biostudies-literatureUnknown14Bian XThe remodeling of synapses in the hippocampus is intricately linked to processes of learning and memory. Research indicates that high-intensity interval training (HIIT) enhances cognitive functions reliant on the hippocampus in mice, although the specific receptor-mediated molecular pathways involved are not fully elucidated. Lactate, which is produced in significant amounts during HIIT, may function as a signaling agent in the brain through the lactate receptor G protein-coupled receptor 81 (GPR81), classified as a Gi-type G protein-coupled receptor. This investigation focused on the lactate/GPR81 pathway's contribution to synaptic remodeling in the hippocampus induced by HIIT and examined its downstream signaling characteristics. <i>In vivo</i> results demonstrated that HIIT led to an inFrontiers in cell and developmental biology1699042https://www.ebi.ac.uk/biostudies/studies/S-EPMC12846946biostudies-literatureHIIT-induced lactate/GPR81 signaling with dual branches converging on ERK1/2 contributes to hippocampal synaptic remodeling and memory improvement.PMC12846946Shang QLiu JWu MLi JZhu LLou SBian XfalseHIIT-induced lactate/GPR81 signaling with dual branches converging on ERK1/2 contributes to hippocampal synaptic remodeling and memory improvement.The remodeling of synapses in the hippocampus is intricately linked to processes of learning and memory. Research indicates that high-intensity interval training (HIIT) enhances cognitive functions reliant on the hippocampus in mice, although the specific receptor-mediated molecular pathways involved are not fully elucidated. Lactate, which is produced in significant amounts during HIIT, may function as a signaling agent in the brain through the lactate receptor G protein-coupled receptor 81 (GPR81), classified as a Gi-type G protein-coupled receptor. This investigation focused on the lactate/GPR81 pathway's contribution to synaptic remodeling in the hippocampus induced by HIIT and examined its downstream signaling characteristics. <i>In vivo</i> results demonstrated that HIIT led to an in2026-01-01T00:00:00Z20262026-06-15T04:48:49.873Z2026-06-15T03:08:51.266ZS-EPMC128469464161405810.3389/fcell.2026.1699042