J. David Gladstone Institutes

The ability to control one’s movements is essential to life. Neural circuits involving the basal ganglia are critical for proper motor control, and disruption of these circuits leads to movement disorders such as Parkinson’s disease and Huntington’s disease. The striatum, which is the input nucleus of the basal ganglia, is a major site of activity-dependent plasticity in both health and disease. Because the striatum lies upstream of other basal ganglia nuclei, cellular and synaptic plasticity within this region alters the transfer of information throughout basal ganglia circuits. However, studies of the striatum have been hampered by difficulties identifying different types of cells during both in vitro and in vivo experiments. Here, we propose to utilize recently developed optical and genetic technologies to characterize the properties of striatal neurons and the neural circuits in which they are embedded. In vivo fiber optic technology will be used in conjunction with expression of channelrhodopsin and halorhodopsin to identify and directly drive neural activity in striatal neurons of awake behaving mice. These experiments will allow us to address how the rate and timing of activity in basal ganglia circuits are causally related to motor behavior. The ultimate goal is to develop a framework that will enable the rational design of novel therapies for devastating disorders affecting the striatum.