Experience-dependent amelioration of motor impairments in adulthood following neonatal medial frontal cortex injury in rats is accompanied by motor map expansion.

One of the most common, and disruptive, neurological symptoms following neonatal brain injury is a motor impairment. Neonatal medial frontal cortical lesions in rats produce enduring motor impairments, and it is thought that lesion-induced abnormal cortical morphology and connectivity may underlie the motor deficits. In order to investigate the functional consequences of the lesion-induced anatomical abnormalities in adulthood, we used intracortical microstimulation to determine the neurophysiologic organization of motor maps within the lesion hemisphere. In addition, groups of neonatal lesion rats were given reach training or complex housing rehabilitation in adulthood and then mapped with intracortical microstimulation. The results demonstrate that neonatal medial frontal cortex lesions produce motor deficits in adulthood that are associated with abnormal motor maps. Further, adult behavioral treatment promoted partial recovery that was supported by reorganization of the motor maps whereby there were increases in the size of the forelimb motor maps. The experience-induced expansion of the forelimb motor maps in adulthood provides a neural mechanism for the experience-dependent improvements in motor performance.

Basic fibroblast growth factor stimulates functional recovery after neonatal lesions of motor cortex in rats.

Rats were given bilateral lesions of the motor cortex on the tenth day of life, and then received a daily subcutaneously injection of either basic fibroblast growth factor (FGF-2) or vehicle for 7 consecutive days. In adulthood, they were trained and assessed on a skilled forelimb reaching task. Although all lesion groups were impaired at skilled reaching, the postnatal day 10-lesioned group that received FGF-2 was less impaired than the lesion group that received the vehicle. Furthermore, the lesioned rats that received FGF-2 showed a filling of the lesion cavity with tissue, whereas the lesioned vehicle-treated rats still had a prominent lesion cavity. The functionality of the tissue filling the cavity, tissue surrounding it, and tissue from the motor cortex (in control rats) was assessed using intracortical microstimulation, and showed that stimulation of some sites from the filled cavity could evoke movement. The rats were perfused and processed for Golgi-Cox staining. Medium spiny neurons from the striatum were drawn and analyzed, and the results suggest that postnatal day 10 lesions of the motor cortex induced an increase in the length and complexity of these cells compared with those of non-lesioned rats. Our results suggest that FGF-2 may play an important role in recovery from early brain damage.

Middle cerebral artery (MCA) stroke produces dysfunction in adjacent motor cortex as detected by intracortical microstimulation in rats.

Middle cerebral artery (MCA) stroke in the rat produces impairments in skilled movements. The lesion damages lateral neocortex but spares primary motor cortex (M1), raising the question of the origin of skilled movement deficits. Here, the behavioral deficits of MCA stroke were identified and then M1 was examined neurophysiologically and neuroanatomically. Rats were trained on a food skilled reaching task then the lateral frontal cortex was damaged by unilateral MCA electrocoagulation contralateral to the reaching forelimb. Reach testing and training on two tasks was conducted over 30 post-surgical days. Later, M1 and the corticospinal tract were investigated using intracortical microstimulation (ICMS), anterograde and retrograde axon tracing. A skilled reaching impairment was observed post-surgery, which partly recovered with time and training. ICMS revealed a diminished forelimb movement representation in MCA rats, but a face representation comparable in size to sham rats. Anterograde and retrograde tract tracing suggest that M1 efferents were intact. Although M1 appears to be in the main anatomically spared after MCA stroke its function as assessed electrophysiologically and behaviorally is disrupted.

Sensitivity of cortical movement representations to motor experience: evidence that skill learning but not strength training induces cortical reorganization.

The topography of forelimb movement representations within the rat motor cortex was examined following forelimb strength training. Adult male rats were allocated to either a Power Reaching, Control Reaching or Non-Reaching Condition. Power Reaching rats were trained to grasp and break progressively larger bundles of dried pasta strands with their preferred forelimb. Control Reaching animals were trained to break a single pasta strand and Non-Reaching animals were not trained. Power Reaching animals exhibited a progressive increase in the maximal size of the pasta bundle that could be retrieved during a 30-day training period. Kinematic analyses showed that this improvement was not due to a change in reaching strategy. Intracortical microelectrode stimulation was used to derive maps of forelimb movement representations within the motor cortex of all animals following training. In comparison to Non-Reaching animals, both Power Reaching and Control Reaching animals exhibited a significant increase in the proportion of motor cortex occupied by distal forelimb movement representations (wrist/digit) and a decrease in the proportion of proximal representations (elbow/shoulder). These results demonstrate that the development of skilled forelimb movements, but not increased forelimb strength, was associated with a reorganization of forelimb movement representations within motor cortex.

Functional reorganization of the rat motor cortex following motor skill learning.

Functional reorganization of the rat motor cortex following motor skill learning. J. Neurophysiol. 80: 3321-3325, 1998. Adult rats were allocated to either a skilled or unskilled reaching condition (SRC and URC, respectively). SRC animals were trained for 10 days on a skilled reaching task while URC animals were trained on a simple bar pressing task. After training, microelectrode stimulation was used to derive high resolution maps of the forelimb and hindlimb representations within the motor cortex. In comparison with URC animals, SRC animals exhibited a significant increase in mean area of the wrist and digit representations but a decrease in elbow/shoulder representation within the caudal forelimb area. No between-group differences in areal representation were found in either the hindlimb or rostral forelimb areas. These results demonstrate that motor skill learning is associated with a reorganization of movement representations within the rodent motor cortex.

Selective synaptic plasticity within the cerebellar cortex following complex motor skill learning.

