UC San Diego

The external segment of the globus pallidus (GPe), a subcortical nucleus centrally located in the indirect pathway of the basal ganglia, plays a pivotal role in processing and broadcasting information received from the striatum and the subthalamic nucleus through its widespread projections across major basal ganglia nuclei. One of the largest neuronal populations of the GPe expresses the Ca2+-binding protein parvalbumin (PV) and projects to multiple nuclei of the basal ganglia and the thalamus and has been shown to be involved in movement disability in Parkinson’s disease (PD). However, most studies to date considered GPe PV neurons as a homogeneous population. We found that the GPe PV neurons can be further subdivided into two non-overlapping populations based on their projections to either the substantia nigra pars reticulata (SNr) or the parafascicular thalamus (PF) and their intrinsic electrophysiological properties. We further investigated the circuit-specific roles of these subpopulations in locomotion and reversal learning as well as their contributions to the impairments of motor and cognitive flexibility in a PD mouse model. Our findings establish the behavioral significance of two distinct GPe PV neuronal populations embedded in discrete neural pathways and their differential contributions to specific subdomains of Parkinsonian-like behaviors.