Exploratory models of cortical consolidation

皮质巩固的探索性模型

基本信息

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
项目类别：
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

项目摘要

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.

概括眼优势可塑性（ODP）是由单眼触发的体内突触可塑性的典型形式剥夺（MD）。它为早期生命中视觉回路如何发展和重塑提供了重要的见解。我们研究表明，猫的 ODP 会因睡眠而增强。我们的目标是更全面地识别潜在的机制以及它们发生的大脑状态。为了实现这一目标，我们将开发一种新的鼠标- 基于睡眠依赖的 ODP 模型。小鼠MD引发生理和形态变化皮质回路与肉食动物中描述的相似。然而，与食肉动物不同，分子用于可视化神经元活动和测量 mRNA 的技术广泛应用于小鼠。有目前还没有研究利用该模型系统来确定经验和睡眠如何影响耗氧量。在这个探索性提案中，我们将使用多导睡眠图和钙离子的新颖组合基于荧光的体内显微镜可记录睡眠和睡眠期间视觉皮层神经元的可塑性变化觉醒。我们还将使用翻译核糖体亲和纯化（TRAP）技术结合微阵列和RNAseq分离睡眠中发生的转录组变化，重塑视觉皮质。这些调查的结果将为更大规模的调查奠定基础经验和睡眠塑造发育中的大脑。