REGULATION OF SPINAL INTERNEURON INPUT OUTPUT FUNCTIONS

脊髓中间神经元输入输出功能的调节

• 批准号: 6394377
• 负责人: Robert E Fyffe
• 金额: $ 28.97万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-28 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394377
• 关键词: cats; chordate locomotion; computational neuroscience; computer simulation; dendrites; electron microscopy; electrophysiology; immunocytochemistry; interneurons; neuroregulation; posture; spinal nerves; synapses

The long-term goal of this project is to define the structural and functional properties that underly the integrative functions and general excitability of spinal cord interneurons involved in the control of locomotion and posture in mammals. Their pivotal role(s) in motor control are well recognized, as is the notion that changes in interneuron excitability are likely to be contributing factors in a variety of locomotor disturbances consequent to disease or trauma. But the details of interneuron structure and function are lacking, particularly concerning the mode of action of descending control systems and cellular input- output characteristics. These gaps are a significant impediment in studies of the effects of spinal injury and the cellular/network mechanisms that underlie the resulting functional impairments. Although different classes of interneurons share some common features, there is striking diversity in terms of synaptology, receptor and ion channel expression, dendritic structure, and axonal projections. It is our hypothesis that these differences are functionally meaningful, and as a consequence they provide different classes of cells with a broad repertoire of potential responses to injury. We propose a comprehensive study of the structural and functional architecture of identified interneurons at the cellular level in the intact (uninjured) spinal cord. We will test the hypotheses that 1) dendritic structure and synapse distribution are two of the key factors that determine the relative amount of synaptic current, from dendritic synaptic sites, that reaches the cell soma and controls cell firing (i.e. input-output properties), and 2) that different classes of ventral horn interneurons are differentially innervated by descending motor control systems and display unique patterns of synaptic organization. This integrated proposal will focus on various well-defined interneurons in the adult cat spinal cord and will employ powerful combinations of quantitative light and electron microscopical, immunocytochemical, electrophysiological, and computational approaches. The new insights to be gained on the significance of dendritic structure and synaptic distribution, and definition of the overall cellular properties and organization of interneurons in spinal cord circuits, will help to establish the essential baseline for understanding the effects of spinal cord injury on interneurons.

该项目的长期目标是确定哺乳动物运动和姿势控制中涉及的脊髓中间神经元的整合功能和一般兴奋性的结构和功能特性。 它们在运动控制中的关键作用是公认的，正如这样的概念，即中间神经元兴奋性的变化可能是疾病或创伤后各种运动障碍的促成因素。 但缺乏中间神经元结构和功能的细节，特别是关于下行控制系统的作用模式和细胞输入输出特性。 这些缺口是研究脊髓损伤的影响和导致功能障碍的细胞/网络机制的重要障碍。虽然不同类别的中间神经元有一些共同的特点，有显着的多样性，突触，受体和离子通道的表达，树突状结构，轴突投射。 我们的假设是，这些差异在功能上是有意义的，因此它们为不同类别的细胞提供了广泛的潜在损伤反应库。 我们提出了一个全面的研究，在细胞水平上的完整（未受伤）的脊髓中确定的中间神经元的结构和功能架构。 我们将检验以下假设：1）树突结构和突触分布是决定从树突突触部位到达细胞索马并控制细胞放电的突触电流的相对量的两个关键因素（即输入-输出特性），和2）不同种类的腹角中间神经元受到下行运动控制系统的不同支配，并显示出独特的突触模式。organization. 这个综合的建议将集中在各种明确的interneurons在成年猫脊髓，并将采用强大的组合，定量光和电子显微镜，免疫细胞化学，电生理和计算方法。 树突状结构和突触分布的意义上获得的新的见解，并在脊髓回路中的整体细胞特性和组织的interneurons的定义，将有助于建立基本的基线了解脊髓损伤对interneurons的影响。