Context dependent contributions of the direct and indirect pathways in the associative and sensorimotor striatum

To determine whether the contributions of striatal projection neurons from the direct (dSPNs) and indirect (iSPNs) pathways of the basal ganglia to action selection and locomotion can be generalized across the associative (DMS) and sensorimotor (DLS) striatum we compared the optogenetic activation or inhibition of these pathways on different tests. We show that self-modulation of dSPNs or iSPNs in either compartment has opposite contributions to real-time place preference, and to selecting an action in the DMS but not in the DLS. During reward seeking displacements, activation of either pathway in both compartments, or inhibition of dSPNs in the DMS slows movement. During spontaneous displacements, dSPNs activation showed opposing effects depending on the compartment modulated. Remarkably, inhibition of either pathway in the DLS decreases while only iSPNs inhibition in the DMS facilitates these displacements. These findings support a model of opposite, complementary and undescribed contributions of the striatal pathways depending on the compartment and context.