Functional study of the Ras-MAP kinase pathway in the nervous system

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The Ras-MAP kinase (MAPK) signaling pathway is known to transmit extracellular signals into the cells and to regulate cell proliferation and differentiation. On the other hand, evidences are emerging for other roles for the pathway in the nervous system, especially in neuronal plasticity. However, its exact functions are not fully understood. This study utilized Caenorhabditis elegans, which has advantages in genetics, anatomy, and ethology, to clarify the functions of the Ras-MAPK pathway in the nervous system.We have previously found that the C. elegans MAPK is activated in the olfactory neurons by odorant stimulus and its functions in the olfactory neurons is necessary for efficient olfaction. The present study pushed forward these findings and revealed that the Ras-MAPK pathway also plays important roles in odor adaptation. We first established a new assay system for odor adaptation and named it early adaptation. In the early adaptation assay, worms exposed to the odorant for five minutes showed dramatically reduced response to the odorant (chemotaxis). Several mutants of the Ras-MAPK pathway showed severe defects in early adaptation. Interestingly, this adaptation is not caused by down-regulation occurring in the olfactory neurons, but was dependent on the neural network. Namely, AIY interneurons, that receive inputs from olfactory neurons, were essential for this form of adaptation. MAPK is activated by odorant stimulus not only in the olfactory neurons but also in AIY interneurons. Cell specific expression of the ras gene revealed that Ras is required in AIY for adaptation. These results suggest that the Ras-MAPK pathway acts in olfactory neurons for odor perception, while its functions in the AIY interneurons are required for odor adaptation.