Analyses of the Distributed Representation of Associative-Learning in an Identified Circuit Using a Combination of Single-Cell Electrophysiology and Multicellular Voltage-Sensitive Dye Recordings

结合单细胞电生理学和多细胞电压敏感染料记录分析已识别电路中联想学习的分布式表示

• 批准号: 10539225
• 负责人: John H Byrne
• 金额: $ 39万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10539225
• 关键词: Address; Aplysia; Association Learning; Behavior; Behavioral; Biological Models; Biophysics; Brain; Cell physiology; Cells; Chemical Synapse; Complex; Computer Models; Coupling; Development; Dimensions; Electrical Synapse; Electrophysiology (science); Environment; Event; Exhibits; Feeding behaviors; Goals; Hodgkin-Huxley model; Human; Image; In Vitro; Individual; Inhibitory Synapse; Invertebrates; Knowledge; Learning; Mediating; Memory; Memory impairment; Methods; Modeling; Molecular; Motor; Neuronal Dysfunction; Neuronal Plasticity; Neurons; Neurosciences; Operant Conditioning; Output; Pattern; Phenotype; Population; Process; Property; Protocols documentation; Resolution; Role; Short-Term Memory; Site; Specificity; Synapses; Synaptic plasticity; System; Techniques; Training; Work; analog; biophysical analysis; brain health; design; extracellular; feeding; improved; in vitro activity; in vivo; insight; long term memory; memory encoding; memory retention; neural circuit; neural patterning; reinforced behavior; shared memory; synergism; voltage sensitive dye

PROJECT SUMMARY/ABSTRACT Although significant advances have been made in elucidating the cellular, biophysical and molecular mechanisms of learning and memory, much less is known about the ways in which mnemonic processes are embedded in neuronal networks. The overall goal of this proposal is to provide insights into the design principles that govern the implementation of memories within the complex environment of a neural circuit. Studies will focus on an established in vitro analogue of operant conditioning (QC) in a relatively complex circuit, which is amenable to population-wide, cellular, and biophysical analyses. A combination of intra- and extracellular electrophysiological techniques, voltage-sensitive dye (VSD) imaging, dimensionality reduction analysis, and computational modeling will identify and characterize loci of non-synaptic and synaptic plasticity. In addition, the project will examine the extent to which plasticity loci are shared between short- and long-term memory. Aim 1 will use intracellular recording techniques to examine loci of QC-induced plasticity. Previous correlates of OC in this model system were restricted to increases in intrinsic excitability or electrical synapses of key neurons in the circuit. Our recent results indicate QC also decreases the strength of an inhibitory synapse and the excitability of a key neuron in the circuit. Aim 1 will examine other prime candidates of QC-induced synaptic and non-synaptic plasticity, which have an established role in mediating the behavior. In addition, we will use intracellular techniques to examine regions of the circuit that our recent VSD recordings have shown to exhibit QC-induced changes in activity. Computational modeling will assess the ways in which loci work unilaterally or synergistically to mediate the OC phenotype. Aim 2 will use a combination of intracellular recordings, VSD imaging, and dimensionality reduction approaches to expand the search for additional sites of QC-induced plasticity and search for low-dimensional 'signatures' of OC. The combined results from Aims 1 and 2 will provide for an assessment of the scope of plasticity mechanisms associated with OC that is unprecedented in any system. A further important question will be addressed by Aim 3, which will determine the extent to which sites for short-term memory persist during long-term memory and, conversely, which sites of plasticity may be unique to long-term memory. The present proposal will help develop a comprehensive understanding of the ways in which memories are encoded in a relatively complex circuit, elucidate design principles of memory encoding, and provide guidance for similar analyses in more complex systems.

项目概要/摘要 尽管在阐明细胞、生物物理和分子生物学方面已经取得了重大进展。 学习和记忆的机制，人们对助记过程的方式知之甚少。 嵌入神经元网络中。该提案的总体目标是提供对设计原则的见解 控制神经回路复杂环境中记忆的实现。研究将集中 在相对复杂的电路中建立了操作性条件反射（QC）的体外类似物，这是可以接受的 进行全人群、细胞和生物物理分析。细胞内和细胞外的结合 电生理学技术、电压敏感染料 (VSD) 成像、降维分析，以及 计算模型将识别和表征非突触可塑性和突触可塑性的位点。此外， 该项目将检查短期记忆和长期记忆之间可塑性基因座的共享程度。目标1 将使用细胞内记录技术来检查 QC 诱导的可塑性位点。之前 OC 的相关性 该模型系统仅限于内在兴奋性或关键神经元电突触的增加 电路。我们最近的结果表明 QC 还会降低抑制性突触的强度和兴奋性 电路中的关键神经元。目标 1 将检查 QC 诱导的突触和非突触的其他主要候选者 可塑性，在调节行为方面具有既定的作用。此外，我们将使用细胞内 技术来检查我们最近的 VSD 记录显示出 QC 诱导的电路区域 活动的变化。计算模型将评估基因座单方面或协同作用的方式 介导 OC 表型。目标 2 将结合使用细胞内记录、VSD 成像和 降维方法以扩大对 QC 诱导可塑性的其他位点的搜索 搜索 OC 的低维“签名”。目标 1 和 2 的综合结果将提供 对与 OC 相关的可塑性机制范围的评估在任何系统中都是前所未有的。一个 目标 3 将解决更重要的问题，该目标将决定短期站点的范围 记忆在长期记忆过程中持续存在，相反，哪些可塑性位点可能是长期记忆所独有的 记忆。本提案将有助于全面了解 存储器编码在相对复杂的电路中，阐明存储器编码的设计原理，以及 为更复杂的系统中的类似分析提供指导。