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Elucidating the Neural Basis for Expression of Estrous Female Odor Preference in Male Mice

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Researchers from the University of Tsukuba investigated the brain circuit that controls social odor preference in male mice, essential for successful reproduction and survival. Their results were the first to demonstrate that estrogen receptor beta-expressing neuronal activity in the medial amygdala is required for an odor preference toward females in estrus over non-estrous ones but not for that between females and males.

Tsukuba, Japan—Social, such as sexual and aggressive, behaviors are pivotal 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, 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.

This work was supported by grant-in-aid for Scientific Research 15H05724 and 22H02941 to SO.

Original Paper

Title of original paper:
Activity of estrogen receptor β expressing neurons in the medial amygdala regulates preference towards receptive females in male mice
Proceedings of the National Academy of Sciences of the United States of America (PNAS)


Dr. OGAWA Sonoko
Laboratory of Behavioral Neuroendocrinology, Institute of Human Sciences, University of Tsukuba
Satoshi Takenawa
Graduate School of Comprehensive Human Sciences, University of Tsukuba

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