Synaptic Integration in Radial Oblique dendrites

径向倾斜树突中的突触整合

• 批准号: 7194145
• 负责人: Sonia Gasparini
• 金额: $ 31.14万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7194145
• 关键词: Acetylcholine; Brain; Caliber; Cations; Cells; Characteristics; Chromosome Pairing; Computer information processing; Dendrites; Dependence; Excitatory Postsynaptic Potentials; Gated Ion Channel; Glutamate Receptor; Hippocampus (Brain); Ions; Membrane; Morphology; Neuromodulator; Neurons; Norepinephrine; Numbers; Optics; Output; Patch-Clamp Techniques; Pattern; Process; Production; Property; Radial; Relative (related person); Research Proposals; Serotonin; Shapes; Site; Stimulus; Synapses; Techniques; Testing; Time; design; extracellular; hippocampal pyramidal neuron; optical imaging; patch clamp; research study; response; voltage

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.

描述（由申请人提供）：本研究计划的总体目标是建立控制传入突触信息的树突处理的机制。在大多数CNS神经元中，传入的突触输入广泛分布在树突分支上，这些树突分支在形态上和电学上都很复杂，并且在这些树突中，成千上万的兴奋性和抑制性突触输入混合在一起以产生相干的输出响应。在海马CA1区锥体神经元中，85%的兴奋性突触输入由放射状斜树突接收。这些是相对短的，小直径的二级分支的主树突干的形态表明，他们可能提供了一个有利的网站高度非线性形式的突触处理。目前，人们对这些树突的活动特性或在其上形成的突触的特性知之甚少。我们建议测试中心的假设，即：斜树突和突触上形成的特定属性提供CA1神经元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突触内电压门控离子通道的可用性。我们设计了实验，使用各种树突状全细胞膜片钳和先进的光学记录技术，以确定1）位于这些分支的电压门控离子通道的类型和性质，2）到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）生理上如何相关的通道调节可以产生不同形式的突触处理，同时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应该能让我们更好地理解中枢神经元中的信息处理过程，从而对正常和病理性大脑功能有更基本的理解。