Project Summary
The long-term goal of this project is to deepen our understanding of how the external globus pallidus (GPe)
within the basal ganglia controls movement and how it goes awry in Parkinson’s disease (PD). Despite
compelling evidence that the GPe plays a critical role in regulating motor activity, its neuronal composition has
been poorly defined. As the neurons that encompass the GPe are heterogeneous, understanding how the
activity of the GPe is regulated in behavioral and disease contexts has posed a challenge. Through a series of
investigations during the last funding cycle, we surveyed the molecular landscape of the mouse GPe. By
characterizing a number of driver and reporter lines, we have now established a near-complete neuron
taxonomy of the GPe. Using the newly available genetic tools in conjunction with cell- and circuit-specific
approaches, we began to understand how GPe neuron subtypes control full-body movements. In this
application, we will examine the activity dynamics of GPe neuron subtypes and their regulation of their
synaptic partners to clarify the mechanisms involved. These experiments will provide new information about
how motor inhibition is produced by the GPe and the basal ganglia as a whole. Using a well-established chronic
model of PD, we will provide unprecedented insights into how alterations in these processes underlie
hypokinetic symptoms of PD. The yielded knowledge will not only inform the processes underlying motor
(dys)function but will also help develop circuit interventions that target the hypokinetic symptoms of PD.