Characterization of metabotropic glutamate receptors in Caenorhabditis elegans

Zeng, Ting (2008) Characterization of metabotropic glutamate receptors in Caenorhabditis elegans. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Glutamate is the principal neurotransmitter in mammals and its signaling is conserved between Caenorhabditis elegans and mammals. An important role of glutamate transmission in C.elegans has been established by genetic investigations of ionotropic glutamate receptors (glr-J, nmr-1), glutamate-gated chloride channels (avr-15) and vesicular glutamate transporters (eat-4). Metabotropic glutamate receptors are hypothesized to modulate the transmission properties of synapses in response to the magnitude and frequency of glutamate signaling. Three mGluR-like genes (mgl-1, mgl-2 and mlg-3) have been identified in C. elegans accordingly. The aim of this MPhil/PhD project is to investigate the roles of metabotropic glutamate receptors (mGluRs) in regulating behaviour, using the nematode C.elegans as a model organism. We obtained, backcrossed and characterized mgl mutants. Accordingly we assume that mgl-1 (1811). mgl-2(tm355) and mgl-3(tm!766) are functional null mutants. We also made double mutants and triple mutants by outcrossing. Behavioural assays were carried out on the mutants, including longevity, growth rates, body bends, pharyngeal pumping, thrashing, forward and backward movement, locomotion towards bacteria, Osmotic Avoidance. The analysis on the mutant strains suggest? that mgl-1 (tml811) mutants have a selectively disrupted switch between forward and backward locomotion. Backward movement is regulated during foraging. When food source is detected by worms, backward movement dramatically decreases. Locomotion towards bacteria is disrupted in mgl-2(tm355) mutants, they could not get to the food source as fast as the wild type. mgt-3 (tml 766) behaves normally in all the tested assays. Existing and self generated reporter strains have allowed us :o study mgl expression patterns. An analysis of MGL-3::GFP suggests mgl-3 is expressed in NSM and some other neurons, which would support further behavioral analysis. This behavioural analysis of mgl mutants and expression pattern study of MGL provides an insight of neuromodulatory roles for these G-protein coupled receptors and suggest they play a broad role in defined circuits that integrate complex behaviour.

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