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Sample records for snb motoneuron development

  1. HuD and the Survival Motor Neuron Protein Interact in Motoneurons and Are Essential for Motoneuron Development, Function, and mRNA Regulation.

    Science.gov (United States)

    Hao le, Thi; Duy, Phan Q; An, Min; Talbot, Jared; Iyer, Chitra C; Wolman, Marc; Beattie, Christine E

    2017-11-29

    Motoneurons establish a critical link between the CNS and muscles. If motoneurons do not develop correctly, they cannot form the required connections, resulting in movement defects or paralysis. Compromised development can also lead to degeneration because the motoneuron is not set up to function properly. Little is known, however, regarding the mechanisms that control vertebrate motoneuron development, particularly the later stages of axon branch and dendrite formation. The motoneuron disease spinal muscular atrophy (SMA) is caused by low levels of the survival motor neuron (SMN) protein leading to defects in vertebrate motoneuron development and synapse formation. Here we show using zebrafish as a model system that SMN interacts with the RNA binding protein (RBP) HuD in motoneurons in vivo during formation of axonal branches and dendrites. To determine the function of HuD in motoneurons, we generated zebrafish HuD mutants and found that they exhibited decreased motor axon branches, dramatically fewer dendrites, and movement defects. These same phenotypes are present in animals expressing low levels of SMN, indicating that both proteins function in motoneuron development. HuD binds and transports mRNAs and one of its target mRNAs, Gap43 , is involved in axonal outgrowth. We found that Gap43 was decreased in both HuD and SMN mutants. Importantly, transgenic expression of HuD in motoneurons of SMN mutants rescued the motoneuron defects, the movement defects, and Gap43 mRNA levels. These data support that the interaction between SMN and HuD is critical for motoneuron development and point to a role for RBPs in SMA. SIGNIFICANCE STATEMENT In zebrafish models of the motoneuron disease spinal muscular atrophy (SMA), motor axons fail to form the normal extent of axonal branches and dendrites leading to decreased motor function. SMA is caused by low levels of the survival motor neuron (SMN) protein. We show in motoneurons in vivo that SMN interacts with the RNA binding

  2. Development and regulation of response properties in spinal cord motoneurons

    DEFF Research Database (Denmark)

    Perrier, J F; Hounsgaard, J

    2000-01-01

    The intrinsic response properties of spinal motoneurons determine how converging premotor neuronal input is translated into the final motor command transmitted to muscles. From the patchy data available it seems that these properties and their underlying currents are highly conserved in terrestrial...... vertebrates in terms of both phylogeny and ontogeny. Spinal motoneurons in adults are remarkably similar in many respects ranging from the resting membrane potential to pacemaker properties. Apart from the axolotls, spinal motoneurons from all species investigated have latent intrinsic response properties...... mediated by L-type Ca2+ channels. This mature phenotype is reached gradually during development through phases in which A-type potassium channels and T-type calcium channels are transiently expressed. The intrinsic response properties of mature spinal motoneurons are subject to short-term adjustments via...

  3. Developing electrical properties of postnatal mouse lumbar motoneurons

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    Jacques eDurand

    2015-09-01

    Full Text Available 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 and rheobase. Both parameters are significantly correlated with the total dendritic surface area of motoneurons, the largest motoneurons having the lowest input resistance 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 whereas the transient firing group has the lowest rheobase and the less mature action potential. 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 type 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

  4. Sentinel node biopsy (SNB) in malignant melanoma as same day procedure vs delayed procedure

    DEFF Research Database (Denmark)

    Rødgaard, Jes Christian; Kramer, Stine; Stolle, Lars B

    2013-01-01

    The aim of this study was to compare a delayed sentinel node biopsy (dSNB) procedure with a same-day procedure (sSNB) in malignant melanoma. In March 2012, Aarhus University Hospital went from the dSNB to the sSNB procedure defined by lymphoscintigraphy (LS) and sentinel node biopsy (SNB) perform......, essential to keep the morbidity and economic costs low, while keeping the quality of the procedure high....

  5. Synaptic control of motoneuronal excitability

    DEFF Research Database (Denmark)

    Rekling, J C; Funk, G D; Bayliss, D A

    2000-01-01

    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...... 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...

  6. Diversification of intrinsic motoneuron electrical properties during normal development and botulinum toxin-induced muscle paralysis in early postnatal mice.

    Science.gov (United States)

    Nakanishi, S T; Whelan, P J

    2010-05-01

    During early postnatal development, between birth and postnatal days 8-11, mice start to achieve weight-bearing locomotion. In association with the progression of weight-bearing locomotion there are presumed developmental changes in the intrinsic electrical properties of spinal -motoneurons. However, these developmental changes in the properties of -motoneuron properties have not been systematically explored in mice. Here, data are presented documenting the developmental changes of selected intrinsic motoneuron electrical properties, including statistically significant changes in action potential half-width, intrinsic excitability and diversity (quantified as coefficient of variation) of rheobase current, afterhyperpolarization half-decay time, and input resistance. In various adult mammalian preparations, the maintenance of intrinsic motoneuron electrical properties is dependent on activity and/or transmission-sensitive motoneuron-muscle interactions. In this study, we show that botulinum toxin-induced muscle paralysis led to statistically significant changes in the normal development of intrinsic motoneuron electrical properties in the postnatal mouse. This suggests that muscle activity during early neonatal life contributes to the development of normal motoneuron electrical properties.

  7. Development and regulation of response properties in spinal cord motoneurons

    DEFF Research Database (Denmark)

    Perrier, J F; Hounsgaard, J

    2000-01-01

    vertebrates in terms of both phylogeny and ontogeny. Spinal motoneurons in adults are remarkably similar in many respects ranging from the resting membrane potential to pacemaker properties. Apart from the axolotls, spinal motoneurons from all species investigated have latent intrinsic response properties...

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

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    Julien Ackermann

    2011-04-01

    Full Text Available 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.

  9. ICF target 2D modeling using Monte Carlo SNB electron thermal transport in DRACO

    Science.gov (United States)

    Chenhall, Jeffrey; Cao, Duc; Moses, Gregory

    2016-10-01

    The iSNB (implicit Schurtz Nicolai Busquet multigroup diffusion electron thermal transport method is adapted into a Monte Carlo (MC) transport method to better model angular and long mean free path non-local effects. The MC model was first implemented in the 1D LILAC code to verify consistency with the iSNB model. Implementation of the MC SNB model in the 2D DRACO code enables higher fidelity non-local thermal transport modeling in 2D implosions such as polar drive experiments on NIF. The final step is to optimize the MC model by hybridizing it with a MC version of the iSNB diffusion method. The hybrid method will combine the efficiency of a diffusion method in intermediate mean free path regions with the accuracy of a transport method in long mean free path regions allowing for improved computational efficiency while maintaining accuracy. Work to date on the method will be presented. This work was supported by Sandia National Laboratories and the Univ. of Rochester Laboratory for Laser Energetics.

  10. Hybrid transport and diffusion modeling using electron thermal transport Monte Carlo SNB in DRACO

    Science.gov (United States)

    Chenhall, Jeffrey; Moses, Gregory

    2017-10-01

    The iSNB (implicit Schurtz Nicolai Busquet) multigroup diffusion electron thermal transport method is adapted into an Electron Thermal Transport Monte Carlo (ETTMC) transport method to better model angular and long mean free path non-local effects. Previously, the ETTMC model had been implemented in the 2D DRACO multiphysics code and found to produce consistent results with the iSNB method. Current work is focused on a hybridization of the computationally slower but higher fidelity ETTMC transport method with the computationally faster iSNB diffusion method in order to maximize computational efficiency. Furthermore, effects on the energy distribution of the heat flux divergence are studied. Work to date on the hybrid method will be presented. This work was supported by Sandia National Laboratories and the Univ. of Rochester Laboratory for Laser Energetics.

  11. The Met receptor tyrosine kinase prevents zebrafish primary motoneurons from expressing an incorrect neurotransmitter

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    Eisen Judith S

    2008-07-01

    Full Text Available Abstract Background Expression of correct neurotransmitters is crucial for normal nervous system function. How neurotransmitter expression is regulated is not well-understood; however, previous studies provide evidence that both environmental signals and intrinsic differentiation programs are involved. One environmental signal known to regulate neurotransmitter expression in vertebrate motoneurons is Hepatocyte growth factor, which acts through the Met receptor tyrosine kinase and also affects other aspects of motoneuron differentiation, including axonal extension. Here we test the role of Met in development of motoneurons in embryonic zebrafish. Results We found that met is expressed in all early developing, individually identified primary motoneurons and in at least some later developing secondary motoneurons. We used morpholino antisense oligonucleotides to knock down Met function and found that Met has distinct roles in primary and secondary motoneurons. Most secondary motoneurons were absent from met morpholino-injected embryos, suggesting that Met is required for their formation. We used chemical inhibitors to test several downstream pathways activated by Met and found that secondary motoneuron development may depend on the p38 and/or Akt pathways. In contrast, primary motoneurons were present in met morpholino-injected embryos. However, a significant fraction of them had truncated axons. Surprisingly, some CaPs in met morpholino antisense oligonucleotide (MO-injected embryos developed a hybrid morphology in which they had both a peripheral axon innervating muscle and an interneuron-like axon within the spinal cord. In addition, in met MO-injected embryos primary motoneurons co-expressed mRNA encoding Choline acetyltransferase, the synthetic enzyme for their normal neurotransmitter, acetylcholine, and mRNA encoding Glutamate decarboxylase 1, the synthetic enzyme for GABA, a neurotransmitter never normally found in these motoneurons, but

  12. Neuroprotective effects of testosterone metabolites and dependency on receptor action on the morphology of somatic motoneurons following the death of neighboring motoneurons.

    Science.gov (United States)

    Cai, Yi; Chew, Cory; Muñoz, Fernando; Sengelaub, Dale R

    2017-06-01

    Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone is neuroprotective, attenuating induced dendritic atrophy. In this study we examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites. Furthermore, to assess whether these neuroprotective effects were mediated through steroid hormone receptors, we used receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion. Motoneurons innervating the vastus medialis muscles of adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were treated with either dihydrotestosterone or estradiol, alone or in combination with their respective receptor antagonists, or left untreated. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Compared with intact normal animals, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons. Dendritic atrophy was attenuated with both dihydrotestosterone and estradiol treatment to a degree similar to that seen with testosterone, and attenuation of atrophy was prevented by receptor blockade. Together, these findings suggest that neuroprotective effects on motoneurons can be mediated by either androgenic or estrogenic hormones and require action via steroid hormone receptors, further supporting a role for hormones as neurotherapeutic agents in the injured nervous system. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 691-707, 2017. © 2016 Wiley Periodicals, Inc.

  13. Design process for applying the nonlocal thermal transport iSNB model to a Polar-Drive ICF simulation

    Science.gov (United States)

    Cao, Duc; Moses, Gregory; Delettrez, Jacques; Collins, Timothy

    2014-10-01

    A design process is presented for the nonlocal thermal transport iSNB (implicit Schurtz, Nicolai, and Busquet) model to provide reliable nonlocal thermal transport in polar-drive ICF simulations. Results from the iSNB model are known to be sensitive to changes in the SNB ``mean free path'' formula, and the latter's original form required modification to obtain realistic preheat levels. In the presented design process, SNB mean free paths are first modified until the model can match temperatures from Goncharov's thermal transport model in 1D temperature relaxation simulations. Afterwards the same mean free paths are tested in a 1D polar-drive surrogate simulation to match adiabats from Goncharov's model. After passing the two previous steps, the model can then be run in a full 2D polar-drive simulation. This research is supported by the University of Rochester Laboratory for Laser Energetics.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yun; Wang, Jing [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Chen, Guian [Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Reproductive Medical Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Fan, Dongsheng, E-mail: dsfan@yahoo.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Deng, Min, E-mail: dengmin1706@yahoo.com.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China)

    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.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

    Research highlights: → Nicotinamide inhibit Sirt1. → MASH1 and Ngn2 activation. → Increase the expression of HB9. → 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 βIII-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 μM) or inhibitor nicotinamide (100 μM). 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.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    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.

  17. Zebrafish Mnx proteins specify one motoneuron subtype and suppress acquisition of interneuron characteristics

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    Seredick Steve D

    2012-11-01

    Full Text Available Abstract Background Precise matching between motoneuron subtypes and the muscles they innervate is a prerequisite for normal behavior. Motoneuron subtype identity is specified by the combination of transcription factors expressed by the cell during its differentiation. Here we investigate the roles of Mnx family transcription factors in specifying the subtypes of individually identified zebrafish primary motoneurons. Results Zebrafish has three Mnx family members. We show that each of them has a distinct and temporally dynamic expression pattern in each primary motoneuron subtype. We also show that two Mnx family members are expressed in identified VeLD interneurons derived from the same progenitor domain that generates primary motoneurons. Surprisingly, we found that Mnx proteins appear unnecessary for differentiation of VeLD interneurons or the CaP motoneuron subtype. Mnx proteins are, however, required for differentiation of the MiP motoneuron subtype. We previously showed that MiPs require two temporally-distinct phases of Islet1 expression for normal development. Here we show that in the absence of Mnx proteins, the later phase of Islet1 expression is initiated but not sustained, and MiPs become hybrids that co-express morphological and molecular features of motoneurons and V2a interneurons. Unexpectedly, these hybrid MiPs often extend CaP-like axons, and some MiPs appear to be entirely transformed to a CaP morphology. Conclusions Our results suggest that Mnx proteins promote MiP subtype identity by suppressing both interneuron development and CaP axon pathfinding. This is, to our knowledge, the first report of transcription factors that act to distinguish CaP and MiP subtype identities. Our results also suggest that MiP motoneurons are more similar to V2 interneurons than are CaP motoneurons.

  18. Voltage-dependent amplification of synaptic inputs in respiratory motoneurones

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    Enríquez Denton, M; Wienecke, J; Zhang, M; Hultborn, H; Kirkwood, P A

    2012-01-01

    The role of persistent inward currents (PICs) in cat respiratory motoneurones (phrenic inspiratory and thoracic expiratory) was investigated by studying the voltage-dependent amplification of central respiratory drive potentials (CRDPs), recorded intracellularly, with action potentials blocked with the local anaesthetic derivative, QX-314. Decerebrate unanaesthetized or barbiturate-anaesthetized preparations were used. In expiratory motoneurones, plateau potentials were observed in the decerebrates, but not under anaesthesia. For phrenic motoneurones, no plateau potentials were observed in either state (except in one motoneurone after the abolition of the respiratory drive by means of a medullary lesion), but all motoneurones showed voltage-dependent amplification of the CRDPs, over a wide range of membrane potentials, too wide to result mainly from PIC activation. The measurements of the amplification were restricted to the phase of excitation, thus excluding the inhibitory phase. Amplification was found to be greatest for the smallest CRDPs in the lowest resistance motoneurones and was reduced or abolished following intracellular injection of the NMDA channel blocker, MK-801. Plateau potentials were readily evoked in non-phrenic cervical motoneurones in the same (decerebrate) preparations. We conclude that the voltage-dependent amplification of synaptic excitation in phrenic motoneurones is mainly the result of NMDA channel modulation rather than the activation of Ca2+ channel mediated PICs, despite phrenic motoneurones being strongly immunohistochemically labelled for CaV1.3 channels. The differential PIC activation in different motoneurones, all of which are CaV1.3 positive, leads us to postulate that the descending modulation of PICs is more selective than has hitherto been believed. PMID:22495582

  19. Voltage-dependent amplification of synaptic inputs in respiratory motoneurones

    DEFF Research Database (Denmark)

    Enríquez Denton, M; Wienecke, Jacob; Zhang, Mengliang

    2012-01-01

    time, the likely amplifying processes at work in respiratory motoneurones. In phrenic motoneurones, which control the most important respiratory muscle, the diaphragm, we found that the mechanism most favoured by investigations in other motoneurones, the activation of persistent inward currents via...

  20. Characterization of axon formation in the embryonic stem cell-derived motoneuron.

    Science.gov (United States)

    Pan, Hung-Chuan; Wu, Ya-Ting; Shen, Shih-Cheng; Wang, Chi-Chung; Tsai, Ming-Shiun; Cheng, Fu-Chou; Lin, Shinn-Zong; Chen, Ching-Wen; Liu, Ching-San; Su, Hong-Lin

    2011-01-01

    The developing neural cell must form a highly organized architecture to properly receive and transmit nerve signals. Neural formation from embryonic stem (ES) cells provides a novel system for studying axonogenesis, which are orchestrated by polarity-regulating molecules. Here the ES-derived motoneurons, identified by HB9 promoter-driven green fluorescent protein (GFP) expression, showed characteristics of motoneuron-specific gene expression. In the majority of motoneurons, one of the bilateral neurites developed into an axon that featured with axonal markers, including Tau1, vesicle acetylcholine transporter, and synaptophysin. Interestingly, one third of the motoneurons developed bi-axonal processes but no multiple axonal GFP cell was found. The neuronal polarity-regulating proteins, including the phosphorylated AKT and ERK, were compartmentalized into both of the bilateral axonal tips. Importantly, this aberrant axon morphology was still present after the engraftment of GFP(+) neurons into the spinal cord, suggesting that even a mature neural environment fails to provide a proper niche to guide normal axon formation. These findings underscore the necessity for evaluating the morphogenesis and functionality of neurons before the clinical trials using ES or somatic stem cells.

  1. Mechanochemical synthesis of 1-stanna-2,3-dicarba-closo-dodecaborane SnB9C2H11

    International Nuclear Information System (INIS)

    Volkov, V.V.; Myakishev, K.G.; Solomatina, L.Ya.

    1990-01-01

    The possibility of synthesis of 1-stanna-2, 3-dicarba-dodecaborane (2), SnB 9 C 2 H 11 by the mechanical activation of solid mixtures of CsB 9 C 2 H 12 , NaH and SnCl 2 has been studied. These solid phase mechano-chemical reactions were performed in vacuum vibration mills without any liquid solvents at room temperature. Crystalline SnB 9 C 2 H 11 was produced by sublimation in vacuum at 140 deg C. Yioeld of the sublimate was 3-6%

  2. Feedback Signal from Motoneurons Influences a Rhythmic Pattern Generator.

    Science.gov (United States)

    Rotstein, Horacio G; Schneider, Elisa; Szczupak, Lidia

    2017-09-20

    Motoneurons are not mere output units of neuronal circuits that control motor behavior but participate in pattern generation. Research on the circuit that controls the crawling motor behavior in leeches indicated that motoneurons participate as modulators of this rhythmic motor pattern. Crawling results from successive bouts of elongation and contraction of the whole leech body. In the isolated segmental ganglia, dopamine can induce a rhythmic antiphasic activity of the motoneurons that control contraction (DE-3 motoneurons) and elongation (CV motoneurons). The study was performed in isolated ganglia where manipulation of the activity of specific motoneurons was performed in the course of fictive crawling ( crawling ). In this study, the membrane potential of CV was manipulated while crawling was monitored through the rhythmic activity of DE-3. Matching behavioral observations that show that elongation dominates the rhythmic pattern, the electrophysiological activity of CV motoneurons dominates the cycle. Brief excitation of CV motoneurons during crawling episodes resets the rhythmic activity of DE-3, indicating that CV feeds back to the rhythmic pattern generator. CV hyperpolarization accelerated the rhythm to an extent that depended on the magnitude of the cycle period, suggesting that CV exerted a positive feedback on the unit(s) of the pattern generator that controls the elongation phase. A simple computational model was implemented to test the consequences of such feedback. The simulations indicate that the duty cycle of CV depended on the strength of the positive feedback between CV and the pattern generator circuit. SIGNIFICANCE STATEMENT Rhythmic movements of animals are controlled by neuronal networks that have been conceived as hierarchical structures. At the basis of this hierarchy, we find the motoneurons, few neurons at the top control global aspects of the behavior (e.g., onset, duration); and within these two ends, specific neuronal circuits control

  3. Role of motoneuron-derived neurotrophin 3 in survival and axonal projection of sensory neurons during neural circuit formation.

    Science.gov (United States)

    Usui, Noriyoshi; Watanabe, Keisuke; Ono, Katsuhiko; Tomita, Koichi; Tamamaki, Nobuaki; Ikenaka, Kazuhiro; Takebayashi, Hirohide

    2012-03-01

    Sensory neurons possess the central and peripheral branches and they form unique spinal neural circuits with motoneurons during development. Peripheral branches of sensory axons fasciculate with the motor axons that extend toward the peripheral muscles from the central nervous system (CNS), whereas the central branches of proprioceptive sensory neurons directly innervate motoneurons. Although anatomically well documented, the molecular mechanism underlying sensory-motor interaction during neural circuit formation is not fully understood. To investigate the role of motoneuron on sensory neuron development, we analyzed sensory neuron phenotypes in the dorsal root ganglia (DRG) of Olig2 knockout (KO) mouse embryos, which lack motoneurons. We found an increased number of apoptotic cells in the DRG of Olig2 KO embryos at embryonic day (E) 10.5. Furthermore, abnormal axonal projections of sensory neurons were observed in both the peripheral branches at E10.5 and central branches at E15.5. To understand the motoneuron-derived factor that regulates sensory neuron development, we focused on neurotrophin 3 (Ntf3; NT-3), because Ntf3 and its receptors (Trk) are strongly expressed in motoneurons and sensory neurons, respectively. The significance of motoneuron-derived Ntf3 was analyzed using Ntf3 conditional knockout (cKO) embryos, in which we observed increased apoptosis and abnormal projection of the central branch innervating motoneuron, the phenotypes being apparently comparable with that of Olig2 KO embryos. Taken together, we show that the motoneuron is a functional source of Ntf3 and motoneuron-derived Ntf3 is an essential pre-target neurotrophin for survival and axonal projection of sensory neurons.

  4. The effects of model composition design choices on high-fidelity simulations of motoneuron recruitment and firing behaviors

    Science.gov (United States)

    Allen, John M.; Elbasiouny, Sherif M.

    2018-06-01

    Objective. Computational models often require tradeoffs, such as balancing detail with efficiency; yet optimal balance should incorporate sound design features that do not bias the results of the specific scientific question under investigation. The present study examines how model design choices impact simulation results. Approach. We developed a rigorously-validated high-fidelity computational model of the spinal motoneuron pool to study three long-standing model design practices which have yet to be examined for their impact on motoneuron recruitment, firing rate, and force simulations. The practices examined were the use of: (1) generic cell models to simulate different motoneuron types, (2) discrete property ranges for different motoneuron types, and (3) biological homogeneity of cell properties within motoneuron types. Main results. Our results show that each of these practices accentuates conditions of motoneuron recruitment based on the size principle, and minimizes conditions of mixed and reversed recruitment orders, which have been observed in animal and human recordings. Specifically, strict motoneuron orderly size recruitment occurs, but in a compressed range, after which mixed and reverse motoneuron recruitment occurs due to the overlap in electrical properties of different motoneuron types. Additionally, these practices underestimate the motoneuron firing rates and force data simulated by existing models. Significance. Our results indicate that current modeling practices increase conditions of motoneuron recruitment based on the size principle, and decrease conditions of mixed and reversed recruitment order, which, in turn, impacts the predictions made by existing models on motoneuron recruitment, firing rate, and force. Additionally, mixed and reverse motoneuron recruitment generated higher muscle force than orderly size motoneuron recruitment in these simulations and represents one potential scheme to increase muscle efficiency. The examined model

  5. Gain control mechanisms in spinal motoneurons

    Directory of Open Access Journals (Sweden)

    Michael David Johnson

    2014-07-01

    Full Text Available Motoneurons provide the only conduit for motor commands to reach muscles. For many years, motoneurons were in fact considered to be little more than passive wires. Systematic studies in the past 25 years however have clearly demonstrated that the intrinsic electrical properties of motoneurons are under strong neuromodulatory control via multiple sources. The discovery of potent neuromodulation from the brainstem and its ability to change the gain of motoneurons shows that the passive view of the motor output stage is no longer tenable. A mechanism for gain control at the motor output stage makes good functional sense considering our capability of generating an enormous range of forces, from very delicate (e.g. putting in a contact lens to highly forceful (emergency reactions. Just as sensory systems need gain control to deal with a wide dynamic range of inputs, so to might motor output need gain control to deal with the wide dynamic range of the normal movement repertoire. Two problems emerge from the potential use of the brainstem monoaminergic projection to motoneurons for gain control. First, the projection is highly diffuse anatomically, so that independent control of the gains of different motor pools is not feasible. In fact, the system is so diffuse that gain for all the motor pools in a limb likely increases in concert. Second, if there is a system that increases gain, probably a system to reduce gain is also needed. In this review, we summarize recent studies that show local inhibitory circuits within the spinal cord, especially reciprocal and recurrent inhibition, have the potential to solve both of these problems as well as constitute another source of gain modulation.

  6. The effects of aging on hypoglossal motoneurons in rats.

    Science.gov (United States)

    Schwarz, Emilie C; Thompson, Jodi M; Connor, Nadine P; Behan, Mary

    2009-03-01

    Aging can result in a loss of neuronal cell bodies and a decrease in neuronal size in some regions of the brain and spinal cord. Motoneuron loss in the spinal cord is thought to contribute to the progressive decline in muscle mass and strength that occurs with age (sarcopenia). Swallowing disorders represent a large clinical problem in elderly persons; however, age-related alterations in cranial motoneurons that innervate muscles involved in swallowing have been understudied. We aimed to determine if age-related alterations occurred in the hypoglossal nucleus in the brainstem. If present, these changes might help explain alterations at the neuromuscular junction and changes in the contractile properties of tongue muscle that have been reported in older rats. We hypothesized that with increasing age there would be a loss of motoneurons and a reduction in neuronal size and the number of primary dendrites associated with each hypoglossal motoneuron. Neurons in the hypoglossal nucleus were visualized with the neuronal marker NeuN in young (9-10 months), middle-aged (24-25 months), and old (32-33 months) male F344/BN rats. Hypoglossal motoneurons were retrograde-labeled with injections of Cholera Toxin beta into the genioglossus muscle of the tongue and visualized using immunocytochemistry. Results indicated that the number of primary dendrites of hypoglossal motoneurons decreased significantly with age, while no age-associated changes were found in the number or size of hypoglossal motoneurons. Loss of primary dendrites could reduce the number of synaptic inputs and thereby impair function.

  7. Preparation of highly infective Leishmania promastigotes by cultivation on SNB-9 biphasic medium

    Czech Academy of Sciences Publication Activity Database

    Grekov, Igor; Svobodová, M.; Nohýnková, E.; Lipoldová, Marie

    2011-01-01

    Roč. 87, č. 3 (2011), s. 273-277 ISSN 0167-7012 R&D Projects: GA MŠk(CZ) LC06009; GA ČR GA310/08/1697 Institutional research plan: CEZ:AV0Z50520514 Keywords : Leishmania * SNB-9 * biphasic culture medium * parasite infectivity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.086, year: 2011

  8. Electrical stimulation of transplanted motoneurons improves motor unit formation

    Science.gov (United States)

    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

  9. Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Gabriel Olmos

    2013-05-01

    Full Text Available Spinal muscular atrophy (SMA is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN protein that affects alpha motoneurons in the spinal cord. Notch signaling is a cell-cell communication system well known as a master regulator of neural development, but also with important roles in the adult central nervous system. Aberrant Notch function is associated with several developmental neurological disorders; however, the potential implication of the Notch pathway in SMA pathogenesis has not been studied yet. We report here that SMN deficiency, induced in the astroglioma cell line U87MG after lentiviral transduction with a shSMN construct, was associated with an increase in the expression of the main components of Notch signaling pathway, namely its ligands, Jagged1 and Delta1, the Notch receptor and its active intracellular form (NICD. In the SMNΔ7 mouse model of SMA we also found increased astrocyte processes positive for Jagged1 and Delta1 in intimate contact with lumbar spinal cord motoneurons. In these motoneurons an increased Notch signaling was found, as denoted by increased NICD levels and reduced expression of the proneural gene neurogenin 3, whose transcription is negatively regulated by Notch. Together, these findings may be relevant to understand some pathologic attributes of SMA motoneurons.

  10. Ca++ dependent bistability induced by serotonin in spinal motoneurons

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Kiehn, O.

    1985-01-01

    The plateau potential, responsible for the bistable state of spinal motoneurons, recently described in the decerebrate cat, was suggested to depend on serotonin (Hounsgaard et al. 1984). In an in vitro preparation of the spinal cord of the turtle we now show that serotonin, applied directly...... to the bath, transforms the intrinsic response properties of motoneurons, uncovering a plateau potential and voltage sensitive bistability. The changes induced by serotonin were blocked by Mn++, while the plateau potential and the bistability remained after application of tetrodotoxin. We conclude...... that serotonin controls the expression of a Ca++ dependent plateau potential in motoneurons....

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

    Directory of Open Access Journals (Sweden)

    Juliane Bremer

    2016-11-01

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Menelaou, Evdokia; Paul, Latoya T. [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Perera, Surangi N. [Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States); Svoboda, Kurt R., E-mail: svobodak@uwm.edu [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States)

    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.

  14. Human motoneurone excitability is depressed by activation of serotonin 1A receptors with buspirone

    DEFF Research Database (Denmark)

    D'Amico, Jessica M; Butler, Annie A; Héroux, Martin E

    2017-01-01

    that activation of 5-HT1Areceptors depresses human motoneurone excitability. Such a depression could contribute to decreased motoneurone output during fatiguing exercise if there is high serotonergic drive to the motoneurones. ABSTRACT: Intense serotonergic drive in the turtle spinal cord results in serotonin...... motoneurone output. Such a mechanism could potentially contribute to fatigue with exercise....

  15. Where Would the EUR/CHF Exchange Rate be Without the SNB's Minimum Exchange Rate Policy?

    DEFF Research Database (Denmark)

    Hanke, Michael; Poulsen, Rolf; Weissensteiner, Alex

    2015-01-01

    Since its announcement made on September 6, 2011, the Swiss National Bank (SNB) has been pursuing the goal of a minimum EUR/CHF exchange rate of 1.20, promising to intervene on currency markets to prevent the exchange rate from falling below this level.We use a compound option pricing approach...

  16. Comparative Analysis of NOAA REFM and SNB3GEO Tools for the Forecast of the Fluxes of High-Energy Electrons at GEO

    Science.gov (United States)

    Balikhin, M. A.; Rodriguez, J. V.; Boynton, R. J.; Walker, S. N.; Aryan, Homayon; Sibeck, D. G.; Billings, S. A.

    2016-01-01

    Reliable forecasts of relativistic electrons at geostationary orbit (GEO) are important for the mitigation of their hazardous effects on spacecraft at GEO. For a number of years the Space Weather Prediction Center at NOAA has provided advanced online forecasts of the fluence of electrons with energy >2 MeV at GEO using the Relativistic Electron Forecast Model (REFM). The REFM forecasts are based on real-time solar wind speed observations at L1. The high reliability of this forecasting tool serves as a benchmark for the assessment of other forecasting tools. Since 2012 the Sheffield SNB3GEO model has been operating online, providing a 24 h ahead forecast of the same fluxes. In addition to solar wind speed, the SNB3GEO forecasts use solar wind density and interplanetary magnetic field B(sub z) observations at L1. The period of joint operation of both of these forecasts has been used to compare their accuracy. Daily averaged measurements of electron fluxes by GOES 13 have been used to estimate the prediction efficiency of both forecasting tools. To assess the reliability of both models to forecast infrequent events of very high fluxes, the Heidke skill score was employed. The results obtained indicate that SNB3GEO provides a more accurate 1 day ahead forecast when compared to REFM. It is shown that the correction methodology utilized by REFM potentially can improve the SNB3GEO forecast.

  17. Comparative analysis of NOAA REFM and SNB3GEO tools for the forecast of the fluxes of high-energy electrons at GEO

    Science.gov (United States)

    Balikhin, M. A.; Rodriguez, J. V.; Boynton, R. J.; Walker, S. N.; Aryan, H.; Sibeck, D. G.; Billings, S. A.

    2016-01-01

    Reliable forecasts of relativistic electrons at geostationary orbit (GEO) are important for the mitigation of their hazardous effects on spacecraft at GEO. For a number of years the Space Weather Prediction Center at NOAA has provided advanced online forecasts of the fluence of electrons with energy >2 MeV at GEO using the Relativistic Electron Forecast Model (REFM). The REFM forecasts are based on real-time solar wind speed observations at L1. The high reliability of this forecasting tool serves as a benchmark for the assessment of other forecasting tools. Since 2012 the Sheffield SNB3GEO model has been operating online, providing a 24 h ahead forecast of the same fluxes. In addition to solar wind speed, the SNB3GEO forecasts use solar wind density and interplanetary magnetic field Bz observations at L1.The period of joint operation of both of these forecasts has been used to compare their accuracy. Daily averaged measurements of electron fluxes by GOES 13 have been used to estimate the prediction efficiency of both forecasting tools. To assess the reliability of both models to forecast infrequent events of very high fluxes, the Heidke skill score was employed. The results obtained indicate that SNB3GEO provides a more accurate 1 day ahead forecast when compared to REFM. It is shown that the correction methodology utilized by REFM potentially can improve the SNB3GEO forecast.

  18. Phrenic motoneuron expression of serotonergic and glutamatergic receptors following upper cervical spinal cord injury

    Science.gov (United States)

    Mantilla, Carlos B.; Bailey, Jeffrey P.; Zhan, Wen-Zhi; Sieck, Gary C.

    2012-01-01

    Following cervical spinal cord injury at C2 (SH hemisection model) there is progressive recovery of phrenic activity. Neuroplasticity in the postsynaptic expression of neurotransmitter receptors may contribute to functional recovery. Phrenic motoneurons express multiple serotonergic (5-HTR) and glutamatergic (GluR) receptors, but the timing and possible role of these different neurotransmitter receptor subtypes in the neuroplasticity following SH are not clear. The current study was designed to test the hypothesis that there is an increased expression of serotonergic and glutamatergic neurotransmitter receptors within phrenic motoneurons after SH. In adult male rats, phrenic motoneurons were labeled retrogradely by intrapleural injection of Alexa 488-conjugated cholera toxin B. In thin (10 μm) frozen sections of the spinal cord, fluorescently-labeled phrenic motoneurons were visualized for laser capture microdissection (LCM). Using quantitative real-time RT-PCR in LCM samples, the time course of changes in 5-HTR and GluR mRNA expression was determined in phrenic motoneurons up to 21 days post-SH. Expression of 5-HTR subtypes 1b, 2a and 2c and GluR subtypes AMPA, NMDA, mGluR1 and mGluR5 was evident in phrenic motoneurons from control and SH rats. Phrenic motoneuron expression of 5-HTR2a increased ~8-fold (relative to control) at 14 days post-SH, whereas NMDA expression increased ~16-fold by 21-days post-SH. There were no other significant changes in receptor expression at any time post-SH. This is the first study to systematically document changes in motoneuron expression of multiple neurotransmitter receptors involved in regulation of motoneuron excitability. By providing information on the neuroplasticity of receptors expressed in a motoneuron pool that is inactivated by a higher-level spinal cord injury, appropriate pharmacological targets can be identified to alter motoneuron excitability. PMID:22227062

  19. Modeling motoneuron firing properties: dependency on size and calcium dynamics

    NARCIS (Netherlands)

    van der Heyden, M. J.; Hilgevoord, A. A.; Bour, L. J.; Ongerboer de Visser, B. W.

    1994-01-01

    The origin of functional differences between motoneurons of varying size was investigated by employing a one-compartmental motoneuron model containing a slow K+ conductance dependent on the intracellular calcium concentration. The size of the cell was included as an explicit parameter. Simulations

  20. Irregular Firing and High-Conductance States in Spinal Motoneurons during Scratching and Swimming

    DEFF Research Database (Denmark)

    Guzulaitis, Robertas; Hounsgaard, Jorn; Alaburda, Aidas

    2016-01-01

    UNLABELLED: Intense synaptic transmission during scratch network activity increases conductance and induces irregular firing in spinal motoneurons. It is not known whether this high-conductance state is a select feature for scratching or a property that goes with spinal motor network activity...... in general. Here we compare conductance and firing patterns in spinal motoneurons during network activity for scratching and swimming in an ex vivo carapace-spinal cord preparation from adult turtles (Trachemys scripta elegans). The pattern and relative engagement of motoneurons are distinctly different...... in scratching and swimming. Nevertheless, we found increased synaptic fluctuations in membrane potential, irregular firing, and increased conductance in spinal motoneurons during scratch and swim network activity. Our finding indicates that intense synaptic activation of motoneurons is a general feature...

  1. Divisive gain modulation of motoneurons by inhibition optimizes muscular control

    DEFF Research Database (Denmark)

    Vestergaard, Mikkel; Berg, Rune W.

    2015-01-01

    unclear whether the motoneuron gain, i.e., the slope of the transformation between synaptic input and spiking output, is also modulated to reduce variability in force. To address this issue, we use turtle hindlimb scratching as a model for fine motor control, since this behavior involves precise limb...... movement to rub the location of somatic nuisance touch. We recorded intracellularly from motoneurons in a reduced preparation where the limbs were removed to increase mechanical stability and the motor nerve activity served as a surrogate for muscle force. We found that not only is the gain of motoneurons...

  2. Opiate-induced suppression of rat hypoglossal motoneuron activity and its reversal by ampakine therapy.

    Directory of Open Access Journals (Sweden)

    Amanda R Lorier

    2010-01-01

    Full Text Available Hypoglossal (XII motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity while maintaining analgesia. Ampakines accentuate alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA receptor responses. The AMPA family of glutamate receptors mediate excitatory transmission to XII motoneurons. Therefore the objectives were to determine whether the depressant actions of mu-opioid receptor activation on inspiratory activity includes a direct inhibitory action at the inspiratory premotoneuron to XII motoneuron synapse, and to identify underlying mechanism(s. We then examined whether ampakines counteract opioid-induced depression of XII motoneuron activity.A medullary slice preparation from neonatal rat that produces inspiratory-related output in vitro was used. Measurements of inspiratory burst amplitude and frequency were made from XII nerve roots. Whole-cell patch recordings from XII motoneurons were used to measure membrane currents and synaptic events. Application of the mu-opioid receptor agonist, DAMGO, to the XII nucleus depressed the output of inspiratory XII motoneurons via presynaptic inhibition of excitatory glutamatergic transmission. Ampakines (CX614 and CX717 alleviated DAMGO-induced depression of XII MN activity through postsynaptic actions on XII motoneurons.The inspiratory-depressant actions of opioid analgesics include presynaptic inhibition of XII motoneuron output. Ampakines counteract mu-opioid receptor-mediated depression of XII motoneuron inspiratory activity. These results suggest that ampakines may be beneficial in countering opiate-induced suppression of XII motoneuron activity and resultant impairment of airway patency.

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

    Directory of Open Access Journals (Sweden)

    Pietro eBalbi

    2015-02-01

    Full Text Available 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 travelling 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.

  4. Identified ankle extensor and flexor motoneurons display different firing profiles in the neonatal rat

    DEFF Research Database (Denmark)

    Cotel, Florence; Antri, Myriam; Barthe, Jean-Yves

    2009-01-01

    population of flexor motoneurons solely exhibited the type II profile, characterized by a frequency-current (F-I) relationship with a clockwise hysteresis. In contrast, in addition to this type II profile, the other three profiles of repetitive firing (type I, III and IV) were observed in extensor...... postnatal development, a significant part of the population of extensor motoneurons, but not flexors, are able to produce self-sustained discharges known to involve the activation of persistent inward currents....

  5. GABAergic inhibition of leg motoneurons is required for normal walking behavior in freely moving Drosophila.

    Science.gov (United States)

    Gowda, Swetha B M; Paranjpe, Pushkar D; Reddy, O Venkateswara; Thiagarajan, Devasena; Palliyil, Sudhir; Reichert, Heinrich; VijayRaghavan, K

    2018-02-27

    Walking is a complex rhythmic locomotor behavior generated by sequential and periodical contraction of muscles essential for coordinated control of movements of legs and leg joints. Studies of walking in vertebrates and invertebrates have revealed that premotor neural circuitry generates a basic rhythmic pattern that is sculpted by sensory feedback and ultimately controls the amplitude and phase of the motor output to leg muscles. However, the identity and functional roles of the premotor interneurons that directly control leg motoneuron activity are poorly understood. Here we take advantage of the powerful genetic methodology available in Drosophila to investigate the role of premotor inhibition in walking by genetically suppressing inhibitory input to leg motoneurons. For this, we have developed an algorithm for automated analysis of leg motion to characterize the walking parameters of wild-type flies from high-speed video recordings. Further, we use genetic reagents for targeted RNAi knockdown of inhibitory neurotransmitter receptors in leg motoneurons together with quantitative analysis of resulting changes in leg movement parameters in freely walking Drosophila Our findings indicate that targeted down-regulation of the GABA A receptor Rdl (Resistance to Dieldrin) in leg motoneurons results in a dramatic reduction of walking speed and step length without the loss of general leg coordination during locomotion. Genetically restricting the knockdown to the adult stage and subsets of motoneurons yields qualitatively identical results. Taken together, these findings identify GABAergic premotor inhibition of motoneurons as an important determinant of correctly coordinated leg movements and speed of walking in freely behaving Drosophila . Copyright © 2018 the Author(s). Published by PNAS.

  6. The 25 MW Super Near Boiling nuclear reactor (SNB25) for supplying co-generation energy to an Arctic Canadian Forces Base

    Energy Technology Data Exchange (ETDEWEB)

    Bonin, H.W.; Paquette, S.; Boucher, P.J. [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada)

    2014-12-15

    Nuclear energy represents a better alternative for the supply of heat and electricity to the Canadian Forces bases in the Arctic (CFS Alert and CFB Nanisivik). In this context, the Super Near-Boiling 25-MWth reactor (SNB25) has been designed as a small unpressurized LWR that displays inherent safety and is intended to run in automatic mode. The reactor employs TRISO fuel particles (20% enrichment) in zirconium-sheathed fuel rods, and is light water cooled and moderated with a normal output temperature is 95 {sup o} C at atmospheric pressure. Control is via 133 control rods and six adjustable radial reflector plates. The design work used the probabilistic simulation code MCNP 5 and the deterministic code WIMS-AECL Version 3.1, permitting a code-to-code comparison of the results. Inherent safety was confirmed and is mostly due to the large negative void reactivity coefficient of -5.17 mk per % void. A kinetic model that includes thermal-hydraulics calculations was developed to determine the reactor's behaviour in transient states, and the results further confirm the inherent safety. Large power excursions temperatures that could compromise structural integrity cannot be produced. If the coolant/moderator temperature exceeds the saturation temperature of 100 {sup o} C, the coolant begins to boil and the large negative void coefficient causes the reactor to become subcritical in 0.84 seconds. The SNB25 reactor's core life exceeds 12 years between refuellings. A group of 4 SNB25 reactors meets both the heating and electricity requirements of a base like CFB Nanisivik via a hot water network and through an organic Rankine cycle conversion plant. (author)

  7. The 25 MW super near boiling nuclear reactor (SNB25) for supplying co-generation energy to an Arctic Canadian Forces base

    Energy Technology Data Exchange (ETDEWEB)

    Bonin, H.W.; Paquette, S.; Boucher, P.J., E-mail: bonin-h@rmc.ca [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada)

    2014-07-01

    Nuclear energy represents a better alternative for the supply of heat and electricity to the Canadian Forces bases in the Arctic (CFS Alert and CFB Nanisivik). In this context, the Super Near-Boiling 25-MWth reactor (SNB25) has been designed as a small unpressurized LWR that displays inherent safety and is intended to run in automatic mode. The reactor employs TRISO fuel particles (20% enrichment) in zirconium-sheathed fuel rods, and is light water cooled and moderated with a normal output temperature is 95{sup o}C at atmospheric pressure. Control is via 133 control rods and six adjustable radial reflector plates. The design work used the probabilistic simulation code MCNP 5 and the deterministic code WIMS-AECL Version 3.1, permitting a code-to-code comparison of the results. Inherent safety was confirmed and is mostly due to the large negative void reactivity coefficient of -5.17 mk per % void. A kinetic model that includes thermal-hydraulics calculations was developed to determine the reactor's behaviour in transient states, and the results further confirm the inherent safety. Large power excursions temperatures that could compromise structural integrity cannot be produced. If the coolant/moderator temperature exceeds the saturation temperature of 100{sup o}C, the coolant begins to boil and the large negative void coefficient causes the reactor to become subcritical in 0.84 seconds. The SNB25 reactor’s core life exceeds 12 years between refuellings. A group of 4 SNB25 reactors meets both the heating and electricity requirements of a base like CFB Nanisivik via a hot water network and through an organic Rankine cycle conversion plant. (author)

  8. The 25 MW super near boiling nuclear reactor (SNB25) for supplying co-generation energy to an Arctic Canadian Forces base

    International Nuclear Information System (INIS)

    Bonin, H.W.; Paquette, S.; Boucher, P.J.

    2014-01-01

    Nuclear energy represents a better alternative for the supply of heat and electricity to the Canadian Forces bases in the Arctic (CFS Alert and CFB Nanisivik). In this context, the Super Near-Boiling 25-MWth reactor (SNB25) has been designed as a small unpressurized LWR that displays inherent safety and is intended to run in automatic mode. The reactor employs TRISO fuel particles (20% enrichment) in zirconium-sheathed fuel rods, and is light water cooled and moderated with a normal output temperature is 95 o C at atmospheric pressure. Control is via 133 control rods and six adjustable radial reflector plates. The design work used the probabilistic simulation code MCNP 5 and the deterministic code WIMS-AECL Version 3.1, permitting a code-to-code comparison of the results. Inherent safety was confirmed and is mostly due to the large negative void reactivity coefficient of -5.17 mk per % void. A kinetic model that includes thermal-hydraulics calculations was developed to determine the reactor's behaviour in transient states, and the results further confirm the inherent safety. Large power excursions temperatures that could compromise structural integrity cannot be produced. If the coolant/moderator temperature exceeds the saturation temperature of 100 o C, the coolant begins to boil and the large negative void coefficient causes the reactor to become subcritical in 0.84 seconds. The SNB25 reactor’s core life exceeds 12 years between refuellings. A group of 4 SNB25 reactors meets both the heating and electricity requirements of a base like CFB Nanisivik via a hot water network and through an organic Rankine cycle conversion plant. (author)

  9. Perineuronal Nets in Spinal Motoneurones: Chondroitin Sulphate Proteoglycan around Alpha Motoneurones

    Directory of Open Access Journals (Sweden)

    Sian F. Irvine

    2018-04-01

    Full Text Available Perineuronal nets (PNNs are extracellular matrix structures surrounding neuronal sub-populations throughout the central nervous system, regulating plasticity. Enzymatically removing PNNs successfully enhances plasticity and thus functional recovery, particularly in spinal cord injury models. While PNNs within various brain regions are well studied, much of the composition and associated populations in the spinal cord is yet unknown. We aim to investigate the populations of PNN neurones involved in this functional motor recovery. Immunohistochemistry for choline acetyltransferase (labelling motoneurones, PNNs using Wisteria floribunda agglutinin (WFA and chondroitin sulphate proteoglycans (CSPGs, including aggrecan, was performed to characterise the molecular heterogeneity of PNNs in rat spinal motoneurones (Mns. CSPG-positive PNNs surrounded ~70–80% of Mns. Using WFA, only ~60% of the CSPG-positive PNNs co-localised with WFA in the spinal Mns, while ~15–30% of Mns showed CSPG-positive but WFA-negative PNNs. Selective labelling revealed that aggrecan encircled ~90% of alpha Mns. The results indicate that (1 aggrecan labels spinal PNNs better than WFA, and (2 there are differences in PNN composition and their associated neuronal populations between the spinal cord and cortex. Insights into the role of PNNs and their molecular heterogeneity in the spinal motor pools could aid in designing targeted strategies to enhance functional recovery post-injury.

  10. Nonlocal electron transport: direct and Greens function solution and comparison of our model with the SNB model

    Science.gov (United States)

    Colombant, Denis; Manheimer, Wallace; Schmitt, Andrew J.

    2013-10-01

    At least two models, ours and SNB (Schurtz-Nicolai-Busquet), and two methods of solution, direct numerical solution (DS) and Greens function (GF) are being used in multi-dimensional radiation hydrodynamics codes. We present results of a laser target implosion using both methods of solution. Although our model and SNB differ in some physical content, direct comparisons have been non-existent up to now. However a paper by Marocchino et al. has recently presented the results of two nanosecond-time-scale test problems, showing that the preheat calculated by the two models are different by about three orders of magnitude. We have rerun these problems and we find much less difference between the two than they do. One can show analytically that the results should be quite similar and are about an order of magnitude less than the maximum, and two orders of magnitude more than the minimum preheating in. We have been able to trace the somewhat different results back to the different physical assumptions made in each model. Work supported by DoE-NNSA and ONR.

  11. Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy

    OpenAIRE

    Jablonka, Sibylle; Beck, Marcus; Lechner, Barbara Dorothea; Mayer, Christine; Sendtner, Michael

    2007-01-01

    Proximal spinal muscular atrophy (SMA) is a motoneuron disease for which there is currently no effective treatment. In animal models of SMA, spinal motoneurons exhibit reduced axon elongation and growth cone size. These defects correlate with reduced β-actin messenger RNA and protein levels in distal axons. We show that survival motoneuron gene (Smn)–deficient motoneurons exhibit severe defects in clustering Cav2.2 channels in axonal growth cones. These defects also correlate with a reduced f...

  12. Monosynaptic inputs from the nucleus tractus solitarii to the laryngeal motoneurons in the nucleus ambiguus of the rat.

    Science.gov (United States)

    Hayakawa, T; Takanaga, A; Maeda, S; Ito, H; Seki, M

    2000-11-01

    The cricothyroid (CT) and the posterior cricoarytenoid (PCA) muscles in the larynx are activated by the laryngeal motoneurons located within the nucleus ambiguus; these motoneurons receive the laryngeal sensory information from the nucleus tractus solitarii (NTS) during respiration and swallowing. We investigated whether the neurons in the NTS projected directly to the laryngeal motoneurons, and what is the synaptic organization of their nerve terminals on the laryngeal motoneurons using the electron microscope. When wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the NTS after cholera toxin subunit B-conjugated HRP (CT-HRP) was injected into the CT muscle or the PCA muscle, the anterogradely WGA-HRP-labeled terminals from the NTS were found to directly contact the retrogradely CT-HRP-labeled dendrites and soma of both the CT and the PCA motoneurons. The labeled NTS terminals comprised about 4% of the axosomatic terminals in a section through the CT motoneurons, and about 9% on both the small (PCA-A) and the large (PCA-B) PCA motoneurons. The number of labeled axosomatic terminals containing round vesicles and making asymmetric synaptic contacts (Gray's type I) was almost equal to that of the labeled terminals containing pleomorphic vesicles and making symmetric synaptic contacts (Gray's type II) on the CT motoneurons. The labeled axosomatic terminals were mostly Gray's type II on the PCA-A motoneurons, while the majority of them were Gray's type I on the PCA-B motoneurons. These results indicate that the laryngeal CT and PCA motoneurons receive a few direct excitatory and inhibitory inputs from the neurons in the NTS.

  13. Modulation of the intrinsic properties of motoneurons by serotonin

    DEFF Research Database (Denmark)

    Perrier, Jean-François; Rasmussen, Hanne Borger; Christensen, Rasmus Kordt

    2013-01-01

    Serotonin (5-HT) is one of the main transmitters in the nervous system. Serotonergic neurons in the raphe nuclei in the brainstem innervate most parts of the central nervous system including motoneurons in the spinal cord and brainstem. This review will focus on the modulatory role that 5-HT exerts...... a sustained depolarization and an amplification of synaptic inputs. Under pathological conditions, such as after a spinal cord injury, the promotion of persistent inward currents by serotonin and/or the overexpression of autoactive serotonergic receptors may contribute to motoneuronal excitability, muscle...

  14. Serotonin‐induced bistability of turtle motoneurones caused by a nifedipine‐sensitive calcium plateau potential

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Kiehn, O.

    1989-01-01

    1. The effect of serotonin on the firing properties of motoneurones was studied in transverse sections of the adult turtle spinal cord in vitro with intracellular recording techniques. 2. In normal medium, turtle motoneurones adapt from an initial high frequency to a low steady firing during...... of the frequency jump was shortened as the amplitude of the activation pulse was increased. From a positive holding potential the after‐depolarization exceeded spike threshold and its duration increased with an increase in steady bias current. The effect of serotonin on turtle motoneurones could be blocked....... It is concluded that serotonin induces a Ca2+‐dependent and nifedipine‐sensitive plateau potential in turtle motoneurones primarily by reducing a K+‐current responsible for the slow after‐hyperpolarization....

  15. Response properties of motoneurones in a slice preparation of the turtle spinal cord

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Kiehn, O.; Mintz, I.

    1988-01-01

    1. Motoneurones in transverse sections of the turtle spinal cord were investigated in vitro with intracellular recording techniques. 2. Turtle motoneurones had a resting membrane potential of ‐60 to ‐80 mV, spike height of 90‐110 mV and were able to maintain rhythmic firing during depolarization......‐dependent inward rectification was selectively blocked by extracellular Cs+ at concentrations below 1 mM. 6. The results show that the response properties of spinal motoneurones of the turtle are closely similar to those known from mammals in vivo. The experiments confirm and extend the identification of the ionic...

  16. Functional expression of T-type Ca2+ channels in spinal motoneurons of the adult turtle.

    Directory of Open Access Journals (Sweden)

    Martha Canto-Bustos

    Full Text Available Voltage-gated Ca2+ (CaV channels are transmembrane proteins comprising three subfamilies named CaV1, CaV2 and CaV3. The CaV3 channel subfamily groups the low-voltage activated Ca2+ channels (LVA or T-type a significant role in regulating neuronal excitability. CaV3 channel activity may lead to the generation of complex patterns of action potential firing such as the postinhibitory rebound (PIR. In the adult spinal cord, these channels have been found in dorsal horn interneurons where they control physiological events near the resting potential and participate in determining excitability. In motoneurons, CaV3 channels have been found during development, but their functional expression has not yet been reported in adult animals. Here, we show evidence for the presence of CaV3 channel-mediated PIR in motoneurons of the adult turtle spinal cord. Our results indicate that Ni2+ and NNC55-0396, two antagonists of CaV3 channel activity, inhibited PIR in the adult turtle spinal cord. Molecular biology and biochemical assays revealed the expression of the CaV3.1 channel isotype and its localization in motoneurons. Together, these results provide evidence for the expression of CaV3.1 channels in the spinal cord of adult animals and show also that these channels may contribute to determine the excitability of motoneurons.

  17. The influence of increased membrane conductance on response properties of spinal motoneurons

    DEFF Research Database (Denmark)

    Grigonis, Ramunas; Guzulaitis, Robertas; Buisas, Rokas

    2016-01-01

    During functional spinal neural network activity motoneurons receive massive synaptic excitation and inhibition, and their membrane conductance increases considerably – they are switched to a high-conductance state. High-conductance states can substantially alter response properties of motoneurons....... In the present study we investigated how an increase in membrane conductance affects spike frequency adaptation, the gain (i.e., the slope of the frequency-current relationship) and the threshold for action potential generation. We used intracellular recordings from adult turtle motoneurons in spinal cord slices....... Membrane conductance was increased pharmacologically by extracellular application of the GABAA receptor agonist muscimol. Our findings suggest that an increase in membrane conductance of about 40–50% increases the magnitude of spike frequency adaptation, but does not change the threshold for action...

  18. The respiratory drive to thoracic motoneurones in the cat and its relation to the connections from expiratory bulbospinal neurones

    Science.gov (United States)

    Saywell, S A; Anissimova, N P; Ford, T W; Meehan, C F; Kirkwood, P A

    2007-01-01

    The descending control of respiratory-related motoneurones in the thoracic spinal cord remains the subject of some debate. In this study, direct connections from expiratory bulbospinal neurones to identified motoneurones were investigated using spike-triggered averaging and the strengths of connection revealed were related to the presence and size of central respiratory drive potentials in the same motoneurones. Intracellular recordings were made from motoneurones in segments T5–T9 of the spinal cord of anaesthetized cats. Spike-triggered averaging from expiratory bulbospinal neurones in the caudal medulla revealed monosynaptic EPSPs in all groups of motoneurones, with the strongest connections to expiratory motoneurones with axons in the internal intercostal nerve. In the latter, connection strength was similar irrespective of the target muscle (e.g. external abdominal oblique or internal intercostal) and the EPSP amplitude was positively correlated with the amplitude of the central respiratory drive potential of the motoneurone. For this group, EPSPs were found in 45/83 bulbospinal neurone/motoneurone pairs, with a mean amplitude of 40.5 μV. The overall strength of the connection supports previous measurements made by cross-correlation, but is about 10 times stronger than that reported in the only previous similar survey to use spike-triggered averaging. Calculations are presented to suggest that this input alone is sufficient to account for all the expiratory depolarization seen in the recorded motoneurones. However, extra sources of input, or amplification of this one, are likely to be necessary to produce a useful motoneurone output. PMID:17204500

  19. Serotonin differentially modulates the intrinsic properties of spinal motoneurons from the adult turtle

    DEFF Research Database (Denmark)

    Perrier, Jean-Francois Marie; Cotel, Florence

    2007-01-01

    turtle. In agreement with previous studies, we had found that 5-HT applied to the extracellular medium promoted a voltage sensitive plateau potential. However, we also reported that this effect was only observed in half of the motoneurons; 5-HT inhibited the firing of the other half of the motoneurons...

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. The respiratory drive to thoracic motoneurones in the cat and its relation to the connections from expiratory bulbospinal neurones

    DEFF Research Database (Denmark)

    Saywell, S A; Anissimova, N P; Ford, T W

    2007-01-01

    of connection revealed were related to the presence and size of central respiratory drive potentials in the same motoneurones. Intracellular recordings were made from motoneurones in segments T5-T9 of the spinal cord of anaesthetized cats. Spike-triggered averaging from expiratory bulbospinal neurones...... in the caudal medulla revealed monosynaptic EPSPs in all groups of motoneurones, with the strongest connections to expiratory motoneurones with axons in the internal intercostal nerve. In the latter, connection strength was similar irrespective of the target muscle (e.g. external abdominal oblique or internal...... intercostal) and the EPSP amplitude was positively correlated with the amplitude of the central respiratory drive potential of the motoneurone. For this group, EPSPs were found in 45/83 bulbospinal neurone/motoneurone pairs, with a mean amplitude of 40.5 microV. The overall strength of the connection supports...

  2. Reciprocal Ia inhibition contributes to motoneuronal hyperpolarisation during the inactive phase of locomotion and scratching in the cat

    DEFF Research Database (Denmark)

    Geertsen, Svend Sparre; Stecina, Katinka; Meehan, Claire Francesca

    2011-01-01

    Despite decades of research, the classical idea that "reciprocal inhibition" is involved in the hyperpolarisation of motoneurones in their inactive phase during rhythmic activity is still under debate. Here, we investigated the contribution of reciprocal Ia inhibition to the hyperpolarisation...... of motoneurones during fictive locomotion (evoked either by electrical stimulation of the brainstem or by L-DOPA administration following a spinal transection at the cervical level) and fictive scratching (evoked by stimulation of the pinna) in decerebrate cats. Simultaneous extracellular recordings of Ia...... inhibitory interneurones and intracellular recordings of lumbar motoneurones revealed the interneurones to be most active when their target motoneurones were hyperpolarised (i.e. in the inactive phase of the target motoneurones). To date, these results are the most direct evidence that Ia inhibitory...

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

    Science.gov (United States)

    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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Plateau potentials in alpha‐motoneurones induced by intravenous injection of L‐dopa and clonidine in the spinal cat

    DEFF Research Database (Denmark)

    Conway, B. A.; Hultborn, H.; Kiehn, O.

    1988-01-01

    1. Intracellular recordings were made from lumbar alpha‐motoneurones in unanaesthetized decerebrate acute spinal cats. The response of motoneurones to direct current pulse injection or synaptic excitation was investigated following intravenous injection of L‐beta‐3,4‐dihydroxyphenylalanine (L....... It is demonstrated that plateau potentials in the motoneurones contribute to the late long‐lasting reflexes observed in L‐DOPA‐treated spinal cats. 7. It is concluded that L‐DOPA (and clonidine) change the response properties of the motoneurones in an analogous way to 5‐hydroxy‐DL‐tryptophan (5‐HTP...

  5. Motoneuron survival is promoted by specific exercise in a mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Deforges, Séverine; Branchu, Julien; Biondi, Olivier; Grondard, Clément; Pariset, Claude; Lécolle, Sylvie; Lopes, Philippe; Vidal, Pierre-Paul; Chanoine, Christophe; Charbonnier, Frédéric

    2009-07-15

    Several studies using transgenic mouse models of familial amyotrophic lateral sclerosis (ALS) have reported a life span increase in exercised animals, as long as animals are submitted to a moderate-intensity training protocol. However, the neuroprotective potential of exercise is still questionable. To gain further insight into the cellular basis of the exercise-induced effects in neuroprotection, we compared the efficiency of a swimming-based training, a high-frequency and -amplitude exercise that preferentially recruits the fast motor units, and of a moderate running-based training, that preferentially triggers the slow motor units, in an ALS mouse model. Surprisingly, we found that the swimming-induced benefits sustained the motor function and increased the ALS mouse life span by about 25 days. The magnitude of this beneficial effect is one of the highest among those induced by any therapeutic strategy in this disease. We have shown that, unlike running, swimming significantly delays spinal motoneuron death and, more specifically, the motoneurons of large soma area. Analysis of the muscular phenotype revealed a swimming-induced relative maintenance of the fast phenotype in fast-twitch muscles. Furthermore, the swimming programme preserved astrocyte and oligodendrocyte populations in ALS spinal cord. As a whole, these data are highly suggestive of a causal relationship not only linking motoneuron activation and protection, but also motoneuron protection and the maintenance of the motoneuron surrounding environment. Basically, exercise-induced neuroprotective mechanisms provide an example of the molecular adaptation of activated motoneurons.

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

    Science.gov (United States)

    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.

  7. Bistability of alpha‐motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5‐hydroxytryptophan

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Hultborn, H.; Jespersen, B.

    1988-01-01

    1. In the preceding paper (Crone, Hultborn, Kiehn, Mazieres & Wigström, 1988) it was shown that a short‐lasting synaptic excitation (‘on’ stimulus) of extensor motoneurones (primarily triceps surae) in the decerebrate cat often resulted in a maintained excitability increase, which could be reset...... be triggered by short‐lasting excitation and inhibition of the motoneurones is referred to as ‘bistable’ behaviour of the motoneurones. 4. After an acute spinal transection, in the unanaesthetized cat, the bistable behaviour of the motoneurones disappeared. However, it reappears following intravenous injection...

  8. Loss of Ranbp2 in motoneurons causes disruption of nucleocytoplasmic and chemokine signaling, proteostasis of hnRNPH3 and Mmp28, and development of amyotrophic lateral sclerosis-like syndromes

    Directory of Open Access Journals (Sweden)

    Kyoung-in Cho

    2017-05-01

    Full Text Available The pathogenic drivers of sporadic and familial motor neuron disease (MND, such amyotrophic lateral sclerosis (ALS, are unknown. MND impairs the Ran GTPase cycle, which controls nucleocytoplasmic transport, ribostasis and proteostasis; however, cause-effect mechanisms of Ran GTPase modulators in motoneuron pathobiology have remained elusive. The cytosolic and peripheral nucleoporin Ranbp2 is a crucial regulator of the Ran GTPase cycle and of the proteostasis of neurological disease-prone substrates, but the roles of Ranbp2 in motoneuron biology and disease remain unknown. This study shows that conditional ablation of Ranbp2 in mouse Thy1 motoneurons causes ALS syndromes with hypoactivity followed by hindlimb paralysis, respiratory distress and, ultimately, death. These phenotypes are accompanied by: a decline in the nerve conduction velocity, free fatty acids and phophatidylcholine of the sciatic nerve; a reduction in the g-ratios of sciatic and phrenic nerves; and hypertrophy of motoneurons. Furthermore, Ranbp2 loss disrupts the nucleocytoplasmic partitioning of the import and export nuclear receptors importin β and exportin 1, respectively, Ran GTPase and histone deacetylase 4. Whole-transcriptome, proteomic and cellular analyses uncovered that the chemokine receptor Cxcr4, its antagonizing ligands Cxcl12 and Cxcl14, and effector, latent and activated Stat3 all undergo early autocrine and proteostatic deregulation, and intracellular sequestration and aggregation as a result of Ranbp2 loss in motoneurons. These effects were accompanied by paracrine and autocrine neuroglial deregulation of hnRNPH3 proteostasis in sciatic nerve and motoneurons, respectively, and post-transcriptional downregulation of metalloproteinase 28 in the sciatic nerve. Mechanistically, our results demonstrate that Ranbp2 controls nucleocytoplasmic, chemokine and metalloproteinase 28 signaling, and proteostasis of substrates that are crucial to motoneuronal homeostasis and

  9. hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons.

    Science.gov (United States)

    Briese, Michael; Saal-Bauernschubert, Lena; Ji, Changhe; Moradi, Mehri; Ghanawi, Hanaa; Uhl, Michael; Appenzeller, Silke; Backofen, Rolf; Sendtner, Michael

    2018-03-20

    Disturbed RNA processing and subcellular transport contribute to the pathomechanisms of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. RNA-binding proteins are involved in these processes, but the mechanisms by which they regulate the subcellular diversity of transcriptomes, particularly in axons, are not understood. Heterogeneous nuclear ribonucleoprotein R (hnRNP R) interacts with several proteins involved in motoneuron diseases. It is located in axons of developing motoneurons, and its depletion causes defects in axon growth. Here, we used individual nucleotide-resolution cross-linking and immunoprecipitation (iCLIP) to determine the RNA interactome of hnRNP R in motoneurons. We identified ∼3,500 RNA targets, predominantly with functions in synaptic transmission and axon guidance. Among the RNA targets identified by iCLIP, the noncoding RNA 7SK was the top interactor of hnRNP R. We detected 7SK in the nucleus and also in the cytosol of motoneurons. In axons, 7SK localized in close proximity to hnRNP R, and depletion of hnRNP R reduced axonal 7SK. Furthermore, suppression of 7SK led to defective axon growth that was accompanied by axonal transcriptome alterations similar to those caused by hnRNP R depletion. Using a series of 7SK-deletion mutants, we show that the function of 7SK in axon elongation depends on its interaction with hnRNP R but not with the PTEF-B complex involved in transcriptional regulation. These results propose a role for 7SK as an essential interactor of hnRNP R to regulate its function in axon maintenance. Copyright © 2018 the Author(s). Published by PNAS.

  10. Modulation of recurrent inhibition from knee extensors to ankle motoneurones during human walking

    DEFF Research Database (Denmark)

    Lamy, Jean-Charles; Iglesias, Caroline; Lackmy, Alexandra

    2008-01-01

    The neural control for muscle coordination during human locomotion involves spinal and supraspinal networks, but little is known about the exact mechanisms implicated. The present study focused on modulation of heteronymous recurrent inhibition from knee extensors to ankle motoneurones at different...... times in the gait cycle, when quadriceps (Quad) muscle activity overlaps that in tibialis anterior (TA) and soleus (Sol). The effects of femoral nerve stimulation on ankle motoneurones were investigated during treadmill walking and during tonic co-contraction of Quad and TA/Sol while standing. Recurrent...... inhibition of TA motoneurones depended on the level of background EMG, and was similar during walking and standing for matched background EMG levels. On the other hand, recurrent inhibition in Sol was reduced in early stance, with respect to standing, and enhanced in late stance. Reduced inhibition in Sol...

  11. ATG5 overexpression is neuroprotective and attenuates cytoskeletal and vesicle-trafficking alterations in axotomized motoneurons.

    Science.gov (United States)

    Leiva-Rodríguez, Tatiana; Romeo-Guitart, David; Marmolejo-Martínez-Artesero, Sara; Herrando-Grabulosa, Mireia; Bosch, Assumpció; Forés, Joaquim; Casas, Caty

    2018-05-24

    Injured neurons should engage endogenous mechanisms of self-protection to limit neurodegeneration. Enhancing efficacy of these mechanisms or correcting dysfunctional pathways may be a successful strategy for inducing neuroprotection. Spinal motoneurons retrogradely degenerate after proximal axotomy due to mechanical detachment (avulsion) of the nerve roots, and this limits recovery of nervous system function in patients after this type of trauma. In a previously reported proteomic analysis, we demonstrated that autophagy is a key endogenous mechanism that may allow motoneuron survival and regeneration after distal axotomy and suture of the nerve. Herein, we show that autophagy flux is dysfunctional or blocked in degenerated motoneurons after root avulsion. We also found that there were abnormalities in anterograde/retrograde motor proteins, key secretory pathway factors, and lysosome function. Further, LAMP1 protein was missorted and underglycosylated as well as the proton pump v-ATPase. In vitro modeling revealed how sequential disruptions in these systems likely lead to neurodegeneration. In vivo, we observed that cytoskeletal alterations, induced by a single injection of nocodazole, were sufficient to promote neurodegeneration of avulsed motoneurons. Besides, only pre-treatment with rapamycin, but not post-treatment, neuroprotected after nerve root avulsion. In agreement, overexpressing ATG5 in injured motoneurons led to neuroprotection and attenuation of cytoskeletal and trafficking-related abnormalities. These discoveries serve as proof of concept for autophagy-target therapy to halting the progression of neurodegenerative processes.

  12. Exploring the limits of the ``SNB'' multi-group diffusion nonlocal model

    Science.gov (United States)

    Brodrick, Jonathan; Ridgers, Christopher; Kingham, Robert

    2014-10-01

    A correct treatment of nonlocal transport in the presence of steep temperature gradients found in laser and inertial fusion plasmas has long been highly desirable over the use of an ad-hoc flux limiter. Therefore, an implementation of the ``SNB'' nonlocal model (G P Schurtz, P D Nicolaï & M Busquet, Phys. Plas. 7, 4238 (2000)) has been benchmarked against a fully-implicit kinetic code: IMPACT. A variety of scenarios, including relaxation of temperature sinusoids and Gaussians in addition to continuous laser heating have been investigated. Results highlight the effect of neglecting electron inertia (∂f1/∂ t) as well as question the feasibility of a nonlocal model that does not continuously track the evolution of the distribution function. Deviations from the Spitzer electric fields used in the model across steep gradients are also investigated. Regimes of validity for such a model are identified and discussed, and possible improvements to the model are suggested.

