Figure 5. Cellular and circuit substrates for functional regulation by GPe neurons.

a. A simplified diagram of the GPe and its associated circuit. PV⁺ neurons and Npas1⁺ neurons are illustrated as the principal cell classes within the GPe and are differentially organized with the input and output of the basal ganglia. Consistent with their distinct electrophysiological properties, PV⁺ neurons and Npas1⁺ neurons have unique behavioral roles: PV⁺ neurons are motor-promoting, while Npas1⁺ neurons are motor-inhibiting. The PV⁺ neuron and Npas1⁺ neuron classes jointly tune motor behavior through a push-pull mechanism; local inhibitory connections between these neuron classes may control this process. Importantly, the same circuit motif is conserved across motor, sensorimotor, and limbic domains of the basal ganglia to support parallel processing of information.

b. A proposed model of circuit alterations in 6-OHDA lesioned mice and therapeutic rescue via PV⁺ neuron stimulation. PV⁺ neuron output to the SNr is functionally weakened (dotted line) in the absence of dopamine. Stimulation of the PV⁺ neuron output has been shown to restore motoric function in mouse models of Parkinson’s disease, putatively through restoring a normal level SNr output (e.g.¹⁴⁹).