Motor skill training, but not voluntary exercise, improves skilled reaching after unilateral ischemic lesions of the sensorimotor cortex in rats

Abstract

Background and purpose: Exercise and rehabilitative training each have been implicated in the promotion of restorative neural plasticity after cerebral injury. Because motor skill training induces synaptic plasticity and exercise increases plasticity-related proteins, we asked if exercise could improve the efficacy of training on a skilled motor task after focal cortical lesions.

Methods: Female young and middle-aged rats were trained on the single-pellet retrieval task and received unilateral ischemic sensorimotor cortex lesions contralateral to the trained limb. Rats then received both, either, or neither voluntary running and/or rehabilitative training for 5 weeks beginning 5 days postlesion. Motor skill training consisted of daily practice of the impaired forelimb in a tray-reaching task. Exercised rats had free access to running wheels for 6 h/day. Reaching function was periodically probed using the single-pellet retrieval task.

Results: In young adults, motor skill training significantly enhanced skilled reaching recovery compared to controls. However, exercise did not significantly enhance performance when administered alone or in combination with skill training. There was also no major benefit of exercise in older rats. Additionally, there were no effects of exercise in a measure of coordinated forelimb placement (the foot-fault test) or in immunocytochemical measures of several plasticity-related proteins in the motor cortex.

Conclusions: In young and middle-aged animals, exercise did not improve motor skill training efficacy following ischemic lesions. Practicing motor skills more effectively improved recovery of these skills than did exercise. It remains possible that an alternative manner of administering exercise would be more effective.

Figure 1

Rats were trained to proficiency on the single-pellet retrieval task preoperatively, and this test was used to probe reaching function after the ischemic lesions (a). The tray-reaching task was used for rehabilitative training (b). Exercised rats (c) had access to a running wheels (via a chicken wire tube) for 6 h/day, whereas no-exercise controls were given access to a novel metal box (d).

Figure 2

Ischemic sensorimotor cortex lesions. Schematic representations of the damage common to all lesions, the range, and a representative lesion within each group. Numbers to the right indicate the distance from bregma of the coronal sections.

Figure 3

Estrous stage effects at the time of lesion induction in young adults. Rats in proestrus (when estrogen and progesterone are at their peak) had (a) significantly more remaining cortical volume in the sensorimotor cortex region and (b) significantly fewer errors on the foot-fault test (a measure of coordinated forelimb use during locomotion) 10 days postinfarct, compared to animals in diestrus and estrous. Estrous stage distributions were approximately equal among experimental groups (see text for details). Most of the older rats were in anestrus at the time of lesion induction. Data are means ± SEM. *P < .05 compared with proestrus.

Figure 4

Voluntary exercise. By the fifth week, both young adults and middle-aged adults increased the distance run compared to the first week (a). Although the average distance run in the middle-aged animals was less than the young adult rats, the performance in the skilled reach task averaged across all 5 weeks was similar (b). There were no significant correlations between distance run and reaching task performance (see text for details).

Figure 5

Single-pellet retrieval task. Young adult rats (a) receiving rehabilitation on the tray-reaching task had a significant improvement in reaching performance in probe trials after lesions, whereas there were no significant main or interaction effects of exercise. In middle-aged animals (b), exercise influenced the pattern of recovery, but not the overall outcome (note that middle-aged animals were trained to a higher preoperative criterion than younger rats and received an additional probe trial prior to rehabilitation training onset). Data are means ± SEM. *P < .05 and **P < .005 rehab significantly different versus no-rehab.

Figure 6

Foot-fault task. Middle-aged animals were found to have a significant increase of errors in the task 4 days after ischemic injury (post-op). However, after 5 weeks, animals were capable of completing the task with fewer errors. There were no significant effects of the exercise condition on this test.