tVTA controls dual dopaminergic inputs to the external Globus Pallidus

Abstract

Midbrain dopamine (DA) neurons critically regulate basal ganglia function through their widespread projections. While the nigrostriatal pathway is well characterized and represents the dominant source of DA in the basal ganglia, other nuclei such as the external Globus Pallidus (GPe) also receive dopaminergic innervation, yet no consensus exists about its precise anatomical origin. In addition, the GABAergic tail of the ventral tegmental area (tVTA) provides a major inhibitory input to midbrain DA neurons, but its influence over DA pathways to the GPe remains unknown. In the rat, we combined retrograde tracing, immunohistochemistry, and ex vivo electrophysiology to identify distinct populations of DA neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) that project to the GPe and display distinct electrophysiological properties. Using optogenetics and electrophysiology, we also demonstrate that these GPe-projecting DA neurons receive powerful inhibitory input from the tVTA. Together, our findings define both the origin and inhibitory control of dopaminergic innervation to the GPe, revealing a previously unrecognized disynaptic circuit (tVTA[->]DA[->]GPe) that refines our understanding of basal ganglia circuit function.