Genetic Regulation of Mating Behavior in C. elegan Males

描述(由申请者提供)：本项目的目标是了解复杂行为中的一个步骤是如何在基因上指定的。这个基本问题将通过研究线虫的雄性交配行为来解决。在交配过程中，雄性会执行一系列刻板的次要行为，导致将交配针刺插入配偶体内，并随后转移精子。尽管线虫的雄性交配行为包括许多步骤，但这个项目将专注于剖析雄性如何将针状物插入配偶的外阴。针刺插入行为是一种简单的反射；然而，男性的神经系统和肌肉系统必须调节许多因素。神经元和肌肉必须计算何时启动行为，并监控行为结果是否成功。如果插入尝试失败，电路必须重新启动行为。如果穿透成功，在下一个行为步骤继续进行时，电路会保持针状体的插入。雄性只在交配时才表现出针刺插入行为。然而，可能会产生突变，导致雄性在没有交配线索的情况下表现出异常的行为。其中一个突变破坏了线虫的UNC-103基因。UNC-103是人类H-ERG编码的电压门控延迟整流K+通道的线虫同源物。在人类中，HERG通道调节心率。降低离子通道功能的h-erg突变会增加自发性致死性心律失常的可能性，这种情况被称为长QT综合征。针刺插入行为需要不同神经元和肌肉之间的协调。UNC-103的突变破坏了这种调节，并导致用于交配的男性特有肌肉的自发癫痫发作。为了了解UNC-103是如何被用来调节行为的，这个项目将确定UNC-103在男性行为回路中的作用。该项目还将确定影响候选基因的突变的身份，这些基因可能与UNC-103一起或与UNC-103并行作用，以调节行为。此外，该项目将确定在交配期间必须由UNC-103减弱的激活途径的组件。

DESCRIPTION (provided by applicant): The goal of this project is to understand how a step in a complex behavior is genetically specified. This fundamental problem will be addressed by studying C. elegans male mating behavior. During mating, the male executes a series of stereotyped sub-behaviors that result in the insertion of his copulatory spicules into his mate and the subsequent transfer of sperm. Although C. elegans male mating behavior consists of many steps, this project will focus on dissecting how the male inserts his spicules into his mate's vulva. Spicule insertion behavior is a simple reflex; however, the male nervous system and musculature must regulate many factors. The neurons and muscles must compute when to initiate the behavior and monitor if the behavioral outcome was successful. If an insertion attempt fails, the circuitry must re-initiate the behavior. If penetration is successful, the circuitry keeps the spicules inserted while the next behavioral step proceeds. Males display spicule insertion behavior only during mating. However, mutations can be generated that will cause males to display this behavior abnormally in the absence of mating cues. One of these mutations disrupts the C. elegans unc-103 gene. Unc-103 is the C. elegans homolog of the human h-erg-encoded voltage-gated delayed rectifying K+ channel. In humans, HERG channels regulate cardiac rhythm. Mutations in h-erg that reduce ion channel function can increase the probability of spontaneous lethal heart arrhythmias, a condition called long QT syndrome. Spicule insertion behavior requires coordination between different neurons and muscles. Mutations in unc-103 disrupt that regulation and result in spontaneous seizures of male-specific muscles that are used for copulation. To understand how unc-103 is used to regulate behavior, this project will identify where unc-103 is acting in the behavioral circuitry of males. The project will also determine the identities of mutations that affect candidate genes that may act with or in parallel to unc-103 to regulate behavior. Additionally, this project will identify components of activating pathways that must be attenuated by unc-103 during periods between mating.