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

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-hr acute restraint stress model, we uncover that stress causes a net decrease in vSUB activity in females that is potent, long-lasting, and driven by adrenergic receptor signaling. By contrast, males exhibit a net increase in vSUB activity that is transient and driven by corticosterone signaling. We further identified sex-dependent changes in vSUB output to the bed nucleus of the stria terminalis and in anxiety-like behavior 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 sex-dependent adaptations that may shape stress-related psychiatric disease risk. HighlightsO_LIvSUB BS cells are uniquely stress sensitive C_LIO_LIStress causes sex-dependent changes to BS cell E/I balance C_LIO_LIStress causes sex-dependent changes to vSUB activity to aBNST in vivo C_LIO_LIStress causes anxiety-like behavior in females, but not males C_LI