CRF neurons of the BNST promote resilience by blunting the internal experience of aversion

Abstract

The Bed Nucleus of the Stria Terminalis (BNST) has been studied extensively for its role in coordinating what appears to be often opposing adaptive behaviors. However, what is missing in the literature is the link between internal affective states and the adaptive stress behaviors they motivate. Previously, we uncovered a stress window during which neuronal activity of Corticotropin-Releasing Factor (CRF) expressing neurons of the oval nucleus of the BNST, (BNSTovCRF) maintains resilient behavior through self-sustained activation1. Here, we explore how BNSTovCRF neurons achieve this through shifting the valence of stress contexts to represent a less aversive experience. Using cell-type-selective optogenetics and transgenic Crf-ChR2 mice, we show that BNSTovCRF induces resiliency through dampening the deleterious effects of social defeat encoding, enhancing the positive salience of both appetitive and aversive stimuli, shifting socio-affective bias, and promoting tolerability of non-social physical stress. Adaptive responses to stress typically emanate as a response to negative internal states by external stimuli; here we show that in resilient mice, stressful environments are less aversive than susceptible mice, suggesting a different motivational capacity to endure stress in this group. Thus, we describe a novel role for BNSTovCRF neurons in resisting the emotional effects of cumulative stress by reducing the internal experience of aversion.