While experience early in life actively refines neural circuits by virtue of a high capacity for plasticity, experience-dependent plasticity and improvement of function is prominently limited in adult brain. However, the molecular and cellular mechanisms underlying how experience-driven neural plasticity is restricted in adult brain remain poorly understood. Removal of the myelin-inhibiting signaling protein, Nogo receptor (NgR1), restores adult neural plasticity. Here we found that, in NgR1-deficient mice, whisker experience-driven synaptic AMPA receptor (AMPAR) insertion in the barrel cortex, normally complete by 2 weeks after birth, lasts into adulthood, leading to a sharpened whisker-barrel map. In vivo live imaging by two-photon microscope revealed more AMPAR on the surface of spines in the adult barrel cortex of NgR1-deficient than wild-type mice. Further, we found that whisker stimulation produced new spines in the adult barrel cortex of mutant but not of wild-type mice, and the newly synthesized spines contained more surface AMPAR than did the existing spines in mutant mice. These results suggest that Nogo signaling limits plasticity by restricting synaptic AMPAR delivery in coordination with anatomical plasticity.