Motor learning and neuroplasticity in an aged mouse model of cerebral ischemia

Stroke is the leading cause of long-lasting disability in the United States and disproportionately affects adults in later life. Age-related decreases in dexterity and neural plasticity may contribute to the poorer prognosis of older stroke survivors, even following rehabilitative physical therapy. The goal of these dissertation studies is to determine how the cortical plasticity underlying motor skill learning, both before and after brain injury, changes in the aged brain. The general hypothesis of these studies is that age-related changes in motor performance and the limited ability to regain function following brain injury are associated with dysfunctional plasticity of the forelimb representation in the motor cortex. This hypothesis was tested in intact C57BL/6 mice by training them on a skilled reaching task and deriving intracortical microstimulation evoked motor cortical representations of the forelimb to determine training-induced changes in the function of the motor cortex. After ischemic lesions, age-dependencies in the effects of rehabilitative training in skilled reaching on forelimb motor cortical representations were investigated. Prior to injury, intact young and aged mice learned a skilled reaching task in similar time frames and with similar success rates. Training-induced reorganization in the young mouse motor cortex occurred in the caudal forelimb area, which is homologous to the primary motor cortex of primates. However, the rostral forelimb area, a potential premotor cortex, was larger in aged mice compared to young mice. Following focal ischemic lesions of the forelimb area of the sensorimotor cortex, aged mice had larger lesions and were more impaired than young mice, but both groups regained reaching ability after 9 weeks of rehabilitative training. Post-operative training resulted in plasticity of the rostral forelimb area in young mice, but we failed to see reorganization in the forelimb map of aged mice following rehabilitative training. These dissertation studies suggest that more severe brain damage in response to ischemia leads to poorer outcome in aged animals. Although the reorganization of motor cortex following initial skill learning and relearning following brain damage changes with age, the ability to learn motor tasks and improve function with rehabilitative training is maintained in healthy aging.