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 (Pnoc) modulate rapid changes in physiological arousal that occur upon exposure to motivationally salient stimuli. Using in vivo two-photon calcium imaging, we find that Pnoc 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 Pnoc neurons encode rapid arousal responses that modulate anxiety states. Further histological, electrophysiological, and single-cell RNA sequencing data reveal that Pnoc neurons are composed of genetically and anatomically identifiable subpopulations that may differentially tune rapid arousal responses to motivational stimuli.