Transcallosal axonal sprouting patterns after ischemic motor cortical lesions and varying forelimb experiences
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In rodent models of motor cortical stroke, skill learning with the non-paretic forelimb worsens rehabilitation outcomes of the paretic forelimb. The neural basis of this effect is not fully understood. A possible mechanism for this effect is activity-dependent synaptic competition between projections from remaining regions of the ipsi- and contralesional motor cortex, specifically from the ipsilesional rostral forelimb area (RFA) and the contralesional caudal forelimb area (CFA). Previous studies have found that this effect is negated by callosal transections or inhibition of the contralesional cortex, suggesting that the contralesional hemisphere plays a key role. The purpose of this study was to investigate the influence of differential forelimb experience on the cortical plasticity of callosal projections from the contralesional CFA, which is known to contribute to the reinnervation of peri-lesion cortex. Since axonal sprouting is activity dependent, one would expect animals trained with the non-paretic forelimb to have an increase in axonal fibers and bouton densities from the contralesional CFA. Adult male Long-Evans rats were trained to proficiency using their dominant (for reaching) forelimb on the single-pellet-retrieval skilled reaching task. Animals subsequently received unilateral cortical ischemic lesions in the CFA of the hemisphere contralateral to the trained forelimb. On post-infarct day five, rats began 15 days of reach training either with their non-paretic forelimb (NPT), their paretic forelimb (rehabilitation training, RT), or no-training control procedures (CTRL). On post-infarct day 23 all animals received an injection of biotinylated dextran amine (BDA) into the contralesional CFA to label callosal projections from the spared hemisphere into peri-infarct motor cortex. Contrary to the hypothesis, results indicate no significant differences in axonal fiber or synaptic bouton densities across any of the groups within any of the examined regions of peri-lesion cortex. This suggests that the mechanism behind the detrimental effects of NPT on the paretic limb does not involve a net change in densities of neural connections from the contralesional CFA. Future research should explore possible changes in the structure of synapses or variations in relative densities of excitatory and inhibitory post-synaptic cells as possible contributors to the neural basis of the deleterious effect of NPT.