The basal ganglia play an important role for selection of behavior, decision making and procedural learning but also underlie various neurological and psychiatric disorders such as Parkinson´s disease, Huntington´s disease, and ADHD, to name just a few. In the mouse, 90% of the output of the basal ganglia is conveyed through the substantia nigra pars reticulata (SNr). SNr neurons are tonically active at rest, providing inhibitory input to various motor centers in the brainstem, midbrain, and thalamus. Until recently, it was believed that the SNr is controlled only by intrinsic basal ganglia nuclei via the direct-, indirect-, and hyperdirect pathways, all of which involve multi-synaptic pathways between cortex and the SNr. Here, we show that in addition to these canonical pathways, SNr neurons receive direct monosynaptic excitation from the primary (M1) and secondary (M2) motor cortex. Using viral-assisted optogenetics and transsynaptic labeling combined with whole-cell recordings and behavioral perturbation experiments, we characterize the functional organization of this corticonigral pathway. We show that in parallel to the direct-, indirect-, and hyperdirect cortico-basal ganglia pathways, it is positioned to control behavior by directly regulating the activity of SNr neurons.
