We then validated the function of miR-501-3p, a DE-miRNA, in a rodent mouse model and delineated the regulatory molecular mechanism by which the loss of schizophrenia-associated down-regulated miR-501-3p in male mice induced sociability, memory, and sensorimotor gating disruptions through mGluR5-mediated excitatory glutamatergic transmission enhancement. This evidence concerns the gene GRM5 and schizophrenia.