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 coordination of opposing adaptive behaviors. Previously, we uncovered a critical role for Corticotropin-Releasing Factor (CRF)-expressing neurons of the oval nucleus of the BNST (BNSTovCRF) in maintaining resilience to social defeat through stress-dependent self-sustaining neuronal activity.1 However, as mice develop resilience, it is not well-understood how affect and motivation are altered to achieve adaptive behavior in the face of ongoing threat. Here, we explore how this neuronal population exerts a powerful influence over internal state in various stress contexts to promote adaptive social responding. Using cell-type-selective optogenetics, a suite of behavioral paradigms, and transgenic Crf-ChR2 mice, we show that BNSTovCRF neurons induce resiliency by altering the encoding of psychosocial stress, enhancing the appetitiveness of social interaction, and enhancing tolerability to 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