Prepronociceptin-Expressing Neurons in the Extended Amygdala Encode and Promote Rapid Arousal Responses to Motivationally Salient Stimuli
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Abstract
ABSTRACT Motivational states are complex and consist of cognitive, emotional, and physiological components controlled by a network across multiple brain regions. An integral component of this neural circuitry is the bed nucleus of the stria terminalis (BNST). Here, we identified a subpopulation of neurons within BNST expressing the gene prepronociceptin ( Pnoc BNST ), that can modulate the rapid changes in physiological arousal that occur upon exposure to stimuli with motivational salience. Using in vivo two-photon calcium imaging we found that excitatory responses from individual Pnoc BNST neurons directly corresponded with rapid increases in pupillary size and occurred upon exposure to both aversive and rewarding odors. Furthermore, optogenetic activation of these neurons increased pupillary size, but did not alter approach/avoidance or locomotor behaviors. These findings suggest that excitatory responses in Pnoc BNST neurons encode rapid arousal responses irrespective of tested behaviors. Further histological, electrophysiological, and single-cell RNA sequencing data revealed that Pnoc BNST neurons are composed of genetically and anatomically identifiable subpopulations that can be further investigated. Taken together, our findings demonstrate a key role for a Pnoc BNST neuronal ensemble in encoding the rapid arousal responses that are triggered by motivational stimuli.
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The BNST exhibits heterogeneity in neural responses, even within genetically defined cell populations.
“This is further complicated by the fact that the BNST exhibits heterogeneity in neural responses, even within genetically defined cell populations (83–85).”
From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [84]
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Sexual differentiation of neural mechanisms of stress sensitivity during puberty
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Self-citation
- Authors
- Rodriguez-Romaguera, J., Ung, R. L., Nomura, H., Otis, J. M., Basiri, M. L., Namboodiri, V. M. K., Zhu, X., Robinson, J. E., van den Munkhof, H. E., McHenry, J. A., Eckman, L. E. H., Kosyk, O., Jhou, T. C., Kash, T. L., Bruchas, M. R., & Stuber, G. D.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Medical University of South Carolina (US)
- Washington University in St. Louis (US)
- Corresponding author
- Stuber, Garret D.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 33
- Issue
- 6
- Pages
- 108362
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC8136285
- OpenAlex
- W3103962445
- Cited by
- 75
- References
- 17
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 11 · 2023: 12 · 2022: 12 · 2021: 13 · 2020: 2
- FWCI
- 5.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion, cc-by-nc-nd)
- UNC Libraries
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- bed nucleus of the stria terminalis, extended amygdala, arousal, pupil size, motivational salience, anxiety-like behavior, neuronal subpopulations, optogenetic stimulation, two-photon calcium imaging
- MeSH terms
- Amygdala, Animals, Arousal, Behavior, Animal, Male, Neurons, Protein Precursors, Receptors, Opioid, Mice
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