Like sisters but not twins – vasopressin and oxytocin excite BNST neurons via cell type-specific expression of oxytocin receptor to reduce anxious arousal

Abstract

AbstractInteroceptive signals dynamically interact with the environment to shape appropriate defensive behaviors. Hypothalamic hormones arginine-vasopressin (AVP) and oxytocin (OT) regulate physiological states, including water and electrolyte balance, circadian rhythmicity, and defensive behaviors. Both AVP and OT neurons project to dorsolateral bed nucleus of stria terminalis (BNSTDL), which expresses oxytocin receptors (OTRs) and vasopressin receptors and mediates fear responses. However, understanding the integrated role of neurohypophysial hormones is complicated by the cross-reactivity of AVP and OT and their mutual receptor promiscuity. Here, we provide evidence that the effects of neurohypophysial hormones on BNSTDLexcitability are driven by input specificity and cell type-specific receptor selectivity. We show that OTR-expressing BNSTDLneurons, excited by hypothalamic OT and AVP inputs, play a major role in regulating BNSTDLexcitability, overcoming threat avoidance, and reducing threat-elicited anxious arousal. Therefore, OTR-BNSTDLneurons are perfectly suited to drive the dynamic interactions balancing external threat risk and physiological needs.Graphical abstractHighlightsExogenous and light-evoked vasopressin peptide excites neurons of the bed nucleus of the stria terminalis (BNST) via oxytocin receptor (OTR) in male ratsThe dorsolateral BNST receives vasopressinergic inputs from suprachiasmatic, supraoptic, and paraventricular nuclei of the hypothalamusThe majority of OTR- and Corticotropin-releasing factor (CRF) neurons of the BNST are classified as Type III neurons of the BNSTDLand are excited by AVPOTR-expressing BNST neurons increase exploration of open spaces and reduce anxious arousal in fear-potentiated startle in male ratsInternal signal-sensitive hypothalamic inputs directly impact BNST excitability via OTR to balance interoceptive signals and defensive behaviors