Exploratory models of cortical consolidation

皮质巩固的探索性模型

• 批准号: 9530674
• 负责人: MARCOS G FRANK
• 金额: $ 19.13万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-18 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9530674
• 关键词: Address; Adult; Affinity Chromatography; Animal Model; Animals; Biological; Biological Assay; Biological Models; Brain; Calcium; Calcium Signaling; Cells; Child; Development; Dissection; Electroencephalography; Exploratory/Developmental Grant; Felis catus; Fluorescence; Foundations; Genetic Translation; Goals; Head; Health; Human; Image; Investigation; Life; Mammals; Measures; Mediating; Messenger RNA; Microscope; Microscopy; Modeling; Modernization; Molecular; Morphology; Mus; Neurobiology; Neurons; Neurosciences; Ocular Dominance; Pathologic; Physiological; Play; Polysomnography; Procedures; Process; Proteins; Psychotropic Drugs; Research; Research Project Grants; Ribosomes; Risk; Role; Shapes; Sleep; Sleep Disorders; Sleep Fragmentations; Solid; Synaptic plasticity; System; Techniques; Technology; Testing; Translating; Vision; Visual; Visual Cortex; Visual system structure; Wakefulness; Work; area striata; base; brain cell; critical period; developmental plasticity; experience; improved; in vitro Model; in vivo; in vivo calcium imaging; insight; instrument; miniaturize; monocular deprivation; mouse model; neurodevelopment; neuronal patterning; novel; perinatal period; rapid eye movement; relating to nervous system; sensory input; sleep abnormalities; synaptogenesis; tool; transcriptome; transcriptome sequencing

Summary Ocular dominance plasticity (ODP) is a canonical form of synaptic plasticity in vivo triggered by monocular deprivation (MD). It has provided crucial insights into how visual circuits develop and remodel in early life. We have shown that ODP in cats is enhanced by sleep. Our goal is to more completely identify the underlying mechanisms and the brain states in which they occur. To achieve this goal we will develop a new mouse- based model of sleep-dependent ODP. MD in mice triggers physiological and morphological changes in cortical circuits similar to those described in carnivore species. However, unlike carnivore species, molecular techniques used to visualize neuronal activity and measure mRNA are widely used in mice. There are currently no studies that have exploited this model system to identify how experience and sleep influence ODP. In this exploratory proposal, we will use a novel combination of polysomnography and calcium- fluorescence based microscopy in vivo to record plastic changes in visual cortical neurons across sleep and wakefulness. We will also use Translating Ribosome Affinity Purification (TRAP) technology combined with microarray and RNAseq to isolate changes in the transcriptome that occur in the sleeping, remodeling visual cortex. The results of these investigations will provide the foundation for a larger investigation of how experience and sleep shape the developing brain.

总结 眼优势可塑性（ODP）是由单眼视诱发的突触可塑性的典型形式 剥夺（MD）。它为了解视觉回路在生命早期的发展和重塑提供了重要的见解。我们 已经证明猫的ODP通过睡眠而增强。我们的目标是更全面地识别 机制和它们发生的大脑状态。为了实现这一目标，我们将开发一种新鼠标- 睡眠依赖ODP模型。小鼠中的MD引发了小鼠的生理和形态学变化， 皮质回路与食肉动物相似。然而，与食肉动物不同， 用于显现神经元活性和测量mRNA的技术广泛用于小鼠。有 目前还没有研究利用这个模型系统来确定经验和睡眠如何影响 ODP。在这个探索性的建议中，我们将使用一种新的多导睡眠图和钙的组合， 基于荧光的显微镜在体内记录整个睡眠过程中视觉皮层神经元的可塑性变化， 清醒我们还将使用翻译核糖体亲和纯化（TRAP）技术， 微阵列和RNAseq分离发生在睡眠，重塑视觉， 皮层这些调查的结果将为更大规模的调查提供基础， 经验和睡眠塑造发育中的大脑。