Sexual experience has marked and long-lasting effects on male behavior in mammals, regulating traits such as the anticipation and display of sexual behavior, aggression and olfaction. We conducted urine preference, habituation-dishabituation and partner choice tests with sexually experienced and naïve male mice and found that wild-type males acquire adaptively significant preferences for the odors of receptive, estrous females with sexual experience, and that these preferences are matched by changes in main olfactory system responses involving the piriform cortex, as indicated by c-Fos expression. We also report that these experiential effects are disrupted in male mice carrying a knockout of the imprinted gene Peg3. This paternally expressed gene regulates maternal care and offspring development, but we here report that Peg3 mutant males suffer a complex olfactory deficit that affects estrous odor preferences and the responses of the main olfactory system to such odors. Peg3 appears to have evolved to regulate the experience-dependent preference for receptive females, an adaptive trait that would enhance male reproductive success and so potentially increase paternal transmission of this paternally expressed gene
