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

说明)： 对调节神经系统功能和BE的热敏机制有完整的了解。 Havior要求他们在一种具有强大的温度驱动行为的动物身上进行研究，这种行为容易受到 定量的行为学、生理学和遗传学分析。当果蝇幼虫被放在一个 温度梯度，它立即导航到更高或更低的温度，以追求一个首选 温度范围。由于幼虫的运动行为相对简单，其神经较小 系统、行为和生理分析可以用来实现对如何 热敏信息的获取和利用由其神经回路完成。通过分析幼虫在体内的运动 响应定义的热敏输入，我们可以发现一整套感应器 在趋热性下的转换，系统地转换特定模式的转换 将热敏输入转化为电机输出的可量化模式。幼虫的身体和它的透明度 Powerfiji遗传工具箱便于使用光学神经生理学来操纵和监测活动 整个神经系统的神经回路。我们建议将遗传分析与新的 高通量行为分析，以确定幼虫神经系统中感觉的位置。 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 塑造驱动寒冷的特定神经元的热敏特性的分子途径 回避和温情回避行为。鉴于神经基因功能的高度保守性 果蝇和高等脊椎动物，我们预计这项工作的结果将导致对更多 复杂的神经系统。 相关性(请参阅说明)： 这项建议研究了色氨酸通道介导的热感觉的分子机制。在……里面 对人类来说，基于色氨酸的体温感觉对疼痛、炎症和体温调节至关重要。 因此，这项建议中研究的机制具有生物医学意义。此外，温度传感是 对传播疟疾和西尼罗河等人类疾病的昆虫寻找宿主很重要。因此，这项研究 体温变化也与控制昆虫传播的人类疾病有关。

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.