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

项目摘要/摘要 记忆是大脑最重要的能力之一。它被定义为行为上的改变 经验。例如，线虫会下调其对先天的趋化反应 如果不与食物搭配，气味会很诱人。这个过程被称为嗅觉经典条件反射。穿过 在这种气味的间隔训练下，线虫将在很长一段时间内保持对这种气味的记忆， 类似于长期记忆的形成。尽管色氨酸通道被经典地认为是主要的感官 有趣的是，据报道，OSM-9TRPV(香草样)通道蛋白需要受体 气味经典条件作用2，并已发现它在长时记忆形成(LTM)中的新作用。 然而，调节TRPV介导的LTM的机制仍然是一个谜。建议的目标是 本研究旨在揭示OSM-9/TRPV介导的LTM在青光眼嗅觉环路中的作用机制。 优雅女装。提出的目标将检验OSM-9在嗅觉中特定细胞中发挥作用的假设 在线虫成虫中通过促进嗅神经元中的钙离子流动来调节气味长时记忆的回路 动物。色氨酸通道是已知的单价和二价阳离子渗透通道3。上一首 研究表明，OSM-9和钙离子是促进条件反射的最下游成分 因此，OSM-9可能导致Ca~(2+)内流至嗅觉感觉神经元或其他 环路内神经元促进LTM。以下具体目标将在AIM扩展这些研究和测试 1：长期气味暴露后OSM-9介导的LTM的时空要求和目标2： OSM-9介导的钙动力学促进嗅觉LTM的机制这些研究将是 通过使用显微镜、功能成像、行为分析和遗传技术来完成。 色氨酸通道在感知有害刺激的能力方面得到了很好的研究3，6但它们也与许多 限制神经可塑性的疾病和障碍，包括帕金森氏症、阿尔茨海默病、中风、 以及包括嗅觉障碍在内的感觉障碍。拟议的研究将阐明色氨酸通道在神经中的作用。 可塑性，具体地说，在嗅觉长期记忆的形成中。这些发现将拓宽我们对 Trp通道作为可塑性的中介发挥作用，这可能有助于理解和治疗 许多疾病和障碍是由色氨酸通道功能障碍引起的。

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.