Prefrontal Cortex Corticotropin-Releasing Factor Neurons Motivate Behavioral Coping Strategies During Various Challenging Situations

Abstract

In response to stressors, individuals adopt different coping strategies that are essential for survival and form the basis of differential susceptibility to stress-related disorders. The corticotropin-releasing factor (CRF) or medial prefrontal cortex (mPFC) has predominantly been studied in stress-coping strategies respectively, while the role of mPFC CRF neurons is scarcely understood. Here, using morphological and electrophysiological approaches, we characterized mPFC CRF neurons as a unique subtype of inhibitory interneurons and identified a monosynaptic, GABAergic CRF-pyramidal connection in mice. Furthermore, genetic ablation or chemogenetic inhibition of mPFC CRF neurons in naive mice induces passive behavioral coping with tail suspension, forced swimming and social defeat stress, whereas chemogenetic activation of these neurons promotes active coping behaviors. These results uncover a critical role of mPFC CRF interneurons in bidirectionally controlling motivated behavioral coping strategies selection and substantially expand our understanding of the mPFC network underlying normal and pathological states of behavioral pattern selection.