STATE DEPENDENT COORDINATION OF RHYTHMIC NEURAL CIRCUITS

这项工作的长期目标是了解，在细胞 水平，中枢神经系统如何选择和产生神经元 协调运动背后的活动模式。这包括 了解不同但行为相关的活动 神经元回路被协调以产生复杂的行为。这项工作 专注于节奏运动回路，例如那些潜在的 运动、呼吸和咀嚼食物。定义明确的模型 系统，螃蟹的胃神经系统将用于 这个目的。以前的工作已经证明，同样的组织 个体节律运动程序的生成是由 在所有的无脊椎动物和脊椎动物中。相对简单的模型系统 比脊椎动物脊柱中的类似系统更容易获得 脊髓和脑干因此，它们对于细胞分析更有用 神经元回路。这项建议旨在扩大以往的研究， 进行细胞分析，研究行为上的活动， 相关的神经回路是协调的。工作假设是， 相关的、有节奏的神经元回路之间的协调 依赖于国家。工作假设是， 有节奏的神经回路之间的联系 依赖。这一假设将通过检查协调 在胃运动模式的不同版本之间， 胃神经节中的胃神经回路和幽门神经回路。 将审查以下四个具体目标。第一：电路间 不同形式的胃磨之间的相互作用不同 和幽门运动程序第二：有不同的细胞 这些不同的电路间相互作用的机制。第三： 这两者之间的相互作用及其功能后果 通过局部释放和循环， 神经调质第四，从这两个回路到 影响它们的投射神经元使这些回路能够 调节和协调这些投射神经元的活动。这些 目的将使用细胞电生理学研究 方法，结合一个名为动态夹的计算机程序， 能够将人工突触原位注入任何神经元 在神经元引起的突触输入被移除之后。的 电生理学实验将包括四个同时进行的 细胞内记录加上多个细胞外记录。这 能够全面记录所有电路活动， 操纵所研究电路的所有成员的能力。尽管 事实上，所有动物的大多数复杂行为都是由 不同运动回路之间的相互作用，没有现有的 运动回路协调的生理模型 水平因此，这些拟议的研究将提供一个有用的 运动模式实验和计算模型模板 协调在数量上较大和技术上较难进入的 脊椎动物中枢神经系统

The long-range goal of this work is to understand, at the cellular level, how the central nervous system selects and generates the neuronal activity patterns underlying coordinated movements. This includes understanding how the activity of distinct but behaviorally-related neuronal circuits is coordinated to generate complex behavior. This work focusses on rhythmic motor circuits, such as those underlying locomotion, respiration and the chewing of food. A well-defined model system, the stomatogastric nervous system of the crab will be used for this purpose. Previous work has documented that the same organizing principals underlie the generation of individual rhythmic motor programs in all invertebrates and vertebrates. Relatively simple model systems are more accessible than the comparable systems in the vertebrate spinal cord and brainstem. Thus, they are more useful for a cellular analysis of neuronal circuits. This proposal aims to extend previous studies by performing a cellular analysis of how the activity of behaviorally- related neuronal circuits is coordinated. The working hypotheses is that the coordination between related, rhythmically active neuronal circuits is state-dependent. The working hypothesis is that the coordination between related, rhythmically active neuronal circuits is state- dependent. This hypothesis will be tested by examining the coordination between different versions of the motor patterns produced by the gastric mill and pyloric neural circuits in the crab stomatogastric ganglion. The following four specific aims will be examined. First: inter-circuit interactions are different between distinct forms of the gastric mill and pyloric motor programs. Second: there are distinct cellular mechanisms subserving these different inter-circuit interactions. Third: the interactions, and their functional consequences, between these two circuits are modified by locally-released and circulating neuromodulators. Fourth: patterned feedback from these two circuits onto the projection neurons that influence them enables these circuits to regulate and coordinate the activity of these projection neurons. These aims will be investigated using a cellular electrophysiological approach, combined with a computer program called the Dynamic Clamp that enables the injection of an artificial synapse, in situ, into any neuron after the neuronally-elicited synaptic input is removed. The electrophysiological experiments will include four simultaneous intracellular recordings plus multiple extracellular recordings. This enables a comprehensive recording of all circuit activity, and the ability to manipulate all members of the studied circuits. Despite the fact that most complex behaviors, in all animals, result from interactions between distinct motor circuits, there are no existing physiological models of motor circuit coordination at the cellular level. Consequently, these proposed studies will provide a useful template for both experimental and computational models of motor pattern coordination in the numerically larger and technically less accessible vertebrate central nervous system.