WorldWideScience

Sample records for axonal plasticity elicits

  1. Axonal plasticity elicits long-term changes in oligodendroglia and myelinated fibers

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Nielsen, Helle Hvilsted; Gardi, Jonathan E;

    2010-01-01

    Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newl...

  2. Right Cortical and Axonal Structures Eliciting Ocular Deviation During Electrical Stimulation Mapping in Awake Patients.

    Science.gov (United States)

    Montemurro, Nicola; Herbet, Guillaume; Duffau, Hugues

    2016-07-01

    To investigate the neural network underpinning eye movements, a cortical and subcortical intraoperative mapping using direct electrical stimulation (DES) was achieved in six awake patients during surgery for a right frontal low-grade glioma. We assessed the relationship between the occurrence of ocular deviation during both cortical and axonal DES and the anatomic location for each response. The corresponding stimulation sites were reported on a standard brain template for visual analysis and between-subjects comparisons. Our results showed that DES of the cortical frontal eye field (FEF) elicited horizontal (anterior FEF) or upward (posterior FEF) eye movements in 3 patients, supporting the fact that FEF comprises several distinct functional subregions. In addition, subcortical stimulation of the white matter tracts underneath the FEF evoked conjugate contraversive ocular deviation in 3 other patients. Interestingly, this region seems to be a crossroad between the fronto-striatal tract, the frontal aslant tract, the inferior fronto-occipital fascicle and the superior longitudinal fascicle. No deficits in eye movements were observed following surgery. To our knowledge, this is the first study reporting ocular deviation during axonal electrostimulation mapping of the white matter fibers in awake patients. Therefore, our original data issued from DES give new insights into the cortical and subcortical structures involved in the control of eye movements and their strong relationships with other functional pathways. PMID:27067598

  3. L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain

    OpenAIRE

    Ueno, Yuji; Koike, Masato; Shimada, Yoshiaki; Shimura, Hideki; Hira, Kenichiro; Tanaka, Ryota; Uchiyama, Yasuo; Hattori, Nobutaka; Urabe, Takao

    2014-01-01

    Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar ...

  4. Structural plasticity of GABAergic axons is regulated by network activity and GABAA receptor activation

    Directory of Open Access Journals (Sweden)

    Anne eSchuemann

    2013-06-01

    Full Text Available Coordinated changes at excitatory and inhibitory synapses are essential for normal brain development and function. It is well established that excitatory neurons undergo structural changes, but our knowledge about inhibitory structural plasticity is rather scarce. Here we present a quantitative analysis of the dynamics of GABAergic boutons in the dendritic region of the hippocampal CA1 area using time-lapse two-photon imaging in organotypic hippocampal cultures from GAD65-GFP mice. We show that ~20% of inhibitory boutons are not stable. They are appearing, disappearing and reappearing at specific locations along the inhibitory axon and reflect immature or incomplete synapses. Furthermore, we observed that persistent boutons show large volume fluctuations over several hours, suggesting that presynaptic content of inhibitory synapses is not constant. Our data show that inhibitory boutons are highly dynamic structures and suggest that inhibitory axons are continuously probing potential locations for inhibitory synapse formation by redistributing presynaptic material along the axon.In addition, we found that neuronal activity affects the exploratory dynamics of inhibitory axons. Blocking network activity rapidly reduces the number of transient boutons, whereas enhancing activity reduces the number of persistent inhibitory boutons, possibly reflecting enhanced competition between boutons along the axon. The latter effect requires signaling through GABAA receptors. We propose that activity-dependent regulation of bouton dynamics contributes to inhibitory synaptic plasticity.

