Synaptic Integration in Radial Oblique dendrites

描述（由申请人提供）：本研究计划的总体目标是建立控制树突处理传入突触信息的机制。在大多数中枢神经系统神经元中，传入的突触输入广泛分布在形态和电性复杂的树突上，正是在这些树突中，成千上万的兴奋性和抑制性突触输入混合在一起，产生连贯的输出反应。在海马CA1锥体神经元中，85%的兴奋性突触输入由径向斜树突接收。这些是相对较短的，直径较小的次级分支，从主要的树突主干上，其形态表明它们可能为高度非线性形式的突触加工提供了一个有利的位置。目前，人们对这些树突的活性特性以及在树突上形成的突触的特性所知甚少。我们拟验证以下中心假设：斜树突的特定特性及其上形成的突触为CA1神经元提供了处理突触输入的多种模式。决定这些细胞中突触整合形式的关键因素应该是输入本身的时空方面和斜肌内电压门控离子通道的可用性。我们设计了实验，使用各种树突全细胞膜片钳和先进的光学记录技术，以确定1)位于这些分支中的电压门控离子通道的类型和性质，2)对分支的突触输入的性质，3)突触输入和活动通道如何精确地相互作用以形成分支内的整合，以及4)生理相关的通道调制如何产生不同形式的突触处理。一直试图将这些发现与海马体自然发生的功能状态联系起来。这些实验产生的信息将使我们对中枢神经元的信息处理过程有更深入的了解，从而对正常和病理大脑功能有更基本的了解。

DESCRIPTION (provided by applicant): The general objectives of this research proposal are to establish the mechanisms that control the dendritic processing of incoming synaptic information. In most CNS neurons, incoming synaptic inputs are widely distributed across dendritic arborizations that are both morphologically and electrically complicated and it is in these dendrites that tens of thousands of excitatory and inhibitory synaptic inputs are blended together to generate a coherent output response. In hippocampal CA1 pyramidal neurons, 85% of excitatory synaptic input is received by radial oblique dendrites. These are relatively short, small diameter secondary branches off the main dendrite trunk whose morphology suggests they might provide a favorable site for highly non-linear forms of synaptic processing. At present very little is known about the active properties of these dendrites or of the properties of the synapses that are formed on them. We propose to test the central hypotheses that: specific properties of oblique dendrites and the synapses formed on them provide CA1 neurons with multiple modes of processing synaptic input. The key players in determining the form of synaptic integration in these cells should be both the spatio-temporal aspects of the input itself and the availability of the voltage-gated ion channels within the obliques. We have designed experiments using a variety of dendritic whole-cell patch-clamp and advanced optical recording techniques to determine 1) the types and properties of voltage-gated ion channels located in these branches, 2) the properties of the synaptic inputs to the branches 3) precisely how synaptic input and active channels interact to shape integration within the branches and 4) how physiologically-relevant channel modulation can produce different forms of synaptic processing, all the while trying to relate the findings to the naturally occurring functional states of the hippocampus. The information produced by these experiments should provide us with a greater understanding of how information processing proceeds in central neurons and therefore a more fundamental understanding of both normal and pathological brain functioning.