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Journal of Neural Transmission (Vienna,... Jul 2016The lateral part of the mesopontine tegmentum contains functionally important structures involved in the control of posture and gait. Specifically, the mesencephalic... (Review)
Review
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.
Topics: Animals; Cats; Decerebrate State; Humans; Locomotion; Midbrain Reticular Formation; Muscle Tonus; Neural Pathways; Pedunculopontine Tegmental Nucleus
PubMed: 26497023
DOI: 10.1007/s00702-015-1475-4 -
American Journal of Physiology. Heart... Jun 2019Autonomic dysreflexia (AD) often occurs in individuals living with spinal cord injury (SCI) and is characterized by uncontrolled hypertension in response to otherwise... (Comparative Study)
Comparative Study
Autonomic dysreflexia (AD) often occurs in individuals living with spinal cord injury (SCI) and is characterized by uncontrolled hypertension in response to otherwise innocuous stimuli originating below the level of the spinal lesion. Visceral stimulation is a predominant cause of AD in humans and effectively replicates the phenotype in rodent models of SCI. Direct assessment of sympathetic responses to viscerosensory stimulation in spinalized animals is challenging and requires invasive surgical procedures necessitating the use of anesthesia. However, administration of anesthesia markedly affects viscerosensory reactivity, and the effects are exacerbated following spinal cord injury (SCI). Therefore, the major goal of the present study was to develop a decerebrate rodent preparation to facilitate quantification of sympathetic responses to visceral stimulation in the spinalized rat. Such a preparation enables the confounding effect of anesthesia to be eliminated. Sprague-Dawley rats were subjected to SCI at the fourth thoracic segment. Four weeks later, renal sympathetic nerve activity (RSNA) responses to visceral stimuli were quantified in urethane/chloralose-anesthetized and decerebrate preparations. Visceral stimulation was elicited via colorectal distension (CRD) for 1 min. In the decerebrate preparation, CRD produced dose-dependent increases in mean arterial pressure (MAP) and RSNA and dose-dependent decreases in heart rate (HR). These responses were significantly greater in magnitude among decerebrate animals when compared with urethane/chloralose-anesthetized controls and were markedly attenuated by the administration of urethane/chloralose anesthesia after decerebration. We conclude that the decerebrate preparation enables high-fidelity quantification of neuronal reactivity to visceral stimulation in spinalized rats. In animal models commonly used to study spinal cord injury, quantification of sympathetic responses is particularly challenging due to the increased susceptibility of spinal reflex circuits to the anesthetic agents generally required for experimentation. This constitutes a major limitation to understanding the mechanisms mediating regionally specific neuronal responses to visceral activation in chronically spinalized animals. In the present study, we describe a spinalized, decerebrate rodent preparation that facilitates quantification of sympathetic reactivity in response to visceral stimuli following spinal cord injury. This preparation enables reliable and reproducible quantification of viscero-sympathetic reflex responses resembling those elicited in conscious animals and may provide added utility for preclinical evaluation of neuropharmacological agents for the management of autonomic dysreflexia.
Topics: Anesthetics, Intravenous; Animals; Autonomic Dysreflexia; Chloralose; Decerebrate State; Disease Models, Animal; Hemodynamics; Kidney; Male; Rats, Sprague-Dawley; Reflex; Spinal Cord; Sympathetic Nervous System; Urethane
PubMed: 30875256
DOI: 10.1152/ajpheart.00724.2018 -
Experimental Brain Research Apr 2017The integration of inputs from vestibular and proprioceptive sensors within the central nervous system is critical to postural regulation. We recently demonstrated in...
The integration of inputs from vestibular and proprioceptive sensors within the central nervous system is critical to postural regulation. We recently demonstrated in both decerebrate and conscious cats that labyrinthine and hindlimb inputs converge onto vestibular nucleus neurons. The pontomedullary reticular formation (pmRF) also plays a key role in postural control, and additionally participates in regulating locomotion. Thus, we hypothesized that like vestibular nucleus neurons, pmRF neurons integrate inputs from the limb and labyrinth. To test this hypothesis, we recorded the responses of pmRF neurons to passive ramp-and-hold movements of the hindlimb and to whole-body tilts, in both decerebrate and conscious felines. We found that pmRF neuronal activity was modulated by hindlimb movement in the rostral-caudal plane. Most neurons in both decerebrate (83% of units) and conscious (61% of units) animals encoded both flexion and extension movements of the hindlimb. In addition, hindlimb somatosensory inputs converged with vestibular inputs onto pmRF neurons in both preparations. Pontomedullary reticular formation neurons receiving convergent vestibular and limb inputs likely participate in balance control by governing reticulospinal outflow.
