Motor skill learning depends on protein synthesis in motor cortex after training

The role of protein synthesis in memory consolidation is well established for hippocampus-dependent learning and synaptic plasticity. Whether protein synthesis is required for motor skill learning is unknown. We hypothesized that skill learning is interrupted by protein synthesis inhibition ( PSI). We intended to test whether local protein synthesis in motor cortex or cerebellum is required during skill acquisition and consolidation. Anisomycin (ANI; 100 mug/mul in 1 mu1 of PBS) injected into motor cortex, posterior parietal cortex, or cerebellum produced 84.0 +/- 1.44% (mean +/- SEM), 85.9 +/- 2.31%, and 87.3 +/- 0.17% of PSI 60 min after administration, respectively. In motor cortex, protein synthesis was still reduced at 24 hr (72.0 +/- 4.68% PSI) but normalized at 48 hr after a second injection given 24 hr after the first. To test for the effects of PSI on learning of a skilled reaching task, ANI was injected into motor cortex contralateral to the trained limb or into ipsilateral cerebellum immediately after daily training sessions 1 and 2. Two control groups received motor cortex injections of vehicle or ANI injections into contralateral parietal cortex. Control and cerebellar animals showed a sigmoid learning curve, which plateaued after day 4. PSI in motor cortex significantly reduced learning during days 1-4. Thereafter, when protein synthesis normalized, learning was reinitiated. ANI injections into motor cortex did not induce a motor deficit, because animals injected during the performance plateau did not deteriorate. This demonstrates that motor skill learning depends on de novo synthesis of proteins in motor cortex after training.