Show simple item record

dc.contributor.authorGarcía, Ana Pen
dc.contributor.authorAitta-Aho, Teemuen
dc.contributor.authorSchaaf, Lauraen
dc.contributor.authorHeeley, Nicholasen
dc.contributor.authorHeuschmid, Lenaen
dc.contributor.authorBai, Yunjingen
dc.contributor.authorBarrantes, Franciscoen
dc.contributor.authorApergis-Schoute, Johnen
dc.date.accessioned2015-07-28T13:30:24Z
dc.date.available2015-07-28T13:30:24Z
dc.date.issued2015-08-06en
dc.identifier.citationGarcia et al. PLOS ONE (2015) Vol. 10 Issue 8, e0133327. doi:10.1371/journal.pone.0133327
dc.identifier.issn1932-6203
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/249102
dc.description.abstractNicotinic acetylcholine receptors (nAChRs) play an important role in regulating appetite and have been shown to do so by influencing neural activity in the hypothalamus. To shed light on the hypothalamic circuits governing acetylcholine’s (ACh) regulation of appetite this study investigated the influence of hypothalamic nAChRs expressing the α4 subunit. We found that antagonizing the α4β2 nAChR locally in the lateral hypothalamus with di-hydro-ß-erythroidine (DHβE), an α4 nAChR antagonist with moderate affinity, caused an increase in food intake following free access to food after a 12 hour fast, compared to saline-infused animals. Immunocytochemical analysis revealed that orexin/hypocretin (HO), oxytocin, and tyrosine hydroxylase (TH)-containing neurons in the A13 and A12 of the hypothalamus expressed the nAChR α4 subunit in varying amounts (34%, 42%, 50%, and 51%, respectively) whereas melanin concentrating hormone (MCH) neurons did not, suggesting that DHβE-mediated increases in food intake may be due to a direct activation of specific hypothalamic circuits. Systemic DHβE (2 mg/kg) administration similarly increased food intake following a 12 hour fast. In these animals a subpopulation of orexin/hypocretin neurons showed elevated activity compared to control animals and MCH neuronal activity was overall lower as measured by expression of the immediate early gene marker for neuronal activity cFos. However, oxytocin neurons in the paraventricular hypothalamus and TH-containing neurons in the A13 and A12 did not show differential activity patterns. These results indicate that various neurochemically distinct hypothalamic populations are under the influence of α4β2 nAChRs and that cholinergic inputs to the lateral hypothalamus can affect satiety signals through activation of local α4β2 nAChR-mediated transmission.
dc.description.sponsorshipThis work was supported by the Royal Society and the European Union (Latin America/European Liason, LAEL).
dc.languageEnglishen
dc.language.isoenen
dc.publisherPLOS
dc.rightsAttribution 2.0 UK: England & Wales
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.subjecthypothalamusen
dc.subjectappetiteen
dc.subjectacetylcholineen
dc.subjectnicotine receptorsen
dc.subjectα4β2en
dc.subjectorexinen
dc.subjectmchen
dc.subjectA13en
dc.subjectoxytocinen
dc.titleNicotinic alpha4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuitsen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from PLOS via http://dx.doi.org/1371/journal.pone.0133327en
prism.numbere0133327en
prism.publicationDate2015en
prism.publicationNamePLOS ONEen
prism.volume10en
dcterms.dateAccepted2015-06-24en
rioxxterms.versionofrecord10.1371/journal.pone.0133327en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-08-06en
dc.identifier.eissn1932-6203
rioxxterms.typeJournal Article/Reviewen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales