Synergistic Nigral Output Pathways Shape Movement

Abstract

Summary: Locomotion relies on the activity of basal ganglia networks, where, as the output, the substantia nigra pars reticulata (SNr) integrates incoming signals and relays them to downstream areas. The cellular and circuit substrates of such a complex function remain unclear. We hypothesized that the SNr controls different aspects of locomotion through coordinated cell-type-specific sub-circuits. Using anatomical mapping, single-cell qPCR, and electrophysiological techniques, we identified two SNr sub-populations: the centromedial-thalamo projectors (CMps) and the SN compacta projectors (SNcps), which are genetically targeted based on vesicular transporter for gamma-aminobutyric acid (VGAT) or parvalbumin (PV) expression, respectively. Optogenetic manipulation of these two sub-types across a series of motor tests provided evidence that they govern different aspects of motor behavior. While CMp activity supports the continuity of motor patterns, SNcp modulates the immediate motor drive behind them. Collectively, our data suggest that at least two different sub-circuits arise from the SNr, engage different behavioral motor components, and collaborate to produce correct locomotion. : Rizzi and Tan show two neuronal populations of the substantia nigra pars reticulata taking part in distinct basal ganglia output pathways. They encode specific locomotion aspects, engaging motor programs or maintaining them, and hence work in collaboration to shape movement. Keywords: basal ganglia, substantia nigra pars reticulata, GABAergic sub-circuits, locomotion, reward, optogenetic