Behavioral relevance of active dendritic mechanisms of integration and plasticity

描述（由申请人提供）：大脑皮层中神经元的树突树执行基本的大脑功能，如信息处理和学习。对大脑切片的研究提供了大量关于树突机制的信息，这些机制可能在行为动物中起作用，以整合来自突触前来源的突触输入并改变其强度。这些机制中的关键是反向传播动作电位和突触输入的非线性整合，导致树突尖峰，这赋予树突树一系列局部和全局信号传导的可能性。由于这些体外发现，出现了许多诱人的信息处理和学习模型，但目前几乎不知道这些机制中的哪一种在清醒的行为动物中起作用。本提案利用了PI开发的最新技术进展，该技术进展使在虚拟现实界面中执行空间行为的头部受限小鼠的海马中具有亚细胞分辨率的钙瞬变的功能成像成为可能。使用这些方法，在这项拨款申请中提出的研究将使我们能够弥合神经科学研究的两个不相关领域：研究表现出行为啮齿动物海马神经元的放电模式，以及研究这些细胞在减少准备中的放电和可塑性机制的实验。具体而言，我们的目标是确定行为相关的基本树突状机制的bAP和dSpikes在海马。这将允许测试基于体外数据开发的可塑性模型，跨越广泛的参数空间，最终确定哪些学习机制与行为相关。

DESCRIPTION (provided by applicant): 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 dendriti tree a host of local and global signaling possibilities. Numerous alluring models of information processing and learning have arisen as a result of these in vitro findings, but currently almost nothing is known about which of these mechanisms are at work in awake, behaving animals. The present proposal leverages recent technical advances developed by the PI that enable functional imaging of calcium transients with sub-cellular 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: studies that characterize the firing patterns of hippocampal neurons in behaving rodents, and experiments that study the mechanisms underlying firing and plasticity in these cells in reduced preparations. Specifically, we aim to determine the behavioral relevance of the fundamental dendritic mechanisms of bAPs and dSpikes in the hippocampus. 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.