  13. Shared Components of Rhythm Generation for Locomotion and Scratching Exist Prior to Motoneurons

    Directory of Open Access Journals (Sweden)

    Zhao-Zhe Hao

    2017-08-01

    Full Text Available Does the spinal cord use a single network to generate locomotor and scratching rhythms or two separate networks? Previous research showed that simultaneous swim and scratch stimulation (“dual stimulation” in immobilized, spinal turtles evokes a single rhythm in hindlimb motor nerves with a frequency often greater than during swim stimulation alone or scratch stimulation alone. This suggests that the signals that trigger swimming and scratching converge and are integrated within the spinal cord. However, these results could not determine whether the integration occurs in motoneurons themselves or earlier, in spinal interneurons. Here, we recorded intracellularly from hindlimb motoneurons during dual stimulation. Motoneuron membrane potentials displayed regular oscillations at a higher frequency during dual stimulation than during swim or scratch stimulation alone. In contrast, arithmetic addition of the oscillations during swimming alone and scratching alone with various delays always generated irregular oscillations. Also, the standard deviation of the phase-normalized membrane potential during dual stimulation was similar to those during swimming or scratching alone. In contrast, the standard deviation was greater when pooling cycles of swimming alone and scratching alone for two of the three forms of scratching. This shows that dual stimulation generates a single rhythm prior to motoneurons. Thus, either swimming and scratching largely share a rhythm generator or the two rhythms are integrated into one rhythm by strong interactions among interneurons.

  14. Segregation of glutamatergic and cholinergic transmission at the mixed motoneuron Renshaw cell synapse.

    OpenAIRE

    Lamotte d Incamps, B.; Bhumbra, G. S.; Foster, J. D.; Beato, M.; Ascher, P.

    2017-01-01

    In neonatal mice motoneurons excite Renshaw cells by releasing both acetylcholine (ACh) and glutamate. These two neurotransmitters activate two types of nicotinic receptors (nAChRs) (the homomeric α7 receptors and the heteromeric α*ß* receptors) as well as the two types of glutamate receptors (GluRs) (AMPARs and NMDARs). Using paired recordings, we confirm that a single motoneuron can release both transmitters on a single post-synaptic Renshaw cell. We then show that co-transmission is prese...

  15. Absence of synergy for monosynaptic Group I inputs between abdominal and internal intercostal motoneurons

    DEFF Research Database (Denmark)

    Ford, T W; Meehan, Claire Francesca; Kirkwood, P A

    2014-01-01

    Internal intercostal and abdominal motoneurons are strongly coactivated during expiration. We investigated whether that synergy was paralleled by synergistic Group I reflex excitation. Intracellular recordings were made from motoneurons of the internal intercostal nerve of T8 in anesthetized cats...... that are synergistically activated in expiration leads us to conclude that such connections from muscle spindle afferents of the thoracic nerves have little role in controlling expiratory movements but, where present, support other motor acts....

  16. Possible functions of transmitter-controlled plateau potentials in α motoneurones

    DEFF Research Database (Denmark)

    Eken, T.; Hultborn, H.; Kiehn, O.

    1989-01-01

    are responsible for this bistable firing property in intact animals. The role of plateau potentials in locomotion is difficult to study. At present there are no clear indications of the utilization of plateau potentials in locomotion in intact animals. However, “clamped frequency” bursts which are observed...... in α motoneurones in reduced preparations is described. Thereafter we present some new data on a bistable behaviour in motor units in unrestrained intact animals during posture. Finally, the possible role of motoneuronal bistability in locomotion and in spasticity is discussed. Recently a bistable...... consequences of a bistable firing behaviour in the intact animal, the firing pattern of individual soleus motor units was studied by means of chronic EMG registration in awake unrestrained rats during quiet standing. Implanted electrodes allowed the delivery of excitatory and inhibitory stimulus trains...

  17. Dedifferentiation of intrinsic response properties of motoneurons in organotypic cultures of the spinal cord of the adult turtle

    DEFF Research Database (Denmark)

    Perrier, J.F.; Noraberg, J.; Simon, M.

    2000-01-01

    Explant cultures from the spinal cord of adult turtles were established and used to study the sensitivity of the intrinsic response properties of motoneurons to the changes in connectivity and milieu imposed by isolation in culture. Transverse sections 700 microm thick were explanted on cover slips...... the ability to fire repetitively. By the second week in culture, a fraction of motoneurons displayed fast and slow transient outward rectification and low-threshold calcium spikes, features not seen in turtle motoneurons in acute slices. On the other hand, properties mediated by L-type Ca2+ channels...

  18. Naturally occurring genetic variability in expression of Gsta4 is associated with differential survival of axotomized rat motoneurons

    DEFF Research Database (Denmark)

    Mikael, Ström; Al Nimer, Faiez; Lindblom, Rickard

    2012-01-01

    A large number of molecular pathways have been implicated in the degeneration of axotomized motoneurons. We previously have demonstrated substantial differences in the survival rate of axotomized motoneurons across different rat strains. Identification of genetic differences underlying such natur...

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

    Directory of Open Access Journals (Sweden)

    Olga Gajewska-Woźniak

    Full Text Available 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

  20. Targeted Delivery of TrkB Receptor to Phrenic Motoneurons Enhances Functional Recovery of Rhythmic Phrenic Activity after Cervical Spinal Hemisection

    Science.gov (United States)

    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 (pphrenic motoneurons is sufficient to enhance recovery of ipsilateral rhythmic phrenic activity after SH, indicating that selectively targeting gene expression in spared motoneurons below the level of spinal cord injury may promote functional recovery. PMID:23724091

  1. Calcium spikes and calcium plateaux evoked by differential polarization in dendrites of turtle motoneurones in vitro

    DEFF Research Database (Denmark)

    Hounsgaard, J; Kiehn, O

    1993-01-01

    The ability of dendrites in turtle motoneurones to support calcium spikes and calcium plateaux was investigated using differential polarization by applied electric fields. 2. Electric fields were generated by passing current through transverse slices of the turtle spinal cord between two plate......+ spikes and Ca2+ plateaux are present in dendrites of spinal motoneurones of the turtle....

  2. Comparative study on the analgesic effect of acute ipsilateral shoulder pain after open thoracotomy between preoperative ultrasound guided suprascapular nerve block (SNB) and intraoperative phrenic nerve infiltration (PNI) in cancer lung patients.

    Science.gov (United States)

    Elfokery, Bassel M; Tawfic, Sahar A; Abdelrahman, Abdelrahman M; Abbas, Dina N; Abdelghaffar, Ikramy M

    2018-03-01

    Acute ipsilateral shoulder pain (ISP) is a common complaint in patients after thoracotomy. The incidence ranges from 21% to 97%. Unfortunately, clinical studies did not put enough focus on ISP post thoracic surgery. This study was designed to compare the effectiveness of suprascapular nerve block (SNB) and phrenic nerve infiltration (PNI) for controlling ISP. One hundred and thirty-five lung cancer patients (135) scheduled for open-lung surgery were randomly allocated into three equal groups; control group: received thoracic epidural with general anesthesia, suprascapular group: (SNB) one hour before the operation with 10 ml bupivacaine plus thoracic epidural with general anesthesia and phrenic nerve group: (PNI) was performed by the operating surgeon with 10 ml bupivacaine plus thoracic epidural with general anesthesia. The visual analogue score (VAS) of ISP, rescue of ketorolac for break through shoulder pain, peak expiratory flow rate (PEFR) and arterial blood gases were measured every 6 h postoperatively for 48 h. The VAS, rescue doses of ketorolc and PEFR were significantly lower in the phrenic nerve group (P-value 0.05). PNI is more effective than SNB for ISP. Production and hosting by Elsevier B.V.

  3. On a method to detect long-latency excitations and inhibitions of single hand muscle motoneurons in man.

    Science.gov (United States)

    Awiszus, F; Feistner, H; Schäfer, S S

    1991-01-01

    The peri-stimulus-time histogram (PSTH) analysis of stimulus-related neuronal spike train data is usually regarded as a method to detect stimulus-induced excitations or inhibitions. However, for a fairly regularly discharging neuron such as the human alpha-motoneuron, long-latency modulations of a PSTH are difficult to interpret as PSTH modulations can also occur as a consequence of a modulated neuronal autocorrelation. The experiments reported here were made (i) to investigate the extent to which a PSTH of a human hand-muscle motoneuron may be contaminated by features of the autocorrelation and (ii) to develop methods that display the motoneuronal excitations and inhibitions without such contamination. Responses of 29 single motor units to electrical ulnar nerve stimulation below motor threshold were investigated in the first dorsal interosseous muscle of three healthy volunteers using an experimental protocol capable of demonstrating the presence of autocorrelative modulations in the neuronal response. It was found for all units that the PSTH as well as the cumulative sum (CUSUM) derived from these responses were severely affected by the presence of autocorrelative features. On the other hand, calculating the CUSUM in a slightly modified form yielded--for all units investigated--a neuronal output feature sensitive only to motoneuronal excitations and inhibitions induced by the afferent volley. The price that has to be paid to arrive at such a modified CUSUM (mCUSUM) was a high computational effort prohibiting the on-line availability of this output feature during the experiment. It was found, however, that an interspike interval superposition plot (IISP)--easily obtainable during the experiment--is also free of autocorrelative features.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

    Directory of Open Access Journals (Sweden)

    Martha Canto-Bustos

    2017-09-01

    Full Text Available Motoneurons, the final common path of the Central Nervous System (CNS, are under a complex control of its excitability in order to precisely translate the interneuronal pattern of activity into skeletal muscle contraction and relaxation. To fulfill this relevant function, motoneurons are provided with a vast repertoire of receptors and channels, including the extrasynaptic GABAA receptors which have been poorly investigated. Here, we confirmed that extrasynaptic α5 subunit-containing GABAA receptors localize with choline acetyltransferase (ChAT positive cells, suggesting that these receptors are expressed in turtle motoneurons as previously reported in rodents. In these cells, α5GABAA receptors are activated by ambient GABA, producing a tonic shunt that reduces motoneurons’ membrane resistance and affects their action potential firing properties. In addition, α5GABAA receptors shunted the synaptic excitatory inputs depressing the monosynaptic reflex (MSR induced by activation of primary afferents. Therefore, our results suggest that α5GABAA receptors may play a relevant physiological role in motor control.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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). (paper)

  6. Effects of the pyrethroid insecticide, deltamethrin, on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice

    DEFF Research Database (Denmark)

    Rekling, J C; Theophilidis, G

    1995-01-01

    We have studied the action of deltamethrin on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice. Deltamethrin depolarized the hypoglossal motoneurons, increased the background synaptic noise and reduced the frequency and amplitude of current elicited action...

  7. Comparison of dendritic calcium transients in juvenile wild type and SOD1G93A mouse lumbar motoneurons

    Directory of Open Access Journals (Sweden)

    Katharina Ann Quinlan

    2015-04-01

    Full Text Available Previous studies of spinal motoneurons in the SOD1 mouse model of amyotrophic lateral sclerosis have shown alterations long before disease onset, including increased dendritic branching, increased persistent Na+ and Ca2+ currents, and impaired axonal transport. In this study dendritic Ca2+ entry was investigated using 2 photon excitation fluorescence microscopy and whole-cell patch-clamp of juvenile (P4-11 motoneurons. Neurons were filled with both Ca2+ Green-1 and Texas Red dextrans, and line scans performed throughout. Steps were taken to account for different sources of variability, including 1 dye filling and laser penetration, 2 dendritic anatomy, and 3 the time elapsed from the start of recording. First, Ca2+ Green-1 fluorescence was normalized by Texas Red; next, neurons were reconstructed so anatomy could be evaluated; finally, time was recorded. Customized software detected the largest Ca2+ transients (area under the curve from each line scan and matched it with parameters above. Overall, larger dendritic diameter and shorter path distance from the soma were significant predictors of larger transients, while time was not significant up to 2 hours (data thereafter was dropped. However, Ca2+ transients showed additional variability. Controlling for previous factors, significant variation was found between Ca2+ signals from different processes of the same neuron in 3/7 neurons. This could reflect differential expression of Ca2+ channels, local neuromodulation or other variations. Finally, Ca2+ transients in SOD1G93A motoneurons were significantly smaller than in non-transgenic motoneurons. In conclusion, motoneuron processes show highly variable Ca2+ transients, but these transients are smaller overall SOD1G93A motoneurons.

  8. Organization of common synaptic drive to motoneurones during fictive locomotion in the spinal cat.

    Science.gov (United States)

    Nielsen, J B; Conway, B A; Halliday, D M; Perreault, M-C; Hultborn, H

    2005-11-15

    The basic locomotor rhythm in the cat is generated by a neuronal network in the spinal cord. The exact organization of this network and its drive to the spinal motoneurones is unknown. The purpose of the present study was to use time (cumulant density) and frequency domain (coherence) analysis to examine the organization of the last order drive to motoneurones during fictive locomotion (evoked by application of nialamide and dihydroxyphenylalanine (DOPA)) in the spinal cat. In all cats, narrow central synchronization peaks (half-width synchronization was observed between the individual intracellular recordings and the ENGs recorded from nerves of the same pool and of close synergists. Recordings from 34 pairs of motoneurones (10 pairs belonged to the same motor pool, 11 pairs to close synergists and 13 pairs to antagonistic pools) failed to reveal any short-lasting synchronization. These data demonstrate that short-term synchronization during fictive locomotion is relatively weak and is restricted to close synergists. In addition, coherence analysis failed to identify any specific rhythmic component in the locomotor drive that could be associated with this synchronization. These results resemble findings obtained during human treadmill walking and imply that the spinal interneurones participating in the generation of the locomotor rhythm are themselves weakly synchronized. The restricted synchronization within the locomotor drive to motoneuronal pools may be a feature of the locomotor generating networks that is related to the ability of these networks to produce highly adaptive patterns of muscle activity during locomotion.

  9. Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons.

    Science.gov (United States)

    Corsini, Silvia; Tortora, Maria; Nistri, Andrea

    2016-11-15

    Impaired uptake of glutamate builds up the extracellular level of this excitatory transmitter to trigger rhythmic neuronal bursting and delayed cell death in the brainstem motor nucleus hypoglossus. This process is the expression of the excitotoxicity that underlies motoneuron degeneration in diseases such as amyotrophic lateral sclerosis affecting bulbar motoneurons. In a model of motoneuron excitotoxicity produced by pharmacological block of glutamate uptake in vitro, rhythmic bursting is suppressed by activation of neuronal nicotinic receptors with their conventional agonist nicotine. Emergence of bursting is facilitated by nicotinic receptor antagonists. Following excitotoxicity, nicotinic receptor activity decreases mitochondrial energy dysfunction, endoplasmic reticulum stress and production of toxic radicals. Globally, these phenomena synergize to provide motoneuron protection. Nicotinic receptors may represent a novel target to contrast pathological overactivity of brainstem motoneurons and therefore to prevent their metabolic distress and death. Excitotoxicity is thought to be one of the early processes in the onset of amyotrophic lateral sclerosis (ALS) because high levels of glutamate have been detected in the cerebrospinal fluid of such patients due to dysfunctional uptake of this transmitter that gradually damages brainstem and spinal motoneurons. To explore potential mechanisms to arrest ALS onset, we used an established in vitro model of rat brainstem slice preparation in which excitotoxicity is induced by the glutamate uptake blocker dl-threo-β-benzyloxyaspartate (TBOA). Because certain brain neurons may be neuroprotected via activation of nicotinic acetylcholine receptors (nAChRs) by nicotine, we investigated if nicotine could arrest excitotoxic damage to highly ALS-vulnerable hypoglossal motoneurons (HMs). On 50% of patch-clamped HMs, TBOA induced intense network bursts that were inhibited by 1-10 μm nicotine, whereas nAChR antagonists

  10. Intrinsic membrane properties causing a bistable behaviour of α-motoneurones

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Hultborn, H.; Jespersen, B.

    1984-01-01

    injected depolarizing current pulse and is terminated by a short train of inhibitory synaptic potentials or a hyperpolarizing current pulse. It is concluded that maintained motor unit firing triggered by a brief train of impulses in Ia afferent reflects an intrinsic bistable behaviour of α-motoneurones....

  11. Physiological consequences of doublet discharges on motoneuronal firing and motor unit force

    Directory of Open Access Journals (Sweden)

    Włodzimierz eMrówczyński

    2015-03-01

    Full Text Available The double discharges are observed at the onset of contractions of mammalian motor units (MUs, especially during their recruitment to strong or fast movements. Doublets lead to MU force increase and improve ability of muscles to maintain high force during prolonged contractions. In this review we discuss an ability to produce doublets by fast and slow motoneurons (MNs, their influence on the course of action potential afterhyperpolarization as well as its role in modulation of the initial stage of the firing pattern of MNs. In conclusion, a generation of doublets is an important strategy of motor control, responsible for fitting the motoneuronal firing rate to the optimal for MUs at the start of their contraction, necessary for increment of muscle force.

  12. The nature of corticospinal paths driving human motoneurones during voluntary contractions

    DEFF Research Database (Denmark)

    Butler, Jane E; Larsen, Thomas S; Gandevia, Simon C

    2007-01-01

    The properties of the human motor cortex can be studied non-invasively using transcranial magnetic stimulation (TMS). Stimulation at high intensity excites corticospinal cells with fast conducting axons that make direct connections to motoneurones of human upper limb muscles, while low...

  13. A functional model and simulation of spinal motor pools and intrafascicular recordings of motoneuron activity in peripheral nerve

    Directory of Open Access Journals (Sweden)

    Mohamed N. Abdelghani

    2014-11-01

    Full Text Available 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.

  14. Transplantation of motoneurons derived from MASH1-transfected mouse ES cells reconstitutes neural networks and improves motor function in hemiplegic mice.

    Science.gov (United States)

    Ikeda, Ritsuko; Kurokawa, Manae S; Chiba, Shunmei; Yoshikawa, Hideshi; Hashimoto, Takuo; Tadokoro, Mamoru; Suzuki, Noboru

    2004-10-01

    Mouse embryonic stem (ES) cells were transfected with a MASH1 expression vector and G418-resistant cells were selected. The MASH1-transfected cells became neuron-like appearance and expressed betaIIItubulin and panNCAM. Glial fibrillary acidic protein (GFAP) and galactocerebroside (GalC)-expressing cells were rarely detected. Half of the neural cells differentiated into the Islet1+ motoneuron lineage. Thus, we obtained motoneuron lineage-enriched neuronal cells by transfection of ES cells with MASH1. A hemiplegic model of mice was developed by cryogenic injury of the motor cortex, and motoneuron lineage-enriched neuronal cells were transplanted underneath the injured motor cortex neighboring the periventricular region. The motor function of the recipients was assessed by a beam walking and rotarod tests, whereby the results gradually improved, but little improvement was observed in vehicle injected control mice. We found that the grafted cells not only remained close to the implantation site, but also exhibited substantial migration, penetrating into the damaged lesion in a directed manner up to the cortical region. Grafted neuronal cells that had migrated into the cortex were elongated axon-positive for neurofilament middle chain (NFM). Synaptophysin immunostaining showed a positive staining pattern around the graft, suggesting that the transplanted neurons interacted with the recipient neurons to form a neural network. Our study suggests that the motoneuron lineage can be induced from ES cells, and grafted cells adapt to the host environment and can reconstitute a neural network to improve motor function of a paralyzed limb.

  15. Knockdown of Laminin gamma-3 (Lamc3 impairs motoneuron guidance in the zebrafish embryo [version 1; referees: 2 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Alexander M. J. Eve

    2017-11-01

    Full Text Available Background: Previous work in the zebrafish embryo has shown that laminin γ-3 (lamc3 is enriched in endothelial cells marked by expression of fli1a, but the role of Lamc3 has been unknown. Methods: We use antisense morpholino oligonucleotides, and CRISPR/Cas9 mutagenesis of F0 embryos, to create zebrafish embryos in which lamc3 expression is compromised. Transgenic imaging, immunofluorescence, and in situ hybridisation reveal that Lamc3 loss-of-function affects the development of muscle pioneers, endothelial cells, and motoneurons. Results: Lamc3 is enriched in endothelial cells during zebrafish development, but it is also expressed by other tissues. Depletion of Lamc3 by use of antisense morpholino oligonucleotides perturbs formation of the parachordal chain and subsequently the thoracic duct, but Lamc3 is not required for sprouting of the cardinal vein. F0 embryos in which lamc3 expression is perturbed by a CRISPR/Cas9 approach also fail to form a parachordal chain, but we were unable to establish a stable lamc3 null line. Lamc3 is dispensable for muscle pioneer specification and for the expression of netrin-1a in these cells. Lamc3 knockdown causes netrin-1a up-regulation in the neural tube and there is increased Netrin-1 protein throughout the trunk of the embryo. Axonal guidance of rostral primary motoneurons is defective in Lamc3 knockdown embryos. Conclusions: We suggest that knockdown of Lamc3 perturbs migration of rostral primary motoneurons at the level of the horizontal myoseptum, indicating that laminin γ3 plays a role in motoneuron guidance.

  16. Corticospinal transmission to leg motoneurones in human subjects with deficient glycinergic inhibition

    NARCIS (Netherlands)

    Nielsen, JB; Tijssen, MAJ; Hansen, NL; Crone, C; Petersen, NT; Brown, P; Van Dijk, JG; Rothwell, JC

    2002-01-01

    Normal coordinated movement requires that the activity of antagonistic motoneurones may be depressed at appropriate times during the movement. Both glycinergic and GABAergic inhibitory mechanisms participate in this control. Patients with the major form of hyperekplexia (hereditary startle disease)

  17. Abnormal motoneuron migration, differentiation, and axon outgrowth in spinal muscular atrophy

    NARCIS (Netherlands)

    Simic, G.; Mladinov, M.; Seso Simic, D.; Jovanov Milosevic, N.; Islam, A.; Pajtak, A.; Barisic, N.; Sertic, J.; Lucassen, P.J.; Hof, P.R.; Kruslin, B.

    2008-01-01

    The role of heterotopic (migratory) motoneurons (HMN) in the pathogenesis of spinal muscular atrophy (SMA) is still controversial. We examined the occurrence and amount of HMN in spinal cord tissue from eight children with SMA (six with SMA-I and two with SMA-II). All affected subjects were carrying

  18. Wildtype motoneurons, ALS-Linked SOD1 mutation and glutamate profoundly modify astrocyte metabolism and lactate shuttling.

    Science.gov (United States)

    Madji Hounoum, Blandine; Mavel, Sylvie; Coque, Emmanuelle; Patin, Franck; Vourc'h, Patrick; Marouillat, Sylviane; Nadal-Desbarats, Lydie; Emond, Patrick; Corcia, Philippe; Andres, Christian R; Raoul, Cédric; Blasco, Hélène

    2017-04-01

    The selective degeneration of motoneuron that typifies amyotrophic lateral sclerosis (ALS) implicates non-cell-autonomous effects of astrocytes. However, mechanisms underlying astrocyte-mediated neurotoxicity remain largely unknown. According to the determinant role of astrocyte metabolism in supporting neuronal function, we propose to explore the metabolic status of astrocytes exposed to ALS-associated conditions. We found a significant metabolic dysregulation including purine, pyrimidine, lysine, and glycerophospholipid metabolism pathways in astrocytes expressing an ALS-causing mutated superoxide dismutase-1 (SOD1) when co-cultured with motoneurons. SOD1 astrocytes exposed to glutamate revealed a significant modification of the astrocyte metabolic fingerprint. More importantly, we observed that SOD1 mutation and glutamate impact the cellular shuttling of lactate between astrocytes and motoneurons with a decreased in extra- and intra-cellular lactate levels in astrocytes. Based on the emergent strategy of metabolomics, this work provides novel insight for understanding metabolic dysfunction of astrocytes in ALS conditions and opens the perspective of therapeutics targets through focusing on these metabolic pathways. GLIA 2017 GLIA 2017;65:592-605. © 2017 Wiley Periodicals, Inc.

  19. Nucleus retroambiguous projections to lumbosacral motoneuronal cell groups in the male cat

    NARCIS (Netherlands)

    Vanderhorst, VGJM; Holstege, G

    1997-01-01

    Recently, in the female cat, nucleus retroambiguus (NRA) projections have been described as distinct motoneuronal cell groups in the lumbar enlargement, possibly involved in lordosis behavior. The present study deals with the NRA-lumbosacral pathway in the male cat, Lumbosacral injections of wheat

  20. Direct projections from the nucleus retroambiguus to cricothyroid motoneurons in the cat

    NARCIS (Netherlands)

    Boers, J.; Klop, E.M.; Hulshoff, A.C.; Weerd, H. de; Holstege, G.

    2002-01-01

    Vocalization can be elicited by stimulation in the periaqueductal gray (PAG). Light-microscopical tracing and physiological studies have revealed that the PAG uses the nucleus retroambiguus (NRA) as a relay to excite the vocalization muscle motoneurons. Direct NRA projections have been demonstrated

  1. CAUDAL MEDULLARY PATHWAYS TO LUMBOSACRAL MOTONEURONAL CELL GROUPS IN THE CAT - EVIDENCE FOR DIRECT PROJECTIONS POSSIBLY REPRESENTING THE FINAL COMMON PATHWAY FOR LORDOSIS

    NARCIS (Netherlands)

    VANDERHORST, VGJM; HOLSTEGE, G

    1995-01-01

    The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase

  2. Caudal Medullary Pathways To Lumbosacral Motoneuronal Cell Groups In The Cat; Evidence For Direct Projections Possibly Representing The Final Common Pathway For Lordosis.

    NARCIS (Netherlands)

    VanderHorst, Veronique G.J.M.; Holstege, Gert

    1995-01-01

    The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase

  3. Synaptic excitation in spinal motoneurons alternates with synaptic inhibition and is balanced by outward rectification during rhythmic motor network activity

    DEFF Research Database (Denmark)

    Guzulaitis, Robertas; Hounsgaard, Jorn

    2017-01-01

    channels. Intrinsic outward rectification facilitates spiking by focusing synaptic depolarization near threshold for action potentials. By direct recording of synaptic currents, we also show that motoneurons are activated by out-of-phase peaks in excitation and inhibition during network activity, whereas......Regular firing in spinal motoneurons of red-eared turtles (Trachemys scripta elegans, either sex) evoked by steady depolarization at rest is replaced by irregular firing during functional network activity. The transition caused by increased input conductance and synaptic fluctuations in membrane...... potential was suggested to originate from intense concurrent inhibition and excitation. We show that the conductance increase in motoneurons during functional network activity is mainly caused by intrinsic outward rectification near threshold for action potentials by activation of voltage and Ca2+ gated K...

  4. A Simulation Based Analysis of Motor Unit Number Index (MUNIX) Technique Using Motoneuron Pool and Surface Electromyogram Models

    Science.gov (United States)

    Li, Xiaoyan; Rymer, William Zev; Zhou, Ping

    2013-01-01

    Motor unit number index (MUNIX) measurement has recently achieved increasing attention as a tool to evaluate the progression of motoneuron diseases. In our current study, the sensitivity of the MUNIX technique to changes in motoneuron and muscle properties was explored by a simulation approach utilizing variations on published motoneuron pool and surface electromyogram (EMG) models. Our simulation results indicate that, when keeping motoneuron pool and muscle parameters unchanged and varying the input motor unit numbers to the model, then MUNIX estimates can appropriately characterize changes in motor unit numbers. Such MUNIX estimates are not sensitive to different motor unit recruitment and rate coding strategies used in the model. Furthermore, alterations in motor unit control properties do not have a significant effect on the MUNIX estimates. Neither adjustment of the motor unit recruitment range nor reduction of the motor unit firing rates jeopardizes the MUNIX estimates. The MUNIX estimates closely correlate with the maximum M wave amplitude. However, if we reduce the amplitude of each motor unit action potential rather than simply reduce motor unit number, then MUNIX estimates substantially underestimate the motor unit numbers in the muscle. These findings suggest that the current MUNIX definition is most suitable for motoneuron diseases that demonstrate secondary evidence of muscle fiber reinnervation. In this regard, when MUNIX is applied, it is of much importance to examine a parallel measurement of motor unit size index (MUSIX), defined as the ratio of the maximum M wave amplitude to the MUNIX. However, there are potential limitations in the application of the MUNIX methods in atrophied muscle, where it is unclear whether the atrophy is accompanied by loss of motor units or loss of muscle fiber size. PMID:22514208

  5. Descending Projections From The Nucleus Retroambiguus To The Iliopsoas Motoneuronal Cell Groups In The Female Golden Hamster : Possible role in reproductive behavior

    NARCIS (Netherlands)

    Gerrits, Peter O.; Holstege, Gert

    1999-01-01

    In the cat, the nucleus retroambiguus (NRA) projects to expiratory motoneurons in the brainstem and spinal cord. Recently, it has been demonstrated that the NRA sends fibers to a specific set of motoneurons in the lumbosacral cord, which pathway is thought to play a crucial role in mating behavior.

  6. Increased activity of pre-motor network does not change the excitability of motoneurons during protracted scratch initiation

    DEFF Research Database (Denmark)

    Guzulaitis, Robertas; Alaburda, Aidas; Hounsgaard, Jørn Dybkjær

    2013-01-01

    of their intrinsic excitability. Here we employed an experimental paradigm of protracted scratch initiation in the integrated carapace-spinal cord preparation of adult turtles (Chrysemys scripta elegans). The protracted initiation of scratch network activity allows us to investigate the excitability of motoneurons...... and pre-motor network activity in the time interval from the start of sensory stimulation until the onset of scratch activity. Our results suggest that increased activity in the pre-motor network facilitates the onset of scratch episodes but does not change the excitability of motoneurons at the onset...... of scratching....

  7. Functional plasticity in the respiratory drive to thoracic motoneurons in the segment above a chronic lateral spinal cord lesion

    DEFF Research Database (Denmark)

    Ford, T W; Anissimova, Natalia P; Meehan, Claire Francesca

    2016-01-01

    A previous neurophysiological investigation demonstrated an increase in functional projections of expiratory bulbospinal neurons (EBSNs) in the segment above a chronic lateral thoracic spinal cord lesion that severed their axons. We have now investigated how this plasticity might be manifested...... in thoracic motoneurons by measuring their respiratory drive and the connections to them from individual EBSNs. In anesthetized cats, simultaneous recordings were made intracellularly from motoneurons in the segment above a left-side chronic (16 wk) lesion of the spinal cord in the rostral part of T8, T9......, or T10 and extracellularly from EBSNs in the right caudal medulla, antidromically excited from just above the lesion but not from below. Spike-triggered averaging was used to measure the connections between pairs of EBSNs and motoneurons. Connections were found to have a very similar distribution...

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

    Science.gov (United States)

    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 (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 such as eating, nonnutritive chewing, clenching, and yawning

  9. Cross-talk between IGF-1 and estrogen receptors attenuates intracellular changes in ventral spinal cord 4.1 motoneuron cells due to interferon-gamma exposure

    Science.gov (United States)

    Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A.; Krause, James S.; Banik, Naren L.

    2014-01-01

    Insulin-like growth factor-1 (IGF-1) is a neuroprotective growth factor that promotes neuronal survival by inhibition of apoptosis. In order to examine whether IGF-1 exerts cytoprotective effects against extracellular inflammatory stimulation, ventral spinal cord 4.1 (VSC4.1) motoneuron cells were treated with interferon-gamma (IFN-γ). Our data demonstrated apoptotic changes, increased calpain:calpastatin and Bax:Bcl-2 ratios, and expression of apoptosis related proteases (caspase-3 and −12) in motoneurons rendered by IFN-γ in a dose-dependent manner. Post-treatment with IGF-1 attenuated these changes. In addition, IGF-1 treatment of motoneurons exposed to IFN-γ decreased expression of inflammatory markers (cyclooxygenase-2 and nuclear factor-kappa B:inhibitor of kappa B ratio). Furthermore, IGF-1 attenuated the loss of expression of IGF-1 receptors (IGF-1Rα and IGF-1Rβ) and estrogen receptors (ERα and ERβ) induced by IFN-γ. To determine whether the protective effects of IGF-1 are associated with ERs, ERs antagonist ICI and selective siRNA targeted against ERα and ERβ were used in VSC4.1 motoneurons. Distinctive morphological changes were observed following siRNA knockdown of ERα and ERβ. In particular, apoptotic cell death assessed by TUNEL assay was enhanced in both ERα and ERβ-silenced VSC4.1 motoneurons following IFN-γ and IGF-1 exposure. These results suggest that IGF-1 protects motoneurons from inflammatory insult by a mechanism involving pivotal interactions with ERα and ERβ. PMID:24188094

  10. Fatigue diminishes motoneuronal excitability during cycling exercise.

    Science.gov (United States)

    Weavil, Joshua C; Sidhu, Simranjit K; Mangum, Tyler S; Richardson, Russell S; Amann, Markus

    2016-10-01

    Exercise-induced fatigue influences the excitability of the motor pathway during single-joint isometric contractions. This study sought to investigate the influence of fatigue on corticospinal excitability during cycling exercise. Eight men performed fatiguing constant-load (80% W peak ; 241 ± 13 W) cycling to exhaustion during which the percent increase in quadriceps electromyography (ΔEMG; vastus lateralis and rectus femoris) was quantified. During a separate trial, subjects performed two brief (∼45 s) nonfatiguing cycling bouts (244 ± 15 and 331 ± 23W) individually chosen to match the ΔEMG across bouts to that observed during fatiguing cycling. Corticospinal excitability during exercise was quantified by transcranial magnetic, electric transmastoid, and femoral nerve stimulation to elicit motor-evoked potentials (MEP), cervicomedullary evoked potentials (CMEP), and M waves in the quadriceps. Peripheral and central fatigue were expressed as pre- to postexercise reductions in quadriceps twitch force (ΔQ tw ) and voluntary quadriceps activation (ΔVA). Whereas nonfatiguing cycling caused no measureable fatigue, fatiguing cycling resulted in significant peripheral (ΔQ tw : 42 ± 6%) and central (ΔVA: 4 ± 1%) fatigue. During nonfatiguing cycling, the area of MEPs and CMEPs, normalized to M waves, similarly increased in the quadriceps (∼40%; P fatiguing cycling. As a consequence, the ratio of MEP to CMEP was unchanged during both trials (P > 0.5). Therefore, although increases in muscle activation promote corticospinal excitability via motoneuronal facilitation during nonfatiguing cycling, this effect is abolished during fatigue. We conclude that the unaltered excitability of the corticospinal pathway from start of intense cycling exercise to exhaustion is, in part, determined by inhibitory influences on spinal motoneurons obscuring the facilitating effects of muscle activation.

  11. Neural control of phrenic motoneuron discharge

    Science.gov (United States)

    Lee, Kun-Ze; Fuller, David D.

    2011-01-01

    Phrenic motoneurons (PMNs) provide a synaptic relay between bulbospinal respiratory pathways and the diaphragm muscle. PMNs also receive propriospinal inputs, although the functional role of these interneuronal projections has not been established. Here we review the literature regarding PMN discharge patterns during breathing and the potential mechanisms that underlie PMN recruitment. Anatomical and neurophysiological studies indicate that PMNs form a heterogeneous pool, with respiratory-related PMN discharge and recruitment patterns likely determined by a balance between intrinsic MN properties and extrinsic synaptic inputs. We also review the limited literature regarding PMN bursting during respiratory plasticity. Differential recruitment or rate modulation of PMN subtypes may underlie phrenic motor plasticity following neural injury and/or respiratory stimulation; however this possibility remains relatively unexplored. PMID:21376841

  12. Organization of the motoneurons innervating the pelvic muscles of the male rat

    DEFF Research Database (Denmark)

    Schrøder, H D

    1980-01-01

    The cytoarchitecture of the motoneuron pool of the male rat was studied at the lumbo-sacral transition area, particularly in L6. In the latter segment a dorso-medial (DM), ventral (V), dorso-lateral (DL), and retrodorso-lateral group (RDL) could be defined. The DL group was associated...

  13. Differentiated NSC-34 motoneuron-like cells as experimental model for cholinergic neurodegeneration.

    Science.gov (United States)

    Maier, Oliver; Böhm, Julia; Dahm, Michael; Brück, Stefan; Beyer, Cordian; Johann, Sonja

    2013-06-01

    Alpha-motoneurons appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Morphological and physiological degeneration of this neuronal phenotype is typically characterized by a marked decrease of neuronal markers and by alterations of cholinergic metabolism such as reduced choline acetyltransferase (ChAT) expression. The motoneuron-like cell line NSC-34 is a hybrid cell line produced by fusion of neuroblastoma with mouse motoneuron-enriched primary spinal cord cells. In order to further establish this cell line as a valid model system to investigate cholinergic neurodegeneration, NSC-34 cells were differentiated by serum deprivation and additional treatment with all-trans retinoic acid (atRA). Cell maturation was characterized by neurite outgrowth and increased expression of neuronal and cholinergic markers, including MAP2, GAP-43 and ChAT. Subsequently, we used differentiated NSC-34 cells to study early degenerative responses following exposure to various neurotoxins (H2O2, TNF-α, and glutamate). Susceptibility to toxin-induced cell death was determined by means of morphological changes, expression of neuronal marker proteins, and the ratio of pro-(Bax) to anti-(Bcl-2) apoptotic proteins. NSC-34 cells respond to low doses of neurotoxins with increased cell death of remaining undifferentiated cells with no obvious adverse effects on differentiated cells. Thus, the different vulnerability of differentiated and undifferentiated NSC-34 cells to neurotoxins is a key characteristic of NSC-34 cells and has to be considered in neurotoxic studies. Nonetheless, application of atRA induced differentiation of NSC-34 cells and provides a suitable model to investigate molecular events linked to neurodegeneration of differentiated neurons. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Cross-talk between IGF-1 and estrogen receptors attenuates intracellular changes in ventral spinal cord 4.1 motoneuron cells because of interferon-gamma exposure.

    Science.gov (United States)

    Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A; Krause, James S; Banik, Naren L

    2014-03-01

    Insulin-like growth factor-1 (IGF-1) is a neuroprotective growth factor that promotes neuronal survival by inhibition of apoptosis. To examine whether IGF-1 exerts cytoprotective effects against extracellular inflammatory stimulation, ventral spinal cord 4.1 (VSC4.1) motoneuron cells were treated with interferon-gamma (IFN-γ). Our data demonstrated apoptotic changes, increased calpain:calpastatin and Bax:Bcl-2 ratios, and expression of apoptosis-related proteases (caspase-3 and -12) in motoneurons rendered by IFN-γ in a dose-dependent manner. Post-treatment with IGF-1 attenuated these changes. In addition, IGF-1 treatment of motoneurons exposed to IFN-γ decreased expression of inflammatory markers (cyclooxygenase-2 and nuclear factor-kappa B:inhibitor of kappa B ratio). Furthermore, IGF-1 attenuated the loss of expression of IGF-1 receptors (IGF-1Rα and IGF-1Rβ) and estrogen receptors (ERα and ERβ) induced by IFN-γ. To determine whether the protective effects of IGF-1 are associated with ERs, ERs antagonist ICI and selective siRNA targeted against ERα and ERβ were used in VSC4.1 motoneurons. Distinctive morphological changes were observed following siRNA knockdown of ERα and ERβ. In particular, apoptotic cell death assessed by TUNEL assay was enhanced in both ERα and ERβ-silenced VSC4.1 motoneurons following IFN-γ and IGF-1 exposure. These results suggest that IGF-1 protects motoneurons from inflammatory insult by a mechanism involving pivotal interactions with ERα and ERβ. © 2013 International Society for Neurochemistry.

  15. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats. The 2nd report

    International Nuclear Information System (INIS)

    Ishihara, Akihiko; Ohira, Yoshinobu; Kawano, Fuminori; Xiao Dong Wang; Nagaoka, Shunji; Nojima, Kumie

    2004-01-01

    We examined the effects of acute exposure of heavy ion on the properties of motoneurons and their innervating muscle fibers. A 40 Gy dose of heavy ion was applied to the lumbar 4th to 6th segments of the spinal cord in five 8-week-old male rats. Five male rats served as controls. Both the control and heavy-ion-exposed rats were sacrificed one month after exposure to heavy ion. The number, cell body size, and oxidative enzyme activity of motoneurons innervating the soleus and plantaris muscles were analyzed. In addition, cell size, oxidative enzyme activity, and expression of myosin heavy chain isoforms in the soleus and plantaris muscles were analyzed. There were no changes in the number of motoneurons between the control and heavy-ion-exposed rats. On the other hand, cell body sizes were decreased and oxidative enzyme activities were disappeared in motoneurons of the heavy-ion-exposed rats. There were no changes in the cell size, oxidative enzyme activity, or expression of myosin heavy chain isoforms of the muscles between the control and heavy-ion-exposed rats. It is concluded that a 40 Gy dose of heavy ion affects the properties of spinal motoneurons, although there were no influences on the properties of muscle fibers which they innervate. (author)

  16. Distribution of serotonin 2A and 2C receptor mRNA expression in the cervical ventral horn and phrenic motoneurons following spinal cord hemisection.

    Science.gov (United States)

    Basura, G J; Zhou, S Y; Walker, P D; Goshgarian, H G

    2001-06-01

    Cervical spinal cord injury leads to a disruption of bulbospinal innervation from medullary respiratory centers to phrenic motoneurons. Animal models utilizing cervical hemisection result in inhibition of ipsilateral phrenic nerve activity, leading to paralysis of the hemidiaphragm. We have previously demonstrated a role for serotonin (5-HT) as one potential modulator of respiratory recovery following cervical hemisection, a mechanism that likely occurs via 5-HT2A and/or 5-HT2C receptors. The present study was designed to specifically examine if 5-HT2A and/or 5-HT2C receptors are colocalized with phrenic motoneurons in both intact and spinal-hemisected rats. Adult female rats (250-350 g; n = 6 per group) received a left cervical (C2) hemisection and were injected with the fluorescent retrograde neuronal tracer Fluorogold into the left hemidiaphragm. Twenty-four hours later, animals were killed and spinal cords processed for in situ hybridization and immunohistochemistry. Using (35)S-labeled cRNA probes, cervical spinal cords were probed for 5-HT2A and 5-HT2C receptor mRNA expression and double-labeled using an antibody to Fluorogold to detect phrenic motoneurons. Expression of both 5-HT2A and 5-HT2C receptor mRNA was detected in motoneurons of the cervical ventral horn. Despite positive expression of both 5-HT2A and 5-HT2C receptor mRNA-hybridization signal over phrenic motoneurons, only 5-HT2A silver grains achieved a signal-to-noise ratio representative of colocalization. 5-HT2A mRNA levels in identified phrenic motoneurons were not significantly altered following cervical hemisection compared to sham-operated controls. Selective colocalization of 5-HT2A receptor mRNA with phrenic motoneurons may have implications for recently observed 5-HT2A receptor-mediated regulation of respiratory activity and/or recovery in both intact and injury-compromised states. Copyright 2001 Academic Press.

  17. Location of bladder and urethral sphincter motoneurons in the male guinea pig (Cavia porcellus)

    NARCIS (Netherlands)

    Kuipers, R; Izhar, Z; Gerrits, PO; Miner, W; Holstege, G; Gerrits, Peter O.

    2004-01-01

    Although the guinea pig is used widely in experimental medical research, including in studies on micturition control, the spinal origin of preganglionic parasympathetic bladder and somatic external urethral sphincter motoneurons is not known. In the male, guinea pig using wheat germ

  18. Failure of activation of spinal motoneurones after muscle fatigue in healthy subjects studied by transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Andersen, Birgit; Westlund, Barbro; Krarup, Christian

    2003-01-01

    During a sustained maximal effort a progressive decline in the ability to drive motoneurones (MNs) develops. We used the recently developed triple stimulation technique (TST) to study corticospinal conduction after fatiguing exercise in healthy subjects. This method employs a collision technique....... This points to increased probability of repetitive spinal MN activation during fatigue even if some MNs in the pool failed to discharge. Silent period duration following cortical stimulation lengthened by an average of 55 ms after the contraction and recovered within a time course similar to that of the TST...

  19. Modulation of leak K(+) channel in hypoglossal motoneurons of rats by serotonin and/or variation of pH value.

    Science.gov (United States)

    Xu, Xue-Feng; Tsai, Hao-Jan; Li, Lin; Chen, Yi-Fan; Zhang, Cheng; Wang, Guang-Fa

    2009-08-25

    The cloned TWIK-related acid-sensitive K(+) channel (TASK-1) is sensitive to the pH changes within physiological pH range (pK~7.4). Recently, the native TASK-1-like channel was suggested to be the main contributor to the background (or leak) K(+) conductance in the motoneurons of the brain stem. Serotonin (5-HT) and variation of pH value in perfused solution could modulate these currents. Here we aimed to examine the properties and modulation of the currents by serotonin or variation of pH value in hypoglossal motoneurons of rats. Transverse slices were prepared from the brainstem of neonatal Sprague-Dawley rats (postnatal days 7-8). Hypoglossal motoneurons were used for the study. The leak K(+) current (TASK-1-like current) and hyperpolarization-activated cationic current (I(h)) were recorded with the whole-cell patch-clamp technique. The results showed that these currents were inhibited by acidified artificial cerebrospinal fluid (ACSF, pH 6.0) and activated by alkalized ACSF (pH 8.5). 5-HT (10 mumol/L) significantly inhibited both leak K(+) current and I(h) with depolarization of membrane potential and the occurrence of oscillation and/or spikes. Bath application of Ketanserine, an antagonist of 5-HT₂ receptor, reversed or reduced the inhibitory effect of acidified solution on leak K(+) current and I(h). The results suggest that 5-HT₂ receptors mediate the effects of acidified media on leak K(+) current and I(h) in hypoglossal motoneurons.

  20. Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF

    Science.gov (United States)

    Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

    2015-01-01

    Background: Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3–5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Results: Motoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Conclusions: Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS. PMID:25653590

  1. Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF.

    Directory of Open Access Journals (Sweden)

    Alexandre eHenriques

    2015-01-01

    Full Text Available ABSTRACTBackgroundAmyotrophic lateral sclerosis (ALS is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. ResultsMotoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age, when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age. Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12.ConclusionsOur data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.

  2. Gene expression changes in spinal motoneurons of the SOD1(G93A) transgenic model for ALS after treatment with G-CSF.

    Science.gov (United States)

    Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1(G93A) mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Motoneurons from SOD1(G93A) mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1(G93A) motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1(G93A) motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.

  3. Drosophila female-specific Ilp7 motoneurons are generated by Fruitless-dependent cell death in males and by a double-assurance survival role for Transformer in females.

    Science.gov (United States)

    Garner, Sarah Rose C; Castellanos, Monica C; Baillie, Katherine E; Lian, Tianshun; Allan, Douglas W

    2018-01-08

    Female-specific Ilp7 neuropeptide-expressing motoneurons (FS-Ilp7 motoneurons) are required in Drosophila for oviduct function in egg laying. Here, we uncover cellular and genetic mechanisms underlying their female-specific generation. We demonstrate that programmed cell death (PCD) eliminates FS-Ilp7 motoneurons in males, and that this requires male-specific splicing of the sex-determination gene fruitless ( fru ) into the Fru MC isoform. However, in females, fru alleles that only generate Fru M isoforms failed to kill FS-Ilp7 motoneurons. This blockade of Fru M -dependent PCD was not attributable to doublesex gene function but to a non-canonical role for transformer ( tra ), a gene encoding the RNA splicing activator that regulates female-specific splicing of fru and dsx transcripts. In both sexes, we show that Tra prevents PCD even when the Fru M isoform is expressed. In addition, we found that Fru MC eliminated FS-Ilp7 motoneurons in both sexes, but only when Tra was absent. Thus, Fru MC -dependent PCD eliminates female-specific neurons in males, and Tra plays a double-assurance function in females to establish and reinforce the decision to generate female-specific neurons. © 2018. Published by The Company of Biologists Ltd.

  4. Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones

    Science.gov (United States)

    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. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats

    International Nuclear Information System (INIS)

    Ishihara, Akihiko; Ohira, Yoshinobu; Kawano, Norifumi; Nagaoka, Shunji; Nojima, Kumie

    2003-01-01

    We investigate effects of localized exposure of heavy ion to the lumbar 4th to 6th segments of the rat spinal cord on the properties of motoneurons and the innervated muscle fibers without surgical treatments. Twenty 7-week-old male Wistar rats were exposed to 5 mm spread-out Bragg peak (SOBP) carbon beam (290 MeV, linear energy transfer (LET)=130 keV/μm): Two doses (15 Gy or 20 Gy) were applied to each group of rats (n=5) in two different depths; one group was exposed only for ventral horn of the spinal cord while other for whole spinal cord. Five rats served as controls. The rats were exposed to carbon irons on October 26, 2002. We will sacrifice the rats soon after they show an abnormal behavior including posture and walking. Cell body size and oxidative enzyme activity of spinal motoneurons of the control and heavy-ion-exposed rats will be analyzed. In addition, cell size, oxidative enzyme activity, and expressions of myosin heavy chain isoforms of the gastrocnemius, soleus, plantaris, extensor digitorum longus, and tibialis anterior muscle fibers will be also determined. This study is performed to test our hypothesis that atrophy and a decrease in cross-sectional area of motoneurons and muscle fibers which they innervate, as well as a decrease in oxidative activity of motoneurons and muscle fibers, will be induced due to exposure to heavy ion. (author)

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    Skydsgaard, Morten Arnika; 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...

  8. EFNS guidelines for the molecular diagnosis of neurogenetic disorders: motoneuron, peripheral nerve and muscle disorders.

    LENUS (Irish Health Repository)

    Burgunder, J-M

    2011-02-01

    These EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated.

  9. Functional motor recovery from motoneuron axotomy is compromised in mice with defective corticospinal projections.

    Directory of Open Access Journals (Sweden)

    Yuetong Ding

    Full Text Available 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.

  10. Inhibition of motoneurons during the cutaneous silent period in the spinal cord of the turtle

    DEFF Research Database (Denmark)

    Guzulaitis, Robertas; Hounsgaard, Jørn Dybkjær; Alaburda, Aidas

    2012-01-01

    motoneurons in the isolated carapace-spinal cord preparation from adult turtles during rhythmic scratch-like reflex. Electrical stimulation of cutaneous nerves induced CSP-like suppression of motor nerve firing during rhythmic network activity. The stimulus that generated the CSP-like suppression of motor...

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

    DEFF Research Database (Denmark)

    Cotel, Florence; Exley, Richard; Cragg, Stephanie

    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......-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...

  12. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats (the 3rd report)

    International Nuclear Information System (INIS)

    Ishihara, Akihiko; Ohira, Yoshinobu; Kawano, Fuminori; Wang, Xiao Dong; Nagaoka, Shunji; Nojima, Kumie

    2005-01-01

    The effects of acute exposure of heavy ion on the properties of spinal motoneurons and their innervating muscle fibers were investigated. A 15, 20, 40, 50, or 70 Gy dose of heavy ion was applied to the lumbar 4th to 6th segments of the spinal cord in 8-week-old male rats. Both the control and heavy-ion-exposed rats were sacrificed one month after exposure to heavy ion. The number, cell body size, and oxidative enzyme activity of spinal motoneurons innervating the soleus and plantaris muscles were analyzed by a computer-assisted image processing system. In addition, cell size, oxidative enzyme activity, and expression of myosin heavy chain isoforms in the soleus and plantaris muscles were analyzed. There were no differences in the number of spinal motoneurons innervating the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. On the other hand, cell body sizes were decreased and oxidative enzyme activities were disappeared in spinal motoneurons of the heavy-ion-exposed rats at the dose levels of 40, 50, and 70 Gy. There were no differences in the cell size, oxidative enzyme activity, or expression of myosin heavy chain isoforms of the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. It is concluded that more than 40 Gy dose of heavy ion affects the properties of spinal motoneurons, although there are no influences on the properties of muscle fibers which they innervate. (author)

  13. Facilitation of plateau potentials in turtle motoneurones by a pathway dependent on calcium and calmodulin

    DEFF Research Database (Denmark)

    Perrier, J F; Mejia-Gervacio, S; Hounsgaard, J

    2000-01-01

    1. The involvement of intracellular calcium and calmodulin in the modulation of plateau potentials in motoneurones was investigated using intracellular recordings from a spinal cord slice preparation. 2. Chelation of intracellular calcium with BAPTA-AM or inactivation of calmodulin with W-7 or tr...

  14. Dihydrotestosterone ameliorates degeneration in muscle, axons and motoneurons and improves motor function in amyotrophic lateral sclerosis model mice.

    Directory of Open Access Journals (Sweden)

    Young-Eun Yoo

    Full Text Available Amyotrophic lateral sclerosis (ALS is a lethal disease characterized by a progressive loss of motoneurons. The clinical symptoms include skeletal muscle weakness and atrophy, which impairs motor performance and eventually leads to respiratory failure. We tested whether dihydrotestosterone (DHT, which has both anabolic effects on muscle and neuroprotective effects on axons and motoneurons, can ameliorate clinical symptoms in ALS. A silastic tube containing DHT crystals was implanted subcutaneously in SOD1-G93A mice at early symptomatic age when decreases in body weight and grip-strength were observed as compared to wild-type mice. DHT-treated SOD1-G93A mice demonstrated ameliorated muscle atrophy and increased body weight, which was associated with stronger grip-strength. DHT treatment increased the expression of insulin-like growth factor-1 in muscle, which can exert myotrophic as well as neurotrophic effects through retrograde transport. DHT treatment attenuated neuromuscular junction denervation, and axonal and motoneuron loss. DHT-treated SOD1-G93A mice demonstrated improvement in motor behavior as assessed by rota-rod and gait analyses, and an increased lifespan. Application of DHT is a relatively simple and non-invasive procedure, which may be translated into therapy to improve the quality of life for ALS patients.

  15. Fast axonal transport of labeled proteins in motoneurons of exercise-trained rats

    International Nuclear Information System (INIS)

    Jasmin, B.J.; Lavoie, P.A.; Gardiner, P.F.

    1988-01-01

    In this study, the fast orthograde axonal transport of radiolabeled proteins was measured to determine the effects of endurance-running training on transport velocity and amounts of transported proteins in rat sciatic motoneurons. Female rats were subjected to a progressive running-training program for 10-12 wk. Twenty-four hours after the last training session, rats underwent right L4-L5 dorsal root ganglionectomy. The next day, 20 microCi of [3H]leucine was injected bilaterally in the vicinity of the motoneuronal cell bodies supplying the sciatic nerve, to study axonal transport parameters. Results showed that peak and average transport velocities of labeled proteins were significantly (P less than 0.05) increased by 22 and 29%, respectively, in the deafferented nerves of the runners as compared with controls. Moreover, the amount of total transported protein-bound radioactivity was increased in both left (40%) and right (37%) sciatic nerves of the runners. An exhaustive exercise session reduced (P less than 0.05) peak displacement (8%) and total transported protein-bound radioactivity (36%) in the sciatic nerves of control rats, whereas no changes were noticed in trained animals. The data suggest that chronic endurance running induces significant adaptations in the fast axonal transport of labeled proteins

  16. Persistent GABAA/C responses to gabazine, taurine and beta-alanine in rat hypoglossal motoneurons.

    Science.gov (United States)

    Chesnoy-Marchais, D

    2016-08-25

    In hypoglossal motoneurons, a sustained anionic current, sensitive to a blocker of ρ-containing GABA receptors, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) and insensitive to bicuculline, was previously shown to be activated by gabazine. In order to better characterize the receptors involved, the sensitivity of this atypical response to pentobarbital (30μM), allopregnanolone (0.3μM) and midazolam (0.5μM) was first investigated. Pentobarbital potentiated the response, whereas the steroid and the benzodiazepine were ineffective. The results indicate the involvement of hybrid heteromeric receptors, including at least a GABA receptor ρ subunit and a γ subunit, accounting for the pentobarbital-sensitivity. The effects of the endogenous β amino acids, taurine and β-alanine, which are released under various pathological conditions and show neuroprotective properties, were then studied. In the presence of the glycine receptor blocker strychnine (1μM), both taurine (0.3-1mM) and β-alanine (0.3mM) activated sustained anionic currents, which were partly blocked by TPMPA (100μM). Thus, both β amino acids activated ρ-containing GABA receptors in hypoglossal motoneurons. Bicuculline (20μM) reduced responses to taurine and β-alanine, but small sustained responses persisted in the presence of both strychnine and bicuculline. Responses to β-alanine were slightly increased by allopregnanolone, indicating a contribution of the bicuculline- and neurosteroid-sensitive GABAA receptors underlying tonic inhibition in these motoneurons. Since sustained activation of anionic channels inhibits most mature principal neurons, the ρ-containing GABA receptors permanently activated by taurine and β-alanine might contribute to some of their neuroprotective properties under damaging overexcitatory situations. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Serotonergic synaptic input to facial motoneurons: localization by electron-microscopic autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Aghajanian, G K; McCall, R B [Yale Univ., New Haven, CT (USA). School of Medicine

    1980-12-01

    Serotonergic nerve terminals in the facial motor nucleus were labelled with (/sup 3/H)5-hydroxytryptamine. When serotonergic nerve terminals were destroyed (by the selective neurotoxin 5,7-dihydroxytryptamine) the labelling was lost. By electron-microscopic autoradiography, labelled serotonergic terminals were found to make axo-dendritic or axo-somatic junctions with facial motor neurons. No axo-axonic junctions were observed. These morphological findings are consistent with physiological studies which indicate that 5-hydroxytryptamine facilitates the excitation of facial motoneurons through a direct postsynaptic action.

  18. CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency.

    Science.gov (United States)

    Brockmann, Sarah J; Freischmidt, Axel; Oeckl, Patrick; Müller, Kathrin; Ponna, Srinivas K; Helferich, Anika M; Paone, Christoph; Reinders, Jörg; Kojer, Kerstin; Orth, Michael; Jokela, Manu; Auranen, Mari; Udd, Bjarne; Hermann, Andreas; Danzer, Karin M; Lichtner, Peter; Walther, Paul; Ludolph, Albert C; Andersen, Peter M; Otto, Markus; Kursula, Petri; Just, Steffen; Weishaupt, Jochen H

    2018-02-15

    Mutations in the mitochondrially located protein CHCHD10 cause motoneuron disease by an unknown mechanism. In this study, we investigate the mutations p.R15L and p.G66V in comparison to wild-type CHCHD10 and the non-pathogenic variant p.P34S in vitro, in patient cells as well as in the vertebrate in vivo model zebrafish. We demonstrate a reduction of CHCHD10 protein levels in p.R15L and p.G66V mutant patient cells to approximately 50%. Quantitative real-time PCR revealed that expression of CHCHD10 p.R15L, but not of CHCHD10 p.G66V, is already abrogated at the mRNA level. Altered secondary structure and rapid protein degradation are observed with regard to the CHCHD10 p.G66V mutant. In contrast, no significant differences in expression, degradation rate or secondary structure of non-pathogenic CHCHD10 p.P34S are detected when compared with wild-type protein. Knockdown of CHCHD10 expression in zebrafish to about 50% causes motoneuron pathology, abnormal myofibrillar structure and motility deficits in vivo. Thus, our data show that the CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease primarily based on haploinsufficiency of CHCHD10. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Estrogen induces axonal outgrowth in the nucleus retroambiguus-lumbosacral motoneuronal pathway in the adult female cat

    NARCIS (Netherlands)

    VanderHorst, VGJM; Holstege, G

    1997-01-01

    In 1995, we discovered a new pathway in the cat, which originates from the nucleus retroambiguus (NRA) and terminates in a distinct set of lumbosacral hindlimb, axial, and pelvic floor motoneuronal cell groups [VanderHorst VG.JM, Holstege G (1995) Caudal medullary pathways to lumbosacral

  20. ATF3 expression precedes death of spinal motoneurons in amyotrophic lateral sclerosis-SOD1 transgenic mice and correlates with c-Jun phosphorylation, CHOP expression, somato-dendritic ubiquitination and Golgi fragmentation

    NARCIS (Netherlands)

    Vlug, Angela S; Teuling, Eva; Haasdijk, Elize D; French, Pim; Hoogenraad, Casper C; Jaarsma, Dick

    2005-01-01

    To obtain insight into the morphological and molecular correlates of motoneuron degeneration in amyotrophic lateral sclerosis (ALS) mice that express G93A mutant superoxide dismutase (SOD)1 (G93A mice), we have mapped and characterized 'sick' motoneurons labelled by the 'stress transcription

  1. Gaze-Stabilizing Central Vestibular Neurons Project Asymmetrically to Extraocular Motoneuron Pools.

    Science.gov (United States)

    Schoppik, David; Bianco, Isaac H; Prober, David A; Douglass, Adam D; Robson, Drew N; Li, Jennifer M B; Greenwood, Joel S F; Soucy, Edward; Engert, Florian; Schier, Alexander F

    2017-11-22

    Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate movements. A major challenge is to relate anatomical features of central neural populations, such as asymmetric connectivity, to the computations the populations perform. To address this problem, we mapped the anatomy, modeled the function, and discovered a new behavioral role for a genetically defined population of central vestibular neurons in rhombomeres 5-7 of larval zebrafish. First, we found that neurons within this central population project preferentially to motoneurons that move the eyes downward. Concordantly, when the entire population of asymmetrically projecting neurons was stimulated collectively, only downward eye rotations were observed, demonstrating a functional correlate of the anatomical bias. When these neurons are ablated, fish failed to rotate their eyes following either nose-up or nose-down body tilts. This asymmetrically projecting central population thus participates in both upward and downward gaze stabilization. In addition to projecting to motoneurons, central vestibular neurons also receive direct sensory input from peripheral afferents. To infer whether asymmetric projections can facilitate sensory encoding or motor output, we modeled differentially projecting sets of central vestibular neurons. Whereas motor command strength was independent of projection allocation, asymmetric projections enabled more accurate representation of nose-up stimuli. The model shows how asymmetric connectivity could enhance the representation of imbalance during nose-up postures while preserving gaze stabilization performance. Finally, we found that central vestibular neurons were necessary for a vital behavior requiring maintenance of a nose-up posture: swim bladder inflation. These observations suggest that asymmetric connectivity in the vestibular system facilitates representation of ethologically relevant stimuli without

  2. Hypoglossal motoneurons in newborn mice receive respiratory drive from both sides of the medulla

    DEFF Research Database (Denmark)

    Tarras-Wahlberg, S; Rekling, J C

    2009-01-01

    Respiratory motor output in bilateral cranial nerves is synchronized, but the underlying synchronizing mechanisms are not clear. We used an in vitro slice preparation from newborn mice to investigate the effect of systematic transsections on respiratory activity in bilateral XII nerves. Complete...... in bilateral XII nerves. Hypoglossal motoneurons receive respiratory drive from both sides of the medulla, possibly mediated by contralaterally projecting dendrites....

  3. Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms.

    Science.gov (United States)

    Bayliss, D A; Viana, F; Talley, E M; Berger, A J

    1997-11-01

    Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and (2) the inhibition of a calcium-dependent spike after hyperpolarization (AHP) by 5-HT and its effect on firing behavior. Potential functional consequences on HM behavior of these different neurotransmitter effects is discussed. In addition, we describe postnatal changes in transmitter effects and suggest potential cellular mechanisms to explain those developmental changes. Most of the data discussed are derived from in vitro electrophysiological recordings performed in preparations from neonatal and adult rats.

  4. Retroambiguus projections to the cutaneus trunci motoneurons may form a pathway in the central control of mating

    NARCIS (Netherlands)

    Gerrits, Peter O.; Vodde, Chris; Holstege, Gert

    Our laboratory has proposed that the nucleus retroambiguus (NRA) generates the specific motor performance displayed by female cats during mating and that it uses direct pathways to the motoneurons of the lower limb muscles involved in this activity. In the hamster a similar NRA-projection system

  5. Developmental plasticity of phrenic motoneuron and diaphragm properties with the inception of inspiratory drive transmission in utero.

    Science.gov (United States)

    Greer, John J; Martin-Caraballo, Miguel

    2017-01-01

    The review outlines data consistent with the hypothesis that inspiratory drive transmission that generates fetal breathing movements (FBMs) is essential for the developmental plasticity of phrenic motoneurons (PMNs) and diaphragm musculature prior to birth. A systematic examination during the perinatal period demonstrated a very marked transformation of PMN and diaphragm properties coinciding with the onset and strengthening of inspiratory drive and FBMs in utero. This included studies of age-dependent changes of: i) morphology, neuronal coupling, passive and electrophysiological properties of PMNs; ii) rhythmic inspiratory activity in vitro; iii) FBMs generated in vivo detected by ultrasonography; iv) contractile and end-plate potential properties of diaphragm musculature. We also propose how the hypothesis can be further evaluated with studies of perinatal hypoglossal motoneuron-tongue musculature and the use of Dbx1 null mice that provide an experimental model lacking descending inspiratory drive transmission in utero. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase

    Directory of Open Access Journals (Sweden)

    Zanon Renata G

    2010-05-01

    Full Text Available Abstract Background Astrocytes play a major role in preserving and restoring structural and physiological integrity following injury to the nervous system. After peripheral axotomy, reactive gliosis propagates within adjacent spinal segments, influenced by the local synthesis of nitric oxide (NO. The present work investigated the importance of inducible nitric oxide synthase (iNOS activity in acute and late glial responses after injury and in major histocompatibility complex class I (MHC I expression and synaptic plasticity of inputs to lesioned alpha motoneurons. Methods In vivo analyses were carried out using C57BL/6J-iNOS knockout (iNOS-/- and C57BL/6J mice. Glial response after axotomy, glial MHC I expression, and the effects of axotomy on synaptic contacts were measured using immunohistochemistry and transmission electron microscopy. For this purpose, 2-month-old animals were sacrificed and fixed one or two weeks after unilateral sciatic nerve transection, and spinal cord sections were incubated with antibodies against classical MHC I, GFAP (glial fibrillary acidic protein - an astroglial marker, Iba-1 (an ionized calcium binding adaptor protein and a microglial marker or synaptophysin (a presynaptic terminal marker. Western blotting analysis of MHC I and nNOS expression one week after lesion were also performed. The data were analyzed using a two-tailed Student's t test for parametric data or a two-tailed Mann-Whitney U test for nonparametric data. Results A statistical difference was shown with respect to astrogliosis between strains at the different time points studied. Also, MHC I expression by iNOS-/- microglial cells did not increase at one or two weeks after unilateral axotomy. There was a difference in synaptophysin expression reflecting synaptic elimination, in which iNOS-/- mice displayed a decreased number of the inputs to alpha motoneurons, in comparison to that of C57BL/6J. Conclusion The findings herein indicate that i

  7. Afferent projections to pharynx and soft palate motoneurons : A light and electron microscopical tracing study in the cat

    NARCIS (Netherlands)

    Boers, J; Hulshoff, AC; De Weerd, H; Mouton, LJ; Kuipers, R; Holstege, G; Hulshoff, Antoinette C.

    2005-01-01

    Pharynx and soft palate are muscles for respiration, vocalization, swallowing, and vomiting. In cat, motoneurons innervating pharynx/soft palate are located in the dorsal group of the nucleus ambiguus (dgNA) in the medulla oblongata. In cat, dgNA is the only part of nucleus ambiguus that can be

  8. 5-HT modulation of multiple inward rectifiers in motoneurons in intact preparations of the neonatal rat spinal cord

    DEFF Research Database (Denmark)

    Kjaerulff, Ole; Kiehn, Ole

    2001-01-01

    This study introduces novel aspects of inward rectification in neonatal rat spinal motoneurons (MNs) and its modulation by serotonin (5-HT). Whole cell tight-seal recordings were made from MNs in an isolated lumbar spinal cord preparation from rats 1-2 days of age. In voltage clamp, hyperpolarizi...

  9. Formation and characterisation of neuromuscular junctions between hiPSC derived motoneurons and myotubes

    Directory of Open Access Journals (Sweden)

    M. Demestre

    2015-09-01

    Full Text Available Striated skeletal muscle cells from humans represent a valuable source for in vitro studies of the motoric system as well as for pathophysiological investigations in the clinical settings. Myoblasts can readily be grown from human muscle tissue. However, if muscle tissue is unavailable, myogenic cells can be generated from human induced pluripotent stem cells (hiPSCs preferably without genetic engineering. Our study aimed to optimize the generation of hiPSCs derived myogenic cells by employing selection of CD34 positive cells and followed by distinct, stepwise culture conditions. Following the expansion of CD34 positive single cells under myogenic cell culture conditions, serum deprived myoblast-like cells finally fused and formed multinucleated striated myotubes that expressed a set of key markers for muscle differentiation. In addition, these myotubes contracted upon electrical stimulation, responded to acetylcholine (Ach and were able to generate action potentials. Finally, we co-cultured motoneurons and myotubes generated from identical hiPSCs cell lines. We could observe the early aggregation of acetylcholine receptors in muscle cells of immature co-cultures. At later stages, we identified and characterised mature neuromuscular junctions (NMJs. In summary, we describe here the successful generation of an iPS cell derived functional cellular system consisting of two distinct communicating cells types. This in vitro co-culture system could therefore contribute to research on diseases in which the motoneurons and the NMJ are predominantly affected, such as in amyotrophic lateral sclerosis or spinal muscular atrophy.

  10. The feasibility of using the 25MW super near boiling nuclear reactor (SNB25) to provide thermal and electrical energy for a large Canadian Forces base in the Canadian Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Paquette, S.; Bonin, H.W.; Baskin, M.; Bowen, K.; Switzer, Z., E-mail: Stephane.Paquette@rmc.ca [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada)

    2014-07-01

    A feasibility study of a power plant using the Super Near Boiling 25 MWt (SNB25) nuclear reactor as a heat source and capable of supporting the electrical and thermal requirements for a base the size of Canadian Forces Base (CFB) Kingston in the Arctic was carried out. Such a power plant would allow the Canadian Armed Forces (CAF) to have a self-sustaining operational base in the Arctic to conduct Search and Rescue (SAR) and sovereignty missions. The thermal and electrical requirements for a base the size of CFB Kingston are determined to be 31.63 MWt and 7.16 MWe, respectively. Using the Heating Degree Days (HDD) approach to account for temperature differences between Southern Ontario and the Arctic, a base the size of CFB Kingston in the Arctic would require 75.16 MWt to operate. A chemical engineering software program, UniSim, was used to simulate the energy cycle of the base which consisted of a district heating loop to provide hot water and an Organic Rankine Cycle (ORC) using n-pentane as the working fluid to provide the electrical energy. The UniSim simulations determined that the cycle would use six shell and tube heat exchangers, two axial gas turbines coupled to generators, and twelve centrifugal pumps, in addition to a group of five SNB25 reactors that could provide 25.03 MWt and 2.63 MWe to a base in the Arctic with energy requirements about a third of those of CFB Kingston. The design foresees redundancy which is essential to safe operation in the Arctic. (author)

  11. Failure of activation of spinal motoneurones after muscle fatigue in healthy subjects studied by transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Andersen, Birgit; Westlund, Barbro; Krarup, Christian

    2003-01-01

    . This points to increased probability of repetitive spinal MN activation during fatigue even if some MNs in the pool failed to discharge. Silent period duration following cortical stimulation lengthened by an average of 55 ms after the contraction and recovered within a time course similar to that of the TST......During a sustained maximal effort a progressive decline in the ability to drive motoneurones (MNs) develops. We used the recently developed triple stimulation technique (TST) to study corticospinal conduction after fatiguing exercise in healthy subjects. This method employs a collision technique...... conventional transcranial magnetic stimulation (TMS) and responses to peripheral nerve stimulation were recorded following the same fatigue protocol. The size of both the MEPs and the peripheral responses increased after the contraction and were in direct contrast to the decrease in size of the TST response...

