Deciphering Inhibition of Visual Plasticity by NgR1

解读 NgR1 对视觉可塑性的抑制

基本信息

批准号：
8658088
负责人：
Aaron W McGee
金额：
$ 39.69万
依托单位：
CHILDREN'S HOSPITAL OF LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8658088
关键词：
Address Adult Alleles Amblyopia Behavioral Calcium-Binding Proteins Child Childhood Chronic Clinical Dendritic Spines Development Electrophysiology (science)Exhibits Genes Genetic Goals Image Interneurons Knock-out Lazy Eyes Measures Modification Mus Mutant Strains Mice Neurons Neuropeptides Ocular Dominance Parvalbumins Phenotype Population Recovery Relative (related person)Research Role Signal Transduction Somatostatin Strabismus Structure Synapses Synaptic plasticity Tamoxifen Testing Therapeutic Vision Vision Disorders Visual Visual Acuity Visual Cortex Visual system structure Water Wild Type Mouse abstracting area striata calretinin critical developmental period critical period effective therapy experience improved in vivo in vivo imaging insight monocular deprivation mouse model mutant neural circuit optical imaging programs promoter receptor recombinase research study two-photon visual process visual processing

项目摘要

Project Summary/Abstract The functional connectivity within primary visual cortex exhibits heightened sensitivity to visual experience during an interval late in development termed the critical period. Abnormal visual experience during the critical period is the cause of amblyopia, a prevalent childhood visual disorder. Treatment is most effective in children before the close of the critical period. Subsequently, plasticity diminishes and effective therapy is more difficult. In a mouse model of amblyopia, monocular deprivation during the critical period, but not thereafter, both shifts the relative responsiveness of neurons in visual cortex and decreases visual acuity. Analogous to clinical findings, these deficits persist if normal vision is restored after the close of the critical period. The nogo-66 receptor (NgR1) is required to close the critical period. In mice lacking NgR1, plasticity during the critical period is normal, but it continues such that adult mice display the same plasticity as during the critical period. This proposal investigates how NgR1 closes the critical period. Specific Aim 1 dissects where NgR1 expression is required with cortical circuitry to close the critical period and limit further OD plasticity with a combination of mouse genetics and electrophysiological recordings. Specific Aim 2 exploits the unique plasticity phenotype of NgR1 mutant mice to study how structural synaptic plasticity contributes to OD plasticity with repeated two-photon in vivo imaging. Specific Aim 3 explores whether blocking NgR1 function after the critical period will reactivate OD plasticity and improve visual acuity in amblyopic mice. The goal of this proposal is to improve understanding of how cortical plasticity is governed in the developing and mature visual system.

项目摘要/摘要一级视觉皮层内的功能连通性表现出增强在开发后期的间隔中对视觉体验的敏感性称为关键时期。在关键时期，视觉体验异常是弱视的原因普遍的童年视觉障碍。治疗在儿童之前最有效关键时期结束。随后，可塑性降低和有效的治疗是更困难。在弱视的小鼠模型中，临界期间的单眼剥夺时期，但此后不转移神经元在视觉中的相对响应能力皮层并降低视力。类似于临床发现，这些赤字仍然存在关键时期结束后，正常视力将恢复。需要NOGO-66受体（NGR1）才能关闭关键时期。在老鼠中缺乏NGR1，关键时期的可塑性是正常的，但是继续成年小鼠表现出与关键时期相同的可塑性。这个建议研究NGR1如何关闭关键时期。特定的目标1解剖NGR1 皮层电路需要表达以结束关键时期并进一步限制 OD可塑性与小鼠遗传学和电生理记录的结合。特定的目标2利用了NGR1突变小鼠的独特可塑性表型研究结构突触可塑性如何在重复的两光子中导致OD可塑性体内成像。特定的目标3探索关键后阻止NGR1功能是否功能周期将重新激活OD可塑性并改善弱视小鼠的视力。目标该提议的是提高对皮质可塑性如何控制的理解开发和成熟的视觉系统。