  5. Sparing of descending axons rescues interneuron plasticity in the lumbar cord to allow adaptive learning after thoracic spinal cord injury

    Directory of Open Access Journals (Sweden)

    Christopher Nelson Hansen

    2016-03-01

    Full Text Available This study evaluated the role of spared axons on structural and behavioral neuroplasticity in the lumbar enlargement after a thoracic spinal cord injury (SCI. Previous work has demonstrated that recovery in the presence of spared axons after an incomplete lesion increases behavioral output after a subsequent complete spinal cord transection (TX. This suggests that spared axons direct adaptive changes in below-level neuronal networks of the lumbar cord. In response to spared fibers, we postulate that lumbar neuron networks support behavioral gains by preventing aberrant plasticity. As such, the present study measured histological and functional changes in the isolated lumbar cord after complete TX or incomplete contusion (SCI. To measure functional plasticity in the lumbar cord, we used an established instrumental learning paradigm. In this paradigm, neural circuits within isolated lumbar segments demonstrate learning by an increase in flexion duration that reduces exposure to a noxious leg shock. We employed this model using a proof-of-principle design to evaluate the role of sparing on lumbar learning and plasticity early (7 days or late (42 days after midthoracic SCI in a rodent model. Early after SCI or TX at 7d, spinal learning was unattainable regardless of whether the animal recovered with or without axonal substrate. Failed learning occurred alongside measures of cell soma atrophy and aberrant dendritic spine expression within interneuron populations responsible for sensorimotor integration and learning. Alternatively, exposure of the lumbar cord to a small amount of spared axons for 6 weeks produced near-normal learning late after SCI. This coincided with greater cell soma volume and fewer aberrant dendritic spines on interneurons. Thus, an opportunity to influence activity-based learning in locomotor networks depends on spared axons limiting maladaptive plasticity. Together, this work identifies a time dependent interaction between

  6. L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain.

    Science.gov (United States)

    Ueno, Yuji; Koike, Masato; Shimada, Yoshiaki; Shimura, Hideki; Hira, Kenichiro; Tanaka, Ryota; Uchiyama, Yasuo; Hattori, Nobutaka; Urabe, Takao

    2015-03-01

    Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-carnitine. L-carnitine-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent with a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapamycin (mTOR) at 28 days after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model. PMID:25465043

  7. Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers.

    Directory of Open Access Journals (Sweden)

    Marta Amigó-Correig

    Full Text Available This study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism.Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed.Sodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos-positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus.Altogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. The fact that sodium tungstate could modulate hypothalamic plasticity and networks in adulthood makes it a possible and interesting therapeutic strategy not only for obesity management, but also for other neurodegenerative illnesses like Alzheimer's disease.

  8. A period of structural plasticity at the axon initial segment in developing visual cortex

    Directory of Open Access Journals (Sweden)

    Petra Wahle

    2014-03-01

    Full Text Available Cortical networks are shaped by sensory experience and are most susceptible to modifications during critical periods characterized by enhanced plasticity at the structural and functional level. A system particularly well-studied in this context is the mammalian visual system. Plasticity has been documented for the somatodendritic compartment of neurons in detail. A neuronal microdomain not yet studied in this context is the axon initial segment (AIS located at the proximal axon segment. It is a specific electrogenic axonal domain and the site of action potential generation. Recent studies showed that structure and function of the AIS can be dynamically regulated. Here we hypothesize that the AIS shows a dynamic regulation during maturation of the visual cortex. We therefore analyzed AIS length development from embryonic day (E 12.5 to adulthood in mice. A tri-phasic time course of AIS length remodeling during development was observed. AIS first appeared at E14.5 and increased in length throughout the postnatal period to a peak between postnatal day (P 10 to P15 (eyes open P13-14. Then, AIS length was reduced significantly around the beginning of the critical period for ocular dominance plasticity (CP, P21. Shortest AIS were observed at the peak of the CP (P28, followed by a moderate elongation towards the end of the CP (P35. To test if the dynamic maturation of the AIS is influenced by eye opening (onset of activity, animals were deprived of visual input before and during the CP. Deprivation for 1 week prior to eye opening did not affect AIS length development. However, deprivation from P0-P28 and P14-P28 resulted in AIS length distribution similar to the peak at P15. In other words, deprivation from birth prevents the transient shortening of the AIS and maintains an immature AIS length. These results are the first to suggest a dynamic maturation of the AIS in cortical neurons and point to novel mechanisms in the development of neuronal

  9. Nogo Receptor 1 Limits Ocular Dominance Plasticity but not Turnover of Axonal Boutons in a Model of Amblyopia.

    Science.gov (United States)

    Frantz, Michael G; Kast, Ryan J; Dorton, Hilary M; Chapman, Katherine S; McGee, Aaron W

