Examining the neural circuit for an instinctive olfactory-induced behavior in lar

描述（由申请人提供）：嗅觉，即嗅觉，是我们感知周围化学物质的主要手段，因此，它对生活质量有着重要的影响。嗅觉神经生物学领域的首要目标之一是了解连接嗅觉刺激的神经通路，它在大脑中的表现为感知，以及驱动下游行为的电路。也许理解这些神经通路的最大障碍是神经系统的复杂性和物理大小。例如，具有许多嗅觉引导行为的小鼠，在嗅球（专门处理嗅觉初始步骤的大脑区域）中有大约1000个不同的气味受体，5-10万个嗅觉感觉神经元，以及1800个不同的轴突和树突集合，称为肾小球。在这个提议中，我们描述了一种研究嗅觉系统的神经回路的策略，该系统至少比小鼠简单10倍，即斑马鱼幼虫。

DESCRIPTION (provided by applicant): Olfaction-the sense of smell-is the major means though which we sense our chemical surroundings, and as such, it has a significant impact on quality of life. One of the overarching goals in the field of olfactory neurobiology is to understad the neural pathways that connect an olfactory stimulus, its representation in the brain as a percept, and the circuits that drive downstream behaviors. Perhaps the greatest obstacle to understanding these neural pathways is the complexity and physical size of the nervous system. For example, mice, which have numerous olfactory-guided behaviors, have ~1000 different odorant receptors, 5-10 million olfactory sensory neurons, and 1800 distinct collections of axons and dendrites, called glomeruli, in the olfactory bulb, the brain area specialized in processing the initial steps of olfaction. In this proposal, we describe a strategy to study the neural circuiry underlying olfaction in a system that is at least 10 times simpler than mice, the zebrafish larvae. The key innovation of this strategy is our use of a recently identified, innate olfactory-guided behavior to study olfactory circuits. Although five-day-old zebrafish exhibit several innate behaviors, until recently there were no known robust olfactory-guided behaviors in zebrafish larvae. Here we demonstrate that zebrafish larvae exhibit a stereotyped, olfactory-guided fear behavior in response to components in an organic solvent extraction of zebrafish skin. Ultimately, using this behavior as a guide, we will be able to connect the sensation of specific molecular structures with the types of olfactory receptors they bind, the types of olfactory sensory neurons they activate, and the neural circuit they excite in order to generate behavior. In Specific Aim 1, we describe experiments to identify which of the three olfactory sensory neuron types is stimulated by the behaviorally active odorants. These results will enable future experiments that allow us to narrow the search for the relevant receptors and signaling pathways underlying this olfactory-guided behavior. In Specific Aim 2, we describe two separate but complementary strategies to identify the anatomy of the olfactory neural circuit at the first olfactory-processing step in the brain, the glomeruli of the olfactory bulb. In Specific Aim 2.1, w identify which glomeruli are a part of the neural circuit underlying the olfactory behavior by imaging their neural activity in response to sensory reception of purified, behaviorally active molecules. In Specific Aim 2.2, we identify the relevant glomeruli by ablating them and looking for a diminished behavioral response. The results of these experiments will increase our understanding of the neural circuits underlying a innate, olfactory-guided behavior, and will provide a solid foundation for an R01 application to support future studies on the elucidation of neural circuits mediating innate behaviors.