Behavioral relevance of active dendritic mechanisms of integration and plasticity

整合和可塑性活跃树突机制的行为相关性

• 批准号: 10112757
• 负责人: Daniel A Dombeck
• 金额: $ 51.54万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-16 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10112757
• 关键词: Action Potentials; Address; Alzheimer' s Disease; Amnesia; Animals; Applications Grants; Area; Back; Behavior; Behavioral; Behavioral Mechanisms; Brain; Calcium; Cells; Characteristics; Chemosensitization; Data; Dendrites; Disease; Environment; Epilepsy; Event; Frequencies; Functional Imaging; Functional disorder; Future; Genetic Techniques; Glutamates; Goals; Head; Hippocampus (Brain); In Vitro; Information Storage; Lead; Learning; Life; Location; Measurement; Mediating; Memory; Methods; Modeling; Mus; Neurons; Neurosciences Research; Optics; Pattern; Play; Preparation; Prevalence; Process; Research; Resolution; Retrieval; Role; Signal Transduction; Slice; Source; Spatial Behavior; Structure; Suggestion; Synapses; Synaptic plasticity; Testing; Time; Trees; Work; awake; base; experimental study; hippocampal pyramidal neuron; information model; information processing; novel; place fields; preference; presynaptic; regenerative; spatial memory; spatiotemporal; virtual environment; virtual reality; way finding

Project Summary/Abstract The dendritic trees of neurons in the brain's cortex conduct elemental brain functions such as information processing and learning. Research in brain slices has provided a wealth of information about the dendritic mechanisms that could be operating in behaving animals to integrate, and alter the strength of, synaptic inputs from presynaptic sources. Key among these mechanisms are back-propagating action potentials and nonlinear integration of synaptic inputs leading to dendritic spiking, which confer to the dendritic tree a host of local and global plasticity and signaling possibilities. Numerous alluring models of information processing and learning rules have arisen as a result of these in vitro findings, and supported by this R01, we have begun to determine which of these mechanisms are at work in awake, behaving animals. The present proposal leverages recent technical advances used and developed by the PI that enable functional imaging of calcium transients with single dendritic branch resolution and of glutamate input with synaptic scale resolution in the hippocampus of head-restrained mice performing spatial behaviors in a virtual-reality interface. Using these methods, the research proposed in this grant application will allow us to bridge two disconnected areas of neuroscience research: research characterizing the firing patterns and changes in firing patterns of hippocampal neurons during behavior, and research in reduced preparations investigating the mechanisms underlying firing and synaptic plasticity. Specifically, we aim to determine the behavioral relevance and synaptic basis of hippocampal dSpikes. This will allow testing of models of plasticity which have been developed based on in vitro data, across a wide range of parameter space, to finally establish which learning mechanisms are behaviorally relevant.

项目摘要/摘要 大脑皮层中的神经元树状结构树负责大脑的基本功能，如信息 处理和学习。对脑片的研究提供了关于树突的丰富信息 在动物的行为中整合和改变突触输入强度的机制 来自突触前来源。这些机制中的关键是反向传播的动作电位和非线性 突触输入的整合导致树突状尖峰，这赋予树突状树大量的局部和 全球可塑性和信号可能性。无数诱人的信息处理和学习模型 由于这些体外研究的结果，规则已经出现，并在R01的支持下，我们已经开始确定 这些机制中的哪一种在清醒的、行为正常的动物中起作用。本提案充分利用了最近的 PI使用和开发的技术进步，使钙瞬变能够通过 大鼠海马单树突分支分辨和谷氨酸输入与突触尺度分辨 头戴约束的小鼠在虚拟现实界面中执行空间行为。使用这些方法， 这项拨款申请中提出的研究将使我们能够在神经科学的两个互不相关的领域之间架起一座桥梁。 研究：研究海马神经元的放电模式和放电模式的变化 在行为过程中，并研究在减少准备调查潜在的机制，激发和 突触可塑性。具体地说，我们的目标是确定行为相关性和突触基础 海马dSpikes。这将允许测试基于 体外数据，跨越广泛的参数空间，最终确定哪些学习机制是 行为上相关的。