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是如何控制行为的。这个问题对精神健康有重大影响，因为精神疾病归根结底是一种行为疾病。采用模型系统的方法，我们将研究线虫线虫行为的神经元基础。线虫神经系统302个神经元的突触连接的完整描述，以及将基因和神经元与这种动物的行为联系起来的广泛的遗传和生理技术的存在，使其非常适合拟议的研究。此外，超过60%的人类疾病基因与线虫有关，包括与毁灭性的神经退行性疾病有关的基因，如帕金森氏症、阿尔茨海默氏症和卢·格里克病。目前的建议侧重于趋化性--面向化学梯度的运动--这是一个重要问题的简单例子，即运动控制中心如何转换感觉信息以产生适应行为。我们之前已经证明，线虫的趋化性遵循一个明确的规则：向下倾斜时转向更频繁，而向上倾斜时转向较少。其他研究人员已经确定了一个神经元网络，该网络控制着直行或转弯的决定，但尚不清楚该网络如何在趋化作用中发挥作用。我们将利用遗传学、电生理学、钙成像和行为分析的非凡组合来解决这个问题，以测试运动调节的数学模型。这项拟议的研究意义重大，因为运动缺陷是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.