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mesencephalic locomotor region

Anke H Snijders, Kaoru Takakusaki, Bettina Debu, Andres M Lozano, Vibhor Krishna, Alfonso Fasano, Tipu Z Aziz, Stella M Papa, Stewart A Factor, Mark Hallett
Freezing of gait (FOG) is a common and debilitating, but largely mysterious, symptom of Parkinson disease. In this review, we will discuss the cerebral substrate of FOG focusing on brain physiology and animal models. Walking is a combination of automatic movement processes, afferent information processing, and intentional adjustments. Thus, normal gait requires a delicate balance between various interacting neuronal systems. To further understand gait control and specifically FOG, we will discuss the basic physiology of gait, animal models of gait disturbance including FOG, alternative etiologies of FOG, and functional magnetic resonance studies investigating FOG...
September 20, 2016: Annals of Neurology
Laurent Goetz, Brigitte Piallat, Manik Bhattacharjee, Hervé Mathieu, Olivier David, Stéphan Chabardès
The mesencephalic reticular formation (MRF) mainly composed by the pedunculopontine and the cuneiform nuclei is involved in the control of several fundamental brain functions such as locomotion, rapid eye movement sleep and waking state. On the one hand, the role of MRF neurons in locomotion has been investigated for decades in different animal models, including in behaving nonhuman primate (NHP) using extracellular recordings. On the other hand, MRF neurons involved in the control of waking state have been consistently shown to constitute the cholinergic component of the reticular ascending system...
July 2016: Journal of Neural Transmission
Laurent Goetz, Brigitte Piallat, Manik Bhattacharjee, Hervé Mathieu, Olivier David, Stéphan Chabardès
UNLABELLED: The mesencephalic reticular formation (MRF) is formed by the pedunculopontine and cuneiform nuclei, two neuronal structures thought to be key elements in the supraspinal control of locomotion, muscle tone, waking, and REM sleep. The role of MRF has also been advocated in modulation of state of arousal leading to transition from wakefulness to sleep and it is further considered to be a main player in the pathophysiology of gait disorders seen in Parkinson's disease. However, the existence of a mesencephalic locomotor region and of an arousal center has not yet been demonstrated in primates...
May 4, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Sandra Gómez-López, Ana Valeria Martínez-Silva, Teresa Montiel, Daniel Osorio-Gómez, Federico Bermúdez-Rattoni, Lourdes Massieu, Diana Escalante-Alcalde
Parkinson's disease (PD) is a multifactorial neurodegenerative disorder, characterised by the progressive loss of midbrain dopaminergic neurons and a variety of motor symptoms. The gene coding for the phospholipid phosphatase 3, PLPP3 (formerly PPAP2B or LPP3), maps within the PARK10 locus, a region that has been linked with increased risk to late-onset PD. PLPP3 modulates the levels of a range of bioactive lipids controlling fundamental cellular processes within the central nervous system. Here we show that PLPP3 is enriched in astroglial cells of the adult murine ventral midbrain...
2016: Scientific Reports
Maria S Esposito, Silvia Arber
A recent study has functionally disentangled the hitherto enigmatic mesencephalic locomotor region of the brain on the basis of cell type diversity and identified differential upstream regulatory pathways.
April 4, 2016: Current Biology: CB
Sun-Uk Lee, Hyo-Jung Kim, Jeong-Jin Park, Ji-Soo Kim
Internuclear ophthalmoplegia (INO) indicates a lesion involving the medial longitudinal fasciculus (MLF) that interconnects the abducens nucleus and medial rectus subnucleus of the oculomotor nuclear complex. In fact, rostral-caudal localization value of the INO is often limited except when it accompanies symptoms and signs owing to involvement of nearby structures. Ataxia is often observed in lesions involving the cerebellum or the fibers to and from it anywhere in the brainstem. Herein, we sought to determine the localizing value of INO plus ataxia in the rostrocaudal axis of the brainstem...
