MECHANISMS OF MAMMALIAN NEURONAL INTEGRATION

描述（改编自申请人摘要） 这个项目的长期目标是了解 脊髓整合功能的机制和突触学 参与哺乳动物运动控制的神经元。现在已被接受 树突，远不是神经元功能的被动参与者， 具有内在的活性特性，可以显著影响 信息传输。因此树突和索马一样， 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 正常整合功能的关键因素，也可能在以下方面发挥作用： 神经元对损伤的反应，研究人员试图了解 这些通道的亚细胞组织，特别是在索马和 树突他们假设，表达和亚细胞 电压门控通道在脊髓神经元中的定位是类型特异性的， 就克隆的通道亚基的功能已知而言， 具有神经元放电的特定方面和/或具有兴奋性变化， 发生于轴突切断术后。他们将使用新的组合， 电生理学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 体内各种生理学鉴定的脊髓神经元类别，以及 将离子通道表达和分布模式与已知的膜 和神经元的放电特性。他们还将决定是否或 不是某些类型的电压门控离子通道与 与某些类型的突触相邻，以及3）确定表达和 电压门控离子通道的分布改变， 运动神经元，以检验假设，即对轴突切断的反应将涉及一个 电压门控离子通道向树突的再分布。通过允许他们 将电压门控离子通道分布的知识与它们的 神经元结构，突触学和受体组织的知识， 结果将提供前所未有的信息和深入了解分子 和节段运动神经元中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.