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

    DEFF Research Database (Denmark)

    Wienecke, Jacob; Denton, Manuel Enríquez; Stecina, Katinka

    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 stu...

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

    DEFF Research Database (Denmark)

    Larsen, Lisbeth Højkjær; Jensen, Thor; Christensen, Mark Schram

    2016-01-01

    ) 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....

  14. Expression of the low affinity neurotrophin receptor p75 in spinal motoneurons in a transgenic mouse model for amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Copray, JCVM; Jaarsma, D; Kust, BM; Bruggeman, RWG; Mantingh, [No Value; Brouwer, N; Boddeke, HWGM

    2003-01-01

    Amyotrophic lateral sclerosis is a lethal neurodegenerative disorder involving motoneuron loss in the cortex, brainstem and spinal cord, resulting in progressive paralysis. Aberrant neurotrophin signalling via the low affinity neurotrophin receptor p75 has been suggested to be involved in the

  15. Organization of common synaptic drive to motoneurones during fictive locomotion in the spinal cat

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo; Conway, B.A.; Halliday, D.M.

    2005-01-01

    pairs to antagonistic pools) failed to reveal any short-lasting synchronization. These data demonstrate that short-term synchronization during fictive locomotion is relatively weak and is restricted to close synergists. In addition, coherence analysis failed to identify any specific rhythmic component......The basic locomotor rhythm in the cat is generated by a neuronal network in the spinal cord. The exact organization of this network and its drive to the spinal motoneurones is unknown. The purpose of the present study was to use time (cumulant density) and frequency domain (coherence) analysis...

  16. Intense synaptic activity enhances temporal resolution in spinal motoneurons.

    Directory of Open Access Journals (Sweden)

    Rune W Berg

    Full Text Available In neurons, spike timing is determined by integration of synaptic potentials in delicate concert with intrinsic properties. Although the integration time is functionally crucial, it remains elusive during network activity. While mechanisms of rapid processing are well documented in sensory systems, agility in motor systems has received little attention. Here we analyze how intense synaptic activity affects integration time in spinal motoneurons during functional motor activity and report a 10-fold decrease. As a result, action potentials can only be predicted from the membrane potential within 10 ms of their occurrence and detected for less than 10 ms after their occurrence. Being shorter than the average inter-spike interval, the AHP has little effect on integration time and spike timing, which instead is entirely determined by fluctuations in membrane potential caused by the barrage of inhibitory and excitatory synaptic activity. By shortening the effective integration time, this intense synaptic input may serve to facilitate the generation of rapid changes in movements.

  17. APP overexpression prevents neuropathic pain and motoneuron death after peripheral nerve injury in mice.

    Science.gov (United States)

    Kotulska, Katarzyna; Larysz-Brysz, Magdalena; LePecheur, Marie; Marcol, Wiesław; Lewin-Kowalik, Joanna; Paly, Evelyn; London, Jacqueline

    2010-03-16

    Despite general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function and sometimes burdened by neuropathic pain. Amyloid precursor protein (APP) was suggested to play a role in neuronal growth, however, its role in peripheral nerve repair was not studied. The aim of this study was to examine the role of APP overexpression in peripheral nerve regeneration and neuropathic pain-related behavior in mice. Sciatic nerves of APP overexpressing and FVB/N wild-type mice were transected and immediately resutured. Evaluation of motor and sensory function and autotomy was carried out during 4-week follow up. We found no autotomy behavior as well as less significant atrophy of denervated muscles in APP overexpressing animals when compared to wild-type ones. Sciatic nerve function index outcome did not differ between groups. Histological evaluation revealed that the intensity of regeneration features, including GAP-43-positive growth cones and Schwann cells number in the distal stump of the transected nerve, was also similar in both groups. However, the regenerating fibers were organized more chaotically in wild-type mice and neuromas were much more often seen in this group. The number of macrophages infiltrating the injury site was significantly higher in control group. The number of surviving motoneurons was higher in transgenic mice than in control animals. Taken together, our findings suggest that APP overexpression is beneficial for nerve regeneration processes due to better organization of regenerating fibers, increased survival of motoneurons after autotomy and prevention of neuropathic pain. Copyright 2009 Elsevier Inc. All rights reserved.

  18. In vivo intracellular recordings from spinal lumbar motoneurones in P0-deficient mice indicate an activity-dependent axonal conduction failure in otherwise functional motoneurones

    DEFF Research Database (Denmark)

    Lehnhoff, Janna; Moldovan, Mihai; Hedegaard, Anne

    2014-01-01

    Mice deficient for the peripheral myelin binding protein zero (P0-/-) show a progressive dysmyelinating neuropathy phenotypically resembling severe forms of Charcot-Marie-Tooth (CMT) disease. Traditionally, the progression of the disease was attributed to axonal loss, but the effect of chronic...... dysmyelination remains poorly understood. In this study, in vivo electrophysiological recordings were used to assess the function of both central and axonal components of spinal lumbar motoneurones in adult P0-/- mice.Three month old P0-/- mice (n=7) and wild type (WT) littermate controls (n=5) were...... anaesthetized with Hypnorm (0.315 mg/mL fentanyl-citrate + 10 mg/mL fluanisone), Midazolam (5 mg/mL), and sterile water, mixed in the ratio 1:1:2 (induction: 0.15mL/25g, maintenance: 0.05 mL/20 minutes, S.C.). Anaesthesia during surgery was assessed by the lack of reflexes to a short noxious pinch on the hind...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Katinka eStecina

    2015-02-01

    Full Text Available 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.

  1. Abdominal and internal intercostal motoneurones are strong synergists for expiration but are not synergists for Group I monosynaptic afferent inputs

    DEFF Research Database (Denmark)

    Ford, Tim W; Meehan, Claire Francesca; Kirkwood, Peter

    2014-01-01

    , 9 being in Group B Dist motoneurones. The complete absence of heteronymous monosynaptic Group I reflex excitation between muscles that are synergistically activated in expiration leads us to conclude that such connections from muscle spindle afferents of the thoracic nerves have little role...... in controlling expiratory movements but, where present, support other motor acts....

  2. Reduction of common synaptic drive to ankle dorsiflexor motoneurons during walking in patients with spinal cord lesion

    DEFF Research Database (Denmark)

    Hansen, N.L.; Conway, B.A.; Halliday, D.M.

    2005-01-01

    It is possible to obtain information about the synaptic drive to motoneurons during walking by analyzing motor-unit coupling in the time and frequency domains. The purpose of the present study was to compare motor-unit coupling during walking in healthy subjects and patients with incomplete spina...... as physiological markers of impaired supraspinal control of gait in SCL patients. Such markers could have diagnostic and prognostic value in relation to the recovery of locomotion in patients with central motor lesions....

  3. The Role of the Heat Shock Protein B8 (HSPB8 in Motoneuron Diseases

    Directory of Open Access Journals (Sweden)

    Paola Rusmini

    2017-06-01

    Full Text Available Amyotrophic lateral sclerosis (ALS and spinal and bulbar muscular atrophy (SBMA are two motoneuron diseases (MNDs characterized by aberrant protein behavior in affected cells. In familial ALS (fALS and in SBMA specific gene mutations lead to the production of neurotoxic proteins or peptides prone to misfold, which then accumulate in form of aggregates. Notably, some of these proteins accumulate into aggregates also in sporadic ALS (sALS even if not mutated. To prevent proteotoxic stresses detrimental to cells, misfolded and/or aggregated proteins must be rapidly removed by the protein quality control (PQC system. The small heat shock protein B8 (HSPB8 is a chaperone induced by harmful events, like proteasome inhibition. HSPB8 is expressed both in motoneuron and muscle cells, which are both targets of misfolded protein toxicity in MNDs. In ALS mice models, in presence of the mutant proteins, HSPB8 is upregulated both in spinal cord and muscle. HSPB8 interacts with the HSP70 co-chaperone BAG3 and enhances the degradation of misfolded proteins linked to sALS, or causative of fALS and of SBMA. HSPB8 acts by facilitating autophagy, thereby preventing misfolded protein accumulation in affected cells. BAG3 and BAG1 compete for HSP70-bound clients and target them for disposal to the autophagy or proteasome, respectively. Enhancing the selective targeting of misfolded proteins by HSPB8-BAG3-HSP70 to autophagy may also decrease their delivery to the proteasome by the BAG1-HSP70 complex, thereby limiting possible proteasome overwhelming. Thus, approaches aimed at potentiating HSPB8-BAG3 may contribute to the maintenance of proteostasis and may delay MNDs progression.

  4. Progranulin modulates zebrafish motoneuron development in vivo and rescues truncation defects associated with knockdown of Survival motor neuron 1

    Directory of Open Access Journals (Sweden)

    Bateman Andrew

    2010-10-01

    Full Text Available Abstract Background Progranulin (PGRN encoded by the GRN gene, is a secreted glycoprotein growth factor that has been implicated in many physiological and pathophysiological processes. PGRN haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to progressive neuronal atrophy in the form of frontotemporal lobar degeneration (FTLD. This form of the disease is associated with neuronal inclusions that bear the ubiquitinated TAR DNA Binding Protein-43 (TDP-43 molecular signature (FTLD-U. The neurotrophic properties of PGRN in vitro have recently been reported but the role of PGRN in neurons is not well understood. Here we document the neuronal expression and functions of PGRN in spinal cord motoneuron (MN maturation and branching in vivo using zebrafish, a well established model of vertebrate embryonic development. Results Whole-mount in situ hybridization and immunohistochemical analyses of zebrafish embryos revealed that zfPGRN-A is expressed within the peripheral and central nervous systems including the caudal primary (CaP MNs within the spinal cord. Knockdown of zfPGRN-A mRNA translation mediated by antisense morpholino oligonucleotides disrupted normal CaP MN development resulting in both truncated MNs and inappropriate early branching. Ectopic over-expression of zfPGRN-A mRNA resulted in increased MN branching and rescued the truncation defects brought about by knockdown of zfPGRN-A expression. The ability of PGRN to interact with established MN developmental pathways was tested. PGRN over-expression was found to reverse the truncation defect resulting from knockdown of Survival of motor neuron 1 (smn1. This is involved in small ribonucleoprotein biogenesis RNA processing, mutations of which cause Spinal Muscular Atrophy (SMA in humans. It did not reverse the MN defects caused by interfering with the neuronal guidance pathway by knockdown of expression of NRP-1, a semaphorin co-receptor. Conclusions Expression of

  5. Adult mouse motor units develop almost all of their force in the subprimary range: a new all-or-none strategy for force recruitment?

    Science.gov (United States)

    Manuel, Marin; Heckman, C J

    2011-10-19

    Classical studies of the mammalian neuromuscular system have shown an impressive adaptation match between the intrinsic properties of motoneurons and the contractile properties of their motor units. In these studies, the rate at which motoneurons start to fire repetitively corresponds to the rate at which individual twitches start to sum, and the firing rate increases linearly with the amount of excitation ("primary range") up to the point where the motor unit develops its maximal force. This allows for the gradation of the force produced by a motor unit by rate modulation. In adult mouse motoneurons, however, we recently described a regime of firing ("subprimary range") that appears at lower excitation than what is required for the primary range, a finding that might challenge the classical conception. To investigate the force production of mouse motor units, we simultaneously recorded, for the first time, the motoneuron discharge elicited by intracellular ramps of current and the force developed by its motor unit. We showed that the motor unit developed nearly its maximal force during the subprimary range. This was found to be the case regardless of the input resistance of the motoneuron, the contraction speed, or the tetanic force of the motor unit. Our work suggests that force modulation in small mammals mainly relies on the number of motor units that are recruited rather than on rate modulation of individual motor units.

  6. Probing the corticospinal link between the motor cortex and motoneurones: some neglected aspects of human motor cortical function

    DEFF Research Database (Denmark)

    Petersen, Nicolas Caesar; Butler, Jane E.; Taylor, Janet L.

    2010-01-01

    of the discharge of motor units have revealed that the rapidly conducting corticospinal axons (stimulated at higher intensities) contribute to drive motoneurones in normal voluntary contractions. There are also major non-linearities generated at a spinal level in the relation between corticospinal output...... magnetic stimulation of the human motor cortex have highlighted the capacity of the cortex to modify its apparent excitability in response to altered afferent inputs, training and various pathologies. Studies using cortical stimulation at 'very low' intensities which elicit only short-latency suppression...

  7. Transmitter-controlled properties of α-motoneurones causing long-lasting motor discharge to brief excitatory inputs

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Hultborn, H.; Kiehn, O.

    1986-01-01

    Brief sensory inputs to intact conscious subjects commonly trigger complex long-lasting motor responses, in which higher cerebral mechanisms, or even voluntary action, may be integrative parts. However, long-lasting motor discharge following brief afferent stimulation is also observed in reduced ...... flipflops, which are set at one of two levels by short excitatory or inhibitory inputs. However, when the whole motoneuronal pool is considered, many different levels can be maintained by recruitment of new units.......Brief sensory inputs to intact conscious subjects commonly trigger complex long-lasting motor responses, in which higher cerebral mechanisms, or even voluntary action, may be integrative parts. However, long-lasting motor discharge following brief afferent stimulation is also observed in reduced...

  8. Improved non-local electron thermal transport model for two-dimensional radiation hydrodynamics simulations

    Science.gov (United States)

    Cao, Duc; Moses, Gregory; Delettrez, Jacques

    2015-08-01

    An implicit, non-local thermal conduction algorithm based on the algorithm developed by Schurtz, Nicolai, and Busquet (SNB) [Schurtz et al., Phys. Plasmas 7, 4238 (2000)] for non-local electron transport is presented and has been implemented in the radiation-hydrodynamics code DRACO. To study the model's effect on DRACO's predictive capability, simulations of shot 60 303 from OMEGA are completed using the iSNB model, and the computed shock speed vs. time is compared to experiment. Temperature outputs from the iSNB model are compared with the non-local transport model of Goncharov et al. [Phys. Plasmas 13, 012702 (2006)]. Effects on adiabat are also examined in a polar drive surrogate simulation. Results show that the iSNB model is not only capable of flux-limitation but also preheat prediction while remaining numerically robust and sacrificing little computational speed. Additionally, the results provide strong incentive to further modify key parameters within the SNB theory, namely, the newly introduced non-local mean free path. This research was supported by the Laboratory for Laser Energetics of the University of Rochester.

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

    Science.gov (United States)

    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.

  10. Improved non-local electron thermal transport model for two-dimensional radiation hydrodynamics simulations

    International Nuclear Information System (INIS)

    Cao, Duc; Moses, Gregory; Delettrez, Jacques

    2015-01-01

    An implicit, non-local thermal conduction algorithm based on the algorithm developed by Schurtz, Nicolai, and Busquet (SNB) [Schurtz et al., Phys. Plasmas 7, 4238 (2000)] for non-local electron transport is presented and has been implemented in the radiation-hydrodynamics code DRACO. To study the model's effect on DRACO's predictive capability, simulations of shot 60 303 from OMEGA are completed using the iSNB model, and the computed shock speed vs. time is compared to experiment. Temperature outputs from the iSNB model are compared with the non-local transport model of Goncharov et al. [Phys. Plasmas 13, 012702 (2006)]. Effects on adiabat are also examined in a polar drive surrogate simulation. Results show that the iSNB model is not only capable of flux-limitation but also preheat prediction while remaining numerically robust and sacrificing little computational speed. Additionally, the results provide strong incentive to further modify key parameters within the SNB theory, namely, the newly introduced non-local mean free path. This research was supported by the Laboratory for Laser Energetics of the University of Rochester

  11. Improved non-local electron thermal transport model for two-dimensional radiation hydrodynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Duc; Moses, Gregory [University of Wisconsin—Madison, 1500 Engineering Drive, Madison, Wisconsin 53706 (United States); Delettrez, Jacques [Laboratory for Laser Energetics of the University of Rochester, 250 East River Road, Rochester, New York 14623 (United States)

    2015-08-15

    An implicit, non-local thermal conduction algorithm based on the algorithm developed by Schurtz, Nicolai, and Busquet (SNB) [Schurtz et al., Phys. Plasmas 7, 4238 (2000)] for non-local electron transport is presented and has been implemented in the radiation-hydrodynamics code DRACO. To study the model's effect on DRACO's predictive capability, simulations of shot 60 303 from OMEGA are completed using the iSNB model, and the computed shock speed vs. time is compared to experiment. Temperature outputs from the iSNB model are compared with the non-local transport model of Goncharov et al. [Phys. Plasmas 13, 012702 (2006)]. Effects on adiabat are also examined in a polar drive surrogate simulation. Results show that the iSNB model is not only capable of flux-limitation but also preheat prediction while remaining numerically robust and sacrificing little computational speed. Additionally, the results provide strong incentive to further modify key parameters within the SNB theory, namely, the newly introduced non-local mean free path. This research was supported by the Laboratory for Laser Energetics of the University of Rochester.

  12. Secondary Analysis of the NCI-60 Whole Exome Sequencing Data Indicates Significant Presence of Propionibacterium acnes Genomic Material in Leukemia (RPMI-8226 and Central Nervous System (SF-295, SF-539, and SNB-19 Cell Lines.

    Directory of Open Access Journals (Sweden)

    Mark Rojas

    Full Text Available The NCI-60 human tumor cell line panel has been used in a broad range of cancer research over the last two decades. A landmark 2013 whole exome sequencing study of this panel added an exceptional new resource for cancer biologists. The complementary analysis of the sequencing data produced by this study suggests the presence of Propionibacterium acnes genomic sequences in almost half of the datasets, with the highest abundance in the leukemia (RPMI-8226 and central nervous system (SF-295, SF-539, and SNB-19 cell lines. While the origin of these contaminating bacterial sequences remains to be determined, observed results suggest that computational control for the presence of microbial genomic material is a necessary step in the analysis of the high throughput sequencing (HTS data.

  13. The motor system plays the violin: a musical metaphor inferred from the oscillatory activity of the α-motoneuron pools during locomotion.

    Science.gov (United States)

    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.

  14. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

    Science.gov (United States)

    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

  15. Phrenic motoneurons: output elements of a highly organized intraspinal network.

    Science.gov (United States)

    Ghali, Michael George Zaki

    2018-03-01

    pontomedullary respiratory network generates the respiratory pattern and relays it to bulbar and spinal respiratory motor outputs. The phrenic motor system controlling diaphragm contraction receives and processes descending commands to produce orderly, synchronous, and cycle-to-cycle-reproducible spatiotemporal firing. Multiple investigators have studied phrenic motoneurons (PhMNs) in an attempt to shed light on local mechanisms underlying phrenic pattern formation. I and colleagues (Marchenko V, Ghali MG, Rogers RF. Am J Physiol Regul Integr Comp Physiol 308: R916-R926, 2015.) recorded PhMNs in unanesthetized, decerebrate rats and related their activity to simultaneous phrenic nerve (PhN) activity by creating a time-frequency representation of PhMN-PhN power and coherence. On the basis of their temporal firing patterns and relationship to PhN activity, we categorized PhMNs into three classes, each of which emerges as a result of intrinsic biophysical and network properties and organizes the orderly contraction of diaphragm motor fibers. For example, early inspiratory diaphragmatic activation by the early coherent burst generated by high-frequency PhMNs may be necessary to prime it to overcome its initial inertia. We have also demonstrated the existence of a prominent role for local intraspinal inhibitory mechanisms in shaping phrenic pattern formation. The objective of this review is to relate and synthesize recent findings with those of previous studies with the aim of demonstrating that the phrenic nucleus is a region of active local processing, rather than a passive relay of descending inputs.

  16. The expression of a motoneuron-specific serine protease, motopsin (PRSS12), after facial nerve axotomy in mice.

    Science.gov (United States)

    Numajiri, Toshiaki; Mitsui, Shinichi; Hisa, Yasuo; Ishida, Toshihiro; Nishino, Kenichi; Yamaguchi, Nozomi

    2006-01-01

    Motopsin (PRSS12) is a mosaic serine protease that is preferentially expressed in motor neurons. To study the relationship between motopsin and motoneuron function, we investigated the expression of motopsin mRNA in facial nerve nuclei after facial nerve axotomy at the anterior margin of the parotid gland in mice. Neuronal function was monitored by assessing vibrissal motion in 3 months. Vibrissal behaviour on the injured side disappeared until the day 14 post-operation, and then recovered between the day 21 and 35. Motopsin expression decreased at the day 14, but markedly recovered by the day 21. In contrast, expression of growth-associated protein-43 (GAP-43) was induced at the day 3. These results suggest that the recovery of motopsin expression is correlated with the recovery of the facial motor neuronal function.

  17. Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain.

    Science.gov (United States)

    Rukhadze, I; Kamani, H; Kubin, L

    2011-12-01

    In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N>GH>GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I>GH>N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70-120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes.

  18. cGMP-Dependent Protein Kinase Inhibition Extends the Upper Temperature Limit of Stimulus-Evoked Calcium Responses in Motoneuronal Boutons of Drosophila melanogaster Larvae.

    Science.gov (United States)

    Krill, Jennifer L; 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.

  19. Peripheral fatigue limits endurance exercise via a sensory feedback-mediated reduction in spinal motoneuronal output.

    Science.gov (United States)

    Amann, Markus; Venturelli, Massimo; Ives, Stephen J; McDaniel, John; Layec, Gwenael; Rossman, Matthew J; Richardson, Russell S

    2013-08-01

    This study sought to determine whether afferent feedback associated with peripheral muscle fatigue inhibits central motor drive (CMD) and thereby limits endurance exercise performance. On two separate days, eight men performed constant-load, single-leg knee extensor exercise to exhaustion (85% of peak power) with each leg (Leg1 and Leg2). On another day, the performance test was repeated with one leg (Leg1) and consecutively (within 10 s) with the other/contralateral leg (Leg2-post). Exercise-induced quadriceps fatigue was assessed by reductions in potentiated quadriceps twitch-force from pre- to postexercise (ΔQtw,pot) in response to supramaximal magnetic femoral nerve stimulation. The output from spinal motoneurons, estimated from quadriceps electromyography (iEMG), was used to reflect changes in CMD. Rating of perceived exertion (RPE) was recorded during exercise. Time to exhaustion (∼9.3 min) and exercise-induced ΔQtw,pot (∼51%) were similar in Leg1 and Leg2 (P > 0.5). In the consecutive leg trial, endurance performance of the first leg was similar to that observed during the initial trial (∼9.3 min; P = 0.8); however, time to exhaustion of the consecutively exercising contralateral leg (Leg2-post) was shorter than the initial Leg2 trial (4.7 ± 0.6 vs. 9.2 ± 0.4 min; P fatigue and associated afferent feedback limits the development of peripheral fatigue and compromises endurance exercise performance by inhibiting CMD.

  20. Increased probability of repetitive spinal motoneuron activation by transcranial magnetic stimulation after muscle fatigue in healthy subjects

    DEFF Research Database (Denmark)

    Andersen, Birgit; Felding, Ulrik Ascanius; Krarup, Christian

    2012-01-01

    Triple stimulation technique (TST) has previously shown that transcranial magnetic stimulation (TMS) fails to activate a proportion of spinal motoneurons (MNs) during motor fatigue. The TST response depression without attenuation of the conventional motor evoked potential suggested increased...... probability of repetitive spinal MN activation during exercise even if some MNs failed to discharge by the brain stimulus. Here we used a modified TST (Quadruple stimulation; QuadS and Quintuple stimulation; QuintS) to examine the influence of fatiguing exercise on second and third MN discharges after......, reflecting that a greater proportion of spinal MNs were activated 2 or 3 times by the transcranial stimulus. The size of QuadS responses did not return to pre-contraction levels during 10 min observation time indicating long-lasting increase in excitatory input to spinal MNs. In addition, the post...

  1. Predicting Pre-planting Risk of Stagonospora nodorum blotch in Winter Wheat Using Machine Learning Models

    Directory of Open Access Journals (Sweden)

    Lucky eMehra

    2016-03-01

    Full Text Available Pre-planting factors have been associated with the late-season severity of Stagonospora nodorum blotch (SNB, caused by the fungal pathogen Parastagonospora nodorum, in winter wheat (Triticum aestivum. The relative importance of these factors in the risk of SNB has not been determined and this knowledge can facilitate disease management decisions prior to planting of the wheat crop. In this study, we examined the performance of multiple regression (MR and three machine learning algorithms namely artificial neural networks, categorical and regression trees, and random forests (RF in predicting the pre-planting risk of SNB in wheat. Pre-planting factors tested as potential predictor variables were cultivar resistance, latitude, longitude, previous crop, seeding rate, seed treatment, tillage type, and wheat residue. Disease severity assessed at the end of the growing season was used as the response variable. The models were developed using 431 disease cases (unique combinations of predictors collected from 2012 to 2014 and these cases were randomly divided into training, validation, and test datasets. Models were evaluated based on the regression of observed against predicted severity values of SNB, sensitivity-specificity ROC analysis, and the Kappa statistic. A strong relationship was observed between late-season severity of SNB and specific pre-planting factors in which latitude, longitude, wheat residue, and cultivar resistance were the most important predictors. The MR model explained 33% of variability in the data, while machine learning models explained 47 to 79% of the total variability. Similarly, the MR model correctly classified 74% of the disease cases, while machine learning models correctly classified 81 to 83% of these cases. Results show that the RF algorithm, which explained 79% of the variability within the data, was the most accurate in predicting the risk of SNB, with an accuracy rate of 93%. The RF algorithm could allow early

  2. Predicting Pre-planting Risk of Stagonospora nodorum blotch in Winter Wheat Using Machine Learning Models.

    Science.gov (United States)

    Mehra, Lucky K; Cowger, Christina; Gross, Kevin; Ojiambo, Peter S

    2016-01-01

    Pre-planting factors have been associated with the late-season severity of Stagonospora nodorum blotch (SNB), caused by the fungal pathogen Parastagonospora nodorum, in winter wheat (Triticum aestivum). The relative importance of these factors in the risk of SNB has not been determined and this knowledge can facilitate disease management decisions prior to planting of the wheat crop. In this study, we examined the performance of multiple regression (MR) and three machine learning algorithms namely artificial neural networks, categorical and regression trees, and random forests (RF), in predicting the pre-planting risk of SNB in wheat. Pre-planting factors tested as potential predictor variables were cultivar resistance, latitude, longitude, previous crop, seeding rate, seed treatment, tillage type, and wheat residue. Disease severity assessed at the end of the growing season was used as the response variable. The models were developed using 431 disease cases (unique combinations of predictors) collected from 2012 to 2014 and these cases were randomly divided into training, validation, and test datasets. Models were evaluated based on the regression of observed against predicted severity values of SNB, sensitivity-specificity ROC analysis, and the Kappa statistic. A strong relationship was observed between late-season severity of SNB and specific pre-planting factors in which latitude, longitude, wheat residue, and cultivar resistance were the most important predictors. The MR model explained 33% of variability in the data, while machine learning models explained 47 to 79% of the total variability. Similarly, the MR model correctly classified 74% of the disease cases, while machine learning models correctly classified 81 to 83% of these cases. Results show that the RF algorithm, which explained 79% of the variability within the data, was the most accurate in predicting the risk of SNB, with an accuracy rate of 93%. The RF algorithm could allow early assessment of

  3. Influence of active dendritic currents on input-output processing in spinal motoneurons in vivo.

    Science.gov (United States)

    Lee, R H; Kuo, J J; Jiang, M C; Heckman, C J

    2003-01-01

    The extensive dendritic tree of the adult spinal motoneuron generates a powerful persistent inward current (PIC). We investigated how this dendritic PIC influenced conversion of synaptic input to rhythmic firing. A linearly increasing, predominantly excitatory synaptic input was generated in triceps ankle extensor motoneurons by slow stretch (duration: 2-10 s) of the Achilles tendon in the decerebrate cat preparation. The firing pattern evoked by stretch was measured by injecting a steady current to depolarize the cell to threshold for firing. The effective synaptic current (I(N), the net synaptic current reaching the soma of the cell) evoked by stretch was measured during voltage clamp. Hyperpolarized holding potentials were used to minimize the activation of the dendritic PIC and thus estimate stretch-evoked I(N) for a passive dendritic tree (I(N,PASS)). Depolarized holding potentials that approximated the average membrane potential during rhythmic firing allowed strong activation of the dendritic PIC and thus resulted in marked enhancement of the total stretch-evoked I(N) (I(N,TOT)). The net effect of the dendritic PIC on the generation of rhythmic firing was assessed by plotting stretch-evoked firing (strong PIC activation) versus stretch-evoked I(N,PASS) (minimal PIC activation). The gain of this input-output function for the neuron (I-O(N)) was found to be ~2.7 times as high as for the standard injected frequency current (F-I) function in low-input conductance neurons. However, about halfway through the stretch, firing rate tended to become constant, resulting in a sharp saturation in I-O(N) that was not present in F-I. In addition, the gain of I-O(N) decreased sharply with increasing input conductance, resulting in much lower stretch-evoked firing rates in high-input conductance cells. All three of these phenomena (high initial gain, saturation, and differences in low- and high-input conductance cells) were also readily apparent in the differences between

  4. Activity blockade and GABAA receptor blockade produce synaptic scaling through chloride accumulation in embryonic spinal motoneurons and interneurons.

    Directory of Open Access Journals (Sweden)

    Casie Lindsly

    Full Text Available 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.

  5. Responses of soil N-fixing bacteria communities to invasive plant species under different types of simulated acid deposition

    Science.gov (United States)

    Wang, Congyan; Zhou, Jiawei; Jiang, Kun; Liu, Jun; Du, Daolin

    2017-06-01

    Biological invasions have incurred serious threats to native ecosystems in China, and soil N-fixing bacteria communities (SNB) may play a vital role in the successful plant invasion. Meanwhile, anthropogenic acid deposition is increasing in China, which may modify or upgrade the effects that invasive plant species can cause on SNB. We analyzed the structure and diversity of SNB by means of new generation sequencing technology in soils with different simulated acid deposition (SAD), i.e., different SO4 2- to NO3 - ratios, and where the invasive ( Amaranthus retroflexus L.) and the native species ( Amaranthus tricolor L.) grew mixed or isolated for 3 months. A. retroflexus itself did not exert significant effects on the diversity and richness of SNB but did it under certain SO4 2- to NO3 - ratios. Compared to soils where the native species grew isolated, the soils where the invasive A. retroflexus grew isolated showed lower relative abundance of some SNB classes under certain SAD treatments. Some types of SAD can alter soil nutrient content which in turn could affect SNB diversity and abundance. Specifically, greater SO4 2- to NO3 - ratios tended to have more toxic effects on SNB likely due to the higher exchange capacity of hydroxyl groups (OH-) between SO4 2- and NO3 -. As a conclusion, it can be expected a change in the structure of SNB after A. retroflexus invasion under acid deposition rich in sulfuric acid. This change may create a plant soil feedback favoring future A. retroflexus invasions.

  6. Doing physics with scientific notebook a problem solving approach

    CERN Document Server

    Gallant, Joseph

    2012-01-01

    The goal of this book is to teach undergraduate students how to use Scientific Notebook (SNB) to solve physics problems. SNB software combines word processing and mathematics in standard notation with the power of symbolic computation. As its name implies, SNB can be used as a notebook in which students set up a math or science problem, write and solve equations, and analyze and discuss their results. Written by a physics teacher with over 20 years experience, this text includes topics that have educational value, fit within the typical physics curriculum, and show the benefits of using SNB.

  7. Giant multimodal heart motoneurons of Achatina fulica: a new cardioregulatory input in pulmonates.

    Science.gov (United States)

    Zhuravlev, V; Bugaj, V; Kodirov, S; Safonova, T; Staruschenko, A

    2001-08-01

    The regulation of the heartbeat by the two largest neurons, d-VLN and d-RPLN, on the dorsal surface of visceral and right parietal ganglia of Giant African snail, Achatina fulica, was examined. Using the new method of animal preparation, for the first time, discrete biphasic inhibitory-excitatory junction potentials (I-EJPs) in the heart and several muscles of the visceral sac were recorded. The duration of hyperpolarizing phase (H-phase) of biphasic I-EJPs was 269+/-5.6 ms (n=5), which is 2-3 times less than that of the cholinergic inhibitory JPs (682+/-68.5 ms, n=5). The H-phase of I-EJPs was not altered by the application of atropine, picrotoxine, succinylcholinchloride, D-tubocurarine and tetraethylammonium or substitution of Cl(-) ions. Even the low-frequency neuronal discharges (1-2 imp/s) evoked significant facilitation and potentiation of the H-phase. Between the multimodal neurons d-VLN/d-RPLN and mantle or visceral organs there is evidence of direct synaptic connections. These neurons were found to have no axonal branches in the intestinal nerve as once suspected but reach the heart through several other nerves. New giant heart motoneurons do not interact with previously identified cardioregulatory neurons.

  8. Ultrastructure and synaptic organization of the spinal accessory nucleus of the rat.

    Science.gov (United States)

    Hayakawa, Tetsu; Takanaga, Akinori; Tanaka, Koichi; Maeda, Seishi; Seki, Makoto

    2002-06-01

    The accessory nucleus is composed of neurons in the medial column that innervate the sternocleidomastoid muscle, and neurons in the lateral column that innervate the trapezius muscle. We retrogradely labeled these neurons by injection of cholera toxin conjugated horseradish peroxidase into the sternomastoid (SM) or the clavotrapezius (CT) muscles, and investigated fine structure and synaptology of these neurons. Almost all SM and CT motoneurons had the appearance of alpha-motoneurons, i.e., large, oval or polygonal cells containing well-developed organelles, Nissl bodies, and a prominent spherical nucleus. More than 60% of the somatic membrane was covered with terminals. The SM motoneurons (34.4 x 52.2 microm, 1,363.1 microm(2) in a section) were slightly larger than the CT motoneurons (32.8 x 54.2 microm, 1,180.8 microm(2)). The average number of axosomatic terminals in a section was 52.2 for the SM, and 54.2 for the CT motoneurons. More than half of them (58.0%) contained pleomorphic vesicles and made symmetric synaptic contacts (Gray's type II) with the SM motoneurons, while 57.9% of them contained round vesicles and made asymmetric synaptic contacts (Gray's type I) with the CT motoneurons. A few C-terminals were present on the SM (3.5) and the CT (3.7) motoneurons. About 60% of the axodendritic terminals were Gray's type I in both the SM and the CT motoneurons. A few labeled small motoneurons were also found among the SM and the CT motoneurons. They were small (19.2 x 26.2 microm, 367.0 microm(2)), round cells containing poorly developed organelles with a few axosomatic terminals (9.3). Only 20% of the somatic membrane was covered with the terminals. Thus, these neurons were presumed to be gamma-motoneurons. These results indicate that the motoneurons in the medial and the lateral column of the accessory nucleus have different ultrastructural characteristics.

  9. Reaction Time and Attention: Toward a New Standard in the Assessment of ADHD? A Pilot Study.

    Science.gov (United States)

    De la Torre, Gabriel G; Barroso, Juan M; León-Carrión, José; Mestre, Jose M; Bozal, Rocío Guil

    2015-12-01

    This pilot study shows results of an experiment comparing reaction times (RTs) and attentional performance between an ADHD group of 30 children and 30 controls, both Spanish speaking. The experiment was carried out using the Seville computerized neuropsychological battery (SNB). This study had two goals: One was to test sensitivity of SNB for attention deficits in ADHD and the second was to detect differences in RTs between ADHD and controls. Possible explanations and implications of such differences are also discussed. SNB computerized system was used to assess RTs and accuracy, and alternate forms of continuous performance task were used. Results showed high sensitivity of some of the SNB tests, especially cancellation tests. RTs were significantly different between groups. SNB represents a helpful tool for detection of attention deficits, and RT indices represent the most significant variable in differentiation of both groups studied. © The Author(s) 2012.

  10. Major trends of work of VNIIKRneft in the area of creating and perfecting drilling solutions on a nonaqaueous base

    Energy Technology Data Exchange (ETDEWEB)

    Kasperskii, B V

    1981-01-01

    Solution on a nonaqueous base (SNB) have good lubricating properties, are resistant to the effect of high temperatures, salt and hydrogen sulfide corrosion. The aqueous component is not filtered out of them into the bed. Carried out at VNIIKRneft were the perfection of recipes and the technology of application of the calcareous-bituminous solutions (CBS) developed at MINKhiGP im. Gubkina and the development of SNB of new types. To stabilize the CBS during drilling of clay rocks we recommend the mineralization of the aqueous component of the CBS by calcium chloride. Developed and incorporated into production is the technology of preliminary processing of a barite weighting compound of surfactants which increase its wetting ability by oil. Great attention is given to the development of methods of regulating structural-rheological properties of SNB by small additives of reagents. This permits a decrease in the formation of excesses of solutions. For CBS such regulators can be products of the interaction of organic acids and amines, particularly the commercially produced emulsifiers emul'tal and ukramine. The most effective agents which decrease viscosity of both nonaqueous and emulsion CBS are products of the low-temperature condensation reaction of polyethylene polyamines and organic acids. As a source of organic acids for synthesis of these products we can use SZhK of the C /sub 17/ fraction and higher, oxidized petrolatum, tall oil, asphalt tars of plant fats. Test results are presented for such additives in drilling boreholes at a depth of 5145 and 5432 m with the use of CBS. A recipe has been developed for a weighting compound of emulsion SNB.

  11. A systematic approach for development of a PWR cladding corrosion model

    International Nuclear Information System (INIS)

    Quecedo, M.; Serna, J.J.; Weiner, R.A.; Kersting, P.J.

    2001-01-01

    A new model for the in-reactor corrosion of Improved (low-tin) Zircaloy-4 cladding irradiated in commercial pressurized water reactors (PWRs) is described. The model is based on an extensive database of PWR fuel cladding corrosion data from fuel irradiated in commercial reactors, with a range of fuel duty and coolant chemistry control strategies which bracket current PWR fuel management practices. The fuel thermal duty with these current fuel management practices is characterized by a significant amount of sub-cooled nucleate boiling (SNB) during the fuel's residence in-core, and the cladding corrosion model is very sensitive to the coolant heat transfer models used to calculate the coolant temperature at the oxide surface. The systematic approach to developing the new corrosion model therefore began with a review and evaluation of several alternative models for the forced convection and SNB coolant heat transfer. The heat transfer literature is not sufficient to determine which of these heat transfer models is most appropriate for PWR fuel rod operating conditions, and the selection of the coolant heat transfer model used in the new cladding corrosion model has been coupled with a statistical analysis of the in-reactor corrosion enhancement factors and their impact on obtaining the best fit to the cladding corrosion data. The in-reactor corrosion enhancement factors considered in this statistical analysis are based on a review of the current literature for PWR cladding corrosion phenomenology and models. Fuel operating condition factors which this literature review indicated could have a significant effect on the cladding corrosion performance were also evaluated in detail in developing the corrosion model. An iterative least squares fitting procedure was used to obtain the model coefficients and select the coolant heat transfer models and in-reactor corrosion enhancement factors. This statistical procedure was completed with an exhaustive analysis of the model

  12. Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones.

    Science.gov (United States)

    Norton, Will H; Mangoli, Maryam; Lele, Zsolt; Pogoda, Hans-Martin; Diamond, Brianne; Mercurio, Sara; Russell, Claire; Teraoka, Hiroki; Stickney, Heather L; Rauch, Gerd-Jörg; Heisenberg, Carl-Philipp; Houart, Corinne; Schilling, Thomas F; Frohnhoefer, Hans-Georg; Rastegar, Sepand; Neumann, Carl J; Gardiner, R Mark; Strähle, Uwe; Geisler, Robert; Rees, Michelle; Talbot, William S; Wilson, Stephen W

    2005-02-01

    In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol-/- embryos, we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol-/- mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves. Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphenucleus and the trochlear motor nucleus are absent in mol-/- embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins.

  13. Review of the role of the sentinel node biopsy in neoadjuvant chemotherapy in women with breast cancer and negative or positive axillary node at diagnosis.

    Science.gov (United States)

    Ruano Pérez, R; Rebollo Aguirre, A C; García-Talavera San Miguel, P; Díaz Expósito, R; Vidal-Sicart, S; Cordero García, J M; Carrera Salazar, D; Rioja Martín, M E

    The role of the selective sentinel node biopsy (SNB) is increasing in relevance in breast cancer women with indication of neoadjuvant chemotherapy (NAC). The Radiosurgery Working Group of the SEMNIM is aware of the necessity of establishing the need for SNB before or after NAC, and also how to manage patients with axillary node-negative or node-positive. There is sufficient data to assess that the SNB with radioisotope techniques are feasible and safe in all these scenarios. An adequate axilla evaluation prior to surgery and the possibility of marking prior to NAC the nodes infiltrated must be the two main pillars to guarantee the success of the SNB. It has been shown that to incorporate the SNB in breast cancer women with indication of NAC increases the rate of a conservative treatment of the axilla that will be a clear benefit for these patients. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  14. Solidago canadensis invasion affects soil N-fixing bacterial communities in heterogeneous landscapes in urban ecosystems in East China.

    Science.gov (United States)

    Wang, Congyan; Jiang, Kun; Zhou, Jiawei; Wu, Bingde

    2018-03-12

    Soil nitrogen-fixing bacterial communities (SNB) can increase the level of available soil N via biological N-fixation to facilitate successful invasion of several invasive plant species (IPS). Meanwhile, landscape heterogeneity can greatly enhance regional invasibility and increase the chances of successful invasion of IPS. Thus, it is important to understand the soil micro-ecological mechanisms driving the successful invasion of IPS in heterogeneous landscapes. This study performed cross-site comparisons, via metagenomics, to comprehensively analyze the effects of Solidago canadensis invasion on SNB in heterogeneous landscapes in urban ecosystems. Rhizospheric soil samples of S. canadensis were obtained from nine urban ecosystems [Three replicate quadrats (including uninvaded sites and invaded sites) for each type of urban ecosystem]. S. canadensis invasion did not significantly affect soil physicochemical properties, the taxonomic diversity of plant communities, or the diversity and richness of SNB. However, some SNB taxa (i.e., f_Micromonosporaceae, f_Oscillatoriaceae, and f_Bacillaceae) changed significantly with S. canadensis invasion. Thus, S. canadensis invasion may alter the community structure, rather than the diversity and richness of SNB, to facilitate its invasion process. Of the nine urban ecosystems, the diversity and richness of SNB was highest in farmland wasteland. Accordingly, the community invasibility of farmland wasteland may be higher than that of the other types of urban ecosystem. In brief, landscape heterogeneity, rather than S. canadensis invasion, was the strongest controlling factor for the diversity and richness of SNB. One possible reason may be the differences in soil electrical conductivity and the taxonomic diversity of plant communities in the nine urban ecosystems, which can cause notable shifts in the diversity and richness of SNB. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. EFNS guidelines for the molecular diagnosis of neurogenetic disorders: motoneuron, peripheral nerve and muscle disorders.

    Science.gov (United States)

    Burgunder, J-M; Schöls, L; Baets, J; Andersen, P; Gasser, T; Szolnoki, Z; Fontaine, B; Van Broeckhoven, C; Di Donato, S; De Jonghe, P; Lynch, T; Mariotti, C; Spinazzola, A; Tabrizi, S J; Tallaksen, C; Zeviani, M; Harbo, H F; Finsterer, J

    2011-02-01

    These EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated. To collect data about planning, conditions and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta-analyses, review papers and guideline recommendations reviewed. The best level of evidence for genetic testing recommendation (B) can be found for the disorders with specific presentations, including familial amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, Charcot-Marie-Tooth 1A, myotonic dystrophy and Duchenne muscular dystrophy. For a number of less common disorders, a precise description of the phenotype, including the use of immunologic methods in the case of myopathies, is considered as good clinical practice to guide molecular genetic testing. These guidelines are provisional and the future availability of molecular-genetic epidemiological data about the neurogenetic disorders under discussion in this article will allow improved recommendation with an increased level of evidence. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.

  16. Effects of tripolar TENS on slow and fast motoneurons: a preliminary study using H-reflex recovery curve method.

    Science.gov (United States)

    Simorgh, L; Torkaman, G; Firoozabadi, S M

    2008-01-01

    This study aimed at examining the effect of tripolar TENS of vertebral column on the activity of slow and fast motoneurons on 10 healthy non-athlete women aged 22.7 +/- 2.21 yrs. H-reflex recovery curve of soleus (slow) and gastrocnemius (fast) muscles were recorded before and after applying tripolar TENS. For recording of this curve, rectangular paired stimuli were applied on tibial nerve (with 40-520 ISI, frequency of 0.2 Hz and pulse width of 600 micros). Our findings showed that maximum H-reflex recovery in gastrocnemius muscle appeared in the shorter ISI, while in soleus muscle, it appeared in the longer ISI and its amplitude slightly decreased after applying tripolar TENS. It is suggested that tripolar TENS excites not only the skin but also Ia and Ib afferents in the dorsal column. A Synaptic interaction of these afferents in spinal cord causes the inhibition of type I MNs and facilitation of type II MNs. This effect can be used in muscle tone modulation.

  17. Validation and head-to-head comparison of three nomograms predicting probability of lymph node invasion of prostate cancer in patients undergoing extended and/or sentinel lymph node dissection

    Energy Technology Data Exchange (ETDEWEB)

    Grivas, Nikolaos; Wit, Esther; Tillier, Corinne; Muilekom, Erik van; Poel, Henk van der [The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Department of Urology, Amsterdam (Netherlands); Pos, Floris [The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Department of Radiation Oncology, Amsterdam (Netherlands); Winter, Alexander [School of Medicine and Health Sciences, Carl von Ossietzky University, University Hospital for Urology, Klinikum Oldenburg, Oldenburg (Germany)

    2017-12-15

    The updated Winter nomogram is the only nomogram predicting lymph node invasion (LNI) in prostate cancer (PCa) patients based on sentinel node (SN) dissection (sLND). The aim of the study was to externally validate the Winter nomogram and examine its performance in patients undergoing extended pelvic lymph node dissection (ePLND), ePLND combined with SN biopsy (SNB) and sLND only. The results were compared with the Memorial Sloan Kettering Cancer Center (MSKCC) and updated Briganti nomograms. This retrospective study included 1183 patients with localized PCa undergoing robot-assisted laparoscopic radical prostatectomy (RARP) combined with pelvic lymphadenectomy and 224 patients treated with sLND and external beam radiotherapy (EBRT), aiming to offer pelvic radiotherapy only in case of histologically positive SNs. In the RARP population, ePLND was applied in 956 (80.8%) patients,while 227 (19.2%) patients were offered ePLND combined with additional SNB. The median numbers of removed nodes were 10 (interquartile range, IQR = 6-14), 15 (IQR = 10-20) and 7 (IQR = 4-10) in the ePLND, ePLND + SNB, and sLND groups, respectively. Corresponding LNI rates were 16.6%, 25.5% and 42%. Based on the AUC, the performance of the Briganti nomogram (0.756) in the ePLND group was superior to both the MSKCC (0.744) and Winter nomogram (0.746). The Winter nomogram, however, was the best predictor of LNI in both the ePLND + SNB (0.735) and sLND (0.709) populations. In the calibration analysis, all nomograms showed better accuracy in the low/intermediate risk patients, while in the high-risk population, an overestimation of the risk for LNI was observed. The SN-based updated nomogram showed better prediction in the SN population. The results were also comparable, relative to predictive tools developed with (e)PLND, suggesting a difference in sampling accuracy between SNB and non-SNB. Patients who benefit most from the nomogram would be those with a low/intermediate risk of LN metastasis

  18. Who put the Holes in the Swiss Cheese? Currency Crisis Under Appreciation Pressure

    Directory of Open Access Journals (Sweden)

    Berthold Kristin

    2018-01-01

    Full Text Available We examine the reasons why the SNB gave up the lower floor of the 1.20 CHF/EUR exchange rate arrangement. Three types of shocks played a role: Exogenous shocks to the autonomous component of money demand, interest rate decreases of the ECB, as well as appreciation expectations. In order to defend these shocks, the SNB intervened heavily in the foreign exchange market. This led to an accumulation of reserves in the central bank’s balance sheet of the size of 80% of Swiss GDP. Interestingly, the SNB did not lower the interest rate into the negative range during the time period where the peg was in place. Hence, the SNB did not do ”whatever it takes” to defend the peg.

  19. Sentinel node biopsy in head and neck cancer

    DEFF Research Database (Denmark)

    Ross, Gary L; Soutar, David S; Gordon MacDonald, D

    2004-01-01

    BACKGROUND: The aim was to determine the reliability and reproducibility of sentinel node biopsy (SNB) as a staging tool in head and neck squamous cell carcinoma (HNSCC) for T1/2 clinically N0 patients by means of a standardized technique. METHODS: Between June 1998 and June 2002, 227 SNB procedu...... cavity/oropharynx in a standardized fashion by centers worldwide. For the majority of these tumors the SNB technique can be used alone as a staging tool....

  20. Interest Rate Dynamics and Monetary Policy Implementation in Switzerland

    OpenAIRE

    Puriya Abbassi; Dieter Nautz; Christian Offermanns

    2010-01-01

    The maturity of the operational target of monetary policy is a distinguishing feature of the SNB's operational framework of monetary policy. While most central banks use targets for the overnight rate to signal the policy-intended interest rate level, the SNB announces a target range for the three-month Libor. This paper investigates the working and the consequences of the SNB's unique operational framework for the behavior of Swiss money market rates before and during the financial crisis.

  1. Neuromodulation of reciprocal glutamatergic inhibition between antagonistic motoneurons by 5-hydroxytryptamine (5-HT) in crayfish walking system.

    Science.gov (United States)

    Pearlstein, E; Clarac, F; Cattaert, D

    1998-01-23

    In an in vitro preparation of the crayfish thoracic locomotor system, paired intracellular recordings were performed from antagonistic depressor (Dep) and levator (Lev) motoneurons (MNs) that control the second joint of walking legs. Connections between these two groups of MNs consist mainly of inhibitory connections and weak electrotonic synapses. Injection of depolarizing current into a Lev MN results in a hyperpolarization in a Dep MN, and vice versa. This reciprocal glutamatergic inhibition, is not changed in the presence of the sodium channel blocker tetrodotoxin (TTX) and therefore is likely supported by a direct connection between MNs. By contrast, reciprocal inhibition is largely reduced in the presence of 5-hydroxytryptamine (5-HT; 10 microM). Direct micro-application of glutamate pressure-ejected close to an intracellularly recorded MN, evoked an inhibitory response in that MN, accompanied by a decrease of input resistance. These two effects were dramatically reduced in the presence of 5-HT. Thus 5-HT could be involved in mechanisms of dynamic reconfigurations of the neural network controlling leg movements in crayfish.

  2. Nb 3d and O 1s core levels and chemical bonding in niobates

    International Nuclear Information System (INIS)

    Atuchin, V.V.; Kalabin, I.E.; Kesler, V.G.; Pervukhina, N.V.

    2005-01-01

    A set of available experimental data on binding energies of Nb 3d 5/2 and O 1s core levels in niobates has been observed with using energy difference (O 1s-Nb 3d 5/2 ) as a robust parameter for compound characterization. An empirical relationship between (O 1s-Nb 3d 5/2 ) values measured with XPS for Nb 5+ -niobates and mean chemical bond length L(Nb-O) has been discussed. A range of (O 1s-Nb 3d 5/2 ) values possible in Nb 5+ -niobates has been defined. An energy gap ∼1.4-1.8 eV is found between (O 1s-Nb 3d 5/2 ) values reasonable for Nb 5+ and Nb 4+ states in niobates

  3. Sciatic nerve blocks for diagnosis of piriformis syndrome

    International Nuclear Information System (INIS)

    Owashi, Kazuya; Harada, Mikio; Utsumi, Hideaki; Sugawara, Hirobumi; Oyama, Kaori; Takei, Isao

    2010-01-01

    We used sciatic nerve block (SNB) to make the differential diagnosis of piriformis syndrome in 188 consecutive patients with sciatica in whom it was impossible to make the diagnosis based on the lumbar MRI findings. We rated the effectiveness of SNB as excellent (60%), good (25%) and poor (15%). After performing SNBs, lumbar radicular blocks, and surgeries based on the initial diagnosis, the final diagnoses were piriformis syndrome (56%), piriformis syndrome complicated with lumbar degenerative disease (4%), lumbar degenerative disease (23%), others or unknown (16%). The prevalence of piriformis syndrome in the excellent effectiveness group was 81%. SNB was effective in all patients with piriformis syndrome and in 66% of the lumbar degeneration patients. The diagnostic value of SNB is of limited value for differentiating piriformis syndrome from lumbar degenerative disease. (author)

  4. Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

    Science.gov (United States)

    Beers, D. R.; Ho, B. K.; Siklos, L.; Alexianu, M. E.; Mosier, D. R.; Mohamed, A. H.; Otsuka, Y.; Kozovska, M. E.; McAlhany, R. E.; Smith, R. G.; hide

    2001-01-01

    Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

  5. Nb 3d and O 1s core levels and chemical bonding in niobates

    Energy Technology Data Exchange (ETDEWEB)

    Atuchin, V.V. [Laboratory of Optical Materials and Structures, Institute of Semiconductor Physics, SB RAS, Novosibirsk 630090 (Russian Federation)]. E-mail: atuchin@thermo.isp.nsc.ru; Kalabin, I.E. [Laboratory of Optical Materials and Structures, Institute of Semiconductor Physics, SB RAS, Novosibirsk 630090 (Russian Federation); Kesler, V.G. [Technical Center, Institute of Semiconductor Physics, SB RAS, Novosibirsk 630090 (Russian Federation); Pervukhina, N.V. [Laboratory of Crystal Chemistry, Institute of Inorganic Chemistry, SB RAS, Novosibirsk 630090 (Russian Federation)

    2005-02-01

    A set of available experimental data on binding energies of Nb 3d{sub 5/2} and O 1s core levels in niobates has been observed with using energy difference (O 1s-Nb 3d{sub 5/2}) as a robust parameter for compound characterization. An empirical relationship between (O 1s-Nb 3d{sub 5/2}) values measured with XPS for Nb{sup 5+}-niobates and mean chemical bond length L(Nb-O) has been discussed. A range of (O 1s-Nb 3d{sub 5/2}) values possible in Nb{sup 5+}-niobates has been defined. An energy gap {approx}1.4-1.8 eV is found between (O 1s-Nb 3d{sub 5/2}) values reasonable for Nb{sup 5+} and Nb{sup 4+} states in niobates.

  6. The surgical importance of an axillary arch in sentinel node biopsy.

    LENUS (Irish Health Repository)

    Ridgway, P F

    2011-03-01

    When Carl Langer described the aberrant axillary arch in 1846 its relevance in sentinel node biopsy (SNB) surgery could not have been contemplated. The authors define an incidence and elucidate relevance of the arch in SNB of the axilla.

  7. Sentinel node status prediction by four statistical models: results from a large bi-institutional series (n = 1132).

    Science.gov (United States)

    Mocellin, Simone; Thompson, John F; Pasquali, Sandro; Montesco, Maria C; Pilati, Pierluigi; Nitti, Donato; Saw, Robyn P; Scolyer, Richard A; Stretch, Jonathan R; Rossi, Carlo R

    2009-12-01

    To improve selection for sentinel node (SN) biopsy (SNB) in patients with cutaneous melanoma using statistical models predicting SN status. About 80% of patients currently undergoing SNB are node negative. In the absence of conclusive evidence of a SNBassociated survival benefit, these patients may be over-treated. Here, we tested the efficiency of 4 different models in predicting SN status. The clinicopathologic data (age, gender, tumor thickness, Clark level, regression, ulceration, histologic subtype, and mitotic index) of 1132 melanoma patients who had undergone SNB at institutions in Italy and Australia were analyzed. Logistic regression, classification tree, random forest, and support vector machine models were fitted to the data. The predictive models were built with the aim of maximizing the negative predictive value (NPV) and reducing the rate of SNB procedures though minimizing the error rate. After cross-validation logistic regression, classification tree, random forest, and support vector machine predictive models obtained clinically relevant NPV (93.6%, 94.0%, 97.1%, and 93.0%, respectively), SNB reduction (27.5%, 29.8%, 18.2%, and 30.1%, respectively), and error rates (1.8%, 1.8%, 0.5%, and 2.1%, respectively). Using commonly available clinicopathologic variables, predictive models can preoperatively identify a proportion of patients ( approximately 25%) who might be spared SNB, with an acceptable (1%-2%) error. If validated in large prospective series, these models might be implemented in the clinical setting for improved patient selection, which ultimately would lead to better quality of life for patients and optimization of resource allocation for the health care system.

  8. Sentinel lymph node biopsy in patients with a needle core biopsy diagnosis of ductal carcinoma in situ: is it justified?

    LENUS (Irish Health Repository)

    Doyle, B

    2012-02-01

    BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has increased markedly with the introduction of population-based mammographic screening. DCIS is usually diagnosed non-operatively. Although sentinel lymph node biopsy (SNB) has become the standard of care for patients with invasive breast carcinoma, its use in patients with DCIS is controversial. AIM: To examine the justification for offering SNB at the time of primary surgery to patients with a needle core biopsy (NCB) diagnosis of DCIS. METHODS: A retrospective analysis was performed of 145 patients with an NCB diagnosis of DCIS who had SNB performed at the time of primary surgery. The study focused on rates of SNB positivity and underestimation of invasive carcinoma by NCB, and sought to identify factors that might predict the presence of invasive carcinoma in the excision specimen. RESULTS: 7\\/145 patients (4.8%) had a positive sentinel lymph node, four macrometastases and three micrometastases. 6\\/7 patients had invasive carcinoma in the final excision specimen. 55\\/145 patients (37.9%) with an NCB diagnosis of DCIS had invasive carcinoma in the excision specimen. The median invasive tumour size was 6 mm. A radiological mass and areas of invasion <1 mm, amounting to "at least microinvasion" on NCB were predictive of invasive carcinoma in the excision specimen. CONCLUSIONS: SNB positivity in pure DCIS is rare. In view of the high rate of underestimation of invasive carcinoma in patients with an NCB diagnosis of DCIS in this study, SNB appears justified in this group of patients.

  9. Predicting pre-planting risk of Stagonospora nodorum blotch in winter wheat using machine learning models

    Science.gov (United States)

    Pre-planting factors have been associated with the late-season severity of Stagonospora nodorum blotch (SNB), caused by the fungal pathogen Parastagonospora nodorum, in winter wheat (Triticum aestivum). The relative importance of these factors in the risk of SNB has not been determined and this know...

  10. Sentinel node biopsy performance after neoadjuvant chemotherapy in locally advanced breast cancer: A systematic review and meta-analysis.

    Science.gov (United States)

    Mocellin, Simone; Goldin, Elena; Marchet, Alberto; Nitti, Donato

    2016-01-15

    The use of sentinel node biopsy (SNB) after neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer is debated. Our aim was to quantitatively review the available evidence on the performance of SNB after NAC in patients with locally advanced breast cancer. We performed a systematic review (by searching the PubMed, Cochrane and Scopus databases) and random effects meta-analysis to investigate on the feasibility and accuracy of SNB in these patients. The two outcomes of interest were the sentinel node identification rate (SIR) and the false negative rate (FNR). Sensitivity analysis and meta-regression were used to investigate the potential sources of between-study heterogeneity. We retrieved 72 eligible studies enrolling 7,451 patients. Upon meta-analysis, summary SIR resulted 89.6% [95% confidence interval (CI): 87.8-91.2; heterogeneity I(2): 76.9%], which poorly compares with the 95% SIR observed in some recent series of early breast cancer. The summary FNR resulted 14.2% (CI: 12.5-16.0; heterogeneity I(2): 29.1%), which was significantly higher than the 8-10% reference value. Considering an average post-NAC lymph node positivity rate of 50%, the downstaging due to false negative SNB would occur in 7/100 patients (with an excess error rate of 2-3/100 as compared to the early-stage setting). No plausible source of between-study heterogeneity was found. Based on the largest series of studies ever meta-analyzed, our findings highlight the limits of SNB performance in this population, where the impact of SNB on patient survival is still to be defined. © 2015 UICC.

  11. Hypoxia triggers short term potentiation of phrenic motoneuron discharge after chronic cervical spinal cord injury

    Science.gov (United States)

    Lee, Kun-Ze; Sandhu, Milapjit S.; Dougherty, Brendan J.; Reier, Paul J.; Fuller, David D.

    2014-01-01

    Repeated exposure to hypoxia can induce spinal neuroplasticity as well as respiratory and somatic motor recovery after spinal cord injury (SCI). The purpose of the present study was to define the capacity for a single bout of hypoxia to trigger short-term plasticity in phrenic output after cervical SCI, and to determine the phrenic motoneuron (PhrMN) bursting and recruitment patterns underlying the response. Hypoxia-induced short term potentiation (STP) of phrenic motor output was quantified in anesthetized rats 11 wks following lateral spinal hemisection at C2 (C2Hx). A 3-min hypoxic episode (12–14% O2) always triggered STP of inspiratory burst amplitude, the magnitude of which was greater in phrenic bursting ipsilateral vs. contralateral to C2Hx. We next determined if STP could be evoked in recruited (silent) PhrMNs ipsilateral to C2Hx. Individual PhrMN action potentials were recorded during and following hypoxia using a “single fiber” approach. STP of bursting activity did not occur in cells initiating bursting at inspiratory onset, but was robust in recruited PhrMNs as well as previously active cells initiating bursting later in the inspiratory effort. We conclude that following chronic C2Hx, a single bout of hypoxia triggers recruitment of PhrMNs in the ipsilateral spinal cord with bursting that persists beyond the hypoxic exposure. The results provide further support for the use of short bouts of hypoxia as a neurorehabilitative training modality following SCI. PMID:25448009

  12. Does Tumor Depth Affect Nodal Upstaging in Squamous Cell Carcinoma of the Head and Neck?

    DEFF Research Database (Denmark)

    Alkureishi, Lee; Ross, Gary; Shoaib, Taimur

    2007-01-01

    AND METHODS:: One hundred seventy-two patients with cT1/2 N0 squamous cell carcinoma (SCC) of the oral cavity/oropharynx undergoing primary resection and either sentinel node biopsy (SNB) or SNB-assisted neck dissection as a staging tool for the cN0 neck. Harvested nodes were examined with hematoxylin...

  13. Handy-type gamma probe-guided sentinel lymph node biopsy for breast cancer under ambulatory local anesthesia

    International Nuclear Information System (INIS)

    Fujiwara, Ikuya; Nagata, Hiroaki; Takaki, Wataru

    2016-01-01

    Prior to surgery for clinically node-negative breast cancer, we diagnosed metastases on the basis of permanent sections and sentinel lymph node biopsy (SNB) using the combined radio isotope (RI)/blue dye method with a hand-type gamma probe under ambulatory local anesthesia. SNB was performed for 99 patients with 103 lesions, including 4 patients with bilateral breast cancer. We achieved an identification rate of 100%, in which the identification pattern included detection by RI and blue-dye in 65 patients (63.1%), detection by RI alone in 37 patients (35.9%), and blue-dye alone in one patient (1.0%). Sentinel lymph node metastasis was macrometastasis in 21 patients (20.4%), micrometastasis in 8 patients (7.8%), and isolated tumor cells in patients (4.9%). In the 80 patients who did not undergo post-SNB axillary lymph node dissection, the median observation period was 33 months and there were no recurrences in the axillary lymph nodes observed. Although the present procedure requires two surgeries, it is a useful method that enables metastasis detection and highly accurate SNB. (author)

  14. Clinical results of sentinel lymph node (SN) biopsy for oral cancer. Relationship between SN localization and metastasis in tongue cancer

    International Nuclear Information System (INIS)

    Shintani, Satoru; Nakashiro, Koh-ichi; Hino, Satoshi; Terakado, Nagaaki; Hamakawa, Hiroyuki

    2005-01-01

    Attempts were made to detect micrometastasis in N0 neck of oral cancer patients using sentinel lymph node (SN) biopsy (SNB). We previously described our approach to identify SN using a radioisotope ( 99m Tc-Tin colloid)-guided and dye-guided method. Micrometastases were detected by means of serial sections and real-time polymerase chain reaction (PCR) based on squamous cell carcinoma (SCC) antigen mRNA. In this study, we evaluated the radiolocalization of SN and identification of metastatic lymph node in N0 oral cancer patients. The positive rate of metastatic lymph node in N0 oral cancer was 35% and the diagnostic sensitivity of SNB was 95%. The SNB detected subclinical metastases in 4 of 10 N0 patients with tongue cancer. Moreover, in 3 of these 4 cases, all metastatic lymph nodes consisted with SNs. Postoperative cervical metastasis was observed in a patient whose SNB was negative. While more experience is needed, we believe the SN concept for tongue cancer is established, and practical application in clinical settings is anticipated. (author)

  15. Monosynaptic Ia projections from intrinsic hand muscles to forearm motoneurones in humans.

    Science.gov (United States)

    Marchand-Pauvert, V; Nicolas, G; Pierrot-Deseilligny, E

    2000-05-15

    Heteronymous Ia excitatory projections from intrinsic hand muscles to human forearm motoneurones (MNs) were investigated. Changes in firing probability of single motor units (MUs) in the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), extensor carpi radialis (ECR), extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) were studied after electrical stimuli were applied to the median and ulnar nerve at wrist level and to the corresponding homonymous nerve at elbow level. Homonymous facilitation, occurring at the same latency as the H reflex, and therefore attributed to monosynaptic Ia EPSPs, was found in all the sampled units. In many MUs an early facilitation was also evoked by heteronymous low-threshold afferents from intrinsic hand muscles. The low threshold (between 0.5 and 0.6 times motor threshold (MT)) and the inability of a pure cutaneous stimulation to reproduce this effect indicate that it is due to stimulation of group I muscle afferents. Evidence for a similar central delay (monosynaptic) in heteronymous as in homonymous pathways was accepted when the difference in latencies of the homonymous and heteronymous peaks did not differ from the estimated supplementary afferent conduction time from wrist to elbow level by more than 0.5 ms (conduction velocity in the fastest Ia afferents between wrist and elbow levels being equal to 69 m s-1). A statistically significant heteronymous monosynaptic Ia excitation from intrinsic hand muscles supplied by both median and ulnar nerves was found in MUs belonging to all forearm motor nuclei tested (although not in ECU MUs after ulnar stimulation). It was, however, more often found in flexors than in extensors, in wrist than in finger muscles and in muscles operating in the radial than in the ulnar side. It is argued that the connections of Ia afferents from intrinsic hand muscles to forearm MNs, which are stronger and more widely distributed than in the cat

  16. A neurochemical map of the developing amphioxus nervous system

    Directory of Open Access Journals (Sweden)

    Candiani Simona

    2012-06-01

    Full Text Available Abstract Background Amphioxus, representing the most basal group of living chordates, is the best available proxy for the last invertebrate ancestor of the chordates. Although the central nervous system (CNS of amphioxus comprises only about 20,000 neurons (as compared to billions in vertebrates, the developmental genetics and neuroanatomy of amphioxus are strikingly vertebrate-like. In the present study, we mapped the distribution of amphioxus CNS cells producing distinctive neurochemicals. To this end, we cloned genes encoding biosynthetic enzymes and/or transporters of the most common neurotransmitters and assayed their developmental expression in the embryo and early larva. Results By single and double in situ hybridization experiments, we identified glutamatergic, GABAergic/glycinergic, serotonergic and cholinergic neurons in developing amphioxus. In addition to characterizing the distribution of excitatory and inhibitory neurons in the developing amphioxus CNS, we observed that cholinergic and GABAergic/glycinergic neurons are segmentally arranged in the hindbrain, whereas serotonergic, glutamatergic and dopaminergic neurons are restricted to specific regions of the cerebral vesicle and the hindbrain. We were further able to identify discrete groups of GABAergic and glutamatergic interneurons and cholinergic motoneurons at the level of the primary motor center (PMC, the major integrative center of sensory and motor stimuli of the amphioxus nerve cord. Conclusions In this study, we assessed neuronal differentiation in the developing amphioxus nervous system and compiled the first neurochemical map of the amphioxus CNS. This map is a first step towards a full characterization of the neurotransmitter signature of previously described nerve cell types in the amphioxus CNS, such as motoneurons and interneurons.

  17. Immature spinal locomotor output in children with Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Germana Cappellini

    2016-10-01

    Full Text Available Detailed descriptions of gait impairments have been reported in cerebral palsy (CP, but it is still unclear how maturation of the spinal motoneuron output is affected. Spatiotemporal alpha-motoneuron activation during walking can be assessed by mapping the electromyographic activity profiles from several, simultaneously recorded muscles onto the anatomical rostrocaudal location of the motoneuron pools in the spinal cord, and by means of factor analysis of the muscle activity profiles. Here, we analysed gait kinematics and EMG activity of 11 pairs of bilateral muscles with lumbosacral innervation in 35 children with CP (19 diplegic, 16 hemiplegic, 2-12 years and 33 typically developing (TD children (1-12 years. TD children showed a progressive reduction of EMG burst durations and a gradual reorganization of the spatiotemporal motoneuron output with increasing age. By contrast, children with CP showed very limited age-related changes of EMG durations and motoneuron output, as well as of limb intersegmental coordination and foot trajectory control (on both sides for diplegic children and the affected side for hemiplegic children. Factorization of the EMG signals revealed a comparable structure of the motor output in children with CP and TD children, but significantly wider temporal activation patterns in children with CP, resembling the patterns of much younger TD infants. A similar picture emerged when considering the spatiotemporal maps of alpha-motoneuron activation. Overall, the results are consistent with the idea that early injuries to developing motor regions of the brain substantially affect the maturation of the spinal locomotor output and consequently the future locomotor behaviour.

  18. Exacerbation of Facial Motoneuron Loss after Facial Nerve Axotomy in CCR3-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Derek A Wainwright

    2009-11-01

    Full Text Available 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.

  19. Support vector machine learning model for the prediction of sentinel node status in patients with cutaneous melanoma.

