Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner
Social animals, including both humans and mice, are highly motivated to engage in social interactions. Short-term social isolation promotes social behavior, but the neural circuits through which it does so remain incompletely understood. Here, we sought to identify neurons that promote social behavi...
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| Format: | Article |
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eLife Sciences Publications Ltd
2025-03-01
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| Online Access: | https://elifesciences.org/articles/94924 |
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| author | Xin Zhao Yurim Chae Destiny Smith Valerie Chen Dylan DeFelipe Joshua W Sokol Archana Sadangi Katherine Tschida |
| author_facet | Xin Zhao Yurim Chae Destiny Smith Valerie Chen Dylan DeFelipe Joshua W Sokol Archana Sadangi Katherine Tschida |
| author_sort | Xin Zhao |
| collection | DOAJ |
| description | Social animals, including both humans and mice, are highly motivated to engage in social interactions. Short-term social isolation promotes social behavior, but the neural circuits through which it does so remain incompletely understood. Here, we sought to identify neurons that promote social behavior in single-housed female mice, which exhibit increased rates of social investigation, social ultrasonic vocalizations (USVs), and mounting during same-sex interactions that follow a period of short-term (3 days) isolation. We first used immunostaining for the immediate early gene Fos to identify a population of neurons in the preoptic hypothalamus (POA) that increase their activity in single-housed females following same-sex interactions (POAsocial neurons) but not in single-housed females that did not engage in social interactions. TRAP2-mediated chemogenetic silencing of POAsocial neurons in single-housed females significantly attenuates the effects of short-term isolation on social investigation, USV production, and mounting. In contrast, caspase-mediated ablation of POAsocial neurons in single-housed females robustly attenuates mounting but does not decrease social investigation or USV production. Optogenetic activation of POAsocial neurons in group-housed females promotes social investigation and USV production but does not recapitulate the effects of short-term isolation on mounting. To understand whether a similar population of POAsocial neurons promotes social behavior in single-housed males, we performed Fos immunostaining in single-housed males following either same-sex or opposite-sex social interactions. These experiments revealed a population of POA neurons that increase Fos expression in single-housed males following opposite-sex, but not same-sex, interactions. Chemogenetic silencing of POAsocial neurons in single-housed males during interactions with females reduces mounting but does not affect social investigation or USV production. These experiments identify a population of hypothalamic neurons that promote social behavior following short-term isolation in a sex- and social context-dependent manner. |
| format | Article |
| id | doaj-art-67674c2b3e2e4b76a0ade377e630890a |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-67674c2b3e2e4b76a0ade377e630890a2025-08-20T03:16:26ZengeLife Sciences Publications LtdeLife2050-084X2025-03-011310.7554/eLife.94924Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent mannerXin Zhao0https://orcid.org/0000-0002-5796-8034Yurim Chae1Destiny Smith2Valerie Chen3Dylan DeFelipe4Joshua W Sokol5Archana Sadangi6Katherine Tschida7https://orcid.org/0000-0002-8171-1722Department of Psychology, Cornell University, Ithaca, United StatesDepartment of Psychology, Cornell University, Ithaca, United StatesDepartment of Psychology, Cornell University, Ithaca, United StatesDepartment of Psychology, Cornell University, Ithaca, United StatesDepartment of Psychology, Cornell University, Ithaca, United StatesDepartment of Psychology, Cornell University, Ithaca, United StatesDepartment of Psychology, Cornell University, Ithaca, United StatesDepartment of Psychology, Cornell University, Ithaca, United StatesSocial animals, including both humans and mice, are highly motivated to engage in social interactions. Short-term social isolation promotes social behavior, but the neural circuits through which it does so remain incompletely understood. Here, we sought to identify neurons that promote social behavior in single-housed female mice, which exhibit increased rates of social investigation, social ultrasonic vocalizations (USVs), and mounting during same-sex interactions that follow a period of short-term (3 days) isolation. We first used immunostaining for the immediate early gene Fos to identify a population of neurons in the preoptic hypothalamus (POA) that increase their activity in single-housed females following same-sex interactions (POAsocial neurons) but not in single-housed females that did not engage in social interactions. TRAP2-mediated chemogenetic silencing of POAsocial neurons in single-housed females significantly attenuates the effects of short-term isolation on social investigation, USV production, and mounting. In contrast, caspase-mediated ablation of POAsocial neurons in single-housed females robustly attenuates mounting but does not decrease social investigation or USV production. Optogenetic activation of POAsocial neurons in group-housed females promotes social investigation and USV production but does not recapitulate the effects of short-term isolation on mounting. To understand whether a similar population of POAsocial neurons promotes social behavior in single-housed males, we performed Fos immunostaining in single-housed males following either same-sex or opposite-sex social interactions. These experiments revealed a population of POA neurons that increase Fos expression in single-housed males following opposite-sex, but not same-sex, interactions. Chemogenetic silencing of POAsocial neurons in single-housed males during interactions with females reduces mounting but does not affect social investigation or USV production. These experiments identify a population of hypothalamic neurons that promote social behavior following short-term isolation in a sex- and social context-dependent manner.https://elifesciences.org/articles/94924social isolationfemaleultrasonic vocalizationsmountingpreoptichypothalamus |
| spellingShingle | Xin Zhao Yurim Chae Destiny Smith Valerie Chen Dylan DeFelipe Joshua W Sokol Archana Sadangi Katherine Tschida Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner eLife social isolation female ultrasonic vocalizations mounting preoptic hypothalamus |
| title | Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner |
| title_full | Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner |
| title_fullStr | Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner |
| title_full_unstemmed | Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner |
| title_short | Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner |
| title_sort | short term social isolation acts on hypothalamic neurons to promote social behavior in a sex and context dependent manner |
| topic | social isolation female ultrasonic vocalizations mounting preoptic hypothalamus |
| url | https://elifesciences.org/articles/94924 |
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