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

项目摘要 动物使用化学感官来评估它们的环境，并指示广泛的 行为。化学传感被用来定位食物和配偶，并避免威胁。是这样的 化学感觉刺激通常是分子的复杂混合物。编码的信息是如何 感觉到这些线索的多个化学感觉神经元被整合在一起，形成了 人们对环境和告知行为知之甚少。 微小的线虫是一个很好的模型，可以用来研究 动物对复杂的化学感觉刺激进行解码，以指导行为。它简单而刻板 它的行为受到来自其环境的化学感觉线索的有力调控。重要的是 强大的遗传工具和光学方法可用于研究加工的电路 化学感官刺激。该项目将重点研究线虫如何利用其化学感官系统。 以区分营养细菌和致病细菌。线虫吃微生物，但它也是 易受病原体感染的。因此，至关重要的是，线虫迅速检测到并 避免病原体，最近的研究表明，这是通过化学感觉完成的。 以前的实验使用光学方法来识别不同激活的神经元 营养和致病细菌，这些研究将通过确定(1)如何 这些微生物的感觉会产生不同的神经活动模式，以及(2)这些 神经活动的模式会产生不同的觅食行为。 该项目将在纽约大学医学院进行，并将帮助 为申请者成为独立研究人员做好准备。申请者将从事 专业发展活动，如指导、教学和赠款编写研讨会。 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。除了促进对感觉的基本过程的理解外，这些 研究还将影响我们如何理解化学感觉处理的缺陷 人类疾病，例如感觉加工障碍，与肥胖等饮食障碍相关 没有感觉到食欲的暗示和导致化学合成丧失的感官缺陷。

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.