Motor Circuit Modulation and its Regulation

项目总结 该项目的长期目标是在细胞水平上了解中央 神经系统选择并产生运动背后的神经元活动模式。 具体地说，该项目侧重于确定电机电路固有的灵活性，即 表达是对来自感觉神经元、激素和调节剂的输入的反应 投射神经元。这包括确定潜在的细胞机制 前述电路灵活性。这项工作的重点是节奏活跃的马达电路，例如 那些潜在的行走、呼吸和咀嚼。一个定义良好的小模型系统，螃蟹 口胃神经系统，将被使用。先前的研究表明，同样的一般情况下 原则是所有动物产生节奏性运动程序的基础。这项提议旨在 通过确定元调制的作用(调制 调节作用)、感觉反馈和共同传递 蟹口胃神经系统中明确的胃磨(咀嚼)运动回路。四 假设将被检验：(1)由不同的CPG电路产生的可比较的运动模式 对荷尔蒙输入和感觉输入的反应不同；(2)多肽荷尔蒙的不同 将相同的感觉(本体感受器)输入门到由 不同的CPG回路；(3)相同的神经调节剂作用于运动系统的多个水平， (4)GABA能共传递对肽能调制有调节作用。这些研究 将使用电生理和药理学方法来监测和 操纵投射神经元、环路神经元、运动神经元、感觉神经元的活动 和肌肉纤维。一种名为动态夹具的计算机程序将被用来注入逼真 将不同版本的突触电流和离子电流转化为单个神经元。口胃系统是 少数几个生物系统，其中详细的细胞内分析和操作 神经元网络活动，在已识别的神经元和肌肉的水平上是可能的。因此， 拟议的研究将为理解可比事件提供有价值的模板 在数量上更大且更难接近的哺乳动物中枢神经系统。它还将促进 了解由于以下事件而导致的感觉和运动功能障碍 脊髓损伤和中风。项目叙事 拟议的研究将提供一个细胞水平的模型生物系统来理解 在数量更大和更难接近的哺乳动物中枢神经中发生的类似事件 系统。这包括对感觉和运动的功能后果的洞察 由于脊髓损伤和中风等事件而导致的功能障碍 下行调节投射和/或感觉反馈受损或其行为受到损害 被更改了。

PROJECT SUMMARY The long-term goals of this project are to understand, at the cellular level, how the central nervous system selects and generates the neuronal activity patterns underlying movement. Specifically, this project focuses on determining the flexibility inherent in motor circuits that is expressed in response to input they receive from sensory neurons, hormones and modulatory projection neurons. This includes determining the cellular mechanisms underlying the aforementioned circuit flexibility. This work focuses on rhythmically active motor circuits, such as those underlying walking, breathing, and chewing. A well-defined small model system, the crab stomatogastric nervous system, will be used. Previous work has shown that the same general principles underlie the generation of rhythmic motor programs in all animals. This proposal aims to extend previous work by determining the roles of metamodulation (modulation of a modulatory action), sensory feedback and cotransmission on motor pattern generation using the well-defined gastric mill (chewing) motor circuit in the crab stomatogastric nervous system. Four hypotheses will be tested: (1) Comparable motor patterns generated by distinct CPG circuits respond differently to a hormonal input and a sensory input; (2) a peptide hormone differentially gates the same sensory (proprioceptor) input to two comparable motor patterns generated by distinct CPG circuits; (3) the same neuromodulator acts at multiple levels of a motor system, and (4) peptidergic modulation can be regulated by GABAergic cotransmission. These studies will be done using electrophysiological and pharmacological approaches to monitor and manipulate the activity of projection neurons, circuit neurons, motor neurons, sensory neurons and muscle fibers. A computer program called the Dynamic Clamp will be used to inject realistic versions of synaptic and ionic currents into single neurons. The stomatogastric system is one of the few biological systems in which a detailed intracellular analysis and manipulation of neuronal network activity, at the level of identified neurons and muscles, is possible. Thus, the proposed studies will provide a valuable template for understanding comparable events in the numerically larger and less accessible mammalian central nervous system. It will also facilitate understanding the sensory and motor dysfunctions that occur as a result of events such as spinal cord injury and stroke. PROJECT NARRATIVE The proposed studies will provide a cellular-level model biological system for understanding comparable events in the numerically larger and less accessible mammalian central nervous system. This includes providing insight into the functional consequences of sensory and motor dysfunctions that occur as a result of events such as spinal cord injury and stroke, when descending modulatory projections and or sensory feedback is compromised or their actions are altered.