    Science.gov (United States)

    Mocellin, Simone; Ambrosi, Alessandro; Montesco, Maria Cristina; Foletto, Mirto; Zavagno, Giorgio; Nitti, Donato; Lise, Mario; Rossi, Carlo Riccardo

    2006-08-01

    Currently, approximately 80% of melanoma patients undergoing sentinel node biopsy (SNB) have negative sentinel lymph nodes (SLNs), and no prediction system is reliable enough to be implemented in the clinical setting to reduce the number of SNB procedures. In this study, the predictive power of support vector machine (SVM)-based statistical analysis was tested. The clinical records of 246 patients who underwent SNB at our institution were used for this analysis. The following clinicopathologic variables were considered: the patient's age and sex and the tumor's histological subtype, Breslow thickness, Clark level, ulceration, mitotic index, lymphocyte infiltration, regression, angiolymphatic invasion, microsatellitosis, and growth phase. The results of SVM-based prediction of SLN status were compared with those achieved with logistic regression. The SLN positivity rate was 22% (52 of 234). When the accuracy was > or = 80%, the negative predictive value, positive predictive value, specificity, and sensitivity were 98%, 54%, 94%, and 77% and 82%, 41%, 69%, and 93% by using SVM and logistic regression, respectively. Moreover, SVM and logistic regression were associated with a diagnostic error and an SNB percentage reduction of (1) 1% and 60% and (2) 15% and 73%, respectively. The results from this pilot study suggest that SVM-based prediction of SLN status might be evaluated as a prognostic method to avoid the SNB procedure in 60% of patients currently eligible, with a very low error rate. If validated in larger series, this strategy would lead to obvious advantages in terms of both patient quality of life and costs for the health care system.

  20. Lymph Drainage Studied by Lymphoscintigraphy in the Arms after Sentinel Node Biopsy Compared with Axillary Lymph Node Dissection Following Conservative Breast Cancer Surgery

    International Nuclear Information System (INIS)

    Celebioglu, F.; Perbeck, L.; Frisell, J.; Groendal, E.; Svensson, L.; Danielsson, R.

    2007-01-01

    Purpose: To investigate lymphatic drainage as measured by lymphoscintigraphy in the arms of patients undergoing either sentinel lymph node biopsy (SNB) or axillary lymph node dissection (ALND). Material and Methods: From January 2001 to December 2002, 30 patients with unilateral invasive breast carcinoma underwent breast-conserving surgery with SNB and 30 patients with ALND. All patients received radiotherapy to the breast. Lymphoscintigraphy was performed, and skin circulation, skin temperature, and arm volume were measured 2-3 years after radiotherapy. Results: None of the 30 patients who underwent SNB showed any clinical manifestation of lymphedema. Of the 30 patients undergoing ALND, six (20%) had clinical lymphedema, with an arm volume that was >10% larger on the operated than on the non-operated side (P<0.01). Scintigraphically, visual analysis revealed lymphatic dysfunction in three patients, manifested as forearm dermal back flow. Two of these patients also had an increased arm volume. Quantitative analysis showed no differences between the groups, apart from a smaller amount of isotope in the axilla in the ALND group. There was no difference in skin circulation or skin temperature. Conclusion: Our study shows that lymph drainage in the operated arm compared with the non-operated arm was less affected by SNB than by ALND, and that morbidity associated with SNB was lower than with ALND. However, the results do not confirm our hypothesis that lymphoscintigraphy can reveal differences in lymph circulation that are not evident clinically in the form of manifest lymphedema. The most sensitive clinical method of assessing lymph drainage seems to be measurement of arm volume

  1. Model Comparison for Electron Thermal Transport

    Science.gov (United States)

    Moses, Gregory; Chenhall, Jeffrey; Cao, Duc; Delettrez, Jacques

    2015-11-01

    Four electron thermal transport models are compared for their ability to accurately and efficiently model non-local behavior in ICF simulations. Goncharov's transport model has accurately predicted shock timing in implosion simulations but is computationally slow and limited to 1D. The iSNB (implicit Schurtz Nicolai Busquet electron thermal transport method of Cao et al. uses multigroup diffusion to speed up the calculation. Chenhall has expanded upon the iSNB diffusion model to a higher order simplified P3 approximation and a Monte Carlo transport model, to bridge the gap between the iSNB and Goncharov models while maintaining computational efficiency. Comparisons of the above models for several test problems will be presented. This work was supported by Sandia National Laboratory - Albuquerque and the University of Rochester Laboratory for Laser Energetics.

  2. Feasibility of Real-Time Near-Infrared Fluorescence Tracer Imaging in Sentinel Node Biopsy for Oral Cavity Cancer Patients

    DEFF Research Database (Denmark)

    Christensen, Anders; Juhl, Karina; Charabi, Birgitte

    2016-01-01

    BACKGROUND: Sentinel node biopsy (SNB) is an established method in oral squamous cell carcinoma (OSCC) for staging the cN0 neck and to select patients who will benefit from a neck dissection. Near-infrared fluorescence (NIRF) imaging has the potential to improve the SNB procedure by facilitating...... intraoperative visual identification of the sentinel lymph node (SN). The purpose of this study was to evaluate the feasibility of fluorescence tracer imaging for SN detection in conjunction with conventional radio-guided technique. METHODS: Prospective study of patients with primary OSCC planned for tumor...... be identified in vivo using NIRF imaging, and the majority of those were located in level 1 close to the primary tumor. CONCLUSIONS: A combined fluorescent and radioactive tracer for SNB is feasible, and the additional use of NIRF imaging may improve the accuracy of SN identification in oral cancer patients...

  3. A predictive tool to estimate the risk of axillary metastases in breast cancer patients with negative axillary ultrasound

    DEFF Research Database (Denmark)

    Meretoja, T J; Heikkilä, P S; Mansfield, A S

    2014-01-01

    of this study was to evaluate the risk factors for axillary metastases in breast cancer patients with negative preoperative axillary ultrasound. METHODS: A total of 1,395 consecutive patients with invasive breast cancer and SNB formed the original patient series. A univariate analysis was conducted to assess...... risk factors for axillary metastases. Binary logistic regression analysis was conducted to form a predictive model based on the risk factors. The predictive model was first validated internally in a patient series of 566 further patients and then externally in a patient series of 2,463 patients from......BACKGROUND: Sentinel node biopsy (SNB) is the "gold standard" in axillary staging in clinically node-negative breast cancer patients. However, axillary treatment is undergoing a paradigm shift and studies are being conducted on whether SNB may be omitted in low-risk patients. The purpose...

  4. Molecular Mechanisms in Amyotrophic Lateral Sclerosis: The Role of Angiogenin, a Secreted RNase

    Directory of Open Access Journals (Sweden)

    Isabela M. Aparicio-Erriu

    2012-11-01

    Full Text Available Amyotrophic lateral sclerosis is a fatal neurodegenerative disease caused by the loss of motoneurons. The precise molecular and cellular basis for neuronal death is not yet well established, but the contemporary view is that it is a culmination of multiple aberrant biological processes. Among the proposed mechanisms of motoneuron degeneration, alterations in the homeostasis of RNA binding proteins (RBP and the consequent changes in RNA metabolism have received attention recently.The ribonuclease, angiogenin was one of the first RBPs associated with familial and sporadic ALS. It is enriched in motoneurons under physiological conditions, and is required for motoneuron survival under stress conditions. Furthermore, delivery of angiogenin protects cultured motoneurons against stress-induced injury, and significantly increases the survival of motoneurons in SODG93A mice. In this overview on the role of angiogenin in RNA metabolism and in the control of motoneuron survival, we discuss potential pathogenic mechanisms of angiogenin dysfunction relevant to ALS and other neurodegenerative disorders. We also discuss recent evidence demonstrating that angiogenin secreted from stressed motoneurons may alter RNA metabolism in astrocytes.

  5. Spatiotemporal organization of alpha-motoneuron activity in the human spinal cord during different gaits and gait transitions.

    Science.gov (United States)

    Ivanenko, Y P; Cappellini, G; Poppele, R E; Lacquaniti, F

    2008-06-01

    Here we studied the spatiotemporal organization of motoneuron (MN) activity during different human gaits. We recorded the electromyographic (EMG) activity patterns in 32 ipsilateral limb and trunk muscles from normal subjects while running and walking on a treadmill (3-12 km/h). In addition, we recorded backward walking and skipping, a distinct human gait that comprises the features of both walking and running. We mapped the recorded EMG activity patterns onto the spinal cord in approximate rostrocaudal locations of the MN pools. The activation of MNs tends to occur in bursts and be segregated by spinal segment in a gait-specific manner. In particular, sacral and cervical activation timings were clearly gait-dependent. Swing-related activity constituted an appreciable fraction (> 30%) of the total MN activity of leg muscles. Locomoting at non-preferred speeds (running and walking at 5 and 9 km/h, respectively) showed clear differences relative to preferred speeds. Running at low speeds was characterized by wider sacral activation. Walking at high non-preferred speeds was accompanied by an 'atypical' locus of activation in the upper lumbar spinal cord during late stance and by a drastically increased activation of lumbosacral segments. The latter findings suggest that the optimal speed of gait transitions may be related to an optimal intensity of the total MN activity, in addition to other factors previously described. The results overall support the idea of flexibility and adaptability of spatiotemporal activity in the spinal circuitry with constraints on the temporal functional connectivity of hypothetical pulsatile burst generators.

  6. Testing nonlocal models of electron thermal conduction for magnetic and inertial confinement fusion applications

    Science.gov (United States)

    Brodrick, J. P.; Kingham, R. J.; Marinak, M. M.; Patel, M. V.; Chankin, A. V.; Omotani, J. T.; Umansky, M. V.; Del Sorbo, D.; Dudson, B.; Parker, J. T.; Kerbel, G. D.; Sherlock, M.; Ridgers, C. P.

    2017-09-01

    Three models for nonlocal electron thermal transport are here compared against Vlasov-Fokker-Planck (VFP) codes to assess their accuracy in situations relevant to both inertial fusion hohlraums and tokamak scrape-off layers. The models tested are (i) a moment-based approach using an eigenvector integral closure (EIC) originally developed by Ji, Held, and Sovinec [Phys. Plasmas 16, 022312 (2009)]; (ii) the non-Fourier Landau-fluid (NFLF) model of Dimits, Joseph, and Umansky [Phys. Plasmas 21, 055907 (2014)]; and (iii) Schurtz, Nicolaï, and Busquet's [Phys. Plasmas 7, 4238 (2000)] multigroup diffusion model (SNB). We find that while the EIC and NFLF models accurately predict the damping rate of a small-amplitude temperature perturbation (within 10% at moderate collisionalities), they overestimate the peak heat flow by as much as 35% and do not predict preheat in the more relevant case where there is a large temperature difference. The SNB model, however, agrees better with VFP results for the latter problem if care is taken with the definition of the mean free path. Additionally, we present for the first time a comparison of the SNB model against a VFP code for a hohlraum-relevant problem with inhomogeneous ionisation and show that the model overestimates the heat flow in the helium gas-fill by a factor of ˜2 despite predicting the peak heat flux to within 16%.

  7. ALS Patient Stem Cells for Unveiling Disease Signatures of Motoneuron Susceptibility: Perspectives on the Deadly Mitochondria, ER Stress and Calcium Triad

    Science.gov (United States)

    Kaus, Anjoscha; Sareen, Dhruv

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a largely sporadic progressive neurodegenerative disease affecting upper and lower motoneurons (MNs) whose specific etiology is incompletely understood. Mutations in superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TARDBP/TDP-43) and C9orf72, have been identified in subsets of familial and sporadic patients. Key associated molecular and neuropathological features include ubiquitinated TDP-43 inclusions, stress granules, aggregated dipeptide proteins from mutant C9orf72 transcripts, altered mitochondrial ultrastructure, dysregulated calcium homeostasis, oxidative and endoplasmic reticulum (ER) stress, and an unfolded protein response (UPR). Such impairments have been documented in ALS animal models; however, whether these mechanisms are initiating factors or later consequential events leading to MN vulnerability in ALS patients is debatable. Human induced pluripotent stem cells (iPSCs) are a valuable tool that could resolve this “chicken or egg” causality dilemma. Relevant systems for probing pathophysiologically affected cells from large numbers of ALS patients and discovering phenotypic disease signatures of early MN susceptibility are described. Performing unbiased ‘OMICS and high-throughput screening in relevant neural cells from a cohort of ALS patient iPSCs, and rescuing mitochondrial and ER stress impairments, can identify targeted therapeutics for increasing MN longevity in ALS. PMID:26635528

  8. Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity.

    Science.gov (United States)

    Bhagat, Ruchi; Fortna, Samuel R; Browning, Kirsteen N

    2015-01-01

    Obesity is recognized as being multifactorial in origin, involving both genetic and environmental factors. The perinatal period is known to be critically important in the development of neural circuits responsible for energy homeostasis and the integration of autonomic reflexes. Diet-induced obesity alters the biophysical, pharmacological and morphological properties of vagal neurocircuits regulating upper gastrointestinal tract functions, including satiety. Less information is available, however, regarding the effects of a high fat diet (HFD) itself on the properties of vagal neurocircuits. The present study was designed to test the hypothesis that exposure to a HFD during the perinatal period alters the electrophysiological, pharmacological and morphological properties of vagal efferent motoneurones innervating the stomach. Our data indicate that perinatal HFD decreases the excitability of gastric-projecting dorsal motor nucleus neurones and dysregulates neurotransmitter release from synaptic inputs and that these alterations occur prior to the development of obesity. These findings represent the first direct evidence that exposure to a HFD modulates the processing of central vagal neurocircuits even in the absence of obesity. The perinatal period is critically important to the development of autonomic neural circuits responsible for energy homeostasis. Vagal neurocircuits are vital to the regulation of upper gastrointestinal functions, including satiety. Diet-induced obesity modulates the excitability and responsiveness of both peripheral vagal afferents and central vagal efferents but less information is available regarding the effects of diet per se on vagal neurocircuit functions. The aims of this study were to investigate whether perinatal exposure to a high fat diet (HFD) dysregulated dorsal motor nucleus of the vagus (DMV) neurones, prior to the development of obesity. Whole cell patch clamp recordings were made from gastric-projecting DMV neurones in thin

  9. Development and aminergic neuromodulation of a spinal locomotor network controlling swimming in Xenopus larvae.

    Science.gov (United States)

    Sillar, K T; Reith, C A; McDearmid, J R

    1998-11-16

    In this article we review our research on the development and intrinsic neuromodulation of a spinal network controlling locomotion in a simple vertebrate. Swimming in hatchling Xenopus embryos is generated by a restricted network of well-characterized spinal neurons. This network produces a stereotyped motor pattern which, like real swimming, involves rhythmic activity that alternates across the body and progresses rostrocaudally with a brief delay between muscle segments. The stereotypy results from motoneurons discharging a single impulse in each cycle; because all motoneurons appear to behave similarly there is little scope for altering the output to the myotomes from one cycle to the next. Just one day later, however, Xenopus larvae generate a more complex and flexible motor pattern in which motoneurons can discharge a variable number of impulses which contribute to ventral root bursts in each cycle. This maturation of swimming is due, in part, to the influence of serotonin released from brain-stem raphespinal interneurons whose axonal projections innervate the cord early in larval life. Larval swimming is differentially modulated by both serotonin and by noradrenaline: serotonin leads to relatively fast, intense swimming whereas noradrenaline favors slower, weaker activity. Thus, these two biogenic amines select opposite extremes from the spectrum of possible output patterns that the swimming network can produce. Our studies on the cellular and synaptic effects of the amines indicate that they can control the strength of reciprocal glycinergic inhibition in the spinal cord. Serotonin and noradrenaline act presynaptically on the terminals of glycinergic commissural interneurons to weaken and strengthen, respectively, crossed glycinergic inhibition during swimming. As a result, serotonin reduces and noradrenaline increases interburst intervals. The membrane properties of spinal neurons are also affected by the amines. In particular, serotonin can induce

  10. Compensatory axon sprouting for very slow axonal die-back in a transgenic model of spinal muscular atrophy type III.

    Science.gov (United States)

    Udina, Esther; Putman, Charles T; Harris, Luke R; Tyreman, Neil; Cook, Victoria E; Gordon, Tessa

    2017-03-01

    Smn +/- transgenic mouse is a model of the mildest form of spinal muscular atrophy. Although there is a loss of spinal motoneurons in 11-month-old animals, muscular force is maintained. This maintained muscular force is mediated by reinnervation of the denervated fibres by surviving motoneurons. The spinal motoneurons in these animals do not show an increased susceptibility to death after nerve injury and they retain their regenerative capacity. We conclude that the hypothesized immaturity of the neuromuscular system in this model cannot explain the loss of motoneurons by systematic die-back. Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the SMN1 gene with the severity of the disease depending on the number of copies of the highly homologous SMN2 gene. Although motoneuron death in the Smn +/- transgenic mouse model of the mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections. Thereby, we investigated whether incomplete maturation of the neuromuscular system induced by survival motoneuron protein (SMN) defects is responsible for die-back of axons relative to survival of motoneurons. First, a reduction of ∼30% of backlabelled motoneurons began relatively late, at 11 months of age, with a significant loss of 19% at 7 months. Motor axon die-back was affirmed by motor unit number estimation. Loss of functional motor units was fully compensated by axonal sprouting to retain normal contractile force in four hindlimb muscles (three fast-twitch and one slow-twitch) innervated by branches of the sciatic nerve. Second, our evaluation of whether axotomy of motoneurons in the adult Smn +/- transgenic mouse increases their susceptibility to cell death demonstrated

  11. Identification of 'Point A' as the prevalent source of error in cephalometric analysis of lateral radiographs.

    Science.gov (United States)

    Grogger, P; Sacher, C; Weber, S; Millesi, G; Seemann, R

    2018-04-10

    Deviations in measuring dentofacial components in a lateral X-ray represent a major hurdle in the subsequent treatment of dysgnathic patients. In a retrospective study, we investigated the most prevalent source of error in the following commonly used cephalometric measurements: the angles Sella-Nasion-Point A (SNA), Sella-Nasion-Point B (SNB) and Point A-Nasion-Point B (ANB); the Wits appraisal; the anteroposterior dysplasia indicator (APDI); and the overbite depth indicator (ODI). Preoperative lateral radiographic images of patients with dentofacial deformities were collected and the landmarks digitally traced by three independent raters. Cephalometric analysis was automatically performed based on 1116 tracings. Error analysis identified the x-coordinate of Point A as the prevalent source of error in all investigated measurements, except SNB, in which it is not incorporated. In SNB, the y-coordinate of Nasion predominated error variance. SNB showed lowest inter-rater variation. In addition, our observations confirmed previous studies showing that landmark identification variance follows characteristic error envelopes in the highest number of tracings analysed up to now. Variance orthogonal to defining planes was of relevance, while variance parallel to planes was not. Taking these findings into account, orthognathic surgeons as well as orthodontists would be able to perform cephalometry more accurately and accomplish better therapeutic results. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  12. Supine MRI for regional breast radiotherapy: imaging axillary lymph nodes before and after sentinel-node biopsy

    Science.gov (United States)

    van Heijst, Tristan C. F.; Eschbach-Zandbergen, Debora; Hoekstra, Nienke; van Asselen, Bram; Lagendijk, Jan J. W.; Verkooijen, Helena M.; Pijnappel, Ruud M.; de Waard, Stephanie N.; Witkamp, Arjen J.; van Dalen, Thijs; Desirée van den Bongard, H. J. G.; Philippens, Marielle E. P.

    2017-08-01

    Regional radiotherapy (RT) is increasingly used in breast cancer treatment. Conventionally, computed tomography (CT) is performed for RT planning. Lymph node (LN) target levels are delineated according to anatomical boundaries. Magnetic resonance imaging (MRI) could enable individual LN delineation. The purpose was to evaluate the applicability of MRI for LN detection in supine treatment position, before and after sentinel-node biopsy (SNB). Twenty-three female breast cancer patients (cTis-3N0M0) underwent 1.5 T MRI, before and after SNB, in addition to CT. Endurance for MRI was monitored. Axillary levels were delineated. LNs were identified and delineated on MRI from before and after SNB, and on CT, and compared by Wilcoxon signed-rank tests. LN locations and LN-based volumes were related to axillary delineations and associated volumes. Although postoperative effects were visible, LN numbers on postoperative MRI (median 26 LNs) were highly reproducible compared to preoperative MRI when adding excised sentinel nodes, and higher than on CT (median 11, p  <  0.001). LN-based volumes were considerably smaller than respective axillary levels. Supine MRI of LNs is feasible and reproducible before and after SNB. This may lead to more accurate RT target definition compared to CT, with potentially lower toxicity. With the MRI techniques described here, initiation of novel MRI-guided RT strategies aiming at individual LNs could be possible.

  13. Postactivation depression of the Ia EPSP in motoneurons is reduced in both the G127X SOD1 model of amyotrophic lateral sclerosis and in aged mice

    DEFF Research Database (Denmark)

    Hedegaard, Anne; Lehnhoff, Janna; Moldovan, Mihai

    2015-01-01

    Post Activation Depression (PActD) of Ia afferent EPSPs in spinal motoneurons results in a long lasting depression of the stretch reflex. 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) C57BL/6J mice is both qualitatively and quantitatively similar to that which has been observed in larger animals with respect to both magnitude (approximately 20% depression of EPSPs at 0.5 ms after a stimuli train) and time course (returning...... Sclerosis (ALS). Using 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 pre-symptomatic (16% depression) and symptomatic (17.3% depression) time points compared to aged-matched controls (22...

  14. Effects of calcium (Ca(2+)) extrusion mechanisms on electrophysiological properties in a hypoglossal motoneuron: insight from a mathematical model.

    Science.gov (United States)

    Horn, Kyle G; Solomon, Irene C

    2014-01-01

    Spike-frequency dynamics and spike shape can provide insight into the types of ion channels present in any given neuron and give a sense for the precise response any neuron may have to a given input stimulus. Motoneuron firing frequency over time is especially important due to its direct effect on motor output. Of particular interest is intracellular Ca(2+), which exerts a powerful influence on both firing properties over time and spike shape. In order to better understand the cellular mechanisms for the regulation of intracellular Ca(2+) and their effect on spiking behavior, we have modified a computational model of an HM to include a variety of Ca(2+) handling processes. For the current study, a series of HM models that include Ca(2+) pumps, Na(+)/Ca(2+) exchangers, and a generic exponential decay of excess Ca(2+) were generated. Simulations from these models indicate that although each extrusion mechanism exerts a similar effect on voltage, the firing properties change distinctly with the inclusion of additional Ca(2+)-related mechanisms: BK channels, Ca(2+) buffering, and diffusion of [Ca(2+)]i modeled via a linear diffusion partial differential equation. While an exponential decay of Ca(2+) seems to adequately capture short-term changes in firing frequency seen in biological data, internal diffusion of Ca(2+) appears to be necessary for capturing longer term frequency changes. © 2014 Elsevier B.V. All rights reserved.

  15. Preferential distribution of nociceptive input to motoneurons with muscle units in the cranial portion of the upper trapezius muscle.

    Science.gov (United States)

    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. Copyright © 2016 the American Physiological Society.

  16. Perinatal Development of the Motor Systems Involved in Postural Control

    Directory of Open Access Journals (Sweden)

    Laurent Vinay

    2005-01-01

    Full Text Available Motor behaviors of some species, such as the rat and the human baby, are quite immature at birth. Here we review recent data on some of the mechanisms underlying the postnatal maturation of posture in the rat, in particular the development of pathways descending from the brain stem and projecting onto the lumbar enlargement of the spinal cord. A short-lasting depletion in serotonin affects both posture and the excitability of motoneurons. Here we try to extrapolate to human development and suggest that the abnormalities in motor control observed in childhood—e.g, deficits in motor coordination—might have their roots in the prenatal period, in particular serotonin depletion due to exposure to several environmental and toxicological factors during pregnancy.

  17. Perawatan Maloklusi Angle Klas II Divisi 1 Menggunakan Bionator Myofungsional

    Directory of Open Access Journals (Sweden)

    Ragil Irawan

    2014-06-01

    Full Text Available Maloklusi Angle klas II divisi 1 mempunyai ciri tonjol mesiobukal molar pertama atas beroklusi dengan interdental premolar kedua  dan molar pertama bawah, jarak gigit yang besar, lengkung gigi sempit dan profil cembung. Bionator pertama kali diperkenalkan oleh Balter dan merupakan alat ortodontik myofungsional yang digunakan untuk merawat diskrepansi rahang. Tujuan pemaparan kasus adalah menyajikan kemajuan kasus maloklusi Angle Klas II divisi 1 disertai diskrepansi rahang menggunakan alat myofunctional bionator. Seorang perempuan berusia 13 tahun mengeluhkan gigi depan atas maju. Diagnosis pasien maloklusi Angle klas II divisi 1, hubungan skeletal klas II dengan protrusif maksila dan retrusif mandibula, protrusif insisivus atas disertai palatal bite, cross bite posterior, jarak gigit 11 mm, tumpang gigit 5,25 mm, SNA 84°, SNB 76°. Pasien dirawat menggunakan alat myofungsional bionator. Hasil perawatan setelah satu tahun overjet menjadi 6,25 mm dan SNB 78°. Kesimpulannya adalah alat myofungsional bionator efektif untuk merawat maloklusi Angle Klas II divisi 1 yang disertai diskrepansi rahang. Class II division 1 Angle Malocclussion Treatment  Using  Myofunctional  Bionator. Malocclusion Angle Class II division I is characterized by the upper mesio-buccal cups first permanent molars occludes in interdental second bicuspid and lower first molar permanent, increased overjet, narrow arch form, and convex profile. Bionator originally developed by Balter and used to treat jaw discrepancy. The goal of this case is to present the progress of myofunctional bionator appliance in treating malocclusion Class II division 1 with jaw discrepancies. A Female 13 years old complained protrusive anterior teeth. Diagnosis is malocclusion Angle Class II division I, class II skeletal relationship with maxilla protrusive, mandible retrusive, protrusive upper incisor, palatal bite, posterior cross bite, overjet 11 mm, overbite 5,25 mm SNA 84°, SNB 76

  18. Electrophysiological and Morphological Properties of α and γ Motoneurons in the Rat Trigeminal Motor Nucleus

    Directory of Open Access Journals (Sweden)

    Kayo Nishimura

    2018-01-01

    Full Text Available The muscle contraction during voluntary movement is regulated by activities of α- and γ-motoneurons (αMNs and γMNs, respectively. The tension of jaw-closing muscles can be finely tuned over a wide range. This excellent function is likely to be achieved by the specific populations of αMNs innervating jaw-closing muscles. Indeed, we have recently demonstrated that in the rat dorsolateral trigeminal motor nucleus (dl-TMN, the size distribution of αMNs was bimodal and the population of smaller αMNs showed a size distribution similar to that of γMNs, by immunohistochemically identifying αMNs and γMNs based on the expressions of estrogen-related receptor gamma (Err3 and neuronal DNA binding protein NeuN together with ChAT. This finding suggests the presence of αMNs as small as γMNs. However, differences in the electrophysiological membrane properties between αMNs and γMNs remain unknown also in the dl-TMN. Therefore, in the present study, we studied the electrophysiological membrane properties of MNs in the dl-TMN of infant rats at postnatal days 7–12 together with their morphological properties using whole-cell current-clamp recordings followed by immunohistochemical staining with an anti-NeuN and anti-ChAT antibodies. We found that the ChAT-positive and NeuN-positive αMNs were divided into two subclasses: the first one had a larger cell body and displayed a 4-aminopyridine (4-AP-sensitive current while the second one had a smaller cell body and displayed a less prominent 4-AP-sensitive current and a low-threshold spike, suitable for their orderly recruitment. We finally found that γMNs showing ChAT-positive and NeuN-negative immunoreactivities had smaller cell bodies and displayed an afterdepolarization mediated by flufenamate-sensitive cation current. It is suggested that these electrophysiological and morphological features of MNs in the dl-TMN are well correlated with the precise control of occlusion.

  19. The Neuronal Network Orchestration behind Motor Behaviors

    DEFF Research Database (Denmark)

    Petersen, Peter Christian

    to motoneurons during rhythmic motor behaviors, and specifically the hypothesis that motoneurons receive concurrent excitatory and inhibitory (E/I) inputs. Berg et al. (2007) presented the concurrent hypothesis, which goes against the classical feed forward reciprocal model for spinal motor networks that has...... gained widespread acceptance. We developed an adult turtle preparation where the spinal motor network was intact, which also allowed us to perform intracellular recordings from motoneurons during rhythmic motor activity. We estimated the synaptic excitatory and inhibitory conductances by two individual...... (Buzsáki and Mizuseki, 2014). Roxin et al. (2011) detailed the firing rate distribution in networks in the balanced regime, and found it to be similar to a lognormal distribution and describing the data from the population studies very well. Our experimental observations and analysis are in agreement...

  20. Development and degeneration of dorsal root ganglia in the absence of the HMG-domain transcription factor Sox10

    DEFF Research Database (Denmark)

    Sonnenberg-Riethmacher, Eva; Miehe, Michaela; Stolt, Claus C.

    2001-01-01

    neurogenesis seemed initially normal. A degeneration of motoneurons and sensory neurons occurred later in development. The mechanism that leads to the dramatic effects on the neural crest derived cell lineages in the dorsal root ganglia (DRG), however, has not been examined up to now. Here, we provide...... a detailed analysis of proliferation and apoptosis in the DRG during the time of their generation and lineage segregation (between E 9.5 and E 11.5). We show that both increased apoptosis as well as decreased proliferation of neural crest cells contribute to the observed hypomorphism....

  1. Evaluation of some geophysical events on 22 September 1979

    International Nuclear Information System (INIS)

    Hones, E.W. Jr.; Baker, D.N.; Feldman, W.C.

    1981-04-01

    TIROS-N plasma data and related geophysical data measured on 22 September 1979 were analyzed to determine whether the electron precipitation event detected by TIROS-N at 00:54:49 universal time could have been related to a surface nuclear burst (SNB). The occurrence of such a burst was inferred from light signals detected by two Vela bhangmeters approx. 2 min before the TIROS-N event. The precipitation was found to be unusually large but not unique. It probably resulted from passage of TIROS-N through The precipitating electrons above a pre-existing auroral arc that may have brightened to an unusually high intensity from natural causes approx. 3 min before the Vela signals. On the othe hand, no data were found that were inconsistent with the SNB interpretation of the 22 September Vela observations. In fact, a patch of auroral light that suddenly appeared in the sky near Syowa Base, Antarctica a few seconds after the Vela event can be interpreted (though not uniquely) as a consequence of the electromagnetic pulse of an SNB

  2. Functional Diversity of Neurotrophin Actions on the Oculomotor System

    Science.gov (United States)

    Benítez-Temiño, Beatriz; Davis-López de Carrizosa, María A.; Morcuende, Sara; Matarredona, Esperanza R.; de la Cruz, Rosa R.; Pastor, Angel M.

    2016-01-01

    Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor) or NT-3 (neurotrophin-3) protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT (choline acetyltransferase). In the adult, in vivo recordings of axotomized extraocular motoneurons have demonstrated that the delivery of NGF, BDNF or NT-3 recovers different components of the firing discharge activity of these cells, with some particularities in the case of NGF. All neurotrophins have also synaptotrophic activity, although to different degrees. Accordingly, neurotrophins can restore the axotomy-induced alterations acting selectively on different properties of the motoneuron. In this review, we summarize these evidences and discuss them in the context of other motor systems. PMID:27916956

  3. Feasibility of Real-Time Near-Infrared Fluorescence Tracer Imaging in Sentinel Node Biopsy for Oral Cavity Cancer Patients.

    Science.gov (United States)

    Christensen, Anders; Juhl, Karina; Charabi, Birgitte; Mortensen, Jann; Kiss, Katalin; Kjær, Andreas; von Buchwald, Christian

    2016-02-01

    Sentinel node biopsy (SNB) is an established method in oral squamous cell carcinoma (OSCC) for staging the cN0 neck and to select patients who will benefit from a neck dissection. Near-infrared fluorescence (NIRF) imaging has the potential to improve the SNB procedure by facilitating intraoperative visual identification of the sentinel lymph node (SN). The purpose of this study was to evaluate the feasibility of fluorescence tracer imaging for SN detection in conjunction with conventional radio-guided technique. Prospective study of patients with primary OSCC planned for tumor resection and SNB. Thirty patients were injected peritumorally with a bimodal tracer (ICG-99mTc-Nanocoll) followed by lymphoscintigraphy and SPECT/CT to define the SNs and their anatomic allocation preoperatively. SNs were detected intraoperatively with a hand-held gamma-probe and a hand-held NIRF camera. In 29 of 30 subjects (97%), all preoperatively defined SNs could be identified intraoperatively using a combination of radioactive and fluorescence guidance. A total of 94 SNs (mean 3, range 1-5) that were both radioactive and fluorescent ex vivo were harvested. Eleven of 94 SNs (12%) could only be identified in vivo using NIRF imaging, and the majority of those were located in level 1 close to the primary tumor. A combined fluorescent and radioactive tracer for SNB is feasible, and the additional use of NIRF imaging may improve the accuracy of SN identification in oral cancer patients. Intraoperative fluorescence guidance seems of particular value when SNs are located in close proximity to the injection site.

  4. SIRT1 activation with neuroheal is neuroprotective but SIRT2 inhibition with AK7 is detrimental for disconnected motoneurons.

    Science.gov (United States)

    Romeo-Guitart, David; Leiva-Rodríguez, Tatiana; Espinosa-Alcantud, María; Sima, Núria; Vaquero, Alejandro; Domínguez-Martín, Helena; Ruano, Diego; Casas, Caty

    2018-05-10

    Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury. SIRT2 has been suggested to exert effects opposite those of SIRT1; however, its roles in neurodegeneration and neuron response after nerve injury remain unclear. Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy. This injury induced a reduction of around half MN population within the hypoglossal nucleus by a non-apoptotic neurodegenerative process triggered by endoplasmic reticulum (ER) stress that resulted in activation of the unfolded protein response mediated by IRE1α and XBP1 by 21 days post injury. Both SIRT1 activation with NeuroHeal and SIRT2 inhibition with AK7 protected NSC-34 motor neuron-like cells against ER stress in vitro. In agreement with the in vitro results, NeuroHeal treatment or SIRT1 overexpression was neuroprotective of axotomized hypoglossal MNs in a transgenic mouse model. In contrast, AK7 treatment or SIRT2 genetic depletion in mice inhibited damaged MN survival. To resolve the in vitro/in vivo discrepancies, we used an organotypic spinal cord culture system that preserves glial cells. In this system, AK7 treatment of ER-stressed organotypic cultures was detrimental for MNs and increased microglial nuclear factor-κB and the consequent transcription of cytotoxic pro-inflammatory factors similarly. The results highlight the importance of glial cells in determining the neuroprotective impact of any treatment.

  5. Discrete Diffusion Monte Carlo for Electron Thermal Transport

    Science.gov (United States)

    Chenhall, Jeffrey; Cao, Duc; Wollaeger, Ryan; Moses, Gregory

    2014-10-01

    The iSNB (implicit Schurtz Nicolai Busquet electron thermal transport method of Cao et al. is adapted to a Discrete Diffusion Monte Carlo (DDMC) solution method for eventual inclusion in a hybrid IMC-DDMC (Implicit Monte Carlo) method. The hybrid method will combine the efficiency of a diffusion method in short mean free path regions with the accuracy of a transport method in long mean free path regions. The Monte Carlo nature of the approach allows the algorithm to be massively parallelized. Work to date on the iSNB-DDMC method will be presented. This work was supported by Sandia National Laboratory - Albuquerque.

  6. Anatomical study of the final common pathway for vocalization in the cat

    Science.gov (United States)

    Holstege, Gert

    1989-01-01

    Results are presented of an anatomical study of the neuronal pathways in the cat, via which the periaqueductal gray (PAG) produces excitation of motoneurons involved in vocalization. It is shown that a specific cell group in the lateral part of the caudal PAG and in the tegmentum just lateral to it projects bilaterally to the nucleus retroambiguus (NRA) in the caudal medulla oblongata. Neurons in the NRA in turn project, via a contralateral pathway through the ventral funiculus of the spinal cord, to the motoneuronal cell groups innervating intercostal and abdominal muscles. In the brainstem, the NRA neurons project to the motoneuronal cell groups innervating mouth-opening and perioral muscles as well as to motoneurons innervating the pharynx, soft palate, and tongue. These results indicate that the projections from PAG via NRA to vocalization motoneurons form the final common pathway in vocalization.

  7. Age-Related Uptake of Heavy Metals in Human Spinal Interneurons.

    Directory of Open Access Journals (Sweden)

    Roger Pamphlett

    Full Text Available Toxic heavy metals have been implicated in the loss of spinal motoneurons in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND. Motoneuron loss in the spinal anterior horn is severe in ALS/MND at the time of death, making this tissue unsuitable for examination. We therefore examined spinal cords of people without muscle weakness to look for any presence of heavy metals that could make these neurons susceptible to damage. Spinal cord samples from 50 individuals aged 1-95 y who had no clinical or histopathological evidence of spinal motoneuron loss were studied. Seven μm formalin-fixed paraffin-embedded sections were stained for heavy metals with silver nitrate autometallography (AMGHM which detects intracellular mercury, silver or bismuth. Neurons in the spinal cord were classified as interneurons or α-motoneurons based on their site and cell body diameter. Spinal interneurons containing heavy metals were present in 8 of 24 people (33% aged 61-95 y, but not at younger ages. These AMGHM interneurons were most numerous in the lumbar spinal cord, with moderate numbers in the caudal cervical cord, few in the rostral cervical cord, and almost none in the thoracic cord. All people with AMGHM interneurons had occasional AMGHM staining in α-motoneurons as well. In one man AMGHM staining was present in addition in dorsomedial nucleus and sensory neurons. In conclusion, heavy metals are present in many spinal interneurons, and in a few α-motoneurons, in a large proportion of older people. Damage to inhibitory interneurons from toxic metals in later life could result in excitotoxic injury to motoneurons and may underlie motoneuron injury or loss in conditions such as ALS/MND, multiple sclerosis, sarcopenia and calf fasciculations.

  8. Reduced phrenic motoneuron recruitment during sustained inspiratory threshold loading compared to single-breath loading: a twitch interpolation study

    Directory of Open Access Journals (Sweden)

    Mathieu Raux

    2016-11-01

    reflecting motoneuron recruitment, this study supports motor reorganisation compatible with diaphragm sparing when an inspiratory threshold load becomes sustained

  9. [Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer. Its relation with molecular subtypes].

    Science.gov (United States)

    Ruano, R; Ramos, M; García-Talavera, J R; Ramos, T; Rosero, A S; González-Orus, J M; Sancho, M

    2014-01-01

    To evaluate the influence of the molecular subtype (MS) in the Sentinel Node Biopsy (SNB) technique after neoadjuvant chemotherapy (NAC) in women with locally advanced breast cancer (BC) and a complete axillary response (CR). A prospective study involving 70 patients with BC treated with NAC was carried out. An axillary lymph node dissection was performed in the first 48 patients (validation group: VG), and in case of micro- or macrometastases in the therapeutic application phase (therapy group:TG). Classified according to MS: 14 luminal A; 16 luminal B HER2-, 13 luminal B HER2+, 10HER2+ non-luminal, 17 triple-negative. SNB was carried out in 98.6% of the cases, with only one false negative result in the VG (FN=2%). Molecular subtype did not affect SN detection. Despite the existence of axillary CR, statistically significant differences were found in the proportion of macrometastasis (16.7% vs. 35.7%, p=0.043) on comparing the pre-NAC cN0 and cN+. Breast tumor response to NAC varied among the different MS, this being lowest in luminal A (21.5%) and highest in non-luminal HER2+ group (80%). HER2+ and triple-negative were the groups with the best axillary histological response both when there was prior clinical involvement and when there was not. Molecular subtype is a predictive factor of the degree of tumor response to NAC in breast cancer. However, it does not affect SNB detection and efficiency. SNB can also be used safely in women with prior node involvement as long as a complete clinical and radiological assessment is made of the node response to NAC. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  10. The Possible Role of TASK Channels in Rank-Ordered Recruitment of Motoneurons in the Dorsolateral Part of the Trigeminal Motor Nucleus.

    Science.gov (United States)

    Okamoto, Keiko; Emura, Norihito; Sato, Hajime; Fukatsu, Yuki; Saito, Mitsuru; Tanaka, Chie; Morita, Yukako; Nishimura, Kayo; Kuramoto, Eriko; Xu Yin, Dong; Furutani, Kazuharu; Okazawa, Makoto; Kurachi, Yoshihisa; Kaneko, Takeshi; Maeda, Yoshinobu; Yamashiro, Takashi; Takada, Kenji; Toyoda, Hiroki; Kang, Youngnam

    2016-01-01

    Because a rank-ordered recruitment of motor units occurs during isometric contraction of jaw-closing muscles, jaw-closing motoneurons (MNs) may be recruited in a manner dependent on their soma sizes or input resistances (IRs). In the dorsolateral part of the trigeminal motor nucleus (dl-TMN) in rats, MNs abundantly express TWIK (two-pore domain weak inwardly rectifying K channel)-related acid-sensitive-K(+) channel (TASK)-1 and TASK3 channels, which determine the IR and resting membrane potential. Here we examined how TASK channels are involved in IR-dependent activation/recruitment of MNs in the rat dl-TMN by using multiple methods. The real-time PCR study revealed that single large MNs (>35 μm) expressed TASK1 and TASK3 mRNAs more abundantly compared with single small MNs (15-20 μm). The immunohistochemistry revealed that TASK1 and TASK3 channels were complementarily distributed in somata and dendrites of MNs, respectively. The density of TASK1 channels seemed to increase with a decrease in soma diameter while there were inverse relationships between the soma size of MNs and IR, resting membrane potential, or spike threshold. Dual whole-cell recordings obtained from smaller and larger MNs revealed that the recruitment of MNs depends on their IRs in response to repetitive stimulation of the presumed Ia afferents. 8-Bromoguanosine-cGMP decreased IRs in small MNs, while it hardly changed those in large MNs, and subsequently decreased the difference in spike-onset latency between the smaller and larger MNs, causing a synchronous activation of MNs. These results suggest that TASK channels play critical roles in rank-ordered recruitment of MNs in the dl-TMN.

  11. Numerically robust and efficient nonlocal electron transport in 2D DRACO simulations

    Science.gov (United States)

    Cao, Duc; Chenhall, Jeff; Moses, Greg; Delettrez, Jacques; Collins, Tim

    2013-10-01

    An improved implicit algorithm based on Schurtz, Nicolai and Busquet (SNB) algorithm for nonlocal electron transport is presented. Validation with direct drive shock timing experiments and verification with the Goncharov nonlocal model in 1D LILAC simulations demonstrate the viability of this efficient algorithm for producing 2D lagrangian radiation hydrodynamics direct drive simulations. Additionally, simulations provide strong incentive to further modify key parameters within the SNB theory, namely the ``mean free path.'' An example 2D polar drive simulation to study 2D effects of the nonlocal flux as well as mean free path modifications will also be presented. This research was supported by the University of Rochester Laboratory for Laser Energetics.

  12. Measurement and analysis of bubble behavior in subcooled nucleate boiling flow field with high fidelity imaging system

    International Nuclear Information System (INIS)

    Wu, W.; Jones, B.G.; Newell, T.A.

    2004-01-01

    Axial offset anomaly (AOA) is an unexpected deviation in the core axial power distribution from the predicted curve. AOA is a current major consideration for reactors operating at increased power levels and is becoming immediate threat to nuclear power's competitiveness in the market. Despite much effort focusing on this topic, a comprehensive understanding is far from being developed. However, previous research indicates first, that a close connection exists between subcooled nucleate boiling occurring in core region and the formation of crud, which directly results in AOA phenomena, secondly, that deposition is greater, and sometimes much greater, on heated than on unheated surfaces. A number of researchers have suggested that boiling promotes deposition, and several observed increased deposition in the subcooled boiling region. Limited detailed information is available on the interaction between heat and mass transfer in subcooled nucleate boiling (SNB) flow. Bubbles formed in SNB region play an important role in helping the formation of crud. This research examines bubble behavior under SNB condition from the dynamic point of view, using a high fidelity digital imaging apparatus. Freon R-134a is chosen as a simulant fluid due to its merit of having smaller surface tension and lower boiling temperature. The apparatus is operated at reduced pressure. Series of images at frame rates up to 4000 frames/s were obtained, showing different characteristics of bubble behavior with varying experimental parameters e.g. flow velocity, fluid subcooled level, etc. Analyses that combine the experimental results with analytical result on flow field in velocity boundary layer are considered. A tentative suggestion is that a rolling movement of a bubble accompanies its sliding along the heating surface in the flow channel. Numerical computations using FLUENT v5.5 have been performed to support this conclusion

  13. Vallisneria 2003-2004

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — We compared nekton use of Vallisneria americana Michx. (submerged aquatic vegetation, SAV) with marsh shoreline vegetation and subtidal nonvegetated bottom (SNB)...

  14. Facilitation of soleus but not tibialis anterior motor evoked potentials before onset of antagonist contraction

    DEFF Research Database (Denmark)

    Geertsen, Svend Sparre; Zuur, Abraham Theodore; Nielsen, Jens Bo

    2008-01-01

    Objective: It is well documented that corticospinal projections to motoneurons of one muscle inhibit antagonist motoneurons through collaterals to reciprocally organized spinal inhibitory interneurons. During and just prior to dorsiflexion of the ankle, soleus motoneurons are thus inhibited...... the MEP is evoked. Methods: Seated subjects (n=11) were instructed to react to an auditory cue by contracting either the tibialis anterior (TA) or soleus muscle of the left ankle to 30% of their maximal dorsiflexion voluntary contraction (MVC) or plantar flexion MVC, respectively. Focal TMS at 1.2 x motor...

  15. Differential autophagy power in the spinal cord and muscle of transgenic ALS mice

    NARCIS (Netherlands)

    Crippa, Valeria; Boncoraglio, Alessandra; Galbiati, Mariarita; Aggarwal, Tanya; Rusmini, Paola; Giorgetti, Elisa; Cristofani, Riccardo; Carra, Serena; Pennuto, Maria; Poletti, Angelo

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a motoneuron disease characterized by misfolded proteins aggregation in affected motoneurons. In mutant SOD1 (mutSOD1) ALS models, aggregation correlates to impaired functions of proteasome and/or autophagy, both essential for the intracellular

  16. Premotor spinal network with balanced excitation and inhibition during motor patterns has high resilience to structural division

    DEFF Research Database (Denmark)

    Petersen, Peter C; Vestergaard, Mikkel; Reveles Jensen, Kristian

    2014-01-01

    Direct measurements of synaptic inhibition (I) and excitation (E) to spinal motoneurons can provide an important insight into the organization of premotor networks. Such measurements of flexor motoneurons participating in motor patterns in turtles have recently demonstrated strong concurrent E...

  17. Nucleus retroambiguus projections to the periaqueductal gray in the cat

    NARCIS (Netherlands)

    Klop, EM; Mouton, LJ; Holstege, G

    2002-01-01

    The nucleus retroambiguus (NRA) of the caudal medulla is a relay nucleus by which neurons of the mesencephalic periaqueductal gray (PAG) reach motoneurons of pharynx, larynx, soft palate, intercostal and abdominal muscles, and several muscles of the hindlimbs. These PAG-NRA-motoneuronal projections

  18. The immobilization of heavy metals in soil by bioaugmentation of a UV-mutant Bacillus subtilis 38 assisted by NovoGro biostimulation and changes of soil microbial community.

    Science.gov (United States)

    Wang, Ting; Sun, Hongwen; Mao, Hongjun; Zhang, Yanfeng; Wang, Cuiping; Zhang, Zhiyuan; Wang, Baolin; Sun, Lei

    2014-08-15

    Bacillus subtilis 38 (B38) is a mutant species of Bacillus subtilis acquired by UV irradiation with high cadmium tolerance. This study revealed that B38 was a good biosorbent for the adsorption of multiple heavy metals (cadmium, chromium, mercury, and lead). Simultaneous application of B38 and NovoGro (SNB) exhibited a synergetic effect on the immobilization of heavy metals in soil. The heavy metal concentrations in the edible part of the tested plants (lettuce, radish, and soybean) under SNB treatment decreased by 55.4-97.9% compared to the control. Three single extraction methods, diethylenetriaminepentaacetic acid (DTPA), Mehlich 3 (M3), and the first step of the Community Bureau of Reference method (BCR1), showed good predictive capacities for metal bioavailability to leafy, rhizome, and leguminous plant, respectively. The polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) profiles revealed that NovoGro could enhance the proliferation of both exotic B38 and native microbes. Finally, the technology was checked in the field, the reduction in heavy metal concentrations in the edible part of radish was in the range between 30.8% and 96.0% after bioremediation by SNB treatment. This study provides a practical strategy for the remediation of farmland contaminated by multiple heavy metals. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Calsyntenins Are Expressed in a Dynamic and Partially Overlapping Manner during Neural Development

    Directory of Open Access Journals (Sweden)

    Gemma de Ramon Francàs

    2017-08-01

    Full Text Available Calsyntenins form a family of linker proteins between distinct populations of vesicles and kinesin motors for axonal transport. They were implicated in synapse formation and synaptic plasticity by findings in worms, mice and humans. These findings were in accordance with the postsynaptic localization of the Calsyntenins in the adult brain. However, they also affect the formation of neural circuits, as loss of Calsyntenin-1 (Clstn1 was shown to interfere with axonal branching and axon guidance. Despite the fact that Calsyntenins were discovered originally in embryonic chicken motoneurons, their distribution in the developing nervous system has not been analyzed in detail so far. Here, we summarize our analysis of the temporal and spatial expression patterns of the cargo-docking proteins Clstn1, Clstn2 and Clstn3 during neural development by comparing the dynamic distribution of their mRNAs by in situ hybridization in the spinal cord, the cerebellum, the retina and the tectum, as well as in the dorsal root ganglia (DRG.

  20. Reassessment of Non-Monosynaptic Excitation from the Motor Cortex to Motoneurons in Single Motor Units of the Human Biceps Brachii.

    Science.gov (United States)

    Nakajima, Tsuyoshi; Tazoe, Toshiki; Sakamoto, Masanori; Endoh, Takashi; Shibuya, Satoshi; Elias, Leonardo A; Mezzarane, Rinaldo A; Komiyama, Tomoyoshi; Ohki, Yukari

    2017-01-01

    Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and

  1. Reassessment of Non-Monosynaptic Excitation from the Motor Cortex to Motoneurons in Single Motor Units of the Human Biceps Brachii

    Science.gov (United States)

    Nakajima, Tsuyoshi; Tazoe, Toshiki; Sakamoto, Masanori; Endoh, Takashi; Shibuya, Satoshi; Elias, Leonardo A.; Mezzarane, Rinaldo A.; Komiyama, Tomoyoshi; Ohki, Yukari

    2017-01-01

    Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and

  2. Elastography in the assessment of sentinel lymph nodes prior to dissection

    Energy Technology Data Exchange (ETDEWEB)

    Tourasse, Christophe, E-mail: christophe.tourasse@radiologie-lyon.com [Radiology Department, Hopital Prive Jean Mermoz, 55 avenue Jean Mermoz, 69008 Lyon (France); Denier, Jean Francois [Anatomopathology Department, Technipath, 41 allee des Cypres, 69760 Limonest (France); Awada, Azzam; Gratadour, Anne-Christel; Nessah-Bousquet, Karima [Gynaecological and Breast Surgery Department, Hopital Prive Jean Mermoz, 69008 Lyon (France); Gay, Joeel [SuperSonic Imagine, Les Jardins de la Duranne - Bat. F, 510, rue Rene Descartes, 13857 Aix-en-Provence Cedex (France)

    2012-11-15

    Objective: Breast cancer starts as a local tumor but can become metastatic and spread via the lymph nodes. When the pre-operative assessment of the axillary lymph nodes is negative patients generally undergo sentinel node biopsy (SNB), followed by a secondary surgical axillary lymph node dissection (ALND) if the SNB is positive. The extemporaneous anatomo-pathological analysis of the sentinel lymph node enables metastases to be detected and an ALND at the same time of the SNB. The goal of this study was to evaluate the added value of ShearWave Elastography (SWE), compared with the conventional pre-operative assessment, in the screening of sentinel lymph nodes with a high metastatic risk, which could then benefit from an extemporaneous anatomo-pathological analysis. Patients and methods: Women undergoing breast surgery with SNB were prospectively enrolled. Before surgery, they underwent ultrasound and elastography imaging of axillary lymph nodes using the SuperSonic Imagine device and its ShearWave Trade-Mark-Sign elastography mode (SWE Trade-Mark-Sign ). The results obtained were compared to the immunohistochemical results for the removed lymph nodes. Results: 65 patients were enrolled. From the 103 lymph nodes examined by elastography and the 185 lymph nodes removed we were able to pair 81; 70 were healthy and 11 were malignant. The stiffness measurements (mean and maximal values) were significantly different between the healthy and metastatic lymph nodes, (p < 0.05). The areas under the ROC curves were 0.76 (95% confidence interval (CI): 0.58-0.94) and 0.75 (95%CI: 0.55-0.95) for the mean and the maximal stiffness, respectively. Conclusion: These encouraging results show a correlation between the metastatic risk of lymph nodes and their increased mean stiffness. Elasticity variables and potential thresholds that seem to predict the metastatic status of axillary lymph nodes were identified. If confirmed by further larger studies, these results could be useful in

  3. Fuzzy Load-Shedding Strategy Considering Photovoltaic Output Fluctuation Characteristics and Static Voltage Stability

    Directory of Open Access Journals (Sweden)

    Sheng Li

    2018-03-01

    Full Text Available Based on the equilibrium point equations of a classic three-node system integrated with a large-scale photovoltaic cell (PV power plant, the impact of PV output fluctuation on the saddle-node bifurcation (SNB was derived and analyzed. When PV runs in a unity power factor and the PV output active power Ppv is not too large (several hundred MW and below, the PV output fluctuation has little effect on the SNB point position and load margin index, so that the load margin index can be calculated online using the SNB point at Ppv = 0 pu. On the other hand, the local reactive power compensation in the load center can effectively raise the load bus voltage and make the voltage stability problem become more concealed; the traditional under-voltage load-shedding (UVLS strategy only carries out load shedding when the bus voltage amplitude is below the specified value and cannot effectively maintain the system static voltage stability in some occasions. In this paper, a fuzzy load-shedding strategy considering the impact of PV output fluctuations for the large-scale PV grid-connected system was designed, taking the load bus voltage amplitude and load margin index as fuzzy input variables, and the load-shedding command as a fuzzy output variable. Nine fuzzy IF-THEN rules were extracted for the fuzzy controller and the corresponding practical calculation method of load-shedding quantity was put forward. The simulation results of the classic three-node system and IEEE 14-bus system, both with a 100 MW PV power plant, verified the effectiveness of the fuzzy load-shedding controller whose input variable load margin index was calculated using the SNB point when the PV active power output was 0. The designed fuzzy load-shedding strategy can compensate for the defect—that the traditional UVLS strategy cannot effectively guarantee the system static voltage stability—and it can be widely used in power grids integrated with PV power plants whose scales are at a

  4. Innervation of periesophageal region of cat's diaphragm - Implication for studies of control of vomiting

    Science.gov (United States)

    Tan, L. K.; Miller, A. D.

    1986-01-01

    The extent of the region of the diaphragm around the esophagus that displays greatly reduced activity during the expulsive phase of vomiting was determined from electromyographic studies in cats to be about 0.75-1.0 cm from the esophagus. Horseradish peroxidase injected into this region retrogradely labeled motoneurons throughout most of the rostral-caudal extent of the phrenic nucleus, with the exception of caudal C6 and rostral C7. This widespread intermingling of motoneurons that innervate the region of reduced activity with other phrenic motoneurons creates a difficulty for needed follow-up studies of diaphragmatic control during vomiting.

  5. The role of SPECT-CT in the lymphoscintigraphic identification of sentinel nodes in patients with oral cancer

    DEFF Research Database (Denmark)

    Bilde, Anders; Von Buchwald, Christian; Mortensen, Jann

    2006-01-01

    SPECT with higher resolution CT scanners are expected to provide more accurate information about the localization of SNs. OBJECTIVE: To assess the role of combined SPECT-CT in SN identification in the clinically negative neck of patients with OSCC. MATERIALS AND METHODS: Lymphoscintigraphy comprising......CONCLUSION: SPECT-CT may improve the localization of sentinel nodes (SNs) in patients with oral squamous cell carcinoma (OSCC). Compared with planar lymphoscintigraphy SPECT-CT detected more SNs and provided additional anatomical and spatial information about their localization. New generation...... planar and SPECT-CT acquisition was performed in 34 consecutive patients with OSCC stage I and II (T1-2N0M0) prior to sentinel node biopsy (SNB) and selective neck dissection. The number of SNs and anatomical location was recorded according to lymphoscintigraphy and operative findings. RESULTS: SNB...

  6. Sentinel node biopsy in penile cancer

    DEFF Research Database (Denmark)

    Jakobsen, J. K.; Krarup, K. P.; Sommer, P.

    2015-01-01

    INTRODUCTION & OBJECTIVES: Nodal involvement is a strong prognosticator in penile cancer and lymph node staging is crucial. Sentinel node biopsy (SNB) has proven a useful staging tool with few complications, but evidence rely mostly on single institution publications with a short follow-up. In th......INTRODUCTION & OBJECTIVES: Nodal involvement is a strong prognosticator in penile cancer and lymph node staging is crucial. Sentinel node biopsy (SNB) has proven a useful staging tool with few complications, but evidence rely mostly on single institution publications with a short follow...... died from complications. CONCLUSIONS: To our knowledge, this is the first complete national study on sentinel node biopsy. Penile cancer sentinel node biopsy with a close follow-up is a reliable lymph node staging and has few complications in a national multicentre setting. Inguinal lymph node...

  7. PyMUS: Python-Based Simulation Software for Virtual Experiments on Motor Unit System.

    Science.gov (United States)

    Kim, Hojeong; Kim, Minjung

    2018-01-01

    We constructed a physiologically plausible computationally efficient model of a motor unit and developed simulation software that allows for integrative investigations of the input-output processing in the motor unit system. The model motor unit was first built by coupling the motoneuron model and muscle unit model to a simplified axon model. To build the motoneuron model, we used a recently reported two-compartment modeling approach that accurately captures the key cell-type-related electrical properties under both passive conditions (somatic input resistance, membrane time constant, and signal attenuation properties between the soma and the dendrites) and active conditions (rheobase current and afterhyperpolarization duration at the soma and plateau behavior at the dendrites). To construct the muscle unit, we used a recently developed muscle modeling approach that reflects the experimentally identified dependencies of muscle activation dynamics on isometric, isokinetic and dynamic variation in muscle length over a full range of stimulation frequencies. Then, we designed the simulation software based on the object-oriented programing paradigm and developed the software using open-source Python language to be fully operational using graphical user interfaces. Using the developed software, separate simulations could be performed for a single motoneuron, muscle unit and motor unit under a wide range of experimental input protocols, and a hierarchical analysis could be performed from a single channel to the entire system behavior. Our model motor unit and simulation software may represent efficient tools not only for researchers studying the neural control of force production from a cellular perspective but also for instructors and students in motor physiology classroom settings.

  8. Sentinel node biopsy for prostate cancer: report from a consensus panel meeting.

    Science.gov (United States)

    van der Poel, Henk G; Wit, Esther M; Acar, Cenk; van den Berg, Nynke S; van Leeuwen, Fijs W B; Valdes Olmos, Renato A; Winter, Alexander; Wawroschek, Friedhelm; Liedberg, Fredrik; Maclennan, Steven; Lam, Thomas

    2017-08-01

    To explore the evidence and knowledge gaps in sentinel node biopsy (SNB) in prostate cancer through a consensus panel of experts. A two-round Delphi survey among experts was followed by a consensus panel meeting of 16 experts in February 2016. Agreement voting was performed using the research and development project/University of California, Los Angeles Appropriateness Methodology on 150 statements in nine domains. The disagreement index based on the interpercentile range, adjusted for symmetry score, was used to assess consensus and non-consensus among panel members. Consensus was obtained on 91 of 150 statements (61%). The main outcomes were: (1) the results from an extended lymph node dissection (eLND) are still considered the 'gold standard', and sentinel node (SN) detection should be combined with eLND, at least in patients with intermediate- and high-risk prostate cancer; (2) the role of SN detection in low-risk prostate cancer is unclear; and (3) future studies should contain oncological endpoints as number of positive nodes outside the eLND template, false-negative and false-positive SN procedures, and recurrence-free survival. A high rate of consensus was obtained regarding outcome measures of future clinical trials on SNB (89%). Consensus on tracer technology was only obtained in 47% of statements, reflecting a need for further research and standardization in this area. The low-level evidence in the available literature and the composition of mainly SNB users in the panel constitute the major limitations of the study. Consensus on a majority of elementary statements on SN detection in prostate cancer was obtained.; therefore, the results from this consensus report will provide a basis for the design of further studies in the field. A group of experts identified evidence and knowledge gaps on SN detection in prostate cancer and its application in daily practice. Information from the consensus statements can be used to direct further studies. © 2017 The

  9. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    Directory of Open Access Journals (Sweden)

    Rosa-Eva Huettl

    2011-02-01

    Full Text Available The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1 in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG, we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  10. PyMUS: Python-Based Simulation Software for Virtual Experiments on Motor Unit System

    Directory of Open Access Journals (Sweden)

    Hojeong Kim

    2018-04-01

    Full Text Available We constructed a physiologically plausible computationally efficient model of a motor unit and developed simulation software that allows for integrative investigations of the input–output processing in the motor unit system. The model motor unit was first built by coupling the motoneuron model and muscle unit model to a simplified axon model. To build the motoneuron model, we used a recently reported two-compartment modeling approach that accurately captures the key cell-type-related electrical properties under both passive conditions (somatic input resistance, membrane time constant, and signal attenuation properties between the soma and the dendrites and active conditions (rheobase current and afterhyperpolarization duration at the soma and plateau behavior at the dendrites. To construct the muscle unit, we used a recently developed muscle modeling approach that reflects the experimentally identified dependencies of muscle activation dynamics on isometric, isokinetic and dynamic variation in muscle length over a full range of stimulation frequencies. Then, we designed the simulation software based on the object-oriented programing paradigm and developed the software using open-source Python language to be fully operational using graphical user interfaces. Using the developed software, separate simulations could be performed for a single motoneuron, muscle unit and motor unit under a wide range of experimental input protocols, and a hierarchical analysis could be performed from a single channel to the entire system behavior. Our model motor unit and simulation software may represent efficient tools not only for researchers studying the neural control of force production from a cellular perspective but also for instructors and students in motor physiology classroom settings.

  11. Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma

    DEFF Research Database (Denmark)

    Alkureishi, Lee W T; Burak, Zeynep; Alvarez, Julio A

    2009-01-01

    Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB...

  12. Regulation of choline acetyltransferase expression by 17 β-oestradiol in NSC-34 cells and in the spinal cord.

    Science.gov (United States)

    Johann, S; Dahm, M; Kipp, M; Zahn, U; Beyer, C

    2011-09-01

    Motoneurones located in the ventral horn of the spinal cord conciliate cholinergic innervation of skeletal muscles. These neurones appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis. The dysfunction of motoneurones is typically accompanied by alterations of cholinergic metabolism and signalling, as demonstrated by a decrease in choline acetyltransferase (ChAT) expression. 17 β-Oestradiol (E(2)) is generally accepted as neuroprotective factor in the brain under acute toxic and neurodegenerative conditions and also appears to exert a protective role for motoneurones. In the present study, we attempted to analyse the role of E(2) signalling on ChAT expression in the motoneurone-like cell line NSC-34 and in vivo. In a first step, we demonstrated the presence of oestrogen receptor α and β in NSC-34 cells, as well as in the cervical and lumbar parts, of the male mouse spinal cord. Subsequently, we investigated the effect of E(2) treatment on ChAT expression. The application of E(2) significantly increased the transcription of ChAT in NSC-34 cells and in the cervical but not lumbar part of the spinal cord. Our results indicate that E(2) can influence the cholinergic system by increasing ChAT expression in the mouse spinal cord. This mechanism might support motoneurones, in addition to survival-promoting mechanisms, in the temporal balance toxic or neurodegenerative challenges. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  13. An assessment of machine and statistical learning approaches to inferring networks of protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Browne Fiona

    2006-12-01

    Full Text Available Protein-protein interactions (PPI play a key role in many biological systems. Over the past few years, an explosion in availability of functional biological data obtained from high-throughput technologies to infer PPI has been observed. However, results obtained from such experiments show high rates of false positives and false negatives predictions as well as systematic predictive bias. Recent research has revealed that several machine and statistical learning methods applied to integrate relatively weak, diverse sources of large-scale functional data may provide improved predictive accuracy and coverage of PPI. In this paper we describe the effects of applying different computational, integrative methods to predict PPI in Saccharomyces cerevisiae. We investigated the predictive ability of combining different sets of relatively strong and weak predictive datasets. We analysed several genomic datasets ranging from mRNA co-expression to marginal essentiality. Moreover, we expanded an existing multi-source dataset from S. cerevisiae by constructing a new set of putative interactions extracted from Gene Ontology (GO- driven annotations in the Saccharomyces Genome Database. Different classification techniques: Simple Naive Bayesian (SNB, Multilayer Perceptron (MLP and K-Nearest Neighbors (KNN were evaluated. Relatively simple classification methods (i.e. less computing intensive and mathematically complex, such as SNB, have been proven to be proficient at predicting PPI. SNB produced the “highest” predictive quality obtaining an area under Receiver Operating Characteristic (ROC curve (AUC value of 0.99. The lowest AUC value of 0.90 was obtained by the KNN classifier. This assessment also demonstrates the strong predictive power of GO-driven models, which offered predictive performance above 0.90 using the different machine learning and statistical techniques. As the predictive power of single-source datasets became weaker MLP and SNB performed

  14. Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma

    DEFF Research Database (Denmark)

    Alkureishi, L W T; Burak, Z; Alvarez, J A

    2009-01-01

    Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB...

  15. Population based study on sentinel node biopsy before or after neoadjuvant chemotherapy in clinically node negative breast cancer patients : Identification rate and influence on axillary treatment

    NARCIS (Netherlands)

    van der Heiden-van der Loo, M.; de Munck, L.; Sonke, G. S.; van Dalen, T.; van Diest, P. J.; van den Bongard, H. J. G. D.; Peeters, P. H. M.; Rutgers, E. J. T.

    The timing of the sentinel lymph node biopsy (SNB) is controversial in clinically node negative patients receiving neoadjuvant chemotherapy (NAC). We studied variation in the timing of axillary staging in breast cancer patients who received NAC and the subsequent axillary treatment in The

  16. Functional and Anatomical Outcomes of Facial Nerve Injury With Application of Polyethylene Glycol in a Rat Model.

    Science.gov (United States)

    Brown, Brandon L; Asante, Tony; Welch, Haley R; Sandelski, Morgan M; Drejet, Sarah M; Shah, Kishan; Runge, Elizabeth M; Shipchandler, Taha Z; Jones, Kathryn J; Walker, Chandler L

    2018-05-17

    Functional and anatomical outcomes after surgical repair of facial nerve injury may be improved with the addition of polyethylene glycol (PEG) to direct suture neurorrhaphy. The application of PEG has shown promise in treating spinal nerve injuries, but its efficacy has not been evaluated in treatment of cranial nerve injuries. To determine whether PEG in addition to neurorrhaphy can improve functional outcomes and synkinesis after facial nerve injury. In this animal experiment, 36 rats underwent right facial nerve transection and neurorrhaphy with addition of PEG. Weekly behavioral scoring was done for 10 rats for 6 weeks and 14 rats for 16 weeks after the operations. In the 16-week study, the buccal branches were labeled and tissue analysis was performed. In the 6-week study, the mandibular and buccal branches were labeled and tissue analysis was performed. Histologic analysis was performed for 10 rats in a 1-week study to assess the association of PEG with axonal continuity and Wallerian degeneration. Six rats served as the uninjured control group. Data were collected from February 8, 2016, through July 10, 2017. Polyethylene glycol applied to the facial nerve after neurorrhaphy. Functional recovery was assessed weekly for the 16- and 6-week studies, as well as motoneuron survival, amount of regrowth, specificity of regrowth, and aberrant branching. Short-term effects of PEG were assessed in the 1-week study. Among the 40 male rats included in the study, PEG addition to neurorrhaphy showed no functional benefit in eye blink reflex (mean [SEM], 3.57 [0.88] weeks; 95% CI, -2.8 to 1.9 weeks; P = .70) or whisking function (mean [SEM], 4.00 [0.72] weeks; 95% CI, -3.6 to 2.4 weeks; P = .69) compared with suturing alone at 16 weeks. Motoneuron survival was not changed by PEG in the 16-week (mean, 132.1 motoneurons per tissue section; 95% CI, -21.0 to 8.4; P = .13) or 6-week (mean, 131.1 motoneurons per tissue section; 95% CI, -11.0 to 10.0; P = .06

  17. Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase-1 mutant mouse in vivo: evidence for increased persistent inward currents

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; Moldovan, Mihai; Marklund, Stefan L.

    2010-01-01

    Aim: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a preferential loss of motoneurones. Previous publications using in vitro neonatal preparations suggest an increased excitability of motoneurones in various superoxide dismutase-1 (SOD1) mutant mice...... of an increased PIC and less spike frequency adaptation which may contribute to excitotoxity of these neurones as the disease progresses....

  18. Relationships between Malocclusion, Body Posture, and Nasopharyngeal Pathology in Pre-Orthodontic Children.

    Science.gov (United States)

    Šidlauskienė, Monika; Smailienė, Dalia; Lopatienė, Kristina; Čekanauskas, Emilis; Pribuišienė, Rūta; Šidlauskas, Mantas

    2015-06-18

    Malocclusion, body posture, and breathing pattern may be correlated, but this issue is still controversial. The aim of the study was to examine the relationship between the type of malocclusion, body posture, and nasopharyngeal obstruction in children aged 7-14 years. The study group comprised 94 patients aged 7-14 years (mean±SD: 11.9±2.1 years); 44 (46.8%) males and 50 (53.2%) females. All patients passed an examination performed by the same orthodontist (study model and cephalometric radiograph analysis), orthopedic surgeon (body posture examined from the front, side, and back), and otorhinolaryngologist (anterior and posterior rhinoscopy and pharyngoscopy) in a blind manner. Postural disorders were observed in 72 (76.6%) patients. Hypertrophy of the adenoids was diagnosed in 54 (57.4%) patients, hypertrophy of the tonsils in 85 (90.3%), nasal septum deviation in 51 (54.3%), and allergic rhinitis in 19 (20.2%) patients. There was a statistically significant correlation between presence of kyphotic posture and a reduction in the SNB angle, representing sagittal position of the mandible. Also, there was a statistically significant association between kyphotic posture and nasopharyngeal obstruction (54.1% of patients with nasopharyngeal obstruction were kyphotic, compared with 25% of patients with no nasopharyngeal obstruction; p=0.02). Kyphotic posture and reduced SNB angle were more common among males. We concluded that: 1) there was a significant association between the sagittal position of the mandible (SNB angle) and a kyphotic posture; 2) kyphotic posture was significantly more common among patients with nasopharyngeal obstruction.