May 2016: Journal of Neurology
X Jin, K Schwabe, J K Krauss, M Alam
Loss of cholinergic neurons in the mesencephalic locomotor region, comprising the pedunculopontine nucleus (PPN) and the cuneiform nucleus (CnF), is related to gait disturbances in late stage Parkinson's disease (PD). We investigate the effect of anterior or posterior cholinergic lesions of the PPN on gait-related motor behavior, and on neuronal network activity of the PPN area and basal ganglia (BG) motor loop in rats. Anterior PPN lesions, posterior PPN lesions or sham lesions were induced by stereotaxic microinjection of the cholinergic toxin AF64-A or vehicle in male Sprague-Dawley rats...
May 13, 2016: Neuroscience
Thomas K Roseberry, A Moses Lee, Arnaud L Lalive, Linda Wilbrecht, Antonello Bonci, Anatol C Kreitzer
The basal ganglia (BG) are critical for adaptive motor control, but the circuit principles underlying their pathway-specific modulation of target regions are not well understood. Here, we dissect the mechanisms underlying BG direct and indirect pathway-mediated control of the mesencephalic locomotor region (MLR), a brainstem target of BG that is critical for locomotion. We optogenetically dissect the locomotor function of the three neurochemically distinct cell types within the MLR: glutamatergic, GABAergic, and cholinergic neurons...
January 28, 2016: Cell
Jeremy Rowe, Aijaz Khan, Charles Romanowski, Claire Isaac, Sadequate Khan, Richard Mair, Tipu Aziz, John Yianni
BACKGROUND: The pedunculopontine nucleus (PPN) is a part of the mesencephalic locomotor region and, in recent years, it has been considered a new surgical target for deep brain stimulation (DBS) for movement disorders including atypical parkinsonian syndromes such as progressive supranuclear palsy (PSP) and multiple system atrophy. Involvement of the PPN may play an important role in gait impairment in these disorders and the development of PPN DBS could potentially provide treatment for this disabling problem...
May 2016: World Neurosurgery
Nan Liang, Jere H Mitchell, Scott A Smith, Masaki Mizuno
The sympathetic and pressor responses to exercise are exaggerated in hypertension. However, the underlying mechanisms causing this abnormality remain to be fully elucidated. Central command, a neural drive originating in higher brain centers, is known to activate cardiovascular and locomotor control circuits concomitantly. As such, it is a viable candidate for the generation of the augmented vascular response to exercise in this disease. We hypothesized that augmentations in central command function contribute to the heightened cardiovascular response to exercise in hypertension...
January 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Kaoru Takakusaki, Ryosuke Chiba, Tsukasa Nozu, Toshikatsu Okumura
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...
July 2016: Journal of Neural Transmission
Dimitri Ryczko, Francois Auclair, Jean-Marie Cabelguen, Réjean Dubuc
In vertebrates, stimulation of the mesencephalic locomotor region (MLR) on one side evokes symmetrical locomotor movements on both sides. How this occurs was previously examined in detail in a swimmer using body undulations (lamprey), but in tetrapods the downstream projections from the MLR to brainstem neurons are not fully understood. Here we examined the brainstem circuits from the MLR to identified reticulospinal neurons in the salamander Notophthalmus viridescens. Using neural tracing, we show that the MLR sends bilateral projections to the middle reticular nucleus (mRN, rostral hindbrain) and the inferior reticular nucleus (iRN, caudal hindbrain)...
May 1, 2016: Journal of Comparative Neurology
C Tard, A Delval, D Devos, R Lopes, P Lenfant, K Dujardin, C Hossein-Foucher, F Semah, A Duhamel, L Defebvre, F Le Jeune, C Moreau
INTRODUCTION: Freezing of gait (FoG) is a debilitating gait disorder in Parkinson's disease (PD). In advanced PD patients with FoG, the supraspinal locomotor network may be dysregulated (relative to similar patients without FoG) during gait. Here, we sought to characterize the metabolism of locomotor networks involved in FoG. METHODS: Twenty-two PD patients (11 with off-drug FoG and 11 without) each underwent two [(18)F]-fluorodeoxyglucose PET brain scans in the off-drug state: one at rest and another during radiotracer uptake while performing a standardized gait trajectory that incorporated the usual triggers for FoG...
