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

项目摘要 学会避免有害食物是一种强大的生存策略，因此在进化上是保守的， 无脊椎动物到人类。使神经系统能够将神经元与神经元之间的相互作用联系起来的潜在信号机制， 一种疾病的内部状态，由食物来源的感官线索引发厌恶记忆的形成 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， 本文提出的工作将在模式生物C中进行。它的优点是 简单的解剖结构和紧凑的神经系统，以及大量的定量成像工具， 基因操控长期接触致病性食物后，C.线虫可以学会避开病原体 在后来的遭遇中。这种习得的厌恶需要来自一对感觉神经元的血清素信号 称为ADF。以下具体目标将解决如何信息的内部状态的动物 改变ADF神经元中感觉激活和5-羟色胺释放之间的耦合：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.血清素参与调节动物王国中与食物相关的行为，包括 人类ADF神经活动响应细菌气味将检查使用钙成像，和C。 线虫对病原菌的行为反应将使用行为病原体学习来表征 测定。本项目的目标是阐明ADF神经元的调制 导致C.优雅这个项目的重点是味觉和嗅觉， 特别是关于化学感觉如何发挥触发回避行为的防御功能。在 特别是，该项目符合理解正常功能和基础生物学的优先领域， 化学感觉了解非神经组织传递信息的信号机制， 大脑对与健康相关的疾病也有影响， 和化疗引起的恶心。

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.