Identifying triggers for memory along the gut-brain axis in Caenorhabditis elegans

项目摘要 习得的避免有害食物是一种强有力的生存策略，因此从进化上讲 从无脊椎动物到人类。基本的信号机制使神经系统能够将 疾病的内在状态与食物来源的感官线索一起触发厌恶记忆的形成 仍然难以捉摸。为了追踪从非神经组织到神经系统的分子信号， 这里提出的工作将在模式生物秀丽线虫中进行，它的优势是 简单的解剖结构和紧凑的神经系统，以及大量的定量成像和 基因操纵。在长期接触致病食物后，线虫可以学会避免病原体 在随后的相遇中。这种习得性厌恶需要一对感觉神经元发出5-羟色胺信号。 名为ADF。以下具体目标将解决有关动物内部状态的信息 改变ADF神经元感觉激活和5-羟色胺释放之间的偶联：1)识别 激活ADF感觉神经元的分子信号；2)表征ADF在病原体学习中的功能 电路。5-羟色胺参与调节整个动物界与食物相关的行为，包括在 人类。ADF神经活动对细菌气味的反应将使用钙成像进行检测，C. 将使用行为病原体学习来表征线虫对病原菌的行为反应 化验。该项目的目标是阐明ADF神经元的调制电路机制 导致线虫习得的病原体回避行为。这个项目的重点是味觉和嗅觉， 特别是关于化学感觉如何起到触发回避行为的防御功能。在……里面 特别是，这个项目符合理解正常功能和基础生物学的优先领域。 化学感受器。了解非神经组织信息传递的信号机制 大脑对与健康相关的疾病有影响，在这些疾病中，这种沟通受到干扰，比如肥胖。 以及化疗引起的恶心。

Project Summary Learned avoidance of harmful food is a powerful survival strategy and therefore evolutionarily conserved from invertebrates to humans. The underlying signaling mechanisms enabling the nervous system to associate the internal state of sickness with the sensory cues of a food source to trigger the formation of an aversive memory have remained elusive. In order to trace a molecular signal from non-nervous tissues to the nervous system, the work proposed here will be conducted in the model organism C. elegans, which has the advantage of simple anatomy and a compact nervous system, as well as an abundance of tools for quantitative imaging and genetic manipulation. After prolonged exposure to pathogenic food, C. elegans can learn to avoid the pathogen upon subsequent encounter. This learned aversion requires serotonin signaling from a pair of sensory neurons called ADF. The following specific aims will address how information about the internal state of the animal changes the coupling between sensory activation and serotonin release in ADF neurons: 1) to identify molecular signals that activate ADF sensory neurons; 2) to characterize ADF function in pathogen learning circuits. Serotonin is involved in modulating food-related behaviors across the animal kingdom including in humans. ADF neural activity in response to bacterial odors will be examined using calcium imaging, and C. elegans behavioral response to pathogenic bacteria will be characterized using behavioral pathogen learning assays. The goal of this project is to elucidate circuit mechanisms through which modulation of ADF neurons leads to learned pathogen avoidance behavior in C. elegans. This project focuses on taste and smell, specifically on how chemosensation serves the defensive function of triggering avoidance behaviors. In particular, this project fits within the priority area of understanding normal function and fundamental biology of chemosensation. Understanding the signaling mechanisms by which information from non-nervous tissues to the brain has implications for health-related conditions where this communication is disrupted such as obesity and nausea induced by chemotherapy treatment.