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

项目摘要 所有动物都依靠感官系统来检测环境和行为线索并做出反应。在大多数 动物，这种感觉信息由不同的感觉神经元感知和处理，允许动物 适当地应对，以最大限度地提高健康和寿命。然而，详细了解潜在的 感官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 未知。解决这些知识上的差距是全面理解 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 暴露在死亡的同种生物中会导致1)厌恶的行为和2)损害寿命。我的研究还表明 死亡的同种异物释放出被嗅觉神经元探测到的“死亡信号”。根据我的发现， 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 对于线虫的死亡感知(目标1)。我的中心假设是细胞内代谢物的检测 由死亡的共特异体释放的物质被两栖嗅觉神经元AWB和/或ASH识别，促进 CGMP依赖的信号级联导致观察到的厌恶行为和寿命缩短。这个 这个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。 线虫的感知(目标2)。作为一名博士后研究员，在Aim 3中，我计划在之前的培训基础上扩展我的 感官知觉和应激研究早期应激如何改变神经回路参与 感官知觉、压力适应能力和情绪相关障碍。拟议的研究将提供新的 了解感官知觉在调节健康和寿命方面的作用的基本知识。

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.