    2016-05-01

    The formation and stability of dendritic spines on excitatory cortical neurons are correlated with adult visual plasticity, yet how the formation, loss, and stability of postsynaptic spines register with that of presynaptic axonal varicosities is unknown. Monocular deprivation has been demonstrated to increase the rate of formation of dendritic spines in visual cortex. However, we find that monocular deprivation does not alter the dynamics of intracortical axonal boutons in visual cortex of either adult wild-type (WT) mice or adult NgR1 mutant (ngr1-/-) mice that retain critical period visual plasticity. Restoring normal vision for a week following long-term monocular deprivation (LTMD), a model of amblyopia, partially restores ocular dominance (OD) in WT andngr1-/- mice but does not alter the formation or stability of axonal boutons. Both WT andngr1-/- mice displayed a rapid return of normal OD within 8 days after LTMD as measured with optical imaging of intrinsic signals. In contrast, single-unit recordings revealed thatngr1-/- exhibited greater recovery of OD by 8 days post-LTMD. Our findings support a model of structural plasticity in which changes in synaptic connectivity are largely postsynaptic. In contrast, axonal boutons appear to be stable during changes in cortical circuit function. PMID:25662716

  10. Cellular and axonal plasticity in the lesioned spinal cord of adult zebrafish

    OpenAIRE

    Kuscha, Veronika

    2011-01-01

    Zebrafish, in contrast to mammals, are capable of functional regeneration after complete transection of the spinal cord. In this system I asked: (1) Which spinal cell types regenerate in the lesioned spinal cord? (2) To what extent do the dopaminergic and 5-HT systems regenerate and (3) do dopaminergic axons from the brain influence cellular regeneration in the spinal cord? (1) Lost motor neurons are replaced by newly born motor neurons that mature and are integrated into the spinal cir...

  11. Plasminogen deficiency causes reduced corticospinal axonal plasticity and functional recovery after stroke in mice.

    Directory of Open Access Journals (Sweden)

    Zhongwu Liu

    Full Text Available Tissue plasminogen activator (tPA has been implicated in neurite outgrowth and neurological recovery post stroke. tPA converts the zymogen plasminogen (Plg into plasmin. In this study, using plasminogen knockout (Plg-/- mice and their Plg-native littermates (Plg+/+, we investigated the role of Plg in axonal remodeling and neurological recovery after stroke. Plg+/+ and Plg-/- mice (n = 10/group were subjected to permanent intraluminal monofilament middle cerebral artery occlusion (MCAo. A foot-fault test and a single pellet reaching test were performed prior to and on day 3 after stroke, and weekly thereafter to monitor functional deficit and recovery. Biotinylated dextran amine (BDA was injected into the left motor cortex to anterogradely label the corticospinal tract (CST. Animals were euthanized 4 weeks after stroke. Neurite outgrowth was also measured in primary cultured cortical neurons harvested from Plg+/+ and Plg-/- embryos. In Plg+/+ mice, the motor functional deficiency after stroke progressively recovered with time. In contrast, recovery in Plg-/- mice was significantly impaired compared to Plg+/+ mice (p0.82, p<0.01. Plg-/- neurons exhibited significantly reduced neurite outgrowth. Our data suggest that plasminogen-dependent proteolysis has a beneficial effect during neurological recovery after stroke, at least in part, by promoting axonal remodeling in the denervated spinal cord.

  12. Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers.

    OpenAIRE

    Marta Amigó-Correig; Sílvia Barceló-Batllori; Guadalupe Soria; Alice Krezymon; Alexandre Benani; Luc Pénicaud; Raúl Tudela; Anna Maria Planas; Eduardo Fernández; Maria del Carmen Carmona; Ramon Gomis

    2012-01-01

    [Objective]: This study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism. [Methods]: Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging...

