Anatomical Location of the Mesencephalic Locomotor Region and Its Possible Role in Locomotion, Posture, Cataplexy, and Parkinsonism.

David Sherman,Clifford B Saper,Ping Zhang,Patrick M Fuller,Jun Yu,Jun Lu,Nancy L Chamberlin,Jacob Marcus

doi:10.3389/fneur.2015.00140

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.

Highlights

Work by Rhines and Magoun [1] provided the first indication that the reticular formation might participate in motor control by demonstrating that electrical stimulation of the reticular formation in decerebrate cats produced changes in muscle tone
Dual labeling for FG and choline acetyltransferase (ChAT) immunoreactivity (Figures 1A,B) or for FG and vesicular glutamate transporter 2 (VGLUT2) mRNA by in situ hybridization showed that the FG-ir cells were exclusively non-cholinergic and almost all the FG-ir neurons were glutamatergic (Figures 1A–C)
We demonstrated that the BD-labeled terminals from the substantia nigra pars reticulata (SNr) targeted the midbrain extrapyramidal area (MEA), which was just lateral to the dorsal mesencephalic locomotor region (MLR) neurons and dorsal to the ventral MLR neurons (Figures 5A,B)

Summary

Introduction

Work by Rhines and Magoun [1] provided the first indication that the reticular formation might participate in motor control by demonstrating that electrical stimulation of the reticular formation in decerebrate cats produced changes in muscle tone. Pontine motor circuit within a confined region of the dorsal reticular formation (at the mesopontine junction) triggered walking and even galloping in otherwise immobile decerebrate cats This confined area of the reticular formation was subsequently termed the mesencephalic locomotor region (MLR), and was considered a part of the cuneiform nucleus. The term is often confused with the much smaller and better delineated nucleus of the same name used in modern literature, based upon the Berman cat atlas [4], which does not contain the MLR To end this confusion, Skinner, Garcia-Rill, and colleagues refined the anatomical boundary of the MLR in rats to a more restricted region of the mesopontine reticular formation that included cholinergic neurons of the pedunculopontine tegmental nucleus (PPT or PPN) [5]. Cholinergic PPT neurons have since been widely considered a key anatomical element of the anatomic and physiologic MLR [5]

Methods

Results

Conclusion