Show simple item record

dc.contributor.authorHolt, MKen
dc.contributor.authorLlewellyn-Smith, IJen
dc.contributor.authorReimann, Franken
dc.contributor.authorGribble, Fionaen
dc.contributor.authorTrapp, Sen
dc.date.accessioned2017-09-01T13:31:46Z
dc.date.available2017-09-01T13:31:46Z
dc.date.issued2017-08-01en
dc.identifier.issn2212-8778
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/266994
dc.description.abstractOBJECTIVE: Glucagon-like peptide-1 (GLP-1) and 5-HT are potent regulators of food intake within the brain. GLP-1 is expressed by preproglucagon (PPG) neurons in the nucleus tractus solitarius (NTS). We have previously shown that PPG neurons innervate 5-HT neurons in the ventral brainstem. Here, we investigate whether PPG neurons receive serotonergic input and respond to 5-HT. METHODS: We employed immunohistochemistry to reveal serotonergic innervation of PPG neurons. We investigated the responsiveness of PPG neurons to 5-HT using in vitro Ca²⁺ imaging in brainstem slices from transgenic mice expressing the Ca²⁺ indicator, GCaMP3, in PPG neurons, and cell-attached patch-clamp recordings. RESULTS: Close appositions from 5-HT-immunoreactive axons occurred on many PPG neurons. Application of 20 μM 5-HT produced robust Ca²⁺ responses in NTS PPG dendrites but little change in somata. Dendritic Ca²⁺ spikes were concentration-dependent (2, 20, and 200 μM) and unaffected by blockade of glutamatergic transmission, suggesting 5-HT receptors on PPG neurons. Neither activation nor blockade of 5-HT₃ receptors affected [Ca²⁺]i. In contrast, inhibition of 5-HT₃ receptors attenuated increases in intracellular Ca²⁺ and 5-HT₂c receptor activation produced Ca²⁺ spikes. Patch-clamp recordings revealed that 44% of cells decreased their firing rate under 5-HT, an effect blocked by 5-HT₁ᴀ receptor antagonism. CONCLUSIONS: PPG neurons respond directly to 5-HT with a 5-HT₂c receptor-dependent increase in dendritic [Ca²⁺]i. Electrical responses to 5-HT revealed additional inhibitory effects due to somatic 5-HT₁ᴀ receptors. Reciprocal innervation between 5-HT and PPG neurons suggests that the coordinated activity of these brainstem neurons may play a role in the regulation of food intake.
dc.description.sponsorshipThis study was supported by grants MR/J013293/2 from the MRC, UK (ST) and Project Grant #1025031 from NHMRC Australia (ILS). MKH holds a UCL Graduate Research Scholarship. FR and FMG are supported by the Wellcome Trust (106262/Z/14/Z, 106263/Z/14/Z) and the MRC (MRC_MC_UU_12012/3).
dc.languageengen
dc.language.isoenen
dc.publisherElsevier
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectSerotoninen
dc.subjectPreproglucagonen
dc.subjectGCaMPen
dc.subjectDendritic calciumen
dc.subjectNTS, nucleus tractus solitariusen
dc.titleSerotonergic modulation of the activity of GLP-1 producing neurons in the nucleus of the solitary tract in mouse.en
dc.typeArticle
prism.endingPage921
prism.issueIdentifier8en
prism.publicationDate2017en
prism.publicationNameMolecular Metabolismen
prism.startingPage909
prism.volume6en
dc.identifier.doi10.17863/CAM.13031
dcterms.dateAccepted2017-06-05en
rioxxterms.versionofrecord10.1016/j.molmet.2017.06.002en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-08-01en
dc.contributor.orcidReimann, Frank [0000-0001-9399-6377]
dc.contributor.orcidGribble, Fiona [0000-0002-4232-2898]
dc.identifier.eissn2212-8778
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12012/3)
pubs.funder-project-idWELLCOME TRUST (106262/Z/14/Z & 106263/Z/14/Z)
cam.issuedOnline2017-06-07en


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International