Serotonergic modulation of the activity of GLP-1 producing neurons in the nucleus of the solitary tract in mouse

Marie K. Holt, Ida J. Llewellyn-Smith, Frank Reimann, Fiona M. Gribble, Stefan Trapp

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    Abstract

    Objective

    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-HT2 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-HT1A 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-HT1A 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.

    Original languageEnglish
    Pages (from-to)909-921
    Number of pages13
    JournalMolecular Metabolism
    Volume6
    Issue number8
    DOIs
    Publication statusPublished - 1 Aug 2017

    Bibliographical note

    Copyright 2017 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

    Keywords

    • Dendritic calcium
    • GCaMP
    • NTS
    • Preproglucagon
    • Serotonin

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