  19. Prediction of Non-sentinel Node Status in Patients with Melanoma and Positive Sentinel Node Biopsy: An Italian Melanoma Intergroup (IMI) Study.

    Science.gov (United States)

    Rossi, Carlo Riccardo; Mocellin, Simone; Campana, Luca Giovanni; Borgognoni, Lorenzo; Sestini, Serena; Giudice, Giuseppe; Caracò, Corrado; Cordova, Adriana; Solari, Nicola; Piazzalunga, Dario; Carcoforo, Paolo; Quaglino, Pietro; Caliendo, Virginia; Ribero, Simone

    2018-01-01

    Approximately 20% of melanoma patients harbor metastases in non-sentinel nodes (NSNs) after a positive sentinel node biopsy (SNB), and recent evidence questions the therapeutic benefit of completion lymph node dissection (CLND). We built a nomogram for prediction of NSN status in melanoma patients with positive SNB. Data on anthropometric and clinicopathological features of patients with cutaneous melanoma who underwent CLND after a positive SNB were collected from nine Italian centers. Multivariate logistic regression was utilized to identify predictors of NSN status in a training set, while model efficiency was validated in a validation set. Data were available for 1220 patients treated from 2000 through 2016. In the training set (n = 810), the risk of NSN involvement was higher when (1) the primary melanoma is thicker or (2) sited in the trunk/head and neck; (3) fewer nodes are excised and (4) more nodes are involved; and (5) the lymph node metastasis is larger or (6) is deeply located. The model showed high discrimination (area under the receiver operating characteristic curve 0.74, 95% confidence interval [CI] 0.70-0.79) and calibration (Brier score 0.16, 95% CI 0.15-0.17) performance in the validation set (n = 410). The nomogram including these six clinicopathological variables performed significantly better than five other previously published models in terms of both discrimination and calibration. Our nomogram could be useful for follow-up personalization in clinical practice, and for patient risk stratification while conducting clinical trials or analyzing their results.

  20. Actin cytoskeleton organization, cell surface modification and invasion rate of 5 glioblastoma cell lines differing in PTEN and p53 status

    International Nuclear Information System (INIS)

    Djuzenova, Cholpon S.; Fiedler, Vanessa; Memmel, Simon; Katzer, Astrid; Hartmann, Susanne; Krohne, Georg; Zimmermann, Heiko; Scholz, Claus-Jürgen; Polat, Bülent; Flentje, Michael

    2015-01-01

    Glioblastoma cells exhibit highly invasive behavior whose mechanisms are not yet fully understood. The present study explores the relationship between the invasion capacity of 5 glioblastoma cell lines differing in p53 and PTEN status, expression of mTOR and several other marker proteins involved in cell invasion, actin cytoskeleton organization and cell morphology. We found that two glioblastoma lines mutated in both p53 and PTEN genes (U373-MG and SNB19) exhibited the highest invasion rates through the Matrigel or collagen matrix. In DK-MG (p53wt/PTENwt) and GaMG (p53mut/PTENwt) cells, F-actin mainly occurred in the numerous stress fibers spanning the cytoplasm, whereas U87-MG (p53wt/PTENmut), U373-MG and SNB19 (both p53mut/PTENmut) cells preferentially expressed F-actin in filopodia and lamellipodia. Scanning electron microscopy confirmed the abundant filopodia and lamellipodia in the PTEN mutated cell lines. Interestingly, the gene profiling analysis revealed two clusters of cell lines, corresponding to the most (U373-MG and SNB19, i.e. p53 and PTEN mutated cells) and less invasive phenotypes. The results of this study might shed new light on the mechanisms of glioblastoma invasion. - Highlights: • We examine 5 glioblastoma lines on the invasion capacity and actin cytoskeleton. • Glioblastoma cell lines mutated in both p53 and PTEN were the most invasive. • Less invasive cells showed much less lamellipodia, but more actin stress fibers. • A mechanism for the differences in tumor cell invasion is proposed

  1. Actin cytoskeleton organization, cell surface modification and invasion rate of 5 glioblastoma cell lines differing in PTEN and p53 status

    Energy Technology Data Exchange (ETDEWEB)

    Djuzenova, Cholpon S., E-mail: djuzenova_t@ukw.de [Department of Radiation Oncology, University Hospital, Josef-Schneider-Strasse 11, D-97080 Würzburg (Germany); Fiedler, Vanessa [Department of Radiation Oncology, University Hospital, Josef-Schneider-Strasse 11, D-97080 Würzburg (Germany); Memmel, Simon [Lehrstuhl für Biotechnologie und Biophysik, Universität Würzburg, Biozentrum Am Hubland, 97070 Würzburg (Germany); Katzer, Astrid; Hartmann, Susanne [Department of Radiation Oncology, University Hospital, Josef-Schneider-Strasse 11, D-97080 Würzburg (Germany); Krohne, Georg [Elektronenmikroskopie, Biozentrum, Universität Würzburg, Am Hubland, 97070 Würzburg (Germany); Zimmermann, Heiko [Hauptabteilung Biophysik and Kryotechnologie, Fraunhofer-Institut für Biomedizinische Technik, Lehrstuhl für Molekulare und Zelluläre Biotechnologie/Nanotechnologie, Universität des Saarlandes, Ensheimer Strasse 48, 66386 St. Ingbert (Germany); Scholz, Claus-Jürgen [Interdisciplinary Center for Clinical Research, University Hospital, Versbacher Strasse 7, 97078 Würzburg (Germany); Polat, Bülent; Flentje, Michael [Department of Radiation Oncology, University Hospital, Josef-Schneider-Strasse 11, D-97080 Würzburg (Germany); and others

    2015-01-15

    Glioblastoma cells exhibit highly invasive behavior whose mechanisms are not yet fully understood. The present study explores the relationship between the invasion capacity of 5 glioblastoma cell lines differing in p53 and PTEN status, expression of mTOR and several other marker proteins involved in cell invasion, actin cytoskeleton organization and cell morphology. We found that two glioblastoma lines mutated in both p53 and PTEN genes (U373-MG and SNB19) exhibited the highest invasion rates through the Matrigel or collagen matrix. In DK-MG (p53wt/PTENwt) and GaMG (p53mut/PTENwt) cells, F-actin mainly occurred in the numerous stress fibers spanning the cytoplasm, whereas U87-MG (p53wt/PTENmut), U373-MG and SNB19 (both p53mut/PTENmut) cells preferentially expressed F-actin in filopodia and lamellipodia. Scanning electron microscopy confirmed the abundant filopodia and lamellipodia in the PTEN mutated cell lines. Interestingly, the gene profiling analysis revealed two clusters of cell lines, corresponding to the most (U373-MG and SNB19, i.e. p53 and PTEN mutated cells) and less invasive phenotypes. The results of this study might shed new light on the mechanisms of glioblastoma invasion. - Highlights: • We examine 5 glioblastoma lines on the invasion capacity and actin cytoskeleton. • Glioblastoma cell lines mutated in both p53 and PTEN were the most invasive. • Less invasive cells showed much less lamellipodia, but more actin stress fibers. • A mechanism for the differences in tumor cell invasion is proposed.

  2. Semaphorin6A acts as a gate keeper between the central and the peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Sadhu Rejina

    2007-12-01

    Full Text Available Abstract Background During spinal cord development, expression of chicken SEMAPHORIN6A (SEMA6A is almost exclusively found in the boundary caps at the ventral motor axon exit point and at the dorsal root entry site. The boundary cap cells are derived from a population of late migrating neural crest cells. They form a transient structure at the transition zone between the peripheral nervous system (PNS and the central nervous system (CNS. Ablation of the boundary cap resulted in emigration of motoneurons from the ventral spinal cord along the ventral roots. Based on its very restricted expression in boundary cap cells, we tested for a role of Sema6A as a gate keeper between the CNS and the PNS. Results Downregulation of Sema6A in boundary cap cells by in ovo RNA interference resulted in motoneurons streaming out of the spinal cord along the ventral roots, and in the failure of dorsal roots to form and segregate properly. PlexinAs interact with class 6 semaphorins and are expressed by both motoneurons and sensory neurons. Knockdown of PlexinA1 reproduced the phenotype seen after loss of Sema6A function both at the ventral motor exit point and at the dorsal root entry site of the lumbosacral spinal cord. Loss of either PlexinA4 or Sema6D function had an effect only at the dorsal root entry site but not at the ventral motor axon exit point. Conclusion Sema6A acts as a gate keeper between the PNS and the CNS both ventrally and dorsally. It is required for the clustering of boundary cap cells at the PNS/CNS interface and, thus, prevents motoneurons from streaming out of the ventral spinal cord. At the dorsal root entry site it organizes the segregation of dorsal roots.

  3. Sentinel European Node Trial (SENT)

    DEFF Research Database (Denmark)

    Schilling, Clare; Stoeckli, Sandro J; Haerle, Stephan K

    2015-01-01

    in patients with early-stage oral squamous cell carcinoma. METHODS: An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB...

  4. Sentinel node biopsy for early-stage melanoma - Accuracy and morbidity in MSLT-I, an international multicenter trial

    NARCIS (Netherlands)

    Morton, DL; Cochran, AJ; Thompson, JF; Elashoff, R; Essner, R; Glass, EC; Mozzillo, N; Nieweg, OE; Roses, DF; Hoekstra, HJ; Karakousis, CP; Reintgen, DS; Coventry, BJ; Wang, HJ

    Objective:The objective of this study was to evaluate, in an international multicenter phase III trial, the accuracy, use, and morbidity of intraoperative lymphatic mapping and sentinel node biopsy (LM/SNB) for staging the regional nodal basin of patients with early-stage melanoma. Summary

  5. Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial

    DEFF Research Database (Denmark)

    Alkureishi, Lee W T; Ross, Gary L; Shoaib, Taimur

    2010-01-01

    Sentinel node biopsy (SNB) may represent an alternative to elective neck dissection for the staging of patients with early head and neck squamous cell carcinoma (HNSCC). To date, the technique has been successfully described in a number of small single-institution studies. This report describes...

  6. A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization.

    Science.gov (United States)

    Jao, Li-En; Appel, Bruce; Wente, Susan R

    2012-04-01

    In humans, GLE1 is mutated in lethal congenital contracture syndrome 1 (LCCS1) leading to prenatal death of all affected fetuses. Although the molecular roles of Gle1 in nuclear mRNA export and translation have been documented, no animal models for this disease have been reported. To elucidate the function of Gle1 in vertebrate development, we used the zebrafish (Danio rerio) model system. gle1 mRNA is maternally deposited and widely expressed. Altering Gle1 using an insertional mutant or antisense morpholinos results in multiple defects, including immobility, small eyes, diminished pharyngeal arches, curved body axis, edema, underdeveloped intestine and cell death in the central nervous system. These phenotypes parallel those observed in LCCS1 human fetuses. Gle1 depletion also results in reduction of motoneurons and aberrant arborization of motor axons. Unexpectedly, the motoneuron deficiency results from apoptosis of neural precursors, not of differentiated motoneurons. Mosaic analyses further indicate that Gle1 activity is required extrinsically in the environment for normal motor axon arborization. Importantly, the zebrafish phenotypes caused by Gle1 deficiency are only rescued by expressing wild-type human GLE1 and not by the disease-linked Fin(Major) mutant form of GLE1. Together, our studies provide the first functional characterization of Gle1 in vertebrate development and reveal its essential role in actively dividing cells. We propose that defective GLE1 function in human LCCS1 results in both neurogenic and non-neurogenic defects linked to the apoptosis of proliferative organ precursors.

  7. Identification of Inhibitory Premotor Interneurons Activated at a Late Phase in a Motor Cycle during Drosophila Larval Locomotion.

    Directory of Open Access Journals (Sweden)

    Yuki Itakura

    Full Text Available Rhythmic motor patterns underlying many types of locomotion are thought to be produced by central pattern generators (CPGs. Our knowledge of how CPG networks generate motor patterns in complex nervous systems remains incomplete, despite decades of work in a variety of model organisms. Substrate borne locomotion in Drosophila larvae is driven by waves of muscular contraction that propagate through multiple body segments. We use the motor circuitry underlying crawling in larval Drosophila as a model to try to understand how segmentally coordinated rhythmic motor patterns are generated. Whereas muscles, motoneurons and sensory neurons have been well investigated in this system, far less is known about the identities and function of interneurons. Our recent study identified a class of glutamatergic premotor interneurons, PMSIs (period-positive median segmental interneurons, that regulate the speed of locomotion. Here, we report on the identification of a distinct class of glutamatergic premotor interneurons called Glutamatergic Ventro-Lateral Interneurons (GVLIs. We used calcium imaging to search for interneurons that show rhythmic activity and identified GVLIs as interneurons showing wave-like activity during peristalsis. Paired GVLIs were present in each abdominal segment A1-A7 and locally extended an axon towards a dorsal neuropile region, where they formed GRASP-positive putative synaptic contacts with motoneurons. The interneurons expressed vesicular glutamate transporter (vGluT and thus likely secrete glutamate, a neurotransmitter known to inhibit motoneurons. These anatomical results suggest that GVLIs are premotor interneurons that locally inhibit motoneurons in the same segment. Consistent with this, optogenetic activation of GVLIs with the red-shifted channelrhodopsin, CsChrimson ceased ongoing peristalsis in crawling larvae. Simultaneous calcium imaging of the activity of GVLIs and motoneurons showed that GVLIs' wave-like activity lagged

  8. Flexibility in the patterning and control of axial locomotor networks in lamprey.

    Science.gov (United States)

    Buchanan, James T

    2011-12-01

    In lower vertebrates, locomotor burst generators for axial muscles generally produce unitary bursts that alternate between the two sides of the body. In lamprey, a lower vertebrate, locomotor activity in the axial ventral roots of the isolated spinal cord can exhibit flexibility in the timings of bursts to dorsally-located myotomal muscle fibers versus ventrally-located myotomal muscle fibers. These episodes of decreased synchrony can occur spontaneously, especially in the rostral spinal cord where the propagating body waves of swimming originate. Application of serotonin, an endogenous spinal neurotransmitter known to presynaptically inhibit excitatory synapses in lamprey, can promote decreased synchrony of dorsal-ventral bursting. These observations suggest the possible existence of dorsal and ventral locomotor networks with modifiable coupling strength between them. Intracellular recordings of motoneurons during locomotor activity provide some support for this model. Pairs of motoneurons innervating myotomal muscle fibers of similar ipsilateral dorsoventral location tend to have higher correlations of fast synaptic activity during fictive locomotion than do pairs of motoneurons innervating myotomes of different ipsilateral dorsoventral locations, suggesting their control by different populations of premotor interneurons. Further, these different motoneuron pools receive different patterns of excitatory and inhibitory inputs from individual reticulospinal neurons, conveyed in part by different sets of premotor interneurons. Perhaps, then, the locomotor network of the lamprey is not simply a unitary burst generator on each side of the spinal cord that activates all ipsilateral body muscles simultaneously. Instead, the burst generator on each side may comprise at least two coupled burst generators, one controlling motoneurons innervating dorsal body muscles and one controlling motoneurons innervating ventral body muscles. The coupling strength between these two

  9. Phrenic motor outputs in response to bronchopulmonary C‐fibre activation following chronic cervical spinal cord injury

    Science.gov (United States)

    2016-01-01

    Key points Activation of bronchopulmonary C‐fibres, the main chemosensitive afferents in the lung, can induce pulmonary chemoreflexes to modulate respiratory activity.Following chronic cervical spinal cord injury, bronchopulmonary C‐fibre activation‐induced inhibition of phrenic activity was exaggerated.Supersensitivity of phrenic motor outputs to the inhibitory effect of bronchopulmonary C‐fibre activation is due to a shift of phrenic motoneuron types and slow recovery of phrenic motoneuron discharge in cervical spinal cord‐injured animals.These data suggest that activation of bronchopulmonary C‐fibres may retard phrenic output recovery following cervical spinal cord injury.The alteration of phenotype and discharge pattern of phrenic motoneuron enables us to understand the impact of spinal cord injury on spinal respiratory activity. Abstract Cervical spinal injury interrupts bulbospinal pathways and results in cessation of phrenic bursting ipsilateral to the lesion. The ipsilateral phrenic activity can partially recover over weeks to months following injury due to the activation of latent crossed spinal pathways and exhibits a greater capacity to increase activity during respiratory challenges than the contralateral phrenic nerve. However, whether the bilateral phrenic nerves demonstrate differential responses to respiratory inhibitory inputs is unclear. Accordingly, the present study examined bilateral phrenic bursting in response to capsaicin‐induced pulmonary chemoreflexes, a robust respiratory inhibitory stimulus. Bilateral phrenic nerve activity was recorded in anaesthetized and mechanically ventilated adult rats at 8–9 weeks after C2 hemisection (C2Hx) or C2 laminectomy. Intra‐jugular capsaicin (1.5 μg kg−1) injection was performed to activate the bronchopulmonary C‐fibres to evoke pulmonary chemoreflexes. The present results indicate that capsaicin‐induced prolongation of expiratory duration was significantly attenuated in C2Hx

  10. Phrenic motor outputs in response to bronchopulmonary C-fibre activation following chronic cervical spinal cord injury.

    Science.gov (United States)

    Lee, Kun-Ze

    2016-10-15

    Activation of bronchopulmonary C-fibres, the main chemosensitive afferents in the lung, can induce pulmonary chemoreflexes to modulate respiratory activity. Following chronic cervical spinal cord injury, bronchopulmonary C-fibre activation-induced inhibition of phrenic activity was exaggerated. Supersensitivity of phrenic motor outputs to the inhibitory effect of bronchopulmonary C-fibre activation is due to a shift of phrenic motoneuron types and slow recovery of phrenic motoneuron discharge in cervical spinal cord-injured animals. These data suggest that activation of bronchopulmonary C-fibres may retard phrenic output recovery following cervical spinal cord injury. The alteration of phenotype and discharge pattern of phrenic motoneuron enables us to understand the impact of spinal cord injury on spinal respiratory activity. Cervical spinal injury interrupts bulbospinal pathways and results in cessation of phrenic bursting ipsilateral to the lesion. The ipsilateral phrenic activity can partially recover over weeks to months following injury due to the activation of latent crossed spinal pathways and exhibits a greater capacity to increase activity during respiratory challenges than the contralateral phrenic nerve. However, whether the bilateral phrenic nerves demonstrate differential responses to respiratory inhibitory inputs is unclear. Accordingly, the present study examined bilateral phrenic bursting in response to capsaicin-induced pulmonary chemoreflexes, a robust respiratory inhibitory stimulus. Bilateral phrenic nerve activity was recorded in anaesthetized and mechanically ventilated adult rats at 8-9 weeks after C2 hemisection (C2Hx) or C2 laminectomy. Intra-jugular capsaicin (1.5 μg kg -1 ) injection was performed to activate the bronchopulmonary C-fibres to evoke pulmonary chemoreflexes. The present results indicate that capsaicin-induced prolongation of expiratory duration was significantly attenuated in C2Hx animals. However, ipsilateral phrenic

  11. Three-year follow-up of sentinel node-negative patients with early oral cavity squamous cell carcinoma

    DEFF Research Database (Denmark)

    Sebbesen, Lars; Bilde, Anders; Therkildsen, Marianne

    2014-01-01

    2009, 53 consecutive SNB-negative patients with oral cavity squamous cell carcinoma (SCC) T1 to T2 were accrued. Follow-up was done continuously with the most recent examination in October 2011. The location of the sentinel lymph nodes was determined using dynamic and planar lymphoscintigraphy...

  12. Thick melanoma: prognostic value of positive sentinel nodes

    NARCIS (Netherlands)

    Vermeeren, Lenka; van der Ent, Fred W. C.; Sastrowijoto, Prapto S. H.; Hulsewé, Karel W. E.

    2009-01-01

    BACKGROUND: Sentinel lymph node biopsy (SNB) is a widely accepted procedure used to accurately stage patients with melanoma. Its value in patients with thick melanoma (Breslow thickness >4 mm) is reason for discussion because of the generally poor prognosis of these patients. The purpose of this

  13. Patterns of Cellular Distribution with the Sentinel Node Positive for Breast Cancer

    International Nuclear Information System (INIS)

    Tsiapali, E.; Schmidt, M.M.; Dizon, D.; Steinhoff, M.; Gass, J.

    2011-01-01

    Background. Sentinel node biopsy (SNB) represents the standard of care in breast cancer axillary evaluation. Our study aims to characterize the patterns of malignant cell distribution within the sentinel nodes (SN). Methods. In a retrospective IRB-approved study, we examined the anatomic location of the nodal area with the highest radioactive signal or most intense blue staining (hot spot) and its distance from the metastatic foci. Results. 58 patients underwent SNB between January 2006 and February 2007. 12 patients with 19 positive SN were suitable for analysis. 4 (21%) metastases were located in the nodal hilum and 15 (79%) in the cortex. 6 (31%) metastases were found adjacent to the hotspot, and 9 (47%) within 4 mm of the hotspot. Conclusions. In our pilot series, SN metastases were within 4 mm of the hotspot in 78% of the cases. Pathologic analysis focused in that area may contribute to the more accurate identification of nodal metastases

  14. BIOLOGY OF SOME NEUROMUSCULAR DISORDERS

    Directory of Open Access Journals (Sweden)

    Gerta Vrbova

    2004-12-01

    Full Text Available In order to understand and possibly interfere/ treat neuromuscular disorders it is important to analyze the biological events that may be causing the disability. We illustrate such attempts on two examples of genetically determined neuromuscular diseases: 1 Duchenne muscular dystrophy (DMD, and 2 Spinal muscular atrophy (SMA.DMD is an x-linked hereditary muscle disease that leads to progressive muscle weakness. The altered gene in DMD affects dystrophin, a muscle membrane associated proteine. Attempts were made to replace the deficient or missing gene/ protein into muscles of Duchenne children. Two main strategies were explored: 1 Myoblast and stem cell transfer and 2 Gene delivery. The possible use of methods other than the introduction of the missing gene for dystrophin into muscle fibres are based on the knowledge about the adaptive potential of muscle to different functional demands and the ability of the muscle to express a new set of genes in response to such stimuli. Stretch or overload is now known to lead to changes of gene expression in normal muscle, and the success of muscle stretch in the management of Duchenne boys is most likely to be due to such adaptive changes. Electrical stimulation of muscles is also a powerful stimulus for inducing the expression of new genes and this method too has produced beneficial effects on the progress of the disease in mice and men.SMA is a heterogeneous group of hereditary neuromuscular disorders where the loss of lower motoneurones leads to progressive weakness and muscle atrophy. The disease subdivides into 3 forms according to the severity of the symptoms and age of onset. All three forms of SMA have been mapped to chromosome 5q11.2-13.2. Clinical features of all these forms of SMA include hypotonia shortly after birth, symmetrical muscle weakness and atrophy, finger tremor, areflexia or hyporeflexia and later contractures. In patients with SMA 1 and 2 the development of all parts of the motor

  15. Sentinel node biopsy for melanoma: a study of 241 patients

    DEFF Research Database (Denmark)

    Chakera, Annette Hougaard; Drzewiecki, Krzysztof Tadeusz; Jakobsen, Annika Loft

    2004-01-01

    The aim of this study was to evaluate the sentinel node biopsy (SNB) technique for melanoma using both radiocolloid and blue dye in 241 clinically N0 patients with melanomas >1.0 mm, or thinner lesions exhibiting regression/ulceration. We showed that an increase in injected radioactivity increased...

  16. Evaluation of sentinel lymph node size and shape as a predictor of occult metastasis in patients with squamous cell carcinoma of the oral cavity

    DEFF Research Database (Denmark)

    Langhans, Linnea; Bilde, Anders; Charabi, Birgitte

    2013-01-01

    node axis lengths were compared with the histopathological results. Data were analysed using Microsoft Excel 2008 for Mac, version 12.0. A total of 167 sentinel nodes was excised with a median of 3.3 per patient. Following SNB 18% of the patients was upstaged at the subsequent histopathological...

  17. New Er{sup 3+} doped antimony oxide based glasses: Thermal analysis, structural and spectral properties

    Energy Technology Data Exchange (ETDEWEB)

    Ouannes, K. [Faculté des Sciences et de la Technologie, Université de Biskra, BP 145 RP, 07000, Biskra (Algeria); Lebbou, K., E-mail: kheirreddine.lebbou@univ-lyon1.fr [Institut Lumière Matière, UMR5306 Université Lyon 1-CNRS, Université de Lyon, 69622, Villeurbanne (France); Walsh, Brian-M. [NASA Langley Research Center, Hampton, VA, 23681 (United States); Poulain, M. [UMR 6226- Verres et Céramiques – Campus de Beaulieu, Université de Rennes1, 35042, Rennes (France); Alombert-Goget, G.; Guyot, Y. [Institut Lumière Matière, UMR5306 Université Lyon 1-CNRS, Université de Lyon, 69622, Villeurbanne (France)

    2015-11-15

    The novel oxide glass compositions based on Sb{sub 2}O{sub 3} are elaborated and characterized, in the system (90-X)Sb{sub 2}O{sub 3}–10Na{sub 2}O–XBi{sub 2}O{sub 3} (SNB). We are interested in bismuth rates incorporated into the glass, its effect on the different physical properties that have been measured, and especially, in radiative and spectroscopic properties of erbium doped SNB glasses. Differential scanning calorimeter (DSC) measurements show an improvement of the stability factor,ΔT, of the glasses, which can indicate a reinforcement of the network. Both FTIR and Raman spectra have also been considered in terms of bismuth influence. As a function of composition, we have principally measured optical absorption, visible and infrared emission, and lifetime. The Judd–Ofelt parameters measured from the absorption spectra have been used to calculate the radiative lifetime (τ{sub r}) and the stimulated emission cross section. The spectroscopic quality factor χ = Ω{sub 4}/Ω{sub 6} = 0.73, low phonon energy of ∼600–700 cm{sup −1}, a reduced quenching effect, and a high quantum efficiency of 90% for the 1.53 μm measured emission, by pumping at 980 nm, are in favor of promising laser applications. - Highlights: • Glass belonging to Er-doped Sb{sub 2}O{sub 3}–Na{sub 2}O–Bi{sub 2}O{sub 3} (SNB) system are elaborated and characterized. • The intensity parameters Ωt were obtained via the Judd–Ofelt theory. • The optical properties were studied as a function of glass composition.

  18. In-situ Monitoring of Sub-cooled Nucleate Boiling on Fuel Cladding Surface in Water at 1 bar and 130 bars using Acoustic Emission Method

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Seung Heon; Wu, Kaige; Shim, Hee-Sang; Lee, Deok Hyun; Hur, Do Haeng [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    Crud deposition increases through a sufficient corrosion product supply around the steam-liquid interface of a boiling bubble. Therefore, the understanding of this SNB phenomenon is important for effective and safe operation of nuclear plants. The experimental SNB studies have been performed in visible conditions at a low pressure using a high speed video camera. Meanwhile, an acoustic emission (AE) method is an on-line non-destructive evaluation method to sense transient elastic wave resulting from a rapid release of energy within a dynamic process. Some researchers have investigated boiling phenomena using the AE method. However, their works were performed at atmospheric pressure conditions. Therefore, the objective of this work is for the first time to detect and monitor SNB on fuel cladding surface in simulated PWR primary water at 325 .deg. C and 130 bars using an AE technique. We successfully observed the boiling AE signals in primary water at 1 bar and 130 bars using AE technique. Visualization test was performed effectively to identify a correlation between water boiling phenomenon and AE signals in a transparent glass cell at 1 bar, and the boiling AE signals were in good agreement with the boiling behavior. Based on the obtained correlations at 1 bar, the AE signals obtained at 130 bars were analyzed. The boiling density and size of the AE signals at 130 bars were decreased by the flow parameters. However, overall AE signals showed characteristics and a trend similar to the AE signals at 1 bar. This indicates that boiling AE signals are detected successfully at 130 bars, and the AE technique can be effectively implemented in non-visualized condition at high pressures.

  19. ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

    Directory of Open Access Journals (Sweden)

    Emmanuelle eCoque

    2014-08-01

    Full Text Available Spinal muscular atrophy (SMA is the most common genetic disease causing infant death, due to an extended loss of motoneurons. This neuromuscular disorder results from deletions and/or mutations within the surviving motor neuron 1 (SMN1 gene, leading to a pathological decreased expression of functional full-length SMN protein. Emerging studies suggest that the small GTPase RhoA and its major downstream effector Rho kinase (ROCK, which both play an instrumental role in cytoskeleton organization, contribute to the pathology of motoneuron diseases. Indeed, an enhanced activation of RhoA and ROCK has been reported in the spinal cord of an SMA mouse model. Moreover, the treatment of SMA mice with ROCK inhibitors leads to an increased lifespan as well as improved skeletal muscle and neuromuscular junction pathology, without preventing motoneuron degeneration. Although motoneurons are the primary target in SMA, an increasing number of reports show that other cell types inside and outside the central nervous system contribute to SMA pathogenesis. As administration of ROCK inhibitors to SMA mice was systemic, the improvement in survival and phenotype could therefore be attributed to specific effects on motoneurons and/or on other non-neuronal cell types. In the present review, we will present the various roles of the RhoA/ROCK pathway in several SMA cellular targets including neurons, myocytes, glial cells, cardiomyocytes and pancreatic cells as well as discuss how ROCK inhibition may ameliorate their health and function. It is most likely a concerted influence of ROCK modulation on all these cell types that ultimately lead to the observed benefits of pharmacological ROCK inhibition in SMA mice.

  20. ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

    Science.gov (United States)

    Coque, Emmanuelle; Raoul, Cédric; Bowerman, Mélissa

    2014-01-01

    Spinal muscular atrophy (SMA) is the most common genetic disease causing infant death, due to an extended loss of motoneurons. This neuromuscular disorder results from deletions and/or mutations within the Survival Motor Neuron 1 (SMN1) gene, leading to a pathological decreased expression of functional full-length SMN protein. Emerging studies suggest that the small GTPase RhoA and its major downstream effector Rho kinase (ROCK), which both play an instrumental role in cytoskeleton organization, contribute to the pathology of motoneuron diseases. Indeed, an enhanced activation of RhoA and ROCK has been reported in the spinal cord of an SMA mouse model. Moreover, the treatment of SMA mice with ROCK inhibitors leads to an increased lifespan as well as improved skeletal muscle and neuromuscular junction pathology, without preventing motoneuron degeneration. Although motoneurons are the primary target in SMA, an increasing number of reports show that other cell types inside and outside the central nervous system contribute to SMA pathogenesis. As administration of ROCK inhibitors to SMA mice was systemic, the improvement in survival and phenotype could therefore be attributed to specific effects on motoneurons and/or on other non-neuronal cell types. In the present review, we will present the various roles of the RhoA/ROCK pathway in several SMA cellular targets including neurons, myoblasts, glial cells, cardiomyocytes and pancreatic cells as well as discuss how ROCK inhibition may ameliorate their health and function. It is most likely a concerted influence of ROCK modulation on all these cell types that ultimately lead to the observed benefits of pharmacological ROCK inhibition in SMA mice. PMID:25221469

  1. Experimental study of motor nerve innervation of uvala muscle%悬雍垂肌运动神经支配的实验研究

    Institute of Scientific and Technical Information of China (English)

    仲维剑; 张奎启; 王宏青

    2001-01-01

    目的探讨悬雍垂肌运动神经来源及走行路径。方法以家兔为研究对象,应用辣根过氧化物酶(horseridish peroxidase,HRP)逆行追踪技术,配合使用颅内的脑神经根切断术。结果悬雍垂肌的运动神经元位于同侧疑核中;切断一侧副神经延脑根后,疑核内的标记神经元消失。结论悬雍垂肌是疑核内运动神经元的轴突,经副神经延脑根出颅,再经由迷走神经咽支进行支配。%Objective To investigate the motor nerve innervation of uvala muscle. Methods Horseridish peroxidase (HRP) retrograde tracing technique was used in conjunction with selective intracranial severing of cranial nerve rootlets in 8 rabbies. Results Following HRP injection into uvala muscles, labeled motoneurons were located in the rostral section of nucleus ambiguus. No labeled motoneurons were found in the facial nucleus. Labled motoneurons were ipslaterally abolished after the cranial rootlets of accessory nerve on one side were intracranially severed. Conclusions Uvala muscles are innervated by the motoneurons in the nucleus ambiguus. The axons of those motoneurons come out of the cranium through the cranial rootlet of the accessory nerve, then join the vagus, distributed via the pharyngeal branches of vagus.

  2. Effects of early nerve repair on experimental brachial plexus injury in neonatal rats.

    Science.gov (United States)

    Bourke, Gráinne; McGrath, Aleksandra M; Wiberg, Mikael; Novikov, Lev N

    2018-03-01

    Obstetrical brachial plexus injury refers to injury observed at the time of delivery, which may lead to major functional impairment in the upper limb. In this study, the neuroprotective effect of early nerve repair following complete brachial plexus injury in neonatal rats was examined. Brachial plexus injury induced 90% loss of spinal motoneurons and 70% decrease in biceps muscle weight at 28 days after injury. Retrograde degeneration in spinal cord was associated with decreased density of dendritic branches and presynaptic boutons and increased density of astrocytes and macrophages/microglial cells. Early repair of the injured brachial plexus significantly delayed retrograde degeneration of spinal motoneurons and reduced the degree of macrophage/microglial reaction but had no effect on muscle atrophy. The results demonstrate that early nerve repair of neonatal brachial plexus injury could promote survival of injured motoneurons and attenuate neuroinflammation in spinal cord.

  3. Morphology and intrinsic excitability of regenerating sensory and motor neurons grown on a line micropattern.

    Directory of Open Access Journals (Sweden)

    Ouafa Benzina

    Full Text Available Axonal regeneration is one of the greatest challenges in severe injuries of peripheral nerve. To provide the bridge needed for regeneration, biological or synthetic tubular nerve constructs with aligned architecture have been developed. A key point for improving axonal regeneration is assessing the effects of substrate geometry on neuronal behavior. In the present study, we used an extracellular matrix-micropatterned substrate comprising 3 µm wide lines aimed to physically mimic the in vivo longitudinal axonal growth of mice peripheral sensory and motor neurons. Adult sensory neurons or embryonic motoneurons were seeded and processed for morphological and electrical activity analyses after two days in vitro. We show that micropattern-guided sensory neurons grow one or two axons without secondary branching. Motoneurons polarity was kept on micropattern with a long axon and small dendrites. The micro-patterned substrate maintains the growth promoting effects of conditioning injury and demonstrates, for the first time, that neurite initiation and extension could be differentially regulated by conditioning injury among DRG sensory neuron subpopulations. The micro-patterned substrate impacts the excitability of sensory neurons and promotes the apparition of firing action potentials characteristic for a subclass of mechanosensitive neurons. The line pattern is quite relevant for assessing the regenerative and developmental growth of sensory and motoneurons and offers a unique model for the analysis of the impact of geometry on the expression and the activity of mechanosensitive channels in DRG sensory neurons.

  4. Evaluation of Avulsion-Induced Neuropathology in Rat Spinal Cords with 18F-FDG Micro-PET/CT.

    Directory of Open Access Journals (Sweden)

    Ze-Min Ling

    Full Text Available Brachial plexus root avulsion (BPRA leads to dramatic motoneuron death and glial reactions in the corresponding spinal segments at the late stage of injury. To protect spinal motoneurons, assessment of the affected spinal segments should be done at an earlier stage of the injury. In this study, we employed 18F-FDG small-animal PET/CT to assess the severity of BPRA-induced cervical spinal cord injuries. Adult Sprague-Dawley rats were randomly treated and divided into three groups: Av+NS (brachial plexus root avulsion (Av treated with normal saline, Av+GM1 (treated with monosialoganglioside, and control. At time points of 3 day (d, 1 week (w, 2 w, 4 w and 8 w post-injury, 18F-FDG micro-PET/CT scans and neuropathology assessments of the injured spinal roots, as well as the spinal cord, were performed. The outcomes of the different treatments were compared. The results showed that BPRA induced local bleeding and typical Wallerian degeneration of the avulsed roots accompanied by 18F-FDG accumulations at the ipsilateral cervical intervertebral foramen. BPRA-induced astrocyte reactions and overexpression of neuronal nitric oxide synthase in the motoneurons correlated with higher 18F-FDG uptake in the ipsilateral cervical spinal cord during the first 2 w post-injury. The GM1 treatment reduced BPRA-induced astrocyte reactions and inhibited the de novo nNOS expressions in spinal motoneurons. The GM1 treatment also protected spinal motoneurons from avulsion within the first 4 w post-injury. The data from this study suggest that 18F-FDG PET/CT could be used to assess the severity of BPRA-induced primary and secondary injuries in the spinal cord. Furthermore, GM1 is an effective drug for reducing primary and secondary spinal cord injuries following BPRA.

  5. Coordination of locomotor and cardiorespiratory networks of Lymnaea stagnalis by a pair of identified interneurones.

    Science.gov (United States)

    Syed, N I; Winlow, W

    1991-07-01

    1. The morphology and electrophysiology of a newly identified bilateral pair of interneurones in the central nervous system of the pulmonate pond snail Lymnaea stagnalis is described. 2. These interneurones, identified as left and right pedal dorsal 11 (L/RPeD11), are electrically coupled to each other as well as to a large number of foot and body wall motoneurones, forming a fast-acting neural network which coordinates the activities of foot and body wall muscles. 3. The left and right sides of the body wall of Lymnaea are innervated by left and right cerebral A cluster neurones. Although these motoneurones have only ipsilateral projections, they are indirectly electrically coupled to their contralateral homologues via their connections with L/RPeD11. Similarly, the activities of left and right pedal G cluster neurones, which are known to be involved in locomotion, are also coordinated by L/RPeD11. 4. Selective ablation of both neurones PeD11 results in the loss of coordination between the bilateral cerebral A clusters. 5. Interneurones L/RPeD11 are multifunctional. In addition to coordinating motoneuronal activity, they make chemical excitatory connections with heart motoneurones. They also synapse upon respiratory motoneurones, hyperpolarizing those involved in pneumostome opening (expiration) and depolarizing those involved in pneumostome closure (inspiration). 6. An identified respiratory interneurone involved in pneumostome closure (visceral dorsal 4) inhibits L/RPeD11 together with all their electrically coupled follower cells. 7. Both L/RPeD11 have strong excitatory effects on another pair of electrically coupled neurones, visceral dorsal 1 and right parietal dorsal 2, which have previously been shown to be sensitive to changes in the partial pressure of environmental oxygen (PO2). 8. Although L/RPeD11 participate in whole-body withdrawal responses, electrical stimulation applied directly to these neurones was not sufficient to induce this behaviour.

  6. Role of the medial medullary reticular formation in relaying vestibular signals to the diaphragm and abdominal muscles

    Science.gov (United States)

    Mori, R. L.; Bergsman, A. E.; Holmes, M. J.; Yates, B. J.

    2001-01-01

    Changes in posture can affect the resting length of respiratory muscles, requiring alterations in the activity of these muscles if ventilation is to be unaffected. Recent studies have shown that the vestibular system contributes to altering respiratory muscle activity during movement and changes in posture. Furthermore, anatomical studies have demonstrated that many bulbospinal neurons in the medial medullary reticular formation (MRF) provide inputs to phrenic and abdominal motoneurons; because this region of the reticular formation receives substantial vestibular and other movement-related input, it seems likely that medial medullary reticulospinal neurons could adjust the activity of respiratory motoneurons during postural alterations. The objective of the present study was to determine whether functional lesions of the MRF affect inspiratory and expiratory muscle responses to activation of the vestibular system. Lidocaine or muscimol injections into the MRF produced a large increase in diaphragm and abdominal muscle responses to vestibular stimulation. These vestibulo-respiratory responses were eliminated following subsequent chemical blockade of descending pathways in the lateral medulla. However, inactivation of pathways coursing through the lateral medulla eliminated excitatory, but not inhibitory, components of vestibulo-respiratory responses. The simplest explanation for these data is that MRF neurons that receive input from the vestibular nuclei make inhibitory connections with diaphragm and abdominal motoneurons, whereas a pathway that courses laterally in the caudal medulla provides excitatory vestibular inputs to these motoneurons.

  7. Fine-needle aspirates CYFRA 21-1 is a useful tumor marker for detecting axillary lymph node metastasis in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Jung Hyun Yoon

    Full Text Available INTRODUCTION: To assess whether the value of CYFRA21-1 in the aspirates of ultrasonography-guided fine-needle aspiration biopsy (US-FNAB can contribute to improving the performances of US-FNAB in the diagnosis of axillary lymph node (LN metastasis in breast cancer patients. METHODS: US-FNAB was performed in 156 axillary LNs in 152 breast cancer patients (mean age: 51.4 years, range: 17-92 years. Concentrations of CYFRA21-1 were measured from washouts of the syringe used during US-FNAB. Tumor marker concentrations, US-FNAB, intraoperative sentinel node biopsy (SNB, and surgical pathology results were reviewed and analyzed. For comparison, the values of CEA and CA15-3 were also measured from washouts. RESULTS: Among the 156 LNs, 75 (48.1% were benign, and 81 (51.9% were metastases. Mean concentrations of CYFRA21-1 were significantly higher in metastasis compared to benign LNs (P<0.001. US-FNAB combined to CYFRA21-1 showed significantly higher sensitivity, NPV, and accuracy compared to US-FNAB alone (all values P<0.05. All diagnostic indices of US-FNAB combined to CYFRA21-1 were significantly higher compared to US-FNAB combined with CEA or CA15-3 (all P<0.001. Of the 28 metastatic LNs which showed metastasis on SNB, CYFRA21-1 showed higher positive rate of 75.0% (CEA or CA15-3∶60.7%, P = 0.076. CONCLUSION: Measuring CYFRA 21-1 concentrations from US-FNAB aspirates improves sensitivity, NPV, and accuracy of US-FNAB alone, and may contribute to reducing up to 75.0% of unnecessary intraoperative SNB. Compared to CEA or CA15-3, CYFRA21-1 shows significantly higher performances when combined to US-FNAB in the preoperative diagnosis of LN metastasis in breast cancer patients.

  8. The immobilization of heavy metals in soil by bioaugmentation of a UV-mutant Bacillus subtilis 38 assisted by NovoGro biostimulation and changes of soil microbial community

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ting [MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300071 (China); Urban Transport Emission Control Research Centre, College of Environmental Science and Engineering, Nankai University, Tianjin 300071 (China); Sun, Hongwen, E-mail: sunhongwen@nankai.edu.cn [MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300071 (China); Mao, Hongjun [Urban Transport Emission Control Research Centre, College of Environmental Science and Engineering, Nankai University, Tianjin 300071 (China); Zhang, Yanfeng; Wang, Cuiping; Zhang, Zhiyuan; Wang, Baolin; Sun, Lei [MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300071 (China)

    2014-08-15

    Highlights: • A UV-mutated species, Bacillus subtilis 38, is a good sorbent for multi-metals (Cd, Cr, Hg and Pb). • B38 mixed with NovoGro exhibited a synergetic effect on the immobilization of heavy metals in soil. • DTPA, M3 and BCR were suitable for predicting metal bioavailability for specific classes of plant. • The NovoGro could enhance the proliferation of both exotic B38 and native microbes. • It's a practical strategy for the remediation of actual farmland polluted by multi-heavy metals. - Abstract: Bacillus subtilis 38 (B38) is a mutant species of Bacillus subtilis acquired by UV irradiation with high cadmium tolerance. This study revealed that B38 was a good biosorbent for the adsorption of multiple heavy metals (cadmium, chromium, mercury, and lead). Simultaneous application of B38 and NovoGro (SNB) exhibited a synergetic effect on the immobilization of heavy metals in soil. The heavy metal concentrations in the edible part of the tested plants (lettuce, radish, and soybean) under SNB treatment decreased by 55.4–97.9% compared to the control. Three single extraction methods, diethylenetriaminepentaacetic acid (DTPA), Mehlich 3 (M3), and the first step of the Community Bureau of Reference method (BCR1), showed good predictive capacities for metal bioavailability to leafy, rhizome, and leguminous plant, respectively. The polymerase chain reaction–denaturing gradient gel electrophoresis (PCR–DGGE) profiles revealed that NovoGro could enhance the proliferation of both exotic B38 and native microbes. Finally, the technology was checked in the field, the reduction in heavy metal concentrations in the edible part of radish was in the range between 30.8% and 96.0% after bioremediation by SNB treatment. This study provides a practical strategy for the remediation of farmland contaminated by multiple heavy metals.

  9. Assessment of Soft Tissue Changes by Cephalometry and Two-Dimensional Photogrammetry in Bilateral Sagittal Split Ramus Osteotomy Cases

    Directory of Open Access Journals (Sweden)

    Jan Rustemeyer

    2011-07-01

    Full Text Available Objectives: We aimed to compare the standard methods of cephalometry and two-dimensional photogrammetry, to evaluate the reliability and accuracy of both methods.Material and Methods: Twenty-six patients (mean age 25.5, standard deviation (SD 5.2 years with Class II relationship and 23 patients with Class III relationship (mean age 26.4, SD 4.7 years who had undergone bilateral sagittal split ramus osteotomy were selected, with a median follow-up of 8 months between pre- and postsurgical evaluation. Pre- and postsurgical cephalograms and lateral photograms were traced and changes were recorded.Results: Pre- and postsurgical measurements of hard tissue angles and distances revealed higher correlations with cephalometrically performed soft tissue measurements of facial convexity (Class II: N-PG, r = - 0.50, P = 0.047; Class III: ANB, r = 0.73, P = 0.005; NaPg , r = 0.71, P = 0.007; and labiomental angle (Class II: SNB, r = 0.72, P = 0.002; ANB, r = - 0.72, P = 0.002; N-B, r = - 0.68, P = 0.004; ANS-Gn, r = 0.71, P = 0.002; Class III: ANS-Gn, r = 0.65, P = 0.043 compared with two-dimensional photogrammetry. However, two-dimensional photogrammetry revealed higher correlation between lower lip length and cephalometrically assessed angular hard tissue changes (Class II: SNB, r = 0.98, P = 0.007; N-B, r = 0.89, P = 0.037; N-Pg, r = 0.90, P = 0.033; Class III: SNB, r = - 0.54, P = 0.060; NAPg, r = - 0.65, P = 0.041; N-Pg, r = 0.58, P = 0.039.Conclusions: Our findings suggest that cephalometry and two-dimensional photogrammetry offer the possibility to complement one another.

  10. Assessment of Soft Tissue Changes by Cephalometry and Two-Dimensional Photogrammetry in Bilateral Sagittal Split Ramus Osteotomy Cases

    Science.gov (United States)

    Martin, Alice

    2011-01-01

    ABSTRACT Objectives We aimed to compare the standard methods of cephalometry and two-dimensional photogrammetry, to evaluate the reliability and accuracy of both methods. Material and Methods Twenty-six patients (mean age 25.5, standard deviation (SD) 5.2 years) with Class II relationship and 23 patients with Class III relationship (mean age 26.4, SD 4.7 years) who had undergone bilateral sagittal split ramus osteotomy were selected, with a median follow-up of 8 months between pre- and postsurgical evaluation. Pre- and postsurgical cephalograms and lateral photograms were traced and changes were recorded. Results Pre- and postsurgical measurements of hard tissue angles and distances revealed higher correlations with cephalometrically performed soft tissue measurements of facial convexity (Class II: N-PG, r = - 0.50, P = 0.047; Class III: ANB, r = 0.73, P = 0.005; NaPg , r = 0.71, P = 0.007;) and labiomental angle (Class II: SNB, r = 0.72, P = 0.002; ANB, r = - 0.72, P = 0.002; N-B, r = - 0.68, P = 0.004; ANS-Gn, r = 0.71, P = 0.002; Class III: ANS-Gn, r = 0.65, P = 0.043) compared with two-dimensional photogrammetry. However, two-dimensional photogrammetry revealed higher correlation between lower lip length and cephalometrically assessed angular hard tissue changes (Class II: SNB, r = 0.98, P = 0.007; N-B, r = 0.89, P = 0.037; N-Pg, r = 0.90, P = 0.033; Class III: SNB, r = - 0.54, P = 0.060; NAPg, r = - 0.65, P = 0.041; N-Pg, r = 0.58, P = 0.039). Conclusions Our findings suggest that cephalometry and two-dimensional photogrammetry offer the possibility to complement one another. PMID:24421994

  11. The immobilization of heavy metals in soil by bioaugmentation of a UV-mutant Bacillus subtilis 38 assisted by NovoGro biostimulation and changes of soil microbial community

    International Nuclear Information System (INIS)

    Wang, Ting; Sun, Hongwen; Mao, Hongjun; Zhang, Yanfeng; Wang, Cuiping; Zhang, Zhiyuan; Wang, Baolin; Sun, Lei

    2014-01-01

    Highlights: • A UV-mutated species, Bacillus subtilis 38, is a good sorbent for multi-metals (Cd, Cr, Hg and Pb). • B38 mixed with NovoGro exhibited a synergetic effect on the immobilization of heavy metals in soil. • DTPA, M3 and BCR were suitable for predicting metal bioavailability for specific classes of plant. • The NovoGro could enhance the proliferation of both exotic B38 and native microbes. • It's a practical strategy for the remediation of actual farmland polluted by multi-heavy metals. - Abstract: Bacillus subtilis 38 (B38) is a mutant species of Bacillus subtilis acquired by UV irradiation with high cadmium tolerance. This study revealed that B38 was a good biosorbent for the adsorption of multiple heavy metals (cadmium, chromium, mercury, and lead). Simultaneous application of B38 and NovoGro (SNB) exhibited a synergetic effect on the immobilization of heavy metals in soil. The heavy metal concentrations in the edible part of the tested plants (lettuce, radish, and soybean) under SNB treatment decreased by 55.4–97.9% compared to the control. Three single extraction methods, diethylenetriaminepentaacetic acid (DTPA), Mehlich 3 (M3), and the first step of the Community Bureau of Reference method (BCR1), showed good predictive capacities for metal bioavailability to leafy, rhizome, and leguminous plant, respectively. The polymerase chain reaction–denaturing gradient gel electrophoresis (PCR–DGGE) profiles revealed that NovoGro could enhance the proliferation of both exotic B38 and native microbes. Finally, the technology was checked in the field, the reduction in heavy metal concentrations in the edible part of radish was in the range between 30.8% and 96.0% after bioremediation by SNB treatment. This study provides a practical strategy for the remediation of farmland contaminated by multiple heavy metals

  12. Progressive paralysis associated with diffuse astrocyte anaplasia in delta 202 mice homozygous for a transgene encoding the SV40 T antigen.

    Science.gov (United States)

    López-Revilla, Rubén; Soto-Zárate, Carlos; Ridaura, Cecilia; Chávez-Dueñas, Lucía; Paul, Dieter

    2004-03-01

    A convenient transgenic astrocytoma model in delta202 mice, homozygous for a construct encoding the early region of the SV40 virus genome, is described. In the offspring of crosses between delta202 mice heterozygous for the transgene nearly 60% were transgenic; one third of these developed progressive paralysis starting in the hindlimbs at approximately 35 days of age and died at 90 +/- 30 days of age. In affected mice proliferating-non-neuronal cells immunostained with antibodies to the GFAP, an astrocyte marker, whose number increased with age were found in the white matter of the brain, cerebellum and spinal cord, and progressive degeneration and necrosis of spinal motoneurons was observed that-may explain the paralysis. The early onset and reproducible time course of the neurological disease suggest that homozygous delta202 mice, whose proliferating astrocytes appear to damage spinal motoneurons, are a useful model to study astrocyte differentiation, function and tumorigenesis.

  13. Motor Control of Drosophila Courtship Song

    Directory of Open Access Journals (Sweden)

    Troy R. Shirangi

    2013-11-01

    Full Text Available Many animals utilize acoustic signals—or songs—to attract mates. During courtship, Drosophila melanogaster males vibrate a wing to produce trains of pulses and extended tone, called pulse and sine song, respectively. Courtship songs in the genus Drosophila are exceedingly diverse, and different song features appear to have evolved independently of each other. How the nervous system allows such diversity to evolve is not understood. Here, we identify a wing muscle in D. melanogaster (hg1 that is uniquely male-enlarged. The hg1 motoneuron and the sexually dimorphic development of the hg1 muscle are required specifically for the sine component of the male song. In contrast, the motoneuron innervating a sexually monomorphic wing muscle, ps1, is required specifically for a feature of pulse song. Thus, individual wing motor pathways can control separate aspects of courtship song and may provide a “modular” anatomical substrate for the evolution of diverse songs.

  14. Non-local electron transport validation using 2D DRACO simulations

    Science.gov (United States)

    Cao, Duc; Chenhall, Jeff; Moll, Eli; Prochaska, Alex; Moses, Gregory; Delettrez, Jacques; Collins, Tim

    2012-10-01

    Comparison of 2D DRACO simulations, using a modified versionfootnotetextprivate communications with M. Marinak and G. Zimmerman, LLNL. of the Schurtz, Nicolai and Busquet (SNB) algorithmfootnotetextSchurtz, Nicolai and Busquet, ``A nonlocal electron conduction model for multidimensional radiation hydrodynamics codes,'' Phys. Plasmas 7, 4238(2000). for non-local electron transport, with direct drive shock timing experimentsfootnotetextT. Boehly, et. al., ``Multiple spherically converging shock waves in liquid deuterium,'' Phys. Plasmas 18, 092706(2011). and with the Goncharov non-local modelfootnotetextV. Goncharov, et. al., ``Early stage of implosion in inertial confinement fusion: Shock timing and perturbation evolution,'' Phys. Plasmas 13, 012702(2006). in 1D LILAC will be presented. Addition of an improved SNB non-local electron transport algorithm in DRACO allows direct drive simulations with no need for an electron conduction flux limiter. Validation with shock timing experiments that mimic the laser pulse profile of direct drive ignition targets gives a higher confidence level in the predictive capability of the DRACO code. This research was supported by the University of Rochester Laboratory for Laser Energetics.

  15. Spontaneous Vesicle Fusion Is Differentially Regulated at Cholinergic and GABAergic Synapses

    Directory of Open Access Journals (Sweden)

    Haowen Liu

    2018-02-01

    Full Text Available The locomotion of C. elegans is balanced by excitatory and inhibitory neurotransmitter release at neuromuscular junctions. However, the molecular mechanisms that maintain the balance of synaptic transmission remain enigmatic. Here, we investigated the function of voltage-gated Ca2+ channels in triggering spontaneous release at cholinergic and GABAergic synapses. Recordings of the miniature excitatory/inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively showed that UNC-2/CaV2 and EGL-19/CaV1 channels are the two major triggers for spontaneous release. Notably, however, Ca2+-independent spontaneous release was observed at GABAergic but not cholinergic synapses. Functional screening led to the identification of hypomorphic unc-64/Syntaxin-1A and snb-1/VAMP2 mutants in which mEPSCs are severely impaired, whereas mIPSCs remain unaltered, indicating differential regulation of these currents at cholinergic and GABAergic synapses. Moreover, Ca2+-independent spontaneous GABA release was nearly abolished in the hypomorphic unc-64 and snb-1 mutants, suggesting distinct mechanisms for Ca2+-dependent and Ca2+-independent spontaneous release.

  16. [Neural mechanisms of mastication].

    Science.gov (United States)

    Inoue, Tomio

    2015-02-01

    Abstract Comminution of food by mastication contributes to an increase in the efficiency of energy intake from food, which supports the high metabolic rate of mammals. The central pattern-generating circuit for mastication produces motor commands for mastication by using sensory information from periodontal mechanoreceptors and muscle spindles in the jaw-closing muscles. The motor commands that are glutamatergic, glycinergic, and GABAergic are transmitted to motoneurons for the jaw, tongue, etc., through premotor neurons that are located in the supratrigeminal region, reticular formation dorsal to the facial nucleus, etc. Our previous studies of N-methyl-D-aspartate-induced fictive suckling using isolated brainstem-spinal cord preparations obtained from neonatal mice revealed that the neuronal network that contributes to the synchronized activity of the jaw and tongue muscles is located in both the right and left sides. The network of either side sends its command to the trigeminal motoneurons mainly via the commissural pathway, while the command is sent to the hypoglossal motoneurons on the same side.

  17. Geochronology and Geochemistry of a Late Cretaceous Granitoid Suite, Santa Rosa Range, Nevada: Linking Arc Magmatism in Northwestern Nevada to the Sierra Nevada Batholith

    Science.gov (United States)

    Brown, K.; Stuck, R.; Hart, W. K.

    2010-12-01

    Throughout the Mesozoic, an arc-trench system dominated the western margin of North America. One of the principal records of this system’s evolution is a discontinuous alignment of deeply eroded batholiths, which represent the once-active roots of ancient volcanic systems. Although these batholiths extend from Alaska to Mexico, there is a prominent (~500 km) gap located in present-day Nevada that contains scattered plutons that are hypothesized to be similar in age and origin to the larger batholiths. The current understanding of these isolated plutons, however, remains limited to regional isotopic studies aimed at identifying major crustal boundaries and structural studies focused on emplacement mechanisms. Therefore, detailed petrogenetic studies of the plutons exposed within the Santa Rosa Range (SRR) of NW Nevada will better characterize magmatism in this region, placing them within a regional context that explores the hypothesized links between the intrusions of NW Nevada to the Sierra Nevada batholith (SNB). A compilation of published geochronology from this region shows that plutons in the SRR are broadly coeval with the Cathedral Range Intrusive Epoch (~95-83 Ma) and the Shaver Sequence (~118-105 Ma) of the SNB. Preliminary Rb-Sr geochronology from the Granite Peak stock reveals a previously unrecognized period of magmatism (ca. 85.0 Ma) in this region. Therefore, ongoing work will more completely characterize the timing of magmatic pulses in this region and their relationships to the SNB. Preliminary petrographic, geochemical, and isotopic observations suggest that two distinct compositional/textural groups exist: the Santa Rosa/ Andorno group (SRA) and Granite Peak/ Sawtooth group (GPS). The chemical and isotopic variations between the two groups suggest that they were not consanguineous. Whereas the SRA group is generally more mafic (64-72 wt% SiO2) and metaluminous, the GPS group is more felsic (72- 76 wt% SiO2) and peraluminous. This observation is

  18. Analysis of the fibroblast growth factor system reveals alterations in a mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Hensel, Niko; Ratzka, Andreas; Brinkmann, Hella; Klimaschewski, Lars; Grothe, Claudia; Claus, Peter

    2012-01-01

    The monogenetic disease Spinal Muscular Atrophy (SMA) is characterized by a progressive loss of motoneurons leading to muscle weakness and atrophy due to severe reduction of the Survival of Motoneuron (SMN) protein. Several models of SMA show deficits in neurite outgrowth and maintenance of neuromuscular junction (NMJ) structure. Survival of motoneurons, axonal outgrowth and formation of NMJ is controlled by neurotrophic factors such as the Fibroblast Growth Factor (FGF) system. Besides their classical role as extracellular ligands, some FGFs exert also intracellular functions controlling neuronal differentiation. We have previously shown that intracellular FGF-2 binds to SMN and regulates the number of a subtype of nuclear bodies which are reduced in SMA patients. In the light of these findings, we systematically analyzed the FGF-system comprising five canonical receptors and 22 ligands in a severe mouse model of SMA. In this study, we demonstrate widespread alterations of the FGF-system in both muscle and spinal cord. Importantly, FGF-receptor 1 is upregulated in spinal cord at a pre-symptomatic stage as well as in a mouse motoneuron-like cell-line NSC34 based model of SMA. Consistent with that, phosphorylations of FGFR-downstream targets Akt and ERK are increased. Moreover, ERK hyper-phosphorylation is functionally linked to FGFR-1 as revealed by receptor inhibition experiments. Our study shows that the FGF system is dysregulated at an early stage in SMA and may contribute to the SMA pathogenesis.

  19. Normally occurring intersexuality and testosterone induced plasticity in the copulatory system of adult leopard geckos.

    Science.gov (United States)

    Holmes, Melissa M; Putz, Oliver; Crews, David; Wade, Juli

    2005-04-01

    The copulatory neuromuscular system of lizards is highly sexually dimorphic. Adult males possess bilateral penises called hemipenes, which are independently controlled by two muscles, the retractor penis magnus (RPM) and transversus penis (TPN). These structures are not obvious in adult females. However, in adult female leopard geckos (Eublepharis macularius), testosterone induces hemipene growth. We investigated whether these structures develop de novo in adulthood or are histologically present as rudimentary structures in the female leopard gecko. We also investigated the extent of sexual dimorphisms and plasticity in the associated neuromuscular components. To do this, we compared copulatory morphology (sizes of hemipenes, RPM and TPN muscle fibers, and associated motoneurons, as well as motoneuron and RPM fiber number) in adult females treated with testosterone, control females, and control males. All of the geckos possessed hemipenes, RPMs and TPNs, but these structures were indeed vestigial in control females. Testosterone induced striking increases in hemipene and copulatory muscle fiber size in females, but not to levels equivalent to control males. In parallel, males with increased levels of androgenic activity had larger hemipenes, suggesting naturally occurring steroid-induced plasticity. Copulatory motoneurons were not sexually dimorphic in size or number, and these measures did not respond to testosterone. The data demonstrate that the copulatory system of leopard geckos, in which gonadal sex is determined by egg incubation temperature, differs from that of many species (both reptilian and mammalian) with genotypic sex determination. Indeed, the system is remarkable in that adult females have normally occurring intersex characteristics and they exhibit substantial steroid-induced morphological plasticity in adulthood.

  20. A multi-pad electrode based functional electrical stimulation system for restoration of grasp

    Directory of Open Access Journals (Sweden)

    Malešević Nebojša M

    2012-09-01

    Full Text Available Abstract Background Functional electrical stimulation (FES applied via transcutaneous electrodes is a common rehabilitation technique for assisting grasp in patients with central nervous system lesions. To improve the stimulation effectiveness of conventional FES, we introduce multi-pad electrodes and a new stimulation paradigm. Methods The new FES system comprises an electrode composed of small pads that can be activated individually. This electrode allows the targeting of motoneurons that activate synergistic muscles and produce a functional movement. The new stimulation paradigm allows asynchronous activation of motoneurons and provides controlled spatial distribution of the electrical charge that is delivered to the motoneurons. We developed an automated technique for the determination of the preferred electrode based on a cost function that considers the required movement of the fingers and the stabilization of the wrist joint. The data used within the cost function come from a sensorized garment that is easy to implement and does not require calibration. The design of the system also includes the possibility for fine-tuning and adaptation with a manually controllable interface. Results The device was tested on three stroke patients. The results show that the multi-pad electrodes provide the desired level of selectivity and can be used for generating a functional grasp. The results also show that the procedure, when performed on a specific user, results in the preferred electrode configuration characteristics for that patient. The findings from this study are of importance for the application of transcutaneous stimulation in the clinical and home environments.

  1. A fully automated temperature-dependent resistance measurement setup using van der Pauw method

    Science.gov (United States)

    Pandey, Shivendra Kumar; Manivannan, Anbarasu

    2018-03-01

    The van der Pauw (VDP) method is widely used to identify the resistance of planar homogeneous samples with four contacts placed on its periphery. We have developed a fully automated thin film resistance measurement setup using the VDP method with the capability of precisely measuring a wide range of thin film resistances from few mΩ up to 10 GΩ under controlled temperatures from room-temperature up to 600 °C. The setup utilizes a robust, custom-designed switching network board (SNB) for measuring current-voltage characteristics automatically at four different source-measure configurations based on the VDP method. Moreover, SNB is connected with low noise shielded coaxial cables that reduce the effect of leakage current as well as the capacitance in the circuit thereby enhancing the accuracy of measurement. In order to enable precise and accurate resistance measurement of the sample, wide range of sourcing currents/voltages are pre-determined with the capability of auto-tuning for ˜12 orders of variation in the resistances. Furthermore, the setup has been calibrated with standard samples and also employed to investigate temperature dependent resistance (few Ω-10 GΩ) measurements for various chalcogenide based phase change thin films (Ge2Sb2Te5, Ag5In5Sb60Te30, and In3SbTe2). This setup would be highly helpful for measurement of temperature-dependent resistance of wide range of materials, i.e., metals, semiconductors, and insulators illuminating information about structural change upon temperature as reflected by change in resistances, which are useful for numerous applications.

  2. [Post-traumatic reconnection of the cervical spinal cord with skeletal striated muscles. Study in adult rats and marmosets].

    Science.gov (United States)

    Horvat, J C; Affane-Boulaid, F; Baillet-Derbin, C; Davarpanah, Y; Destombes, J; Duchossoy, Y; Emery, E; Kassar-Duchossoy, L; Mira, J C; Moissonnier, P; Pécot-Dechavassine, M; Reviron, T; Rhrich-Haddout, F; Tadié, M; Ye, J H

    1997-01-01

    In an attempt at repairing the injured spinal cord of adult mammals (rat, dog and marmoset) and its damaged muscular connections, we are currently using: 1) peripheral nerve autografts (PNG), containing Schwann cells, to trigger and direct axonal regrowth from host and/or transplanted motoneurons towards denervated muscular targets; 2) foetal spinal cord transplants to replace lost neurons. In adult rats and marmosets, a PNG bridge was used to joint the injured cervical spinal cord to a denervated skeletal muscle (longissimus atlantis [rat] or biceps brachii [rat and marmoset]). The spinal lesion was obtained by the implantation procedure of the PNG. After a post-operative delay ranging from 2 to 22 months, the animals were checked electrophysiologically for functional muscular reconnection and processed for a morphological study including retrograde axonal tracing (HRP, Fast Blue, True Blue), histochemistry (AChE, ATPase), immunocytochemistry (ChAT) and EM. It was thus demonstrated that host motoneurons of the cervical enlargement could extend axons all the way through the PNG bridge as: a) in anaesthetized animals, contraction of the reconnected muscle could be obtained by electrical stimulation of the grafted nerve; b) the retrograde axonal tracing studies indicated that a great number of host cervical neurons extended axons into the PNG bridge up to the muscle; c) many of them were assumed to be motoneurons (double labelling with True Blue and an antibody against ChAT); and even alpha-motoneurons (type C axosomatic synapses in HRP labelled neurons seen in EM in the rat); d) numerous ectopic endplates were seen around the intramuscular tip of the PNG. In larger (cavitation) spinal lesions (rat), foetal motoneurons contained in E14 spinal cord transplants could similarly grow axons through PNG bridges up to the reconnected muscle. Taking all these data into account, it can be concluded that neural transplants are interesting tools for evaluating both the

  3. Twin - Arch technique. Revival of the "edgewise -Technique"?

    Directory of Open Access Journals (Sweden)

    Jacob Karp

    2012-01-01

    The SNB – Bracket brings a new dimension into the orthodontic world which is most apparent in extraction cases. Its Teflon – like material has a very low friction coefficient thus, reducing the treatment time considerably. Through the use of low dimensioned arch wires, the Twin – Arch Technique becomes a Light – wire system and simultaneously provides good anchorage and torque control.

  4. F response and H reflex analysis of physiological unity of gravity and antigravity muscles in man.

    Science.gov (United States)

    García, H A; Fisher, M A

    1977-01-01

    Observational differences between reflex (H reflex) and antidromic (F response) activation of segmental motoneurons by a peripheral electrical stimulus are described. In contrast to H reflexes, the percentage of F responses found after a series of stimuli is directly related to the pick-up field of the recording electrode consistent with this response being due to the variable activation of a small fraction of the available motoneuron pool. Despite the differing physiological mechanisms, both F responses and H reflexes can be used to demonstrate similar relative "central excitatory states" for antigravity muscles (i.e. extensors in the lower extremity and flexors in the upper extremity) and their antagonist gravity muscles. H reflexes were elicited not only in their usual location in certain antigravity muscles but also in unusual locations by length/tension changes in agonist and antagonist groups as well as by passive stretch. The data argue for the physiological unity of similarly acting gravity and antigravity muscles as well as supporting a meaningful role of group II afferents in normal segmental motoneuron pool excitability.

  5. Estimation of Muscle Force Based on Neural Drive in a Hemispheric Stroke Survivor.

    Science.gov (United States)

    Dai, Chenyun; Zheng, Yang; Hu, Xiaogang

    2018-01-01

    Robotic assistant-based therapy holds great promise to improve the functional recovery of stroke survivors. Numerous neural-machine interface techniques have been used to decode the intended movement to control robotic systems for rehabilitation therapies. In this case report, we tested the feasibility of estimating finger extensor muscle forces of a stroke survivor, based on the decoded descending neural drive through population motoneuron discharge timings. Motoneuron discharge events were obtained by decomposing high-density surface electromyogram (sEMG) signals of the finger extensor muscle. The neural drive was extracted from the normalized frequency of the composite discharge of the motoneuron pool. The neural-drive-based estimation was also compared with the classic myoelectric-based estimation. Our results showed that the neural-drive-based approach can better predict the force output, quantified by lower estimation errors and higher correlations with the muscle force, compared with the myoelectric-based estimation. Our findings suggest that the neural-drive-based approach can potentially be used as a more robust interface signal for robotic therapies during the stroke rehabilitation.

  6. Femoral Nerve Injury Following a Lumbar Plexus Blockade

    Directory of Open Access Journals (Sweden)

    İrfan Güngör

    2014-06-01

    Full Text Available Background: Lumbar plexus blockade (LPB combined with sciatic nerve block (SNB is frequently used for lower extremity surgery. Perioperative nerve injury is a rarely encountered complication of peripheral nerve blocks (PNB. Case Report: Here we report a 44-year-old male patient who developed a partial femoral nerve injury (FNI following a LPB which was performed before the surgery of a patellar fracture. The clinical and electroneuromyographic findings of the patient were recovered almost completely within the following six months. Conclusion: The presented case demonstrated a FNI despite the absence of any pain or paresthesia sensation, with the disappearance of motor response under 0.3 mA of neurostimulation in the experienced hands.

  7. Ferroelectricity of Sn-doped SrTiO3 perovskites with tin at both A and B sites

    Science.gov (United States)

    Suzuki, Shoichiro; Honda, Atsushi; Iwaji, Naoki; Higai, Shin'ichi; Ando, Akira; Takagi, Hiroshi; Kasatani, Hirofumi; Deguchi, Kiyoshi

    2012-08-01

    We successfully obtained Sn-doped SrTiO3 (SSTO) perovskites, and clarified their ferroelectricity and structural properties by using first-principles theoretical calculations. The ferroelectricity of SSTO was confirmed by the appearance of a dielectric permittivity maximum and a clear hysteresis loop of the relationship between the external electric field and the electric flux density below 180 K. X-ray diffraction and Raman spectra revealed the structural phase transition of SSTO at approximately 200 K. We directly observed by spherical aberration corrected scanning transmission electron microscopy with energy-dispersive x-ray spectroscopy that Sn ions are doped into both Sr and Ti sites (SnA and SnB), and that SnA is located at an off-centered position. We also performed theoretical analyses of SSTO and related perovskites, and found that SnA is preferentially located in an off-centered position and that SnA and the O6 octahedron, which includes SnB in its center, oscillate along the antiphase direction in the soft mode. Thus, we propose that the ferroelectricity of SSTO originates from the antiphase off-centering, which induces ferroelectric nanoregions in paraelectric SrTiO3.

