Neuronal and theoretical analysis of spatial orientation

描述（由申请人提供）：拟议研究的长期目标是了解神经系统如何控制行为。这个问题对心理健康有着重要的影响，因为精神疾病最终是一种行为疾病。采用模型系统方法，我们将研究秀丽隐杆线虫行为的神经元基础。对秀丽隐杆线虫神经系统302个神经元突触连通性的完整描述，以及将这种动物的基因和神经元与行为联系起来的广泛的遗传和生理技术，使得它非常适合提出的研究。此外，超过60%的人类疾病基因与秀丽隐杆线虫相关，包括与帕金森病、阿尔茨海默病和卢伽雷氏病等破坏性神经退行性疾病有关的基因。目前的建议集中在化学趋向性-运动导向的化学梯度-一个简单的例子，感觉信息是如何通过运动控制中心转换，以产生适应性行为的重要问题。我们之前已经证明，秀丽隐杆线虫的趋化性遵循一个明确的规则：在梯度下降时转向更频繁，而在梯度上升时转向更少。其他研究人员已经确定了一个神经元网络，它控制着直线或转弯的决定，但还不知道这个网络在趋化性中是如何起作用的。我们将利用遗传学、电生理学、钙成像和行为分析的显著结合来解决这个问题，以测试运动调节的数学模型。这项研究意义重大，因为运动缺陷是秀丽隐杆线虫神经退行性疾病基因功能改变的主要后果之一。

DESCRIPTION (provided by applicant): The long-term objective of the proposed research is to understand how the nervous system controls behavior. This question has significant implications for mental health, for mental illness is, ultimately, a disease of behavior. Taking a model systems approach, we will study the neuronal basis of behavior in the nematode worm Caenorhabditis elegans. The existence of a complete description of the synaptic connectivity of the 302 neurons of the C. elegans nervous system, and the wide range of genetic and physiological techniques for linking genes and neurons to behavior in this animal, makes it unusually well-suited to the proposed studies. In addition, more than 60% of all human disease genes have a correlate in C. elegans, including genes implicated in devastating neurodegenerative conditions such as Parkinson's, Alzheimer's, and Lou Gehrig's disease. The present proposal focuses on chemotaxis -locomotion oriented to a chemical gradient -a simple example of the important problem of how sensory information is transformed by movement control centers to generate adaptive behavior. We have previously shown that chemotaxis in C. elegans follows a well-defined rule: turn more frequently when going down the gradient, and turn less frequently when going up the gradient. Other researchers have identified a network of neurons that controls the decision to go straight or to turn, but it is not yet known how this network functions in chemotaxis. We will address this question using a remarkable combination of genetics, electrophysiology, calcium imaging, and behavioral analysis to test a mathematical model of locomotory regulation. The proposed research is significant because locomotion defects are one of the main consequences of altering the function of neurodegenerative disease genes in C. elegans.