Parvalbumin¹ and Npas1¹ pallidal neurons have distinct circuit topology and function

The external globus pallidus (GPe) is a critical node within the basal ganglia circuit. Phasic changes in the activity of GPe neurons during movement and their alterations in Parkinson’s disease (PD) argue that the GPe is important in motor control. Parvalbumin-positive (PV¹) neurons and Npas1¹ neurons are the two principal neuron classes in the GPe. The distinct electrophysiological properties and axonal projection patterns argue that these two neuron classes serve different roles in regulating motor output. However, the causal relationship between GPe neuron classes and movement remains to be established. Here, by using optogenetic approaches in mice (both males and females), we showed that PV¹ neurons and Npas1¹ neurons promoted and suppressed locomotion, respectively. Moreover, PV¹ neurons and Npas1¹ neurons are under different synaptic influences from the subthalamic nucleus (STN). Additionally, we found a selective weakening of STN inputs to PV¹ neurons in the chronic 6-hydroxydopamine lesion model of PD. This finding reinforces the idea that the reciprocally connected GPe–STN network plays a key role in disease symptomatology and thus provides the basis for future circuit-based therapies.