Browsing by Subject "Motor cortex"
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Item The coordinated plasticity of astrocytes and synapses in learning and post-stroke recovery(2011-05) Kim, Soo Young, 1980-; Jones, Theresa A.; Gore, Andrea C.; Harris, Kristen M.; Schallert, Timothy; Delville, YvonStroke typically occurs in one hemisphere and often results in long-term disability in the contralateral body side (paretic side). Greater reliance on the non-paretic body side is used to compensate for this disability. Meanwhile, the brain undergoes degenerative and plastic changes in both hemispheres. Many previous studies have investigated post-stroke brain plasticity, and explored how it is shaped by behavioral experiences, to better understand the mechanisms of functional recovery. However, these studies have primarily focused on neurons and synapses. Given the abundant evidence that astrocytes actively control activity and plasticity of synapses, it seems reasonable to investigate how astrocytes are involved in behavior- and injury-driven brain plasticity. The central hypothesis of these studies is that synaptic plasticity underlying motor skill learning and post-stroke motor rehabilitation is coordinated with structural and functional plasticity of perisynaptic astrocytes. This was tested in a rat model of motor learning and "re-learning" after unilateral stroke-like damage to sensorimotor cortex. In the contralesional homotopic cortex, astrocytic volume varied with lesion size, as did the number of synapses. In the remaining motor cortex of the injured hemisphere, rehabilitative training with the paretic limb increased the proportion of astrocytic membrane apposed with synapses along with density of synapses. Furthermore, the percentage of synapses with astrocytic contacts was significantly correlated with functional outcome. Training with the non-paretic limb also induced greater synaptic density than controls in peri-infarct cortex, but functional outcome was negatively correlated with this and was not correlated with astrocytic contacts with synapses. These findings suggest that plasticity of, and association between, synapses and astrocytes vary with the type of experiences. Moreover, pharmacological upregulation of astrocytic glutamate uptake, which is one of the key ways that astrocytes modulate synaptic activity, interfered with functional recovery, supporting a critical role for astrocytic glutamate uptake in functional outcome following a stroke. Taken together, these studies contribute to better understanding of how lesions and experiences affect plasticity of astrocytes and synapses. These findings suggest that post-injury experiences alter astrocytic association with synapses, and that the coordinated plasticity of astrocytes and synapses is likely to be a critical mediator to functional outcome.Item Experience-dependent neuroplasticity in the perilesion cortex after focal cortical infarcts in rats(2007-12) Hsu, Jui-En Edward, 1977-; Jones, Theresa A.The leading cause of long-term disability among adults in industrialized countries is stroke. Exploration of the brain mechanisms involved during recovery from stroke is likely to yield information that can be used to promote better functional outcome. After focal motor cortical infarcts, reorganization of movement representations in the remaining motor cortex has been linked to both spontaneous recovery and recovery induced by rehabilitative training. However, the mechanisms and nature of cortical reorganization remain poorly understood. The central hypothesis of these dissertation studies is that synaptogenesis and structural reorganization in the cortex near the lesion are linked to spontaneous partial recovery and the beneficial effects of motor rehabilitative training after stroke-like injury. This was tested in a rat model of focal cortical ischemia by both behavioral and neuroanatomical measures in perilesion cortex. In separate studies, it was found that motor rehabilitative training on a skilled reaching task using the impaired forelimb after a unilateral ischemic lesion improved forelimb functional outcome and facilitated synaptogenesis in perilesion cortex. In addition, this improved functional recovery was disrupted by focal protein synthesis inhibition in perilesion cortex, suggesting the structural plasticity in this area plays an important role in regained function. Finally, it was also hypothesized that a therapy that enhances the efficacy of motor rehabilitation also enhances synaptic structural plasticity in perilesion cortex. Cortical electrical stimulation (CS) during motor rehabilitation has previously been shown to improve the efficacy of rehabilitation. Increased density of axodendritic synapses in perilesion cortex was found in rats that received cortical electrical stimulation of perilesion cortex during rehabilitation compared to rehabilitation alone, and the synaptic density was positively correlated with post-rehabilitation reaching performance. These findings suggest that CS-induced functional improvements may be mediated by synaptic structural plasticity in stimulated cortex. Together these