NEURONAL AND THEORETICAL ANALYSIS OF SPATIAL ORIENTATION

描述（改编自申请人摘要）：神经元如何控制行为是理解精神疾病生理基础的核心问题。线虫302个神经元的形态学和突触连通性的完整描述为首次全面了解整个神经系统提供了前景。该研究的长期目标是了解该模型系统中行为的神经元基础。目前的建议集中在一个单一的行为：趋化性，动物的运动方向向上（或向下）的化学梯度的能力。在秀丽隐杆线虫中，这个问题提供了一个难得的机会来整合四个不同层次的分析：遗传学、电生理学、建模和行为。选择基因突变的趋化行为将使用自动跟踪系统来研究取向化学刺激的行为机制。电生理记录将从正常和突变动物的神经元中进行，以确定化学感觉信息是如何编码的，以及这一过程的分子基础。这些信息将用于构建趋化神经网络的计算机模型。该模型将被分析以产生关于趋化性的神经基础的假设。这些假设将通过进一步的电生理记录和研究消除趋化网络中特定神经元对模型和真实动物的影响来验证。从趋化性研究中学到的东西将作为解决秀丽隐杆线虫其他行为的基础。

DESCRIPTION (Adapted From The Applicant's Abstract): The question of how neurons control behavior is central to understanding the physiological bases of mental illness. The complete description of the morphology and synaptic connectivity of all 302 neurons in the nematode C. elegans raised the prospect of the first comprehensive understanding of an entire nervous system. The long-term objective of the proposed research is to understand the neuronal basis of behavior in this model system. The present proposal focuses on a single behavior: chemotaxis, the ability of an animal to direct its locomotion up (or down) a chemical gradient. In C. elegans, this problem provides an unusual opportunity to integrate four different levels of analysis: genetics, electrophysiology, modeling, and behavior. The chemotaxis behavior of selected genetic mutations will be studied using an automated tracking system to probe the behavioral mechanism of orientation to chemical stimuli. Electrophysiological recordings will be made from neurons in normal and mutant animals to determine how chemosensory information is encoded and the molecular basis of this process. This information will be used to construct a computer model of the neural network for chemotaxis. The model will be analyzed to generate hypotheses as to the neural basis of chemotaxis. These hypotheses will be tested by further electrophysiological recordings and by studying the effects on model and real animals of eliminating specific neurons in the chemotaxis network. What is learned from studies of chemotaxis will serve as the basis for tackling other behaviors in the repertoire of C. elegans.