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Sample records for microglial-mediated motoneuron injury

  1. Progesterone neuroprotection in traumatic CNS injury and motoneuron degeneration.

    PubMed

    De Nicola, Alejandro F; Labombarda, Florencia; Gonzalez Deniselle, Maria Claudia; Gonzalez, Susana L; Garay, Laura; Meyer, Maria; Gargiulo, Gisella; Guennoun, Rachida; Schumacher, Michael

    2009-07-01

    Studies on the neuroprotective and promyelinating effects of progesterone in the nervous system are of great interest due to their potential clinical connotations. In peripheral neuropathies, progesterone and reduced derivatives promote remyelination, axonal regeneration and the recovery of function. In traumatic brain injury (TBI), progesterone has the ability to reduce edema and inflammatory cytokines, prevent neuronal loss and improve functional outcomes. Clinical trials have shown that short-and long-term progesterone treatment induces a significant improvement in the level of disability among patients with brain injury. In experimental spinal cord injury (SCI), molecular markers of functional motoneurons become impaired, including brain-derived neurotrophic factor (BDNF) mRNA, Na,K-ATPase mRNA, microtubule-associated protein 2 and choline acetyltransferase (ChAT). SCI also produces motoneuron chromatolysis. Progesterone treatment restores the expression of these molecules while chromatolysis subsided. SCI also causes oligodendrocyte loss and demyelination. In this case, a short progesterone treatment enhances proliferation and differentiation of oligodendrocyte progenitors into mature myelin-producing cells, whereas prolonged treatment increases a transcription factor (Olig1) needed to repair injury-induced demyelination. Progesterone neuroprotection has also been shown in motoneuron neurodegeneration. In Wobbler mice spinal cord, progesterone reverses the impaired expression of BDNF, ChAT and Na,K-ATPase, prevents vacuolar motoneuron degeneration and the development of mitochondrial abnormalities, while functionally increases muscle strength and the survival of Wobbler mice. Multiple mechanisms contribute to these progesterone effects, and the role played by classical nuclear receptors, extra nuclear receptors, membrane receptors, and the reduced metabolites of progesterone in neuroprotection and myelin formation remain an exciting field worth of exploration.

  2. Induction of phosphorylated c-Jun in neonatal spinal motoneurons after axonal injury is coincident with both motoneuron death and regeneration.

    PubMed

    Yuan, Qiuju; Su, Huanxing; Guo, Jiasong; Wu, Wutian; Lin, Zhi-Xiu

    2014-05-01

    c-Jun activation has been implicated not only in neuronal degeneration, but also in survival and regeneration. Here, we investigated c-Jun activation in injured motoneurons by using a nerve crush model in neonatal rats. We identified two distinct subpopulations of motoneurons: about 60% underwent degeneration following injury whereas the remaining 40% survived and induced a regeneration response at 3 weeks post injury. However, all motoneurons examined expressed phosphorylated-c-Jun-immunoreactivity (p-c-Jun-IR) at the early stage of 3 days following injury. These results suggest that active c-Jun was induced in all neonatal motoneurons following nerve crush injury, regardless of whether they were destined to degenerate or undergo successful regeneration at a later stage. Our findings therefore support the hypothesis that active c-Jun is involved in both neuronal degeneration and regeneration.

  3. Induction of phosphorylated c-Jun in neonatal spinal motoneurons after axonal injury is coincident with both motoneuron death and regeneration

    PubMed Central

    Yuan, Qiuju; Su, Huanxing; Guo, Jiasong; Wu, Wutian; Lin, Zhi-Xiu

    2014-01-01

    c-Jun activation has been implicated not only in neuronal degeneration, but also in survival and regeneration. Here, we investigated c-Jun activation in injured motoneurons by using a nerve crush model in neonatal rats. We identified two distinct subpopulations of motoneurons: about 60% underwent degeneration following injury whereas the remaining 40% survived and induced a regeneration response at 3 weeks post injury. However, all motoneurons examined expressed phosphorylated-c-Jun-immunoreactivity (p-c-Jun-IR) at the early stage of 3 days following injury. These results suggest that active c-Jun was induced in all neonatal motoneurons following nerve crush injury, regardless of whether they were destined to degenerate or undergo successful regeneration at a later stage. Our findings therefore support the hypothesis that active c-Jun is involved in both neuronal degeneration and regeneration. PMID:24506149

  4. Normal distribution of VGLUT1 synapses on spinal motoneuron dendrites and their reorganization after nerve injury.

    PubMed

    Rotterman, Travis M; Nardelli, Paul; Cope, Timothy C; Alvarez, Francisco J

    2014-03-05

    Peripheral nerve injury induces permanent alterations in spinal cord circuitries that are not reversed by regeneration. Nerve injury provokes the loss of many proprioceptive IA afferent synapses (VGLUT1-IR boutons) from motoneurons, the reduction of IA EPSPs in motoneurons, and the disappearance of stretch reflexes. After motor and sensory axons successfully reinnervate muscle, lost IA VGLUT1 synapses are not re-established and the stretch reflex does not recover; however, electrically evoked EPSPs do recover. The reasons why remaining IA synapses can evoke EPSPs on motoneurons, but fail to transmit useful stretch signals are unknown. To better understand changes in the organization of VGLUT1 IA synapses that might influence their input strength, we analyzed their distribution over the entire dendritic arbor of motoneurons before and after nerve injury. Adult rats underwent complete tibial nerve transection followed by microsurgical reattachment and 1 year later motoneurons were intracellularly recorded and filled with neurobiotin to map the distribution of VGLUT1 synapses along their dendrites. We found in control motoneurons an average of 911 VGLUT1 synapses; ~62% of them were lost after injury. In controls, VGLUT1 synapses were focused to proximal dendrites where they were grouped in tight clusters. After injury, most synaptic loses occurred in the proximal dendrites and remaining synapses were declustered, smaller, and uniformly distributed throughout the dendritic arbor. We conclude that this loss and reorganization renders IA afferent synapses incompetent for efficient motoneuron synaptic depolarization in response to natural stretch, while still capable of eliciting EPSPs when synchronously fired by electrical volleys.

  5. Permanent reorganization of Ia afferent synapses on motoneurons after peripheral nerve injuries

    PubMed Central

    Alvarez, Francisco J.; Bullinger, Katie L.; Titus, Haley E.; Nardelli, Paul; Cope, Timothy C.

    2010-01-01

    After peripheral nerve injuries to a motor nerve the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons. PMID:20536938

  6. Functional recovery after cervical spinal cord injury: Role of neurotrophin and glutamatergic signaling in phrenic motoneurons.

    PubMed

    Gill, Luther C; Gransee, Heather M; Sieck, Gary C; Mantilla, Carlos B

    2016-06-01

    Cervical spinal cord injury (SCI) interrupts descending neural drive to phrenic motoneurons causing diaphragm muscle (DIAm) paralysis. Recent studies using a well-established model of SCI, unilateral spinal hemisection of the C2 segment of the cervical spinal cord (SH), provide novel information regarding the molecular and cellular mechanisms of functional recovery after SCI. Over time post-SH, gradual recovery of rhythmic ipsilateral DIAm activity occurs. Recovery of ipsilateral DIAm electromyogram (EMG) activity following SH is enhanced by increasing brain-derived neurotrophic factor (BDNF) in the region of the phrenic motoneuron pool. Delivery of exogenous BDNF either via intrathecal infusion or via mesenchymal stem cells engineered to release BDNF similarly enhance recovery. Conversely, recovery after SH is blunted by quenching endogenous BDNF with the fusion-protein TrkB-Fc in the region of the phrenic motoneuron pool or by selective inhibition of TrkB kinase activity using a chemical-genetic approach in TrkB(F616A) mice. Furthermore, the importance of BDNF signaling via TrkB receptors at phrenic motoneurons is highlighted by the blunting of recovery by siRNA-mediated downregulation of TrkB receptor expression in phrenic motoneurons and by the enhancement of recovery evident following virally-induced increases in TrkB expression specifically in phrenic motoneurons. BDNF/TrkB signaling regulates synaptic plasticity in various neuronal systems, including glutamatergic pathways. Glutamatergic neurotransmission constitutes the main inspiratory-related, excitatory drive to motoneurons, and following SH, spontaneous neuroplasticity is associated with increased expression of ionotropic N-methyl-d-aspartate (NMDA) receptors in phrenic motoneurons. Evidence for the role of BDNF/TrkB and glutamatergic signaling in recovery of DIAm activity following cervical SCI is reviewed.

  7. Motoneuron BDNF/TrkB signaling enhances functional recovery after cervical spinal cord injury.

    PubMed

    Mantilla, Carlos B; Gransee, Heather M; Zhan, Wen-Zhi; Sieck, Gary C

    2013-09-01

    A C2 cervical spinal cord hemisection (SH) interrupts descending inspiratory-related drive to phrenic motoneurons located between C3 and C5 in rats, paralyzing the ipsilateral hemidiaphragm muscle. There is gradual recovery of rhythmic diaphragm muscle activity ipsilateral to cervical spinal cord injury over time, consistent with neuroplasticity and strengthening of spared, contralateral descending premotor input to phrenic motoneurons. Brain-derived neurotrophic factor (BDNF) signaling through the tropomyosin related kinase receptor subtype B (TrkB) plays an important role in neuroplasticity following spinal cord injury. We hypothesized that 1) increasing BDNF/TrkB signaling at the level of the phrenic motoneuron pool by intrathecal BDNF delivery enhances functional recovery of rhythmic diaphragm activity after SH, and 2) inhibiting BDNF/TrkB signaling by quenching endogenous neurotrophins with the soluble fusion protein TrkB-Fc or by knocking down TrkB receptor expression in phrenic motoneurons using intrapleurally-delivered siRNA impairs functional recovery after SH. Diaphragm EMG electrodes were implanted bilaterally to verify complete hemisection at the time of SH and 3days post-SH. After SH surgery in adult rats, an intrathecal catheter was placed at C4 to chronically infuse BDNF or TrkB-Fc using an implanted mini-osmotic pump. At 14days post-SH, all intrathecal BDNF treated rats (n=9) displayed recovery of ipsilateral hemidiaphragm EMG activity, compared to 3 out of 8 untreated SH rats (p<0.01). During eupnea, BDNF treated rats exhibited 76±17% of pre-SH root mean squared EMG vs. only 5±3% in untreated SH rats (p<0.01). In contrast, quenching endogenous BDNF with intrathecal TrkB-Fc treatment completely prevented functional recovery up to 14days post-SH (n=7). Immunoreactivity of the transcription factor cAMP response element-binding protein (CREB), a downstream effector of TrkB signaling, increased in phrenic motoneurons following BDNF treatment (n=6

  8. Reorganization of laryngeal motoneurons after crush injury in the recurrent laryngeal nerve of the rat

    PubMed Central

    Hernández-Morato, Ignacio; Valderrama-Canales, Francisco J; Berdugo, Gabriel; Arias, Gonzalo; McHanwell, Stephen; Sañudo, José; Vázquez, Teresa; Pascual-Font, Arán

    2013-01-01

    Motoneurons innervating laryngeal muscles are located in the nucleus ambiguus (Amb), but there is no general agreement on the somatotopic representation and even less is known on how an injury in the recurrent laryngeal nerve (RLN) affects this pattern. This study analyzes the normal somatotopy of those motoneurons and describes its changes over time after a crush injury to the RLN. In the control group (control group 1, n = 9 rats), the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were injected with cholera toxin-B. In the experimental groups the left RLN of each animal was crushed with a fine tip forceps and, after several survival periods (1, 2, 4, 8, 12 weeks; minimum six rats per time), the PCA and TA muscles were injected as described above. After each surgery, the motility of the vocal folds was evaluated. Additional control experiments were performed; the second control experiment (control group 2, n = 6 rats) was performed labeling the TA and PCA immediately prior to the section of the superior laryngeal nerve (SLN), in order to eliminate the possibility of accidental labeling of the cricothyroid (CT) muscle by spread from the injection site. The third control group (control group 3, n = 5 rats) was included to determine if there is some sprouting from the SLN into the territories of the RLN after a crush of this last nerve. One week after the crush injury of the RLN, the PCA and TA muscles were injected immediately before the section of the SLN. The results show that a single population of neurons represents each muscle with the PCA in the most rostral position followed caudalwards by the TA. One week post-RLN injury, both the somatotopy and the number of labeled motoneurons changed, where the labeled neurons were distributed randomly; in addition, an area of topographical overlap of the two populations was observed and vocal fold mobility was lost. In the rest of the survival periods, the overlapping area is larger, but the movement of

  9. Reorganization of laryngeal motoneurons after crush injury in the recurrent laryngeal nerve of the rat.

    PubMed

    Hernández-Morato, Ignacio; Valderrama-Canales, Francisco J; Berdugo, Gabriel; Arias, Gonzalo; McHanwell, Stephen; Sañudo, José; Vázquez, Teresa; Pascual-Font, Arán

    2013-04-01

    Motoneurons innervating laryngeal muscles are located in the nucleus ambiguus (Amb), but there is no general agreement on the somatotopic representation and even less is known on how an injury in the recurrent laryngeal nerve (RLN) affects this pattern. This study analyzes the normal somatotopy of those motoneurons and describes its changes over time after a crush injury to the RLN. In the control group (control group 1, n = 9 rats), the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were injected with cholera toxin-B. In the experimental groups the left RLN of each animal was crushed with a fine tip forceps and, after several survival periods (1, 2, 4, 8, 12 weeks; minimum six rats per time), the PCA and TA muscles were injected as described above. After each surgery, the motility of the vocal folds was evaluated. Additional control experiments were performed; the second control experiment (control group 2, n = 6 rats) was performed labeling the TA and PCA immediately prior to the section of the superior laryngeal nerve (SLN), in order to eliminate the possibility of accidental labeling of the cricothyroid (CT) muscle by spread from the injection site. The third control group (control group 3, n = 5 rats) was included to determine if there is some sprouting from the SLN into the territories of the RLN after a crush of this last nerve. One week after the crush injury of the RLN, the PCA and TA muscles were injected immediately before the section of the SLN. The results show that a single population of neurons represents each muscle with the PCA in the most rostral position followed caudalwards by the TA. One week post-RLN injury, both the somatotopy and the number of labeled motoneurons changed, where the labeled neurons were distributed randomly; in addition, an area of topographical overlap of the two populations was observed and vocal fold mobility was lost. In the rest of the survival periods, the overlapping area is larger, but

  10. Motoneuron model of self-sustained firing after spinal cord injury

    PubMed Central

    Kurian, Mini; Jung, Ranu

    2016-01-01

    Under many conditions spinal motoneurons produce plateau potentials, resulting in self-sustained firing and providing a mechanism for translating short-lasting synaptic inputs into long-lasting motor output. During the acute-stage of spinal cord injury (SCI), the endogenous ability to generate plateaus is lost; however, during the chronic-stage of SCI, plateau potentials reappear with prolonged self-sustained firing that has been implicated in the development of spasticity. In this work, we extend previous modeling studies to systematically investigate the mechanisms underlying the generation of plateau potentials in motoneurons, including the influences of specific ionic currents, the morphological characteristics of the soma and dendrite, and the interactions between persistent inward currents and synaptic input. In particular, the goal of these computational studies is to explore the possible interactions between morphological and electrophysiological changes that occur after incomplete SCI. Model results predict that some of the morphological changes generally associated with the chronic-stage for some types of spinal cord injuries can cause a decrease in self-sustained firing. This and other computational results presented here suggest that the observed increases in self-sustained firing following some types of SCI may occur mainly due to changes in membrane conductances and changes in synaptic activity, particularly changes in the strength and timing of inhibition. PMID:21526348

  11. Differential effects on KCC2 expression and spasticity of ALS and traumatic injuries to motoneurons

    PubMed Central

    Mòdol, Laura; Mancuso, Renzo; Alé, Albert; Francos-Quijorna, Isaac; Navarro, Xavier

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease manifested by progressive muscle atrophy and paralysis due to the loss of upper and lower motoneurons (MN). Spasticity appears in ALS patients leading to further disabling consequences. Loss of the inhibitory tone induced by downregulation of the potassium chloride cotransporter 2 (KCC2) in MN has been proposed to importantly contribute to the spastic behavior after spinal cord injury (SCI). The aim of the present study was to test whether the alterations in the expression of KCC2 are linked to the appearance of spasticity in the SODG93A ALS murine model. We compared SODG93A mice to wild type mice subjected to SCI to mimic the spinal MN disconnection from motor descending pathways, and to sciatic nerve lesion to mimic the loss of MN connectivity to muscle. Electrophysiological results show that loss of motor function is observed at presymptomatic stage (8 weeks) in SODG93A mice but hyperreflexia and spasticity do not appear until a late stage (16 weeks). However, KCC2 was not downregulated despite MN suffered disconnection both from muscles and upper MNs. Further experiments revealed decreased gephyrin expression, as a general marker of inhibitory systems, accompanied by a reduction in the number of Renshaw interneurons. Moreover, 5-HT fibers were increased in the ventral horn of the lumbar spinal cord at late stage of disease progression in SOD1G93A mice. Taken together, the present results indicate that spasticity appears late in the ALS model, and may be mediated by a decrease in inhibitory interneurons and an increase of 5-HT transmission, while the absence of down-regulation of KCC2 could rather indicate an inability of MNs to respond to insults. PMID:24478630

  12. Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons.

    PubMed

    Alvarez, Francisco J; Titus-Mitchell, Haley E; Bullinger, Katie L; Kraszpulski, Michal; Nardelli, Paul; Cope, Timothy C

    2011-11-01

    Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped from motoneurons, but while other excitatory and inhibitory inputs eventually recover, VGLUT1 synapses are permanently lost on the cell body (75-95% synaptic losses) and on the proximal 100 μm of dendrite (50% loss). Lost VGLUT1 synapses did not recover, even many months after muscle reinnervation. Interestingly, VGLUT1 density in more distal dendrites did not change. To investigate whether losses are due to VGLUT1 downregulation in injured IA afferents or to complete synaptic disassembly and regression of IA ventral projections, we studied the central trajectories and synaptic varicosities of axon collaterals from control and regenerated afferents with IA-like responses to stretch that were intracellularly filled with neurobiotin. VGLUT1 was present in all synaptic varicosities, identified with the synaptic marker SV2, of control and regenerated afferents. However, regenerated afferents lacked axon collaterals and synapses in lamina IX. In conjunction with the companion electrophysiological study [Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01097.2010], we conclude that peripheral nerve injuries cause a permanent retraction of IA afferent synaptic varicosities from lamina IX and disconnection with motoneurons that is not recovered after peripheral regeneration and reinnervation of muscle by sensory and motor axons.

  13. Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. II. Loss of functional connectivity with motoneurons.

    PubMed

    Bullinger, Katie L; Nardelli, Paul; Pinter, Martin J; Alvarez, Francisco J; Cope, Timothy C

    2011-11-01

    Regeneration of a cut muscle nerve fails to restore the stretch reflex, and the companion paper to this article [Alvarez FJ, Titus-Mitchell HE, Bullinger KL, Kraszpulski M, Nardelli P, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01095.2010] suggests an important central contribution from substantial and persistent disassembly of synapses between regenerated primary afferents and motoneurons. In the present study we tested for physiological correlates of synaptic disruption. Anesthetized adult rats were studied 6 mo or more after a muscle nerve was severed and surgically rejoined. We recorded action potentials (spikes) from individual muscle afferents classified as IA like (*IA) by several criteria and tested for their capacity to produce excitatory postsynaptic potentials (EPSPs) in homonymous motoneurons, using spike-triggered averaging (STA). Nearly every paired recording from a *IA afferent and homonymous motoneuron (93%) produced a STA EPSP in normal rats, but that percentage was only 17% in rats with regenerated nerves. In addition, the number of motoneurons that produced aggregate excitatory stretch synaptic potentials (eSSPs) in response to stretch of the reinnervated muscle was reduced from 100% normally to 60% after nerve regeneration. The decline in functional connectivity was not attributable to synaptic depression, which returned to its normally low level after regeneration. From these findings and those in the companion paper, we put forward a model in which synaptic excitation of motoneurons by muscle stretch is reduced not only by misguided axon regeneration that reconnects afferents to the wrong receptor type but also by retraction of synapses with motoneurons by spindle afferents that successfully reconnect with spindle receptors in the periphery.

  14. Dental pulp cells produce neurotrophic factors, interact with trigeminal neurons in vitro, and rescue motoneurons after spinal cord injury.

    PubMed

    Nosrat, I V; Widenfalk, J; Olson, L; Nosrat, C A

    2001-10-01

    Interactions between ingrowing nerve fibers and their target tissues form the basis for functional connectivity with the central nervous system. Studies of the developing dental pulp innervation by nerve fibers from the trigeminal ganglion is an excellent example of nerve-target tissue interactions and will allow specific questions regarding development of the dental pulp nerve system to be addressed. Dental pulp cells (DPC) produce an array of neurotrophic factors during development, suggesting that these proteins might be involved in supporting trigeminal nerve fibers that innervate the dental pulp. We have established an in vitro culture system to study the interactions between the dental pulp cells and trigeminal neurons. We show that dental pulp cells produce several neurotrophic factors in culture. When DPC are cocultured with trigeminal neurons, they promote survival and a specific and elaborate neurite outgrowth pattern from trigeminal neurons, whereas skin fibroblasts do not provide a similar support. In addition, we show that dental pulp tissue becomes innervated when transplanted ectopically into the anterior chamber of the eye in rats, and upregulates the catecholaminergic nerve fiber density of the irises. Interestingly, grafting the dental pulp tissue into hemisected spinal cord increases the number of surviving motoneurons, indicating a functional bioactivity of the dental pulp-derived neurotrophic factors in vivo by rescuing motoneurons. Based on these findings, we propose that dental pulp-derived neurotrophic factors play an important role in orchestrating the dental pulp innervation.

  15. Bilateral Bulbospinal Projections to Pudendal Motoneuron Circuitry after Chronic Spinal Cord Hemisection Injury as Revealed by Transsynaptic Tracing with Pseudorabies Virus

    PubMed Central

    Chadha, Harpreet K.; Dugan, Victoria P.; Gupta, Daya S.; Ferrero, Sunny L.; Hubscher, Charles H.

    2011-01-01

    Abstract Complications of spinal cord injury in males include losing brainstem control of pudendal nerve–innervated perineal muscles involved in erection and ejaculation. We previously described, in adult male rats, a bulbospinal pathway originating in a discrete area within the medullary gigantocellularis (GiA/Gi), and lateral paragigantocellularis (LPGi) nuclei, which when electrically microstimulated unilaterally, produces a bilateral inhibition of pudendal motoneuron reflex circuitry after crossing to the contralateral spinal cord below T8. Microstimulation following a long-term lateral hemisection, however, revealed reflex inhibition from both sides of the medulla, suggesting the development or unmasking of an injury-induced bulbospinal pathway crossing the midline cranial to the spinal lesion. In the present study, we investigated this pathway anatomically using the transsynaptic neuronal tracer pseudorabies virus (PRV) injected unilaterally into the bulbospongiosus muscle in uninjured controls, and ipsilateral to a chronic (1–2 months) unilateral lesion of the lateral funiculus. At 4.75 days post-injection, PRV-labeled cells were found bilaterally in the GiA/Gi/LPGi with equal side-to-side labeling in uninjured controls, and with significantly greater labeling contralateral to the lesion/injection in lesioned animals. The finding of PRV-labeled neurons on both sides of the medulla after removing the mid-thoracic spinal pathway on one side provides anatomical evidence for the bilaterality in both the brainstem origin and the lumbosacral pudendal circuit termination of the spared lateral funicular bulbospinal pathway. This also suggests that this bilaterality may contribute to the quick functional recovery of bladder and sexual functions observed in animals and humans with lateral hemisection injury. PMID:21265606

  16. Bilateral bulbospinal projections to pudendal motoneuron circuitry after chronic spinal cord hemisection injury as revealed by transsynaptic tracing with pseudorabies virus.

    PubMed

    Johnson, Richard D; Chadha, Harpreet K; Dugan, Victoria P; Gupta, Daya S; Ferrero, Sunny L; Hubscher, Charles H

    2011-04-01

    Complications of spinal cord injury in males include losing brainstem control of pudendal nerve-innervated perineal muscles involved in erection and ejaculation. We previously described, in adult male rats, a bulbospinal pathway originating in a discrete area within the medullary gigantocellularis (GiA/Gi), and lateral paragigantocellularis (LPGi) nuclei, which when electrically microstimulated unilaterally, produces a bilateral inhibition of pudendal motoneuron reflex circuitry after crossing to the contralateral spinal cord below T8. Microstimulation following a long-term lateral hemisection, however, revealed reflex inhibition from both sides of the medulla, suggesting the development or unmasking of an injury-induced bulbospinal pathway crossing the midline cranial to the spinal lesion. In the present study, we investigated this pathway anatomically using the transsynaptic neuronal tracer pseudorabies virus (PRV) injected unilaterally into the bulbospongiosus muscle in uninjured controls, and ipsilateral to a chronic (1-2 months) unilateral lesion of the lateral funiculus. At 4.75 days post-injection, PRV-labeled cells were found bilaterally in the GiA/Gi/LPGi with equal side-to-side labeling in uninjured controls, and with significantly greater labeling contralateral to the lesion/injection in lesioned animals. The finding of PRV-labeled neurons on both sides of the medulla after removing the mid-thoracic spinal pathway on one side provides anatomical evidence for the bilaterality in both the brainstem origin and the lumbosacral pudendal circuit termination of the spared lateral funicular bulbospinal pathway. This also suggests that this bilaterality may contribute to the quick functional recovery of bladder and sexual functions observed in animals and humans with lateral hemisection injury.

  17. Reduced expression of regeneration associated genes in chronically axotomized facial motoneurons.

    PubMed

    Gordon, T; You, S; Cassar, S L; Tetzlaff, W

    2015-02-01

    Chronically axotomized motoneurons progressively fail to regenerate their axons. Since axonal regeneration is associated with the increased expression of tubulin, actin and GAP-43, we examined whether the regenerative failure is due to failure of chronically axotomized motoneurons to express and sustain the expression of these regeneration associated genes (RAGs). Chronically axotomized facial motoneurons were subjected to a second axotomy to mimic the clinical surgical procedure of refreshing the proximal nerve stump prior to nerve repair. Expression of α1-tubulin, actin and GAP-43 was analyzed in axotomized motoneurons using in situ hybridization followed by autoradiography and silver grain quantification. The expression of these RAGs by acutely axotomized motoneurons declined over several months. The chronically injured motoneurons responded to a refreshment axotomy with a re-increase in RAG expression. However, this response to a refreshment axotomy of chronically injured facial motoneurons was less than that seen in acutely axotomized facial motoneurons. These data demonstrate that the neuronal RAG expression can be induced by injury-related signals and does not require acute deprivation of target derived factors. The transient expression is consistent with a transient inflammatory response to the injury. We conclude that transient RAG expression in chronically axotomized motoneurons and the weak response of the chronically axotomized motoneurons to a refreshment axotomy provides a plausible explanation for the progressive decline in regenerative capacity of chronically axotomized motoneurons.

  18. Phase relation changes between the firings of alpha and gamma-motoneurons and muscle spindle afferents in the sacral micturition centre during continence functions in brain-dead human and patients with spinal cord injury.

    PubMed

    Schalow, G

    2010-01-01

    1. Single-nerve fibre action potentials (APs) were recorded with 2 pairs of wire electrodes from lower sacral nerve roots during surgery in patients with spinal cord injury and in a brain-dead human. Conduction velocity distribution histograms were constructed for afferent and efferent fibres, nerve fibre groups were identified and simultaneous impulse patterns of alpha and gamma-motoneurons and secondary muscle spindle afferents (SP2) were constructed. Temporal relations between afferent and efferent APs were analyzed by interspike interval (II) and phase relation changes to explore the coordinated self-organization of somatic and parasympathetic neuronal networks in the sacral micturition centre during continence functions under physiologic (brain-dead) and pathophysiologic conditions (spinal cord injury). 2. In a paraplegic with hyperreflexia of the bladder, urinary bladder stretch (S1) and tension receptor afferents (ST) fired already when the bladder was empty, and showed a several times higher bladder afferent activity increase upon retrograde bladder filling than observed in the brain-dead individual. Two alpha2-motoneurons (FR) innervating the external bladder sphincter were already oscillatory firing to generate high activity levels when the bladder was empty. They showed activity levels with no bladder filling, comparable to those measured at a bladder filling of 600 ml in the brain-dead individual. A bladder storage volume of 600 ml was thus lost in the paraplegic, due to a too high bladder afferent input to the sacral micturition center, secondary to inflammation and hypertrophy of the detrusor. 3. In a brain-dead human, 2 phase relations existed per oscillation period of 160 ms between the APs of a sphincteric oscillatory firing alpha2-motoneuron, a dynamic fusimotor and a secondary muscle spindle afferent fibre. Following stimulation of mainly somatic afferent fibres, the phase relations changed only little. 4. In a paraplegic with dyssynergia of the

  19. Androgen regulation of axon growth and neurite extension in motoneurons

    PubMed Central

    Fargo, Keith N.; Galbiati, Mariarita; Foecking, Eileen M.; Poletti, Angelo; Jones, Kathryn J.

    2008-01-01

    Androgens act on the CNS to affect motor function through interaction with a widespread distribution of intracellular androgen receptors (AR). This review highlights our work on androgens and process outgrowth in motoneurons, both in vitro and in vivo. The actions of androgens on motoneurons involve the generation of novel neuronal interactions that are mediated by the induction of androgen-dependent neurite or axonal outgrowth. Here, we summarize the experimental evidence for the androgenic regulation of the extension and regeneration of motoneuron neurites in vitro using cultured immortalized motoneurons, and axons in vivo using the hamster facial nerve crush paradigm. We place particular emphasis on the relevance of these effects to SBMA and peripheral nerve injuries. PMID:18387610

  20. Co-expression of GAP-43 and nNOS in avulsed motoneurons and their potential role for motoneuron regeneration.

    PubMed

    Yuan, Qiuju; Hu, Bing; Chu, Tak-Ho; Su, Huanxing; Zhang, Wenming; So, Kwok-Fai; Lin, Zhixiu; Wu, Wutian

    2010-12-15

    Neuronal nitric oxide synthase (nNOS) is induced after axonal injury. The role of induced nNOS in injured neurons is not well established. In the present study, we investigated the co-expression of nNOS with GAP-43 in spinal motoneurons following axonal injury. The role of induced nNOS was discussed and evaluated. In normal rats, spinal motoneurons do not express nNOS or GAP-43. Following spinal root avulsion, expression of nNOS and GAP-43 were induced and colocalized in avulsed motoneurons. Reimplantation of avulsed roots resulted in a remarkable decrease of GAP-43- and nNOS-IR in the soma of the injured motoneurons. A number of GAP-43-IR regenerating motor axons were found in the reimplanted nerve. In contrast, the nNOS-IR was absent in reimplanted nerve. These results suggest that expression of GAP-43 in avulsed motoneurons is related to axonal regeneration whereas nNOS is not.

  1. Synaptic Control of Motoneuronal Excitability

    PubMed Central

    Rekling, Jens C.; Funk, Gregory D.; Bayliss, Douglas A.; Dong, Xiao-Wei; Feldman, Jack L.

    2016-01-01

    Movement, the fundamental component of behavior and the principal extrinsic action of the brain, is produced when skeletal muscles contract and relax in response to patterns of action potentials generated by motoneurons. The processes that determine the firing behavior of motoneurons are therefore important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre- and postsynaptic actions, signal transduction, and functional role. Glutamate is the main excitatory, and GABA and glycine are the main inhibitory transmitters acting through ionotropic receptors. These amino acids signal the principal motor commands from peripheral, spinal, and supraspinal structures. Amines, such as serotonin and norepinephrine, and neuropeptides, as well as the glutamate and GABA acting at metabotropic receptors, modulate motoneuronal excitability through pre- and postsynaptic actions. Acting principally via second messenger systems, their actions converge on common effectors, e.g., leak K+ current, cationic inward current, hyperpolarization-activated inward current, Ca2+ channels, or presynaptic release processes. Together, these numerous inputs mediate and modify incoming motor commands, ultimately generating the coordinated firing patterns that underlie muscle contractions during motor behavior. PMID:10747207

  2. Motoneuron differentiation of immortalized human spinal cord cell lines.

    PubMed

    Li, R; Thode, S; Zhou, J; Richard, N; Pardinas, J; Rao, M S; Sah, D W

    2000-02-01

    Human motoneuron cell lines will be valuable tools for spinal cord research and drug discovery. To create such cell lines, we immortalized NCAM(+)/neurofilament(+) precursors from human embryonic spinal cord with a tetracycline repressible v-myc oncogene. Clonal NCAM(+)/neurofilament(+) cell lines differentiated exclusively into neurons within 1 week. These neurons displayed extensive processes, exhibited immunoreactivity for mature neuron-specific markers such as tau and synaptophysin, and fired action potentials upon current injection. Moreover, a clonal precursor cell line gave rise to multiple types of spinal cord neurons, including ChAT(+)/Lhx3(+)/Lhx4(+) motoneurons and GABA(+) interneurons. These neuronal restricted precursor cell lines will expedite the elucidation of molecular mechanisms that regulate the differentiation, maturation and survival of specific subsets of spinal cord neurons, and the identification and validation of novel drug targets for motoneuron diseases and spinal cord injury.

  3. Regeneration-associated genes decline in chronically injured rat sciatic motoneurons.

    PubMed

    Gordon, Tessa; Tetzlaff, Wolfram

    2015-11-01

    Chronic nerve injuries are notorious for their poor regenerative outcomes. Here, we addressed the question of whether the established reduced ability of injured motoneurons to regenerate their axons with time of disconnection with targets (chronic axotomy) is associated with a failure of injured motoneurons to express and sustain their expression of regeneration-associated genes. Sciatic motoneurons were prevented from regenerating by ligation of the transected nerves (chronic axotomy), and then subjected to a second nerve transection (acute axotomy) to mimic the clinical surgical procedure of refreshing the proximal nerve stump prior to delayed nerve repair. The expression of α1-tubulin, actin and GAP-43 mRNA was analysed in axotomized sciatic motoneurons by the use of in situ hybridization followed by autoradiography and silver grain quantification. The expression of these regeneration-associated genes by naive (acutely) axotomized motoneurons declined exponentially, to reach baseline levels within 6 months. These chronically injured motoneurons responded to a refreshment axotomy by elevating the expression of the genes to the same levels as in acutely (i.e. for the first time) axotomized sciatic motoneurons. However, the expression of these declined more rapidly than after acute axotomy. We conclude that a progressive decline in the expression of the regeneration-associated genes in chronically axotomized motoneurons and the even more rapid decline in their expression in response to a refreshment axotomy may explain why the regenerative capacity of chronically axotomized neurons declines with time.

  4. Postnatal growth of genioglossal motoneurons.

    PubMed

    Brozanski, B S; Guthrie, R D; Volk, E A; Cameron, W E

    1989-01-01

    The postnatal growth of kitten genioglossal motoneurons were examined in six different age groups (newborn, 2, 4, 8, and 12 weeks and adult) using the technique of retrograde transport of horseradish peroxidase (HRP). The cell bodies of 100-150 motoneurons in each age group were analyzed in a transverse plane of section using standard techniques. Somatic genioglossal motoneuron growth occurred primarily along the major axis, which increased from 25.2 microns to 41.3 microns between birth and 8 weeks of postnatal age, after which time there was no further increase in either major or minor dimension of the cell body. The form factor decreased from 0.94 to 0.80 from birth to adulthood indicating an increased eccentricity of the cell body. The number of primary dendrites visible with this technique remained constant throughout the postnatal period. Calculated somal surface area increased in a linear fashion from birth through 8 weeks of postnatal life. There was no further increase in surface area beyond this age. The rate of increase in somal surface area with age was significantly different from both the rate of increase of animal weight and animal surface area with age. The correlations between the demonstrated immature genioglossal morphology and its cellular electrophysiology or integrated respiratory function remain unknown. The recent demonstration of decreased activation of the genioglossus muscle following airway occlusion in premature infants with apnea suggests that the relationships between developing genioglossal motoneuron structure and function warrant further investigation.

  5. P75 and phosphorylated c-Jun are differentially regulated in spinal motoneurons following axotomy in rats.

    PubMed

    Yuan, Qiuju; Su, Huanxing; Wu, Wutian; Lin, Zhi-Xiu

    2012-09-15

    The neurotrophin receptor (p75) activates the c-Jun N-terminal kinase (JNK) pathway. Activation of JNK and its substrate c-Jun can cause apoptosis. Here we evaluate the role of p75 in spinal motoneurons by comparing immunoreactivity for p75 and phosphorylated c-Jun (p-c-Jun), the production of JNK activation in axotomized motoneurons in postnatal day (PN)1, PN7, PN14 and adult rats. Intensive p-c-Jun was induced in axotomized motoneurons in PN1 and PN7. In PN14, p-c-Jun expression was sharply reduced after the same injury. The decreased expression of p-c-Jun at this age coincided with a developmental switch of re-expression of p75 in axotomized cells. In adult animals, no p-c-Jun but intensive p75 was detected in axotomized motoneurons. These results indicate differential expression or turnover of phosphorylation of c-Jun and p75 in immature versus mature spinal motoneurons in response to axonal injury. The non-co-occurrence of p75 and p-c-Jun in injured motoneurons indicated that p75 may not activate JNK pathway, suggesting that the p75 may not be involved in cell death in axotomized motoneurons.

  6. Acute stimulation of transplanted neurons improves motoneuron survival, axon growth, and muscle reinnervation.

    PubMed

    Grumbles, Robert M; Liu, Yang; Thomas, Christie M; Wood, Patrick M; Thomas, Christine K

    2013-06-15

    Few options exist for treatment of pervasive motoneuron death after spinal cord injury or in neurodegenerative diseases such as amyotrophic lateral sclerosis. Local transplantation of embryonic motoneurons into an axotomized peripheral nerve is a promising approach to arrest the atrophy of denervated muscles; however, muscle reinnervation is limited by poor motoneuron survival. The aim of the present study was to test whether acute electrical stimulation of transplanted embryonic neurons promotes motoneuron survival, axon growth, and muscle reinnervation. The sciatic nerve of adult Fischer rats was transected to mimic the widespread denervation seen after disease or injury. Acutely dissociated rat embryonic ventral spinal cord cells were transplanted into the distal tibial nerve stump as a neuron source for muscle reinnervation. Immediately post-transplantation, the cells were stimulated at 20 Hz for 1 h. Other groups were used to control for the cell transplantation and stimulation. When neurons were stimulated acutely, there were significantly more neurons, including cholinergic neurons, 10 weeks after transplantation. This led to enhanced numbers of myelinated axons, reinnervation of more muscle fibers, and more medial and lateral gastrocnemius muscles were functionally connected to the transplant. Reinnervation reduced muscle atrophy significantly. These data support the concept that electrical stimulation rescues transplanted motoneurons and facilitates muscle reinnervation.

  7. Adaptability of the oxidative capacity of motoneurons

    NASA Technical Reports Server (NTRS)

    Chalmers, G. R.; Roy, R. R.; Edgerton, V. R.

    1992-01-01

    Previous studies have demonstrated that a chronic change in neuronal activation can produce a change in soma oxidative capacity, suggesting that: (i) these 2 variables are directly related in neurons and (ii) ion pumping is an important energy requiring activity of a neuron. Most of these studies, however, have focused on reduced activation levels of sensory systems. In the present study the effect of a chronic increase or decrease in motoneuronal activity on motoneuron oxidative capacity and soma size was studied. In addition, the effect of chronic axotomy was studied as an indicator of whether cytoplasmic volume may also be related to the oxidative capacity of motoneurons. A quantitative histochemical assay for succinate dehydrogenase activity was used as a measure of motoneuron oxidative capacity in experimental models in which chronic electromyography has been used to verify neuronal activity levels. Spinal transection reduced, and spinal isolation virtually eliminated lumbar motoneuron electrical activity. Functional overload of the plantaris by removal of its major synergists was used to chronically increase neural activity of the plantaris motor pool. No change in oxidative capacity or soma size resulted from either a chronic increase or decrease in neuronal activity level. These data indicate that the chronic modulation of ionic transport and neurotransmitter turnover associated with action potentials do not induce compensatory metabolic responses in the metabolic capacity of the soma of lumbar motoneurons. Soma oxidative capacity was reduced in the axotomized motoneurons, suggesting that a combination of axoplasmic transport, intracellular biosynthesis and perhaps neurotransmitter turnover represent the major energy demands on a motoneuron. While soma oxidative capacity may be closely related to neural activity in some neural systems, e.g. visual and auditory, lumbar motoneurons appear to be much less sensitive to modulations in chronic activity levels.

  8. Sigma-1 Receptor in Motoneuron Disease.

    PubMed

    Mancuso, Renzo; Navarro, Xavier

    2017-01-01

    Amyotrophic Lateral Sclerosis (ALS ) is a neurodegenerative disease affecting spinal cord and brain motoneurons , leading to paralysis and early death. Multiple etiopathogenic mechanisms appear to contribute in the development of ALS , including glutamate excitotoxicity, oxidative stress , protein misfolding, mitochondrial defects, impaired axonal transport, inflammation and glial cell alterations. The Sigma-1 receptor is highly expressed in motoneurons of the spinal cord, particularly enriched in the endoplasmic reticulum (ER) at postsynaptic cisternae of cholinergic C-terminals. Several evidences point to participation of Sigma-1R alterations in motoneuron degeneration. Thus, mutations of the transmembrane domain of the Sigma-1R have been described in familial ALS cases. Interestingly, Sigma-1R KO mice display muscle weakness and motoneuron loss. On the other hand, Sigma-1R agonists promote neuroprotection and neurite elongation through activation of protein kinase C on motoneurons in vitro and in vivo after ventral root avulsion. Remarkably, treatment of SOD1 mice, the most usual animal model of ALS , with Sigma-1R agonists resulted in significantly enhanced motoneuron function and preservation, and increased animal survival. Sigma-1R activation also reduced microglial reactivity and increased the glial expression of neurotrophic factors. Two main interconnected mechanisms seem to underlie the effects of Sigma-1R manipulation on motoneurons: modulation of neuronal excitability and regulation of calcium homeostasis. In addition, Sigma-1R also contributes to regulating protein degradation, and reducing oxidative stress. Therefore, the multi-functional nature of the Sigma-1R represents an attractive target for treating aspects of ALS and other motoneuron diseases .

  9. Neonatal motoneurons overexpressing the bcl-2 protooncogene in transgenic mice are protected from axotomy-induced cell death.

    PubMed Central

    Dubois-Dauphin, M; Frankowski, H; Tsujimoto, Y; Huarte, J; Martinou, J C

    1994-01-01

    In vitro, the overexpression of the bcl-2 protooncogene in cultured neurons has been shown to prevent apoptosis induced by neurotrophic factor deprivation. We have generated transgenic mice overexpressing the Bcl-2 protein in neurons, including motoneurons of the facial nucleus. We have tested whether Bcl-2 could protect these motoneurons from experimentally induced cell death in new born mice. To address this question, we performed unilateral lesion of the facial nerve of wild-type and transgenic 2-day-old mice. In wild-type mice, the lesioned nerve and the corresponding motoneuron cell bodies in the facial nucleus underwent rapid degeneration. In contrast, in transgenic mice, facial motoneurons survived axotomy. Not only their cell bodies but also their axons were protected up to the lesion site. These results demonstrate that in vivo Bcl-2 protects neonatal motoneurons from degeneration after axonal injury. A better understanding of the mechanisms by which Bcl-2 prevents neuronal cell death in vivo could lead to the development of strategies for the treatment of motoneuron degenerative diseases. Images PMID:8159744

  10. Modulation of motoneuron activity by serotonin.

    PubMed

    Perrier, Jean-François

    2016-02-01

    Serotonin is a major neuromodulator in the central nervous system involved in most physiological functions including appetite regulation, sexual arousal, sleep regulation and motor control. The activity of neurons from the raphe spinal tract, which release serotonin on motoneurons, is positively correlated with motor behaviour. During moderate physical activity, serotonin is released from synaptic terminals onto the dendrites and cell bodies of motoneurons. Serotonin increases the excitability of motoneurons and thereby facilitate muscle contraction by acting on several parallel intracellular pathways. By activating 5-HT1A receptors, serotonin inhibits TWIK-related acid-sensitive potassium channels and small conductance calcium-activated potassium channels. In parallel, serotonin binds to 5-HT2 receptors, which promotes the low-threshold L-type Ca(2+) channels. During intense physical activity, more serotonin is released. The reuptake systems saturate and serotonin spills over to reach extrasynaptic 5-HT1A receptors located on the axon initial segment of motoneurons. This in turn induces the inhibition of the Na(+) channels responsible for the initiation of action potentials. Fewer nerve impulses are generated and muscle contraction becomes weaker. By decreasing the gain of motoneurons, serotonin triggers central fatigue.

  11. Defects in Motoneuron-Astrocyte Interactions in Spinal Muscular Atrophy.

    PubMed

    Zhou, Chunyi; Feng, Zhihua; Ko, Chien-Ping

    2016-02-24

    Spinal muscular atrophy (SMA) is a motoneuron disease caused by loss or mutation in Survival of Motor Neuron 1 (SMN1) gene. Recent studies have shown that selective restoration of SMN protein in astrocytes partially alleviates pathology in an SMA mouse model, suggesting important roles for astrocytes in SMA. Addressing these underlying mechanisms may provide new therapeutic avenues to fight SMA. Using primary cultures of pure motoneurons or astrocytes from SMNΔ7 (SMA) and wild-type (WT) mice, as well as their mixed and matched cocultures, we characterized the contributions of motoneurons, astrocytes, and their interactions to synapse loss in SMA. In pure motoneuron cultures, SMA motoneurons exhibited normal survival but intrinsic defects in synapse formation and synaptic transmission. In pure astrocyte cultures, SMA astrocytes exhibited defects in calcium homeostasis. In motoneuron-astrocyte contact cocultures, synapse formation and synaptic transmission were significantly reduced when either motoneurons, astrocytes or both were from SMA mice compared with those in WT motoneurons cocultured with WT astrocytes. The reduced synaptic activity is unlikely due to changes in motoneuron excitability. This disruption in synapse formation and synaptic transmission by SMN deficiency was not detected in motoneuron-astrocyte noncontact cocultures. Additionally, we observed a downregulation of Ephrin B2 in SMA astrocytes. These findings suggest that there are both cell autonomous and non-cell-autonomous defects in SMA motoneurons and astrocytes. Defects in contact interactions between SMA motoneurons and astrocytes impair synaptogenesis seen in SMA pathology, possibly due to the disruption of the Ephrin B2 pathway.

  12. Estimating the time course of population excitatory postsynaptic potentials in motoneurons of spastic stroke survivors.

    PubMed

    Hu, Xiaogang; Suresh, Nina L; Rymer, William Z

    2015-03-15

    Hyperexcitable motoneurons are likely to contribute to muscle hypertonia after a stroke injury; however, the origins of this hyperexcitability are not clear. One possibility is that the effective duration of the Ia excitatory postsynaptic potential (EPSP) is prolonged, increasing the potential for temporal summation of EPSPs, making action potential initiation easier. Accordingly, the purpose of this study was to quantify the time course of EPSPs in motoneurons of stroke survivors. The experimental protocol, which was based on parameters derived from simulation, involved sequential subthreshold electrical stimuli delivered to the median nerve of hemispheric stroke survivors. The resulting H-reflex responses were recorded in the flexor carpi radialis muscle. H-reflex response probability was then used to quantify the time course of the underlying EPSPs in the motoneuron pool. A population EPSP was estimated based on the probability of evoking an H reflex from the second electrical stimulus in the absence of a reflex response to the first stimulus. The accuracy of this time-course estimate was quantified using a computer simulation that explored a range of feasible EPSP parameters. Our experimental results showed that in all five hemispheric stroke survivors the rate of decay of the population EPSP was consistently slower in spastic compared with the contralateral motoneuron pools. We propose that one potential mechanism for hyperexcitability of motoneurons in spastic stroke survivors may be linked to this prolongation of the Ia EPSP time course. Our subthreshold double-stimulation approach also provides a noninvasive tool for quantifying the time course of EPSPs in both healthy and pathological conditions.

  13. The Differential Expression of Calcitonin Gene Related Peptide, alpha CGRP mRNA, Choline Acetyltransferase, and Low Affinity Nerve Growth Factor Receptor in Cranial Motoneurons After Hypoglossal Nerve Injury During Postnatal Development

    DTIC Science & Technology

    1996-08-21

    postnatal weeks, produced rapid apoptosis of Schwann cells but the same injury resulted in negligible Schwann ce1110ss in 25 dpn rats (Trachtenberg & Thompson...in rapid apoptosis of’Schwann cells (Trachtenberg and Thompson, 1996). Whether comparable Schwann cell death also occurs 71 after nerve crush in rats...age in rats is not known. It may be relevant that axonal injury during the first two postnatal weeks resulted in rapid apoptosis ofSchwann cells but

  14. Postnatal development of phrenic motoneurons in the cat.

    PubMed

    Cameron, W E; Brozanski, B S; Guthrie, R D

    1990-01-01

    The postnatal growth of phrenic motoneurons in the cat was studied using retrograde transport of horseradish peroxidase (HRP). The mean somal surface area of these developing motoneurons increased 2.5 times from day 3 to adult while the mean somal volume increased four-fold. This change in mean somal surface area during postnatal development was found to be correlated with the change in mean axonal conduction velocity measured from phrenic motoneurons.

  15. Electrical Stimulation of Low-Threshold Proprioceptive Fibers in the Adult Rat Increases Density of Glutamatergic and Cholinergic Terminals on Ankle Extensor α-Motoneurons

    PubMed Central

    Gajewska-Woźniak, Olga; Grycz, Kamil; Czarkowska-Bauch, Julita; Skup, Małgorzata

    2016-01-01

    The effects of stimulation of low-threshold proprioceptive afferents in the tibial nerve on two types of excitatory inputs to α-motoneurons were tested. The first input is formed by glutamatergic Ia sensory afferents contacting monosynaptically α-motoneurons. The second one is the cholinergic input originating from V0c—interneurons, located in lamina X of the spinal cord, modulating activity of α-motoneurons via C-terminals. Our aim was to clarify whether enhancement of signaling to ankle extensor α-motoneurons, via direct electrical stimulation addressed predominantly to low-threshold proprioceptive fibers in the tibial nerve of awake rats, will affect Ia glutamatergic and cholinergic innervation of α-motoneurons of lateral gastrocnemius (LG). LG motoneurons were identified with True Blue tracer injected intramuscularly. Tibial nerve was stimulated for 7 days with continuous bursts of three pulses applied in four 20 min sessions daily. The Hoffmann reflex and motor responses recorded from the soleus muscle, LG synergist, allowed controlling stimulation. Ia terminals and C-terminals abutting on LG-labeled α-motoneurons were detected by immunofluorescence (IF) using input-specific anti- VGLUT1 and anti-VAChT antibodies, respectively. Quantitative analysis of confocal images revealed that the number of VGLUT1 IF and VAChT IF terminals contacting the soma of LG α-motoneurons increased after stimulation by 35% and by 26%, respectively, comparing to the sham-stimulated side. The aggregate volume of VGLUT1 IF and VAChT IF terminals increased by 35% and by 30%, respectively. Labeling intensity of boutons was also increased, suggesting an increase of signaling to LG α-motoneurons after stimulation. To conclude, one week of continuous burst stimulation of proprioceptive input to LG α-motoneurons is effective in enrichment of their direct glutamatergic but also indirect cholinergic inputs. The effectiveness of such and longer stimulation in models of injury is a

  16. Retrograde response in axotomized motoneurons: nitric oxide as a key player in triggering reversion toward a dedifferentiated phenotype.

    PubMed

    González-Forero, D; Moreno-López, B

    2014-12-26

    The adult brain retains a considerable capacity to functionally reorganize its circuits, which mainly relies on the prevalence of three basic processes that confer plastic potential: synaptic plasticity, plastic changes in intrinsic excitability and, in certain central nervous system (CNS) regions, also neurogenesis. Experimental models of peripheral nerve injury have provided a useful paradigm for studying injury-induced mechanisms of central plasticity. In particular, axotomy of somatic motoneurons triggers a robust retrograde reaction in the CNS, characterized by the expression of plastic changes affecting motoneurons, their synaptic inputs and surrounding glia. Axotomized motoneurons undergo a reprograming of their gene expression and biosynthetic machineries which produce cell components required for axonal regrowth and lead them to resume a functionally dedifferentiated phenotype characterized by the removal of afferent synaptic contacts, atrophy of dendritic arbors and an enhanced somato-dendritic excitability. Although experimental research has provided valuable clues to unravel many basic aspects of this central response, we are still lacking detailed information on the cellular/molecular mechanisms underlying its expression. It becomes clear, however, that the state-switch must be orchestrated by motoneuron-derived signals produced under the direction of the re-activated growth program. Our group has identified the highly reactive gas nitric oxide (NO) as one of these signals, by providing robust evidence for its key role to induce synapse elimination and increases in intrinsic excitability following motor axon damage. We have elucidated operational principles of the NO-triggered downstream transduction pathways mediating each of these changes. Our findings further demonstrate that de novo NO synthesis is not only "necessary" but also "sufficient" to promote the expression of at least some of the features that reflect reversion toward a dedifferentiated

  17. Development of Connectivity in a Motoneuronal Network in Drosophila Larvae

    PubMed Central

    Couton, Louise; Mauss, Alex S.; Yunusov, Temur; Diegelmann, Soeren; Evers, Jan Felix; Landgraf, Matthias

    2015-01-01

    Summary Background Much of our understanding of how neural networks develop is based on studies of sensory systems, revealing often highly stereotyped patterns of connections, particularly as these diverge from the presynaptic terminals of sensory neurons. We know considerably less about the wiring strategies of motor networks, where connections converge onto the dendrites of motoneurons. Here, we investigated patterns of synaptic connections between identified motoneurons with sensory neurons and interneurons in the motor network of the Drosophila larva and how these change as it develops. Results We find that as animals grow, motoneurons increase the number of synapses with existing presynaptic partners. Different motoneurons form characteristic cell-type-specific patterns of connections. At the same time, there is considerable variability in the number of synapses formed on motoneuron dendrites, which contrasts with the stereotypy reported for presynaptic terminals of sensory neurons. Where two motoneurons of the same cell type contact a common interneuron partner, each postsynaptic cell can arrive at a different connectivity outcome. Experimentally changing the positioning of motoneuron dendrites shows that the geography of dendritic arbors in relation to presynaptic partner terminals is an important determinant in shaping patterns of connectivity. Conclusions In the Drosophila larval motor network, the sets of connections that form between identified neurons manifest an unexpected level of variability. Synapse number and the likelihood of forming connections appear to be regulated on a cell-by-cell basis, determined primarily by the postsynaptic dendrites of motoneuron terminals. PMID:25702582

  18. Testing the evolutionary conservation of vocal motoneurons in vertebrates.

    PubMed

    Albersheim-Carter, Jacob; Blubaum, Aleksandar; Ballagh, Irene H; Missaghi, Kianoush; Siuda, Edward R; McMurray, George; Bass, Andrew H; Dubuc, Réjean; Kelley, Darcy B; Schmidt, Marc F; Wilson, Richard J A; Gray, Paul A

    2016-04-01

    Medullary motoneurons drive vocalization in many vertebrate lineages including fish, amphibians, birds, and mammals. The developmental history of vocal motoneuron populations in each of these lineages remains largely unknown. The highly conserved transcription factor Paired-like Homeobox 2b (Phox2b) is presumed to be expressed in all vertebrate hindbrain branchial motoneurons, including laryngeal motoneurons essential for vocalization in humans. We used immunohistochemistry and in situ hybridization to examine Phox2b protein and mRNA expression in caudal hindbrain and rostral spinal cord motoneuron populations in seven species across five chordate classes. Phox2b was present in motoneurons dedicated to sound production in mice and frogs (bullfrog, African clawed frog), but not those in bird (zebra finch) or bony fish (midshipman, channel catfish). Overall, the pattern of caudal medullary motoneuron Phox2b expression was conserved across vertebrates and similar to expression in sea lamprey. These observations suggest that motoneurons dedicated to sound production in vertebrates are not derived from a single developmentally or evolutionarily conserved progenitor pool.

  19. Intramuscular AAV delivery of NT-3 alters synaptic transmission to motoneurons in adult rats

    PubMed Central

    Petruska, Jeffrey C.; Kitay, Brandon; Boyce, Vanessa S.; Kaspar, Brian; Pearse, Damien; Gage, Fred H.; Mendell, Lorne M.

    2010-01-01

    We examined whether elevating levels of neurotrophin-3 (NT-3) in the spinal cord and dorsal root ganglion (DRG) would alter connections made by muscle spindle afferent fibers on motoneurons. Adeno-associated virus (AAV) serotypes AAV1, AAV2 and AAV5, selected for their tropism profile, were engineered with the NT-3 gene and administered to the medial gastrocnemius muscle in adult rats. ELISA studies in muscle, DRG and spinal cord revealed that NT-3 concentration in all tissues peaked about 3 months after a single viral injection; after 6 months NT-3 concentration returned to normal values. Intracellular recording in triceps surae motoneurons revealed complex electrophysiological changes. Moderate elevation in cord NT-3 resulted in diminished segmental excitatory postsynaptic potential (EPSP) amplitude, perhaps as a result of the observed decrease in motoneuron input resistance. With further elevation in NT-3 expression, the decline in EPSP amplitude was reversed indicating that NT-3 at higher concentration could increase EPSP amplitude. No correlation was observed between EPSP amplitude and NT-3 concentration in the DRG. Treatment with control viruses could elevate NT-3 levels minimally resulting in measurable electrophysiological effects, perhaps as a result of inflammation associated with injection. EPSPs elicited by stimulation of the ventrolateral funiculus underwent a consistent decline in amplitude independent of NT-3 level. These novel correlations between modified NT-3 expression and single-cell electrophysiological parameters indicate that intramuscular administration of AAV(NT-3) can exert long lasting effects on synaptic transmission to motoneurons. This approach to neurotrophin delivery could be useful in modifying spinal function after injury. PMID:20849530

  20. Shaping the Output of Lumbar Flexor Motoneurons by Sacral Neuronal Networks.

    PubMed

    Cherniak, Meir; Anglister, Lili; Lev-Tov, Aharon

    2017-02-01

    The ability to improve motor function in spinal cord injury patients by reactivating spinal central pattern generators (CPGs) requires the elucidation of neurons and pathways involved in activation and modulation of spinal networks in accessible experimental models. Previously we reported on adrenoceptor-dependent sacral control of lumbar flexor motoneuron firing in newborn rats. The current work focuses on clarification of the circuitry and connectivity involved in this unique modulation and its potential use. Using surgical manipulations of the spinal gray and white matter, electrophysiological recordings, and confocal microscopy mapping, we found that methoxamine (METH) activation of sacral networks within the ventral aspect of S2 segments was sufficient to produce alternating rhythmic bursting (0.15-1 Hz) in lumbar flexor motoneurons. This lumbar rhythm depended on continuity of the ventral funiculus (VF) along the S2-L2 segments. Interrupting the VF abolished the rhythm and replaced it by slow unstable bursting. Calcium imaging of S1-S2 neurons, back-labeled via the VF, revealed that ∼40% responded to METH, mostly by rhythmic firing. All uncrossed projecting METH responders and ∼70% of crossed projecting METH responders fired with the concurrent ipsilateral motor output, while the rest (∼30%) fired with the contralateral motor output. We suggest that METH-activated sacral CPGs excite ventral clusters of sacral VF neurons to deliver the ascending drive required for direct rhythmic activation of lumbar flexor motoneurons. The capacity of noradrenergic-activated sacral CPGs to modulate the activity of lumbar networks via sacral VF neurons provides a novel way to recruit rostral lumbar motoneurons and modulate the output required to execute various motor behaviors.

  1. Effect of prolonged riluzole exposure on cultured motoneurons in a mouse model of ALS

    PubMed Central

    Schuster, J. E.; Fu, R.; Siddique, T.

    2012-01-01

    Riluzole is the only FDA-approved drug to treat amyotrophic lateral sclerosis, but its long-term effects on motoneurons are unknown. Therefore, we treated primary mouse spinal cord cultures with 2 μM riluzole for 4–9 days and then used whole cell patch clamp to record the passive and active properties of both wild-type and SOD1G93A motoneurons. At this concentration, riluzole blocks >50% of the sodium component of a persistent inward current that plays a major role in determining motoneuron excitability. Prolonged riluzole treatment significantly decreased the amplitude of the persistent inward current. This effect was specific for SOD1G93A motoneurons, where the amplitude decreased by 55.4%. In addition, prolonged treatment hyperpolarized the resting membrane potential as well as the voltage onset and voltage maximum of the persistent inward current (∼2–3 mV in each case). These effects appeared to offset one another and resulted in no change in the firing properties. In a subset of cells, acute reapplication of 2 μM riluzole during the recording decreased repetitive firing and the persistent inward current, which is consistent with the normal effects of riluzole. The downregulation of the persistent inward current in response to prolonged riluzole administration is in contrast to the strong upregulation of this same current after descending neuromodulatory drive to the cord is lost following spinal injury. This dichotomy suggests that decreased activation of G protein-coupled pathways can induce upregulation in the persistent inward current but that direct channel block is ineffective. PMID:22013234

  2. Dopamine effects on identified rat vagal motoneurons

    PubMed Central

    Zheng, Zhongling; Travagli, R. Alberto

    2011-01-01

    Catecholaminergic neurons of the A2 area play a prominent role in brain stem vagal circuits. It is not clear, however, whether these neurons are noradrenergic or adrenergic, i.e., display tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DβH) immunoreactivity (-IR) or dopaminergic (i.e., TH- but not DβH-IR). Our aims were to investigate whether a subpopulation of neurons in the A2 area was dopaminergic and, if so, to investigate the effects of dopamine (DA) on the membrane of gastric-projecting vagal motoneurons. We observed that although the majority of A2 neurons were both TH- and DβH-IR, a small percentage of nucleus tractus solitarius neurons were TH-IR only, suggesting that DA itself may play role in these circuits. Whole cell recordings from thin brain stem slices showed that 71% of identified gastric-projecting motoneurons responded to DA (1–300 µM) with either an excitation (28%) or an inhibition (43%) of the membrane; the remaining 29% of the neurons were unresponsive. The DA-induced depolarization was mimicked by SK 38393 and prevented by pretreatment with SCH 23390. Conversely, the DA-induced inhibition was mimicked by bromoergocryptine and prevented by pretreatment with L741626. When tested on the same neuron, the effects of DA and NE were not always similar. In fact, in neurons in which DA induced a membrane depolarization, 77% were inhibited by NE, whereas 75% of neurons unresponsive to DA were inhibited by NE. Our data suggest that DA modulates the membrane properties of gastric-projecting motoneurons via D1- and D2-like receptors, and DA may play different roles than norepinephrine in brain stem vagal circuits. PMID:17170022

  3. Cat hindlimb motoneurons during locomotion. II. Normal activity patterns.

    PubMed

    Hoffer, J A; Sugano, N; Loeb, G E; Marks, W B; O'Donovan, M J; Pratt, C A

    1987-02-01

    Activity patterns were recorded from 51 motoneurons in the fifth lumbar ventral root of cats walking on a motorized treadmill at a range of speeds between 0.1 and 1.3 m/s. The muscle of destination of recorded motoneurons was identified by spike-triggered averaging of EMG recordings from each of the anterior thigh muscles. Forty-three motoneurons projected to one of the quadriceps (vastus medialis, vastus lateralis, vastus intermedius, or rectus femoris) or sartorius (anterior or medial) muscles of the anterior thigh. Anterior thigh motoneurons always discharged a single burst of action potentials per step cycle, even in multifunctional muscles (e.g., sartorius anterior) that exhibited more than one burst of EMG activity per step cycle. The instantaneous firing rates of most motoneurons were lowest upon recruitment and increased progressively during a burst, as long as the EMG was still increasing. Firing rates peaked midway through each burst and tended to decline toward the end of the burst. The initial, mean, and peak firing rates of single motoneurons typically increased for faster walking speeds. At any given walking speed, early recruited motoneurons typically reached higher firing rates than late recruited motoneurons. In contrast to decerebrated cats, initial doublets at the beginning of bursts were seen only rarely. In the 4/51 motoneurons that showed initial doublets, both the instantaneous frequency of the doublet and the probability of starting a burst with a doublet decreased for faster walking speeds. The modulations in firing rate of every motoneuron were found to be closely correlated to the smoothed electromyogram of its target muscle. For 32 identified motoneurons, the unit's instantaneous frequencygram was scaled linearly by computer to the rectified smoothed EMG recorded from each of the anterior thigh muscles. The covariance between unitary frequencygram and muscle EMG was computed for each muscle. Typically, the EMG profile of the target

  4. Nicotinic excitation of rat hypoglossal motoneurons.

    PubMed

    Chamberlin, N L; Bocchiaro, C M; Greene, R W; Feldman, J L

    2002-01-01

    Hypoglossal motoneurons (HMNs), which innervate the tongue muscles, are involved in several important physiological functions, including the maintenance of upper airway patency. The neural mechanisms that affect HMN excitability are therefore important determinants of effective breathing. Obstructive sleep apnea is a disorder characterized by recurrent collapse of the upper airway that is likely due to decline of pharyngeal motoneuron activity during sleep. Because cholinergic neuronal activity is closely coupled to wake and sleep states, we tested the effects and pharmacology of nicotinic acetylcholine receptor (nAChR) activation on HMNs. We made intracellular recordings from HMNs in medullary slices from neonatal rats and found that local application of the nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium iodide, excited HMNs by a Ca(2+)-sensitive, and TTX-insensitive inward current that was blocked by dihydro-beta-erythroidine (IC(50): 19+/-3 nM), methyllycaconitine (IC(50): 32+/-7 nM), and mecamylamine (IC(50): 88+/-11 nM), but not by alpha-bungarotoxin (10 nM). This is consistent with responses being mediated by postsynaptic nAChRs that do not contain the alpha7 subunit. These results suggest that nAChR activation may contribute to central maintenance of upper airway patency and that the decline in firing rate of cholinergic neurons during sleep could potentially disfacilitate airway dilator muscle activity, contributing to airway obstruction.

  5. Type C botulinum toxin causes degeneration of motoneurons in vivo.

    PubMed

    Zhao, Li-Chun; Yang, Bo; Wang, Rengang; Lipton, Stuart A; Zhang, Dongxian

    2010-01-06

    All botulinum toxins (BoNTs, types A-G) inhibit synaptic transmitter release from motoneurons, and thus result in respiratory arrest and death. Rapid treatment with anti-BoNT antibodies can prevent progression, but recovery still requires weeks on a ventilator. Even after recovery, there is a potential for persistent fatigue in some cases of botulism even years after the insult, possibly because of motoneuron dropout for previously unknown reasons. Unique among BoNTs, the C-type (BoNT/C) cleaves two proteins involved in neurotransmitter release, syntaxin and SNAP-25, and induces apoptotic cell death in cultured cerebellar neurons. It is not clear, however, whether BoNT/C also affects neurons that encounter toxin in vivo, namely motoneurons. Here, we provide experimental evidence that BoNT/C causes a slow degeneration of motoneurons both in vitro and in vivo. This novel form of BoNT/C-induced cell death may require new treatment strategies.

  6. Myosin phosphatase Fine-tunes Zebrafish Motoneuron Position during Axonogenesis

    PubMed Central

    Granato, Michael

    2016-01-01

    During embryogenesis the spinal cord shifts position along the anterior-posterior axis relative to adjacent tissues. How motor neurons whose cell bodies are located in the spinal cord while their axons reside in adjacent tissues compensate for such tissue shift is not well understood. Using live cell imaging in zebrafish, we show that as motor axons exit from the spinal cord and extend through extracellular matrix produced by adjacent notochord cells, these cells shift several cell diameters caudally. Despite this pronounced shift, individual motoneuron cell bodies stay aligned with their extending axons. We find that this alignment requires myosin phosphatase activity within motoneurons, and that mutations in the myosin phosphatase subunit mypt1 increase myosin phosphorylation causing a displacement between motoneuron cell bodies and their axons. Thus, we demonstrate that spinal motoneurons fine-tune their position during axonogenesis and we identify the myosin II regulatory network as a key regulator. PMID:27855159

  7. Saccular and utricular inputs to sternocleidomastoid motoneurons of decerebrate cats.

    PubMed

    Kushiro, K; Zakir, M; Ogawa, Y; Sato, H; Uchino, Y

    1999-06-01

    Connections from the otolithic organs to sternocleidomastoid (SCM) motoneurons were studied in 20 decerebrate cats. The electrical stimulation was selective for the saccular or the utricular nerves. Postsynaptic potentials were recorded from antidromically identified SCM motoneurons; these muscles participate mainly in neck rotation and flexion. Partial transections of the brainstem at the level of the obex were performed to identify the possible pathway from the otolithic organs to the SCM motoneurons. Saccular or utricular nerve stimulation mainly evoked inhibitory postsynaptic potentials (IPSPs) in the ipsilateral SCM motoneurons. Some of the sacculus-induced IPSPs were preceded by small-amplitude excitatory PSPs (EPSPs). The latencies of the PSPs ranged from 1.8 to 3.1 ms after saccular nerve stimulation and from 1.7 to 2.8 ms after utricular nerve stimulation, indicating that most of the ipsilateral connections were disynaptic. In the contralateral SCM motoneurons, saccular nerve stimulation had no or faint effects, whereas utricular nerve stimulation evoked EPSPs in about two-thirds of neurons, and no visible PSPs in about one-third of neurons. The latencies of the EPSPs ranged from 1.5 to 2.0 ms, indicating the disynaptic connection. Thus, the results suggest a difference between the two otolithic innervating patterns of SCM motoneurons. After transection of the medial vestibulospinal tract (MVST), saccular nerve stimulation did not evoke IPSPs at all in ipsilateral SCM motoneurons, but some (11/40) neurons showed small-amplitude EPSPs. Most (24/33) of the utricular-activated IPSPs disappeared after transection, whereas the other 9 neurons still indicated IPSPs. In the contralateral SCM motoneurons, no utricular-activated EPSPs were recorded after transection. These MVST transection results suggest that most of the otolith-SCM pathways are located in the MVST at the obex level. However, the results also suggest the possibility that other otolith-SCM pathways

  8. Discharge patterns of hindlimb motoneurons during normal cat locomotion.

    PubMed

    Hoffer, J A; O'Donovan, M J; Pratt, C A; Loeb, G E

    1981-07-24

    Long-term recording from single lumbar motoneurons of intact cats revealed activation patterns fundamentally different from those seen in decerebrate preparations. In intact cats, motoneuron bursts showed marked rate modulation without initial doublets. Each unit's frequencygram generally resembled the envelope of the gross electromyogram simultaneously recorded from the corresponding muscle. Average and peak discharge rates increased for faster gaits. These findings suggest that, in cat locomotion, rate modulation is a more important contributor to force regulation than was previously thought.

  9. Distribution of vestibulospinal synaptic input to cat triceps surae motoneurons.

    PubMed

    Westcott, S L; Powers, R K; Robinson, F R; Binder, M D

    1995-01-01

    We applied supramaximal, repetitive stimulation to the lateral vestibular nucleus (Deiters' nucleus, DN) at 200 Hz to evoke stead-state synaptic potentials in ipsilateral triceps surae motoneurons of the cat. The effective synaptic currents underlying these potentials were measured using a modified voltage-clamp technique. The steady-state effective synaptic currents evoked by activating DN were generally small and depolarizing (mean 2.5 +/- 2.6 nA). DN stimulation generated hyperpolarizing synaptic currents in 2 of the 34 triceps motoneurons studied. The effective synaptic currents from DN tended to be larger in putative type F motoneurons than in putative type S cells (type F mean 3.0 +/- 3.1 nA; type S mean 1.8 +/- 1.0 nA). There was a statistically significant difference between the inputs to putative type FF and putative type S motoneurons (mean difference 2.8 nA, t = 2.87, P < 0.01). The synaptic input from DN to medial gastrocnemius motoneurons had approximately the same amplitude as that from homonymous Ia afferent fibers. However, the distribution of DN input with respect to putative motor unit type was the opposite of that previously reported for Ia afferent input. Thus, the synaptic input from DN might act to compress the range of recruitment thresholds within the motoneuron pool and thereby increase the gain of its input-output function.

  10. Targeted delivery of TrkB receptor to phrenic motoneurons enhances functional recovery of rhythmic phrenic activity after cervical spinal hemisection.

    PubMed

    Gransee, Heather M; Zhan, Wen-Zhi; Sieck, Gary C; Mantilla, Carlos B

    2013-01-01

    Progressive recovery of rhythmic phrenic activity occurs over time after a spinal cord hemisection involving unilateral transection of anterolateral funiculi at C2 (SH). Brain-derived neurotrophic factor (BDNF) acting through its full-length tropomyosin related kinase receptor subtype B (TrkB.FL) contributes to neuroplasticity after spinal cord injury, but the specific cellular substrates remain unclear. We hypothesized that selectively targeting increased TrkB.FL expression to phrenic motoneurons would be sufficient to enhance recovery of rhythmic phrenic activity after SH. Several adeno-associated virus (AAV) serotypes expressing GFP were screened to determine specificity for phrenic motoneuron transduction via intrapleural injection in adult rats. GFP expression was present in the cervical spinal cord 3 weeks after treatment with AAV serotypes 7, 8, and 9, but not with AAV2, 6, or rhesus-10. Overall, AAV7 produced the most consistent GFP expression in phrenic motoneurons. SH was performed 3 weeks after intrapleural injection of AAV7 expressing human TrkB.FL-FLAG or saline. Delivery of TrkB.FL-FLAG to phrenic motoneurons was confirmed by FLAG protein expression in the phrenic motor nucleus and human TrkB.FL mRNA expression in microdissected phrenic motoneurons. In all SH rats, absence of ipsilateral diaphragm EMG activity was confirmed at 3 days post-SH, verifying complete interruption of ipsilateral descending drive to phrenic motoneurons. At 14 days post-SH, all AAV7-TrkB.FL treated rats (n = 11) displayed recovery of ipsilateral diaphragm EMG activity compared to 3 out of 8 untreated SH rats (p<0.01). During eupnea, AAV7-TrkB.FL treated rats exhibited 73±7% of pre-SH root mean squared EMG vs. only 31±11% in untreated SH rats displaying recovery (p<0.01). This study provides direct evidence that increased TrkB.FL expression in phrenic motoneurons is sufficient to enhance recovery of ipsilateral rhythmic phrenic activity after SH, indicating that

  11. Changes in GABAA receptor subunit gamma2 in extensor and flexor motoneurons and astrocytes after spinal cord transection and motor training

    PubMed Central

    Khristy, Windyanne; Ali, Noore J.; Bravo, Arlene B.; de Leon, Ray; Roy, Roland R.; Zhong, Hui; London, Nik J. L.; Edgerton, V. Reggie; Tillakaratne, Niranjala J. K.

