Functional analysis of olfactory Eik/MAPK in olfactory plasticity

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We examined whether continuous odorant stimuli would affect olfactory-related behavior as a final output of olfactory processing. By our behavioral assay, we analyzed odorant dose -dependency after isoamyl-acetate (IAA) was continuously delivered to mice for several weeks. We have found that continuous odorant delivery augments olfactory sensitivity to IAA up to 10 times. Our preferential test using IAA and other odorant have shown that these mice have a preference to IAA. To elucidate the mechanism of this olfactory sensitization, we examined the effect of Erk/MAPK, a principal kinase in neuron, on this behavioral augmentation. Administration of specific inhibitor of Erk/MAPK abolished this augmentation, reducing the sensitivity to normal level. We, next, examined olfactory sensitization at the level of olfactory epithelium. Brief administration of IAA transiently activated Erk/MAPK in olfactory neurons. Continuous administration of IAA increased the number of BrdU-immunopositive olfactory neurons. These results indicated that continuous delivery of odorant promotes survival of olfactory neurons through undefined mechanisms possibly mediating Erk/MAPK activation. This could underlie olfactory sensitization at the level of olfactory epithelium. We are examining molecular events in olfactory neurons under this condition to elucidate the mechanism of survival of olfactory neurons.