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

Jose Rodriguez-Romaguera; Randall L Ung; Hiroshi Nomura; James M Otis; Marcus L Basiri; Vijay M K Namboodiri; Xueqi Zhu; J Elliott Robinson; Hanna E van den Munkhof; Jenna A McHenry; Louisa E H Eckman; Oksana Kosyk; Thomas C Jhou; Thomas L Kash; Michael R Bruchas; Garret D Stuber

doi:10.1016/j.celrep.2020.108362

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

Cell Rep. 2020 Nov 10;33(6):108362. doi: 10.1016/j.celrep.2020.108362.

Authors

Jose Rodriguez-Romaguera¹, Randall L Ung², Hiroshi Nomura¹, James M Otis¹, Marcus L Basiri², Vijay M K Namboodiri¹, Xueqi Zhu¹, J Elliott Robinson², Hanna E van den Munkhof¹, Jenna A McHenry¹, Louisa E H Eckman¹, Oksana Kosyk¹, Thomas C Jhou³, Thomas L Kash⁴, Michael R Bruchas⁵, Garret D Stuber⁶

Affiliations

¹ Department of Psychiatry, University of North Carolina, Chapel Hill, NC 72599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 72599, USA.
² Neuroscience Center, University of North Carolina, Chapel Hill, NC 72599, USA; Neuroscience Curriculum, University of North Carolina, Chapel Hill, NC 72599, USA.
³ Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA.
⁴ Neuroscience Curriculum, University of North Carolina, Chapel Hill, NC 72599, USA; Bowles Center for Alcohol Studies, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 72599, USA.
⁵ Department of Anesthesiology, Washington University Pain Center, Department of Neuroscience, Division of Biology & Biomedical Sciences; and Department of Biomedical Engineering, Washington University, St. Louis, MO 63130, USA.
⁶ Department of Psychiatry, University of North Carolina, Chapel Hill, NC 72599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 72599, USA; Neuroscience Curriculum, University of North Carolina, Chapel Hill, NC 72599, USA; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 72599, USA. Electronic address: gstuber@uw.edu.

Abstract

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^BNST) 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^BNST 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^BNST neurons encode rapid arousal responses that modulate anxiety states. Further histological, electrophysiological, and single-cell RNA sequencing data reveal that Pnoc^BNST neurons are composed of genetically and anatomically identifiable subpopulations that may differentially tune rapid arousal responses to motivational stimuli.

Keywords: BNST; and pupillometry; anxiety-like behavior; aversion; hyperarousal; reward.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amygdala / metabolism*
Animals
Arousal
Behavior, Animal / physiology*
Male
Mice
Neurons / metabolism*
Protein Precursors / metabolism*
Receptors, Opioid / metabolism*

Substances

Protein Precursors
Receptors, Opioid
prepronociceptin

Abstract

Publication types

MeSH terms

Substances

Grants and funding