    2009-01-01

    GABA signaling plays an important role in the spinal cord response to injury and subsequent motor training. Since benzodiazepines are commonly used to treat muscle spasticity in spinal cord injured subjects and the γ2 subunit of the GABAA receptor is necessary for benzodiazepine binding, this subunit may be an important factor modulating sensorimotor function after an injury. Changes in γ2 levels in muscle-specific motoneurons and surrounding astrocytes were determined ~3 months after a complete mid-thoracic spinal cord transection at P5 in non-trained and in step-trained spinal rats. Soleus (ankle extensor) and tibialis anterior (TA, ankle flexor) motor pools were identified using retrograde labeling via intramuscular injections of Fast Blue or Fluoro Gold, respectively. Lumbar spinal cord sections showed γ2 immunostaining in both soleus and TA motoneurons and astrocytes. γ2 immunoreactivity on the soma of soleus and TA motoneurons in spinal rats was differentially modulated. Compared to intact rats, spinal rats had higher levels of γ2 in TA, and lower levels in soleus motoneurons. Step training restored GABAA γ2 levels towards control values in motoneuronal pools of both muscles. In contrast, the γ2 levels were elevated in surrounding astrocytes of both motor pools in spinal rats, and step training had no further effect. Thus, motor training had a specific effect on those neurons that were directly involved with the motor task. Since the γ2 subunit is involved with GABAA receptor trafficking and synaptic clustering, it appears that this subunit could be an important component of the activity-dependent response of the spinal cord after a spinal injury. PMID:19358834

  12. Developing electrical properties of postnatal mouse lumbar motoneurons

    PubMed Central

    Durand, Jacques; Filipchuk, Anton; Pambo-Pambo, Arnaud; Amendola, Julien; Borisovna Kulagina, Iryna; Guéritaud, Jean-Patrick

    2015-01-01

    We studied the rapid changes in electrical properties of lumbar motoneurons between postnatal days 3 and 9 just before mice weight-bear and walk. The input conductance and rheobase significantly increased up to P8. A negative correlation exists between the input resistance (Rin) and rheobase. Both parameters are significantly correlated with the total dendritic surface area of motoneurons, the largest motoneurons having the lowest Rin and the highest rheobase. We classified the motoneurons into three groups according to their discharge firing patterns during current pulse injection (transient, delayed onset, sustained). The delayed onset firing type has the highest rheobase and the fastest action potential (AP) whereas the transient firing group has the lowest rheobase and the less mature AP. We found 32 and 10% of motoneurons with a transient firing at P3–P5 and P8, respectively. About 20% of motoneurons with delayed onset firing were detected at P8. At P9, all motoneurons exhibit a sustained firing. We defined five groups of motoneurons according to their discharge firing patterns in response to ascending and descending current ramps. In addition to the four classical types, we defined a fifth type called transient for the quasi-absence of discharge during the descending phase of the ramp. This transient type represents about 40% between P3–P5 and tends to disappear with age. Types 1 and 2 (linear and clockwise hysteresis) are the most preponderant at P6–P7. Types 3 and 4 (prolonged sustained and counter clockwise hysteresis) emerge at P8–P9. The emergence of types 3 and 4 probably depends on the maturation of L type calcium channels in the dendrites of motoneurons. No correlation was found between groups defined by step or triangular ramp of currents with the exception of transient firing patterns. Our data support the idea that a switch in the electrical properties of lumbar motoneurons might exist in the second postnatal week of life in mice. PMID

  13. Functional Motor Recovery from Motoneuron Axotomy Is Compromised in Mice with Defective Corticospinal Projections

    PubMed Central

    Ding, Yuetong; Qu, Yibo; Feng, Jia; Wang, Meizhi; Han, Qi; So, Kwok-Fai; Wu, Wutian; Zhou, Libing

    2014-01-01

    Brachial plexus injury (BPI) and experimental spinal root avulsion result in loss of motor function in the affected segments. After root avulsion, significant motoneuron function is restored by re-implantation of the avulsed root. How much this functional recovery depends on corticospinal inputs is not known. Here, we studied that question using Celsr3|Emx1 mice, in which the corticospinal tract (CST) is genetically absent. In adult mice, we tore off right C5–C7 motor and sensory roots and re-implanted the right C6 roots. Behavioral studies showed impaired recovery of elbow flexion in Celsr3|Emx1 mice compared to controls. Five months after surgery, a reduced number of small axons, and higher G-ratio of inner to outer diameter of myelin sheaths were observed in mutant versus control mice. At early stages post-surgery, mutant mice displayed lower expression of GAP-43 in spinal cord and of myelin basic protein (MBP) in peripheral nerves than control animals. After five months, mutant animals had atrophy of the right biceps brachii, with less newly formed neuromuscular junctions (NMJs) and reduced peak-to-peak amplitudes in electromyogram (EMG), than controls. However, quite unexpectedly, a higher motoneuron survival rate was found in mutant than in control mice. Thus, following root avulsion/re-implantation, the absence of the CST is probably an important reason to hamper axonal regeneration and remyelination, as well as target re-innervation and formation of new NMJ, resulting in lower functional recovery, while fostering motoneuron survival. These results indicate that manipulation of corticospinal transmission may help improve functional recovery following BPI. PMID:25003601

  14. Behaviour of the motoneurone pool in a fatiguing submaximal contraction.

    PubMed

    McNeil, Chris J; Giesebrecht, Sabine; Gandevia, Simon C; Taylor, Janet L

    2011-07-15

    During fatigue caused by a sustained maximal voluntary contraction (MVC), motoneurones become markedly less responsive when tested during the silent period following transcranial magnetic stimulation (TMS). To determine whether this reduction depends on the repetitive activation of the motoneurones, responses to TMS (motor evoked potentials, MEPs) and to cervicomedullary stimulation (cervicomedullary motor evoked potentials, CMEPs) were tested during a sustained submaximal contraction at a constant level of electromyographic activity (EMG). In such a contraction, some motoneurones are repetitively activated whereas others are not active. On four visits, eight subjects performed a 10 min maintained-EMG elbow flexor contraction of 25% maximum. Test stimuli were delivered with and without conditioning by TMS given 100 ms prior. Test responses were MEPs or CMEPs (two visits each, small responses evoked by weak stimuli on one visit and large responses on the other). During the sustained contraction, unconditioned CMEPs decreased ∼20% whereas conditioned CMEPs decreased ∼75 and 30% with weak and strong stimuli, respectively. Conditioned MEPs were reduced to the same extent as CMEPs of the same size. The data reveal a novel decrease in motoneurone excitability during a submaximal contraction if EMG is maintained. Further, the much greater reduction of conditioned than unconditioned CMEPs shows the critical influence of voluntary drive on motoneurone responsiveness. Strong test stimuli attenuate the reduction of conditioned CMEPs which indicates that low-threshold motoneurones active in the contraction are most affected. The equivalent reduction of conditioned MEPs and CMEPs suggests that, similar to findings with a sustained MVC, impaired motoneurone responsiveness rather than intracortical inhibition is responsible for the fatigue-related impairment of the MEP during a sustained submaximal contraction.

  15. Cat hindlimb motoneurons during locomotion. III. Functional segregation in sartorius.

    PubMed

    Hoffer, J A; Loeb, G E; Sugano, N; Marks, W B; O'Donovan, M J; Pratt, C A

    1987-02-01

    Cat sartorius has two distinct anatomical portions, anterior (SA-a) and medial (SA-m). SA-a acts to extend the knee and also to flex the hip. SA-m acts to flex both the knee and the hip. The objective of this study was to investigate how a "single motoneuron pool" is used to control at least three separate functions mediated by the two anatomical portions of one muscle. Discharge patterns of single motoneurons projecting to the sartorius muscle were recorded using floating microelectrodes implanted in the L5 ventral root of cats. The electromyographic activity generated by the anterior and medial portions of sartorius was recorded with chronically implanted electrodes. The muscle portion innervated by each motoneuron was determined by spike-triggered averaging of the EMGs during walking on a motorized treadmill. During normal locomotion, SA-a exhibited two bursts of EMG activity per step cycle, one during the stance phase and one during the late swing phase. In contrast, every recorded motoneuron projecting to SA-a discharged a single burst of action potentials per step cycle. Some SA-a motoneurons discharged only during the stance phase, whereas other motoneurons discharged only during the late swing phase. In all cases, the instantaneous frequencygram of the motoneuron was well fit by the rectified smoothed EMG envelope generated by SA-a during the appropriate phase of the step cycle. During normal locomotion, SA-m exhibited a single burst of EMG activity per step cycle, during the swing phase. The temporal characteristics of the EMG bursts recorded from SA-m differed from the swing-phase EMG bursts generated by SA-a.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. MiR-7-1 potentiated estrogen receptor agonists for functional neuroprotection in VSC4.1 motoneurons.

    PubMed

    Chakrabarti, M; Banik, N L; Ray, S K

    2014-01-03

    Protection of motoneurons is an important goal in the treatment of spinal cord injury (SCI). We tested whether neuroprotective microRNAs (miRs) like miR-206, miR-17, miR-21, miR-7-1, and miR-106a could enhance efficacy of estrogen receptor (ER) agonists such as 1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT, ERα agonist), Way200070 (WAY, ERβ agonist), and estrogen (EST, ERα and ERβ agonist) in preventing apoptosis in the calcium ionophore (CI)-insulted ventral spinal cord 4.1 (VSC4.1) motoneurons. We determined that 200 nM CI induced 70% cell death. Treatment with 50 nM PPT, 100 nM WAY, and 150 nM EST induced overexpression of ERα, ERβ, and both receptors, respectively, at mRNA and protein levels. Treatment with ER agonists significantly upregulated miR-206, miR-17, and miR-7-1 in the CI-insulted VSC4.1 motoneurons. Transfection with miR-206, miR-17, or miR-7-1 mimic potentiated WAY or EST to inhibit apoptosis in the CI-insulted VSC4.1 motoneurons. Overexpression of miR-7-1 maximally increased efficacy of WAY and EST for down regulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2. A search using microRNA database (miRDB) indicated that miR-7-1 could inhibit the expression of L-type Ca(2+) channel protein alpha 1C (CPα1C). miR-7-1 overexpression and WAY or EST treatment down regulated CPα1C but upregulated p-Akt to trigger cell survival signaling. The same therapeutic strategy increased expression of the Ca(2+)/calmodulin-dependent protein kinase II beta (CaMKIIβ) and the phosphorylated cAMP response element binding protein (p-CREB) so as to promote Bcl-2 transcription. Whole cell membrane potential and mitochondrial membrane potential studies indicated that miR-7-1 highly potentiated EST to preserve functionality in the CI-insulted VSC4.1 motoneurons. In conclusion, our data indicated that miR-7-1 most significantly potentiated efficacy of EST for functional neuroprotection and this therapeutic strategy could be used in the future

  17. GABA and glycine actions on spinal motoneurons.

    PubMed

    Krnjević, K; Puil, E; Werman, R

    1977-06-01

    Applied microiontophoretically in the spinal cord of cats, glycine is consistently more powerful than gamma-aminobutyric acid (GABA) in raising the membrane conductance of lumbosacral motoneurons (mean ratio of equipotent iontophoretic currents tested on same cells is 5.6:1). This is the reverse of the situation in cerebral cortex. The effect of glycine is well maintained during applications lasting about 1 min, but that of GABA, after an early peak, drops to a much lower plateau (mean plateau-over-peak ratio is 0.23). The reversal potentials for the action of GABA and glycine are initially similar but they behave differently during a prolonged application; that for glycine usually remains constant or becomes more negative whereas that for GABA tends to shift in the positive direction. Various explanations of these phenomena are considered. It is suggested that a single process, electrogenic uptake of GABA, may account for both desensitization (by removing GABA from its site of action) and the positive shift in GABA reversal potential (became uptake is probably associated with an influx of Na+).

  18. Characterization of the AMPA-activated receptors present on motoneurons.

    PubMed

    Greig, A; Donevan, S D; Mujtaba, T J; Parks, T N; Rao, M S

    2000-01-01

    Motoneurons have been shown to be particularly sensitive to Ca2+-dependent glutamate excitotoxicity, mediated via AMPA receptors (AMPARs). To determine the molecular basis for this susceptibility we have used immunocytochemistry, RT-PCR, and electrophysiology to profile AMPARs on embryonic day 14.5 rat motoneurons. Motoneurons show detectable AMPAR-mediated calcium permeability in vitro and in vivo as determined by cobalt uptake and electrophysiology. Motoneurons express all four AMPAR subunit mRNAs, with glutamate receptor (GluR) 2 being the most abundant (63.9+/-4.8%). GluR2 is present almost exclusively in the edited form, and electrophysiology confirms that most AMPARs present are calcium-impermeant. However, the kainate current in motoneurons was blocked an average of 32.0% by Joro spider toxin, indicating that a subset of the AM PARs is Ca2+-permeable. Therefore, heterogeneity of AMPARs, rather than the absence of GluR2 or the presence of unedited GluR2, explains AMPAR-mediated Ca2+ permeability. The relative levels of flip/flop isoforms of each subunit were also examined by semiquantitative PCR. Both isoforms were present, but the relative proportion varied for each subunit, and the flip isoform predominated. Thus, our data show that despite high levels of edited GluR2 mRNA, some AMPARs are Ca2+-permeable, and this subset of AMPARs can account for the AMPAR-mediated Ca2+ inflow inferred from cobalt uptake and electrophysiology studies.

  19. Intrinsic excitability differs between murine hypoglossal and spinal motoneurons.

    PubMed

    Tadros, M A; Fuglevand, A J; Brichta, A M; Callister, R J

    2016-05-01

    Motoneurons differ in the behaviors they control and their vulnerability to disease and aging. For example, brain stem motoneurons such as hypoglossal motoneurons (HMs) are involved in licking, suckling, swallowing, respiration, and vocalization. In contrast, spinal motoneurons (SMs) innervating the limbs are involved in postural and locomotor tasks requiring higher loads and lower movement velocities. Surprisingly, the properties of these two motoneuron pools have not been directly compared, even though studies on HMs predominate in the literature compared with SMs, especially for adult animals. Here we used whole cell patch-clamp recording to compare the electrophysiological properties of HMs and SMs in age-matched neonatal mice (P7-P10). Passive membrane properties were remarkably similar in HMs and SMs, and afterhyperpolarization properties did not differ markedly between the two populations. HMs had narrower action potentials (APs) and a faster upstroke on their APs compared with SMs. Furthermore, HMs discharged APs at higher frequencies in response to both step and ramp current injection than SMs. Therefore, while HMs and SMs have similar passive properties, they differ in their response to similar levels of depolarizing current. This suggests that each population possesses differing suites of ion channels that allow them to discharge at rates matched to the different mechanical properties of the muscle fibers that drive their distinct motor functions.

  20. Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system.

    PubMed

    Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman H; Hickman, James J

    2011-12-01

    Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time-lapse recordings and their subsequent quenching by d-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair.

  1. Cramps: a sign of motoneurone 'bistability' in a human patient.

    PubMed

    Baldissera, F; Cavallari, P; Dworzak, F

    1991-12-09

    In a patient suffering from severe long-lasting cramps, cramps were triggered in the triceps surae by volleys in homonymous Ia afferents (elicited by electrical stimulation or by tendon taps) and were interrupted by antidromic invasion and Renshaw inhibition of triceps surae motoneurones (evoked by a single maximal stimulation of motor axons). This result suggests that the mechanisms which generate the cramps are intrinsic to alpha-motoneurone somata. A similar on-off switching of a self-sustained motor discharge has been observed in the decerebrate cat and recognized to depend on 'bistability' of the motoneuronal membrane. We propose that the same mechanism may be at the origin of the cramp discharge.

  2. Electrical stimulation of transplanted motoneurons improves motor unit formation.

    PubMed

    Liu, Yang; Grumbles, Robert M; Thomas, Christine K

    2014-08-01

    Motoneurons die following spinal cord trauma and with neurological disease. Intact axons reinnervate nearby muscle fibers to compensate for the death of motoneurons, but when an entire motoneuron pool dies, there is complete denervation. To reduce denervation atrophy, we have reinnervated muscles in Fisher rats from local transplants of embryonic motoneurons in peripheral nerve. Since growth of axons from embryonic neurons is activity dependent, our aim was to test whether brief electrical stimulation of the neurons immediately after transplantation altered motor unit numbers and muscle properties 10 wk later. All surgical procedures and recordings were done in anesthetized animals. The muscle consequences of motoneuron death were mimicked by unilateral sciatic nerve section. One week later, 200,000 embryonic day 14 and 15 ventral spinal cord cells, purified for motoneurons, were injected into the tibial nerve 10-15 mm from the gastrocnemii muscles as the only neuron source for muscle reinnervation. The cells were stimulated immediately after transplantation for up to 1 h using protocols designed to examine differential effects due to pulse number, stimulation frequency, pattern, and duration. Electrical stimulation that included short rests and lasted for 1 h resulted in higher motor unit counts. Muscles with higher motor unit counts had more reinnervated fibers and were stronger. Denervated muscles had to be stimulated directly to evoke contractions. These results show that brief electrical stimulation of embryonic neurons, in vivo, has long-term effects on motor unit formation and muscle force. This muscle reinnervation provides the opportunity to use patterned electrical stimulation to produce functional movements.

  3. Electrical stimulation of transplanted motoneurons improves motor unit formation

    PubMed Central

    Liu, Yang; Grumbles, Robert M.

    2014-01-01

    Motoneurons die following spinal cord trauma and with neurological disease. Intact axons reinnervate nearby muscle fibers to compensate for the death of motoneurons, but when an entire motoneuron pool dies, there is complete denervation. To reduce denervation atrophy, we have reinnervated muscles in Fisher rats from local transplants of embryonic motoneurons in peripheral nerve. Since growth of axons from embryonic neurons is activity dependent, our aim was to test whether brief electrical stimulation of the neurons immediately after transplantation altered motor unit numbers and muscle properties 10 wk later. All surgical procedures and recordings were done in anesthetized animals. The muscle consequences of motoneuron death were mimicked by unilateral sciatic nerve section. One week later, 200,000 embryonic day 14 and 15 ventral spinal cord cells, purified for motoneurons, were injected into the tibial nerve 10–15 mm from the gastrocnemii muscles as the only neuron source for muscle reinnervation. The cells were stimulated immediately after transplantation for up to 1 h using protocols designed to examine differential effects due to pulse number, stimulation frequency, pattern, and duration. Electrical stimulation that included short rests and lasted for 1 h resulted in higher motor unit counts. Muscles with higher motor unit counts had more reinnervated fibers and were stronger. Denervated muscles had to be stimulated directly to evoke contractions. These results show that brief electrical stimulation of embryonic neurons, in vivo, has long-term effects on motor unit formation and muscle force. This muscle reinnervation provides the opportunity to use patterned electrical stimulation to produce functional movements. PMID:24848463

  4. The postnatal growth of motoneurons at three levels of the cat neuraxis.

    PubMed

    Cameron, W E; Fang, H; Brozanski, B S; Guthrie, R D

    1989-10-09

    The postnatal growth of motoneuron cell bodies located in the brainstem, cervical and lumbosacral spinal cord was investigated using retrograde transport of horseradish peroxidase in kittens ages 2, 12, 30, 55, 82 and 114 postnatal days and in an adult. The motoneurons innervating an extrinsic tongue muscle, the genioglossus, reached their adult size by eight weeks after birth. In contrast, the phrenic motoneurons innervating the diaphragm achieved adult size by 12 weeks and the motoneurons innervating the medial gastrocnemius muscle continued to grow beyond the twelfth postnatal week. The sizes of these motoneurons relative to one another remained constant during periods of development.

  5. Modulation of human motoneuron activity by a mental arithmetic task.

    PubMed

    Bensoussan, Laurent; Duclos, Yann; Rossi-Durand, Christiane

    2012-10-01

    This study aimed to determine whether the performance of a mental task affects motoneuron activity. To this end, the tonic discharge pattern of wrist extensor motor units was analyzed in healthy subjects while they were required to maintain a steady wrist extension force and to concurrently perform a mental arithmetic (MA) task. A shortening of the mean inter-spike interval (ISI) and a decrease in ISI variability occurred when MA task was superimposed to the motor task. Aloud and silent MA affected equally the rate and variability of motoneuron discharge. Increases in surface EMG activity and force level were consistent with the modulation of the motor unit discharge rate. Trial-by-trial analysis of the characteristics of motor unit firing revealed that performing MA increases activation of wrist extensor SMU. It is suggested that increase in muscle spindle afferent activity, resulting from fusimotor drive activation by MA, may have contributed to the increase in synaptic inputs to motoneurons during the mental task performance, likely together with enhancement in the descending drive. The finding that a mental task affects motoneuron activity could have consequences in assessment of motor disabilities and in rehabilitation in motor pathologies.

  6. Motoneuron glutamatergic receptor expression following recovery from cervical spinal hemisection.

    PubMed

    Gransee, Heather M; Gonzalez Porras, Maria A; Zhan, Wen-Zhi; Sieck, Gary C; Mantilla, Carlos B

    2017-04-01

    Cervical spinal hemisection at C2 (SH) removes premotor drive to phrenic motoneurons located in segments C3-C5 in rats. Spontaneous recovery of ipsilateral diaphragm muscle activity is associated with increased phrenic motoneuron expression of glutamatergic N-methyl-D-aspartate (NMDA) receptors and decreased expression of α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptors. Glutamatergic receptor expression is regulated by tropomyosin-related kinase receptor subtype B (TrkB) signaling in various neuronal systems, and increased TrkB receptor expression in phrenic motoneurons enhances recovery post-SH. Accordingly, we hypothesize that recovery of ipsilateral diaphragm muscle activity post-SH, whether spontaneous or enhanced by adenoassociated virus (AAV)-mediated upregulation of TrkB receptor expression, is associated with increased expression of glutamatergic NMDA receptors in phrenic motoneurons. Adult male Sprague-Dawley rats underwent diaphragm electromyography electrode implantation and SH surgery. Rats were injected intrapleurally with AAV expressing TrkB or GFP 3 weeks before SH. At 14 days post-SH, the proportion of animals displaying recovery of ipsilateral diaphragm activity increased in AAV-TrkB-treated (9/9) compared with untreated (3/5) or AAV-GFP-treated (4/10; P < 0.027) animals. Phrenic motoneuron NMDA NR1 subunit mRNA expression was approximately fourfold greater in AAV-TrkB- vs. AAV-GFP-treated SH animals (P < 0.004) and in animals displaying recovery vs. those not recovering (P < 0.005). Phrenic motoneuron AMPA glutamate receptor 2 (GluR2) subunit mRNA expression decreased after SH, and, albeit increased in animals displaying recovery vs. those not recovering, levels remained lower than control. We conclude that increased phrenic motoneuron expression of glutamatergic NMDA receptors is associated with spontaneous recovery after SH and enhanced recovery after AAV-TrkB treatment. J. Comp. Neurol. 525:1192-1205, 2017.

  7. Evidence for the maintenance of motoneurone properties by msucel activity.

    PubMed Central

    Czéh, G; Gallego, R; Kudo, N; Kuno, M

    1978-01-01

    1. Electrophysiological properties of soleus motoneurones in adult cats were examined with intracellular electrodes following alterations of activity of the soleus muscle induced by transection of the thoracic spinal cord or by conduction block of the muscle nerve with tetrodotoxin (TTX) cuffs. Attempts were also made to maintain muscle activity by daily stimulation of the maintain muscle activity by daily stimulation of the peripheral nerve. 2. Within 8 days after transection of the thoracic cord, soleus motoneurones showed a significant decrease in the duration of afterhyperpolarization following action potentials. This change in motoneurone properties induced by cord transection was prevented by daily stimulation of the sciatic nerve. 3. Soleus motoneurones showed a significant decrease in the duration of after-hyperpolarization within 8 days after conduction block of the soleus nerve with TTX. This change in montoneurone properties was prevented by daily stimulation of the nerve peripheral to the TTX cuff but not central to the cuff. 4. The soleus muscle showed a significant decrease in weight relative to body weight within 8 days after transection of the thoracic cord. This decrease in muscle weight following cord transection was prevented by daily stimulation of the sciatic nerve. 5. No fibrillation was detected in the soleus muscle 8 days after conduction block of the soleus nerve with TTX. The maximum twitch tension of the soleus muscle evoked by nerve stimulation showed no significant difference between the two sides treated and untreated with TTX. Fast axoplasmic transport measured with cholinesterase as a marker was not affected by TTX. Thus, there was no sign of functional although morphological abnormalities were found in some nerve fibres. 6. It is concluded that motoneurone properties in an adult depend partly upon some factors associated with activity of the innervated muscles and that such trophic signals are retrogradely carried by the motor axons

  8. Early intrinsic hyperexcitability does not contribute to motoneuron degeneration in amyotrophic lateral sclerosis

    PubMed Central

    Leroy, Félix; Lamotte d'Incamps, Boris; Imhoff-Manuel, Rebecca D; Zytnicki, Daniel

    2014-01-01

    In amyotrophic lateral sclerosis (ALS) the large motoneurons that innervate the fast-contracting muscle fibers (F-type motoneurons) are vulnerable and degenerate in adulthood. In contrast, the small motoneurons that innervate the slow-contracting fibers (S-type motoneurons) are resistant and do not degenerate. Intrinsic hyperexcitability of F-type motoneurons during early postnatal development has long been hypothesized to contribute to neural degeneration in the adult. Here, we performed a critical test of this hypothesis by recording from identified F- and S-type motoneurons in the superoxide dismutase-1 mutant G93A (mSOD1), a mouse model of ALS at a neonatal age when early pathophysiological changes are observed. Contrary to the standard hypothesis, excitability of F-type motoneurons was unchanged in the mutant mice. Surprisingly, the S-type motoneurons of mSDO1 mice did display intrinsic hyperexcitability (lower rheobase, hyperpolarized spiking threshold). As S-type motoneurons are resistant in ALS, we conclude that early intrinsic hyperexcitability does not contribute to motoneuron degeneration. DOI: http://dx.doi.org/10.7554/eLife.04046.001 PMID:25313866

  9. Motoneurons dedicated to either forward or backward locomotion in the nematode Caenorhabditis elegans.

    PubMed

    Haspel, Gal; O'Donovan, Michael J; Hart, Anne C

    2010-08-18

    Multifunctional motoneurons and muscles, which are active during forward and backward locomotion are ubiquitous in animal models. However, studies in the nematode Caenorhabditis elegans suggest that some locomotor motoneurons are necessary only for forward locomotion (dorsal B-motoneurons, DB), while others (dorsal A-motoneurons, DA) are necessary only for backward locomotion. We tested this hypothesis directly by recording the activity of these motoneurons during semirestrained locomotion. For this purpose, we used epifluorescence imaging of the genetically encoded calcium sensor cameleon, expressed in specific motoneurons, while monitoring locomotor behavior through the microscope condenser using a second camera. We found that ventral and dorsal B-motoneurons (DB and VB) were coactive during forward locomotion while ventral A-motoneurons (VA) were only active during backward locomotion. The signals we recorded correlated with the direction of locomotion but not with the faster undulatory cycles. To our knowledge, these are the first recordings of motoneuron activity in C. elegans and the only direction-dedicated motoneurons described to date.

  10. Dual encoding of muscle tension and eye position by abducens motoneurons

    PubMed Central

    Davis-López de Carrizosa, María A.; Morado-Díaz, Camilo J.; Miller, Joel M.; de la Cruz, Rosa R.; Pastor, Ángel M.

    2011-01-01

    Extraocular muscle tension associated with spontaneous eye movements has a pulse-slide-step profile similar to that of motoneuron firing rate. Existing models only relate motoneuron firing to eye position, velocity and acceleration. We measured and quantitatively compared lateral rectus muscle force and eye position with the firing of abducens motoneurons in the cat to determine fundamental encoding correlations. During fixations (step), muscle force increased exponentially with eccentric eye position, consistent with a model of estimate ensemble motor innervation based on neuronal sensitivities and recruitment order. Moreover, firing rate in all motoneurons tested was better related to eye position than to muscle tension during fixations. In contrast, during the postsaccadic slide phase, the time constant of firing rate decay was closely related to that of muscle force decay, suggesting that all motoneurons encode muscle tension as well. Discharge characteristics of abducens motoneurons formed overlapping clusters of phasic and tonic motoneurons, thus, tonic units recruited earlier and had a larger slide signal. We conclude that the slide signal is a discharge characteristic of the motoneuron that controls muscle tension during the post-saccadic phase and that motoneurons are specialized for both tension and position-related properties. The organization of signal content in the pool of abducens motoneurons from the very phasic to the very tonic units is possibly a result of the differential trophic background received from distinct types of muscle fibers. PMID:21307263

  11. Succinate dehydrogenase activity and soma size of motoneurons innervating different portions of the rat tibialis anterior

    NASA Technical Reports Server (NTRS)

    Ishihara, A.; Roy, R. R.; Edgerton, V. R.

    1995-01-01

    The spatial distribution, soma size and oxidative enzyme activity of gamma and alpha motoneurons innervating muscle fibres in the deep (away from the surface of the muscle) and superficial (close to the surface of the muscle) portions of the tibialis anterior in normal rats were determined. The deep portion had a higher percentage of high oxidative fibres than the superficial portion of the muscle. Motoneurons were labelled by retrograde neuronal transport of fluorescent tracers: Fast Blue and Nuclear Yellow were injected into the deep portion and Nuclear Yellow into the superficial portion of the muscle. Therefore, motoneurons innervating the deep portion were identified by both a blue fluorescent cytoplasm and a golden-yellow fluorescent nucleus, while motoneurons innervating the superficial portion were identified by only a golden-yellow fluorescent nucleus. After staining for succinate dehydrogenase activity on the same section used for the identification of the motoneurons, soma size and succinate dehydrogenase activity of the motoneurons were measured. The gamma and alpha motoneurons innervating both the deep and superficial portions were located primarily at L4 and were intermingled within the same region of the dorsolateral portion of the ventral horn in the spinal cord. Mean soma size was similar for either gamma or alpha motoneurons in the two portions of the muscle. The alpha motoneurons innervating the superficial portion had a lower mean succinate dehydrogenase activity than those innervating the deep portion of the muscle. An inverse relationship between soma size and succinate dehydrogenase activity of alpha, but not gamma, motoneurons innervating both the deep and superficial portions was observed. Based on three-dimensional reconstructions within the spinal cord, there were no apparent differences in the spatial distribution of the motoneurons, either gamma or alpha, associated with the deep and superficial compartments of the muscle. The data

  12. Motonuclear changes after cranial nerve injury and regeneration.

    PubMed

    Fernandez, E; Pallini, R; Lauretti, L; La Marca, F; Scogna, A; Rossi, G F

    1997-09-01

    Little is known about the mechanisms at play in nerve regeneration after nerve injury. Personal studies are reported regarding motonuclear changes after regeneration of injured cranial nerves, in particular of the facial and oculomotor nerves, as well as the influence that the natural molecule acetyl-L-carnitine (ALC) has on post-axotomy cranial nerve motoneuron degeneration after facial and vagus nerve lesions. Adult and newborn animal models were used. Massive motoneuron response after nerve section and reconstruction was observed in the motonuclei of all nerves studied. ALC showed to have significant neuroprotective effects on the degeneration of axotomized motoneurons. Complex quantitative, morphological and somatotopic nuclear changes occurred that sustain new hypotheses regarding the capacities of motoneurons to regenerate and the possibilities of new neuron proliferation. The particularities of such observations are described and discussed.

  13. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells

    SciTech Connect

    Zhang, Yun; Wang, Jing; Chen, Guian; Fan, Dongsheng; Deng, Min

    2011-01-14

    Research highlights: {yields} Nicotinamide inhibit Sirt1. {yields} MASH1 and Ngn2 activation. {yields} Increase the expression of HB9. {yields} Motoneurons formation increases significantly. -- Abstract: Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increased motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and {beta}III-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 {mu}M) or inhibitor nicotinamide (100 {mu}M). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease.

  14. Innovations in motoneuron synchrony drive rapid temporal modulations in vertebrate acoustic signaling

    PubMed Central

    Chagnaud, Boris P.; Zee, Michele C.; Baker, Robert

    2012-01-01

    Rapid temporal modulation of acoustic signals among several vertebrate lineages has recently been shown to depend on the actions of superfast muscles. We hypothesized that such fast events, known to require synchronous activation of muscle fibers, would rely on motoneuronal properties adapted to generating a highly synchronous output to sonic muscles. Using intracellular in vivo recordings, we identified a suite of premotor network inputs and intrinsic motoneuronal properties synchronizing the oscillatory-like, simultaneous activation of superfast muscles at high gamma frequencies in fish. Motoneurons lacked spontaneous activity, firing synchronously only at the frequency of premotor excitatory input. Population-level motoneuronal output generated a spike-like, vocal nerve volley that directly determines muscle contraction rate and, in turn, natural call frequency. In the absence of vocal output, motoneurons showed low excitability and a weak afterhyperpolarization, leading to rapid accommodation in firing rate. By contrast, vocal activity was accompanied by a prominent afterhyperpolarization, indicating a dependency on network activity. Local injection of a GABAA receptor antagonist demonstrated the necessity of electrophysiologically and immunohistochemically confirmed inhibitory GABAergic input for motoneuronal synchrony and vocalization. Numerous transneuronally labeled motoneurons following single-cell neurobiotin injection together with electrophysiological collision experiments confirmed gap junctional coupling, known to contribute to synchronous activity in other neural networks. Motoneuronal synchrony at the premotor input frequency was maintained during differential recruitment of variably sized motoneurons. Differential motoneuron recruitment led, however, to amplitude modulation (AM) of vocal output and, hence, natural call AM. In summary, motoneuronal intrinsic properties, in particular low excitability, predisposed vocal motoneurons to the

  15. Significance of 2,4-dinitrophenol action on spinal motoneurones.

    PubMed

    Krnjević, K; Puil, E; Werman, R

    1978-02-01

    1. Extracellular iontophoretic applications of DNP lead to an increase in the membrane conductance of cat spinal motoneurones, manifested by a rise in input conductance, a slower rate of rise and fall of action potentials, and occlusion of the afterhyperpolarization. 2. There is also some hyperpolarization, but the reversal potential for the action of DNP is only about 12 mV more negative than the resting potential. 3. These effect of DNP can be abolished or significantly reduced by intracellular injections of EGTA. On the other hand, DNP can partly reverse the decreased conductance and the depression of the slow afterhyperpolarization caused by EGTA. 4. Intracellular injections of DNP also induce a rise in input conductance; when repeated, they tend to have a depolarizing effect, mainly irreversible. 5. It is concluded that DNP acts principally inside the motoneurone, by liberating bound internal Ca, the free Ca ions then raising membrane conductance, especially GK.

  16. Programmed Cell Death of Embryonic Motoneurons Triggered through the FAS Death Receptor

    PubMed Central

    Raoul, Cédric; Henderson, Christopher E.; Pettmann, Brigitte

    1999-01-01

    About 50% of spinal motoneurons undergo programmed cell death (PCD) after target contact, but little is known about how this process is initiated. Embryonic motoneurons coexpress the death receptor Fas and its ligand FasL at the stage at which PCD is about to begin. In the absence of trophic factors, many motoneurons die in culture within 2 d. Most (75%) of these were saved by Fas-Fc receptor body, which blocks interactions between Fas and FasL, or by the caspase-8 inhibitor tetrapeptide IETD. Therefore, activation of Fas by endogenous FasL underlies cell death induced by trophic deprivation. In the presence of neurotrophic factors, exogenous Fas activators such as soluble FasL or anti-Fas antibodies triggered PCD of 40–50% of purified motoneurons over the following 3–5 d; this treatment led to activation of caspase-3, and was blocked by IETD. Sensitivity to Fas activation is regulated: motoneurons cultured for 3 d with neurotrophic factors became completely resistant. Levels of Fas expressed by motoneurons varied little, but FasL was upregulated in the absence of neurotrophic factors. Motoneurons resistant to Fas activation expressed high levels of FLICE-inhibitory protein (FLIP), an endogenous inhibitor of caspase-8 activation. Our results suggest that Fas can act as a driving force for motoneuron PCD, and raise the possibility that active triggering of PCD may contribute to motoneuron loss during normal development and/or in pathological situations. PMID:10579724

  17. BDNF-mediated modulation of glycine transmission on rat spinal motoneurons.

    PubMed

    Ding, Jian-Dong; Tang, Xian-Ye; Shi, Jian-Gang; Jia, Lian-Shun

    2014-08-22

    BDNF has a widespread distribution in the central and peripheral nervous systems, suggesting that BDNF may play a role in the regulation of motor control. However, the direct actions of BDNF on the motoneurons and their underlying mechanisms are still largely unknown to date. Therefore, by using whole-cell patch clamp recordings, quantitative RT-PCR and immunocytochemistry, the present study was designed to investigate the effects of BDNF on electrical activity and glycinergic transmission on the motoneurons and the underlying receptor mechanism. The results reveal: (i) BDNF did not produce a direct excitatory or inhibitory effect on the motoneurons; (ii) BDNF dose-dependently increased the glycinergic transmission on the motoneurons; (iii) glycinergic transmission on motoneurons was a direct postsynaptic effect; (iv) BDNF-induced enhancement of the glycinergic transmission was mediated by the activation of TrkB receptors; and (v) BDNF and its receptors TrkB had an extensive expression in the motoneurons. These results suggest that BDNF is directly involved in the regulation of glycinergic transmission on the motoneurons through postsynaptic TrkB receptors. Considering that the glycinergic synaptic transmission of motoneurons mainly comes from Renshaw cells, the important inhibitory interneurons of spinal cord, we speculate that BDNF may play an important role in the information integration in the spinal cord and participate in the sensitivity of motoneurons.

  18. Extraocular motoneuron pools develop along a dorsoventral axis in zebrafish, Danio rerio

    PubMed Central

    Privorotskiy, Ann E.; D'Elia, Kristen P.

    2016-01-01

    ABSTRACT Both spatial and temporal cues determine the fate of immature neurons. A major challenge at the interface of developmental and systems neuroscience is to relate this spatiotemporal trajectory of maturation to circuit‐level functional organization. This study examined the development of two extraocular motor nuclei (nIII and nIV), structures in which a motoneuron's identity, or choice of muscle partner, defines its behavioral role. We used retro‐orbital dye fills, in combination with fluorescent markers for motoneuron location and birthdate, to probe spatial and temporal organization of the oculomotor (nIII) and trochlear (nIV) nuclei in the larval zebrafish. We describe a dorsoventral organization of the four nIII motoneuron pools, in which inferior and medial rectus motoneurons occupy dorsal nIII, while inferior oblique and superior rectus motoneurons occupy distinct divisions of ventral nIII. Dorsal nIII motoneurons are, moreover, born before motoneurons of ventral nIII and nIV. The order of neurogenesis can therefore account for the dorsoventral organization of nIII and may play a primary role in determining motoneuron identity. We propose that the temporal development of extraocular motoneurons plays a key role in assembling a functional oculomotor circuit. J. Comp. Neurol. 525:65–78, 2017. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27197595

  19. Brainstem origin of preganglionic cardiac motoneurons in the muskrat.

    PubMed

    Panneton, W M; McCulloch, P F; Tan, Y; Tan, Y; Yavari, P

    1996-11-04

    The muskrat, and aquatic rodent with a brisk and reliable diving response, shows a remarkable bradycardia after nasal stimulation. However, the medullary origin of cardiac preganglionic motoneurons is unknown in this species. We injected fat pads near the base of the heart of muskrats with a WGA-HRP solution to label retrogradely preganglionic parasympathetic neurons that project to the cardiac plexi. Results showed that the preponderance of labeled neurons was in ventrolateral parts of the medulla from 1.5 mm caudal to the obex to 2.0 mm rostral. Eighty-nine percent of the labeled neurons were located bilaterally in the external formation of the nucleus ambiguus, 5.6% were in the lateral extreme of the dorsal motor nucleus of the vagus nerve and 5.3% were found in the intermediate area in between these two nuclei. Although controversy still exists concerning the medullary origin of preganglionic cardiac motoneurons, our results from muskrats agree with those from most other species where preganglionic cardiac motoneurons were located just ventral to the nucleus ambiguus.

  20. Motoneuron activity in patients with different types of tremor.

    PubMed

    Milanov, I

    2001-12-01

    The aim of this work was to examine the segmental motoneuron activity as a possible mechanism of tremor generation. Eighty-three patients with different types of tremor (25 with Parkinsonian, 29 with essential, and 30 with enhanced physiological tremor due to anxiety), 25 Parkinsonian patients without tremor and 30 healthy volunteers were examined. The tremor was studied clinically and by electromyography in all limb positions. The F wave was examined for assessment of motoneuron activity. The wave was recorded after stimulation of the ulnar, median, tibial and fibular nerves. The maximal and mean F wave amplitudes, frequency of occurrence and number of phases were increased, and the duration was prolonged in all group of patients as compared to the healthy persons. The maximal and the mean F/M amplitude ratios, as well as the Fmean./Fmax amplitude ratio were increased in all groups of patients. All F wave parameters were most altered in Parkinsonian tremor patients followed by patients with rigidity. In conclusion increased motoneuron activity participates in generation of different types of tremor and in Parkinsonian rigidity.

  1. Direct excitation of rat spinal motoneurones by serotonin.

    PubMed Central

    Takahashi, T; Berger, A J

    1990-01-01

    1. The effects of serotonin (5-HT) on visually identified motoneurones were investigated using the whole-cell recording technique in a neonatal rat spinal cord slice preparation. 2. In current-clamp recordings, bath application of 5-HT depolarized motoneurones. This effect was observed after synaptic inputs were abolished by replacing external Ca2+ with Mg2+. 3. In voltage-clamp recordings at holding potentials of -70 to -90 mV, 5-HT induced an inward current (I5-HT) in motoneurones in a Ca2(+)-free-Mg2+ solution containing tetrodotoxin. This inward current was accompanied by an increase in membrane conductance, which was prominent at voltages negative to the holding potential. 4. The inward I5-HT response declined with repeated short applications of 5-HT. I5-HT produced by a single prolonged application (5 min) was only slightly diminished during the application period. 5. The minimum effective dose of 5-HT for initiating the inward I5-HT was less than 10 nM. At 10 microM, I5-HT approached maximal levels. The averaged dissociation constant (Kd) for 5-HT was approximately 120 nM. 6. Application of spiperone, the mixed 5-HT1A, 5-HT2 receptor antagonist, blocked the inward I5-HT. Application of (+)-8-OH-dipropylaminotetralin (8-OHDPAT), a 5-HT1A agonist, mimicked the action of 5-HT. 7. Various K+ channel blockers including tetraethylammonium chloride (30 mM), 4-aminopyridine (4 mM) and apamin (100 nM) did not abolish I5-HT. Application of extracellular Cs+ (10 mM) blocked I5-HT. 8. Peak inward I5-HT became larger with increasing extracellular K+. With low Cl- pipette solution (less than 1 mM), or in low extracellular Na+ solution (26 mM), the inward I5-HT was not abolished. 9. The current-voltage relation of I5-HT displayed inward rectification. In high external K+ concentration (20 mM), the reversal potential was about -29 mV, which is close to that of the inward rectifier evoked in motoneurones by membrane hyperpolarization. 10. The current generated by 5-HT

  2. Transcriptional enhancement of Smn levels in motoneurons is crucial for proper axon morphology in zebrafish

    PubMed Central

    Spiró, Zoltán; Koh, Angela; Tay, Shermaine; See, Kelvin; Winkler, Christoph

    2016-01-01

    An unresolved mystery in the field of spinal muscular atrophy (SMA) is why a reduction of the ubiquitously expressed Smn protein causes defects mostly in motoneurons. We addressed the possibility that this restricted vulnerability stems from elevated Smn expression in motoneurons. To explore this, we established an ex vivo zebrafish culture system of GFP-marked motoneurons to quantitatively measure Smn protein and smn mRNA levels as well as promoter activity in motoneurons versus other cell types. Importantly, we uncovered that Smn levels are elevated in motoneurons by means of transcriptional activation. In addition, we identified the ETS family transcription factor Etv5b to be responsible for increased smn transcription in motoneurons. Moreover, we established that the additional supply of Smn protein in motoneurons is necessary for proper axonogenesis in a cell-autonomous manner. These findings demonstrate the reliance of motoneurons on more Smn, thereby adding a novel piece of evidence for their increased vulnerability under SMA conditions. PMID:27273160

  3. The giant fiber and pectoral fin adductor motoneuron system in the hatchetfish.

    PubMed

    Gilat, E; Hall, D H; Bennett, M V

    1986-02-12

    In the medulla of the hatchetfish each Mauthner fiber forms chemical synapses on a number of large myelinated axons termed giant fibers. The giant fibers form rectifying electrotonic synapses on pectoral fin adductor motoneurons, and in this fish bilateral pectoral fin adduction is an important component of the Mauthner fiber-mediated escape reflex. The branching patterns of giant fibers were determined by intracellular injection of Lucifer yellow. Dye coupling to the motoneuron somata was not observed, although a low level of transfer might have been obscured by autofluorescence. Individual giant fibers terminate primarily on pectoral fin motoneurons contralateral to their cell bodies, but may also send a branch back across the midline to ipsilateral motoneurons. The rostral process of each giant fiber ends on neurons presumably associated with cranial musculature. The number and geometry of the pectoral fin motoneurons were determined using Golgi and Nissl staining and serial reconstruction methods.

  4. Molecular determinants of emerging excitability in rat embryonic motoneurons

    PubMed Central

    Alessandri-Haber, Nicole; Alcaraz, Giséle; Deleuze, Charlotte; Jullien, Florence; Manrique, Christine; Couraud, François; Crest, Marcel; Giraud, Pierre

    2002-01-01

    Molecular determinants of excitability were studied in pure cultures of rat embryonic motoneurons. Using RT-PCR, we have shown here that the spike-generating Na+ current is supported by Nav1.2 and/or Nav1.3 α-subunits. Nav1.1 and Nav1.6 transcripts were also identified. We have demonstrated that alternatively spliced isoforms of Nav1.1 and Nav1.6, resulting in truncated proteins, were predominant during the first week in culture. However, Nav1.6 protein could be detected after 12 days in vitro. The Navβ2.1 transcript was not detected, whereas the Nav β1.1 transcript was present. Even in the absence of Navβ2.1, α-subunits were correctly inserted into the initial segment. RT-PCR (at semi-quantitative and single-cell levels) and immunocytochemistry showed that transient K+ currents result from the expression of Kv4.2 and Kv4.3 subunits. This is the first identification of subunits responsible for a transient K+ current in spinal motoneurons. The blockage of Kv4.2/Kv4.3 using a specific toxin modified the shape of the action potential demonstrating the involvement of these conductance channels in regulating spike repolarization and the discharge frequency. Among the other Kv α-subunits (Kv1.3, 1.4, 1.6, 2.1, 3.1 and 3.3), we showed that the Kv1.6 subunit was partly responsible for the sustained K+ current. In conclusion, this study has established the first correlation between the molecular nature of voltage-dependent Na+ and K+ channels expressed in embryonic rat motoneurons in culture and their electrophysiological characteristics in the period when excitability appears. PMID:12015418

  5. Enrichment of spinal cord cell cultures with motoneurons

    PubMed Central

    1978-01-01

    Spinal cord cell cultures contain several types of neurons. Two methods are described for enriching such cultures with motoneurons (defined here simply as cholinergic cells that are capable of innervating muscle). In the first method, 7-day embryonic chick spinal cord neurons were separated according to size by 1 g velocity sedimentation. It is assumed that cholinergic motoneurons are among the largest cells present at this stage. The spinal cords were dissociated vigorously so that 95-98% of the cells in the initial suspension were isolated from one another. Cells in leading fractions (large cell fractions: LCFs) contain about seven times as much choline acetyltransferase (CAT) activity per unit cytoplasm as do cells in trailing fractions (small cell fractions: SCFs). Muscle cultures seeded with LCFs develop 10-70 times as much CAT as cultures seeded with SCFs and six times as much CAT as cultures seeded with control (unfractionated) spinal cord cells. More than 20% of the large neurons in LCF-muscle cultures innervate nearby myotubes. In the second method, neurons were gently dissociated from 4-day embryonic spinal cords and maintained in vitro. This approach is based on earlier observations that cholinergic neurons are among the first cells to withdraw form the mitotic cycle in the developing chick embryo (Hamburger, V. 1948. J. Comp. Neurol. 88:221- 283; and Levi-Montalcini, R. 1950. J. Morphol. 86:253-283). 4-Day spinal cord-muscle cultures develop three times as much CAT as do 7-day spinal cord-muscle plates, prepared in the same (gentle) manner. More than 50% of the relatively large 4-day neurons innervate nearby myotubes. Thus, both methods are useful first steps toward the complete isolation of motoneurons. Both methods should facilitate study of the development of cholinergic neurons and of nerve-muscle synapse formation. PMID:566275

  6. Effects of background noise on the response of rat and cat motoneurones to excitatory current transients.

    PubMed Central

    Poliakov, A V; Powers, R K; Sawczuk, A; Binder, M D

    1996-01-01

    1. We studied the responses of rat hypoglossal motoneurones to excitatory current transients (ECTs) using a brainstem slice preparation. Steady, repetitive discharge at rates of 12-25 impulses s-1 was elicited from the motoneurones by injecting long (40 s) steps of constant current. Poisson trains of the ECTs were superimposed on these steps. The effects of additional synaptic noise was simulated by adding a zero-mean random process to the stimuli. 2. We measured the effects of the ECTs on motoneurone discharge probability by compiling peristimulus time histograms (PSTHs) between the times of occurrence of the ECTs and the motoneurone spikes. The ECTs produced modulation of motoneurone discharge similar to that produced by excitatory postsynaptic currents. 3. The addition of noise altered the pattern of the motoneurone response to the current transients: both the amplitude and the area of the PSTH peaks decreased as the power of the superimposed noise was increased. Noise tended to reduce the efficacy of the ECTs, particularly when the motoneurones were firing at lower frequencies. Although noise also increased the firing frequency of the motoneurones slightly, the effects of noise on ECT efficacy did not simply result from noise-induced changes in mean firing rate. 4. A modified version of the experimental protocol was performed in lumbar motoneurones of intact, pentobarbitone-anaesthetized cats. These recordings yielded results similar to those obtained in rat hypoglossal motoneurones in vitro. 5. Our results suggest that the presence of concurrent synaptic inputs reduces the efficacy of any one input. The implications of this change in efficacy and the possible underlying mechanisms are discussed. PMID:8866358

  7. Implantable optical-electrode device for stimulation of spinal motoneurons

    NASA Astrophysics Data System (ADS)

    Matveev, M. V.; Erofeev, A. I.; Zakharova, O. A.; Pyatyshev, E. N.; Kazakin, A. N.; Vlasova, O. L.

    2016-08-01

    Recent years, optogenetic method of scientific research has proved its effectiveness in the nerve cell stimulation tasks. In our article we demonstrate an implanted device for the spinal optogenetic motoneurons activation. This work is carried out in the Laboratory of Molecular Neurodegeneration of the Peter the Great St. Petersburg Polytechnic University, together with Nano and Microsystem Technology Laboratory. The work of the developed device is based on the principle of combining fiber optic light stimulation of genetically modified cells with the microelectrode multichannel recording of neurons biopotentials. The paper presents a part of the electrode implant manufacturing technique, combined with the optical waveguide of ThorLabs (USA).

  8. Adaptation of cat motoneurons to sustained and intermittent extracellular activation.

    PubMed Central

    Spielmann, J M; Laouris, Y; Nordstrom, M A; Robinson, G A; Reinking, R M; Stuart, D G

    1993-01-01

    1. The main purpose of this study was to quantify the adaptation of spinal motoneurons to sustained and intermittent activation, using an extracellular route of stimulating current application to single test cells, in contrast to an intracellular route, as has been used previously. In addition, associations were tested between firing rate properties of the tested cells and other type (size)-related properties of these cells and their motor units. 2. Motoneurons supplying the medial gastrocnemius muscle of the deeply anaesthetized cat were stimulated for 240 s with microelectrodes which passed sustained extracellular current at 1.25 times the threshold for repetitive firing. Many cells were also tested following a rest period with intermittent 1 s current pulses (duration 600 ms) at the same relative stimulus strength. Cell discharge was assessed from the EMG of the motor unit innervated by the test neuron. The motoneurons and their motor units were assigned to four categories (i.e. types FF, FR, S and F; where F = FF + FR) based on conventional criteria. In all, twenty F (16 FF, 4 FR) and fourteen S cells were studied with sustained stimulation. Thirty of these cells (17 F, 13 S) and an additional two cells (1 F, 1 S) were studied with intermittent stimulation. 3. The mean threshold current required for sustained firing for a period of > or = 2 s was not significantly different for F and S cells. However, most of the other measured parameters of motoneuron firing differed significantly for these two cell groups. For example, at 1.25 times the threshold current for repetitive firing, the mean firing duration in response to 240 s of sustained activation was 123 +/- 88 s (+/- S.D.) for F cells vs. 233 +/- 19 s for S cells. These values were significantly longer than those from a comparable, previously reported study that employed intracellular stimulation. With intermittent stimulation, the firing durations of F and S cells were not significantly different from each

  9. Electrophysiological properties of neonatal rat motoneurones studied in vitro.

    PubMed Central

    Fulton, B P; Walton, K

    1986-01-01

    The electroresponsive properties of neonatal lumbar spinal motoneurones were studied using isolated, hemisected spinal cords from neonatal rats aged 3-12 days. The extracellular and intracellular responses to electrical stimulation of the ventral and dorsal root were studied as well as the intracellular response to current injection. Field potentials recorded in the lateral motor area following electrical stimulation of lumbar ventral roots had a triphasic positive-negative-positive wave form. The negative component did not return to the base line smoothly but exhibited a 'shoulder' where the negativity increased in duration. Following electrical stimulation of the dorsal root, presynaptic field potentials were recorded upon activation of the afferent axons as well as following synaptic activation of interneurones and motoneurones. The input resistances of neonatal motoneurones determined from the slope of current-voltage plots were high compared with the adult. The resistance decreased with age with a mean of 18.1 M omega for animals 3-5 days old, 8.8 M omega for animals 6-8 days old and 5.4 M omega for animals 9-11 days old. Values for the membrane time constant were similar to those in the adult with a mean of 4.5 ms. Action potentials elicited by ventral or dorsal root stimulation or by intracellular current injection were marked by a pronounced after-depolarization (a.d.p.) and an after-hyperpolarization (a.h.p.). The amplitude of the a.h.p. varied with that of the a.d.p. The amplitude of excitatory post-synaptic potentials (e.p.s.p.s) elicited by electrical stimulation of the dorsal root was affected by intracellular current injection. Two types of e.p.s.p.s were distinguished: those with a biphasic reversal (early phase first) and those in which the early phase was unaffected by inward current injection while the later phase was reversed. Unlike in the adult, the reversals could be achieved with low current levels and the amplitude of both types of e

  10. Exacerbation of facial motoneuron loss after facial nerve axotomy in CCR3-deficient mice.

    PubMed

    Wainwright, Derek A; Xin, Junping; Mesnard, Nichole A; Beahrs, Taylor R; Politis, Christine M; Sanders, Virginia M; Jones, Kathryn J

    2009-12-11

    We have previously demonstrated a neuroprotective mechanism of FMN (facial motoneuron) survival after facial nerve axotomy that is dependent on CD4(+) Th2 cell interaction with peripheral antigen-presenting cells, as well as CNS (central nervous system)-resident microglia. PACAP (pituitary adenylate cyclase-activating polypeptide) is expressed by injured FMN and increases Th2-associated chemokine expression in cultured murine microglia. Collectively, these results suggest a model involving CD4(+) Th2 cell migration to the facial motor nucleus after injury via microglial expression of Th2-associated chemokines. However, to respond to Th2-associated chemokines, Th2 cells must express the appropriate Th2-associated chemokine receptors. In the present study, we tested the hypothesis that Th2-associated chemokine receptors increase in the facial motor nucleus after facial nerve axotomy at timepoints consistent with significant T-cell infiltration. Microarray analysis of Th2-associated chemokine receptors was followed up with real-time PCR for CCR3, which indicated that facial nerve injury increases CCR3 mRNA levels in mouse facial motor nucleus. Unexpectedly, quantitative- and co-immunofluorescence revealed increased CCR3 expression localizing to FMN in the facial motor nucleus after facial nerve axotomy. Compared with WT (wild-type), a significant decrease in FMN survival 4 weeks after axotomy was observed in CCR3(-/-) mice. Additionally, compared with WT, a significant decrease in FMN survival 4 weeks after axotomy was observed in Rag2(-/-) (recombination activating gene-2-deficient) mice adoptively transferred CD4(+) T-cells isolated from CCR3(-/-) mice, but not in CCR3(-/-) mice adoptively transferred CD4(+) T-cells derived from WT mice. These results provide a basis for further investigation into the co-operation between CD4(+) T-cell- and CCR3-mediated neuroprotection after FMN injury.

  11. Whole-cell patch clamp recordings from rhythmically active motoneurons in the isolated spinal cord of the chick embryo.

    PubMed

    Sernagor, E; O'Donovan, M J

    1991-07-22

    Whole-cell patch clamp recordings were obtained during motor activity from electrically identified motoneurons within the spinal cord of the chick embryo maintained in vitro. Most recordings were performed on E11-E13 motoneurons although it was also possible to record from younger cells (E7-E9). Voltage clamp recordings were used to characterize the synaptic currents expressed in femoro-tibialis (extensor) motoneurons during motor activity. These motoneurons exhibited rhythmic excitatory currents with reversal potentials near 0 mV. This powerful technique enables high resolution recordings from identified motoneurons in situ and allows investigation of the membrane and synaptic mechanisms involved in the development of embryonic motility.

  12. The Impact of Midcervical Contusion Injury on Diaphragm Muscle Function

    PubMed Central

    Alvarez-Argote, Santiago; Gransee, Heather M.; Mora, Juan C.; Stowe, Jessica M.; Jorgenson, Amy J.; Sieck, Gary C.

    2016-01-01

    Abstract Midcervical contusion injuries disrupt descending ipsilateral excitatory bulbospinal projections to phrenic motoneurons, compromising ventilation. We hypothesized that a unilateral contusion injury at C3 versus C5 would differentially impact phrenic activity reflecting more prominent disruption of ipsilateral descending excitatory drive to more caudal segments of the phrenic motor pool with more cranial injuries. Phrenic motoneuron counts and evidence of diaphragm muscle denervation at individual neuromuscular junctions (NMJ) were evaluated at 14 days post-injury after unilateral contusion injury (100 kDynes). Whole body plethysmography and chronic diaphragm EMG were measured before the injury and at 3, 7, and 14 days post-injury. Contusion injuries at either level resulted in a similarly sized cavity. C3 contusion resulted in loss of 39 ± 13% of ipsilateral phrenic motoneurons compared with 13 ± 21% after C5 contusion (p = 0.003). Cervical contusion injuries resulted in diaphragm muscle denervation (C3 contusion: 17 ± 4%; C5 contusion: 7 ± 4%; p = 0.047). The pattern of denervation revealed segmental innervation of the diaphragm muscle, with greater denervation ventrally after C3 contusion and dorsally after C5 contusion. Overall, diaphragm root mean square electromyography activity did not change ipsilaterally after C3 or C5 contusion, but increased contralaterally (∼11%) after C3 contusion only on the first day post-injury (p = 0.026). Similarly, there were no significant changes in breathing parameters during eupnea or exposure to hypoxia (10% O2) – hypercapnia (5% CO2) at any time post-injury. Unilateral midcervical contusions minimally impair ventilatory behaviors despite phrenic motoneuron loss and diaphragm muscle denervation. PMID:26413840

  13. Pharmacological characterization of the rhythmic synaptic drive onto lumbosacral motoneurons in the chick embryo spinal cord.

    PubMed

    Sernagor, E; Chub, N; Ritter, A; O'Donovan, M J

    1995-11-01

    The isolated spinal cord of the chick embryo generates episodes of rhythmic bursting in which sartorius (hip flexor) and femorotibialis (knee extensor) motoneurons exhibit characteristic patterns of activity. At the beginning of each cycle both sets of motoneurons discharge synchronously. Following this brief synchronous activation sartorius motoneurons stop firing at the time of peak femorotibialis activity, producing a period of alternation between the two sets of motoneurons. Intracellular recording from motoneurons has suggested that the pause is mediated by a synaptically induced shunt conductance. However, the pharmacological basis for this shunt and the nature of the excitatory drive to motoneurons is unknown. To address these questions we have investigated the pharmacology of the rhythmic, synaptic drive to lumbosacral motoneurons using local and bath application of several excitatory and inhibitory antagonists, and documenting their effects on motor output in E10-E12 chick embryos. Local application of bicuculline or picrotoxin over sartorius motoneurons abolished the pause in firing recorded from the sartorius muscle nerve. As a consequence, the pattern of sartorius and femorotibialis activity was similar and the motoneurons were coactive. The pause in sartorius firing was shortened following local application of the glycine antagonist strychnine the nicotinic, cholinergic antagonists mecamylamine, and dihydro-beta-erythroidine and several excitatory amino acid antagonists. Application of the GABA uptake inhibitor nipecotic acid depressed the slow potentials and discharge recorded from the sartorius muscle nerve. These findings suggest that the pause is determined primarily by synaptic inputs acting at motoneuron GABAA receptors with contributions from glycinergic, cholinergic, and glutamatergic inputs. The actions of locally applied GABA onto spinal neurons are consistent with these findings because the neurotransmitter depolarizes spinal neurons and

  14. Regional variations in the extent and timing of motoneuron cell death in the lumbosacral spinal cord of the chick embryo.

    PubMed

    Williams, C; Wohlenberg, G; O'Donovan, M J

    1987-08-01

    We have examined the distribution of motoneurons in different segments of the chick lumbosacral spinal cord before and after the period of motoneuron cell death. The extent of cell death was found to be greatest at the boundaries of the lumbosacral cord where over 60% of the motoneurons died and least in the central region where only 30% died. After cell death at stage 40 the number of motoneurons in each segment was linearly correlated with segment length, suggesting that growth of the segment and motoneuron numbers may be regulated by a common factor. The time of completion of motoneuron cell death exhibited a rostrocaudal gradient along the lumbar cord. Cell death was complete in the anterior segments by stage 35 but not until stage 38 in the caudal 4 segments. The regional variations in the extent and timing of motoneuron cell death suggest that the relative importance of the factors mediating cell death vary in different regions of the lumbar cord.

  15. Axotomized neonatal motoneurons overexpressing the bcl2 proto-oncogene retain functional electrophysiological properties.

    PubMed Central

    Alberi, S; Raggenbass, M; de Bilbao, F; Dubois-Dauphin, M

    1996-01-01

    Bcl2 overexpression prevents axotomy-induced neuronal death of neonatal facial motoneurons, as defined by morphological criteria. However, the functional properties of these surviving lesioned transgenic neurons are unknown. Using transgenic mice overexpressing the protein Bcl2, we have investigated the bioelectrical properties of transgenic facial motoneurons from 7 to 20 days after neonatal unilateral axotomy using brain-stem slices and whole cell patch-clamp recording. Nonaxotomized facial motoneurons from wild-type and transgenic mice had similar properties; they had an input resistance of 38 +/- 6 M omega and fired repetitively after injection of positive current pulses. When cells were voltage-clamped at or near their resting membrane potential, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartic acid (NMDA), or vasopressin generated sustained inward currents. In transgenic axotomized mice, facial motoneurons could be found located ipsilaterally to the lesion; they had an input resistance of 150 +/- 30 M omega, indicating that they were smaller in size, fired repetitively, and were also responsive to AMPA, NMDA, and vasopressin. Morphological measurements achieved 1 week after the lesion have shown that application of brain-derived neurotrophic factor prevented the reduction in size of axotomized transgenic motoneurons. These data indicate that Bcl2 not only prevents morphological apoptotic death of axotomized neonatal transgenic motoneurons but also permits motoneurons to conserve functional electrophysiological properties. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8633001

  16. Noradrenergic Modulation of Intrinsic and Synaptic Properties of Lumbar Motoneurons in the Neonatal Rat Spinal Cord

    PubMed Central

    Tartas, Maylis; Morin, France; Barrière, Grégory; Goillandeau, Michel; Lacaille, Jean-Claude; Cazalets, Jean-René; Bertrand, Sandrine S.

    2009-01-01

    Although it is known that noradrenaline (NA) powerfully controls spinal motor networks, few data are available regarding the noradrenergic (NAergic) modulation of intrinsic and synaptic properties of neurons in motor networks. Our work explores the cellular basis of NAergic modulation in the rat motor spinal cord. We first show that lumbar motoneurons express the three classes of adrenergic receptors at birth. Using patch-clamp recordings in the newborn rat spinal cord preparation, we characterized the effects of NA and of specific agonists of the three classes of adrenoreceptors on motoneuron membrane properties. NA increases the motoneuron excitability partly via the inhibition of a KIR like current. Methoxamine (α1), clonidine (α2) and isoproterenol (β) differentially modulate the motoneuron membrane potential but also increase motoneuron excitability, these effects being respectively inhibited by the antagonists prazosin (α1), yohimbine (α2) and propranolol (β). We show that the glutamatergic synaptic drive arising from the T13-L2 network is enhanced in motoneurons by NA, methoxamine and isoproterenol. On the other hand, NA, isoproterenol and clonidine inhibit both the frequency and amplitude of miniature glutamatergic EPSCs while methoxamine increases their frequency. The T13-L2 synaptic drive is thereby differentially modulated from the other glutamatergic synapses converging onto motoneurons and enhanced by presynaptic α1 and β receptor activation. Our data thus show that the NAergic system exerts a powerful and complex neuromodulation of lumbar motor networks in the neonatal rat spinal cord. PMID:20300468

  17. Neuronal pathways from foot pad afferents to hindlimb motoneurons in the low spinalized cats.

    PubMed

    Wada, N; Kanda, Y; Takayama, R

    1998-07-01

    Experiments were performed on 16 adult spinalized (L2) cats. Postsynaptic potentials (PSPs) produced by electrical stimulation of afferent nerves innervating foot pads were recorded from hindlimb motoneurons innervating the following hindlimb muscles: the posterior biceps and semitendinosus (PBSt), anterior biceps and semimembranosus (ABSm), lateral gastrocnemius and soleus (LGS), medial gastrocnemius (MG), plantaris (P1), tibialis anterior (TA), popliteus (Pop), flexor digitorum longus and flexor hallucis longus (FDHL) and peroneus longus (Per.l). The rate of occurrence of different types of PSPs (EPSPs, IPSPs and mixed PSPs), the size of the PSPs and their central latencies were analyzed for each group of motoneurons to identify the neural pathways from the afferents innervating foot pads to hindlimb motoneurons. The rates of occurrence of different types of PSPs did not depend on the foot pad stimulated in PBSt, ABSm and LGS motoneurons, but for other groups of motoneurons their rates of occurrence depended on the foot pad stimulated. It was often noted that the size of PSPs in the same motoneurons differed according to the foot pad stimulated. Measurements of the central latencies of the PSPs indicated that the shortest neural pathways for EPSPs and IPSPs were disynaptic (central latencies < 1.8 ms). The functional role of neuronal pathways from afferent nerves innervating foot pads to hindlimb motoneurons could be to maintain stability of the foot during different postural and motor activities.

  18. Segmental differences in firing properties and potassium currents in Drosophila larval motoneurons

    PubMed Central

    Srinivasan, Subhashini; Lance, Kimberley

    2012-01-01

    Potassium currents play key roles in regulating motoneuron activity, including functional specializations that are important for locomotion. The thoracic and abdominal segments in the Drosophila larval ganglion have repeated arrays of motoneurons that innervate body-wall muscles used for peristaltic movements during crawling. Although abdominal motoneurons and their muscle targets have been studied in detail, owing, in part, to their involvement in locomotion, little is known about the cellular properties of motoneurons in thoracic segments. The goal of this study was to compare firing properties among thoracic motoneurons and the potassium currents that influence them. Whole-cell, patch-clamp recordings performed from motoneurons in two thoracic and one abdominal segment revealed both transient and sustained voltage-activated K+ currents, each with Ca++-sensitive and Ca++-insensitive [A-type, voltage-dependent transient K+ current (IAv)] components. Segmental differences in the expression of voltage-activated K+ currents were observed. In addition, we demonstrate that Shal contributes to IAv currents in the motoneurons of the first thoracic segment. PMID:22157123

  19. Neuroprotective effects of NGF, BDNF, NT-3 and GDNF on axotomized extraocular motoneurons in neonatal rats.

    PubMed

    Morcuende, S; Muñoz-Hernández, R; Benítez-Temiño, B; Pastor, A M; de la Cruz, R R

    2013-10-10

    Neurotrophic factors delivered from target muscles are essential for motoneuronal survival, mainly during development and early postnatal maturation. It has been shown that the disconnection between motoneurons and their innervated muscle by means of axotomy produces a vast neuronal death in neonatal animals. In the present work, we have evaluated the effects of different neurotrophic factors on motoneuronal survival after neonatal axotomy, using as a model the motoneurons innervating the extraocular eye muscles. With this purpose, neonatal rats were monocularly enucleated at the day of birth (postnatal day 0) and different neurotrophic treatments (NGF, BDNF, NT-3, GDNF and the mixture of BDNF+GDNF) were applied intraorbitally by means of a Gelfoam implant (a single dose of 5 μg of each factor). We first demonstrated that extraocular eye muscles of neonatal rats expressed these neurotrophic factors and therefore constituted a natural source of retrograde delivery for their innervating motoneurons. By histological and immunocytochemical methods we determined that all treatments significantly rescued extraocular motoneurons from axotomy-induced cell death. For the dose used, NGF and GDNF were the most potent survival factors for these motoneurons, followed by BDNF and lastly by NT-3. The simultaneous administration of BDNF and GDNF did not increase the survival-promoting effects above those obtained by GDNF alone. Interestingly, the rescue effects of all neurotrophic treatments persisted even 30 days after lesion. The administration of these neurotrophic factors, with the exception of NT-3, also prevented the loss of the cholinergic phenotype observed by 10 days after axotomy. At the dosage applied, NGF and GDNF were revealed again as the most effective neuroprotective agents against the axotomy-induced decrease in ChAT. Two remarkable findings highlighted in the present work that contrasted with other motoneuronal types after neonatal axotomy: first, the extremely

  20. Resistance of extraocular motoneuron terminals to effects of amyotrophic lateral sclerosis sera

    NASA Technical Reports Server (NTRS)

    Mosier, D. R.; Siklos, L.; Appel, S. H.

    2000-01-01

    In sporadic ALS (s-ALS), axon terminals contain increased intracellular calcium. Passively transferred sera from patients with s-ALS increase intracellular calcium in spinal motoneuron terminals in vivo and enhance spontaneous transmitter release, a calcium-dependent process. In this study, passive transfer of s-ALS sera increased spontaneous release from spinal but not extraocular motoneuron terminals, suggesting that the resistance to physiologic abnormalities induced by s-ALS sera in mice parallels the resistance of extraocular motoneurons to dysfunction and degeneration in ALS.

  1. Lithium enhances survival and regrowth of spinal motoneurons after ventral root avulsion

    PubMed Central

    2014-01-01

    Background During the clinical treatment of the brachial plexus root avulsion (BPRA), reimplantation surgery can not completely repair the motor function of the hand because the axonal growth velocity of the spinal motoneurons (MNs) is too slow to re-innervate the intrinsic hand muscles before muscle atrophy. Here, we investigated whether lithium can enhance the regenerative capacity of the spinal MNs in a rat model of BPRA. Results The avulsion and immediate reimplantation of the C7 and C8 ventral roots were performed and followed with daily intraperitoneal administration of a therapeutic concentrationof LiCl. After a 20 week long-term rehabilitation, the motor function recovery of the injured forepaw was studied by a grasping test. The survival and regeneration of MNs were checked by choline acetyltransferase (ChAT) immunofluorescence and by Fluoro-Gold (FG) retrograde labeling through the median and ulnar nerves of the ventral horn MNs. The number and diameter of the nerve fibers in the median nerve were assessed by toluidine blue staining. Our results showed that lithium plus reimplantation therapy resulted in a significantly higher grasping strength of the digits of the injured forepaw. Lithium plus reimplantation allowed 45.1% ± 8.11% of ChAT-positive MNs to survive the injury and increased the number and diameter of nerve fibers in the median nerve. The number of FG-labeled regenerative MNs was significantly elevated in all of the reimplantation animals. Our present data proved that lithium can enhance the regenerative capacity of spinal MNs. Conclusions These results suggest that immediate administration of lithium could be used to assist reimplantation surgery in repairing BPRA injuries in clinical treatment. PMID:24985061

  2. Sigma-1R agonist improves motor function and motoneuron survival in ALS mice.

    PubMed

    Mancuso, Renzo; Oliván, Sara; Rando, Amaya; Casas, Caty; Osta, Rosario; Navarro, Xavier

    2012-10-01

    Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by progressive weakness, muscle atrophy, and paralysis due to the loss of upper and lower motoneurons (MNs). Sigma-1 receptor (sigma-1R) activation promotes neuroprotection after ischemic and traumatic injuries to the central nervous system. We recently reported that sigma-1R agonist (PRE-084) improves the survival of MNs after root avulsion injury in rats. Moreover, a mutation of the sigma-1R leading to frontotemporal lobar degeneration/amyotrophic lateral sclerosis (ALS) was recently described in human patients. In the present study, we analyzed the potential therapeutic effect of the sigma-1R agonist (PRE-084) in the SOD1(G93A) mouse model of ALS. Mice were daily administered with PRE-084 (0.25 mg/kg) from 8 to 16 weeks of age. Functional outcome was assessed by electrophysiological tests and computerized analysis of locomotion. Histological, immunohistochemical analyses and Western blot of the spinal cord were performed. PRE-084 administration from 8 weeks of age improved the function of MNs, which was manifested by maintenance of the amplitude of muscle action potentials and locomotor behavior, and preserved neuromuscular connections and MNs in the spinal cord. Moreover, it extended survival in both female and male mice by more than 15 %. Delayed administration of PRE-084 from 12 weeks of age also significantly improved functional outcome and preservation of the MNs. There was an induction of protein kinase C-specific phosphorylation of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor in SOD1(G93A) animals, and a reduction of the microglial reactivity compared with untreated mice. PRE-084 exerts a dual therapeutic contribution, modulating NMDA Ca(2+) influx to protect MNs, and the microglial reactivity to ameliorate the MN environment. In conclusion, sigma-1R agonists, such as PRE-084, may be promising candidates for a therapeutical strategy of ALS.

  3. RNA content in spinal cord motoneurons during hypokinesia

    NASA Technical Reports Server (NTRS)

    Gorbunova, A. V.

    1980-01-01

    The effect of a diminished motor activity of rats upon the ribonucleic and (RNA) content in a single isolated motoneuron of frontal of their spinal cord was studied. Within a 1 to 30 day exposure of rats to the hypokinetic conditions, RNA content was found to decrease on the 1st, 3rd, and 5th day and to return to the initial level by the 7th day. No changes in RNA content were observed during the subsequent stages of the xperiments. The volume of the nerve cells declined on the 3rd and 5th day, whereas RNA concentration reduced on the 1st, 3rd, 5th, and 30th day.

  4. Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord

    PubMed Central

    Mentis, George Z.; Alvarez, Francisco J.; Bonnot, Agnes; Richards, Dannette S.; Gonzalez-Forero, David; Zerda, Ricardo; O'Donovan, Michael J.

    2005-01-01

    Mammalian spinal motoneurons are considered to be output elements of the spinal cord that generate exclusively cholinergic actions on Renshaw cells, their intraspinal synaptic targets. Here, we show that antidromic stimulation of motor axons evokes depolarizing monosynaptic potentials in Renshaw cells that are depressed, but not abolished, by cholinergic antagonists. This residual potential was abolished by 2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. In the presence of cholinergic antagonists, motor axon stimulation triggered locomotor-like activity that was blocked by 2-amino-5-phosphonovaleric acid. Some cholinergic motoneuronal terminals on both Renshaw cells and motoneurons were enriched in glutamate, but none expressed vesicular glutamate transporters. Our results raise the possibility that motoneurons release an excitatory amino acid in addition to acetylcholine and that they may be more directly involved in the genesis of mammalian locomotion than previously believed. PMID:15883359

  5. Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord.

    PubMed

    Mentis, George Z; Alvarez, Francisco J; Bonnot, Agnes; Richards, Dannette S; Gonzalez-Forero, David; Zerda, Ricardo; O'Donovan, Michael J

    2005-05-17

    Mammalian spinal motoneurons are considered to be output elements of the spinal cord that generate exclusively cholinergic actions on Renshaw cells, their intraspinal synaptic targets. Here, we show that antidromic stimulation of motor axons evokes depolarizing monosynaptic potentials in Renshaw cells that are depressed, but not abolished, by cholinergic antagonists. This residual potential was abolished by 2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. In the presence of cholinergic antagonists, motor axon stimulation triggered locomotor-like activity that was blocked by 2-amino-5-phosphonovaleric acid. Some cholinergic motoneuronal terminals on both Renshaw cells and motoneurons were enriched in glutamate, but none expressed vesicular glutamate transporters. Our results raise the possibility that motoneurons release an excitatory amino acid in addition to acetylcholine and that they may be more directly involved in the genesis of mammalian locomotion than previously believed.

  6. Somatic and axonal LIGHT signaling elicit degenerative and regenerative responses in motoneurons, respectively

    PubMed Central

    Otsmane, Belkacem; Moumen, Anice; Aebischer, Julianne; Coque, Emmanuelle; Sar, Chamroeun; Sunyach, Claire; Salsac, Céline; Valmier, Jean; Salinas, Sara; Bowerman, Melissa; Raoul, Cédric

    2014-01-01

    A receptor–ligand interaction can evoke a broad range of biological activities in different cell types depending on receptor identity and cell type-specific post-receptor signaling intermediates. Here, we show that the TNF family member LIGHT, known to act as a death-triggering factor in motoneurons through LT-βR, can also promote axon outgrowth and branching in motoneurons through the same receptor. LIGHT-induced axonal elongation and branching require ERK and caspase-9 pathways. This distinct response involves a compartment-specific activation of LIGHT signals, with somatic activation-inducing death, while axonal stimulation promotes axon elongation and branching in motoneurons. Following peripheral nerve damage, LIGHT increases at the lesion site through expression by invading B lymphocytes, and genetic deletion of Light significantly delays functional recovery. We propose that a central and peripheral activation of the LIGHT pathway elicits different functional responses in motoneurons. PMID:24668263

  7. A quantitative ultrastructural comparison of alpha and gamma motoneurons in the thoracic region of the spinal cord of the adult cat.

