Proline‐Rich Transmembrane Protein 2 Is Variably Expressed Across Excitatory and Inhibitory Neurons in Mouse Motor Circuits

Proline-rich transmembrane protein 2 (PRRT2) plays a pivotal role in the control of voluntary movements, as PRRT2 mutations cause paroxysmal kinesigenic dyskinesia (PKD) in a loss-of-function manner. Although the cerebellum is considered a region responsible for PKD, we recently reported that Prrt2 also regulates dopaminergic activity in the striatum, suggesting that Prrt2 functions not only in the cerebellum but also in the basal ganglia motor circuits. However, the relationship between neuronal cell types expressing Prrt2 and motor functions remains poorly understood. In this study, we determined the neurochemical types of Prrt2-positive neurons using immunofluorescence staining of mouse midbrain primary neurons and brain sections. Prrt2 was expressed mainly in glutamatergic and GABAergic neurons, but not in dopaminergic or cholinergic neurons. We found that Prrt2 was expressed preferentially in Vglut1-positive, rather than Vglut2-positive, cortical projection neurons and cerebellar granule cells, and in GABAergic medium spiny neurons of the basal ganglia, where Prrt2 was localized in axonal tracts and at or near presynaptic terminals. Taken together, we conclude that Prrt2 is variably expressed across excitatory and inhibitory neurons in motor-related neural circuits, where it might play more diverse roles in the regulation of neuronal excitability and voluntary movement.