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涉及的丘脑皮质网络机制 在视觉系统中巩固依赖经验的可塑性。睡眠对过程有益影响 取决于突触可塑性，例如记忆巩固。最近的研究表明皮质 随后的慢波睡眠（SWS），醒来的感官体验参与的区域被“重新激活”， 局部脑电图（EEG）振荡活性的局部变化。因为这些脑电图振荡是 由节奏，丘脑和皮质神经元的同步发射产生，一个未经测试的假设是 SWS丘脑皮质活性导致突触靶标的增强或抑郁。特定于方向 小鼠视觉系统中的响应增强（OSRP）涉及对视觉的神经元反应的增强 特定方向的刺激。 OSRP是通过短暂暴露于方向的光栅刺激来开始的，并且是 在视觉体验之后，立即在几个小时内合并“离线”。我的初步数据表明 SWS期间的丘脑皮层主轴（7-14 Hz）活性可能在OSRP巩固中起关键作用。在 拟议奖项的指导阶段（AIM 1），我将：（a）测试SWS和SWS主轴振荡是否为 OSRP所需的以及（b）评估在合并期间SWS纺锤体1）激活丘脑皮质 以非特异性方式连接，或2）以某种方式介导丘脑皮质连接的“重新激活” 与先前的视觉体验一致。我将通过录制持续的活动和视觉响应来做到这一点 视觉皮层中神经元种群的特性和自由行为小鼠的侧向核核的特性 在基线，唤醒视觉体验以及随后的合并期间：ad lib睡眠，总计 睡眠剥夺，快速的眼睛运动睡眠（REM）剥夺或选择性中断SWS纺锤体。 这些研究将基于我先前的多电极记录和数据分析的研究经验， 在Drs的联合统治下。马科斯·弗兰克（Marcos Frank）（我目前的博士后顾问和领域的专家 睡眠和视觉皮层可塑性）和迭戈·孔特雷拉（Diego Contreras）（国家依赖性领域的专家 视觉中涉及的丘脑皮质网络特性和网络机制）。在指导阶段 该奖项，我还将在使用光遗传技术与多电极的使用方面发展专业知识 在自由行为的小鼠中记录，以准备在AIM 2中概述的实验。在独立阶段 在奖项（AIM 2）中，我将使用这种最先进的技术的组合来沉默定义的人群 特定状态（唤醒，REM或SWS）的丘脑皮质，网状丘脑或皮质丘脑神经元至 测试每个州内丘脑皮质活性的必要性以进行OSRP巩固。我假设这一点 SWS期间这些神经元种群对纺锤体的产生和协调对于此过程至关重要。 总之，这些研究将揭示巩固可塑性所需的国家依赖性网络机制 遵循视觉体验。