Glutamate is an essential neurotransmitter in the nervous system. How glutamate-mediated synaptic transmission is controlled in neural circuit, however, remains to be fully understood. In order to reveal the glutamate-mediated synaptic transmission at neural circuit level, we are using the simple neural circuit for thermotaxis in C. elegans (1). The <U>v</U>esicular <U>glu</U>tamate <U>t</U>ransporter (VGLUT) is known as a critical molecule for transporting glutamate into synaptic vesicle. The loss-of-function mutations in the sole VGLUT homologue encoded by eat-4
gene (2) led to defective thermotaxis. We found that defective thermotaxis in eat-4
mutants was rescued by expressing EAT-4 in AFD thermosensory neurons and RIA interneurons, both of which are essential for thermotaxis neural circuit. As previously reported, we speculated that neurotransmission from AFD to its downstream interneuron AIY is regulated by similar mechanisms to mammalian photo signal transduction, where glutamate is released from photoreceptor cell and is received by <U>m</U>etabotropic <U>glu</U>tamate <U>r</U>eceptor (mGluR) in the downstream bipolar cell. In C. elegans genome database, three mGluR genes (mgl-1
) are predicted. We found that loss-of-function mutation in respective mGluR genes however did not lead to thermotaxis defect. We are then constructing double and triple mutants to investigate redundant function of three mGluR genes. The downstream neurons for RIA in thermotaxis circuit have not been determined. Interestingly, about 90% of RIA presynapses connect to SMD or RMD motor neurons regulating contraction of head swing muscle (3). Now we are investigating importance of head swing for thermotaxis through monitoring head swing movement during thermotaxis in the SMD and RMD-ablated animals, and in the mutants lacking glutamate receptors. Through our analysis, we are hoping to reveal the glutamate-mediated neural signaling from sensory input to behavioral motor output in the neural circuit for thermotaxis, the most complex behavior in C. elegans. (1) Mori and Ohshima, 1995, Nature. (2) Lee et. al., 1999, J Neurosci. (3) White et. al., 1986, Philos trans R Soc London Ser B Biol Sci.