Deciphering Inhibition of Visual Plasticity by NgR1

解读 NgR1 对视觉可塑性的抑制

• 批准号: 9754152
• 负责人: Aaron W McGee
• 金额: $ 38.5万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 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 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9754152
• 关键词: Address; Adult; Alleles; Amblyopia; Behavioral; Behavioral Assay; Binocular Vision; Brain; Calcium; Child; Childhood; Data; Development; Disease; Disinhibition; Electrophysiology (science); Exhibits; Eye; Frequencies; Genetic; Head; Image; Interneurons; Knowledge; Lasers; Lateral Geniculate Body; Lazy Eyes; Location; Maps; Measures; Mediating; Mission; Modeling; Modification; Mus; Mutant Strains Mice; Neurons; Ocular Dominance; Parvalbumins; Phenotype; Population; Public Health; Receptor Gene; Recovery; Research; Scanning; Strabismus; Synapses; Synaptic plasticity; Testing; Thalamic structure; Therapeutic; Therapeutic Intervention; Time; Vision; Vision Disorders; Visual; Visual Acuity; Visual Cortex; Visual impairment; Visual system structure; Water; brain circuitry; critical period; effective therapy; excitatory neuron; experience; experimental study; flexibility; improved; in vivo calcium imaging; inhibitory neuron; monocular deprivation; mouse model; neural circuit; optogenetics; postsynaptic; programs; response; spatial vision; targeted treatment; visual deprivation; visual plasticity; visual processing

Abstract The visual system exhibits a heightened sensitivity to the quality visual experience during an interval late in development termed the `critical period'. Discordant vision during the critical period is the cause of amblyopia, a prevalent visual disorder in children. Treatment of amblyopia is most effective in children before the close of the critical period. Subsequently, the flexibility with brain circuitry diminishes in adulthood and effective therapy is more difficult. In a mouse model of amblyopia, disrupting normal vision by closing one (monocular deprivation, MD) for the duration of the critical period, but not thereafter, decreases visual acuity and perturbs the normal eye dominance of neurons in visual cortex. The nogo-66 receptor gene (ngr1) is required to close the critical period. In ngr1 mutant mice, plasticity during the critical period is normal, but it is retained in adult mice. Importantly, ngr1 mutant mice spontaneously recover visual acuity in this model of amblyopia. Our overall hypothesis is that recovery of acuity and eye dominance are independent. In the proposed research, we take advantage of this extended critical period in ngr1 mice to identify with location and mechanisms of plasticity that mediate recovery of acuity and eye dominance with a combination of conditional mouse genetics, behavioural assays, electrophysiology, sophisticated repeated in vivo calcium imaging and laser-scanning photostimulation circuit mapping. We will begin to unravel how plasticity within visual circuitry mediates recovery of visual function following early abnormal vision (MD), as well as how this plasticity is restricted to the critical period with these experiments. In addition to improving understanding of how experience-dependent plasticity changes the function of brain circuits, these studies may reveal new avenues for developing therapeutic approaches to treat amblyopia. .

抽象的 在后期的一段时间里，视觉系统对高质量的视觉体验表现出高度的敏感性。 发展的关键时期被称为“关键时期”。关键期视力不协调是弱视的原因 儿童中普遍存在的视觉障碍。临终前治疗儿童弱视最有效 关键期。随后，大脑回路的灵活性在成年后会减弱，有效的治疗 比较困难。在弱视小鼠模型中，通过关闭一只眼睛（单眼）来破坏正常视力 剥夺（医学博士）在关键期期间（但在此后）会降低视力并造成干扰 视觉皮层神经元的正常眼睛优势。 nogo-66 受体基因 (ngr1) 是关闭关键期所必需的。在ngr1突变小鼠中，可塑性 在关键时期是正常的，但在成年小鼠中则保留。重要的是，ngr1突变小鼠自发地 恢复该弱视模型的视力。我们的总体假设是，视力和视力恢复 统治地位是独立的。在拟议的研究中，我们利用了这一延长的关键期 ngr1小鼠识别介导视力和眼睛恢复的可塑性的位置和机制 结合条件小鼠遗传学、行为分析、电生理学、 复杂的重复体内钙成像和激光扫描光刺激电路映射。我们将 开始揭示视觉回路内的可塑性如何介导早期视觉功能的恢复 异常视力（MD），以及如何通过这些实验将这种可塑性限制在关键时期。在 除了增进对经验依赖性可塑性如何改变大脑功能的理解之外 电路，这些研究可能揭示开发弱视治疗方法的新途径。 。