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bioRxiv · 10.1101/2023.03.24.534059

Activity of estrogen receptor beta expressing neurons in the medial amygdala regulates preference towards receptive females in male mice.

Takenawa, S.·Nagasawa, Y.·Go, K.·Cherasse, Y.·Mizuno, S.·Sano, K.·Ogawa, S.
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Abstract

The processing of information regarding the sex and reproductive state of conspecific individuals is critical for successful reproduction and survival in males. Generally, male mice exhibit a preference towards sexually receptive (RF) over non-receptive females (XF) or gonadally intact males (IM). Previous studies suggested the involvement of estrogen receptor beta (ER{beta}) expressed in the medial amygdala (MeA) in male preference towards RF. To further delineate the role played by ER{beta} in the MeA in the neuronal network regulating male preference, we developed a new ER{beta}-iCre mouse line using the CRISPR-Cas9 system. Fiber-photometry Ca2+ imaging revealed that ER{beta} expressing neurons in the postero-dorsal part of the MeA (MeApd-ER{beta}+ neurons) were more active during social investigation towards RF compared to copresented XF or IM mice in a preference test. Chemogenetic inhibition of MeApd-ER{beta}+ neuronal activity abolished a preference to RF in "RF vs. XF", but not "RF vs. IM", tests. Analysis with cre-dependent retrograde tracing viral vectors identified the principal part of the bed nucleus of stria terminalis (BNSTp) as a primary projection site of MeApd-ER{beta}+ neurons. Fiber-photometry recording in the BNSTp during a preference test revealed that chemogenetic inhibition of MeApd-ER{beta}+ neurons abolished differential neuronal activity of BNSTp cells as well as a preference to RF against XF but not against IM mice. Collectively, these findings demonstrate for the first time that MeApd-ER{beta}+ neuronal activity is required for expression of receptivity-based preference (i.e., RF vs XF) but not sex-based preference (i.e., RF vs IM) in male mice. Significance StatementIn this study, by introducing a new Cre mice line for ER{beta}+ cells, we described the function of MeApd-ER{beta}+ neurons and characteristics of their neuronal activity during preference tests. Using fiber photometry and DREADD techniques we have found MeApd-ER{beta}+ neurons have a specific role in receptivity-based (receptive female vs. non-receptive female) preference but not in sexbased (receptive female vs. intact male) preference in male mice. We have also described this specific role of MeApd-ER{beta}+ neurons is achieved by regulating the neuronal activity of downstream BNSTp neurons during receptivity-based, but not sex-based, preference tests. Our findings contribute to a better understating of the function of estrogen receptor expressing neurons in the neuronal network for the male-typical reproductive behaviors.

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Takenawa, S., Nagasawa, Y., Go, K., Cherasse, Y., Mizuno, S., Sano, K., Ogawa, S.. 2023-03-25. Activity of estrogen receptor beta expressing neurons in the medial amygdala regulates preference towards receptive females in male mice.. https://doi.org/10.1101/2023.03.24.534059

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