  8. Deficient functional recovery after facial nerve crush in rats is associated with restricted rearrangements of synaptic terminals in the facial nucleus.

    Science.gov (United States)

    Hundeshagen, G; Szameit, K; Thieme, H; Finkensieper, M; Angelov, D N; Guntinas-Lichius, O; Irintchev, A

    2013-09-17

    Crush injuries of peripheral nerves typically lead to axonotmesis, axonal damage without disruption of connective tissue sheaths. Generally, human patients and experimental animals recover well after axonotmesis and the favorable outcome has been attributed to precise axonal reinnervation of the original peripheral targets. Here we assessed functionally and morphologically the long-term consequences of facial nerve axonotmesis in rats. Expectedly, we found that 5 months after crush or cryogenic nerve lesion, the numbers of motoneurons with regenerated axons and their projection pattern into the main branches of the facial nerve were similar to those in control animals suggesting precise target reinnervation. Unexpectedly, however, we found that functional recovery, estimated by vibrissal motion analysis, was incomplete at 2 months after injury and did not improve thereafter. The maximum amplitude of whisking remained substantially, by more than 30% lower than control values even 5 months after axonotmesis. Morphological analyses showed that the facial motoneurons ipsilateral to injury were innervated by lower numbers of glutamatergic terminals (-15%) and cholinergic perisomatic boutons (-26%) compared with the contralateral non-injured motoneurons. The structural deficits were correlated with functional performance of individual animals and associated with microgliosis in the facial nucleus but not with polyinnervation of muscle fibers. These results support the idea that restricted CNS plasticity and insufficient afferent inputs to motoneurons may substantially contribute to functional deficits after facial nerve injuries, possibly including pathologic conditions in humans like axonotmesis in idiopathic facial nerve (Bell's) palsy. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Cephalometric study of facial growth in children after combined pushback and pharyngeal flap operations.

    Science.gov (United States)

    Pearl, R M; Kaplan, E N

    1976-04-01

    Linear and angular cephalometric measurements of children who had had combined palatal pushbacks and superiorly-based pharyngeal flaps do not show later growth retardation of the face. There was an inherent tendency for children with overt clefts of the secondary palate, classic submucous clefts, or occult submucous clefts to demonstrate pre-operatively a narrow SNA and SNB--but the difference between these angles (ANB) was normal.

  10. Sensing of phosgene by a porous-like nanocrystalline diamond layer with buried metallic electrodes

    Czech Academy of Sciences Publication Activity Database

    Davydova, Marina; Stuchlík, M.; Rezek, Bohuslav; Larsson, K.; Kromka, Alexander

    2013-01-01

    Roč. 188, NOV (2013), s. 675-680 ISSN 0925-4005 R&D Projects: GA MPO FR-TI2/736; GA ČR GAP108/12/0996 Institutional support: RVO:68378271 Keywords : nanocrystalline diamond * phosgene * surface conductivity * gas sensor * SEM Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.840, year: 2013 http://dx.doi.org/10.1016/j.snb.2013.07.079

  11. Intraoperative immunohistochemistry staining of sentinel nodes in breast cancer: Clinical and economical implications

    DEFF Research Database (Denmark)

    Holm, M.; Paaschburg, B.; Balslev, E.

    2008-01-01

    .0001) for isolated tumor cell metastasis, from 56 to 36.4% (p analysis showed an overall...... of the surgical procedures before (n = 706) and after (n = 503) introducing intraoperatice IHC on frozen section. We also did a cost analysis. Intraoperative IHC staining led to a lowering of the late positive SNB rate. Introducing IHC gave a decrease in the late positive rate from 93 to 52% (p

  12. Regional nodal relapse in surgically staged Merkel cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hoeller, Ulrike; Mueller, Thomas; Schubert, Tina; Budach, Volker; Ghadjar, Pirus [Charite Universitaetsmedizin Berlin, Department of Radiation Oncology, Berlin (Germany); Brenner, Winfried [Charite Universitaetsmedizin Berlin, Department of Nuclear Medicine, Berlin (Germany); Kiecker, Felix [Charite Universitaetsmedizin Berlin, Department of Dermatology, Berlin (Germany); Schicke, Bernd [Tumor Center Berlin, Berlin (Germany); Haase, Oliver [Charite Universitaetsmedizin Berlin, Department of Surgery, Berlin (Germany)

    2014-10-08

    The nodal relapse pattern of surgically staged Merkel cell carcinoma (MCC) with/without elective nodal radiotherapy (RT) was studied in a single institution. A total of 51 patients with MCC, 33 % UICC stage I, 14 % II, 53 % III (4 lymph node metastases of unknown primary) were eligible. All patients had surgical staging: 23 patients sentinel node biopsy (SNB), 22 patients SNB followed by lymphadenectomy (LAD) and 6 patients LAD. In all, 94 % of the primary tumors (PT) were completely resected; 57 % of patients received RT, 51 % of known PT sites, 33 % (8/24 patients) regional RT to snN0 nodes and 68 % (17/27 patients) to pN+ nodes, mean reference dose 51.5 and 50 Gy, respectively. Mean follow-up was 6 years (range 2-14 years). A total of 22 % (11/51) patients developed regional relapses (RR); the 5-year RR rate was 27 %. In snN0 sites (stage I/II), relapse occurred in 5 of 14 nonirradiated vs. none of 8 irradiated sites (p = 0.054), resulting in a 5-year RR rate of 33 % versus 0 % (p = 0.16). The crude RR rate was lower in stage I (12 %, 2/17 patients) than for stage II (43 %, 3/7 patients). In stage III (pN+), RR appeared to be less frequent in irradiated sites (18 %, 3/14 patients) compared with nonirradiated sites (33 %, 3/10 patients, p = 0.45) with 5-year RR rates of 23 % vs. 34 %, respectively. Our data suggest that adjuvant nodal RT plays a major role even if the sentinel nodes were negative. Adjuvant RT of the lymph nodes in patients with stage IIa tumors and RT after LAD in stage III tumors is proposed and should be evaluated prospectively. (orig.) [German] Untersucht wurde das regionaere Rezidivmuster des Merkelzell-Karzinoms (MCC) nach chirurgischem Staging und stadienadaptierter Therapie. Eingeschlossen wurden 51 Patienten mit lokalisiertem MCC: 33 % hatten UICC-Stadium-I-, 14 % -II-, 53 % -III-Tumoren (davon 4 Lymphknotenmetastasen eines unbekannten Primaertumors). Alle Patienten erhielten ein chirurgisches Staging: 23 Waechterlymphknotenbiopsien (SNB

  13. Multiple Identified Neurons and Peripheral Nerves Innervating the Prothoracic Defense Glands in Stick Insects Reveal Evolutionary Conserved and Novel Elements of a Chemical Defense System

    Directory of Open Access Journals (Sweden)

    Johannes Strauß

    2017-11-01

    Full Text Available The defense glands in the dorsal prothorax are an important autapomorphic trait of stick insects (Phasmatodea. Here, we study the functional anatomy and neuronal innervation of the defense glands in Anisomorpha paromalus (Westwood, 1859 (Pseudophasmatinae, a species which sprays its defense secretions when disturbed or attacked. We use a neuroanatomical approach to identify the nerves innervating the gland muscles and the motoneurons with axons in the different nerves. The defense gland is innervated by nerves originating from two segments, the subesophageal ganglion (SOG, and the prothoracic ganglion. Axonal tracing confirms the gland innervation via the anterior subesophageal nerve, and two intersegmental nerves, the posterior subesophageal nerve, and the anterior prothoracic nerve. Axonal tracing of individual nerves reveals eight identified neuron types in the subesophageal or prothoracic ganglion. The strongest innervating nerve of the gland is the anterior subesophageal nerve, which also supplies dorsal longitudinal thorax muscles (neck muscles by separate nerve branches. Tracing of individual nerve branches reveals different sets of motoneurons innervating the defense gland (one ipsilateral and one contralateral subesophageal neuron or the neck muscle (ventral median neurons. The ipsilateral and contralateral subesophageal neurons have no homologs in related taxa like locusts and crickets, and thus evolved within stick insects with the differentiation of the defense glands. The overall innervation pattern suggests that the longitudinal gland muscles derived from dorsal longitudinal neck muscles. In sum, the innervating nerves for dorsal longitudinal muscles are conserved in stick insects, while the neuronal control system was specialized with conserved motoneurons for the persisting neck muscles, and evolutionarily novel subesophageal and prothoracic motoneurons innervating the defense gland.

  14. Use it or lose it: tonic activity of slow motoneurons promotes their survival and preferentially increases slow fiber-type groupings in muscles of old lifelong recreational sportsmen

    Directory of Open Access Journals (Sweden)

    Simone Mosole

    2016-11-01

    more active, i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging. Trial Registration: ClinicalTrials.gov: NCT01679977.

  15. Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen

    Science.gov (United States)

    Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

    2016-01-01

    , i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging. Trial Registration: ClinicalTrials.gov: NCT01679977 PMID:28078066

  16. Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen.

    Science.gov (United States)

    Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

    2016-09-15

    , i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging. ClinicalTrials.gov: NCT01679977.

  17. Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Karen K Y Ling

    2010-11-01

    Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

  18. Glucose transporters GLUT4 and GLUT8 are upregulated after facial nerve axotomy in adult mice.

    Science.gov (United States)

    Gómez, Olga; Ballester-Lurbe, Begoña; Mesonero, José E; Terrado, José

    2011-10-01

    Peripheral nerve axotomy in adult mice elicits a complex response that includes increased glucose uptake in regenerating nerve cells. This work analyses the expression of the neuronal glucose transporters GLUT3, GLUT4 and GLUT8 in the facial nucleus of adult mice during the first days after facial nerve axotomy. Our results show that whereas GLUT3 levels do not vary, GLUT4 and GLUT8 immunoreactivity increases in the cell body of the injured motoneurons after the lesion. A sharp increase in GLUT4 immunoreactivity was detected 3 days after the nerve injury and levels remained high on Day 8, but to a lesser extent. GLUT8 also increased the levels but later than GLUT4, as they only rose on Day 8 post-lesion. These results indicate that glucose transport is activated in regenerating motoneurons and that GLUT4 plays a main role in this function. These results also suggest that metabolic defects involving impairment of glucose transporters may be principal components of the neurotoxic mechanisms leading to motoneuron death. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

  19. 1,3-Oxazin-6-one Derivatives and Bohemamine-Type Pyrrolizidine Alkaloids from a Marine-Derived Streptomyces spinoverrucosus.

    Science.gov (United States)

    Fu, Peng; La, Scott; MacMillan, John B

    2016-03-25

    Two new 1,3-oxazin-6-one derivatives (1 and 2) and six new bohemamine-type pyrrolizidine alkaloids (3-8) were isolated from the marine-derived Streptomyces spinoverrucosus strain SNB-048. Their structures including the absolute configurations were fully elucidated on the basis of spectroscopic analysis, ECD spectra, quantum chemical calculations, and chemical methods. Compounds 1 and 2 possess a γ-lactam moiety and a 1,3-oxazin-6-one system.

  20. Chapter 11 - Electrical Coupling in the Generation of Vertebrate Motor Rhythms

    DEFF Research Database (Denmark)

    Li, W.C.; Rekling, Jens Christian

    2017-01-01

    Many forms of vertebrate motor activity like chewing, breathing, and locomotion are rhythmic. This requires synchronized discharges of motoneurons controlling different muscle groups in an orchestrated manner. We provide a brief review of the presence and role of electrical coupling in a few well...... of electrical coupling in vertebrate motor rhythms appears to be critically dependent on developmental age, with more crucial functions in the early postnatal period than in the adult.......-studied systems: the pacemaker nucleus in weakly electric fish; mesencephalic trigeminal nucleus involved in chewing rhythms; mammalian spinal motoneurons and excitatory interneurons in the Xenopus tadpole swimming circuit, brainstem circuits underlying breathing rhythm, and central respiratory chemosensitivity...

  1. Immobilization of cadmium in soils by UV-mutated Bacillus subtilis 38 bioaugmentation and NovoGro amendment

    International Nuclear Information System (INIS)

    Jiang Chunxiao; Sun Hongwen; Sun Tieheng; Zhang Qingmin; Zhang Yanfeng

    2009-01-01

    Immobilization of cadmium (10 mg Cd per kilogram soil) in soil by bioaugmentation of a UV-mutated microorganism, Bacillus subtilis 38 accompanied with amendment of a bio-fertilizer, NovoGro was investigated using extractable cadmium (E-Cd) by DTPA. B. subtilis 38, the mutant with the strongest resistance against Cd, could bioaccumulate Cd four times greater than the original wild type. Single bioaugmentation of B. subtilis 38 (SB treatment) to soil however did not reduce E-Cd significantly, while the amendment of NovoGro (SN treatment) reduced E-Cd remarkably. Simultaneous application of B. subtilis 38 and NovoGro (SNB treatment) exhibited a synergetic effect compared to the single SB and SN treatment. The immobilization effect was significantly affected by temperature, soil moisture, and pH. It seems that the immobilization on Cd reached the maximum when environmental conditions favored the activity of microorganisms. Under the optimum conditions, after 90 days incubation, E-Cd was 3.34, 3.39, 2.25 and 0.87 mg kg -1 in the control soil, SB, SN and SNB soils, respectively. NovoGro not only showed a great capacity for Cd adsorption, but also promoted the growth of B. subtilis 38. This study provides a potential cost-effective technique for in situ remediation of Cd contaminated soils with bioaugmentation.

  2. An estimate of the bulk viscosity of the hadronic medium

    Science.gov (United States)

    Sarwar, Golam; Chatterjee, Sandeep; Alam, Jane

    2017-05-01

    The bulk viscosity (ζ) of the hadronic medium has been estimated within the ambit of the Hadron Resonance Gas (HRG) model including the Hagedorn density of states. The HRG thermodynamics within a grand canonical ensemble provides the mean hadron number as well as its fluctuation. The fluctuation in the chemical composition of the hadronic medium in the grand canonical ensemble can result in non-zero divergence of the hadronic fluid flow velocity, allowing us to estimate the ζ of the hadronic matter up to a relaxation time. We study the influence of the hadronic spectrum on ζ and find its correlation with the conformal symmetry breaking measure, ε -3P. We estimate ζ along the contours with constant, S/{N}B (total entropy/net baryon number) in the T-μ plane (temperature-baryonic chemical potential) for S/{N}B=30,45 and 300. We also assess the value of ζ on the chemical freeze-out curve for various centers of mass energy (\\sqrt{{s}{NN}}) and find that the bulk viscosity to entropy density ratio, \\zeta /s is larger in the energy range of the beam energy scan program of RHIC, low energy SPS run, AGS, NICA and FAIR, than LHC energies.

  3. A hereditary spastic paraplegia mouse model supports a role of ZFYVE26/SPASTIZIN for the endolysosomal system.

    Directory of Open Access Journals (Sweden)

    Mukhran Khundadze

    Full Text Available Hereditary spastic paraplegias (HSPs are characterized by progressive weakness and spasticity of the legs because of the degeneration of cortical motoneuron axons. SPG15 is a recessively inherited HSP variant caused by mutations in the ZFYVE26 gene and is additionally characterized by cerebellar ataxia, mental decline, and progressive thinning of the corpus callosum. ZFYVE26 encodes the FYVE domain-containing protein ZFYVE26/SPASTIZIN, which has been suggested to be associated with the newly discovered adaptor protein 5 (AP5 complex. We show that Zfyve26 is broadly expressed in neurons, associates with intracellular vesicles immunopositive for the early endosomal marker EEA1, and co-fractionates with a component of the AP5 complex. As the function of ZFYVE26 in neurons was largely unknown, we disrupted Zfyve26 in mice. Zfyve26 knockout mice do not show developmental defects but develop late-onset spastic paraplegia with cerebellar ataxia confirming that SPG15 is caused by ZFYVE26 deficiency. The morphological analysis reveals axon degeneration and progressive loss of both cortical motoneurons and Purkinje cells in the cerebellum. Importantly, neuron loss is preceded by accumulation of large intraneuronal deposits of membrane-surrounded material, which co-stains with the lysosomal marker Lamp1. A density gradient analysis of brain lysates shows an increase of Lamp1-positive membrane compartments with higher densities in Zfyve26 knockout mice. Increased levels of lysosomal enzymes in brains of aged knockout mice further support an alteration of the lysosomal compartment upon disruption of Zfyve26. We propose that SPG15 is caused by an endolysosomal membrane trafficking defect, which results in endolysosomal dysfunction. This appears to be particularly relevant in neurons with highly specialized neurites such as cortical motoneurons and Purkinje cells.

  4. Alterations in Muscle Mass and Contractile Phenotype in Response to Unloading Models: Role of Transcriptional/Pretranslational Mechanisms

    Directory of Open Access Journals (Sweden)

    Kenneth M Baldwin

    2013-10-01

    Full Text Available Skeletal muscle is the largest organ system in mammalian organisms providing postural control and movement patterns of varying intensity. Through evolution, skeletal muscle fibers have evolved into three phenotype clusters defined as a muscle unit which consists of all muscle fibers innervated by a single motoneuron linking varying numbers of fibers of similar phenotype. This fundamental organization of the motor unit reflects the fact that there is a remarkable interdependence of gene regulation between the motoneurons and the muscle mainly via activity-dependent mechanisms. These fiber types can be classified via the primary type of myosin heavy chain (MHC gene expressed in the motor unit. Four MHC gene encoded proteins have been identified in striated muscle: slow type I MHC and three fast MHC types, IIa, IIx, and IIb. These MHCs dictate the intrinsic contraction speed of the myofiber with the type I generating the slowest and IIb the fastest contractile speed. Over the last ~35 years, a large body of knowledge suggests that altered loading state cause both fiber atrophy/wasting and a slow to fast shift in the contractile phenotype in the target muscle(s. Hence, this review will examine findings from three different animal models of unloading: 1 space flight (SF, i.e., microgravity; 2 hindlimb suspension (HS, a procedure that chronically eliminates weight bearing of the lower limbs; and 3 spinal cord isolation (SI, a surgical procedure that eliminates neural activation of the motoneurons and associated muscles while maintaining neurotrophic motoneuron-muscle connectivity. The collective findings demonstrate: 1 all three models show a similar pattern of fiber atrophy with differences mainly in the magnitude and kinetics of alteration; 2 transcriptional/pretranslational processes play a major role in both the atrophy process and phenotype shifts; and 3 signaling pathways impacting these alterations appear to be similar in each of the models

  5. Neuromorphic meets neuromechanics, part I: the methodology and implementation

    Science.gov (United States)

    Niu, Chuanxin M.; Jalaleddini, Kian; Sohn, Won Joon; Rocamora, John; Sanger, Terence D.; Valero-Cuevas, Francisco J.

    2017-04-01

    Objective: One goal of neuromorphic engineering is to create ‘realistic’ robotic systems that interact with the physical world by adopting neuromechanical principles from biology. Critical to this is the methodology to implement the spinal circuitry responsible for the behavior of afferented muscles. At its core, muscle afferentation is the closed-loop behavior arising from the interactions among populations of muscle spindle afferents, alpha and gamma motoneurons, and muscle fibers to enable useful behaviors. Approach. We used programmable very- large-scale-circuit (VLSI) hardware to implement simple models of spiking neurons, skeletal muscles, muscle spindle proprioceptors, alpha-motoneuron recruitment, gamma motoneuron control of spindle sensitivity, and the monosynaptic circuitry connecting them. This multi-scale system of populations of spiking neurons emulated the physiological properties of a pair of antagonistic afferented mammalian muscles (each simulated by 1024 alpha- and gamma-motoneurones) acting on a joint via long tendons. Main results. This integrated system was able to maintain a joint angle, and reproduced stretch reflex responses even when driving the nonlinear biomechanics of an actual cadaveric finger. Moreover, this system allowed us to explore numerous values and combinations of gamma-static and gamma-dynamic gains when driving a robotic finger, some of which replicated some human pathological conditions. Lastly, we explored the behavioral consequences of adopting three alternative models of isometric muscle force production. We found that the dynamic responses to rate-coded spike trains produce force ramps that can be very sensitive to tendon elasticity, especially at high force output. Significance. Our methodology produced, to our knowledge, the first example of an autonomous, multi-scale, neuromorphic, neuromechanical system capable of creating realistic reflex behavior in cadaveric fingers. This research platform allows us to explore

  6. Bistable firing properties of soleus motor units in unrestrained rats

    DEFF Research Database (Denmark)

    EKEN, T.; KIEHN, O.

    1989-01-01

    of the motoneuron pool by stimulation of la afferents, or inhibition by stimulation of skin afferents. The shifts were not related to gross limb movements. This phenomenon is referred to as a bistable firing pattern. Bistable firing also occurred spontaneously during quiet standing. Typically the firing frequency...... was unchanged or only phasically influenced. These results demonstrate for the first time a bistable firing pattern during postural activity in the intact animal. The firing pattern closely resembles the bistable behaviour described in spinal motoneurons in reduced preparations, where it is due to the presence...... of a plateau potential. This suggests that the bistable firing is unexplained by plateau potentials also in the intact animal....

  7. Contribution of 5-HT2A receptors on diaphragmatic recovery after chronic cervical spinal cord injury.

    Science.gov (United States)

    Lee, Kun-Ze; Gonzalez-Rothi, Elisa J

    2017-10-01

    Unilateral C2 spinal cord hemisection (C2Hx) interrupts bulbospinal respiratory pathways innervating ipsilateral phrenic motoneurons, resulting in cessation of ipsilateral diaphragm motor output. Plasticity within the spinal neural circuitry controlling the diaphragm can induce partial recovery of phrenic bursting which correlates with the time-dependent return of spinal serotonin (5-HT) immunoreactivity in the vicinity of phrenic motoneurons. The 5-HT 2A receptor subtype is present on phrenic motoneurons and its expression is up-regulated after cervical spinal cord injury; however the functional role of these receptors following injury has not been clearly defined. The present study evaluated the functional role of 5-HT 2A receptors by testing the hypothesis that pharmacologic blockade would attenuate diaphragm activity in rats with chronic cervical spinal cord injury. Bilateral diaphragm electromyography (EMG) was performed in vagal-intact and spontaneously breathing rats before and after intravenous administration of the 5-HT 2A receptor antagonist Ketanserin (1mg/kg). Intravenous ketanserin significantly attenuated ipsilateral diaphragm EMG activity in C2Hx animals but had no impact on diaphragm output in uninjured animals. We conclude that 5-HT 2A receptor activation contributes to the recovery of ipsilateral phrenic motor output after chronic cervical spinal cord injury. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Cephalometric evaluation of the effects of the Twin Block appliance in subjects with Class II, Division 1 malocclusion amongst different cervical vertebral maturation stages

    Directory of Open Access Journals (Sweden)

    Aisha Khoja

    Full Text Available ABSTRACT Objectives: To evaluate the cephalometric changes in skeletal, dentoalveolar and soft tissue variables induced by Clark's Twin Block (CTB in Class II, Division 1 malocclusion patients and to compare these changes in different cervical vertebral maturation stages. Methods: Pre- and post-treatment/observation lateral cephalograms of 53 Class II, Division 1 malocclusion patients and 60 controls were compared to evaluate skeletal, dentoalveolar and soft tissue changes. Skeletal maturity was assessed according to cervical vertebral maturation stages. Pre- and post-treatment/observation mean changes and differences (T2-T1 were compared by means of Wilcoxon sign rank and Mann-Whitney U-tests, respectively. Intergroup comparisons between different cervical stages were performed by means of Kruskal-Wallis test and Mann-Whitney U-test (p ≤ 0.05 . Results: When compared with controls, there was a significant reduction in ANB angle (p < 0.001, which was due to a change in SNB angle in CS-2 and CS-3 (p < 0.001, and in SNA (p < 0.001 and SNB (p = 0.016 angles in the CS-4 group. There was significant increase in the GoGn-SN angle in CS-2 (p = 0.007 and CS-4 (p = 0.024, and increase in Co-Gn and Go-Gn amongst all cervical stages (p < 0.05. There was significant decrease in U1-SN and increase in IMPA amongst all cervical stages (p < 0.05. There was significant retraction of the upper lip in CS-3 (p = 0.001, protrusion of the lower lip in CS-2 (p = 0.005, increase in nasolabial angle in CS-4 (p = 0.006 and Z-angle in CS-3 (p = 0.016, reduction in H-angle in CS-2 (p = 0.013 and CS-3 (p = 0.002 groups. When pre- and post-treatment mean differences were compared between different cervical stages, significant differences were found for SNA, SNB and UI-SN angles and overjet. . Conclusions: The Twin-Block along with the normal craniofacial growth improves facial esthetics in Class II, Division 1 malocclusion by changes in underlying skeletal and

  9. Fostering Sustainable Nutrition Behavior through Gamification

    Directory of Open Access Journals (Sweden)

    Verena Berger

    2016-01-01

    Full Text Available The food choices consumers make have considerable consequences for the environment. In the Western world, about one-third of all negative environmental impact is directly related to food consumption. Although many consumers are concerned about environmental issues, this frequently has little effect on actual nutritional behavior and new approaches are needed to convert good intentions into action. Gamification could be a possible way to encourage both self-efficacy on the part of the consumer as well as normalizing such behavior socially. In this paper, central elements of the behavioral change model HAPA (health action process approach are introduced to a gamification concept. The underlying frameworks of both concepts are then analyzed in order to develop propositions for use in the design of an effective gamification setting to promote sustainable nutritional behavior (SNB.

  10. Electrical coupling and excitatory synaptic transmission between rhythmogenic respiratory neurons in the preBötzinger complex

    DEFF Research Database (Denmark)

    Rekling, J C; Shao, X M; Feldman, J L

    2000-01-01

    Breathing pattern is postulated to be generated by brainstem neurons. However, determination of the underlying cellular mechanisms, and in particular the synaptic interactions between respiratory neurons, has been difficult. Here we used dual recordings from two distinct populations of brainstem...... respiratory neurons, hypoglossal (XII) motoneurons, and rhythmogenic (type-1) neurons in the preBötzinger complex (preBötC), the hypothesized site for respiratory rhythm generation, to determine whether electrical and chemical transmission is present. Using an in vitro brainstem slice preparation from newborn...... mice, we found that intracellularly recorded pairs of XII motoneurons and pairs of preBötC inspiratory type-1 neurons showed bidirectional electrical coupling. Coupling strength was low (neurons was heavily filtered (corner frequency,

  11. The value of preoperative ultrasound guided fine-needle aspiration cytology of radiologically suspicious axillary lymph nodes in breast cancer

    Directory of Open Access Journals (Sweden)

    Torill Sauer

    2014-01-01

    Full Text Available Background: Preoperative ultrasound (US and eventually US-guided fine-needle aspiration cytology (FNAC of suspicious axillary lymph nodes (ALN is a standard procedure in the work-up of suspicious breast lesions. Preoperative US FNAC may prevent sentinel node biopsy (SNB procedure in 24-30% of patients with early stage breast carcinoma. The aim of this study was to evaluate the institutional results of this preoperative diagnostic procedure. Materials and Methods: A total of 182 cases of preoperative FNAC of suspicious ALN where retrieved from the pathology files. The results were compared with the final histology and staging. False negative (FN FNAC cases were reviewed and possibly missed metastatic cases (2 were immunostained with the epithelial marker AE1/AE3. Results: There were no false positives, whereas 16 cases were FN. In all but one case the FN′s represented sampling error. Half of the 16 FN cases in this series were macrometastases. Discussion: About 83% of the preoperatively aspirated cases were N+, indicating that a radiologically suspicious ALN has a very high risk of being metastatic. Preoperative US guided FNAC from radiologically suspicious ALN is highly efficient in detecting metastases. Depending on national guidelines, a preoperative, positive ALN FNAC might help to stratify the patients as to SNB and/or ALN dissection.

  12. Is Switzerland an interest rate island after all? Time series and non-linear switching regime evidence

    OpenAIRE

    Feld, Lars P.; Köhler, Ekkehard A.

    2015-01-01

    Has the “Swiss interest rate anomaly” persisted after the financial crisis? Regarding the hypothesis that the Swiss interest rate anomaly results from systemic risk anticipation, we discuss whether Switzerland remains an interest rate island in the wake of the financial crisis. We find evidence for the demise of the interest rate bonus of the Swiss franc (CHF) vis-à-vis the Euro (EUR) after the Swiss National Bank (SNB) started to advocate an exchange rate floor with the Euro. After the compr...

  13. Time Course of the Soleus M Response and H Reflex after Lidocaine Tibial Nerve Block in the Rat

    Directory of Open Access Journals (Sweden)

    Kévin Buffenoir

    2013-01-01

    Full Text Available Aims. In spastic subjects, lidocaine is often used to induce a block predictive of the result provided by subsequent surgery. Lidocaine has been demonstrated to inhibit the Hoffmann (H reflex to a greater extent than the direct motor (M response induced by electrical stimulation, but the timecourse of these responses has not been investigated. Methods. An animal (rat model of the effects of lidocaine on M and H responses was therefore developed to assess this time course. M and H responses were recorded in 18 adult rats before and after application of lidocaine to the sciatic nerve. Results. Two to five minutes after lidocaine injection, M responses were markedly reduced (mean reduction of 44% and H reflexes were completely abolished. Changes were observed more rapidly for the H reflex. The effects of lidocaine then persisted for 100 minutes. The effect of lidocaine was therefore more prolonged on the H reflex than on the M response. Conclusion. This study confirms that lidocaine blocks not only alpha motoneurons but also Ia afferent fibres responsible for the H reflex. The authors describe, for the first time, the detailed time course of the effect of lidocaine on direct or reflex activation of motoneurons in the rat.

  14. A Fab fragment directed against the neural cell adhesion molecule L1 enhances functional recovery after injury of the adult mouse spinal cord.

    Science.gov (United States)

    Loers, Gabriele; Cui, Yi-Fang; Neumaier, Irmgard; Schachner, Melitta; Skerra, Arne

    2014-06-15

    Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to the failure of functional recovery, which leads to severe disabilities in motor functions or pain. Previous studies have indicated that the neural cell adhesion molecule L1 constitutes a viable target to promote regeneration. In the present study, we describe the cloning, functional expression in Escherichia coli cells and purification of a recombinant αL1 Fab fragment that binds to L1 with comparable activity as the function-triggering monoclonal antibody 557.B6 and induces neurite outgrowth and neuronal survival in cultured neurons, despite its monovalent function. Infusion of αL1 Fab into the lesioned spinal cord of mice enhanced functional recovery after thoracic spinal cord compression injury. αL1 Fab treatment resulted in reduced scar volume, enhanced number of tyrosine hydroxylase-positive axons and increased linear density of VGLUT1 (vesicular glutamate transporter 1) on motoneurons. Furthermore, the number and soma size of ChAT (choline acetyltransferase)-positive motoneurons and the linear density of ChAT-positive boutons on motoneurons as well as parvalbumin-positive interneurons in the lumbar spinal cord were elevated. Stimulation of endogenous L1 by application of the αL1 Fab opens new avenues for recombinant antibody technology, offering prospects for therapeutic applications after traumatic nervous system lesions.

  15. The action of chlorphenesin carbamate on the frog spinal cord.

    Science.gov (United States)

    Aihara, H; Kurachi, M; Nakane, S; Sasajima, M; Ohzeki, M

    1980-02-01

    Studies were carried out to elucidate the mechanism of action of chlorphenesin carbamate (CPC) and to compare the effect of the drug with that of mephenesin on the isolated bullfrog spinal cord. Ventral and dorsal root potentials were recorded by means of the sucrose-gap method. CPC caused marked hyperpolarizations and depressed spontaneous activities in both of the primary afferent terminals (PAT) and motoneurons (MN). These hyperpolarizations were observed even in high-Mg2+ and Ca2+-free Ringer's solution, suggesting that CPC has direct actions on PAT and MN. Various reflex potentials (dorsal and ventral root potentials elicited by stimulating dorsal and ventral root, respectively) tended to be depressed by CPC as well as by mephenesin. Excitatory amino acids (L-aspartic acid and L-glutamic acid) caused marked depolarizations in PAT and MN, and increased the firing rate in MN. CPC did not modify the depolarization but abolished the motoneuron firing induced by these amino acids. However, mephenesin reduced both the depolarization and the motoneuron firing. The dorsal and ventral root potentials evoked by tetanic stimulation (40 Hz) of the dorsal root were depressed by the drugs. These results indicate that CPC has an apparent depressing action on the spinal neuron, and this action may be ascribed to the slight hyperpolarization and/or the prolongation of refractory period.

  16. Motor recovery and synaptic preservation after ventral root avulsion and repair with a fibrin sealant derived from snake venom.

    Directory of Open Access Journals (Sweden)

    Roberta Barbizan

    Full Text Available BACKGROUND: Ventral root avulsion is an experimental model of proximal axonal injury at the central/peripheral nervous system interface that results in paralysis and poor clinical outcome after restorative surgery. Root reimplantation may decrease neuronal degeneration in such cases. We describe the use of a snake venom-derived fibrin sealant during surgical reconnection of avulsed roots at the spinal cord surface. The present work investigates the effects of this fibrin sealant on functional recovery, neuronal survival, synaptic plasticity, and glial reaction in the spinal motoneuron microenvironment after ventral root reimplantation. METHODOLOGY/PRINCIPAL FINDINGS: Female Lewis rats (7 weeks old were subjected to VRA and root replantation. The animals were divided into two groups: 1 avulsion only and 2 replanted roots with fibrin sealant derived from snake venom. Post-surgical motor performance was evaluated using the CatWalk system twice a week for 12 weeks. The rats were sacrificed 12 weeks after surgery, and their lumbar intumescences were processed for motoneuron counting and immunohistochemistry (GFAP, Iba-1 and synaptophysin antisera. Array based qRT-PCR was used to evaluate gene regulation of several neurotrophic factors and receptors as well as inflammatory related molecules. The results indicated that the root reimplantation with fibrin sealant enhanced motor recovery, preserved the synaptic covering of the motoneurons and improved neuronal survival. The replanted group did not show significant changes in microglial response compared to VRA-only. However, the astroglial reaction was significantly reduced in this group. CONCLUSIONS/SIGNIFICANCE: In conclusion, the present data suggest that the repair of avulsed roots with snake venom fibrin glue at the exact point of detachment results in neuroprotection and preservation of the synaptic network at the microenvironment of the lesioned motoneurons. Also such procedure reduced the

  17. Unlike physical exercise, modified environment increases the lifespan of SOD1G93A mice however both conditions induce cellular changes.

    Directory of Open Access Journals (Sweden)

    Yannick N Gerber

    Full Text Available Amyotrophic lateral sclerosis (ALS is characterized by a gradual muscular paralysis resulting from progressive motoneurons death. ALS etiology remains unknown although it has been demonstrated to be a multifactorial disease involving several cellular partners. There is currently no effective treatment. Even if the effect of exercise is under investigation for many years, whether physical exercise is beneficial or harmful is still under debate.We investigated the effect of three different intensities of running exercises on the survival of SOD1(G93A mice. At the early-symptomatic stage (P60, males were isolated and randomly assigned to 5 conditions: 2 sedentary groups ("sedentary" and "sedentary treadmill" placed on the inert treadmill, and 3 different training intensity groups (5 cm/s, 10 cm/s and 21 cm/s; 15 min/day, 5days/week. We first demonstrated that an appropriate "control" of the environment is of the utmost importance since comparison of the two sedentary groups evidenced an 11.6% increase in survival in the "sedentary treadmill" group. Moreover, we showed by immunohistochemistry that this increased lifespan is accompanied with motoneurons survival and increased glial reactivity in the spinal cord. In a second step, we showed that when compared with the proper control, all three running-based training did not modify lifespan of the animals, but result in motoneurons preservation and changes in glial cells activation.We demonstrate that increase in survival induced by a slight daily modification of the environment is associated with motoneurons preservation and strong glial modifications in the lumbar spinal cord of SOD1(G93A. Using the appropriate control, we then demonstrate that all running intensities have no effect on the survival of ALS mice but induce cellular modifications. Our results highlight the critical importance of the control of the environment in ALS studies and may explain discrepancy in the literature regarding the

  18. Motor Recovery and Synaptic Preservation after Ventral Root Avulsion and Repair with a Fibrin Sealant Derived from Snake Venom

    Science.gov (United States)

    Barbizan, Roberta; Castro, Mateus V.; Rodrigues, Antônio C.; Barraviera, Benedito; Ferreira, Rui S.; Oliveira, Alexandre L. R.

    2013-01-01

    Background Ventral root avulsion is an experimental model of proximal axonal injury at the central/peripheral nervous system interface that results in paralysis and poor clinical outcome after restorative surgery. Root reimplantation may decrease neuronal degeneration in such cases. We describe the use of a snake venom-derived fibrin sealant during surgical reconnection of avulsed roots at the spinal cord surface. The present work investigates the effects of this fibrin sealant on functional recovery, neuronal survival, synaptic plasticity, and glial reaction in the spinal motoneuron microenvironment after ventral root reimplantation. Methodology/Principal Findings Female Lewis rats (7 weeks old) were subjected to VRA and root replantation. The animals were divided into two groups: 1) avulsion only and 2) replanted roots with fibrin sealant derived from snake venom. Post-surgical motor performance was evaluated using the CatWalk system twice a week for 12 weeks. The rats were sacrificed 12 weeks after surgery, and their lumbar intumescences were processed for motoneuron counting and immunohistochemistry (GFAP, Iba-1 and synaptophysin antisera). Array based qRT-PCR was used to evaluate gene regulation of several neurotrophic factors and receptors as well as inflammatory related molecules. The results indicated that the root reimplantation with fibrin sealant enhanced motor recovery, preserved the synaptic covering of the motoneurons and improved neuronal survival. The replanted group did not show significant changes in microglial response compared to VRA-only. However, the astroglial reaction was significantly reduced in this group. Conclusions/Significance In conclusion, the present data suggest that the repair of avulsed roots with snake venom fibrin glue at the exact point of detachment results in neuroprotection and preservation of the synaptic network at the microenvironment of the lesioned motoneurons. Also such procedure reduced the astroglial reaction and

  19. Diaphragm electromyographic activity following unilateral midcervical contusion injury in rats

    Science.gov (United States)

    Sieck, Gary C.

    2016-01-01

    Contusion-type injuries to the spinal cord are characterized by tissue loss and disruption of spinal pathways. Midcervical spinal cord injuries impair the function of respiratory muscles and may contribute to significant respiratory complications. This study systematically assessed the impact of a 100-kDy unilateral C4 contusion injury on diaphragm muscle activity across a range of motor behaviors in rats. Chronic diaphragm electromyography (EMG) was recorded before injury and at 1 and 7 days postinjury (DPI). Histological analyses assessed the extent of perineuronal net formation, white-matter sparing, and phrenic motoneuron loss. At 7 DPI, ∼45% of phrenic motoneurons were lost ipsilaterally. Relative diaphragm root mean square (RMS) EMG activity increased bilaterally across a range of motor behaviors by 7 DPI. The increase in diaphragm RMS EMG activity was associated with an increase in neural drive (RMS value at 75 ms after the onset of diaphragm activity) and was more pronounced during higher force, nonventilatory motor behaviors. Animals in the contusion group displayed a transient decrease in respiratory rate and an increase in burst duration at 1 DPI. By 7 days, following midcervical contusion, there was significant perineuronal net formation and white-matter loss that spanned 1 mm around the injury epicenter. Taken together, these findings are consistent with increased recruitment of remaining motor units, including more fatigable, high-threshold motor units, during higher force, nonventilatory behaviors. Changes in diaphragm EMG activity following midcervical contusion injury reflect complex adaptations in neuromotor control that may increase the risk of motor-unit fatigue and compromise the ability to sustain higher force diaphragm efforts. NEW & NOTEWORTHY The present study shows that unilateral contusion injury at C4 results in substantial loss of phrenic motoneurons but increased diaphragm muscle activity across a range of ventilatory and higher

  20. A prolongation of the postspike afterhyperpolarization following spike trains can partly explain the lower firing rates at derecruitment than those at recruitment

    DEFF Research Database (Denmark)

    Wienecke, Jacob; Zhang, Mengliang; Hultborn, Hans

    2009-01-01

    rates at derecruitment correlated with a change in the postspike afterhyperpolarization (AHP) after preceding spike trains? This question was investigated by intracellular recordings from cat motor neurons in both unanesthetized and anesthetized preparations. The firing frequencies at recruitment...... for the lower frequencies at derecruitment. This was independent of whether the current injection had activated persistent inward current (PIC; plateau potentials, secondary range firing). It was found that a preceding spike train could prolong the AHP duration following a subsequent spike. The lower rate...... from AHP duration in fast motoneurons and higher than expected in slow motoneurons. It is suggested that these deviations are explained by the presence of synaptic noise as well as recruitment of PICs below firing threshold. Thus synaptic noise may allow spike discharge even after the end of the AHP...

  1. Increased central facilitation of antagonist reciprocal inhibition at the onset of dorsiflexion following explosive strength training

    DEFF Research Database (Denmark)

    Geertsen, Svend Sparre; Jensen, Jesper Lundbye; Nielsen, Jens Bo

    2008-01-01

    At the onset of dorsiflexion disynaptic reciprocal inhibition (DRI) of soleus motoneurons is increased to prevent activation of the antagonistic plantar flexors. This is caused by descending facilitation of transmission in the DRI pathway. Because the risk of eliciting stretch reflexes in the ankle...... of the ankle dorsiflexor muscles 3 times a week for 4 wk. Test sessions were conducted before, shortly after, and 2 wk after the training period. The rate of torque development measured at 30, 50, 100, and 200 ms after onset of voluntary explosive isometric dorsiflexion increased by 24-33% (P

  2. Surgical-site infection following lymph node excision indicates susceptibility for lymphedema

    DEFF Research Database (Denmark)

    Jørgensen, Mads Gustaf; Toyserkani, Navid Mohamadpour; Thomsen, Jørn Bo

    2018-01-01

    BACKGROUND AND OBJECTIVES: Cancer-related lymphedema is a common complication following lymph node excision. Prevention of lymphedema is essential, as treatment options are limited. Known risk factors are firmly anchored to the cancer treatment itself; however potentially preventable factors...... such as seroma and surgical-site infection (SSI) have yet to be asserted. METHODS: All malignant melanoma patients treated with sentinel lymph node biopsy (SNB) and/or complete lymph node dissection (CLND) in the axilla or groin between January 2008 and December 2014 were retrospectively identified. Identified...

  3. Utility of 18F-fluoro-deoxyglucose emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in combination with ultrasonography for axillary staging in primary breast cancer

    International Nuclear Information System (INIS)

    Ueda, Shigeto; Ishida, Jiro; Abe, Yoshiyuki; Mochizuki, Hidetaka; Tsuda, Hitoshi; Asakawa, Hideki; Omata, Jiro; Fukatsu, Kazuhiko; Kondo, Nobuo; Kondo, Tadaharu; Hama, Yukihiro; Tamura, Katsumi

    2008-01-01

    Accurate evaluation of axillary lymph node (ALN) involvement is mandatory before treatment of primary breast cancer. The aim of this study is to compare preoperative diagnostic accuracy between positron emission tomography/computed tomography with 18 F-fluorodeoxyglucose ( 18 F-FDG PET/CT) and axillary ultrasonography (AUS) for detecting ALN metastasis in patients having operable breast cancer, and to assess the clinical management of axillary 18 F-FDG PET/CT for therapeutic indication of sentinel node biopsy (SNB) and preoperative systemic chemotherapy (PSC). One hundred eighty-three patients with primary operable breast cancer were recruited. All patients underwent 18 F-FDG PET/CT and AUS followed by SNB and/or ALN dissection (ALND). Using 18 F-FDG PET/CT, we studied both a visual assessment of 18 F-FDG uptake and standardized uptake value (SUV) for axillary staging. In a visual assessment of 18 F-FDG PET/CT, the diagnostic accuracy of ALN metastasis was 83% with 58% in sensitivity and 95% in specificity, and when cut-off point of SUV was set at 1.8, sensitivity, specificity, and accuracy were 36, 100, and 79%, respectively. On the other hand, the diagnostic accuracy of AUS was 85% with 54% in sensitivity and 99% in specificity. By the combination of 18 F-FDG PET/CT and AUS to the axilla, the sensitivity, specificity, and accuracy were 64, 94, and 85%, respectively. If either 18 F-FDG PET uptake or AUS was positive in allixa, the probability of axillary metastasis was high; 50% (6 of 12) in 18 F-FDG PET uptake only, 80% (4 of 5) in AUS positive only, and 100% (28 of 28) in dual positive. By the combination of AUS and 18 F-FDG PET/CT, candidates of SNB were more appropriately selected. The axillary 18 F-FDG uptake was correlated with the maximum size and nuclear grade of metastatic foci (p = 0.006 and p = 0.03). The diagnostic accuracy of 18 F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their limited sensitivities, the high radiation

  4. The diagnostic value of adding dynamic scintigraphy to standard delayed planar imaging for sentinel node identification in melanoma patients

    International Nuclear Information System (INIS)

    Nielsen, Kristina Rue; Nielsen, Michael B.; Chakera, Annette H.; Hesse, Birger; Oturai, Peter S.; Scolyer, Richard A.; Stretch, Jonathan F.; Thompson, John F.; Uren, Roger F.

    2011-01-01

    The aim of this study was to compare early dynamic imaging combined with delayed static imaging and single photon emission computed tomography (SPECT)/CT with delayed, planar, static imaging alone for sentinel node (SN) identification in melanoma patients. Three hundred and seven consecutive melanoma patients referred for SN biopsy (SNB) were examined using combined imaging. Secondary interpretation of only the delayed static images was subsequently performed. In 220 patients (72%), complete surgical and pathological information relating to the SNB was available. The number of SNs identified and number of patients with positive SNs were compared between the two interpretations of the imaging studies and, when available, related to pathology data. A slightly higher number of SNs (mean 0.12/patient) was identified when interpreting only delayed static images compared to combined imaging. In a direct patient-to-patient comparison, the number of SN(s) identified on the combined vs static images only showed moderate agreement (kappa value 0.56). In 38 patients (17%), positive SNs were identified by the combined procedure compared to 35 (16%) by static imaging only. Thus by static imaging only, tumour-positive SNs were not identified in 3 of 38 patients (8%). For SN identification in melanoma patients, dynamic imaging combined with delayed static imaging and SPECT/CT is superior to delayed static imaging only because the latter is more likely to fail to identify SNs containing metastases. (orig.)

  5. Clinical significance of lymphadenectomy in patients with gastric cancer.

    Science.gov (United States)

    Tóth, Dezső; Plósz, János; Török, Miklós

    2016-02-15

    Approximately thirty percent of patients with gastric cancer undergo an avoidable lymph node dissection with a higher rate of postoperative complication. Comparing the D1 and D2 dissections, it was found that there is a significant difference in morbidity, favoured D1 dissection without any difference in overall survival. Subgroup analysis of patients with T3 tumor shows a survival difference favoring D2 lymphadenectomy, and there is a better gastric cancer-related death and non-statistically significant improvement of survival for node-positive disease in patients with D2 dissection. However, the extended lymphadenectomy could improve stage-specific survival owing to the stage migration phenomenon. The deployment of centralization and application of national guidelines could improve the surgical outcomes. The Japanese and European guidelines enclose the D2 lymphadenectomy as the gold standard in R0 resection. In the individualized, stage-adapted gastric cancer surgery the Maruyama computer program (MCP) can estimate lymph node involvement preoperatively with high accuracy and in addition the Maruyama Index less than 5 has a better impact on survival, than D-level guided surgery. For these reasons, the preoperative application of MCP is recommended routinely, with an aim to perform "low Maruyama Index surgery". The sentinel lymph node biopsy (SNB) may decrease the number of redundant lymphadenectomy intraoperatively with a high detection rate (93.7%) and an accuracy of 92%. More accurate stage-adapted surgery could be performed using the MCP and SNB in parallel fashion in gastric cancer.

  6. Correlation of cephalometric and anthropometric measures with obstructive sleep apnea severity

    Science.gov (United States)

    Borges, Paulo de Tarso M; Filho, Edson Santos Ferreira; Araujo, Telma Maria Evangelista de; Neto, Jose Machado Moita; Borges, Nubia Evangelista de Sa; Neto, Baltasar Melo; Campelo, Viriato; Paschoal, Jorge Rizzato; Li, Li M

    2013-01-01

    Summary Introduction: Patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) often have associated changes in craniofacial morphology and distribution of body fat, either alone or in combination. Aim: To correlate cephalometric and anthropometric measures with OSAHS severity by using the apnea-hypopnea index (AHI). Method: A retrospective cephalometry study of 93 patients with OSAHS was conducted from July 2010 to July 2012. The following measurements were evaluated: body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC), the angles formed by the cranial base and the maxilla (SNA) and the mandible (SNB), the difference between SNA and SNB (ANB), the distance from the mandibular plane to the hyoid bone (MP-H), the space between the base of the tongue and the posterior pharyngeal wall (PAS), and the distance between the posterior nasal spine and the tip of the uvula (PNS-P). Means, standard deviations, and Pearson's correlation coefficients were calculated and analyzed. Results: AHI correlated significantly with BMI (r = 0.207, p = 0.047), NC (r = 0.365, p = 0.000), WC (r = 0.337, p = 0.001), PNS-P (r = 0.282, p = 0.006), and MP-H (r = 0.235, p = 0.023). Conclusion: Anthropometric measurements (BMI, NC, and WC) and cephalometric measurements (MP-H and PNS-P) can be used as predictors of OSAHS severity. PMID:25992029

  7. Orthodontic camouflage versus orthognathic surgery for class III deformity: comparative cephalometric analysis.

    Science.gov (United States)

    Martinez, P; Bellot-Arcís, C; Llamas, J M; Cibrian, R; Gandia, J L; Paredes-Gallardo, V

    2017-04-01

    The objective of this study was to compare different cephalometric variables in adult patients with class III malocclusions before and after treatment, in order to determine which variables are indicative of orthodontic camouflage or orthognathic surgery. The cases of 156 adult patients were assessed: 77 treated with orthodontic camouflage and 79 treated with orthodontics and orthognathic surgery. The following cephalometric variables were measured on pre-treatment (T1) and post-treatment (T2) lateral cephalograms: sella-nasion-A-point (SNA), sella-nasion-B-point (SNB), and A-point-nasion-B-point (ANB) angles, Wits appraisal, facial axis angle, mandibular plane angle, upper and lower incisor inclination, and inter-incisal angle. There were statistically significant differences in cephalometric variables before and after treatment between the two groups. The percentage of normal pre-treatment measurements in the camouflage orthodontics group was 30.7%, which worsened slightly to 28.4% post-treatment. However in the group receiving surgery, this was 24.5% pre-treatment, improving to 33.5% after surgery. SNA, SNB, Wits appraisal, lower incisor inclination, and inter-incisal angle showed differences between the two groups before and after treatment. Wits appraisal, lower incisor inclination, and inter-incisal angle were indicative of one or other treatment. Upper and lower incisor decompensation in both groups did not reach ideal values, which impeded complete skeletal correction in 52% of surgical cases. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  8. Hierarchical control of motor units in voluntary contractions.

    Science.gov (United States)

    De Luca, Carlo J; Contessa, Paola

    2012-01-01

    For the past five decades there has been wide acceptance of a relationship between the firing rate of motor units and the afterhyperpolarization of motoneurons. It has been promulgated that the higher-threshold, larger-soma, motoneurons fire faster than the lower-threshold, smaller-soma, motor units. This relationship was based on studies on anesthetized cats with electrically stimulated motoneurons. We questioned its applicability to motor unit control during voluntary contractions in humans. We found that during linearly force-increasing contractions, firing rates increased as exponential functions. At any time and force level, including at recruitment, the firing rate values were inversely related to the recruitment threshold of the motor unit. The time constants of the exponential functions were directly related to the recruitment threshold. From the Henneman size principle it follows that the characteristics of the firing rates are also related to the size of the soma. The "firing rate spectrum" presents a beautifully simple control scheme in which, at any given time or force, the firing rate value of earlier-recruited motor units is greater than that of later-recruited motor units. This hierarchical control scheme describes a mechanism that provides an effective economy of force generation for the earlier-recruited lower force-twitch motor units, and reduces the fatigue of later-recruited higher force-twitch motor units-both characteristics being well suited for generating and sustaining force during the fight-or-flight response.

  9. Vagal gustatory reflex circuits for intraoral food sorting behavior in the goldfish: cellular organization and neurotransmitters.

    Science.gov (United States)

    Ikenaga, Takanori; Ogura, Tatsuya; Finger, Thomas E

    2009-09-20

    The sense of taste is crucial in an animal's determination as to what is edible and what is not. This gustatory function is especially important in goldfish, who utilize a sophisticated oropharyngeal sorting mechanism to separate food from substrate material. The computational aspects of this detection are carried out by the medullary vagal lobe, which is a large, laminated structure combining elements of both the gustatory nucleus of the solitary tract and the nucleus ambiguus. The sensory layers of the vagal lobe are coupled to the motor layers via a simple reflex arc. Details of this reflex circuit were investigated with histology and calcium imaging. Biocytin injections into the motor layer labeled vagal reflex interneurons that have radially directed dendrites ramifying within the layers of primary afferent terminals. Axons of reflex interneurons extend radially inward to terminate onto both vagal motoneurons and small, GABAergic interneurons in the motor layer. Functional imaging shows increases in intracellular Ca++ of vagal motoneurons following electrical stimulation in the sensory layer. These responses were suppressed under Ca(++)-free conditions and by interruption of the axons bridging between the sensory and motor layers. Pharmacological experiments showed that glutamate acting via (+/-)-alpha-amino-3-hydroxy- 5-ethylisoxazole-4-propioinc acid (AMPA)/kainate and N-methyl-D-aspartic acid (NMDA) receptors mediate neurotransmission between reflex interneurons and vagal motoneurons. Thus, the vagal gustatory portion of the viscerosensory complex is linked to branchiomotor neurons of the pharynx via a glutamatergic interneuronal system.

  10. Vagal gustatory reflex circuits for intraoral food sorting behavior in the goldfish Cellular organization and neurotransmitters

    Science.gov (United States)

    Ikenaga, Takanori; Ogura, Tatsuya; Finger, Thomas E.

    2009-01-01

    The sense of taste is crucial in an animal’s determination as to what is edible and what is not. This gustatory function is especially important in goldfish who utilize a sophisticated oropharyngeal sorting mechanism to separate food from substrate material. The computational aspects of this detection are carried out by the medullary vagal lobe which is a large, laminated structure combining elements of both the gustatory nucleus of the solitary tract and the nucleus ambiguus. The sensory layers of the vagal lobe are coupled to the motor layers via a simple reflex arc. Details of this reflex circuit were investigated with histology and calcium imaging. Biocytin injections into the motor layer labeled vagal reflex interneurons which have radially-directed dendrites ramifying within the layers of primary afferent terminals. Axons of reflex interneurons extend radially inward to terminate onto both vagal motoneurons and small, GABAergic interneurons in the motor layer. Functional imaging shows increases in intracellular Ca++ of vagal motoneurons following electrical stimulation in the sensory layer. These responses were suppressed under Ca++-free conditions and by interruption of the axons bridging between the sensory and motor layers. Pharmacological experiments showed that glutamate acting via (±)-α-amino-3-hydroxy-5-ethylisoxazole-4-propioinc acid (AMPA)/kainate and N-methyl-D-aspartic acid (NMDA) receptors mediates neurotransmission between reflex interneurons and vagal motoneurons. Thus the vagal gustatory portion of the viscerosensory complex is linked to branchiomotor neurons of the pharynx via a glutamatergic interneuronal system. PMID:19598285

  11. Midcervical neuronal discharge patterns during and following hypoxia

    Science.gov (United States)

    Sandhu, M. S.; Baekey, D. M.; Maling, N. G.; Sanchez, J. C.; Reier, P. J.

    2014-01-01

    Anatomical evidence indicates that midcervical interneurons can be synaptically coupled with phrenic motoneurons. Accordingly, we hypothesized that interneurons in the C3–C4 spinal cord can display discharge patterns temporally linked with inspiratory phrenic motor output. Anesthetized adult rats were studied before, during, and after a 4-min bout of moderate hypoxia. Neuronal discharge in C3–C4 lamina I–IX was monitored using a multielectrode array while phrenic nerve activity was extracellularly recorded. For the majority of cells, spike-triggered averaging (STA) of ipsilateral inspiratory phrenic nerve activity based on neuronal discharge provided no evidence of discharge synchrony. However, a distinct STA phrenic peak with a 6.83 ± 1.1 ms lag was present for 5% of neurons, a result that indicates a monosynaptic connection with phrenic motoneurons. The majority (93%) of neurons changed discharge rate during hypoxia, and the diverse responses included both increased and decreased firing. Hypoxia did not change the incidence of STA peaks in the phrenic nerve signal. Following hypoxia, 40% of neurons continued to discharge at rates above prehypoxia values (i.e., short-term potentiation, STP), and cells with initially low discharge rates were more likely to show STP (P phrenic motoneuron pool, and these cells can modulate inspiratory phrenic output. In addition, the C3–C4 propriospinal network shows a robust and complex pattern of activation both during and following an acute bout of hypoxia. PMID:25552641

  12. Voluntary activation of ankle muscles is accompanied by subcortical facilitation of their antagonists

    DEFF Research Database (Denmark)

    Geertsen, Svend S.; Zuur, Abraham Theodoor; Nielsen, Jens B.

    2010-01-01

    Flexion and extension movements are organized reciprocally, so that extensor motoneurones in the spinal cord are inhibited when flexor muscles are active and vice versa. During and just prior to dorsiflexion of the ankle, soleus motoneurones are thus inhibited as evidenced by a depression......) or soleus muscle of the left ankle. TMS was applied to the hotspot of TA and soleus muscles on separate days. Stimuli were delivered prior to and at the beginning of contraction. Soleus MEPs were significantly facilitated when TMS was applied 50 ms prior to onset of plantar flexion. Surprisingly, soleus...... was increased prior to plantar flexion, but not prior to dorsiflexion. These findings suggest that voluntary contraction at the ankle is accompanied by preceding facilitation of antagonists by a subcortical motor programme. This may help to ensure that the direction of movement may be changed quickly...

  13. Chapter 24: Electrical stimulation for improving nerve regeneration: where do we stand?

    Science.gov (United States)

    Gordon, Tessa; Sulaiman, Olewale A R; Ladak, Adil

    2009-01-01

    While injured neurons regenerate their axons in the peripheral nervous system, it is well recognized that functional recovery is frequently poor. Animal experiments in which injured motoneurons remain without peripheral targets (chronic axotomy) and Schwann cells in distal nerve stumps remain without innervation (chronic denervation) revealed that it is the duration of chronic axotomy and Schwann cell denervation that accounts for this poor functional recovery and not irreversible muscle atrophy that has been so commonly thought to be the reason. More recently, we demonstrated that axon outgrowth across lesion sites is a major contributing factor to the long delays incurred between the injury and the reinnervation of denervated targets. In the rat, a period of 1 month transpires before all motoneurons regenerate their axons across a lesion site. We have developed a technique of 1 h low-frequency electrical stimulation (ES) of the proximal nerve stump just after surgical repair of a transected peripheral nerve that greatly accelerates axon outgrowth. This technique has been applied in patients after carpal tunnel release surgery where the ES promoted the regeneration of all median nerves to reinnervate thenar muscles within 6-8 months, which contrasted with failure of any injured nerves to reinnervate muscles in the same time frame without ES. These findings are very promising such that the ES method could become a clinically viable tool for accelerating axon regeneration and muscle reinnervation.

  14. Dynamic neural network models of the premotoneuronal circuitry controlling wrist movements in primates.

    Science.gov (United States)

    Maier, M A; Shupe, L E; Fetz, E E

    2005-10-01

    Dynamic recurrent neural networks were derived to simulate neuronal populations generating bidirectional wrist movements in the monkey. The models incorporate anatomical connections of cortical and rubral neurons, muscle afferents, segmental interneurons and motoneurons; they also incorporate the response profiles of four populations of neurons observed in behaving monkeys. The networks were derived by gradient descent algorithms to generate the eight characteristic patterns of motor unit activations observed during alternating flexion-extension wrist movements. The resulting model generated the appropriate input-output transforms and developed connection strengths resembling those in physiological pathways. We found that this network could be further trained to simulate additional tasks, such as experimentally observed reflex responses to limb perturbations that stretched or shortened the active muscles, and scaling of response amplitudes in proportion to inputs. In the final comprehensive network, motor units are driven by the combined activity of cortical, rubral, spinal and afferent units during step tracking and perturbations. The model displayed many emergent properties corresponding to physiological characteristics. The resulting neural network provides a working model of premotoneuronal circuitry and elucidates the neural mechanisms controlling motoneuron activity. It also predicts several features to be experimentally tested, for example the consequences of eliminating inhibitory connections in cortex and red nucleus. It also reveals that co-contraction can be achieved by simultaneous activation of the flexor and extensor circuits without invoking features specific to co-contraction.

  15. Suppression of inflammation by dexamethasone prolongs adenoviral vector-mediated transgene expression in the facial nucleus of the rat

    NARCIS (Netherlands)

    Hermens, W.T.J.M.C.; Verhaagen, J

    1998-01-01

    Adenoviral vector directed gene transfer to rat facial motoneurons occurs efficiently following intra-parenchymal injection of relatively high dosages (> or =10(7) pfu per injection) of a prototype first generation adenoviral vector. However, high level of transgene expression, as observed during

  16. Potassium channel abnormalities are consistent with early axon degeneration of motor axons in the G127X SOD1 mouse model of amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Maglemose, Rikke; Hedegaard, Anne; Lehnhoff, Janna

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease, which selectively affects upper and lower motoneurones. The underlying pathophysiology of the disease is complex but electrophysiological studies of peripheral nerves in ALS patients as well as human autopsy studies indicate...

  17. Generation of functional neuromuscular junctions from human pluripotent stem cell lines

    Directory of Open Access Journals (Sweden)

    Katja ePuttonen

    2015-12-01

    Full Text Available Several neuromuscular diseases involve dysfunction of neuromuscular junctions (NMJs, yet there are no patient-specific human models for electrophysiological characterization of NMJ. We seeded cells of neurally-induced embryoid body-like spheres derived from induced pluripotent stem cell (iPSC or embryonic stem cell (ESC lines as monolayers without basic fibroblast factor (bFGF and observed differentiation of neuronal as well as spontaneously contracting, multinucleated skeletal myotubes. The myotubes showed striation, immunoreactivity for myosin heavy chain, actin bundles typical for myo-oriented cells, and generated spontaneous and evoked action potentials (APs. The myogenic differentiation was associated with expression of MyoD1, myogenin and type I ryanodine receptor. Neurons formed end plate like structures with strong binding of α-bungarotoxin, a marker of nicotinic acetylcholine receptors highly expressed in the postsynaptic membrane of NMJs, and expressed SMI-32, a motoneuron marker, as well as SV2, a marker for synapses. Pharmacological stimulation of cholinergic receptors resulted in strong depolarization of myotube membrane and raised Ca2+ concentration in sarcoplasm, while electrical stimulation evoked Ca2+ transients in myotubes. Stimulation of motoneurons with N-Methyl-D-aspartate resulted in reproducible APs in myotubes and end plates displayed typical MEPs and tonic activity depolarizing myotubes of about 10 mV. We conclude that simultaneous differentiation of neurons and myotubes from patient-specific iPSCs or ESCs results also in the development of functional NMJs. Our human model of NMJ may serve as an important tool to investigate normal development, mechanisms of diseases and novel drug targets involving NMJ dysfunction and degeneration.

  18. Accuracy of computer-assisted orthognathic surgery.

    Science.gov (United States)

    De Riu, Giacomo; Virdis, Paola Ilaria; Meloni, Silvio Mario; Lumbau, Aurea; Vaira, Luigi Angelo

    2018-02-01

    The purpose of this study was to retrospectively evaluate the difference between the planned and the actual movements of the jaws, using three-dimensional (3D) software for PC-assisted orthognathic surgery, to establish the accuracy of the procedure. A retrospective study was performed with 49 patients who had undergone PC-guided bimaxillary surgery. The accuracy of the protocol was determined by comparing planned movements of the jaws with the actual surgical movements, analysing frontal and lateral cephalometries. The overall results were deemed accurate, and differences among 12 of the 15 parameters were considered nonsignificant. Significant differences were reported for SNA (p = 0.008), SNB (p = 0.006), and anterior facial height (p = 0.033). The latter was significantly different in patients who had undergone genioplasty when compared with patients who had not. Virtual surgical planning presented a good degree of accuracy for most of the parameters assessed, with an average error of 1.98 mm for linear measures and 1.19° for angular measures. In general, a tendency towards under-projection in jaws was detected, probably due to imperfect condylar seating. A slight overcorrection of SNA and SNB during virtual planning (approximately 2°) could be beneficial. Further progress is required in the development of 3D simulation of the soft tissue, which currently does not allow an accurate management of the facial height and the chin position. Virtual planning cannot replace the need for constant intraoperative monitoring of the jaws' movements and real-time comparisons between planned and actual outcomes. It is therefore appropriate to leave some margin for correction of inaccuracies in the virtual planning. In this sense, it may be appropriate to use only the intermediate splint, and then use the planned occlusion and clinical measurements to guide repositioning of the second jaw and chin, respectively. Copyright © 2017 European Association for Cranio

  19. Radiographic cephalometry analysis of head posture and craniofacial morphology in oral breathing children

    Directory of Open Access Journals (Sweden)

    Vukićević Vladanka

    2017-01-01

    Full Text Available Background/Aim. Nasal breathing plays an important role in overall physical growth and mental development, as well as in the growth of the craniofacial complex. Oral breathing over a long period of time, can cause changes in position of the head relative to the cervical spine and jaw relationship. It can cause an open bite and the narrowness of the maxillary arch due to increased pressure of strained face. The aim of this study was to analyze the position of the head and craniofacial morphology in oral breathing children, and compare the values obtained compared with those of the same parameters in nasal brething children. Methods. We analyzed the profile cephalometric radiographs of 60 patients who had various orthodontic problems. In the first group there were 30 patients aged 8–14 years, in which oral breathing is confirmed by clinical examination. In the second group there were 30 patients of the same age who had orthodontic problems, but did not show clinical signs of oral breathing. The analyses covered the following: craniocervical angle (NS/OPT, the length of the anterior cranial base (NS, anterior facial height (N-Me, posterior facial height (S-Go, the angle of maxillary prognathism (SNA, angle of mandibular prognathism (SNB, difference between angles SNA and SNB (ANB angle, the angle of the basal planes of the jaws (SpP/MP, cranial base angle (NSB, and the angle of facial convexity (NA/Apg. Results. The average value of the craniocervical angle (NS/OPT was significantly higher in OB children (p = 0.004. There were significantly different values of SNA (p < 0.001, ANB (p < 0.001, NA/APg (p < 0.001 and length of the anterior cranial base (NS (p = 0.024 between groups. Conclusion. Oral breathing children have pronounced retroflexion of the head in relation to the cervical spine compared to nasal breathing children, and the most prominent characteristics of the craniofacial morphology of skeletal jaw relationship of class II and

  20. [Mechanism of disorders of inhibition of electrogenesis in spinal alpha-motor neurons in experimental local botulin poisoning].

    Science.gov (United States)

    Mikhaĭlov, V V; Barashkov, G N

    1977-06-01

    Disorders of postsynaptic inhibition and of the spinal cord alpha-motoneurons were studied in cats with experimental local botulinum intoxication. A significant decrease of the reciprocal, and, to a lesser extent, of polysynaptic inhibitory postsynaptic potential (IPSP) was noted. With the appearance of total paralysis of the muscles in the poisoned extremity there proved to be an even greater depression of the reciprocal and polysynaptic IPSP; however, they never disappeared or turned into depolarization potentials. Synaptic permeability of motor neurons as a rule decreased during the IPSP development, this indirectly indicating a reduction of ion transport.

  1. Differential autophagy power in the spinal cord and muscle of transgenic ALS mice.

    Directory of Open Access Journals (Sweden)

    Valeria eCrippa

    2013-11-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a motoneuron disease characterized by misfolded proteins aggregation in affected motoneurons. In mutant SOD1 (mutSOD1 ALS models, aggregation correlates to impaired functions of proteasome and/or autophagy, both essential for the intracellular chaperone-mediated protein quality control (PQC, and a reduced mutSOD1 clearance from motoneurons. Skeletal muscle cells are also sensitive to mutSOD1 toxicity, but no mutSOD1 aggregates are formed in these cells, that might better manage mutSOD1 than motoneurons. Thus, we analysed in spinal cord and in muscle of transgenic (tg G93A-SOD1 at presymptomatic (PS, 8 weeks and symptomatic (S, 16 weeks stages, and in age-matched control mice, whether mutSOD1 differentially modulates relevant PQC players, such as HSPB8, BAG3, and BAG1. Possible sex differences were also considered. No changes of HSPB8, BAG3 and BAG1 at PS stage (8 weeks were seen in all tissues examined in tg G93A-SOD1 and control mice. At S stage (16 weeks, HSPB8 dramatically increased in skeletal muscle of tg G93A-SOD1 mice, while a minor increase occurred in spinal cord of male, but not female tg G93A-SOD1 mice. BAG3 expression increased both in muscle and spinal cord of tg G93A-SOD1 mice at S stage, BAG1 expression increased only in muscle of the same mice. Since, HSPB8-BAG3 complex assists mutSOD1 autophagic removal, we analysed two well-known autophagic markers, LC3 and p62. Both LC3 and p62 mRNAs were significantly up-regulated in skeletal muscle of tg G93A-SOD1 mice at S stage (16 weeks. This suggests that mutSOD1 expression induces a robust autophagic response specifically in muscle. Together these results demonstrate that, in muscle mutSOD1-induced autophagic response is much higher than in spinal cords. In addition, if mutSOD1 exerts toxicity in muscle, this may not be mediated by misfolded protein accumulation. It remains unclear whether in muscle mutSOD1 toxicity is related to aberrant autophagy

  2. Organization of projection-specific interneurons in the spinal cord of the red-eared turtle

    DEFF Research Database (Denmark)

    Nissen, Ulla Vig; Moldovan, Mihai; Hounsgaard, Jørn

    2008-01-01

    Using differential retrograde axonal tracing, we identified motoneurons (MNs) and projection-specific interneuron (IN) classes in lumbar segment D9 of the adult red-eared turtle spinal cord. We characterized the distribution of these neurons in the transverse plane, and estimated their numbers...

