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

James Dillon, Christopher J. Franks, Caitriona Murray, Richard J. Edwards, Fernando Calahorro, Takeshi Ishihara, Isao Katsura, Lindy Holden-Dye, Vincent O'Connor

Research output: Contribution to journalArticle

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Abstract

Glutamatergic neurotransmission is evolutionarily conserved across animal phyla. A major class of glutamate receptors consists of the metabotropic glutamate receptors (mGluRs). In C. elegans, three mGluR genes, mgl-1, mgl-2, and mgl-3, are organized into three subgroups, 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 behavior. The overlapping expression of mgls within this circuit allowed the investigation of receptor signaling per se and in the context of receptor interactions within a neural network that regulates feeding.Weutilized the pharmacological manipulation of neuronally regulated pumping of the pharyngeal muscle in the wild-type and mutants to investigate MGL function. This defined a net mgl-1-dependent inhibition of pharyngeal pumping that 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 behavior 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 describe the molecular and cellular organization 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. Behavioral 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 behavior.

Original languageEnglish
Pages (from-to)15052-15065
Number of pages14
JournalJournal of Biological Chemistry
Volume290
Issue number24
DOIs
Publication statusPublished - Jun 12 2015

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Pharyngeal Muscles
Metabotropic Glutamate Receptors
Feeding Behavior
Modulators
Optogenetics
Pharmacology
Glutamate Receptors
Synaptic Transmission
Nervous System
Glutamic Acid
Muscle
Food
Genes
Neurology
Animals
Chemical activation
Modulation
Neural networks
Networks (circuits)
Inhibition (Psychology)

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Dillon, J., Franks, C. J., Murray, C., Edwards, R. J., Calahorro, F., Ishihara, T., ... O'Connor, V. (2015). Metabotropic glutamate receptors: Modulators of context-dependent feeding behaviour in C. elegans. Journal of Biological Chemistry, 290(24), 15052-15065. https://doi.org/10.1074/jbc.M114.606608

Metabotropic glutamate receptors : Modulators of context-dependent feeding behaviour in C. elegans. / Dillon, James; Franks, Christopher J.; Murray, Caitriona; Edwards, Richard J.; Calahorro, Fernando; Ishihara, Takeshi; Katsura, Isao; Holden-Dye, Lindy; O'Connor, Vincent.

In: Journal of Biological Chemistry, Vol. 290, No. 24, 12.06.2015, p. 15052-15065.

Research output: Contribution to journalArticle

Dillon, J, Franks, CJ, Murray, C, Edwards, RJ, Calahorro, F, Ishihara, T, Katsura, I, Holden-Dye, L & O'Connor, V 2015, 'Metabotropic glutamate receptors: Modulators of context-dependent feeding behaviour in C. elegans', Journal of Biological Chemistry, vol. 290, no. 24, pp. 15052-15065. https://doi.org/10.1074/jbc.M114.606608
Dillon, James ; Franks, Christopher J. ; Murray, Caitriona ; Edwards, Richard J. ; Calahorro, Fernando ; Ishihara, Takeshi ; Katsura, Isao ; Holden-Dye, Lindy ; O'Connor, Vincent. / Metabotropic glutamate receptors : Modulators of context-dependent feeding behaviour in C. elegans. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 24. pp. 15052-15065.
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