Network mechanisms for state-dependent consolidation of visual system plasticity

视觉系统可塑性的状态依赖巩固的网络机制

• 批准号: 8513442
• 负责人: SARA J ATON
• 金额: $ 24.89万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8513442
• 关键词: Affect; Alzheimer' s Disease; Area; Autistic Disorder; Award; Behavioral; Cells; Chemosensitization; Chronic; Cognition; Cognitive; Communication; Data; Data Analyses; Dependence; Disease; Electroencephalogram; Event; Exposure to; Frequencies; Generations; Goals; Hour; Interruption; Lateral Geniculate Body; Lead; Light; Long-Term Potentiation; Mediating; Memory; Mentors; Mentorship; Mus; Neurons; Organism; Pattern; Phase; Photic Stimulation; Play; Population; Preparation; Process; Property; Proton Pump; REM Sleep; Research; Role; Schizophrenia; Sensory; Signal Transduction; Site; Sleep; Sleep Deprivation; Slow-Wave Sleep; Stimulus; Synaptic plasticity; Techniques; Testing; Thalamic structure; V1 neuron; Vision; Visual; Visual Cortex; Visual system structure; Work; abstracting; area striata; base; cell type; deprivation; experience; insight; neuromechanism; novel; optogenetics; research study; response; synaptic depression; tool; visual stimulus

Abstract: The long-term goal of this project is to identify thalamocortical network mechanisms involved in consolidating experience-dependent plasticity in the visual system. Sleep has beneficial effects for processes dependent upon synaptic plasticity, such as memory consolidation. Recent studies have shown that cortical areas engaged by waking sensory experience are "reactivated" during subsequent slow wave sleep (SWS), with local changes in electroencephalogram (EEG) oscillatory activity. Because these EEG oscillations are generated by rhythmic, synchronous firing of thalamic and cortical neurons, one untested hypothesis is that SWS thalamocortical activity leads to potentiation or depression of synaptic targets. Orientation-specific response potentiation (OSRP) in the mouse visual system involves potentiation of neuronal responses to visual stimuli of a specific orientation. OSRP is initiated by brief exposure to an oriented grating stimulus, and is consolidated "offline" in the hours immediately following visual experience. My preliminary data suggest that thalamocortical spindle (7-14 Hz) activity during SWS may play a critical role in OSRP consolidation. In the mentored phase of the proposed award (Aim 1), I will: (a) test whether SWS and SWS spindle oscillations are required for OSRP, and (b) assess whether during consolidation, SWS spindles 1) activate thalamocortical connections in a non-specific manner, or 2) mediate "reactivation" of thalamocortical connections in a manner consistent with prior visual experience. I will do this by recording ongoing activity and visual response properties in populations of neurons in the visual cortex and lateral geniculate nucleus of freely-behaving mice during baseline, waking visual experience, and a subsequent consolidation period of either: ad lib sleep, total sleep deprivation, rapid eye movement sleep (REM) deprivation, or selective interruption of SWS spindles. These studies will build upon the my prior research experience with multielectrode recording and data analysis, under the co-mentorship of Drs. Marcos Frank (my current postdoctoral advisor and an expert in the areas of sleep and visual cortex plasticity) and Diego Contreras (an expert in the areas of state-dependent thalamocortical network properties and network mechanisms involved in vision). During the mentored phase of the award, I will also develop expertise in using optogenetic techniques in combination with multielectrode recording in freely-behaving mice, in preparation for experiments outlined in Aim 2. In the independent phase of the award (Aim 2), I will use this combination of state of the art techniques to silence defined populations of thalamocortical, reticular thalamic, or corticothalamic neurons during particular states (wake, REM, or SWS), to test the necessity of thalamocortical activity within each state for OSRP consolidation. I hypothesize that generation and coordination of spindles by these neuronal populations during SWS is critical for this process. Together, these studies will reveal state-dependent network mechanisms necessary for consolidating plasticity following visual experience.

摘要：该项目的长期目标是确定丘脑皮质网络机制 巩固视觉系统中依赖于经验的可塑性。睡眠对过程有有益的影响 依赖于突触可塑性，例如记忆巩固。最近的研究表明，皮质 清醒时感官体验所涉及的区域在随后的慢波睡眠（SWS）期间被“重新激活”， 脑电图 (EEG) 振荡活动的局部变化。因为这些脑电图振荡 由丘脑和皮质神经元有节奏、同步放电产生，一种未经检验的假设是 SWS 丘脑皮质活动导致突触目标的增强或抑制。特定方向 小鼠视觉系统中的反应增强（OSRP）涉及神经元对视觉反应的增强 特定方向的刺激。 OSRP 是通过短暂暴露于定向光栅刺激来启动的，并且是 在视觉体验之后的几个小时内整合“离线”。我的初步数据表明 SWS 期间的丘脑皮质纺锤体 (7-14 Hz) 活动可能在 OSRP 巩固中发挥关键作用。在 在拟议奖励的指导阶段（目标 1），我将： (a) 测试 SWS 和 SWS 主轴振荡是否 OSRP 所需的，以及 (b) 评估在巩固期间，SWS 纺锤体是否 1) 激活丘脑皮质 以非特定方式连接，或 2）以某种方式介导丘脑皮质连接的“重新激活” 与之前的视觉经验一致。我将通过记录正在进行的活动和视觉反应来做到这一点 自由行为小鼠视觉皮层和外侧膝状核神经元群体的特性 在基线期间，清醒时的视觉体验，以及随后的巩固期：即兴睡眠，总计 睡眠剥夺、快速眼动睡眠 (REM) 剥夺或 SWS 纺锤波的选择性中断。 这些研究将建立在我之前的多电极记录和数据分析研究经验的基础上， 在博士的共同指导下。马科斯·弗兰克（Marcos Frank）（我目前的博士后导师，也是以下领域的专家 睡眠和视觉皮层可塑性）和迭戈·孔特雷拉斯（Diego Contreras）（状态依赖性领域的专家） 丘脑皮质网络特性和视觉涉及的网络机制）。在辅导阶段 获得该奖项后，我还将发展光遗传学技术与多电极相结合的专业知识 在自由行为的小鼠中进行记录，为目标 2 中概述的实验做准备。在独立阶段 的奖励（目标 2），我将使用这种最先进的技术组合来压制特定人群 丘脑皮质、网状丘脑或皮质丘脑神经元在特定状态（清醒、快速眼动或快速睡眠）期间 测试每个状态下丘脑皮质活动对于 OSRP 巩固的必要性。我假设 SWS 期间这些神经元群体产生和协调纺锤体对于这一过程至关重要。 这些研究将共同​​揭示巩固可塑性所必需的状态依赖网络机制 以下视觉体验。