Glutamate is an essential neurotransmitter in the nervous system. Thermotaxis, a sensory behavior controlled by the simple neural circuit in C. elegans, is an ideal system to study regulation of glutamate-mediated synaptic transmission through neural circuit (1, 2). The loss-of-function mutations in VGLUT (Vesicular Glutamate Transporter) encoded by
eat-4 (3) led to thermotaxis defect appeared as a poor response to temperature. Expression of EAT-4 in the sensory neuron AFD and its downstream interneuron RIA of
eat-4 mutant induced migration to lower temperature than cultivation temperature, whereas expression of EAT-4 in the sensory neuron AWC and its downstream interneuron RIA of
eat-4 mutant induced migration to higher temperature than cultivation temperature. In addition, expression of EAT-4 in AFD, AWC and RIA restored partially the thermotaxis defect of
eat-4. These results suggest that thermal signals from AFD, AWC or RIA to their postsynaptic neurons are transmitted by glutamate through EAT-4 VGLUT, and that glutamate signals from AFD and from AWC have opposite effect on thermotaxis each other. Interestingly, AIY interneuron, postsynaptic to both AFD and AWC neurons, could receive and distinguish glutamate signals from AFD and AWC. We found that mutation in chloride channel type inhibitory glutamate receptor GLC-3 (4) led to thermotaxis defect restored by expression of GLC-3 in AIY, implying that GLC-3 functions in AIY as receptor of glutamate signals from AFD or AWC. To investigate whether GLC-3 receives glutamate signals from AFD or from AWC, we examined the effect of several mutations on
glc-3 mutant. Defect of
gcy-23 gcy-8 gcy-18 triple mutant, which lacks thermal response of AFD, masked the defect of
glc-3. Likewise, defect of the transgenic
eat-4 mutant expressing EAT-4 in AWC and RIA, which exhibits abnormal glutamate transmission of AFD, masked the defect of
glc-3. On the other hand, defect of
odr-3 mutant, which lacks thermal response of AWC, influenced additively on the defect of
glc-3. These results are consistent with a model that GLC-3 inactivates AIY with reception of EAT-4-mediated glutamate signals from AFD. To test this model, we are in the process of calcium imaging of AIY in
eat-4 mutant and
glc-3 mutant. (1) Mori and Ohshima, 1995, Nature. (2) Kuhara, Okumura et al., 2008, Science. (3) Lee et al., 1999, J Neurosci. (4) Horoszok et al., 2001, Br J Pharmacol.