Topics: Action Potentials; Animals; Brain Mapping; Cats; Consciousness; Decerebrate State; Electric Stimulation; Female; Hindlimb; Male; Motor Neurons; Movement; Reticular Formation; Rotation; Vestibule, Labyrinth
PubMed: 28188328
DOI: 10.1007/s00221-017-4875-x -
Experimental Neurology Jul 2017Impaired breathing is a devastating result of high cervical spinal cord injuries (SCI) due to partial or full denervation of phrenic motoneurons, which innervate the...
Impaired breathing is a devastating result of high cervical spinal cord injuries (SCI) due to partial or full denervation of phrenic motoneurons, which innervate the diaphragm - a primary muscle of respiration. Consequently, people with cervical level injuries often become dependent on assisted ventilation and are susceptible to secondary complications. However, there is mounting evidence for limited spontaneous recovery of respiratory function following injury, demonstrating the neuroplastic potential of respiratory networks. Although many studies have shown such plasticity at the level of the spinal cord, much less is known about the changes occurring at supraspinal levels post-SCI. The goal of this study was to determine functional reorganization of respiratory neurons in the medulla acutely (>4h) following high cervical SCI. Experiments were conducted in decerebrate, unanesthetized, vagus intact and artificially ventilated rats. In this preparation, spontaneous recovery of ipsilateral phrenic nerve activity was observed within 4 to 6h following an incomplete, C2 hemisection (C2Hx). Electrophysiological mapping of the ventrolateral medulla showed a reorganization of inspiratory and expiratory sites ipsilateral to injury. These changes included i) decreased respiratory activity within the caudal ventral respiratory group (cVRG; location of bulbospinal expiratory neurons); ii) increased proportion of expiratory phase activity within the rostral ventral respiratory group (rVRG; location of inspiratory bulbo-spinal neurons); iii) increased respiratory activity within ventral reticular nuclei, including lateral reticular (LRN) and paragigantocellular (LPGi) nuclei. We conclude that disruption of descending and ascending connections between the medulla and spinal cord leads to immediate functional reorganization within the supraspinal respiratory network, including neurons within the ventral respiratory column and adjacent reticular nuclei.
Topics: Action Potentials; Animals; Brain Mapping; Cervical Cord; Decerebrate State; Diaphragm; Disease Models, Animal; Functional Laterality; Male; Neuronal Plasticity; Neurons; Phrenic Nerve; Rats; Rats, Sprague-Dawley; Respiratory Center; Spinal Cord Injuries; Sympathectomy, Chemical; Time Factors
PubMed: 28433644
DOI: 10.1016/j.expneurol.2017.04.003 -
Journal of Neurophysiology Sep 2020We recorded membrane potentialp changes in 45 pharyngeal motoneurons (PMs) including 33 expiratory modulated and 12 nonrespiratory neurons during breathing, swallowing,...
We recorded membrane potentialp changes in 45 pharyngeal motoneurons (PMs) including 33 expiratory modulated and 12 nonrespiratory neurons during breathing, swallowing, and coughing in decerebrate paralyzed cats. Four types of membrane potential changes were observed during swallowing: ) depolarization during swallowing ( = 27), ) depolarization preceded by a brief (≤ 0.1 s) hyperpolarization ( = 4), ) longer term (> 0.3 s) hyperpolarization followed by depolarization ( = 11), and ) hyperpolarization during the latter period of swallowing ( = 3). During coughing, PMs showed two types of membrane potential changes ( = 10). Nine neurons exhibited a ramp-like depolarization during the expiratory phase of coughing with the potential peak at the end of expiratory phase. This depolarization was interrupted by a transient repolarization just before the potential peak. The membrane potential of the remaining neuron abruptly depolarized at the onset of the expiratory phase and then gradually decreased even after the end of the expiratory phase. Single-shock stimulation of the superior laryngeal nerve (SLN) induced inhibitory postsynaptic potentials in 19 of 21 PMs. Two motoneurons exhibited an SLN-induced excitatory postsynaptic potential. The present study revealed that PMs receive the central drive, consisting of a combination of excitation and inhibition, from the pattern generator circuitry of breathing, swallowing, and coughing, which changes the properties of their membrane potential to generate these motor behaviors of the pharynx. Our data will provide the basis of studies of pharyngeal activity and its control from the medullary neuronal circuitry responsible for the upper airway motor activity. We have provided the first demonstration of the multifunctional activity of the pharyngeal motoneurons at the level of membrane potential during respiration, swallowing, and coughing.
