Post-ejaculatory inhibition of female sexual drive via heterogeneous neuronal ensembles in the medial preoptic area
Male ejaculation acutely suppresses sexual motivation in male mice. In contrast, relatively little is known about how male ejaculation affects sexual motivation and sexual behavior in female mice. How the brain responds to the completion of mating is also unclear. Here, by using a self-paced mating...
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eLife Sciences Publications Ltd
2025-03-01
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| Online Access: | https://elifesciences.org/articles/91765 |
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| author | Kentaro K Ishii Koichi Hashikawa Jane Chea Shihan Yin Rebecca Erin Fox Suyang Kan Meha Shah Zhe Charles Zhou Jovana Navarrete Alexandria D Murry Eric R Szelenyi Sam A Golden Garret D Stuber |
| author_facet | Kentaro K Ishii Koichi Hashikawa Jane Chea Shihan Yin Rebecca Erin Fox Suyang Kan Meha Shah Zhe Charles Zhou Jovana Navarrete Alexandria D Murry Eric R Szelenyi Sam A Golden Garret D Stuber |
| author_sort | Kentaro K Ishii |
| collection | DOAJ |
| description | Male ejaculation acutely suppresses sexual motivation in male mice. In contrast, relatively little is known about how male ejaculation affects sexual motivation and sexual behavior in female mice. How the brain responds to the completion of mating is also unclear. Here, by using a self-paced mating assay, we first demonstrate that female mice show decreased sexual motivation acutely after experiencing male ejaculation. By using brain-wide analysis of activity-dependent labeling, we next pin-pointed the medial preoptic area as a brain region strongly activated during the post-ejaculatory period. Furthermore, using freely moving in vivo calcium imaging to compare the neural activity of inhibitory and excitatory neurons in the medial preoptic area, we revealed that a subset of the neurons in this region responds significantly and specifically to male ejaculation but not to female-to-male sniffing or to male mounting. While there were excitatory and inhibitory neurons that showed increased response to male ejaculation, the response magnitude as well as the proportion of neurons responding to the event was significantly larger in the inhibitory neuron population. Next, by unbiased classification of their responses, we also found a subpopulation of neurons that increase their activity late after the onset of male ejaculation. These neurons were all inhibitory indicating that male ejaculation induces a prolonged inhibitory activity in the medial preoptic area. Lastly, we found that chemogenetic activation of medial preoptic area neurons that were active during the post-ejaculatory period, but not during appetitive or consummatory periods, were sufficient to suppress female sexual motivation. Together, our data illuminate the importance of the medial preoptic area as a brain node which encodes a negative signal that sustains a low sexual motivation state after the female mice experience ejaculation. |
| format | Article |
| id | doaj-art-1944988a479540d98b1eb32798f94b21 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-1944988a479540d98b1eb32798f94b212025-08-20T02:46:43ZengeLife Sciences Publications LtdeLife2050-084X2025-03-011210.7554/eLife.91765Post-ejaculatory inhibition of female sexual drive via heterogeneous neuronal ensembles in the medial preoptic areaKentaro K Ishii0https://orcid.org/0000-0002-7956-0806Koichi Hashikawa1Jane Chea2Shihan Yin3Rebecca Erin Fox4Suyang Kan5Meha Shah6Zhe Charles Zhou7Jovana Navarrete8Alexandria D Murry9Eric R Szelenyi10Sam A Golden11Garret D Stuber12https://orcid.org/0000-0003-1730-4855Center for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Biological Structure, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Biological Structure, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Biological Structure, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Biological Structure, University of Washington, Seattle, United StatesCenter for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, United States; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United States; Department of Pharmacology, University of Washington, Seattle, United StatesMale ejaculation acutely suppresses sexual motivation in male mice. In contrast, relatively little is known about how male ejaculation affects sexual motivation and sexual behavior in female mice. How the brain responds to the completion of mating is also unclear. Here, by using a self-paced mating assay, we first demonstrate that female mice show decreased sexual motivation acutely after experiencing male ejaculation. By using brain-wide analysis of activity-dependent labeling, we next pin-pointed the medial preoptic area as a brain region strongly activated during the post-ejaculatory period. Furthermore, using freely moving in vivo calcium imaging to compare the neural activity of inhibitory and excitatory neurons in the medial preoptic area, we revealed that a subset of the neurons in this region responds significantly and specifically to male ejaculation but not to female-to-male sniffing or to male mounting. While there were excitatory and inhibitory neurons that showed increased response to male ejaculation, the response magnitude as well as the proportion of neurons responding to the event was significantly larger in the inhibitory neuron population. Next, by unbiased classification of their responses, we also found a subpopulation of neurons that increase their activity late after the onset of male ejaculation. These neurons were all inhibitory indicating that male ejaculation induces a prolonged inhibitory activity in the medial preoptic area. Lastly, we found that chemogenetic activation of medial preoptic area neurons that were active during the post-ejaculatory period, but not during appetitive or consummatory periods, were sufficient to suppress female sexual motivation. Together, our data illuminate the importance of the medial preoptic area as a brain node which encodes a negative signal that sustains a low sexual motivation state after the female mice experience ejaculation.https://elifesciences.org/articles/91765sexual behaviorsocial behaviorhypothalamuscalcium imagingtissue clearing |
| spellingShingle | Kentaro K Ishii Koichi Hashikawa Jane Chea Shihan Yin Rebecca Erin Fox Suyang Kan Meha Shah Zhe Charles Zhou Jovana Navarrete Alexandria D Murry Eric R Szelenyi Sam A Golden Garret D Stuber Post-ejaculatory inhibition of female sexual drive via heterogeneous neuronal ensembles in the medial preoptic area eLife sexual behavior social behavior hypothalamus calcium imaging tissue clearing |
| title | Post-ejaculatory inhibition of female sexual drive via heterogeneous neuronal ensembles in the medial preoptic area |
| title_full | Post-ejaculatory inhibition of female sexual drive via heterogeneous neuronal ensembles in the medial preoptic area |
| title_fullStr | Post-ejaculatory inhibition of female sexual drive via heterogeneous neuronal ensembles in the medial preoptic area |
| title_full_unstemmed | Post-ejaculatory inhibition of female sexual drive via heterogeneous neuronal ensembles in the medial preoptic area |
| title_short | Post-ejaculatory inhibition of female sexual drive via heterogeneous neuronal ensembles in the medial preoptic area |
| title_sort | post ejaculatory inhibition of female sexual drive via heterogeneous neuronal ensembles in the medial preoptic area |
| topic | sexual behavior social behavior hypothalamus calcium imaging tissue clearing |
| url | https://elifesciences.org/articles/91765 |
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