Optogenetic Analysis of Olfactory Circuits

描述（由申请人提供）：化学结构信息由1000个嗅觉感觉神经元群体编码，每个神经元投射到嗅球中定义的肾小球。每个肾小球和相关的嗅球神经元被认为是嗅觉加工的功能单位。了解嗅球中神经元之间的功能连接对于了解嗅觉系统如何工作至关重要。虽然传统的解剖技术可以揭示神经元回路的结构，但确定哪些神经细胞在复杂回路中实际上相互通信更具挑战性。这项计划的目标是开发一种光遗传学方法来绘制小鼠嗅球中的功能电路。使用基因靶向，我们在遗传定义的神经元群体中表达光激活通道，使我们能够选择性地使用光激活肾小球。使用这种基于光刺激的方法，我们正在绘制嗅球神经元的感受野，并确定与特定肾小球相关的神经元在功能上是否相似。这里所描述的研究将使我们能够解决有关感觉处理的基本问题，这些问题是使用现有技术无法解决的。我们开发的方法也将在哺乳动物大脑的其他部分有用的地图电路。 公共卫生相关性：我们建议应用新的光遗传学技术，利用光映射哺乳动物嗅觉系统中的神经元回路。这里描述的研究将使我们能够解决以前无法使用传统技术解决的感觉处理的基本问题。

DESCRIPTION (provided by applicant): Information about chemical structure is encoded by 1000 populations of olfactory sensory neurons, each of which projects to defined glomeruli in the olfactory bulb. Each glomerulus and associated olfactory bulb neurons are thought to be functional units in olfactory processing. Understanding the functional connections among neurons in the olfactory bulb is critical to understanding how the olfactory system works. While traditional anatomical techniques can reveal the structure of neuronal circuits, determining which nerve cells actually communicate with one another in a complex circuit is more challenging. The goal of this proposal is to develop an optogenetic approach to map functional circuits in the mouse olfactory bulb. Using gene targeting, we are expressing a light-activated channel in genetically-defined populations of neurons, allowing us to selectively activate glomeruli using light. Using this photostimulation-based approach, we are mapping the receptive fields of olfactory bulb neurons and determining whether neurons associated with a specific glomerulus are functionally similar. The research described here will allow us to address fundamental questions about sensory processing that are not possible to address using available techniques. The methods that we develop will also be useful map circuits in other parts of the mammalian brain. PUBLIC HEALTH RELEVANCE: We propose to apply novel optogenetic technologies to map neuronal circuits in the mammalian olfactory system using light. The research described here will allow us to address fundamental questions about sensory processing that were previously not possible to address using traditional techniques.