Neurobiology of an Oxytocin Analog that Generates Reproductive Behavior

加压素和催产素是所有生物中最高度保守的分子之一，无论是在分子结构还是在功能上。它们是控制生殖行为的小肽激素（例如，求爱、交配、婴儿护理、配对）在从蜗牛和蠕虫到啮齿动物和人类的广泛动物中。然而，激素本身并不能产生这些重要的行为。相反，它们作用于神经系统，改变其活动，从而改变行为。这项研究将使用一种相对简单的模式生物，欧洲药用水蛭，来研究神经元回路是如何被动物的催产素激活并产生求爱行为的。研究人员将使用现代分子技术（质谱法）来识别水蛭版本的催产素，并将使用尖端的电学和光学技术来表征由激素激活的神经元组。基于他们之前的发现，他们希望发现水蛭像包括人类在内的哺乳动物一样，使用催产素类似物作为特定神经元之间的神经递质，并作为改变所有神经元特性的激素。他们将能够从分子机制到产生的行为来追踪这些效应。对水蛭系统的这种描述将是对任何生殖行为背后的电路的第一次完整描述，它将展示同一个分子如何既能激活行为又能帮助产生行为。这些结果将作为一个跳板，激发神经网络在更复杂的动物（包括哺乳动物）中的生殖行为的类似特征。该项目将为参与该研究项目每个阶段的学生提供独特的培训机会。

Vasopressin and oxytocin are among the most highly conserved molecules in all of biology, both in their molecular structure and in their functions. They are small peptide hormones that control reproductive behaviors (e.g., courting, copulation, infant care, pair-bonding) in a broad range of animals from snails and worms to rodents and humans. However, hormones do not by themselves produce these important behaviors. Instead, they act on the nervous system, changing its activity and as a result, changing behavior. This study will use a relatively simple model organism, the European medicinal leech, to study how a neuronal circuit is activated by the animal's version of oxytocin and produces courtship behaviors. The investigators will use modern molecular techniques (mass spectroscopy) to identify the leech version of oxytocin, and will use cutting-edge electrical and optical techniques to characterize the set of neurons that are activated by the hormone. Based upon their previous findings, they expect to find that the leech, like mammals including humans, uses the oxytocin analog both as a neurotransmitter between specific neurons and as a hormone that modifies the properties of all the neurons. They will be able to trace these effects from the molecular mechanisms to the behavior produced. This characterization of the leech system will be the first complete description of the circuitry underlying any reproductive behavior, and it will show how the same molecule can function both to activate behaviors and help to produce them. The results will serve as a springboard to inspire similar characterizations of neural networks for reproductive behaviors in more complicated animals, including mammals. This project will offer unique training opportunities for students who will participate in every phase of this research project.