Friday, 17 April 2015

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

Dillon J, Franks CJ, Murray C, Edwards RJ, Calahorro F, Ishihara T, Katsura I, Holden-Dye L, O’Connor V (in press). Metabotropic glutamate receptors: modulators of context-dependent feeding behaviour in C. elegans. J Biol Chem. Apr 13. pii: jbc.M114.606608.


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.

PMID: 25869139

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