Chronic exercise induces a pathway-dependent electrophysiological signature in the mouse hippocampus

Chronic physical exercise enhances hippocampal function, yet its impact on network activity remains poorly defined. We explored whether treadmill running leaves durable imprints detectable through electrophysiological techniques and spatial transcriptomics. Field potentials (FPs) were recorded in anesthetized male C57BL/6 J mice after a chronic exercise protocol. Using machine learning to analyze FP generators, we were able to reliably classify animals into their correct group by Lateral Perforant Path (LPP) activity alone. Classification rested on a multifeatured signature rather than any single feature. Schaffer Collateral and Lacunosum-Moleculare generators showed changes that did not achieve statistical significance. Exploratory spatial transcriptomics identified a coordinated enrichment of calcium signaling and long-term potentiation programs in the dentate gyrus. These findings demonstrate that exercise-induced plasticity is not a global shift but a localized remodeling of specific synaptic inputs, with changes detectable at both circuit and molecular levels. These durable, pathway-specific imprints persist in the absence of active task engagement, suggesting a reorganization of the brain’s memory circuitry.