Neuronal and theoretical analysis of spatial orientation

描述（由申请人提供）：本研究的长期目标是了解神经系统如何控制行为。这一目标意义重大，因为精神疾病是一种行为疾病。挑战在于了解健康的神经系统如何产生正常行为，以便了解患病的神经系统如何产生异常行为。这个研究问题将在理解一个简单的生物体行为的遗传和神经基础的背景下进行：线虫。证明了C. elegans基因组，以及C. elegans大脑，使其非常适合拟议的研究。目前的建议集中在几个行为之一，在C。elegans：趋化性，动物根据化学梯度定向运动的能力。将蠕虫置于琼脂表面，使其进行正弦曲线游泳运动，偶尔会被短暂的转动打断。在C.大家都知道，雅利安人有一个简单的规则--向下倾斜时转弯更频繁，向上倾斜时转弯更不频繁。控制游泳和转弯之间转换的神经元已经被识别出来，但尚不清楚它们在趋化性中的功能。拟议中的研究使用遗传学，电生理学，钙成像，行为分析和数学建模的显着组合来解决这个问题。有三个具体目标。具体目标1是通过测试转换神经元的数学模型来阐明在游泳和转动之间转换的神经元机制，具体目标2是通过用激光杀死各种神经元并测试定向缺陷来识别包括从化学感觉神经元到转换网络的通路的中间神经元。具体目的3是研究C.线虫通过记录蠕虫中可能具有味觉基因突变的化学感觉神经元的活动来编码和复制化学感觉信息。具体目标3将促进对味觉传导机制的更好理解，并可能导致影响估计200万美国人的化学感觉障碍的新疗法。

DESCRIPTION (provided by applicant): The long-term objective of this research is to understand how the nervous system controls behavior. This objective is significant because mental illness is a disease of behavior. The challenge is to understand how the healthy nervous system produces normal behavior in order to understand how the diseased nervous system produces abnormal behavior. This research question will be pursued in the context of understanding the genetic and neuronal basis of behavior in a simple organism: the round worm Caenorhabditis elegans. The existence of the complete sequence of the C. elegans genome, together with the complete description of the synaptic connectivity of the 302 neurons of the C. elegans brain, makes it well-suited to the proposed studies. The present proposal focuses on one of several behaviors in C. elegans: chemotaxis, the ability of an animal to orient its locomotion with respect to a chemical gradient. A worm placed on an agar surface makes sinusoidal swimming movements that are occasionally interrupted by a brief tum. Orientation in C. elegans is known to involve a simple rule--turn more frequently when going down the gradient and turn less frequently when going up the gradient. Neurons that control the switch between swimming and turning have been identified, but it is not yet known how they function in chemotaxis. The proposed research addresses this question using a remarkable combination of genetics, electrophysiology, calcium imaging, behavioral analysis, and mathematical modeling. There are three specific aims. Specific Aim 1 is to elucidate the neuronal mechanism for switching between swimming and turning by testing a mathematical model of the switching neurons, Specific Aim 2 is to identify the interneurons that comprise the pathways from chemosensory neurons to the switching network by killing various neurons with a laser and testing for defects in orientation. Specific Aim 3 is to investigate how taste receptor neurons in C. elegans encode and transduce chemosensory information by recording the activity of chemosensory neurons in worms that have mutations in likely taste genes. Specific Aim 3 will promote a better understanding of taste transduction mechanisms and could lead to new treatments for chemosensory disorders affecting an estimated two million Americans.