DEVELOPMENT OF NEURONAL CIRCUITS FOR SIMPLE BEHAVIORS

这项研究的目的是了解神经元是如何发育的 在特定神经元上形成突触，形成功能神经元 巡回赛。这些机制将在一个相对简单的神经学中研究 药用水蛭的系统，因为它的许多神经元可以 甚至在它们开始增长之前就确定了，这将是 突触的位置。此外，人们还知道很多关于 这些可识别神经元的形态和生理特性， 包括他们中的许多人在产生行为方面所起的作用。 实验将集中在两口井中的连接发展- 定义神经回路：一对已识别的神经回路之间的连接 运动神经元，两者都支配着身体壁中的同一块肌肉， 以反射路径的方式连接，包括感官 感受器、效应神经元和少量的介入层 中间神经元。 专一性的产生将使用以下方法进行探讨 技术：对空间的详细形态检查 神经分支之间的关系，因为接触是第一 已建立的；来自突触连接的生理记录 它们的形成；单个神经元、神经元分支的消融或 外周靶点，扰乱神经元的环境 正在发展中。这些实验将确定哪些机制是 在这个定义明确的系统中运作。例如，我们将测试是否 神经元与它们所在的任何其他神经元形成突触 在特定时间足够接近；是否潜在的突触 目标对环境信号的反应方式使他们的 分支紧密相连，即使这两个神经元 相互独立；是否会出现突触竞争 神经元之间的空间，可能有资格形成突触 同样的神经元；神经元的外周目标如何控制 它将接受的突触；以及电活动对 建立或维持突触联系的。在其他设备上进行实验 包括高等哺乳动物在内的物种已经表明，这些 在人类中，机制控制突触的特异性。实验性的 胚胎水蛭神经系统的易操纵性使其有可能 研究这些机制是如何相互作用形成功能神经元回路的 在同一物种中的许多已识别的神经元中，从而 阐明在我们的大脑中功能神经元回路是如何建立的 自己的神经系统。

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 path way 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 he 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.