Development of Neuronal Circuits for Simple Behaviors

描述(由申请人提供)：本研究的目的是 了解发育中的神经元如何形成突触到特定的神经元上形成 一种功能正常的神经元回路。我们将对这些机制进行相对深入的研究。 简单的神经系统--药用水蛭的神经系统--因为它的许多神经元 甚至在他们开始发展进程之前就可以识别 突触的位置。此外，有关形态的知识也很多。 以及这些可识别神经元的生理特性，包括 他们中的许多人在产生行为方面发挥了作用。实验将集中在 两个明确定义的神经回路中的连接的发展：连接 在一对已识别的运动神经元之间，这两个神经元都支配着相同的 体壁上的肌肉，以及反射通路中的连接，包括 一个感觉感受器，一个效应器神经元，以及一个小的 中间神经元的数量。 专一性的产生将使用以下方法进行探讨 技术：空间关系的详细形态检查 第一次建立联系时在神经元分支之间；生理学的 形成突触连接时的录音；以及消融单个 神经元、神经元分支或外围靶点，以扰乱 神经元发育的环境。这些实验将 确定哪些机制在这个定义明确的系统中运行。为 例如，我们将测试神经元是否与任何其他神经元形成突触 它们在特定时间足够接近；是否有潜力 突触靶标对环境信号的反应方式使它们的 分支紧密相连，即使这两个神经元 相互独立；是否存在对突触空间的竞争 可能有资格在同一神经元上形成突触的神经元之间； 神经元的外周靶点如何控制它的突触 接受；以及电活动是否对建立或 维持突触联系。在其他物种上的实验，包括更高的 哺乳动物认为，这些相同的机制控制突触的专一性 在人类身上。胚胎水蚤神经系统的实验可控性 使我们能够研究这些机制如何相互作用以形成功能 在同一物种中的许多已识别神经元之间的神经元回路， 从而阐明了脑内功能神经元回路是如何建立的。 我们自己的神经系统。

DESCRIPTION (provided by applicant): The objective of this research is to understand how developing neurons form synapses onto particular neurons to form a functional neuronal circuit. These mechanisms will be studied in a relatively simple nervous system--that of the medicinal leech--because many of its neurons can be identified even before they start to grow the processes that will be the sites of synapses. In addition, a great deal is known about the morphological and physiological properties of these identifiable neurons, including the role that many of them play in generating behavior. Experiments will focus on the development of connections in two well-defined neural circuits: the connection between a pair of identified motor neurons, both of which innervate the same muscles in the body wall, and the connections in a reflex pathway that includes a sensory receptor, an effector neuron, and an intervening layer of a small number of interneurons. The generation of specificity will be approached using the following techniques: detailed morphological examinations of the spatial relationship between neuronal branches as the contacts are first established; physiological recordings from the synaptic connections as they form; and ablations of single neurons, of branches of neurons, or of peripheral targets, to perturb the environment in which the neurons are developing. These experiments will determine which mechanisms are operating in this well-defined system. For example, we will test whether neurons form synapses with any other neurons to which they are sufficiently close at a particular time; whether potential synaptic targets respond to environmental signals in a way that puts their branches in close proximity, even though the two neurons are behaving independently of one another; whether competition occurs for synaptic space between neurons that might be eligible to form synapses onto the same neuron; how the peripheral target of a neuron can control which synapses it will accept; and whether electrical activity is important for establishing or maintaining synaptic contacts. Experiments on other species, including higher mammals, have suggested that these same mechanisms control synaptic specificity in humans. The experimental tractability of the embryonic leech nervous system makes it possible to examine how the mechanisms interact to form a functional neuronal circuit among a number of identified neurons in a single species, thereby shedding light on how functional neuronal circuits are established in our own nervous system.