    PubMed

    Johnson, I P

    1986-08-01

    The cell bodies of motoneurons supplying both the levator costae and external intercostal muscles were identified after retrograde labelling with horseradish peroxidase. A quantitative ultrastructural comparison of cell bodies of large (greater than 40 microns) and small (less than 30 microns) diameter revealed that the intracellular appearance of large and small motoneurons was similar. However, small motoneurons had less than half the synaptic terminal frequency or cover of large motoneurons. Furthermore, only synapses of the S- and F-type were seen on small motoneurons, while S- T- F- and C-type terminals were consistently seen on large motoneurons. The variation between individual small motoneurons for various aspects of their synaptic features was more than twice that found for large motoneurons. No correlation between small motoneuronal ultrastructure and cell body diameter was found, although scatter diagrams of synaptic terminal cover against cell body size indicated the presence of two groups of small motoneurons: one with relatively high values for synaptic cover and the other with relatively low values. On the basis of the similarity of their cell body diameters to those of electrophysiologically identified alpha and gamma motoneurons, it is concluded that the large and small motoneurons examined in the present study are alpha and gamma motoneurons respectively. The synaptic difference found between alpha and gamma motoneurons is discussed in relation to both their different functional properties and the different natures of their respective peripheral targets.

  8. Marked and variable inhibition by chemical fixation of cytochrome oxidase and succinate dehydrogenase in single motoneurons

    NASA Technical Reports Server (NTRS)

    Chalmers, G. R.; Edgerton, V. R.

    1989-01-01

    The effect of tissue fixation on succinate dehydrogenase and cytochrome oxidase activity in single motoneurons of the rat was demonstrated using a computer image processing system. Inhibition of enzyme activity by chemical fixation was variable, with some motoneurons being affected more than others. It was concluded that quantification of enzymatic activity in chemically fixed tissue provides an imprecise estimate of enzyme activities found in fresh-frozen tissues.

  9. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    SciTech Connect

    Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  10. Mutant SOD1-expressing astrocytes release toxic factors that trigger motoneuron death by inducing hyperexcitability

    PubMed Central

    Fritz, Elsa; Izaurieta, Pamela; Weiss, Alexandra; Mir, Franco R.; Rojas, Patricio; Gonzalez, David; Rojas, Fabiola; Brown, Robert H.; Madrid, Rodolfo

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motoneurons starting in adulthood. Recent studies using cell or animal models document that astrocytes expressing disease-causing mutations of human superoxide dismutase 1 (hSOD1) contribute to the pathogenesis of ALS by releasing a neurotoxic factor(s). Neither the mechanism by which this neurotoxic factor induces motoneuron death nor its cellular site of action has been elucidated. Here we show that acute exposure of primary wild-type spinal cord cultures to conditioned medium derived from astrocytes expressing mutant SOD1 (ACM-hSOD1G93A) increases persistent sodium inward currents (PCNa), repetitive firing, and intracellular calcium transients, leading to specific motoneuron death days later. In contrast to TTX, which paradoxically increased twofold the amplitude of calcium transients and killed motoneurons, reduction of hyperexcitability by other specific (mexiletine) and nonspecific (spermidine and riluzole) blockers of voltage-sensitive sodium (Nav) channels restored basal calcium transients and prevented motoneuron death induced by ACM-hSOD1G93A. These findings suggest that riluzole, the only FDA-approved drug with known benefits for ALS patients, acts by inhibiting hyperexcitability. Together, our data document that a critical element mediating the non-cell-autonomous toxicity of ACM-hSOD1G93A on motoneurons is increased excitability, an observation with direct implications for therapy of ALS. PMID:23486205

  11. Pattern of innervation and recruitment of different classes of motoneurons in adult zebrafish.

    PubMed

    Ampatzis, Konstantinos; Song, Jianren; Ausborn, Jessica; El Manira, Abdeljabbar

    2013-06-26

    In vertebrates, spinal circuits drive rhythmic firing in motoneurons in the appropriate sequence to produce locomotor movements. These circuits become active early during development and mature gradually to acquire the flexibility necessary to accommodate the increased behavioral repertoire of adult animals. The focus here is to elucidate how different pools of motoneurons are organized and recruited and how membrane properties contribute to their mode of operation. For this purpose, we have used the in vitro preparation of adult zebrafish. We show that different motoneuron pools are organized in a somatotopic fashion in the motor column related to the type of muscle fibers (slow, intermediate, fast) they innervate. During swimming, the different motoneuron pools are recruited in a stepwise manner from slow, to intermediate, to fast to cover the full range of locomotor frequencies seen in intact animals. The spike threshold, filtering properties, and firing patterns of the different motoneuron pools are graded in a manner that relates to their order of recruitment. Our results thus show that motoneurons in adult zebrafish are organized into distinct modules, each with defined locations, properties, and recruitment patterns tuned to precisely match the muscle properties and hence produce swimming of different speeds and modalities.

  12. Muscle atrophy is associated with cervical spinal motoneuron loss in BACHD mouse model for Huntington's disease.

    PubMed

    Valadão, Priscila Aparecida Costa; de Aragão, Bárbara Campos; Andrade, Jéssica Neves; Magalhães-Gomes, Matheus Proença S; Foureaux, Giselle; Joviano-Santos, Julliane Vasconcelos; Nogueira, José Carlos; Ribeiro, Fabíola Mara; Tapia, Juan Carlos; Guatimosim, Cristina

    2017-03-01

    Involuntary choreiform movements are clinical hallmark of Huntington's disease, an autosomal dominant neurodegenerative disorder caused by an increased number of CAG trinucleotide repeats in the huntingtin gene. Involuntary movements start with an impairment of facial muscles and then affect trunk and limbs muscles. Huntington's disease symptoms are caused by changes in cortex and striatum neurons induced by mutated huntingtin protein. However, little is known about the impact of this abnormal protein in spinal cord motoneurons that control movement. Therefore, in this study we evaluated abnormalities in the motor unit (spinal cervical motoneurons, motor axons, neuromuscular junctions and muscle) in a mouse model for Huntington's disease (BACHD). Using light, fluorescence, confocal, and electron microscopy, we showed significant changes such as muscle fibers atrophy, fragmentation of neuromuscular junctions, axonal alterations, and motoneurons death in BACHD mice. Noteworthy, the surviving motoneurons from BACHD spinal cords were smaller than WT. We suggest that this loss of larger putative motoneurons is accompanied by a decrease in the expression of fast glycolytic muscle fibers in this model for Huntington's disease. These observations show spinal cord motoneurons loss in BACHD that might help to understand neuromuscular changes in Huntington's disease.

  13. Acidotoxicity and acid-sensing ion channels contribute to motoneuron degeneration.

    PubMed

    Behan, A T; Breen, B; Hogg, M; Woods, I; Coughlan, K; Mitchem, M; Prehn, J H M

    2013-04-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition with no cure. Mitochondrial dysfunction, Ca(2+) overloading and local hypoxic/ischemic environments have been implicated in the pathophysiology of ALS and are conditions that may initiate metabolic acidosis in the affected tissue. We tested the hypothesis that acidotoxicity and acid-sensing ion channels (ASICs) are involved in the pathophysiology of ALS. We found that motoneurons were selectively vulnerable to acidotoxicity in vitro, and that acidotoxicity was partially reduced in asic1a-deficient motoneuron cultures. Cross-breeding of SOD1(G93A) ALS mice with asic1a-deficient mice delayed the onset and progression of motor dysfunction in SOD1 mice. Interestingly, we also noted a strong increase in ASIC2 expression in motoneurons of SOD1 mice and sporadic ALS patients during disease progression. Pharmacological pan-inhibition of ASIC channels with the lipophilic amiloride derivative, 5-(N,N-dimethyl)-amiloride hydrochloride, potently protected cultured motoneurons against acidotoxicity, and, given post-symptom onset, significantly improved lifespan, motor performance and motoneuron survival in SOD1 mice. Together, our data provide strong evidence for the involvement of acidotoxicity and ASIC channels in motoneuron degeneration, and highlight the potential of ASIC inhibitors as a new treatment approach for ALS.

  14. Toll-like receptor 2-mediated alternative activation of microglia is protective after spinal cord injury.

    PubMed

    Stirling, David P; Cummins, Karen; Mishra, Manoj; Teo, Wulin; Yong, V Wee; Stys, Peter

    2014-03-01

    Improving neurological outcome after spinal cord injury is a major clinical challenge because axons, once severed, do not regenerate but 'dieback' from the lesion site. Although microglia, the immunocompetent cells of the brain and spinal cord respond rapidly to spinal cord injury, their role in subsequent injury or repair remains unclear. To assess the role of microglia in spinal cord white matter injury we used time-lapse two-photon and spectral confocal imaging of green fluorescent protein-labelled microglia, yellow fluorescent protein-labelled axons, and Nile Red-labelled myelin of living murine spinal cord and revealed dynamic changes in white matter elements after laser-induced spinal cord injury in real time. Importantly, our model of acute axonal injury closely mimics the axonopathy described in well-characterized clinically relevant models of spinal cord injury including contusive-, compressive- and transection-based models. Time-lapse recordings revealed that microglia were associated with some acute pathophysiological changes in axons and myelin acutely after laser-induced spinal cord injury. These pathophysiological changes included myelin and axonal spheroid formation, spectral shifts in Nile Red emission spectra in axonal endbulbs detected with spectral microscopy, and 'bystander' degeneration of axons that survived the initial injury, but then succumbed to secondary degeneration. Surprisingly, modulation of microglial-mediated release of neurotoxic molecules failed to protect axons and myelin. In contrast, sterile stimulation of microglia with the specific toll-like receptor 2 agonist Pam2CSK4 robustly increased the microglial response to ablation, reduced secondary degeneration of central myelinated fibres, and induced an alternative (mixed M1:M2) microglial activation profile. Conversely, Tlr2 knock out: Thy1 yellow fluorescent protein double transgenic mice experienced greater axonal dieback than littermate controls. Thus, promoting an alternative

  15. Differential synaptic effects on physiological flexor hindlimb motoneurons from cutaneous nerve inputs in spinal cat.

    PubMed

    Leahy, J C; Durkovic, R G

    1991-08-01

    1. We previously demonstrated in the spinal cat that superficial peroneal cutaneous nerve stimulation produced strong reflex contraction in tibialis anterior (TA) and semitendinosus (St) muscles but unexpectedly produced mixed effects in another physiological flexor muscle, extensor digitorum longus (EDL). The goal of the present study was to further characterize the organization of ipsilateral cutaneous reflexes by examining the postsynaptic potentials (PSPs) produced in St, TA, and EDL motoneurons by superficial peroneal and saphenous nerve stimulation in decerebrate, spinal cats. 2. In TA and St motoneurons, low-intensity cutaneous nerve stimulation that activated only large (A alpha) fibers [i.e., approximately 2-3 times threshold (T)], typically produced biphasic PSPs consisting of an initial excitatory phase and subsequent inhibitory phase (EPSP, IPSP). Increasing the stimulus intensity to activate both large (A alpha) and small (A delta) myelinated cutaneous fibers supramaximally (15-45 T) tended to enhance later excitatory components in TA and St motoneurons. 3. In EDL motoneurons, 2-3 T stimulation of the superficial peroneal nerve evoked initial inhibition (of variable magnitude) in 7/10 EDL motoneurons tested, with either excitation (n = 2) or mixed effects (n = 1) observed in the remaining EDL motoneurons. Saphenous nerve stimuli produced excitation either alone, or preceded by an inhibitory phase in EDL. Increasing the stimulus intensity enhanced later inhibitory influences from superficial peroneal and excitatory influences both from superficial peroneal and saphenous nerve inputs in EDL motoneurons. 4. Short-latency (less than 1.8 ms) EPSPs were observed in a few motoneurons in all reflex pathways examined, except for EPSPs in EDL motoneurons evoked by saphenous stimulation. IPSPs with central latencies less than 1.8 ms were also produced by both saphenous (TA, n = 1; EDL, n = 2) and superficial peroneal (EDL, n = 4) nerve stimulation. 5. The results

  16. Organization of hindlimb muscle afferent projections to lumbosacral motoneurons in the chick embryo.

    PubMed

    Lee, M T; O'Donovan, M J

    1991-08-01

    We have examined the organization of muscle afferent projections to motoneurons in the lumbosacral spinal cord of chick embryos between stage 37, when muscle afferents first reach the motor nucleus, and stage 44, which is just before hatching. Connectivity between afferents and motoneurons was assessed by stimulating individual muscle nerves and recording the resulting motoneuron synaptic potentials intracellularly or electrotonically from other muscle nerves. Most of the recordings were made in the presence of DL-2-amino-5-phosphonovaleric acid (APV), picrotoxin, and strychnine to block long-latency excitatory and inhibitory pathways. Activation of muscle afferents evoked slow, positive potentials in muscle nerves but not in cutaneous nerves. These potentials were abolished in 0 mM Ca2+, 2mM Mn2+ solutions, indicating that they were generated by the action of chemical synapses. The muscle nerve recordings revealed a wide-spread pattern of excitatory connections between afferents and motoneurons innervating six different thigh muscles, which were not organized according to synergist-antagonist relationships. This pattern of connectivity was confirmed using intracellular recording from identified motoneurons, which allowed the latency of the responses to be determined. Short-latency potentials in motoneurons were produced by activation of homonymous afferents and the heteronymous afferents innervating the hip flexors sartorius and anterior iliotibialis. Stimulation of anterior iliotibialis afferents also resulted in some short-latency excitatory postsynaptic potentials (EPSPs) in motoneurons innervating the knee extensor femorotibialis, though other connections were of longer latency. Afferents from the adductor, a hip extensor, did not evoke short-latency EPSPs in any of these three types of motoneurons. Short-latency, but not long-latency EPSPs, persisted during repetitive stimulation at 5 Hz, suggesting that they were mediated monosynaptically. Long

  17. Fluctuations of excitability in the monosynaptic reflex pathway to lumbar motoneurons in the cat.

    PubMed

    Gossard, J P; Floeter, M K; Kawai, Y; Burke, R E; Chang, T; Schiff, S J

    1994-09-01

    1. It is well known that the amplitude of successive monosynaptic reflexes (MSR), elicited by afferent stimuli of constant strength, fluctuate from trial to trial. Previous evidence suggests that such excitability fluctuations within the motor pool can be introduced either pre- and/or postsynaptically. Using unanesthetized decerebrate or decerebrate/spinal cats, we attempted to evaluate the relative importance of pre- and postsynaptic mechanisms to MSR variability and the potential contribution of changes in the identities of responding motoneurons to such variability. 2. Comparisons between the MSR amplitude, measured in a severed ventral root, and the probability of firing of up to three individual motoneurons in fine filaments teased from the same root, confirmed that both correlated and uncorrelated fluctuations of motoneuron excitability are involved in MSR variability. Linear regression analysis from concurrent intracellular recordings from homonymous motoneurons showed that the MSR fluctuations were correlated with the variations in membrane potential baseline, as well as with the fluctuations in the monosynaptic excitatory postsynaptic potential peak amplitude. In all 11 cases tested, the former correlation was stronger than the latter. 3. Stimulation of the caudal cutaneous sural nerve (CCS) was used to alter the postsynaptic potential background on which triceps surae (GS) MSRs were generated. The interval chosen between CCS conditioning and the GS stimulation excluded the involvement of presynaptic inhibition. When conditioned by preceding CCS stimulation, GS population MSRs generally (8/9 cases tested) increased in amplitude without much change in their overall variance. However, the individual motoneurons that contributed to the population responses did show changes in both relative excitability and in the uncorrelated component of their response variance. About half of the concurrently recorded motoneurons (6/13) showed a decrease in relative

  18. Synaptic Connectivity between Renshaw Cells and Motoneurons in the Recurrent Inhibitory Circuit of the Spinal Cord

    PubMed Central

    Moore, Niall J.; Bhumbra, Gardave S.; Foster, Joshua D.

    2015-01-01

    Renshaw cells represent a fundamental component of one of the first discovered neuronal circuits, but their function in motor control has not been established. They are the only central neurons that receive collateral projections from motor outputs, yet the efficacy of the excitatory synapses from single and converging motoneurons remains unknown. Here we present the results of dual whole-cell recordings from identified, synaptically connected Renshaw cell-motoneuron pairs in the mouse lumbar spinal cord. The responses from single Renshaw cells demonstrate that motoneuron synapses elicit large excitatory conductances with few or no failures. We show that the strong excitatory input from motoneurons results from a high probability of neurotransmitter release onto multiple postsynaptic contacts. Dual current-clamp recordings confirm that single motoneuron inputs were sufficient to depolarize the Renshaw cell beyond threshold for firing. Reciprocal connectivity was observed in approximately one-third of the paired recordings tested. Ventral root stimulation was used to evoke currents from Renshaw cells or motoneurons to characterize responses of single neurons to the activation of their corresponding presynaptic cell populations. Excitatory or inhibitory synaptic inputs in the recurrent inhibitory loop induced substantial effects on the excitability of respective postsynaptic cells. Quantal analysis estimates showed a large number of converging inputs from presynaptic motoneuron and Renshaw cell populations. The combination of considerable synaptic efficacy and extensive connectivity within the recurrent circuitry indicates a role of Renshaw cells in modulating motor outputs that may be considerably more important than has been previously supposed. SIGNIFICANCE STATEMENT We have recently shown that Renshaw cells mediate powerful shunt inhibition on motoneuron excitability. Here we complete a quantitative description of the recurrent circuit using recordings of

  19. The activation patterns of embryonic chick motoneurones projecting to inappropriate muscles.

    PubMed Central

    Landmesser, L T; O'Donovan, M J

    1984-01-01

    Chick lumbosacral motoneurones were caused to innervate foreign muscles by surgically rotating or shifting the limb bud about the anterior-posterior axis in stage 17-18 embryos. The activation pattern of such wrongly projecting motoneurones was assessed at stages 35-38 by recording electromyographic activity from muscles in an isolated spinal cord/hind limb preparation. Muscle activity was classed as flexor- or extensor-like according to the characteristics of the patterned sequence of bursts elicited by a single shock to the thoracic cord. Wrongly projecting motoneurones did not have their activation pattern altered to one appropriate for the muscle innervated; therefore in some cases a particular muscle was activated with a pattern similar to its original one, and in other cases in an opposite manner. Mixed flexor-extensor-like activation of a single muscle was, however, rare. The identity of motoneurones projecting to a muscle was determined by their cord location following retrograde labelling with horseradish peroxidase. This allowed us to conclude that motoneurones could develop their normal pattern of activation even when projecting to foreign muscles. It is concluded that the cord circuits (presumably composed of local interneurones responsible for the activation of motoneurones in the isolated cord preparation are not altered by retrograde influences from the muscle. Wrongly projecting motoneurones, which were maintained throughout the normal cell death period, were activated during spontaneous embryonic movements, and in many cases were found to have a behaviourally inappropriate activation pattern. These observations are discussed in relation to proposed mechanisms by which developmental errors in connectivity are corrected. Images Fig. 1 PMID:6707957

  20. The activation patterns of embryonic chick motoneurones projecting to inappropriate muscles.

    PubMed

    Landmesser, L T; O'Donovan, M J

    1984-02-01

    Chick lumbosacral motoneurones were caused to innervate foreign muscles by surgically rotating or shifting the limb bud about the anterior-posterior axis in stage 17-18 embryos. The activation pattern of such wrongly projecting motoneurones was assessed at stages 35-38 by recording electromyographic activity from muscles in an isolated spinal cord/hind limb preparation. Muscle activity was classed as flexor- or extensor-like according to the characteristics of the patterned sequence of bursts elicited by a single shock to the thoracic cord. Wrongly projecting motoneurones did not have their activation pattern altered to one appropriate for the muscle innervated; therefore in some cases a particular muscle was activated with a pattern similar to its original one, and in other cases in an opposite manner. Mixed flexor-extensor-like activation of a single muscle was, however, rare. The identity of motoneurones projecting to a muscle was determined by their cord location following retrograde labelling with horseradish peroxidase. This allowed us to conclude that motoneurones could develop their normal pattern of activation even when projecting to foreign muscles. It is concluded that the cord circuits (presumably composed of local interneurones responsible for the activation of motoneurones in the isolated cord preparation are not altered by retrograde influences from the muscle. Wrongly projecting motoneurones, which were maintained throughout the normal cell death period, were activated during spontaneous embryonic movements, and in many cases were found to have a behaviourally inappropriate activation pattern. These observations are discussed in relation to proposed mechanisms by which developmental errors in connectivity are corrected.

  1. Increase in group II excitation from ankle muscles to thigh motoneurones during human standing

    PubMed Central

    Marchand-Pauvert, Véronique; Nicolas, Guillaume; Marque, Philippe; Iglesias, Caroline; Pierrot-Deseilligny, Emmanuel

    2005-01-01

    In standing subjects, we investigated the excitation of quadriceps (Q) motoneurones by muscle afferents from tibialis anterior (TA) and the excitation of semitendinosus (ST) motoneurones by muscle afferents from gastrocnemius medialis (GM). Standing with a backward lean stretches the anterior muscle pair (TA and Q) and they must be cocontracted to maintain balance. Equally, forward lean stretches the posterior muscle pair (GM and ST) and they must be cocontracted. We used these conditions of enhanced lean to increase the influence of γ static motoneurones on muscle spindle afferents, which enhances the background input from these afferents to extrafusal motoneurones. The effects of the conditioning volleys on motoneurone excitability was estimated using the modulation of the on-going rectified EMG and of the H reflex. Stimulation of afferents from TA in the deep peroneal nerve at 1.5–2 × MT (motor threshold) evoked early group I and late group II excitation of Q motoneurones. Stimulation of afferents in the GM nerve at 1.3–1.8 MT evoked only late group II excitation of ST motoneurones. The late excitation produced by the group II afferents was significantly greater when subjects were standing and leaning than when they voluntarily cocontracted the same muscle pairs at the same levels of activation. The early effect produced by the group I afferents was unchanged. We propose that this increase in excitation by group II afferents reflects a posture-related withdrawal of a tonic inhibition that is exerted by descending noradrenergic control and is specific to the synaptic actions of group II afferents. PMID:15860524

  2. Decreased c-Jun expression correlates with impaired spinal motoneuron regeneration in aged mice following sciatic nerve crush.

    PubMed

    Yuan, Qiuju; Su, Huanxing; Guo, Jiasong; Tsang, Kwok Yeung; Cheah, Kathryn S E; Chiu, Kin; Yang, Jian; Wong, Wai-Man; So, Kwok-Fai; Huang, Jian-Dong; Wu, Wutian; Lin, Zhi-xiu

    2012-04-01

    Post-injury nerve regeneration of the peripheral nervous system declines with age, but the mechanisms underlying the weakened axonal regeneration are not well understood. Increased synthesis and activity of the AP-1 transcription factor c-Jun have been implicated in efficient motor axonal regeneration. In the present study, we evaluated the hypothesis that the impaired regenerative capacity in the aged is associated with impaired induction of c-Jun. In non-manipulated young adult or aged mice, no c-Jun and its phosphorylated form were detected in the ventral horn of the spinal cord. Following nerve crush, significant c-Jun and phosphorylated c-Jun occurred in the injured motoneurons of young adult mice, but not in aged animals. In accord with the immunohistochemistry, Western blots also showed that sciatic nerve crush induced c-Jun and its phosphorylation expression in the ventral horn of young adult but not in aged mice. Changes in c-Jun mRNA level detected by in situ hybridization are congruent with that in c-Jun protein content, showing an increase at 5 days after crush in young adult but not aged. Moreover, compared with young adult mice, aged mice showed impaired motor axonal regeneration. These results demonstrate that the impaired motor axonal regeneration seen in aged mice is correlated with impaired c-Jun expression and phosphorylation following injury. These data provide a neurobiological explanation for the poor outcome associated with nerve repair in the aged.

  3. Characterization of postsynaptic potentials evoked by sural nerve stimulation in hindlimb motoneurons from acute and chronic spinal cats.

    PubMed

    Baker, L L; Chandler, S H

    1987-09-15

    The purpose of this study was to characterize the changes in postsynaptic potentials recorded in ankle extensor motoneurons resulting from activation of the sural nerve after spinal cord transection in the adult cat. Eight acute and nine chronic animals were spinalized at T12. Intracellular recordings from motoneurons innervating the triceps surae were performed. Sural nerve stimulation evoked complex synaptic potentials consisting of early and late components in all motoneurons. Early excitatory and inhibitory postsynaptic potentials (PSPs), as well as long latency excitatory postsynaptic potentials were recorded and averaged for assessment of PSP amplitude and duration. Early PSPs, both excitatory and inhibitory, were significantly larger in the motoneurons of cats spinalized 4-6 months earlier. Central latency of excitatory potentials were similar in the two samples of motoneurons, but the central latency associated with the initial inhibitory PSP was significantly shorter in the recordings from motoneurons of chronic spinal cats. In most recordings, an additional inhibitory PSP followed the initial excitatory PSP in motoneurons, and this secondary inhibitory PSP was similar in peak amplitude and duration in both samples of motoneurons. Also, a long latency excitatory PSP was recorded in a large percentage of motoneurons from both samples. This potential was typically of greater amplitude and longer duration in the motoneurons from chronic animals, when compared to recordings from acute animals. Although changes in amplitude and duration of PSP activity could be documented, there was no marked alteration in the frequency of occurrence of each PSP pattern recorded from the two preparations. This suggests that the synaptic pathways mediating the sural nerve reflexes have not qualitatively changed in the chronic spinal animal. The changes in amplitudes and durations of the PSPs in the chronic spinal cat indicate, however, that quantitative changes have occurred

  4. A study of the interaction between motoneurones in the frog spinal cord

    PubMed Central

    Grinnell, A. D.

    1966-01-01

    1. A short-latency interaction between motoneurones has been studied with intracellular and root potential recordings from the isolated spinal cord of the frog. Antidromic stimulation of one ventral root causes brief depolarization (VR-EPSP) of the motoneurones of adjacent, non-excited motoneurones. The summed activity of many such VR-EPSPs can be seen as a brief depolarization (VR-VRP) passing out an adjacent ventral root. 2. Both intracellular and root-recorded signs of this interaction are graded in amplitude. 3. It was found that this interaction decreased with increasing temperature. This is in contrast to the behaviour of the ventral root potential resulting from dorsal root stimulation (DR-VRP) or the dorsal root potentials resulting from either dorsal root (DR-DRP) or ventral root (VR-DRP) stimulation, all of which increased in amplitude from below 10 to about 17° C. 4. Pharmacological evidence suggests that the interaction between motoneurones is not chemically mediated. The VR-VRP was not affected by a large variety of transmitter blocking agents, including curare, dihydro-β-erythroidine, atropine, succinylcholine, hexamethonium and DOPA, while the VR-DRP, which probably originates with the release of ACh from an axon collateral, was consistently blocked. 5. Mg2+ suppressed the VR-VRP more slowly than the other potentials, and this suppression was increased by adding Ca2+, rather than reversed, as in the case of the other root potentials, which are presumably mediated by chemical transmission. 6. The interaction between motoneurones is strongly facilitated by orthodromic depolarization of the motoneurones being antidromically stimulated. Extracellular recordings within the cord support the conclusion that this facilitation is a result of the enhancement of antidromic invasion, perhaps especially of the dendrites, by slight depolarization. 7. One VR-VRP (or VR-EPSP) first suppresses response to another (for about 10 msec), then facilitates response to

  5. Postsynaptic muscarinic m2 receptors at cholinergic and glutamatergic synapses of mouse brainstem motoneurons.

    PubMed

    Csaba, Zsolt; Krejci, Eric; Bernard, Véronique

    2013-06-15

    In many brain areas, few cholinergic synapses are identified. Acetylcholine is released into the extracellular space and acts through diffuse transmission. Motoneurons, however, are contacted by numerous cholinergic terminals, indicating synaptic cholinergic transmission on them. The muscarinic m2 receptor is the major acetylcholine receptor subtype of motoneurons; therefore, we analyzed the localization of the m2 receptor in correlation with synapses by electron microscopic immunohistochemistry in the mouse trigeminal, facial, and hypoglossal motor nuclei. In all nuclei, m2 receptors were localized at the membrane of motoneuronal perikarya and dendrites. The m2 receptors were concentrated at cholinergic synapses located on the perikarya and most proximal dendrites. However, m2 receptors at cholinergic synapses represented only a minority (<10%) of surface m2 receptors. The m2 receptors were also enriched at glutamatergic synapses in both motoneuronal perikarya and dendrites. A relatively large proportion (20-30%) of plasma membrane-associated m2 receptors were located at glutamatergic synapses. In conclusion, the effect of acetylcholine on motoneuron populations might be mediated through a synaptic as well as diffuse type of transmission.

  6. A perimotor framework reveals functional segmentation in the motoneuronal network controlling locomotion in Caenorhabditis elegans.

    PubMed

    Haspel, Gal; O'Donovan, Michael J

    2011-10-12

    The neuronal connectivity dataset of the nematode Caenorhabditis elegans attracts wide attention from computational neuroscientists and experimentalists. However, the dataset is incomplete. The ventral and dorsal nerve cords of a single nematode were reconstructed halfway along the body and the posterior data are missing, leaving 21 of 75 motoneurons of the locomotor network with partial or no connectivity data. Using a new framework for network analysis, the perimotor space, we identified rules of connectivity that allowed us to approximate the missing data by extrapolation. Motoneurons were mapped into perimotor space in which each motoneuron is located according to the muscle cells it innervates. In this framework, a pattern of iterative connections emerges which includes most (0.90) of the connections. We identified a repeating unit consisting of 12 motoneurons and 12 muscle cells. The cell bodies of the motoneurons of such a unit are not necessarily anatomical neighbors and there is no obvious anatomical segmentation. A connectivity model, composed of six repeating units, is a description of the network that is both simplified (modular and without noniterative connections) and more complete (includes the posterior part) than the original dataset. The perimotor framework of observed connectivity and the segmented connectivity model give insights and advance the study of the neuronal infrastructure underlying locomotion in C. elegans. Furthermore, we suggest that the tools used herein may be useful to interpret, simplify, and represent connectivity data of other motor systems.

  7. Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice

    PubMed Central

    Witts, Emily C.; Nascimento, Filipe

    2015-01-01

    Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925–1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within in vitro mouse spinal cord slice preparations. We found that adenosine hyperpolarized interneurons and reduced the frequency and amplitude of synaptic inputs to interneurons. Both effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis of miniature postsynaptic currents recorded from interneurons revealed that adenosine reduced their frequency but not amplitude, suggesting that adenosine acts on presynaptic receptors to modulate synaptic transmission. In contrast to interneurons, recordings from motoneurons revealed an adenosine-mediated depolarization. The frequency and amplitude of synaptic inputs to motoneurons were again reduced by adenosine, but we saw no effect on miniature postsynaptic currents. Again these effects on motoneurons were blocked by DPCPX. Taken together, these results demonstrate differential effects of adenosine, acting via A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action on ventral horn interneurons while potentially maintaining motoneuron excitability. This may allow for adaptation of the locomotor pattern generated by interneuronal networks while helping to ensure the maintenance of overall motor output. PMID:26311185

  8. Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish

    SciTech Connect

    Welsh, Lillian; Tanguay, Robert L.; Svoboda, Kurt R.

    2009-05-15

    Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development and that their axons made pathfinding errors (Svoboda, K.R., Vijayaraghaven, S., Tanguay, R.L., 2002. Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. J. Neurosci. 22, 10731-10741). In that study, we did not consider the potential role that altered skeletal muscle development caused by nicotine exposure could play in contributing to the errors in spinal motoneuron axon pathfinding. In this study, we show that an alteration in skeletal muscle development occurs in tandem with alterations in spinal motoneuron development upon exposure to nicotine. The alteration in the muscle involves the binding of nicotine to the muscle-specific AChRs. The nicotine-induced alteration in muscle development does not occur in the zebrafish mutant (sofa potato, [sop]), which lacks muscle-specific AChRs. Even though muscle development is unaffected by nicotine exposure in sop mutants, motoneuron axonal pathfinding errors still occur in these mutants, indicating a direct effect of nicotine exposure on nervous system development.

  9. Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice.

    PubMed

    Witts, Emily C; Nascimento, Filipe; Miles, Gareth B

    2015-10-01

    Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925-1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within in vitro mouse spinal cord slice preparations. We found that adenosine hyperpolarized interneurons and reduced the frequency and amplitude of synaptic inputs to interneurons. Both effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis of miniature postsynaptic currents recorded from interneurons revealed that adenosine reduced their frequency but not amplitude, suggesting that adenosine acts on presynaptic receptors to modulate synaptic transmission. In contrast to interneurons, recordings from motoneurons revealed an adenosine-mediated depolarization. The frequency and amplitude of synaptic inputs to motoneurons were again reduced by adenosine, but we saw no effect on miniature postsynaptic currents. Again these effects on motoneurons were blocked by DPCPX. Taken together, these results demonstrate differential effects of adenosine, acting via A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action on ventral horn interneurons while potentially maintaining motoneuron excitability. This may allow for adaptation of the locomotor pattern generated by interneuronal networks while helping to ensure the maintenance of overall motor output.

  10. Selective reinnervation of transplanted muscles by their original motoneurons in the axolotl.

    PubMed

    Wigston, D J; Kennedy, P R

    1987-06-01

    The motoneurons innervating 3 hindlimb extensor muscles, anterior and posterior iliotibialis and iliofibularis, were studied separately by retrograde labeling with HRP. The motor pools for these 3 muscles overlapped to such an extent that individual motoneurons between ventral roots 16 and 17 could not be assigned unambiguously to one pool or another. Thus, conventional retrograde labeling could not identify particular axolotl motoneurons. Instead, a double retrograde-labeling technique was employed to mark the motoneurons innervating a particular muscle, the left posterior iliotibialis. Either diamidino yellow (DY) or HRP satisfactorily labeled axolotl motoneurons for at least 3 months in vivo. After labeling, both anterior and posterior iliotibialis muscles were removed from the injected limb and replaced with their counterparts from the opposite limb, in reversed anterior-posterior orientation. Several weeks later, a second marker (DY or HRP) injected into the posterior iliotibialis muscle in its new, more anterior, position labeled the neurons that reinnervated this muscle; the number of neurons labeled with both first and second tracers gave an indication of the selectivity of reinnervation. Using this approach, we have found that the majority of neurons reinnervating a particular muscle are members of that muscle's original motor pool.

  11. Mild Hyperbaric Oxygen Improves Decreased Oxidative Capacity of Spinal Motoneurons Innervating the Soleus Muscle of Rats with Type 2 Diabetes.

    PubMed

    Takemura, Ai; Ishihara, Akihiko

    2016-09-01

    Rats with type 2 diabetes exhibit decreased oxidative capacity, such as reduced oxidative enzyme activity, low-intensity staining for oxidative enzymes in fibers, and no high-oxidative type IIA fibers, in the skeletal muscle, especially in the soleus muscle. In contrast, there are no data available concerning the oxidative capacity of spinal motoneurons innervating skeletal muscle of rats with type 2 diabetes. This study examined the oxidative capacity of motoneurons innervating the soleus muscle of non-obese rats with type 2 diabetes. In addition, this study examined the effects of mild hyperbaric oxygen at 1.25 atmospheres absolute with 36 % oxygen for 10 weeks on the oxidative capacity of motoneurons innervating the soleus muscle because mild hyperbaric oxygen improves the decreased oxidative capacity of the soleus muscle in non-obese rats with type 2 diabetes. Spinal motoneurons innervating the soleus muscle were identified using nuclear yellow, a retrograde fluorescent neuronal tracer. Thereafter, the cell body sizes and succinate dehydrogenase activity of identified motoneurons were analyzed. Decreased succinate dehydrogenase activity of small-sized alpha motoneurons innervating the soleus muscle was observed in rats with type 2 diabetes. The decreased succinate dehydrogenase activity of these motoneurons was improved by mild hyperbaric oxygen. Therefore, we concluded that rats with type 2 diabetes have decreased oxidative capacity in motoneurons innervating the soleus muscle and this decreased oxidative capacity is improved by mild hyperbaric oxygen.

  12. Motor activity in the isolated spinal cord of the chick embryo: synaptic drive and firing pattern of single motoneurons.

    PubMed

    O'Donovan, M J

    1989-03-01

    The cellular mechanisms underlying embryonic motility were investigated using intracellular recording from motoneurons and electrotonic recording from muscle nerves during motor activity generated by an isolated spinal cord preparation of 12- to 15-d-old chick embryos. DC-coupled recordings from sartorius (a flexor) and femorotibialis (an extensor) muscle nerves revealed that both sets of motoneurons were depolarized at the same time in each cycle even when the motoneurons fired out of phase. Sartorius motoneurons fired briefly on the rising phase of the depolarization and then stopped firing before discharging a second burst of spikes as the depolarization decayed. By contrast, femorotibialis motoneurons fired at the peak of their depolarization, which was coincident with the interruption in sartorius activity. Intracellular recordings from antidromically identified motoneurons confirmed that flexor and extensor motoneurons were depolarized at the same time during each cycle of activity. The discharge of femorotibialis motoneurons, and others presumed to be extensors, followed changes in membrane potential so that maximal firing occurred during peak depolarization. The relationship between discharge and membrane potential was different in sartorius motoneurons (and in others presumed to be flexors) because they fired briefly on the rising phase of the depolarization and then stopped firing during peak depolarization. In some of these cells firing resumed as the membrane potential decayed back to rest. Intracellular injection of depolarizing current into sartorius motoneurons during motor activity reversed the direction of the membrane potential change from depolarizing to hyperpolarizing during the pause in sartorius discharge. In addition, the discharge evoked by the depolarizing current was blocked during the reversed part of the synaptic potential revealing its inhibitory nature. The occurrence of the IPSP was accompanied by a large reduction in motoneuronal

  13. Neuroplasticity and Repair in Rodent Neurotoxic Models of Spinal Motoneuron Disease

    PubMed Central

    Gulino, Rosario

    2016-01-01

    Retrogradely transported toxins are widely used to set up protocols for selective lesioning of the nervous system. These methods could be collectively named “molecular neurosurgery” because they are able to destroy specific types of neurons by using targeted neurotoxins. Lectins such as ricin, volkensin, or modeccin and neuropeptide- or antibody-conjugated saporin represent the most effective toxins used for neuronal lesioning. Some of these specific neurotoxins could be used to induce selective depletion of spinal motoneurons. In this review, we extensively describe two rodent models of motoneuron degeneration induced by volkensin or cholera toxin-B saporin. In particular, we focus on the possible experimental use of these models to mimic neurodegenerative diseases, to dissect the molecular mechanisms of neuroplastic changes underlying the spontaneous functional recovery after motoneuron death, and finally to test different strategies of neural repair. The potential clinical applications of these approaches are also discussed. PMID:26862439

  14. Analyzing the Effects of Gap Junction Blockade on Neural Synchrony via a Motoneuron Network Computational Model

    PubMed Central

    Memelli, Heraldo; Horn, Kyle G.; Wittie, Larry D.; Solomon, Irene C.

    2012-01-01

    In specific regions of the central nervous system (CNS), gap junctions have been shown to participate in neuronal synchrony. Amongst the CNS regions identified, some populations of brainstem motoneurons are known to be coupled by gap junctions. The application of various gap junction blockers to these motoneuron populations, however, has led to mixed results regarding their synchronous firing behavior, with some studies reporting a decrease in synchrony while others surprisingly find an increase in synchrony. To address this discrepancy, we employ a neuronal network model of Hodgkin-Huxley-style motoneurons connected by gap junctions. Using this model, we implement a series of simulations and rigorously analyze their outcome, including the calculation of a measure of neuronal synchrony. Our simulations demonstrate that under specific conditions, uncoupling of gap junctions is capable of producing either a decrease or an increase in neuronal synchrony. Subsequently, these simulations provide mechanistic insight into these different outcomes. PMID:23365560

  15. Calcium dynamics and buffering in motoneurones of the mouse spinal cord

    PubMed Central

    Palecek, Jiri; Lips, Mario B; Keller, Bernhard U

    1999-01-01

    A quantitative analysis of endogenous calcium homeostasis was performed on 65 motoneurones in slices of the lumbar spinal cord from 2- to 8-day-old mice by simultaneous patch-clamp and microfluorometric calcium measurements. Somatic calcium concentrations were monitored with a temporal resolution in the millisecond time domain. Measurements were performed by using a monochromator for excitation and a photomultiplier detection system. Somatic calcium signalling was investigated during defined voltage-clamp protocols. Calcium responses were observed for membrane depolarizations positive to −50 mV. A linear relation between depolarization time and free calcium concentrations ([Ca2+]i) indicated that voltage-dependent calcium influx dominated the response. Endogenous calcium homeostasis was quantified by using the ‘added buffer’ approach. In the presence of fura-2 and mag-fura-5, calcium transients decayed according to a monoexponential function. Decay-time constants showed a linear dependence on dye concentration and the extrapolated constant in the absence of indicator dye was 371 ± 120 ms (n= 13 cells, 21 °C). For moderate elevations (< 1 μm), recovery kinetics of depolarization-induced calcium transients were characterized by a calcium-independent, ‘effective’ extrusion rate γ = 140 ± 47 s−1 (n= 13 cells, 21 °C). The endogenous calcium binding ratio for fixed buffers in spinal motoneurones was κB’ = 50 ± 17 (n= 13 cells), indicating that less than 2% of cytosolic calcium ions contributed to [Ca2+]i. Endogenous binding ratios in spinal motoneurones were small compared to those found in hippocampal or cerebellar Purkinje neurones. From a functional perspective, they provided motoneurones with rapid dynamics of cytosolic [Ca2+]i for a given set of influx, extrusion and uptake mechanisms. With respect to pathophysiological conditions, our measurements are in agreement with a model where the selective vulnerability of spinal motoneurones during

  16. Retrograde Gene Delivery to Hypoglossal Motoneurons Using Adeno-Associated Virus Serotype 9

    PubMed Central

    ElMallah, Mai K.; Falk, Darin J.; Lane, Michael A.; Conlon, Thomas J.; Lee, Kun-Ze; Shafi, Nadeem I.; Reier, Paul J.

    2012-01-01

    Abstract Retrograde viral transport (i.e., muscle to motoneuron) enables targeted gene delivery to specific motor pools. Recombinant adeno-associated virus serotype 9 (AAV9) robustly infects motoneurons, but the retrograde transport capabilities of AAV9 have not been systematically evaluated. Accordingly, we evaluated the retrograde transduction efficiency of AAV9 after direct tongue injection in 129SVE mice as well as a mouse model that displays neuromuscular pathology (Gaa−/−). Hypoglossal (XII) motoneurons were histologically evaluated 8 weeks after tongue injection with AAV9 encoding green fluorescent protein (GFP) with expression driven by the chicken β-actin promoter (1×1011 vector genomes). On average, GFP expression was detected in 234±43 XII motoneurons 8 weeks after AAV9-GFP tongue injection. In contrast, tongue injection with a highly efficient retrograde anatomical tracer (cholera toxin β subunit, CT-β) resulted in infection of 818±88 XII motoneurons per mouse. The retrograde transduction efficiency of AAV9 was similar between the 129SVE mice and those with neuromuscular disease (Gaa−/−). Routine hematoxylin and eosin staining and cluster of differentiation (CD) immunostaining for T cells (CD3) indicated no persistent inflammation within the tongue or XII nucleus after AAV9 injection. Additional experiments indicated no adverse effects of AAV9 on the pattern of breathing. We conclude that AAV9 can retrogradely infect a significant portion of a given motoneuron pool in normal and dystrophic mice, and that its transduction efficiency is approximately 30% of what can be achieved with CT-β. PMID:22693957

  17. Morphology of motoneurons in different subdivisions of the rat facial nucleus stained intracellularly with horseradish peroxidase.

    PubMed

    Friauf, E

    1986-11-08

    Horseradish peroxidase was injected into single facial motoneurons of the rat. Neurons were identified by antidromic stimulation of either the buccal or the marginal mandibular or the posterior auricular nerve branches. Motoneuronal cell bodies supplying the buccal branch were located in the lateral subdivision of the facial nucleus, those supplying the marginal mandibular branch were in the intermediate subdivision, and those supplying the posterior auricular branch were in the medial subdivision. Eleven motoneurons were reconstructed with a computer-assisted technique. Their soma diameters averaged 20 microns; the average number of primary dendrites was 7.9 and the combined lengths of the dendritic trees averaged 17,650 microns. There was no distinction between the three motoneuron groups in terms of these and other quantitative data. However, on the basis of reconstructed dendritic tree orientation (i.e., dendritic distribution), major differences were observed between motoneurons of the three groups. Dendrites from all groups extended beyond the boundaries of the facial nucleus into the reticular formation. The border between the intermediate and the lateral subdivision was crossed by some dendrites but the overlap was small. In contrast, no dendrite of a motoneuron in the medial subdivision entered the intermediate subdivision and vice versa. The dendritic extent was totally restricted by the borders between these two subdivisions. Outside the Nissl-defined nuclear border, however, dendrites from cells in adjacent subdivisions overlapped. It is concluded that the medial subdivision of the facial nucleus can be distinguished from the intermediate and lateral subdivisions not only by its sharp Nissl-defined border but also by the discrete organization of its dendritic field.

  18. Non-Cell-Autonomous Regulation of Retrograde Motoneuronal Axonal Transport in an SBMA Mouse Model

    PubMed Central

    Halievski, Katherine; Kemp, Michael Q.; Breedlove, S. Marc; Miller, Kyle E.

    2016-01-01

    Abstract Defects in axonal transport are seen in motoneuronal diseases, but how that impairment comes about is not well understood. In spinal bulbar muscular atrophy (SBMA), a disorder linked to a CAG/polyglutamine repeat expansion in the androgen receptor (AR) gene, the disease-causing AR disrupts axonal transport by acting in both a cell-autonomous fashion in the motoneurons themselves, and in a non-cell-autonomous fashion in muscle. The non-cell-autonomous mechanism is suggested by data from a unique “myogenic” transgenic (TG) mouse model in which an AR transgene expressed exclusively in skeletal muscle fibers triggers an androgen-dependent SBMA phenotype, including defects in retrograde transport. However, motoneurons in this TG model retain the endogenous AR gene, leaving open the possibility that impairments in transport in this model also depend on ARs in the motoneurons themselves. To test whether non-cell-autonomous mechanisms alone can perturb retrograde transport, we generated male TG mice in which the endogenous AR allele has the testicular feminization mutation (Tfm) and, consequently, is nonfunctional. Males carrying the Tfm allele alone show no deficits in motor function or axonal transport, with or without testosterone treatment. However, when Tfm males carrying the myogenic transgene (Tfm/TG) are treated with testosterone, they develop impaired motor function and defects in retrograde transport, having fewer retrogradely labeled motoneurons and deficits in endosomal flux based on time-lapse video microscopy of living axons. These findings demonstrate that non-cell-autonomous disease mechanisms originating in muscle are sufficient to induce defects in retrograde transport in motoneurons. PMID:27517091

  19. Non-Cell-Autonomous Regulation of Retrograde Motoneuronal Axonal Transport in an SBMA Mouse Model.

    PubMed

    Halievski, Katherine; Kemp, Michael Q; Breedlove, S Marc; Miller, Kyle E; Jordan, Cynthia L

    2016-01-01

    Defects in axonal transport are seen in motoneuronal diseases, but how that impairment comes about is not well understood. In spinal bulbar muscular atrophy (SBMA), a disorder linked to a CAG/polyglutamine repeat expansion in the androgen receptor (AR) gene, the disease-causing AR disrupts axonal transport by acting in both a cell-autonomous fashion in the motoneurons themselves, and in a non-cell-autonomous fashion in muscle. The non-cell-autonomous mechanism is suggested by data from a unique "myogenic" transgenic (TG) mouse model in which an AR transgene expressed exclusively in skeletal muscle fibers triggers an androgen-dependent SBMA phenotype, including defects in retrograde transport. However, motoneurons in this TG model retain the endogenous AR gene, leaving open the possibility that impairments in transport in this model also depend on ARs in the motoneurons themselves. To test whether non-cell-autonomous mechanisms alone can perturb retrograde transport, we generated male TG mice in which the endogenous AR allele has the testicular feminization mutation (Tfm) and, consequently, is nonfunctional. Males carrying the Tfm allele alone show no deficits in motor function or axonal transport, with or without testosterone treatment. However, when Tfm males carrying the myogenic transgene (Tfm/TG) are treated with testosterone, they develop impaired motor function and defects in retrograde transport, having fewer retrogradely labeled motoneurons and deficits in endosomal flux based on time-lapse video microscopy of living axons. These findings demonstrate that non-cell-autonomous disease mechanisms originating in muscle are sufficient to induce defects in retrograde transport in motoneurons.

  20. Cat hindlimb motoneurons during locomotion. I. Destination, axonal conduction velocity, and recruitment threshold.

    PubMed

    Hoffer, J A; Loeb, G E; Marks, W B; O'Donovan, M J; Pratt, C A; Sugano, N

    1987-02-01

    Fine flexible wire microelectrodes chronically implanted in the fifth lumbar ventral root (L5 VR) of 17 cats rendered stable records of the natural discharge patterns of 164 individual axons during locomotion on a treadmill. Fifty-one out of 164 axons were identified as motoneurons projecting to the anterior thigh muscle group. For these axons, the centrifugal propagation of action potentials was demonstrated by the technique of spike-triggered averaging using signals recorded from cuff electrodes implanted around the femoral nerve. The axonal conduction velocity was measured from the femoral nerve cuff records. For 43/51 motoneurons, the corresponding target muscle was identified by spike-triggered averaging of signals recorded from bipolar EMG electrodes implanted in each of the anterior thigh muscles: vastus intermedius, medialis and lateralis, sartorius anterior and medialis, and rectus femoris. For 32/51 motoneurons, the recruitment threshold during locomotion was determined from the mean value of the rectified digitally smoothed EMG of the target muscle measured at the time when the motoneuron fired its first spike for each step. The recruitment threshold of every motoneuron was relatively constant for a given speed of walking, but for some units there were small systematic variations as a function of treadmill speed (range: 0.1-1.3 m/s). Recruitment thresholds were standardized with respect to the mean value of peak EMG activity of the target muscle during 16 s of walking at 0.5 m/s. For 28/51 motoneurons recorded in nine cats, recruitment thresholds (range: 3-93% of peak target muscle EMG) were linearly correlated (r = 0.51, P less than 0.02) to axonal conduction velocities (range: 57-117 m/s). In addition, for seven recorded pairs of motoneurons that projected to the same muscle in the same cat, the recruitment thresholds were ordered by relative conduction velocities. Taken together, these results are consistent with the notion that, in normal cat

  1. Reflex origin for the slowing of motoneurone firing rates in fatigue of human voluntary contractions.

    PubMed Central

    Bigland-Ritchie, B R; Dawson, N J; Johansson, R S; Lippold, O C

    1986-01-01

    During fatigue from a sustained maximal voluntary contraction (m.v.c.) the mean motoneurone discharge rates decline. In the present experiments we found no recovery of firing rates after 3 min of rest if the fatigued muscle was kept ischaemic, but near full recovery 3 min after the blood supply was restored. Since 3 min is thus sufficient time for recovery of any central changes in excitability, the results support the hypothesis that, during fatigue, motoneurone firing rates may be regulated by a peripheral reflex originating in response to fatigue-induced changes within the muscle. PMID:3560001

  2. Mechanisms of spinal motoneurons survival in rats under simulated hypogravity on earth

    NASA Astrophysics Data System (ADS)

    Islamov, R. R.; Mishagina, E. A.; Tyapkina, O. V.; Shajmardanova, G. F.; Eremeev, A. A.; Kozlovskaya, I. B.; Nikolskij, E. E.; Grigorjev, A. I.

    2011-05-01

    It was previously shown that different cell types in vivo and in vitro may die via apoptosis under weightlessness conditions in space as well as in simulated hypogravity on the Earth. We assessed survivability of spinal motoneurons of rats after 35-day antiorthostatic hind limb suspension. Following weight bearing, unloading the total protein content in lumbar spinal cord is dropped by 21%. The electrophysiological studies of m. gastrocnemius revealed an elevated motoneurons' reflex excitability and conduction disturbances in the sciatic nerve axons. The number of myelinated fibers in the ventral root of experimental animals was insignificantly increased by 35-day of antiorthostatic hind limb suspension, although the retrograde axonal transport was significantly decreased during the first week of simulated hypogravity. The results of the immunohistochemical assay with antibodies against proapoptotic protein caspase 9 and cytotoxicity marker neuron specific nitric oxide synthase (nNOS) and the TUNEL staining did not reveal any signs of apoptosis in motoneurons of suspended and control animals. To examine the possible adaptation mechanisms activated in motoneurons in response to simulated hypogravity we investigated immunoexpression of Hsp25 and Hsp70 in lumbar spinal cord of the rats after 35-day antiorthostatic hind limb suspension. Comparative analysis of the immunohistochemical reaction with anti-Hsp25 antibodies revealed differential staining of motoneurons in intact and experimental animals. The density of immunoprecipitate with anti-Hsp25 antibodies was substantially higher in motoneurons of the 35-day suspended than control rats and the more intensive precipitate in this reaction was observed in motoneuron neuritis. Quantitative analysis of Hsp25 expression demonstrated an increase in the Hsp25 level by 95% in experimental rats compared to the control. The immunoexpression of Hsp70 found no qualitative and quantitative differences in control and experimental

  3. TrkB Gene Therapy by Adeno-Associated Virus Enhances Recovery after Cervical Spinal Cord Injury

    PubMed Central

    Martínez-Gálvez, Gabriel; Zambrano, Juan M.; Diaz Soto, Juan C.; Zhan, Wen-Zhi; Gransee, Heather M.; Sieck, Gary C.; Mantilla, Carlos B.

    2015-01-01

    Unilateral cervical spinal cord hemisection at C2 (C2SH) interrupts descending bulbospinal inputs to phrenic motoneurons, paralyzing the diaphragm muscle. Recovery after C2SH is enhanced by brain derived neurotrophic factor (BDNF) signaling via the tropomyosin-related kinase subtype B (TrkB) receptor in phrenic motoneurons. The role for gene therapy using adeno-associated virus (AAV)-mediated delivery of TrkB to phrenic motoneurons is not known. The present study determined the therapeutic efficacy of intrapleural delivery of AAV7 encoding for full-length TrkB (AAV-TrkB) to phrenic motoneurons 3 days post-C2SH. Diaphragm EMG was recorded chronically in male rats (n = 26) up to 21 days post-C2SH. Absent ipsilateral diaphragm EMG activity was verified 3 days post-C2SH. A greater proportion of animals displayed recovery of ipsilateral diaphragm EMG activity during eupnea by 14 and 21 days post-SH after AAV-TrkB (10/15) compared to AAV-GFP treatment (2/11; p = 0.031). Diaphragm EMG amplitude increased over time post-C2SH (p < 0.001), and by 14 days post-C2SH, AAV-TrkB treated animals displaying recovery achieved 48% of the pre-injury values compared to 27% in AAV-GFP treated animals. Phrenic motoneuron mRNA expression of glutamatergic AMPA and NMDA receptors revealed a significant, positive correlation (r2 = 0.82), with increased motoneuron NMDA expression evident in animals treated with AAV-TrkB and that displayed recovery after C2SH. Overall, gene therapy using intrapleural delivery of AAV-TrkB to phrenic motoneurons is sufficient to promote recovery of diaphragm activity, adding a novel potential intervention that can be administered after upper cervical spinal cord injury to improve impaired respiratory function. PMID:26607912

  4. TrkB gene therapy by adeno-associated virus enhances recovery after cervical spinal cord injury.

    PubMed

    Martínez-Gálvez, Gabriel; Zambrano, Juan M; Diaz Soto, Juan C; Zhan, Wen-Zhi; Gransee, Heather M; Sieck, Gary C; Mantilla, Carlos B

    2016-02-01

    Unilateral cervical spinal cord hemisection at C2 (C2SH) interrupts descending bulbospinal inputs to phrenic motoneurons, paralyzing the diaphragm muscle. Recovery after C2SH is enhanced by brain derived neurotrophic factor (BDNF) signaling via the tropomyosin-related kinase subtype B (TrkB) receptor in phrenic motoneurons. The role for gene therapy using adeno-associated virus (AAV)-mediated delivery of TrkB to phrenic motoneurons is not known. The present study determined the therapeutic efficacy of intrapleural delivery of AAV7 encoding for full-length TrkB (AAV-TrkB) to phrenic motoneurons 3 days post-C2SH. Diaphragm EMG was recorded chronically in male rats (n=26) up to 21 days post-C2SH. Absent ipsilateral diaphragm EMG activity was verified 3 days post-C2SH. A greater proportion of animals displayed recovery of ipsilateral diaphragm EMG activity during eupnea by 14 and 21 days post-SH after AAV-TrkB (10/15) compared to AAV-GFP treatment (2/11; p=0.031). Diaphragm EMG amplitude increased over time post-C2SH (p<0.001), and by 14 days post-C2SH, AAV-TrkB treated animals displaying recovery achieved 48% of the pre-injury values compared to 27% in AAV-GFP treated animals. Phrenic motoneuron mRNA expression of glutamatergic AMPA and NMDA receptors revealed a significant, positive correlation (r(2)=0.82), with increased motoneuron NMDA expression evident in animals treated with AAV-TrkB and that displayed recovery after C2SH. Overall, gene therapy using intrapleural delivery of AAV-TrkB to phrenic motoneurons is sufficient to promote recovery of diaphragm activity, adding a novel potential intervention that can be administered after upper cervical spinal cord injury to improve impaired respiratory function.

  5. Neuromuscular junction formation between human stem-cell-derived motoneurons and rat skeletal muscle in a defined system.

    PubMed

    Guo, Xiufang; Das, Mainak; Rumsey, John; Gonzalez, Mercedes; Stancescu, Maria; Hickman, James

    2010-12-01

    To date, the coculture of motoneurons (MNs) and skeletal muscle in a defined in vitro system has only been described in one study and that was between rat MNs and rat skeletal muscle. No in vitro studies have demonstrated human MN to rat muscle synapse formation, although numerous studies have attempted to implant human stem cells into rat models to determine if they could be of therapeutic use in disease or spinal injury models, although with little evidence of neuromuscular junction (NMJ) formation. In this report, MNs differentiated from human spinal cord stem cells, together with rat skeletal myotubes, were used to build a coculture system to demonstrate that NMJ formation between human MNs and rat skeletal muscles is possible. The culture was characterized by morphology, immunocytochemistry, and electrophysiology, while NMJ formation was demonstrated by immunocytochemistry and videography. This defined system provides a highly controlled reproducible model for studying the formation, regulation, maintenance, and repair of NMJs. The in vitro coculture system developed here will be an important model system to study NMJ development, the physiological and functional mechanism of synaptic transmission, and NMJ- or synapse-related disorders such as amyotrophic lateral sclerosis, as well as for drug screening and therapy design.

  6. Muscle biopsies show that FES of denervated muscles reverses human muscle degeneration from permanent spinal motoneuron lesion.

    PubMed

    Kern, Helmut; Rossini, Katia; Carraro, Ugo; Mayr, Winfried; Vogelauer, Michael; Hoellwarth, Ursula; Hofer, Christian

    2005-01-01

    This paper presents biopsy analyses in support of the clinical evidence of muscle recovery induced by a new system of life-long functional-electrical-stimulation (FES) training in permanent spinal-motoneuron-denervated human muscle. Not earlier than 1 year after subjects experienced complete conus cauda lesion, their thigh muscles were electrically stimulated at home for several years with large skin surface electrodes and an expressly designed stimulator that delivered much longer impulses than those presently available for clinical use. The poor excitability of long-term denervated muscles was first improved by several months of twitch-contraction training. Then, the muscles were tetanically stimulated against progressively increased loads. Needle biopsies of vastus lateralis from long-term denervated subjects showed severe myofiber atrophy or lipodystrophy beginning 2 years after spinal cord injury (SCI). Muscle biopsies from a group of 3.6- to 13.5-year denervated subjects, who underwent 2.4 to 9.3 years of FES, show that this progressive training almost reverted long-term muscle atrophy/degeneration.

  7. Noggin and Sonic hedgehog are involved in compensatory changes within the motoneuron-depleted mouse spinal cord.

    PubMed

    Gulino, Rosario; Gulisano, Massimo

    2013-09-15

    Sonic hedgehog and Noggin are morphogenetic factors involved in neural induction and ventralization of the neural tube, but recent findings suggest that they could participate in regeneration and functional recovery after injury. Here, in order to verify if these mechanisms could occur in the spinal cord and involve synaptic plasticity, we measured the expression levels of Sonic hedgehog, Noggin, Choline Acetyltransferase, Synapsin-I and Glutamate receptor subunits (GluR1, GluR2, GluR4), in a motoneuron-depleted mouse spinal cord lesion model obtained by intramuscular injection of Cholera toxin-B saporin. The lesion caused differential expression changes of the analyzed proteins. Moreover, motor performance was found correlated with Sonic hedgehog and Noggin expression in lesioned animals. The results also suggest that Sonic hedgehog could collaborate in modulating synaptic plasticity. Together, these findings confirm that the injured mammalian spinal cord has intrinsic potential for repair and that some proteins classically involved in development, such as Sonic hedgehog and Noggin could have important roles in regeneration and functional restoration, by mechanisms including synaptic plasticity.

  8. The Drosophila Hox gene Ultrabithorax acts in both muscles and motoneurons to orchestrate formation of specific neuromuscular connections

    PubMed Central

    Hessinger, Christian; Technau, Gerhard M.

    2017-01-01

    Hox genes are known to specify motoneuron pools in the developing vertebrate spinal cord and to control motoneuronal targeting in several species. However, the mechanisms controlling axial diversification of muscle innervation patterns are still largely unknown. We present data showing that the Drosophila Hox gene Ultrabithorax (Ubx) acts in the late embryo to establish target specificity of ventrally projecting RP motoneurons. In abdominal segments A2 to A7, RP motoneurons innervate the ventrolateral muscles VL1-4, with VL1 and VL2 being innervated in a Wnt4-dependent manner. In Ubx mutants, these motoneurons fail to make correct contacts with muscle VL1, a phenotype partially resembling that of the Wnt4 mutant. We show that Ubx regulates expression of Wnt4 in muscle VL2 and that it interacts with the Wnt4 response pathway in the respective motoneurons. Ubx thus orchestrates the interaction between two cell types, muscles and motoneurons, to regulate establishment of the ventrolateral neuromuscular network. PMID:27913640

  9. Regulation of locomotion and motoneuron trajectory selection and targeting by the Drosophila homolog of Olig family transcription factors

    PubMed Central

    Oyallon, Justine; Apitz, Holger; Miguel-Aliaga, Irene; Timofeev, Katarina; Ferreira, Lauren; Salecker, Iris

    2012-01-01

    During the development of locomotion circuits it is essential that motoneurons with distinct subtype identities select the correct trajectories and target muscles. In vertebrates, the generation of motoneurons and myelinating glia depends on Olig2, one of the five Olig family bHLH transcription factors. We investigated the so far unknown function of the single Drosophila homolog Oli. Combining behavioral and genetic approaches, we demonstrate that oli is not required for gliogenesis, but plays pivotal roles in regulating larval and adult locomotion, and axon pathfinding and targeting of embryonic motoneurons. In the embryonic nervous system, Oli is primarily expressed in postmitotic progeny, and in particular, in distinct ventral motoneuron subtypes. oli mediates axonal trajectory selection of these motoneurons within the ventral nerve cord and targeting to specific muscles. Genetic interaction assays suggest that oli acts as part of a conserved transcription factor ensemble including Lim3, Islet and Hb9. Moreover, oli is expressed in postembryonic leg-innervating motoneuron lineages and required in glutamatergic neurons for walking. Finally, over-expression of vertebrate Olig2 partially rescues the walking defects of oli-deficient flies. Thus, our findings reveal a remarkably conserved role of Drosophila Oli and vertebrate family members in regulating motoneuron development, while the steps that require their function differ in detail. PMID:22796650

  10. Dual effect of GABA on descending monosynaptic excitatory postsynaptic potential in frog lumbar motoneurons.

    PubMed

    Ovsepian, S V; Vesselkin, N P

    2004-01-01

    Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by stimulating ipsilateral ventrolateral column (VLC) in the thoracic section were recorded in lumbar motoneurons within the isolated spinal cord of the frog Rana ridibunda. Bath application of the selective GABAB receptor agonist (-)-baclofen (0.05 mM) caused a reduction in the peak amplitude of VLC EPSP. Baclofen did not cause any consistent change in the membrane potential or in the EPSP waveform within frog motoneurones. The selective GABA(B) receptor antagonist saclofen (0.1 mM) completely blocked the effect of (-)-baclofen on VLC EPSP. A decrease in VLC EPSP peak amplitude was also observed during GABA (0.5 mM) application. Unlike (-)-baclofen, inhibition of VLC EPSP induced by GABA was accompanied by a shortening of the EPSP time course and a reduction in membrane input resistance within lumbar motoneurons. The decrease in VLC EPSP peak amplitude induced by (-)-baclofen and GABA was accompanied by an increase in the paired-pulse facilitation. These data provide evidence for a dual pre- and postsynaptic GABAergic inhibition of the VLC monosynaptic EPSP in lumbar motoneurons within the frog spinal cord.

  11. Neurotrophic factors improve motoneuron survival and function of muscle reinnervated by embryonic neurons.

    PubMed

    Grumbles, Robert M; Sesodia, Sanjay; Wood, Patrick M; Thomas, Christine K

    2009-07-01

    Motoneuron death can occur over several spinal levels with disease or trauma, resulting in muscle denervation. We tested whether cotransplantation of embryonic neurons with 1 or more neurotrophic factors into peripheral nerve improved axon regeneration, muscle fiber area, reinnervation, and function to a greater degree than cell transplantation alone. Sciatic nerves of adult Fischer rats were cut to denervate muscles; 1 week later, embryonic ventral spinal cord cells (days 14-15) were transplanted into the tibial nerve stump as the only source of neurons for muscle reinnervation. Factors that promote motoneuron survival (cardiotrophin 1; fibroblast growth factor 2; glial cell line-derived neurotrophic factor; insulin-like growth factor 1; leukemia inhibitory factor; and hepatocyte growth factor) were added to the transplant individually or in combinations. Inclusion of a single factor with the cells resulted in comparable myelinated axon counts, muscle fiber areas, and evoked electromyographic activity to cells alone 10 weeks after transplantation. Only cell transplantation with glial cell line-derived neurotrophic factor, hepatocyte growth factor, and insulin-like growth factor 1 significantly increased motoneuron survival, myelinated axon counts, muscle reinnervation, and evoked electromyographic activity compared with cells alone. Thus, immediate application of a specific combination of factors to dissociated embryonic neurons improves survival of motoneurons and the long-term function of reinnervated muscle.

  12. Spinal organization and steroid sensitivity of motoneurons innervating the pubococcygeus muscle in the male rat.

    PubMed

    Manzo, J; Nicolas, L; Hernandez, M E; Cruz, M R; Carrillo, P; Pacheco, P

    1999-07-05

    Male rat motoneurons innervating the pubococcygeus muscle were located in the ventral nucleus of lamina IX at the sixth lumbar (L6) and first sacral (S1) spinal cord segments. Retrograde labeling with horseradish peroxidase-wheat germ agglutinin was transported up to second-order dendrites and revealed that these motoneurons have a "U-shaped arborization" of dendrites toward the intermediolateral and intermediomedial nuclei area of lamina VII. This dendritic organization makes a wide "final common path" that probably integrates afferent information from several sources, accounting for the participation of the pubococcygeus muscle in autonomic and somatic processes, such as those related to micturition and reproduction. Castration produced a decrement in the morphometry of these motoneurons. A main effect was a decrement in dendritic length. Steroid replacement indicated that testosterone and estradiol, but not dihydrotestosterone, are able to induce a recovery of morphometric alterations. However, estrogen induced recovery after 2 weeks of treatment, whereas testosterone took 4 weeks. Thus, it is proposed that supraspinal aromatization of testosterone in the male central nervous system might be an important process for the appropriate organization of the pubococcygeus muscle motoneurons and that estradiol seems to need a shorter time of action than testosterone because of differential up-regulation and down-regulation of steroid receptors.

  13. Output of human motoneuron pools to corticospinal inputs during voluntary contractions.

    PubMed

    Martin, P G; Gandevia, S C; Taylor, J L

    2006-06-01

    This study investigated transmission of corticospinal output through motoneurons over a wide range of voluntary contraction strengths in humans. During voluntary contraction of biceps brachii, motor evoked potentials (MEPs) to transcranial magnetic stimulation of the motor cortex grow up to about 50% maximal force and then decrease. To determine whether the decrease reflects events at a cortical or spinal level, responses to stimulation of the cortex and corticospinal tract (cervicomedullary motor evoked potentials, CMEPs) as well as maximal M-waves (M(max)) were recorded during strong contractions at 50 to 100% maximum. In biceps and brachioradialis, MEPs and CMEPs (normalized to M(max)) evoked by strong stimuli decreased during strong elbow flexions. Responses were largest during contractions at 75% maximum and both potentials decreased by about 25% M(max) during maximal efforts (P < 0.001). Reductions were smaller with weaker stimuli, but again similar for MEPs and CMEPs. Thus the reduction in MEPs during strong voluntary contractions can be accounted for by reduced responsiveness of the motoneuron pool to stimulation. During strong contractions of the first dorsal interosseous, a muscle that increases voluntary force largely by frequency modulation, MEPs declined more than in either elbow flexor muscle (35% M(max), P < 0.001). This suggests that motoneuron firing rates are important determinants of evoked output from the motoneuron pool. However, motor cortical output does not appear to be limited at high contraction strengths.

  14. Loss of ATF2 function leads to cranial motoneuron degeneration during embryonic mouse development.

    PubMed

    Ackermann, Julien; Ashton, Garry; Lyons, Steve; James, Dominic; Hornung, Jean-Pierre; Jones, Nic; Breitwieser, Wolfgang

    2011-04-21

    The AP-1 family transcription factor ATF2 is essential for development and tissue maintenance in mammals. In particular, ATF2 is highly expressed and activated in the brain and previous studies using mouse knockouts have confirmed its requirement in the cerebellum as well as in vestibular sense organs. Here we present the analysis of the requirement for ATF2 in CNS development in mouse embryos, specifically in the brainstem. We discovered that neuron-specific inactivation of ATF2 leads to significant loss of motoneurons of the hypoglossal, abducens and facial nuclei. While the generation of ATF2 mutant motoneurons appears normal during early development, they undergo caspase-dependent and independent cell death during later embryonic and foetal stages. The loss of these motoneurons correlates with increased levels of stress activated MAP kinases, JNK and p38, as well as aberrant accumulation of phosphorylated neurofilament proteins, NF-H and NF-M, known substrates for these kinases. This, together with other neuropathological phenotypes, including aberrant vacuolisation and lipid accumulation, indicates that deficiency in ATF2 leads to neurodegeneration of subsets of somatic and visceral motoneurons of the brainstem. It also confirms that ATF2 has a critical role in limiting the activities of stress kinases JNK and p38 which are potent inducers of cell death in the CNS.

  15. Influence of proprioceptive feedback on the firing rate and recruitment of motoneurons

    NASA Astrophysics Data System (ADS)

    De Luca, C. J.; Kline, J. C.

    2012-02-01

    We investigated the relationships of the firing rate and maximal recruitment threshold of motoneurons recorded during isometric contraction with the number of spindles in individual muscles. At force levels above 10% of maximal voluntary contraction, the firing rate was inversely related to the number of spindles in a muscle, with the slope of the relationship increasing with force. The maximal recruitment threshold of motor units increased linearly with the number of spindles in the muscle. Thus, muscles with a greater number of spindles had lower firing rates and a greater maximal recruitment threshold. These findings may be explained by a mechanical interaction between muscle fibres and adjacent spindles. During low-level (0% to 10%) voluntary contractions, muscle fibres of recruited motor units produce force twitches that activate nearby spindles to respond with an immediate excitatory feedback that reaches maximal level. As the force increases further, the twitches overlap and tend towards tetanization, the muscle fibres shorten, the spindles slacken, their excitatory firings decrease, and the net excitation to the homonymous motoneurons decreases. Motoneurons of muscles with greater number of spindles receive a greater decrease in excitation which reduces their firing rates, increases their maximal recruitment threshold, and changes the motoneuron recruitment distribution.

  16. Impaired motoneuronal retrograde transport in two models of SBMA implicates two sites of androgen action.

    PubMed

    Kemp, Michael Q; Poort, Jessica L; Baqri, Rehan M; Lieberman, Andrew P; Breedlove, S Marc; Miller, Kyle E; Jordan, Cynthia L

    2011-11-15

    Spinal and bulbar muscular atrophy (SBMA) impairs motor function in men and is linked to a CAG repeat mutation in the androgen receptor (AR) gene. Defects in motoneuronal retrograde axonal transport may critically mediate motor dysfunction in SBMA, but the site(s) where AR disrupts transport is unknown. We find deficits in retrograde labeling of spinal motoneurons in both a knock-in (KI) and a myogenic transgenic (TG) mouse model of SBMA. Likewise, live imaging of endosomal trafficking in sciatic nerve axons reveals disease-induced deficits in the flux and run length of retrogradely transported endosomes in both KI and TG males, demonstrating that disease triggered in muscle can impair retrograde transport of cargo in motoneuron axons, possibly via defective retrograde signaling. Supporting the idea of impaired retrograde signaling, we find that vascular endothelial growth factor treatment of diseased muscles reverses the transport/trafficking deficit. Transport velocity is also affected in KI males, suggesting a neurogenic component. These results demonstrate that androgens could act via both cell autonomous and non-cell autonomous mechanisms to disrupt axonal transport in motoneurons affected by SBMA.

  17. Emerging Roles of Filopodia and Dendritic Spines in Motoneuron Plasticity during Development and Disease

    PubMed Central

    Kanjhan, Refik; Noakes, Peter G.; Bellingham, Mark C.

    2016-01-01

    Motoneurons develop extensive dendritic trees for receiving excitatory and inhibitory synaptic inputs to perform a variety of complex motor tasks. At birth, the somatodendritic domains of mouse hypoglossal and lumbar motoneurons have dense filopodia and spines. Consistent with Vaughn's synaptotropic hypothesis, we propose a developmental unified-hybrid model implicating filopodia in motoneuron spinogenesis/synaptogenesis and dendritic growth and branching critical for circuit formation and synaptic plasticity at embryonic/prenatal/neonatal period. Filopodia density decreases and spine density initially increases until postnatal day 15 (P15) and then decreases by P30. Spine distribution shifts towards the distal dendrites, and spines become shorter (stubby), coinciding with decreases in frequency and increases in amplitude of excitatory postsynaptic currents with maturation. In transgenic mice, either overexpressing the mutated human Cu/Zn-superoxide dismutase (hSOD1G93A) gene or deficient in GABAergic/glycinergic synaptic transmission (gephyrin, GAD-67, or VGAT gene knockout), hypoglossal motoneurons develop excitatory glutamatergic synaptic hyperactivity. Functional synaptic hyperactivity is associated with increased dendritic growth, branching, and increased spine and filopodia density, involving actin-based cytoskeletal and structural remodelling. Energy-dependent ionic pumps that maintain intracellular sodium/calcium homeostasis are chronically challenged by activity and selectively overwhelmed by hyperactivity which eventually causes sustained membrane depolarization leading to excitotoxicity, activating microglia to phagocytose degenerating neurons under neuropathological conditions. PMID:26843990

  18. Extrasynaptic α6 Subunit-Containing GABAA Receptors Modulate Excitability in Turtle Spinal Motoneurons

    PubMed Central

    Andres, Carmen; Aguilar, Justo; González-Ramírez, Ricardo; Elias-Viñas, David; Felix, Ricardo; Delgado-Lezama, Rodolfo

    2014-01-01

    Motoneurons are furnished with a vast repertoire of ionotropic and metabotropic receptors as well as ion channels responsible for maintaining the resting membrane potential and involved in the regulation of the mechanisms underlying its membrane excitability and firing properties. Among them, the GABAA receptors, which respond to GABA binding by allowing the flow of Cl− ions across the membrane, mediate two distinct forms of inhibition in the mature nervous system, phasic and tonic, upon activation of synaptic or extrasynaptic receptors, respectively. In a previous work we showed that furosemide facilitates the monosynaptic reflex without affecting the dorsal root potential. Our data also revealed a tonic inhibition mediated by GABAA receptors activated in motoneurons by ambient GABA. These data suggested that the high affinity GABAA extrasynaptic receptors may have an important role in motor control, though the molecular nature of these receptors was not determined. By combining electrophysiological, immunofluorescence and molecular biology techniques with pharmacological tools here we show that GABAA receptors containing the α6 subunit are expressed in adult turtle spinal motoneurons and can function as extrasynaptic receptors responsible for tonic inhibition. These results expand our understanding of the role of GABAA receptors in motoneuron tonic inhibition. PMID:25531288

  19. Does alpha-motoneurone size correlate with motor unit type in cat triceps surae?

    PubMed

    Ulfhake, B; Kellerth, J O

    1982-11-18

    The cell bodies and first-order dendrites of alpha-motoneurones supplying different functional types of muscle units in the cat gastrocnemius (type FF, FR and S units) and soleus (type SOL-S units) muscles, were studied after intracellular injection of horseradish peroxidase. The SOL-S neurones had smaller values for cell body diameter in comparison with both the FF and FR neurones. The SOL-S neurones also had significantly thinner first-order dendrites than the FF, FR and S neurones. In the gastrocnemius pool the S neurones had smaller values for dendritic diameters than the FF and FR cells. The values for combined diameter of the first-order dendrites indicated that the dendritic trees of the FF and FR neurones are, on the average, larger than those of the S and SOL-S neurones. Furthermore, the relationship between the combined dendritic diameter and the mean soma diameter, indicated that a difference in relative scaling of soma and dendrites exists between the FF and FR neurones on the one hand and the S and SOL-S neurones on the other. Similar results were obtained also when relating the combined dendritic parameter sigma d3/2 to the soma surface area. Although a certain statistical relation seems to exist between motoneurone size and motoneurone type, it should be emphasized, however, that the range of values for each parameter studied overlapped considerably between the different types of motoneurones.

