Circuit Mechanisms of Information Processing and Storage in Brain Slices

脑切片信息处理和存储的电路机制

• 批准号: 9320901
• 负责人: MEYER B. JACKSON
• 金额: $ 31.8万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9320901
• 关键词: Address; Adrenergic Receptor; Alzheimer' s Disease; Animal Testing; Animals; Architecture; Behavior; Biological Neural Networks; Brain; Brain region; Cells; Cholinergic Receptors; Computer Simulation; Dementia; Development; Dimensions; Discipline; Environment; Event; Experimental Models; Exposure to; FOS gene; Foundations; Gene Expression; Generations; Hippocampus (Brain); Hybrids; Image; Immediate-Early Genes; Impaired cognition; In Vitro; Individual; Information Storage; Information Theory; Label; Laboratories; Learning; Learning Disabilities; Ligands; Link; Long-Term Potentiation; Maps; Mathematics; Memory; Mental Retardation; Mental disorders; Methods; Modeling; Molecular; Mus; Muscarinic Acetylcholine Receptor; Nervous system structure; Neurodegenerative Disorders; Neuromodulator; Neurons; Nicotine; Norepinephrine Receptors; Operating System; Pathology; Pattern; Performance; Population; Process; Role; Site; Slice; Spatial Distribution; Study models; Synapses; Synaptic Potentials; Synaptic plasticity; Technology; Testing; Time; Work; base; behavior influence; behavioral study; brain cell; cognitive function; digital imaging; experience; experimental study; image processing; imprint; improved; information processing; interest; nervous system disorder; network models; neural circuit; neural model; novel; novel strategies; operation; public health relevance; response; sensor; sensory input; theories; tool; voltage

 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.

 描述(申请人提供)：神经系统通过产生和转换稀疏分布在大量相互连接的神经元中的电活动模式来运作。这些模式对最终来自感觉输入的信息进行编码。在这个框架内，神经系统对信息的存储可以被视为一个印记过程，使网络能够概括根据先前经验存储的活动模式。模式补全的规范操作是神经学家设想的最基本的网络操作形式之一，这一概念对认知功能的理解产生了重大影响。当通过选择性地加强参与神经元之间的突触来存储表示时，模式完成就会产生。当随后的事件只激活了这些神经元中的一个子集，代表了这种模式的一部分，这种活动就可以通过新加强的突触扩散到整个神经元集，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出来的，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研究，留下了关于神经网络功能的重要假设，没有直接的实验测试。这项研究将使用电压成像来测试关于海马片模式完成的假说。电压成像生成了分布在切片上的电活动地图，这些地图代表了电活动的“模式”。通过使用来自数字图像处理和信息论的方法来量化图像的相似性，这些地图的比较提供了对模式完成的严格的实验测试。该实验室最近的工作为这种实验方法奠定了基础，并证明了通过长时程增强(LTP)，可以在海马片的CA3区存储一种活动模式。然后，随后的部分输入检索到完整的模式。本项目将发展这一体外方法来研究信息存储和回忆。目的1将评估已知的影响LTP和行为的神经调节剂，以确定乙酰胆碱和去甲肾上腺素受体是否可以改变海马CA3区的信息存储和模式完成。目标2将解决信息存储的时间方面，首先测试输入计时的作用(尖峰计时依赖的可塑性)，然后研究信息痕迹的持久性与不同形式的LTP衰退有关的互补问题。Aim 3将使用一个基因编码的电压传感器来评估动物体验期间存储的信息。这一目标还将在单细胞和突触水平上评估模式完成假说。这项工作将为神经网络功能的计算模型提供新颖的实验测试，并促进我们对神经电路存储、回忆和处理信息的机制的理解。