Functional analysis of olfactory Eik/MAPK in olfactory plasticity

我们研究了连续的气味刺激是否会影响嗅觉相关的行为，作为嗅觉处理的最终输出。通过行为学实验，我们分析了醋酸异戊酯（IAA）连续给药数周后小鼠的气味剂量依赖性。我们发现，持续的气味传递增加嗅觉灵敏度的IAA高达10倍。我们对IAA和其他气味剂的偏好测试表明，这些小鼠对IAA有偏好。为了阐明这种嗅觉增敏的机制，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，我们在嗅上皮水平上检查了嗅觉致敏。短暂给药IAA可瞬时激活嗅觉神经元中的Erk/MAPK。持续给药IAA增加了brdu免疫阳性嗅觉神经元的数量。这些结果表明，持续的气味传递促进了嗅觉神经元的存活，其机制可能介导了Erk/MAPK的激活。这可能是嗅觉上皮水平的嗅觉致敏的基础。在这种情况下，我们通过观察嗅觉神经元的分子事件来阐明嗅觉神经元的存活机制。

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.