Motor cortex directly excites the substantia nigra pars reticulata, the basal ganglia output nucleus

Inhibitory neurons of the substantia nigra pars reticulata (SNr) serve as a primary output through which the basal ganglia regulate behavior. Using a virally targeted optogenetic approach, combined with whole cell patch-clamp recordings of SNr neurons, we show that, in mice, projection neurons of both primary and secondary motor cortices (M1 and M2) form monosynaptic excitatory connections onto different subpopulations of GABAergic SNr neurons. Furthermore, photostimulation of these cortical axon terminals markedly increases SNr neuron firing rate. To investigate the spatial organization of cortical input to the SNr, we employed a transsynaptic viral-labelling approach to identify SNr neurons receiving monosynaptic input from either M1 or M2. We found a topographical organization of the M1 and M2 projections in SNr. Chemogenetic inhibition of M1- and M2-targeted SNr neurons induced opposing changes in spontaneous behavior. These findings reveal functional pathways by which the motor cortex can directly modulate basal ganglia output to downstream targets.