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规范形式剥夺（MD）。它为视觉电路在早期生活中如何发展和改造提供了关键的见解。我们已经表明，猫中的ODP通过睡眠增强。我们的目标是更彻底地识别基础机制及其发生的大脑状态。为了实现这一目标，我们将开发新的鼠标 - 基于睡眠依赖性ODP的模型。小鼠中的MD触发生理和形态学变化皮质回路类似于食肉动物中描述的电路。但是，与食肉动物不同，分子用于可视化神经元活性和测量mRNA的技术被广泛用于小鼠中。有目前尚无研究模型系统来确定经验和睡眠的影响的研究 ODP。在这项探索性建议中，我们将使用多摄影和钙的新型组合体内基于荧光的显微镜检查，以记录整个睡眠和清醒。我们还将使用翻译核糖体亲和力净化（TRAP）技术与微阵列和rnaseq隔离了在睡眠中发生的转录组的变化，重塑视觉皮质。这些调查的结果将为对如何进行更大的调查为基础体验和睡眠塑造发育中的大脑。