  20. Effects of Motoneuron Properties on Reflex Stability in Spastic Subjects: A Simulation Study

    DTIC Science & Technology

    2007-11-02

    was tested using a comprehensive model of the reflex pathway. This model included the passive and active components of the triceps surae muscles...became unstable and oscillations developed similar to those observed in spastic patients. In parallel, when reflex delay times typical for triceps ... surae in man were chosen, and motoneuron excitability increased progressively, oscillatory ankle movements were readily elicited. Conversely, as pathway

  1. Sensitization of neonatal rat lumbar motoneuron by the inflammatory pain mediator bradykinin

    PubMed Central

    Bouhadfane, Mouloud; Kaszás, Attila; Rózsa, Balázs; Harris-Warrick, Ronald M; Vinay, Laurent; Brocard, Frédéric

    2015-01-01

    Bradykinin (Bk) is a potent inflammatory mediator that causes hyperalgesia. The action of Bk on the sensory system is well documented but its effects on motoneurons, the final pathway of the motor system, are unknown. By a combination of patch-clamp recordings and two-photon calcium imaging, we found that Bk strongly sensitizes spinal motoneurons. Sensitization was characterized by an increased ability to generate self-sustained spiking in response to excitatory inputs. Our pharmacological study described a dual ionic mechanism to sensitize motoneurons, including inhibition of a barium-sensitive resting K+ conductance and activation of a nonselective cationic conductance primarily mediated by Na+. Examination of the upstream signaling pathways provided evidence for postsynaptic activation of B2 receptors, G protein activation of phospholipase C, InsP3 synthesis, and calmodulin activation. This study questions the influence of motoneurons in the assessment of hyperalgesia since the withdrawal motor reflex is commonly used as a surrogate pain model. DOI: http://dx.doi.org/10.7554/eLife.06195.001 PMID:25781633

  2. F-wave of single firing motor units: correct or misleading criterion of motoneuron excitability in humans?

    PubMed

    Kudina, Lydia P; Andreeva, Regina E

    2017-03-01

    Motoneuron excitability is a critical property for information processing during motor control. F-wave (a motoneuronal recurrent discharge evoked by a motor antidromic volley) is often used as a criterion of motoneuron pool excitability in normal and neuromuscular diseases. However, such using of F-wave calls in question. The present study was designed to explore excitability of single low-threshold motoneurons during their natural firing in healthy humans and to ascertain whether F-wave is a correct measure of motoneuronal excitability. Single motor units (MUs) were activated by gentle voluntary muscle contractions. MU peri-stimulus time histograms and motoneuron excitability changes within a target interspike interval were analysed during testing by motor antidromic and Ia-afferent volleys. It was found that F-waves could be occasionally recorded in some low-threshold MUs. However, during evoking F-wave, in contrast with the H-reflex, peri-stimulus time histograms revealed no statistically significant increase in MU discharge probability. Moreover, surprisingly, motoneurons appeared commonly incapable to fire a recurrent discharge within the most excitable part of a target interval. Thus, the F-wave, unlike the H-reflex, is the incorrect criterion of motoneuron excitability resulting in misleading conclusions. However, it does not exclude the validity of the F-wave as a clinical tool for other aims. It was concluded that the F-wave was first explored in low-threshold MUs during their natural firing. The findings may be useful at interpretations of changes in the motoneuron pool excitability in neuromuscular diseases.

  3. Calcium imaging of motoneuron activity in the en-bloc spinal cord preparation of the neonatal rat.

    PubMed

    Lev-Tov, A; O'Donovan, M J

    1995-09-01

    1. This paper describes the use of calcium imaging to monitor patterns of activity in neonatal rat motoneurons retrogradely labeled with the calcium-sensitive dye, calcium green-dextran. 2. Pressure ejection of calcium green-dextran into ventral roots and into the surgically peeled ventrolateral funiculi (VLF) at the lumbar cord labeled spinal motoneurons and interneurons. The back labeled motoneurons often formed two or three discrete clusters of cells. 3. Fluorescent changes (10-20%) could be detected in labeled motoneurons after a single antidromic stimulus of the segmental ventral root. These changes progressively increased in amplitude during stimulus trains (1-5 s) at frequencies from 5 to 50 Hz, presumably reflecting a frequency-dependent increase in free intracellular calcium. 4. Stimulation of the ipsilateral VLF at the caudal lumbar level (L6), elicited frequency-dependent, synaptically induced motoneuronal discharge. Frequency-dependent fluorescent changes could be detected in calcium green-labeled motoneurons during the VLF-induced synaptic activation. 5. The spatial spread of synaptic activity among calcium green-labeled clusters of motoneurons could be resolved after dorsal root stimulation. Low-intensity stimulation of the roots produced fluorescence changes restricted to the lateral clusters of motoneurons. With increasing stimulation intensity the fluorescence change increased in the lateral cells and could spread into the medial motoneuronal group. After a single supramaximal stimulus a similar pattern was observed with activity beginning laterally and spreading medially. 6. Substantial changes in fluorescence of calcium green-labeled motoneurons were also observed during motoneuron bursting induced by bath application of the glycine receptor antagonist strychnine or the potassium channel blocker 4-aminopyridine (4-AP). 7. Our results show that membrane-impermeant fluorescent calcium indicators can be used as a tool to study the activity of

  4. Discharge profiles of abducens, accessory abducens, and orbicularis oculi motoneurons during reflex and conditioned blinks in alert cats.

    PubMed

    Trigo, J A; Gruart, A; Delgado-García, J M

    1999-04-01

    The discharge profiles of identified abducens, accessory abducens, and orbicularis oculi motoneurons have been recorded extra- and intracellularly in alert behaving cats during spontaneous, reflexively evoked, and classically conditioned eyelid responses. The movement of the upper lid and the electromyographic activity of the orbicularis oculi muscle also were recorded. Animals were conditioned by short, weak air puffs or 350-ms tones as conditioned stimuli (CS) and long, strong air puffs as unconditioned stimulus (US) using both trace and delayed conditioning paradigms. Motoneurons were identified by antidromic activation from their respective cranial nerves. Orbicularis oculi and accessory abducens motoneurons fired an early, double burst of action potentials (at 4-6 and 10-16 ms) in response to air puffs or to the electrical stimulation of the supraorbital nerve. Orbicularis oculi, but not accessory abducens, motoneurons fired in response to flash and tone presentations. Only 10-15% of recorded abducens motoneurons fired a late, weak burst after air puff, supraorbital nerve, and flash stimulations. Spontaneous fasciculations of the orbicularis oculi muscle and the activity of single orbicularis oculi motoneurons that generated them also were recorded. The activation of orbicularis oculi motoneurons during the acquisition of classically conditioned eyelid responses happened in a gradual, sequential manner. Initially, some putative excitatory synaptic potentials were observed in the time window corresponding to the CS-US interval; by the second to the fourth conditioning session, some isolated action potentials appeared that increased in number until some small movements were noticed in eyelid position traces. No accessory abducens motoneuron fired and no abducens motoneuron modified their discharge rate for conditioned eyelid responses. The firing of orbicularis oculi motoneurons was related linearly to lid velocity during reflex blinks but to lid position during

  5. Electrical coupling synchronises spinal motoneuron activity during swimming in hatchling Xenopus tadpoles.

    PubMed

    Zhang, Hong-Yan; Li, Wen-Chang; Heitler, William J; Sillar, Keith T

    2009-09-15

    The role of electrical coupling between neurons in the swimming rhythm generator of Xenopus embryos has been studied using pharmacological blockade of gap junctions. A conspicuous effect of 18beta-glycyrrhetinic acid (18beta-GA) and carbenoxolone, which have been shown to block electrical coupling in this preparation, was to increase the duration of ventral root bursts throughout the spinal cord during swimming. The left-right coordination, the swimming frequency and the duration of swimming episodes were not affected by concentrations of 18beta-GA which significantly increased burst durations. However, the longitudinal coupling was affected such that 18beta-GA led to a significant correlation between rostrocaudal delays and cycle periods, which is usually only present in older larval animals. Patch clamp recordings from spinal motoneurons tested whether gap junction blockers affect the spike timing and/or firing pattern of motoneurons during fictive swimming. In the presence of 18beta-GA motoneurons continued to fire a single, but broader action potential in each cycle of swimming, and the timing of their spikes relative to the ventral root burst became more variable. 18beta-GA had no detectable effect on the resting membrane potential of motoneurons, but led to a significant increase in input resistance, consistent with the block of gap junctions. This effect did not result in increased firing during swimming, despite the fact that multiple spikes can occur in response to current injection. Applications of 18beta-GA at larval stage 42 had no discernible effect on locomotion. The results, which suggest that electrical coupling primarily functions to synchronize activity in synergistic motoneurons during embryo swimming, are discussed in the context of motor system development.

  6. Eye Movements and Abducens Motoneuron Behavior During Cholinergically Induced REM Sleep

    PubMed Central

    Marquez-Ruiz, Javier; Escudero, Miguel

    2009-01-01

    Study objectives: The injection of cholinergic drugs in the pons has been largely used to induce REM sleep as a useful model to study different processes during this period. In the present study, microinjections of carbachol in the nucleus reticularis pontis oralis (NRPO) were performed to test the hypothesis that eye movements and the behavior of extraocular motoneurons during induced REM sleep do not differ from those during spontaneous REM sleep. Methods: Six female adult cats were prepared for chronic recording of eye movements (by means of the search-coil technique) and electroencephalography, electromyography, ponto-geniculo-occipital (PGO) waves at the lateral geniculate nucleus, and identified abducens motoneuron activities after microinjections of the cholinergic agonist carbachol into the NRPO. Results: Unilateral microinjections (n = 13) of carbachol in the NRPO induced REM sleep-like periods in which the eyes performed a convergence and downward rotation interrupted by phasic complex rapid eye movements associated to PGO waves. During induced-REM sleep abducens motoneurons lost their tonic activity and eye position codification, but continued codifying eye velocity during the burst of eye movements. Conclusion: The present results show that eye movements and the underlying behavior of abducens motoneurons are very similar to those present during natural REM sleep. Thus, microinjection of carbachol seems to activate the structures responsible for the exclusive oculomotor behavior observed during REM sleep, validating this pharmacological model and enabling a more efficient exploration of phasic and tonic phenomena underlying eye movements during REM sleep. Citation: Marquez-Ruiz J; Escudero M. Eye movements and abducens motoneuron behavior during cholinergically induced REM sleep. SLEEP 2009;32(4):471–481. PMID:19413141

  7. Repeated Baclofen treatment ameliorates motor dysfunction, suppresses reflex activity and decreases the expression of signaling proteins in reticular nuclei and lumbar motoneurons after spinal trauma in rats.

    PubMed

    Kucharíková, Andrea; Schreiberová, Andrea; Závodská, Monika; Gedrová, Štefánia; Hricová, Ľudmila; Pavel, Jaroslav; Gálik, Ján; Maršala, Martin; Lukáčová, Nadežda

    2014-03-01

    The interruption of supraspinal input to the spinal cord leads to motor dysfunction and the development of spasticity. Clinical studies have shown that Baclofen (a GABAB agonist), while effective in modulating spasticity is associated with side-effects and the development of tolerance. The aim of the present study was to assess if discontinued Baclofen treatment and its repeated application leads antispasticity effects, and whether such changes affect neuronal nitric oxide synthase (nNOS) in the brainstem, nNOS and parvalbumin (PV) in lumbar α-motoneurons and glial fibrillary acidic protein in the ventral horn of the spinal cord. Adult male Wistar rats were exposed to Th9 spinal cord transection. Baclofen (30mg/b.w.) diluted in drinking water, was administered for 6 days, starting at week 1 after injury and then repeated till week 4 after injury. The behavior of the animals was tested (tail-flick test, BBB locomotor score) from 1 to 8 weeks. Our results clearly indicate the role of nitric oxide, produced by nNOS in the initiation and the maintenance of spasticity states 1, 6 and 8 weeks after spinal trauma. A considerable decrease of nNOS staining after Baclofen treatment correlates with improvement of motor dysfunction. The findings also show that parvalbumin and astrocytes participate in the regulation of ion concentrations in the sub-acute phase after the injury.

  8. Influence of the paraventricular nucleus and oxytocin on the retrograde stain of pubococcygeus muscle motoneurons in male rats.

    PubMed

    Pérez, César Antonio; Concha, Adriana; Hernández, María Elena; Manzo, Jorge

    2005-04-11

    Lumbosacral cord motoneurons innervating the pubococcygeus muscle (Pcm) at the pelvic floor of male rats were analyzed. We showed previously that these motoneurons participate in sexual functions and are sensitive to fluctuations of systemic androgen and estrogen. Though estrogen receptors have not been identified in Lamina IX at these spinal areas, the release of oxytocin from the paraventricular nucleus of the hypothalamus (PvN) has been found to control pelvic sexual physiology. We therefore worked on the hypothesis that steroid hormones in the PvN induce the release of oxytocin at the lumbosacral level to modulate the function of Pcm motoneurons. Four experiments were developed, and results were observed with the retrograde staining of motoneurons with horseradish peroxidase. Data indicated that morphometric parameters of Pcm motoneurons were significantly reduced after castration or blocking of the steroids at the PvN site, or following complete transection of the spinal cord at the T8 level. In each case, the reduction of the stain was recovered after intrathecal treatment with oxytocin. Thus, present results show that Pcm motoneurons respond to spinal oxytocin. The conclusive model that we propose is that steroids stimulate the PvN, causing the nucleus to release oxytocin at the level of the lumbosacral spinal cord, and the release of the peptide regulates the spread of the stain of Pcm motoneurons. This work also shows that motoneurons distal to a transected area in the spinal cord could respond to exogenous oxytocin, an important finding for the research of spinal cord lesioned subjects.

  9. Excitatory effect of histamine on rat spinal motoneurons by activation of both H₁ and H₂ receptors in vitro.

    PubMed

    Wu, Guan-Yi; Han, Xiao-Hu; Zhuang, Qian-Xing; Zhang, Jun; Yung, Wing-Ho; Chan, Ying-Shing; Zhu, Jing-Ning; Wang, Jian-Jun

    2012-01-01

    The central histaminergic nervous system, originating from the tuberomammillary nucleus of the hypothalamus, widely innervates almost the whole brain as well as the spinal cord. However, the effect of histamine on spinal motoneurons, the final common path for motor control, is still unknown. By using 8-14-day-old rat spinal slice preparations and intracellular recordings, the effect of histamine on motoneurons in lumbar spinal cord and the underlying mechanisms were studied. Bath application of histamine (30-300 μM) induced a membrane depolarization in the majority of recorded spinal motoneurons (78/90, 86%). Perfusing slices with tetrodotoxin or low-Ca(2+) /high-Mg(2+) medium did not block the histamine-induced excitation, indicating a direct postsynaptic action of histamine on motoneurons. Separate application of the selective histamine H(1) receptor antagonist mepyramine or the selective histamine H(2) receptor antagonist ranitidine partially suppressed the histamine-induced excitation, whereas a combination of ranitidine and mepyramine totally blocked the excitatory effect of histamine on motoneurons. On the other hand, both the selective histamine H(1) receptor agonist 2-pyridylethylamine and the selective histamine H(2) receptor agonist dimaprit mimicked the excitation of histamine on spinal motoneurons. These agonist-induced excitations were also blocked by mepyramine or ranitidine. Furthermore, histamine affected membrane input resistance and potentiated repetitive firing behavior of spinal motoneurons. These results demonstrate that histamine excites rat spinal motoneurons via the histamine H(1) and H(2) receptors and increases their excitability, suggesting that the hypothalamospinal histaminergic fibers may directly modulate final motor outputs and actively regulate ongoing motor execution andspinal motor reflexes.

  10. Electrical interaction between antidromically stimulated frog motoneurones and dorsal root afferents: enhancement by gallamine and TEA

    PubMed Central

    Grinnell, Alan D.

    1970-01-01

    1. Electrical interactions have been studied in the isolated frog spinal cord preparation. It is found that gallamine and tetraethylammonium chloride (TEA) markedly enhance all non-cholinergic synaptic interactions, including the electrical interaction between motoneurones (VR-VRP). In addition, in the presence of either of these drugs, a short-latency interaction is seen to exist between antidromically stimulated motoneurones and dorsal root afferents (early VR-DRP). The early VR-DRP is rarely seen in the absence of gallamine or TEA. 2. The early VR-DRP is of the same short latency as the VR-VRP and fulfils the same criteria for electrical interaction: it increases in amplitude with cooling from 17-10° C, it is not blocked by a wide variety of pharmacological blocking agents, and it is suppressed by both Mg2+ and Ca2+, with no antagonism of action between the two. 3. The early VR-DRP appears as a cluster of unitary events: all-or-none spikes conducted out the dorsal root fibres. No initial graded slow potentials are seen. Often there are two peaks in the response. 4. The early VR-DRP is facilitated by a dorsal root volley, with a time course normally intermediate between that of the orthodromic ventral root potential (DR-VRP) and the dorsal root potential (DR-DRP). This orthodromic facilitation apparently is achieved by increasing invasion of motoneurone dendritic trees and depolarization of dorsal root afferents toward threshold. 5. If the same ventral root is stimulated twice, or adjacent roots stimulated at different intervals, the second early VR-DRP, like the VR-VRP, is seen to be occluded for 10-20 msec, then facilitated to supranormal amplitudes. It is concluded that motoneurone dendrites are presynaptic to both interactions. 6. Evidence is presented that gallamine and TEA act by increasing the duration of activity both in axon terminals and in antidromically invaded motoneurones. Often second or multiple spikes result. The increased duration of

  11. Bone marrow transplantation in hindlimb muscles of motoneuron degenerative mice reduces neuronal death and improves motor function.

    PubMed

    Pastor, Diego; Viso-León, Mari Carmen; Botella-López, Arancha; Jaramillo-Merchan, Jesus; Moraleda, Jose M; Jones, Jonathan; Martínez, Salvador

    2013-06-01

    Bone marrow has proved to be an adequate source of stem cells for the treatment of numerous disorders, including neurodegenerative diseases. Bone marrow can be easily and relatively painlessly extracted from a patient or allogenic donor and then transplanted into the degenerative area. Here, the grafted cells will activate a number of mechanisms in order to protect, repair, and/or regenerate the damaged tissue. These properties make the bone marrow a feasible source for cell therapy. In this work, we transplanted bone marrow cells into a mouse model of motoneuron degeneration, with the particularity of placing the cells in the hindlimb muscles rather than in the spinal cord where neuronal degeneration occurs. To this end, we analyze the possibility for the transplanted cells to increase the survival rate of the spinal cord motoneurons by axonal-guided retrograde neurotrophism. As a result, the mice significantly improved their motor functions. This coincided with an increased number of motoneurons innervating the treated muscle compared with the neurons innervating the non-treated contralateral symmetric muscle. In addition, we detected an increase in glial-derived neurotrophic factor in the spinal cord, a neurotrophic factor known to be involved in the rescue of degenerating motoneurons, exerting a neuroprotective effect. Thus, we have proved that bone marrow injected into the muscles is capable of rescuing these motoneurons from death, which may be a possible therapeutic approach for spinal cord motoneuron degenerative diseases, such as amyotrophic lateral sclerosis.

  12. Restricted patterns of Hoxd10 and Hoxd11 set segmental differences in motoneuron subtype complement in the lumbosacral spinal cord

    PubMed Central

    Misra, Mala; Shah, Veeral; Carpenter, Ellen; McCaffery, Peter; Lance-Jones, Cynthia

    2009-01-01

    During normal vertebrate development, Hoxd10 and Hoxd11 are expressed by differentiating motoneurons in restricted patterns along the rostrocaudal axis of the lumbosacral (LS) spinal cord. To assess the roles of these genes in the attainment of motoneuron subtypes characteristic of LS subdomains, we examined subtype complement after overexpression of Hoxd10 or Hoxd11 in the embryonic chick LS cord and in a Hoxd10 loss-of-function mouse embryo. Data presented here provide evidence that Hoxd10 defines the position of the lateral motor column (LMC) as a whole and, in rostral LS segments, specifically promotes the development of motoneurons of the lateral subdivision of the lateral motor column (LMCl). In contrast, Hoxd11 appears to impart a caudal and medial LMC (LMCm) identity to some motoneurons and molecular profiles suggestive of a suppression of LMC development in others. We also provide evidence that Hoxd11 suppresses the expression of Hoxd10 and the retinoic acid synthetic enzyme, retinaldehyde dehydrogenase 2 (RALDH2). In a normal chick embryo, Hoxd10 and RALDH2 are expressed throughout the LS region at early stages of motoneuron differentiation but their levels decline in Hoxd11-expressing caudal LS segments that ultimately contain few LMCl motoneurons. We hypothesize that one of the roles played by Hoxd11 is to modulate Hoxd10 and local retinoic acid levels and thus, perhaps define the caudal boundaries of the LMC and its subtype complement. PMID:19306865

  13. The influence of a 5-wk whole body vibration on electrophysiological properties of rat hindlimb spinal motoneurons.

    PubMed

    Baczyk, M; Hałuszka, A; Mrówczyński, W; Celichowski, J; Krutki, P

    2013-06-01

    The study aimed at determining the influence of a whole body vibration (WBV) on electrophysiological properties of spinal motoneurons. The WBV training was performed on adult male Wistar rats, 5 days a week, for 5 wk, and each daily session consisted of four 30-s runs of vibration at 50 Hz. Motoneuron properties were investigated intracellularly during experiments on deeply anesthetized animals. The experimental group subjected to the WBV consisted of seven rats, and the control group of nine rats. The WBV treatment induced no significant changes in the passive membrane properties of motoneurons. However, the WBV-evoked adaptations in excitability and firing properties were observed, and they were limited to fast-type motoneurons. A significant decrease in rheobase current and a decrease in the minimum and the maximum currents required to evoke steady-state firing in motoneurons were revealed. These changes resulted in a leftward shift of the frequency-current relationship, combined with an increase in slope of this curve. The functional relevance of the described adaptive changes is the ability of fast motoneurons of rats subjected to the WBV to produce series of action potentials at higher frequencies in a response to the same intensity of activation. Previous studies proved that WBV induces changes in the contractile parameters predominantly of fast motor units (MUs). The data obtained in our experiment shed a new light to possible explanation of these results, suggesting that neuronal factors also play a substantial role in MU adaptation.

  14. Inhibitory synaptic drive patterns motoneuronal activity in rhythmic preparations of isolated thoracic ganglia in the stick insect.

    PubMed

    Büschges, A

    1998-02-09

    During active leg movements of an insect leg, the activity of the motoneuron pools of each individual leg joint is generated by the interaction between signals from central rhythm generating sources, peripheral signals as well as coordinating signals from other leg joints and legs. The nature of the synaptic drive from the central rhythm generators onto the motoneuron pools of the individual leg joints during rhythmic motor activity of the stick insect (Carausius morosus) middle leg has been investigated. In the isolated mesothoracic ganglion central rhythm generators were activated pharmacologically by topical application of the muscarinic agonist pilocarpine. Motoneurons supplying the femur-tibia (FT) joint were investigated in detail. Recordings from neuropil processes of these motoneurons revealed that patterning of their rhythmic activity is based on cyclic hyperpolarizing synaptic inputs. These inputs are in clear antiphase for extensor and flexor motoneurons. DCC (discontinuous current clamp) and dSEVC (discontinuous single electrode voltage clamp) recordings showed reversal potentials of the inhibitory inputs between -80 to -85 mV (FETi, N=7; Flex MN, N=3). After intracellular injection of TEA rhythmic inhibition in FETi was decreased by about 84% (N=4). Both findings indicate that the cyclic inhibition is mediated by potassium ions. Thus, it appears that central rhythm generators pattern motor activity in antagonistic tibial motoneuron pools by cyclic alternating inhibition.

  15. Potassium currents dynamically set the recruitment and firing properties of F-type motoneurons in neonatal mice

    PubMed Central

    Lamotte d'Incamps, Boris; Zytnicki, Daniel

    2015-01-01

    In neonatal mice, fast- and slow-type motoneurons display different patterns of discharge. In response to a long liminal current pulse, the discharge is delayed up to several seconds in fast-type motoneurons and their firing frequency accelerates. In contrast, slow-type motoneurons discharge immediately, and their firing frequency decreases at the beginning of the pulse. Here, we identify the ionic currents that underlie the delayed firing of fast-type motoneurons. We find that the firing delay is caused by a combination of an A-like potassium current that transiently suppresses firing on a short time scale and a slowly-inactivating potassium current that inhibits the discharge over a much longer time scale. We then show how these intrinsic currents dynamically shape the discharge threshold and the frequency-input function of fast-type motoneurons. These currents contribute to the orderly recruitment of motoneurons in neonates and might play a role in the postnatal maturation of motor units. PMID:26269551

  16. Bone Marrow Transplantation in Hindlimb Muscles of Motoneuron Degenerative Mice Reduces Neuronal Death and Improves Motor Function

    PubMed Central

    Viso-León, Mari Carmen; Botella-López, Arancha; Jaramillo-Merchan, Jesus; Moraleda, Jose M.; Jones, Jonathan; Martínez, Salvador

    2013-01-01

    Bone marrow has proved to be an adequate source of stem cells for the treatment of numerous disorders, including neurodegenerative diseases. Bone marrow can be easily and relatively painlessly extracted from a patient or allogenic donor and then transplanted into the degenerative area. Here, the grafted cells will activate a number of mechanisms in order to protect, repair, and/or regenerate the damaged tissue. These properties make the bone marrow a feasible source for cell therapy. In this work, we transplanted bone marrow cells into a mouse model of motoneuron degeneration, with the particularity of placing the cells in the hindlimb muscles rather than in the spinal cord where neuronal degeneration occurs. To this end, we analyze the possibility for the transplanted cells to increase the survival rate of the spinal cord motoneurons by axonal-guided retrograde neurotrophism. As a result, the mice significantly improved their motor functions. This coincided with an increased number of motoneurons innervating the treated muscle compared with the neurons innervating the non-treated contralateral symmetric muscle. In addition, we detected an increase in glial-derived neurotrophic factor in the spinal cord, a neurotrophic factor known to be involved in the rescue of degenerating motoneurons, exerting a neuroprotective effect. Thus, we have proved that bone marrow injected into the muscles is capable of rescuing these motoneurons from death, which may be a possible therapeutic approach for spinal cord motoneuron degenerative diseases, such as amyotrophic lateral sclerosis. PMID:23282201

  17. Increased intramuscular nerve branching and inhibition of programmed cell death of chick embryo motoneurons by immunoglobulins from patients with motoneuron disease.

    PubMed

    Hernández, Sara; Texidó, Laura; Calderó, Jordi; Ciutat, Dolors; Piedrafita, Lídia; Casanovas, Anna; Blasi, Joan; Solsona, Carles; Povedano, Mònica; Rojas, Ricardo; Illa, Isabel; Caress, James; Prevette, David; Oppenheim, Ronald W; Milligan, Carol; Esquerda, Josep E

    2010-12-15

    Massive programmed cell death (PCD) of developing chick embryo motoneurons (MNs) occurs in a well defined temporal and spatial sequence between embryonic day (E) 6 and E10. We have found that, when administered in ovo, either circulating immunoglobulins G (IgGs) or cerebrospinal fluid from patients with MN disease can rescue a significant number of chick embryo MNs from normally occurring PCD. An increase of branching of intramuscular nerves was also observed that may account for the rescuing effects of pathologic IgGs. Proteomic analysis and further analysis by ELISA indicated that these effects may be mediated by the interaction of circulating human immunoglobulins with proteins of the semaphorin family.

  18. The lumbar cord location of the motoneurons innervating psoas and iliacus muscles: a single and double labeling study in the female Syrian golden hamster.

    PubMed

    Gerrits, P O; Boers, J; Holstege, G

    1997-11-21

    The spinal cord location of the motoneurons innervating the psoas and iliacus muscles was determined in the golden hamster. The results of single and double labeling studies, using the retrograde tracers horseradish peroxidase (HRP) and cholera toxin B-subunit (CTB), showed that both psoas and iliacus motoneurons were present ventrolaterally in the ventral horn in the caudal L1 to rostral L5 lumbar spinal segments with their motoneurons intermingled in one cell group. Further retrograde tracing studies demonstrated abdominal muscle motoneurons ventrolaterally in the ventral horn of the L1 and upper L2 segments. Double labeling experiments revealed that at these levels (caudal L1 and rostral L2), the abdominal muscle motoneurons were located dorsomedial to the psoas and iliacus motoneurons.

  19. Involvement of brain-derived neurotrophic factor and sonic hedgehog in the spinal cord plasticity after neurotoxic partial removal of lumbar motoneurons.

    PubMed

    Gulino, Rosario; Gulisano, Massimo

    2012-07-01

    Adult mammals could spontaneously achieve a partial sensory-motor recovery after spinal cord injury, by mechanisms including synaptic plasticity. We previously showed that this recovery is associated to the expression of synapsin-I, and that sonic hedgehog and Notch-1 could be also involved in plasticity. The role of brain-derived neurotrophic factor and glutamate receptors in regulating synaptic efficacy has been explored in the last decade but, although these mechanisms are now well-defined in the brain, the molecular mechanisms underlying the so called "spinal learning" are still less clear. Here, we measured the expression levels of choline acetyltransferase, synapsin-I, sonic hedgehog, Notch-1, glutamate receptor subunits (GluR1, GluR2, GluR4, NMDAR1) and brain-derived neurotrophic factor, in a motoneuron-depleted mouse spinal lesion model obtained by intramuscular injection of cholera toxin-B saporin. The lesion caused the down-regulation of the majority of analysed proteins. Moreover, we found that in lesioned but not in control spinal tissue, synapsin-I expression is associated to that of both brain-derived neurotrophic factor and sonic hedgehog, whereas GluR2 expression is linked to that of Shh. These results suggest that brain-derived neurotrophic factor and sonic hedgehog could collaborate in modulating synaptic plasticity after the removal of motoneurons, by a mechanism involving both pre- and post-synaptic processes. Interestingly, the involvement of sonic hedgehog showed here is novel, and offers new routes to address spinal cord plasticity and repair.

  20. Descending pathways to the cutaneus trunci muscle motoneuronal cell group in the cat

    NASA Technical Reports Server (NTRS)

    Holstege, Gert; Blok, Bertil F.

    1989-01-01

    The descending pathways to the motoneuronal cell group of the cutaneous trunci muscle (CTM) of the cat were investigated by injecting H-3-labeled lucine into the brain stem, the diencephalon, or the C1, C2, C6, and C8 segments of the spinal cord, and examining fixed autoradiographic sections of the spinal cord and brain regions. Results demonstrate presence of specific supraspinal projectons to the CTM motor nucleus originating in the contralateral nucleus retroambiguous and the ipsilateral dorsolateral pontine tegmentum. Results also suggest that propriospinal pathways to the CTM motor nucleus originating in the cervical cord do not exist, although these propriospinal projections to all other motoneuronal cell groups surrounding the CTM nucleus are very strong.

  1. Neuropathology in respiratory-related motoneurons in young Pompe (Gaa(-/-)) mice.

    PubMed

    Turner, Sara M F; Hoyt, Aaron K; ElMallah, Mai K; Falk, Darin J; Byrne, Barry J; Fuller, David D

    2016-06-15

    Respiratory and/or lingual dysfunction are among the first motor symptoms in Pompe disease, a disorder resulting from absence or dysfunction of the lysosomal enzyme acid α-glucosidase (GAA). Here, we histologically evaluated the medulla, cervical and thoracic spinal cords in 6 weeks old asymptomatic Pompe (Gaa(-/-)) mice to determine if neuropathology in respiratory motor regions has an early onset. Periodic acid-Schiff (PAS) staining indicated glycogen accumulation was exclusively occurring in Gaa(-/-) hypoglossal, mid-cervical and upper thoracic motoneurons. Markers of DNA damage (Tunel) and ongoing apoptosis (Cleaved Caspase 3) did not co-localize with PAS staining, but were prominent in a medullary region which included the nucleus tractus solitarius, and also in the thoracic spinal dorsal horn. We conclude that respiratory-related motoneurons are particularly susceptible to GAA deficiency and that neuronal glycogen accumulation and neurodegeneration may occur independently in early stage disease. The data support early therapeutic intervention in Pompe disease.

  2. The ER proteostasis network in ALS: Determining the differential motoneuron vulnerability.

    PubMed

    Rozas, Pablo; Bargsted, Leslie; Martínez, Francisca; Hetz, Claudio; Medinas, Danilo B

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal late-onset neurodegenerative disease characterized by the selective loss of motoneurons. The mechanisms underlying neuronal degeneration in ALS are starting to be elucidated, highlighting abnormal protein aggregation and altered mRNA metabolism as common phenomena. ALS involves the selective vulnerablility of a subpopulation of motoneurons, suggesting that intrinsic factors may determine ALS pathogenesis. Accumulating evidence indicates that alterations to endoplasmic reticulum (ER) proteostasis play a critical role on disease progression, representing one of the earliests pathological signatures of the disease. Here we discuss recent studies uncovering a fundamental role of ER stress as the driver of selective neuronal vulnerability in ALS and discuss the potential of targeting the unfolded protein response (UPR) as a therapeutic strategy to treat ALS.

  3. Multiple ionic mechanisms mediate inhibition of rat motoneurones by inhalation anaesthetics

    PubMed Central

    Sirois, Jay E; Pancrazio, Joseph J; Lynch, Carl; Bayliss, Douglas A

    1998-01-01

    We studied the effects of inhalation anaesthetics on the membrane properties of hypoglossal motoneurones in a neonatal rat brainstem slice preparation. In current clamp, halothane caused a membrane hyperpolarization that was invariably associated with decreased input resistance; in voltage clamp, halothane induced an outward current and increased input conductance. Qualitatively similar results were obtained with isoflurane and sevoflurane. The halothane current reversed near the predicted K+ equilibrium potential (EK) and was reduced in elevated extracellular K+ and in the presence of Ba2+ (2 mm). Moreover, the Ba2+-sensitive component of halothane current was linear and reversed near EK. The halothane current was not sensitive to glibenclamide or thyrotropin-releasing hormone (TRH). Therefore, the halothane current was mediated, in part, by activation of a Ba2+-sensitive K+ current distinct from the ATP- and neurotransmitter-sensitive K+ currents in hypoglossal motoneurones. Halothane also inhibited Ih, a hyperpolarization-activated cationic current; this was primarily due to a decrease in the absolute amount of current, although halothane also caused a small, but statistically significant, shift in the voltage dependence of Ih activation. Extracellular Cs+ (3 mm) blocked Ih and a component of halothane-sensitive current with properties reminiscent of Ih. A small component of halothane current, resistant to Ba2+ and Cs+, was observed in TTX-containing solutions at potentials depolarized to ∼−70 mV. Partial Na+ substitution by N-methyl-D-glucamine completely abolished this residual current, indicating that halothane also inhibited a TTX-resistant Na+ current active near rest potentials. Thus, halothane activates a Ba2+-sensitive, relatively voltage-independent K+ current and inhibits both Ih and a TTX-insensitive persistent Na+ current in hypoglossal motoneurones. These effects of halothane decrease motoneuronal excitability and may contribute to the

  4. Eye Movements and Abducens Motoneuron Behavior after Cholinergic Activation of the Nucleus Reticularis Pontis Caudalis

    PubMed Central

    Márquez-Ruiz, Javier; Escudero, Miguel

    2010-01-01

    Study Objectives: The aim of this work was to characterize eye movements and abducens (ABD) motoneuron behavior after cholinergic activation of the nucleus reticularis pontis caudalis (NRPC). Methods: Six female adult cats were prepared for chronic recording of eye movements (using the scleral search-coil technique), electroencephalography, electromyography, ponto-geniculo-occipital (PGO) waves in the lateral geniculate nucleus, and ABD motoneuron activities after microinjections of the cholinergic agonist carbachol into the NRPC. Results: Unilateral microinjections of carbachol in the NRPC induced tonic and phasic phenomena in the oculomotor system. Tonic effects consisted of ipsiversive rotation to the injected side, convergence, and downward rotation of the eyes. Phasic effects consisted of bursts of rhythmic rapid eye movements directed contralaterally to the injected side along with PGO-like waves in the lateral geniculate and ABD nuclei. Although tonic effects were dependent on the level of drowsiness, phasic effects were always present and appeared along with normal saccades when the animal was vigilant. ABD motoneurons showed phasic activities associated with ABD PGO-like waves during bursts of rapid eye movements, and tonic and phasic activities related to eye position and velocity during alertness. Conclusion The cholinergic activation of the NRPC induces oculomotor phenomena that are somewhat similar to those described during REM sleep. A precise comparison of the dynamics and timing of the eye movements further suggests that a temporal organization of both NRPCs is needed to reproduce the complexity of the oculomotor behavior during REM sleep. Citation: Márquez-Ruiz J; Escudero M. Eye movements and abducens motoneuron behavior after cholinergic activation of the nucleus reticularis pontis caudalis. SLEEP 2010;33(11):1517-1527. PMID:21102994

  5. Corticospinal Inputs to Primate Motoneurons Innervating the Forelimb from Two Divisions of Primary Motor Cortex and Area 3a

    PubMed Central

    Witham, Claire L.; Fisher, Karen M.; Edgley, Steve A.

    2016-01-01

    Previous anatomical work in primates has suggested that only corticospinal axons originating in caudal primary motor cortex (“new M1”) and area 3a make monosynaptic cortico-motoneuronal connections with limb motoneurons. By contrast, the more rostral “old M1” is proposed to control motoneurons disynaptically via spinal interneurons. In six macaque monkeys, we examined the effects from focal stimulation within old and new M1 and area 3a on 135 antidromically identified motoneurons projecting to the upper limb. EPSPs with segmental latency shorter than 1.2 ms were classified as definitively monosynaptic; these were seen only after stimulation within new M1 or at the new M1/3a border (incidence 6.6% and 1.3%, respectively; total n = 27). However, most responses had longer latencies. Using measures of the response facilitation after a second stimulus compared with the first, and the reduction in response latency after a third stimulus compared with the first, we classified these late responses as likely mediated by either long-latency monosynaptic (n = 108) or non-monosynaptic linkages (n = 108). Both old and new M1 generated putative long-latency monosynaptic and non-monosynaptic effects; the majority of responses from area 3a were non-monosynaptic. Both types of responses from new M1 had significantly greater amplitude than those from old M1. We suggest that slowly conducting corticospinal fibers from old M1 generate weak late monosynaptic effects in motoneurons. These may represent a stage in control of primate motoneurons by the cortex intermediate between disynaptic output via an interposed interneuron seen in nonprimates and the fast direct monosynaptic connections present in new M1. SIGNIFICANCE STATEMENT The corticospinal tract in Old World primates makes monosynaptic connections to motoneurons; previous anatomical work suggests that these connections come only from corticospinal tract (CST) neurons in the subdivision of primary motor cortex within the

  6. Comparison of cell body size and oxidative enzyme activity in motoneurons between the cervical and lumbar segments in the rat spinal cord after spaceflight and recovery.

    PubMed

    Ishihara, A; Yamashiro, J; Matsumoto, A; Higashibata, A; Ishioka, N; Shimazu, T; Ohira, Y

    2006-03-01

    The cell body sizes and succinate dehydrogenase (SDH) activities of motoneurons in the dorsolateral region of the ventral horn at the cervical and lumbar segments in the rat spinal cord were determined following 9 days of spaceflight with or without 10 days of recovery on Earth. The motoneurons were divided into three types based on their cell body sizes; small-, medium-, and large-sized motoneurons. In control rats, there was no difference in the cell body size or SDH activity of small- and large-sized motoneurons between the cervical and lumbar segments. The SDH activity of medium-sized motoneurons in control rats was higher in the lumbar segment than in the cervical segment, while the cell body sizes of medium-sized motoneurons were identical. The SDH activity of medium-sized motoneurons in the lumbar segment decreased to a level similar to that in the cervical segment of control rats following spaceflight. In addition, the decreased SDH activity of medium-sized motoneurons persisted for at least 10 days of recovery on Earth. It is concluded that spaceflight selectively affects the SDH activity of medium-sized motoneurons in the lumbar segment of the spinal cord, which presumably innervate skeletal muscles having an antigravity function.

  7. Axon-somatic back-propagation in detailed models of spinal alpha motoneurons

    PubMed Central

    Balbi, Pietro; Martinoia, Sergio; Massobrio, Paolo

    2015-01-01

    Antidromic action potentials following distal stimulation of motor axons occasionally fail to invade the soma of alpha motoneurons in spinal cord, due to their passing through regions of high non-uniformity. Morphologically detailed conductance-based models of cat spinal alpha motoneurons have been developed, with the aim to reproduce and clarify some aspects of the electrophysiological behavior of the antidromic axon-somatic spike propagation. Fourteen 3D morphologically detailed somata and dendrites of cat spinal alpha motoneurons have been imported from an open-access web-based database of neuronal morphologies, NeuroMorpho.org, and instantiated in neurocomputational models. An axon hillock, an axonal initial segment and a myelinated axon are added to each model. By sweeping the diameter of the axonal initial segment (AIS) and the axon hillock, as well as the maximal conductances of sodium channels at the AIS and at the soma, the developed models are able to show the relationships between different geometric and electrophysiological configurations and the voltage attenuation of the antidromically traveling wave. In particular, a greater than usually admitted sodium conductance at AIS is necessary and sufficient to overcome the dramatic voltage attenuation occurring during antidromic spike propagation both at the myelinated axon-AIS and at the AIS-soma transitions. PMID:25729362

  8. Supraspinal control of a short-latency cutaneous pathway to hindlimb motoneurons.

    PubMed

    Fleshman, J W; Rudomin, P; Burke, R E

    1988-01-01

    The effects of two supraspinal systems on transmission through a short latency hindlimb cutaneous reflex pathway were studied in cats anesthetized with pentobarbital or alpha-chloralose. Fleshman et al. (1984) described a mixed excitatory-inhibitory input from low threshold superficial peroneal (SP) afferents to flexor digitorum longus (FDL) motoneurons with central latencies so short as to suggest a disynaptic component in the initial excitatory phase of the PSP. In the present study, conditioning stimulation of either the red nucleus (RN) or the pyramidal tract (PT) caused a marked decrease in latency and increase in amplitude of both the excitatory and inhibitory components of the SP PSP in FDL motoneurons and several other motoneuron species. The minimal central latencies of the conditioned initial excitatory phase of the PSPs were on the order of 1.5 ms, consistent with the possibility of a disynaptic linkage. The facilitatory effects of RN and PT conditioning were observed in both anesthetic conditions, although preparation-specific differences in latency were observed. Lesion experiments suggested that the interneurons involved in this pathway are located caudal to the L5 segment, most likely in segments L6 and L7.

  9. The projection of jaw elevator muscle spindle afferents to fifth nerve motoneurones in the cat.

    PubMed Central

    Appenteng, K; O'Donovan, M J; Somjen, G; Stephens, J A; Taylor, A

    1978-01-01

    1. By spike-triggered averaging of intracellular synaptic noise it has been shown in pentobarbitone anaesthetized cats that jaw elevator muscle spindle afferents with their cell bodies in the mid-brain have a relatively weak monosynaptic projection to masseter and temporalis motoneurones. 2. Extending the spike-triggered averaging method to recording extracellular excitatory field potentials it has been shown that virtually all the spindles do project monosynaptically to the motoneurone pool. It is concluded that the general weakness of the projection is due to its restriction to a small proportion of the motoneurones, possibly those concerned most with tonic postural functions. 3. The shape of individual intracellular e.p.s.p.s together with the spatial distribution of extracellular excitatory potential fields provide some evidence for a dentrically weighted distribution of the synapses. 4. Evidence is presented that both primary- and secondary-type spindle afferents project monosynaptically, the secondary effects being some 71% of the strength of the primary ones. PMID:149860

  10. Glutamatergic motoneurons in the stomatogastric ganglion of the mantis shrimp Squilla oratoria.

    PubMed

    Chiba, C; Tazaki, K

    1992-07-01

    1. Transmitters of motoneurons in the stomatogastric ganglion (STG) of Squilla were identified by analyzing the excitatory neuromuscular properties of muscles in the posterior cardiac plate (pcp) and pyloric regions. 2. Bath and iontophoretic applications of glutamate produce depolarizations in these muscles. The pharmacological experiments and desensitization of the junctional receptors elucidate the glutamatergic nature of the excitatory junctional potentials (EJPs) evoked in the constrictor and dilator muscles. The reversal potentials for the excitatory junctional current (EJC) and for the glutamate-induced current are almost the same. 3. Some types of dilator muscle show sensitivity to both glutamate and acetylcholine (ACh) exogenously applied. The pharmacological evidence and desensitization of the junctional receptors indicate the glutamatergic nature of neuromuscular junctions in these dually sensitive muscles. The reversal potentials for the EJC and for the ACh-induced current are not identical. 4. Glutamate is a candidate as an excitatory neuro-transmitter at the neuromuscular junctions which the STG motoneurons named PCP, PY, PD, LA and VC make with the identified muscles. Kainic and quisqualic acids which act on glutamate receptors are potent excitants of these muscles. Extrajunctional receptors to ACh are present in two types of the muscle innervated by LA and VC. 5. Neurotransmitters used by the STG motoneurons of stomatopods are compared to those of decapods.

  11. The projection of jaw elevator muscle spindle afferents to fifth nerve motoneurones in the cat.

    PubMed

    Appenteng, K; O'Donovan, M J; Somjen, G; Stephens, J A; Taylor, A

    1978-06-01

    1. By spike-triggered averaging of intracellular synaptic noise it has been shown in pentobarbitone anaesthetized cats that jaw elevator muscle spindle afferents with their cell bodies in the mid-brain have a relatively weak monosynaptic projection to masseter and temporalis motoneurones. 2. Extending the spike-triggered averaging method to recording extracellular excitatory field potentials it has been shown that virtually all the spindles do project monosynaptically to the motoneurone pool. It is concluded that the general weakness of the projection is due to its restriction to a small proportion of the motoneurones, possibly those concerned most with tonic postural functions. 3. The shape of individual intracellular e.p.s.p.s together with the spatial distribution of extracellular excitatory potential fields provide some evidence for a dentrically weighted distribution of the synapses. 4. Evidence is presented that both primary- and secondary-type spindle afferents project monosynaptically, the secondary effects being some 71% of the strength of the primary ones.

  12. Neuroprotective effects of N-acetyl-cysteine and acetyl-L-carnitine after spinal cord injury in adult rats.

    PubMed

    Karalija, Amar; Novikova, Liudmila N; Kingham, Paul J; Wiberg, Mikael; Novikov, Lev N

    2012-01-01

    Following the initial acute stage of spinal cord injury, a cascade of cellular and inflammatory responses will lead to progressive secondary damage of the nerve tissue surrounding the primary injury site. The degeneration is manifested by loss of neurons and glial cells, demyelination and cyst formation. Injury to the mammalian spinal cord results in nearly complete failure of the severed axons to regenerate. We have previously demonstrated that the antioxidants N-acetyl-cysteine (NAC) and acetyl-L-carnitine (ALC) can attenuate retrograde neuronal degeneration after peripheral nerve and ventral root injury. The present study evaluates the effects of NAC and ALC on neuronal survival, axonal sprouting and glial cell reactions after spinal cord injury in adult rats. Tibial motoneurons in the spinal cord were pre-labeled with fluorescent tracer Fast Blue one week before lumbar L5 hemisection. Continuous intrathecal infusion of NAC (2.4 mg/day) or ALC (0.9 mg/day) was initiated immediately after spinal injury using Alzet 2002 osmotic minipumps. Neuroprotective effects of treatment were assessed by counting surviving motoneurons and by using quantitative immunohistochemistry and Western blotting for neuronal and glial cell markers 4 weeks after hemisection. Spinal cord injury induced significant loss of tibial motoneurons in L4-L6 segments. Neuronal degeneration was associated with decreased immunostaining for microtubular-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker GFAP and microglial marker OX42 was increased. Treatment with NAC and ALC rescued approximately half of the motoneurons destined to die. In addition, antioxidants restored MAP2 and synaptophysin immunoreactivity. However, the perineuronal synaptophysin labeling was not recovered. Although both treatments promoted axonal sprouting, there was no effect on reactive astrocytes. In contrast, the

  13. Chloride-sensitive MEQ fluorescence in chick embryo motoneurons following manipulations of chloride and during spontaneous network activity.

    PubMed

    Chub, Nikolai; Mentis, George Z; O'donovan, Michael J

    2006-01-01

    Intracellular Cl(-) ([Cl(-)](in)) homeostasis is thought to be an important regulator of spontaneous activity in the spinal cord of the chick embryo. We investigated this idea by visualizing the variations of [Cl(-)](in) in motoneurons retrogradely labeled with the Cl-sensitive dye 6-methoxy-N-ethylquinolinium iodide (MEQ) applied to cut muscle nerves in the isolated E10-E12 spinal cord. This labeling procedure obviated the need for synthesizing the reduced, cell-permeable dihydro-MEQ (DiH-MEQ). The specificity of motoneuron labeling was confirmed using retrograde co-labeling with Texas Red Dextran and immunocytochemistry for choline acetyltransferase (ChAT). In MEQ-labeled motoneurons, the GABA(A) receptor agonist isoguvacine (100 muM) increased somatic and dendritic fluorescence by 7.4 and 16.7%, respectively. The time course of this fluorescence change mirrored that of the depolarization recorded from the axons of the labeled motoneurons. Blockade of the inward Na(+)/K(-)/2Cl(-) co-transporter (NKCC1) with bumetanide (20 microM) or with a low-Na(+) bath solution (12 mM), increased MEQ fluorescence by 5.3 and 11.4%, respectively, consistent with a decrease of [Cl(-)](in). After spontaneous episodes of activity, MEQ fluorescence increased and then declined to the pre-episode level during the interepisode interval. The largest fluorescence changes occurred over motoneuron dendrites (19.7%) with significantly smaller changes (5.2%) over somata. Collectively, these results show that retrogradely loaded MEQ can be used to detect [Cl(-)](in) in motoneurons, that the bumetanide-sensitive NKCC1 co-transporter is at least partially responsible for the elevated [Cl(-)](in) of developing motoneurons, and that dendritic [Cl(-)](in) decreases during spontaneous episodes and recovers during the inter-episode interval, presumably due to the action of NKCC1.

  14. Organization of the sural cutaneous input regulating the discharge of triceps surae gamma-motoneurones in the cat.

    PubMed

    Ellaway, P H; Davey, N J; Ljubisavljevic, M

    1997-01-01

    The organization of the cutaneous afferent influence on the discharge of gamma-motoneurones has been investigated in the decerebrated, spinal cat. gamma-Motoneurone discharges were recorded from cut nerve filaments. Time and frequency domain analyses were used to reveal the strength of coupling between gamma-motoneurone discharge and cutaneous afferents excited by natural skin stimulation. Time domain analysis (cross-correlation) was also used to reveal the sigh (facilitation or inhibition) and time course of the cutaneous influence on individual gamma-motoneurones. Mechanical stimulation of discrete areas of skin within the sural nerve field caused facilitation or inhibition of individual gamma-motoneurones supplying the gastrocnemius and soleus muscles. In a few cases, a gamma-motoneurone facilitated by stimulation at one site could be inhibited from another location. The effect of cutaneous afferent stimulation was not evident in the decerebrated cat with intact spinal cord. The intensity of facilitation and inhibition was mapped for the sural nerve field. Facilitation had focus of highest intensity to stimulation applied between the calcaneum and lateral malleolus. The focus for inhibition was either the same as for facilitation or, more frequently, tended to be lateral and dorsal to the calcaneum at the edge of the sural field. Cutaneous stimulation at the edge of the sural field could also reduce the coherence between the discharges of gamma-motoneurones, particularly at low frequencies of association (1-5 Hz), indicating disfacilitation of other sources of afferent input. The results reveal a detailed pattern of cutaneous inputs to the fusimotor system that could participate in a wide range of behavioural adjustments to stretch or contact of the skin at the heel.

  15. Ammodytoxins efficiently release arachidonic acid and induce apoptosis in a motoneuronal cell line in an enzymatic activity-dependent manner.

    PubMed

    Jenko-Pražnikar, Zala; Petan, Toni; Pungerčar, Jože

    2013-03-01

    Secreted phospholipases A2 (sPLA2s) are phospholipolytic enzymes and receptor ligands whose action affects cell death and survival. We have previously shown that ammodytoxin A (AtxA), a snake venom sPLA2, is rapidly internalized into motoneuronal NSC34 cells, inducing characteristic neurotoxic sPLA2 cell damage and apoptosis. In this study, we have analyzed the role of sPLA2 enzymatic activity, including arachidonic acid (AA) release, in the induction of motoneuronal apoptosis by AtxA and homologous recombinant sPLA2s with different enzymatic properties: an AtxA mutant (V31W) with very high enzymatic activity, enzymatically inactive S49-sPLA2 (ammodytin L, AtnL), its mutant (LW) with restored enzymatic activity, and non-toxic, enzymatically active sPLA2 (AtnI2). Addition of AA, AtxA, AtxA-V31W and AtnL-LW, but not AtnL and AtnI2, to NSC34 cells resulted in caspase-3 activation, DNA fragmentation and disruption of mitochondrial membrane potential, leading to a significant and rapid decrease in motoneuronal cell viability that was not observed in C2C12 myoblasts and HEK293 cells. AtxA, AtxA-V31W and AtnL-LW, but not AtnL and AtnI2, also liberated large amounts of AA specifically from motoneuronal cells, and this ability correlated well with the ability to induce apoptotic changes and decrease cell viability. The enzymatic activity of AtxA and similar sPLA2s is thus necessary, but not sufficient, for inducing motoneuronal apoptosis. This suggests that specific binding to the motoneuronal cell surface, followed by internalization and enzymatic activity-dependent induction of apoptosis, possibly as a consequence of extensive extra- and intracellular AA release, is necessary for Atx-induced motoneuronal cell death.

  16. Static γ-motoneurones couple group Ia and II afferents of single muscle spindles in anaesthetised and decerebrate cats

    PubMed Central

    Gladden, M H; Matsuzaki, H

    2002-01-01

    Ideas about the functions of static γ-motoneurones are based on the responses of primary and secondary endings to electrical stimulation of single static γ-axons, usually at high frequencies. We compared these effects with the actions of spontaneously active γ-motoneurones. In anaesthetised cats, afferents and efferents were recorded in intramuscular nerve branches to single muscle spindles. The occurrence of γ-spikes, identified by a spike shape recognition system, was linked to video-taped contractions of type-identified intrafusal fibres in the dissected muscle spindles. When some static γ-motoneurones were active at low frequency (< 15 Hz) they coupled the firing of group Ia and II afferents. Activity of other static γ-motoneurones which tensed the intrafusal fibres appeared to enhance this effect. Under these conditions the secondary ending responded at shorter latency than the primary ending. In another series of experiments on decerebrate cats, responses of primary and secondary endings of single muscle spindles to activation of γ-motoneurones by natural stimuli were compared with their responses to electrical stimulation of single γ-axons supplying the same spindle. Electrical stimulation mimicked the natural actions of γ-motoneurones on either the primary or the secondary ending, but not on both together. However, γ-activity evoked by natural stimuli coupled the firing of afferents with the muscle at constant length, and also when it was stretched. Analysis showed that the timing and tightness of this coupling determined the degree of summation of excitatory postsynaptic potentials (EPSPs) evoked by each afferent in α-motoneurones and interneurones contacted by terminals of both endings, and thus the degree of facilitation of reflex actions of group II afferents. PMID:12181298

  17. A modelling study of locomotion-induced hyperpolarization of voltage threshold in cat lumbar motoneurones

    PubMed Central

    Dai, Yue; Jones, Kelvin E; Fedirchuk, Brent; McCrea, David A; Jordan, Larry M

    2002-01-01

    During fictive locomotion the excitability of adult cat lumbar motoneurones is increased by a reduction (a mean hyperpolarization of ≈6.0 mV) of voltage threshold (Vth) for action potential (AP) initiation that is accompanied by only small changes in AP height and width. Further examination of the experimental data in the present study confirms that Vth lowering is present to a similar degree in both the hyperpolarized and depolarized portions of the locomotor step cycle. This indicates that Vth reduction is a modulation of motoneurone membrane currents throughout the locomotor state rather than being related to the phasic synaptic input within the locomotor cycle. Potential ionic mechanisms of this locomotor-state-dependent increase in excitability were examined using three five-compartment models of the motoneurone innervating slow, fast fatigue resistant and fast fatigable muscle fibres. Passive and active membrane conductances were set to produce input resistance, rheobase, afterhyperpolarization (AHP) and membrane time constant values similar to those measured in adult cat motoneurones in non-locomoting conditions. The parameters of 10 membrane conductances were then individually altered in an attempt to replicate the hyperpolarization of Vth that occurs in decerebrate cats during fictive locomotion. The goal was to find conductance changes that could produce a greater than 3 mV hyperpolarization of Vth with only small changes in AP height (< 3 mV) and width (< 1.2 ms). Vth reduction without large changes in AP shape could be produced either by increasing fast sodium current or by reducing delayed rectifier potassium current. The most effective Vth reductions were achieved by either increasing the conductance of fast sodium channels or by hyperpolarizing the voltage dependency of their activation. These changes were particularly effective when localized to the initial segment. Reducing the conductance of delayed rectifier channels or depolarizing their

  18. Improved lentiviral transduction of ALS motoneurons in vivo via dual targeting.

    PubMed

    O'Leary, Valerie B; Ovsepian, Saak V; Bodeker, Macdara; Dolly, J Oliver

    2013-11-04

    Treatment of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, is hampered by its complex etiology and lack of efficient means for targeted transfer of therapeutics into motoneurons. The objective of this research was engineering of a versatile motoneuron targeting adapter--a full-length atoxic tetanus toxin fused to core-streptavidin (CS-TeTIM)--for retro-axonal transduction of viral vectors; validation of the targeting efficiency of CS-TeTIM in vivo, by expression of green fluorescence protein (GFP) reporter in motoneurons of presymptomatic and symptomatic ALS-like SOD1(G93A) mice, and comparison with age-matched controls; and appraisal of lentiviral transduction with CS-TeTIM relative to (1) a HC binding fragment of tetanus toxin CS-TeTx(HC), (2) rabies glycoprotein (RG), and (3) a CS-TeTIM-RG dual targeting approach. CS-TeTIM and CS-TeTx(HC) were engineered using recombinant technology and site-directed mutagenesis. Biotinylated vectors, pseudotyped with vesicular stomatitis virus glycoprotein (VSV-G) or RG, were linked to these adaptors and injected intraperitoneally (ip) into presymptomatic (12 weeks old), symptomatic SOD1(G93A) (22 weeks old) or wild type control mice, followed by monitoring of GFP expression in the spinal cord and supraspinal motor structures with quantitative PCR and immuno-histochemistry. Transcripts were detected in the spinal cord and supraspinal motor structures of all mice 2 weeks after receiving a single ip injection, although in symptomatic SOD1(G93A) animals reporter RNA levels were lower compared to presymptomatic and wild-type controls irrespective of the targeting approach. GFP transduction with CS-TeTIM proved more efficient than CS-TeTx(HC) across all groups while CS-TeTIM-RG dual-targeted vectors yielded the highest transcript numbers. Importantly, in both wild-type and presymptomatic SOD1(G93A) mice strong colabeling of choline-acetyltransferase (ChAT) and GFP was visualized in neurons of the

  19. Control by Preynaptic Correlation: a mechanism affecting information transmission from Ia fibers to motoneurons.

    PubMed

    Rudomin, P; Burke, R E; Núñez, R; Madrid, J; Dutton, H

    1975-03-01

    1. In the unanesthetized spinal cord of the cat, simultaneous intracellular recordings were made from two motoneurons belonging to the gastronemius motor nucleus. 2. Supramaximal iterative stimulation of small branches of the gastrocnemius nerve produced monosynaptic EPSPs (Ia EPSPs) of varying amplitude superimposed on a fluctuating base line. 3. In most cases the variance of the motoneuron membrane potential was increased above base-line levels with a time course approximately matching the Ia EPSP. This suggests that Ia EPSP fluctuations are greater than can be accounted for by the base-line fluctuations alone. 4. For a given series of Ia EPSPs, the smaller responses in the series had about the same decay phase as the larger EPSPs, suggesting that most of the Ia EPSP fluctuations were not due to systematic changes in postsynaptic conductances produced by ongoing activity, but rather to a presynaptic mechanism. 5. Simultaneous recording from two motoneurons showed that base-line fluctuations were positively correlated. In most cases, however, there was an additional increased correlation above base-line levels resembling the time course of the Ia EPSPs, indicating positive correlation between EPSP fluctuations which is attributed to a presynaptic mechanism. 6. Conditioning volleys to group I muscle afferents or to low-threshold cutaneous afferents reduced the variance of the Ia EPSPs and also their correlation in motoneuron pairs, often without changing the mean Ia EPSPs. 7. It is concluded that, in the unanesthetized spinal cord, in addition to the random process which governs transmitter release intrinsic to a given synaptic terminal, there is another stochastic process affecting, in a correlated manner, transmitter release in large sets of Ia synaptic terminals. Most likely, the correlation in transmitter release is achieved by membrane potential fluctuations imposed on the Ia terminal arborizations by ongoing activity of the segmental mechanism mediating

  20. Mechanism and function of mixed-mode oscillations in vibrissa motoneurons.

    PubMed

    Golomb, David

    2014-01-01

    Vibrissa motoneurons in the facial nucleus innervate the intrinsic and extrinsic muscles that move the whiskers. Their intrinsic properties affect the way they process fast synaptic input from the vIRT and Bötzinger nuclei together with serotonergic neuromodulation. In response to constant current (I(app)) injection, vibrissa motoneurons may respond with mixed mode oscillations (MMOs), in which sub-threshold oscillations (STOs) are intermittently mixed with spikes. This study investigates the mechanisms involved in generating MMOs in vibrissa motoneurons and their function in motor control. It presents a conductance-based model that includes the M-type K+ conductance, g(M), the persistent Na+ conductance, g(NaP), and the cationic h conductance, g(h). For g(h) = 0 and moderate values of g(M) and g(NaP), the model neuron generates STOs, but not MMOs, in response to I(app) injection. STOs transform abruptly to tonic spiking as the current increases. In addition to STOs, MMOs are generated for g(h)>0 for larger values of I(app); the I(app) range in which MMOs appear increases linearly with g(h). In the MMOs regime, the firing rate increases with I(app) like a Devil's staircase. Stochastic noise disrupts the temporal structure of the MMOs, but for a moderate noise level, the coefficient of variation (CV) is much less than one and varies non-monotonically with I(app). Furthermore, the estimated time period between voltage peaks, based on Bernoulli process statistics, is much higher in the MMOs regime than in the tonic regime. These two phenomena do not appear when moderate noise generates MMOs without an intrinsic MMO mechanism. Therefore, and since STOs do not appear in spinal motoneurons, the analysis can be used to differentiate different MMOs mechanisms. MMO firing activity in vibrissa motoneurons suggests a scenario in which moderate periodic inputs from the vIRT and Bötzinger nuclei control whisking frequency, whereas serotonergic neuromodulation controls

  1. The pattern of excitation of human lower limb motoneurones by probable group II muscle afferents

    PubMed Central

    Simonetta-Moreau, M; Marque, P; Marchand-Pauvert, V; Pierrot-Deseilligny, E

    1999-01-01

    Heteronymous group II effects were investigated in the human lower limb. Changes in firing probability of single motor units in quadriceps (Q), biceps (Bi), semitendinosus (ST), gastrocnemius medialis (GM) and tibialis anterior (TA) were studied after electrical stimuli between 1 and 3 times motor threshold (MT) applied to common peroneal (CP), superficial (SP) and deep (DP) peroneal, Bi and GM nerves in those nerve-muscle combinations without recurrent inhibition. Stimulation of the CP and Bi nerves evoked in almost all of the explored Q motor units a biphasic excitation with a low-threshold early peak, attributable to non-monosynaptic group I excitation, and a higher threshold late peak. When the CP nerve was cooled (or the stimulation applied to a distal branch, DP), the increase in latency was greater for the late than for the early peak, indicating that the late excitation is due to stimulation of afferents with a slower conduction velocity than group I fibres, presumably in the group II range. In ST motor units the group II excitation elicited by stimulation of the GM and SP nerves was particularly large and frequent, and the non-monosynaptic group I excitation was often replaced by an inhibition. A late group II-induced excitation from CP to Q motoneurones and from GM and SP to ST motoneurones was also observed when using the H reflex as a test. The electrical threshold and conduction velocity of the largest diameter fibres evoking the group II excitation were estimated to be 2·1 and 0·65 times those of the fastest Ia afferents, respectively. In the combinations tested in the present investigation the group II input seemed to be primarily of muscle origin. The potent heteronymous group II excitation of motoneurones of both flexors and extensors of the knee contrasted with the absence of a group II effect from DP to GM and from GM to TA. In none of the combinations explored was there any evidence for group II inhibition of motoneurones. The possible

  2. The electrical geometry, electrical properties and synaptic connections onto rat V motoneurones in vitro.

    PubMed Central

    Curtis, J C; Appenteng, K

    1993-01-01

    1. We have developed a tissue slice preparation which allows the study of the actions of single presynaptic neurones onto single trigeminal motoneurones in the immature rat. Our aim in this first stage of the work has been to assess the validity of this preparation as a model for responses obtained in vivo from trigeminal motoneurones in adult rats. We have quantified the integrative properties of the motoneurones and also the variability in transmission at synapses of single presynaptic neurones onto the motoneurones. This data has then been compared to similar published data obtained from adult (rat) trigeminal motoneurones in vivo. 2. Quantitative reconstructions were made of the morphology of three motoneurones which had been labelled with biocytin by intracellular injection. The neurones gave off six to nine dendrites, of mean length 522 microns (S.D. = 160; n = 22), which branched on average 10.5 times to produce 11.45 end-terminations per dendrite (S.D. = 8.57; n = 22). The mean surface area of the dendrites was 0.92 x 10(4) microns2 (S.D. = 0.67; n = 22), and, for individual cells, the ratio of the combined dendritic surface area to the total neuronal surface area ranged from 98.3 to 99.2% (n = 3). At dendritic branch points the ratio of the summed diameters of the daughter dendrites to the 3/2 power against the parent dendrite to the 3/2 power was 1.09 (S.D. = 0.21; n = 217), allowing branch points to be collapsed into a single cylinder. The equivalent cylinder diameter of the combined dendritic tree remained approximately constant over the proximal 25-40% of the equivalent electrical length of the dendritic tree and then showed tapering. The tapering could be ascribed to termination of dendrites at different electrical distances from the soma. 3. Electrical properties were determined for a total of eighty-seven motoneurones, all with membrane potentials more negative than 60 mV (mean = 66.0 mV; S.D. = 5.2) and spikes which overshot zero (mean spike

  3. Intracellular autogenetic and synergistic effects of muscular contraction on flexor motoneurones

    PubMed Central

    Green, D. G.; Kellerth, J.-O.

    1967-01-01

    1. Intracellular records have been taken from cat motoneurones innervating flexor muscles of the hind limb. Contractions of the ankle flexors tibialis anterior and extensor digitorum longus were elicited by stimulation of the peripheral end of the cut L 7 ventral root and the reflex effects of these contractions were recorded in silent and repetitively firing motoneurones. 2. Contraction usually produces a hyperpolarizing response inside flexor motoneurones. This hyperpolarization is tension-sensitive in the sense that when, at constant muscle extension, the strength of the contraction is increased, the magnitude of the inhibitory response is augmented. 3. Increasing the resting length of the muscles, while using a stimulus of constant strength to the ventral root, causes this inhibitory response to increase in some cells. More often, however, the hyperpolarization caused by contraction is gradually reduced in duration and/or amplitude as the muscles are extended. 4. Even with the muscles slackened, so that they develop no tension at their ends, contraction usually produces prominent hyperpolarization of the motoneurones. 5. By passing polarizing currents or injecting chloride ions through the intracellular micro-electrode, the hyperpolarizing potentials produced by contraction of the slack and extended muscles are shown to be, at least in part, genuinely post-synaptic inhibitory events. 6. When the neurone is fired repetitively by injected current, the `silent period' in contraction corresponds to the hyperpolarization of the post-synaptic membrane. 7. Monosynaptic testing of the flexor motoneurone pool has been used to confirm the essential features of the intracellularly recorded activity. 8. Acutely spinalizing the animal increases the magnitude of the inhibitory responses caused by contraction. 9. Recordings from dorsal root fibres show that Golgi tendon organs of the ankle flexors are very sensitive to contraction and are indeed often activated by the

  4. Motoneuronal pre-compensation for the low-pass filter characteristics of muscle. A quantitative appraisal in cat muscle units.

    PubMed

    Baldissera, F; Cavallari, P; Cerri, G

    1998-09-01

    1. The relevance of motoneurone dynamic sensitivity in compensating for the low-pass filter properties of muscle was assessed by stimulating cat muscle units (MUs) with impulse discharges generated by two current-to-rate converters: (i) a spinal motoneurone, sensitive to both the input intensity and its first derivative, and (ii) a linear current-to-rate converter, i.e. a neurone model with the same static sensitivity as the motoneurone but lacking dynamic sensitivity. 2. Discharges generated by injection of sine-wave currents in three motoneurones of the 'fast' type and in the three related model versions were applied to the axon of forty-six MUs. The MU isometric tension was modulated at the frequency of the current sine wave (0.5-20 Hz). Phase and gain of the current-to-force transduction were measured. 3. When MUs were driven by the model, the force lagged the current by 90 deg at 1 Hz in slow MUs and at around 5 Hz in fast MUs. Under motoneurone drive, the 90 deg phase lag was attained at frequencies about twice as high. 4. The gain of the transduction (peak-to-peak force modulation/peak-to-peak current modulation) decayed when the modulation frequency was increased. In all but five units, the cut-off frequency, Fco (gain attenuated by -3 dB), was higher when the unit was motoneurone driven (FcoCell) then when it was model driven (FcoMod). In both conditions, Fco was inversely correlated with the MU's time-to-peak. The advantage conferred by the motoneurone dynamic sensitivity was expressed by the Fco ratio (FcoCell/FcoMod). Across the MU population this ratio ranged from 0. 6-2.8, was inversely correlated with the time-to peak, and was directly correlated with the half-tension rate, i.e. the impulse rate at which MUs develop 50 % of their maximal tetanic force. The largest improvement (Fco ratio > 2.0) was found in units with mechanical features similar to those presumably coupled 'in vivo' to the motoneurones utilized for stimulation. 5. This estimate was

  5. FUS Mislocalization and Vulnerability to DNA Damage in ALS Patients Derived hiPSCs and Aging Motoneurons

    PubMed Central

    Higelin, Julia; Demestre, Maria; Putz, Stefan; Delling, Jan P.; Jacob, Christian; Lutz, Anne-Kathrin; Bausinger, Julia; Huber, Anne-Kathrin; Klingenstein, Moritz; Barbi, Gotthold; Speit, Günter; Huebers, Annemarie; Weishaupt, Jochen H.; Hermann, Andreas; Liebau, Stefan; Ludolph, Albert C.; Boeckers, Tobias M.

    2016-01-01

    Mutations within the FUS gene (Fused in Sarcoma) are known to cause Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease affecting upper and lower motoneurons. The FUS gene codes for a multifunctional RNA/DNA-binding protein that is primarily localized in the nucleus and is involved in cellular processes such as splicing, translation, mRNA transport and DNA damage response. In this study, we analyzed pathophysiological alterations associated with ALS related FUS mutations (mFUS) in human induced pluripotent stem cells (hiPSCs) and hiPSC derived motoneurons. To that end, we compared cells carrying a mild or severe mFUS in physiological- and/or stress conditions as well as after induced DNA damage. Following hyperosmolar stress or irradiation, mFUS hiPS cells recruited significantly more cytoplasmatic FUS into stress granules accompanied by impaired DNA-damage repair. In motoneurons wild-type FUS was localized in the nucleus but also deposited as small punctae within neurites. In motoneurons expressing mFUS the protein was additionally detected in the cytoplasm and a significantly increased number of large, densely packed FUS positive stress granules were seen along neurites. The amount of FUS mislocalization correlated positively with both the onset of the human disease (the earlier the onset the higher the FUS mislocalization) and the maturation status of the motoneurons. Moreover, even in non-stressed post-mitotic mFUS motoneurons clear signs of DNA-damage could be detected. In summary, we found that the susceptibility to cell stress was higher in mFUS hiPSCs and hiPSC derived motoneurons than in controls and the degree of FUS mislocalization correlated well with the clinical severity of the underlying ALS related mFUS. The accumulation of DNA damage and the cellular response to DNA damage stressors was more pronounced in post-mitotic mFUS motoneurons than in dividing hiPSCs suggesting that mFUS motoneurons accumulate foci of DNA damage, which in turn

  6. Dscam1 is required for normal dendrite growth and branching but not for dendritic spacing in Drosophila motoneurons.

    PubMed

    Hutchinson, Katie M; Vonhoff, Fernando; Duch, Carsten

    2014-01-29

    Down syndrome cell adhesion molecule, Dscam, serves diverse neurodevelopmental functions, including axon guidance and synaptic adhesion, as well as self-recognition and self-avoidance, depending on the neuron type, brain region, or species under investigation. In Drosophila, the extensive molecular diversity that results from alternative splicing of Dscam1 into >38,000 isoforms provides neurons with a unique molecular code for self-recognition in the nervous system. Each neuron produces only a small subset of Dscam1 isoforms, and distinct Dscam1 isoforms mediate homophilic interactions, which in turn, result in repulsion and even spacing of self-processes, while allowing contact with neighboring cells. While these mechanisms have been shown to underlie mushroom body development and spacing of mechanosensory neuron dendrites, here we report that Dscam1 plays no role in adult Drosophila motoneuron dendrite spacing, but is required for motoneuron dendritic growth. Targeted expression of Dscam-RNAi in an identified flight motoneuron did not impact dendrite spacing, but instead produced overgrowth. Increasing the knockdown strength severely reduced dendritic growth and branching. Similarly, Dscam mutant motoneurons in an otherwise control background (MARCM) were completely devoid of mature dendrites. These data suggest that Dscam1 is required cell autonomously for normal adult motoneuron dendrite growth in Drosophila. This demonstrates a previously unreported role of Drosophila Dscam1 in central neuron development, and expands the current understanding that Dscam1 operates as a cell adhesion molecule that mediates homophilic repulsion.

