Motor cortex directly excites the output nucleus of the basal ganglia, the substantia nigra pars reticulata.
Inhibitory neurons of the substantia nigra pars reticulata (SNr) serve as a primary output through which the basal ganglia regulate behaviour. Projections to the SNr from beyond the basal ganglia have also been identified anatomically. Using a virally-targeted optogenetic approach, combined with whole cell patch-clamp recordings of SNr neurons in acute brain slices, we show that projection neurons of the primary and secondary motor cortices (M1 and M2) make functional excitatory synapses with subpopulations of inhibitory SNr neurons. Furthermore, we demonstrate that photostimulation of these cortical axon terminals increases SNr neuron firing rate. To further investigate the spatial organisation of cortical input to SNr, we employed a transsynaptic viral-labelling approach to identify SNr neurons receiving monosynaptic input from M1 and M2. We found a topographical relationship between motor cortex and SNr, and identified downstream targets of cortical-recipient SNr subpopulations. These findings reveal functional pathways by which M1 and M2 can directly modulate basal ganglia output to different downstream targets.