PROJECT 2: THE MOLECULAR AND CELLULAR BASIS OF THERMOSENSORY NAVIGATION IN DROSO

项目 2：DROSO 热传感导航的分子和细胞基础

• 批准号: 8485958
• 负责人: ARAVINTHAN D. SAMUEL
• 金额: $ 25.29万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8485958
• 关键词: Affect; Animals; Behavior; Behavior Control; Behavioral; Behavioral Assay; Biological Assay; Body Temperature; Calcium; Cations; Cells; Complex; Coupled; Detection; Development; Disease; Dissection; Drosophila genus; Esthesia; Financial compensation; G-Protein Signaling Pathway; GTP-Binding Proteins; Genes; Genetic; Growth; Health; High temperature of physical object; Human; Image; Individual; Inflammation; Insect Control; Insect Vectors; Insecta; Larva; Lead; Malaria; Measures; Mediating; Molecular; Molecular Genetics; Monitor; Motor output; Movement; Nervous System Physiology; Nervous system structure; Neurons; Optics; Pain; Pathway interactions; Pattern; Physiologic Thermoregulation; Physiological; Physiology; Principal Investigator; Property; Protein Isoforms; Regulation; Relative (related person); Rhodopsin; Shapes; Signal Transduction; Signaling Molecule; TRPA1 Channel; Temperature; Testing; Variant; Vertebrates; West Nile virus; Work; avoidance behavior; base; cold temperature; detector; driving behavior; gene function; genetic analysis; human disease; in vivo; insight; mutant; neural circuit; neurophysiology; receptor; relating to nervous system; response; sensor; tool

instmctions): A complete understanding of the thermosensory mechanisms that regulate nervous system function and be- havior requires their study in an animal with robust temperature-driven behaviors that is amenable to quantitative behavioral, physiological, and genetic analysis. When the Drosophila larva is placed in a temperature gradient, it immediately navigates towards higher or lower temperatures in pursuit of a preferred temperature range. Owing to the relative simplicity of larval motile behavior and the small size of its nervous system, behavioral and physiological analysis can be used to achieve a complete understanding of how thermosensory information is acquired and used by its neural circuits. By analyzing larval movements in response to defined thermosensory inputs, we can uncover the complete set of sensorimotor transformations that underiie thermotaxis, transformations that systematically convert specific patterns of thermosensory inputs into quantifiable patterns of motor output. The transparency of the larva body and its powerfiji genetic toolbox facilitates the use of optical neurophysiology to manipulate and monitor the activity of neural circuits throughout the lan/al nervous system. We propose to combine genetic analysis with new high-throughput behavioral assays to define the locus of themiosensation in the larval nervous system. Furthermore, combining genetic analysis with optical neurophysiology will allow us to understand the molecular pathways that shape the thermosensory properties of the specific neurons that drive cold avoidance and warm avoidance behavior. Given the high conservation of neuronal gene functions between Drosophila and higher vertebrates, we expect that results from this work will lead to major insights into more complex nervous sys-tems. RELEVANCE (See instmctions): This proposal investigates the molecular mechanisms of TRP channel-mediated thermal sensation. In humans, TRP-based thermosensation is critical for pain, inflammation and body temperature regulation. Thus, the mechanisms studied in thie proposal are of biomedical relevance. In addition, thermosensation is important for host-seeking by insect vectors of human diseases like malaria and West Nile. Thus the study of thermosensation is also relevant to the control of insect-borne human disease.

Instmctions）： 完全理解调节神经系统功能并进行的热敏机制 Havior需要在具有强大温度驱动行为的动物中进行研究 定量行为，生理和遗传分析。当果蝇幼虫放在一个 温度梯度，它立即朝着较高或较低的温度导航。 温度范围。由于幼虫运动行为的相对简单性和紧张的小尺寸 系统，行为和生理分析可用于完全了解如何 热敏信息是由其神经回路获取和使用的。通过分析幼虫运动 对定义的热感觉输入的响应，我们可以揭示完整的感觉运动集 不足的热触觉的转换，系统地转换特定模式的转换 热感觉输入到可量化的电动机输出模式中。幼虫体的透明度及其 Powerfiji遗传工具箱有助于使用光学神经生理学来操纵和监测活动 整个LAN/AL神经系统中的神经回路。我们建议将遗传分析与新的 高通量行为分析以定义幼虫神经系统中命中的轨迹。 此外，将遗传分析与光学神经生理学相结合将使我们能够理解 塑造特定神经元的热感应特性的分子途径 避免和温暖的避免行为。鉴于神经元基因的高度保守性在 果蝇和更高的脊椎动物，我们预计这项工作的结果将导致更多的见解 复杂的神经系统。 相关性（请参阅Instmctions）： 该建议研究了TRP通道介导的热感觉的分子机制。在 人类，基于TRP的热敏度对于疼痛，炎症和体温调节至关重要。 因此，提案中研究的机制具有生物医学相关性。另外，热敏度为 对于疟疾和西尼罗河等人类疾病的昆虫媒介寻求宿主的重要性。因此研究 热效率也与控制昆虫传播的人类疾病有关。