studies indicate that, after a cortical lesion in rats, motor rehabilitation alone or in conjunction with other efficacious therapies can greatly enhance synaptic structural plasticity in perilesion cortex. Furthermore, these studies suggest that rehabilitation induced improvements in functional outcome are dependent upon the structural and functional integrity of the reorganized perilesion cortex.Item Frontal-lobe mediated word retrieval in Parkinson's disease(Texas Tech University, 1996-12) Thomason, Christine K.Parkinsonians have been shown to have difficulty with executive functioning, which is mediated by the frontal lobes of the brain. Tests of verbal fluency have been used to evaluate frontal lobe dysfunction. Letter fluency, however, may require different processes and mechanisms than semantic fluency. Martin and colleagues (1994) found that letter fluency seemed to be mediated by the frontal lobes whereas semantic fluency seemed to be mediated by the temporal lobes. It follows that Parkinsonians would have difficulty with letter fluency tasks, given their problems with frontal lobe functions. Differences between 30 Parkinsonian patients and 30 age-matched controls on both semantic and letter fluency tasks were examined and the relationship of performance on these tasks to executive function was evaluated. Results indicated that when executive functioning and depression are accounted for. Parkinsonians demonstrated poorer performance on letter but not category fluency relative to controls. Before accounting for depression and executive functioning, there were no differences between groups on letter fluency, however, controls performed significantly better than Parkinsonians on category fluency. Both category and letter fluency tasks correlated highly with a measure of executive function, the EXIT, but only for Parkinsonians. Screening for both executive impairment and depression are important when examining cognitive function in Parkinson's disease.Item Promoting restorative neural plasticity with motor cortical stimulation after stroke-like injury in rats.(2011-05) O'Bryant, Amber Jo; Jones, Theresa A.; Schallert, Tim; Huk, Alex; Delville, Yvon; Dunn, AndrewIn adult rats, following unilateral stroke-like injury to the motor cortex, there is significant loss of function in the forelimb contralateral to the ischemic damage. In the remaining motor cortex, changes in neuronal activation patterns and connectivity are induced following motor learning and rehabilitation in the brains of adult animals. Rehabilitative training promotes functional recovery of the impaired forelimb following motor cortical strokes; however, its benefits are most efficacious when coupled with other rehabilitative treatments. Multiple lines of evidence suggest that focal cortical electrical stimulation (CS) enhances the effectiveness of rehabilitative training (RT) and promotes changes in neural activation and plasticity in the peri-lesion motor cortex. Specific examples of plastic events include increases in dendritic and synaptic density in the peri-lesion cortex following CS/RT compared to rehabilitative training alone. The objective of these studies was to investigate which conditions, such as timing and method of delivery of CS, when coupled with RT, are most efficacious in promoting neuronal plasticity and functional recovery of the impaired forelimb following ischemic cortical injury in adult animals. The central hypothesis of these dissertation studies is that, following unilateral stroke-like injury, CS improves the functional recovery of the impaired forelimb and promotes neural plasticity in remaining motor cortex when combined with RT. This hypothesis was tested in a series of experiments manipulating post-ischemic behavioral experience with the impaired forelimb. Adult rats were proficient in a motor skill (Single Pellet Retrieval Task) and received ischemic motor cortex lesion that caused impairments in the forelimb. Rats received daily rehabilitative training on a tray reaching task with or without concurrent cortical stimulation. Epidural cortical stimulation, when paired with rehabilitative training, resulted in enhanced reaching performance compared to RT alone when initiated 14 days after lesion. These results were found to be maintained well after the treatment period ended. Rats tested 9-10 months post-rehabilitative training on the single pellet retrieval task continued to have greater reaching performance compared to RT alone. However, delayed onset of rehabilitative training (3 months post-infarct) indicated that CS does not further improve forelimb function compared to RT along. It was further established that CS delivered over the intact skull (transcranial stimulation) of the lesioned motor cortex was not a beneficial adjunct to rehabilitative training. Together these dissertation studies provide insight into the effectiveness and limitations of CS on behavioral recovery. The findings in these studies are likely to be important for understanding how post-stroke behavioral interventions and adjunct therapies could be used to optimize brain reorganization and functional outcome.