MECHANISMS OF MAMMALIAN NEURONAL INTEGRATION

描述(改编自申请人的摘要) 这个项目持续的长期目标是理解 脊髓整合功能的机制和突触学研究 参与哺乳动物运动控制的神经元。现在它被接受了 树突，远远不是神经元功能的被动参与者， 具有内在的活性属性，可以显著影响 信息的传递。因此，树突和胞体一样， 可能显示了广泛的电压门控离子通道 这些活跃的属性。因为电压门控通道的分布是 是正常综合功能的关键因素，也可能在 神经元对损伤的反应，研究人员试图理解 这些通道的亚细胞组织，特别是在胞体和 树枝状结构。他们假设，无论是表达还是亚细胞 电压门控通道在脊髓神经元中的定位是特定类型的， 就已知的克隆通道亚基的功能而言，它们是相关的 神经元放电的特定方面和/或兴奋性变化 发生于对轴突切断的反应。他们将使用新颖的组合 电生理和免疫组织化学方法1)证明 电压门控离子通道的表达和亚细胞定位 体内各种生理鉴定的脊髓神经元类别，以及 离子通道表达和分布模式与已知细胞膜的关系 以及神经元的放电特性。他们还将决定是否或 不是某些类别的电压门控离子通道与或 与某些类型的突触相邻，以及3)决定表达和 轴突切断后电压门控离子通道的分布发生改变 运动神经元用于测试对轴突切断的反应将涉及 电压门控离子通道向枝晶的重新分布。通过允许他们 将电压门控离子通道分布的知识与其 关于神经元结构、突触和受体组织的知识， 结果将提供前所未有的信息和对分子的洞察 节段性运动神经元的神经元特性的结构基础， 中间神经元和投射神经元。

DESCRIPTION (adapted from applicant's abstract) The continuing long term goal of this project is to understand the intrinsic mechanisms and synaptology underlying the integrative functions of spinal cord neurons involved in the control of locomotion in mammals. It is now accepted that dendrites, far from being passive participants in neuronal function, possess intrinsic active properties that can significantly influence the transmission of information. Therefore the dendrites, as well as the soma, likely display a broad complement of voltage-gated ion channels that underlie these active properties. Because the distribution of voltage-gated channels is a critical factor for normal integrative function, and may also play a role in the reaction of neurons to injury, the investigator seeks to understand the subcellular organization of these channels, particularly in the soma and dendrites. They hypothesize that both the expression and subcellular localization of voltage-gated channels in spinal neurons are type specific and, insofar as the function of cloned channel subunits is known, are correlated with specific aspects of neuronal firing and/or with excitability changes that occur in response to axotomy. They will use novel combinations of electrophysiological and immunohistochemical approaches 1) to demonstrate the expression and subcellular localization of voltage gated ion channels in various physiologically identified classes of spinal neuron in vivo, and to correlate ion channel expression and distribution patterns with known membrane and firing properties of the neurons. They will also 2) determine whether or not certain classes of voltage gated ion channels are associated with or are adjacent to certain types of synapses, and 3) determine how the expression and distribution of voltage gated ions channels is altered in axotomized motoneurons to test the hypothesis that the response to axotomy will involve a redistribution of voltage gated ion channels to the dendrites. By allowing them to integrate knowledge of voltage gated ion channel distribution with their knowledge of neuron structure, synaptology, and receptor organization, the results will provide unprecedented information and insight into the molecular and structural basis of neuronal properties in segmental motoneurons, interneurons, and projection neurons.