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在特定的神经元上形成突触 一个功能性的神经回路这些机制将在一个相对 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 甚至可以在它们开始增长之前就被识别出来， 突触的位置。此外，大量的是已知的形态 以及这些可识别神经元的生理特性，包括 许多基因在产生行为的过程中起着重要作用。实验将集中在 在两个定义明确的神经回路中发展连接：连接 在一对识别的运动神经元之间，这两个神经元都支配同一个神经元， 体壁中的肌肉，以及反射通路中的连接，包括 一个感觉受体，一个效应神经元，和一个小的中间层。 interneurons的数量 特异性的生成将使用以下方法进行处理 技术：空间关系的详细形态学检查 在神经元分支之间的接触是第一次建立;生理 记录从突触连接，因为他们形成;和消融的单一 神经元、神经元分支或外周靶点，以干扰神经元， 神经元发育的环境。这些实验将 确定在这个定义明确的系统中运行的机制。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， 他们在特定的时间足够接近;是否可能 突触目标对环境信号的反应方式， 尽管这两个神经元的行为 彼此独立;是否发生突触空间的竞争 在可能有资格在同一个神经元上形成突触的神经元之间; 一个神经元的外围目标是如何控制它将 接受;以及电活动是否对建立或 保持突触接触对其他物种的实验，包括高等动物 哺乳动物，已经表明这些相同的机制控制突触特异性， 在人类身上。胚胎水蛭神经系统的实验易处理性 使得研究机制如何相互作用以形成函数成为可能 在一个物种中的许多已识别的神经元之间的神经元回路， 从而揭示了功能性神经回路是如何在大脑中建立的， 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.