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

基本信息

批准号：
8722038
负责人：
Daniel A Dombeck
金额：
$ 38.61万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-16 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8722038
关键词：
Accounting Action Potentials Affect Alzheimer&apos s Disease Amnesia Animals Applications Grants Area Auditory Back Behavior Behavioral Brain Brain region Calcium Cells Characteristics Conflict (Psychology)Cues Data Dendrites Dendritic Cells Development Disease Effectiveness Environment Epilepsy Fire - disasters Functional Imaging Functional disorder Genetic Techniques Goals Head Hippocampus (Brain)Image In Vitro Individual Information Storage Invaded Learning Life Location Measures Mediating Memory Modeling Mus Neurons Neurosciences Research Optics Pattern Preparation Process Research Research Methodology Resolution Retrieval Rodent Signal Induction Signal Transduction Slice Source Spatial Behavior Stream Structure Synapses System Testing Trees Visuospatial Work awake base hippocampal pyramidal neuron information processing neuronal cell body presynaptic public health relevance research study virtual reality way finding

项目摘要

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.

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，例如信息处理和学习。对大脑切片的研究提供了有关树突机制的大量信息，这些机制可能在行为动物中发挥作用，整合并改变来自突触前来源的突触输入的强度。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，这赋予树突树许多局部和全局信号传导的可能性。这些体外研究结果催生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些机制在清醒、有行为的动物中发挥作用。本提案利用了 PI 开发的最新技术进展，能够对在虚拟现实界面中执行空间行为的头部受限小鼠的海马体中的钙瞬变进行亚细胞分辨率的功能成像。使用这些方法，本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互不相关的领域：研究行为啮齿类动物海马神经元的放电模式，以及研究这些细胞的放电和可塑性机制的实验。减少准备工作。具体来说，我们的目标是确定海马 bAP 和 dSpike 基本树突机制的行为相关性。这将允许在广泛的参数空间中测试基于体外数据开发的可塑性模型，最终确定哪些学习机制与行为相关。