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      Brainstem control of locomotion and muscle tone with special reference to the role of the mesopontine tegmentum and medullary reticulospinal systems

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          Abstract

          The lateral part of the mesopontine tegmentum contains functionally important structures involved in the control of posture and gait. Specifically, the mesencephalic locomotor region, which may consist of the cuneiform nucleus and pedunculopontine tegmental nucleus (PPN), occupies the interest with respect to the pathophysiology of posture-gait disorders. The purpose of this article is to review the mechanisms involved in the control of postural muscle tone and locomotion by the mesopontine tegmentum and the pontomedullary reticulospinal system. To make interpretation and discussion more robust, the above issue is considered largely based on our findings in the experiments using decerebrate cat preparations in addition to the results in animal experimentations and clinical investigations in other laboratories. Our investigations revealed the presence of functional topographical organizations with respect to the regulation of postural muscle tone and locomotion in both the mesopontine tegmentum and the pontomedullary reticulospinal system. These organizations were modified by neurotransmitter systems, particularly the cholinergic PPN projection to the pontine reticular formation. Because efferents from the forebrain structures as well as the cerebellum converge to the mesencephalic and pontomedullary reticular formation, changes in these organizations may be involved in the appropriate regulation of posture-gait synergy depending on the behavioral context. On the other hand, abnormal signals from the higher motor centers may produce dysfunction of the mesencephalic-reticulospinal system. Here we highlight the significance of elucidating the mechanisms of the mesencephalic-reticulospinal control of posture and locomotion so that thorough understanding of the pathophysiological mechanisms of posture-gait disorders can be made.

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          Reduced number of hypocretin neurons in human narcolepsy.

          Murine and canine narcolepsy can be caused by mutations of the hypocretin (Hcrt) (orexin) precursor or Hcrt receptor genes. In contrast to these animal models, most human narcolepsy is not familial, is discordant in identical twins, and has not been linked to mutations of the Hcrt system. Thus, the cause of human narcolepsy remains unknown. Here we show that human narcoleptics have an 85%-95% reduction in the number of Hcrt neurons. Melanin-concentrating hormone (MCH) neurons, which are intermixed with Hcrt cells in the normal brain, are not reduced in number, indicating that cell loss is relatively specific for Hcrt neurons. The presence of gliosis in the hypocretin cell region is consistent with a degenerative process being the cause of the Hcrt cell loss in narcolepsy.
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            The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness.

            Sleep and wakefulness are regulated to occur at appropriate times that are in accordance with our internal and external environments. Avoiding danger and finding food, which are life-essential activities that are regulated by emotion, reward and energy balance, require vigilance and therefore, by definition, wakefulness. The orexin (hypocretin) system regulates sleep and wakefulness through interactions with systems that regulate emotion, reward and energy homeostasis.
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              Thalamocortical oscillations in the sleeping and aroused brain.

              Sleep is characterized by synchronized events in billions of synaptically coupled neurons in thalamocortical systems. The activation of a series of neuromodulatory transmitter systems during awakening blocks low-frequency oscillations, induces fast rhythms, and allows the brain to recover full responsiveness. Analysis of cortical and thalamic networks at many levels, from molecules to single neurons to large neuronal assemblies, with a variety of techniques, ranging from intracellular recordings in vivo and in vitro to computer simulations, is beginning to yield insights into the mechanisms of the generation, modulation, and function of brain oscillations.
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                Author and article information

                Contributors
                +81-166-68-2884 , kusaki@asahikawa-med.ac.jp
                Journal
                J Neural Transm (Vienna)
                J Neural Transm (Vienna)
                Journal of Neural Transmission
                Springer Vienna (Vienna )
                0300-9564
                1435-1463
                26 October 2015
                26 October 2015
                2016
                : 123
                : 695-729
                Affiliations
                [ ]Research Center for Brain Function and Medical Engineering, Asahikawa Medical University, Midorigaoka-Higashi 2-1, 1-1, Asahikawa, 078-8511 Japan
                [ ]Department of Regional Medicine and Education, Asahikawa Medical University, Asahikawa, Japan
                [ ]Department of General Medicine, Asahikawa Medical University, Asahikawa, Japan
                Article
                1475
                10.1007/s00702-015-1475-4
                4919383
                26497023
                b28fd719-a544-486e-a5f6-a1fc41fcdea7
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 9 July 2015
                : 13 October 2015
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science (JP);
                Award ID: 26120004
                Award ID: 25290001
                Award ID: 26120006
                Award ID: 15K06131
                Award ID: 26460955
                Award ID: 26460287
                Award Recipient :
                Funded by: QOLAR Rhehabilitation Hospital Foundation
                Funded by: SASSON Hospital Foundation
                Categories
                Neurology and Preclinical Neurological Studies - Review Article
                Custom metadata
                © Springer-Verlag Wien 2016

                postural muscle tone,locomotor region,pedunculopontine tegmental nucleus,reticulospinal neurons,behavioral state,decerebrate cat preparation

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