Early-life stress alters affective behaviors in adult mice through persistent activation of CRH-BDNF signaling in the oval bed nucleus of the stria terminalis

• DOI: 10.1038/s41398-020-01070-3
• Publication Date: 2020-11-11T14:03:14Z
• Authors: Pu Hu; Isabella Maita; Mimi L. Phan; Edward Gu; Christopher Kwok; Andrew Dieterich; Mark M. Gergues; Christine N. Yohn; Yu Wang; Jiang-Ning Zhou; Xin-Rui Qi; Dick F. Swaab; Zhiping P. Pang; Paul J. Lucassen; Troy A. Roepke; Benjamin A. Samuels
• Keywords: Corticotropin-releasing hormone

Abstract Early-life stress (ELS) leads to stress-related psychopathology in adulthood. Although dysfunction of corticotropin-releasing hormone (CRH) signaling the bed nucleus stria terminalis (BNST) mediates chronic stress-induced maladaptive affective behaviors that are historically associated with mood disorders such as anxiety and depression, it remains unknown whether ELS affects CRH function adult BNST. Here we applied a well-established paradigm (24 h maternal separation (MS) at postnatal day 3) assessed effects on electrophysiology oval BNST (ovBNST) male mouse offspring. increased behaviors, amplified mEPSCs decreased M-currents (a voltage-gated K + current critical for stabilizing membrane potential) ovBNST neurons, suggesting enhanced cellular excitability. Furthermore, numbers PACAP (the pituitary adenylate cyclase-activating polypeptide, an upstream regulator) cells STEP (striatal-enriched protein tyrosine phosphatase, inhibitor) Interestingly, also brain-derived neurotrophic factor (BDNF) expression, indicating neuronal plasticity. These electrophysiological behavioral were reversed by application CRHR1-selective antagonist R121919 into ovBNST, but not when BDNF was co-administered. In addition, neurophysiological neurons mimic abolished PKC antagonism. Together, our findings indicate results long-lasting activation ovBNST. data highlight regulatory role CRHR1 mediating ELS-induced long-term changes.