Regulation of Anatomical Plasticity and Perceptual Learning by NgR1

描述(申请人提供)：新颖的感觉体验和改善的运动能力改变了大脑皮层的结构突触连接，但这种解剖可塑性对知觉学习的功能贡献尚不清楚。最近，在活体内重复成像神经元结构的新兴技术将注意力集中在树突棘的重塑作为潜在的学习底物上。然而，解决脊柱重塑和学习之间的关系的一个主要障碍是确定脊柱动力学是否特定于皮质区域、神经元身份和学习任务。由于胡须的地形性表现和胡须使用的可控、可量化的性质，躯体感觉皮质(桶状皮质)中的桶状视野一直是检查感觉体验期间脊柱重塑的首选系统。跨越差距任务是一项自动化的定量感知学习任务，依赖于通过胡须检测两个平台之间的差距。这些实验将桶形皮质树突棘的长期活体成像与知觉学习任务结合起来，以研究脊柱重塑的速度是否以及如何指定知觉学习的速度。为了验证脊柱重塑速度报告知觉学习速度的假设，随后的联合成像和学习实验利用了NOGO-66受体(NgR1)突变小鼠的表型，这些小鼠学习这一任务的速度更快。NgR1是一种神经元蛋白，调节受损和完整中枢神经系统的可塑性。NgR1突变体从脊髓损伤和中风中恢复得更好；成年NgR1突变体也表现出某种形式的视觉可塑性，通常局限于发育关键期。NgR1如何调控脊柱重塑和知觉学习，不仅可能促进对解剖可塑性如何促进学习的理解，而且可能揭示该受体调控损伤后和发育期间可塑性的保守机制。

DESCRIPTION (provided by applicant): Novel sensory experience and improved motor performance modify structural synaptic connectivity in the cerebral cortex, yet the functional contribution of this anatomical plasticity to perceptual learning is unclear. Recently, emerging techniques for repeatedly imaging neuronal structures in vivo has focused attention upon the remodeling of dendritic spines as a potential substrate for learning. However, a major obstacle to resolving the relationship between spine remodeling and learning is determining if spine dynamics are specific to cortical region, neuronal identity and learning task. The barrel field in somatosensory cortex (barrel cortex) has been a favored system for examining spine remodeling during sensory experience due to the topographical representation of whiskers and controlled, quantifiable nature of whisker use. The gap crossing task is an automated, quantitative perceptual learning task that relies on detection of a gap between two platforms by the whiskers. These experiments combine chronic in vivo imaging of dendritic spines in barrel cortex with this perceptual learning task to investigate if and how the rate of spine remodeling may specify the rate of perceptual learning. To test the hypothesis that the rate of spine remodeling reports the rate of perceptual learning, subsequent combined imaging and learning experiments exploit the phenotype of nogo-66 receptor (NgR1) mutant mice that learn this task faster. NgR1 is a neuronal protein that regulates plasticity in both the injured and intact central nervous system. NgR1 mutants recover better from spinal cord injury and stroke; adult NgR1 mutants also display a form of visual plasticity normally confined to a developmental critical period. How NgR1 regulates both spine remodeling and perceptual learning may improve not only understanding of how anatomical plasticity contributes to learning, but may reveal conserved mechanisms by which this receptor governs plasticity after injury and during development as well.