Antagonistic but Not Symmetric Regulation of Primary Motor Cortex by Basal Ganglia Direct and Indirect Pathways

Motor cortex, basal ganglia (BG), and thalamus are arranged in a recurrent loop whose activity guides motor actions. In the dominant model of the function of the BG and their role in Parkinson's disease, direct (dSPNs) and indirect (iSPNs) striatal projection neurons are proposed to oppositely modulate cortical activity via BG outputs to thalamus. Here, we test this model by determining how striatal activity modulates primary motor cortex in awake head-restrained mice. We find that, within 200 ms, dSPN and iSPN activation exert robust and opposite effects on the majority of cortical neurons. However, these effects are heterogeneous, with certain cortical neurons biphasically modulated by iSPN stimulation. Moreover, these striatal effects are diminished when the animal performs a motor action. Thus, the effects of dSPN and iSPN activity on cortex are at times antagonistic, consistent with classic models, whereas in other contexts these effects can be occluded or coactive.