Acute stress causes sex-specific changes to ventral subiculum synapses, circuitry, and anxiety-like behavior

Abstract Experiencing a single severe stressor is sufficient to drive sexually dimorphic psychiatric disease development. The ventral subiculum (vSUB) emerges as a site where stress may induce sexually dimorphic adaptations due to its sex-specific organization and pivotal role in stress integration....

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Main Authors: Carley N. Miller, Yuan Li, Kevin T. Beier, Jason Aoto
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60512-y
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author Carley N. Miller
Yuan Li
Kevin T. Beier
Jason Aoto
author_facet Carley N. Miller
Yuan Li
Kevin T. Beier
Jason Aoto
author_sort Carley N. Miller
collection DOAJ
description Abstract Experiencing a single severe stressor is sufficient to drive sexually dimorphic psychiatric disease development. The ventral subiculum (vSUB) emerges as a site where stress may induce sexually dimorphic adaptations due to its sex-specific organization and pivotal role in stress integration. Using a 1 h acute restraint stress model in mice, we uncover that stress causes a net decrease in vSUB activity in females driven by adrenergic receptor signaling. By contrast, males exhibit a net increase in vSUB activity that is driven by corticosterone signaling. We further identified sexually dimorphic changes in vSUB output to the anterior bed nucleus of the stria terminalis and in anxiety-like behaviors in response to stress. These findings reveal striking changes in psychiatric disease-relevant brain regions and behavior following stress with sex-, cell-type, and synapse-specificity that contribute to our understanding of sexually dimorphic adaptations that may shape stress-related psychiatric disease risk.
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spelling doaj-art-c57f62416dab49999fdcc666d29fb6f82025-08-20T03:37:37ZengNature PortfolioNature Communications2041-17232025-07-0116112010.1038/s41467-025-60512-yAcute stress causes sex-specific changes to ventral subiculum synapses, circuitry, and anxiety-like behaviorCarley N. Miller0Yuan Li1Kevin T. Beier2Jason Aoto3Department of Pharmacology, University of Colorado Anschutz Medical CampusDepartment of Physiology and Biophysics, University of CaliforniaDepartment of Physiology and Biophysics, University of CaliforniaDepartment of Pharmacology, University of Colorado Anschutz Medical CampusAbstract Experiencing a single severe stressor is sufficient to drive sexually dimorphic psychiatric disease development. The ventral subiculum (vSUB) emerges as a site where stress may induce sexually dimorphic adaptations due to its sex-specific organization and pivotal role in stress integration. Using a 1 h acute restraint stress model in mice, we uncover that stress causes a net decrease in vSUB activity in females driven by adrenergic receptor signaling. By contrast, males exhibit a net increase in vSUB activity that is driven by corticosterone signaling. We further identified sexually dimorphic changes in vSUB output to the anterior bed nucleus of the stria terminalis and in anxiety-like behaviors in response to stress. These findings reveal striking changes in psychiatric disease-relevant brain regions and behavior following stress with sex-, cell-type, and synapse-specificity that contribute to our understanding of sexually dimorphic adaptations that may shape stress-related psychiatric disease risk.https://doi.org/10.1038/s41467-025-60512-y
spellingShingle Carley N. Miller
Yuan Li
Kevin T. Beier
Jason Aoto
Acute stress causes sex-specific changes to ventral subiculum synapses, circuitry, and anxiety-like behavior
Nature Communications
title Acute stress causes sex-specific changes to ventral subiculum synapses, circuitry, and anxiety-like behavior
title_full Acute stress causes sex-specific changes to ventral subiculum synapses, circuitry, and anxiety-like behavior
title_fullStr Acute stress causes sex-specific changes to ventral subiculum synapses, circuitry, and anxiety-like behavior
title_full_unstemmed Acute stress causes sex-specific changes to ventral subiculum synapses, circuitry, and anxiety-like behavior
title_short Acute stress causes sex-specific changes to ventral subiculum synapses, circuitry, and anxiety-like behavior
title_sort acute stress causes sex specific changes to ventral subiculum synapses circuitry and anxiety like behavior
url https://doi.org/10.1038/s41467-025-60512-y
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