  13. AT2-receptor stimulation enhances axonal plasticity after spinal cord injury by upregulating BDNF expression

    DEFF Research Database (Denmark)

    Namsolleck, Pawel; Boato, Francesco; Schwengel, Katja;

    2013-01-01

    21). Complementary experiments in primary neurons and organotypic cultures served to identify underlying mechanisms. Functional recovery and plasticity of corticospinal tract (CST) fibers following SCI were monitored after application of C21 (0,3mg/kg/dayi.p.) or vehicle for 4weeks. Organotypic co...... recovery after SCI compared to controls, and this significantly correlated with the increased the number of CST fibers caudal to the lesion site. In vitro, C21 significantly promoted reinnervation in organotypic brain slice co-cultures (+50%) and neurite outgrowth of primary neurons (+25%). C21-induced...... neurite outgrowth was absent in neurons derived from AT2R-KO mice. In primary neurons, treatment with C21 further induced RNA expression of anti-apoptotic Bcl-2 (+75.7%), brain-derived neurotrophic factor (BDNF) (+53.7%), the neurotrophin receptors TrkA (+57.4%) and TrkB (+67.9%) and a marker for neurite...

  14. An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK

    Science.gov (United States)

    Hao, Yan; Frey, Erin; Yoon, Choya; Wong, Hetty; Nestorovski, Douglas; Holzman, Lawrence B; Giger, Roman J; DiAntonio, Aaron; Collins, Catherine

    2016-01-01

    A broadly known method to stimulate the growth potential of axons is to elevate intracellular levels of cAMP, however the cellular pathway(s) that mediate this are not known. Here we identify the Dual Leucine-zipper Kinase (DLK, Wnd in Drosophila) as a critical target and effector of cAMP in injured axons. DLK/Wnd is thought to function as an injury ‘sensor’, as it becomes activated after axonal damage. Our findings in both Drosophila and mammalian neurons indicate that the cAMP effector kinase PKA is a conserved and direct upstream activator of Wnd/DLK. PKA is required for the induction of Wnd signaling in injured axons, and DLK is essential for the regenerative effects of cAMP in mammalian DRG neurons. These findings link two important mediators of responses to axonal injury, DLK/Wnd and cAMP/PKA, into a unified and evolutionarily conserved molecular pathway for stimulating the regenerative potential of injured axons. DOI: http://dx.doi.org/10.7554/eLife.14048.001 PMID:27268300

  15. Synapse plasticity in motor, sensory, and limbo-prefrontal cortex areas as measured by degrading axon terminals in an environment model of gerbils (Meriones unguiculatus).

    Science.gov (United States)

    Neufeld, Janina; Teuchert-Noodt, Gertraud; Grafen, Keren; Winter, York; Witte, A Veronica

    2009-01-01

    Still little is known about naturally occurring synaptogenesis in the adult neocortex and related impacts of epigenetic influences. We therefore investigated (pre)synaptic plasticity in various cortices of adult rodents, visualized by secondary lysosome accumulations (LA) in remodeling axon terminals. Twenty-two male gerbils from either enriched (ER) or impoverished rearing (IR) were used for quantification of silver-stained LA. ER-animals showed rather low LA densities in most primary fields, whereas barrel and secondary/associative cortices exhibited higher densities and layer-specific differences. In IR-animals, these differences were evened out or even inverted. Basic plastic capacities might be linked with remodeling of local intrinsic circuits in the context of cortical map adaptation in both IR- and ER-animals. Frequently described disturbances due to IR in multiple corticocortical and extracortical afferent systems, including the mesocortical dopamine projection, might have led to maladaptations in the plastic capacities of prefronto-limbic areas, as indicated by different LA densities in IR- compared with ER-animals. PMID:19809517

  16. Synapse Plasticity in Motor, Sensory, and Limbo-Prefrontal Cortex Areas as Measured by Degrading Axon Terminals in an Environment Model of Gerbils (Meriones unguiculatus

    Directory of Open Access Journals (Sweden)

    Janina Neufeld

    2009-01-01

    Full Text Available Still little is known about naturally occurring synaptogenesis in the adult neocortex and related impacts of epigenetic influences. We therefore investigated (presynaptic plasticity in various cortices of adult rodents, visualized by secondary lysosome accumulations (LA in remodeling axon terminals. Twenty-two male gerbils from either enriched (ER or impoverished rearing (IR were used for quantification of silver-stained LA. ER-animals showed rather low LA densities in most primary fields, whereas barrel and secondary/associative cortices exhibited higher densities and layer-specific differences. In IR-animals, these differences were evened out or even inverted. Basic plastic capacities might be linked with remodeling of local intrinsic circuits in the context of cortical map adaptation in both IR- and ER-animals. Frequently described disturbances due to IR in multiple corticocortical and extracortical afferent systems, including the mesocortical dopamine projection, might have led to maladaptations in the plastic capacities of prefronto-limbic areas, as indicated by different LA densities in IR- compared with ER-animals.

