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: 10083235
• 负责人: John H Byrne
• 金额: $ 33.45万
• 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 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10083235
• 关键词: Address; Aplysia; Behavior; Behavioral; Biological Models; Biophysics; Brain; Cell physiology; Cells; Chemical Synapse; Chemicals; Complex; Coupling; Data; Development; Electrophysiology (science); Environment; Feeding behaviors; Goals; Human; Image; In Vitro; Individual; Invertebrates; Learning; Mediating; Memory; Memory impairment; Methods; Modeling; Molecular; Monitor; Motor; Nervous system structure; Neuronal Dysfunction; Neurons; Neurosciences; Operant Conditioning; Output; Pattern; Process; Property; Protocols documentation; Publishing; Research; Resolution; Short-Term Memory; Site; Synapses; Synaptic plasticity; System; Techniques; Time; Training; analog; biophysical analysis; brain health; classical conditioning; design; extracellular; feeding; improved; in vitro activity; in vivo; insight; long term memory; memory encoding; memory process; neural circuit; neural patterning; presynaptic; reinforced behavior; relating to nervous system; shared memory; 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, thereby storing and expressing a memory via changes in neural activity. 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 (OC) in a relatively complex neural circuit, which is amenable to cellular and biophysical analyses. A combination of intracellular electrophysiological recording techniques and voltage- sensitive dye (VSD) recordings will locate and analyze loci of non-synaptic plasticity and synaptic plasticity. In addition, the project will examine the extent to which short- and long-term memory share plasticity loci. Aim 1 will use intracellular recording techniques to examine loci of OC-induced plasticity. Previous studies of OC in this model system focused primarily on non-synaptic plasticity mechanisms. However, preliminary data indicate that OC also modifies the strength of several synaptic connections in the network. Therefore, Aim 1 will examine OC-induced synaptic and non-synaptic plasticity. Aim 2 will use a combination of intracellular and VSD recordings to identify additional sites of OC-induced plasticity. To date, published studies have examined only five of the ~100 neurons and none of the hundreds of synaptic connections that comprise the neural circuit. To address this shortcoming, large-scale VSD recordings, in combination with intracellular recordings, will be used to identify OC-induced changes in activity and synaptic properties in a substantial proportion of the neurons in the circuit. Aim 3 will determine the extent to which short- and long-term memory share common loci and plasticity mechanisms. Our previous studies indicate that at least one locus of plasticity is common to both short- and long-term memory. Thus, an important question in memory research is to determine the extent to which sites for short-term memory are also sites for long-term memory, or conversely, which sites of plasticity may be unique to long-term memory. By examining these three aims, the project will provide insights into the ways in which the many components of a nervous system orchestrate learning and generate behavior.

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，从而通过神经活动的变化来存储和表达记忆。这 该提案的总体目标是提供对管理实施的设计原则的见解 神经回路的复杂环境中的记忆。研究将集中于已建立的体外 相对复杂的神经回路中的操作性条件反射（OC）的类似物，它适合细胞和 生物物理分析。细胞内电生理记录技术和电压记录技术的结合 敏感染料（VSD）记录将定位和分析非突触可塑性和突触可塑性的位点。在 此外，该项目还将研究短期记忆和长期记忆共享可塑性基因座的程度。目标1 将使用细胞内记录技术来检查 OC 诱导的可塑性位点。以前对 OC 的研究 该模型系统主要关注非突触可塑性机制。但初步数据表明 OC 还改变网络中几个突触连接的强度。因此，目标 1 将检查 OC 诱导的突触和非突触可塑性。目标 2 将使用细胞内和 VSD 的组合 记录以确定 OC 诱导的可塑性的其他位点。迄今为止，已发表的研究仅考察了 构成神经回路的约 100 个神经元中的 5 个，以及数百个突触连接中的一个都没有。到 为了解决这个缺点，将使用大规模 VSD 记录与细胞内记录相结合 识别 OC 诱导的大部分神经元的活动和突触特性的变化 电路。目标 3 将确定短期记忆和长期记忆共享共同基因座的程度 可塑性机制。我们之前的研究表明，至少有一个可塑性位点对于两种短链是共同的。 和长期记忆。因此，记忆研究中的一个重要问题是确定记忆的程度。 短期记忆的位点也是长期记忆的位点，或者相反，可塑性的位点可能是 长期记忆所独有的。通过研究这三个目标，该项目将提供对以下方面的见解： 神经系统的许多组成部分协调学习并产生行为。