Elucidating the neural basis for expression of estrous female odor preference in male mice

Social behaviors, such as sexual and aggressive behaviors, are important for successful reproduction and territorial defense in mice as a social species. For adaptive and efficient exhibition of these behaviors, accurate sex, reproductive state, and other opponent characteristics-related information processing is essential.

Male mice reportedly prefer the odor of estrous females over that of non-estrous females (receptivity-based preference) and males (sex-based preference). However, the neural circuit control of these preferences has not been unraveled yet.

In this study, published in Proceedings of the National Academy of Sciences, the researchers focused on the medial amygdala, reportedly involved in social information processing, and investigated the role of estrogen receptor beta-positive (MeA-ERβ+) neurons that are widely distributed in this region.

Using genetically-engineered male mice (ERβ-iCre) in which MeA-ERβ+ neurons are selectively manipulatable, the researchers performed three main sets of experiments to compare receptivity- and sex-based preferences: fiber photometry recording of MeA-ERβ+ neuronal activity during social preference tests, assessment of how pharmacogenetic MeA-ERβ+ neuronal activity suppression affected preference behavior, and neuronal activity recording of the bed nucleus of stria terminalis (BNST), a primary MeA-ERβ+ neuronal projection site, during preference tests under pharmacogenetic suppression of MeA-ERβ+ neuronal activity.

The results revealed that MeA-ERβ+ neurons exhibit different roles for the two preference types. Specifically, an excitatory MeA-ERβ+ neuronal activity input to the BNST is required for receptivity-based preference, whereas the BNST neurons control sex-based preference independently of the MeA-ERβ+ neuronal excitation.