Circuit Mechanisms of Information Processing and Storage in Brain Slices

 描述（由申请人提供）：神经系统通过产生和转换稀疏分布在大量互连神经元中的电活动模式来运行。这些模式编码的信息最终来自感官输入。在这个框架内，神经系统对信息的存储可以被看作是一个印记过程，它使网络能够重现先前经验存储的活动模式。模式完成的规范操作是神经科学家设想的网络操作的最基本形式之一，这个概念对理解认知功能的努力产生了重大影响。当一个表征通过选择性地加强参与神经元之间的突触而被存储时，模式完成就产生了。当随后的事件只激活这些神经元的一个子集时，代表这个模式的一部分，这个活动然后可以通过新加强的突触传播到整个神经元集合，以重建原始模式。这些想法是在两个非常不同的学科中发展起来的，神经网络的数学/计算机建模和行为的实验研究。直到最近，这些想法还没有在完整的神经回路中进行过研究，因此关于神经网络功能的重要假设没有直接的实验测试。本研究将使用电压成像来测试海马脑片中关于模式完成的假设。电压成像生成通过切片分布的电活动的图，并且这些图表示电活动的“模式”。通过使用来自数字图像处理和信息论的方法量化图像相似性，这些地图的比较提供了一个严格的实验测试模式完成。该实验室最近的工作为这种实验方法奠定了基础，并证明了活动模式可以通过长时程增强（LTP）存储在海马切片的CA 3区。随后的部分输入然后检索完整的模式。本项目将开发这种体外方法用于信息存储和回忆的研究。目的1将评估已知影响LTP和行为的神经调质，以确定乙酰胆碱和去甲肾上腺素受体是否可以改变海马CA 3区的信息存储和模式完成。目标2将解决时间方面的信息存储，首先测试的作用，输入时间（尖峰定时依赖可塑性），然后调查的补充问题的持久性的信息跟踪有关的衰减不同形式的LTP。Aim 3将使用基因编码的电压传感器来评估动物在经历过程中存储的信息。这一目标也将评估在单细胞和突触水平上的模式完成的假设。这项工作将为神经网络功能的计算模型提供新的实验测试，并促进我们对神经回路存储，回忆和处理信息的机制的理解。

 DESCRIPTION (provided by applicant): The nervous system operates through the generation and transformation of patterns of electrical activity distributed sparsely through a vast array of interconnected neurons. These patterns encode information ultimately arising from sensory inputs. Within this framework the storage of information by the nervous system can be viewed as an imprinting process that enables a network to recapitulate patterns of activity stored by prior experience. The canonical operation of pattern completion is one of the most fundamental forms of network operation envisaged by neuroscientists, and this concept has had a major influence on efforts to understand cognitive function. Pattern completion results when a representation has been stored by selective strengthening of synapses between participating neurons. When a subsequent event activates only a subset of these neurons, representing a part of this pattern, this activity can then spread to the entire set of neurons through the newly strengthened synapses to reconstruct the original pattern. These ideas have been developed within two very different disciplines, mathematical/computer modeling of neural networks and experimental studies of behavior. Until recently these ideas had not been studied in an intact neural circuit, leaving important hypotheses about neural network function without direct experimental tests. The present study will use voltage imaging to test hypotheses about pattern completion in hippocampal slices. Voltage imaging generates maps of electrical activity distributed through a slice, and these maps represent 'patterns' of electrical activity. By quantification of image similarity using methods derived from digital image processing and information theory, comparisons of these maps provide a rigorous experimental test of pattern completion. Recent work from this laboratory laid the foundation for this experimental approach and demonstrated that a pattern of activity can be stored in the CA3 region of a hippocampal slice by long-term potentiation (LTP). Subsequent partial inputs then retrieved the complete pattern. The present project will develop this in vitro approach for the study of information storage and recall. Aim 1 will evaluate neuromodulators known to influence both LTP and behavior to determine whether acetylcholine and norepinephrine receptors can modify information storage and pattern completion in the hippocampal CA3 region. Aim 2 will address temporal aspects of information storage, first testing the role of input timing (spike-timing dependent plasticity), and then investigating the complementary issue of persistence of the information trace in relation to the decay of different forms of LTP. Aim 3 will use a genetically-encoded voltage sensor to evaluate information stored during an animal's experience. This Aim will also evaluate the hypothesis of pattern completion at the level of single cells and synapses. This work will provide novel experimental tests for computational models of neural network function, and advance our understanding of the mechanisms by which neural circuits store, recall, and process information.