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

检查 lar 中本能嗅觉诱发行为的神经回路

• 批准号: 8576294
• 负责人: Scott T. Laughlin
• 金额: $ 5.8万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8576294
• 关键词: Adult; Afferent Neurons; Aggressive behavior; Anatomy; Animal Model; Anxiety; Area; Attenuated; Axon; Behavior; Behavioral; Biological Assay; Biological Models; Brain; Chemicals; Chondroitin; Chronic; Collection; Data; Dendrites; Environment; Esthesia; Exhibits; Fishes; Foundations; Fright; Future; Goals; Human; Human Biology; Hypoxanthines; Image; Imagery; Individual; Instinct; Larva; Lead; Lesion; Mediating; Mental Health; Modeling; Molecular; Molecular Structure; Mus; Nature; Nervous system structure; Neural Pathways; Neurobiology; Neurons; Neuropil; Nose; Odorant Receptors; Organic solvent product; Perception; Pheromone; Positioning Attribute; Process; Proteins; Quality of life; Receptor Signaling; Research; Research Design; Rodent Model; Sensory; Signal Pathway; Signal Transduction; Skin; Smell Perception; Solid; Stereotyping; Stress; Structure; System; Techniques; Testing; Time; Zebrafish; cell type; innovation; insight; neural circuit; neuromechanism; novel; olfactory bulb; olfactory receptor; olfactory stimulus; optical imaging; public health relevance; receptor; receptor binding; relating to nervous system; research study; response; solvent extraction; tool; urinary

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.

描述（由申请人提供）：嗅觉 - 嗅觉 - 这是我们感觉到化学环境的主要手段，因此，它对生活质量产生了重大影响。嗅觉神经生物学领域的总体目标之一是将连接嗅觉刺激的神经途径，其在大脑中作为感知的表示以及驱动下游行为的电路。理解这些神经途径的最大障碍也许是神经系统的复杂性和身体大小。例如，具有众多嗅觉引导行为的小鼠具有约1000种不同的气味受体，5-100万种嗅觉感觉神经元，以及在嗅球中的轴突和树突的1800个不同的轴突和树突收集，称为glomeruli，在嗅球中，这是大脑区域，专门处理嗅觉的最初步骤。在此提案中，我们描述了一种研究神经电路的策略，该策略至少比小鼠（斑马鱼幼虫）简单10倍。 该策略的关键创新是我们使用最近确定的，先天的嗅觉引导的行为来研究嗅觉电路。尽管五天大的斑马鱼表现出几种先天的行为，但直到最近，斑马鱼幼虫还没有已知的强大嗅觉引导行为。在这里，我们证明斑马鱼幼虫表现出对有机溶剂提取斑马鱼皮肤中成分的刻板印象，嗅觉引导的恐惧行为。最终，使用此行为作为指导，我们将能够将特定分子结构的感觉与它们结合的嗅觉受体的类型，它们激活的嗅觉感觉神经元的类型以及它们激发的神经回路的类型，以产生行为。在特定目标1中，我们描述了实验，以识别行为活跃的气味剂刺激三种嗅觉感觉神经元类型中的哪些。这些结果将实现未来的实验，使我们能够缩小搜索相关受体和这种嗅觉引导行为的信号传导途径。在特定的目标2中，我们描述了在大脑的第一个嗅觉加工步骤中识别嗅觉神经回路的解剖结构的两种独立但互补的策略，即嗅球的肾小球。在特定的目标2.1中，w确定哪个肾小球是通过对纯化的，行为活跃的分子的感觉接收来对其神经活性进行成像的神经活性来成像的神经回路的一部分。在特定的目标2.2中，我们通过消融相关的肾小球并寻找行为响应减少来识别它们。这些实验的结果将增加我们对先天性嗅觉引导行为背后的神经回路的理解，并将为R01应用提供坚实的基础，以支持对介导的先天行为的神经回路的未来研究。