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Serotonergic modulation of the activity of GLP-1 producing neurons in the nucleus of the solitary tract in mouse
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Holt, Marie K., Llewellyn-Smith, Ida J., Reimann, Frank, Gribble, Fiona M. and Trapp, Stefan (2017) Serotonergic modulation of the activity of GLP-1 producing neurons in the nucleus of the solitary tract in mouse. Molecular Metabolism, 6 (8). pp. 909-921. doi:10.1016/j.molmet.2017.06.002 ISSN 2212-8778.
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Official URL: http://doi.org/10.1016/j.molmet.2017.06.002
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.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
Journal or Publication Title: | Molecular Metabolism | ||||||
Publisher: | Elsevier BV | ||||||
ISSN: | 2212-8778 | ||||||
Official Date: | August 2017 | ||||||
Dates: |
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Volume: | 6 | ||||||
Number: | 8 | ||||||
Page Range: | pp. 909-921 | ||||||
DOI: | 10.1016/j.molmet.2017.06.002 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) |
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