Limits on recovery in the corticospinal tract of the rat: partial lesions impair skilled reaching and the topographic representation of the forelimb in motor cortex.

Although evidence suggests that there are impairments in skilled movements following very large lesions of the pyramidal component of the corticospinal tract, the behavioral and electrophysiological effects of partial lesion has not received equal attention. Here, rats with complete lesions or partial lesions (medial, central, or lateral third) of the pyramidal tract at the medullary pyramids were evaluated for their quantitative and qualitative postsurgical performance on a skilled reaching task, following which the topographic representation of their forelimb was mapped with intracortical microstimulation (ICMS). Complete lesions impaired reaching success, impaired the qualitative features of reaching movements, and abolished ICMS evoked movement from the forelimb region of motor cortex. Although partial lesions did not impair reaching success, they did impair qualitative aspects of limb movement including forepaw aiming, supination, and food pellet release. ICMS indicated a reduction in the size of the forelimb area, especially the distal area of the caudal forelimb area (CFA), of the motor map. The behavioral and electrophysiological impairments did not vary with lesion location within the pyramidal tract. The incomplete recovery, as measured both behaviorally and electrophysiologically, demonstrates that plasticity within the corticospinal system is limited even with lesions that permit substantial sparing of pyramidal tract fibers.

Preserved ipsilateral-to-lesion motor map organization in the unilateral 6-OHDA-treated rat model of Parkinson's disease.

The classic view of dopamine (DA) loss in Parkinson's disease is that it produces a functional deafferentation in striatal-cortical circuitry that, in turn, contributes to sensorimotor deficits. The present study examines this view in the rat by assessing how DA-depletion affects the intracortical microstimulation (ICMS) topographic representation of movement in the rostral and caudal motor areas of the motor cortex. The ICMS map is used as an index of motor cortex function because it has been shown to reflect motor function and experience. Groups of rats received no training or skilled reach training and were then given unilateral 6-hydroxydopamine (6-OHDA) or sham lesions of the nigrostriatal bundle to deplete nigrostriatal DA. Lesion success was confirmed by abnormalities in skilled reaching, by apomorphine-induced rotation, and by loss of DA neurons in the substantia nigra. The size and threshold of the motor map in naive and skilled reach trained DA-depleted rats were preserved. In addition, there was an increase in distal limb representation in the caudal forelimb area (CFA) in the DA-depleted rats suggesting a possible plastic response to the behavioral effects of DA-depletion. The presence of preserved size and modified map organization in DA-depleted rats is discussed in relation to the hypothesis that preserved motor cortex functionality despite DA loss underlies the spared motor abilities of DA-depleted rats.

Unilateral frontal lobe contusion and forelimb function: chronic quantitative and qualitative impairments in reflexive and skilled forelimb movements in rats.

Traumatic brain injury induced by mechanical impacts of the head can be modeled in rats in order to investigate acute and chronic therapy. Because frontal lobe contusion affects the neural representation of the forelimb in both the neocortex and basal ganglia, the purpose of the present experiments was to examine the chronic changes in reflexive and skilled forelimb induced by the injury. Contusions produced a cavity in the sensorimotor cortex, accompanied by shrinkage of the pyramidal tract, loss of cells in the dorsolateral striatum, and enlargement of the lateral ventricle. There were substantial individual differences in lesion size despite use of two different contusion forces, but all rats receiving contusions displayed chronic forelimb deficits. Reflexive tests of forelimb use (limb posture, placing, and support) indicated that impairments were most pronounced in the forelimb contralateral to the lesion. Tests of limb preference indicated that the contusion rats displayed a forelimb asymmetry: they were more likely to lean on their ipsilateral-to-lesion forelimb for support when rearing in a test cylinder, and this impairment was amplified in a home cage test. They also displayed a preference for the forelimb ipsilateral to the lesion when reaching for food, although both forelimbs were equally impaired on measures of success when reaching for food from a tray and reaching for a single food pellet on a shelf. A qualitative analysis from frame-by-frame video records indicated that when reaching for single pellets, impairments in forelimb use primarily affected the contralateral-to-lesion limb, especially limb aiming, supination, and food pellet release. Impairments in the ipsilateral-to-lesion forelimb were generally, but not exclusively, secondary to postural abnormalities. The wide range of chronic impairments in forelimb use following contusion injuries are discussed in relation to the anatomical and behavioral origins of the impairments and the potential use of forelimb tests in the assessment of therapy for traumatic brain injury to the frontal cortex.

Complete and partial lesions of the pyramidal tract in the rat affect qualitative measures of skilled movements: impairment in fixations as a model for clumsy behavior.

Little is known about prenatal and perinatal brain injury resulting in subsequent clumsy behavior in children. One candidate motor system is the pyramidal tract. The tract traverses the entire central nervous system and, through direct and indirect connections to the brainstem and spinal cord sensory and motor nuclei, is involved in the learning and execution of skilled movements. Here, rats, either naive or pretrained on a number of motor tasks, were assessed for acute and chronic impairments following complete or incomplete pyramidal tract lesions. Postsurgery rats with complete lesions were impaired on the qualitative measures of limb aiming, supination, and posture. Impaired movements require fixations, complementary movements in different body segments. The impairment in fixations was manifest acutely and underwent no improvement with subsequent training/testing. The finding that complete and partial pyramidal tract lesions produce chronic impairment in fixations provides insight for understanding clumsy behavior in humans and its potential remediation via specific training in making fixations.

Acute alcohol administration improves skilled reaching success in intact but not 6-OHDA dopamine depleted rats: a subsystems analysis of the motoric and anxiolytic effects of alcohol.

Low doses of alcohol impair movement and reduce anxiety. Most assessments of movement under ethyl alcohol (alcohol) in the rat have been tests of whole body movements, however. There has been no examination of the effects of alcohol on skilled limb movements, such as reaching for food with a forelimb. This was the purpose of the present study. Rats were trained to reach through a slot of a box with a forelimb in order to obtain a food pellet located on an external shelf. Once asymptotic performance was achieved, rats were given alcohol (20 ml of 8, 12 or 20% (v/v) solution) in separate tests to establish a relationship between alcohol ingestion and skilled reaching performance. Acute treatment with all doses of alcohol impaired postural support, but doses of 8 and 12% alcohol improved skilled reaching success. Qualitative analysis of the movements used for reaching at doses of 8 and 12% indicated that some limb components of the reaching movement were also impaired, perhaps secondarily due to impaired posture. In contrast, the reaching success of rats with unilateral dopamine depletion, induced with the neurotoxin 6-hydroxydopamine (6-OHDA) in the nigrostriatal bundle, was impaired by the same dose of alcohol that improved reaching success in control rats. The finding of improved success in reaching associated with reduced postural support in normal rats suggests a differential action of alcohol on movement subsystems underlying posture relative to skilled movement that depends upon an intact dopaminergic system. The results are also discussed with respect to the relationship of subsystems of movement and anxiety.