Mapping Molecular and Cellular Responses to Odorants

描述（来自申请人的摘要）：本项目的目标是 在细胞和分子水平上表征嗅觉感知。初级 嗅觉神经元输入在空间上在嗅球中被组织， 哺乳动物，我们假设这种空间组织被保存在 更高水平的感官处理。 实验方法将基于 一种神经元激活的测定，其提供了时间和细胞分辨率， 清醒的自由活动的老鼠 的表达和细胞内定位 通过荧光原位杂交确定的立即早期基因Arc 和共聚焦显微镜将被验证为神经元激活的衡量标准， 嗅球 然后神经元激活的模式将被确定 在嗅球和前脑的其他区域， 结构相关的气味。 下一个结构相关的气味 将通过线索条件作用赋予行为意义;两者 在训练中，将采用食欲和厌恶性非条件刺激 sessions. 在条件反射之后， 对条件气味剂的反应将与未受刺激的人中的模式进行比较。 以及由结构相关分子产生的模式 要么是行为中立的，要么是相反的行为 意义 总之，这些研究将提供一个功能图， 嗅球中的嗅觉和更高水平的感觉 为了验证我们的假设。 此外，这构成了一个 在学习过程中定义突触的重要一步 在哺乳动物中进行这一过程，并在转基因小鼠中开发功能测定， 将认知功能障碍与疾病模型中的解剖学变化相关联， 阿尔茨海默病和其他神经退行性疾病。 在这项由医学博士理查德阿克塞尔赞助的研究过程中，的 候选人将接受创造性和严格的分子方法培训， 神经系统科学问题。 此外，候选人将接受以下培训： 认知神经学在Richard Mayeux，M.D.的指导下，在哥伦比亚 大学

DESCRIPTION (from applicant's abstract): The goal of this project is to characterize olfactory perception at both cellular and molecular levels. Primary olfactory neuronal input is spatially organized in the olfactory bulb in mammals, and we hypothesize that this spatial organization is preserved at higher levels of sensory processing. The experimental approach will be based on an assay for neuronal activation that offers temporal and cellular resolution in awake, freely behaving mice. The expression and intracellular localization of an immediate early gene Arc, as determined by fluorescent in-situ hybridization and confocal microscopy will be validated as a measure of neuronal activation in the olfactory bulb. Then the pattern of neuronal activation will be determined in the olfactory bulb and other areas of the forebrain in response to two structurally related odorants. Next one of the structurally related odorants will be afforded a behavioral significance through cue conditioning; both appetitive and aversive unconditioned stimuli will be employed in the training sessions. Following conditioning, the pattern of neuronal activation in response to the conditioned odorant will be compared to the pattern in the naive mouse as well as to the pattern generated by the structurally related molecule that is either behaviorally neutral or afforded the opposite behavioral significance. Together, these studies will provide a functional map for olfactory perception in the olfactory bulb and higher levels of sensory processing in order to test our hypothesis. In addition, this constitutes an important step towards defining synapses that are modified during a learning process in mammals, and developing a functional assay in transgenic mice to correlate cognitive dysfunction with anatomical changes in disease models of Alzheimer's disease and other neurodegenerative diseases. During the course of this research sponsored by Richard Axel, M.D., the candidate will be trained in creative and rigorous molecular approaches to systems level neuroscience problems. Moreover, the candidate will be trained in cognitive neurology under the direction of Richard Mayeux, M.D. at Columbia University.