Modulation of Network Feedback Shifts the Locus of Rhythm Generation

中央模式产生器(CPG)网络控制重要的节律行为，如咀嚼、呼吸、 和运动。CPGS必须持续适应生理和环境挑战，通过 感官通路，以维持健康的功能。神经性CPG或其输入功能障碍 疾病或中风导致的损害改变了CPG的功能和适应性，从而降低了健康和质量 生活的一部分。CPG网络适应的一种方式是通过改变其活动的空间分布 各组成部分，如哺乳动物呼吸CPG活性沿脑干柱变化。然而，几乎没有什么是 已知感觉通路触发空间变化的细胞水平机制 CPG的分布，以及这种变化可能如何改变节奏产生的机制。感官 通路直接或通过激活投射神经元对CPG的输入来影响CPG。投射神经元活动， 这进一步受到来自其靶CPG的突触反馈的调节，决定了CPG的输出。CPG 反馈力度灵活，反馈可以链接不同的神经系统区域。因此，中央 这一假设是CPG反馈的感觉调节可以改变节律产生 轨迹和机构。小型无脊椎动物神经网络使人们能够深入了解网络的可塑性 由于具有良好连接的神经元较少，并且可以在 体外培养。在这项建议中，一种来自螃蟹(癌症)的体外口胃神经系统(STNS)制剂 北极熊)将提供对识别的感觉、咀嚼CPG、反馈和投射的特殊访问 神经元。不同咀嚼节律的感觉激活，识别的神经元和神经元的光灭活 分区、混合计算-生物网络以及本地和远程的独立操作 反馈神经元的突触作用将被用来识别细胞和突触控制机制 不同调制状态下的节律生成轨迹。人们期待着一种改变CPG的新机制 将确定空间分布，即CPG反馈强度的调制和合并 反馈到节奏生成中。进一步预测，以这种方式改变节奏产生轨迹是 调节感觉通路进入运动系统的新机制。更高的细胞级别 了解节律产生轨迹的动力学对于未来研究如何产生节律轨迹很重要 损伤或功能障碍可能会改变CPG的适应性。在一小本定义明确的书中确定新的原则 系统将指导对调节CPG的感觉和CPG反馈通路之间相互作用的研究 功能状态和功能障碍状态下较大神经系统的空间分布。此外，这一点 计划将为学生提供研究和网络机会，包括尖端经验 电生理技术、定量数据分析技能和口头和书面科学交流 技能，帮助填补了迈阿密大学对神经科学研究机会的大量未得到满足的需求。

Central pattern generator (CPG) networks control important rhythmic behaviors such as chewing, breathing, and locomotion. CPGs must continuously adapt to physiological and environmental challenges, conveyed via sensory pathways, to maintain healthy function. Dysfunction of CPGs or their inputs due to neurological disorders or stroke-induced damage alters CPG function and adaptability, which decreases health and quality of life. One way in which CPG networks adapt is through changes in the spatial distribution of their active components, such as mammalian respiratory CPG activity varying along a brainstem column. However, little is known about the cellular-level mechanisms by which sensory pathways trigger changes in the spatial distribution of CPGs, and how such changes may alter the mechanisms of rhythm generation. Sensory pathways influence CPGs directly or by activating projection neuron inputs to CPGs. Projection neuron activity, which is further regulated by synaptic feedback from their target CPGs, determines CPG output. CPG feedback strength is flexible, and feedback can link different nervous system regions. Thus, the central hypothesis of this proposal is that sensory modulation of CPG feedback can alter rhythm generation locus and mechanism. Small invertebrate neural networks have enabled much insight into network plasticity due to having fewer neurons with well-described connectivity, and complete CPGs that can be maintained in vitro. In this proposal, an in vitro stomatogastric nervous system (STNS) preparation from the crab (Cancer borealis) will provide exceptional access to identified sensory, chewing CPG, feedback, and projection neurons. Sensory activation of distinct chewing rhythms, photoinactivation of identified neurons and neuronal compartments, hybrid computational-biological networks, and independent manipulation of local and distant synaptic actions of a feedback neuron will be used to identify cellular and synaptic mechanisms controlling rhythm generation locus in different modulatory states. It is expected that a novel mechanism for altering CPG spatial distribution will be identified, namely modulation of CPG feedback strength and incorporation of this feedback into rhythm generation. It is further predicted that altering rhythm generation locus in this manner is a novel mechanism for regulating the access of sensory pathways to a motor system. An increased cellular-level understanding of the dynamics of rhythm generation locus is important for future investigation into how damage or dysfunction may change CPG adaptability. Identifying novel principles in a small well-defined system will guide studies of interactions between sensory and CPG feedback pathways that regulate CPG spatial distribution in larger nervous systems during both functional and dysfunctional states. Further, this proposal will provide research and networking opportunities for students, including experience in cutting-edge electrophysiological techniques, quantitative data analysis skills, and oral and written scientific communication skills, helping to fill a large, unmet demand for neuroscience research opportunities at Miami University.