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

项目摘要 所有动物都依赖感觉系统来检测和响应环境和行为线索。在大多数 动物，这种感觉信息被不同的感觉神经元感知和处理，使动物能够 做出适当的反应，以最大限度地提高健康和寿命。然而，详细了解底层 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 未知解决这些知识差距对于全面了解 感官知觉对整体健康的影响。我对秀丽隐杆线虫的初步研究表明， 暴露于死亡同种导致1）厌恶行为和2）寿命受损。我的研究还表明 死亡的同种会释放出“死亡信号”，嗅觉神经元会检测到这些信号。根据我的发现， 本研究的长期目标是了解死亡知觉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 C.死亡知觉elegans（Aim 1）。我的核心假设是检测细胞内代谢物 由死亡同种释放的神经元被两栖类嗅觉神经元AWB和/或ASH识别， cGMP依赖性信号级联导致观察到的厌恶行为和寿命缩短。的 本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 感知C。elegans（Aim 2）。作为一名博士后研究员，在目标3中，我计划扩展我以前的培训， 感官知觉和压力，以调查如何早期生活压力可能会改变神经回路参与 感官知觉、压力恢复力和情绪相关障碍。这项研究将提供新的 基本的知识，在调节健康和寿命的感官知觉的作用。

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.