  17. Axonal accumulation of synaptic markers in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity

    DEFF Research Database (Denmark)

    Rusu, Patricia; Jansen, Anna; Soba, Peter;

    2007-01-01

    Alzheimer's disease (AD) is characterized by neurofibrillary tangles and extracellular plaques, which consist mainly of beta-amyloid derived from the beta-amyloid precursor protein (APP). An additional feature of AD is axonopathy, which might contribute to impairment of cognitive functions....... Specifically, axonal transport defects have been reported in AD animal models, including mice and flies that overexpress APP and tau. Here we demonstrate that the APP-induced traffic jam of vesicles in peripheral nerves of Drosophila melanogaster larvae depends on the four residues NPTY motif in the APP...... intracellular domain. Furthermore, heterologous expression of Fe65 and JIP1b, scaffolding proteins interacting with the NPTY motif, also perturb axonal transport. Together, these data indicate that JIP1b or Fe65 may be involved in the APP-induced axonal transport defect. Moreover, we have characterized...

  18. Increased Cx32 expression in spinal cord TrkB oligodendrocytes following peripheral axon injury.

    Science.gov (United States)

    Coulibaly, Aminata P; Isaacson, Lori G

    2016-08-01

    Following injury to motor axons in the periphery, retrograde influences from the injury site lead to glial cell plasticity in the vicinity of the injured neurons. Following the transection of peripherally located preganglionic axons of the cervical sympathetic trunk (CST), a population of oligodendrocyte (OL) lineage cells expressing full length TrkB, the cognate receptor for brain derived neurotrophic factor (BDNF), is significantly increased in number in the spinal cord. Such robust plasticity in OL lineage cells in the spinal cord following peripheral axon transection led to the hypothesis that the gap junction communication protein connexin 32 (Cx32), which is specific to OL lineage cells, was influenced by the injury. Following CST transection, Cx32 expression in the spinal cord intermediolateral cell column (IML), the location of the parent cell bodies, was significantly increased. The increased Cx32 expression was localized specifically to TrkB OLs in the IML, rather than other cell types in the OL cell lineage, with the population of Cx32/TrkB cells increased by 59%. Cx32 expression in association with OPCs was significantly decreased at one week following the injury. The results of this study provide evidence that peripheral axon injury can differentially affect the gap junction protein expression in OL lineage cells in the adult rat spinal cord. We conclude that the retrograde influences originating from the peripheral injury site elicit dramatic changes in the CNS expression of Cx32, which in turn may mediate the plasticity of OL lineage cells observed in the spinal cord following peripheral axon injury. PMID:27246301

  19. Computing along the axon

    Institute of Scientific and Technical Information of China (English)

    Chen Haiming; Tseren-Onolt Ishdorj; Gheorghe Pǎun

    2007-01-01

    A special form of spiking neural P systems, called axon P systems, corresponding to the activity of Ranvier nodes of neuron axon, is considered and a class of SN-like P systems where the computation is done along the axon is introduced and their language generative power is investigated.

  20. Motor Axon Pathfinding

    OpenAIRE

    Bonanomi, Dario; Pfaff, Samuel L

    2010-01-01

    Motor neurons are functionally related, but represent a diverse collection of cells that show strict preferences for specific axon pathways during embryonic development. In this article, we describe the ligands and receptors that guide motor axons as they extend toward their peripheral muscle targets. Motor neurons share similar guidance molecules with many other neuronal types, thus one challenge in the field of axon guidance has been to understand how the vast complexity of brain connection...