Topics: Animals; Cats; Central Pattern Generators; Cough; Decerebrate State; Deglutition; Electric Stimulation; Female; Laryngeal Nerves; Male; Motor Neurons; Pharynx; Respiration; Synaptic Potentials
PubMed: 32727254
DOI: 10.1152/jn.00093.2020 -
The Journal of Neuroscience : the... May 2018Higher vertebrates, including humans, are capable not only of forward (FW) locomotion but also of walking in other directions relative to the body axis [backward (BW),...
Higher vertebrates, including humans, are capable not only of forward (FW) locomotion but also of walking in other directions relative to the body axis [backward (BW), sideways, etc.]. Although the neural mechanisms responsible for controlling FW locomotion have been studied in considerable detail, the mechanisms controlling steps in other directions are mostly unknown. The aim of the present study was to investigate the distribution of spinal neuronal networks controlling FW and BW locomotion. First, we applied electrical epidural stimulation (ES) to different segments of the spinal cord from L2 to S2 to reveal zones triggering FW and BW locomotion in decerebrate cats of either sex. Second, to determine the location of spinal neurons activated during FW and BW locomotion, we used c-Fos immunostaining. We found that the neuronal networks responsible for FW locomotion were distributed broadly in the lumbosacral spinal cord and could be activated by ES of any segment from L3 to S2. By contrast, networks generating BW locomotion were activated by ES of a limited zone from the caudal part of L5 to the caudal part of L7. In the intermediate part of the gray matter within this zone, a significantly higher number of c-Fos-positive interneurons was revealed in BW-stepping cats compared with FW-stepping cats. We suggest that this region of the spinal cord contains the network that determines the BW direction of locomotion. Sequential and single steps in various directions relative to the body axis [forward (FW), backward (BW), sideways, etc.] are used during locomotion and to correct for perturbations, respectively. The mechanisms controlling step direction are unknown. In the present study, for the first time we compared the distributions of spinal neuronal networks controlling FW and BW locomotion. Using a marker to visualize active neurons, we demonstrated that in the intermediate part of the gray matter within L6 and L7 spinal segments, significantly more neurons were activated during BW locomotion than during FW locomotion. We suggest that the network determining the BW direction of stepping is located in this area.
Topics: Animals; Biomechanical Phenomena; Cats; Decerebrate State; Electric Stimulation; Electrophysiological Phenomena; Epidural Space; Female; Gray Matter; Immunohistochemistry; Locomotion; Lumbosacral Region; Male; Nerve Net; Proto-Oncogene Proteins c-fos; Spinal Cord
PubMed: 29678875
DOI: 10.1523/JNEUROSCI.2951-17.2018 -
American Journal of Physiology.... May 2019Recent findings have shown that muscle contraction evokes an exaggerated pressor response in type 1 diabetes mellitus (T1DM) rats; however, it is not known whether the...
Recent findings have shown that muscle contraction evokes an exaggerated pressor response in type 1 diabetes mellitus (T1DM) rats; however, it is not known whether the mechanoreflex, which is commonly stimulated by stretching the Achilles tendon, contributes to this abnormal response. Furthermore, the role of mechano-gated Piezo channels, found on thin-fiber afferent endings, in evoking the mechanoreflex in T1DM is also unknown. Therefore, in male and female streptozotocin (STZ, 50 mg/kg)-induced T1DM and healthy control (CTL) rats, we examined the pressor and cardioaccelerator responses to tendon stretch during the early stage of the disease. To determine the role of Piezo channels, GsMTx-4, a selective Piezo channel inhibitor, was injected into the arterial supply of the hindlimb. At 1 wk after STZ injection in anesthetized, decerebrate rats, we stretched the Achilles tendon for 30 s and measured pressor and cardioaccelerator responses. We then compared pressor and cardioaccelerator responses to tendon stretch before and after GsMTx-4 injection (10 µg/100 ml). We found that the pressor (change in mean arterial pressure) response [41 ± 5 mmHg ( = 15) for STZ and 18 ± 3 mmHg ( = 11) for CTL ( < 0.01)] and cardioaccelerator (change in heart rate) response [18 ± 4 beats/min for STZ ( = 15) and 8 ± 2 beats/min ( = 11) for CTL ( < 0.05)] to tendon stretch were exaggerated in STZ rats. Local injection of GsMTx-4 attenuated the pressor [55 ± 7 mmHg ( = 6) before and 27 ± 9 mmHg ( = 6) after GsMTx-4 ( < 0.01)], but not the cardioaccelerator, response to tendon stretch in STZ rats and had no effect on either response in CTL rats. These data suggest that T1DM exaggerates the mechanoreflex response to tendon stretch and that Piezo channels play a role in this exaggeration.
