Figure 1. Simplified schematic illustrating the model concept for the brainstem control of locomotion.

The brainstem compartment on each (left and right) side contains three major structures: the cuneiform (CnF) and pedunculopontine (PPN) nuclei, comprising the mesencephalic locomotor region (MLR), and the pontomedullary reticular formation represented by the lateral paragigantocellular nucleus (LPGi). Each of these structures contain excitatory (glutamatergic, Glu) and inhibitory (Gly/GABA) populations. The bilaterally interacting CnF and PPN control spinal circuits, including rhythm generators (RGs), by descending drives originating from their glutamatergic populations and mediated by the bilaterally located LPGi. Spinal projections from each LPGi are organized in two pathways involving two distinct glutamatergic LPGi populations: ‘1’ and ‘2’. The LPGi-Glu-1 population relays excitation from glutamatergic neurons in both CnF and PPN and projects to the rhythm generating circuits in the spinal cord. This pathway controls locomotor frequency. The LPGi-Glu-2 population relays excitation from the CnF and projects to inhibitory relay neurons (dIni) in the spinal cord controlling the activity of V0 commissural neurons securing left-right interactions between the RGs and therefore locomotor gait. For simplicity, only the left-right RGs and their connections for the cervical spinal cord are shown. Spheres represent neuronal populations and lines represent synaptic connections with arrowheads for excitatory and circles for inhibitory influences.