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: 6650749
• 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/6650749
• 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定义涉及哺乳动物运动和姿势的脊髓中间神经元的综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得到了充分认识，这一观点是，间神经元兴奋性的变化很可能是导致疾病或创伤引起的多种运动障碍的因素。 但是缺乏中间神经元结构和功能的细节，尤其是关于下降控制系统和细胞输出特征的作用方式。 这些间隙是研究脊柱损伤的影响以及所产生功能障碍的基础的细胞/网络机制的重要障碍。尽管不同类别的中间神经元具有一些共同的特征，但在突触学，受体和离子通道表达，树突结构和轴突投影方面，多样性具有惊人的多样性。 我们的假设是这些差异在功能上是有意义的，因此它们提供了不同类别的细胞，并具有广泛的对伤害的潜在反应。 我们提出了一项全面研究，对完整（未受伤）脊髓中细胞水平上鉴定的中间神经元的结构和功能结构。 我们将测试以下假设：1）树突结构和突触分布是确定突触电流相对量的两个关键因素，这些因素是从树突突触部位到达细胞躯体并控制细胞发射并控制腹膜跨膜间膜的不同类别的综合模式和构成独特的模式的不同类别。 该综合建议将集中在成年猫脊髓中各种定义明确的中间神经元上，并将采用定量光和电子显微镜，免疫细胞化学，电生理和计算方法的强大组合。 关于树突状结构和突触分布的重要性以及脊髓回路中神经元的整体细胞特性和组织的定义，将获得新的见解，这将有助于确定理解脊髓损伤对中间神经元的影响的基准。