Study of the functions of the Ras-MAPK pathway and the insulin pathway in neural plasticity of C. elegans

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1)We reported before that the Ras-MAPK pathway acts in the olfactory neurons in C.elegans and is required for efficient odor responses (Hirotsu et al., 2000). In this study, we found that the Ras-MAPK pathway is also involved in olfactory adaptation and conducted detailed analyses on this role. We found that this form of olfactory adaptation, which we call "early adaptation", depends not only on sensory neurons, but also on a class of interneurons, AIY. AIY is a class of interneurons that receive synaptic inputs from sensory neurons including olfactory neurons AWA and AWC. Several mutants of the Ras-MAPK pathway showed defects in early adaptation. Moreover, we showed that Ras acts in AIY neurons, because expression of let-60 rasgene in AIY neurons rescues the defect of the let-60 mutants in early adaptation. By immunohistochemistry, we observed that MAPK is activated in olfactory neurons and in AIY interneurons by odor stimulation.2)We have previously established an assay system for associative learning. C.elegansis usually attracted to NaCl. However, after experiencing NaCl in the absence of food, they learn to avoid NaCl. Mutants for insulin INS-1, insulin receptor, and the downstream factors PI-3 kinase, PDK kinase and Akt kinase showed defects in associative learning. Through cell-specific expression experiments, we found that INS-1 acts in the interneuron AIA, and PI 3-kinase acts in ASE neurons, a pair of sensory neurons that sense NaCl. These results suggest that AIA neurons, which receive synaptic inputs from sensory neurons, send a retrograde signal via INS-1 to sensory neurons. ASE neurons consist of a bilaterally symmetrical pair of neurons. Of these, PI-3-kinase acts only in the right member.