Perception of Dead Conspecifics modulates neural signaling and lifespan in Caenorhabditis elegans

对死亡同种的感知调节秀丽隐杆线虫的神经信号和寿命

基本信息

批准号：
10828478
负责人：
Mirella Hernandez
金额：
$ 4.18万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-29 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10828478
关键词：
Ablation Address Adult Adverse effects Adverse event Affect Afferent Neurons Aging Animal Model Animals Award Behavior Behavioral Biology Caenorhabditis elegans Calcium Cessation of life Communication Complex Cues Cyclic AMP-Dependent Protein Kinases Cyclic GMP Data Detection Disease Environment Exposure to Faculty Functional Imaging G Protein-Coupled Receptor Signaling G-Protein-Coupled Receptors Gene Expression Genetic Glutamates Goals Guanylate Cyclase Health Human Impairment Interneurons Invertebrates Knowledge Leadership Learning Life Expectancy Link Longevity Mediating Mental Depression Mental Health Mentors Modeling Moods Motor Neurons Mus Nematoda Nervous System Neurons Neurotransmitters Perception Peripheral Phase Physiological Physiology Positioning Attribute Postdoctoral Fellow Process Publications Publishing Regulation Reporter Reporting Research Research Project Grants Role Sensory Signal Transduction Smell Perception Stimulus Stress Stressful Event Taxes Technical Expertise Testing Training Work Writing career early life adversity early life stress emotion dysregulation experimental study follow-up healthspan imaging approach improved insight loved ones neural circuit neuronal circuitry neuropsychiatric disorder neurotransmission physical conditioning prevent programs receptor release of sequestered calcium ion into cytoplasm response sensory system skills stress resilience tenure track

项目摘要

Project Abstract All animals rely on sensory systems to detect and respond to environmental and behavioral cues. In most animals, this sensory information is perceived and processed by different sensory neurons, allowing animals to respond appropriately to maximize health- and lifespan. However, a detailed understanding of the underlying cues and mechanisms by which the sensory nervous system regulates health- and lifespan remains largely unknown. Addressing these gaps in knowledge is imperative to obtain a comprehensive understanding of the impact of sensory perception on overall health. My preliminary work in Caenorhabditis elegans shows that exposure to dead conspecifics result in 1) aversive behavior and 2) impaired lifespan. My studies also suggest that dead conspecifics release “death cues” that are detected by the olfactory neurons. Given my findings, the long-term objective of this research is to understand how death perception regulates animal’s physiology, health- and lifespan. In preliminary work, I have identified the sensory neurons and neurotransmitters required for death perception in C. elegans (Aim 1). My central hypothesis is that detection of intracellular metabolites released by dead conspecifics are recognized by amphid olfactory neurons AWB and/or ASH, promoting a cGMP-dependent signaling cascade leading to the observed aversive behavior and lifespan shortening. The objective of this project is to identify the neuronal circuitry and neuronal activity status involved in death perception in C. elegans (Aim 2). As a postdoctoral fellow, in Aim 3 I plan to expand on my previous training in sensory perception and stress to investigate how early-life stress may alter neuronal circuits involved in sensory perception, stress resilience, and mood-related disorders. The proposed research will provide new fundamental knowledge into the role of sensory perception in the regulation of both health-and lifespan.

项目摘要大多数动物都依靠感觉系统来检测环境和行为线索并做出反应。动物中，这种感觉信息由不同的感觉神经元感知和处理，使动物能够采取适当的应对措施以最大限度地提高健康和寿命。但是，需要详细了解其背后的原因。感觉神经系统调节健康和寿命的线索和机制在很大程度上仍然存在解决这些知识空白对于全面了解这一点至关重要。我对秀丽隐杆线虫的初步研究表明，感官知觉对整体健康的影响。我的研究还表明，接触死亡同种动物会导致 1）厌恶行为和 2）寿命缩短。根据我的发现，死亡的同种动物会释放出由嗅觉神经元检测到的“死亡线索”。这项研究的长期目标是了解死亡感知如何调节动物的生理机能，在初步工作中，我已经确定了所需的感觉神经元和神经递质。线虫的死亡感知（目标 1）。死亡同种释放的气味被两栖动物嗅觉神经元 AWB 和/或 ASH 识别，促进 cGMP 依赖性信号级联导致观察到的厌恶行为和寿命缩短。该项目的目的是确定与死亡有关的神经元回路和神经元活动状态作为一名博士后研究员，在目标 3 中，我计划扩展我之前的培训。感官知觉和压力，以研究早期生活压力如何改变参与的神经回路拟议的研究将提供新的感觉知觉、压力恢复能力和情绪相关疾病。关于感官知觉在健康和寿命调节中的作用的基础知识。