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（由申请人提供）：神经系统通过大量相互连接的神经元稀疏分布的电活动模式的生成和转换来运作，这些模式最终由感觉输入产生的信息进行编码。神经系统可以被视为一种印记过程，使网络能够重述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。当通过选择性加强参与神经元之间的突触来存储表示时，模式完成结果对理解认知功能产生了重大影响。然后，活动可以通过新强化的突触传播到整个神经元，以重建原始模式。这些想法是在两个截然不同的学科中发展起来的，即神经网络的数学/计算机建模和行为的实验研究。尚未在完整的神经系统中进行研究电路，留下关于神经网络功能的重要假设而无需直接实验测试，本研究将使用电压成像来测试关于海马切片中的模式完成的假设，电压成像生成分布在切片中的电活动图，这些图代表“模式”。通过使用源自数字图像处理和信息论的方法对图像相似性进行量化，这些图的比较提供了模式完成的严格实验测试，为该实验方法奠定了基础，并证明了一种模式。的活动可以存储在通过长期增强 (LTP) 的海马切片的 CA3 区域，然后检索完整的模式，本项目将开发这种体外方法来研究信息存储和回忆，目标 1 将评估已知的影响神经调节剂。 LTP 和行为来确定乙酰胆碱和去甲肾上腺素受体是否可以修改海马 CA3 区域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，首先测试其作用。目标 3 将使用基因编码的电压传感器来评估在一个过程中存储的信息。该目标还将评估单细胞和突触水平的模式完成假设，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，并增进我们对神经回路存储机制的理解。记起，和处理信息。