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

识别秀丽隐杆线虫肠脑轴记忆的触发因素

基本信息

批准号：
10162300
负责人：
Audrey Harnagel
金额：
$ 4.6万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10162300
关键词：
Address Adult Affect Afferent Neurons Anatomy Animal Model Animals Area Behavior Behavioral Biological Assay Biology Brain Caenorhabditis elegans Calcium Candidate Disease Gene Communication Coupling Cues Detection Exposure to Food Goals Health Human Image Invertebrates Learning Ligands Mediating Medical Memory Microfluidic Microchips Mind Molecular Nausea Nematoda Nervous system structure Neurons Nutritional Obesity Odors Organism Outcome Pathogenicity Pattern Pharmaceutical Preparations Protocols documentation Research Role Sensory Serotonin Signal Transduction Smell Perception Source Stimulus Taste Perception Tissues Training Work avoidance behavior behavioral response chemotherapy genetic manipulation gut-brain axis integration site learned behavior mutant optogenetics pathogen pathogen exposure pathogenic bacteria quantitative imaging receptor relating to nervous system response tool

项目摘要

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.

项目概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对人类。使神经系统能够关联的潜在信号机制疾病的内部状态与食物来源的感官线索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隐杆线虫中进行，其优点是简单的解剖结构和紧凑的神经系统，以及丰富的定量成像和分析工具基因操纵。长时间接触致病食物后，线虫可以学会避开病原体在以后的相遇中。这种习得性厌恶需要来自一对感觉神经元的血清素信号传导称为 ADF。以下具体目标将解决有关动物内部状态的信息如何改变 ADF 神经元中感觉激活和血清素释放之间的耦合：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。血清素参与调节整个动物界的食物相关行为，包括人类。将使用钙成像检查对细菌气味做出反应的 ADF 神经活动，以及 C. 线虫对致病细菌的行为反应将通过行为病原体学习来表征化验。该项目的目标是阐明调节 ADF 神经元的电路机制导致线虫习得病原体回避行为。该项目重点关注味觉和嗅觉，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，该项目适合理解正常功能和基础生物学的优先领域化学感觉。了解非神经组织信息传递的信号传导机制大脑对与健康相关的疾病有影响，其中这种沟通被破坏，例如肥胖以及化疗引起的恶心。