Neural and molecular mechanisms of microbe-sensing in the control of animal behavior - Resubmission - 1

项目摘要 动物利用化学感觉来评估它们的环境，并指导广泛的化学反应。 行为。化学感觉被用来寻找食物和配偶，并避免威胁。等 化学感觉刺激通常是分子的复杂混合物。如何编码的信息 感觉这些线索的多个化学感觉神经元被整合以形成对 对环境和知情行为知之甚少。 显微镜下的蛔虫C.秀丽线虫是一个很好的研究模型， 动物解码复杂的化学感觉刺激来指导行为。它的简单和刻板 行为受到来自其环境的化学感觉线索的强烈调节。重要的是， 强大的遗传学工具和光学方法可以用来研究 化学感觉刺激本项目将重点研究C.秀丽线虫用它的化学感受系统 来区分营养菌和致病菌。C.秀丽线虫吃微生物，但它也是 易受病原体感染的。因此，C.秀丽线虫能迅速检测到 避免病原体，最近的研究表明这是通过化学感觉来实现的。 以前的实验使用光学方法来识别差异激活的神经元 通过营养和致病细菌，这些研究将通过确定（1）如何扩展 这些微生物的感觉产生了不同的神经活动模式，以及（2）这些微生物是如何产生的？ 神经活动的模式产生不同的觅食行为。 该项目将在纽约大学医学院进行， 准备申请人作为一个独立的研究人员的职业生涯。申请人将从事 专业发展活动，如辅导，教学和赠款写作研讨会。 他们还将定期在机构和国际会议上介绍这项工作。 总之，这些研究将确定复杂的化学感觉刺激的机制， 已处理。除了推进对感觉的基本过程的理解，这些 研究也将影响我们如何理解化学感觉处理的缺陷， 人类疾病，例如感觉处理障碍、进食障碍如肥胖相关的 无法感知食欲线索和感官缺陷，导致化学感觉丧失。

Project Summary Animals use chemosensation to evaluate their environment and instruct a wide range of behaviors. Chemosensation is used to locate food and mates and to avoid threats. Such chemosensory stimuli are often complex blends of molecules. How information encoded by the multiple chemosensory neurons that sense these cues is integrated to form a representation of the environment and inform behavior is poorly understood. The microscopic roundworm C. elegans is an excellent model to study in order to determine how animals decode complex chemosensory stimuli to instruct behavior. Its simple and stereotyped behaviors are robustly regulated by chemosensory cues from its environment. Importantly, powerful genetic tools and optical methods are available to study the circuits that process chemosensory stimuli. This project will focus on how C. elegans uses its chemosensory system to distinguish nutritive from pathogenic bacteria. C. elegans eats microbes, but it is also susceptible to infection by pathogens. It is, therefore, critical that C. elegans rapidly detect and avoid pathogens, and recent studies indicate that this is accomplished by chemosensation. Previous experiments used an optical method to identify neurons that are differentially activated by nutritive and pathogenic bacteria, and these studies will be extended by determining (1) how the sensation of these microbes generates different patterns of neural activity and (2) how these patterns of neural activity generate distinct foraging behaviors. This project will be conducted at the New York University School of Medicine and will aid in preparing the applicant for a career as an independent researcher. The applicant will engage in professional development activities such as mentoring, teaching, and grant-writing workshops. They will also present this work at institutional and international conferences on a regular basis. Together, these studies will determine mechanisms by which complex chemosensory stimuli are processed. In addition to advancing understanding of a fundamental process in sensation, these studies will also impact how we understand defects of chemosensory processing that underlie human diseases, e.g. sensory processing disorder, eating disorders such as obesity associated with a failure to sense appetitive cues and sensory deficiencies that cause loss of chemesthesis.