The cold-sensing circuit of Drosophila larvae

果蝇幼虫的冷感电路

• 批准号: 8536150
• 负责人: Ashley James Vonner
• 金额: $ 1.55万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536150
• 关键词: Ablation; Address; Adult; Architecture; Automobile Driving; Behavior; Biological Models; Bladder Diseases; Brain; Calcium; Calcium Signaling; Cations; Cells; Chronic; Chronic Obstructive Airway Disease; Code; Conflict (Psychology); Consensus; Custom; Data; Decision Making; Defect; Development; Discrimination; Disease; Dorsal; Drops; Drosophila genus; Drosophila melanogaster; Environment; Gastroesophageal reflux disease; Genes; Genetic; Goals; Head; Heart Hypertrophy; Homologous Gene; Human; Image; Impairment; Journals; Larva; Lead; Light; Location; Lung; Malignant Neoplasms; Methods; Modeling; Molecular; Nature; Nervous system structure; Neurons; Neurosciences; Nose; Olfactory Receptor Neurons; Organ; Organism; Photoreceptors; Phototransduction; Physiological; Physiology; Property; Public Health; Relative (related person); Reporting; Role; Science; Sensory; Signal Transduction; Smell Perception; Software Design; Staging; System; TRPV channel; Taste Perception; Temperature; Temperature Sense; United States National Academy of Sciences; Vision; avoidance behavior; awake; calcium indicator; deafness; fly; high throughput analysis; human disease; in vivo; insight; mutant; nervous system disorder; optogenetics; receptor; research study; response; sensor; tool

DESCRIPTION (provided by applicant): The ultimate goal of systems neuroscience is to explain human behavior, but as the human nervous system contains billions of neurons, simpler but still relevant model systems may assist in approaching this goal. To gain insight into simple neuronal circuits with relevance in humans, temperature sensing by Drosophila larvae serves as a meaningful but scaled down model due to broad conservation of sensory TRP (transient receptor protein) superfamily cation channels. Although a consensus model exists for the larval warm circuit, the cold-sensing circuit remains controversial, with disagreement over the role of relevant temperature-sensing molecules, such as TRPL (TRP-like), a TRP channel famous for its canonical role in phototransduction for fly vision. Importantly, TRP channel defects are relevant for human diseases and impairments, such as deafness, vestibular difficulties, neurological disorders, cardiac hypertrophy, gastroesophageal reflux disease, bladder diseases, several cancers, and chronic obstructive pulmonary disease. In addition, the location of larval cold-sensing neurons has not been firmly established. Here, Drosophila larvae are used to study thermotaxis, or navigation in response to changes in environmental temperature, to provide insights into decision-making behaviors in higher organisms. This proposal focuses on the cold-sensing circuit to characterize specific cold-responsive neurons and to quantitatively examine the cold sensor candidate TRPL. To accomplish these aims, genetic tools, such as genetically encoded calcium indicators, optogenetics, and the GAL4-UAS system, are used in conjunction with custom hardware and software designed to quantitatively track thermotaxis and perform three-dimensional in vivo calcium imaging in awake immobilized larvae subjected to temperature modulations.

描述（由申请人提供）：系统神经科学的最终目标是解释人类行为，但由于人类神经系统包含数十亿个神经元，更简单但仍然相关的模型系统可能有助于实现这一目标。为了深入了解与人类相关的简单神经元回路，由于感觉 TRP（瞬时受体蛋白）超家族阳离子通道的广泛保守，果蝇幼虫的温度传感可以作为有意义但按比例缩小的模型。尽管幼虫暖电路存在共识模型，但冷感应电路仍然存在争议，人们对相关温度感应分子的作用存在分歧，例如 TRPL（TRP 样），一种以其在光转导中的典型作用而闻名的 TRP 通道用于飞行视觉。重要的是，TRP 通道缺陷与人类疾病和损伤有关，例如耳聋、前庭困难、神经系统疾病、心脏肥大、胃食管反流病、膀胱疾病、多种癌症和慢性阻塞性肺病。此外，幼虫冷感神经元的位置尚未确定。在这里，果蝇幼虫被用来研究趋热性，或响应环境温度变化的导航，以深入了解高等生物的决策行为。该提案重点关注冷传感电路，以表征特定的冷响应神经元并定量检查冷传感器候选 TRPL。为了实现这些目标，遗传工具（例如基因编码钙指示剂、光遗传学和 GAL4-UAS 系统）与定制硬件和软件结合使用，旨在定量跟踪趋热性并在清醒固定状态下执行三维体内钙成像幼虫受到温度调节。