Complex motor skill learning, but not mere motor activity, leads to an increase in synapse number within the cerebellar cortex. The present experiment used quantitative electron microscopy to determine which synapse types were altered in number. Adult female rats were allocated to either an acrobatic condition (AC), a voluntary exercise condition (VX), or an inactive condition (IC). AC animals were trained to traverse an elevated obstacle course requiring substantial motor coordination to complete. VX animals were housed with unlimited access to running wheels and IC animals received no motor training but were handled briefly each day. Results showed the AC animals to have significantly more parallel fiber to Purkinje cell synapses than both the VX and IC animals. No other synapse type was significantly altered. Thus, the learning-dependent increase in synapse number observed within the cerebellar cortex is accomplished primarily through the addition of parallel fiber synapses.

Structural stability within the lateral cerebellar nucleus of the rat following complex motor learning.

Complex motor learning, but not mere motor activity, has been previously shown to induce structural modifications within the cerebellar cortex. The present experiment examined whether similar changes occur within one of the primary output targets of the region of the cerebellar cortex in which these structural changes were described, the lateral cerebellar nucleus (LCN; dentate nucleus). Adult female rats were randomly allocated to one of three training conditions. Acrobatic condition (AC) rats were trained to complete a complex motor learning task consisting of a series of elevated obstacles while motor control (MC) condition animals were forced to traverse a flat obstacle-free runway equal in length to the AC task. Inactive condition (IC) animals received no motor training. Unbiased stereological techniques and electron microscopy were used to obtain estimates of synapse number and postsynaptic density (PSD) length within the LCN. Results showed that neither synapse number nor PSD length was significantly altered as a function of training condition. These results indicate that complex motor skill learning is associated with structural plasticity within the cerebellar cortex and with structural stability within the lateral cerebellar nucleus.

Learning-dependent dendritic hypertrophy of cerebellar stellate cells: plasticity of local circuit neurons.

Recent work has shown that motor learning, but not mere motor activity, changes the morphology of Purkinje cells, the major projection neurons of the cerebellar cortex. In the present study we examined how motor skill learning affects the dendritic morphology of the stellate local circuit neurons. Adult female rats were either trained to complete a complex motor learning task or forced to traverse a flat, obstacle-free runway. Golgi impregnated stellate cells were then traced via camera lucida and their dendritic arborizations examined with a concentric ring analysis. Results showed the motor learning animals to have significantly greater stellate cell dendritic arborizations than the activity controls. Thus these local circuit neurons exhibit morphological plasticity.

Learning-dependent synaptic modifications in the cerebellar cortex of the adult rat persist for at least four weeks.

Several experiments have demonstrated increased synapse number within the cerebellar cortex in association with motor skill learning but not with motor activity alone. The persistence of these synaptic changes in the absence of continued training was examined in the present experiment. Adult female rats were randomly allocated to either an acrobatic condition (AC) or a motor activity condition (MC). The AC animals were trained to traverse a complex series of obstacles, and each AC animal was pair-matched with an MC animal that traversed an obstacle-free runway. These animals were further assigned to one of three training conditions. Animals in the EARLY condition were trained for 10 consecutive days before being killed, animals in the DELAY, condition received the same 10 d of training followed by a 28 d period without training, and animals in the CONTINUOUS condition were trained for the entire 38 d. Unbiased stereological techniques were used to obtain estimates of the number of synapses per Purkinje cell within the cerebellar paramedian lobule. Results showed the AC animals to have significantly more synapses per Purkinje cell than the MC animals in all three training conditions. There were no differences in the number of synapses per Purkinje cell among the EARLY, DELAY, and CONTINUOUS conditions. These data demonstrate that both the motor skills and the increases in synapse number presumed to support them persist in the absence of continued training.

Synaptogenesis and dendritic growth in the cortex opposite unilateral sensorimotor cortex damage in adult rats: a quantitative electron microscopic examination.

Unilateral lesions of the forelimb area of the sensorimotor cortex in adult rats resulted in time-dependent increases in the number of synapses per neuron and the volume and membrane surface area of dendritic processes per neuron within layer V of the contralateral motor cortex in comparison to sham-operated rats. Based on previous findings of a behavioral relationship with increased dendritic arborization, these changes may be related to lesion-induced compensatory changes in the use of the non-impaired (ipsilateral to the lesion) forelimb.

Synaptogenesis and Fos expression in the motor cortex of the adult rat after motor skill learning.

Recent work has suggested that changes in synapse number as well as changes in the expression of the Fos protein may occur within the motor cortex in association with motor learning. The number of synapses per neuron and the percentage of Fos-positive neurons within layer II/III of the rat motor cortex was measured after training on a complex motor learning task. Adult female rats were allocated randomly to either an acrobatic condition (AC), a motor control condition (MC), or an inactive control condition (IC). AC animals were trained to traverse a complex series of obstacles, and each AC animal was pair matched with an MC animal that traversed an obstacle-free runway. IC animals received no motor training. Animals from each condition were killed at various points during training, and unbiased stereological techniques were used to estimate the number of synapses per neuron and the percentage of Fos-positive cells within layer II/III of the motor cortex. AC animals exhibited an overall increase in the number of synapses per neuron in comparison to MC and IC animals at later stages of training. AC animals also had a significantly higher overall percentage of Fos-positive cells in comparison to both controls, with a trend for the increase to be greater during the acquisition versus the maintenance phase. These data suggest that Fos may be involved in the biochemical processes underlying skill acquisition and that motor learning, as opposed to motor activity, leads to increases in synapse number in the motor cortex.