Topics: Animals; Blood Pressure; Decerebrate State; Diabetes Mellitus, Experimental; Female; Hindlimb; Intercellular Signaling Peptides and Proteins; Male; Muscle Contraction; Muscle, Skeletal; Physical Conditioning, Animal; Rats, Sprague-Dawley; Reflex; Spider Venoms
PubMed: 30840487
DOI: 10.1152/ajpregu.00294.2018 -
BMJ Case Reports Nov 2015The control of body posture is a complex activity that needs a very close relationship between different structures, such as the vestibular system, and the muscle and... (Review)
Review
The control of body posture is a complex activity that needs a very close relationship between different structures, such as the vestibular system, and the muscle and joint receptors of the neck. Damage of even one of these structures can lead to abnormal postural reflexes. We describe a case of a woman with a left pontine ischaemia who developed a 'dystonic' extensor posture of the left limbs while turned on the right side. This clinical picture differs from previous reports on the subject, and may relate to ischaemic damage of a pontine structure involved in posture control, or of adjacent neural connections to be yet identified. To the best of our knowledge, this is the first case reported in the literature. Clinical examples of an altered interplay between vestibular and neck receptors are rare.
Topics: Aged, 80 and over; Decerebrate State; Female; Humans; Ischemia; Neck; Pons; Posture; Reflex, Abnormal; Seizures; Sleep Stages; Tomography, X-Ray Computed; Vestibule, Labyrinth
PubMed: 26561222
DOI: 10.1136/bcr-2015-210616 -
Acta Otorrinolaringologica Espanola 2015
Review
Topics: Adenocarcinoma, Papillary; Calcinosis; Child; Coma; Craniotomy; Decerebrate State; Ear Neoplasms; Emergencies; Endolymphatic Sac; Fatal Outcome; Female; Humans; Hydrocephalus; Magnetic Resonance Imaging; Postoperative Complications; Shock, Septic; Skull Neoplasms; Temporal Bone; Tomography, X-Ray Computed; Urinary Tract Infections
PubMed: 24060358
DOI: 10.1016/j.otorri.2013.06.002 -
Experimental Physiology Apr 2020What is the central question of this study? What is the contribution of the main acidic compounds accumulated during contractions, namely H , lactic acid and inorganic...
NEW FINDINGS
What is the central question of this study? What is the contribution of the main acidic compounds accumulated during contractions, namely H , lactic acid and inorganic phosphate, to evoke the metabolic component of the exercise pressor reflex? What is the main finding and its importance? We found that the pressor response to acidic stimuli is driven by the concentration of hydrogen ions and that lactate and inorganic phosphate act as potentiating agents.
ABSTRACT
H ions, lactate and inorganic phosphate are produced by contracting skeletal muscles and evoke, in part, the metabolic component of the exercise pressor reflex. Owing to their disparate dissociation constants (i.e. pK ), the contribution of each acid to the muscle metaboreflex is unclear. This lack of information prompted us to determine the reflex pressor responses to injection of acidic saline, lactate (24 mm) and inorganic phosphate (86 mm) at various values of pH (from 2.66 to 7.5), alone or in combination, into the arterial supply of hindlimb skeletal muscle of decerebrate rats. In particular, we tested the hypothesis that the pressor response to an injection of a combination of lactate and phosphate at an acidic pH is greater than that evoked by injection of either phosphate or lactate alone at the same pH. We found that injection of acidic saline produced a pressor response only at a pH of 2.66 (7 ± 4 mmHg), an effect that was potentiated when the solution contained lactate (50 ± 20 mmHg). At a pH of 6.0, however, this effect was lost. At a pH of 6.0, only the injection of inorganic phosphate produced a significant pressor response (23 ± 12 mmHg). A large potentiating effect was found when lactate was added to the inorganic phosphate solution (39 ± 18 mmHg), an effect that was lost at a pH >7.0. Our findings led to the conclusion that the pressor response to injection of acidic solutions was driven by H ions and that inorganic phosphate and lactate functioned as sensitizing agents.
Topics: Animals; Blood Pressure; Hindlimb; Lactic Acid; Male; Muscle Contraction; Muscle, Skeletal; Phosphates; Physical Conditioning, Animal; Physical Exertion; Rats; Rats, Sprague-Dawley; Reflex
PubMed: 31982004
DOI: 10.1113/EP088349