Hippocampal long-term potentiation is modulated by exercise-induced alterations in dopaminergic synaptic transmission in mice selectively bred for high voluntary wheel running.

This article investigates how intense voluntary running in High-Runner (HR) mice, selectively bred for high wheel-running activity, affects hippocampal long-term potentiation (LTP) and dopaminergic synaptic transmission compared to non-selected control (C) mice. The study found that HR mice with wheel access exhibited significantly enhanced LTP in the hippocampal CA1 region, an effect not observed in control mice, and that this enhancement was reduced by pharmacological activation of dopamine D1/D5 receptors or inhibition of the dopamine transporter (DAT). Western blot analyses revealed that HR mice have lower hippocampal D1/D5 receptor levels and higher DAT levels than controls, regardless of wheel access, suggesting genotype-driven alterations in dopaminergic function. These findings imply that exercise-induced changes in dopamine signaling contribute to synaptic plasticity differences in HR mice and support their potential use as a model for studying hyperactivity, motivation for exercise, and related neurophysiological conditions.