  3. Intense Activity of the Raphe Spinal Pathway Depresses Motor Activity via a Serotonin Dependent Mechanism

    DEFF Research Database (Denmark)

    Perrier, Jean-François; Rasmussen, Hanne B; Jørgensen, Lone K

    2018-01-01

    Motor fatigue occurring during prolonged physical activity has both peripheral and central origins. It was previously demonstrated that the excitability of motoneurons was decreased when a spillover of serotonin could activate extrasynaptic 5-HT1A receptors at the axon initial segment (AIS...

  4. Robust upregulation of serotonin 2A receptors after chronic spinal transection of rats: An immunohistochemical study

    DEFF Research Database (Denmark)

    Kong, Xiang-Yu; Wienecke, Jacob; Hultborn, Hans

    2010-01-01

    It is well known that spinal motoneurons below a spinal transection become supersensitive to a systemic administration of serotonin (5-HT) precursors, such as 5-hydroxytryptophan. This supersensitivity has been implicated in both the process of functional recovery following chronic lesions, and a...

  5. Conditional intrinsic voltage oscillations in mature vertebrate neurons undergo specific changes in culture

    DEFF Research Database (Denmark)

    Guertin, Pierre A; Hounsgaard, Jørn

    2006-01-01

    cord of adult turtles maintainable for several weeks in culture conditions. N-methyl-D-aspartate (NMDA)-induced-tetrodotoxin (TTX)-resistant voltage oscillations in motoneurons were approximately 10 times faster in culture than in acute preparations. Oscillations in culture were abolished by NMDA...

  6. Preservation of the nucleus X-pelvic floor motosystem in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Schrøder, H D; Reske-Nielsen, E

    1984-01-01

    to the neuropathological findings, and the observations are compared with previous neuropathological studies concerning Onuf's nucleus X as well with experimental studies including this nucleus. It is pointed out that structural and biochemical differences must exist between nucleus X neurons and other motoneurons....

  7. Habituation in the tail withdrawal reflex circuit is impaired during aging in Aplysia californica

    Directory of Open Access Journals (Sweden)

    Andrew T Kempsell

    2016-02-01

    Full Text Available The relevance of putative contributors to age-related memory loss are poorly understood. The tail withdrawal circuit of the sea hare, a straightforward neural model, was used to investigate the aging characteristics of rudimentary learning. The simplicity of this neuronal circuit permits attribution of declines in the function of specific neurons to aging declines. Memory was impaired in advanced age animals compared to their performance at the peak of sexual maturity, with habituation training failing to attenuate the tail withdrawal response or to reduce tail motoneuron excitability, as occurred in peak maturity siblings. Baseline motoneuron excitability of aged animals was significantly lower, perhaps contributing to a smaller scope for attenuation. Conduction velocity in afferent fibers to tail sensory neurons decreased during aging. The findings suggest that age-related changes in tail sensory and motor neurons result in deterioration of a simple form of learning in Aplysia.

  8. Cellular basis for singing motor pattern generation in the field cricket (Gryllus bimaculatus DeGeer)

    Science.gov (United States)

    Schöneich, Stefan; Hedwig, Berthold

    2012-01-01

    The singing behavior of male crickets allows analyzing a central pattern generator (CPG) that was shaped by sexual selection for reliable production of species-specific communication signals. After localizing the essential ganglia for singing in Gryllus bimaculatus, we now studied the calling song CPG at the cellular level. Fictive singing was initiated by pharmacological brain stimulation. The motor pattern underlying syllables and chirps was recorded as alternating spike bursts of wing-opener and wing-closer motoneurons in a truncated wing nerve; it precisely reflected the natural calling song. During fictive singing, we intracellularly recorded and stained interneurons in thoracic and abdominal ganglia and tested their impact on the song pattern by intracellular current injections. We identified three interneurons of the metathoracic and first unfused abdominal ganglion that rhythmically de- and hyperpolarized in phase with the syllable pattern and spiked strictly before the wing-opener motoneurons. Depolarizing current injection in two of these opener interneurons caused additional rhythmic singing activity, which reliably reset the ongoing chirp rhythm. The closely intermeshing arborizations of the singing interneurons revealed the dorsal midline neuropiles of the metathoracic and three most anterior abdominal neuromeres as the anatomical location of singing pattern generation. In the same neuropiles, we also recorded several closer interneurons that rhythmically hyper- and depolarized in the syllable rhythm and spiked strictly before the wing-closer motoneurons. Some of them received pronounced inhibition at the beginning of each chirp. Hyperpolarizing current injection in the dendrite revealed postinhibitory rebound depolarization as one functional mechanism of central pattern generation in singing crickets. PMID:23170234

  9. Anatomical architecture and responses to acidosis of a novel respiratory neuron group in the high cervical spinal cord (HCRG) of the neonatal rat.

    Science.gov (United States)

    Okada, Y; Yokota, S; Shinozaki, Y; Aoyama, R; Yasui, Y; Ishiguro, M; Oku, Y

    2009-01-01

    It has been postulated that there exists a neuronal mechanism that generates respiratory rhythm and modulates respiratory output pattern in the high cervical spinal cord. Recently, we have found a novel respiratory neuron group in the ventral portion of the high cervical spinal cord, and named it the high cervical spinal cord respiratory group (HCRG). In the present study, we analyzed the detailed anatomical architecture of the HCRG region by double immunostaining of the region using a neuron-specific marker (NeuN) and a marker for motoneurons (ChAT) in the neonatal rat. We found a large number of small NeuN-positive cells without ChAT-immunoreactivity, which were considered interneurons. We also found two and three clusters of motoneurons in the ventral portion of the ventral horn at C1 and C2 levels, respectively. Next, we examined responses of HCRG neurons to respiratory and metabolic acidosis in vitro by voltage-imaging together with cross correlation techniques, i.e., by correlation coefficient imaging, in order to understand the functional role of HCRG neurons. Both respiratory and metabolic acidosis caused the same pattern of changes in their spatiotemporal activation profiles, and the respiratory-related area was enlarged in the HCRG region. After acidosis was introduced, preinspiratory phase-dominant activity was recruited in a number of pixels, and more remarkably inspiratory phase-dominant activity was recruited in a large number of pixels. We suggest that the HCRG composes a local respiratory neuronal network consisting of interneurons and motoneurons and plays an important role in respiratory augmentation in response to acidosis.

  10. Convergence of pattern generator outputs on a common mechanism of diaphragm motor unit recruitment.

    Science.gov (United States)

    Mantilla, Carlos B; Seven, Yasin B; Sieck, Gary C

    2014-01-01

    Motor units are the final element of neuromotor control. In manner analogous to the organization of neuromotor control in other skeletal muscles, diaphragm motor units comprise phrenic motoneurons located in the cervical spinal cord that innervate the diaphragm muscle, the main inspiratory muscle in mammals. Diaphragm motor units play a primary role in sustaining ventilation but are also active in other nonventilatory behaviors, including coughing, sneezing, vomiting, defecation, and parturition. Diaphragm muscle fibers comprise all fiber types. Thus, diaphragm motor units display substantial differences in contractile and fatigue properties, but importantly, properties of the motoneuron and muscle fibers within a motor unit are matched. As in other skeletal muscles, diaphragm motor units are recruited in order such that motor units that display greater fatigue resistance are recruited earlier and more often than more fatigable motor units. The properties of the motor unit population are critical determinants of the function of a skeletal muscle across the range of possible motor tasks. Accordingly, fatigue-resistant motor units are sufficient to generate the forces necessary for ventilatory behaviors, whereas more fatigable units are only activated during expulsive behaviors important for airway clearance. Neuromotor control of diaphragm motor units may reflect selective inputs from distinct pattern generators distributed according to the motor unit properties necessary to accomplish these different motor tasks. In contrast, widely distributed inputs to phrenic motoneurons from various pattern generators (e.g., for breathing, coughing, or vocalization) would dictate recruitment order based on intrinsic electrophysiological properties. © 2014 Elsevier B.V. All rights reserved.

  11. Discharge properties of upper airway motor units during wakefulness and sleep.

    Science.gov (United States)

    Trinder, John; Jordan, Amy S; Nicholas, Christian L

    2014-01-01

    Upper airway muscle motoneurons, as assessed at the level of the motor unit, have a range of different discharge patterns, varying as to whether their activity is modulated in phase with the respiratory cycle, are predominantly inspiratory or expiratory, or are phasic as opposed to tonic. Two fundamental questions raised by this observation are: how are synaptic inputs from premotor neurons distributed over motoneurons to achieve these different discharge patterns; and how do different discharge patterns contribute to muscle function? We and others have studied the behavior of genioglossus (GG) and tensor palatini (TP) single motor units at transitions from wakefulness to sleep (sleep onset), from sleep to wakefulness (arousal from sleep), and during hypercapnia. Results indicate that decreases or increases in GG and TP muscle activity occur as a consequence of derecruitment or recruitment, respectively, of phasic and tonic inspiratory-modulated motoneurons, with only minor changes in rate coding. Further, sleep-wake state and chemical inputs to this "inspiratory system" appear to be mediated through the respiratory pattern generator. In contrast, phasic and tonic expiratory units and units with a purely tonic pattern, the "tonic system," are largely unaffected by sleep-wake state, and are only weakly influenced by chemical stimuli and the respiratory cycle. We speculate that the "inspiratory system" produces gross changes in upper airway muscle activity in response to changes in respiratory drive, while the "tonic system" fine tunes airway configuration with activity in this system being determined by local mechanical conditions. © 2014 Elsevier B.V. All rights reserved.

  12. Motoneuron firing in amyotrophic lateral sclerosis (ALS

    Directory of Open Access Journals (Sweden)

    Mamede eDe Carvalho

    2014-09-01

    Full Text Available Amyotrophic lateral sclerosis is an inexorably progressive neurodegenerative disorder involving the classical motor system and the frontal effector brain, causing muscular weakness and atrophy, with variable upper motor neuron signs and often an associated fronto-temporal dementia. The physiological disturbance consequent on the motor system degeneration is beginning to be well understood. In this review we describe aspects of the motor cortical, neuronal and lower motor neuron dysfunction. We show how studies of the changes in the pattern of motor unit firing help delineate the underlying pathophysiological disturbance as the disease progresses. Such studies are beginning to illuminate the underlying disordered pathophysiological processes in the disease, and are important in designing new approaches to therapy and especially for clinical trials.

  13. Serotonergic modulation of spinal motor control

    DEFF Research Database (Denmark)

    Perrier, Jean-Francois Marie; Cotel, Florence

    2015-01-01

    Serotonin (5-HT) is a monoamine that powerfully modulates spinal motor control by acting on intrasynaptic and extrasynaptic receptors. Here we review the diversity of 5-HT actions on locomotor and motoneuronal activities. Two approaches have been used on in vitro spinal cord preparations: either...

  14. Modulation of human exteroceptive jaw reflexes during simulated mastication

    NARCIS (Netherlands)

    Lobbezoo, F.; Sowman, P.F.; Türker, K.S.

    2009-01-01

    Objective: To investigate changes in synaptic input from lower lip afferents to human jaw muscle motoneurons during simulated mastication. Methods: The lower lip of 14 subjects was stimulated electrically under static and dynamic conditions. In the static condition, subjects bit at mid-open position

  15. Motor unit firing during and after voluntary contractions of human thenar muscles weakened by spinal cord injury

    NARCIS (Netherlands)

    Zijdewind, Inge; Thomas, CK

    Spinal cord injury may change both the distribution and the strength of the synaptic input within a motoneuron pool and therefore alter force gradation. Here, we have studied the relative contributions of motor unit recruitment and rate modulation to force gradation during voluntary contractions of

  16. Firing patterns of spontaneously active motor units in spinal cord-injured subjects

    NARCIS (Netherlands)

    Zijdewind, Inge; Thomas, Christine K.

    Involuntary motor unit activity at low rates is common in hand muscles paralysed by spinal cord injury. Our aim was to describe these patterns of motor unit behaviour in relation to motoneurone and motor unit properties. Intramuscular electromyographic activity (EMG), surface EMG and force were

  17. Evidence for a periaqueductal gray-nucleus retroambiguus spinal cord pathway in the rat

    NARCIS (Netherlands)

    Holstege, G.; Kerstens, Lenka; Moes, M.C.; Horst, V.G.J.M. van der

    1997-01-01

    The nucleus retroambiguus in the cat has been shown to receive strong projections from the periaqueductal gray and to send fibres to distinct motoneuronal cell groups in brainstem and spinal cord. The nucleus retroambiguus plays a role in the production of vocalization and possibly copulatory

  18. Cephalometric evaluation of surgical mandibular advancement

    Directory of Open Access Journals (Sweden)

    Eloísa Marcantônio Boeck

    2010-06-01

    Full Text Available The treatment of Class II adult individuals with mandibular deficiency has been the combination of orthodontic treatment and orthognathic surgery. Therefore, a study was conducted in which cephalometric analysis was used to evaluate the influence of dentoalveolar decompensation in Class II patients submitted to orthodontic and surgical treatment for mandibular advancement, by bilateral osteotomy of the mandibular ramus. A sample of 15 leukoderma adult female patients were selected and three cephalometric radiographs of each patient, taken before the orthodontic treatment, before surgery and after at least 6 months postoperatively, were analyzed in a total of 45 roentgenograms. The tracings were made by the manual method and the points were digitalized using software. The results showed that values of SNB increased from 75.6 to 78.6°. The measures BNP and PGNP were reduced from -12.7 to -7.7 mm and -12.7 to -6.6 mm, respectively. For ANB there was a reduction of 3.23° (from 8.1° to 4.9°. Likewise, the values of AOBO were diminished by 6.3 mm (from 7.6 to 1.3 mm, and in the values of OJ there was a reduction of 5.7 mm (from 9 to 3.3 mm. It was concluded that the pre-surgical orthodontic treatment promoted minimal and variable dental and skeletal changes in the final result. The surgical treatment caused significant skeletal changes, especially in the measurements related to the mandible (SNB, BNP, PGNP and SNPM or indirectly to it (ANB, AOBO and OJ.

  19. Cephalometric evaluation of surgical mandibular advancement.

    Science.gov (United States)

    Boeck, Eloísa Marcantônio; Kuramae, Mayury; Lunardi, Nádia; Santos-Pinto, Ary dos; Mazzonetto, Renato

    2010-01-01

    The treatment of Class II adult individuals with mandibular deficiency has been the combination of orthodontic treatment and orthognathic surgery. Therefore, a study was conducted in which cephalometric analysis was used to evaluate the influence of dentoalveolar decompensation in Class II patients submitted to orthodontic and surgical treatment for mandibular advancement, by bilateral osteotomy of the mandibular ramus. A sample of 15 leukoderma adult female patients were selected and three cephalometric radiographs of each patient, taken before the orthodontic treatment, before surgery and after at least 6 months postoperatively, were analyzed in a total of 45 roentgenograms. The tracings were made by the manual method and the points were digitalized using software. The results showed that values of SNB increased from 75.6 to 78.6 degrees. The measures BNP and PGNP were reduced from -12.7 to -7.7 mm and -12.7 to -6.6 mm, respectively. For ANB there was a reduction of 3.23 degrees (from 8.1 degrees to 4.9 degrees). Likewise, the values of AOBO were diminished by 6.3 mm (from 7.6 to 1.3 mm), and in the values of OJ there was a reduction of 5.7 mm (from 9 to 3.3 mm). It was concluded that the pre-surgical orthodontic treatment promoted minimal and variable dental and skeletal changes in the final result. The surgical treatment caused significant skeletal changes, especially in the measurements related to the mandible (SNB, BNP, PGNP and SNPM) or indirectly to it (ANB, AOBO and OJ).

  20. Medico-economic impact of MSKCC non-sentinel node prediction nomogram for ER-positive HER2-negative breast cancers.

    Directory of Open Access Journals (Sweden)

    Hélène Bonsang-Kitzis

    Full Text Available Avoiding axillary lymph node dissection (ALND for invasive breast cancers with isolated tumor cells or micrometastatic sentinel node biopsy (SNB could decrease morbidity with minimal clinical significance.The aim of this study is to simulate the medico-economic impact of the routine use of the MSKCC non-sentinel node (NSN prediction nomogram for ER+ HER2- breast cancer patients.We studied 1036 ER+ HER2- breast cancer patients with a metastatic SNB. All had a complementary ALND. For each patient, we calculated the probability of the NSN positivity using the MSKCC nomogram. After validation of this nomogram in the population, we described how the patients' characteristics spread as the threshold value changed. Then, we performed an economic simulation study to estimate the total cost of caring for patients treated according to the MSKCC predictive nomogram results.A 0.3 threshold discriminate the type of sentinel node (SN metastases: 98.8% of patients with pN0(i+ and 91.6% of patients with pN1(mic had a MSKCC score under 0.3 (false negative rate = 6.4%. If we use the 0.3 threshold for economic simulation, 43% of ALND could be avoided, reducing the costs of caring by 1 051 980 EUROS among the 1036 patients.We demonstrated the cost-effectiveness of using the MSKCC NSN prediction nomogram by avoiding ALND for the pN0(i+ or pN1(mic ER+ HER2- breast cancer patients with a MSKCC score of less than or equal to 0.3.

  1. The anatomy of the central control of posture : Consistency and plasticity

    NARCIS (Netherlands)

    Holstege, G

    Posture is usually thought to be steered by brainstem and cortical structures that have access to the motoneurons and their premotor interneurons of the axial and neck muscles. The present paper describes these pathways and their relation with gaze control structures. All these systems belong to the

  2. The role of muscle spindles in constraining motor control

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2002-01-01

    support to the idea that gamma-motoneuron activity might be essential for cancelling expected stimuli rather than only for programming servo-controlled equilibrium positions of the limbs. It is concluded that the best performance of a movement is obtained when expected afference is cancelled by gamma...

  3. Axonal sprouting of a brainstem-spinal pathway after estrogen administration in the adult female rhesus monkey

    NARCIS (Netherlands)

    Vanderhorst, VGJM; Terasawa, E; Ralston, HJ

    2002-01-01

    The nucleus retroambiguus (NRA) is located in the caudal medulla oblongata and contains premotor neurons that project to motoneuronal cell groups in the brainstem and spinal cord. NRA projections to the lumbosacral cord are species specific and might be involved in mating behavior. In the female

  4. Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence.

    Science.gov (United States)

    Romeo-Guitart, David; Forés, Joaquim; Herrando-Grabulosa, Mireia; Valls, Raquel; Leiva-Rodríguez, Tatiana; Galea, Elena; González-Pérez, Francisco; Navarro, Xavier; Petegnief, Valerie; Bosch, Assumpció; Coma, Mireia; Mas, José Manuel; Casas, Caty

    2018-01-30

    Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on mathematical solutions. Solutions allowed us to identify combinations of repurposed drugs as potential neuroprotective agents and we validated them in our preclinical models. The best one, NeuroHeal, neuroprotected motoneurons, exerted anti-inflammatory properties and promoted functional locomotor recovery. NeuroHeal endorsed the activation of Sirtuin 1, which was essential for its neuroprotective effect. These results support the value of network-centric approaches for drug discovery and demonstrate the efficacy of NeuroHeal as adjuvant treatment with surgical repair for nervous system trauma.

  5. Utility of 18F-fluoro-deoxyglucose emission tomography/computed tomography fusion imaging (18F-FDG PET/CT in combination with ultrasonography for axillary staging in primary breast cancer

    Directory of Open Access Journals (Sweden)

    Tamura Katsumi

    2008-06-01

    Full Text Available Abstract Background Accurate evaluation of axillary lymph node (ALN involvement is mandatory before treatment of primary breast cancer. The aim of this study is to compare preoperative diagnostic accuracy between positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT and axillary ultrasonography (AUS for detecting ALN metastasis in patients having operable breast cancer, and to assess the clinical management of axillary 18F-FDG PET/CT for therapeutic indication of sentinel node biopsy (SNB and preoperative systemic chemotherapy (PSC. Methods One hundred eighty-three patients with primary operable breast cancer were recruited. All patients underwent 18F-FDG PET/CT and AUS followed by SNB and/or ALN dissection (ALND. Using 18F-FDG PET/CT, we studied both a visual assessment of 18F-FDG uptake and standardized uptake value (SUV for axillary staging. Results In a visual assessment of 18F-FDG PET/CT, the diagnostic accuracy of ALN metastasis was 83% with 58% in sensitivity and 95% in specificity, and when cut-off point of SUV was set at 1.8, sensitivity, specificity, and accuracy were 36, 100, and 79%, respectively. On the other hand, the diagnostic accuracy of AUS was 85% with 54% in sensitivity and 99% in specificity. By the combination of 18F-FDG PET/CT and AUS to the axilla, the sensitivity, specificity, and accuracy were 64, 94, and 85%, respectively. If either 18F-FDG PET uptake or AUS was positive in allixa, the probability of axillary metastasis was high; 50% (6 of 12 in 18F-FDG PET uptake only, 80% (4 of 5 in AUS positive only, and 100% (28 of 28 in dual positive. By the combination of AUS and 18F-FDG PET/CT, candidates of SNB were more appropriately selected. The axillary 18F-FDG uptake was correlated with the maximum size and nuclear grade of metastatic foci (p = 0.006 and p = 0.03. Conclusion The diagnostic accuracy of 18F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their

  6. CONTRACTION CHARACTERISTICS AND MYOSIN HEAVY-CHAIN COMPOSITION OF RABBIT MASSETER MOTOR UNITS

    NARCIS (Netherlands)

    KWA, SHS; WEIJS, WA; JUCH, PJW

    1. We studied isometric twitch peak force (TPF) and twitch contraction time (TCT) of 249 motor units of the masseter muscle in 41 rabbits after extracellular electrical stimulation of single trigeminal motoneurons in the brain stem. In 41 of these units we determined the amount of tension decrease

  7. Human spinal cord injury : motor unit properties and behaviour

    NARCIS (Netherlands)

    Thomas, C. K.; Bakels, R.; Klein, C. S.; Zijdewind, I.

    Spinal cord injury (SCI) results in widespread variation in muscle function. Review of motor unit data shows that changes in the amount and balance of excitatory and inhibitory inputs after SCI alter management of motoneurons. Not only are units recruited up to higher than usual relative forces when

  8. Inhibition of excitatory synaptic transmission in the trigeminal motor nucleus by the nitric oxide-cyclic GMP signaling pathway.

    Science.gov (United States)

    Pose, Inés; Silveira, Valentina; Morales, Francisco R

    2011-06-01

    Nitric oxide (NO) and cyclic GMP (cGMP) suppressed glutamatergic synaptic transmission to trigeminal motoneurons in brain stem slices of neonatal rats. Histological studies showed guanylate cyclase (GC) containing fibers in the trigeminal motor pool. Glutamatergic excitatory postsynaptic currents (EPSCs) were recorded from neonatal trigeminal motoneurons in response to stimulation of the supratrigeminal nucleus (SuV). The NO donors DETA/NONOate (DETA/NO), at a concentration which released 275.1 nM of NO, and Spermine/NONOate (Sper/NO) reduced the amplitude of the EPSC to 52.7±0.6% and 60.1±10.8% of control values, respectively. These actions were not blocked by the GC inhibitors, ODQ or NS-2028. However, in the presence of YC-1 or BAY41-2272, modulators of GC that act as NO sensitizers, lower and otherwise ineffective concentrations of DETA/NO induced a reduction of the EPSC to 60.6±5.2%. Moreover, NO effects were mimicked by 8BrcGMP and by Zaprinast, an inhibitor of Phosphodiesterase 5. Glutamatergic currents evoked by exogenous glutamate were not reduced by DETA/NO nor 8BrcGMP. Paired-pulse facilitation was increased by NO donors. Under "minimal stimulation" conditions NO donors and cGMP increased the failure rate of evoked EPSCs. Protein kinase inhibitors antagonized cGMP effects. The results suggest that NO, through the synthesis of cGMP, presynaptically inhibits glutamatergic synaptic transmission on trigeminal motoneurons. We propose that NO has complex actions on motor pools; specific studies are needed to elucidate their physiological significance in the behaving animal. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Neuromuscular mechanisms and neural strategies in the control of time-varying muscle contractions.

    Science.gov (United States)

    Erimaki, Sophia; Agapaki, Orsalia M; Christakos, Constantinos N

    2013-09-01

    The organization of the neural input to motoneurons that underlies time-varying muscle force is assumed to depend on muscle transfer characteristics and neural strategies or control modes utilizing sensory signals. We jointly addressed these interlinked, but previously studied individually and partially, issues for sinusoidal (range 0.5-5.0 Hz) force-tracking contractions of a human finger muscle. Using spectral and correlation analyses of target signal, force signal, and motor unit (MU) discharges, we studied 1) patterns of such discharges, allowing inferences on the motoneuronal input; 2) transformation of MU population activity (EMG) into quasi-sinusoidal force; and 3) relation of force oscillation to target, carrying information on the input's organization. A broad view of force control mechanisms and strategies emerged. Specifically, synchronized MU and EMG modulations, reflecting a frequency-modulated motoneuronal input, accompanied the force variations. Gain and delay drops between EMG modulation and force oscillation, critical for the appropriate organization of this input, occurred with increasing target frequency. According to our analyses, gain compensation was achieved primarily through rhythmical activation/deactivation of higher-threshold MUs and secondarily through the adaptation of the input's strength expected during tracking tasks. However, the input's timing was not adapted to delay behaviors and seemed to depend on the control modes employed. Thus, for low-frequency targets, the force oscillation was highly coherent with, but led, a target, this timing error being compatible with predictive feedforward control partly based on the target's derivatives. In contrast, the force oscillation was weakly coherent, but in phase, with high-frequency targets, suggesting control mainly based on a target's rhythm.

  10. Similar alteration of motor unit recruitment strategies during the anticipation and experience of pain.

    Science.gov (United States)

    Tucker, Kylie; Larsson, Anna-Karin; Oknelid, Stina; Hodges, Paul

    2012-03-01

    A motor unit consists of a motoneurone and the multiple muscle fibres that it innervates, and forms the final neural pathway that influences movement. Discharge of motor units is altered (decreased discharge rate and/or cessation of firing; and increased discharge rate and/or recruitment of new units) during matched-force contractions with pain. This is thought to be mediated by nociceptive (pain) input on motoneurones, as demonstrated in animal studies. It is also possible that motoneurone excitability is altered by pain related descending inputs, that these changes persist after noxious stimuli cease, and that direct nociceptive input is not necessary to induce pain related changes in movement. We aimed to determine whether anticipation of pain (descending pain related inputs without nociceptor discharge) alters motor unit discharge, and to observe motor unit discharge recovery after pain has ceased. Motor unit discharge was recorded with fine-wire electrodes in the quadriceps of 9 volunteers. Subjects matched isometric knee-extension force during anticipation of pain (anticipation: electrical shocks randomly applied over the infrapatellar fat-pad); pain (hypertonic saline injected into the fat-pad); and 3 intervening control conditions. Discharge rate of motor units decreased during pain (Precruitment of 1 population of units and new recruitment of another population were observed during both anticipation and pain; some changes in motor unit recruitment persisted after pain ceased. This challenges the fundamental theory that pain-related changes in muscle activity result from direct nociceptor discharge, and provides a mechanism that may underlie long-term changes in movement/chronicity in some musculoskeletal conditions. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  11. Motor unit recruitment strategies and muscle properties determine the influence of synaptic noise on force steadiness

    Science.gov (United States)

    Dideriksen, Jakob L.; Negro, Francesco; Enoka, Roger M.

    2012-01-01

    Motoneurons receive synaptic inputs from tens of thousands of connections that cause membrane potential to fluctuate continuously (synaptic noise), which introduces variability in discharge times of action potentials. We hypothesized that the influence of synaptic noise on force steadiness during voluntary contractions is limited to low muscle forces. The hypothesis was examined with an analytical description of transduction of motor unit spike trains into muscle force, a computational model of motor unit recruitment and rate coding, and experimental analysis of interspike interval variability during steady contractions with the abductor digiti minimi muscle. Simulations varied contraction force, level of synaptic noise, size of motor unit population, recruitment range, twitch contraction times, and level of motor unit short-term synchronization. Consistent with the analytical derivations, simulations and experimental data showed that force variability at target forces above a threshold was primarily due to low-frequency oscillations in neural drive, whereas the influence of synaptic noise was almost completely attenuated by two low-pass filters, one related to convolution of motoneuron spike trains with motor unit twitches (temporal summation) and the other attributable to summation of single motor unit forces (spatial summation). The threshold force above which synaptic noise ceased to influence force steadiness depended on recruitment range, size of motor unit population, and muscle contractile properties. This threshold was low (motor unit recruitment and muscle properties of a typical muscle are tuned to limit the influence of synaptic noise on force steadiness to low forces and that the inability to produce a constant force during stronger contractions is mainly attributable to the common low-frequency oscillations in motoneuron discharge rates. PMID:22423000

  12. Neurotrophic Factor-Secreting Autologous Muscle Stem Cell Therapy for the Treatment of Laryngeal Denervation Injury

    Science.gov (United States)

    Halum, Stacey L.; McRae, Bryan; Bijangi-Vishehsaraei, Khadijeh; Hiatt, Kelly

    2012-01-01

    Objectives To determine if the spontaneous reinnervation that characteristically ensues after recurrent laryngeal nerve (RLN) injury could be selectively promoted and directed to certain laryngeal muscles with the use of neurotrophic factor (NF)-secreting muscle stem cell (MSC) vectors while antagonistic reinnervation is inhibited with vincristine (VNC). Study Design Basic science investigations involving primary cell cultures, gene cloning/transfer, and animal experiments. Methods (i.) MSC survival assays were used to test multiple individual NFs in vitro. (ii.) Motoneuron outgrowth assays assessed the trophic effects of identified NF on cranial nerve X-derived (CNX) motoneurons in vitro. (iii.) Therapeutic NF was cloned into a lentiviral vector, and MSCs were tranduced to secrete NF. 60 rats underwent left RLN transection injury, and at 3 weeks received injections of either MSCs (n=24), MSCs secreting NF (n=24), or saline (n=12) into the left thyroarytenoid muscle complex (TA); half of the animals in the MSC groups simultaneously received left posterior cricoarytenoid (PCA) injections of vincristine (VNC) while half the animals received saline. Results (i.) Ciliary-derived neurotrophic factor (CNTF) had the greatest survival-promoting effect on MSCs in culture. (ii.) Addition of CNTF (50 ng/mL) to CN X motoneuron cultures resulted in enhanced neurite outgrowth and branching. (iii.) In the animal model, the injected MSCs fused with the denervated myofibers, immunohistochemistry demonstrated enhanced reinnervation based on motor endplate to nerve contact, and RT-PCR confirmed stable CNTF expression at longest follow-up (4 months) in the CNTF-secreting MSC treated groups. Conclusions MSC therapy may have a future role in selectively promoting and directing laryngeal reinnervation after RLN injury. Level of evidence: NA PMID:22965802

  13. The digastric muscle is less involved in pharyngeal swallowing in rabbits.

    Science.gov (United States)

    Tsujimura, Takanori; Yamada, Aki; Nakamura, Yuki; Fukuhara, Takako; Yamamura, Kensuke; Inoue, Makoto

    2012-06-01

    The swallowing reflex is centrally programmed by the lower brain stem, the so-called swallowing central pattern generator (CPG), and once the reflex is initiated, many muscles in the oral, pharyngeal, laryngeal, and esophageal regions are systematically activated. The mylohyoid (MH) muscle has been considered to be a "leading muscle" according to previous studies, but the functional role of the digastric (DIG) muscle in the swallowing reflex remains unclear. In the present study, therefore, the activities of single units of MH and DIG neurons were recorded extracellularly, and the functional involvement of these neurons in the swallowing reflex was investigated. The experiments were carried out on eight adult male Japanese white rabbits anesthetized with urethane. To identify DIG and MH neurons, the peripheral nerve (either DIG or MH) was stimulated to evoke action potentials of single motoneurons. Motoneurons were identified as such if they either (1) responded to antidromic nerve stimulation of DIG or MH in an all-or-none manner at threshold intensities and (2) followed stimulation frequencies of up to 0.5 kHz. As a result, all 11 MH neurons recorded were synchronously activated during the swallowing reflex, while there was no activity in any of the 7 DIG neurons recorded during the swallowing reflex. All neurons were anatomically localized ventromedially at the level of the caudal portion of the trigeminal motor nucleus, and there were no differences between the MH and DIG neuron sites. The present results strongly suggest that at least in the rabbit, DIG motoneurons are not tightly controlled by the swallowing CPG and, hence, the DIG muscle is less involved in the swallowing reflex.

  14. Role of the trochlear nerve in eye abduction and frontal vision of the red-eared slider turtle (Trachemys scripta elegans).

    Science.gov (United States)

    Dearworth, J R; Ashworth, A L; Kaye, J M; Bednarz, D T; Blaum, J F; Vacca, J M; McNeish, J E; Higgins, K A; Michael, C L; Skrobola, M G; Jones, M S; Ariel, M

    2013-10-15

    Horizontal head rotation evokes significant responses from trochlear motoneurons of turtle that suggests they have a functional role in abduction of the eyes like that in frontal-eyed mammals. The finding is unexpected given that the turtle is generally considered lateral-eyed and assumed to have eye movements instead like that of lateral-eyed mammals, in which innervation of the superior oblique muscle by the trochlear nerve (nIV) produces intorsion, elevation, and adduction (not abduction). Using an isolated turtle head preparation with the brain removed, glass suction electrodes were used to stimulate nIV with trains of current pulses. Eyes were monitored via an infrared camera with the head placed in a gimble to quantify eye rotations and their directions. Stimulations of nIV evoked intorsion, elevation, and abduction. Dissection of the superior oblique muscle identified lines of action and a location of insertion on the eye, which supported kinematics evoked by nIV stimulation. Eye positions in alert behaving turtles with their head extended were compared with that when their heads were retracted in the carapace. When the head was retracted, there was a reduction in interpupillary distance and an increase in binocular overlap. Occlusion of peripheral fields by the carapace forces the turtle to a more frontal-eyed state, perhaps the reason for the action of abduction by the superior oblique muscle. These findings support why trochlear motoneurons in turtle respond in the same way as abducens motoneurons to horizontal rotations, an unusual characteristic of vestibulo-ocular physiology in comparison with other mammalian lateral-eyed species. Copyright © 2013 Wiley Periodicals, Inc.

  15. Task-dependent output of human parasternal intercostal motor units across spinal levels.

    Science.gov (United States)

    Hudson, Anna L; Gandevia, Simon C; Butler, Jane E

    2017-12-01

    During breathing, there is differential activity in the human parasternal intercostal muscles and the activity is tightly coupled to the known mechanical advantages for inspiration of the same regions of muscles. It is not known whether differential activity is preserved for the non-respiratory task of ipsilateral trunk rotation. In the present study, we compared single motor units during resting breathing and axial rotation of the trunk during apnoea. We not only confirmed non-uniform recruitment of motor units across parasternal intercostal muscles in breathing, but also demonstrated that the same motor units show an altered pattern of recruitment in the non-respiratory task of trunk rotation. The output of parasternal intercostal motoneurones is modulated differently across spinal levels depending on the task and these results help us understand the mechanisms that may govern task-dependent differences in motoneurone output. During inspiration, there is differential activity in the human parasternal intercostal muscles across interspaces. We investigated whether the earlier recruitment of motor units in the rostral interspaces compared to more caudal spaces during inspiration is preserved for the non-respiratory task of ipsilateral trunk rotation. Single motor unit activity (SMU) was recorded from the first, second and fourth parasternal interspaces on the right side in five participants in two tasks: resting breathing and 'isometric' axial rotation of the trunk during apnoea. Recruitment of the same SMUs was compared between tasks (n = 123). During resting breathing, differential activity was indicated by earlier recruitment of SMUs in the first and second interspaces compared to the fourth space in inspiration (P motor units showed an altered pattern of recruitment because SMUs in the first interspace were recruited later and at a higher rotation torque than those in the second and fourth interspaces (P recruitment measures, was good-excellent [intraclass

  16. Synergic prodegradative activity of Bicalutamide and trehalose on the mutant androgen receptor responsible for spinal and bulbar muscular atrophy

    NARCIS (Netherlands)

    Giorgetti, Elise; Rusmini, Paola; Crippa, Valeria; Cristofani, Riccardo; Boncoraglio, Alessandra; Cicardi, Maria E.; Galbiati, Mariarita; Poletti, Angelo

    2015-01-01

    Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease due to a CAG triplet-repeat expansion in the androgen receptor (AR) gene, which is translated into an elongated polyglutamine (polyQ) tract in AR protein (ARpolyQ). ARpolyQ toxicity is activated by the AR ligand testosterone

  17. Effects of real and sham whole-body mechanical vibration on spinal excitability at rest and during muscle contraction

    NARCIS (Netherlands)

    Hortobagyi, T.; Rider, P.; DeVita, P.

    2014-01-01

    We examined the effects of whole-body mechanical vibration (WBV) on indices of motoneuronal excitability at rest and during muscle contraction in healthy humans. Real and sham WBV at 30Hz had no effect on reflexes measured during muscle contraction. Real WBV at 30 and 50Hz depressed the H-reflex

  18. Comparison of 99mTc-MIBI scanning and sentinel node biopsy in the detection of occult melanoma lymph node metastases

    International Nuclear Information System (INIS)

    Alonso, O.; Lago, G.; Lopes de Amorim, M.C.; Juri, C.; Larre Borges, A.; Martinez, M.; De Boni, D.; Espasandin, J.; Priario, J.

    2002-01-01

    Aim: Sentinel node biopsy (SNB) is a highly accurate technique for detecting occult metastatic disease in the regional lymph nodes. Our group has reported that 99m Tc-MIBI scintigraphy is an imaging technique that can detect clinically undetectable metastases. This prospective study shows preliminary results on the comparison of both techniques for the detection of lymph node invasion. Material and Methods: Twenty-two consecutive patients (15 women, 7 men; mean age, 55 years) with primary melanoma > 1.0 mm thick were enrolled (mean 2.6 mm). Patients underwent 99m Tc-MIBI scintigraphy of regional lymph nodes 1-2 weeks before surgery, acquiring 10-minute planar images with a LFOV gamma camera. A preoperative lymphoscintigraphy using 99m Tc-colloidal (Re) sulphide was performed the day before surgery, using a dose of 74-93 MBq. Radio guided SNB was performed with a hand-held gamma probe. Lymph nodes were examined histologically and immunostained for S-100 and HMB-45. Results: The sentinel node (SN) was identified in 21/22 patients. An average of 1.6 SN/lesion were harvested from melanomas located in the following regions: head and neck (n=3), trunk (n=6), extremities (n=12). All patients with negative SN (n=11) were also negative with MIBI. In 10 cases the SN demonstrated metastatic involvement, whereas 99m Tc-MIBI was positive in 8 of them (80%). In cases with positive SN/negative 99m Tc-MIBI, the pathology report revealed micro metastatic disease. Conclusion: These preliminary results suggest that 99m Tc-MIBI scanning has the potential of selecting a group of patients who might benefit from a selective complete lymphadenectomy

  19. THE EFFECTS OF MAXILLARY EXPANSION ON THE SOFT TISSUE FACIAL PROFILE

    Directory of Open Access Journals (Sweden)

    Işıl ARAS

    2017-10-01

    Full Text Available Purpose: The aims of this retrospective study were to evaluate the possible changes in soft tissue facial profile induced by orthopedic rapid maxillary expansion (RME and surgically assisted rapid maxillary expansion (SARME, and to correlate them with the underlying hard tissue alterations. Materials and Methods: 16 patients who received bone borne SARME and 25 patients who were subjected to RME using metal cast splint hyrax appliance were analyzed retrospectively. This research was conducted on lateral cephalometric radiographs taken on 2 occasions: before expansion (T1 and at the beginning of any further orthodontic treatment (T2. Investigated lateral cephalometric parameters consisted of Holdaway soft tissue measurements with some supplementary soft tissue, skeletal and dental assessments. Results: The acquisition of T2 cephalograms which conforms to the initiation of further orthodontic treatment corresponded to 83.25±3.51 days for SARME and 85.68±4.37 days for RME after the expansion was completed. The only significant change in soft tissue profile of the SARME group was a decrease in upper lip thickness (p<0.05, whereas in the RME group, decrease in soft tissue facial profile angle and increase in H angle were found to be statistically significant (p<0.05 for each. For the RME group, the changes in soft tissue facial profile angle and H angle correlated only with the changes in SNB angle (p<0.05. Conclusion: While bone-borne SARME did not seem to possess the potential to alter soft tissue profile, tooth-borne RME caused a more convex soft tissue profile related to a reduction in SNB.

  20. Fault structure and kinematics of the Long Valley Caldera region, California, revealed by high-accuracy earthquake hypocenters and focal mechanism stress inversions

    Science.gov (United States)

    Prejean, Stephanie; Ellsworth, William L.; Zoback, Mark; Waldhauser, Felix

    2002-01-01

    We have determined high-resolution hypocenters for 45,000+ earthquakes that occurred between 1980 and 2000 in the Long Valley caldera area using a double-difference earthquake location algorithm and routinely determined arrival times. The locations reveal numerous discrete fault planes in the southern caldera and adjacent Sierra Nevada block (SNB). Intracaldera faults include a series of east/west-striking right-lateral strike-slip faults beneath the caldera's south moat and a series of more northerly striking strike-slip/normal faults beneath the caldera's resurgent dome. Seismicity in the SNB south of the caldera is confined to a crustal block bounded on the west by an east-dipping oblique normal fault and on the east by the Hilton Creek fault. Two NE-striking left-lateral strike-slip faults are responsible for most seismicity within this block. To understand better the stresses driving seismicity, we performed stress inversions using focal mechanisms with 50 or more first motions. This analysis reveals that the least principal stress direction systematically rotates across the studied region, from NE to SW in the caldera's south moat to WNW-ESE in Round Valley, 25 km to the SE. Because WNW-ESE extension is characteristic of the western boundary of the Basin and Range province, caldera area stresses appear to be locally perturbed. This stress perturbation does not seem to result from magma chamber inflation but may be related to the significant (???20 km) left step in the locus of extension along the Sierra Nevada/Basin and Range province boundary. This implies that regional-scale tectonic processes are driving seismic deformation in the Long Valley caldera.

  1. The role of lymphoscintigraphy, sentinel mode biopsy and positron emission tomography in the staging of the neck in early oral squamous cell carcinoma

    Science.gov (United States)

    Hyde, Nicholas Charles

    This thesis explores the limitations of current imaging modalities in the evaluation of the clinically node negative (N0) neck in early oral squamous cell carcinoma and evaluates the utility of two new interventions. It will become evident that the use of clinical parameters and conventional imaging to detect clinically occult cervical lymph node metastases is an imprecise science. The presence of metastases in the neck is the single most important determinant of survival. Hitherto the lack of timely intervention in this regard may have been contributory in amplifying their effect upon survival. There is an obvious requirement for a more accurate technique to stage the neck in this patient group. Therefore the application of lymphoscintigraphy in combination with sentinel node biopsy (SNB), and positron emission tomography (PET) have been investigated. It appears that PET, whilst having a number of useful roles in the generic head and neck oncology patient, has little to contribute in the diagnosis of occult neck disease. In contra-distinction lymphoscintigraphy and SNB are not only feasible in the diagnosis of occult metastases, but also enhance our knowledge of lymphatic drainage from the oral cavity. This has, in some circumstances, led to the modification of initially prescribed treatment plans. Such is the current pace of technological advance that over the course of this research an entirely new imaging modality has emerged - PET/CT. Whilst it has not been possible to apply this retrospectively to the original patient population early experience of this novel technique in head and neck malignancy is explored and reported. The results of these initial applications are encouraging.

  2. Efficacy of Pectoral Nerve Block Type II for Breast-Conserving Surgery and Sentinel Lymph Node Biopsy: A Prospective Randomized Controlled Study

    Directory of Open Access Journals (Sweden)

    Doo-Hwan Kim

    2018-01-01

    Full Text Available Objectives. The pectoral nerve block type II (PECS II block is widely used for postoperative analgesia after breast surgery. This study evaluated the analgesic efficacy of PECS II block in patients undergoing breast-conserving surgery (BCS and sentinel lymph node biopsy (SNB. Methods. Patients were randomized to the control group (n=40 and the PECS II group (n=40. An ultrasound-guided PECS II block was performed after induction of anesthesia. The primary outcome measure was opioid consumption, and the secondary outcome was pain at the breast and axillary measured using the Numerical Rating Scale (NRS 24 hours after surgery. Opioid requirement was assessed according to tumor location. Results. Opioid requirement was lower in the PECS II than in the control group (43.8 ± 28.5 µg versus 77.0 ± 41.9 µg, p<0.001. However, the frequency of rescue analgesics did not differ between these groups. Opioid consumption in the PECS II group was significantly lower in patients with tumors in the outer area than that in patients with tumors in the inner area (32.5 ± 23.0 µg versus 58.0 ± 29.3 µg, p=0.007. The axillary NRS was consistently lower through 24 hr in the PECS II group. Conclusion. Although the PECS II block seemed to reduce pain intensity and opioid requirements for 24 h after BCS and SNB, these reductions may not be clinically significant. This trial is registered with Clinical Research Information Service KCT0002509.

  3. The Effect of Tongue Exercise on Serotonergic Input to the Hypoglossal Nucleus in Young and Old Rats

    Science.gov (United States)

    Behan, Mary; Moeser, Adam E.; Thomas, Cathy F.; Russell, John A.; Wang, Hao; Leverson, Glen E.; Connor, Nadine P.

    2012-01-01

    Purpose: Breathing and swallowing problems affect elderly people and may be related to age-associated tongue dysfunction. Hypoglossal motoneurons that innervate the tongue receive a robust, excitatory serotonergic (5HT) input and may be affected by aging. We used a rat model of aging and progressive resistance tongue exercise to determine whether…

  4. Need for intensive histopathologic analysis to determine lymph node metastases when using sentinel node biopsy in oral cancer

    DEFF Research Database (Denmark)

    Bilde, Anders; von Buchwald, Christian; Therkildsen, Marianne Hamilton

    2008-01-01

    OBJECTIVE: To determine the predictive value of sentinel node biopsy (SNB)-assisted neck dissection in patients with oral squamous cell carcinoma (SCC) stage T1 to 2N0M0 and to determine the incidence of subclinical metastases. STUDY DESIGN: Prospective cohort study. METHODS: Fifty-one patients...... feasible in identifying subclinical metastasis, thus accurately staging the neck with a high degree of sensitivity in patients with oral SCC T1 to 2N0M0 when additional histopathology was performed. The vast majority of patients in this study would have been spared selective neck dissection had reliance...... dissection in patients with oral SCC....

  5. The main conditions ensured problemless implementation of 235U high enriched fuel in Kozloduy NPP (Bulgaria) - WWER-1000 Units

    International Nuclear Information System (INIS)

    Dobrevski, I.; Zaharieva, N.; Minkova, K.; Michaylov, G.; Penev, P.; Gerchev, N.

    2009-01-01

    The collected water chemistry and radiochemistry data during the operation of the Kozloduy NPP Unit 5 for the period 2006-2009 (12-th, 13-th 14-th and 15-th fuel cycles) undoubtedly indicate for WWER-1000 Units (whose specific features are: Steam generators with austenitic stainless steel 08Cr18N10T tubing; Steam generators are with horizontal straight tubing and Fuel elements cladding material is Zr-1%Nb (Zr1Nb) alloy), that one realistic way for problemless implementation of 235 U high enriched fuel have been found. The main feature characteristics of this way are: Implementation of solid neutron burnable absorbers together with the dissolved in coolant neutron absorber - natural boric acid; Application of fuel cladding materials with enough corrosion resistance by the specific fuel cladding environment created by presence of SNB; Keeping of suitable coolant water chemistry which ensures low corrosion rates of core- and out-of-core- materials and limits in core (cladding) depositions and restricts out-of-core radioactivity buildup. The realization of this way in WWER-1000 Units in Kozloduy NPP was practically carried out through: 1) Implementation of Russian fuel assemblies TVSA which have as fuel cladding material E-110 alloy (Zr1Nb) with enough high corrosion resistance by presence of sub-cooled nucleate boiling (SNB) and use burnable absorber (Gd) integrated in the uranium-gadolinium (U-Gd 2 O 3 ) fuel (fuel rod with 5.0% Gd 2 O 3 ); 2) Development and implementation of water chemistry primary circuit guidelines, which require the relation between boric acid concentration and total alkalising agent concentrations to ensure coolant pH 300 = 7.0 - 7.2 values during the whole operation period. The above mentioned conditions by the passing of WWER-1000 Units in NPP Kozloduy to uranium fuel with 4.4% 235 U (TVSA fuel assemblies) practically ensured avoidance of the creation of the necessary conditions for AOA onset. The operational experience (2006-2009) of the

  6. Recommended reactor coolant water chemistry requirements for WWER-1000 units with 235U higher enriched fuel

    International Nuclear Information System (INIS)

    Dobrevski, I.; Zaharieva, N.

    2011-01-01

    The last decade worldwide experience of PWRs and WWERs confirms the trends for the improvement of the nuclear power industry electricity production through the implementation of high burn-up or high fuel duty, which are usually accompanied with the usage of UO 2 fuel with higher content of 235 U - 4.0% - 4.5% (5.0%). It was concluded that the onset of sub-cooled nucleate boiling (SNB) on the fuel cladding surfaces and the initial excess reactivity of the core are the primary and basic factors accompanying the implementation of uranium fuel with higher 235 U content, aiming extended fuel cycles and higher burn-up of the fuel in Pressurized Water Reactors. As main consequences of the presence of these factors the modifications of chemical / electrochemical environments of nuclear fuel cladding- and reactor coolant system- surfaces are evaluated. These conclusions are the reason for: 1) The determination of the choices of the type of fuel cladding materials in respect with their enough corrosion resistance to the specific fuel cladding environment, created by the presence of SNB; 2) The development and implementation of primary circuit water chemistry guidelines ensuring the necessary low corrosion rates of primary circuit materials and limitation of cladding deposition and out-of-core radioactivity buildup; 3) Implementation of additional neutron absorbers which allow enough decrease of the initial concentration of H 3 BO 3 in coolant, so that its neutralization will be possible with the permitted alkalising agent concentrations. In this paper the specific features of WWER-1000 units in Bulgarian Nuclear Power Plant; use of 235 U higher enriched fuel in the WWER-1000 reactors in the Kozloduy NPP; coolant water chemistry and radiochemistry plant data during the power operation period of the Kozloduy NPP Unit 5, 15 th fuel cycle; evaluation of the approaches and results by the conversion of the WWER-1000 Units at the Kozloduy NPP to the uranium fuel with 4.3% 235 U as

  7. A neuro-mechanical model of a single leg joint highlighting the basic physiological role of fast and slow muscle fibres of an insect muscle system.

    Directory of Open Access Journals (Sweden)

    Tibor Istvan Toth

    Full Text Available In legged animals, the muscle system has a dual function: to produce forces and torques necessary to move the limbs in a systematic way, and to maintain the body in a static position. These two functions are performed by the contribution of specialized motor units, i.e. motoneurons driving sets of specialized muscle fibres. With reference to their overall contraction and metabolic properties they are called fast and slow muscle fibres and can be found ubiquitously in skeletal muscles. Both fibre types are active during stepping, but only the slow ones maintain the posture of the body. From these findings, the general hypothesis on a functional segregation between both fibre types and their neuronal control has arisen. Earlier muscle models did not fully take this aspect into account. They either focused on certain aspects of muscular function or were developed to describe specific behaviours only. By contrast, our neuro-mechanical model is more general as it allows functionally to differentiate between static and dynamic aspects of movement control. It does so by including both muscle fibre types and separate motoneuron drives. Our model helps to gain a deeper insight into how the nervous system might combine neuronal control of locomotion and posture. It predicts that (1 positioning the leg at a specific retraction angle in steady state is most likely due to the extent of recruitment of slow muscle fibres and not to the force developed in the individual fibres of the antagonistic muscles; (2 the fast muscle fibres of antagonistic muscles contract alternately during stepping, while co-contraction of the slow muscle fibres takes place during steady state; (3 there are several possible ways of transition between movement and steady state of the leg achieved by varying the time course of recruitment of the fibres in the participating muscles.

  8. Neuronal activity in the isolated mouse spinal cord during spontaneous deletions in fictive locomotion: insights into locomotor central pattern generator organization

    Science.gov (United States)

    Zhong, Guisheng; Shevtsova, Natalia A; Rybak, Ilya A; Harris-Warrick, Ronald M

    2012-01-01

    We explored the organization of the spinal central pattern generator (CPG) for locomotion by analysing the activity of spinal interneurons and motoneurons during spontaneous deletions occurring during fictive locomotion in the isolated neonatal mouse spinal cord, following earlier work on locomotor deletions in the cat. In the isolated mouse spinal cord, most spontaneous deletions were non-resetting, with rhythmic activity resuming after an integer number of cycles. Flexor and extensor deletions showed marked asymmetry: flexor deletions were accompanied by sustained ipsilateral extensor activity, whereas rhythmic flexor bursting was not perturbed during extensor deletions. Rhythmic activity on one side of the cord was not perturbed during non-resetting spontaneous deletions on the other side, and these deletions could occur with no input from the other side of the cord. These results suggest that the locomotor CPG has a two-level organization with rhythm-generating (RG) and pattern-forming (PF) networks, in which only the flexor RG network is intrinsically rhythmic. To further explore the neuronal organization of the CPG, we monitored activity of motoneurons and selected identified interneurons during spontaneous non-resetting deletions. Motoneurons lost rhythmic synaptic drive during ipsilateral deletions. Flexor-related commissural interneurons continued to fire rhythmically during non-resetting ipsilateral flexor deletions. Deletion analysis revealed two classes of rhythmic V2a interneurons. Type I V2a interneurons retained rhythmic synaptic drive and firing during ipsilateral motor deletions, while type II V2a interneurons lost rhythmic synaptic input and fell silent during deletions. This suggests that the type I neurons are components of the RG, whereas the type II neurons are components of the PF network. We propose a computational model of the spinal locomotor CPG that reproduces our experimental results. The results may provide novel insights into the

  9. Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CpG of the rat spinal cord in vitro.

    Directory of Open Access Journals (Sweden)

    Francesco Dose

    Full Text Available Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 μM generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in

  10. Slit2 as a β-catenin/Ctnnb1-dependent retrograde signal for presynaptic differentiation

    Science.gov (United States)

    Wu, Haitao; Barik, Arnab; Lu, Yisheng; Shen, Chengyong; Bowman, Andrew; Li, Lei; Sathyamurthy, Anupama; Lin, Thiri W; Xiong, Wen-Cheng; Mei, Lin

    2015-01-01

    Neuromuscular junction formation requires proper interaction between motoneurons and muscle cells. β-Catenin (Ctnnb1) in muscle is critical for motoneuron differentiation; however, little is known about the relevant retrograde signal. In this paper, we dissected which functions of muscle Ctnnb1 are critical by an in vivo transgenic approach. We show that Ctnnb1 mutant without the transactivation domain was unable to rescue presynaptic deficits of Ctnnb1 mutation, indicating the involvement of transcription regulation. On the other hand, the cell-adhesion function of Ctnnb1 is dispensable. We screened for proteins that may serve as a Ctnnb1-directed retrograde factor and identified Slit2. Transgenic expression of Slit2 specifically in the muscle was able to diminish presynaptic deficits by Ctnnb1 mutation in mice. Slit2 immobilized on beads was able to induce synaptophysin puncta in axons of spinal cord explants. Together, these observations suggest that Slit2 serves as a factor utilized by muscle Ctnnb1 to direct presynaptic differentiation. DOI: http://dx.doi.org/10.7554/eLife.07266.001 PMID:26159615

  11. Genetic specification of left–right asymmetry in the diaphragm muscles and their motor innervation

    Science.gov (United States)

    Charoy, Camille; Dinvaut, Sarah; Chaix, Yohan; Morlé, Laurette; Sanyas, Isabelle; Bozon, Muriel; Kindbeiter, Karine; Durand, Bénédicte; Skidmore, Jennifer M; De Groef, Lies; Seki, Motoaki; Moons, Lieve; Ruhrberg, Christiana; Martin, James F; Martin, Donna M; Falk, Julien; Castellani, Valerie

    2017-01-01

    The diaphragm muscle is essential for breathing in mammals. Its asymmetric elevation during contraction correlates with morphological features suggestive of inherent left–right (L/R) asymmetry. Whether this asymmetry is due to L versus R differences in the muscle or in the phrenic nerve activity is unknown. Here, we have combined the analysis of genetically modified mouse models with transcriptomic analysis to show that both the diaphragm muscle and phrenic nerves have asymmetries, which can be established independently of each other during early embryogenesis in pathway instructed by Nodal, a morphogen that also conveys asymmetry in other organs. We further found that phrenic motoneurons receive an early L/R genetic imprint, with L versus R differences both in Slit/Robo signaling and MMP2 activity and in the contribution of both pathways to establish phrenic nerve asymmetry. Our study therefore demonstrates L–R imprinting of spinal motoneurons and describes how L/R modulation of axon guidance signaling helps to match neural circuit formation to organ asymmetry. DOI: http://dx.doi.org/10.7554/eLife.18481.001 PMID:28639940

  12. Neural control of muscle force: indications from a simulation model

    Science.gov (United States)

    Luca, Carlo J. De

    2013-01-01

    We developed a model to investigate the influence of the muscle force twitch on the simulated firing behavior of motoneurons and muscle force production during voluntary isometric contractions. The input consists of an excitatory signal common to all the motor units in the pool of a muscle, consistent with the “common drive” property. Motor units respond with a hierarchically structured firing behavior wherein at any time and force, firing rates are inversely proportional to recruitment threshold, as described by the “onion skin” property. Time- and force-dependent changes in muscle force production are introduced by varying the motor unit force twitches as a function of time or by varying the number of active motor units. A force feedback adjusts the input excitation, maintaining the simulated force at a target level. The simulations replicate motor unit behavior characteristics similar to those reported in previous empirical studies of sustained contractions: 1) the initial decrease and subsequent increase of firing rates, 2) the derecruitment and recruitment of motor units throughout sustained contractions, and 3) the continual increase in the force fluctuation caused by the progressive recruitment of larger motor units. The model cautions the use of motor unit behavior at recruitment and derecruitment without consideration of changes in the muscle force generation capacity. It describes an alternative mechanism for the reserve capacity of motor units to generate extraordinary force. It supports the hypothesis that the control of motoneurons remains invariant during force-varying and sustained isometric contractions. PMID:23236008

  13. The compensatory interaction between motor unit firing behavior and muscle force during fatigue.

    Science.gov (United States)

    Contessa, Paola; De Luca, Carlo J; Kline, Joshua C

    2016-10-01

    Throughout the literature, different observations of motor unit firing behavior during muscle fatigue have been reported and explained with varieties of conjectures. The disagreement amongst previous studies has resulted, in part, from the limited number of available motor units and from the misleading practice of grouping motor unit data across different subjects, contractions, and force levels. To establish a more clear understanding of motor unit control during fatigue, we investigated the firing behavior of motor units from the vastus lateralis muscle of individual subjects during a fatigue protocol of repeated voluntary constant force isometric contractions. Surface electromyographic decomposition technology provided the firings of 1,890 motor unit firing trains. These data revealed that to sustain the contraction force as the muscle fatigued, the following occurred: 1) motor unit firing rates increased; 2) new motor units were recruited; and 3) motor unit recruitment thresholds decreased. Although the degree of these adaptations was subject specific, the behavior was consistent in all subjects. When we compared our empirical observations with those obtained from simulation, we found that the fatigue-induced changes in motor unit firing behavior can be explained by increasing excitation to the motoneuron pool that compensates for the fatigue-induced decrease in muscle force twitch reported in empirical studies. Yet, the fundamental motor unit control scheme remains invariant throughout the development of fatigue. These findings indicate that the central nervous system regulates motor unit firing behavior by adjusting the operating point of the excitation to the motoneuron pool to sustain the contraction force as the muscle fatigues. Copyright © 2016 the American Physiological Society.

  14. Excitability properties of motor axons in adults with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Cliff S. Klein

    2015-06-01

    Full Text Available Cerebral Palsy (CP is a permanent disorder caused by a lesion to the developing brain that significantly impairs motor function. The neurophysiological mechanisms underlying motor impairment are not well understood. Specifically, few have addressed whether motoneuron or peripheral axon properties are altered in CP, even though disruption of descending inputs to the spinal cord may cause them to change. In the present study, we have compared nerve excitability properties in seven adults with CP and fourteen healthy controls using threshold tracking techniques by stimulating the median nerve at the wrist and recording the compound muscle action potential (CMAP over the abductor pollicis brevis. The excitability properties in the CP subjects were found to be abnormal. Early and late depolarizing and hyperpolarizing threshold electrotonus was significantly larger (i.e., fanning out, and resting current-threshold (I/V slope was smaller, in CP compared to control. In addition resting threshold and rheobase tended to be larger in CP. According to a modeling analysis of the data, an increase in leakage current under or through the myelin sheath, i.e., the Barrett-Barrett conductance (GBB, combined with a slight hyperpolarization of the resting membrane potential, best explained the group differences in excitability properties. There was a trend for those with greater impairment in gross motor function to have more abnormal axon properties. The findings indicate plasticity of motor axon properties far removed from the site of the lesion. We suspect that this plasticity is caused by disruption of descending inputs to the motoneurons at an early age around the time of their injury.

  15. Parasympathetic preganglionic cardiac motoneurons labeled after voluntary diving

    Directory of Open Access Journals (Sweden)

    W Michael ePanneton

    2014-01-01

    Full Text Available A dramatic bradycardia is induced by underwater submersion in vertebrates. The location of parasympathetic preganglionic cardiac motor neurons driving this aspect of the diving response was investigated using cFos immunohistochemistry combined with retrograde transport of cholera toxin subunit B (CTB to double-label neurons. After pericardial injections of CTB, trained rats voluntarily dove underwater, and their heart rates dropped immediately to 95±2bpm, an 80% reduction. After immunohistochemical processing, the vast majority of CTB labeled neurons were located in the reticular formation from the rostral cervical spinal cord to the facial motor nucleus, confirming previous studies. Labeled neurons caudal to the rostral ventrolateral medulla were usually spindle-shaped aligned along an oblique line running from the dorsal vagal nucleus to the ventrolateral reticular formation, while those more rostrally were multipolar with extended dendrites. Nine percent of retrogradely-labeled neurons were positive for both cFos and CTB after diving and 74% of these were found rostral to the obex. CTB also was transported transganglionically in primary afferent fibers, resulting in large granular deposits in dorsolateral, ventrolateral, and commissural subnuclei of the nucleus tractus solitarii and finer deposits in lamina I and IV-V of the trigeminocervical complex. The overlap of parasympathetic preganglionic cardiac motor neurons activated by diving with those activated by baro- and chemoreceptors in the rostral ventrolateral medulla is discussed. Thus the profound bradycardia seen with underwater submersion reinforces the notion that the mammalian diving response is the most powerful autonomic reflex known.

  16. Intra-articular Analgesia and Discharge to Home Enhance Recovery Following Total Knee Replacement.

    Science.gov (United States)

    Duggal, Shivi; Flics, Susan; Cornell, Charles N

    2015-02-01

    The increasing demand for total knee arthroplasty (TKR) and the initiatives to reduce health care spending have put the responsibility for efficient care on hospitals and providers. Multidisciplinary care pathways have been shown to shorten length of stay and result in improved short-term outcomes. However, common problems such as post-op nausea, orthostasis, and quad weakness remain, while reliance on discharge to rehabilitation facilities may also prolong hospital stay. Our aim was to document that combined modifications of our traditional clinical pathway for unilateral TKR could lead to improved short-term outcomes. We pose the following research questions. Can pathway modifications which include intra-articular infusion and saphenous nerve block (SNB) provide adequate pain relief and eliminate common side effects promoting earlier mobilization? Can planning for discharge to home avoid in-patient rehab stays? Can these combined modifications decrease length of stay even in patients with complex comorbidities indicated by higher ASA class? Will discharge to home incur an increase in complications or a failure to achieve knee range of motion? A retrospective review was performed and identified two cohorts. Group A included 116 patients that underwent unilateral TKR for osteoarthritis between August 2009 and August 2010. Group B included 171 patients that underwent unilateral TKR for osteoarthritis between February 2012 to February 2013. Group A patients were treated with spinal anesthesia with patient-controlled epidural analgesia (PCEA)/femoral nerve block (FNB) for the first 48 h after surgery. Discharge planning was initiated after admission. Group B had spinal anesthesia with SNB and received a continuous intra-articular infusion of 0.2% ropivicaine for 48 h post-op. Discharge planning was initiated with a case manager prior to hospitalization and discharge to home was declared the preferred approach. An intensive home PT program was made available through

  17. Role of brain-derived neurotrophic factor in the excitatory-inhibitory imbalance during the critical period of postnatal respiratory development in the rat.

    Science.gov (United States)

    Gao, Xiu-Ping; Zhang, Hanmeng; Wong-Riley, Margaret

    2015-11-01

    The critical period of respiratory development in rats is a narrow window toward the end of the second postnatal week (P12-13), when abrupt neurochemical, electrophysiological, and ventilatory changes occur, when inhibition dominates over excitation, and when the animals' response to hypoxia is the weakest. The goal of this study was to further test our hypothesis that a major mechanism underlying the synaptic imbalance during the critical period is a reduced expression of brain-derived neurotrophic factor (BDNF) and its TrkB receptors. Our aims were to determine (1) that the inhibitory dominance observed in hypoglossal motoneurons during the critical period was also demonstrable in a key respiratory chemosensor, NTSVL; (2) if in vivo application of a TrkB agonist, 7,8-DHF, would prevent, but a TrkB antagonist, ANA-12, would accentuate the synaptic imbalance; and (3) if hypoxia would also heighten the imbalance. Our results indicate that (1) the synaptic imbalance was evident in the NTSVL during the critical period; (2) intraperitoneal injections of 7,8-DHF prevented the synaptic imbalance during the critical period, whereas ANA-12 in vivo accentuated such an imbalance; and (3) acute hypoxia induced the weakest response in both the amplitude and frequency of sEPSCs during the critical period, but it increased the frequency of sIPSCs during the critical period. Thus, our findings are consistent with and strengthen our hypothesis that BDNF and TrkB play a significant role in inducing a synaptic imbalance during the critical period of respiratory development in the rat. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  18. Radiative transfer modelling in combusting systems using discrete ordinates method on three-dimensional unstructured grids; Modelisation des transferts radiatifs en combustion par methode aux ordonnees discretes sur des maillages non structures tridimensionnels

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, D.

    2004-04-01

    The prediction of pollutant species such as soots and NO{sub x} emissions and lifetime of the walls in a combustion chamber is strongly dependant on heat transfer by radiation at high temperatures. This work deals with the development of a code based on the Discrete Ordinates Method (DOM) aiming at providing radiative source terms and wall fluxes with a good compromise between cpu time and accuracy. Radiative heat transfers are calculated using the unstructured grids defined by the Computational Fluid Dynamics (CFD) codes. The spectral properties of the combustion gases are taken into account by a statistical narrow bands correlated-k model (SNB-ck). Various types of angular quadrature are tested and three different spatial differencing schemes were integrated and compared. The validation tests show the limit at strong optical thicknesses of the finite volume approximation used the Discrete Ordinates Method. The first calculations performed on LES solutions are presented, it provides instantaneous radiative source terms and wall heat fluxes. Those results represent a first step towards radiation/combustion coupling. (author)

  19. Moessbauer spectra as a 'fingerprint' in tin-lithium compounds: Applications to Li-ion batteries

    International Nuclear Information System (INIS)

    Robert, F.; Lippens, P.E.; Olivier-Fourcade, J.; Jumas, J.-C.; Gillot, F.; Morcrette, M.; Tarascon, J.-M.

    2007-01-01

    Several Li-Sn crystalline phases, i.e. Li 2 Sn 5 , LiSn, Li 7 Sn 3 , Li 5 Sn 2 , Li 13 Sn 5 , Li 7 Sn 2 and Li 22 Sn 5 were prepared by ball-milling and characterized by X-ray powder diffraction and 119 Sn Moessbauer spectroscopy. The analysis of the Moessbauer hyperfine parameters, i.e. isomer shift (δ) and quadrupole splitting (Δ), made it possible to define two types of Li-Sn compounds: the Sn-richest compounds (Li 2 Sn 5 , LiSn) and the Li-richest compounds (Li 7 Sn 3 , Li 5 Sn 2 , Li 13 Sn 5 , Li 7 Sn 2 , Li 22 Sn 5 ). The isomer shift values ranged from 2.56 to 2.38 mm s -1 for Li 2 Sn 5 , LiSn and from 2.07 to 1.83 mm s -1 for Li 7 Sn 3 , Li 5 Sn 2 , Li 13 Sn 5 , Li 7 Sn 2 and Li 22 Sn 5 , respectively. A Δ-δ correlation diagram is introduced in order to identify the different phases observed during the electrochemical process of new Sn-based materials. This approach is illustrated by the identification of the phases obtained at the end of the first discharge of η-Cu 6 Sn 5 and SnB 0.6 P 0.4 O 2.9 . - Graphical abstract: Δ-δ correlation diagram for the different tin sites of the Li-Sn compounds. The symbols denote the different Li-Sn phases and the products obtained at the end of the discharge of η-Cu 6 Sn 5 and SnB 0.6 P 0.4 O 2.9 . The grey and the light-grey areas show Sn-centred polyhedra without and with one Sn first-nearest neighbours, respectively

  20. The effectiveness of the Herbst appliance for patients with Class II malocclusion: a meta-analysis

    Science.gov (United States)

    Yang, Xin; Zhu, Yafen; Long, Hu; Zhou, Yang; Jian, Fan; Ye, Niansong; Gao, Meiya

    2016-01-01

    Summary Objective: To systematically investigate review in literature the effects of the Herbst appliance for patients with Class II malocclusion patients. Method: We performed a comprehensive literature survey on PubMed, Web of Science, Embase, CENTRAL, SIGLE, and ClinicalTrial.gov up to December 2014. The selection criteria: randomized controlled trials or clinical controlled trials; using any kind of Herbst appliances to correct Class II division 1 malocclusions; skeletal and/or dental changes evaluated through lateral cephalograms. And the exclusion criteria: syndromic patients; individual case reports and series of cases; surgical interventions. Article screening, data extraction, assessment of risk of bias, and evaluation of evidence quality through GRADE were conducted independently by two well-trained orthodontic doctors. Consensus was made via group discussion of all authors when there is inconsistent information from the two. After that, sensitivity analysis and subgroup analysis were performed to evaluate the robustness of the meta-analysis. Results: Twelve clinical controlled trials meet the above-mentioned criteria, and were included in this analysis. All included studies have eleven measures taken during both active treatment effect and long term effect periods, including four angular ones (i.e., SNA, SNB, ANB, mandibular plane angle) and seven linear ones (i.e. Co-Go, Co-Gn, overjet, overbite, molar relationship, A point-OLp, Pg-OLp) during active treatment effect period were statistically pooled. Meta-analysis and sensitivity analysis demonstrated that all these measures showed consistent results except for SNA, ANB, and overbite. Subgroup analysis showed significant changes in SNA, overbite, and Pg-OLp. Publication bias was detected in SNB, mandibular plane angle, and A point-OLp. Conclusion: The Herbst appliance is effective for patients with Class II malocclusion in active treatment period. Especially, there are obvious changes on dental

  1. Recycling Improves Soil Fertility Management in Smallholdings in Tanzania

    Directory of Open Access Journals (Sweden)

    Ariane Krause

    2018-02-01

    Full Text Available Residues from bioenergy and ecological sanitation (EcoSan can be utilized to sustain soil fertility and productivity. With regard to certain cooking and sanitation technologies used in smallholder households (hh, we systematically analyzed how utilization of the respective potentials to recover residues for farming affects (i soil nutrient balances, (ii the potential for subsistence production of composts, and (iii environmental emissions. On the example of an intercropping farming system in Karagwe, Tanzania, we studied specific farming practices including (1 current practices of using standard compost only; (2 a combination of using biogas slurry, urine, and standard compost; (3 a combination of using so-called “CaSa-compost” (containing biochar and sanitized human excreta, Project “Carbonization and Sanitation”, urine, and standard compost. The system analysis combines a soil nutrient balance (SNB with material flow analysis (MFA. Currently, nitrogen (N and phosphorus (P are depleted by −54 ± 3 and −8 ± 1 kg∙ha−1∙year−1, respectively. Our analysis shows, however, a clear potential to reduce depletion rates of N, and to reverse the SNB of P, to bring about a positive outcome. Composts and biogas slurry supply sufficient P to crops, while urine effectively supplements N. By using resources recovered from cooking and sanitation, sufficient compost for subsistence farming may be produced. Human excreta contribute especially to total N and total P in CaSa-compost, whilst biochar recovered from cooking with microgasifier stoves adds to total carbon (C and total P. We conclude that the combined recycling of household residues from cooking and from sanitation, and CaSa-compost in particular, is especially suitable for sustainable soil management, as it mitigates existing P-deficiency and soil acidity, and also restores soil organic matter.

