Figure 1.

Effects of site-specific depletion of basal forebrain cholinergic corticopetal inputs on skilled motor learning. (A) Global depletion of cortical cholinergic innervation (filled diamonds) following 192-SAP injections into the nucleus basalis/substantia innominata significantly impaired acquisition of a skilled forelimb reaching behavior (P < 0.0001, overall repeated measures ANOVA; P < 0.0001 post hoc Fisher's comparing global SAP-lesioned animals to vehicle-injected controls). Focal depletion of cholinergic inputs to the motor cortex (filled circles) also resulted in significant impairments in task acquisition relative to vehicle-treated controls (P < 0.05 post hoc Fisher's). However, animals with selective depletion of the motor cortex performed significantly better than animals with global cholinergic depletions (P < 0.005 post hoc Fisher's). (B) Final levels of reaching performance, determined as the average reaching accuracy over the last 3 days of training, were also significantly reduced in rats with either global cholinergic lesions (P < 0.0001, overall ANOVA; P < 0.0001 post hoc Fisher's) or cholinergic depletion of the motor cortex (P < 0.005, post hoc Fisher's) relative to vehicle-treated controls. Animals with global depletion of cortical cholinergic innervation performed significantly worse than animals with focal cholinergic depletion of the motor cortex (P < 0.05, post hoc Fisher's). Focal cholinergic depletion of either PFC or AUD had no significant effect on either skilled motor acquisition (A) or final reaching performance (B) relative to vehicle-treated animals.