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Horizontally-oriented intracortical connections have been proposed to serve as a substrate for plastic reorganizations of adult motor cortex. N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) of synaptic efficacy is a candidate mechanism of these reorganizations in mammalian species ranking from rats to humans. The acquisition of a motor skill is accompanied by increased strength of synaptic connections within adult rat primary motor cortex, most likely due to LTP-like mechanisms.