Conner JM, Chiba AA, Tuszynski MH (2004) The basal forebrain cholinergic system is essential for cortical plasticity and functional recovery following brain injury. Neuroscience 2004 Abstracts 685.12. Society for Neuroscience, San Diego, CA.
Summary: Localized damage to the motor cortex typically results in impaired motor function. Functional recovery following focal brain injury presumably requires the reorganization of cortical circuitry, enabling undamaged areas remote from the lesion site to take over function. Neuronal mechanisms mediating plasticity of cortical representations are not fully understood, but recent studies have indicated that the basal forebrain cholinergic system may play an essential role. In the present study, we investigated the hypothesis that the basal forebrain cholinergic system is essential for enabling cortical reorganization required for functional recovery following focal motor cortex lesions. Following focal cortical injury, performance in a previously learned skilled reaching task dropped by ~75%. After 5-weeks of rehabilitative training, normal (cholinergically-intact) rats recovered 55.2 ± 4.4% of their pre-lesion reaching performance. Rats with specific lesions of the cholinergic neurons projecting to the cortex showed only 18.1 ± 7.7% recovery (p<0.002). Intracortical mapping revealed that massive reorganization of motor representations had occurred in the cortex following focal cortical injury and rehabilitative training. A significant 48.6 ± 12.2% increase (p=0.001) in the size of the rostral forelimb area (RFA) was seen in cholinergically-intact, functionally recovered, rats. In contrast, the size of the RFA did not change in cholinergic-lesioned animals. Subsequent ablation of the RFA completely disrupted skilled reaching performance, suggesting the RFA was essential to the recovered function. These results demonstrate that functional recovery following discrete cortical injury requires basal forebrain cholinergic mechanisms and suggest that the basis for this recovery is the cholinergic-dependent reorganization of motor representations.
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