Skilled motor training, lesions, and rehabilitation. (A) Animals underwent 2 wk of skilled forelimb reach and grasp training. (B) Motor training resulted in gradual increases in pellet retrieval accuracy [repeated measures ANOVA F(11,165) = 92.7; P < 0.001]. (C) Electrolytic lesions were then placed in the motor cortex controlling movement of the caudal forelimb (6). (D) Lesions resulted in an 85% reduction in the ability of rats to performed the skilled forelimb reach and grasp task compared with their prelesion levels of performance [n = 4 rats per group (12 total); t test t(1) = 0.03; P < 0.001]. Animals with intact or lesioned cholinergic systems exhibited the same degree of initial deficit postlesion [t test t(7) = 0.03; P = 0.97]. (E) Over 5 wk of rehabilitation training, rats with intact cholinergic systems recovered 60.9% ± 8.3% of their prelesion grasping ability (n = 4 animals). Animals with cholinergic lesions recovered only 20.7% ± 6.6% of their prelesion grasping performance (n = 4 animals), representing a significant impairment relative to animals with functioning cholinergic system [two-way mixed ANOVA (group × week) F(4,24) = 6.90; P < 0.001]. Asterisks indicate comparisons on individual weeks (Fisher’s posthoc test). Error bars ± SEM. *P < 0.05; **P < 0.01. (F) All animals then underwent injections of retrograde tracers in the C8 spinal cord segment, which controls muscles related to the skilled forelimb reach and grasp task (5). Chol, cholinergic.