GPe Projections to the Retrorubral Field Give Rise to Diverging GABAergic and DAergic Circuits

The external segment of the globus pallidus (GPe) is involved in the modulation of the motor output and limbic components of behavior. The circuitry by which the GPe contributes to limbic components of behavior remains unknown. While many investigations have focused on the local circuitry within the basal ganglia, numerous GPe projections to target regions outside of the basal ganglia including the midbrain, thalamus, and cortex exist and remain largely unexplored. Here, by anatomical and electrophysiological means, we investigate the projections of the GPe to the retrorubral field (RRF), a dopaminergic nucleus in the caudal midbrain, in both male and female mice. We find that the GPe targets both GABAergic and DAergic neurons in the RRF (RRF_DA and RRF_GABA). Viral-assisted circuit mapping to trace the cell-type-specific projection patterns of RRF_DA and RRF_GABA populations revealed diverging pathways. The connectivity of GPe-recipient RRF_DA neurons followed the traditional medial forebrain bundle path, innervating the ventral striatum and to a lesser extent the dorsal striatum. GPe-recipient RRF_GABA neurons, on the other hand, displayed broad projections targeting numerous brain regions involved in limbic function including the parabrachial nucleus, amygdala, and hypothalamus. These contrasting projection profiles reveal multiple nodes by which the GPe is disynaptically connected to the limbic system, representing novel access points for the GPe to modulate limbic components of behavior.