Optogenetic Analysis of Olfactory Circuits

描述(申请人提供)：有关化学结构的信息由1000个嗅觉感觉神经元群体编码，每个群体投射到嗅球中明确的肾小球。每个肾小球和相关的嗅球神经元被认为是嗅觉处理的功能单位。了解嗅球神经元之间的功能联系对于了解嗅觉系统是如何工作的至关重要。虽然传统的解剖学技术可以揭示神经元回路的结构，但要确定在复杂的回路中哪些神经细胞实际上相互通信更具挑战性。这项提议的目标是开发一种光遗传学方法来绘制小鼠嗅球的功能回路。通过基因打靶，我们在基因定义的神经元群体中表达了一种光激活通道，使我们能够有选择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，这些问题不可能使用现有技术来解决。我们开发的方法也将在哺乳动物大脑的其他部分提供有用的映射电路。 与公共健康相关：我们建议应用新的光基因技术来利用光绘制哺乳动物嗅觉系统中的神经元电路。这里描述的研究将使我们能够解决有关感觉处理的基本问题，这些问题以前不可能用传统技术解决。

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.