The University of Southampton
University of Southampton Institutional Repository

Metabotropic glutamate receptors: modulators of context-dependent feeding behaviour in C. elegans.

Metabotropic glutamate receptors: modulators of context-dependent feeding behaviour in C. elegans.
Metabotropic glutamate receptors: modulators of context-dependent feeding behaviour in C. elegans.
Glutamatergic neurotransmission is evolutionarily conserved across animal phyla. A major class of glutamate receptors are the metabotropic glutamate receptors (mGluRs). In C. elegans three mGluR genes mgl-1, mgl-2 and mgl-3 are organised into three sub-groups, similar to their mammalian counterparts. Cellular reporters identified expression of the mgls in the nervous system of C. elegans and overlapping expression in the pharyngeal microcircuit that controls pharyngeal muscle activity and feeding behaviour. The overlapping expression of mgls within this circuit allowed investigation of receptor signalling per se and in the context of receptor interactions within a neural network that regulates feeding. We utilized the pharmacological manipulation of neuronally regulated pumping of the pharyngeal muscle in wild type and mutants to investigate mgl function. This defined a net mgl-1 dependent inhibition of pharyngeal pumping which is modulated by mgl-3 excitation. Optogenetic activation of the pharyngeal glutamatergic inputs combined with electrophysiological recordings from the isolated pharyngeal preparations provided further evidence for a presynaptic mgl-1 dependent regulation of pharyngeal activity. Analysis of mgl-1, mgl-2 and mgl-3 mutant feeding behaviour in the intact organism after acute food removal identified a significant role for mgl-1 in the regulation of an adaptive feeding response. Our data describes the molecular and cellular organisation of mgl-1, mgl-2 and mgl-3. Pharmacological analysis identified that in these paradigms mgl-1 and mgl-3, but not mgl-2, can modulate the pharyngeal microcircuit. Behavioural analysis identified mgl-1 as a significant determinant of the glutamate-dependent modulation of feeding, further highlighting the significance of mGluRs in complex C. elegans behaviour.
metabotropic glutamate receptors (mGluR), optogenetics, Caenorhabditis elegans (C. elegans), electrophysiology, invertebrate
0021-9258
1-28
Dillon, James
f406e30a-3ad4-4a53-80db-6694bab5e3ed
Franks, Christopher J
4927f50e-1b16-42f1-bc4c-760ff3548417
Murray, Caitriona
6fcb874d-75d7-49aa-9219-8f9723d862fe
Edwards, Richard J
9d25e74f-dc0d-455a-832c-5f363d864c43
Calahorro, Fernando
dddfa373-d3cc-433f-8851-9ca37f2f3950
Ishihara, Takeshi
f0b9ae17-b73c-4a8c-8ac6-607820eef42e
Katsura, Isao
31c65a0a-2d8e-430b-9e51-8f03b972f1ce
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
O'Connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Dillon, James
f406e30a-3ad4-4a53-80db-6694bab5e3ed
Franks, Christopher J
4927f50e-1b16-42f1-bc4c-760ff3548417
Murray, Caitriona
6fcb874d-75d7-49aa-9219-8f9723d862fe
Edwards, Richard J
9d25e74f-dc0d-455a-832c-5f363d864c43
Calahorro, Fernando
dddfa373-d3cc-433f-8851-9ca37f2f3950
Ishihara, Takeshi
f0b9ae17-b73c-4a8c-8ac6-607820eef42e
Katsura, Isao
31c65a0a-2d8e-430b-9e51-8f03b972f1ce
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
O'Connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca

Dillon, James, Franks, Christopher J, Murray, Caitriona, Edwards, Richard J, Calahorro, Fernando, Ishihara, Takeshi, Katsura, Isao, Holden-Dye, Lindy and O'Connor, Vincent (2015) Metabotropic glutamate receptors: modulators of context-dependent feeding behaviour in C. elegans. The Journal of Biological Chemistry, 1-28. (doi:10.1074/jbc.M114.606608). (PMID:25869139)

Record type: Article

Abstract

Glutamatergic neurotransmission is evolutionarily conserved across animal phyla. A major class of glutamate receptors are the metabotropic glutamate receptors (mGluRs). In C. elegans three mGluR genes mgl-1, mgl-2 and mgl-3 are organised into three sub-groups, similar to their mammalian counterparts. Cellular reporters identified expression of the mgls in the nervous system of C. elegans and overlapping expression in the pharyngeal microcircuit that controls pharyngeal muscle activity and feeding behaviour. The overlapping expression of mgls within this circuit allowed investigation of receptor signalling per se and in the context of receptor interactions within a neural network that regulates feeding. We utilized the pharmacological manipulation of neuronally regulated pumping of the pharyngeal muscle in wild type and mutants to investigate mgl function. This defined a net mgl-1 dependent inhibition of pharyngeal pumping which is modulated by mgl-3 excitation. Optogenetic activation of the pharyngeal glutamatergic inputs combined with electrophysiological recordings from the isolated pharyngeal preparations provided further evidence for a presynaptic mgl-1 dependent regulation of pharyngeal activity. Analysis of mgl-1, mgl-2 and mgl-3 mutant feeding behaviour in the intact organism after acute food removal identified a significant role for mgl-1 in the regulation of an adaptive feeding response. Our data describes the molecular and cellular organisation of mgl-1, mgl-2 and mgl-3. Pharmacological analysis identified that in these paradigms mgl-1 and mgl-3, but not mgl-2, can modulate the pharyngeal microcircuit. Behavioural analysis identified mgl-1 as a significant determinant of the glutamate-dependent modulation of feeding, further highlighting the significance of mGluRs in complex C. elegans behaviour.

Text
J. Biol. Chem.-2015-Dillon-jbc.M114.606608.pdf - Accepted Manuscript
Download (1MB)

More information

e-pub ahead of print date: 13 April 2015
Keywords: metabotropic glutamate receptors (mGluR), optogenetics, Caenorhabditis elegans (C. elegans), electrophysiology, invertebrate
Organisations: Biomedicine

Identifiers

Local EPrints ID: 377230
URI: https://eprints.soton.ac.uk/id/eprint/377230
ISSN: 0021-9258
PURE UUID: 9151f7e0-64d9-4b79-9784-0851cb758eb1
ORCID for Fernando Calahorro: ORCID iD orcid.org/0000-0003-0659-7728

Catalogue record

Date deposited: 08 Jun 2015 10:02
Last modified: 20 Jul 2019 00:39

Export record

Altmetrics

Contributors

Author: James Dillon
Author: Christopher J Franks
Author: Caitriona Murray
Author: Richard J Edwards
Author: Fernando Calahorro ORCID iD
Author: Takeshi Ishihara
Author: Isao Katsura

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×