Prepronociceptin-Expressing Neurons in the Extended Amygdala Encode and Promote Rapid Arousal Responses to Motivationally Salient Stimuli

Motivational states consist of cognitive, emotional, and physiological components controlled by multiple brain regions. An integral component of this neural circuitry is the bed nucleus of the stria terminalis (BNST). Here, we identify that neurons within BNST that express the gene prepronociceptin (PnocBNST) modulate rapid changes in physiological arousal that occur upon exposure to motivationally salient stimuli. Using in vivo two-photon calcium imaging, we find that PnocBNST neuronal responses directly correspond with rapid increases in pupillary size when mice are exposed to aversive and rewarding odors. Furthermore, optogenetic activation of these neurons increases pupillary size and anxiety-like behaviors but does not induce approach, avoidance, or locomotion. These findings suggest that excitatory responses in PnocBNST neurons encode rapid arousal responses that modulate anxiety states. Further histological, electrophysiological, and single-cell RNA sequencing data reveal that PnocBNST neurons are composed of genetically and anatomically identifiable subpopulations that may differentially tune rapid arousal responses to motivational stimuli. [Display omitted] •Prepronociceptin (Pnoc) defines a subpopulation of GABAergic neurons within BNST•PnocBNST neurons encode rapid changes in arousal to motivationally salient stimuli•Activation of PnocBNST neurons drives arousal responses and anxiety-like behavior•PnocBNST neurons exhibit diversity in both anatomical connectivity and genetic identity Rodriguez-Romaguera et al. find an ensemble of neurons within the extended amygdala (BNST) that expresses the prepronociceptin gene and functions to encode the rapid arousal responses that are triggered by motivational stimuli.