Deciphering Inhibition of Visual Plasticity by NgR1

摘要 视觉系统表现出对高质量视觉体验的高度敏感性， 发展被称为“关键时期”。关键期视力不一致是弱视的原因， 儿童普遍存在的视觉障碍。弱视的治疗最有效的是在儿童近视前， 关键时期。随后，大脑回路的灵活性在成年期和有效的治疗中减少 更困难。在弱视小鼠模型中，通过关闭一个（单眼）视觉来破坏正常视觉， 剥夺，MD）的关键期的持续时间，但不是之后，降低视力和干扰 视觉皮层神经元的正常眼优势。 nogo-66受体基因（ngr 1）是关闭关键期所必需的。在ngr 1突变小鼠中， 在关键期是正常的，但它保留在成年小鼠。重要的是，ngr 1突变小鼠自发地 在这个弱视模型中恢复视力。我们的总体假设是视力和视力的恢复 优势是独立的。在拟议的研究中，我们利用这一延长的关键期， NGR 1小鼠，以确定介导敏锐度和眼睛恢复的可塑性的位置和机制 优势与条件小鼠遗传学，行为测定，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 开始揭示视觉回路中的可塑性如何介导早期后视觉功能的恢复。 异常视力（MD），以及如何这种可塑性是有限的关键时期与这些实验。在 除了提高对经验依赖性可塑性如何改变大脑功能的理解外， 这些研究可能会揭示开发治疗弱视的治疗方法的新途径。 .

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. .