A Unique Mouse Model of Early Life Exercise Enables Hippocampal Memory and Synaptic Plasticity

Physical exercise is a powerful modulator of learning and memory. Mechanisms underlying the cognitive benefits of exercise are well documented in adult rodents. Exercise studies targeting postnatal periods of hippocampal maturation (specifically targeting periods of synaptic reorganization and plasticity) are lacking. We characterize a model of early-life exercise (ELE) in male and female mice designed with the goal of identifying critical periods by which exercise may have a lasting impact on hippocampal memory and synaptic plasticity. Mice freely accessed a running wheel during three postnatal periods: the 4^th postnatal week (juvenile ELE, P21–27), 6^th postnatal week (adolescent ELE, P35–41), or 4^th-6^th postnatal weeks (juvenile-adolescent ELE, P21–41). All exercise groups increased their running distances during ELE. When exposed to a subthreshold learning stimulus, juv ELE and juv-adol ELE formed lasting long-term memory for an object location memory task, whereas sedentary and adol ELE mice did not. Electrophysiological experiments revealed enhanced long-term potentiation in hippocampal CA1 in the juvenile-adolescent ELE group. I/O curves were also significantly modulated in all mice that underwent ELE. Our results suggest that early-life exercise, specifically during the 4^th postnatal week, can enable hippocampal memory, synaptic plasticity, and alter hippocampal excitability when occurring during postnatal periods of hippocampal maturation.