Deciphering Inhibition of Visual Plasticity by NgR1

解读 NgR1 对视觉可塑性的抑制

• 批准号: 8463201
• 负责人: Aaron W McGee
• 金额: $ 38.48万
• 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/8463201
• 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; 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.

项目总结/摘要 初级视觉皮层内的功能连接表现出高度的 在发育后期的一段时间内，对视觉体验的敏感性被称为关键性 期关键期的异常视觉体验是弱视的原因， 普遍的儿童视觉障碍。治疗对儿童最有效， 关键时期的结束。随后，可塑性减弱，有效的治疗是 更加困难.在弱视的小鼠模型中，在关键的 一段时间，但不是之后，都改变了视觉神经元的相对反应性， 皮质和视力下降。类似于临床发现，这些缺陷持续存在，如果 在关键期结束后恢复正常视力。 Nogo-66受体（NgR 1）是关闭关键期所必需的。小鼠 缺乏NgR 1，在关键时期的可塑性是正常的，但它继续这样， 成年小鼠表现出与关键期相同的可塑性。这项建议 研究NgR 1如何关闭关键期。具体目标1剖析NgR 1 皮质回路需要表达来关闭关键期并进一步限制 OD可塑性与小鼠遗传学和电生理记录的组合。 特异性目的2利用NgR 1突变小鼠的独特可塑性表型进行研究 结构突触可塑性如何在重复双光子作用下对OD可塑性做出贡献 活体成像具体目标3探讨了在关键性免疫后阻断NgR 1功能是否 周期将重新激活OD可塑性并改善弱视小鼠的视力。目标 这项建议的目的是提高对大脑皮层可塑性如何在大脑皮层中控制的理解。 发展成熟的视觉系统。