  7. A peri-motor framework reveals functional segmentation in the motoneuronal network controlling locomotion in Caenorhabditis elegans

    PubMed Central

    Haspel, Gal; O'Donovan, Michael J

    2011-01-01

    The neuronal connectivity dataset of the nematode Caenorhabditis elegans attracts wide attention from computational neuroscientists and experimentalists. However, the dataset is incomplete. The ventral and dorsal nerve cords of a single nematode were reconstructed halfway along the body and the posterior data is missing, leaving 21 of 75 motoneurons of the locomotor network with partial or no connectivity data. Using a new framework for network analysis, the peri-motor space, we identified rules of connectivity that allowed us to approximate the missing data by extrapolation. Motoneurons were mapped into peri-motor space in which each motoneuron is located according to the muscle cells it innervates. In this framework, a pattern of iterative connections emerges which includes most (0.90) of the connections. We identified a repeating unit consisting of 12 motoneurons and 12 muscle cells. The cell bodies of the motoneurons of such a unit are not necessarily anatomical neighbors and there is no obvious anatomical segmentation. A connectivity model, comprised of six repeating units, is a description of the network that is both simplified (modular and without non-iterative connections) and more complete (includes the posterior part) than the original dataset. The peri-motor framework of observed connectivity and the segmented connectivity model give insights and advance the study of the neuronal infrastructure underlying locomotion in C. elegans. Furthermore, we suggest that the tools used herein may be useful to interpret, simplify and represent connectivity data of other motor systems. PMID:21994377

  8. Neuroprotective and Neurorestorative Processes after Spinal Cord Injury: The Case of the Bulbospinal Respiratory Neurons

    PubMed Central

    2016-01-01

    High cervical spinal cord injuries interrupt the bulbospinal respiratory pathways projecting to the cervical phrenic motoneurons resulting in important respiratory defects. In the case of a lateralized injury that maintains the respiratory drive on the opposite side, a partial recovery of the ipsilateral respiratory function occurs spontaneously over time, as observed in animal models. The rodent respiratory system is therefore a relevant model to investigate the neuroplastic and neuroprotective mechanisms that will trigger such phrenic motoneurons reactivation by supraspinal pathways. Since part of this recovery is dependent on the damaged side of the spinal cord, the present review highlights our current understanding of the anatomical neuroplasticity processes that are developed by the surviving damaged bulbospinal neurons, notably axonal sprouting and rerouting. Such anatomical neuroplasticity relies also on coordinated molecular mechanisms at the level of the axotomized bulbospinal neurons that will promote both neuroprotection and axon growth. PMID:27563469

  9. Influence of stretch-evoked synaptic potentials on firing probability of cat spinal motoneurones.

    PubMed

    Gustafsson, B; McCrea, D

    1984-02-01

    Shapes of post-synaptic potentials (p.s.p.s) in cat motoneurones were compared with the time course of correlated changes in firing probability during repetitive firing. Excitatory and inhibitory post-synaptic potentials (e.p.s.p.s. and i.p.s.p.s) were evoked by brief triangular stretches of the triceps surae-plantaris muscles. Depolarizing current was injected through the recording micro-electrode to evoke repetitive firing and the post-stimulus time histogram of motoneurone spikes was obtained. E.p.s.p.s (n = 80) of different sizes (30-1040 microV) and rise times (1.1-8.2 ms) were investigated in fifty-nine motoneurones. The majority of the e.p.s.p.s were recorded in triceps surae-plantaris motoneurones with high levels of synaptic noise (estimated peak-to-peak fluctuations of 1.5-3.5 mV). This noise was generated by keeping the triceps surae-plantaris muscles stretched to a near maximal degree. The remaining e.p.s.p.s were recorded in motoneurones to other hind-limb muscles with a low level of synaptic noise. The height of the primary peak of the correlogram with respect to base-line firing rate increased in proportion to both amplitude and rising slope of the e.p.s.p.s. Using normalization procedures or using e.p.s.p.s of constant amplitude but different slopes and vice versa, the relative peak height increased with e.p.s.p. peak derivative with a slope of around 6/mV per millisecond and with e.p.s.p peak amplitude with a slope of about 1/mV. The shape of the correlogram (peak and trough) seemed well described by a linear combination of the shape of the e.p.s.p. derivative and that of the e.p.s.p. itself. The relative e.p.s.p. contribution (e.p.s.p.:e.p.s.p. derivative ratio) varied with e.p.s.p. amplitude and noise level, being largest (mostly 0.25-1.0) for small e.p.s.p.s (100-300 microV) in high levels of synaptic noise and smaller (0-0.25) for larger e.p.s.p.s and for e.p.s.p.s in a low noise background. In conformity with the above finding, a leaky

  10. Activation properties of trigeminal motoneurons in participants with and without bruxism

    PubMed Central

    D'Amico, Jessica M.; Yavuz, Ş. Utku; Saraçoğlu, Ahmet; Atiş, Elif Sibel; Türker, Kemal S.

    2013-01-01

    In animals, sodium- and calcium-mediated persistent inward currents (PICs), which produce long-lasting periods of depolarization under conditions of low synaptic drive, can be activated in trigeminal motoneurons following the application of the monoamine serotonin. Here we examined if PICs are activated in human trigeminal motoneurons during voluntary contractions and under physiological levels of monoaminergic drive (e.g., serotonin and norepinephrine) using a paired motor unit analysis technique. We also examined if PICs activated during voluntary contractions are larger in participants who demonstrate involuntary chewing during sleep (bruxism), which is accompanied by periods of high monoaminergic drive. In control participants, during a slowly increasing and then decreasing isometric contraction, the firing rate of an earlier-recruited masseter motor unit, which served as a measure of synaptic input to a later-recruited test unit, was consistently lower during derecruitment of the test unit compared with at recruitment (ΔF = 4.6 ± 1.5 imp/s). The ΔF, therefore, is a measure of the reduction in synaptic input needed to counteract the depolarization from the PIC to provide an indirect estimate of PIC amplitude. The range of ΔF values measured in the bruxer participants during similar voluntary contractions was the same as in controls, suggesting that abnormally high levels of monoaminergic drive are not continually present in the absence of involuntary motor activity. We also observed a consistent “onion skin effect” during the moderately sized contractions (<20% of maximal), whereby the firing rate of higher threshold motor units discharged at slower rates (by 4–7 imp/s) compared with motor units with relatively lower thresholds. The presence of lower firing rates in the more fatigue-prone, higher threshold trigeminal motoneurons, in addition to the activation of PICs, likely facilitates the activation of the masseter muscle during motor activities

  11. Frequency-dependent amplification of stretch-evoked excitatory input in spinal motoneurons.

    PubMed

    Powers, Randall K; Nardelli, Paul; Cope, T C

    2012-08-01

    Voltage-dependent calcium and sodium channels mediating persistent inward currents (PICs) amplify the effects of synaptic inputs on the membrane potential and firing rate of motoneurons. CaPIC channels are thought to be relatively slow, whereas the NaPIC channels have fast kinetics. These different characteristics influence how synaptic inputs with different frequency content are amplified; the slow kinetics of Ca channels suggest that they can only contribute to amplification of low frequency inputs (<5 Hz). To characterize frequency-dependent amplification of excitatory postsynaptic potentials (EPSPs), we measured the averaged stretch-evoked EPSPs in cat medial gastrocnemius motoneurons in decerebrate cats at different subthreshold levels of membrane potential. EPSPs were produced by muscle spindle afferents activated by stretching the homonymous and synergist muscles at frequencies of 5-50 Hz. We adjusted the stretch amplitudes at different frequencies to produce approximately the same peak-to-peak EPSP amplitude and quantified the amount of amplification by expressing the EPSP integral at different levels of depolarization as a percentage of that measured with the membrane hyperpolarized. Amplification was observed at all stretch frequencies but generally decreased with increasing stretch frequency. However, in many cells the amount of amplification was greater at 10 Hz than at 5 Hz. Fast amplification was generally reduced or absent when the lidocaine derivative QX-314 was included in the electrode solution, supporting a strong contribution from Na channels. These results suggest that NaPICs can combine with CaPICs to enhance motoneuron responses to modulations of synaptic drive over a physiologically significant range of frequencies.

  12. Multimodal distribution of amplitudes of miniature and spontaneous EPSPs recorded in rat trigeminal motoneurones.

    PubMed Central

    Min, M Y; Appenteng, K

    1996-01-01

    1. The whole-cell variant of the patch recording method has been used to obtain voltage recordings from trigeminal motoneurones in tissue slices (500 microns thick) taken from rats aged 8 days. Membrane properties (input resistance, membrane time constant and rheobase, i.e. threshold current required to elicit an action potential) of the motoneurones were determined and recordings made of the (untriggered) EPSP activity. 2. Untriggered EPSP activity was recorded in standard artificial cerebrospinal fluid (ACSF), ACSF with added tetrodotoxin (TTX) and in nominally Ca(2+)-free ACSF with added TTX. In each case the amplitude distributions of single EPSPs were peaky and could be fitted by a model consisting of the sum of equidistant Gaussians (n = 7/9 cells). In contrast, the amplitude distribution of the noise was always unimodal. 3. All EPSP activity recorded in the presence of TTX was abolished by addition of 6-cyano-7-nitroquinoxaline-2-3-dione (CNQX; 10 microM), suggesting the activity was all mediated by glutamate acting primarily at AMPA/kainate receptors. 4. In the majority of cases, there was no correlation between the amplitude of EPSPs underlying each Gaussian and the EPSP rise time but there was a positive correlation between the EPSP half-width and EPSP rise time. The rise times of EPSPs underlying the first, and all, fitted Gaussians were similar to that for the total sample of EPSPs in each motoneurone. Taken together, this suggests that the EPSPs underlying each Gaussian arise from inputs to different dendritic compartments, and that the range of compartments is similar for EPSPs underlying successive Gaussians. 5. Two conclusions are drawn. First, EPSPs of different dendritic origin have similar amplitudes at the soma. Second, the multimodal distribution of EPSP amplitudes recorded in the presence of TTX raises the possibility that individual boutons may contain multiple release sites, with each perhaps operating on a separate functional group of

  13. Motoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics

    PubMed Central

    Lazarenko, Roman M.; Willcox, Sarah C.; Shu, Shaofang; Berg, Allison P.; Jevtovic-Todorovic, Vesna; Talley, Edmund M.; Chen, Xiangdong; Bayliss, Douglas A.

    2010-01-01

    General anesthetics cause sedation, hypnosis and immobilization via central nervous system mechanisms that remain incompletely understood; contributions of particular anesthetic targets in specific neural pathways remain largely unexplored. Among potential molecular targets for mediating anesthetic actions, the TASK subgroup (TASK-1, K2P3.1& TASK-3, K2P9.1) of background K+ channels are appealing candidates since they are expressed in CNS sites relevant to anesthetic actions and activated by clinically relevant concentrations of inhaled anesthetics. Here, we used global and conditional TASK channel single and double subunit knockout mice to demonstrate definitively that TASK channels account for motoneuronal anesthetic-activated K+ currents and to test their contributions to sedative, hypnotic and immobilizing anesthetic actions. In motoneurons from all knockout mice lines, TASK-like currents were reduced and cells were less sensitive to hyperpolarizing effects of halothane and isoflurane. In an immobilization assay, higher concentrations of both halothane and isoflurane were required to render TASK knockout animals unresponsive to a tail pinch; in assays of sedation (loss of movement) and hypnosis (loss-of-righting reflex), TASK knockout mice showed a modest decrease in sensitivity, and only for halothane. In conditional knockout mice, with TASK channel deletion restricted to cholinergic neurons, immobilizing actions of the inhaled anesthetics and sedative effects of halothane were reduced to the same extent as in global knockout lines. These data indicate that TASK channels in cholinergic neurons are a molecular substrate for select actions of inhaled anesthetics; for immobilization, which is spinally mediated, these data implicate motoneurons as the likely neuronal substrate. PMID:20519544

  14. Motoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics.

    PubMed

    Lazarenko, Roman M; Willcox, Sarah C; Shu, Shaofang; Berg, Allison P; Jevtovic-Todorovic, Vesna; Talley, Edmund M; Chen, Xiangdong; Bayliss, Douglas A

    2010-06-02

    General anesthetics cause sedation, hypnosis, and immobilization via CNS mechanisms that remain incompletely understood; contributions of particular anesthetic targets in specific neural pathways remain largely unexplored. Among potential molecular targets for mediating anesthetic actions, members of the TASK subgroup [TASK-1 (K2P3.1) and TASK-3 (K2P9.1)] of background K(+) channels are appealing candidates since they are expressed in CNS sites relevant to anesthetic actions and activated by clinically relevant concentrations of inhaled anesthetics. Here, we used global and conditional TASK channel single and double subunit knock-out mice to demonstrate definitively that TASK channels account for motoneuronal, anesthetic-activated K(+) currents and to test their contributions to sedative, hypnotic, and immobilizing anesthetic actions. In motoneurons from all knock-out mice lines, TASK-like currents were reduced and cells were less sensitive to hyperpolarizing effects of halothane and isoflurane. In an immobilization assay, higher concentrations of both halothane and isoflurane were required to render TASK knock-out animals unresponsive to a tail pinch; in assays of sedation (loss of movement) and hypnosis (loss-of-righting reflex), TASK knock-out mice showed a modest decrease in sensitivity, and only for halothane. In conditional knock-out mice, with TASK channel deletion restricted to cholinergic neurons, immobilizing actions of the inhaled anesthetics and sedative effects of halothane were reduced to the same extent as in global knock-out lines. These data indicate that TASK channels in cholinergic neurons are molecular substrates for select actions of inhaled anesthetics; for immobilization, which is spinally mediated, these data implicate motoneurons as the likely neuronal substrates.

  15. Astrocytes expressing mutant SOD1 and TDP43 trigger motoneuron death that is mediated via sodium channels and nitroxidative stress

    PubMed Central

    Rojas, Fabiola; Cortes, Nicole; Abarzua, Sebastian; Dyrda, Agnieszka; van Zundert, Brigitte

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal paralytic disorder caused by dysfunction and degeneration of motor neurons. Multiple disease-causing mutations, including in the genes for SOD1 and TDP-43, have been identified in ALS. Astrocytes expressing mutant SOD1 are strongly implicated in the pathogenesis of ALS: we have shown that media conditioned by astrocytes carrying mutant SOD1G93A contains toxic factor(s) that kill motoneurons by activating voltage-sensitive sodium (Nav) channels. In contrast, a recent study suggests that astrocytes expressing mutated TDP43 contribute to ALS pathology, but do so via cell-autonomous processes and lack non-cell-autonomous toxicity. Here we investigate whether astrocytes that express diverse ALS-causing mutations release toxic factor(s) that induce motoneuron death, and if so, whether they do so via a common pathogenic pathway. We exposed primary cultures of wild-type spinal cord cells to conditioned medium derived from astrocytes (ACM) that express SOD1 (ACM-SOD1G93A and ACM-SOD1G86R) or TDP43 (ACM-TDP43A315T) mutants; we show that such exposure rapidly (within 30–60 min) increases dichlorofluorescein (DCF) fluorescence (indicative of nitroxidative stress) and leads to extensive motoneuron-specific death within a few days. Co-application of the diverse ACMs with anti-oxidants Trolox or esculetin (but not with resveratrol) strongly improves motoneuron survival. We also find that co-incubation of the cultures in the ACMs with Nav channel blockers (including mexiletine, spermidine, or riluzole) prevents both intracellular nitroxidative stress and motoneuron death. Together, our data document that two completely unrelated ALS models lead to the death of motoneuron via non-cell-autonomous processes, and show that astrocytes expressing mutations in SOD1 and TDP43 trigger such cell death through a common pathogenic pathway that involves nitroxidative stress, induced at least in part by Nav channel activity. PMID:24570655

  16. A HRP study of the relation between cell size and motor unit type in cat ankle extensor motoneurons.

    PubMed

    Burke, R E; Dum, R P; Fleshman, J W; Glenn, L L; Lev-Tov, A; O'Donovan, M J; Pinter, M J

    1982-07-20

    The dimensions of the somata and stem dendrites of 57 alpha- and three gamma-motoneurons, identified as to motor unit type and labeled by intracellular injection of horseradish peroxidase, were measured in the triceps surae and plantaris motor pools. The somata of type S motoneurons tended to be smaller (mean diameter 47.9 micrometers) than those of FF and FR units (52.5 and 53.1 micrometer, respectively) but these mean values were not significantly different and the data distributions showed considerable overlap between the unit types. The mean numbers and diameters of stem dendrites exhibited somewhat larger differences related to motor unit type and some of these were statistically significant. The total membrane area (AN) of each cell was estimated from measurements of the soma and stem dendrites, by using recent data and Ulfhake and Kellerth ('81) to calculate the membrane area of a dendritic tree from stem dendrite diameter. Mean AN varied with motor unit type in the sequence FF greater than FR greater than S (average values: 369 X 100(3) micrometers 2, 323 X 100(3) micrometers 2, and 250 X 100(3) micrometers 2, respectively). There was covariation between AN and the conduction velocity of the motor axon as well as with the force output from the muscle unit. Comparison of AN and motoneuron input resistance (RN) in 19 alpha-motoneurons suggested that the specific resistivity of the cell membrane in type S motoneurons was systematically higher than that characteristic of type FF or FR motoneurons.

  17. Distribution and density of contacts from noradrenergic and serotonergic boutons on the dendrites of neck flexor motoneurons in the adult cat.

    PubMed

    Maratta, Robert; Fenrich, Keith K; Zhao, Ethan; Neuber-Hess, Monica S; Rose, P Ken

    2015-08-01

    Serotonergic (5-HT) and noradrenergic (NA) input to spinal motoneurons is essential for generating plateau potentials and self-sustained discharges. Extensor motoneurons are densely innervated by 5-HT and NA synapses and have robust plateau potentials and self-sustained discharges. Conversely, plateau potentials and self-sustained discharges are very rare in flexor motoneurons. The most likely reasons for this difference are that flexor motoneurons have few 5-HT and NA synapses and/or they are distributed distant to the channels responsible for plateau potentials and self-sustained discharges. However, the distribution of 5-HT and NA synapses on flexor motoneurons is unknown. Here we describe the distribution and density of 5-HT and NA synapses on motoneurons that innervate the flexor neck muscle, rectus capitis anterior (RCA), in the adult cat. Using a combination of intracellular staining, fluorescent immunohistochemistry, and 3D reconstruction techniques, we found that 5-HT and NA synapses are widely distributed throughout the dendritic trees of RCA motoneurons, albeit with a strong bias to small-diameter dendrites and to medial dendrites in the case of NA contacts. The number of 5-HT and NA contacts per motoneuron ranged, respectively, from 381 to 1,430 and from 642 to 1,382, which is 2.3- and 1.4-fold less than neck extensor motoneurons (Montague et al., J Comp Neurol 2013;521:638-656). These results suggest that 5-HT and NA synapses on flexor motoneurons may provide a powerful means of amplifying synaptic currents without incurring plateau potentials or self-sustained discharges. This feature is well suited to meet the biomechanical demands imposed on flexor muscles during different motor tasks.

  18. Modulation of voltage-gated sodium channels hyperpolarizes the voltage threshold for activation in spinal motoneurones.

    PubMed

    Power, Kevin E; Carlin, Kevin P; Fedirchuk, Brent

    2012-03-01

    Previous work has shown that motoneurone excitability is enhanced by a hyperpolarization of the membrane potential at which an action potential is initiated (V(th)) at the onset, and throughout brainstem-evoked fictive locomotion in the adult decerebrate cat and neonatal rat. Modeling work has suggested the modulation of Na(+) conductance as a putative mechanism underlying this state-dependent change in excitability. This study sought to determine whether modulation of voltage-gated sodium channels could induce V(th) hyperpolarization. Whole-cell patch-clamp recordings were made from antidromically identified lumbar spinal motoneurones in an isolated neonatal rat spinal cord preparation. Recordings were made with and without the bath application of veratridine, a plant alkaloid neurotoxin that acts as a sodium channel modulator. As seen in HEK 293 cells expressing Nav1.2 channels, veratridine-modified channels demonstrated a hyperpolarizing shift in their voltage-dependence of activation and a slowing of inactivation that resulted in an enhanced inward current in response to voltage ramp stimulations. In the native rat motoneurones, veratridine-modified sodium channels induced a hyperpolarization of V(th) in all 29 neonatal rat motoneurones examined (mean hyperpolarization: -6.6 ± 4.3 mV). V(th) hyperpolarization was not due to the effects on Ca(2+) and/or K(+) channels as blockade of these currents did not alter V(th). Veratridine also significantly increased the amplitude of persistent inward currents (PICs; mean increase: 72.5 ± 98.5 pA) evoked in response to slow depolarizing current ramps. However, the enhancement of the PIC amplitude had a slower time course than the hyperpolarization of V(th), and the PIC onset voltage could be either depolarized or hyperpolarized, suggesting that PIC facilitation did not mediate the V(th) hyperpolarization. We therefore suggest that central neuronal circuitry in mammals could affect V(th) in a mechanism similar to that of

  19. Evidence for interneuronally mediated Ia excitatory effects to human quadriceps motoneurones.

    PubMed Central

    Fournier, E; Meunier, S; Pierrot-Deseilligny, E; Shindo, M

    1986-01-01

    The possibility was investigated that interneuronal pathways contribute to Ia excitation of quadriceps motoneurones in normal man. Two techniques were used: the indirect spatial facilitation technique for investigating summation of Ia excitatory effects in interneurones which may be interposed in pathways to quadriceps motoneurones; the post-stimulus time histogram method for time course measurement of the firing probability of voluntarily activated motor units following femoral nerve stimulation. The spatial facilitation technique was applied while using the quadriceps H reflex to assess the excitability of the whole motoneurone pool: the comparison was made between the excitatory effects of two conditioning stimuli applied either separately or together. Summation of effects at a premotoneuronal level is suggested if facilitation of the reflex evoked on combined conditioning stimulation is larger than the algebraic sum of facilitations evoked by separate stimuli. Quadriceps tendon tap and electrical stimulations applied to either the femoral nerve or to two of its branches, the nerves to the vastus lateralis and vastus medialis muscles, were used as conditioning stimuli. Since these stimuli were very weak (their strength being about at the threshold for facilitation of the test reflex), it can be assumed that they activated predominantly Ia fibres. The facilitation of the quadriceps H reflex evoked on combined stimulation was significantly larger than the algebraic sum of facilitations evoked by separate stimuli. In many experiments, although conditioning stimuli did not evoke any reflex facilitation when applied alone, a significant facilitation appeared on combined stimulation. This 'extra' facilitation of the reflex on combined stimulation appeared with a central latency of 4-5 ms. It is argued that the only mechanism compatible with such a latency is summation at a premotoneuronal level. Post-stimulus time histograms (p.s.t.h.s) of voluntarily activated

  20. Immobile survival of motoneuron (SMN) protein stored in Cajal bodies can be mobilized by protein interactions.

    PubMed

    Förthmann, Benjamin; Brinkmann, Hella; Ratzka, Andreas; Stachowiak, Michal K; Grothe, Claudia; Claus, Peter

    2013-07-01

    Reduced levels of survival of motoneuron (SMN) protein lead to spinal muscular atrophy, but it is still unknown how SMN protects motoneurons in the spinal cord against degeneration. In the nucleus, SMN is associated with two types of nuclear bodies denoted as gems and Cajal bodies (CBs). The 23 kDa isoform of fibroblast growth factor-2 (FGF-2(23)) is a nuclear protein that binds to SMN and destabilizes the SMN-Gemin2 complex. In the present study, we show that FGF-2(23) depletes SMN from CBs without affecting their general structure. FRAP analysis of SMN-EGFP in CBs demonstrated that the majority of SMN in CBs remained mobile and allowed quantification of fast, slow and immobile nuclear SMN populations. The potential for SMN release was confirmed by in vivo photoconversion of SMN-Dendra2, indicating that CBs concentrate immobile SMN that could have a specialized function in CBs. FGF-2(23) accelerated SMN release from CBs, accompanied by a conversion of immobile SMN into a mobile population. Furthermore, FGF-2(23) caused snRNP accumulation in CBs. We propose a model in which Cajal bodies store immobile SMN that can be mobilized by its nuclear interaction partner FGF-2(23), leading to U4 snRNP accumulation in CBs, indicating a role for immobile SMN in tri-snRNP assembly.

  1. Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior.

    PubMed

    Feiguin, Fabian; Godena, Vinay K; Romano, Giulia; D'Ambrogio, Andrea; Klima, Raffaella; Baralle, Francisco E

    2009-05-19

    Pathological modifications in the highly conserved and ubiquitously expressed heterogeneous ribonucleoprotein TDP-43 were recently associated to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a late-onset disorder that affects predominantly motoneurons [Neumann, M. et al. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133, Sreedharan, J. et al. (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668-1672, Kabashi, E. et al. (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 40, 572-574]. However, the function of TDP-43 in vivo is unknown and a possible direct role in neurodegeneration remains speculative. Here, we report that flies lacking Drosophila TDP-43 appeared externally normal but presented deficient locomotive behaviors, reduced life span and anatomical defects at the neuromuscular junctions. These phenotypes were rescued by expression of the human protein in a restricted group of neurons including motoneurons. Our results demonstrate the role of this protein in vivo and suggest an alternative explanation to ALS pathogenesis that may be more due to the lack of TDP 43 function than to the toxicity of the aggregates.

  2. Participation of estradiol and progesterone in the retrograde labeling of pubococcygeus motoneurons of the female rat.

    PubMed

    Cuevas, E; Camacho, M; Alvarado, M; Hudson, R; Pacheco, P

    2006-07-21

    Retrograde labeling with horseradish peroxidase conjugated to wheat germ agglutinin showed that the pubococcygeus muscles of the female rat are innervated by a population of motoneurons located in a column approximately 2 mm in length in the central region of lamina IX of the sixth lumbar-first sacral spinal cord segments. These neurons have a dendritic distribution that projects to the lateral, medial and ventral regions of the gray matter. Values for soma size, primary dendrite length and arborization area obtained from intact animals that were in diestrous-2, were significantly reduced following ovariectomy. After hormone priming of the ovariectomized animals with estradiol benzoate and progesterone, an additional injection of estradiol benzoate alone or followed by progesterone increased the labeled length of the primary dendrites distributed to the lateral, but not to the medial or ventral regions of the gray matter in the spinal cord. However, dendritic labeling was not significantly increased when only progesterone was additionally injected. It therefore seems that pubococcygeus muscle motoneurons of the female rat are sensitive to the effects of gonadal hormones.

  3. The mouse mutation muscle deficient (mdf) is characterized by a progressive motoneuron disease.

    PubMed

    Blot, S; Poirier, C; Dreyfus, P A

    1995-11-01

    Muscle deficient (mdf) is an autosomal-recessive mutation mapped to mouse chromosome 19. The clinical phenotype and the muscle histopathology, briefly described in 1980, and the nervous system histopathology are detailed in the present study. Homozygotes develop a posterior waddle at 4 to 8 weeks of age. Soon thereafter, the hindlimbs become paralyzed and weakness appears in forelimbs, leading to a serious disability. The disease progresses slowly and the mean lifespan is reduced to 8 months. Skeletal muscles exhibit a neurogenic atrophy with signs of reinnervation. Peripheral nerves display axonal degeneration. Neurons within the spinal cord ventral horn, and some motor nuclei of the brain stem, are affected by a cytoplasmic vacuolar degeneration. Ascending and descending spinal cord tracts appear normal. An astrogliosis, restricted to the ventral horn of the spinal cord, occurs in mdf/mdf mice of 10 weeks of age. These clinical and histological features are indicative of a progressive motor neuronopathy. Among the murine spinal muscular atrophies, the programmed cell death of the mdf motoneurons is morphologically similar to wobbler. Because of the long time course, the mdf mutation may represent a valuable tool for understanding juvenile motoneuron diseases with chronic evolution, even though the murine locus is not syntenic with the human ones.

  4. Perineal striated muscles: Anatomy, spinal motoneurons, and participation on copulatory behavior in male rabbits (Oryctolagus cuniculus).

    PubMed

    Zempoalteca, R; Lucio, R A; Eguibar, J R

    2008-09-01

    Despite the importance of rabbits in reproductive studies, little information is available on the anatomy and participation of the striated-perineal muscles in male copulatory behavior. In our study, we describe the gross anatomy of two striated-perineal muscles: the ischiocavernosus (ICm) and the bulbospongiosus (BSm). Both muscles have their origin at the ischiadic arc, but the ICm is inserted into the penile crura and the BSm onto the ligamentum suspensorium of the penis. The motoneurons of both muscles were identified using retrograde labeling with horseradish peroxidase coupled to wheat-germ agglutinin. Motoneurons were dispersed in the lower-lumbar and upper-sacral spinal-cord segments, instead of being aggregated in the neuronal nucleus as in other species: the rat, mouse, gerbil, cat, and man. Bilateral dennervation of the ICm or BSm or both in sexually experienced male rabbits did not affect copulatory variables measured at 10, 20, and 30 days after surgery. However, muscular dennervation produced extravaginal ejaculations in 42% of copulatory tests and no ejaculation in 7% of tests, although male pelvic thrusting occurred. These results suggest the participation of the ICm and BSm perineal muscles in penile orientation during copulation but not in seminal emission as described in other mammalian species.

  5. Neuropathology in respiratory-related motoneurons in young Pompe (Gaa−/−) mice

    PubMed Central

    Turner, Sara M.F.; Hoyt, Aaron K.; ElMallah, Mai K.; Falk, Darin J.; Byrne, Barry J.; Fuller, David D.

    2016-01-01

    Respiratory and/or lingual dysfunction are among the first motor symptoms in Pompe disease, a disorder resulting from absence or dysfunction of the lysosomal enzyme acid α-glucosidase (GAA). Here, we histologically evaluated the medulla, cervical and thoracic spinal cords in 6 weeks old asymptomatic Pompe (Gaa−/−) mice to determine if neuropathology in respiratory motor regions has an early onset. Periodic acid-Schiff (PAS) staining indicated glycogen accumulation was exclusively occurring in Gaa−/− hypoglossal, mid-cervical and upper thoracic motoneurons. Markers of DNA damage (Tunel) and ongoing apoptosis (Cleaved Caspase 3) did not co-localize with PAS staining, but were prominent in a medullary region which included the nucleus tractus solitarius, and also in the thoracic spinal dorsal horn. We conclude that respiratory-related motoneurons are particularly susceptible to GAA deficiency and that neuronal glycogen accumulation and neurodegeneration may occur independently in early stage disease. The data support early therapeutic intervention in Pompe disease. PMID:26921786

  6. Dynamic expression of neurotrophic factor receptors in postnatal spinal motoneurons and in mouse model of ALS.

    PubMed

    Zhang, Jiasheng; Huang, Eric J

    2006-07-01

    Neurotrophic factors support the survival of spinal motoneurons (MNs) and have been considered as strong candidates for treating motoneuron diseases. However, it is unclear if the right combination of neurotrophic factor receptors is present in postnatal spinal MNs. In this study, we show that the level of c-ret expression remains relatively stable in embryonic and postnatal spinal MNs. In contrast, the mRNA and protein of GFRalpha1 and -2 are progressively down-regulated in postnatal life. By 3 and 6 months of age, both receptors are barely detectable in spinal MNs. The down-regulation of GFRalpha1 appears accelerated in transgenic mice expressing mutant SOD1(G93A). Despite the progressive loss of GFRalpha1 and -2, phosphorylation of c-ret shows no detectable reduction on tyrosine residues or on serine 696. In addition to the GFRalpha subunits, expression of TrkB also shows a dynamic change. During embryogenesis, there is twice as much full-length TrkB as the truncated TrkB isoform. However, this ratio is reversed in postnatal spinal cord. Expression of the mutant SOD1(G93A) appears to have no effect on the TrkB receptor ratio. Taken together, our data indicate that the expression of neurotrophic factor receptors, GFRalpha1, -2, and TrkB, is not static, but undergoes dynamic changes in postnatal spinal MNs. These results provide insights into the use of neurotrophic factors as therapeutic agents for ALS.

  7. Ultrastructural evidence for a direct excitatory pathway from the nucleus retroambiguus to lateral longissimus and quadratus lumborum motoneurons in the female golden hamster.

    PubMed

    Gerrits, Peter O; Mouton, Leonora J; de Weerd, Henk; Georgiadis, Janniko R; Krukerink, Marco; Holstege, Gert

    2004-12-20

    During mating, the female golden hamster displays a stereotyped specific receptive posture, characterized by lordosis of the back, elevation of the tail, and extension of the legs. Muscles involved in this posture are thought to be iliopsoas, cutaneus trunci, lateral longissimus (LL), and quadratus lumborum (QL). Lesion studies in rats suggest that mating behavior is controlled by the mesencephalic periaqueductal gray (PAG). The PAG does not project directly to the motoneurons innervating the muscles involved in mating, but is thought to make use of the nucleus retroambiguus (NRA) as relay. The NRA is located ventrolaterally in the most caudal medulla, and projects directly to iliopsoas and cutaneus trunci motoneuronal cell groups. The question is whether this is also true for LL and QL muscles. Retrograde HRP tracing experiments revealed that LL and QL motoneurons are located medially in the ventral horn of the T12-L6 and T13-L4 segments, respectively. A subsequent ultrastructural study combined wheatgerm agglutinin-conjugated horseradish peroxidase injections in the NRA with cholera-toxin B-subunit injections in LL and QL muscles. The results revealed monosynaptic contacts between anterogradely labeled NRA-fiber terminals with retrogradely labeled dendrites of both LL and QL motoneurons. Almost all these terminals had asymmetrical synapses and contained spherical vesicles, suggesting an excitatory function of this NRA-motoneuronal pathway. These results correspond with the hypothesis that in hamster the PAG-NRA-motoneuronal projection not only involves motoneurons of iliopsoas and cutaneus trunci but also of LL and QL.

  8. PTX-induced hyperexcitability affects dendritic shape and GABAergic synapse density but not synapse distribution during Manduca postembryonic motoneuron development.

    PubMed

    Meseke, Maurice; Evers, Jan Felix; Duch, Carsten

    2009-05-01

    During the metamorphosis of the holometabolous insect, Manduca sexta, the postembryonic acquisition of adult specific motor behaviors is accompanied by changes in dendritic architecture, membrane currents, and input synapses of identified motoneurons. This study aims to test whether increased activity affects dendritic architecture and sub-dendritic input synapse distribution of the identified flight motoneuron 5 (MN5). Systemic injections of the chloride channel blocker, picrotoxin (PTX), during early pupal stages increase pupal reflex responsiveness, but overall development is not impaired. MN5 input resistance, resting membrane potential, and spiking threshold are not affected. Bath application of PTX to isolated ventral nerve cords evokes spiking in pupal and adult flight motoneurons. Quantitative three-dimensional reconstructions of the dendritic tree of the adult MN5 show that systemic PTX injections into early pupae cause dendritic overgrowth and reduce the density of GABAergic inputs. In contrast, the distribution patterns of GABAergic terminals throughout the dendritic tree remain unaltered. This indicates that increased overall excitability might cause dendritic overgrowth and decreased inhibitory input during postembryonic motoneuron remodeling, whereas sub-dendritic synapse targeting might be controlled by activity-independent signals. Behavioral testing reveals that these neuronal changes do not impede the animal's ability to fly, but impair maximum flight performance.

  9. Selective Requirement for Maintenance of Synaptic Contacts onto Motoneurons by Target-Derived trkB Receptors.

    PubMed

    Zhu, Xiya; Ward, Patricia J; English, Arthur W

    2016-01-01

    Synaptic contacts onto motoneurons were studied in mice in which the gene for the trkB neurotrophin receptor was knocked out selectively in a subset of spinal motoneurons. The extent of contacts by structures immunoreactive for either of two different vesicular glutamate transporters (VGLUT1 and VGLUT2), the vesicular GABA transporter, or glutamic acid decarboxylase 67 (GAD67) with the somata of motoneurons, was studied in wild type and trkB knockout cells in tamoxifen treated male and female SLICK-trkB(-/-) mice. Selective knockout of the trkB gene resulted in a marked reduction in contacts made by VGLUT2- and GAD67-immunoreactive structures in both sexes and a significant reduction in contacts containing only glycine in male mice. No reduction was found for glycinergic contacts in female mice or for VGLUT1 immunoreactive contacts in either sex. Signaling through postsynaptic trkB receptors is considered to be an essential part of a cellular mechanism for maintaining the contacts of some, but not all, synaptic contacts onto motoneurons.

  10. The control of eye movements by the cerebellar nuclei: polysynaptic projections from the fastigial, interpositus posterior and dentate nuclei to lateral rectus motoneurons in primates.

    PubMed

    Prevosto, Vincent; Graf, Werner; Ugolini, Gabriella

    2017-02-22

    Premotor circuits driving extraocular motoneurons and downstream motor outputs of cerebellar nuclei are well known. However, there is, as yet, no unequivocal account of cerebellar output pathways controlling eye movements in primates. Using retrograde transneuronal transfer of rabies virus from the lateral rectus (LR) eye muscle, we studied polysynaptic pathways to LR motoneurons in primates. Injections were placed either into the central or distal muscle portion, to identify innervation differences of LR motoneurons supplying singly innervated (SIFs) or multiply innervated muscle fibers (MIFs). We found that SIF motoneurons receive major cerebellar 'output channels' bilaterally, while oligosynaptic cerebellar innervation of MIF motoneurons is negligible and/or more indirect. Inputs originate from the fastigial nuclei di- and trisynaptically, and from a circumscribed rostral portion of the ventrolateral interpositus posterior and from the caudal pole of the dentate nuclei trisynaptically. While disynaptic cerebellar inputs to LR motoneurons stem exclusively from the caudal fastigial region involved in saccades, pursuit and convergence (via its projections to brainstem oculomotor populations), minor trisynaptic inputs from the rostral fastigial nucleus, which contributes to gaze shifts, may reflect access to vestibular and reticular eye-head control pathways. Trisynaptic inputs to LR motoneurons from the rostral ventrolateral interpositus posterior, involved in divergence (far-response), is likely mediated by projections to the supraoculomotor area, contributing to LR motoneuron activation during divergence. Trisynaptic inputs to LR motoneurons from the caudal dentate, which also innervates disynaptically the frontal and parietal eye fields, can be explained by its superior colliculus projections, and likely target saccade-related burst neurons.

  11. Immunohistochemical study of motoneurons in lumbar spinal cord of c57black/6 mice after 30-days space flight

    NASA Astrophysics Data System (ADS)

    Tyapkina, Oksana; Islamov, Rustem; Nurullin, Leniz; Petrov, Konstantin.; Rezvyakov, Pavel; Nikolsky, Evgeny

    To investigate mechanisms of hypogravity motor syndrome development the immunoexpression of heat shock proteins (Hsp27 and Hsp70), proteins of synaptic transmission (Synaptophysin and PSD95) and neuroprotective proteins (VEGF and Flt-1) in motoneurons of lumbar spinal cord in c57black/6 control mice (n=2) and after 30-days space flight (n=2) was studied. For a quantitative assessment of target proteins level in motoneurons frozen cross sections of lumbar spinal cord were underwent to immunohistochemical staining. Primary antibodies against VEGF, Flt-1, Hsp27 and Hsp70 (SantaCruz Biotechnology, inc. USA), against Synaptophysin and PSD95 (Abcam plc, UK) were visualized by streptavidin-biotin method. Images of spinal cords were received using OlympusBX51WI microscope with AxioCamMRm camera (CarlZeiss, Germany) and the AxioVisionRel. 4.6.3 software (CarlZeiss, Germany). The digitized data were analyzed using ImageJ 1.43 software (NIH, the USA). Quantitively, protein level in motoneurons was estimated by the density of immunoprecipitation. Results of research have not revealed any reliable changes in the immunnoexpression of vascular endothelial growth factor (VEGF) and its Flt-1 receptor in motoneurons of lumbar spinal cord in control and in mice after 30-day space flight. Studying of heat shock proteins, such as Hsp27 and Hsp70, revealed the decrease in level of these proteins immunoexpression in motoneurons of mice from flight group by 15% and 10%, respectively. Some decrease in level of immunnoexpression of presynaptic membrane proteins (synaptophysin, by 21%) and proteins of postsynaptic area (PSD95, by 55%) was observed after space flight. The data obtained testify to possible changes in a functional state (synaptic activity and stress resistance) of motoneurons of lumbar spinal cord in mice after space flight. Thus, we obtained new data on involvement of motoneurons innervating skeletal muscles in development of hypogravity motor syndrome. Research was supported

  12. The reduction in human motoneurone responsiveness during muscle fatigue is not prevented by increased muscle spindle discharge.

    PubMed

    McNeil, Chris J; Giesebrecht, Sabine; Khan, Serajul I; Gandevia, Simon C; Taylor, Janet L

    2011-08-01

    Motoneurone excitability is rapidly and profoundly reduced during a sustained maximal voluntary contraction (MVC) when tested in the transient silent period which follows transcranial magnetic stimulation (TMS) of the motor cortex. One possible cause of this reduction in excitability is a fatigue-induced withdrawal of excitatory input to motoneurones from muscle spindle afferents. We aimed to test if muscle spindle input produced by tendon vibration would ameliorate suppression of the cervicomedullary motor-evoked potential (CMEP) in the silent period during a sustained MVC. Seven subjects performed a 2 min MVC of the elbow flexors. Stimulation of the corticospinal tract at the level of the mastoids was preceded 100 ms earlier by TMS. These stimulus pairs were delivered every 10 s during the 2 min MVC. Stimulus pairs at 30, 50, 70, 90 and 110 s were delivered while vibration (-80 Hz) was applied to the distal tendon of biceps. On a separate day, the protocol was repeated with both stimuli delivered to the motor cortex. The CMEP in the silent period decreased rapidly with fatigue (to -9% of control) and was not affected by tendon vibration (P = 0.766). The motor-evoked potential in the silent period also declined rapidly (to -5% of control) and was similarly unaffected by tendon vibration (P = 0.075). These data suggest motoneurone disfacilitation due to a fatigue-related decrease of muscle spindle discharge does not contribute significantly to the profound suppression of motoneurone excitability during the silent period. Therefore, a change to intrinsic motoneurone properties caused by repetitive discharge is most probably responsible.

  13. Glycinergic and GABA(A)-mediated inhibition of somatic motoneurons does not mediate rapid eye movement sleep motor atonia.

    PubMed

    Brooks, Patricia L; Peever, John H

    2008-04-02

    A hallmark of rapid eye movement (REM) sleep is a potent suppression of postural muscle tone. Motor control in REM sleep is unique because it is characterized by flurries of intermittent muscle twitches that punctuate muscle atonia. Because somatic motoneurons are bombarded by strychnine-sensitive IPSPs during REM sleep, it is assumed that glycinergic inhibition underlies REM atonia. However, it has never been determined whether glycinergic inhibition of motoneurons is indeed responsible for triggering the loss of postural muscle tone during REM sleep. Therefore, we used reverse microdialysis, electrophysiology, and pharmacological and histological methods to determine whether glycinergic and/or GABA(A)-mediated neurotransmission at the trigeminal motor pool mediates masseter muscle atonia during REM sleep in rats. By antagonizing glycine and GABA(A) receptors on trigeminal motoneurons, we unmasked a tonic glycinergic/GABAergic drive at the trigeminal motor pool during waking and non-rapid eye movement (NREM) sleep. Blockade of this drive potently increased masseter muscle tone during both waking and NREM sleep. This glycinergic/GABAergic drive was immediately switched-off and converted into a phasic glycinergic drive during REM sleep. Blockade of this phasic drive potently provoked muscle twitch activity in REM sleep; however, it did not prevent or reverse REM atonia. Muscle atonia in REM even persisted when glycine and GABA(A) receptors were simultaneously antagonized and trigeminal motoneurons were directly activated by glutamatergic excitation, indicating that a powerful, yet unidentified, inhibitory mechanism overrides motoneuron excitation during REM sleep. Our data refute the prevailing hypothesis that REM atonia is caused by glycinergic inhibition. The inhibitory mechanism mediating REM atonia therefore requires reevaluation.

  14. Membrane currents in visually identified motoneurones of neonatal rat spinal cord.

    PubMed Central

    Takahashi, T

    1990-01-01

    1. Ionic currents induced by depolarization of motoneurones were analysed by tight-seal, whole-cell recording in thin slices of neonatal rat lumbar spinal cord. Identification of motoneurones viewed under Nomarski optics was confirmed by retrograde labelling with the fluorescent dye, Evans Blue. 2. Under whole-cell voltage clamp, depolarizing command pulses from a holding potential of about -70 mV evoked a fast inward current followed by an outward current. The former was suppressed either by lowering external Na+ concentration or by application of tetrodotoxin (TTX). The apparent dissociation constant of TTX was about 13 nM. 3. The outward current remaining after TTX application was activated by depolarization above -50 mV, showing marked outward rectification in the current-voltage relation. Outward tail currents reversed in polarity near the K+ equilibrium potential calculated from the external and pipette K+ concentrations. 4. When external Ca2+ was replaced by Mg2+, the outward K+ current was suppressed markedly and reversibly. Subtraction of current recorded in Ca2+-free-Mg2+ solution from that in control solution revealed a Ca2(+)-dependent K+ current, IK(Ca) with both a transient, IC, and a sustained component IAHP; its tail current lasted for several hundred milliseconds. 5. The sustained outward current observed in Ca2(+)-free-Mg2+ solution was largely suppressed by external application of tetraethylammonium chloride (30 mM), suggesting that it was mostly the delayed rectifier current, IK. In Ca2(+)-free-Mg2+ solution containing TEA and TTX, another transient outward current was observed, which was inactivated by depolarizing pre-pulses in a time- and voltage-dependent manner. The steady-state inactivation curve indicated 50% inactivation at about -77 mV. 4-Aminopyridine (4-AP, 4 mM) largely and reversibly suppressed this current, whereas it did not affect IK observed in the absence of TEA. It is suggested that the transient outward current corresponds to

  15. Activity-dependent depression of the recurrent discharge of human motoneurones after maximal voluntary contractions.

    PubMed

    Khan, Serajul I; Giesebrecht, Sabine; Gandevia, Simon C; Taylor, Janet L

    2012-10-01

    Despite maximal voluntary effort, the output of human motoneurone pools diminishes during fatigue. To assess motoneurone behaviour, we measured recurrent discharges evoked antidromically by supramaximal nerve stimulation after isometric maximal voluntary contractions (MVCs).They were measured as F-waves in the electromyographic activity (EMG). Supramaximal stimuli to the common peroneal and ulnar nerves evoked F-waves at rest before and after MVCs in tibialis anterior (TA) and abductor digit minimi (ADM), respectively. F-waves were depressed immediately after a sustained MVC. For TA, the size and time course of depression of the F-wave area (26 ± 13%; mean ± SD; P =0.007) and persistence (∼20%) were similar after a 10-s or 1-min MVC. For ADM, the decline in F-wave area (39.8 ± 19.6%; P <0.01) was similar after the two contractions but the decline in persistence (probability of occurrence) of the F-wave differed (14.6 ± 10.5% and 32.5 ± 17.1% after 10-s and 1-min MVCs respectively). Comparison of a very long (2-min) with a very short (2-s)MVC in ADM showed that the depression of F-wave area, as well as persistence, was greater after the longer contraction. This suggests, at least for ADM, that the depression is related to the duration of voluntary activity and that the decrease in F-waves could contribute to central fatigue. To examine whether changes in motor axon excitability caused the depression, we measured compound muscle action potentials (M-waves) to submaximal stimulation of the ulnar nerve after a 2-s and 2-min MVC. Submaximal M-waves were not depressed after a 2-s MVC. They were depressed by a 2-min MVC, but the time course of depression of the F- and M-waves differed. Thus, depression of F-waves does not simply reflect reduced excitability of peripheral motor axons.Hence, we propose that activity-dependent changes at the soma or the initial segment depress the recurrent discharge of human motoneurones and that this may contribute to central

  16. Back Injuries

    MedlinePlus

    ... extending from your neck to your pelvis. Back injuries can result from sports injuries, work around the house or in the garden, ... back is the most common site of back injuries and back pain. Common back injuries include Sprains ...

  17. Head Injuries

    MedlinePlus

    ... before. Often, the injury is minor because your skull is hard and it protects your brain. But ... injuries can be more severe, such as a skull fracture, concussion, or traumatic brain injury. Head injuries ...

  18. Effects of loading on upper airway and respiratory pump muscle motoneurons.

    PubMed

    Hill, Kylie; Eastwood, Peter

    2011-10-15

    The functional outcomes of respiratory muscle loading by chemical (e.g. hypercapnia), mechanical (i.e. external mechanical loading) or ventilatory (e.g. exercise) factors can be either positive, such as through an increase in pressure-generating capacity of the inspiratory muscles or detrimental, such as by fatigue. Neurophysiological responses to respiratory muscle loading can occur at one or more points along the pathway from motor cortex to muscle. This paper describes the respiratory pump and upper airway motoneuron responses to the imposition of acute loads including processes of pre-activation, respiratory reflexes, potentiation and fatigue. It also considers changes suggestive of adaptation to chronic loading either from specific respiratory muscle training programs or as part of disease processes such as chronic obstructive pulmonary disease or obstructive sleep apnoea.

  19. Descending pathways to the cutaneus trunci muscle motoneuronal cell group in the cat

    NASA Technical Reports Server (NTRS)

    Holstege, Gert; Blok, Bertil F.

    1989-01-01

    Pathways involved in the cutaneous trunci muscle (CTM) reflex in the cat were investigated. Experimental animals were injected with tritium-labeled L-leucine into their spinal cord, brain stem, or diencephalon and, after six weeks, perfused with 10-percent formalin. The brains and spinal cords were postfixed in formalin and were cut into transverse 25-micron-thick frozen sections for autoradiography. Results based on injections in the C1, C2, C6, and C8 segments suggest that propriospinal pathways to the CTM motor nucleus originating in the cervical cord do no exist, although these propriospinal projections are very strong to all other motoneuronal cell groups surrounding the CTM motor nucleus. The results also demonstrate presence of specific supraspinal projections to the CTM motor nucleus, originating in the contralateral nucleus retroambiguous and the ipsilateral dorsolateral pontine tegmentum.

  20. Activation of brainstem serotoninergic pathways decreases homosynaptic depression of monosynaptic responses of frog spinal motoneurons.

    PubMed

    Cardona, A; Rudomin, P

    1983-12-05

    In the isolated neuraxis of the frog, low frequency stimulation (0.5-2 Hz) of the lateral columns produces monosynaptic responses in the ventral roots which are depressed with an exponential time course. Serotonin (10 mumol/liter) added to the bath, or stimulation of the brain-stem midline raphe nuclei, but not of the lateral reticular formation, reduced the magnitude of the low frequency depression of the responses. The above actions were abolished by methysergide (1 mumol/liter), a specific antagonist of serotonin. These observations show that the magnitude of the homosynaptic depression of monosynaptic responses of motoneurons can be controlled by descending serotonergic mechanisms. This action is considered to be an important component of the arousal behavior mediated by the brain-stem raphe nuclei.

  1. Shaker and Shal Mediate Transient Calcium-Independent Potassium Current in a Drosophila Flight Motoneuron

    PubMed Central

    Duch, Carsten

    2009-01-01

    Ionic currents underlie the firing patterns, excitability, and synaptic integration of neurons. Despite complete sequence information in multiple species, our knowledge about ion channel function in central neurons remains incomplete. This study analyzes the potassium currents of an identified Drosophila flight motoneuron, MN5, in situ. MN5 exhibits four different potassium currents, two fast-activating transient ones and two sustained ones, one of each is calcium activated. Pharmacological and genetic manipulations unravel the specific contributions of Shaker and Shal to the calcium independent transient A-type potassium currents. α-dendrotoxin (Shaker specific) and phrixotoxin-2 (Shal specific) block different portions of the transient calcium independent A-type potassium current. Following targeted expression of a Shaker dominant negative transgene in MN5, the remaining A-type potassium current is α-dendrotoxin insensitive. In Shal RNAi knock down the remaining A-type potassium current is phrixotoxin-2 insensitive. Additionally, barium blocks calcium-activated potassium currents but also a large portion of phrixotoxin-2-sensitive A-type currents. Targeted knock down of Shaker or Shal channels each cause identical reduction in total potassium current amplitude as acute application of α-dendrotoxin or phrixotoxin-2, respectively. This shows that the knock downs do not cause upregulation of potassium channels underlying other A-type channels during development. Immunocytochemistry and targeted expression of modified GFP-tagged Shaker channels with intact targeting sequence in MN5 indicate predominant axonal localization. These data can now be used to investigate the roles of Shaker and Shal for motoneuron intrinsic properties, synaptic integration, and spiking output during behavior by targeted genetic manipulations. PMID:19828724

  2. Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons.

    PubMed

    Liu, Zi-Long; Wu, Xu; Luo, Yan-Jia; Wang, Lu; Qu, Wei-Min; Li, Shan-Qun; Huang, Zhi-Li

    2016-04-01

    Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (GG) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (HMNs) and the underlying signaling mechanisms have remained elusive. Here, whole-cell patch-clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited HMNs with an inward current under voltage-clamp and a depolarization membrane potential under current-clamp via histamine H1 receptors (H1Rs). The phospholipase C inhibitor U-73122 blocked H1Rs-mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on HMNs were H1R/Gq/11 /phospholipase C/inositol-1,4,5-trisphosphate (IP3). The effects of histamine were also dependent on extracellular Na(+) and intracellular Ca(2+), which took place via activation of Na(+)-Ca(2+) exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on HMNs. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea. We proposed the post-synaptic mechanisms underlying the modulation effect of histamine on hypoglossal motoneuron. Histamine activates the H1Rs via PLC and IP3, increases Ca(2+) releases from intracellular stores, promotes Na(+) influx and Ca(2+) efflux via the NCXs, and then produces an inward current and depolarizes the neurons. Histamine modulates the excitability of HMNs with other neuromodulators, such as noradrenaline, serotonin and orexin. We think that these findings should provide an important new direction for drug development for the treatment of obstructive sleep apnea.

  3. Spatial integration of local transmitter responses in motoneurones of the turtle spinal cord in vitro.

    PubMed Central

    Skydsgaard, M; Hounsgaard, J

    1994-01-01

    1. Integration of responses to local activation of transmitter receptors in the dendrites of motoneurones was investigated in a slice preparation of the turtle spinal cord. Membrane-active substances were applied from up to three independent iontophoresis electrodes during intracellular recording from the cell body. 2. Responses to glutamate could be evoked from dendrites closer than 20 microns from the tip of the glutamate electrode. The effects of other substances were more widespread. 3. In normal medium the configuration of a glutamate response was affected by time-dependent anomalous rectification. In the presence of muscarine the sum of glutamate responses from two different dendrites recruited a voltage-sensitive plateau potential. 4. The response to glutamate from one dendrite could be attenuated by local application of gamma-aminobutyric acid (GABA) without effects on soma conductance or glutamate responses from other dendrites. 5. The response to glutamate from one dendrite could be selectively enhanced by local application of tetraethylammonium (TEA) or N-methyl-D-aspartate (NMDA) without effects on soma conductance or glutamate responses from other dendrites. 6. NMDA could convert a tonic glutamate response from one dendrite into a phasic response without affecting the configuration of glutamate responses from other dendrites. 7. The effects of TEA and NMDA were facilitated by depolarization and reduced by hyperpolarization. 8. We conclude that the cable structure of motoneurones and the distribution of synapses and voltage-sensitive ion channels provide relative autonomy to non-linear synaptic processing and modulation in confined dendritic regions. PMID:7799223

  4. Topographic position of forelimb motoneuron pools is conserved in vertebrate evolution.

    PubMed

    Ryan, J M; Cushman, J; Jordan, B; Samuels, A; Frazer, H; Baier, C

    1998-01-01

    The neuromotor conservatism hypothesis predicts that neuromotor patterns in homologous tetrapod muscles are conserved evolutionarily despite the musculoskeletal modifications of vertebrate limbs. A complete description of the anatomical organization of the neurons innervating homologous limb muscles is a prerequisite to any test of the neuromotor conservatism hypothesis. This study uses the retrograde neuronal tracer WGA-HRP to selectively label the motor neuron pools of seven homologous forelimb muscles in mice (Mus musculus) and iguanas (Iguana iguana): Mm. pectoralis, spinodeltoideus, biceps brachii, lateral and long heads of triceps brachii, and the supraspinatus and infraspinatus (in mice) or their reptilian homolog, the supracoracoideus (in iguanas). In vertebrates, motoneurons are arranged in longitudinal columns of cells in the ventral horn of the spinal cord. Mouse motor pools average 1,952 microns in length, except the pectoralis pool which averaged 2,949 microns in length. Iguana pools average 3,196 microns in length. The number of neurons per pool ranged from 70-199 in mice and from 58-114 neurons in iguanas. In both iguanas and mice the motor pools for the spinodeltoids, biceps, and the supracoracoideus (or its mammalian homologs) lie anterior to the pectoralis and triceps motor pools. In the transverse plane, the pectoralis pool lies medial to those of the triceps. The pools of the biceps and spinodeltoids are located dorsal and lateral to those of the pectoralis and supracoracoideus (or its homologs in mammals). The resulting motor pool maps support the hypothesis that the anatomical organization of motoneurons in ancestral reptiles has been retained in these two tetrapod descendents.

  5. Differences in Dysfunction of Thenar and Hypothenar Motoneurons in Amyotrophic Lateral Sclerosis

    PubMed Central

    Fang, Jia; Cui, Liying; Liu, Mingsheng; Guan, Yuzhou; Li, Xiaoguang; Li, Dawei; Cui, Bo; Shen, Dongchao; Ding, Qingyun

    2016-01-01

    This study aimed to determine differences in spinal motoneuron dysfunction between the abductor pollicis brevis (APB) and the abductor digiti minimi (ADM) in amyotrophic lateral sclerosis (ALS) patients based on studying F-waves. Forty ALS patients and 20 normal controls (NCs) underwent motor nerve conduction studies on both median and ulnar nerves, including F-waves elicited by 100 electrical stimuli. The F-wave persistence (P < 0.05), index repeating neuron (RN; P < 0.001), and index repeater F-waves (Freps; P < 0.001) significantly differed between the APB and the ADM in the NC participants. For the hands of the ALS patients that lacked detectable wasting or weakness and exhibited either no or mild impairment of discrete finger movements, significantly reduced F-wave persistence (P < 0.001), increased index RN (P < 0.001), and increased index Freps (P < 0.001) were observed in APB in comparison with the normal participants, with relatively normal ADM F-wave parameters. For the hands of ALS patients that exhibited wasting and weakness, the mean F-wave amplitude (P < 0.05), the F/M amplitude ratio (P < 0.05), F-wave persistence (P < 0.001), index RN (P < 0.05), and index Freps (P < 0.05) significantly differed between APB and ADM. The differences in the dysfunction of motoneurons innervating APB and ADM are unique manifestations in ALS patients. The F-wave persistence (P = 0.002), index RN (P < 0.001), and index Freps (P < 0.001) in the APB seemed to differentiate ALS from the NCs more robustly than the ADM/APB Compound muscle action potential (CMAP) amplitude ratio. Thus, F-waves may reveal subclinical alterations in anterior horn cells, and may potentially help to distinguish ALS from mimic disorders. PMID:27014030

  6. [The influence of afferent inputs from the foot load receptors onto spinal alpha-motoneurons excitability in air-stepping condition].

    PubMed

    Selionov, V A; Solopova, I A

    2011-01-01

    We investigated excitability of alpha-motoneurons during voluntary and passive locomotor-like movements under air-stepping conditions during the imitation of foot loading. Limb loading notably inhibited the H-reflex during both static condition and active or passive stepping. Thus, load-related afferent inputs play an essentially role in phase-dependence H-reflex modulation. The excitability of alpha-motoneurons in the most degree is influenced by afferent inflow from foot receptors.

  7. Heterogeneity of group Ia synapses on homonymous alpha-motoneurons as revealed by high-frequency stimulation of Ia afferent fibers.

    PubMed

    Collins, W F; Honig, M G; Mendell, L M

    1984-11-01

    Excitatory postsynaptic potentials (EPSPs) were recorded in medial gastrocnemius (MG) motoneurons following intraaxonal electrical stimulation of single spindle afferent fibers in anesthetized cats. High-frequency bursts of 32 shocks were delivered to the afferent axon and the EPSPs were averaged in the motoneuron. EPSP amplitude generally changed during the burst, in some cases increasing and in other cases decreasing, depending on the connection. Interpretation of these changes was complicated by potentiation of the initial EPSPs in the burst that occurred with the repeated bursts. The extent of the potentiation varied from connection to connection. The magnitude of facilitation or depression during a burst of standard frequency (167 Hz) was determined by comparison of EPSPs at the end of the burst with the mean EPSP obtained during low-frequency stimulation (18 Hz). Large amplitude EPSPs tended to depress, whereas the small amplitude EPSPs facilitated. Facilitation was more prevalent in motoneurons with large rheobases and depression was more often observed in small rheobase motoneurons. The use of partial correlations, which was necessary because of the inverse correlation between EPSP amplitude and motoneuron rheobase, revealed that facilitation-depression behavior during repetitive stimulation is correlated primarily with EPSP amplitude rather than with motoneuron rheobase. Acute transection of the spinal cord resulted in no change in motoneuron rheobase but considerable enlargement of mean EPSP amplitude at low frequencies of stimulation. A significant increase in the amount of depression during repetitive stimulation was noted under these conditions. These results indicate considerable heterogeneity in the response of individual connections to repetitive stimulation. We suggest that this heterogeneity results from differences in transmitter release at different connections. This heterogeneity must also have functional consequences related to susceptibility

  8. Cross-reinnervated motor units in cat muscle. I. Flexor digitorum longus muscle units reinnervated by soleus motoneurons.

    PubMed

    Dum, R P; O'Donovan, M J; Toop, J; Burke, R E

    1985-10-01

    The properties of flexor digitorum longus (FDL) muscles and of individual motor units were studied in cats 30-50 wk after self-reinnervation by FDL motoneurons (FDL----FDL) or cross-reinnervation by soleus (SOL) motoneurons (SOL----FDL). Individual motor units were functionally isolated by intracellular recording and stimulation of identified SOL alpha-motoneurons. Glycogen-depletion methods permitted histochemical study of muscle fibers belonging to physiologically characterized muscle units. The observations were compared with data from normal cat FDL muscles and motor units (27). Intentionally self-reinnervated FDL muscles (FDL----FDL; n = 5) were normal in size and wet weight. FDL----FDL motor units could be classified into the same physiological categories found in normal FDL [types: fast contracting, fatigable (FF), fast contracting, fatigue resistant (FR), and slow (S); n = 24], with approximately the same proportions as normal. The histochemical muscle fiber types associated with these categories were also qualitatively normal although there was evidence of marked distortion of the normal histochemical mosaic. These data confirm other studies of self-reinnervation and suggest that self-reinnervation can produce complete interconversion of muscle fiber types. Cross-reinnervation of FDL muscle by SOL motoneurons (SOL----FDL; n = 12) produced muscles that were smaller (about half the normal wet weight) and more red than normal. SOL----FDL muscle contracted more slowly than normal or FDL----FDL muscles and had much higher proportions of histochemical type I muscle fibers. In those SOL----FDL muscles, in which little or no unwanted self-reinnervation could be demonstrated, greater than 95% of the muscle fibers were type I. Forty-one individual motor units in SOL----FDL muscles were isolated by intracellular penetration in functionally identified SOL alpha-motoneurons. Their muscle units were all type S by physiological criteria (absence of "sag" in unfused

  9. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation.

    PubMed

    Cotel, Florence; Exley, Richard; Cragg, Stephanie J; Perrier, Jean-François

    2013-03-19

    Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle adequately independently of the muscle physiology. Indirect evidence indicates that central fatigue is caused by serotonin (5-HT), but the cellular mechanisms are unknown. In a slice preparation from the spinal cord of the adult turtle, we found that prolonged stimulation of the raphe-spinal pathway--as during motor exercise--activated 5-HT1A receptors that decreased motoneuronal excitability. Electrophysiological tests combined with pharmacology showed that focal activation of 5-HT1A receptors at the axon initial segment (AIS), but not on other motoneuronal compartments, inhibited the action potential initiation by modulating a Na(+) current. Immunohistochemical staining against 5-HT revealed a high-density innervation of 5-HT terminals on the somatodendritic membrane and a complete absence on the AIS. This observation raised the hypothesis that a 5-HT spillover activates receptors at this latter compartment. We tested it by measuring the level of extracellular 5-HT with cyclic voltammetry and found that prolonged stimulations of the raphe-spinal pathway increased the level of 5-HT to a concentration sufficient to activate 5-HT1A receptors. Together our results demonstrate that prolonged release of 5-HT during motor activity spills over from its release sites to the AIS of motoneurons. Here, activated 5-HT1A receptors inhibit firing and, thereby, muscle contraction. Hence, this is a cellular mechanism for central fatigue.

  10. Evidence for restricted central convergence of cutaneous afferents on an excitatory reflex pathway to medial gastrocnemius motoneurons.

    PubMed

    LaBella, L A; McCrea, D A

    1990-08-01

    1. We previously reported that excitatory postsynaptic potentials (EPSPs) produced by low-threshold electrical stimulation of the caudal cutaneous sural nerve (CCS) occur preferentially and with the shortest central latencies in the medial gastrocnemius (MG) portion of the triceps surae motor nuclei. The present study employs the spatial facilitation technique to assess interneuronal convergence on the short-latency excitatory pathway from CCS to MG by several other ipsilateral hindlimb afferents [the lateral cutaneous sural (LCS), caudal cutaneous femoral (CCF), saphenous (SAPH), superficial peroneal (SP), posterior tibial (TIB), and posterior articular (Joint) nerves]. 2. Spatial facilitation of CCF EPSPs in MG motoneurons was demonstrated with conditioning stimulation of the LCS, CCF, SAPH, SP, and TIB nerves, but was most readily and consistently observed with CCF conditioning. Facilitation of CCS and CCF EPSPs was obtained in individual MG motoneurons with a wide range of condition-test intervals. 3. CCF EPSPs in MG motoneurons produced by twice threshold (2T) afferent stimulation had a mean latency of 4.8 ms and often appeared as slowly rising, asynchronous potentials. On the other hand, 2T CCS EPSPs had a mean latency of 2.8 ms and appeared as sharper rising, less variable depolarizations. The optimum condition-test interval for facilitation of CCS and CCF EPSPs was found to be 5.2 ms on average, with CCS stimulation delayed from that of CCF. The longer latency of CCF EPSPs and the finding that the minimum condition-test interval was on the order of 3.9 ms suggests that convergence occurs late in the excitatory CCF pathway to MG motoneurons. 4. Convergence between excitatory pathways to MG from CCF and CCS afferents is discussed with regard to the original observations of Hagbarth on the location of cutaneous receptive fields and excitation of ankle extensors. In addition, evidence for the segregation of these specialized reflex pathways from those involved

  11. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

    PubMed Central

    Cotel, Florence; Exley, Richard; Cragg, Stephanie J.; Perrier, Jean-François

    2013-01-01

    Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle adequately independently of the muscle physiology. Indirect evidence indicates that central fatigue is caused by serotonin (5-HT), but the cellular mechanisms are unknown. In a slice preparation from the spinal cord of the adult turtle, we found that prolonged stimulation of the raphe-spinal pathway—as during motor exercise—activated 5-HT1A receptors that decreased motoneuronal excitability. Electrophysiological tests combined with pharmacology showed that focal activation of 5-HT1A receptors at the axon initial segment (AIS), but not on other motoneuronal compartments, inhibited the action potential initiation by modulating a Na+ current. Immunohistochemical staining against 5-HT revealed a high-density innervation of 5-HT terminals on the somatodendritic membrane and a complete absence on the AIS. This observation raised the hypothesis that a 5-HT spillover activates receptors at this latter compartment. We tested it by measuring the level of extracellular 5-HT with cyclic voltammetry and found that prolonged stimulations of the raphe-spinal pathway increased the level of 5-HT to a concentration sufficient to activate 5-HT1A receptors. Together our results demonstrate that prolonged release of 5-HT during motor activity spills over from its release sites to the AIS of motoneurons. Here, activated 5-HT1A receptors inhibit firing and, thereby, muscle contraction. Hence, this is a cellular mechanism for central fatigue. PMID:23487756

  12. Biphasic effects of baclofen on phrenic motoneurons: possible involvement of two types of gamma-aminobutyric acid (GABA) receptors.

    PubMed

    Lalley, P M

    1983-08-01

    Intravenous injections of baclofen have two general dose-dependent effects on phrenic motoneurons in anesthetized cats. Small doses (0.5-1.5 mg/kg) increase the frequency of action potentials recorded from single motoneurons and from the phrenic nerve, whereas large doses (2-10 mg/kg) reduce or abolish action potentials. The increase in frequency produced by small doses is accompanied by membrane depolarization and, in most experiments, by increased input resistance. Large doses hyperpolarize phrenic motoneurons and produce greater increases in input resistance. Extracellular recording during microelectrophoretic application of baclofen reveals only one effect, depression of cell firing, at all effective current strengths. The low dose stimulatory effect of i.v. baclofen is attributed to disinhibition, whereas the depression by large doses is attributed to disfacilitation. During incomplete inhibition by baclofen, CO2 administration further depresses phrenic nerve activity. Bicuculline (100-600 micrograms/kg i.v.) and picrotoxin (900 micrograms/kg i.v.) restore firing depressed by baclofen, whereas strychnine (80-1280 micrograms/kg) does not. 3-Aminopropanesulfonic acid (5-75 mg/kg i.v.) an agonist at gamma-aminobutyric acid-A receptor sites, depresses phrenic nerve activity. It is suggested that the low dose stimulatory effects are related to actions at gamma-aminobutyric acid-B receptors, whereas the high dose depressant effects are related, at least in part, to activation of gamma-aminobutyric acid-A receptors.

  13. Identification of an interneuronal population that mediates recurrent inhibition of motoneurons in the developing chick spinal cord.

    PubMed

    Wenner, P; O'Donovan, M J

    1999-09-01

    Studies on the development of synaptic specificity, embryonic activity, and neuronal specification in the spinal cord have all been limited by the absence of a functionally identified interneuron class (defined by its unique set of connections). Here, we identify an interneuron population in the embryonic chick spinal cord that appears to be the avian equivalent of the mammalian Renshaw cell (R-interneurons). These cells receive monosynaptic nicotinic, cholinergic input from motoneuron recurrent collaterals. They make predominately GABAergic connections back onto motoneurons and to other R-interneurons but project rarely to other spinal interneurons. The similarity between the connections of the developing R-interneuron, shortly after circuit formation, and the mature mammalian Renshaw cell raises the possibility that R-interneuronal connections are formed precisely from the onset. Using a newly developed optical approach, we identified the location of R-interneurons in a column, dorsomedial to the motor nucleus. Functional characterization of the R-interneuron population provides the basis for analyses that have so far only been possible for motoneurons.

  14. Specification of motoneuron fate in Drosophila: integration of positive and negative transcription factor inputs by a minimal eve enhancer.

    PubMed

    McDonald, Jocelyn A; Fujioka, Miki; Odden, Joanne P; Jaynes, James B; Doe, Chris Q

    2003-11-01

    We are interested in the mechanisms that generate neuronal diversity within the Drosophila central nervous system (CNS), and in particular in the development of a single identified motoneuron called RP2. Expression of the homeodomain transcription factor Even-skipped (Eve) is required for RP2 to establish proper connectivity with its muscle target. Here we investigate the mechanisms by which eve is specifically expressed within the RP2 motoneuron lineage. Within the NB4-2 lineage, expression of eve first occurs in the precursor of RP2, called GMC4-2a. We identify a small 500 base pair eve enhancer that mediates eve expression in GMC4-2a. We show that four different transcription factors (Prospero, Huckebein, Fushi tarazu, and Pdm1) are all expressed in GMC4-2a, and are required to activate eve via this minimal enhancer, and that one transcription factor (Klumpfuss) represses eve expression via this element. All four positively acting transcription factors act independently, regulating eve but not each other. Thus, the eve enhancer integrates multiple positive and negative transcription factor inputs to restrict eve expression to a single precursor cell (GMC4-2a) and its RP2 motoneuron progeny.

  15. Conditioned medium of periodontal ligament mesenchymal stem cells exert anti-inflammatory effects in lipopolysaccharide-activated mouse motoneurons.

    PubMed

    Rajan, Thangavelu Soundara; Giacoppo, Sabrina; Trubiani, Oriana; Diomede, Francesca; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela

    2016-11-15

    Conditioned medium derived from mesenchymal stem cells (MSCs) shows immunomodulatory and neuroprotective effects in preclinical models. Given the difficulty to harvest MSCs from bone marrow and adipose tissues, research has been focused to find alternative resources for MSCs, such as oral-derived tissues. Recently, we have demonstrated the protective effects of MSCs obtained from healthy human periodontal ligament tissue (hPDLSCs) in murine experimental autoimmune encephalomyelitis model. In the present in vitro study, we have investigated the immunomodulatory and neuroprotective effects of conditioned medium obtained from hPDLSCs of Relapsing Remitting- Multiple sclerosis (RR-MS) patients on NSC34 mouse motoneurons stimulated with lipopolysaccharide (LPS). Immunocytochemistry and western blotting were performed. Increased level of TLR4 and NFκB, and reduced level of IκB-α were observed in LPS-stimulated motoneurons, which were modulated by pre-conditioning with hPDLSC-conditioned medium. Inflammatory cytokines (TNF-α, IL-10), neuroprotective markers (Nestin, NFL 70, NGF, GAP43), and apoptotic markers (Bax, Bcl-2, p21) were modulated. Moreover, extracellular vesicles of hPDLSC-conditioned medium showed the presence of anti-inflammatory cytokines IL-10 and TGF-β. Our results demonstrate the immunosuppressive properties of hPDLSC-conditioned medium of RR-MS patients in motoneurons subjected to inflammation. Our findings warrant further preclinical and clinical studies to elucidate the autologous therapeutic efficacy of hPDLSC-conditioned medium in neurodegenerative diseases.

  16. Knee Injuries

    MedlinePlus

    ... injuries. Try weightlifting to strengthen your muscles and stretching, Pilates, and yoga to improve your flexibility because ... lead to injuries and inflammation from overuse. Regular stretching can help. After an injury or surgery has ...

  17. Eye Injuries

    MedlinePlus

    The structure of your face helps protect your eyes from injury. Still, injuries can damage your eye, sometimes severely enough that you could lose your vision. Most eye injuries are preventable. If you play sports or ...

  18. Sports Injuries

    MedlinePlus

    ... sometimes you can injure yourself when you play sports or exercise. Accidents, poor training practices, or improper ... can also lead to injuries. The most common sports injuries are Sprains and strains Knee injuries Swollen ...

  19. The attenuation of passively propagating dendritic potentials in a motoneurone cable model

    PubMed Central

    Redman, S. J.

    1973-01-01

    1. The Rall model of the motoneurone, which consists of a lumped resistance and capacitance, representing the soma, in parallel with a number of distributed resistance-capacitance networks of finite and equal electrical length, representing equivalent dendritic cables, has been used to study the effects of varying electrical and geometrical parameters on the time course and amplitude of transients generated at different locations on the dendritic cables. 2. An analytical solution has been obtained for the time course of the voltage transient generated at the point of current injection on the parallel combination of all dendritic cables, in terms of the distance from the soma to the current injection point, the electrotonic length of the equivalent dendritic cable, the dendritic to soma conductance ratio and the membrane time constant. The current applied is a current impulse, and the response to any synaptic current time course may be obtained from the analytical expression for the current impulse response. A smooth current time course of the form Te—αT has been used in computations. 3. An analytical expression has been obtained for the early part of the voltage response at the point of current injection, when the current is applied to a fraction of the total dendritic cable. This response is in terms of all the cable parameters, and the assumed fraction of the dendritic cable which receives the synaptic current. Computations of this response have been carried out assuming a smooth time course of synaptic current. 4. The computations of the peak amplitude of the voltage transient obtained from these expressions, together with similar computations for the peak amplitude of the voltage transient after propagation to the soma (Jack & Redman, 1971b), have been used to derive a set of attenuation curves for dendritic propagation. These curves give the ratio of the peak amplitude of the voltage transient at the synaptic location on the dendritic cable, and the peak

  20. Thresholds of cortical activation of muscle spindles and α motoneurones of the baboon's hand

    PubMed Central

    Koeze, T. H.; Phillips, C. G.; Sheridan, J. D.

