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Warm sensitive neurons that control body temperature

控制体温的热敏感神经元

基本信息

批准号：
9900878
负责人：
Zachary A. Knight
金额：
$ 33.48万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9900878
关键词：
Anatomy Anterior Hypothalamus Axon Behavior Behavior Control Behavioral Biological Assay Body Temperature Brain Brain region Brown Fat Cells Conflict (Psychology)Cues Cutaneous Data Drug abuse Elements Fever Generations Goals Heat Losses Homeostasis Hyperthermia Hypothalamic structure Impairment Infection Ion Channel Label Lead Literature Mammals Maps Measures Mediating Medical Modeling Modernization Molecular Motivation Mus Neural Pathways Neurons Neuropeptides Neurosciences Nutritional Pathway interactions Peripheral Pharmacology Physiologic Thermoregulation Physiological Population Preoptic Areas Pyrogens Rewards Role Signal Transduction Site Stroke Structure Surface System Tail Temperature Testing Thermogenesis Vasodilation Viral Visceral Work awake base behavioral response cell type genetic approach in vivo molecular marker neural circuit neurochemistry neuromechanism novel novel therapeutic intervention optogenetics pituitary adenylate cyclase activating polypeptide preference public health relevance relating to nervous system response stressor transcriptome sequencing treatment strategy warm temperature willingness

项目摘要

DESCRIPTION (provided by applicant): A better understanding of the mammalian thermoregulatory system may lead to new therapeutic strategies for the treatment of conditions associated with hyperthermia such as infection, drug abuse, and stroke. Classical studies identified the preoptic area (POA) of the anterior hypothalamus as the principal site of mammalian thermoregulation. This region is postulated to contain "warm-sensitive" neurons that are activated by environmental heat and in response trigger an array of autonomic and behavioral responses that restore temperature homeostasis. An extensive scientific literature accumulated over the past 75 years has supported the existence and importance of these warm-sensitive cells, yet their neurochemical identity remains unknown. For this reason key components of the mammalian thermoregulatory circuit have remained inaccessible to modern genetically-targeted approaches in neuroscience. Recently we have used an approach for activity- based RNA sequencing to identify molecular markers that selectively label these long-sought warm-sensitive cells. We have shown using cell-type-specific optogenetic manipulations that activation of these neurons inhibits brown adipose tissue thermogenesis and lowers body temperature. We have also recorded the activity of these neurons in awake behaving mice and shown that they are activated by ambient heat and inhibited by ambient cold. Thus we have identified a novel, molecularly-defined neural population that functionally resembles the long-sought warm-sensitive cells of the POA. We propose here to apply approaches for genetic and projection-targeted neural manipulation and recording to elucidate the downstream circuit by which these cells control behavioral and autonomic thermoregulation.