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Cited by 297Regulation of Appetite and ObesityEating Disorders and BehaviorsNeuropeptides and Animal Physiology

Genetically and functionally defined NTS to PBN brain circuits mediating anorexia

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Roman, Carolyn W., Derkach, Victor A., Palmiter, Richard D.·2016·Nature Communications
DOI 10.1038/ncomms11905PMC PMC4912612
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Abstract

The central nervous system controls food consumption to maintain metabolic homoeostasis. In response to a meal, visceral signals from the gut activate neurons in the nucleus of the solitary tract (NTS) via the vagus nerve. These NTS neurons then excite brain regions known to mediate feeding behaviour, such as the lateral parabrachial nucleus (PBN). We previously described a neural circuit for appetite suppression involving calcitonin gene-related protein (CGRP)-expressing PBN (CGRP PBN ) neurons; however, the molecular identity of the inputs to these neurons was not established. Here we identify cholecystokinin (CCK) and noradrenergic, dopamine β-hydroxylase (DBH)-expressing NTS neurons as two separate populations that directly excite CGRP PBN neurons. When these NTS neurons are activated using optogenetic or chemogenetic methods, food intake decreases and with chronic stimulation mice lose body weight. Our optogenetic results reveal that CCK and DBH neurons in the NTS directly engage CGRP PBN neurons to promote anorexia.

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  • Activation of projections of CCK and immunopositive neurons to the parabrachial nucleus results in decreased food intake without influencing anxiety-related behavior.

    “activation of projections of CCK and immunopositive neurons to the parabrachial nucleus results in decreased food intake without influencing anxiety-related behavior (Roman et al., 2016).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Roman et al., 2016

    The Results section, “NTS to PBN axon stimulation decreases food intake” (page unavailable), reports reduced food consumption when CCKNTS or DBHNTS terminals in the PBN were stimulated. The anxiety-related evidence is narrower: “Activation does not induce anxiety-like behaviour” reports an open-field test after activation of the neurons, not their PBN projections. The Discussion says the stimulation paradigms did not induce freezing, but does not establish that projection activation left anxiety-related behavior generally unchanged. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • NTS neurons express a variety of neuropeptides including cholecystokinin (CCK), prolactin-releasing peptide or pro-opiomelanocortin (POMC), and their receptors.

    “NTS neurons express a variety of neuropeptides including cholecystokinin (CCK), prolactin-releasing peptide or pro-opiomelanocortin (Roman et al., 2016), and their receptors.”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Roman et al., 2016

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Authors
Roman, C. W., Derkach, V. A., & Palmiter, R. D.
Affiliations
  • University of Washington (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Palmiter, Richard D.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2016-06-15
Volume
7
Issue
1
Pages
11905-11905
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms11905
PMC
PMC4912612
OpenAlex
W2439903663
Cited by
297
References
61
Citations by year
2026: 29 · 2025: 38 · 2024: 39 · 2023: 28 · 2022: 31 · 2021: 25 · 2020: 26 · 2019: 29 · 2018: 25 · 2017: 24 · 2016: 3
FWCI
17.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health
  • National Institute on Drug Abuse (R01DA024908)
  • National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007247)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
anorexia, nucleus tractus solitarius, lateral parabrachial nucleus, cholecystokinin, dopamine beta-hydroxylase, noradrenergic neurons, vagus nerve, appetite suppression, food intake regulation, neural circuits, gut-brain signaling, optogenetics, chemogenetics
MeSH terms
Action Potentials, Animals, Anorexia, Anxiety, Cholecystokinin, Dopamine beta-Hydroxylase, Eating, Mice, Inbred C57BL, Neural Pathways, Neurons, Calcitonin Gene-Related Peptide, Proto-Oncogene Proteins c-fos, Solitary Nucleus, Parabrachial Nucleus

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