    1968-01-01

    1. Much current thinking about voluntary movement assumes that the segmental γ loops can function as a servomechanism operated by the brain. However, the α motoneurones of the baboon's hand receive a powerful monosynaptic (CM) projection from the precentral gyrus. If servo-driving from the same cortical area is to be possible, it must project independently to the fusimotor neurones and have sufficient power to increase the afferent signalling from the muscle spindles. The cortical thresholds for contraction of m. extensor digitorum communis and for acceleration of the discharges of its muscle spindles have therefore been compared. 2. Significant results in this context require that the spindles studied be coupled in parallel with the responding extrafusal muscle fibres. Many spindles were not unloaded by the submaximal contractions evoked by cortical stimulation, although all so tested were unloaded by maximal motor nerve twitches. Reasons are given for thinking that such apparent lack of parallel coupling is an artifact of complex intramuscular anatomy and limitation of shortening by `isometric' myography. 3. A brief burst of corticospinal volleys at 500/sec, which is specially effective in exciting α motoneurones over the CM projection, failed to excite spindle afferents at or below the threshold for a cortical `twitch'. 4. In a few epileptiform discharges, bursts of spindle acceleration occurred independently of the clonic contractions. A relatively direct and independent cortico-fusimotor (CF) projection may therefore exist. 5. Prolonged near-threshold stimulation at 50-100/sec, which allows time for temporal summation in the less direct projections (e.g. cortico-interneuronal, cortico-rubro-spinal) and does not cause frequency-potentiation at CM synapses, gives abundant evidence of independent α and fusimotor projections, whose actions hardly outlast the stimulation period. 6. Although independent CF projections would permit servo-driving in natural

  1. Doublecortin is expressed in trigeminal motoneurons that innervate the velar musculature of lampreys: considerations on the evolution and development of the trigeminal system.

    PubMed

    Barreiro-Iglesias, Antón; Romaus-Sanjurjo, Daniel; Senra-Martínez, Pablo; Anadón, Ramón; Rodicio, María Celina

    2011-01-01

    Studies in lampreys have revealed interesting aspects of the evolution of the trigeminal system and the jaw. In the present study, we found a marker that distinguishes subpopulations of trigeminal motoneurons innervating two different kinds of oropharyngeal muscles. Immunofluorescence with an antibody against doublecortin (DCX; a neuron-specific phosphoprotein) enabled identification of the trigeminal motoneurons that innervate the velar musculature of larval and recently transformed sea lampreys. DCX-immunoreactive (-ir) motoneurons were observed in the rostro-lateral part of the trigeminal motor nucleus of these animals, but not in lampreys 1 month or more after metamorphosis. Combined double DCX/tubulin and serotonin/tubulin immunofluorescence and tract-tracing experiments with neurobiotin (NB) were also performed in larvae for further characterization of this system. Rich innervation by DCX-ir fibers was observed on the muscle fibers of the velum but not on the upper lip or lower lip muscles, which were innervated by tubulin-ir/DCX-negative fibers. No double-labelled DCX-ir motoneurons were observed in experiments in which the tracer NB was applied to the upper lip. Innervation of velar muscles by serotonergic fibers is also reported. The present results indicate that development of the trigeminal motoneurons innervating the velum differs from that of the trigeminal motoneurons innervating the lips, which is probably related to the dramatic regression of the velum during metamorphosis. The absence of data on a similar subsystem in the trigeminal motor nucleus of gnathostomes suggests that they may be lamprey-specific motoneurons. These results provide support for the "heterotopic theory" of jaw evolution and are inconsistent with the theories of a velar origin for the gnathostome jaw.

  2. Connexin36 in gap junctions forming electrical synapses between motoneurons in sexually dimorphic motor nuclei in spinal cord of rat and mouse

    PubMed Central

    Bautista, W.; Nagy, J. I.

    2014-01-01

    Pools of motoneurons in lumbar spinal cord innervate sexually dimorphic perineal musculature and are themselves sexually dimorphic, displaying differences in numbers and size in male vs. female rodents. In two of these pools, the dorsomedial nucleus (DMN) and the dorsolateral nucleus (DLN), dimorphic motoneurons are intermixed with non-dimorphic neurons innervating anal and external urethral sphincter (EUS) muscles. As motoneurons in these nuclei are reportedly linked by gap junctions, we examined immunofluorescence labelling for the gap junction-forming protein connexin36 (Cx36) in male and female mouse and rat. Fluorescent Cx36-puncta occurred in distinctly greater abundance in the DMN and DLN of male rodents than observed in other spinal cord regions. These puncta were localized to motoneuron somata, proximal dendrites and neuronal appositions, and were distributed either as isolated or large patches of puncta. In both rat and mouse, Cx36-puncta were associated with nearly all (> 94%) DMN and DLN motoneurons. The density of Cx36-puncta increased dramatically from postnatal day 9 to 15, unlike developmental decreases of these puncta observed in other CNS regions. In females, Cx36-puncta in DLN was similar to that in males, but was sparse in the DMN. In EGFP-Cx36 transgenic mice, motoneurons in the DMN and DLN were intensely labelled for EGFP reporter in males, but less so in females. The results indicate the presence of Cx36-containing gap junctions in the sexually dimorphic DMN and DLN of male as well as female rodents, suggesting coupling of not only sexually dimorphic but also non-dimorphic motoneurons in these nuclei. PMID:24304165

  3. Actions on gamma-motoneurones elicited by electrical stimulation of cutaneous afferent fibres in the hind limb of the cat.

    PubMed

    Johansson, H; Sojka, P

    1985-09-01

    The reflex actions elicited by graded electrical stimulation of hind-limb cutaneous (sural, superficial peroneal and tibial) nerves were investigated with intra- and extracellular micro-electrode recordings in gamma-motoneurones projecting to hind-limb muscles in twenty-four cats anaesthetized with alpha-chloralose. In total, reflex responses of 100 gamma-motoneurones were analysed. 82 of the gamma-cells were classified as dynamic (43) or static (39) using the method of mesencephalic stimulation (Appelberg, Hulliger, Johansson & Sojka, 1982). The general responsiveness (i.e. number of input nerves with effect/number of input nerves tested) of the whole sample of gamma-cells to stimulation of skin nerves was extremely high (94.8%). All negative observations were encountered among static and non-classified gamma-cells. Generally, the stimulation strengths needed for evoking effects in the gamma-cells were very low. A majority of the excitatory effects in the dynamic cells appeared with stimulation intensities below 1.5 threshold (T), while most static cells were excited with stimulation strengths between 1.5 and 2 T. Also a statistical comparison of the populations of stimulation strength thresholds for the excitatory effects revealed a significant difference (P less than 0.0009) between dynamic and static gamma-cells. By contrast, the thresholds for inhibitory effects in dynamic cells were slightly higher than for excitatory effects (P less than 0.0009). As regards excitation of static cells, inhibition of dynamic cells and inhibition of static cells, no statistically significant threshold differences were found. A strong dominance of excitation over inhibition was found in both dynamic and static flexor (posterior biceps and semitendinosus) gamma-motoneurones from all input nerves. In comparison to flexor gamma-motoneurones, there was a much higher incidence of inhibitory and mixed (excitatory and inhibitory) responses in extensor (triceps) gamma-motoneurones, from

  4. Aberrant Crossed Corticospinal Facilitation in Muscles Distant from a Spinal Cord Injury

    PubMed Central

    Bunday, Karen L.; Oudega, Martin; Perez, Monica A.

    2013-01-01

    Crossed facilitatory interactions in the corticospinal pathway are impaired in humans with chronic incomplete spinal cord injury (SCI). The extent to which crossed facilitation is affected in muscles above and below the injury remains unknown. To address this question we tested 51 patients with neurological injuries between C2-T12 and 17 age-matched healthy controls. Using transcranial magnetic stimulation we elicited motor evoked potentials (MEPs) in the resting first dorsal interosseous, biceps brachii, and tibialis anterior muscles when the contralateral side remained at rest or performed 70% of maximal voluntary contraction (MVC) into index finger abduction, elbow flexion, and ankle dorsiflexion, respectively. By testing MEPs in muscles with motoneurons located at different spinal cord segments we were able to relate the neurological level of injury to be above, at, or below the location of the motoneurons of the muscle tested. We demonstrate that in patients the size of MEPs was increased to a similar extent as in controls in muscles above the injury during 70% of MVC compared to rest. MEPs remained unchanged in muscles at and within 5 segments below the injury during 70% of MVC compared to rest. However, in muscles beyond 5 segments below the injury the size of MEPs increased similar to controls and was aberrantly high, 2-fold above controls, in muscles distant (>15 segments) from the injury. These aberrantly large MEPs were accompanied by larger F-wave amplitudes compared to controls. Thus, our findings support the view that corticospinal degeneration does not spread rostral to the lesion, and highlights the potential of caudal regions distant from an injury to facilitate residual corticospinal output after SCI. PMID:24146921

  5. Inhibition of cathepsin X reduces the strength of microglial-mediated neuroinflammation.

    PubMed

    Pišlar, Anja; Božić, Biljana; Zidar, Nace; Kos, Janko

    2017-03-01

    Inflammation plays a central role in the processes associated with neurodegeneration. The inflammatory response is mediated by activated microglia that release inflammatory mediators to the neuronal environment. Microglia-derived lysosomal cathepsins, including cathepsin X, are increasingly recognized as important mediators of the inflammation involved in lipopolysaccharide (LPS)-induced neuroinflammation. The current study was undertaken to investigate the role of cathepsin X and its molecular target, γ-enolase, in neuroinflammation and to elucidate the underlying mechanism. We determined that the exposure of activated BV2 and EOC 13.31 cells to LPS led to increased levels of cathepsin X protein and activity in the culture supernatants in a concentration- and time-dependent manner. In contrast, LPS stimulation of these two cells reduced the release of active γ-enolase in a manner regulated by the cathepsin X activity. Cathepsin X inhibitor AMS36 significantly reduced LPS-induced production of nitric oxide, reactive oxygen species and the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α from BV2 cells. Inhibition of cathepsin X suppressed microglial activation through the reduced caspase-3 activity, together with diminished microglial cell death and apoptosis, and also through inhibition of the activity of the mitogen-activated protein kinases. Further, SH-SY5Y treatment with culture supernatants of activated microglial cells showed that cathepsin X inhibition reduces microglia-mediated neurotoxicity. These results indicate that up-regulated expression and increased release and activity of microglial cathepsin X leads to microglia activation-mediated neurodegeneration. Cathepsin X inhibitor caused neuroprotection via its inhibition of the activation of microglia. Cathepsin X could thus be a potential therapeutic target for neuroinflammatory disorders.

  6. Identification of a fatty acid binding protein4-UCP2 axis regulating microglial mediated neuroinflammation.

    PubMed

    Duffy, Cayla M; Xu, Hongliang; Nixon, Joshua P; Bernlohr, David A; Butterick, Tammy A

    2017-02-16

    Hypothalamic inflammation contributes to metabolic dysregulation and the onset of obesity. Dietary saturated fats activate microglia via a nuclear factor-kappa B (NFκB) mediated pathway to release pro-inflammatory cytokines resulting in dysfunction or death of surrounding neurons. Fatty acid binding proteins (FABPs) are lipid chaperones regulating metabolic and inflammatory pathways in response to fatty acids. Loss of FABP4 in peripheral macrophages via either molecular or pharmacologic mechanisms results in reduced obesity-induced inflammation via a UCP2-redox based mechanism. Despite the widespread appreciation for the role of FABP4 in mediating peripheral inflammation, the expression of FABP4 and a potential FABP4-UCP2 axis regulating microglial inflammatory capacity is largely uncharacterized. To that end, we hypothesized that microglial cells express FABP4 and that inhibition would upregulate UCP2 and attenuate palmitic acid (PA)-induced pro-inflammatory response. Gene expression confirmed expression of FABP4 in brain tissue lysate from C57Bl/6J mice and BV2 microglia. Treatment of microglial cells with an FABP inhibitor (HTS01037) increased expression of Ucp2 and arginase in the presence or absence of PA. Moreover, cells exposed to HTS01037 exhibited attenuated expression of inducible nitric oxide synthase (iNOS) compared to PA alone indicating reduced NFκB signaling. Hypothalamic tissue from mice lacking FABP4 exhibit increased UCP2 expression and reduced iNOS, tumor necrosis factor-alpha (TNF-α), and ionized calcium-binding adapter molecule 1 (Iba1; microglial activation marker) expression compared to wild type mice. Further, this effect is negated in microglia lacking UCP2, indicating the FABP4-UCP2 axis is pivotal in obesity induced neuroinflammation. To our knowledge, this is the first report demonstrating a FABP4-UCP2 axis with the potential to modulate the microglial inflammatory response.

  7. Search and Neutralize Factors (Cspgs) that Induce Decline in Transmission to Motoneurons from Spared Fibers after Chronic Spinal Cord Injury

    DTIC Science & Technology

    2014-04-01

    monoclonal NG2-Antibody delivered via osmotic mini- pump can neutralize NG2-induced blockade of axonal conduction, in addition to improving axonal...Project is completed: (1) Proved that delivery of NG2-Ab via mini- pump improves plasticity, axonal conduction, retrograde transport of anatomical...osmotic mini- pump following lateral hemisection (HX) SCI, as described in our SOW. During year 3 we have completed most of research tasks for year 3

  8. Search and Neutralize Factors (CSPGs) that Induce Decline in Transmission to Motoneurons from Spared Fibers after Chronic Spinal Cord Injury

    DTIC Science & Technology

    2013-10-01

    apply for 6- moths no-cost extension to conduct immunochemistry analyses of spinal cord tissue from this completed experiment. 15. SUBJECT TERMS...Neuroscience Forum, Prague 9/10/2013). We apply for 6- moths no-cost extension to complete post-mortem immunochemistry analyses in order to...Thus all 4 specific aims of the project have been successfully accomplished. We apply for 6- moths no-cost extension to complete post-mortem

  9. Sleep bruxism is related to decreased inhibitory control of trigeminal motoneurons, but not with reticulobulbar system.

    PubMed

    İnan, Rahşan; Şenel, Gülçin Benbir; Yavlal, Figen; Karadeniz, Derya; Gündüz, Ayşegül; Kızıltan, Meral E

    2017-01-01

    Sleep bruxism (SB) is a stereotyped movement disorder characterized by grinding or clenching of the teeth during sleep. We aimed to understand the abnormal networks related to the excitability of masticatory pathways in patients with SB. Eleven patients with SB and age- and gender-matched 20 healthy subjects were prospectively enrolled in our study. The masseter inhibitory reflex (MIR) after electrical stimulation and auditory startle reaction (ASR) were examined. For MIR responses, durations of early and late silent period (SP) were shorter and the degree of suppression of SPs was significantly lower in SB group in comparison to those obtained in healthy subjects. The ASR responses even of the masseter muscle, however, were similar between patients with SB and healthy individuals. Abnormal MIR provides support for the decreased inhibitory control of the central masticatory circuits in SB whereas normal ASR suggests the integrity and normal functioning of brainstem pathways mediating startle reaction. Although the sample size is small, our results are in line with previous findings and suggest an abnormally decreased inhibition in trigeminal motoneurons to masseter muscle rather than reticulobulbar pathways in patients with SB.

  10. Contribution of the Runx1 transcription factor to axonal pathfinding and muscle innervation by hypoglossal motoneurons.

    PubMed

    Yoshikawa, Masaaki; Hirabayashi, Mizuki; Ito, Ryota; Ozaki, Shigeru; Aizawa, Shin; Masuda, Tomoyuki; Senzaki, Kouji; Shiga, Takashi

    2015-11-01

    The runt-related transcription factor Runx1 contributes to cell type specification and axonal targeting projections of the nociceptive dorsal root ganglion neurons. Runx1 is also expressed in the central nervous system, but little is known of its functions in brain development. At mouse embryonic day (E) 17.5, Runx1-positive neurons were detected in the ventrocaudal subdivision of the hypoglossal nucleus. Runx1-positive neurons lacked calcitonin gene-related peptide (CGRP) expression, whereas Runx1-negative neurons expressed CGRP. Expression of CGRP was not changed in Runx1-deficient mice at E17.5, suggesting that Runx1 alone does not suppress CGRP expression. Hypoglossal axon projections to the intrinsic vertical (V) and transverse (T) tongue muscles were sparser in Runx1-deficient mice at E17.5 compared to age-matched wild-type littermates. Concomitantly, vesicular acetylcholine transporter-positive axon terminals and acetylcholine receptor clusters were less dense in the V and T tongue muscles of Runx1-deficient mice. These abnormalities in axonal projection were not caused by a reduction in the total number hypoglossal neurons, failed synaptogenesis, or tongue muscles deficits. Our results implicate Runx1 in the targeting of ventrocaudal hypoglossal axons to specific tongue muscles. However, Runx1 deficiency did not alter neuronal survival or the expression of multiple motoneuron markers as in other neuronal populations. Thus, Runx1 appears to have distinct developmental functions in different brain regions.

  11. Role of the trigeminal nerve in regrowth of hypoglossal motoneurons after hypoglossal-facial anastomosis.

    PubMed

    Mameli, Ombretta; Pellitteri, Rosalia; Russo, Antonella; Stanzani, Stefania; Caria, Marcello Alessandro; De Riu, Pier Luigi

    2006-12-01

    Conclusion. Functional recovery of facial muscles following hypoglossal-facial anastomosis (HFA) may be dependent not only on sensory information, relayed via the trigeminal nuclei to the hypoglossal nucleus, but also on extratrigeminal fibers, originating from the hypoglossal nucleus that travel in the infraorbital nerve (ION). This fact helps to explain the ability of hypoglossal neurons, after HFA, to induce contractions of muscles originally innervated from other nervous structures. Objective. The aim of the study was to better understand the role of the trigeminal nerve in reinnervation of facial muscles by hypoglossal motoneurons following HFA. Materials and methods. Central afferences of the ION were analyzed in rats by labeling the exposed nerve with horseradish peroxidase (HRP), whereas central organization of the efferent projections to the vibrissal area was analyzed by labeling the whisker pad muscles of the rat with a 5% solution of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) in N,N-dimethylformamide. Results. The results show that extratrigeminal fibers, originating in the hypoglossal nucleus, travel along the ION. Retrograde tracing applied to ION or injected into the whisker pad showed labeled neurons in the Pr5 nucleus and all Sp5 trigeminal subnuclei. Small labeled neurons (10-15 microm diameter; 10-12 neurons per section), were also found in the hypoglossal nucleus.

  12. NKCC1 cotransporter inactivation underlies embryonic development of chloride-mediated inhibition in mouse spinal motoneuron

    PubMed Central

    Delpy, Alain; Allain, Anne-Emilie; Meyrand, Pierre; Branchereau, Pascal

    2008-01-01

    Early in development, GABA and glycine exert excitatory action that turns to inhibition due to modification of the chloride equilibrium potential (ECl) controlled by the KCC2 and NKCC1 transporters. This switch is thought to be due to a late expression of KCC2 associated with a NKCC1 down-regulation. Here, we show in mouse embryonic spinal cord that both KCC2 and NKCC1 are expressed and functional early in development (E11.5–E13.5) when GABAA receptor activation induces strong excitatory action. After E15.5, a switch occurs rendering GABA unable to provide excitation. At these subsequent stages, NKCC1 becomes both inactive and less abundant in motoneurons while KCC2 remains functional and hyperpolarizes ECl. In conclusion, in contrast to other systems, the cotransporters are concomitantly expressed early in the development of the mouse spinal cord. Moreover, whereas NKCC1 follows a classical functional extinction, KCC2 is highly expressed throughout both early and late embryonic life. PMID:18096599

  13. Corticospinal and reciprocal inhibition actions on human soleus motoneuron activity during standing and walking

    PubMed Central

    Hanna-Boutros, Berthe; Sangari, Sina; Giboin, Louis-Solal; El Mendili, Mohamed-Mounir; Lackmy-Vallée, Alexandra; Marchand-Pauvert, Véronique; Knikou, Maria

    2015-01-01

    Reciprocal Ia inhibition constitutes a key segmental neuronal pathway for coordination of antagonist muscles. In this study, we investigated the soleus H-reflex and reciprocal inhibition exerted from flexor group Ia afferents on soleus motoneurons during standing and walking in 15 healthy subjects following transcranial magnetic stimulation (TMS). The effects of separate TMS or deep peroneal nerve (DPN) stimulation and the effects of combined (TMS + DPN) stimuli on the soleus H-reflex were assessed during standing and at mid- and late stance phases of walking. Subthreshold TMS induced short-latency facilitation on the soleus H-reflex that was present during standing and at midstance but not at late stance of walking. Reciprocal inhibition was increased during standing and at late stance but not at the midstance phase of walking. The effects of combined TMS and DPN stimuli on the soleus H-reflex significantly changed between tasks, resulting in an extra facilitation of the soleus H-reflex during standing and not during walking. Our findings indicate that corticospinal inputs and Ia inhibitory interneurons interact at the spinal level in a task-dependent manner, and that corticospinal modulation of reciprocal Ia inhibition is stronger during standing than during walking. PMID:25825912

  14. Laser ablation of Drosophila embryonic motoneurons causes ectopic innervation of target muscle fibers

    NASA Technical Reports Server (NTRS)

    Chang, T. N.; Keshishian, H.

    1996-01-01

    We have tested the effects of neuromuscular denervation in Drosophila by laser-ablating the RP motoneurons in intact embryos before synaptogenesis. We examined the consequences of this ablation on local synaptic connectivity in both 1st and 3rd instar larvae. We find that the partial or complete loss of native innervation correlates with the appearance of alternate inputs from neighboring motor endings and axons. These collateral inputs are found at ectopic sites on the denervated target muscle fibers. The foreign motor endings are electrophysiologically functional and are observed on the denervated muscle fibers by the 1st instar larval stage. Our data are consistent with the existence of a local signal from the target environment, which is regulated by innervation and influences synaptic connectivity. Our results show that, despite the stereotypy of Drosophila neuromuscular connections, denervation can induce local changes in connectivity in wild-type Drosophila, suggesting that mechanisms of synaptic plasticity may also be involved in normal Drosophila neuromuscular development.

  15. Maternal care effects on SNB motoneuron development: the mediating role of sensory afferent distribution and activity.

    PubMed

    Lenz, Kathryn M; Sengelaub, Dale R

    2009-08-01

    Maternal licking in rats affects the development of the spinal nucleus of the bulbocavernosus (SNB), a sexually dimorphic motor nucleus that controls penile reflexes involved with copulation. Reduced maternal licking produces decreased motoneuron number, size, and dendritic length in the rostral portion of the adult SNB as well as deficits in adult male copulatory behavior. Previous research suggests that decreases in perineal tactile stimulation may be responsible for these effects. To determine whether the regional effects of maternal licking on SNB morphology are driven by sensory afferent innervation of the lumbosacral spinal cord, we used WGA-HRP to reconstruct the location of sensory afferent fibers from the perineal skin. We found that these fibers are caudally concentrated relative to the area of the SNB dendritic field, with the rostral dendritic arbor receiving little perineal afferent innervation. We also assessed Fos expression following perineal tactile stimulation to determine whether it increased local spinal cord activity in the SNB dendritic field. Sixty seconds of licking-like perineal stimulation produced a transient 115% increase in Fos expression in the area of the SNB dendritic field. This effect was driven by a significant increase in Fos in the caudal portion of the SNB dendritic field, matching the pattern of perineal afferent fiber labeling. Perineal tactile stimulation also produced significantly greater Fos expression in male pups than in female pups. Together, these results suggest that perineal sensory afferent activity mediates the effects of early maternal care on the masculinization of the SNB and resultant male copulatory behavior.

  16. Natural cutaneous stimulation induces late and long-lasting facilitation of extensor motoneurons in the cat.

    PubMed

    Schieppati, M; Crenna, P

    1984-02-20

    An investigation was made of the effects of physiological cutaneous stimulation on the excitability of extensor motoneurons in spinal unanesthetized cats. The time course of changes in the monosynaptic reflex (MSR) amplitude of the soleus (Sol) and gastrocnemius medialis (GM) and lateralis (GL) was studied after conditioning stimulation with air jets (delivered to different regions of the skin of the ipsilateral hind limb), pinpricks, or stretching of the skin of the heel induced by passive rotation of the tibio-tarsal joint. Low-intensity electrical stimulation of the sural or saphenous nerves was also employed in order to condition the MSRs of the triceps surae muscles. Hair bending, skin indentation or stretching, as well as electrical nerve stimulation, can induce a similar biphasic excitability cycle of the extensor MSRs, characterized by an early inhibition followed by a late facilitatory period (LFP). The LFP started approximately 20 ms after the arrival of the cutaneous afferent volley, and lasted about 80 ms. Conditioned MSRs could attain values corresponding to 200% or more of controls. The receptive field of the LFP evoked by the air jet proved to be as large as the whole leg and foot skin surface. No significant differences were found in the extent of the late facilitation in the MSRs of Sol, GM and GL, conditioned by electrical stimulation. The LFP was also present, after conditioning stimulation of the same types as above, in intact (and spinal) chloralose-anesthetized cats.

  17. Intensity and frequency dependence of laryngeal afferent inputs to respiratory hypoglossal motoneurons.

    PubMed

    Mifflin, S W

    1997-12-01

    Inspiratory hypoglossal motoneurons (IHMs) mediate contraction of the genioglossus muscle and contribute to the regulation of upper airway patency. Intracellular recordings were obtained from antidromically identified IHMs in anesthetized, vagotomized cats, and IHM responses to electrical activation of superior laryngeal nerve (SLN) afferent fibers at various frequencies and intensities were examined. SLN stimulus frequencies <2 Hz evoked an excitatory-inhibitory postsynaptic potential (EPSP-IPSP) sequence or only an IPSP in most IHMs that did not change in amplitude as the stimulus was maintained. During sustained stimulus frequencies of 5-10 Hz, there was a reduction in the amplitude of SLN-evoked IPSPs with time with variable changes in the EPSP. At stimulus frequencies >25 Hz, the amplitude of EPSPs and IPSPs was reduced over time. At a given stimulus frequency, increasing stimulus intensity enhanced the decay of the SLN-evoked postsynaptic potentials (PSPs). Frequency-dependent attenuation of SLN inputs to IHMs also occurred in newborn kittens. These results suggest that activation of SLN afferents evokes different PSP responses in IHMs depending on the stimulus frequency. At intermediate frequencies, inhibitory inputs are selectively filtered so that excitatory inputs predominate. At higher frequencies there was no discernible SLN-evoked PSP temporally locked to the SLN stimuli. Alterations in SLN-evoked PSPs could play a role in the coordination of genioglossal contraction during respiration, swallowing, and other complex motor acts where laryngeal afferents are activated.

  18. Spatiotemporal pattern of motoneuron activation in the rostral lumbar and the sacral segments during locomotor-like activity in the neonatal mouse spinal cord.

    PubMed

    Bonnot, Agnès; Whelan, Patrick J; Mentis, George Z; O'Donovan, Michael J

    2002-02-01

    We used calcium imaging to visualize the spatiotemporal pattern of motoneuron activity during dorsal root-evoked locomotor-like bursting in the lumbosacral spinal cord of the neonatal mouse. Dorsal root stimuli elicited a tonic discharge in motoneurons on which alternating left-right rhythmic discharges were superimposed. Both the tonic and the rhythmic components could be recorded optically from populations of motoneurons labeled with calcium-green dextran. Optical and electrical recordings revealed that rhythmic signals from different parts of the lumbar (L1, L2) and sacral (S1-S3) segments rose, peaked, and decayed in a rostrocaudal sequence. This pattern gave rise to a rostrocaudal "wave" in the activation of motoneurons during each cycle of locomotor-like activity. A similar rostrocaudal delay was observed during episodes of alternation that occurred in the absence of stimulation, suggesting that this delay was not caused by the train of dorsal root stimuli. It is hypothesized that this behavior may simplify the appropriate sequencing of motoneurons during locomotion.

  19. Serotonergic transmission after spinal cord injury.

    PubMed

    Nardone, Raffaele; Höller, Yvonne; Thomschewski, Aljoscha; Höller, Peter; Lochner, Piergiorgio; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2015-02-01

    Changes in descending serotonergic innervation of spinal neural activity have been implicated in symptoms of paralysis, spasticity, sensory disturbances and pain following spinal cord injury (SCI). Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury, including SCI. Current research suggests that serotonine (5-HT) release within the ventral horn of the spinal cord plays a critical role in motor function, and activation of 5-HT receptors mediates locomotor control. 5-HT originating from the brain stem inhibits sensory afferent transmission and associated spinal reflexes; by abolishing 5-HT innervation SCI leads to a disinhibition of sensory transmission. 5-HT denervation supersensitivity is one of the key mechanisms underlying the increased motoneuron excitability that occurs after SCI, and this hyperexcitability has been demonstrated to underlie the pathogenesis of spasticity after SCI. Moreover, emerging evidence implicates serotonergic descending facilitatory pathways from the brainstem to the spinal cord in the maintenance of pathologic pain. There are functional relevant connections between the descending serotonergic system from the rostral ventromedial medulla in the brainstem, the 5-HT receptors in the spinal dorsal horn, and the descending pain facilitation after tissue and nerve injury. This narrative review focussed on the most important studies that have investigated the above-mentioned effects of impaired 5-HT-transmission in humans after SCI. We also briefly discussed the promising therapeutical approaches with serotonergic drugs, monoclonal antibodies and intraspinal cell transplantation.

  20. Knockdown of the Drosophila fused in sarcoma (FUS) homologue causes deficient locomotive behavior and shortening of motoneuron terminal branches.

    PubMed

    Sasayama, Hiroshi; Shimamura, Mai; Tokuda, Takahiko; Azuma, Yumiko; Yoshida, Tomokatsu; Mizuno, Toshiki; Nakagawa, Masanori; Fujikake, Nobuhiro; Nagai, Yoshitaka; Yamaguchi, Masamitsu

    2012-01-01

    Mutations in the fused in sarcoma/translated in liposarcoma gene (FUS/TLS, FUS) have been identified in sporadic and familial forms of amyotrophic lateral sclerosis (ALS). FUS is an RNA-binding protein that is normally localized in the nucleus, but is mislocalized to the cytoplasm in ALS, and comprises cytoplasmic inclusions in ALS-affected areas. However, it is still unknown whether the neurodegeneration that occurs in ALS is caused by the loss of FUS nuclear function, or by the gain of toxic function due to cytoplasmic FUS aggregation. Cabeza (Caz) is a Drosophila orthologue of human FUS. Here, we generated Drosophila models with Caz knockdown, and investigated their phenotypes. In wild-type Drosophila, Caz was strongly expressed in the central nervous system of larvae and adults. Caz did not colocalize with a presynaptic marker, suggesting that Caz physiologically functions in neuronal cell bodies and/or their axons. Fly models with neuron-specific Caz knockdown exhibited reduced climbing ability in adulthood and anatomical defects in presynaptic terminals of motoneurons in third instar larvae. Our results demonstrated that decreased expression of Drosophila Caz is sufficient to cause degeneration of motoneurons and locomotive disability in the absence of abnormal cytoplasmic Caz aggregates, suggesting that the pathogenic mechanism underlying FUS-related ALS should be ascribed more to the loss of physiological FUS functions in the nucleus than to the toxicity of cytoplasmic FUS aggregates. Since the Caz-knockdown Drosophila model we presented recapitulates key features of human ALS, it would be a suitable animal model for the screening of genes and chemicals that might modify the pathogenic processes that lead to the degeneration of motoneurons in ALS.

  1. Homeostatic Dysregulation in Membrane Properties of Masticatory Motoneurons Compared with Oculomotor Neurons in a Mouse Model for Amyotrophic Lateral Sclerosis

    PubMed Central

    Venugopal, Sharmila; Hsiao, Chie-Fang; Sonoda, Takuma; Wiedau-Pazos, Martina

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motoneuron disease with presently no cure. Motoneuron (MN) hyperexcitability is commonly observed in ALS and is suggested to be a precursor for excitotoxic cell death. However, it is unknown whether hyperexcitability also occurs in MNs that are resistant to degeneration. Second, it is unclear whether all the MNs within homogeneous motor pools would present similar susceptibility to excitability changes since high-threshold MNs innervating fast fatigable muscle fibers selectively degenerate compared with low-threshold MNs innervating fatigue resistant slow muscle fibers. Therefore, we concurrently examined the excitability of ALS-vulnerable trigeminal motoneurons (TMNs) controlling jaw musculature and ALS-resistant oculomotor neurons (OMNs) controlling eye musculature in a well studied SOD1G93A ALS mouse model using in vitro patch-clamp electrophysiology at presymptomatic ages P8–P12. Our results show that hyperexcitability is not a global change among all the MNs, although mutant SOD1 is ubiquitously expressed. Instead, complex changes occur in ALS-vulnerable TMNs based on motor unit type and discharge characteristics. Firing threshold decreases among high-threshold TMNs and increases in a subpopulation of low-threshold TMNs. The latter group was identified based on their linear frequency–current responses to triangular ramp current injections. Such complex changes in MN recruitment were absent in ALS-resistant OMNs. We simulated the observed complex changes in TMN excitability using a computer-based jaw closer motor pool model. Model results suggest that hypoexcitability may indeed represent emerging disease symptomology that causes resistance in muscle force initiation. Identifying the cellular and molecular properties of these hypoexcitable cells may guide effective therapeutic strategies in ALS. PMID:25589764

  2. Modulation of spontaneous locomotor and respiratory drives to hindlimb motoneurons temporally related to sympathetic drives as revealed by Mayer waves

    PubMed Central

    Wienecke, Jacob; Enríquez Denton, Manuel; Stecina, Katinka; Kirkwood, Peter A.; Hultborn, Hans

    2015-01-01

    In this study we investigated how the networks mediating respiratory and locomotor drives to lumbar motoneurons interact and how this interaction is modulated in relation to periodic variations in blood pressure (Mayer waves). Seven decerebrate cats, under neuromuscular blockade, were used to study central respiratory drive potentials (CRDPs, usually enhanced by added CO2) and spontaneously occurring locomotor drive potentials (LDPs) in hindlimb motoneurons, together with hindlimb and phrenic nerve discharges. In four of the cats both drives and their voltage-dependent amplification were absent or modest, but in the other three, one or other of these drives was common and the voltage-dependent amplification was frequently strong. Moreover, in these three cats the blood pressure showed marked periodic variation (Mayer waves), with a slow rate (periods 9–104 s, mean 39 ± 17 SD). Profound modulation, synchronized with the Mayer waves was seen in the occurrence and/or in the amplification of the CRDPs or LDPs. In one animal, where CRDPs were present in most cells and the amplification was strong, the CRDP consistently triggered sustained plateaux at one phase of the Mayer wave cycle. In the other two animals, LDPs were common, and the occurrence of the locomotor drive was gated by the Mayer wave cycle, sometimes in alternation with the respiratory drive. Other interactions between the two drives involved respiration providing leading events, including co-activation of flexors and extensors during post-inspiration or a locomotor drive gated or sometimes entrained by respiration. We conclude that the respiratory drive in hindlimb motoneurons is transmitted via elements of the locomotor central pattern generator. The rapid modulation related to Mayer waves suggests the existence of a more direct and specific descending modulatory control than has previously been demonstrated. PMID:25713515

  3. Fewer active motors per vesicle may explain slowed vesicle transport in chick motoneurons after three days in vitro.

    PubMed

    Macosko, Jed C; Newbern, Jason M; Rockford, Jean; Chisena, Ernest N; Brown, Charlotte M; Holzwarth, George M; Milligan, Carol E

    2008-05-23

    Vesicle transport in cultured chick motoneurons was studied over a period of 3 days using motion-enhanced differential interference contrast (MEDIC) microscopy, an improved version of video-enhanced DIC. After 3 days in vitro (DIV), the average vesicle velocity was about 30% less than after 1 DIV. In observations at 1, 2 and 3 DIV, larger vesicles moved more slowly than small vesicles, and retrograde vesicles were larger than anterograde vesicles. The number of retrograde vesicles increased relative to anterograde vesicles after 3 DIV, but this fact alone could not explain the decrease in velocity, since the slowing of vesicle transport in maturing motoneurons was observed independently for both anterograde and retrograde vesicles. In order to better understand the slowing trend, the distance vs. time trajectories of individual vesicles were examined at a frame rate of 8.3/s. Qualitatively, these trajectories consisted of short (1-2 s) segments of constant velocity, and the changes in velocity between segments were abrupt (<0.2 s). The trajectories were therefore fit to a series of connected straight lines. Surprisingly, the slopes of theses lines, i.e. the vesicle velocities, were often found to be multiples of ~0.6 mum/s. The velocity histogram showed multiple peaks, which, when fit with Gaussians using a least squares minimization, yielded an average spacing of 0.57 mum/s (taken as the slope of a fit to peak position vs. peak number, R(2)=0.994). We propose that the abrupt velocity changes occur when 1 or 2 motors suddenly begin or cease actively participating in vesicle transport. Under this hypothesis, the decrease in average vesicle velocity observed for maturing motoneurons is due to a decrease in the average number of active motors per vesicle.

  4. Inhibition of Electrical Activity by Retroviral Infection with Kir2.1 Transgenes Disrupts Electrical Differentiation of Motoneurons

    PubMed Central

    Yoon, Yone Jung; Kominami, Hisashi; Trimarchi, Thomas; Martin-Caraballo, Miguel

    2008-01-01

    Network-driven spontaneous electrical activity in the chicken spinal cord regulates a variety of developmental processes including neuronal differentiation and formation of neuromuscular structures. In this study we have examined the effect of chronic inhibition of spinal cord activity on motoneuron survival and differentiation. Early spinal cord activity in chick embryos was blocked using an avian replication-competent retroviral vector RCASBP (B) carrying the inward rectifier potassium channel Kir2.1. Chicken embryos were infected with one of the following constructs: RCASBP(B), RCASBP(B)-Kir2.1, or RCASBP(B)-GFP. Infection of chicken embryos at E2 resulted in widespread expression of the viral protein marker p27 gag throughout the spinal cord. Electrophysiological recordings revealed the presence of functional Kir2.1 channels in RCASBP(B)-Kir2.1 but not in RCASBP(B)-infected embryos. Kir2.1 expression significantly reduced the generation of spontaneous motor movements in chicken embryos developing in ovo. Suppression of spontaneous electrical activity was not due to a reduction in the number of surviving motoneurons or the number of synapses in hindlimb muscle tissue. Disruption of the normal pattern of activity in chicken embryos resulted in a significant downregulation in the functional expression of large-conductance Ca2+-dependent K+ channels. Reduction of spinal cord activity also generates a significant acceleration in the inactivation rate of A-type K+ currents without any significant change in current density. Kir2.1 expression did not affect the expression of voltage-gated Na+ channels or cell capacitance. These experiments demonstrate that chronic inhibition of chicken spinal cord activity causes a significant change in the electrical properties of developing motoneurons. PMID:18698433

  5. THE PARKINSONIAN NEUROTOXIN ROTENONE ACTIVATES CALPAIN AND CASPASE-3 LEADING TO MOTONEURON DEGENERATION IN SPINAL CORD OF LEWIS RATS

    PubMed Central

    SAMANTARAY, S.; KNARYAN, V. H.; GUYTON, M. K.; MATZELLE, D. D.; RAY, S. K.; BANIK, N. L.

    2007-01-01

    Exposure to environmental toxins increases the risk of neurodegenerative diseases including Parkinson’s disease (PD). Rotenone is a neurotoxin that has been used to induce experimental parkinsonism in rats. We used the rotenone model of experimental parkinsonism to explore a novel aspect of extra-nigral degeneration, the neurodegeneration of spinal cord (SC), in PD. Rotenone administration to male Lewis rats caused significant neuronal cell death in cervical and lumbar SC as compared to control animals. Dying neurons were motoneurons as identified by double immunofluorescent labeling for TUNEL+ cells and ChAT-immunoreactivity. Neuronal death was accompanied by abundant astrogliosis and microgliosis as evidenced from GFAP-immunoreactivity and OX-42-immunoreactivity, respectively, implicating an inflammatory component during neurodegeneration in SC. However, the integrity of the white matter in SC was not affected by rotenone administration as evidenced from the non co-localization of any TUNEL+ cells with GFAP-immunoreactivity and MBP-immunoreactivity, the selective markers for astrocytes and oligodendrocytes, respectively. Increased activities of 76 kD active m-calpain and 17/19 kD active caspase-3 further demonstrated involvement of these enzymes in cell death in SC. The finding of ChAT+ cell death also suggested degeneration of SC motoneurons in rotenone-induced experimental parkinsonism. Thus, this is the first report of its kind in which the selective vulnerability of a putative parkinsonian target outside of nigrostriatal system has been tested using an environmental toxin to understand the pathophysiology of PD. Moreover, rotenone-induced degeneration of SC motoneuron in this model of experimental parkinsonism progressed with upregulation of calpain and caspase-3. PMID:17367952

  6. Age-Related Changes in Pre- and Postsynaptic Partners of the Cholinergic C-Boutons in Wild-Type and SOD1G93A Lumbar Motoneurons.

    PubMed

    Milan, Léa; Courtand, Gilles; Cardoit, Laura; Masmejean, Frédérique; Barrière, Grégory; Cazalets, Jean-René; Garret, Maurice; Bertrand, Sandrine S

    2015-01-01

    Large cholinergic synaptic terminals known as C-boutons densely innervate the soma and proximal dendrites of motoneurons that are prone to neurodegeneration in amyotrophic lateral sclerosis (ALS). Studies using the Cu/Zn-superoxide dismutase (SOD1) mouse model of ALS have generated conflicting data regarding C-bouton alterations exhibited during ALS pathogenesis. In the present work, a longitudinal study combining immunohistochemistry, biochemical approaches and extra- and intra-cellular electrophysiological recordings revealed that the whole spinal cholinergic system is modified in the SOD1 mouse model of ALS compared to wild type (WT) mice as early as the second postnatal week. In WT motoneurons, both C-bouton terminals and associated M2 postsynaptic receptors presented a complex age-related dynamic that appeared completely disrupted in SOD1 motoneurons. Indeed, parallel to C-bouton morphological alterations, analysis of confocal images revealed a clustering process of M2 receptors during WT motoneuron development and maturation that was absent in SOD1 motoneurons. Our data demonstrated for the first time that the lamina X cholinergic interneurons, the neuronal source of C-boutons, are over-abundant in high lumbar segments in SOD1 mice and are subject to neurodegeneration in the SOD1 animal model. Finally, we showed that early C-bouton system alterations have no physiological impact on the cholinergic neuromodulation of newborn motoneurons. Altogether, these data suggest a complete reconfiguration of the spinal cholinergic system in SOD1 spinal networks that could be part of the compensatory mechanisms established during spinal development.

  7. Age-Related Changes in Pre- and Postsynaptic Partners of the Cholinergic C-Boutons in Wild-Type and SOD1G93A Lumbar Motoneurons

    PubMed Central

    Milan, Léa; Courtand, Gilles; Cardoit, Laura; Masmejean, Frédérique; Barrière, Grégory; Cazalets, Jean-René; Garret, Maurice; Bertrand, Sandrine S.

    2015-01-01

    Large cholinergic synaptic terminals known as C-boutons densely innervate the soma and proximal dendrites of motoneurons that are prone to neurodegeneration in amyotrophic lateral sclerosis (ALS). Studies using the Cu/Zn-superoxide dismutase (SOD1) mouse model of ALS have generated conflicting data regarding C-bouton alterations exhibited during ALS pathogenesis. In the present work, a longitudinal study combining immunohistochemistry, biochemical approaches and extra- and intra-cellular electrophysiological recordings revealed that the whole spinal cholinergic system is modified in the SOD1 mouse model of ALS compared to wild type (WT) mice as early as the second postnatal week. In WT motoneurons, both C-bouton terminals and associated M2 postsynaptic receptors presented a complex age-related dynamic that appeared completely disrupted in SOD1 motoneurons. Indeed, parallel to C-bouton morphological alterations, analysis of confocal images revealed a clustering process of M2 receptors during WT motoneuron development and maturation that was absent in SOD1 motoneurons. Our data demonstrated for the first time that the lamina X cholinergic interneurons, the neuronal source of C-boutons, are over-abundant in high lumbar segments in SOD1 mice and are subject to neurodegeneration in the SOD1 animal model. Finally, we showed that early C-bouton system alterations have no physiological impact on the cholinergic neuromodulation of newborn motoneurons. Altogether, these data suggest a complete reconfiguration of the spinal cholinergic system in SOD1 spinal networks that could be part of the compensatory mechanisms established during spinal development. PMID:26305672

  8. The Extent of Synaptic Stripping of Motoneurons after Axotomy Is Not Correlated to Activation of Surrounding Glia or Downregulation of Postsynaptic Adhesion Molecules

    PubMed Central

    Berg, Alexander; Zelano, Johan; Thams, Sebastian; Cullheim, Staffan

    2013-01-01

    Synapse elimination in the adult central nervous system can be modelled by axotomy of spinal motoneurons which triggers removal of synapses from the cell surface of lesioned motoneurons by processes that remain elusive. Proposed candidate mechanisms are removal of synapses by reactive microglia and astrocytes, based on the remarkable activation of these cell types in the vicinity of motoneurons following axon lesion, and/or decreased expression of synaptic adhesion molecules in lesioned motoneurons. In the present study, we investigated glia activation and adhesion molecule expression in motoneurons in two mouse strains with deviant patterns of synapse elimination following axotomy. Mice deficient in complement protein C3 display a markedly reduced loss of synapses from axotomized motoneurons, whereas mice with impaired function of major histocompatibility complex (MHC) class Ia display an augmented degree of stripping after axotomy. Activation of microglia and astrocytes was assessed by semiquantative immunohistochemistry for Iba 1 (microglia) and GFAP (astrocytes), while expression of synaptic adhesion molecules was determined by in situ hybridization. In spite of the fact that the two mouse strains display very different degrees of synapse elimination, no differences in terms of glial activation or in the downregulation of the studied adhesion molecules (SynCAM1, neuroligin-2,-3 and netrin G-2 ligand) could be detected. We conclude that neither glia activation nor downregulation of synaptic adhesion molecules are correlated to the different extent of the synaptic stripping in the two studied strains. Instead the magnitude of the stripping event is most likely a consequence of a precise molecular signaling, which at least in part is mediated by immune molecules. PMID:23527240

  9. The Use of PRV-Bartha to Define Premotor Inputs to Lumbar Motoneurons in the Neonatal Spinal Cord of the Mouse

    PubMed Central

    Jovanovic, Ksenija; Pastor, Angel M.; O'Donovan, Michael J.

    2010-01-01

    Background The neonatal mouse has become a model system for studying the locomotor function of the lumbar spinal cord. However, information about the synaptic connectivity within the governing neural network remains scarce. A neurotropic pseudorabies virus (PRV) Bartha has been used to map neuronal connectivity in other parts of the nervous system, due to its ability to travel trans-neuronally. Its use in spinal circuits regulating locomotion has been limited and no study has defined the time course of labelling for neurons known to project monosynaptically to motoneurons. Methodology/Principal Findings Here we investigated the ability of PRV Bartha, expressing green and/or red fluorescence, to label spinal neurons projecting monosynaptically to motoneurons of two principal hindlimb muscles, the tibialis anterior (TA) and gastrocnemius (GC). As revealed by combined immunocytochemistry and confocal microscopy, 24–32 h after the viral muscle injection the label was restricted to the motoneuron pool while at 32–40 h the fluorescence was seen in interneurons throughout the medial and lateral ventral grey matter. Two classes of ipsilateral interneurons known to project monosynaptically to motoneurons (Renshaw cells and cells of origin of C-terminals) were consistently labeled at 40 h post-injection but also a group in the ventral grey matter contralaterally. Our results suggest that the labeling of last order interneurons occurred 8–12 h after motoneuron labeling and we presume this is the time taken by the virus to cross one synapse, to travel retrogradely and to replicate in the labeled cells. Conclusions/Significance The study establishes the time window for virally - labelling monosynaptic projections to lumbar motoneurons following viral injection into hindlimb muscles. Moreover, it provides a good foundation for intracellular targeting of the labeled neurons in future physiological studies and better understanding the functional organization of the lumbar

  10. Snowboard injuries.

    PubMed

    Pino, E C; Colville, M R

    1989-01-01

    A retrospective survey of 267 snowboarders was undertaken to determine the population at risk and types and mechanisms of injuries sustained in this sport. Snowboarders are young (average age, 21 years), male (greater than 90%), view themselves in average or above average physical condition (96%), and have varied sports interests. One hundred ten injuries that resulted in a physician visit were reported. Ligament sprains, fractures, and contusions were the most frequent types of injury. Fifty percent of all injuries occurred in the lower extremities, with ankle injuries being the most common. Snowboard riders using equipment with increased ankle support seem to be more protected from lower extremity injuries. The lower extremity injuries were concentrated in the forward limb of the snowboarder, where the rider's weight is disproportionately distributed. Differences in the mechanism and spectrum of injury between snowboarding and skiing injuries were noted, including: impact rather than torsion as the major mechanism of injury, a significant lack of thumb injuries, comparative increase in ankle injuries, a decrease in knee injuries, and a higher percentage of upper extremity injuries.

  11. The synaptic current evoked in cat spinal motoneurones by impulses in single group 1a axons.

    PubMed Central

    Finkel, A S; Redman, S J

    1983-01-01

    Excitatory post-synaptic potentials (e.p.s.p.s) were evoked in motoneurones of anaesthetized cats by impulses in single group 1 a axons. E.p.s.p.s with a time course which indicated a somatic site of origin were voltage-clamped using a single micro-electrode clamp. Excitatory post-synaptic currents (e.p.s.c.s) were found to peak in less than 0.2 ms, and to decay with an exponential time course. The time constant of decay was usually in the range 0.3-0.4 ms (at 37 degrees C). At the resting membrane potential, an e.p.s.p. with a peak of 100 microV was generated by an average peak e.p.s.c. of 330 pA. This corresponded to an average peak conductance increase of 5 nS. The e.p.s.c. decreased with membrane depolarization, and reversed to become an outward current at a null potential of +4.6 +/- 2 mV (+/- S.E. of mean; n = 7). Membrane hyperpolarization caused the peak e.p.s.c. to increase and the time constant of decay of the e.p.s.c. to decrease. The total charge in the synaptic current did not increase with hyperpolarization. This observation can explain earlier observations which showed that the peak amplitude of the e.p.s.p. did not increase with hyperpolarization. The number of ion channels opened by transmitter release at a single somatic bouton was estimated to be in the range 40-240. PMID:6313911

  12. Spinal motoneuron synaptic plasticity during the course of an animal model of multiple sclerosis.

    PubMed

    Marques, K B; Santos, L M B; Oliveira, A L R

    2006-12-01

    During the course of experimental autoimmune encephalomyelitis, a massive loss of motor and sensitive function occurs, which has been classically attributed to the demyelination process. In rats, the clinical signs disappear within 5 days following complete tetraplegia, indicating that demyelination might not be the only cause for the rapid evolution of the disease. The present work investigated the occurrence of experimental autoimmune encephalomyelitis-induced changes of the synaptic covering of spinal motoneurons during exacerbation and after remission. The terminals were typed with transmission electron microscopy as C-, F- and S-type. Immunohistochemical analysis of synaptophysin, glial fibrillary acidic protein and the microglia/macrophage marker F4/80 were also used in order to draw a correlation between the synaptic changes and the glial reaction. The ultrastructural analysis showed that, during exacerbation, there was a strong retraction of both F- and S-type terminals. In this sense, both the covering as well as the length of the remaining terminals suffered great reductions. However, the retracted terminals rapidly returned to apposition, although the mean length remained shorter. A certain level of sprouting may have occurred as, after remission, the number of F-terminals was greater than in the control group. The immunohistochemical analysis showed that the peak of synaptic loss was coincident with an increased macro- and microglial reaction. Our results suggest that the major changes occurring in the spinal cord network during the time course of the disease may contribute significantly to the origin of the clinical signs as well as help to explain their rapid recovery.

  13. Current injection and receptor-mediated excitation produce similar maximal firing rates in hypoglossal motoneurons.

    PubMed

    Wakefield, Hilary E; Fregosi, Ralph F; Fuglevand, Andrew J

    2016-03-01

    The maximum firing rates of motoneurons (MNs), activated in response to synaptic drive, appear to be much lower than that elicited by current injection. It could be that the decrease in input resistance associated with increased synaptic activity (but not current injection) might blunt overall changes in membrane depolarization and thereby limit spike-frequency output. To test this idea, we recorded, in the same cells, maximal firing responses to current injection and to synaptic activation. We prepared 300 μm medullary slices in neonatal rats that contained hypoglossal MNs and used whole-cell patch-clamp electrophysiology to record their maximum firing rates in response to triangular-ramp current injections and to glutamate receptor-mediated excitation. Brief pressure pulses of high-concentration glutamate led to significant depolarization, high firing rates, and temporary cessation of spiking due to spike inactivation. In the same cells, we applied current clamp protocols that approximated the time course of membrane potential change associated with glutamate application and with peak current levels large enough to cause spike inactivation. Means (SD) of maximum firing rates obtained in response to glutamate application were nearly identical to those obtained in response to ramp current injection [glutamate 47.1 ± 12.0 impulses (imp)/s, current injection 47.5 ± 11.2 imp/s], even though input resistance was 40% less during glutamate application compared with current injection. Therefore, these data suggest that the reduction in input resistance associated with receptor-mediated excitation does not, by itself, limit the maximal firing rate responses in MNs.

  14. Effects of gravitational unloading on activity of motoneurones of m. soleus in man

    NASA Astrophysics Data System (ADS)

    Zakirova, Albina; Shigueva, Tatiana; Tomilovskaya, Elena

    The aim of recent work was to study of participation of spinal and supraspinal structures (motor cortex) in the development of hypogravitational hyperreflexia of stretch reflexes observed under weightlessness (Kozlovskaya I.B. et. al., 1981; Reschke M.F. et al., 1984; Saenko I.V., 2007). Methods. 11 healthy volunteers took part in the research. Dry immersion (DI) with the duration of 3 and 5 days was used as onground model of weightlessness. Before and after DI thresholds and amplitudes of m. soleus H-reflex; as well as thresholds and amplitudes of m. soleus motor potentials (MEPs) evoked by magnetic stimulation of spinal roots at L5-S1 segments and cortex motor zones were defined. Results. Exposure to DI was accompanied with significant decrease of the H-reflex threshold by 23.8±8.2%, and with an increase of the relative H-reflex amplitudes by 12.89±8.3% in comparison with background. At the same time thresholds of spinal MEPs were reduced by 5% as well as and their amplitudes were increased significantly by 13.8±4.2%. The obtained data indicate an increase of motoneurones pool’s excitability of m. soleus under gravitational unloading conditions. At the same time after DI exposure a tendency to increase of thresholds of cortical MEPs was observed by 11.7±6.8% from background, and their amplitudes didn’t change in comparison with background, which gives evidence of a non-changed excitability of the motor cortex structures. In general the results of the experiments indicate the spinal nature of the hypogravitational hyperreflexia. The work was supported by RFBR projects NN 13-04-12091 Ofi-m and 11-04-01240-а.

  15. Changes in corticospinal drive to spinal motoneurones following tablet-based practice of manual dexterity.

    PubMed

    Larsen, Lisbeth H; Jensen, Thor; Christensen, Mark S; Lundbye-Jensen, Jesper; Langberg, Henning; Nielsen, Jens B

    2016-02-01

    The use of touch screens, which require a high level of manual dexterity, has exploded since the development of smartphone and tablet technology. Manual dexterity relies on effective corticospinal control of finger muscles, and we therefore hypothesized that corticospinal drive to finger muscles can be optimized by tablet-based motor practice. To investigate this, sixteen able-bodied females practiced a tablet-based game (3 × 10 min) with their nondominant hand requiring incrementally fast and precise pinching movements involving the thumb and index fingers. The study was designed as a semirandomized crossover study where the participants attended one practice- and one control session. Before and after each session electrophysiological recordings were obtained during three blocks of 50 precision pinch movements in a standardized setup resembling the practiced task. Data recorded during movements included electroencephalographic (EEG) activity from primary motor cortex and electromyographic (EMG) activity from first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles. Changes in the corticospinal drive were evaluated from coupling in the frequency domain (coherence) between EEG-EMG and EMG-EMG activity. Following motor practice performance improved significantly and a significant increase in EEG-EMGAPB and EMGAPB-EMGFDI coherence in the beta band (15-30 Hz) was observed. No changes were observed after the control session. Our results show that tablet-based motor practice is associated with changes in the common corticospinal drive to spinal motoneurons involved in manual dexterity. Tablet-based motor practice may be a motivating training tool for stroke patients who struggle with loss of dexterity.

  16. Intrinsic and synaptic homeostatic plasticity in motoneurons from mice with glycine receptor mutations

    PubMed Central

    Tadros, M. A.; Farrell, K. E.; Schofield, P. R.; Brichta, A. M.; Graham, B. A.; Fuglevand, A. J.

    2014-01-01

    Inhibitory synaptic inputs to hypoglossal motoneurons (HMs) are important for modulating excitability in brainstem circuits. Here we ask whether reduced inhibition, as occurs in three murine mutants with distinct naturally occurring mutations in the glycine receptor (GlyR), leads to intrinsic and/or synaptic homeostatic plasticity. Whole cell recordings were obtained from HMs in transverse brainstem slices from wild-type (wt), spasmodic (spd), spastic (spa), and oscillator (ot) mice (C57Bl/6, approximately postnatal day 21). Passive and action potential (AP) properties in spd and ot HMs were similar to wt. In contrast, spa HMs had lower input resistances, more depolarized resting membrane potentials, higher rheobase currents, smaller AP amplitudes, and slower afterhyperpolarization current decay times. The excitability of HMs, assessed by “gain” in injected current/firing-frequency plots, was similar in all strains whereas the incidence of rebound spiking was increased in spd. The difference between recruitment and derecruitment current (i.e., ΔI) for AP discharge during ramp current injection was more negative in spa and ot. GABAA miniature inhibitory postsynaptic current (mIPSC) amplitude was increased in spa and ot but not spd, suggesting diminished glycinergic drive leads to compensatory adjustments in the other major fast inhibitory synaptic transmitter system in these mutants. Overall, our data suggest long-term reduction in glycinergic drive to HMs results in changes in intrinsic and synaptic properties that are consistent with homeostatic plasticity in spa and ot but not in spd. We propose such plasticity is an attempt to stabilize HM output, which succeeds in spa but fails in ot. PMID:24401707

  17. Cross-reinnervated motor units in cat muscle. II. Soleus muscle reinnervated by flexor digitorum longus motoneurons.

    PubMed

    Dum, R P; O'Donovan, M J; Toop, J; Tsairis, P; Pinter, M J; Burke, R E

    1985-10-01

    The properties of whole soleus (SOL) muscles and of individual motor units were studied in cats 30-50 wk after self-reinnervation by soleus (SOL) motoneurons (SOL----SOL) or cross-reinnervation by flexor digitorum longus (FDL) motoneurons (FDL----SOL). As in the preceding paper (22), intracellular and glycogen-depletion methods were used to examine the physiological and histochemical properties of individual motor units. The results were compared with data from normal SOL motor units (8, 12). Intentionally self-reinnervated SOL muscles (SOL----SOL; n = 6) were normal in size and wet weight, and all of the five SOL----SOL motor units studied had physiological and histochemical characteristics that matched those of normal SOL units. Cross-reinnervation of SOL by FDL alpha-motoneurons (FDL----SOL; n = 7) produced muscles with wet weights and appearance essentially identical to normal SOL. However, whole-muscle twitch contraction times were much shorter (mean 60.4 ms) than those of normal (mean 136.9 ms, n = 18) or SOL----SOL muscles (mean 115.3 ms; n = 6). Despite this difference, none of the FDL----SOL muscles contained more than 7% histochemical type II muscle fibers, all of which were type IIA. Normal cat SOL muscles can contain up to 5% type IIA fibers, but none of our SOL----SOL muscles showed any type II fibers. Two FDL----SOL muscles had significant amounts of unintended self-reinnervation, permitting side-by-side comparison of FDL----SOL and SOL----SOL muscle fibers. The twitch contraction times of the two populations differed markedly, but they were histochemically indistinguishable except for the fact that SOL----SOL fibers had high neutral fat content (as do normal SOL fibers), whereas FDL----SOL showed much lower fat content. The 23 FDL----SOL muscle units studied were classified as physiological type S by criteria ("sag" test and fatigue resistance) used to identify motor-unit types in normal cat muscles. All five of the FDL----SOL units studied

  18. Topochemical differences in the amount of RNA in the motoneurons of the spinal chord in hypoxia and hypokinesia

    NASA Technical Reports Server (NTRS)

    Brumberg, V. A.; Gazenko, O. G.; Demin, N. N.; Malkin, V. B.; Pevzner, L. Z.

    1980-01-01

    Reactions to hypoxia and hypoknesia were compared by measuring charges in the amount of ribonucleic acid (RNA) in the cytoplasm of neurons of the intumescentia cervicalis and lumbalis. Animals were subjected to hypoxia, hypokinesia and both combined and a control group to neither. A total of two groups of motoneurons were compared, one innervating the respiratory musculature, the other the musculature of the lower extremities, so that hypoxic hypoxia would probably affect the first group primarily and hypokinesia the second. Results indicate that neither affect the amount of RNA in the neurons of the first group but a significant increase is noted in neurons of the second group. Other significant results are reported.

  19. [The Effect of memantine on spinal alpha-motoneurons and on the content of dopamine, noradrenaline and serotonin in the striatum and lumbar spinal cord].

    PubMed

    Sontag, K H; Wand, P; Schwarz, M; Wesemann, W; Osborne, N N

    1982-01-01

    In the present paper the pharmacological effect of 1,3-dimethyl-5-aminoadamantane (DMAA, D-145, memantine, Memantine was investigated on the reflex activity of spinal alpha-motoneurones of the cat and on spontaneous hyperactivity of alpha-motoneurones of spastic Han-Wist rats. The activity of both systems is reduced by the drug. Furthermore the content of dopamine, noradrenaline, and serotonin of striatum and lumbar spinal cord of normals and mutants is dose dependently decreased. It is assumed that memantine depresses the activation of central nervous membranes and reduces repetitive discharges of axons and in addition acts by release of neurotransmitters.

  20. Snowboarding injuries.

    PubMed

    Sachtleben, Thomas R

    2011-01-01

    Snowboarding has gained immense popularity during the past 30 years and continues to appeal to many young participants. Injury patterns and characteristics of injuries seen commonly in snowboarders have rapidly evolved during this time. Risk factors have emerged, and various methods of reducing injuries to snowboarders have been investigated. It is important that medical providers are knowledgeable about this growing sport and are prepared to adequately evaluate and treat snowboarding injuries. This article will review the issues and discuss diagnostic and treatment principles regarding injuries seen commonly in snowboarders. Injury prevention should be emphasized, particularly with young riders and beginners.

  1. Constitutively active 5-HT2/α1 receptors facilitate muscle spasms after human spinal cord injury

    PubMed Central

    D'Amico, Jessica M.; Murray, Katherine C.; Li, Yaqing; Chan, K. Ming; Finlay, Mark G.; Bennett, David J.

    2013-01-01

    In animals, the recovery of motoneuron excitability in the months following a complete spinal cord injury is mediated, in part, by increases in constitutive serotonin (5-HT2) and norepinephrine (α1) receptor activity, which facilitates the reactivation of calcium-mediated persistent inward currents (CaPICs) without the ligands serotonin and norepinephrine below the injury. In this study we sought evidence for a similar role of constitutive monoamine receptor activity in the development of spasticity in human spinal cord injury. In chronically injured participants with partially preserved sensory and motor function, the serotonin reuptake inhibitor citalopram facilitated long-lasting reflex responses (spasms) previously shown to be mediated by CaPICs, suggesting that in incomplete spinal cord injury, functional descending sources of monoamines are present to activate monoamine receptors below the lesion. However, in participants with motor or motor/sensory complete injuries, the inverse agonist cyproheptadine, which blocks both ligand and constitutive 5-HT2/α1 receptor activity, decreased long-lasting reflexes, whereas the neutral antagonist chlorpromazine, which only blocks ligand activation of these receptors, had no effect. When tested in noninjured control participants having functional descending sources of monoamines, chlorpromazine was effective in reducing CaPIC-mediated motor unit activity. On the basis of these combined results, it appears that in severe spinal cord injury, facilitation of persistent inward currents and muscle spasms is mainly mediated by the activation of constitutive 5-HT2 and α1 receptor activity. Drugs that more selectively block these constitutively active monoamine receptors may provide better oral control of spasticity, especially in motor complete spinal cord injury where reducing motoneuron excitability is the primary goal. PMID:23221402

  2. Misdirection of regenerating motor axons after nerve injury and repair in the rat sciatic nerve model

    PubMed Central

    de Ruiter, Godard C. W.; Malessy, Martijn J. A.; Alaid, Awad O.; Spinner, Robert J.; Engelstad, JaNean K.; Sorenson, E. J.; Kaufman, K. R.; Dyck, Peter J.; Windebank, Anthony J.

    2010-01-01

    Misdirection of regenerating axons is one of the factors that can explain the poor results often found after nerve injury and repair. In this study, we quantified the degree of misdirection and the effect on recovery of function after different types of nerve injury and repair in the rat sciatic nerve model; crush injury, direct coaptation, and autograft repair. Sequential tracing with retrograde labeling of the peroneal nerve before and 8 weeks after nerve injury and repair was performed to quantify the accuracy of motor axon regeneration. Digital video analysis of ankle motion was used to investigate the recovery of function. In addition, serial compound action potential recordings and nerve and muscle morphometry were performed. In our study, accuracy of motor axon regeneration was found to be limited; only 71% (±4.9%) of the peroneal motoneurons were correctly directed 2 months after sciatic crush injury, 42% (±4.2%) after direct coaptation, and 25% (±6.6%) after autograft repair. Recovery of ankle motion was incomplete after all types of nerve injury and repair and demonstrated a disturbed balance of ankle plantar and dorsiflexion. The number of motoneurons from which axons had regenerated was not significantly different from normal. The number of myelinated axons was significantly increased distal to the site of injury. Misdirection of regenerating motor axons is a major factor in the poor recovery of nerves that innervate different muscles. The results of this study can be used as basis for developing new nerve repair techniques that may improve the accuracy of regeneration. PMID:18448099

  3. Corneal injury

    MedlinePlus

    ... as sand or dust Ultraviolet injuries: Caused by sunlight, sun lamps, snow or water reflections, or arc- ... a corneal injury if you: Are exposed to sunlight or artificial ultraviolet light for long periods of ...

  4. Inhalation Injuries

    MedlinePlus

    ... you can inhale that can cause acute internal injuries. Particles in the air from fires and toxic ... and lung diseases worse. Symptoms of acute inhalation injuries may include Coughing and phlegm A scratchy throat ...

  5. ACL Injuries

    MedlinePlus

    ... Diet Plans Nutrients and Nutritional Info Sugar and Sugar Substitutes Exercise and Fitness Exercise Basics Sports Safety Injury ... Diet Plans Nutrients and Nutritional Info Sugar and Sugar Substitutes Exercise and Fitness Exercise Basics Sports Safety Injury ...

  6. Head Injuries

    MedlinePlus

    ... scalp internal head injuries, which may involve the skull, the blood vessels within the skull, or the brain Fortunately, most childhood falls or ... knock the brain into the side of the skull or tear blood vessels. Some internal head injuries ...

  7. Urethral Injuries

    MedlinePlus

    ... and Related Injuries (Video) Rotator Cuff Injury (News) Violent Video Games May Not 'Desensitize' Players, Brain Scans ... Comfort Am I Correct? More Videos News HealthDay Violent Video Games May Not 'Desensitize' Players, Brain Scans ...

  8. Cycling injuries.

    PubMed Central

    Cohen, G. C.

    1993-01-01

    Bicycle-related injuries have increased as cycling has become more popular. Most injuries to recreational riders are associated with overuse or improper fit of the bicycle. Injuries to racers often result from high speeds, which predispose riders to muscle strains, collisions, and falls. Cyclists contact bicycles at the pedals, seat, and handlebars. Each is associated with particular cycling injuries. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8471908

  9. Orienteering injuries

    PubMed Central

    Folan, Jean M.

    1982-01-01

    At the Irish National Orienteering Championships in 1981 a survey of the injuries occurring over the two days of competition was carried out. Of 285 individual competitors there was a percentage injury rate of 5.26%. The article discusses the injuries and aspects of safety in orienteering. Imagesp236-ap237-ap237-bp238-ap239-ap240-a PMID:7159815

  10. The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model.

    PubMed

    Marques, K B; Scorisa, J M; Zanon, R; Freria, C M; Santos, L M B; Damasceno, B P; Oliveira, A L R

    2009-02-01

    The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model--experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis.

  11. Splicing changes in SMA mouse motoneurons and SMN-depleted neuroblastoma cells: Evidence for involvement of splicing regulatory proteins

    PubMed Central

    Huo, Qing; Kayikci, Melis; Odermatt, Philipp; Meyer, Kathrin; Michels, Olivia; Saxena, Smita; Ule, Jernej; Schümperli, Daniel

    2014-01-01

    Spinal Muscular Atrophy (SMA) is caused by deletions or mutations in the Survival Motor Neuron 1 (SMN1) gene. The second gene copy, SMN2, produces some, but not enough, functional SMN protein. SMN is essential to assemble small nuclear ribonucleoproteins (snRNPs) that form the spliceosome. However, it is not clear whether SMA is caused by defects in this function that could lead to splicing changes in all tissues, or by the impairment of an additional, less well characterized, but motoneuron-specific SMN function. We addressed the first possibility by exon junction microarray analysis of motoneurons (MNs) isolated by laser capture microdissection from a severe SMA mouse model. This revealed changes in multiple U2-dependent splicing events. Moreover, splicing appeared to be more strongly affected in MNs than in other cells. By testing mutiple genes in a model of progressive SMN depletion in NB2a neuroblastoma cells, we obtained evidence that U2-dependent splicing changes occur earlier than U12-dependent ones. As several of these changes affect genes coding for splicing regulators, this may acerbate the splicing response induced by low SMN levels and induce secondary waves of splicing alterations. PMID:25692239

  12. A functional model and simulation of spinal motor pools and intrafascicular recordings of motoneuron activity in peripheral nerve

    PubMed Central

    Abdelghani, Mohamed N.; Abbas, James J.; Horch, Kenneth W.; Jung, Ranu

    2014-01-01

    Decoding motor intent from recorded neural signals is essential for the development of effective neural-controlled prostheses. To facilitate the development of online decoding algorithms we have developed a software platform to simulate neural motor signals recorded with peripheral nerve electrodes, such as longitudinal intrafascicular electrodes (LIFEs). The simulator uses stored motor intent signals to drive a pool of simulated motoneurons with various spike shapes, recruitment characteristics, and firing frequencies. Each electrode records a weighted sum of a subset of simulated motoneuron activity patterns. As designed, the simulator facilitates development of a suite of test scenarios that would not be possible with actual data sets because, unlike with actual recordings, in the simulator the individual contributions to the simulated composite recordings are known and can be methodically varied across a set of simulation runs. In this manner, the simulation tool is suitable for iterative development of real-time decoding algorithms prior to definitive evaluation in amputee subjects with implanted electrodes. The simulation tool was used to produce data sets that demonstrate its ability to capture some features of neural recordings that pose challenges for decoding algorithms. PMID:25452711

  13. Estimates of EPSP amplitude based on changes in motoneuron discharge rate and probability.

    PubMed

    Powers, Randall K; Türker, K S

    2010-10-01

    When motor units are discharging tonically, transient excitatory synaptic inputs produce an increase in the probability of spike occurrence and also increase the instantaneous discharge rate. Several researchers have proposed that these induced changes in discharge rate and probability can be used to estimate the amplitude of the underlying excitatory post-synaptic potential (EPSP). We tested two different methods of estimating EPSP amplitude by comparing the amplitude of simulated EPSPs with their effects on the discharge of rat hypoglossal motoneurons recorded in an in vitro brainstem slice preparation. The first estimation method (simplified-trajectory method) is based on the assumptions that the membrane potential trajectory between spikes can be approximated by a 10 mV post-spike hyperpolarization followed by a linear rise to the next spike and that EPSPs sum linearly with this trajectory. We hypothesized that this estimation method would not be accurate due to interspike variations in membrane conductance and firing threshold that are not included in the model and that an alternative method based on estimating the effective distance to threshold would provide more accurate estimates of EPSP amplitude. This second method (distance-to-threshold method) uses interspike interval statistics to estimate the effective distance to threshold throughout the interspike interval and incorporates this distance-to-threshold trajectory into a threshold-crossing model. We found that the first method systematically overestimated the amplitude of small (<5 mV) EPSPs and underestimated the amplitude of large (>5 mV EPSPs). For large EPSPs, the degree of underestimation increased with increasing background discharge rate. Estimates based on the second method were more accurate for small EPSPs than those based on the first model, but estimation errors were still large for large EPSPs. These errors were likely due to two factors: (1) the distance to threshold can only be

  14. Group I projections from intrinsic foot muscles to motoneurones of leg and thigh muscles in humans

    PubMed Central

    Marque, Philippe; Nicolas, Guillaume; Marchand-Pauvert, Véronique; Gautier, Julien; Simonetta-Moreau, Marion; Pierrot-Deseilligny, Emmanuel

    2001-01-01

    Group I projections from intrinsic plantar muscles to motoneurones (MNs) of human leg and thigh muscles were investigated. Changes in firing probability of single motor units (MUs) in the tibialis anterior (TA), peroneus brevis (Per brev), soleus (Sol), gastrocnemius medialis (GM), vastus lateralis (VL), semitendinosus (ST) and biceps (Bi) were studied after electrical stimuli applied to: (i) the tibial nerve (TN) at ankle level, (ii) the corresponding homonymous nerve, and (iii) the skin of the heel, to mimic the TN-induced cutaneous sensation.Homonymous facilitation, attributable to monosynaptic Ia excitation, was found in all the sampled units. Early heteronymous excitation elicited by TN stimulation was found in many MUs. Later effects (3–5 ms central delay) were bigger and more frequently observed: excitation in most TA and Per brev MUs, and inhibition in most Sol, GM and Bi MUs and in many ST and VL MUs. The low threshold (∼0.5–0.6 × motor threshold) and the inability of a pure cutaneous stimulation to reproduce these effects (except the late excitation in TA MUs) indicate that they were due to stimulation of group I muscle afferents.The early excitation was accepted to be monosynaptic when its central delay differed from that of the homonymous Ia excitation by less than 0.5 ms. Such a significant TN-induced monosynaptic Ia excitation was found in MUs belonging to all leg and thigh motor nuclei tested. Although its mean strength was relatively weak, it is argued that these monosynaptic connections might affect already depolarized MNs.The late excitation found in TA and Per brev MUs is argued to be mediated through interneurones located rostral to MNs.The late suppression, found in most Sol, GM and Bi MUs, and in many ST and VL MUs, was the dominant effect. It was accompanied by an inhibition of the Sol and quadriceps H reflexes at rest, and therefore reflects an inhibition directed to MNs. Its long latency is argued to reflect transmission by

  15. Waterbike injuries.

    PubMed Central

    Jeffery, R S; Caiach, S

    1991-01-01

    Jet skiing is a rapidly growing sport. The craft incorporate safety features and the manufacturers issue detailed safety instructions. Racing is conducted with adequate attention to clothing, safety and insurance. However, casual use is widespread and is sometimes irresponsible. Serious injuries to riders are uncommon: dental and knee injuries are described. A case of renal contusion and a head injury were caused by other riders and two potentially fatal injuries illustrate the risk for other water users. The number of injuries associated with the use of personal watercraft is likely to increase and may be influenced by appropriate organization or regulation. Images Figure 2 Figure 3 Figure 4 PMID:1810620

  16. Chronic infusion of SOD1(G93A) astrocyte-secreted factors induces spinal motoneuron degeneration and neuromuscular dysfunction in healthy rats.

    PubMed

    Ramírez-Jarquín, Uri N; Rojas, Fabiola; van Zundert, Brigitte; Tapia, Ricardo

    2017-01-27

    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease and studies in vitro show that motoneuron degeneration is triggered by non-cell-autonomous mechanisms. However, whether soluble toxic factor(s) released by mutant superoxide dismutase 1 (SOD1) expressing astrocytes induces death of motoneurons and leads to motor dysfunction in vivo is not known. To directly test this, healthy adult rats were treated with conditioned media derived from primary mouse astrocytes (ACM) that express human (h) SOD1(G93A) (ACM-hG93A) via chronic osmotic pump infusion in the lumbar spinal cord. Controls included ACM derived from transgenic mice expressing hSOD1(WT) (ACM-hWT) or non-transgenic mouse SOD1(WT) (ACM-WT) astrocytes. Rats chronically infused with ACM-hG93A started to develop motor dysfunction at 8 days, as measured by rotarod performance. Additionally, immunohistochemical analyses at day 16 revealed reactive astrogliosis and significant loss of motoneurons in the ventral horn of the infused region. Controls did not show significant motor behavior alterations or neuronal damage. Thus, we demonstrate that factors released in vitro from astrocytes derived from ALS mice cause spinal motoneuron death and consequent neuromuscular dysfunction in vivo.

