Modulation of Network Feedback Shifts the Locus of Rhythm Generation

网络反馈的调制改变了节奏生成的轨迹

• 批准号: 10515097
• 负责人: DAWN MARIE BLITZ
• 金额: $ 42.06万
• 依托单位: MIAMI UNIVERSITY OXFORD
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10515097
• 关键词: Afferent Neurons; Behavior; Biological; Biological Models; Brain Stem; Breathing; Cancer borealis; Communication; Congenital Disorders; Crabs; Crustacea; Data; Data Analyses; Deglutition; Distant; Electrophysiology (science); Feedback; Functional disorder; Future; Generations; Health; Hybrids; In Vitro; Injury; Interneurons; Invertebrates; Investigation; Lead; Link; Location; Locomotion; Manuscripts; Mastication; Mentors; Metabolic; Motor; Mus; Nature; Nervous system structure; Neurons; Neurosciences Research; Oral; Output; Pathway interactions; Periodicity; Physiological; Population; Preparation; Proprioceptor; Quality of life; Regulation; Research; Sensory; Site; Spatial Distribution; Stimulus; Stomach; Stroke; Students; Synapses; Synaptic Transmission; System; Techniques; Testing; Training; Universities; Walking; Work; base; central pattern generator; computer studies; doctoral student; experience; extracellular; feeding; flexibility; innovation; insight; nervous system disorder; neural network; novel; outreach; recruit; respiratory; skills; symposium; undergraduate student

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.

中央模式发生器（CPG）网络控制重要的节律行为，如咀嚼，呼吸， 和运动。CPG必须不断适应生理和环境挑战，通过 感官通路，以维持健康的功能。由于神经系统疾病引起的CPG或其输入功能障碍 疾病或中风引起的损伤改变CPG功能和适应性，从而降低健康和质量 生命CPG网络适应的一种方式是通过改变它们的活性蛋白的空间分布， 成分，如哺乳动物呼吸CPG活性沿脑干柱沿着变化。然而， 已知细胞水平的机制，通过该机制，感觉通路触发空间的变化， CPG的分布，以及这些变化如何改变节律产生的机制。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， 其进一步由来自其目标CPG的突触反馈调节，确定CPG输出。CPG 反馈的强度是灵活的，反馈可以连接不同的神经系统区域。因此，中央 该建议假设是CPG反馈的感觉调制可以改变节律产生 轨迹与机制小型无脊椎动物神经网络使人们对网络可塑性有了更深入的了解 由于具有较少的具有良好描述的连接性的神经元，以及可以在 体外在这项建议中，在体外口胃神经系统（STNS）制备从螃蟹（癌症）， borealis）将提供特殊的访问识别的感觉，咀嚼CPG，反馈和投影 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失活， 隔间，混合计算-生物网络，以及独立操纵本地和远程 反馈神经元的突触动作将用于识别控制神经元的细胞和突触机制。 不同调节状态下的节律产生轨迹。预期改变CPG的新机制 将识别空间分布，即CPG反馈强度的调制和该反馈强度的并入。 反馈到节奏生成中。进一步预测，以这种方式改变节律产生位点是一种有效的方法。 调节感觉通路进入运动系统的新机制。增加的细胞水平 了解节奏产生轨迹的动力学对于将来研究如何产生节奏是很重要的。 损伤或功能障碍可改变CPG适应性。在一个小的定义明确的 该系统将指导对调节CPG的感觉和CPG反馈通路之间相互作用的研究 空间分布在较大的神经系统在功能和功能障碍状态。此外，这 该提案将为学生提供研究和网络机会，包括尖端技术的经验。 电生理技术，定量数据分析技能，口头和书面科学交流 技能，帮助填补了大量的，未满足的需求神经科学研究的机会，在迈阿密大学。