  2. Formas de cultura de Trypanosoma rotatorium Mayer, 1843: isolado da rã Leptodactylus ocellatus do Brasil Culture forms of T. rotatorum Mayer, 1843

    Directory of Open Access Journals (Sweden)

    Neize M. Pereira

    1973-01-01

    Full Text Available Os autores estudaram o comportamento "in vitro" do Trypanosoma encontrado nas rãs brasileiras, visando critérios adicionais na caracterização específica deste grupo. Utilizaram diferentes meios de cultura (NNN, Novy e Mac Neal, SNB 9 de Diamond 1954, Boné & Steinert, 1956 Boné & Parent 1963 e Halevy & Gisry 1964 no isolamento do Trypanosoma rotatorium encontrado com certa freqüência na rã Leptodactylus com larga distribuição na região Neotropical. Observamso que o comportamento do T. rotatorium das rãs desta região em meios de cultura mostra características bem diferentes daquelas observadas com tripanosomas de outras regiões, quer seja pela dificuldade de manutenção em subcultura, quer pelas formas de divisão desenvolvidas. Empregamos os mesmos meios de cultura utilizados nos isolamentos dos tripanosomas de rã da Europa e como pode ser visto no Quadro I os resultados obtidos com material da região Neotropical são concordantes, surgerindo, pelo menos uma variação dentro da espécie.Different culture media were employed to isolate T. rotatorium, a common parasite in the blood of brazilian frog Leptodactylus ocellatus. Although we have isolated the parasite in three different media (SNB-9, Boné Parent and Boné Steinert media, subcultures were not obtained. Theses facts confirm the results also pointed out by Machado 1911 with T. rotatorium from hosts collected in the same region. In accordance with the factes observed in the litterature (see table I in this work our results suggest an important difference between the T. rotatorium of neotropical region and that of the other regions, which are easily cultivated in subcultures. The culture forms present some differential aspects in T. rotatorium mainly by production of "Somatelas".

  3. Ab initio structure determination and refinement of a scorpion protein toxin.

    Science.gov (United States)

    Smith, G D; Blessing, R H; Ealick, S E; Fontecilla-Camps, J C; Hauptman, H A; Housset, D; Langs, D A; Miller, R

    1997-09-01

    The structure of toxin II from the scorpion Androctonus australis Hector has been determined ab initio by direct methods using SnB at 0.96 A resolution. For the purpose of this structure redetermination, undertaken as a test of the minimal function and the SnB program, the identity and sequence of the protein was withheld from part of the research team. A single solution obtained from 1 619 random atom trials was clearly revealed by the bimodal distribution of the final value of the minimal function associated with each individual trial. Five peptide fragments were identified from a conservative analysis of the initial E-map, and following several refinement cycles with X-PLOR, a model was built of the complete structure. At the end of the X-PLOR refinement, the sequence was compared with the published sequence and 57 of the 64 residues had been correctly identified. Two errors in sequence resulted from side chains with similar size while the rest of the errors were a result of severe disorder or high thermal motion in the side chains. Given the amino-acid sequence, it is estimated that the initial E-map could have produced a model containing 99% of all main-chain and 81% of side-chain atoms. The structure refinement was completed with PROFFT, including the contributions of protein H atoms, and converged at a residual of 0.158 for 30 609 data with F >or= 2sigma(F) in the resolution range 8.0-0.964 A. The final model consisted of 518 non-H protein atoms (36 disordered), 407 H atoms, and 129 water molecules (43 with occupancies less than unity). This total of 647 non-H atoms represents the largest light-atom structure solved to date.

  4. The low-lying quartet electronic states of group 14 diatomic borides XB (X = C, Si, Ge, Sn, Pb)

    Science.gov (United States)

    Pontes, Marcelo A. P.; de Oliveira, Marcos H.; Fernandes, Gabriel F. S.; Da Motta Neto, Joaquim D.; Ferrão, Luiz F. A.; Machado, Francisco B. C.

    2018-04-01

    The present work focuses in the characterization of the low-lying quartet electronic and spin-orbit states of diatomic borides XB, in which X is an element of group 14 (C, Si, Ge, Sn, PB). The wavefunction was obtained at the CASSCF/MRCI level with a quintuple-ζ quality basis set. Scalar relativistic effects were also taken into account. A systematic and comparative analysis of the spectroscopic properties for the title molecular series was carried out, showing that the (1)4Π→X4Σ- transition band is expected to be measurable by emission spectroscopy to the GeB, SnB and PbB molecules, as already observed for the lighter CB and SiB species.

  5. Complete rat spinal cord transection as a faithful model of spinal cord injury for translational cell transplantation

    Czech Academy of Sciences Publication Activity Database

    Lukovic, D.; Moreno-Manzano, V.; Lopez-Mocholi, E.; Rodriguez-Jiménez, F.J.; Jendelová, Pavla; Syková, Eva; Erceg, Slaven; Oria, M.; Stojkovic, M.

    2015-01-01

    Roč. 5, APR 10 (2015), s. 9640 ISSN 2045-2322 R&D Projects: GA MŠk(CZ) LO1309; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:68378041 Keywords : bryonic steemm-cells * motor evoked-potentials * promotes functional recovery * locomotor recovery * bone-marrow * motoneuron progenitors * regeneration * tissue * oligodendrocyte * scaffold Subject RIV: FH - Neurology Impact factor: 5.228, year: 2015

  6. Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2 regulates axon integrity in the mouse embryo.

    Directory of Open Access Journals (Sweden)

    Amy N Hicks

    Full Text Available Using transposon-mediated gene-trap mutagenesis, we have generated a novel mouse mutant termed Blad (Bloated Bladder. Homozygous mutant mice die perinatally showing a greatly distended bladder, underdeveloped diaphragm and a reduction in total skeletal muscle mass. Wild type and heterozygote mice appear normal. Using PCR, we identified a transposon insertion site in the first intron of Nmnat2 (Nicotinamide mononucleotide adenyltransferase 2. Nmnat2 is expressed predominantly in the brain and nervous system and has been linked to the survival of axons. Expression of this gene is undetectable in Nmnat2(blad/blad mutants. Examination of the brains of E18.5 Nmnat2(blad/blad mutant embryos did not reveal any obvious morphological changes. In contrast, E18.5 Nmnat2(blad/blad homozygotes showed an approximate 60% reduction of spinal motoneurons in the lumbar region and a more than 80% reduction in the sensory neurons of the dorsal root ganglion (DRG. In addition, facial motoneuron numbers were severely reduced, and there was virtually a complete absence of axons in the hind limb. Our observations suggest that during embryogenesis, Nmnat2 plays an important role in axonal growth or maintenance. It appears that in the absence of Nmnat2, major target organs and tissues (e.g., muscle are not functionally innervated resulting in perinatal lethality. In addition, neither Nmnat1 nor 3 can compensate for the loss of Nmnat2. Whilst there have been recent suggestions that Nmnat2 may be an endogenous modulator of axon integrity, this work represents the first in vivo study demonstrating that Nmnat2 is involved in axon development or survival in a mammal.

  7. Effects of thoracic dorsal rhizotomy or vagotomy on inspiratory muscle activity at various levels of chemical drive.

    Science.gov (United States)

    D'Angelo, E; Schieppati, M

    1982-11-01

    The relationship between relative peak activity (moving average EMG) of the diaphragm (Adi) and of the cranial (2nd and 3rd) external intercostal or parasternal muscles (Aic) was assessed during rebreathing in animals before and after bilateral thoracic (T1-T4) dorsal rhizotomy (TDR) and/or bilateral vagotomy (VGT). The relationship had the form Aic=a Adib under all conditions. In intact rabbits and cats mean values for b were 1.48 and 1.79, respectively, a being unity by definition. Neither TDR nor VGT changed b; a decreased to about 0.15 with TDR and halved with VGT only if performed before TDR. Selective reflex facilitation of inspiratory intercostals with occlusions at FRC was observed after VGT and was abolished by TDR. Neither VGT nor TDR affected Adi time course. Hence: (1) central command to alpha-motoneurones of the major inspiratory muscles differs; (2) proprioceptive feedback markedly increases external intercostal activity, apparently by multiplying Aic due to central command to alpha-motoneurones by a factor independent of chemical drive; (3) vagally mediated augmentation of Aic depends entirely on intact proprioceptive feedback. The possible role of fusimotor drive is discussed.

  8. Effect of a muscle relaxant, chlorphenesin carbamate, on the spinal neurons of rats.

    Science.gov (United States)

    Kurachi, M; Aihara, H

    1984-09-01

    The effects of chlorphenesin carbamate (CPC) and mephenesin on spinal neurons were investigated in spinal rats. CPC (50 mg/kg i.v.) inhibited the mono-(MSR) and poly-synaptic reflex (PSR), the latter being more susceptible than the former to CPC depression. Mephenesin also inhibited MSR and PSR, though the effects were short in duration. CPC had no effect on the dorsal root potential evoked by the stimulation of the dorsal root, while mephenesin reduced the dorsal root-dorsal root reflex. The excitability of motoneuron was reduced by the administration of CPC or mephenesin. The excitability of primary afferent terminal was unchanged by CPC, while it was inhibited by mephenesin. Neither CPC nor mephenesin influenced the field potential evoked by the dorsal root stimulation. Both CPC and mephenesin had no effect on the synaptic recovery. These results suggest that both CPC and mephenesin inhibit the firing of motoneurons by stabilizing the neuronal membrane, while mephenesin additionally suppresses the dorsal root reflex and the excitability of the primary afferent terminal. These inhibitory actions of CPC on spinal activities may contribute, at least partly, to its muscle relaxing action.

  9. Reduction of common motoneuronal drive on the affected side during walking in hemiplegic stroke patients

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo; Brittain, John-Stuart; Halliday, David M.

    2008-01-01

    walking in eight subjects with unilateral stroke. RESULTS: On the unaffected side, short-term synchronization was evident from the presence of a narrow central peak in cumulant densities and from the presence of significant coherence between these signals in the 10-25 Hz band. Such indicators of short...... on the affected side in hemiplegic patients during walking. SIGNIFICANCE: This is of importance for understanding the mechanisms responsible for reduced gait ability and development of new strategies for gait restoration....

  10. Bioelectrical activity of limb muscles during cold shivering of stimulation of the vestibular apparatus

    Science.gov (United States)

    Kuzmina, G. I.

    1980-01-01

    The effects of caloric and electric stimulation of the vestibular receptors on the EMG activity of limb muslces in anesthetized cats during cold induced shivering involved flexor muscles alone. Both types of stimulation suppressed bioelectrical activity more effectively in the ipsilateral muscles. The suppression of shivering activity seems to be due to the increased inhibitory effect of descending labyrinth pathways on the function of flexor motoneurons.

  11. Cerebral correlates of psychotic syndromes in neurodegenerative diseases

    OpenAIRE

    Jellinger, Kurt A

    2012-01-01

    Abstract Psychosis has been recognized as a common feature in neurodegenerative diseases and a core feature of dementia that worsens most clinical courses. It includes hallucinations, delusions including paranoia, aggressive behaviour, apathy and other psychotic phenomena that occur in a wide range of degenerative disorders including Alzheimer?s disease, synucleinopathies (Parkinson?s disease, dementia with Lewy bodies), Huntington?s disease, frontotemporal degenerations, motoneuron and prion...

  12. Human neural stem cell replacement therapy for amyotrophic lateral sclerosis by spinal transplantation.

    Directory of Open Access Journals (Sweden)

    Michael P Hefferan

    Full Text Available Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1 causes an inherited form of Amyotrophic Lateral Sclerosis (ALS. Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs into the lumbar spinal cord of SOD1(G93A rats leads to a moderate therapeutical effect as evidenced by local α-motoneuron sparing and extension of lifespan. The aim of the present study was to analyze the degree of therapeutical effect of hNSCs once grafted into the lumbar spinal ventral horn in presymptomatic immunosuppressed SOD1(G93A rats and to assess the presence and functional integrity of the descending motor system in symptomatic SOD1(G93A animals.Presymptomatic SOD1(G93A rats (60-65 days old received spinal lumbar injections of hNSCs. After cell grafting, disease onset, disease progression and lifespan were analyzed. In separate symptomatic SOD1(G93A rats, the presence and functional conductivity of descending motor tracts (corticospinal and rubrospinal was analyzed by spinal surface recording electrodes after electrical stimulation of the motor cortex. Silver impregnation of lumbar spinal cord sections and descending motor axon counting in plastic spinal cord sections were used to validate morphologically the integrity of descending motor tracts. Grafting of hNSCs into the lumbar spinal cord of SOD1(G93A rats protected α-motoneurons in the vicinity of grafted cells, provided transient functional improvement, but offered no protection to α-motoneuron pools distant from grafted lumbar segments. Analysis of motor-evoked potentials recorded from the thoracic spinal cord of symptomatic SOD1(G93A rats showed a near complete loss of descending motor tract conduction, corresponding to a significant (50-65% loss of large caliber descending motor axons.These data demonstrate that in order to achieve a more

  13. Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects

    Science.gov (United States)

    Koh, J.; Brown, T. E.; Beightol, L. A.; Ha, C. Y.; Eckberg, D. L.

    1994-01-01

    1. We studied eight young men (age range: 20-37 years) with chronic, clinically complete high cervical spinal cord injuries and ten age-matched healthy men to determine how interruption of connections between the central nervous system and spinal sympathetic motoneurones affects autonomic cardiovascular control. 2. Baseline diastolic pressures and R-R intervals (heart periods) were similar in the two groups. Slopes of R-R interval responses to brief neck pressure changes were significantly lower in tetraplegic than in healthy subjects, but slopes of R-R interval responses to steady-state arterial pressure reductions and increases were comparable. Plasma noradrenaline levels did not change significantly during steady-state arterial pressure reductions in tetraplegic patients, but rose sharply in healthy subjects. The range of arterial pressure and R-R interval responses to vasoactive drugs (nitroprusside and phenylephrine) was significantly greater in tetraplegic than healthy subjects. 3. Resting R-R interval spectral power at respiratory and low frequencies was similar in the two groups. During infusions of vasoactive drugs, low-frequency R-R interval spectral power was directly proportional to arterial pressure in tetraplegic patients, but was unrelated to arterial pressure in healthy subjects. Vagolytic doses of atropine nearly abolished both low- and respiratory-frequency R-R interval spectral power in both groups. 4. Our conclusions are as follows. First, since tetraplegic patients have significant levels of low-frequency arterial pressure and R-R interval spectral power, human Mayer arterial pressure waves may result from mechanisms that do not involve stimulation of spinal sympathetic motoneurones by brainstem neurones. Second, since in tetraplegic patients, low-frequency R-R interval spectral power is proportional to arterial pressure, it is likely to be mediated by a baroreflex mechanism. Third, since low-frequency R-R interval rhythms were nearly abolished

  14. Vascular endothelial growth factor gene therapy improves nerve regeneration in a model of obstetric brachial plexus palsy.

    Science.gov (United States)

    Hillenbrand, Matthias; Holzbach, Thomas; Matiasek, Kaspar; Schlegel, Jürgen; Giunta, Riccardo E

    2015-03-01

    The treatment of obstetric brachial plexus palsy has been limited to conservative therapies and surgical reconstruction of peripheral nerves. In addition to the damage of the brachial plexus itself, it also leads to a loss of the corresponding motoneurons in the spinal cord, which raises the need for supportive strategies that take the participation of the central nervous system into account. Based on the protective and regenerative effects of VEGF on neural tissue, our aim was to analyse the effect on nerve regeneration by adenoviral gene transfer of vascular endothelial growth factor (VEGF) in postpartum nerve injury of the brachial plexus in rats. In the present study, we induced a selective crush injury to the left spinal roots C5 and C6 in 18 rats within 24 hours after birth and examined the effect of VEGF-gene therapy on nerve regeneration. For gene transduction an adenoviral vector encoding for VEGF165 (AdCMV.VEGF165) was used. In a period of 11 weeks, starting 3 weeks post-operatively, functional regeneration was assessed weekly by behavioural analysis and force measurement of the upper limb. Morphometric evaluation was carried out 8 months post-operatively and consisted of a histological examination of the deltoid muscle and the brachial plexus according to defined criteria of degeneration. In addition, atrophy of the deltoid muscle was evaluated by weight determination comparing the left with the right side. VEGF expression in the brachial plexus was quantified by an enzyme-linked immunosorbent assay (ELISA). Furthermore the motoneurons of the spinal cord segment C5 were counted comparing the left with the right side. On the functional level, VEGF-treated animals showed faster nerve regeneration. It was found less degeneration and smaller mass reduction of the deltoid muscle in VEGF-treated animals. We observed significantly less degeneration of the brachial plexus and a greater number of surviving motoneurons (P reason for these effects. The clinical use

  15. Targeted retrograde transfection of adenovirus vector carrying brain-derived neurotrophic factor gene prevents loss of mouse (twy/twy) anterior horn neurons in vivo sustaining mechanical compression.

    Science.gov (United States)

    Xu, Kan; Uchida, Kenzo; Nakajima, Hideaki; Kobayashi, Shigeru; Baba, Hisatoshi

    2006-08-01

    Immunohistochemical analysis after adenovirus (AdV)-mediated BDNF gene transfer in and around the area of mechanical compression in the cervical spinal cord of the hyperostotic mouse (twy/twy). To investigate the neuroprotective effect of targeted AdV-BDNF gene transfection in the twy mouse with spontaneous chronic compression of the spinal cord motoneurons. Several studies reported the neuroprotective effects of neurotrophins on injured spinal cord. However, no report has described the effect of targeted retrograde neurotrophic gene delivery on motoneuron survival in chronic compression lesions of the cervical spinal cord resembling lesions of myelopathy. LacZ marker gene using adenoviral vector (AdV-LacZ) was used to evaluate retrograde delivery from the sternomastoid muscle in adult twy mice (16-week-old) and (control). Four weeks after the AdV-LacZ or AdV-BDNF injection, the compressed cervical spinal cord was removed en bloc for immunohistologic investigation of b-galactosidase activity and immunoreactivity and immunoblot analyses of BDNF. The number of anterior horn neurons was counted using Nissl, ChAT and AChE staining. Spinal accessory motoneurons between C1 and C3 segments were successfully transfected by AdV-LacZ in both twy and ICR mice after targeted intramuscular injection. Immunoreactivity to BDNF was significantly stronger in AdV-BDNF-gene transfected twy mice than in AdV-LacZ-gene transfected mice. At the cord level showing the maximum compression in AdV-BDNF-transfected twy mice, the number of anterior horn neurons was sinificantly higher in the topographic neuronal cell counting of Nissl-, ChAT-, and AChE-stained samples than in AdV-LacZ-injected twy mice. Targeted AdV-BDNF-gene delivery significantly increased Nissl-stained anterior horn neurons and enhanced cholinergic enzyme activities in the twy. Our results suggest that targeted retrograde AdV-BDNF-gene in vivo delivery may enhance neuronal survival even under chronic mechanical compression.

  16. Shal/K(v4 channels are required for maintaining excitability during repetitive firing and normal locomotion in Drosophila.

    Directory of Open Access Journals (Sweden)

    Yong Ping

    2011-01-01

    Full Text Available Rhythmic behaviors, such as walking and breathing, involve the coordinated activity of central pattern generators in the CNS, sensory feedback from the PNS, to motoneuron output to muscles. Unraveling the intrinsic electrical properties of these cellular components is essential to understanding this coordinated activity. Here, we examine the significance of the transient A-type K(+ current (I(A, encoded by the highly conserved Shal/K(v4 gene, in neuronal firing patterns and repetitive behaviors. While I(A is present in nearly all neurons across species, elimination of I(A has been complicated in mammals because of multiple genes underlying I(A, and/or electrical remodeling that occurs in response to affecting one gene.In Drosophila, the single Shal/K(v4 gene encodes the predominant I(A current in many neuronal cell bodies. Using a transgenically expressed dominant-negative subunit (DNK(v4, we show that I(A is completely eliminated from cell bodies, with no effect on other currents. Most notably, DNK(v4 neurons display multiple defects during prolonged stimuli. DNK(v4 neurons display shortened latency to firing, a lower threshold for repetitive firing, and a progressive decrement in AP amplitude to an adapted state. We record from identified motoneurons and show that Shal/K(v4 channels are similarly required for maintaining excitability during repetitive firing. We then examine larval crawling, and adult climbing and grooming, all behaviors that rely on repetitive firing. We show that all are defective in the absence of Shal/K(v4 function. Further, knock-out of Shal/K(v4 function specifically in motoneurons significantly affects the locomotion behaviors tested.Based on our results, Shal/K(v4 channels regulate the initiation of firing, enable neurons to continuously fire throughout a prolonged stimulus, and also influence firing frequency. This study shows that Shal/K(v4 channels play a key role in repetitively firing neurons during prolonged

  17. Gap junctions and inhibitory synapses modulate inspiratory motoneuron synchronization.

    Science.gov (United States)

    Bou-Flores, C; Berger, A J

    2001-04-01

    Interneuronal electrical coupling via gap junctions and chemical synaptic inhibitory transmission are known to have roles in the generation and synchronization of activity in neuronal networks. Uncertainty exists regarding the roles of these two modes of interneuronal communication in the central respiratory rhythm-generating system. To assess their roles, we performed studies on both the neonatal mouse medullary slice and en bloc brain stem-spinal cord preparations where rhythmic inspiratory motor activity can readily be recorded from both hypoglossal and phrenic nerve roots. The rhythmic inspiratory activity observed had two temporal characteristics: the basic respiratory frequency occurring on a long time scale and the synchronous neuronal discharge within the inspiratory burst occurring on a short time scale. In both preparations, we observed that bath application of gap-junction blockers, including 18 alpha-glycyrrhetinic acid, 18 beta-glycyrrhetinic acid, and carbenoxolone, all caused a reduction in respiratory frequency. In contrast, peak integrated phrenic and hypoglossal inspiratory activity was not significantly changed by gap-junction blockade. On a short-time-scale, gap-junction blockade increased the degree of synchronization within an inspiratory burst observed in both nerves. In contrast, opposite results were observed with blockade of GABA(A) and glycine receptors. We found that respiratory frequency increased with receptor blockade, and simultaneous blockade of both receptors consistently resulted in a reduction in short-time-scale synchronized activity observed in phrenic and hypoglossal inspiratory bursts. These results support the concept that the central respiratory system has two components: a rhythm generator responsible for the production of respiratory cycle timing and an inspiratory pattern generator that is involved in short-time-scale synchronization. In the neonatal rodent, properties of both components can be regulated by interneuronal communication via gap junctions and inhibitory synaptic transmission.

  18. Intense synaptic activity enhances temporal resolution in spinal motoneurons

    DEFF Research Database (Denmark)

    Berg, Rune W; Ditlevsen, Susanne; Hounsgaard, Jørn Dybkjær

    2008-01-01

    In neurons, spike timing is determined by integration of synaptic potentials in delicate concert with intrinsic properties. Although the integration time is functionally crucial, it remains elusive during network activity. While mechanisms of rapid processing are well documented in sensory systems...... of their occurrence and detected for less than 10 ms after their occurrence. Being shorter than the average inter-spike interval, the AHP has little effect on integration time and spike timing, which instead is entirely determined by fluctuations in membrane potential caused by the barrage of inhibitory...

  19. Monte Carlo Transport for Electron Thermal Transport

    Science.gov (United States)

    Chenhall, Jeffrey; Cao, Duc; Moses, Gregory

    2015-11-01

    The iSNB (implicit Schurtz Nicolai Busquet multigroup electron thermal transport method of Cao et al. is adapted into a Monte Carlo transport method in order to better model the effects of non-local behavior. The end goal is a hybrid transport-diffusion method that combines Monte Carlo Transport with a discrete diffusion Monte Carlo (DDMC). The hybrid method will combine the efficiency of a diffusion method in short mean free path regions with the accuracy of a transport method in long mean free path regions. The Monte Carlo nature of the approach allows the algorithm to be massively parallelized. Work to date on the method will be presented. This work was supported by Sandia National Laboratory - Albuquerque and the University of Rochester Laboratory for Laser Energetics.

  20. Mechanism of Action of Presynaptic Neurotoxins

    Science.gov (United States)

    1985-09-01

    lGTb 1Db. gnlisde RE-105 cells and their structures were verified by partial hydrolysis studies performed by the principal Investigator in...internalized 12sI-tetanus toxin migrates with authentic toxin on SDS gels ( Staub et al., 1985). This is consistent with recent reports that tetanus...for a Transsynaptic Migration of Tetanus Toxin in Spinal Cord Motoneurons: An Autoradiographic and Morphometric Study. Brain Res. 105, 213-227. Simpson

  1. Substance P immunoreactivity in the lumbar spinal cord of the turtle Trachemys dorbigni following peripheral nerve injury

    OpenAIRE

    Partata, Wania Aparecida; Krepsky, Ana Maria Rocha; Xavier, Leder Leal; Marques, Maria; Achaval-Elena, Matilde

    2003-01-01

    Immunoreactive substance P was investigated in turtle lumbar spinal cord after sciatic nerve transection. In control animals immunoreactive fibers were densest in synaptic field Ia, where the longest axons invaded synaptic field III. Positive neuronal bodies were identified in the lateral column of the dorsal horn and substance P immunoreactive varicosities were observed in the ventral horn, in close relationship with presumed motoneurons. Other varicosities appeared in the lateral and anteri...

  2. From Neurons to Newtons

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2001-01-01

    proteins generate forces, to the macroscopic levels where overt arm movements are vol- untarily controlled within an unpredictable environment by legions of neurons¯ring in orderly fashion. An extensive computer simulation system has been developed for this thesis, which at present contains a neural...... network scripting language for specifying arbitrary neural architectures, de¯nition ¯les for detailed spinal networks, various biologically realistic models of neurons, and dynamic synapses. Also included are structurally accurate models of intrafusal and extra-fusal muscle ¯bers and a general body...... that an explicit function may be derived which expresses the force that the spindle contractile elements must produce to exactly counter spindle unloading during muscle shortening. This information was used to calculate the corresponding "optimal" °-motoneuronal activity level. For some simple arm movement tasks...

  3. Large-scale synchronized activity in the embryonic brainstem and spinal cord

    Directory of Open Access Journals (Sweden)

    Yoko eMomose-Sato

    2013-04-01

    Full Text Available In the developing central nervous system, spontaneous activity appears well before the brain responds to external sensory inputs. One of the earliest activities is observed in the hindbrain and spinal cord, which is detected as rhythmic electrical discharges of cranial and spinal motoneurons or oscillations of Ca2+- and voltage-related optical signals. Shortly after the initial expression, the spontaneous activity appearing in the hindbrain and spinal cord exhibits a large-scale correlated wave that propagates over a wide region of the central nervous system, maximally extending to the lumbosacral cord and to the forebrain. In this review, we describe several aspects of this synchronized activity by focusing on the basic properties, development, origin, propagation pattern, pharmacological characteristics, and possible mechanisms underlying the generation of the activity. These profiles differ from those of the respiratory and locomotion pattern generators observed in the mature brainstem and spinal cord, suggesting that the wave is primordial activity that appears during a specific period of embryonic development and plays some important roles in the development of the central nervous system.

  4. Drosophila Syd-1, liprin-α, and protein phosphatase 2A B' subunit Wrd function in a linear pathway to prevent ectopic accumulation of synaptic materials in distal axons.

    Science.gov (United States)

    Li, Long; Tian, Xiaolin; Zhu, Mingwei; Bulgari, Dinara; Böhme, Mathias A; Goettfert, Fabian; Wichmann, Carolin; Sigrist, Stephan J; Levitan, Edwin S; Wu, Chunlai

    2014-06-18

    During synaptic development, presynaptic differentiation occurs as an intrinsic property of axons to form specialized areas of plasma membrane [active zones (AZs)] that regulate exocytosis and endocytosis of synaptic vesicles. Genetic and biochemical studies in vertebrate and invertebrate model systems have identified a number of proteins involved in AZ assembly. However, elucidating the molecular events of AZ assembly in a spatiotemporal manner remains a challenge. Syd-1 (synapse defective-1) and Liprin-α have been identified as two master organizers of AZ assembly. Genetic and imaging analyses in invertebrates show that Syd-1 works upstream of Liprin-α in synaptic assembly through undefined mechanisms. To understand molecular pathways downstream of Liprin-α, we performed a proteomic screen of Liprin-α-interacting proteins in Drosophila brains. We identify Drosophila protein phosphatase 2A (PP2A) regulatory subunit B' [Wrd (Well Rounded)] as a Liprin-α-interacting protein, and we demonstrate that it mediates the interaction of Liprin-α with PP2A holoenzyme and the Liprin-α-dependent synaptic localization of PP2A. Interestingly, loss of function in syd-1, liprin-α, or wrd shares a common defect in which a portion of synaptic vesicles, dense-core vesicles, and presynaptic cytomatrix proteins ectopically accumulate at the distal, but not proximal, region of motoneuron axons. Strong genetic data show that a linear syd-1/liprin-α/wrd pathway in the motoneuron antagonizes glycogen synthase kinase-3β kinase activity to prevent the ectopic accumulation of synaptic materials. Furthermore, we provide data suggesting that the syd-1/liprin-α/wrd pathway stabilizes AZ specification at the nerve terminal and that such a novel function is independent of the roles of syd-1/liprin-α in regulating the morphology of the T-bar structural protein BRP (Bruchpilot). Copyright © 2014 the authors 0270-6474/14/348474-14$15.00/0.

  5. Drosophila Syd-1, Liprin-α, and Protein Phosphatase 2A B′ Subunit Wrd Function in a Linear Pathway to Prevent Ectopic Accumulation of Synaptic Materials in Distal Axons

    Science.gov (United States)

    Li, Long; Tian, Xiaolin; Zhu, Mingwei; Bulgari, Dinara; Böhme, Mathias A.; Goettfert, Fabian; Wichmann, Carolin; Sigrist, Stephan J.; Levitan, Edwin S.

    2014-01-01

    During synaptic development, presynaptic differentiation occurs as an intrinsic property of axons to form specialized areas of plasma membrane [active zones (AZs)] that regulate exocytosis and endocytosis of synaptic vesicles. Genetic and biochemical studies in vertebrate and invertebrate model systems have identified a number of proteins involved in AZ assembly. However, elucidating the molecular events of AZ assembly in a spatiotemporal manner remains a challenge. Syd-1 (synapse defective-1) and Liprin-α have been identified as two master organizers of AZ assembly. Genetic and imaging analyses in invertebrates show that Syd-1 works upstream of Liprin-α in synaptic assembly through undefined mechanisms. To understand molecular pathways downstream of Liprin-α, we performed a proteomic screen of Liprin-α-interacting proteins in Drosophila brains. We identify Drosophila protein phosphatase 2A (PP2A) regulatory subunit B′ [Wrd (Well Rounded)] as a Liprin-α-interacting protein, and we demonstrate that it mediates the interaction of Liprin-α with PP2A holoenzyme and the Liprin-α-dependent synaptic localization of PP2A. Interestingly, loss of function in syd-1, liprin-α, or wrd shares a common defect in which a portion of synaptic vesicles, dense-core vesicles, and presynaptic cytomatrix proteins ectopically accumulate at the distal, but not proximal, region of motoneuron axons. Strong genetic data show that a linear syd-1/liprin-α/wrd pathway in the motoneuron antagonizes glycogen synthase kinase-3β kinase activity to prevent the ectopic accumulation of synaptic materials. Furthermore, we provide data suggesting that the syd-1/liprin-α/wrd pathway stabilizes AZ specification at the nerve terminal and that such a novel function is independent of the roles of syd-1/liprin-α in regulating the morphology of the T-bar structural protein BRP (Bruchpilot). PMID:24948803

  6. Altered Neuromodulatory Drive May Contribute to Exaggerated Tonic Vibration Reflexes in Chronic Hemiparetic Stroke

    Directory of Open Access Journals (Sweden)

    Jacob G. McPherson

    2018-04-01

    Full Text Available Exaggerated stretch-sensitive reflexes are a common finding in elbow flexors of the contralesional arm in chronic hemiparetic stroke, particularly when muscles are not voluntarily activated prior to stretch. Previous investigations have suggested that this exaggeration could arise either from an abnormal tonic ionotropic drive to motoneuron pools innervating the paretic limbs, which could bring additional motor units near firing threshold, or from an increased influence of descending monoaminergic neuromodulatory pathways, which could depolarize motoneurons and amplify their responses to synaptic inputs. However, previous investigations have been unable to differentiate between these explanations, leaving the source(s of this excitability increase unclear. Here, we used tonic vibration reflexes (TVRs during voluntary muscle contractions of increasing magnitude to infer the sources of spinal motor excitability in individuals with chronic hemiparetic stroke. We show that when the paretic and non-paretic elbow flexors are preactivated to the same percentage of maximum prior to vibration, TVRs remain significantly elevated in the paretic arm. We also show that the rate of vibration-induced torque development increases as a function of increasing preactivation in the paretic limb, even though the amplitude of vibration-induced torque remains conspicuously unchanged as preactivation increases. It is highly unlikely that these findings could be explained by a source that is either purely ionotropic or purely neuromodulatory, because matching preactivation should control for the effects of a potential ionotropic drive (and lead to comparable tonic vibration reflex responses between limbs, while a purely monoaminergic mechanism would increase reflex magnitude as a function of preactivation. Thus, our results suggest that increased excitability of motor pools innervating the paretic limb post-stroke is likely to arise from both ionotropic and

  7. Changes in contractile properties and action potentials of motor units in the rat medial gastrocnemius muscle during maturation.

    Science.gov (United States)

    Dobrzynska, Z; Celichowski, J

    2016-02-01

    The early phase of development of muscles stops following the disappearance of embryonic and neonatal myosin and the elimination of polyneuronal innervation of muscle fibres with the formation of motor units (MUs), but later the muscle mass still considerably increases. It is unknown whether the three types are visible among newly formed MUs soon after the early postnatal period and whether their proportion is similar to that in adult muscle. Moreover, the processes responsible for MU-force regulation by changes in motoneuronal firing rate as well as properties of motor unit action potentials (MUAPs) during maturation are unknown. Three groups of Wistar rats were investigated - 1 month old, 2 months old and the adult, 9 months old. The basic contractile properties and action potentials of MUs in the medial gastrocnemius (MG) muscle were analysed. The three types of MUs were distinguishable in all age groups, but higher proportion of slow MUs was noticed in young rats (29%, 18% and 11% in 1, 2 and 9 months rats, respectively). The fatigue index for fast fatigable MUs in 1 month old rats was about 2 times higher than in 9 months old rats. The twitch time parameters of fast MUs were shortened during the maturation; for these units, the force-frequency curves in young rats were shifted towards lower frequencies, which suggested that fast motoneurons of young animals generate lower firing rates. Higher twitch-to-tetanus ratios noted for the three MU types in young rats suggested the smaller role of rate coding in force regulation processes, and the higher role of MU recruitment in young rats. No significant differences in MUAP parameters between two groups of young and adult animals were observed. Concluding, the maturation process evokes deeper changes in fast MUs than in slow ones.

  8. Axonal and dendritic localization of mRNAs for glycogen-metabolizing enzymes in cultured rodent neurons.

    Science.gov (United States)

    Pfeiffer-Guglielmi, Brigitte; Dombert, Benjamin; Jablonka, Sibylle; Hausherr, Vanessa; van Thriel, Christoph; Schöbel, Nicole; Jansen, Ralf-Peter

    2014-06-04

    Localization of mRNAs encoding cytoskeletal or signaling proteins to neuronal processes is known to contribute to axon growth, synaptic differentiation and plasticity. In addition, a still increasing spectrum of mRNAs has been demonstrated to be localized under different conditions and developing stages thus reflecting a highly regulated mechanism and a role of mRNA localization in a broad range of cellular processes. Applying fluorescence in-situ-hybridization with specific riboprobes on cultured neurons and nervous tissue sections, we investigated whether the mRNAs for two metabolic enzymes, namely glycogen synthase (GS) and glycogen phosphorylase (GP), the key enzymes of glycogen metabolism, may also be targeted to neuronal processes. If it were so, this might contribute to clarify the so far enigmatic role of neuronal glycogen. We found that the mRNAs for both enzymes are localized to axonal and dendritic processes in cultured lumbar spinal motoneurons, but not in cultured trigeminal neurons. In cultured cortical neurons which do not store glycogen but nevertheless express glycogen synthase, the GS mRNA is also subject to axonal and dendritic localization. In spinal motoneurons and trigeminal neurons in situ, however, the mRNAs could only be demonstrated in the neuronal somata but not in the nerves. We could demonstrate that the mRNAs for major enzymes of neural energy metabolism can be localized to neuronal processes. The heterogeneous pattern of mRNA localization in different culture types and developmental stages stresses that mRNA localization is a versatile mechanism for the fine-tuning of cellular events. Our findings suggest that mRNA localization for enzymes of glycogen metabolism could allow adaptation to spatial and temporal energy demands in neuronal events like growth, repair and synaptic transmission.

  9. Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor

    Directory of Open Access Journals (Sweden)

    Hong-en Qu

    2017-01-01

    Full Text Available Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.

  10. Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor.

    Science.gov (United States)

    Qu, Hong-En; Niu, Chuanxin M; Li, Si; Hao, Man-Zhao; Hu, Zi-Xiang; Xie, Qing; Lan, Ning

    2017-12-01

    Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.

  11. Organic cation transporter 2 (SLC22A2), a low-affinity and high-capacity choline transporter, is preferentially enriched on synaptic vesicles in cholinergic neurons.

    Science.gov (United States)

    Nakata, T; Matsui, T; Kobayashi, K; Kobayashi, Y; Anzai, N

    2013-11-12

    Organic cation transporters (OCTs) are expressed mainly in the kidney and liver. OCTs transport intrinsic organic cations, including monoamine, dopamine, serotonine and choline, across the plasma membrane. Here, we demonstrate that OCT2 (SLC22A2) is expressed in cholinergic neurons, motoneurons in the anterior horn of the spinal cord, and is implicated in acetylcholine (Ach) recycling in presynaptic terminals. Application of rabbit anti-peptide antibody revealed that OCT2 was expressed in the anterior horn of the spinal cord. Double immunostaining of muscle sections with anti-OCT2 and alpha-bungarotoxin (BTX) revealed that OCT2 was localized in the neuromuscular junctions (NMJs). Immunoelectron microscopy revealed that OCT2 was localized both in synaptic vesicles (SVs) in presynaptic terminals around the motoneurons (C-terminals) and in SVs in nerve terminals in NMJs. The similarity in the distribution of OCT2 in cholinergic neurons and that of vesicular acetyl choline transporter (VAchT), and the fact that OCT2 can transport choline suggest that OCT2 could work as a low-affinity and high-capacity choline transporter at presynaptic terminals in cholinergic neurons in a firing-dependent manner. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Termination of supraspinal descending pathways in the spinal cord of the tegu lizard, Tupinambis nigropunctatus.

    Science.gov (United States)

    Cruce, W L

    1975-01-01

    Descending fiber projections to the lizard spinal cord were studied using anterograde axonal degeneration. Following hemisection of the cord at the first spinal segment, degeneration was found in the white and gray matter as far down as the 31st (caudal) segment. Degenerating fibers in the white matter were confined to the ipsilateral side and were found in the medial longitudinal fasiculus and the outer half ot the lateral and ventral funiculi. Degeneration was more intense in the dorsolateral and ventromedial funiculi than in the ventrolateral funiculus. In the gray matter, REXED's criteria were applied to Nissl-stained material to delimit boundaries of ten laminae. Degeneration of suprospinal axons was most intense in the medial part of VII, dorsal and ventral commissures to ramify contralaterally in the medial part of VII, in VII, and in medial IX. No degeneration was present in the lateral part of the spinal gray on the contralateral side. In Golgi-stained material, dendrites of lateral IX cells were seen to extend into lamina VII, the dorsolateral part of VII, and the lateral funiculus. Thus, fibers of the ventromedial supraspinal pathway may make axodendritic contact with motoneurons of lateral IX as well as medial IX, ipsilaterally. In addition, there is a possibility of a crossed connection to contralateral motoneurons.

  13. Spinal cord excitability is not influenced by elevated blood lactate levels.

    Science.gov (United States)

    Coco, Marinella; Alagona, Giovanna; Perciavalle, Valentina; Cicirata, Valentina; Perciavalle, Vincenzo

    2011-01-01

    The aim of the present study was to examine the association of high blood lactate levels, induced with a maximal cycling or with an intravenous infusion, with spinal cord excitability. The study was carried out on 17 male athletes; all the subjects performed a maximal cycling test on a mechanically braked cycloergometer, while 6 of them were submitted to the intravenous infusion of a lactate solution (3 mg/kg in 1 min). Before the exercise or the injection, also at the end as well as 5 and 10 min after the conclusion, venous blood lactate was measured and excitability of the spinal α-motoneurons was evaluated by using the H reflex technique. In both experimental conditions, it has been observed that an exhaustive exercise is associated with a strong increase of blood lactate (but not of blood glucose) and with a significant reduction of spinal excitability. Since a similar augment of blood lactate induced by an intravenous infusion, in subjects not performing any exercise, is not associated with significant changes of spinal excitability, it can be concluded that the increase of blood lactate levels during a maximal exercise is not per se capable of modifying the excitability of spinal α-motoneurons.

  14. Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction.

    Science.gov (United States)

    Liao, Edward H; Gray, Lindsay; Tsurudome, Kazuya; El-Mounzer, Wassim; Elazzouzi, Fatima; Baim, Christopher; Farzin, Sarah; Calderon, Mario R; Kauwe, Grant; Haghighi, A Pejmun

    2018-01-01

    Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end directed microtubule motor protein, as a regulator of sorting of endosomes in Drosophila larval motor neurons. The number of synaptic boutons and the amount of neurotransmitter release at the Khc-73 mutant larval neuromuscular junction (NMJ) are normal, but we find a significant decrease in the number of presynaptic release sites. This defect in Khc-73 mutant larvae can be genetically enhanced by a partial genetic loss of Bone Morphogenic Protein (BMP) signaling or suppressed by activation of BMP signaling in motoneurons. Consistently, activation of BMP signaling that normally enhances the accumulation of phosphorylated form of BMP transcription factor Mad in the nuclei, can be suppressed by genetic removal of Khc-73. Using a number of assays including live imaging in larval motor neurons, we show that loss of Khc-73 curbs the ability of retrograde-bound endosomes to leave the synaptic area and join the retrograde axonal pathway. Our findings identify Khc-73 as a regulator of endosomal traffic at the synapse and modulator of retrograde BMP signaling in motoneurons.

  15. Central representation of sensory inputs from the cardio-renal system in Aplysia depilans.

    Science.gov (United States)

    Rózsa, K S; Salánki, J; Véró, M; Kovacević, N; Konjevic, D

    1980-01-01

    Studying the central representation of sensory inputs originating from the heart in Aplysia depilans, it was found that: 1. Neurons responding to heart stimulation can be found in the abdominal, pedal and pleural ganglia alike. 2. The representation of heart input signals was more abundant in the left hemisphere of the abdominal ganglion and in the left pedal and pleural ganglia. 3. The giant neurons of Aplysia depilans can be compared to the homologous cells of Aplysia californica. Two motoneurons (RBHE, LDHI) and one interneuron (L10) proved to be identical in the two subspecies. 4. Sensory inputs originating from the heart may modify the pattern of both heart regulatory motoneurons and interneurons. 5. Nine giant and 19 small neurons of the abdominal ganglion, 3--3 neurons of the right and left pleural ganglion, 6 neurons of the left pedal ganglion responded to heart stimulation. 6. The bursting patterns of cells R15 and L4 were modified to tonic discharge in response to heart stimulation. 7. The representation of sensory inputs originating from the heart is scattered throughout the CNS of Aplysia depilans and heart regulation is based on a feedback mechanism similar to that found in other gastropod species.

  16. Two novel COLVI long chains in zebrafish that are essential for muscle development.

    Science.gov (United States)

    Ramanoudjame, Laetitia; Rocancourt, Claire; Lainé, Jeanne; Klein, Arnaud; Joassard, Lucette; Gartioux, Corine; Fleury, Marjory; Lyphout, Laura; Kabashi, Edor; Ciura, Sorana; Cousin, Xavier; Allamand, Valérie

    2015-12-01

    Collagen VI (COLVI), a protein ubiquitously expressed in connective tissues, is crucial for structural integrity, cellular adhesion, migration and survival. Six different genes are recognized in mammalians, encoding six COLVI-chains that assemble as two 'short' (α1, α2) and one 'long' chain (theoretically any one of α3-6). In humans, defects in the most widely expressed heterotrimer (α123), due to mutations in the COL6A1-3 genes, cause a heterogeneous group of neuromuscular disorders, collectively termed COLVI-related muscle disorders. Little is known about the function(s) of the recently described α4-6 chains and no mutations have been detected yet. In this study, we characterized two novel COLVI long chains in zebrafish that are most homologous to the mammalian α4 chain; therefore, we named the corresponding genes col6a4a and col6a4b. These orthologues represent ancestors of the mammalian Col6a4-6 genes. By in situ hybridization and RT-qPCR, we unveiled a distinctive expression kinetics for col6a4b, compared with the other col6a genes. Using morpholino antisense oligonucleotides targeting col6a4a, col6a4b and col6a2, we modelled partial and complete COLVI deficiency, respectively. All morphant embryos presented altered muscle structure and impaired motility. While apoptosis was not drastically increased, autophagy induction was defective in all morphants. Furthermore, motoneuron axon growth was abnormal in these morphants. Importantly, some phenotypical differences emerged between col6a4a and col6a4b morphants, suggesting only partial functional redundancy. Overall, our results further confirm the importance of COLVI in zebrafish muscle development and may provide important clues for potential human phenotypes associated with deficiency of the recently described COLVI-chains. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence

    OpenAIRE

    Romeo-Guitart, David; Forés, Joaquim; Herrando-Grabulosa, Mireia; Valls, Raquel; Leiva-Rodríguez, Tatiana; Galea, Elena; González-Pérez, Francisco; Navarro, Xavier; Petegnief, Valerie; Bosch, Assumpció; Coma, Mireia; Mas, José Manuel; Casas, Caty

    2018-01-01

    Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on m...

  18. Conditionally immortalized stem cell lines from human spinal cord retain regional identity and generate functional V2a interneurons and motorneurons

    Czech Academy of Sciences Publication Activity Database

    Cocks, G.; Romanyuk, Nataliya; Amemori, Takashi; Jendelová, Pavla; Forostyak, Oksana; Jeffries, A. R.; Perfect, L.; Thuret, S.; Dayanithi, Govindan; Syková, Eva; Price, J.

    2013-01-01

    Roč. 4, č. 3 (2013), s. 69 ISSN 1757-6512 R&D Projects: GA AV ČR IAA500390902; GA ČR GAP304/11/2373; GA ČR GA13-00939S; GA ČR(CZ) GBP304/12/G069 Institutional research plan: CEZ:AV0Z50390703 Institutional support: RVO:68378041 Keywords : neural stem cells * spinal cord * motoneurons Subject RIV: FH - Neurology Impact factor: 4.634, year: 2013

  19. Neurobiology of Caenorhabditis elegans Locomotion: Where Do We Stand?

    OpenAIRE

    Gjorgjieva, Julijana; Biron, David; Haspel, Gal

    2014-01-01

    Animals use a nervous system for locomotion in some stage of their life cycle. The nematode Caenorhabditis elegans, a major animal model for almost all fields of experimental biology, has long been used for detailed studies of genetic and physiological locomotion mechanisms. Of its 959 somatic cells, 302 are neurons that are identifiable by lineage, location, morphology, and neurochemistry in every adult hermaphrodite. Of those, 75 motoneurons innervate body wall muscles that provide the thru...

  20. Temporal Evolution of “Automatic Gain-Scaling”

    OpenAIRE

    Pruszynski, J. Andrew; Kurtzer, Isaac; Lillicrap, Timothy P.; Scott, Stephen H.

    2009-01-01

    The earliest neural response to a mechanical perturbation, the short-latency stretch response (R1: 20–45 ms), is known to exhibit “automatic gain-scaling” whereby its magnitude is proportional to preperturbation muscle activity. Because gain-scaling likely reflects an intrinsic property of the motoneuron pool (via the size-recruitment principle), counteracting this property poses a fundamental challenge for the nervous system, which must ultimately counter the absolute change in load regardle...

  1. Phrenicotomy alters phrenic long-term facilitation following intermittent hypoxia in anesthetized rats

    OpenAIRE

    Sandhu, M. S.; Lee, K. Z.; Fregosi, R. F.; Fuller, D. D.

    2010-01-01

    Intermittent hypoxia (IH) can induce a persistent increase in neural drive to the respiratory muscles known as long-term facilitation (LTF). LTF of phrenic inspiratory activity is often studied in anesthetized animals after phrenicotomy (PhrX), with subsequent recordings being made from the proximal stump of the phrenic nerve. However, severing afferent and efferent axons in the phrenic nerve has the potential to alter the excitability of phrenic motoneurons, which has been hypothesized to be...

  2. Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H-quino[3,4-b][1,4]benzothiazine Derivatives

    Directory of Open Access Journals (Sweden)

    Andrzej Zięba

    2016-11-01

    Full Text Available A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group in position 10 of the parent (quinobenzothiazine system. Antiproliferative activity of the synthesized compounds was studied using cultured neoplastic cells (MDA-MB-231, SNB-19, and C-32 cell lines. Four selected compounds were investigated in more detail for cytotoxicity and antiproliferative effect. Transcriptional activity of genes regulating cell cycle (TP53, apoptosis (BAX, BCL-2, as well as proliferation (H3 were assessed. Finally, the ability of the selected compounds to bind DNA was checked in the presence of ethidium bromide.

  3. Inflammation Induces TDP-43 Mislocalization and Aggregation.

    Directory of Open Access Journals (Sweden)

    Ana Sofia Correia

    Full Text Available TAR DNA-binding protein 43 (TDP-43 is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Here we report that lipopolysaccharide (LPS-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS. Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF-α increased the cytoplasmic levels of TDP-43. In addition, the chronic intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T transgenic mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal motor neurons and it enhanced the levels of TDP-43 aggregation. These results suggest that inflammation may contribute to development or exacerbation of TDP-43 proteinopathies in neurodegenerative disorders.

  4. [The investigation of control mechanisms of stepping rhythm in human in the air-stepping conditions during passive and voluntary leg movements].

    Science.gov (United States)

    Solopova, I A; Selionon, V A; Grishin, A A

    2010-01-01

    In unloading condition the degree of activation of the central stepping program was investigated during passive leg movements in healthy subjects, as well as the excitability of spinal motoneurons during passive and voluntary stepping movement. Passive stepping movements with characteristics maximally approximated to those during voluntary stepping were accomplished by experimenter. The comparison of the muscle activity bursts during voluntary and imposed movements was made. In addition to that the influence of artificially created loading onto the foot to the leg movement characteristics was analyzed. Spinal motoneuron excitability was estimated by means of evaluation of amplitude modulation of the soleus H-reflex. The changes of H-reflexes under the fixation of knee or hip joints were also studied. In majority of subjects the passive movements were accompanied by bursts of EMG activity of hip muscles (and sometimes of knee muscles), which timing during step cycle was coincided with burst timing of voluntary step cycle. In many cases the bursts of EMG activity during passive movements exceeded activity in homonymous muscles during voluntary stepping. The foot loading imitation exerted essential influence on distal parts of moving extremity during voluntary as well passive movements, that was expressed in the appearance of movements in the ankle joint and accompanied by emergence and increasing of phasic EMG activity of shank muscles. The excitability of motoneurons during passive movements was greater then during voluntary ones. The changes and modulation of H-reflex throughout the step cycle without restriction of joint mobility and during exclusion of hip joint mobility were similar. The knee joint fixation exerted the greater influence. It is supposed that imposed movements activate the same mechanisms of rhythm generation as a supraspinal commands during voluntary movements. In the conditions of passive movements the presynaptic inhibition depend on afferent

  5. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  6. Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies Against Prostate Cancer

    Science.gov (United States)

    2001-07-01

    Rogers, H. Ragde, G. M. Kenny, et al. 1999. Follow-up evaluation of a phase II prostate cancer vaccine trial. Prostate 40: 125-129. 69. Troyer, J. K., M...Slusher, D. Price, and J. T. Coyle. 1993. Abnormal acidic amino acids and N-acetylaspartylglutamate in hereditary canine motoneuron disease. Brain Res...levels were at least 10-fold higher, re- promoter, that of the herpesvirus thymidine kinase flecting the greater basal activity of these promoters in gene

  7. Motoneuron membrane potentials follow a time inhomogeneous jump diffusion process

    DEFF Research Database (Denmark)

    Jahn, Patrick; Berg, Rune W; Hounsgaard, Jørn

    2011-01-01

    models can only be applied over short time windows. However, experimental data show varying time constants, state dependent noise, a graded firing threshold and time-inhomogeneous input. In the present study we build a jump diffusion model that incorporates these features, and introduce a firing...

  8. Phrenic motoneuron discharge patterns following chronic cervical spinal cord injury

    Science.gov (United States)

    Lee, Kun-Ze; Dougherty, Brendan J.; Sandhu, Milapjit S.; Lane, Michael A.; Reier, Paul J.; Fuller, David D.

    2013-01-01

    Cervical spinal cord injury (SCI) dramatically disrupts synaptic inputs and triggers biochemical, as well as morphological, plasticity in relation to the phrenic motor neuron (PhMN) pool. Accordingly, our primary purpose was to determine if chronic SCI induces fundamental changes in the recruitment profile and discharge patterns of PhMNs. Individual PhMN action potentials were recorded from the phrenic nerve ipsilateral to lateral cervical (C2) hemisection injury (C2Hx) in anesthetized adult male rats at 2, 4 or 8 wks post-injury and in uninjured controls. PhMNs were phenotypically classified as early (Early-I) or late inspiratory (Late-I), or silent according to discharge patterns. Following C2Hx, the distribution of PhMNs was dominated by Late-I and silent cells. Late-I burst parameters (e.g., spikes per breath, burst frequency and duration) were initially reduced but returned towards control values by 8 wks post-injury. In addition, a unique PhMN burst pattern emerged after C2Hx in which Early-I cells burst tonically during hypocapnic inspiratory apnea. We also quantified the impact of gradual reductions in end-tidal CO2 partial pressure (PETCO2) on bilateral phrenic nerve activity. Compared to control rats, as PETCO2 declined, the C2Hx animals had greater inspiratory frequencies (breaths*min−1) and more substantial decreases in ipsilateral phrenic burst amplitude. We conclude that the primary physiological impact of C2Hx on ipsilateral PhMN burst patterns is a persistent delay in burst onset, transient reductions in burst frequency, and the emergence of tonic burst patterns. The inspiratory frequency data suggest that plasticity in brainstem networks is likely to play an important role in phrenic motor output after cervical SCI. PMID:23954215

  9. Phrenic motoneuron discharge patterns following chronic cervical spinal cord injury.

    Science.gov (United States)

    Lee, Kun-Ze; Dougherty, Brendan J; Sandhu, Milapjit S; Lane, Michael A; Reier, Paul J; Fuller, David D

    2013-11-01

    Cervical spinal cord injury (SCI) dramatically disrupts synaptic inputs and triggers biochemical, as well as morphological, plasticity in relation to the phrenic motor neuron (PhMN) pool. Accordingly, our primary purpose was to determine if chronic SCI induces fundamental changes in the recruitment profile and discharge patterns of PhMNs. Individual PhMN action potentials were recorded from the phrenic nerve ipsilateral to lateral cervical (C2) hemisection injury (C2Hx) in anesthetized adult male rats at 2, 4 or 8 wks post-injury and in uninjured controls. PhMNs were phenotypically classified as early (Early-I) or late inspiratory (Late-I), or silent according to discharge patterns. Following C2Hx, the distribution of PhMNs was dominated by Late-I and silent cells. Late-I burst parameters (e.g., spikes per breath, burst frequency and duration) were initially reduced but returned towards control values by 8wks post-injury. In addition, a unique PhMN burst pattern emerged after C2Hx in which Early-I cells burst tonically during hypocapnic inspiratory apnea. We also quantified the impact of gradual reductions in end-tidal CO2 partial pressure (PETCO2) on bilateral phrenic nerve activity. Compared to control rats, as PETCO2 declined, the C2Hx animals had greater inspiratory frequencies (breaths∗min(-1)) and more substantial decreases in ipsilateral phrenic burst amplitude. We conclude that the primary physiological impact of C2Hx on ipsilateral PhMN burst patterns is a persistent delay in burst onset, transient reductions in burst frequency, and the emergence of tonic burst patterns. The inspiratory frequency data suggest that plasticity in brainstem networks is likely to play an important role in phrenic motor output after cervical SCI. © 2013.

  10. Evaluation of feedforward and feedback contributions to hand stiffness and variability in multijoint arm control.

    Science.gov (United States)

    He, Xin; Du, Yu-Fan; Lan, Ning

    2013-07-01

    The purpose of this study is to validate a neuromechanical model of the virtual arm (VA) by comparing emerging behaviors of the model to those of experimental observations. Hand stiffness of the VA model was obtained by either theoretical computation or simulated perturbations. Variability in hand position of the VA was generated by adding signal dependent noise (SDN) to the motoneuron pools of muscles. Reflex circuits of Ia, Ib and Renshaw cells were included to regulate the motoneuron pool outputs. Evaluation of hand stiffness and variability was conducted in simulations with and without afferent feedback under different patterns of muscle activations during postural maintenance. The simulated hand stiffness and variability ellipses captured the experimentally observed features in shape, magnitude and orientation. Steady state afferent feedback contributed significantly to the increase in hand stiffness by 35.75±16.99% in area, 18.37±7.80% and 16.15±7.15% in major and minor axes; and to the reduction of hand variability by 49.41±21.19% in area, 36.89±12.78% and 18.87±23.32% in major and minor axes. The VA model reproduced the neuromechanical behaviors that were consistent with experimental data, and it could be a useful tool for study of neural control of posture and movement, as well as for application to rehabilitation.

  11. ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles.

    Science.gov (United States)

    Bonafede, Roberta; Mariotti, Raffaella

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle paralysis determined by the degeneration of motoneurons in the motor cortex brainstem and spinal cord. The ALS pathogenetic mechanisms are still unclear, despite the wealth of studies demonstrating the involvement of several altered signaling pathways, such as mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress and neuroinflammation. To date, the proposed therapeutic strategies are targeted to one or a few of these alterations, resulting in only a minimal effect on disease course and survival of ALS patients. The involvement of different mechanisms in ALS pathogenesis underlines the need for a therapeutic approach targeted to multiple aspects. Mesenchymal stem cells (MSC) can support motoneurons and surrounding cells, reduce inflammation, stimulate tissue regeneration and release growth factors. On this basis, MSC have been proposed as promising candidates to treat ALS. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles (EVs) released by stem cells is raising increasing interest. The present review summarizes the main pathological mechanisms involved in ALS and the related therapeutic approaches proposed to date, focusing on MSC therapy and their preclinical and clinical applications. Moreover, the nature and characteristics of EVs and their role in recapitulating the effect of stem cells are discussed, elucidating how and why these vesicles could provide novel opportunities for ALS treatment.

  12. Neural Spike Train Synchronisation Indices: Definitions, Interpretations and Applications.

    Science.gov (United States)

    Halliday, D M; Rosenberg, J R

    2017-04-24

    A comparison of previously defined spike train syncrhonization indices is undertaken within a stochastic point process framework. The second order cumulant density (covariance density) is shown to be common to all the indices. Simulation studies were used to investigate the sampling variability of a single index based on the second order cumulant. The simulations used a paired motoneurone model and a paired regular spiking cortical neurone model. The sampling variability of spike trains generated under identical conditions from the paired motoneurone model varied from 50% { 160% of the estimated value. On theoretical grounds, and on the basis of simulated data a rate dependence is present in all synchronization indices. The application of coherence and pooled coherence estimates to the issue of synchronization indices is considered. This alternative frequency domain approach allows an arbitrary number of spike train pairs to be evaluated for statistically significant differences, and combined into a single population measure. The pooled coherence framework allows pooled time domain measures to be derived, application of this to the simulated data is illustrated. Data from the cortical neurone model is generated over a wide range of firing rates (1 - 250 spikes/sec). The pooled coherence framework correctly characterizes the sampling variability as not significant over this wide operating range. The broader applicability of this approach to multi electrode array data is briefly discussed.

  13. Reorganization of the human central nervous system.

    Science.gov (United States)

    Schalow, G; Zäch, G A

    2000-10-01

    The key strategies on which the discovery of the functional organization of the central nervous system (CNS) under physiologic and pathophysiologic conditions have been based included (1) our measurements of phase and frequency coordination between the firings of alpha- and gamma-motoneurons and secondary muscle spindle afferents in the human spinal cord, (2) knowledge on CNS reorganization derived upon the improvement of the functions of the lesioned CNS in our patients in the short-term memory and the long-term memory (reorganization), and (3) the dynamic pattern approach for re-learning rhythmic coordinated behavior. The theory of self-organization and pattern formation in nonequilibrium systems is explicitly related to our measurements of the natural firing patterns of sets of identified single neurons in the human spinal premotor network and re-learned coordinated movements following spinal cord and brain lesions. Therapy induced cell proliferation, and maybe, neurogenesis seem to contribute to the host of structural changes during the process of re-learning of the lesioned CNS. So far, coordinated functions like movements could substantially be improved in every of the more than 100 patients with a CNS lesion by applying coordination dynamic therapy. As suggested by the data of our patients on re-learning, the human CNS seems to have a second integrative strategy for learning, re-learning, storing and recalling, which makes an essential contribution of the functional plasticity following a CNS lesion. A method has been developed by us for the simultaneous recording with wire electrodes of extracellular action potentials from single human afferent and efferent nerve fibres of undamaged sacral nerve roots. A classification scheme of the nerve fibres in the human peripheral nervous system (PNS) could be set up in which the individual classes of nerve fibres are characterized by group conduction velocities and group nerve fibre diameters. Natural impulse patterns

  14. Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Feldman, J L

    1997-01-01

    Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro. J. Neurophysiol. 78: 2483-2492, 1997. The nucleus ambiguus contains vagal and glossopharyngeal motoneurons and preganglionic neurons involved in respiration, swallowing, vocalization......-stimulus orthodromic activation, using an electrode placed in the dorsomedial slice near the nucleus tractus solitarius, evoked single excitatory postsynaptic potentials (EPSPs) or short trains of EPSPs (500 ms to 1 s). However, tetanic stimulation (5 pulses, 10 Hz) induced voltage-dependent afterdepolarizations...

  15. Axotomy increases NADPH-diaphorase activity in the dorsal root ganglia and lumbar spinal cord of the turtle Trachemys dorbigni

    OpenAIRE

    Partata,W.A.; Krepsky,A.M.R.; Marques,M.; Achaval,M.

    1999-01-01

    Seven days after transection of the sciatic nerve NADPH-diaphorase activity increased in the small and medium neurons of the dorsal root ganglia of the turtle. However, this increase was observed only in medium neurons for up to 90 days. At this time a bilateral increase of NADPH-diaphorase staining was observed in all areas and neuronal types of the dorsal horn, and in positive motoneurons in the lumbar spinal cord, ipsilateral to the lesion. A similar increase was also demonstrable in spina...

  16. The somatic shunt cable model for neurons.

    OpenAIRE

    Durand, D

    1984-01-01

    The derivation of the equations for an electrical model of nerve cells is presented. The model consists of an equivalent cylinder, a lumped somatic impedance, and a variable shunt at the soma. This shunt was introduced to take into account the fast voltage decays observed following the injections of current pulses in some motoneurons and hippocampal granule cells that could not be explained by existing models. The shunt can be interpreted either by penetration damage with the electrode or by ...

  17. Repetitive activation of the corticospinal pathway by means of rTMS may reduce the efficiency of corticomotoneuronal synapses

    DEFF Research Database (Denmark)

    Taube, Wolfgang; Leukel, Christian; Nielsen, Jens Bo

    2015-01-01

    Low-frequency rTMS applied to the primary motor cortex (M1) may produce depression of motor-evoked potentials (MEPs). This depression is commonly assumed to reflect changes in cortical circuits. However, little is known about rTMS-induced effects on subcortical circuits. Therefore, the present st......-either at M1 and/or the CM synapse. As the early facilitation reflects activation of direct CM projections, the most likely site of action is the synapse of the CM neurons onto spinal motoneurons....

  18. A Facile Synthesis of Deaza-Analogues of the Bisindole Marine Alkaloid Topsentin

    Directory of Open Access Journals (Sweden)

    Gianfranco Favi

    2013-02-01

    Full Text Available A series of substituted ethyl 1-[(tert-butoxycarbonylamino]-2-methyl-5- (1-methyl-1H-indol-3-yl-4-[(1-methyl-1H-indol-3-ylcarbonyl]-1H-pyrrole-3-carboxylates were prepared in excellent yields (82-98% by one-pot reactions between β-dicarbonyl compounds 12a–e and 1,2-diaza-1,3-diene (DD 13. Derivatives 10a,c–e, deazaanalogues of the bis-indole alkaloid topsentin, screened by the National Cancer Institute (Bethesda, MD, USA in the in vitro one dose primary anticancer assay against a panel of about 60 human tumor cell lines, showed no significant activity, with the exception of compound 9e, which showed moderate activity against the HOP-92 cell line of the non small cell lung cancer sub-panel and the SNB-75 cell line of the CNS sub-panel.

  19. DNA fingerprinting of the NCI-60 cell line panel.

    Science.gov (United States)

    Lorenzi, Philip L; Reinhold, William C; Varma, Sudhir; Hutchinson, Amy A; Pommier, Yves; Chanock, Stephen J; Weinstein, John N

    2009-04-01

    The National Cancer Institute's NCI-60 cell line panel, the most extensively characterized set of cells in existence and a public resource, is frequently used as a screening tool for drug discovery. Because many laboratories around the world rely on data from the NCI-60 cells, confirmation of their genetic identities represents an essential step in validating results from them. Given the consequences of cell line contamination or misidentification, quality control measures should routinely include DNA fingerprinting. We have, therefore, used standard DNA microsatellite short tandem repeats to profile the NCI-60, and the resulting DNA fingerprints are provided here as a reference. Consistent with previous reports, the fingerprints suggest that several NCI-60 lines have common origins: the melanoma lines MDA-MB-435, MDA-N, and M14; the central nervous system lines U251 and SNB-19; the ovarian lines OVCAR-8 and OVCAR-8/ADR (also called NCI/ADR); and the prostate lines DU-145, DU-145 (ATCC), and RC0.1. Those lines also show that the ability to connect two fingerprints to the same origin is not affected by stable transfection or by the development of multidrug resistance. As expected, DNA fingerprints were not able to distinguish different tissues-of-origin. The fingerprints serve principally as a barcodes.

  20. In vitro Differentiation of Functional Human Skeletal Myotubes in a Defined System.

    Science.gov (United States)

    Guo, Xiufang; Greene, Keshel; Akanda, Nesar; Smith, Alec; Stancescu, Maria; Lambert, Stephen; Vandenburgh, Herman; Hickman, James

    2014-01-01

    In vitro human skeletal muscle systems are valuable tools for the study of human muscular development, disease and treatment. However, published in vitro human muscle systems have so far only demonstrated limited differentiation capacities. Advanced differentiation features such as cross-striations and contractility have only been observed in co-cultures with motoneurons. Furthermore, it is commonly regarded that cultured human myotubes do not spontaneously contract, and any contraction has been considered to originate from innervation. This study developed a serum-free culture system in which human skeletal myotubes demonstrated advanced differentiation. Characterization by immunocytochemistry, electrophysiology and analysis of contractile function revealed these major features: A) well defined sarcomeric development, as demonstrated by the presence of cross-striations. B) finely developed excitation-contraction coupling apparatus characterized by the close apposition of dihydropyridine receptors on T-tubules and Ryanodine receptors on sarcoplasmic reticulum membranes. C) spontaneous and electrically controlled contractility. This report not only demonstrates an improved level of differentiation of cultured human skeletal myotubes, but also provides the first published evidence that such myotubes are capable of spontaneous contraction. Use of this functional in vitro human skeletal muscle system would advance studies concerning human skeletal muscle development and physiology, as well as muscle-related disease and therapy.