  17. Goji fruit (Lycium barbarum) protects sciatic nerve function against crush injury in a model of diabetic stress.

    PubMed

    Simonyan, K V; Avetisyan, L G; Chavushyan, V A

    2016-09-01

    Excess fructose consumption causes changes in functioning of the central and peripheral nervous systems, which increase the vulnerability of peripheral nerves to traumatic injury. The aim of this study was to evaluate the electrophysiological parameters of responses of motoneurons of the spinal cord at high-frequency stimulation of the distal part of the injured sciatic nerve in a model of diabetic stress under action of Lycium barbarum (LB). Male albino rats were given with drinking water with 50% concentration of dietary fructose for 6 weeks. Starting on the 7th week a crush injury of the left sciatic nerve was carried out. Some of the animals received fructose post-injury for 3 weeks and some of the animals received fructose+dry LB fruits for 3 weeks. In the fructose+crush+LВ group a relatively proportional division of tetanic and posttetanic potentiation and depression in responses of ipsilateral and contralateral motoneurons was observed, which would suggest the modulatory role of LB in short-term synaptic plasticity formation. Generally, LB fruit is able to modulate central nervous system reorganization, amplifying positive adaptive changes that improve functional recovery and promote selective target reinnervation in high fructose-diet rats with sciatic nerve crush-injury.

  18. Bicycling injuries.

    PubMed

    Silberman, Marc R

    2013-01-01

    Bicycling injuries can be classified into bicycle contact, traumatic, and overuse injuries. Despite the popularity of cycling, there are few scientific studies regarding injuries. Epidemiological studies are difficult to compare due to different methodologies and the diverse population of cyclists studied. There are only three studies conducted on top level professionals. Ninety-four percent of professionals in 1 year have experienced at least one overuse injury. Most overuse injuries are mild with limited time off the bike. The most common site of overuse injury is the knee, and the most common site of traumatic injury is the shoulder, with the clavicle having the most common fracture. Many overuse and bicycle contact ailments are relieved with simple bike adjustments.

  19. Reduced synaptic activity precedes synaptic stripping in vagal motoneurons after axotomy.

    PubMed

    Yamada, Jun; Hayashi, Yoshinori; Jinno, Shozo; Wu, Zhou; Inoue, Kazuhide; Kohsaka, Shinichi; Nakanishi, Hiroshi

    2008-10-01

    Activated microglia, which spread on the motor neurons following nerve injury, engage in the displacement of detached afferent synaptic boutons from the surface of regenerating motor neurons. This phenomenon is known as "synaptic stripping." The present study attempted to examine whether changes in the synaptic inputs after motor nerve injury correlated with the microglial attachment to the dorsal motor neurons of the vagus (DMV). DMV neurons in Wistar rats could survive after nerve injury, whereas most of injured DMV neurons in the C57BL/6 mice died. At 2 days after nerve injury, a significant decrease was observed in the frequencies of both spontaneous and miniature EPSCs and IPSCs recorded from DMV neurons in the slice preparation but not from the mechanically dissociated neurons in the Wistar rats. At this stage, no direct apposition of microglia on the injured neurons was observed. High-K(+) stimulation restored their frequencies to control levels. Furthermore, PPADS and DPCPX, antagonists of P2 and adenosine receptors, respectively, also stimulated the recovery of their frequencies. In contrast, no significant change was detected in the spontaneous EPSCs frequency recorded from the severely injured DMV neurons in the slice preparation of the C57BL/6 mice. These observations strongly suggest that presynaptic inhibition through glia-derived ATP and adenosine, thus precedes synaptic stripping in regenerating DMV neurons following nerve injury.

  20. Calcium dynamics and buffering in oculomotor neurones from mouse that are particularly resistant during amyotrophic lateral sclerosis (ALS)-related motoneurone disease

    PubMed Central

    Vanselow, Bodo K; Keller, Bernhard U

    2000-01-01

    Motoneurones are particularly vulnerable both in human forms of amyotrophic lateral sclerosis (ALS) and corresponding animal models of the disease. While most motoneurone populations are selectively impaired, oculomotor neurones are essentially resistant to ALS-related damage. Motoneurone vulnerability has been closely linked to disruptions of calcium signalling. To investigate underlying events, we performed a quantitative analysis of calcium homeostasis in oculomotor neurones from mice by simultaneous patch-clamp recordings in sliced tissue and microfluorometric-calcium measurements. Somatic calcium dynamics were investigated by using a computer-controlled microfluorometric system. In oculomotor neurones, basal calcium concentrations were around 80 nm and depolarisation-induced calcium responses were observed for membrane voltages positive to −40 mV. Endogenous calcium homeostasis was quantified by using the ‘added buffer’ approach. The recovery phase of depolarisation-induced calcium transients was well approximated by a mono-exponential function with a decay time constant that showed a linear dependence on dye concentration. The extrapolated time constant in the absence of indicator dye was 1.7 ± 0.2 s (n = 11 cells, 21°C). Endogenous calcium binding ratios (κs) were found to be 264 ± 25 (n = 11 cells), indicating that 99.6 % of cytosolic calcium ions were taken up by endogenous buffers. Recovery of calcium transients was characterised by an ‘effective’ extrusion rate γ= 156 ± 20 s−1 (n = 11 cells, 21 °C). Endogenous calcium binding ratios in oculomotor neurones were 5- to 6-fold larger compared with those of more vulnerable motoneurones in the nucleus hypoglossus and spinal cord. In a first order approximation, they reduced the volume of local calcium elevations around open calcium channels, lowered peak amplitudes of global calcium transients for a given influx and prolonged calcium recovery times for a given set of uptake and extrusion

  1. Asymmetries in sensory pathways from skin to motoneurons on each side of the body determine the direction of an avoidance response in hatchling Xenopus tadpoles.

    PubMed

    Zhao, F Y; Burton, B G; Wolf, E; Roberts, A

    1998-01-15

    1. When swimming is initiated by tail stimulation in hatchling Xenopus tadpoles, the first trunk contraction is usually on the opposite side and directs the animal away from the stimulus. We have investigated how asymmetries in the skin sensory pathways mediate this response. 2. In alpha-bungarotoxin-immobilized tadpoles, intracellular recordings were made of responses to ipsilateral (ISS) and contralateral skin stimulation (CSS) in thirty-two presumed motoneurons. ISS evokes an inhibitory postsynaptic potential (IPSP) followed by an excitatory postsynaptic potential (EPSP) whereas CSS only evokes an EPSP. Blocking the short latency IPSP evoked by ISS with strychnine reduced the difference in spike latency on the two sides but spikes still occurred first to CSS. 3. Motoneuron EPSPs evoked by ISS and CSS were therefore recorded during microperfusion of strychnine to block the short latency IPSP. We found: (a) the CSS-EPSPs have lower threshold, larger amplitude at a given intensity of stimulus, faster rising phase, and shorter latencies than those of ISS-EPSPs; (b) the ISS-EPSP onset latencies were longer than CSS-EPSPs and became shorter as the stimulus intensity increased while those of CSS-EPSPs remained little changed. At high stimulus intensities, EPSPs caused by CSS and ISS became similar; and (c) onset latencies of ISS-EPSPs had higher variance than those of CSS-EPSPs. However, this difference was reduced as the stimulus intensity was increased. 4. Since motoneuron EPSP onset latencies varied with stimulus intensity, we proposed that the pathway from the opposite side had stronger synapses from afferents to sensory interneurons. To test this proposal we built a neuronal population model of the spinal pathway from skin afferents, via sensory interneurons to ipsilateral and contralateral motoneurons incorporating this asymmetry. Inhibition was omitted from the model. 5. Simulated motoneuron EPSPs in response to skin stimulation on each side of the body showed

  2. Properties of synaptic transmission from the reticular formation dorsal to the facial nucleus to trigeminal motoneurons during early postnatal development in rats.

    PubMed

    Gemba-Nishimura, A; Inoue, T; Nakamura, S; Nakayama, K; Mochizuki, A; Shintani, S; Yoshimura, S

    2010-03-31

    We previously reported that electrical stimulation of the reticular formation dorsal to the facial nucleus (RdVII) elicited excitatory masseter responses at short latencies and that RdVII neurons were antidromically activated by stimulation of the trigeminal motor nucleus (MoV), suggesting that excitatory premotor neurons targeting the MoV are likely located in the RdVII. We thus examined the properties of synaptic transmission from the RdVII to jaw-closing and jaw-opening motoneurons in horizontal brainstem preparations from developing rats using voltage-sensitive dye, patch-clamp recordings and laser photostimulation. Electrical stimulation of the RdVII evoked optical responses in the MoV. Combined bath application of the non-N-methyl-d-aspartate (non-NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (APV) reduced these optical responses, and addition of the glycine receptor antagonist strychnine and the GABA(A) receptor antagonist bicuculline further reduced the remaining responses. Electrical stimulation of the RdVII evoked postsynaptic currents (PSCs) in all 19 masseter motoneurons tested in postnatal day (P)1-4 rats, and application of CNQX and the NMDA receptor antagonist (+/-)-3(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) reduced the PSC amplitudes by more than 50%. In the presence of CNQX and CPP, the GABA(A) receptor antagonist SR95531 further reduced PSC amplitude, and addition of strychnine abolished the remaining PSCs. Photostimulation of the RdVII with caged glutamate also evoked PSCs in masseter motoneurons of P3-4 rats. In P8-11 rats, electrical stimulation of the RdVII also evoked PSCs in all 14 masseter motoneurons tested, and the effects of the antagonists on the PSCs were similar to those in P1-4 rats. On the other hand, RdVII stimulation evoked PSCs in only three of 16 digastric motoneurons tested. These results suggest that both neonatal and

  3. Injury - kidney and ureter

    MedlinePlus

    Kidney damage; Toxic injury of the kidney; Kidney injury; Traumatic injury of the kidney; Fractured kidney; Inflammatory injury of the kidney; Bruised kidney; Ureteral injury; Pre-renal failure - injury, ...

  4. Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones

    PubMed Central

    Sirois, Jay E; Lynch, Carl; Bayliss, Douglas A

    2002-01-01

    Neurotransmitters and volatile anaesthetics have opposing effects on motoneuronal excitability which appear to reflect contrasting modulation of two types of subthreshold currents. Neurotransmitters increase motoneuronal excitability by inhibiting TWIK-related acid-sensitive K+ channels (TASK) and shifting activation of a hyperpolarization-activated cationic current (Ih) to more depolarized potentials; on the other hand, anaesthetics decrease excitability by activating a TASK-like current and inducing a hyperpolarizing shift in Ih activation. Here, we used whole-cell recording from motoneurones in brainstem slices to test if neurotransmitters (serotonin (5-HT) and noradrenaline (NA)) and an anaesthetic (halothane) indeed compete for modulation of the same ion channels - and we determined which prevails. When applied together under current clamp conditions, 5-HT reversed anaesthetic-induced membrane hyperpolarization and increased motoneuronal excitability. Under voltage clamp conditions, 5-HT and NA overcame most, but not all, of the halothane-induced current. When Ih was blocked with ZD 7288, the neurotransmitters completely inhibited the K+ current activated by halothane; the halothane-sensitive neurotransmitter current reversed at the equilibrium potential for potassium (EK) and displayed properties expected of acid-sensitive, open-rectifier TASK channels. To characterize modulation of Ih in relative isolation, effects of 5-HT and halothane were examined in acidified bath solutions that blocked TASK channels. Under these conditions, 5-HT and halothane each caused their characteristic shift in voltage-dependent gating of Ih. When tested concurrently, however, halothane decreased the neurotransmitter-induced depolarizing shift in Ih activation. Thus, halothane and neurotransmitters converge on TASK and Ih channels with opposite effects; transmitter action prevailed over anaesthetic effects on TASK channels, but not over effects on Ih. These data suggest that

  5. Contribution of potassium conductances to a time-dependent transition in electrical properties of a cockroach motoneuron soma.

    PubMed

    Mills, J D; Pitman, R M

    1999-05-01

    Contribution of potassium conductances to a time-dependent transition in electrical properties of a cockroach motoneuron soma. The cell body of the cockroach (Periplaneta americana) fast coxal depressor motoneuron (Df) displays a time-dependent change in excitability. Immediately after dissection, depolarization evokes plateau potentials, but after several hours all-or-none action potentials are evoked. Because K channel blockers have been shown to produce a similar transition in electrical properties, we have used current-clamp, voltage-clamp and action-potential-clamp recording to elucidate the contribution of different classes of K channel to the transition in electrical activity of the neuron. Apamin had no detectable effect on the neuron, but charybdotoxin (ChTX) caused a rapid transition from plateau potentials to spikes in the somatic response of Df to depolarization. In neurons that already produced spikes when depolarized, ChTX increased spike amplitude but did not increase their duration nor decrease the amplitude of their afterhyperpolarization. 4-Aminopyridine (4-AP) (which selectively blocks transient K currents) did not cause a transition from plateau potentials to spikes but did enhance oscillations superimposed on plateau potentials. When applied to neurons that already generated spikes when depolarized, 4-AP could augment spike amplitude, decrease the latency to the first spike, and prolong the afterhyperpolarization. Evidence suggests that the time-dependent transition in electrical properties of this motoneuron soma may result, at least in part, from a fall in calcium-dependent potassium current (IK,Ca), consequent on a gradual reduction in [Ca2+ ]i. Voltage-clamp experiments demonstrated directly that outward K currents in this neuron do fall with a time course that could be significant in the transition of electrical properties. Voltage-clamp experiments also confirmed the ineffectiveness of apamin and showed that ChTX blocked most of IK

  6. Environmental injuries.

    PubMed

    Leikin, J B; Aks, S E; Andrews, S; Auerbach, P S; Cooper, M A; Jacobsen, T D; Krenzelok, E P; Shicker, L; Weiner, S L

    1997-12-01

    Environmental injuries and illnesses can happen in home, work, or recreational settings. The variety and severity of these injuries might require the clinician to call on skills from internal medicine, emergency medicine, and toxicology. Diseases of thermoregulation are hypothermia and hyperthermia. In each instance, treatment is based on the need to restore the patient's core temperature to normal and on monitoring for complications. The victim of a fire might suffer inhalation injury in addition to burns, and it is more likely that the inhalation injury will be fatal. Oxygen deprivation and inhalation of irritant or asphyxiant chemicals contribute to injury. Toxic plants can be the source of poisoning emergencies, especially in children. Misinformation and myths that surround common plants can create diagnostic problems (i.e., which plants really are toxic and require emergency measures). Venomous marine organisms can cause a wide range of injury, from cutaneous eruption to fatal envenomation. Most are encountered in a recreational setting, such as water sports, but keepers of home aquariums are subject to stings from venomous fish. Lightning injury can present many diagnostic and treatment dilemmas. An important point in this regard is that lightning injury and high-voltage electrical injury are different in pathology and require different approaches for treatment. A discussion of electrical, chemical, and thermal burns makes such differences apparent.

  7. Paragliding injuries.

    PubMed Central

    Krüger-Franke, M; Siebert, C H; Pförringer, W

    1991-01-01

    Regulations controlling the sport of paragliding were issued in April 1987 by the German Department of Transportation. The growing popularity of this sport has led to a steady increase in the number of associated injuries. This study presents the incidence, localization and degree of injuries associated with paragliding documented in Germany, Austria and Switzerland. The 283 injuries suffered by 218 paragliders were documented in the period 1987-1989: 181 occurred during landing, 28 during starting procedures and nine during flight. The mean patient age was 29.6 years. There were 34.9% spinal injuries, 13.4% upper extremity injuries and 41.3% lower limb injuries. Over half of these injuries were treated surgically and in 54 instances permanent disability remained. In paragliding the lower extremities are at greatest risk of injury during landing. Proper equipment, especially sturdy footwear, exact training in landing techniques as well as improved instruction in procedures during aborted or crash landings is required to reduce the frequency of these injuries. Images p99-a p100-a p100-b p100-c PMID:1751899

  8. Paragliding injuries.

    PubMed

    Krüger-Franke, M; Siebert, C H; Pförringer, W

    1991-06-01

    Regulations controlling the sport of paragliding were issued in April 1987 by the German Department of Transportation. The growing popularity of this sport has led to a steady increase in the number of associated injuries. This study presents the incidence, localization and degree of injuries associated with paragliding documented in Germany, Austria and Switzerland. The 283 injuries suffered by 218 paragliders were documented in the period 1987-1989: 181 occurred during landing, 28 during starting procedures and nine during flight. The mean patient age was 29.6 years. There were 34.9% spinal injuries, 13.4% upper extremity injuries and 41.3% lower limb injuries. Over half of these injuries were treated surgically and in 54 instances permanent disability remained. In paragliding the lower extremities are at greatest risk of injury during landing. Proper equipment, especially sturdy footwear, exact training in landing techniques as well as improved instruction in procedures during aborted or crash landings is required to reduce the frequency of these injuries.

  9. Head Injuries

    MedlinePlus

    ... injury, cerebral contusion, cerebral laceration, coma, head trauma, hematoma, impaired consciousness, postconcussion syndrome, skull fracture, skull penetration, stupor, vegetative state Family Health, Infants ...

  10. Hamstring Injury

    MedlinePlus

    ... result. Hamstring injury risk factors include: Sports participation. Sports that require sprinting or running, or other activities such as dancing that might require extreme stretching, make a hamstring ...

  11. NMDA-induced burst discharge in guinea pig trigeminal motoneurons in vitro.

    PubMed

    Kim, Y I; Chandler, S H

    1995-07-01

    1. The responses of guinea pig trigeminal motoneurons (TMNs) to N-methyl-D,L-aspartate (NMA) were studied using brain stem slice preparations and whole cell patch-clamp (n = 89) or conventional microelectrode (n = 22) recording techniques. The primary goals of this study were to determine whether N-methyl-D-aspartate (NMDA) receptor activation would produce spontaneous bursting activity in TMNs and, if so, the underlying mechanisms responsible for the generation of these bursts. 2. Bath-applied NMA (100-300 microM, n = 80) in standard perfusion medium elicited depolarization, increase in apparent input resistance (Rinp), and rhythmic burst discharges (1-90 s in duration) from TMNs. These effects were blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5, 30 microM, n = 6), but not by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM, n = 10). Furthermore, the burst-inducing effect of NMA was not mimicked by the non-NMDA receptor agonists kainate (KA, 5-10 microM, n = 6) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 5-10 microM, n = 5). 3. In tetrodotoxin (TTX) treatment conditions (n = 13), NMA elicited depolarization, an increase in apparent Rinp, and rhythmic membrane potential oscillations without action potential bursts (i.e., plateau potentials), suggesting that the effects of NMA observed in the TTX-free condition resulted from activation of postsynaptic NMDA receptors. 4. Graded depolarization of neurons (n = 20) by intracellular direct current injection generally led to a graded increase in frequency and duration of the NMA-induced bursts and plateau potentials until these rhythmic events eventually became transformed into continuous spike discharge and maintained depolarization, respectively. Removal of Mg2+ from the perfusion medium (n = 11) also turned the bursts and plateau potentials into continuous spike discharge and maintained depolarization, respectively

  12. Ionic basis of membrane potential changes induced by anoxia in rat dorsal vagal motoneurones.

    PubMed Central

    Cowan, A I; Martin, R L

    1992-01-01

    1. The effects of anoxia on membrane properties of 119 dorsal vagal motoneurones (DVMs) were investigated in an in vitro slice preparation of the rat medulla. 2. Membrane potential was unaffected by anoxia in 11% of DVMs. An hyperpolarization accompanied by a decrease in input resistance occurred in 44% of DVMs; the remaining 45% depolarized with either an increase (60%) or decrease in input resistance (40%). TTX at a concentration of 0.3-1 microM did not significantly affect these responses. 3. Anoxic artificial cerebrospinal fluid (ACSF) containing 20 mM-TEA reversed the response of DVMs that hyperpolarized in standard ACSF to reveal a depolarization of 7.4 +/- 2.1 mV, and increased the anoxic depolarization from 5.0 +/- 0.7 to 8.7 +/- 1.4 mV. 4. Anoxic depolarization was converted to an hyperpolarization of 7.3 +/- 2.1 mV in ACSF containing 5 mM-4-aminopyridine (4-AP) and 1 microM-TTX. A residual depolarization of 4.5 +/- 3.5 mV was then observed in ACSF containing 5 mM-4-AP, 1 microM-TTX and 20 mM-TEA. Anoxic hyperpolarization was increased from 7.8 +/- 1.8 to 10.0 +/- 3.9 mV in 5 mM-4-AP and 1 microM-TTX and converted to a depolarization of 5.3 +/- 4.5 mV in 5 mM-4-AP, 1 microM-TTX and 20 mM-TEA. 5. In anoxic ACSF containing TEA, the action potential width was increased from 0.92 +/- 0.04 to 8.1 +/- 1.1 ms in hyperpolarizing DVMs, and from 0.85 +/- 0.01 to 2.4 +/- 1.0 ms in depolarizing DVMs. The increase in width was prevented by 2-3 mM-Mn2+. 6. The long after-hyperpolarization (AHP) of DVMs, which is contributed to by both an apamin-sensitive IK(Ca) and an apamin, charybdotoxin and TEA insensitive IK(Ca) was decreased in duration from 2.59 +/- 0.14 to 1.94 +/- 0.12 s during anoxia. 7. It is concluded that anoxia enhances the delayed rectifier current (IK(DR)) and an inward current, probably ICa, but suppresses the A currents (IA). In DVMs that hyperpolarize during anoxia, the increase in IK(DR) outweighs the increase in ICa and the decrease in IA. In

  13. Effects of support unloading on inhibitory processes in motoneurons pools of postural muscles

    NASA Astrophysics Data System (ADS)

    Shigueva, Tatiana; Zakirova, Albina; Tomilovskaya, Elena

    The purpose of the study was to investigate the effect of support unloading on characteristics of shin extensor muscles (m.soleus and m.gastrocnemius lat.) motor units` (MU) activity evoked by electrical stimulation and intensity of spinal inhibitory processes. Conditions of support unloading were reproduced by "dry" immersion (DI), that it seen to be is the most adequate ground simulation model of weightlessness [Shulzhenko E.B. et al, 1976]. The experiments were performed with participation of 10 healthy men of 20-27 years old. The subjects were divided into 2 groups. In the first one (control group) the subjects stayed in DI for 3 days without any other influences; in the second one (experimental group) in the course of DI the mechanical stimulation of soles’ support zones in the regimen of locomotion was applied daily for 20 min at the beginning of each hour for 6 hours per day [Kozlovskaya I.B., 2007]. MUs’ activity of shin muscles (mm. gastrocnemius lat. and soleus) was recorded with needle concentric electrodes during execution of the task of maintaining a small plantar flexion effort (not stronger than 7% of maximal voluntary contraction force). Single electrical pulses 0,1 ms duration were applied to n.tibialis during spontaneous MU activity. The duration of silent period (SP) following H-reflex response and presence of rebound phenomenon - an increase of MU activity at the end of SP, that is usually observed under normal conditions and reflects trace of inhibitory and excitatory processes in motoneurons pools, were analyzed [Person R.S., 1985]. Experiments were performed before, on the 2nd and 3d day of DI and on the 2nd day after its accomplishment. The Wilcoxon nonparametric criteria were used for statistical data analysis. Exposure to the conditions of support unloading was followed by significant decline of SP duration. The mean of SP duration in shin muscles before DI was 227±31,4 ms. On the 2nd and 3rd days of DI in the control group it

  14. Anatomical evidence for red nucleus projections to motoneuronal cell groups in the spinal cord of the monkey

    NASA Technical Reports Server (NTRS)

    Holstege, Gert; Blok, Bertil F.; Ralston, Diane Daly

    1988-01-01

    In four rhesus monkeys wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections were made in the mesencephalic tegmentum. In three cases with injections involving the red nucleus (RN), rubrospinal fibers descended mainly contralaterally to terminate in laminae V, VI and dorsal VII of the spinal cord and in the lateral motoneuronal cell groups at the level of the cervical and lumbosacral enlargements. In all four cases the area of the interstitial nucleus of Cajal (INC) was injected, which resulted in labeled interstitiospinal fibers in the medial part of the ipsilateral ventral funiculus of the spinal cord. The results indicate that there is no major qualitative difference between the mesencephalic (RN and INC) and motor cortical projections to the spinal cord.

  15. Dual role for Hox genes and Hox co-factors in conferring leg motoneuron survival and identity in Drosophila.

    PubMed

    Baek, Myungin; Enriquez, Jonathan; Mann, Richard S

    2013-05-01

    Adult Drosophila walk using six multi-jointed legs, each controlled by ∼50 leg motoneurons (MNs). Although MNs have stereotyped morphologies, little is known about how they are specified. Here, we describe the function of Hox genes and homothorax (hth), which encodes a Hox co-factor, in Drosophila leg MN development. Removing either Hox or Hth function from a single neuroblast (NB) lineage results in MN apoptosis. A single Hox gene, Antennapedia (Antp), is primarily responsible for MN survival in all three thoracic segments. When cell death is blocked, partially penetrant axon branching errors are observed in Hox mutant MNs. When single MNs are mutant, errors in both dendritic and axon arborizations are observed. Our data also suggest that Antp levels in post-mitotic MNs are important for specifying their identities. Thus, in addition to being essential for survival, Hox and hth are required to specify accurate MN morphologies in a level-dependent manner.

  16. Expression of postsynaptic Ca2+-activated K+ (SK) channels at C-bouton synapses in mammalian lumbar α-motoneurons

    PubMed Central

    Deardorff, Adam S; Romer, Shannon H; Deng, Zhihui; Bullinger, Katie L; Nardelli, Paul; Cope, Timothy C; Fyffe, Robert E W

    2013-01-01

    Small-conductance calcium-activated potassium (SK) channels mediate medium after-hyperpolarization (AHP) conductances in neurons throughout the central nervous system. However, the expression profile and subcellular localization of different SK channel isoforms in lumbar spinal α-motoneurons (α-MNs) is unknown. Using immunohistochemical labelling of rat, mouse and cat spinal cord, we reveal a differential and overlapping expression of SK2 and SK3 isoforms across specific types of α-MNs. In rodents, SK2 is expressed in all α-MNs, whereas SK3 is expressed preferentially in small-diameter α-MNs; in cats, SK3 is expressed in all α-MNs. Function-specific expression of SK3 was explored using post hoc immunostaining of electrophysiologically characterized rat α-MNs in vivo. These studies revealed strong relationships between SK3 expression and medium AHP properties. Motoneurons with SK3-immunoreactivity exhibit significantly longer AHP half-decay times (24.67 vs. 11.02 ms) and greater AHP amplitudes (3.27 vs. 1.56 mV) than MNs lacking SK3-immunoreactivity. We conclude that the differential expression of SK isoforms in rat and mouse spinal cord may contribute to the range of medium AHP durations across specific MN functional types and may be a molecular factor distinguishing between slow- and fast-type α-MNs in rodents. Furthermore, our results show that SK2- and SK3-immunoreactivity is enriched in distinct postsynaptic domains that contain Kv2.1 channel clusters associated with cholinergic C-boutons on the soma and proximal dendrites of α-MNs. We suggest that this remarkably specific subcellular membrane localization of SK channels is likely to represent the basis for a cholinergic mechanism for effective regulation of channel function and cell excitability. PMID:23129791

  17. Jaw muscle spindle afferents coordinate multiple orofacial motoneurons via common premotor neurons in rats: an electrophysiological and anatomical study.

    PubMed

    Zhang, Jingdong; Luo, Pifu; Ro, Jin Y; Xiong, Huangui

    2012-12-13

    Jaw muscle spindle afferents (JMSA) in the mesencephalic trigeminal nucleus (Vme) project to the parvocellular reticular nucleus (PCRt) and dorsomedial spinal trigeminal nucleus (dm-Vsp). A number of premotor neurons that project to the trigeminal motor nucleus (Vmo), facial nucleus (VII) and hypoglossal nucleus (XII) are also located in the PCRt and dm-Vsp. In this study, we examined whether these premotor neurons serve as common relay pool for relaying JMSA to multiple orofacial motoneurons. JMSA inputs to the PCRt and dm-Vsp neurons were verified by recording extracellular responses to electrical stimulation of the caudal Vme or masseter nerve, mechanical stimulation of jaw muscles and jaw opening. After recording, biocytin in recording electrode was inotophorized into recording sites. Biocytin-Iabeled fibers traveled to the Vmo, VII, XII, and the nucleus ambiguus (Amb). Labeled boutons were seen in close apposition with Nissl-stained motoneurons in the Vmo, VII, XII and Amb. In addition, an anterograde tracer (biotinylated dextran amine) was iontophorized into the caudal Vme, and a retrograde tracer (Cholera toxin B subunit) was delivered into either the VII or Xll to identify VII and XII premotor neurons that receive JMSA input. Contacts between labeled Vme neuronal boutons and premotor neurons were observed in the PCRt and adjacent dm-Vsp. Confocal microscopic observations confirmed close contacts between Vme boutons and VII and XII premotor neurons. This study provides evidence that JMSA may coordinate activities of multiple orofacial motor nuclei, including Vmo, VII, XII and Amb in the brainstem via a common premotor neuron pool.

  18. Asymmetry in signal propagation between the soma and dendrites plays a key role in determining dendritic excitability in motoneurons.

    PubMed

    Kim, Hojeong; Jones, Kelvin E; Heckman, C J

    2014-01-01

    It is widely recognized that propagation of electrophysiological signals between the soma and dendrites of neurons differs depending on direction, i.e. it is asymmetric. How this asymmetry influences the activation of voltage-gated dendritic channels, and consequent neuronal behavior, remains unclear. Based on the analysis of asymmetry in several types of motoneurons, we extended our previous methodology for reducing a fully reconstructed motoneuron model to a two-compartment representation that preserved asymmetric signal propagation. The reduced models accurately replicated the dendritic excitability and the dynamics of the anatomical model involving a persistent inward current (PIC) dispersed over the dendrites. The relationship between asymmetric signal propagation and dendritic excitability was investigated using the reduced models while varying the asymmetry in signal propagation between the soma and the dendrite with PIC density constant. We found that increases in signal attenuation from soma to dendrites increased the activation threshold of a PIC (hypo-excitability), whereas increases in signal attenuation from dendrites to soma decreased the activation threshold of a PIC (hyper-excitability). These effects were so strong that reversing the asymmetry in the soma-to-dendrite vs. dendrite-to-soma attenuation, reversed the correlation between PIC threshold and distance of this current source from the soma. We propose the tight relation of the asymmetric signal propagation to the input resistance in the dendrites as a mechanism underlying the influence of the asymmetric signal propagation on the dendritic excitability. All these results emphasize the importance of maintaining the physiological asymmetry in dendritic signaling not only for normal function of the cells but also for biophysically realistic simulations of dendritic excitability.

  19. Population synaptic potentials evoked in lumbar motoneurons following stimulation of the nucleus reticularis gigantocellularis during carbachol-induced atonia.

    PubMed

    Yamuy, J; Jiménez, I; Morales, F; Rudomin, P; Chase, M

    1994-03-14

    The effect of electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on lumbar spinal cord motoneurons was studied in the decerebrate cat using sucrose-gap recordings from ventral roots. The NRGc was stimulated ipsi- and contralaterally before and during atonia elicited by the microinjection of carbachol into the pontine reticular formation. Prior to carbachol administration, the NRGc-induced response recorded from the sucrose-gap consisted of two consecutive excitatory population synaptic potentials followed by a long-lasting, small amplitude inhibitory population synaptic potential. Following carbachol injection, the same NRGc stimulus evoked a distinct, large amplitude inhibitory population synaptic potential, whereas the excitatory population synaptic potentials decreased in amplitude. In addition, after carbachol administration, the amplitude of the monosynaptic excitatory population synaptic potential, which was evoked by stimulation of group Ia afferents in hindlimb nerves, was reduced by 18 to 43%. When evoked at the peak of the NRGc-induced inhibitory response, this potential was further decreased in amplitude. Systemic strychnine administration (0.07-0.1 mg/kg, i.v.) blocked the NRGc-induced inhibitory population synaptic potential and promoted an increase in the amplitude of the excitatory population synaptic potentials induced by stimulation of the NRGc and group Ia afferents. These data indicate that during the state of carbachol-induced atonia, the NRGc effects on ipsi- and contralateral spinal cord motoneurons are predominantly inhibitory and that glycine is likely to be involved in this inhibitory process. These results support the hypothesis that the nucleus reticularis gigantocellularis is part of the system responsible for state-dependent somatomotor inhibition that occurs during active sleep.

  20. Dual role for Drosophila lethal of scute in CNS midline precursor formation and dopaminergic neuron and motoneuron cell fate.

    PubMed

    Stagg, Stephanie B; Guardiola, Amaris R; Crews, Stephen T

    2011-06-01

    Dopaminergic neurons play important behavioral roles in locomotion, reward and aggression. The Drosophila H-cell is a dopaminergic neuron that resides at the midline of the ventral nerve cord. Both the H-cell and the glutamatergic H-cell sib are the asymmetric progeny of the MP3 midline precursor cell. H-cell sib cell fate is dependent on Notch signaling, whereas H-cell fate is Notch independent. Genetic analysis of genes that could potentially regulate H-cell fate revealed that the lethal of scute [l(1)sc], tailup and SoxNeuro transcription factor genes act together to control H-cell gene expression. The l(1)sc bHLH gene is required for all H-cell-specific gene transcription, whereas tailup acts in parallel to l(1)sc and controls genes involved in dopamine metabolism. SoxNeuro functions downstream of l(1)sc and controls expression of a peptide neurotransmitter receptor gene. The role of l(1)sc may be more widespread, as a l(1)sc mutant shows reductions in gene expression in non-midline dopaminergic neurons. In addition, l(1)sc mutant embryos possess defects in the formation of MP4-6 midline precursor and the median neuroblast stem cell, revealing a proneural role for l(1)sc in midline cells. The Notch-dependent progeny of MP4-6 are the mVUM motoneurons, and these cells also require l(1)sc for mVUM-specific gene expression. Thus, l(1)sc plays an important regulatory role in both neurogenesis and specifying dopaminergic neuron and motoneuron identities.

  1. Critical period for estrogen-dependent motoneuron dendrite growth is coincident with ERα expression in target musculature.

    PubMed

    Rudolph, Lauren M; Sengelaub, Dale R

    2013-01-01

    The spinal cord of rats contains the sexually dimorphic, steroid-sensitive motoneurons of the spinal nucleus of the bulbocavernosus (SNB). In males, SNB dendrite growth is dependent on gonadal steroids: dendrite growth is inhibited after castration, but supported in androgen- or estrogen-treated castrated males. Furthermore, estrogenic support of SNB dendrite growth is mediated by estrogen action at the target musculature, inhibited by estrogen receptor (ER) blockade at the muscle and supported by local estradiol treatment. However, this estrogenic support is restricted to the early postnatal period, after which the morphology of SNB dendrites is insensitive to estrogens. To test if the developmentally restricted effects of estrogens on SNB dendrite growth coincide with the transient expression of ER in the target musculature, ERα expression was assessed during development and in adulthood. ERα expression in extra-Muscle fiber cells was greatest from postnatal day 7 (P7) to P14 and declined after P21. Because this pattern of ERα expression coincided with the period of estrogen-dependent dendrite growth, we tested if limiting hormone exposure to the period of maximal ERα expression in extra-muscle fiber cells could fully support estrogen-dependent SNB dendrite growth. We restricted estradiol treatment in castrated males from P7 to P21 and assessed SNB dendritic morphology at P28. Treating castrates with estradiol implants at the muscle from P7 to P21 supported dendrite growth to normal levels through P28. These data suggest that the transient ERα expression in target muscle could potentially define the critical period for estrogen-dependent dendrite growth in SNB motoneurons.

  2. Castration-induced upregulation of muscle ERα supports estrogen sensitivity of motoneuron dendrites in a sexually dimorphic neuromuscular system.

    PubMed

    Rudolph, Lauren M; Sengelaub, Dale R

    2013-12-01

    The spinal cord of rats contains the sexually dimorphic motoneurons of the spinal nucleus of the bulbocavernosus (SNB). In males, SNB dendrites fail to grow after castration, but androgen or estrogen treatment supports dendritic growth in castrated males. Estrogenic support of SNB dendrite growth is mediated by estrogen receptors (ER) in the target muscle. ERα expression in cells lacking a basal lamina (referred to as "extra-muscle fiber cells") of the SNB target musculature coincides with the period of estrogen-dependent SNB dendrite growth. In the SNB target muscle, extra-muscle fiber ERα expression declines with age and is typically absent after postnatal (P) day 21 (P21). Given that estradiol downregulates ERα in skeletal muscle, we tested the hypothesis that depleting gonadal hormones would prevent the postnatal decline in ERα expression in the SNB target musculature. We castrated male rats at P7 and assessed ERα immunolabeling at P21; ERα expression was significantly greater in castrated males compared with normal animals. Because ERα expression in SNB target muscles mediates estrogen-dependent SNB dendrogenesis, we further hypothesized that the castration-induced increase in muscle ERα would heighten the estrogen sensitivity of SNB dendrites. Male rats were castrated at P7 and treated with estradiol from P21 to P28; estradiol treatment in castrates resulted in dendritic hypertrophy in SNB motoneurons compared with normal males. We conclude that early castration results in an increase in ERα expression in the SNB target muscle, and this upregulation of ERα supports estrogen sensitivity of SNB dendrites, allowing for hypermasculinization of SNB dendritic arbors.

  3. Role of Direct vs. Indirect Pathways from the Motor Cortex to Spinal Motoneurons in the Control of Hand Dexterity

    PubMed Central

    Isa, Tadashi; Kinoshita, Masaharu; Nishimura, Yukio

    2013-01-01

    Evolutionally, development of the direct connection from the motor cortex to spinal motoneurons [corticomotoneuronal (CM) pathway] parallels the ability of hand dexterity. Damage to the corticofugal fibers in higher primates resulted in deficit of fractionated digit movements. Based on such observations, it was generally believed that the CM pathway plays a critical role in the control of hand dexterity. On the other hand, a number of “phylogenetically older” indirect pathways from the motor cortex to motoneurons still exist in primates. The indirect pathways are mediated by intercalated neurons such as segmental interneurons (sINs), propriospinal neurons (PNs) reticulospinal neurons (RSNs), or rubrospinal neurons (RuSNs). However, their contribution to hand dexterity remains elusive. Lesion of the brainstem pyramid sparing the transmission through the RuSNs and RSNs, resulted in permanent deficit of fractionated digit movements in macaque monkeys. On the other hand, in our recent study, after lesion of the dorsolateral funiculus (DLF) at the C5 segment, which removed the lateral corticospinal tract (l-CST) including the CM pathway and the transmission through sINs and RuSNs but spared the processing through the PNs and RSNs, fractionated digit movements recovered within several weeks. These results suggest that the PNs can be involved in the recovery of fractionated digit movements, but the RSNs and RuSNs have less capacity in this regard. However, on closer inspection, it was found that the activation pattern of hand and arm muscles considerably changed after the C5 lesion, suggesting limitation of PNs for the compensation of hand dexterity. Altogether, it is suggested that PNs, RSNs RuSNs, and the CM pathway (plus sINs) make a different contribution to the hand dexterity and appearance of motor deficit of the hand dexterity caused by damage to the corticofugal fibers and potential of recovery varies depending on the rostrocaudal level of the lesion. PMID

  4. Asymmetry in Signal Propagation between the Soma and Dendrites Plays a Key Role in Determining Dendritic Excitability in Motoneurons

    PubMed Central

    Kim, Hojeong; Jones, Kelvin E.; Heckman, C. J.

    2014-01-01

    It is widely recognized that propagation of electrophysiological signals between the soma and dendrites of neurons differs depending on direction, i.e. it is asymmetric. How this asymmetry influences the activation of voltage-gated dendritic channels, and consequent neuronal behavior, remains unclear. Based on the analysis of asymmetry in several types of motoneurons, we extended our previous methodology for reducing a fully reconstructed motoneuron model to a two-compartment representation that preserved asymmetric signal propagation. The reduced models accurately replicated the dendritic excitability and the dynamics of the anatomical model involving a persistent inward current (PIC) dispersed over the dendrites. The relationship between asymmetric signal propagation and dendritic excitability was investigated using the reduced models while varying the asymmetry in signal propagation between the soma and the dendrite with PIC density constant. We found that increases in signal attenuation from soma to dendrites increased the activation threshold of a PIC (hypo-excitability), whereas increases in signal attenuation from dendrites to soma decreased the activation threshold of a PIC (hyper-excitability). These effects were so strong that reversing the asymmetry in the soma-to-dendrite vs. dendrite-to-soma attenuation, reversed the correlation between PIC threshold and distance of this current source from the soma. We propose the tight relation of the asymmetric signal propagation to the input resistance in the dendrites as a mechanism underlying the influence of the asymmetric signal propagation on the dendritic excitability. All these results emphasize the importance of maintaining the physiological asymmetry in dendritic signaling not only for normal function of the cells but also for biophysically realistic simulations of dendritic excitability. PMID:25083794

  5. Whiplash injuries.

    PubMed

    Malanga, Gerard; Peter, Jason

    2005-10-01

    Whiplash injuries are very common and usually are associated with rear-end collisions. However, a whiplash injury can be caused by any event that results in hyperextension and flexion of the cervical spine. These injuries are of serious concern to all consumers due to escalating cost of diagnosis, treatment, insurance, and litigation. Most acute whiplash injury cases respond well to conservative treatments, which result in resolution of symptoms usually within weeks to a few months after the injury occurred. Chronic whiplash injuries often are harder to diagnose and treat and often result in poor outcomes. Current research shows that various structures in the cervical spine receive nociceptive innervation and potentially may be the cause of chronic pain symptoms. One potential pain generator showing promise is the facet or zygapophyseal joints. Various researchers have proven that these joints are injured during whiplash injuries and that diagnosis and temporary pain relief can be obtained with facet joint injections. The initial evaluation of any patient should follow an organized and stepwise approach, and more serious causes of neck pain must first be ruled out through the history, physical examination, and diagnostic testing. Treatment regimens should be evidence-based, focusing on treatments that have proven to be effective in treating acute and chronic whiplash injuries.

  6. Head injuries.

    PubMed

    Yanko, J

    1984-08-01

    In summary, the broad term "head injury" represents a large variety of more specific injuries. In order to anticipate and plan appropriate patient care, nurses need information regarding the cause of injury, the impact site, and the patient's clinical course in addition to current assessment findings. The nurse must also anticipate sequelae from secondary brain injury due to hypoxia, edema, increased intracranial pressure, changes in regional blood flows, or hypovolemic shock due to internal bleeding in another body system or cavity. The head-injured patient is a complex patient requiring intensive nursing care, observation, and assessment. By incorporating knowledge of the mechanisms of injury into nursing observations and assessments, nurses can provide more effective nursing interventions.

  7. The Therapeutic Effectiveness of Delayed Fetal Spinal Cord Tissue Transplantation on Respiratory Function Following Mid-Cervical Spinal Cord Injury.

    PubMed

    Lin, Chia-Ching; Lai, Sih-Rong; Shao, Yu-Han; Chen, Chun-Lin; Lee, Kun-Ze

    2017-01-17

    Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury. The histological results showed that FSC-derived grafts can survive, fill the lesion cavity, and differentiate into neurons and astrocytes at 8 weeks post-transplantation. Some FSC-derived graft neurons exhibited specific neurochemical markers of neurotransmitter (e.g., serotonin, noradrenalin, or acetylcholine). Moreover, a robust expression of glutamatergic and γ-aminobutyric acid-ergic fibers was observed within FSC-derived grafts. Retrograde tracing results indicated that there was a connection between FSC-derived grafts and host phrenic nucleus. Neurophysiological recording of the phrenic nerve demonstrated that phrenic burst amplitude ipsilateral to the lesion was significantly greater in injured animals that received FSC transplantation than in those that received buffer transplantation under high respiratory drives. These results suggest that delayed FSC transplantation may have the potential to repair the injured spinal cord and promote respiratory functional recovery after mid-cervical spinal cord injury.

  8. Mild Traumatic Brain Injury

    MedlinePlus

    ... Questions Glossary Contact Us Visitor Feedback mild Traumatic Brain Injury mild Traumatic Brain Injury VIDEO STORIES What is TBI Measuring Severity ... most common deployment injuries is a mild Traumatic Brain Injury (TBI). A mild TBI is an injury ...

  9. Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury

    PubMed Central

    Wenger, Nikolaus; Moraud, Eduardo Martin; Gandar, Jerome; Musienko, Pavel; Capogrosso, Marco; Baud, Laetitia; Le Goff, Camille G.; Barraud, Quentin; Pavlova, Natalia; Dominici, Nadia; Minev, Ivan R.; Asboth, Leonie; Hirsch, Arthur; Duis, Simone; Kreider, Julie; Mortera, Andrea; Haverbeck, Oliver; Kraus, Silvio; Schmitz, Felix; DiGiovanna, Jack; van den Brand, Rubia; Bloch, Jocelyne; Detemple, Peter; Lacour, Stéphanie P.; Bézard, Erwan; Micera, Silvestro; Courtine, Grégoire

    2016-01-01

    Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited this therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here, we developed novel stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real–time control software that modulate extensor versus flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight–bearing capacities, endurance and skilled locomotion in multiple rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans. PMID:26779815

  10. Nerve injury enhances rat neuronal glutamate transporter expression: identification by differential display PCR.

    PubMed

    Kiryu, S; Yao, G L; Morita, N; Kato, H; Kiyama, H

    1995-12-01

    An increase in neuronal glutamate transporter expression after nerve injury was demonstrated by means of differential display PCR (DD-PCR) coupled with in situ hybridization. DD-PCR was carried out to compare differences in expression of mRNAs between axotomized and normal hypoglossal motoneurons in the rat. The expression of several gene fragments were found to be increased following nerve injury; the full length cDNA corresponding to one fragment was cloned by subsequent rat cDNA library screening. The close homology of glutamate transporters with our rat cDNA led us to conclude that this clone corresponds to the rat neuronal glutamate transporter (rat EAAC1). We speculate that the upregulation of this glutamate uptake system may increase the resistance of these cells against neurotoxic glutamate accumulation during the process of nerve regeneration.

  11. Pharmacological characterization of D-aminophosphonovaleric acid antagonism of amino acid and synaptically evoked excitations on frog motoneurones in vitro: an intracellular study.

    PubMed Central

    Corradetti, R.; King, A. E.; Nistri, A.; Rovira, C.; Sivilotti, L.

    1985-01-01

    The effect of D-aminophosphonovaleric acid (D-APV) on the depolarizations induced by N-methyl-D-aspartate (NMDA), glutamate, aspartate or quisqualate was studied with intracellular recordings from frog motoneurones in vitro. D-APV (0.5-10 microM) produced a slight hyperpolarization of the motoneuronal membrane without significant changes in input conductance. In control and tetrodotoxin-containing solutions the depolarizations induced by NMDA were strongly reduced by D-APV while quisqualate depolarizations were unaffected. Responses to glutamate and aspartate were antagonized to an intermediate level. The relatively small conductance increases evoked by excitatory amino acids were unaltered in solutions containing D-APV. The amplitude of monosynaptic excitatory postsynaptic potentials (e.p.s.ps) was strongly depressed by D-APV. The amplitude of polysynaptic e.p.s.ps was little changed but their decay time was reduced. It is suggested that D-APV is a powerful and selective NMDA receptor antagonist and that an endogenous amino acid acting via NMDA receptors may be the transmitter of monosynaptic e.p.s.ps on frog motoneurones. PMID:2864968

  12. The action of knee joint afferents and the concomitant influence of cutaneous (sural) afferents on the discharge of triceps surae gamma-motoneurones in the cat.

    PubMed

    Ellaway, P H; Davey, N J; Ferrell, W R; Baxendale, R H

    1996-01-01

    Electrical stimulation of group II joint afferents of the posterior articular nerve (PAN) to the knee evoked short-latency facilitation and/or inhibition of the background discharge of gastrocnemius-soleus (GS) gamma-motoneurones in decerebrated spinal cats. The latencies of these responses were consistent with mediation via segmental oligosynaptic spinal pathways. In addition, a longer-latency facilitation was frequently observed. Mechanical non-noxious stimulation of the skin within the field of innervation of the sural nerve, on the lateral aspect of the heel, suppressed the short-latency facilitation, but not the inhibition or long-latency facilitation. Brief mechanical indentation of the posterior aspect of the knee joint capsule could elicit facilitation or inhibition of gamma-motoneurones. Facilitation, but not inhibition, was blocked by anaesthesia or section of the PAN. Both actions could be suppressed by mechanical stimulation of the heel. We conclude that GS gamma-motoneurones receive both facilitatory and inhibitory segmental inputs from group II articular afferents arising in the knee joint. Cutaneous afferents from the sural field exert a selective inhibitory influence over the facilitation of fusimotor discharge by articular afferents.

  13. Electrical injury

    MedlinePlus

    ... damage, especially to the heart, muscles, or brain. Electric current can cause injury in three ways: Cardiac arrest ... How long you were in contact with the electricity How the electricity moved through your body Your ...

  14. Testicular Injuries

    MedlinePlus

    ... Also, the location of the testicles makes them prime targets to be accidentally struck on the playing ... you might also feel nauseated for a short time. If it's a minor testicular injury, the pain ...

  15. Inhalation Injuries

    MedlinePlus

    ... devastating types of trauma resulting from exposure to fire and smoke. PREVENT you and your loved ones! ... people die annually in the United States from fire injuries. • Over half of these deaths result from ...

  16. Birth Injury

    MedlinePlus

    ... cesarean delivery may be done in certain circumstances. Did You Know... Serious birth injuries are now quite ... are typically not needed. Resources In This Article Did You Know 1 Did You Know... Sidebar 1 ...

  17. Ear Injury

    MedlinePlus

    ... doctors usually give an antibiotic to prevent infection. Did You Know... If left untreated, a swollen, bruised ... can be corrected surgically. Resources In This Article Did You Know 1 Did You Know... Facial Injuries ...

  18. Lightning Injuries

    MedlinePlus

    ... cause internal burns than electrical injuries from generated electricity. However, it can kill a person by instantaneously ... water do not attract lightning but easily transmit electricity once they are hit. Electricity from lightning can ...

  19. Spinal injury

    MedlinePlus

    ... and drive. Do not dive into pools, lakes, rivers, and other bodies of water, particularly if you cannot determine the depth of the ... Central nervous system Spinal cord injury Spinal anatomy Two person roll - ...

  20. Electric injury, Part II: Specific injuries.

    PubMed

    Fish, R M

    2000-01-01

    Electric injury can cause disruption of cardiac rhythm and breathing, burns, fractures, dislocations, rhabdomyolysis, eye and ear injury, oral and gastrointestinal injury, vascular damage, disseminated intravascular coagulation, peripheral and spinal cord injury, and Reflex Sympathetic Dystrophy. Secondary trauma from falls, fires, flying debris, and inhalation injury can complicate the clinical picture. Diagnostic and treatment considerations for electric injuries are described in this article, which is the second part of a three-part series on electric injuries.

  1. Cold injuries.

    PubMed

    Kruse, R J

    1995-01-01

    There are two categories of cold injury. The first is hypothermia, which is a systemic injury to cold, and the second is frostbite, which is a local injury. Throughout history, entire armies, from George Washington to the Germans on the Russian Front in World War II, have fallen prey to prolonged cold exposure. Cold injury is common and can occur in all seasons if ambient temperature is lower than the core body temperature. In the 1985 Boston Marathon, even though it was 76 degrees and sunny, there were 75 runners treated for hypothermia. In general, humans adapt poorly to cold exposure. Children are at particular risk because of their relatively greater surface area/body mass ratio, causing them to cool even more rapidly than adults. Because of this, the human's best defense against cold injury is to limit his/her exposure to cold and to dress appropriately. If cold injury has occurred and is mild, often simple passive rewarming such as dry blankets and a warm room are sufficient treatment.

  2. Mechanisms intrinsic to 5-HT2B receptor-induced potentiation of NMDA receptor responses in frog motoneurones.

    PubMed

    Holohean, Alice M; Hackman, John C

    2004-10-01

    In the presence of NMDA receptor open-channel blockers [Mg(2+); (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801); 1-amino-3,5-dimethyladamantane (memantine)] and TTX, high concentrations (30-100 microm) of either 5-hydroxytryptamine (5-HT) or alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT) significantly potentiated NMDA-induced depolarizations of frog spinal cord motoneurones. Potentiation was blocked by LY-53,857 (10-30 microm), SB 206553 (10 microm), and SB 204741 (30 microm), but not by spiroxatrine (10 microm), WAY 100,635 (1-30 microm), ketanserin (10 microm), RS 102221 (10 microm), or RS 39604 (10-20 microm). Therefore, alpha-Me-5-HT's facilitatory effects appear to involve 5-HT(2B) receptors. These effects were G-protein dependent as they were prevented by prior treatment with guanylyl-5'-imidodiphosphate (GMP-PNP, 100 microm) and H-Arg-Pro-Lys-Pro-Gln-Gln-D-Trp-Phe-D-Trp-D-Trp-Met-NH(2) (GP antagonist 2A, 3-6 microm), but not by pertussis toxin (PTX, 3-6 ng ml(-1), 48 h preincubation). This potentiation was not reduced by protein kinase C inhibition with staurosporine (2.0 microm), U73122 (10 microm) or N-(2-aminoethyl)-5-isoquinolinesulfonamide HCl (H9) (77 microm) or by intracellular Ca(2+) depletion with thapsigargin (0.1 microm) (which inhibits Ca(2+)/ATPase). Exposure of the spinal cord to the L-type Ca(2+) channel blockers nifedipine (10 microm), KN-62 (5 microm) or gallopamil (100 microm) eliminated alpha-Me-5-HT's effects. The calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide (W7) (100 microm) diminished the potentiation. However, the calcium/calmodulin-dependent protein kinase II (CaM Kinase II) blocker KN-93 (10 microm) did not block the 5-HT enhancement of the NMDA responses. In summary, activation of 5-HT(2B) receptors by alpha-Me-5-HT facilitates NMDA-depolarizations of frog motoneurones via a G-protein, a rise in [Ca(2+)](i) from the entry of extracellular Ca(2+) through L-type Ca(2

  3. The effect of firing on the excitability of a model motoneurone and its implications for cortical stimulation

    PubMed Central

    Matthews, Peter B C

    1999-01-01

    To help clarify the use of measurements of ‘excitability’, a simple model motoneurone receiving noisy tonic background excitation was tested with brief stimuli. Its response was determined from its PSTH (post-stimulus time histogram). The tonic background was varied from well below to well above the threshold for tonic firing. The conclusions should apply to many other neurones.The response of the model to a stimulus depended upon a number of factors, including stimulus strength, synaptic membrane noise and especially whether or not the background drive elicited tonic firing. With the onset of firing, the shape of the stimulus-response curve changed drastically and the model then responded to the smallest stimulus without a threshold. When the drive was subthreshold, increasing the background excitation always increased the response to a given stimulus. However, what happened when the tonic drive exceeded the threshold for tonic firing depended upon the stimulus strength. With weak stimuli, the response increased with the drive to reach a plateau level where it was independent of the background firing rate; this occurred for stimuli comparable in size to the synaptic noise. With stronger stimuli, the response rose to a maximum for very low firing rates, but then decreased by up to 50 % to a plateau for high firing rates. Increasing the membrane noise reduced or abolished the maximum.The model was also used to simulate a monosynaptic conditioning-testing paradigm. The effect of a given conditioning stimulus was then found to change with the onset of firing, including when the strength of the testing stimulus was adjusted to make the size of the test response the same in the presence and absence of firing.The behaviour of real motoneurones can be expected to be at least as complex with the transition from silence to firing, so H reflex and other tests of ‘excitability’ must then be treated with caution. In particular, as has been observed experimentally, the

  4. Monosynaptic EPSPs in cat lumbosacral motoneurones from group Ia afferents and fibres descending in the spinal cord.

    PubMed Central

    Harrison, P J; Jack, J J; Kullmann, D M

    1989-01-01

    1. Excitatory postsynaptic potentials (EPSPs) were elicited in lumbosacral motoneurones of pentobarbitone-anaesthetized cats by stimulating the ventral quadrants (VQ) of the thoracic spinal cord. These EPSPs were compared with monosynaptic EPSPs from small numbers of group Ia afferents, obtained by stimulating hindlimb muscle nerves with most of the dorsal roots severed. 2. EPSPs with average peak amplitude less than 1 mV were selected for fluctuation analysis. Three out of fourteen (21%) VQ EPSPs with peak voltage less than 150 mu V fluctuated in amplitude from trial to trial no more than could be accounted for by the background intracellular noise. Similarly, nine out of thirty-nine (23%) Ia EPSPs smaller than 150 mu V fluctuated to a comparable extent as the noise. These results are consistent with the view that there is little variation in the postsynaptic signal produced by an individual transmitter release event. 3. Of the EPSPs which did fluctuate more than the background noise, maximum likelihood estimates were obtained for the fluctuation patterns of ten VQ and fourteen Ia EPSPs. This was achieved by assuming that synaptic signals sum linearly with noise, but without constraining the results to conform to a statistical description of transmitter release. The fluctuation of both VQ and Ia EPSPs was made up of discrete amplitudes separated by roughly equal increments, in accordance with the quantal hypothesis of synaptic transmission. 4. Fluctuation patterns were obtained simultaneously for VQ and Ia EPSPs in seven motoneurones. The amplitudes of the quanta, defined as the mean increments between discrete amplitudes, were correlated (r = 0.90), suggesting common postsynaptic mechanisms. 5. For most EPSPs the time course of the voltage transient could be used to estimate the electrical distance from the soma at which the synaptic current was injected. There was a comparable distribution for VQ and Ia EPSPs. For those in which a quantal analysis was performed

  5. Reactive oxygen species trigger motoneuron death in non-cell-autonomous models of ALS through activation of c-Abl signaling.

    PubMed

    Rojas, Fabiola; Gonzalez, David; Cortes, Nicole; Ampuero, Estibaliz; Hernández, Diego E; Fritz, Elsa; Abarzua, Sebastián; Martinez, Alexis; Elorza, Alvaro A; Alvarez, Alejandra; Court, Felipe; van Zundert, Brigitte

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which pathogenesis and death of motor neurons are triggered by non-cell-autonomous mechanisms. We showed earlier that exposing primary rat spinal cord cultures to conditioned media derived from primary mouse astrocyte conditioned media (ACM) that express human SOD1(G93A) (ACM-hSOD1(G93A)) quickly enhances Nav channel-mediated excitability and calcium influx, generates intracellular reactive oxygen species (ROS), and leads to death of motoneurons within days. Here we examined the role of mitochondrial structure and physiology and of the activation of c-Abl, a tyrosine kinase that induces apoptosis. We show that ACM-hSOD1(G93A), but not ACM-hSOD1(WT), increases c-Abl activity in motoneurons, interneurons and glial cells, starting at 60 min; the c-Abl inhibitor STI571 (imatinib) prevents this ACM-hSOD1(G93A)-mediated motoneuron death. Interestingly, similar results were obtained with ACM derived from astrocytes expressing SOD1(G86R) or TDP43(A315T). We further find that co-application of ACM-SOD1(G93A) with blockers of Nav channels (spermidine, mexiletine, or riluzole) or anti-oxidants (Trolox, esculetin, or tiron) effectively prevent c-Abl activation and motoneuron death. In addition, ACM-SOD1(G93A) induces alterations in the morphology of neuronal mitochondria that are related with their membrane depolarization. Finally, we find that blocking the opening of the mitochondrial permeability transition pore with cyclosporine A, or inhibiting mitochondrial calcium uptake with Ru360, reduces ROS production and c-Abl activation. Together, our data point to a sequence of events in which a toxic factor(s) released by ALS-expressing astrocytes rapidly induces hyper-excitability, which in turn increases calcium influx and affects mitochondrial structure and physiology. ROS production, mediated at least in part through mitochondrial alterations, trigger c-Abl signaling and lead to motoneuron death.

  6. Reactive oxygen species trigger motoneuron death in non-cell-autonomous models of ALS through activation of c-Abl signaling

    PubMed Central

    Rojas, Fabiola; Gonzalez, David; Cortes, Nicole; Ampuero, Estibaliz; Hernández, Diego E.; Fritz, Elsa; Abarzua, Sebastián; Martinez, Alexis; Elorza, Alvaro A.; Alvarez, Alejandra; Court, Felipe; van Zundert, Brigitte

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which pathogenesis and death of motor neurons are triggered by non-cell-autonomous mechanisms. We showed earlier that exposing primary rat spinal cord cultures to conditioned media derived from primary mouse astrocyte conditioned media (ACM) that express human SOD1G93A (ACM-hSOD1G93A) quickly enhances Nav channel-mediated excitability and calcium influx, generates intracellular reactive oxygen species (ROS), and leads to death of motoneurons within days. Here we examined the role of mitochondrial structure and physiology and of the activation of c-Abl, a tyrosine kinase that induces apoptosis. We show that ACM-hSOD1G93A, but not ACM-hSOD1WT, increases c-Abl activity in motoneurons, interneurons and glial cells, starting at 60 min; the c-Abl inhibitor STI571 (imatinib) prevents this ACM-hSOD1G93A-mediated motoneuron death. Interestingly, similar results were obtained with ACM derived from astrocytes expressing SOD1G86R or TDP43A315T. We further find that co-application of ACM-SOD1G93A with blockers of Nav channels (spermidine, mexiletine, or riluzole) or anti-oxidants (Trolox, esculetin, or tiron) effectively prevent c-Abl activation and motoneuron death. In addition, ACM-SOD1G93A induces alterations in the morphology of neuronal mitochondria that are related with their membrane depolarization. Finally, we find that blocking the opening of the mitochondrial permeability transition pore with cyclosporine A, or inhibiting mitochondrial calcium uptake with Ru360, reduces ROS production and c-Abl activation. Together, our data point to a sequence of events in which a toxic factor(s) released by ALS-expressing astrocytes rapidly induces hyper-excitability, which in turn increases calcium influx and affects mitochondrial structure and physiology. ROS production, mediated at least in part through mitochondrial alterations, trigger c-Abl signaling and lead to motoneuron death. PMID:26106294

  7. Sprouting capacity of lumbar motoneurons in normal and hemisected spinal cords of the rat

    PubMed Central

    Gordon, T; Tyreman, N

    2010-01-01

    Nerve sprouting to reinnervate partially denervated muscles is important in several disease and injury states. To examine the effectiveness of sprouting of active and inactive motor units (MUs) and the basis for a limit to sprouting, one of three rat lumbar spinal roots was cut under normal conditions and when the spinal cord was hemisected at T12. Muscle and MU isometric contractile forces were recorded and muscle fibres in glycogen-depleted single muscle units enumerated 23 to 380 days after surgery. Enlargement of intact MUs by sprouting was effective in compensating for up to 80% loss of innervation. For injuries that removed >70–80% of the intact MUs, muscle contractile force and weight dropped sharply. For partial denervation of <70%, all MUs increased contractile force by the same factor in both normally active muscles and muscles whose activity was reduced by T12 hemisection. Direct measurements of MU size by counting glycogen-depleted muscle fibres in physiologically and histochemically defined muscle units, provided direct evidence for a limit in MU size, whether or not the activity of the muscles was reduced by spinal cord hemisection. Analysis of spatial distribution of muscle fibres within the outer boundaries of the muscle unit demonstrated a progressive increase in fibres within the territory to the limit of sprouting when most of the muscle unit fibres were adjacent to each other. We conclude that the upper limit of MU enlargement may be explained by the reinnervation of denervated muscle fibres by axon sprouts within the spatial territory of the muscle unit, formerly distributed in a mosaic pattern. PMID:20519315

  8. Cold injuries.

    PubMed

    Long, William B; Edlich, Richard F; Winters, Kathryne L; Britt, L D

    2005-01-01

    Exposure to cold can produce a variety of injuries that occur as a result of man's inability to adapt to cold. These injuries can be divided into localized injury to a body part, systemic hypothermia, or a combination of both. Body temperature may fall as a result of heat loss by radiation, evaporation, conduction, and convection. Hypothermia or systemic cold injury occurs when the core body temperature has decreased to 35 degrees C (95 degrees F) or less. The causes of hypothermia are either primary or secondary. Primary, or accidental, hypothermia occurs in healthy individuals inadequately clothed and exposed to severe cooling. In secondary hypothermia, another illness predisposes the individual to accidental hypothermia. Hypothermia affects multiple organs with symptoms of hypothermia that vary according to the severity of cold injury. The diagnosis of hypothermia is easy if the patient is a mountaineer who is stranded in cold weather. However, it may be more difficult in an elderly patient who has been exposed to a cold environment. In either case, the rectal temperature should be checked with a low-reading thermometer. The general principals of prehospital management are to (1) prevent further heat loss, (2) rewarm the body core temperature in advance of the shell, and (3) avoid precipitating ventricular fibrillation. There are two general techniques of rewarming--passive and active. The mechanisms of peripheral cold injury can be divided into phenomena that affect cells and extracellular fluids (direct effects) and those that disrupt the function of the organized tissue and the integrity of the circulation (indirect effects). Generally, no serious damage is seen until tissue freezing occurs. The mildest form of peripheral cold injury is frostnip. Chilblains represent a more severe form of cold injury than frostnip and occur after exposure to nonfreezing temperatures and damp conditions. Immersion (trench) foot, a disease of the sympathetic nerves and blood

  9. Distinct and developmentally regulated activity-dependent plasticity at descending glutamatergic synapses on flexor and extensor motoneurons

    PubMed Central

    Lenschow, Constanze; Cazalets, Jean-René; Bertrand, Sandrine S.

    2016-01-01

    Activity-dependent synaptic plasticity (ADSP) is paramount to synaptic processing and maturation. However, identifying the ADSP capabilities of the numerous synapses converging onto spinal motoneurons (MNs) remain elusive. Using spinal cord slices from mice at two developmental stages, 1–4 and 8–12 postnatal days (P1–P4; P8–P12), we found that high-frequency stimulation of presumed reticulospinal neuron axons in the ventrolateral funiculus (VLF) induced either an NMDA receptor-dependent-long-term depression (LTD), a short-term depression (STD) or no synaptic modulation in limb MNs. Our study shows that P1–P4 cervical MNs expressed the same plasticity profiles as P8–P12 lumbar MNs rather than P1–P4 lumbar MNs indicating that ADSP expression at VLF-MN synapses is linked to the rostrocaudal development of spinal motor circuitry. Interestingly, we observed that the ADSP expressed at VLF-MN was related to the functional flexor or extensor MN subtype. Moreover, heterosynaptic plasticity was triggered in MNs by VLF axon tetanisation at neighbouring synapses not directly involved in the plasticity induction. ADSP at VLF-MN synapses specify differential integrative synaptic processing by flexor and extensor MNs and could contribute to the maturation of spinal motor circuits and developmental acquisition of weight-bearing locomotion. PMID:27329279

  10. Morphometric evidence from C-synapses for phased Nissl body response in alpha-motoneurones retrogradely intoxicated with diphtheria toxin.

    PubMed

    Pullen, A H

    1990-02-12

    Diphtheria toxin (DTX) kills cells by inactivating ribosomal translocation and when used to retrogradely intoxicate cat intercostal motoneurones produces marked morphological alterations in Nissl bodies, including those specifically sited postsynaptic to C-type axon terminals. Here, qualitative examinations of 'intoxicated' postsynaptic Nissl bodies reveal a progressive structural alteration marked by rER dilatation, rER lamellae fragmentation but retention of both the highly ordered multilamellate organization and ribosomal attachment until final stages of Nissl body dissolution. Morphometric results identified 3 broad phases to the postintoxication response which differed in the degree of rER cisternal dilation, and the numerical and spatial relationships between rER-lamellae, rER-bound ribosomes and rER-associated polyribosomes. These phases reflect the known molecular basis of diphtheritic toxicity and contrast with the fast developing Nissl body reaction associated with the neurotoxin ricin which also invokes ribosomal dysfunction and has been used to mimic certain features of motor neurone disease. The cytopathology of DTX and ricin are compared in the Discussion.

  11. N- and P/Q-type Ca2+ channels regulate synaptic efficacy between spinal dorsolateral funiculus terminals and motoneurons.

    PubMed

    Aguilar, Justo; Escobedo, Lourdes; Bautista, Wendy; Felix, Ricardo; Delgado-Lezama, Rodolfo

    2004-04-30

    Ca2+ influx through voltage-gated Ca2+ channels mediates synaptic transmission at numerous central synapses. However, electrophysiological and pharmacological evidence linking Ca+ channel activity with neurotransmitter release in the vertebrate mature spinal cord is scarce. In the current report, we investigated in a slice preparation from the adult turtle spinal cord, the effects of various Ca+ channel antagonists on neurotransmission at terminals from the dorsolateral funiculus synapsing motoneurons. Bath application of tetrodotoxin or NiCl2 prevented the monosynaptic excitatory postsynaptic potentials (EPSPs), and this effect was mimicked by exposure to a zero-Ca2+ solution. Application of polypeptide toxins that block N- and P/Q-type channels (omega-CTx-GVIA and omega-Aga-IVA) reduced the EPSP amplitude in a dose-dependent manner. By analyzing the input resistance and the EPSP time course, and using a paired pulse protocol we determined that both toxins act at presynaptic level to modulate neurotransmitter release. RT-PCR studies showed the expression of N- and P/Q-type channel mRNAs in the turtle spinal cord. Together, these results indicate that N- and P/Q-type Ca2+ channels may play a central role in the regulation of neurotransmitter release in the adult turtle spinal cord.

  12. A Toll receptor–FoxO pathway represses Pavarotti/MKLP1 to promote microtubule dynamics in motoneurons

    PubMed Central

    Liu, Nan

    2016-01-01

    FoxO proteins are evolutionarily conserved regulators of neuronal structure and function, yet the neuron-specific pathways within which they act are poorly understood. To elucidate neuronal FoxO function in Drosophila melanogaster, we first screened for FoxO’s upstream regulators and downstream effectors. On the upstream side, we present genetic and molecular pathway analyses indicating that the Toll-6 receptor, the Toll/interleukin-1 receptor domain adaptor dSARM, and FoxO function in a linear pathway. On the downstream side, we find that Toll-6–FoxO signaling represses the mitotic kinesin Pavarotti/MKLP1 (Pav-KLP), which itself attenuates microtubule (MT) dynamics. We next probed in vivo functions for this novel pathway and found that it is essential for axon transport and structural plasticity in motoneurons. We demonstrate that elevated expression of Pav-KLP underlies transport and plasticity phenotypes in pathway mutants, indicating that Toll-6–FoxO signaling promotes MT dynamics by limiting Pav-KLP expression. In addition to uncovering a novel molecular pathway, our work reveals an unexpected function for dynamic MTs in enabling rapid activity-dependent structural plasticity. PMID:27502486

  13. Reflex transmission to lumbar α-motoneurones in the mouse similar and different to those in the cat.

    PubMed

    Schomburg, Eike D; Kalezic, Ivana; Dibaj, Payam; Steffens, Heinz

    2013-07-01

    Investigation and interpretation of defective motor circuitries in transgenic mice required further basic results from wild-type mice. Therefore, we investigated the lumbar motor reflex pattern in anaesthetised mice using intracellular motoneuronal recording and monosynaptic reflex testing. Thresholds and latencies in mice were similar to those in cats: thresholds for monosynaptic (group I) EPSPs were slightly above 1T (T=threshold for the lowest threshold fibres), around 1.5T for group II EPSPs and above 10T for group III EPSPs; group I EPSPs were maximal with a stimulus strength around 2T, group II EPSPs were maximal with 5-8T; latencies to the group I incoming volley were below 1ms for monosynaptic group I EPSPs, around 3ms for polysynaptic group II EPSPs and above 4ms for polysynaptic group III EPSPs. In contrast to reflex actions in the cat, monosynaptic gastrocnemius-soleus reflexes were facilitated by conditioning stimulation of the peroneal, sural and tibial nerves, i.e. by a variety of different, probably flexor reflex afferents. This facilitation persisted after high lumbar spinalisation indicating an independency to supraspinal influences. Nociceptive muscle afferents facilitated the peroneal monosynaptic reflex while nociceptive cutaneous afferents from the foot sole inhibited the ipsilateral but facilitated the contralateral peroneal reflex.

  14. Activity blockade and GABAA receptor blockade produce synaptic scaling through chloride accumulation in embryonic spinal motoneurons and interneurons.

    PubMed

    Lindsly, Casie; Gonzalez-Islas, Carlos; Wenner, Peter

    2014-01-01

    Synaptic scaling represents a process whereby the distribution of a cell's synaptic strengths are altered by a multiplicative scaling factor. Scaling is thought to be a compensatory response that homeostatically controls spiking activity levels in the cell or network. Previously, we observed GABAergic synaptic scaling in embryonic spinal motoneurons following in vivo blockade of either spiking activity or GABAA receptors (GABAARs). We had determined that activity blockade triggered upward GABAergic scaling through chloride accumulation, thus increasing the driving force for these currents. To determine whether chloride accumulation also underlies GABAergic scaling following GABAAR blockade we have developed a new technique. We expressed a genetically encoded chloride-indicator, Clomeleon, in the embryonic chick spinal cord, which provides a non-invasive fast measure of intracellular chloride. Using this technique we now show that chloride accumulation underlies GABAergic scaling following blockade of either spiking activity or the GABAAR. The finding that GABAAR blockade and activity blockade trigger scaling via a common mechanism supports our hypothesis that activity blockade reduces GABAAR activation, which triggers synaptic scaling. In addition, Clomeleon imaging demonstrated the time course and widespread nature of GABAergic scaling through chloride accumulation, as it was also observed in spinal interneurons. This suggests that homeostatic scaling via chloride accumulation is a common feature in many neuronal classes within the embryonic spinal cord and opens the possibility that this process may occur throughout the nervous system at early stages of development.

  15. Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability

    PubMed Central

    Devlin, Anna-Claire; Burr, Karen; Borooah, Shyamanga; Foster, Joshua D.; Cleary, Elaine M.; Geti, Imbisaat; Vallier, Ludovic; Shaw, Christopher E.; Chandran, Siddharthan; Miles, Gareth B.

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease for which a greater understanding of early disease mechanisms is needed to reveal novel therapeutic targets. We report the use of human induced pluripotent stem cell (iPSC)-derived motoneurons (MNs) to study the pathophysiology of ALS. We demonstrate that MNs derived from iPSCs obtained from healthy individuals or patients harbouring TARDBP or C9ORF72 ALS-causing mutations are able to develop appropriate physiological properties. However, patient iPSC-derived MNs, independent of genotype, display an initial hyperexcitability followed by progressive loss of action potential output and synaptic activity. This loss of functional output reflects a progressive decrease in voltage-activated Na+ and K+ currents, which occurs in the absence of overt changes in cell viability. These data implicate early dysfunction or loss of ion channels as a convergent point that may contribute to the initiation of downstream degenerative pathways that ultimately lead to MN loss in ALS. PMID:25580746

  16. Preferential distribution of nociceptive input to motoneurons with muscle units in the cranial portion of the upper trapezius muscle.

    PubMed

    Dideriksen, Jakob L; Holobar, Ales; Falla, Deborah

    2016-08-01

    Pain is associated with changes in the neural drive to muscles. For the upper trapezius muscle, surface electromyography (EMG) recordings have indicated that acute noxious stimulation in either the cranial or the caudal region of the muscle leads to a relative decrease in muscle activity in the cranial region. It is, however, not known if this adaption reflects different recruitment thresholds of the upper trapezius motor units in the cranial and caudal region or a nonuniform nociceptive input to the motor units of both regions. This study investigated these potential mechanisms by direct motor unit identification. Motor unit activity was investigated with high-density surface EMG signals recorded from the upper trapezius muscle of 12 healthy volunteers during baseline, control (intramuscular injection of isotonic saline), and painful (hypertonic saline) conditions. The EMG was decomposed into individual motor unit spike trains. Motor unit discharge rates decreased significantly from control to pain conditions by 4.0 ± 3.6 pulses/s (pps) in the cranial region but not in the caudal region (1.4 ± 2.8 pps; not significant). These changes were compatible with variations in the synaptic input to the motoneurons of the two regions. These adjustments were observed, irrespective of the location of noxious stimulation. These results strongly indicate that the nociceptive synaptic input is distributed in a nonuniform way across regions of the upper trapezius muscle.

  17. Lightning injuries.

    PubMed

    O'Keefe Gatewood, Medley; Zane, Richard D

    2004-05-01

    Lightning is persistently one of the leading causes of death caused by environmental or natural disaster. To understand the pathophysiology and treatment of lightning injuries one must first discount the innumerable myths, superstitions, and misconceptions surrounding lightning. The fundamental difference between high voltage electrical injury and lightning is the duration of exposure to current. Reverse triage should be instituted in lightning strike victims because victims in cardiopulmonary arrest might gain the greatest benefit from resuscitation efforts, although there is no good evidence suggesting that lightning strike victims might benefit from longer than usual resuscitation times. Many of the injuries suffered by lightning strike victims are unique to lightning, and long-term sequelae should be anticipated and addressed in the lightning victim.

