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Cited by 24Nicotinic Acetylcholine Receptors StudyRegulation of Appetite and ObesityNeuroscience and Neuropharmacology Research

Molecular and cellular characterization of nicotinic acetylcholine receptor subtypes in the arcuate nucleus of the mouse hypothalamus

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Calarco, Cali A., Li, Zhiying, Taylor, Seth R., Lee, Somin, Zhou, Wenliang, Friedman, Jeffrey M., Mineur, Yann S., Gotti, Cecilia +1 more·2018·European Journal of Neuroscience
DOI 10.1111/ejn.13966PMC PMC6251769
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Abstract

Nicotine, acting through nicotinic acetylcholine receptors (nAChR s), increases the firing rate of both orexigenic agouti‐related peptide (Ag RP) and anorexigenic pro‐opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC), yet nicotine and other nAChR agonists decrease food intake in mice. Viral‐mediated knockdown of the β4 nAChR subunit in all neuronal cell types in the ARC prevents the nicotinic agonist cytisine from decreasing food intake, but it is not known whether the β4 subunit is selectively expressed in anorexigenic neurons or how other nAChR subtypes are distributed in this nucleus. Using translating ribosome affinity purification (TRAP) on ARC tissue from mice with ribosomes tagged in either Ag RP or POMC cells, we examined nAChR subunit mRNA levels using real‐time PCR. Both Ag RP and POMC cells express a comparable panel of nAChR subunits with differences in α7 mRNA levels and a trend for difference in α4 levels, but no differences in β4 expression. Immunoprecipitation of assembled nAChR s revealed that the β4 subunit forms assembled channels with α3, β2 and α4, but not other subunits found in the ARC. Finally, using cell type‐selective, virally delivered small hairpin RNA s targeting either the β4 or α7 subunit, we examined the contribution of each subunit in either Ag RP or POMC cells to the behavioural response to nicotine, refining the understanding of nicotinic regulation of this feeding circuit. These experiments identify a more complex set of nAChR s expressed in ARC than in other hypothalamic regions. Thus, the ARC appears to be a particular target of nicotinic modulation.

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  • Deletion of the β4 nAChR subunit from either POMC or NPY neurons is sufficient to attenuate nicotinic-induced decreases in food intake.

    “deletion of the β4 nAChR subunit from either subtype is sufficient to attenuate nicotinic-induced decreases in food intake (Calarco et al. 2018).”

    From Mechanisms of Nicotine Addiction (2021) · cites this paper as Calarco et al. 2018

    The Results section (page not provided) reports that β4 knockdown in POMC or AgRP neurons blunted the decrease in food intake caused by nicotine. The cited study used knockdown, not deletion, and tested AgRP neurons rather than identifying the tested population as NPY neurons. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Both POMC and NPY neurons express almost all nAChR subunits.

    “both POMC and NPY neurons express almost all nAChR subunits”

    From Mechanisms of Nicotine Addiction (2021) · cites this paper as Calarco et al. 2018

    The Results section (page not available) detects mRNAs for six nAChR subunits in both POMC and AgRP cell populations, which supports expression of several subunits. It also says α2, α5 and β3 were not reliably detected in either population, so “almost all” overstates the finding. The study measures AgRP rather than NPY neurons specifically, and its Discussion cautions that not every AgRP or POMC cell expresses each subunit. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Authors
Calarco, C. A., Li, Z., Taylor, S. R., Lee, S., Zhou, W., Friedman, J. M., Mineur, Y. S., Gotti, C., & Picciotto, M. R.
Affiliations
  • Yale University (US)
  • Rockefeller University (US)
  • Department of Psychiatry and Interdepartmental Neuroscience Program Yale University School of Medicine New Haven Connecticut
  • National Research Council (IT)
Corresponding author
Picciotto, Marina R.
ORCID
Venue
European Journal of Neuroscience
Publisher
Wiley
Published
2018-06-19
Volume
48
Issue
1
Pages
1600-1619
ISSN
  • 0953-816X (ISSN-L)
  • 1460-9568
DOI
10.1111/ejn.13966
PMC
PMC6251769
OpenAlex
W2803971519
Cited by
24
References
12
Citations by year
2026: 4 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 1
FWCI
0.98
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • European Journal of Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (DA037566, DA14241)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
nicotinic acetylcholine receptors, arcuate nucleus, hypothalamus, nicotine, food intake regulation, AgRP neurons, POMC neurons, alpha7 subunit, beta4 subunit, alpha4 subunit, receptor subunit assembly, feeding circuits, translating ribosome affinity purification

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