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

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

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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.

项目摘要所有动物都依靠感觉系统来检测和响应环境和行为提示。大多数动物，这种感官信息是由不同的感觉神经元感知和处理的，使动物能够适当地回应最大化健康和寿命。但是，对基础的详细理解感觉神经系统调节健康和寿命的提示和机制在很大程度上保持未知。在Knowle中解决这些差距必须获得对感官感知对整体健康的影响。我在秀丽隐杆线虫的初步工作表明接触死亡概念会导致1）厌恶行为和2）寿命受损。我的研究也暗示死者概念释放了嗅觉神经元检测到的“死亡线索”。考虑到我的发现，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，健康和寿命。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秀丽隐杆线虫中的死亡感知（AIM 1）。我的中心假设是检测细胞内代谢物由死亡概念发布的嗅觉神经元AWB和/或灰烬所认可的 CGMP依赖性信号传导级联反应导致观察到的厌恶行为和寿命缩短。这该项目的目的是确定死亡涉及的神经元电路和神经元活动状态秀丽隐杆线虫的感知（AIM 2）。作为博士后研究员，在AIM 3中，我计划扩展我以前的培训感官感知和压力，以调查早期寿命应力如何改变涉及的神经元回路感官感知，压力弹性和与情绪有关的疾病。拟议的研究将提供新的感官感知在调节健康和寿命中的作用的基本知识。