Multiple dynamic interactions from basal ganglia direct and indirect pathways mediate action selection

The basal ganglia are known to be essential for action selection. However, the functional role of basal ganglia direct and indirect pathways in action selection remains unresolved. Here, by employing cell-type-specific neuronal recording and manipulation in mice trained in a choice task, we demonstrate that multiple dynamic interactions from the direct and indirect pathways control the action selection. While the direct pathway regulates the behavioral choice in a linear manner, the indirect pathway exerts a nonlinear inverted-U-shaped control over action selection, depending on the inputs and the network state. We propose a new center (direct)-surround (indirect)-context (indirect) ‘Triple-control’ functional model of basal ganglia, which can replicate the physiological and behavioral experimental observations that cannot be simply explained by either the traditional ‘Go/No-go’ or more recent ‘Co-activation’ model. These findings have important implications on understanding the basal ganglia circuitry and action selection in health and disease.