The Investigation of the Role of the TRPV Channel OSM-9 in Olfactory Long-term Memory Formation

TRPV 通道 OSM-9 在嗅觉长期记忆形成中作用的研究

• 批准号: 9402016
• 负责人: Kelli Leilani Benedetti
• 金额: $ 3.84万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-11-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9402016
• 关键词: Adult; Affect; Alzheimer' s Disease; Animals; Anosmia; Aplysia; Behavior; Behavioral; Brain; Caenorhabditis elegans; Calcium; Cations; Cells; Complement; Complex; Cues; Cyclic GMP-Dependent Protein Kinases; Defect; Disease; Divalent Cations; Exhibits; Exposure to; Food; Functional Imaging; Functional disorder; Future; Genes; Genetic Screening; Genetic Techniques; Gills; Goals; Image; In Vitro; Individual; Information Storage; Interneurons; Investigation; Knowledge; Lead; Learning; Light; Mediating; Mediator of activation protein; Medical; Membrane; Memory; Microscopy; Molecular; Molecular Genetics; Monovalent Cations; Nematoda; Neuronal Plasticity; Neurons; Nociception; Nuclear; Odors; Olfactory Pathways; Parkinson Disease; Permeability; Pharmacology; Physiology; Play; Process; Proteins; RNA Interference; Reflex action; Reporting; Research; Role; Sensory; Sensory Receptors; Signal Transduction; Specific qualifier value; Starvation; Stimulus; Stroke; Structure; Synaptic plasticity; Testing; Time; Training; Transgenes; Vanilloid; Withdrawal; Work; classical conditioning; conditioning; experience; experimental study; imaging approach; knock-down; long term memory; mutant; nervous system disorder; neural circuit; olfactory sensory neurons; promoter; protein function; public health relevance; receptor; response; sensor; spatiotemporal

Project Summary/Abstract Memory is one of the most important abilities of the brain. It is defined as an alteration in behavior from an experience. For example, the C. elegans nematode will downregulate its chemotactic response to an innately attractive odor if it is not paired with food1. This process is termed olfactory classical conditioning. Through spaced training with this odor, C. elegans will maintain this memory of the odor for a prolonged period of time, akin to long-term memory formation. Although TRP channels are classically thought of as primary sensory receptors, intriguingly, it has been reported that the OSM-9 TRPV (vanilloid) channel protein is required for odor classical conditioning2, and a new role has been discovered for it in long-term memory formation (LTM). Nevertheless, the mechanisms that regulate TRPV-mediated LTM remain a mystery. The goal of the proposed research is to uncover the mechanism of OSM-9/TRPV-mediated LTM in the olfactory sensory circuit of C. elegans. The proposed aims will test the hypothesis that OSM-9 functions in specific cells in the olfactory circuit by facilitating Ca2+ flux in the olfactory neurons to mediate odor long-term memory in adult C. elegans animals. TRP channels are known to be monovalent and divalent cation-permeable channels3. Previous research shows that OSM-9 and Ca2+ are the most downstream components in the conditioning-promoting pathway4,5. Thus, OSM-9 may cause an influx of Ca2+ into the olfactory sensory neurons or potentially other neurons within the circuit to promote LTM. The following specific aims will extend these studies and test in aim 1: the spatiotemporal requirements for OSM-9-mediated LTM after long-term odor exposure and in aim 2: the mechanism of OSM-9-mediated Ca2+ dynamics in promoting olfactory LTM. These studies will be accomplished through the use of microscopy, functional imaging, behavioral analysis, and genetic techniques. TRP channels are well studied in their ability to sense noxious stimuli3,6, yet they are also implicated in many diseases and disorders that limit neural plasticity, including Parkinson’s disease, Alzheimer’s disease, stroke, and sense disorders including anosmia. The proposed studies will elucidate the role of TRP channels in neural plasticity, specifically, in olfactory long-term memory formation. These findings will broaden our knowledge of TRP channel function as a mediator of plasticity, which could potentially aid in understanding and treating the many diseases and disorders caused by TRP channel dysfunction.

项目总结/摘要 记忆力是大脑最重要的能力之一。它被定义为一种行为上的改变， 体验.例如，C.秀丽线虫将下调其趋化反应， 诱人的气味，如果它不与食物配对1。这个过程被称为嗅觉经典条件反射。通过 用这种气味进行间隔训练，C。秀丽线虫会长时间保持这种气味的记忆， 类似于长期记忆的形成。尽管TRP通道被经典地认为是初级感觉通道， 有趣的是，据报道，OSM-9 TRPV（香草素）通道蛋白是 气味经典条件反射2，并且已经发现它在长期记忆形成（LTM）中的新作用。 然而，调节TRPV介导的LTM的机制仍然是一个谜。建议的目标 本研究旨在揭示OSM-9/TRPV介导的LTM在C. 优美的所提出的目标将测试OSM-9在嗅觉中的特定细胞中起作用的假设。 通过促进嗅神经元内Ca ~（2+）流介导成年C. elegans 动物已知TRP通道是单价和二价阳离子可渗透通道3。先前 研究表明，OSM-9和Ca ~（2+）是调节-促进作用的最下游组分 路径4，5.因此，OSM-9可能导致Ca 2+流入嗅觉感觉神经元或潜在的其他神经元。 神经元内的电路，以促进LTM。以下具体目标将扩展这些研究和测试的目的 1：在长期气味暴露后对OSM-9介导的LTM的时空要求，以及在目标2中： OSM-9介导的Ca 2+动力学促进嗅觉LTM的机制。这些研究报告将 通过使用显微镜，功能成像，行为分析和遗传技术来完成。 TRP通道在其感知有害刺激的能力方面得到了很好的研究3，6，但它们也涉及许多 限制神经可塑性的疾病和障碍，包括帕金森病、阿尔茨海默病、中风， 以及包括嗅觉丧失在内的感觉障碍。这些研究将阐明TRP通道在神经细胞中的作用。 可塑性，特别是嗅觉长期记忆的形成。这些发现将扩大我们对 TRP通道作为可塑性介质发挥作用，这可能有助于理解和治疗 TRP通道功能障碍引起的许多疾病和障碍。