Genetic Analysis of Glomerular Map Formation

描述(由申请人提供)：对感觉系统的研究对我们理解正常的大脑功能有很大的贡献。小鼠嗅觉系统是一个遗传上易于处理的实验模型，在这个模型中研究感觉信息是如何由神经元电路编码的。在这个系统中，1000组嗅觉感觉神经元将轴突投射到大脑，在那里它们根据身份进行分类，并在嗅球表面形成一系列肾小球。肾小球的空间排列被认为在气味编码中起作用。我们最近发现，嗅觉上皮含有表型不同类型的感觉神经元，这些细胞类型在将I类和II类气味受体映射到嗅球的区域中发挥作用。一般来说，我们的假设是，这些感觉神经元类型在组织肾小球阵列方面发挥着关键作用。前两个具体目标试图定义这些细胞类型的身份。第三个具体目标是研究一类感觉神经元的功能特性。这些实验将使我们能够测试和扩展我们的细胞类型假说，并解决神经元在嗅觉系统中建立特定连接的机制。 公共卫生相关性：神经科学中的一个基本问题是大脑如何在正常和病理条件下处理信息。嗅觉系统是一个很好的模型，可以用来研究化学信息是如何在遗传上易处理的神经元回路中表现出来的。这项建议中描述的实验检验了一种新的模型，以了解外周嗅觉系统中的神经元如何组织嗅球中的电路。我们希望这项工作的洞察力将导致对神经元如何自组装成功能神经元网络的更好理解。

DESCRIPTION (provided by applicant): Studies of sensory systems have contributed greatly to our understanding of normal brain function. The mouse olfactory system is a genetically tractable experimental model in which to study how sensory information is encoded by neuronal circuits. In this system, 1000 populations of olfactory sensory neurons project axons to the brain where they sort out by identity and form an array of glomeruli on the surface of the olfactory bulb. The spatial arrangement of glomeruli is thought to play a role in odor coding. We have recently discovered that the olfactory epithelium contains phenotypically distinct types of sensory neurons, and that these cell types play a role in mapping Class I and Class II odorant receptors to domains in the olfactory bulb. Generally, our hypothesis is that these sensory neuron types play a key role in organizing the glomerular array. The first two Specific Aims seek to define the identity of these cell types. The third Specific Aim seeks to examine the functional properties of one Class of these sensory neurons. These experiments will allow us to test and expand our cell-type hypothesis and to address the mechanisms by which neurons make specific connections in the olfactory system. PUBLIC HEALTH RELEVANCE: A fundamental question in neuroscience is how the brain processes information under normal and pathological conditions. The olfactory system is an excellent model in which to study how chemical information is represented in genetically tractable neuronal circuits. The experiments described in this proposal examine a new model for understanding how neurons in the peripheral olfactory system organize circuits in the olfactory bulb. We hope that the insights from this work will lead to a better understanding of how neurons self-assemble into functional neuronal networks.