REGULATION OF SPINAL INTERNEURON INPUT OUTPUT FUNCTIONS

该项目的长期目标是确定哺乳动物参与运动和姿势控制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已得到充分认识，正如神经元间兴奋性的变化可能是疾病或创伤引起的各种运动障碍的促成因素一样。但是关于中间神经元结构和功能的细节还缺乏，特别是关于下行控制系统的作用方式和细胞输入输出特性。这些空白是研究脊髓损伤影响和导致功能损伤的细胞/网络机制的重大障碍。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、受体和离子通道表达、树突结构和轴突投射方面存在显著的差异。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。我们建议在完整（未损伤）脊髓的细胞水平上对鉴定的中间神经元的结构和功能结构进行全面研究。我们将测试以下假设：1)树突结构和突触分布是决定突触电流相对数量的两个关键因素，从树突突触位置到达细胞体细胞并控制细胞放电（即输入-输出特性）；2)不同类别的腹角中间神经元受下行运动控制系统的不同支配，并显示独特的突触组织模式。这一综合建议将关注成年猫脊髓中各种定义明确的中间神经元，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。在树突结构和突触分布的意义上获得的新见解，以及对脊髓回路中中间神经元的整体细胞特性和组织的定义，将有助于为理解脊髓损伤对中间神经元的影响建立必要的基线。

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.