Mesencephalic Locomotor Region

The mesencephalic locomotor region (MLR) is a functionally defined area of the brainstem that is associated with the initiation and control of locomotor movements in vertebrate species.

The MLR was first described by Shik and colleagues in 1966 when they observed that electrical stimulation of a region of the midbrain in decerebrate cats produced walking and running behavior on a treadmill. Twenty-eight years later, Masdeu and colleagues described the presence of a MLR in humans. It is now widely acknowledged that, along with other motor control centers of the brain, the MLR plays an active role in initiating and modulating the spinal neural circuitry to control posture and gait. Anatomically, as the name suggests, the MLR is located in the mesencephalon (or midbrain), ventral to the inferior colliculus and near the cuneiform nucleus. Although identifying the exact anatomical substrates of the MLR has been subject to considerable debate, the pedunculopontine nucleus (PPN), lateral cuneiform nucleus, and midbrain extrapyramidal area are thought to form the neuroanatomical basis of the MLR. Nuclei within the MLR receive inputs from the substantia nigra of the basal ganglia and neural centers within the limbic system. Projections from the MLR descend via the medullary and pontine reticulospinal tracts to act on spinal motor neurons supplying the trunk and proximal limb flexors and extensors.

The PPN within the MLR is composed of a diverse population of neurons containing the neurotransmitters gamma-amino-butyric acid (GABA), glutamate, and acetylcholine (ACh). Results from animal and clinical studies suggest that cholinergic neurons in the PPN play a crucial role in modulating both the rhythm of locomotion and postural muscle tone.Glutamatergic and cholinergic inputs from the MLR may be responsible for regulating the excitability of reticulospinal neurons that in turn project to spinal central pattern generators to initiate stepping.

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