Neostriatal visual processing and initiation of movement

Parkinson's disease (PD) is a common neurodegenerative disorder affecting approximately 1% of Americans over the age of 60. It is caused by a derangement in the function of the basal ganglia secondary to the loss of dopaminergic cells in the substantia nigra. The disease is characterized by a number of abnormalities in movement including rigidity, tremor, bradykinesia (slowness of movement), and akinesia (inability to initiate movement). Akinesia, one of cardinal symptoms of PD and one of the most debilitating, can be at least partially overcome with sensory cues. For example, patients who are unable to initiate gait can do so if lines are drawn on the floor. This effect may be due to direct or indirect visual input to the basal ganglia. However, these inputs have been largely ignored in current models of movement control which have focused on the interconnections of the basal ganglia with premotor and motor areas of the frontal cortex. The goal of the experiments outlined in this proposal is to understand how sensory input affects the activity of neurons in the neostriatum, which are the input nuclei of the basal ganglia, in the initiation of movement. We will record the activity of neurons in the striatum of awake, behaving macaque monkeys. will first assess the basic visual responsiveness of neurons in the striatum while the animals perform a simple spatial attention task. We then look more directly at the role of visual inputs in initiating movement using a behavioral task designed to reveal the differences between visually cued and self-initiated movement. We will further examine neuronal responses in striatum projection neurons and interneurons, to test a specific hypothesis that the effect of visual stimuli may be relayed to the projection neurons through a specific set of striatal interneurons. The results of these studies will illuminate an important facet of basal ganglia physiology, namely their role in integrating visual information in the initiation of movement. These data will be useful in understanding the pathophysiology of PD and in continuing to develop rational treatment strategies for this crippling neurologic disorder.