long-term memory consolidation, allowing memory formation to occur under inadequate, subthreshold learning conditions. These findings demonstrate Acvr1c to be an essential, novel bidirectional regulator and driver of long-term memory consolidation in the adult brain.
Acvr1c expression is impaired in the aging and Alzheimer’s Disease brain, and over-expression ameliorates plasticity and cognitive impairments. Promoting ACVR1C may protect against cognitive impairment, providing a novel druggable target and pathway as a potential disease-modifying treatment for Alzheimer’s Disease. These findings also open a new area of exploring how specific exercise parameters may allow for periods of maintained molecular changes through sedentary periods that facilitate cognitive function.