Temperature Sensation and Its Behavioral Consequences

温度感觉及其行为后果

基本信息

批准号：
7360220
负责人：
Miriam B Goodman
金额：
$ 20.74万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7360220
关键词：
Acclimatization Affect Alleles Animals Area Award Behavior Behavioral Biology Body Temperature Caenorhabditis elegans Cells Collaborations Complex Computer software Condition Cutaneous Data Defect Development Disease Electrophysiology (science)Environment Esthesia Exhibits Feedback Figs - dietary Functional disorder Funding Genes Genetic Genetic Epistasis Genetic Screening Genetic Techniques Goals Health Homeostasis Human Hypothalamic structure Interneurons Laboratories Learning Letters Link Location Mammals Methods Modification Motor Motor Neurons Motor output Movement Mutation Nematoda Nervous system structure Neurons Optics Oregon Output Physiologic Thermoregulation Physiology Process Recreational Drugs Research Role Screening procedure Sensory Shivering Signal Transduction Skin Staging Study models Sweat Techniques Temperature Temperature Sense Thermogenesis Thermoreceptors Thinking Universities Vertebrates Work base behavior measurement ecstasy improved in vivo insight mutant novel patch clamp programs response sensory mechanism temperature jump tool

项目摘要

DESCRIPTION (provided by applicant): Body temperature has profound influences on all aspects of animal biology. Mammals have the ability to control body temperature by adjusting their physiology (e.g. non-shivering thermogenesis, perspiration) and by behavioral measures (e.g. huddling, locating areas of more favorable temperatures or thermotaxis). This process is thought to involve an internal set point and complex feedback loops that rely on thermoreceptor neurons in the skin and in the hypothalamus. Our understanding of the connections between such thermoreceptor neurons and motor centers is incomplete at best. Even less is known about the mechanisms of sensorimotor integration responsible for behavioral thermoregulation and its modification during short-term and long-term acclimation. In the nematode C. elegans, by contrast, a single pair of thermoreceptor neurons is linked to changes in behavioral responses to thermal gradients (thermotaxis). Their connections with interneurons and, ultimately, with motor neurons are known. Thus, in C. elegans, it is possible to understand how thermoreceptor neuron signaling affects behavior at a level of detail that is not possible in mammals. In this exploratory proposal, we seek to expand understanding of the link between temperature sensation and behavior by investigating the mechanism by which mutations can disrupt this link and by developing new tools for altering neuronal function. We focus on a mutant isolated in our laboratory that exhibits an intriguing defect in sensorimotor integration. We seek to extend this work by screening for genes responsible for the development and/or function of neurons that link thermosensation to motor output and to develop new tools for analyzing behavioral responses to neuron activation. The general strategy is to combine classical genetics with quantitative behavioral analysis and in vivo whole-cell patch-clamp recording in order to elucidate the relationship between temperature sensation and its behavioral consequences. The long-term objective of the proposed is to establish C. elegans as a new model for the study of behavioral thermoregulation and sensorimotor integration. The relevance of this project to human health lies in its potential to uncover universal motifs in sensorimotor integration and to provide insight into thermal dysregulation. All animals, including humans, have the ability to regulate their body temperature by moving to favorable areas in the environment. This ability relies on nerve cells that sense temperature and communicate with the nervous system to produce the needed movements. This complex process is only poorly understood. To improve understanding, we will study a simple roundworm that has only 302 neurons. Two of these neurons sense temperature and appear to aid a form of thermoregulation. What is learned from this study will clarify basic mechanisms of temperature sensation as well as learning and could improve understanding of thermoregulation and its dysfunction in disease and in response to recreational drugs such as ecstasy.

描述（由申请人提供）：体温对动物生物学的各个方面都有深远的影响。哺乳动物有能力通过调整生理（例如非颤抖产热、排汗）和行为措施（例如挤作一团、寻找温度更有利的区域或趋热性）来控制体温。该过程被认为涉及内部设定点和复杂的反馈回路，这些反馈回路依赖于皮肤和下丘脑中的温度感受器神经元。我们对这种温度感受器神经元和运动中枢之间的联系的理解充其量是不完整的。对于负责行为体温调节及其在短期和长期适应过程中的修改的感觉运动整合机制知之甚少。相比之下，在线虫中，一对温度感受器神经元与对热梯度（趋热性）的行为反应的变化有关。它们与中间神经元以及最终与运动神经元的联系是已知的。因此，在秀丽隐杆线虫中，有可能以哺乳动物无法做到的详细程度了解温度感受器神经元信号传导如何影响行为。在这个探索性提案中，我们试图通过研究突变破坏这种联系的机制以及开发改变神经元功能的新工具来扩大对温度感觉和行为之间联系的理解。我们关注的是我们实验室分离出的一个突变体，它在感觉运动整合方面表现出有趣的缺陷。我们寻求通过筛选负责将热感觉与运动输出联系起来的神经元发育和/或功能的基因来扩展这项工作，并开发用于分析对神经元激活的行为反应的新工具。总体策略是将经典遗传学与定量行为分析和体内全细胞膜片钳记录相结合，以阐明温度感觉与其行为后果之间的关系。该提案的长期目标是将线虫建立为研究行为温度调节和感觉运动整合的新模型。该项目与人类健康的相关性在于它有可能揭示感觉运动整合的普遍主题并提供对热失调的洞察。所有动物，包括人类，都有能力通过移动到环境中有利的区域来调节体温。这种能力依赖于感知温度并与神经系统通信以产生所需运动的神经细胞。人们对这个复杂的过程知之甚少。为了加深理解，我们将研究一种只有 302 个神经元的简单蛔虫。其中两个神经元感知温度并似乎有助于某种形式的温度调节。从这项研究中学到的知识将阐明温度感觉和学习的基本机制，并可以提高对温度调节及其在疾病中的功能障碍以及对摇头丸等消遣性药物的反应的理解。