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.