Unilateral sensorimotor cortex lesions in adult rats facilitate motor skill learning with the "unaffected" forelimb and training-induced dendritic structural plasticity in the motor cortex

Abstract

In humans and other animals, sufficient unilateral damage to the sensorimotor cortex can cause impairments in the opposite forelimb and the development of a hyper-reliance on the nonimpaired limb. This hyper-reliance is adaptive to the extent that it contributes to functional compensation for lesion-induced impairments. We have found that unilateral lesions of the forelimb region of the sensorimotor cortex (FLsmc) in rats, or callosal transections, cause neurons of the opposite motor cortex to become exceptionally responsive to changes in forelimb behavior. This enhanced responsiveness might facilitate learning of compensatory strategies with the nonimpaired forelimb after unilateral FLsmc lesions. The possibility that these lesions facilitate learning with the nonimpaired forelimb was addressed in this study. Rats were required to learn a skilled forelimb reaching task after either unilateral FLsmc lesions or sham operations. The trained limb in animals with lesions was the nonimpaired limb. Compared with shams, rats with unilateral lesions had a greater rate of acquisition and asymptotic performance level on the task, which was especially evident on more difficult trials. Quantitative measures of microtubule associated protein-2 (MAP2) immunostained dendrites indicated an enhancement of training-induced dendritic cytoskeletal changes in the motor cortex opposite lesions. Thus, unilateral FLsmc lesions facilitate learning of at least some types of motor skills using the nonimpaired forelimb as well as some of the neuronal changes associated with this learning. This facilitation could be a substrate underlying behavioral compensation for unilateral FLsmc damage and may contribute to the phenomenon of learned nonuse of the impaired limb.

Fig. 1.

Reach training apparatus (A), and sequential photographs of a rat approaching (B), grasping (C), and retrieving and beginning to eat (D) a food pellet (arrows). An inner chamber wall is to the animal's right.

Fig. 2.

Reconstructions of the extent and placement of unilateral lesions of the forelimb region of the sensorimotor cortex (FLsmc) (A, C–E) and regions of quantification of MAP2 immunoreactive processes in the motor cortex [lateral agranular region (AGl)] and granular insular cortex (GI) opposite the lesion (B). The regions outlined inblack in A andC–E indicate the largest extent of all lesions combined, whereas gray areas indicate the damaged tissue common to all lesions in that group.Numbers in B and E are approximate coordinates in millimeters relative to bregma.

Fig. 3.

Successful reaches with the preferred forelimb on the pellet retrieval task for each group before surgery (A) and with the previously nonpreferred limb after unilateral FLsmc lesions or sham operations (B). The trained limb in animals with unilateral lesions was the nonimpaired forelimb (ipsilateral to the lesion). Lesion animals performed significantly better than shams on most postlesion days of training. On more difficult, remote pellet trials, rats with lesions rapidly acquired a proficiency equivalent to the performance in retrieving close pellets, whereas sham animals had more gradual and subtle improvements over days of training. To theright of the graphs are schematic illustrations of rat brains and the side of the lesion and the training relative to the preoperatively preferred forelimb. Data are means ± SEM percentage of successful reaches/total reach attempts. *p < 0.05, ^† p< 0.01 significantly different from shams.

Fig. 4.

The percentage of successful reaches on the pellet retrieval task after unilateral FLsmc lesions or sham operations when no extensive training with the other limb was provided before surgery (i.e., experiment 2). The postsurgical training was with the preoperatively nonpreferred limb and in animals with unilateral FLsmc lesions, the nonimpaired limb (see illustrations to theright). Rats with unilateral FLsmc lesions demonstrated a faster rate of acquisition on the task in comparison with their sham counterparts on both close and remote pellets trails. Data are means ± SEM. *p < 0.05 significantly different from shams.

Fig. 5.

The percentage of reach attempts made with the previously preferred forelimb during postsurgical training in animals from experiment 1 (A) and experiment 2 (B). The design of the apparatus prevented reach attempts with this limb from being successful. Particularly in the first 3 d of training, sham animals with extensive preoperative training of the preferred forelimb (experiment 1, A) tended to make more reach attempts with this limb than the lesion group of this experiment and both groups of experiment 2 (B) that had no extensive presurgical training. However, there was not a significant group or group by day interaction effect on two-way ANOVA in either experiment. Data are means ± SEM.

Fig. 6.

Representative photomicrographs of MAP2-IR dendrites in layer V (A) and layer II/III (B) of the motor cortex opposite unilateral lesions and opposite the trained forelimb. Quantitative results are shown in Figure 7. Scale bar, 25 μm.

Fig. 7.

The surface density of MAP2-immunoreactive dendrites in layer V (A) and layer II/III (B) of the motor cortex opposite the lesion and/or trained limb. In layer V, increases in MAP2-IR were especially evident after unilateral lesions, although there were also significant increases after reach training in intact animals (Sham +Training). Reach training after lesions (Lesion + Training) produced further increases in MAP2-IR dendrites than that found after lesions alone or training alone. In Layer II/III (B), increases in the surface density of MAP2-IR dendrites were greatest in intact animals receiving unilateral reach training, whereas lesions alone produced a smaller but significant increase in comparison with Sham + No-Training. Reach training after the lesions increased MAP2-IR in comparison with lesions alone, but not in comparison with training alone in layer II/III. Data are means ± SEM. *p < 0.05; ^† p< 0.01.

Fig. 8.

The percentage of errors per step taken with the nontrained and contralateral-to-the-lesion forelimb while wandering the grid floor of the footfault test. Errors were misplacements of the forepaw that resulted in slips through the grid openings. Animals with unilateral FLsmc lesions demonstrated an initial dramatic impairment in placements with the contralateral forelimb in comparison with shams that improved over time. Although there were no significant differences between the two lesion groups, rats receiving postlesion reach training with the nonimpaired forelimb (Lesion + Training) remained significantly different from shams on days 8 and 18, whereasLesion + No-Training returned to nonsignificant levels in comparison with the shams by day 8. On day 19, animals were observed on the footfault test with the nonimpaired/trained forelimb anesthetized (Lidocaine Challenge), which tests the reliance on this limb for traversing the grid floor. This resulted in greater errors with the impaired limb in both lesion groups. In theLesion + Training and Sham +Training groups, errors with the nontrained limb were increased relative to animals of the same lesion condition that had not undergone reach training, suggesting that the reach training resulted in an increased reliance on the trained limb for the task. Data are means ± SEM. *p < 0.05 significantly different from sham of the same training condition.^† p < 0.05 significantly different from the No-Training group of the same lesion condition.