  18. Blast Injury

    PubMed Central

    de Candole, C. A.

    1967-01-01

    The shock wave generated by an explosion (“blast wave”) may cause injury in any or all of the following: (1) direct impact on the tissues of variations in environmental pressure; (2) flying glass and other debris set in motion by it; (3) propulsion of the body. Injuries in the first category affect gas-containing organs (ears, lungs and intestines), and acute death is attributed to air forced into the coronary vessels via damaged pulmonary alveoli. It is estimated that overpressure sufficient to cause lung injury may occur up to five miles from a 20-megaton nuclear explosion. The greatest single hazard from blast is, however, flying glass, and serious wounding from this cause is possible up to 12 miles from an explosion of this magnitude. PMID:6015742

  19. Hamstring injuries

    PubMed Central

    Guanche, Carlos A.

    2015-01-01

    There is a continuum of hamstring injuries that can range from musculotendinous strains to avulsion injuries. Although the proximal hamstring complex has a strong bony attachment on the ischial tuberosity, hamstring injuries are common in athletic population and can affect all levels of athletes. Nonoperative treatment is mostly recommended in the setting of low-grade partial tears and insertional tendinosis. However, failure of nonoperative treatment of partial tears may benefit from surgical debridement and repair. The technique presented on this article allows for the endoscopic management of proximal hamstring tears and chronic ischial bursitis, which until now has been managed exclusively with much larger open approaches. The procedure allows for complete exposure of the posterior aspect of the hip in a safe, minimally invasive fashion. PMID:27011828

  20. Kallikrein 6 Signals through PAR1 and PAR2 to Promote Neuron Injury and Exacerbate Glutamate Neurotoxicity

    PubMed Central

    Yoon, Hyesook; Radulovic, Maja; Wu, Jianmin; Blaber, Sachiko I.; Blaber, Michael; Fehlings, Michael G.; Scarisbrick, Isobel A.

    2014-01-01

    CNS trauma generates a proteolytic imbalance contributing to secondary injury, including axonopathy and neuron degeneration. Kallikrein 6 (Klk6) is a serine protease implicated in neurodegeneration and here we investigate the role of protease activated receptors 1 (PAR1) and PAR2 in mediating these effects. First we demonstrate Klk6 and the prototypical activator of PAR1, thrombin, as well as PAR1 and PAR2, are each elevated in murine experimental traumatic spinal cord injury (SCI) at acute or subacute time points. Recombinant Klk6 triggered ERK1/2 signaling in cerebellar granule neurons and in the NSC34 spinal cord motoneuron cell line, in a PI3K and MEK-dependent fashion. Importantly, lipopeptide inhibitors of PAR1 or PAR2, and PAR1 genetic deletion, each reduced Klk6-ERK1/2 activation. In addition, Klk6 and thrombin promoted degeneration of cerebellar neurons and exacerbated glutamate neurotoxicity. Moreover, genetic deletion of PAR1 blocked thrombin-mediated cerebellar neurotoxicity and reduced the neurotoxic effects of Klk6. Klk6 also increased glutamate-mediated Bim signaling, PARP cleavage and lactate dehydrogenase (LDH) release in NSC34 motoneurons and these effects were blocked by PAR1 and PAR2 lipopeptide inhibitors. Taken together these data point to a novel Klk6-signaling axis in CNS neurons that is mediated by PAR1 and PAR2 and is positioned to contribute to neurodegeneration. PMID:23647384

  1. A Consistent, Quantifiable, and Graded Rat Lumbosacral Spinal Cord Injury Model

    PubMed Central

    Wen, Junxiang; Sun, Dongming; Tan, Jun

    2015-01-01

    Abstract The purpose of this study is to develop a rat lumbosacral spinal cord injury (SCI) model that causes consistent motoneuronal loss and behavior deficits. Most SCI models focus on the thoracic or cervical spinal cord. Lumbosacral SCI accounts for about one third of human SCI but no standardized lumbosacral model is available for evaluating therapies. Twenty-six adult female Sprague-Dawley rats were randomized to three groups: sham (n=9), 25 mm (n=8), and 50 mm (n=9). Sham rats had laminectomy only, while 25 mm and 50 mm rats were injured by dropping a 10 g rod from a height of 25 mm or 50 mm, respectively, onto the L4-5 spinal cord at the T13/L1 vertebral junction. We measured footprint length (FL), toe spreading (TS), intermediate toe spreading (ITS), and sciatic function index (SFI) from walking footprints, and static toe spreading (STS), static intermediate toe spreading (SITS), and static sciatic index (SSI) from standing footprints. At six weeks, we assessed neuronal and white matter loss, quantified axons, diameter, and myelin thickness in the peroneal and tibial nerves, and measured cross-sectional areas of tibialis anterior and gastrocnemius muscle fibers. The result shows that peroneal and tibial motoneurons were respectively distributed in 4.71 mm and 5.01 mm columns in the spinal cord. Dropping a 10-g weight from 25 mm or 50 mm caused 1.5 mm or 3.75 mm gaps in peroneal and tibial motoneuronal columns, respectively, and increased spinal cord white matter loss. Fifty millimeter contusions significantly increased FL and reduced TS, ITS, STS, SITS, SFI, and SSI more than 25 mm contusions, and resulted in smaller axon and myelinated axon diameters in tibial and peroneal nerves and greater atrophy of gastrocnemius and anterior tibialis muscles, than 25 mm contusions. This model of lumbosacral SCI produces consistent and graded loss of white matter, motoneuronal loss, peripheral nerve axonal changes, and anterior tibialis

  2. Expression of some neurotrophins in the spinal motoneurons after cord hemisection in adult rats.

    PubMed

    Qin, Dan Xia; Zou, Xiao Li; Luo, Wei; Zhang, Wei; Zhang, Hong Tian; Li, Xiao Li; Zhang, Han; Wang, Xu Yang; Wang, Ting-Hua

    2006-12-27

    There are numerous studies reporting on the crucial roles of neurotrophins (NTFs) in neuronal survival and sprouting after spinal cord injury (SCI). But studies on endogenous changes of neurotrophins after SCI are few. In this study we explored by means of immunohistochemistry the localization of NGF, BDNF and NT-3 in the normal adult spinal cord (SC) and the changes in the expression of these chemicals in the ventral horn after right cord hemisection at T9-10. The results showed an obvious increase in the numbers of NGF, BDNF and NT-3-immunoreactive neurons in the ventral horn and also an increase in their intracellular optical density (O.D.) at 3, 7 and 21 days after cord hemisection, when compared with sham-operated rats. The expression of NGF peaked at 7 days postoperation (dpo), while BDNF and NT-3 expressions peaked at 3 dpo. Evaluation of hindlimb functions by Basso Beattie Bresnahan (BBB) scoring showed that the hindlimb support and stepping function improved very quickly at 7 dpo. This study indicated that NGF, BDNF and NT-3 could play important but different roles in the mechanisms of spinal neuroplasticity at different times after SCI.

  3. Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity

    PubMed Central

    D'Amico, Jessica M.; Condliffe, Elizabeth G.; Martins, Karen J. B.; Bennett, David J.; Gorassini, Monica A.

    2014-01-01

    The state of areflexia and muscle weakness that immediately follows a spinal cord injury (SCI) is gradually replaced by the recovery of neuronal and network excitability, leading to both improvements in residual motor function and the development of spasticity. In this review we summarize recent animal and human studies that describe how motoneurons and their activation by sensory pathways become hyperexcitable to compensate for the reduction of functional activation of the spinal cord and the eventual impact on the muscle. Specifically, decreases in the inhibitory control of sensory transmission and increases in intrinsic motoneuron excitability are described. We present the idea that replacing lost patterned activation of the spinal cord by activating synaptic inputs via assisted movements, pharmacology or electrical stimulation may help to recover lost spinal inhibition. This may lead to a reduction of uncontrolled activation of the spinal cord and thus, improve its controlled activation by synaptic inputs to ultimately normalize circuit function. Increasing the excitation of the spinal cord with spared descending and/or peripheral inputs by facilitating movement, instead of suppressing it pharmacologically, may provide the best avenue to improve residual motor function and manage spasticity after SCI. PMID:24860447

  4. Electrical Injuries

    MedlinePlus

    ... your injuries are depends on how strong the electric current was, what type of current it was, how it moved through your body, and how long you were exposed. Other factors include how ... you should see a doctor. You may have internal damage and not realize it.

  5. Pediatric Injury

    MedlinePlus

    ... Control and Prevention’s Safe Child website . What is pediatric critical care? Children who have severe or life-threatening injuries ... are staffed by physicians with specialized training in pediatric critical care medicine ("pediatric intensivists"). Because children can experience a ...

  6. G-protein-coupled GABAB receptors inhibit Ca2+ channels and modulate transmitter release in descending turtle spinal cord terminal synapsing motoneurons.

    PubMed

    Castro, Alberto; Aguilar, Justo; Elias, David; Felix, Ricardo; Delgado-Lezama, Rodolfo

    2007-08-10

    Presynaptic gamma-aminobutyric acid type B receptors (GABA(B)Rs) regulate transmitter release at many central synapses by inhibiting Ca(2+) channels. However, the mechanisms by which GABA(B)Rs modulate neurotransmission at descending terminals synapsing on motoneurons in the spinal cord remain unexplored. To address this issue, we characterized the effects of baclofen, an agonist of GABA(B)Rs, on the monosynaptic excitatory postsynaptic potentials (EPSPs) evoked in motoneurons by stimulation of the dorsolateral funiculus (DLF) terminals in a slice preparation from the turtle spinal cord. We found that baclofen depressed neurotransmission in a dose-dependent manner (IC(50) of approximately 2 microM). The membrane time constant of the motoneurons did not change, whereas the amplitude ratio of the evoked EPSPs in response to a paired pulse was altered in the presence of the drug, suggesting a presynaptic mechanism. Likewise, the use of N- and P/Q-type Ca(2+) channel antagonists (omega-conotoxin GVIA and omega-agatoxin IVA, respectively) also depressed EPSPs significantly. Therefore, these channels are likely involved in the Ca(2+) influx that triggers transmitter release from DLF terminals. To determine whether the N and P/Q channels were regulated by GABA(B)R activation, we analyzed the action of the toxins in the presence of baclofen. Interestingly, baclofen occluded omega-conotoxin GVIA action by approximately 50% without affecting omega-agatoxin IVA inhibition, indicating that the N-type channels are the target of GABA(B)Rs. Lastly, the mechanism underlying this effect was further assessed by inhibiting G-proteins with N-ethylmaleimide (NEM). Our data show that EPSP depression caused by baclofen was prevented by NEM, suggesting that GABA(B)Rs inhibit N-type channels via G-protein activation.

  7. The vasopressin-induced excitation of hypoglossal and facial motoneurons in young rats is mediated by V1a but not V1b receptors, and is independent of intracellular calcium signalling.

    PubMed

    Reymond-Marron, I; Tribollet, E; Raggenbass, M

    2006-09-01

    As a hormone, vasopressin binds to three distinct receptors: V1a and V1b receptors, which induce phospholipase-Cbeta (PLCbeta) activation and Ca2+ mobilization; and V2 receptors, which are coupled to adenylyl cyclase. V1a and V1b receptors are also present in neurons. In particular, hypoglossal (XII) and facial (VII) motoneurons are excited following vasopressin-V1a receptor binding. The aim of the present study was double: (i) to determine whether V1b receptors contribute to the excitatory effect of vasopressin in XII and VII motoneurons; and (ii) to establish whether the action of vasopressin on motoneurons is mediated by Ca2+ signalling. Patch-clamp recordings were performed in brainstem slices of young rats. Vasopressin depolarized the membrane or generated an inward current. By contrast, [1-deamino-4-cyclohexylalanine] arginine vasopressin (d[Cha4]AVP), a V1b agonist, had no effect. The action of vasopressin was suppressed by Phaa-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2, a V1a antagonist, but not by SSR149415, a V1b antagonist. Thus, the vasopressin-induced excitation of brainstem motoneurons was exclusively mediated by V1a receptors. Light microscopic autoradiography failed to detect V1b binding sites in the facial nucleus. In motoneurons loaded with GTP-gamma-S, a non-hydrolysable analogue of GTP, the effect of vasopressin was suppressed, indicating that neuronal V1a receptors are G-protein-coupled. Intracellular Ca2+ chelation suppressed a Ca2+-activated potassium current, but did not affect the vasopressin-evoked current. H7 and GF109203, inhibitors of protein kinase C, were without effect on the vasopressin-induced excitation. U73122 and D609, PLCbeta inhibitors, were also without effect. Thus, excitation of brainstem motoneurons by V1a receptor activation is probably mediated by a second messenger distinct from that associated with peripheral V1a receptors.

  8. Computer simulation study of the relationship between the profile of excitatory postsynaptic potential and stimulus-correlated motoneuron firing.

    PubMed

    Piotrkiewicz, Maria; Kudina, Lydia; Jakubiec, Michal

    2009-03-01

    This paper shows the results of computer simulation of changes in motoneuron (MN) firing evoked by a repetitively applied synaptic volley that consists of a single excitatory postsynaptic potential (EPSP). Spike trains produced by the threshold-crossing MN model were analyzed as experimental results. Various output functions were applied for analysis; the most useful was a peristimulus time histogram, a special modification of a raster plot and a peristimulus time frequencygram (PSTF). It has been shown that all functions complement each other in distinguishing between the genuine results evoked by the excitatory volley and the secondary results of the EPSP-evoked synchronization. The EPSP rising edge was best reproduced by the PSTF. However, whereas the EPSP rise time could be estimated quite accurately, especially for high EPSP amplitudes at high MN firing rates, the EPSP amplitude estimate was also influenced by factors unrelated to the synaptic volley, such as the afterhyperpolarization duration of the MN or the amplitude of synaptic noise, which cannot be directly assessed in human experiments. Thus, the attempts to scale any estimate of the EPSP amplitude in millivolts appear to be useless. The decaying phase of the EPSP cannot be reproduced accurately by any of the functions. For the short EPSPs, it is extinguished by the generation of an action potential and a subsequent decrease in the MN excitability. For longer EPSPs, it is inseparable from the secondary effects of synchronization. Thus, the methods aimed at extracting information about long-lasting and complex postsynaptic potentials from stimulus-correlated MN firing, should be refined, and the theoretical considerations checked in computer simulations.

  9. Statistical computer model analysis of the reciprocal and recurrent inhibitions of the Ia-EPSP in α-motoneurons.

    PubMed

    Gradwohl, G; Grossman, Y

    2013-01-01

    We simulate the inhibition of Ia-glutamatergic excitatory postsynaptic potential (EPSP) by preceding it with glycinergic recurrent (REN) and reciprocal (REC) inhibitory postsynaptic potentials (IPSPs). The inhibition is evaluated in the presence of voltage-dependent conductances of sodium, delayed rectifier potassium, and slow potassium in five α-motoneurons (MNs). We distribute the channels along the neuronal dendrites using, alternatively, a density function of exponential rise (ER), exponential decay (ED), or a step function (ST). We examine the change in EPSP amplitude, the rate of rise (RR), and the time integral (TI) due to inhibition. The results yield six major conclusions. First, the EPSP peak and the kinetics depending on the time interval are either amplified or depressed by the REC and REN shunting inhibitions. Second, the mean EPSP peak, its TI, and RR inhibition of ST, ER, and ED distributions turn out to be similar for analogous ranges of G. Third, for identical G, the large variations in the parameters' values can be attributed to the sodium conductance step (g(Na_step)) and the active dendritic area. We find that small g(Na_step) on a few dendrites maintains the EPSP peak, its TI, and RR inhibition similar to the passive state, but high g(Na_step) on many dendrites decrease the inhibition and sometimes generates even an excitatory effect. Fourth, the MN's input resistance does not alter the efficacy of EPSP inhibition. Fifth, the REC and REN inhibitions slightly change the EPSP peak and its RR. However, EPSP TI is depressed by the REN inhibition more than the REC inhibition. Finally, only an inhibitory effect shows up during the EPSP TI inhibition, while there are both inhibitory and excitatory impacts on the EPSP peak and its RR.

  10. [The influence of vibration on spinal alpha-motoneurons excitability in static conditions and during evoked stepping in human].

    PubMed

    Solopova, I A; Selionov, V A

    2012-01-01

    In healthy human the excitability of spinal alpha-motoneurons under application of vibrostimulation (20-60 Hz) to different leg muscles was investigated both in stationary condition and during stepping movements caused by vibration in the condition of suspended leg. In 15 subjects the amplitude of H-reflex were compared under vibration of rectus femoris (RF) and biceps femoris (BF) muscles of left leg as well during vibration of rectus femoris of contralateral, motionless leg in three spatial positions: upright, supine and on right side of body with suspended left leg. In dynamic conditions the amount of H-reflex was compared during evoked and voluntary stepping at 8 intervals of step cycle. In all body positions the vibration of each ipsilateral leg muscles caused significant suppression of H-reflex, this suppression was more prominent in the air-stepping conditions. The vibration of contralateral leg RF muscle had a weak influence on the amplitude of H-reflex. In 7 subjects the muscle vibration of ipsilateral and contralateral legs generated stepping movements. During evoked "air-stepping" H-reflex had different amplitudes in different phases of step cycle. At the same time the differences between responses under voluntary and non-voluntary stepping were revealed only in stance phase. Thus, different degree of H-reflex suppression by vibration under different body position in space depends on, it seems to be, from summary afferent inflows to spinal cord interneurons, which participate in regulation of posture and locomotion. Seemingly, the increasing of spinal cord neurons excitability occurs under involuntary air-stepping in swing phase, which is necessary for activation of locomotor automatism under unloading leg conditions.

  11. Temporal coherency between receptor expression, neural activity and AP-1-dependent transcription regulates Drosophila motoneuron dendrite development.

    PubMed

    Vonhoff, Fernando; Kuehn, Claudia; Blumenstock, Sonja; Sanyal, Subhabrata; Duch, Carsten

    2013-02-01

    Neural activity has profound effects on the development of dendritic structure. Mechanisms that link neural activity to nuclear gene expression include activity-regulated factors, such as CREB, Crest or Mef2, as well as activity-regulated immediate-early genes, such as fos and jun. This study investigates the role of the transcriptional regulator AP-1, a Fos-Jun heterodimer, in activity-dependent dendritic structure development. We combine genetic manipulation, imaging and quantitative dendritic architecture analysis in a Drosophila single neuron model, the individually identified motoneuron MN5. First, Dα7 nicotinic acetylcholine receptors (nAChRs) and AP-1 are required for normal MN5 dendritic growth. Second, AP-1 functions downstream of activity during MN5 dendritic growth. Third, using a newly engineered AP-1 reporter we demonstrate that AP-1 transcriptional activity is downstream of Dα7 nAChRs and Calcium/calmodulin-dependent protein kinase II (CaMKII) signaling. Fourth, AP-1 can have opposite effects on dendritic development, depending on the timing of activation. Enhancing excitability or AP-1 activity after MN5 cholinergic synapses and primary dendrites have formed causes dendritic branching, whereas premature AP-1 expression or induced activity prior to excitatory synapse formation disrupts dendritic growth. Finally, AP-1 transcriptional activity and dendritic growth are affected by MN5 firing only during development but not in the adult. Our results highlight the importance of timing in the growth and plasticity of neuronal dendrites by defining a developmental period of activity-dependent AP-1 induction that is temporally locked to cholinergic synapse formation and dendritic refinement, thus significantly refining prior models derived from chronic expression studies.

  12. Small conductance Ca2+-activated K+ channels regulate firing properties and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus.

    PubMed

    Lin, Min; Hatcher, Jeff T; Chen, Qin-Hui; Wurster, Robert D; Cheng, Zixi Jack

    2010-12-01

    Small conductance Ca(2+)-activated K(+) channels (SK) regulate action potential (AP) firing properties and excitability in many central neurons. However, the functional roles of SK channels of parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus have not yet been well characterized. In this study, the tracer X-rhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal days 7-9. Two days later, XRITC-labeled PCMNs in brain stem slices were identified. With the use of whole cell current clamp, single APs and spike trains of different frequencies were evoked by current injections. We found that 1) PCMNs have two different firing patterns: the majority of PCMNs (90%) exhibited spike frequency adaptation (SFA) and the rest (10%) showed less or no adaptation; 2) application of the specific SK channel blocker apamin significantly increased spike half-width in single APs and trains and reduced the spike frequency-dependent AP broadening in trains; 3) SK channel blockade suppressed afterhyperpolarization (AHP) amplitude following single APs and trains and abolished spike-frequency dependence of AHP in trains; and 4) SK channel blockade increased the spike frequency but did not alter the pattern of SFA. Using whole cell voltage clamp, we measured outward currents and afterhyperpolarization current (I(AHP)). SK channel blockade revealed that SK-mediated outward currents had both transient and persistent components. After bath application of apamin and Ca(2+)-free solution, we found that apamin-sensitive and Ca(2+)-sensitive I(AHP) were comparable, confirming that SK channels may contribute to a major portion of Ca(2+)-activated K(+) channel-mediated I(AHP). These results suggest that PCMNs have SK channels that significantly regulate AP repolarization, AHP, and spike frequency but do not affect SFA. We conclude that activation of SK channels underlies one of the mechanisms for negative

  13. Reduced Phrenic Motoneuron Recruitment during Sustained Inspiratory Threshold Loading Compared to Single-Breath Loading: A Twitch Interpolation Study.

    PubMed

    Raux, Mathieu; Demoule, Alexandre; Redolfi, Stefania; Morelot-Panzini, Capucine; Similowski, Thomas

    2016-01-01

    as reflecting motoneuron recruitment, this study supports motor reorganization compatible with "diaphragm sparing" when an inspiratory threshold load becomes sustained.

  14. The motor system plays the violin: a musical metaphor inferred from the oscillatory activity of the α-motoneuron pools during locomotion.

    PubMed

    Chiovetto, Enrico

    2011-04-01

    Despite substantial advances in the field, particularly resulting from physiological studies in animals, the neural mechanisms underlying the generation of many motor behaviors in humans remain unclear. A recent study (Cappellini G et al. J Neurophysiol 104: 3064-3073, 2010) sheds more light on this topic. Like the string of a violin, the α-motoneuron pools in the spinal cord during locomotion show continuous and oscillatory patterns of activation. In this report, the implications and relevance of this finding are discussed in a general framework that includes neurophysiology, optimal control theory, and robotics.

  15. Effect of restricted mobility on RNA content and nucleotide composition and on protein content in motoneurons of spinal cord anterior horns

    NASA Technical Reports Server (NTRS)

    Gorbunova, A. V.

    1980-01-01

    An investigation into the effect of hypokinesia on the ribonucleic acid (RNA) content, the nucleotide composition, and dynamics of protein content in the motoneuron of the rat spinal cord anterior horns is described. Methodology and findings are presented. The study results showed that the nucleotide composition of the total cellular RNA at all the studied periods of hypokinesia remained unchanged and is characteristic for the cytoplasmic, high polymer ribosomal RNA. This means that with a change in the functional state of the neuron the newly formed RNA of the nerve cell has the same composition of bases as the original RNA that belongs to the ribosomal type.

  16. Loss of the Coffin-Lowry syndrome-associated gene RSK2 alters ERK activity, synaptic function and axonal transport in Drosophila motoneurons.

    PubMed

    Beck, Katherina; Ehmann, Nadine; Andlauer, Till F M; Ljaschenko, Dmitrij; Strecker, Katrin; Fischer, Matthias; Kittel, Robert J; Raabe, Thomas

    2015-11-01

    Plastic changes in synaptic properties are considered as fundamental for adaptive behaviors. Extracellular-signal-regulated kinase (ERK)-mediated signaling has been implicated in regulation of synaptic plasticity. Ribosomal S6 kinase 2 (RSK2) acts as a regulator and downstream effector of ERK. In the brain, RSK2 is predominantly expressed in regions required for learning and memory. Loss-of-function mutations in human RSK2 cause Coffin-Lowry syndrome, which is characterized by severe mental retardation and low IQ scores in affected males. Knockout of RSK2 in mice or the RSK ortholog in Drosophila results in a variety of learning and memory defects. However, overall brain structure in these animals is not affected, leaving open the question of the pathophysiological consequences. Using the fly neuromuscular system as a model for excitatory glutamatergic synapses, we show that removal of RSK function causes distinct defects in motoneurons and at the neuromuscular junction. Based on histochemical and electrophysiological analyses, we conclude that RSK is required for normal synaptic morphology and function. Furthermore, loss of RSK function interferes with ERK signaling at different levels. Elevated ERK activity was evident in the somata of motoneurons, whereas decreased ERK activity was observed in axons and the presynapse. In addition, we uncovered a novel function of RSK in anterograde axonal transport. Our results emphasize the importance of fine-tuning ERK activity in neuronal processes underlying higher brain functions. In this context, RSK acts as a modulator of ERK signaling.

  17. cGMP-Dependent Protein Kinase Inhibition Extends the Upper Temperature Limit of Stimulus-Evoked Calcium Responses in Motoneuronal Boutons of Drosophila melanogaster Larvae

    PubMed Central

    Dawson-Scully, Ken

    2016-01-01

    While the mammalian brain functions within a very narrow range of oxygen concentrations and temperatures, the fruit fly, Drosophila melanogaster, has employed strategies to deal with a much wider range of acute environmental stressors. The foraging (for) gene encodes the cGMP-dependent protein kinase (PKG), has been shown to regulate thermotolerance in many stress-adapted species, including Drosophila, and could be a potential therapeutic target in the treatment of hyperthermia in mammals. Whereas previous thermotolerance studies have looked at the effects of PKG variation on Drosophila behavior or excitatory postsynaptic potentials at the neuromuscular junction (NMJ), little is known about PKG effects on presynaptic mechanisms. In this study, we characterize presynaptic calcium ([Ca2+]i) dynamics at the Drosophila larval NMJ to determine the effects of high temperature stress on synaptic transmission. We investigated the neuroprotective role of PKG modulation both genetically using RNA interference (RNAi), and pharmacologically, to determine if and how PKG affects presynaptic [Ca2+]i dynamics during hyperthermia. We found that PKG activity modulates presynaptic neuronal Ca2+ responses during acute hyperthermia, where PKG activation makes neurons more sensitive to temperature-induced failure of Ca2+ flux and PKG inhibition confers thermotolerance and maintains normal Ca2+ dynamics under the same conditions. Targeted motoneuronal knockdown of PKG using RNAi demonstrated that decreased PKG expression was sufficient to confer thermoprotection. These results demonstrate that the PKG pathway regulates presynaptic motoneuronal Ca2+ signaling to influence thermotolerance of presynaptic function during acute hyperthermia. PMID:27711243

  18. Loss of the Coffin-Lowry syndrome-associated gene RSK2 alters ERK activity, synaptic function and axonal transport in Drosophila motoneurons

    PubMed Central

    Beck, Katherina; Ehmann, Nadine; Andlauer, Till F. M.; Ljaschenko, Dmitrij; Strecker, Katrin; Fischer, Matthias; Kittel, Robert J.; Raabe, Thomas

    2015-01-01

    ABSTRACT Plastic changes in synaptic properties are considered as fundamental for adaptive behaviors. Extracellular-signal-regulated kinase (ERK)-mediated signaling has been implicated in regulation of synaptic plasticity. Ribosomal S6 kinase 2 (RSK2) acts as a regulator and downstream effector of ERK. In the brain, RSK2 is predominantly expressed in regions required for learning and memory. Loss-of-function mutations in human RSK2 cause Coffin-Lowry syndrome, which is characterized by severe mental retardation and low IQ scores in affected males. Knockout of RSK2 in mice or the RSK ortholog in Drosophila results in a variety of learning and memory defects. However, overall brain structure in these animals is not affected, leaving open the question of the pathophysiological consequences. Using the fly neuromuscular system as a model for excitatory glutamatergic synapses, we show that removal of RSK function causes distinct defects in motoneurons and at the neuromuscular junction. Based on histochemical and electrophysiological analyses, we conclude that RSK is required for normal synaptic morphology and function. Furthermore, loss of RSK function interferes with ERK signaling at different levels. Elevated ERK activity was evident in the somata of motoneurons, whereas decreased ERK activity was observed in axons and the presynapse. In addition, we uncovered a novel function of RSK in anterograde axonal transport. Our results emphasize the importance of fine-tuning ERK activity in neuronal processes underlying higher brain functions. In this context, RSK acts as a modulator of ERK signaling. PMID:26398944

  19. Traumatic Brain Injury

    MedlinePlus

    Traumatic brain injury (TBI) happens when a bump, blow, jolt, or other head injury causes damage to the brain. Every year, millions of people in the U.S. suffer brain injuries. More than half are bad enough that ...

  20. "Floating shoulder" injuries.

    PubMed

    Heng, Kenneth

    2016-12-01

    "Floating shoulder" is a rare injury complex resulting from high-energy blunt force trauma to the shoulder, resulting in scapulothoracic dissociation. It is commonly associated with catastrophic neurovascular injury. Two cases of motorcyclists with floating shoulder injuries are described.

  1. Spinal Cord Injury

    MedlinePlus

    ... Types of illnesses and disabilities Spinal cord injury Spinal cord injury Read advice from Dr. Jeffrey Rabin , a ... your health on a daily basis. Living with spinal cord injury — your questions answered top What are pediatric ...

  2. Preventing Eye Injuries

    MedlinePlus

    ... Stories Español Eye Health / Eye Health A-Z Eye Injuries Sections Preventing Eye Injuries Recognizing and Treating ... Infographic Five Steps to Safer Champagne Celebrations Preventing Eye Injuries Reviewed by: Brenda Pagan-Duran MD Mar. ...

  3. Eye Injuries at Work

    MedlinePlus

    ... Ophthalmologist Patient Stories Español Eye Health / Tips & Prevention Eye Injuries Sections Preventing Eye Injuries Recognizing and Treating ... Numbers — Infographic Five Steps to Safer Champagne Celebrations Eye Injuries at Work Edited by: Shirley Dang Feb. ...

  4. Eye Injuries at Home

    MedlinePlus

    ... Ophthalmologist Patient Stories Español Eye Health / Tips & Prevention Eye Injuries Sections Preventing Eye Injuries Recognizing and Treating ... Numbers — Infographic Five Steps to Safer Champagne Celebrations Eye Injuries at Home Reviewed by: Brenda Pagan-Duran ...

  5. Head injury - first aid

    MedlinePlus

    ... happen from a gunshot to the head. Head injuries include: Concussion , in which the brain is shaken, is the most common type of traumatic brain injury. Scalp wounds. Skull fractures. Head injuries ...

  6. Nerve Injuries in Athletes.

    ERIC Educational Resources Information Center

    Collins, Kathryn; And Others

    1988-01-01

    Over a two-year period this study evaluated the condition of 65 athletes with nerve injuries. These injuries represent the spectrum of nerve injuries likely to be encountered in sports medicine clinics. (Author/MT)

  7. Head injury. Second edition

    SciTech Connect

    Cooper, P.R.

    1987-01-01

    This book contains 22 chapters. Some of the chapter titles are: Radiographic Evaluation; Epidemiology of Head Injury; Emergency Care and Initial Evaluation; Skull Fracture and Traumatic Cerebrospinal Fluid Fistulas; Mild Head Injury; and Injuries of the Cranial Nerves.

  8. Spinal Cord Injury Map

    MedlinePlus

    ... Counseling About Blog Facing Disability Jeff Shannon Donate Spinal Cord Injury Map Loss of function depends on what ... control. Learn more about spinal cord injuries. A spinal cord injury affects the entire family FacingDisability is designed ...

  9. Methods for a Randomized Trial of Weight-Supported Treadmill Training versus Conventional Training for Walking during Inpatient Rehabilitation after Incomplete Traumatic Spinal Cord Injury

    PubMed Central

    Dobkin, Bruce H.; Apple, David; Barbeau, Hugues; Basso, Michele; Behrman, Andrea; Deforge, Dan; Ditunno, John; Dudley, Gary; Elashoff, Robert; Fugate, Lisa; Harkema, Susan; Saulino, Michael; Scott, Michael

    2014-01-01

    The authors describe the rationale and methodology for the first prospective, multicenter, randomized clinical trial (RCT) of a task-oriented walking intervention for subjects during early rehabilitation for an acute traumatic spinal cord injury (SCI). The experimental strategy, body weight–supported treadmill training (BWSTT), allows physical therapists to systematically train patients to walk on a treadmill at increasing speeds typical of community ambulation with increasing weight bearing. The therapists provide verbal and tactile cues to facilitate the kinematic, kinetic, and temporal features of walking. Subjects were randomly assigned to a conventional therapy program for mobility versus the same intensity and duration of a combination of BWSTT and over-ground locomotor retraining. Subjects had an incomplete SCI (American Spinal Injury Association grades B, C, and D) from C-4 to T-10 (upper motoneuron group) or from T-11 to L-3 (lower motoneuron group). Within 8 weeks of a SCI, 146 subjects were entered for 12 weeks of intervention. The 2 single-blinded primary outcome measures are the level of independence for ambulation and, for those who are able to walk, the maximal speed for walking 50 feet, tested 6 and 12 months after randomization. The trial’s methodology offers a model for the feasibility of translating neuroscientific experiments into a RCT to develop evidence-based rehabilitation practices. PMID:14503436

  10. Reduced Phrenic Motoneuron Recruitment during Sustained Inspiratory Threshold Loading Compared to Single-Breath Loading: A Twitch Interpolation Study

    PubMed Central

    Raux, Mathieu; Demoule, Alexandre; Redolfi, Stefania; Morelot-Panzini, Capucine; Similowski, Thomas

    2016-01-01

    unequivocal. If twitch interpolation is interpreted as reflecting motoneuron recruitment, this study supports motor reorganization compatible with “diaphragm sparing” when an inspiratory threshold load becomes sustained. PMID:27891099

  11. Injuries in orienteering.

    PubMed

    Linde, F

    1986-09-01

    In a one-year prospective study of 42 elite orienteers, 73 recent injuries (1.7 per runner per year) were found. Acute injuries totalled 52% and 48% were due to overuse. Ankle sprains made up 37% of acute injuries while the remaining were mainly contusions caused by falls or bumps against branches or rocks. Medial shin pain, Achilles peritendinitis, peroneal tenosynovitis and iliotibial band friction syndrome were the most frequent overuse injuries. All overuse injuries were located in the lower extremity while 18% of acute injuries was located elsewhere. Acute injuries were most frequent in the competitive season while overuse injuries occurred most often during the continuous training period.

  12. Basketball Injuries: An Overview.

    ERIC Educational Resources Information Center

    Apple Jr., David F.

    1988-01-01

    This article discusses reasons for the increase in basketball-related injuries, describes common injuries, outlines steps for diagnosis and treatment, and offers recovery and prevention strategies. (IAH)

  13. Myelin-associated glycoprotein modulates apoptosis of motoneurons during early postnatal development via NgR/p75NTR receptor-mediated activation of RhoA signaling pathways

    PubMed Central

    Palandri, A; Salvador, V R; Wojnacki, J; Vivinetto, A L; Schnaar, R L; Lopez, P H H

    2015-01-01

    Myelin-associated glycoprotein (MAG) is a minor constituent of nervous system myelin, selectively expressed on the periaxonal myelin wrap. By engaging multiple axonal receptors, including Nogo-receptors (NgRs), MAG exerts a nurturing and protective effect the axons it ensheaths. Pharmacological activation of NgRs has a modulatory role on p75NTR-dependent postnatal apoptosis of motoneurons (MNs). However, it is not clear whether this reflects a physiological role of NgRs in MN development. NgRs are part of a multimeric receptor complex, which includes p75NTR, Lingo-1 and gangliosides. Upon ligand binding, this multimeric complex activates RhoA/ROCK signaling in a p75NTR-dependent manner. The aim of this study was to analyze a possible modulatory role of MAG on MN apoptosis during postnatal development. A time course study showed that Mag-null mice suffer a loss of MNs during the first postnatal week. Also, these mice exhibited increased susceptibility in an animal model of p75NTR-dependent MN apoptosis induced by nerve-crush injury, which was prevented by treatment with a soluble form of MAG (MAG-Fc). The protective role of MAG was confirmed in in vitro models of p75NTR-dependent MN apoptosis using the MN1 cell line and primary cultures. Lentiviral expression of shRNA sequences targeting NgRs on these cells abolished protection by MAG-Fc. Analysis of RhoA activity using a FRET-based RhoA biosensor showed that MAG-Fc activates RhoA. Pharmacological inhibition of p75NTR/RhoA/ROCK pathway, or overexpression of a p75NTR mutant unable to activate RhoA, completely blocked MAG-Fc protection against apoptosis. The role of RhoA/ROCK signaling was further confirmed in the nerve-crush model, where pretreatment with ROCK inhibitor Y-27632 blocked the pro-survival effect of MAG-Fc. These findings identify a new protective role of MAG as a modulator of apoptosis of MNs during postnatal development by a mechanism involving the p75NTR/RhoA/ROCK signaling pathway. Also, our results

  14. Myelin-associated glycoprotein modulates apoptosis of motoneurons during early postnatal development via NgR/p75(NTR) receptor-mediated activation of RhoA signaling pathways.

    PubMed

    Palandri, A; Salvador, V R; Wojnacki, J; Vivinetto, A L; Schnaar, R L; Lopez, P H H

    2015-09-03

    Myelin-associated glycoprotein (MAG) is a minor constituent of nervous system myelin, selectively expressed on the periaxonal myelin wrap. By engaging multiple axonal receptors, including Nogo-receptors (NgRs), MAG exerts a nurturing and protective effect the axons it ensheaths. Pharmacological activation of NgRs has a modulatory role on p75(NTR)-dependent postnatal apoptosis of motoneurons (MNs). However, it is not clear whether this reflects a physiological role of NgRs in MN development. NgRs are part of a multimeric receptor complex, which includes p75(NTR), Lingo-1 and gangliosides. Upon ligand binding, this multimeric complex activates RhoA/ROCK signaling in a p75(NTR)-dependent manner. The aim of this study was to analyze a possible modulatory role of MAG on MN apoptosis during postnatal development. A time course study showed that Mag-null mice suffer a loss of MNs during the first postnatal week. Also, these mice exhibited increased susceptibility in an animal model of p75(NTR)-dependent MN apoptosis induced by nerve-crush injury, which was prevented by treatment with a soluble form of MAG (MAG-Fc). The protective role of MAG was confirmed in in vitro models of p75(NTR)-dependent MN apoptosis using the MN1 cell line and primary cultures. Lentiviral expression of shRNA sequences targeting NgRs on these cells abolished protection by MAG-Fc. Analysis of RhoA activity using a FRET-based RhoA biosensor showed that MAG-Fc activates RhoA. Pharmacological inhibition of p75(NTR)/RhoA/ROCK pathway, or overexpression of a p75(NTR) mutant unable to activate RhoA, completely blocked MAG-Fc protection against apoptosis. The role of RhoA/ROCK signaling was further confirmed in the nerve-crush model, where pretreatment with ROCK inhibitor Y-27632 blocked the pro-survival effect of MAG-Fc. These findings identify a new protective role of MAG as a modulator of apoptosis of MNs during postnatal development by a mechanism involving the p75(NTR)/RhoA/ROCK signaling pathway

  15. Injury surveillance in construction: eye injuries.

    PubMed

    Welch, L S; Hunting, K L; Mawudeku, A

    2001-07-01

    Occupational eye injuries are both common and preventable. About 20% of occupational eye injuries occur in construction. To investigate the nature of eye injuries among construction workers, we analyzed a large data set of construction worker injuries. In addition, we interviewed 62 workers with eye injuries to further explore circumstances of eye injury and workers' attitudes and behavior toward the use of eye protection. Eleven percent (363 cases) of the 3,390 construction workers in our data set were treated for eye injuries. Welders, plumbers, insulators, painters/glaziers, supervisors, and electricians had a higher proportion of all injuries due to eye injuries than other trades. Nearly half of the diagnoses were abrasions (46%) followed by foreign objects or splash in the eye (29%), conjunctivitis (10%), and burns (5%). In the interviews with 62 workers, we found that employers very frequently required eye protection for all tasks or for high-risk tasks, and workers report wearing eye protection regularly. However, most did not wear eye protection with top and side shields; if we believe the injuries occurred because a particle or liquid passed between the glasses and the workers' faces, increased use of goggles or full shields would have prevented two-thirds of this group of injuries.

  16. Ice Hockey Injuries.

    ERIC Educational Resources Information Center

    Sim, Franklin H.; Simonet, William T.

    1988-01-01

    The article describes the mechanisms, management, and prevention of each type of injury to which hockey players are prone. It surveys the injuries sustained by ice hockey players and discusses treatment of specific injuries, including those injuries to the head, eye, shoulder, hand, thigh, scalp, and face. (JL)

  17. Emergencies in motoneuron disease.

    PubMed

    Finsterer, Josef; Stöllberger, Claudia

    2017-03-09

    Genetic and acquired motor-neuron-disorders (MNDs) may undergo acute deterioration resulting in various emergency situations. This literature review aims at summarising and discussing current knowledge about emergencies in MNDs. Emergencies that have been reported in MND patients include: respiratory, bulbar, cardiac, septic, epileptic, psychiatric, pain-related, and traumatic emergencies. Emergencies due to respiratory insufficiency have the strongest impact on morbidity and mortality in MNDs. To optimise the management of emergencies in MNDs, it is recommended to discuss these topics with the patient prior to their occurrence. After informed consent, patients may indicate their decision by signing an advance directive as to how such emergencies should be managed in case they arise. Generally, treatment of emergencies in MNDs is not at variance from treatment of similar emergencies due to other causes, but some peculiarities need to be pointed out. It is concluded that patients with MNDs may experience various emergencies during the disease course. Management of these conditions should be discussed with the patient prior to their appearance. Management of these emergencies follows general guidelines, which widely vary between countries, and depend on the availability of a patient's advance directive.

  18. Synaptic potentials of primary afferent fibers and motoneurons evoked by single intermediate nucleus interneurons in the cat spinal cord.

    PubMed

    Rudomin, P; Solodkin, M; Jiménez, I

    1987-05-01

    Spike-triggered averaging of dorsal and ventral root potentials was used in anesthetized cats to disclose possible synaptic connections of spinal interneurons in the intermediate nucleus with afferent fibers and/or motoneurons. With this method we have been able to document the existence of a distinct group of interneurons whose activity was associated with the recording of inhibitory potentials in the ventral roots (iVRPs), but not with negative dorsal root potentials (nDRPs). The iVRPs had mean durations of 60.8 +/- 22.1 ms and latencies between 1.7 and 5.1 ms relative to the onset of the interneuronal spikes. Within this group of neurons it was possible to characterize two categories depending on their responses to segmental inputs. Most type A interneurons were mono- or disynaptically activated by group I muscle afferents and polysynaptically by low threshold (1.08-1.69 X T) cutaneous fibers. Type B interneurons were instead polysynaptically activated by group II muscle and by cutaneous fibers with thresholds ranging from 1.02 to 3.1 X T. Whenever tested, both type A and B interneurons could be antidromically activated from Clarke's columns. There was a second group of interneurons whose activity was associated with the generation of both iVRPs and nDRPs. These potentials had mean durations of 107.5 +/- 35.6 and 131.5 +/- 32 ms, respectively, and onset latencies between 1.7 and 6.1 ms. The interneurons belonging to this group, which appear not to send axonal projections to Clarke's column, could be classified in three categories depending on their responses to peripheral inputs. Type C interneurons responded mono- or disynaptically to group I muscle volleys and polysynaptically to intermediate threshold (1.22-2.7 X T) cutaneous afferents. Type D interneurons were polysynaptically activated by group II muscle afferents (2.3-8.5 X T) and by intermediate threshold (1.4-3 X T) cutaneous fibers and type E interneurons only by group I muscle afferents with mono- or

  19. Intrauterine Arrow Injury

    PubMed Central

    Goswami, Jayanta Kumar; Lahiri, Kaushik

    2017-01-01

    Injury of a pregnant lady risks both mother and fetus. Various modes of injuries are possible. But arrow injury is not usually heard of in today's world. We have reported a male child delivered with a cut injury on the face. It was caused by a penetrating arrow hitting his mother in her lower abdomen at term. The injury of the baby was repaired successfully. PMID:28082780

  20. Injury to the prepuce.

    PubMed

    Yip, A; Ng, S K; Wong, W C; Li, M K; Lam, K H

    1989-05-01

    Injury to the prepuce is uncommon. A total of 32 patients were treated within a 3-year period. A difference in the aetiology between boys and adults was noted. Accidental injury to the prepuce occurred in 6 boys, with zipper injuries being the commonest among children. Coital and self-inflicted injuries accounted for 85% of adult cases. In patients with coital injuries, predisposing phimosis or a short frenulum was common.

  1. Postactivation depression of the Ia EPSP in motoneurons is reduced in both the G127X SOD1 model of amyotrophic lateral sclerosis and in aged mice.

    PubMed

    Hedegaard, A; Lehnhoff, J; Moldovan, M; Grøndahl, L; Petersen, N C; Meehan, C F

    2015-08-01

    Postactivation depression (PActD) of Ia afferent excitatory postsynaptic potentials (EPSPs) in spinal motoneurons results in a long-lasting depression of the stretch reflex. This phenomenon (PActD) is of clinical interest as it has been shown to be reduced in a number of spastic disorders. Using in vivo intracellular recordings of Ia EPSPs in adult mice, we demonstrate that PActD in adult (100-220 days old) C57BL/6J mice is both qualitatively and quantitatively similar to that which has been observed in larger animals with respect to both the magnitude (with ∼20% depression of EPSPs at 0.5 ms after a train of stimuli) and the time course (returning to almost normal amplitudes by 5 ms after the train). This validates the use of mouse models to study PActD. Changes in such excitatory inputs to spinal motoneurons may have important implications for hyperreflexia and/or glutamate-induced excitotoxicity in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). With the use of the G127X SOD1 mutant mouse, an ALS model with a prolonged asymptomatic phase and fulminant symptom onset, we observed that PActD is significantly reduced at both presymptomatic (16% depression) and symptomatic (17.3% depression) time points compared with aged-matched controls (22.4% depression). The PActD reduction was not markedly altered by symptom onset. Comparing these PActD changes at the EPSP with the known effect of the depression on the monosynaptic reflex, we conclude that this is likely to have a much larger effect on the reflex itself (a 20-40% difference). Nevertheless, it should also be accounted that in aged (580 day old) C57BL/6J mice there was also a reduction in PActD although, aging is not usually associated with spasticity.

  2. Sequential acquisition of cacophony calcium currents, sodium channels and voltage-dependent potassium currents affects spike shape and dendrite growth during postembryonic maturation of an identified Drosophila motoneuron.

    PubMed

    Ryglewski, Stefanie; Kilo, Lukas; Duch, Carsten

    2014-05-01

    During metamorphosis the CNS undergoes profound changes to accommodate the switch from larval to adult behaviors. In Drosophila and other holometabolous insects, adult neurons differentiate either from respecified larval neurons, newly born neurons, or are born embryonically but remain developmentally arrested until differentiation during pupal life. This study addresses the latter in the identified Drosophila flight motoneuron 5. In situ patch-clamp recordings, intracellular dye fills and immunocytochemistry address the interplay between dendritic shape, excitability and ionic current development. During pupal life, changes in excitability and spike shape correspond to a stereotyped, progressive appearance of voltage-gated ion channels. High-voltage-activated calcium current is the first current to appear at pupal stage P4, prior to the onset of dendrite growth. This is followed by voltage-gated sodium as well as transient potassium channel expression, when first dendrites grow, and sodium-dependent action potentials can be evoked by somatic current injection. Sustained potassium current appears later than transient potassium current. During the early stages of rapid dendritic growth, sodium-dependent action potentials are broadened by a calcium component. Narrowing of spike shape coincides with sequential increases in transient and sustained potassium currents during stages when dendritic growth ceases. Targeted RNAi knockdown of pupal calcium current significantly reduces dendritic growth. These data indicate that the stereotyped sequential acquisition of different voltage-gated ion channels affects spike shape and excitability such that activity-dependent calcium influx serves as a partner of genetic programs during critical stages of motoneuron dendrite growth.

  3. Enhanced heat shock protein 25 immunoreactivity in cranial nerve motoneurons and their related fiber tracts in rats prenatally-exposed to X-irradiation.

    PubMed

    Sawada, Kazuhiko; Saito, Shigeyoshi; Horiuchi-Hirose, Miwa; Murase, Kenya

    2014-05-01

    Alterations in histoarchitecture of the brainstem were examined immunohistochemically in 4-week-old rats with a single whole body X-irradiation at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 using anti-heat shock protein 25 (HSP25). HSP25 immunostaining was seen in the neuronal perikarya of cranial nerve motoneurons, that is, the motor and mesencephalic nuclei of the trigeminal nerve, facial nucleus, abducens nucleus and accessory facial nucleus in the pons, and the ambiguous nucleus, dorsal nucleus of vagus nerve and hypoglossus nucleus in the medulla oblongata of intact controls. In 0.5 to 1.5 Gy-irradiated rats, HSP25 immunostaining in those neurons was more intense than in controls, while the most intense immunostaining was marked in 1.5 Gy-irradiated rats. HSP25 immunostaining was also apparent in the spinal tract of the trigeminal nerve and facial nerve tracts in 0.5 to 1.5 Gy-irradiated rats, but was faint in controls. Interestingly, HSP25 immunostaining was aberrantly enhanced in dendritic arbors in the magnocellular region of medial vestibular nucleus of 0.5-1.5 Gy-irradiated rats. Those arbors were identified as excitatory secondary vestibulo-ocular neurons by double immunofluorescence for HSP25 and SMI-32. The results suggest an increase of HSP25 expression in cranial nerve motoneurons and their related fiber tracts from prenatal exposure to ionizing irradiation. This may be an adaptive response to chronic hypoxia due to malformed brain arteries caused by prenatal ionizing irradiation.

  4. Trigemino-cervical reflex in spinal cord injury.

    PubMed

    Gündüz, Ayşegül; Uzun, Nurten; Örnek, Nurettin İrem; Ünalan, Halil; Karamehmetoğlu, Şafak Sahir; Kızıltan, Meral E

    2014-09-19

    Abnormal enhancement of polysynaptic brainstem reflexes has been previously reported in patients with spinal cord injury (SCI). We aimed to investigate trigemino-cervical reflex (TCR) in SCI since it may reflect alterations in the connections of trigeminal proprioceptive system and cervical motoneurons. Consecutive 14 patients with SCI and 16 healthy subjects were included in this study. All patients were in the chronic phase. TCR was recorded over sternocleidomastoid (SCM) and splenius capitis (SC) muscles by stimulation of infraorbital nerve. We measured onset latency, amplitudes and durations of responses and compared between groups. We obtained stable responses over both muscles after one sided stimulation in healthy volunteers whereas probability of TCR was decreased in patients over both SCM (78.6% vs. 100%, p=0.050) and SC (71.4% vs. 100%, p=0.022). The absence of TCR was related to use of oral baclofen (≥50mg/day). However, when present, responses of SCI group had higher amplitudes and were more persistent. We demonstrated that TCR probability was similar to healthy subjects in SCI patients who used no or low dose oral baclofen. But it had higher amplitudes and longer durations. It was not obtained in only two patients who used oral baclofen more than 50mg/day.

  5. Traumatic Brachial Artery Injuries

    PubMed Central

    Ergunes, Kazim; Yilik, Levent; Ozsoyler, Ibrahim; Kestelli, Mert; Ozbek, Cengiz; Gurbuz, Ali

    2006-01-01

    We performed this retrospective study to analyze our strategies for managing and surgically treating brachial artery injuries. Fifty-seven patients with a total of 58 traumatic brachial artery injuries underwent surgery at our institution, from August 1996 through November 2004. Fifty-four patients were male and 3 were female (age range, 7 to 75 years; mean, 29.4 years). Forty-four of the patients had penetrating injuries (18 had stab wounds; 16, window glass injuries; and 10, industrial accidents), 10 had blunt trauma injuries (traffic accidents), and 3 had gunshot injuries. Fourteen patients (24.6%) had peripheral nerve injury. All patients underwent Doppler ultrasonographic examination. The repair of the 58 arterial injuries involved end-to-end anastomosis for 32 injuries (55.2%), reverse saphenous vein graft interpositional grafts for 18 (31%), and primary repair for 8 (13.8%). Venous continuity was achieved in 11 (84.6%) of 13 patients who had major venous injuries. Nine of the 57 patients (15.8%) required primary fasciotomy. Follow-up showed that 5 of the 14 patients with peripheral nerve injury had apparent disabilities due to nerve injury. One patient underwent amputation. There were no deaths. We believe that good results can be achieved in patients with brachial artery injuries by use of careful physical examination, Doppler ultrasonography, and restoration of viability with vascular repair and dbridement of nonviable tissues. Traumatic neurologic injury frequently leads to disability of the extremities. PMID:16572866

  6. Injury in rugby league.

    PubMed

    Hoskins, W; Pollard, H; Hough, K; Tully, C

    2006-05-01

    It was the purpose of this review to document the range, incidence, location and mechanism of injury occurring in the sport of rugby league. Rugby league is a collision sport played in Europe and the Pacific regions including Australia. The sport is well established and has competitions ranging from junior to elite professional. Due to the contact nature of the game, injury is relatively common. The most common injuries are musculotendinous in nature and afflict the lower limb more frequently than elsewhere. Despite the high incidence of minor (sprains/strains) to moderate musculoskeletal injury (fracture, ligament and joint injury) and minor head injuries such as lacerations, nasal fractures and concussions, rare more serious spinal cord and other injuries causing death have also been recorded. The literature on rugby league injury is small but growing and suffers from a lack of consistent definition of what an injury is, thereby causing variability in the nature and incidence/prevalence of injury. Information is lacking on the injury profiles of different age groups. Importantly, there has been little attempt to establish a coordinated injury surveillance program in rugby league in the junior or professional levels. The implementation of such programs would require a universal definition of injury and a focus on important events and competitions. The implementation could provide important information in the identification and prevention of risk factors for injury.

  7. Bodygraphic Injury Surveillance System

    NASA Astrophysics Data System (ADS)

    Tsuboi, Toshiki; Kitamura, Koji; Nishida, Yoshihumi; Motomura, Yoichi; Takano, Tachio; Yamanaka, Tatsuhiro; Mizoguchi, Hiroshi

    This paper proposes a new technology,``a bodygraphic injury surveillance system (BISS)'' that not only accumulates accident situation data but also represents injury data based on a human body coordinate system in a standardized and multilayered way. Standardized and multilayered representation of injury enables accumulation, retrieval, sharing, statistical analysis, and modeling causalities of injury across different fields such as medicine, engineering, and industry. To confirm the effectiveness of the developed system, the authors collected 3,685 children's injury data in cooperation with a hospital. As new analyses based on the developed BISS, this paper shows bodygraphically statistical analysis and childhood injury modeling using the developed BISS and Bayesian network technology.

  8. Upper extremity golf injuries.

    PubMed

    Cohn, Michael A; Lee, Steven K; Strauss, Eric J

    2013-01-01

    Golf is a global sport enjoyed by an estimated 60 million people around the world. Despite the common misconception that the risk of injury during the play of golf is minimal, golfers are subject to a myriad of potential pathologies. While the majority of injuries in golf are attributable to overuse, acute traumatic injuries can also occur. As the body's direct link to the golf club, the upper extremities are especially prone to injury. A thorough appreciation of the risk factors and patterns of injury will afford accurate diagnosis, treatment, and prevention of further injury.

  9. Rehabilitation of basketball injuries.

    PubMed

    Malanga, Gerard A; Chimes, Gary P

    2006-08-01

    Basketball is one of the most popular sports in the United States and throughout the world, and therefore represents one of the most common sources of sports-related injuries. Basketball injuries should be managed by the same general rehabilitation principles as other sports injuries. Additionally, the clinician should be aware not only of general sports injuries but of those injuries most commonly seen in basketball players. By maintaining knowledge of the most common basketball injuries as well as their diagnosis and treatment, the clinician can help to optimize the athlete's return to play and enjoyment of the sport.

  10. Medial Collateral Ligament (MCL) Injuries

    MedlinePlus

    ... of Healthy Breakfasts Shyness Medial Collateral Ligament (MCL) Injuries KidsHealth > For Teens > Medial Collateral Ligament (MCL) Injuries ... Treatment Coping With an MCL Injury About MCL Injuries A torn medial collateral ligament (MCL) is a ...

  11. Football injuries: current concepts.

    PubMed

    Olson, David E; Sikka, Robby Singh; Hamilton, Abigail; Krohn, Austin

    2011-01-01

    Football is one of the most popular sports in the United States and is the leading cause of sports-related injury. A large focus in recent years has been on concussions, sudden cardiac death, and heat illness, all thought to be largely preventable health issues in the young athlete. Injury prevention through better understanding of injury mechanisms, education, proper equipment, and practice techniques and preseason screening may aid in reducing the number of injuries. Proper management of on-field injuries and health emergencies can reduce the morbidity associated with these injuries and may lead to faster return to play and reduced risk of future injury. This article reviews current concepts surrounding frequently seen football-related injuries.

  12. Spinal Cord Injury

    MedlinePlus

    ... care for people with spinal cord injuries and aggressive treatment and rehabilitation can minimize damage to the ... care for people with spinal cord injuries and aggressive treatment and rehabilitation can minimize damage to the ...

  13. Experimental traumatic brain injury

    PubMed Central

    2010-01-01

    Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury. PMID:20707892

  14. Elbow Injuries and Disorders

    MedlinePlus

    ... Many things can make your elbow hurt. A common cause is tendinitis, an inflammation or injury to the tendons that attach muscle to bone. Tendinitis of the elbow is a sports injury, often from playing tennis or golf. You ...

  15. Preventing Knee Injuries

    MedlinePlus

    ... as a result of a twisting or pivoting motion. This injury may cause susceptibility to repeat injuries and knee instability, and therefore often requires surgery. Occasionally, a twisting or hyperextension force to the knee may result in a tibial ...

  16. Facial Injuries and Disorders

    MedlinePlus

    Face injuries and disorders can cause pain and affect how you look. In severe cases, they can affect sight, ... your nose, cheekbone and jaw, are common facial injuries. Certain diseases also lead to facial disorders. For ...

  17. Rotator Cuff Injuries

    MedlinePlus

    ... cuff are common. They include tendinitis, bursitis, and injuries such as tears. Rotator cuff tendons can become ... cuff depends on age, health, how severe the injury is, and how long you've had the ...

  18. Brachial Plexus Injuries

    MedlinePlus

    ... to the shoulder, arm, and hand. Brachial plexus injuries are caused by damage to those nerves. Symptoms ... sensation in the arm or hand Brachial plexus injuries can occur as a result of shoulder trauma, ...

  19. Eye Injuries (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Eye Injuries KidsHealth > For Parents > Eye Injuries Print A ... sand, dirt, and other foreign bodies on the eye surface) Wash your hands thoroughly before touching the ...

  20. Wounds and Injuries

    MedlinePlus

    ... cannot close it yourself, you cannot stop the bleeding or get the dirt out, or it does not heal. Other common types of injuries include Animal bites Bruises Burns Dislocations Electrical injuries Fractures Sprains and strains

  1. Head Injuries in Soccer.

    ERIC Educational Resources Information Center

    Fields, Karl B.

    1989-01-01

    This article reviews the medical literature on head injuries in soccer and concludes that protective headgear to reduce these injuries may not be as effective as rule changes and other measures, such as padding goal posts. (IAH)

  2. Dealing with Sports Injuries

    MedlinePlus

    ... happen over time, usually from repetitive training , like running, overhand throwing, or serving a ball in tennis. ... injury in sports that involve a lot of running. Another reason for foot injuries is wearing the ...

  3. Spinal injury - resources

    MedlinePlus

    Resources - spinal injury ... The following organizations are good resources for information on spinal injury : National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/Disorders/All-Disorders/Spinal-Cord- ...

  4. Ocular injuries in sports.

    PubMed

    Cass, Shane P

    2012-01-01

    Eye injuries are common in sports. Team physicians need to be able to recognize and treat common injuries and know when to refer other problems. This article highlights the current treatment of common sports-related eye injuries and reviews some of the new literature. Nearly 90% of all sports-related eye injuries can be prevented with adequate eye protection and will be discussed in some detail in the article.

  5. Rotator cuff injuries.

    PubMed

    Crusher, R H

    2000-07-01

    Different types of rotator cuff injuries frequently present to Accident and Emergency departments and minor injury units but can be difficult to differentiate clinically. This brief case study describes the examination and diagnosis of related shoulder injuries, specifically rotator cuff tears/disruption and calcifying supraspinatus tendinitis. The relevant anatomy and current therapies for these injuries is also discussed to enable the emergency nurse practitioner to have a greater understanding of the theory surrounding their diagnosis and treatments.

  6. Smoke inhalation injury

    NASA Astrophysics Data System (ADS)

    Birky, M.

    The cause of death by fires was studied. The present results and information are, however, not enough to reduce loss of life or inhalation injury. The magnitude and type of inhalation injury for civilians and firefighters represents the most inadequately defined human element of accidental fires. Little information is available on compounds other than carbon monoxide, which are responsible for respiration injury or toxicological syndrome. Effective treatment methods for inhalation victims and studies on fatalities, inhalation injury and animals are suggested.

  7. Editorial. Bicycle injuries and injury prevention.

    PubMed

    Pless, I B

    2014-07-01

    In 1989, long before this journal added injuries to its title, it published two papers on childhood injuries and I was asked to write an editorial for this occasion. I chose the title "Challenges for Injury Prevention: Two Neglected Aspects" because I thought the papers neglected to mention the inadequacy of injury statistics (at the time there were no emergency department data) and also failed to emphasize the public health importance of childhood injuries. It is instructive, therefore, to compare this issue's offerings with how matters stood nearly 25 years ago and see what progress we've made. Papers in this and the previous issue of this journal discuss bicycle safety in general and helmet use in particular. Although this is a somewhat narrow focus, it serves as one indicator of how the field has evolved and what remains to be done to improve both the science and policy in this domain.

  8. Injuries from break dancing.

    PubMed

    Norman, R A; Grodin, M A

    1984-10-01

    Break dancing is a popular contemporary activity that has important medical implications. Some dancers have complained of lower back pain and difficulty in bending over-the "breakdance back syndrome." Break dancing injuries are often comparable to the orthopedic injuries that occur in unsupervised athletic activities. Careful screening, instruction, supervision and training of break dancers will help prevent injuries.

  9. Lightning injury: a review.

    PubMed

    Ritenour, Amber E; Morton, Melinda J; McManus, John G; Barillo, David J; Cancio, Leopoldo C

    2008-08-01

    Lightning is an uncommon but potentially devastating cause of injury in patients presenting to burn centers. These injuries feature unusual symptoms, high mortality, and significant long-term morbidity. This paper will review the epidemiology, physics, clinical presentation, management principles, and prevention of lightning injuries.

  10. Prevention of Football Injuries

    PubMed Central

    Kirkendall, Donald T; Junge, Astrid; Dvorak, Jiri

    2010-01-01

    Purpose Every sport has a unique profile of injury and risk of injury. In recent years, there have been numerous attempts at conducting injury prevention trials for specific injuries or for injuries within specific sports to provide evidence useful to the sports medicine and sport community. Football has been a focus of a number of randomized injury prevention trials. Methods MEDLINE was searched with the first order keywords of “injury prevention” and “sport”. This list was restricted to “clinical trial” or “randomized controlled trial” which had been conducted on children and adults whose goal was preventing common football injuries. Our objective was to find studies with an exercise-based training program, thus projects that used mechanical interventions were excluded. Results A structured, generalized warm-up has been shown to be effective at preventing common injuries in football, reducing injuries by about one-third. Conclusion The huge participation numbers in the worldwide family of football would suggest that any reduction in injury should have a public health impact. Professionals in sports medicine need to promote injury prevention programs that have been shown to be effective. PMID:22375195

  11. Mania following head injury.

    PubMed

    Yatham, L N; Benbow, J C; Jeffers, A M

    1988-03-01

    A case of mania following head injury in an individual with a genetic predisposition to schizophrenia is reported. It is argued that the head injury is probably causative in his case and suggested that head injury should be considered as one of the aetiological factors in secondary mania.

  12. Spinal Cord Injuries

    MedlinePlus

    ... your body and your brain. A spinal cord injury disrupts the signals. Spinal cord injuries usually begin with a blow that fractures or ... bone disks that make up your spine. Most injuries don't cut through your spinal cord. Instead, ...

  13. Repetitive Stress Injuries

    MedlinePlus

    ... any problems since. What Are Repetitive Stress Injuries? Repetitive stress injuries (RSIs) are injuries that happen when too much stress is placed on a part of the body, resulting in inflammation (pain and swelling), muscle strain, or tissue damage. This stress generally occurs from ...

  14. Assessment of Ankle Injuries

    ERIC Educational Resources Information Center

    Mai, Nicholas; Cooper, Leslie

    2009-01-01

    School nurses are faced with the challenge of identifying and treating ankle injuries in the school setting. There is little information guiding the assessment and treatment of these children when an injury occurs. It is essential for school nurses to understand ankle anatomy, pathophysiology of the acute ankle injury, general and orthopedic…

  15. Rotator Cuff Injuries.

    ERIC Educational Resources Information Center

    Connors, G. Patrick

    Many baseball players suffer from shoulder injuries related to the rotator cuff muscles. These injuries may be classified as muscular strain, tendonitis or tenosynovitis, and impingement syndrome. Treatment varies from simple rest to surgery, so it is important to be seen by a physician as soon as possible. In order to prevent these injuries, the…

  16. Direct Spinal Ventral Root Repair following Avulsion: Effectiveness of a New Heterologous Fibrin Sealant on Motoneuron Survival and Regeneration

    PubMed Central

    Barbizan, Roberta; Seabra Ferreira, Rui

    2016-01-01

    Axonal injuries at the interface between central and peripheral nervous system, such as ventral root avulsion (VRA), induce important degenerative processes, mostly resulting in neuronal and motor function loss. In the present work, we have compared two different fibrin sealants, one derived from human blood and another derived from animal blood and Crotalus durissus terrificus venom, as a promising treatment for this type of injury. Lewis rats were submitted to VRA (L4–L6) and had the avulsed roots reimplanted to the surface of the spinal cord, with the aid of fibrin sealant. The spinal cords were processed to evaluate neuronal survival, synaptic stability, and glial reactivity, 4 and 12 weeks after lesion. Sciatic nerves were processed to investigate Schwann cell activity by p75NTR expression (4 weeks after surgery) and to count myelinated axons and morphometric evaluation (12 weeks after surgery). Walking track test was used to evaluate gait recovery, up to 12 weeks. The results indicate that both fibrin sealants are similarly efficient. However, the snake-derived fibrin glue is a potentially safer alternative for being a biological and biodegradable product which does not contain human blood derivatives. Therefore, the venom glue can be a useful tool for the scientific community due to its advantages and variety of applications. PMID:27642524

  17. Pharmacologic analysis of inhibition produced by last-order intermediate nucleus interneurons mediating nonreciprocal inhibition of motoneurons in cat spinal cord.

    PubMed

    Rudomin, P; Jiménez, I; Quevedo, J; Solodkin, M

    1990-01-01

    1. The aim of this study was to investigate the effects of drugs blocking glycinergic and GABAergic transmission on the postsynaptic inhibition of hindlimb motoneurons produced by activation of last-order laminae V-VI interneurons, which are coexcited by muscle and cutaneous afferents and have axonal branches projecting to the Clarke's column. 2. In anesthetized cats with right spinal cord hemisected and both dorsal columns cut between L4 and L5 segments, stimulation of the Clarke's column (CC) at L3-L4 level produced a short-latency, presumably monosynaptic, inhibitory potential that could be recorded either from L7 or S1 ventral rootlets by means of the sucrose-gap technique (iVRP) or intracellularly from hindlimb motoneurons (IPSP). These potentials have been attributed to antidromic activation of a population of last-order interneurons mediating nonreciprocal inhibition of motoneurons. 3. The early iVRP and IPSP produced by CC stimulation was practically abolished 10-20 s after the intravenous injection of strychnine (0.1 mg/kg) and replaced by an excitatory synaptic potential followed by delayed, slow, strychnine-resistant inhibitory potential. 4. Monosynaptic reflexes (MSR) elicited by stimulation of group I gastrocnemius (GS) afferents were inhibited during the occurrence of the CC-iVRP. This inhibition was significantly reduced after intravenous strychnine. On the other hand, the inhibition of the GS-MSR, produced by conditioning stimulation of the posterior biceps and semitendinosus (PBSt) nerve with trains of pulses applied 25-35 ms before the test stimulus, was practically unchanged after the intravenous injection of strychnine. 5. The CC-iVRP and the associated inhibition of GS-MSRs were not significantly affected after the intravenous injection of 0.1 mg/kg of picrotoxin, which clearly reduced the dorsal root potentials (DRP), the late component of the iVRP, and the inhibition of MSRs produced by PBSt volleys. 6. The effect of strychnine and picrotoxin

  18. Triathlon: running injuries.

    PubMed

    Spiker, Andrea M; Dixit, Sameer; Cosgarea, Andrew J

    2012-12-01

    The running portion of the triathlon represents the final leg of the competition and, by some reports, the most important part in determining a triathlete's overall success. Although most triathletes spend most of their training time on cycling, running injuries are the most common injuries encountered. Common causes of running injuries include overuse, lack of rest, and activities that aggravate biomechanical predisposers of specific injuries. We discuss the running-associated injuries in the hip, knee, lower leg, ankle, and foot of the triathlete, and the causes, presentation, evaluation, and treatment of each.

  19. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

    PubMed

    Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

    2013-05-01

    Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

  20. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones

    PubMed Central

    Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

    2013-01-01

    Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12–14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

  1. Injuries in Swedish skydiving

    PubMed Central

    Westman, Anton; Björnstig, Ulf

    2007-01-01

    Objective To create a basis for prevention of modern skydiving injuries. Design Descriptive epidemiological study. Setting National total material. Patients Data on all reported injury events (n = 257) in Swedish skydiving 1999–2003 (total 539 885 jumps) were retrieved from the Swedish Parachute Association. Non‐fatally injured skydivers were sent a questionnaire asking for event and injury details (response rate 89%), and supplementary hospital records were retrieved for the most serious injuries (n = 85). Human, equipment and environmental factors were assessed for risk. Main Outcome Measurements Frequency and severity of injuries. Results Incidence of non‐fatal injury events was 48 per 100 000 jumps. The lower extremities, spine and shoulders were important regions of injury. The most serious injuries were experienced by licensed skydivers, but students in training had a higher injury rate and more often left the sport because of the injury. Of two student‐training systems, one had an incidence less than half that of the other. Conclusions A basis for prevention was created, showing a potential for reduction of frequency and severity of injuries with training and technical interventions. PMID:17224436

  2. Imaging of triathlon injuries.

    PubMed

    Tuite, Michael J

    2010-11-01

    Injuries in triathletes are common and are mostly overuse injuries. Rotator cuff tendinitis is the most common complaint from swimming, but the incidence of tendinopathy and rotator cuff tears on magnetic resonance imaging is comparable in triathletes without and with shoulder pain. Cycling injuries are mainly to the knee, including patellar tendinosis, iliotibial band syndrome, and patellofemoral stress syndrome, and to the Achilles tendon and the cervical and lumbar spine. Running is associated with most injuries in triathletes, during both training and racing, causing the athlete to discontinue the triathlon. In addition to knee injuries from running, triathletes may also develop foot and ankle, lower leg, and hip injuries similar to single-sport distance runners. Some injuries in triathletes may be mainly symptomatic during one of the three sports but are exacerbated by one or both of the other disciplines.

  3. [Management of ureteral injuries].

    PubMed

    Benoit, L; Spie, R; Favoulet, P; Cheynel, N; Kretz, B; Gouy, S; Dubruille, T; Fraisse, J; Cuisenier, J

    2005-09-01

    Ureteral injury is a rare but potential serious complication that can occur during a variety of general surgical procedures. Knowledge of the course of the ureter is the first step toward preventing ureteral injuries. While some injuries are noticed intraoperatively, most are missed and present later with pain, sepsis, urinary drainage or renal loss. The choice of treatment is based on the location, type and extend of ureteral injury. For injuries recognized during open surgery, when involving the distal 5 cm of the ureter, an antireflux ureterocystostomy such as the Politano-Leadbetter procedure or a vesicopsoas hitch can be performed. For the middle ureter, an ureteroureterostomy is satisfactory and for the proximal ureter, most injuries can be managed by transureteroureterostomy. In complex situations intestinal interposition, autotransplantation or even nephrectomy can be considered. The majority of patients with delayed diagnosed ureteral injuries should be managed by an initial endo-urologic approach.

  4. Regulation of neuropilin 1 by spinal cord injury in adult rats.

    PubMed

    Agudo, Marta; Robinson, Michelle; Cafferty, William; Bradbury, Elizabeth J; Kilkenny, Carol; Hunt, Stephen P; McMahon, Stephen B

    2005-03-01

    Using RT-PCR, in situ hybridization, Western blotting, and immunofluorescence, we have analyzed the expression of neuropilin 1 (Np1) in two models of spinal cord injury (spinal cord hemisection and dorsal column crush) and following dorsal root rhizotomy in adult rats. Our results show that Np1 RNA and protein are up-regulated in the spinal cord after all these lesions but remain unaltered in the adjacent dorsal root ganglia. In control animals, Np1 levels in the spinal cord are low and appear to be localized mainly in blood vessels, motoneurons, and in the superficial layers of the dorsal horn. After DCC and rhizotomy, Np1 is expressed de novo around the injury and in the deafferentated dorsal horn, respectively, mainly by OX42-positive microglial cells. Both lesions affect the sensory projections, and interestingly a consistent increase of Np1 signal is additionally seen in the dorsal horn where these projections terminate. Unexpectedly, this increase is bilateral after unilateral rhizotomy.

  5. Overuse Injury: How to Prevent Training Injuries

    MedlinePlus

    ... type of muscle or joint injury, such as tendinitis or a stress fracture, that's caused by repetitive ... Khan K, et al. Overview of chronic (overuse) tendinopathies. http://www.uptodate.com/home. Accessed Dec. 21, ...

  6. Biomechanics of whiplash injury.

    PubMed

    Chen, Hai-bin; Yang, King H; Wang, Zheng-guo

    2009-10-01

    Despite a large number of rear-end collisions on the road and a high frequency of whiplash injuries reported, the mechanism of whiplash injuries is not completely understood. One of the reasons is that the injury is not necessarily accompanied by obvious tissue damage detectable by X-ray or MRI. An extensive series of biomechanics studies, including injury epidemiology, neck kinematics, facet capsule ligament mechanics, injury mechanisms and injury criteria, were undertaken to help elucidate these whiplash injury mechanisms and gain a better understanding of cervical facet pain. These studies provide the following evidences to help explain the mechanisms of the whiplash injury: (1) Whiplash injuries are generally considered to be a soft tissue injury of the neck with symptoms such as neck pain and stiffness, shoulder weakness, dizziness, headache and memory loss, etc. (2) Based on kinematical studies on the cadaver and volunteers, there are three distinct periods that have the potential to cause injury to the neck. In the first stage, flexural deformation of the neck is observed along with a loss of cervical lordosis; in the second stage, the cervical spine assumes an S-shaped curve as the lower vertebrae begin to extend and gradually cause the upper vertebrae to extend; during the final stage, the entire neck is extended due to the extension moments at both ends. (3) The in vivo environment afforded by rodent models of injury offers particular utility for linking mechanics, nociception and behavioral outcomes. Experimental findings have examined strains across the facet joint as a mechanism of whiplash injury, and suggested a capsular strain threshold or a vertebral distraction threshold for whiplash-related injury, potentially producing neck pain. (4) Injuries to the facet capsule region of the neck are a major source of post-crash pain. There are several hypotheses on how whiplash-associated injury may occur and three of these injuries are related to strains

  7. [Blunt thoracic injury].

    PubMed

    Miura, H; Taira, O; Hiraguri, S; Uchida, O; Hagiwara, M; Ikeda, T; Kato, H

    1998-06-01

    Of 161 patients with blunt thoracic injury, 135 were male (83.9%) and 26 were female. The most common cause of injury was traffic accidents (130 patients, 80.7%), followed by falls (22 patients), and crushing (7 patients). There were 46 third decade and 36 second decade patients. Thirty-two patients had single thoracic injury and the other had multiple organ injury. The most