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Molecular and cellular characterization of nicotinic acetylcholine receptor subtypes in the arcuate nucleus of the mouse hypothalamus
- Source :
- European Journal of Neuroscience. 48:1600-1619
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- Nicotine, acting through nicotinic acetylcholine receptors (nAChRs), increases the firing rate of both orexigenic agouti-related peptide (AgRP) 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 AgRP or POMC cells, we examined nAChR subunit mRNA levels using real-time PCR. Both AgRP 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 nAChRs 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 RNAs targeting either the β4 or α7 subunit, we examined the contribution of each subunit in either AgRP 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 nAChRs expressed in ARC than in other hypothalamic regions. Thus, the ARC appears to be a particular target of nicotinic modulation.
- Subjects :
- 0301 basic medicine
Arc (protein)
Chemistry
General Neuroscience
Protein subunit
digestive, oral, and skin physiology
Article
Cell biology
Nicotine
03 medical and health sciences
Nicotinic acetylcholine receptor
Cytisine
chemistry.chemical_compound
030104 developmental biology
0302 clinical medicine
Nicotinic agonist
nervous system
Arcuate nucleus
medicine
hormones, hormone substitutes, and hormone antagonists
030217 neurology & neurosurgery
Acetylcholine receptor
medicine.drug
Subjects
Details
- ISSN :
- 0953816X
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- European Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....929be33a661203eb1bf9df6f8f800b9f
- Full Text :
- https://doi.org/10.1111/ejn.13966