title: Anatomical Location of the Mesencephalic Locomotor Region and Its Possible Role in Locomotion, Posture, Cataplexy, and Parkinsonism.
abstract: The mesencephalic (or midbrain) locomotor region (MLR) was first described in 1966 by Shik and colleagues, who demonstrated that electrical stimulation of this region induced locomotion in decerebrate (intercollicular transection) cats. The pedunculopontine tegmental nucleus (PPT) cholinergic neurons and midbrain extrapyramidal area (MEA) have been suggested to form the neuroanatomical basis for the MLR, but direct evidence for the role of these structures in locomotor behavior has been lacking. Here, we tested the hypothesis that the MLR is composed of non-cholinergic spinally projecting cells in the lateral pontine tegmentum. Our results showed that putative MLR neurons medial to the PPT and MEA in rats were non-cholinergic, glutamatergic, and express the orexin (hypocretin) type 2 receptors. Fos mapping correlated with motor behaviors revealed that the dorsal and ventral MLR are activated, respectively, in association with locomotion and an erect posture. Consistent with these findings, chemical stimulation of the dorsal MLR produced locomotion, whereas stimulation of the ventral MLR caused standing. Lesions of the MLR (dorsal and ventral regions together) resulted in cataplexy and episodic immobility of gait. Finally, trans-neuronal tracing with pseudorabies virus demonstrated disynaptic input to the MLR from the substantia nigra via the MEA. These findings offer a new perspective on the neuroanatomic basis of the MLR, and suggest that MLR dysfunction may contribute to the postural and gait abnormalities in Parkinsonism.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center , Boston, MA , USA.
authors.forename: David
authors.initials: D
authors.lastname: Sherman
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center , Boston, MA , USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Fuller
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center , Boston, MA , USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Marcus
authors.affiliation: Department of Neurosurgery, Dalian Municipal Central Hospital , Dalian , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, The Second Hospital of Dalian Medical University , Dalian , China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center , Boston, MA , USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Chamberlin
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center , Boston, MA , USA.
authors.forename: Clifford B
authors.initials: CB
authors.lastname: Saper
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center , Boston, MA , USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
keywords: basal ganglia; cataplexy; dopamine; pontine motor; sleep