Genetic Analysis of Nematode Behavior

描述（由申请人提供）：本研究旨在了解单个神经元的活动如何在定义的回路中组合联合收割机以产生神经系统的行为输出。所要研究的行为是秀丽隐杆线虫雄性的交配行为。利用连续切片电子显微照片的重建，已经确定了产生交配行为的雄性神经系统区域的突触连接的完整模式。这个神经网络包含由大约8000个突触（4000个化学突触，4000个电突触）连接的175个神经元的过程。接线图由一个复杂的相互作用网络组成，是检查单个神经元在产生行为输出中的作用的基础。C.秀丽隐杆线虫雄性交配行为由一系列根据感觉输入执行的子行为组成，以允许雄性将硬化的骨针插入雌雄同体的外阴并转移精子。神经元已经被识别出，通过它们的连接模式，它们似乎与这些子行为中的每一个相关联。我们将通过杀死细胞将这些神经元从回路中消除来验证我们对这些神经元功能的假设。由此产生的行为缺陷将表明神经元在回路中的作用。需要解决的一个重要问题是，网络是否包含专用于特定子行为的电路或模块，或者具有分布式架构，生成多个行为作为整体功能的替代模式。为了评估网络内化学和电通信的相对重要性，将确定所使用的神经递质。将使用突变体或通过细胞特异性RNAi方法来阻断化学神经传递，以揭示电路的功能。布线图包含一个重复的网络基序，其中感觉神经元和中间神经元直接连接，并通过一对共同的中间神经元连接，形成三角形电路。这个基序可能对网络的功能有几种可能的影响之一，这取决于共同的神经元对中间神经元是兴奋性的还是抑制性的。为了确定该基序的功能特征，将确定回路中的神经递质和受体类型，并确定激活或抑制回路的结果。 公共卫生相关性：专注于无脊椎动物遗传模型动物秀丽隐杆线虫的神经系统的一个区域，最近已经确定了突触连接的完整模式，将检查在一个完全定义的神经网络中单个神经元的功能，以了解神经系统中的电路如何产生复杂的动物行为。

DESCRIPTION (provided by applicant): This research seeks to understand how the activities of individual neurons combine together in defined circuits to generate the behavioral output of the nervous system. The behavior to be studied is the copulatory behavior of the nematode Caenorhabditis elegans male. Using reconstruction from serial section electron micrographs, the complete pattern of synaptic connectivity has been determined for the region of the male nervous system that generates copulatory behavior. This neuropil contains the processes of 175 neurons connected by some 8000 synapses (4000 chemical, 4000 electrical). The wiring diagram, which consists of a complex network of interactions, serves as the basis for examining the role of individual neurons in generating behavioral output. C. elegans male copulatory behavior consists of a series of sub-behaviors executed according to sensory input to allow the male to insert hardened spicules into the hermaphrodite vulva and transfer sperm. Neurons have been identified that by their pattern of connectivity appear to be associated with each of these sub-behaviors. We will test our hypothesis for the function of these neurons by eliminating them from the circuit by cell killing. The behavioral deficit that results will indicate the role of the neuron in the circuit. An important question to be addressed is whether the network contains circuits or modules dedicated to specific sub-behaviors or instead have a distributed type of architecture, generating multiple behaviors as alternative modes of function of the whole. To assess the relative importance of chemical and electrical communication within the network, the neurotransmitters utilized will be determined. Chemical neurotransmission will be blocked using mutants or through cell-specific RNAi approaches to reveal the function of the electrical circuit. The wiring diagram contains a repeated network motif in which a sensory neuron and an interneuron are connected both directly and via a pair of interneurons that is common to all, forming a triangular circuit. This motif may have one of several possible influences on the function of the network, depending on whether the common neuron pair is excitatory or inhibitory on the interneuron. In order to determine the functional characteristics of this motif, the neurotransmitter and receptor types in the circuit will be determined and the result of activating or inhibiting the circuit will be determined. PUBLIC HEALTH RELEVANCE: Focusing on a region of the nervous system of the invertebrate genetic model animal Caenorhabditis elegans where the complete pattern of synaptic connectivity has been recently determined, the function of individual neurons in a completely defined neural network will be examined in order to understand how circuits in the nervous system generate complex animal behavior.