October 29, 2015: Neuroscience
A Collomb-Clerc, M-L Welter
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) provides an efficient treatment for the alleviation of motor signs in patients with Parkinson's disease. The effects of DBS on gait and balance disorders are less successful and may even lead to an aggravation of freezing of gait and imbalance. The identification of a substantia nigra pars reticulata (SNr)-mesencephalic locomotor region (MLR) network in the control of locomotion and postural control and of its dysfunction/lesion in PD patients with gait and balance disorders led to suggestion that DBS should be targeting the SNr and the pedunculopontine nucleus (part of the MLR) for PD patients with these disabling axial motor signs...
November 2015: Neurophysiologie Clinique, Clinical Neurophysiology
David Sherman, Patrick M Fuller, Jacob Marcus, Jun Yu, Ping Zhang, Nancy L Chamberlin, Clifford B Saper, Jun Lu
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...
2015: Frontiers in Neurology
Peter H Weiss, Jan Herzog, Monika Pötter-Nerger, Daniela Falk, Hans Herzog, Günther Deuschl, Jens Volkmann, Gereon R Fink
BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) can ameliorate gait disturbances in Parkinson's disease (PD). Using motor imagery and positron emission tomography (PET), we investigated how STN-DBS interacts with supraspinal locomotor centers in PD. METHODS: Ten PD patients with bilateral STN-DBS actually walked or stood still under STN-DBS ON or OFF conditions. Directly thereafter, subjects imagined walking or standing while changes in regional cerebral blood flow were measured by PET...
July 2015: Movement Disorders: Official Journal of the Movement Disorder Society
C W MacDonell, K E Power, J W Chopek, K R Gardiner, P F Gardiner
This study examined motoneurone properties during fictive locomotion in the adult rat for the first time. Fictive locomotion was induced via electrical stimulation of the mesencephalic locomotor region in decerebrate adult rats under neuromuscular blockade to compare basic and rhythmic motoneurone properties in antidromically identified extensor motoneurones during: (1) quiescence, before and after fictive locomotion; (2) the 'tonic' period immediately preceding locomotor-like activity, whereby the amplitude of peripheral flexor (peroneal) and extensor (tibial) nerves are increased but alternation has not yet occurred; and (3) locomotor-like episodes...
May 15, 2015: Journal of Physiology
Valentina Fioravanti, Francesca Benuzzi, Luca Codeluppi, Sara Contardi, Francesco Cavallieri, Paolo Nichelli, Franco Valzania
We investigated structural brain differences between a group of early-mild PD patients at different phases of the disease and healthy subjects using voxel-based morphometry (VBM). 20 mild PD patients compared to 15 healthy at baseline and after 2 years of follow-up. VBM is a fully automated technique, which allows the identification of regional differences in the gray matter enabling an objective analysis of the whole brain between groups of subjects. With respect to controls, PD patients exhibited decreased GM volumes in right putamen and right parietal cortex...
2015: Parkinson's Disease
Hokuto Morita, Chris J Hass, Elena Moro, Atchar Sudhyadhom, Rajeev Kumar, Michael S Okun
Falls and gait impairment in Parkinson's Disease (PD) is a leading cause of morbidity and mortality, significantly impacting quality of life and contributing heavily to disability. Thus far axial symptoms, such as postural instability and gait freezing, have been refractory to current treatment approaches and remain a critical unmet need. There has been increased excitement surrounding the surgical targeting of the pedunculopontine nucleus (PPN) for addressing axial symptoms in PD. The PPN and cuneate nucleus comprise the mesencephalic locomotor region, and electrophysiologic studies in animal models and human imaging studies have revealed a key role for the PPN in gait and postural control, underscoring a potential role for DBS surgery...
2014: Frontiers in Neurology
A Moses Lee, Jennifer L Hoy, Antonello Bonci, Linda Wilbrecht, Michael P Stryker, Cristopher M Niell
Sensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses...
July 16, 2014: Neuron
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