Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/124391
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Type: Journal article
Title: Serotonergic modulation of the activity of GLP-1 producing neurons in the nucleus of the solitary tract in mouse
Author: Holt, M.K.
Llewellyn-Smith, I.J.
Reimann, F.
Gribble, F.M.
Trapp, S.
Citation: Molecular Metabolism, 2017; 6(8):909-921
Publisher: Elsevier
Issue Date: 2017
ISSN: 2212-8778
2212-8778
Statement of
Responsibility: 
Marie K.Holt, Ida J.Llewellyn-Smith, Frank Reimann, Fiona M.Gribble, Stefan Trapp
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.
Keywords: Serotonin; Preproglucagon; GCaMP; Dendritic calcium; NTS1
Rights: © 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/).
DOI: 10.1016/j.molmet.2017.06.002
Grant ID: http://purl.org/au-research/grants/nhmrc/1025031
Published version: http://dx.doi.org/10.1016/j.molmet.2017.06.002
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