Deciphering Inhibition of Visual Plasticity by NgR1

摘要 在后期的间隔期间，视觉系统对质量视觉体验表现出高度的敏感度 发展被称为“关键时期”。关键时期视力不协调是弱视的原因， 儿童普遍存在的视力障碍。弱视的治疗在儿童弱视关闭前最有效 关键时期。随后，大脑回路的灵活性在成年后会减弱，并得到有效的治疗 就更难了。在弱视的小鼠模型中，闭上一个(单眼)而扰乱正常视力 在关键时期，但不是之后，剥夺)会降低视力和烦躁不安 视皮层神经元的正常眼优势。 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 在临界期是正常的，但在成年小鼠中保留。重要的是，ngr1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眼睛的恢复 主导权是独立的。在拟议的研究中，我们利用了这一延长的关键期 Ngr1小鼠识别调节视力和眼睛恢复的可塑性的位置和机制 优势结合了条件小鼠遗传学，行为分析，电生理学， 复杂的重复活体钙成像和激光扫描光刺激电路标测。我们会 开始解开视觉回路内的可塑性如何调节早期视觉功能的恢复 异常视觉(MD)，以及这些实验如何将这种可塑性限制在关键期。在……里面 除了提高对依赖经验的可塑性如何改变大脑功能的理解之外 这些研究可能会为开发治疗弱视的治疗方法提供新的途径。 。

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. .