Regulation of Anatomical Plasticity and Perceptual Learning by NgR1

NgR1 对解剖可塑性和知觉学习的调节

• 批准号: 8227408
• 负责人: Aaron W McGee
• 金额: $ 25.72万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8227408
• 关键词: Adult; Attention; Axon; Behavioral; Brain; Cerebral cortex; Chronic; Dendritic Spines; Detection; Development; Discrimination; Environment; Exhibits; Exposure to; Goals; Image; In Vitro; Injury; Learning; Letters; Mediating; Modification; Motor; Mus; Mutant Strains Mice; Myelin; Nature; Neuraxis; Neurons; Perceptual learning; Performance; Phenotype; Proteins; Reading; Recovery; Regimen; Regulation; Reporting; Research; Sensory; Somatosensory Cortex; Specific qualifier value; Specificity; Spinal cord injury; Stroke; Structure; Synapses; Synaptic plasticity; System; Tactile; Techniques; Testing; Training; Vertebral column; Vibrissae; Visual; Wild Type Mouse; braille; central nervous system injury; critical developmental period; excitatory neuron; experience; improved; in vivo; inhibitor/antagonist; injured; mutant; neural circuit; novel; receptor; research study

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. PUBLIC HEALTH RELEVANCE: How does 'practice make perfect'? This research both examines how learning a perceptual task, for example reading Braille letters, changes the structure of circuits in the brain and explores how the rate of learning is governed.

描述（由申请人提供）：新颖的感觉体验和改善的运动性能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，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上，作为学习的潜在基础。然而，解决脊柱重塑和学习之间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。 由于胡须的地形表征以及胡须使用的受控、可量化性质，体感皮层（桶状皮层）中的桶状场一直是检查感官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。这些实验将桶状皮层树突棘的长期体内成像与感知学习任务结合起来，以研究脊柱重塑的速率是否以及如何指定感知学习的速率。 为了检验脊柱重塑率报告感知学习率的假设，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，这些小鼠可以更快地学习这项任务。 NgR1 是一种神经元蛋白，可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 突变体还表现出一种通常局限于发育关键期的视觉可塑性。 NgR1 如何调节脊柱重塑和知觉学习不仅可以增进对解剖可塑性如何促进学习的理解，还可以揭示该受体在损伤后和发育过程中控制可塑性的保守机制。 公共卫生相关性：如何“熟能生巧”？这项研究既考察了学习感知任务（例如阅读盲文字母）如何改变大脑回路的结构，又探讨了学习速度是如何控制的。