Functional analysis of olfactory Eik/MAPK in olfactory plasticity

我们研究了作为嗅觉处理的最终输出，持续气味刺激是否会影响与嗅觉相关的行为。通过我们的行为测试，我们分析了醋酸异戊酯(IAA)连续给药几周后气味的剂量依赖关系。我们发现，持续的气味传递可将嗅觉对IAA的敏感度提高10倍。我们使用IAA和其他气味物质进行的优先试验表明，这些小鼠对IAA有偏好。为了阐明这种嗅觉敏化的机制，我们研究了神经元中的主要激酶Erk/MAPK对这种行为增强的影响。给予ERK/MAPK的特异性抑制剂可消除这种增强，使敏感性降至正常水平。接下来，我们在嗅觉上皮的水平上研究了嗅觉敏化。短暂应用IAA可短暂激活嗅觉神经元的ERK/MAPK。持续给予IAA可增加BrdU免疫阳性嗅觉神经元的数量。这些结果表明，持续的气味传递可能通过调节ERK/MAPK激活的未知机制来促进嗅觉神经元的存活。这可能是在嗅觉上皮水平上进行嗅觉敏化的基础。我们正在研究这种情况下嗅觉神经元的分子事件，以阐明嗅觉神经元存活的机制。

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.