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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.

SUBMITTER: Sherman D

PROVIDER: S-EPMC4478394 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Sherman David D Fuller Patrick M PM Marcus Jacob J Yu Jun J Zhang Ping P Chamberlin Nancy L NL Saper Clifford B CB Lu Jun J

Frontiers in neurology 20150624

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. ...[more]

PMID: 26157418

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Project description:Introduction During cyclical steady state ambulation, such as walking, variability in stride intervals can indicate the state of the system. In order to define locomotor system function, observed variability in motor patterns, stride regulation and gait complexity must be assessed in the presence of a perturbation. Common perturbations, especially for military populations, are load carriage and an imposed locomotion pattern known as forced marching (FM). We examined the interactive effects of load magnitude and locomotion pattern on motor variability, stride regulation and gait complexity during bipedal ambulation in recruit-aged females. Methods Eleven healthy physically active females (18–30 years) completed 1-min trials of running and FM at three load conditions: no additional weight/bodyweight (BW), an additional 25% of BW (BW + 25%), and an additional 45% of BW (BW + 45%). A goal equivalent manifold (GEM) approach was used to assess motor variability yielding relative variability (RV; ratio of “good” to “bad” variability) and detrended fluctuation analysis (DFA) to determine gait complexity on stride length (SL) and stride time (ST) parameters. DFA was also used on GEM outcomes to calculate stride regulation. Results There was a main effect of load (p = 0.01) on RV; as load increased, RV decreased. There was a main effect of locomotion (p = 0.01), with FM exhibiting greater RV than running. Strides were regulated more tightly and corrected quicker at BW + 45% compared (p < 0.05) to BW. Stride regulation was greater for FM compared to running. There was a main effect of load for gait complexity (p = 0.002); as load increased gait complexity decreased, likewise FM had less (p = 0.02) gait complexity than running. Discussion This study is the first to employ a GEM approach and a complexity analysis to gait tasks under load carriage. Reduction in “good” variability as load increases potentially exposes anatomical structures to repetitive site-specific loading. Furthermore, load carriage magnitudes of BW + 45% potentially destabilize the system making individuals less adaptable to additional perturbations. This is further evidenced by the decrease in gait complexity, which all participants demonstrated values similarly observed in neurologically impaired populations during the BW + 45% load condition.

Dataset Information

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

Publications

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

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