Deciphering Inhibition of Visual Plasticity by NgR1

解读 NgR1 对视觉可塑性的抑制

• 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
• 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

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 初级视觉皮质内的功能连接表现出高度的增强 在发育后期阶段对视觉体验的敏感度称为关键 句号。关键时期的异常视觉体验是弱视的原因， 儿童时期普遍存在的视力障碍。治疗对儿童来说是最有效的。 关键时期结束。随后，可塑性减弱，有效的治疗方法是 更难了。在弱视小鼠模型中，关键时期的单眼剥夺 期间，但不是之后，两者都改变了视觉中神经元的相对反应性 并降低视觉敏锐度。与临床发现类似，这些缺陷持续存在，如果 关键期结束后，视力恢复正常。 NOGO-66受体(NgR1)是关闭关键期所必需的。在小鼠身上 缺乏NgR1，关键期的可塑性是正常的，但它持续到 成年小鼠表现出与关键期相同的可塑性。这项建议 调查NgR1如何关闭关键期。特定目标1剖析了NgR1在哪里 大脑皮质回路需要表达以关闭临界期并进一步限制 小鼠遗传学和电生理记录相结合的外径可塑性。 特殊目的2利用NgR1突变小鼠独特的可塑性表型来研究 重复双光子研究结构突触可塑性对外径可塑性的影响 活体成像。具体目标3探索在关键时刻之后阻断NgR1的功能 能恢复弱视小鼠的OD可塑性，提高视力。目标是 这一建议的目的是提高人们对大脑皮质可塑性是如何在 发展和成熟的视觉系统。