Regulation of Anatomical Plasticity and Perceptual Learning by NgR1

NgR1 对解剖可塑性和知觉学习的调节

基本信息

批准号：
8320118
负责人：
Aaron W McGee
金额：
$ 20.28万
依托单位：
CHILDREN'S HOSPITAL OF LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2014-08-31
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：新型的感官体验和改善的运动性能修改了大脑皮层中的结构突触连通性，但是这种解剖学可塑性对感知学习的功能贡献尚不清楚。最近，在体内反复成像神经元结构的新兴技术将注意力集中在树突状棘的重塑上，作为潜在的学习底物。但是，解决脊柱重塑和学习之间关系的主要障碍是确定脊柱动力学是否针对皮质区域，神经元身份和学习任务。体感皮质（桶形皮层）中的枪管场一直是一个偏爱的系统，该系统是在感觉体验期间检查脊柱重塑的系统，这是由于晶须的地形和可控的，可量化的晶须使用性质。差距交叉任务是一项自动化的定量感知学习任务，依赖于检测晶须两个平台之间的差距。这些实验结合了枪管皮层中树突状棘的慢性成像以及这项感知学习任务，以研究脊柱重塑的速率是否以及如何指定感知学习率。为了测试脊柱重塑速率报告感知学习率的假设，随后的组合成像和学习实验利用了Nogo-66受体（NGR1）突变小鼠的表型，这些突变小鼠的学习速度更快。 NGR1是一种神经元蛋白，可调节受伤和完整的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更好。成年NGR1突变体还显示出一种通常局限于发育关键时期的视觉可塑性形式。 NGR1如何调节脊柱的重塑和感知学习不仅可以改善对解剖学可塑性如何有助于学习的理解，而且可能揭示了该受体在受伤后和发育过程中控制可塑性的保守机制。