BNST transient activity associates with approach behavior in a stressful environment and is modulated by the parabrachial nucleus

Abstract

Studies demonstrate a role for the bed nucleus of the stria terminalis (BNST) in modulating affective behavior and stress-reward integration. To explore the dynamic nature of in vivo BNST activity associated with anxiety-like behavior in a stress-inducing context, we utilized fiber photometry and detected BNST calcium transients in mice during the novelty-suppressed feeding task (NSFT). Phasic BNST activity emerged time-locked to novel object or food pellet approach during NSFT. The parabrachial nucleus (PBN) has a large input to the BNST and is thought to function as a danger signal, in arousal responses and in feeding behavior. To explore a potential role for the PBN as a contributor to BNST activity in NSFT, we investigated whether chemogenetic regulation of PBN activity altered the dynamic BNST response synchronized to NSFT approach behavior. We found that activation of the hM3D(G_q) DREADD in the PBN enhanced the observed transient signal in the BNST synchronized to the consummatory food approach, and was associated at the behavioral level with increased latency to consume food. Because the PBN has multiple efferent pathways, we next used a transsynaptic anterograde AAV-based strategy to express hM3D(G_q) specifically in PBN-innervated BNST (BNST^PBN) neurons in male and female mice. Activation of hM3D(G_q) in these BNST^PBN neurons increased latency to consume food in female, but not male mice. To further explore the population of BNST neurons contributing to phasic BNST activity associated with NSFT, we turned to PKCδ neurons in BNST. BNST(PKCδ) neurons are implicated in stress and food-related behavior, and we previously found that the expression of this kinase is regulated in the BNST by stress in a sex-dependent manner. Here, we demonstrate close apposition of CGRP, a marker of PBN terminals, adjacent to BNST(PKCδ) cells. Finally, we find that PKCδ-expressing BNST cells exhibit a large transient signal synchronized to the consummatory food approach similar to that seen with bulk BNST activity measures. Taken together these data demonstrate phasic BNST activity at a global and cell-specific level that is driven in part by PBN activity at the time of NSFT consummatory approach behavior.