UC San Diego

Advanced age is associated with diverse behavioral and neurobiological deficits in comparison to adults. Potential mechanisms underlying age-related declines in neural function include impairments in neural plasticity. Here, we employ the motor system as a model to examine experience-dependent cortical plasticity in aged animals, as the motor cortex of young adult animals has been demonstrated to undergo a variety of plastic adaptations in the context of both normal learning and recovery from injury. This thesis first examined the ability of the aged motor cortex to undergo plasticity in association with acquisition of a skilled motor task. Gene expression changes were assessed using microarray analysis; spine density plasticity was assessed using intracellular filling techniques; and cortical map reorganization was assessed using intracortical microstimulation. Results indicate that aged animals exhibit impaired cortical plasticity in all measured parameters relative to young adults. These impairments were associated with motor performance deficits. The demand for neural plasticity in the context of injury is particularly important in aging, given the increased incidence of cortical trauma along with the reduced capacity for recovery in aged individuals. Thus, this thesis next investigated whether aged animals exhibited impaired plasticity in the context of recovery from focal cortical injury. Plasticity was assessed by quantifying the extent of map reorganization using intracortical microstimulation. Aged animals exhibited a complete absence of cortical map plasticity in association with rehabilitative training after cortical injury compared to young adults. Impaired plasticity and recovery were associated with age-related decreases in the cholinergic system, a system known to be essential for cortical plasticity and optimization of behavioral performance in young adults. Combined, the results of this thesis indicate that aged animals have impaired cortical plasticity mechanisms in the context of novel skill learning and recovery from focal cortical injury. These age-related impairments in plasticity likely contribute to deficits in behavioral performance in both the intact and injured aged brain