Tonic modulation of central CRF circuits by oxytocin in response to peripheral salt loading

Abstract

Central oxytocinergic neurons can likely modulate stress-related circuits through both paracrine and synaptic release of oxytocin (OT). One classic hallmark of a stress response is the activation of the HPA axis by corticotrophin releasing factor (CRF) positive neurons in the paraventricular nucleus of the hypothalamus (PVN). However, OT neurons in the PVN may also contribute via a synaptic pathway to the modulation of CRF neurons in the central amygdala (CeA), an area that helps integrate neuroendocrine and autonomic responses to stress. Prior studies have shown that peripheral salt loading activates OT neurons in the PVN but reduces anxiety-like behavior and the HPA response to restraint stress. In the present study, we examined a possible crosstalk between OT-mediated signaling and CRF neurons following peripheral salt loading using a Cre-lox based mouse model that selectively expresses red fluorescent protein in CRF neurons. The CRF-reporter mice received an injection of either isotonic or hypertonic saline one hour prior to euthanasia. Whole-cell patch clamp recordings were then made from identified CRF neurons in acute PVN and CeA slices. Compared with mice that received isotonic saline, hypertonic mice showed a significant OT receptor (OTR) mediated inhibitory tone on CRF neurons within the PVN and the CeA. Interestingly, within the PVN, this inhibitory tone was independent of activity-mediated release of classic excitatory and inhibitory neurotransmitters. Together, these data reveal novel ways by which OT can impact CRF microcircuitry to curb stress responsiveness, and furthers our understanding of the neuromodulatory role of endogenous OT with regard to complex social behaviors. Support: 13PRE17100047 (DP), HL096830 (EGK)