  1. How Schwann Cells Sort Axons: New Concepts.

    Science.gov (United States)

    Feltri, M Laura; Poitelon, Yannick; Previtali, Stefano Carlo

    2016-06-01

    Peripheral nerves contain large myelinated and small unmyelinated (Remak) fibers that perform different functions. The choice to myelinate or not is dictated to Schwann cells by the axon itself, based on the amount of neuregulin I-type III exposed on its membrane. Peripheral axons are more important in determining the final myelination fate than central axons, and the implications for this difference in Schwann cells and oligodendrocytes are discussed. Interestingly, this choice is reversible during pathology, accounting for the remarkable plasticity of Schwann cells, and contributing to the regenerative potential of the peripheral nervous system. Radial sorting is the process by which Schwann cells choose larger axons to myelinate during development. This crucial morphogenetic step is a prerequisite for myelination and for differentiation of Remak fibers, and is arrested in human diseases due to mutations in genes coding for extracellular matrix and linkage molecules. In this review we will summarize progresses made in the last years by a flurry of reverse genetic experiments in mice and fish. This work revealed novel molecules that control radial sorting, and contributed unexpected ideas to our understanding of the cellular and molecular mechanisms that control radial sorting of axons. PMID:25686621

  2. Determinants of axonal regeneration

    OpenAIRE

    Frisén, J

    1997-01-01

    Axons often regrow to their targets and lost functions may be restored after an injury in the peripheral nervous system. In contrast, axonal regeneration is generally very limited after injuries in the central nervous system, and functional impairment is usually permanent. The regenerative capacity depends on intrinsic neuronal factors as weil as the interaction of neurons with other cells. Glial cells may, in different situations, either support or inhibit axo...

  3. Adult Brain Plasticity Elicited by Anomia Treatment

    OpenAIRE

    Cornelissen, Katri; Laine, Matti; Tarkiainen, Antti; Järvensivu, Tiina; Martin, Nadine; Salmelin, Riitta

    2003-01-01

    We describe a study where a specific treatment method for word-finding difficulty (so-called contextual priming technique, which combines massive repetition priming with semantic priming) was applied with three chronic left hemisphere-damaged aphasics. Both before and after treatment, which focused on naming of a series of pictures, naming-related brain activity was measured by magnetoencephalography (MEG). Due to its excellent temporal resolution and good spatial resolution, we were able to ...

  4. Current and calcium responses to local activation of axonal NMDA receptors in developing cerebellar molecular layer interneurons.

    Directory of Open Access Journals (Sweden)

    Bénédicte Rossi

    Full Text Available In developing cerebellar molecular layer interneurons (MLIs, NMDA increases spontaneous GABA release. This effect had been attributed to either direct activation of presynaptic NMDA receptors (preNMDARs or an indirect pathway involving activation of somato-dendritic NMDARs followed by passive spread of somatic depolarization along the axon and activation of axonal voltage dependent Ca(2+ channels (VDCCs. Using Ca(2+ imaging and electrophysiology, we searched for preNMDARs by uncaging NMDAR agonists either broadly throughout the whole field or locally at specific axonal locations. Releasing either NMDA or glutamate in the presence of NBQX using short laser pulses elicited current transients that were highly sensitive to the location of the spot and restricted to a small number of varicosities. The signal was abolished in the presence of high Mg(2+ or by the addition of APV. Similar paradigms yielded restricted Ca(2+ transients in interneurons loaded with a Ca(2+ indicator. We found that the synaptic effects of NMDA were not inhibited by blocking VDCCs but were impaired in the presence of the ryanodine receptor antagonist dantrolene. Furthermore, in voltage clamped cells, bath applied NMDA triggers Ca(2+ elevations and induces neurotransmitter release in the axonal compartment. Our results suggest the existence of preNMDARs in developing MLIs and propose their involvement in the NMDA-evoked increase in GABA release by triggering a Ca(2+-induced Ca(2+ release process mediated by presynaptic Ca(2+ stores. Such a mechanism is likely to exert a crucial role in various forms of Ca(2+-mediated synaptic plasticity.

  5. Modality-Specific Axonal Regeneration: Towards selective regenerative neural interfaces

    Directory of Open Access Journals (Sweden)

    Mario I Romero

    2011-10-01

    Full Text Available Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control of robotic prosthetic devices. However, sensory and motor axons at the neural interface are of mixed submodality types, which difficult the specific recording from motor axons and the eliciting of precise sensory modalities through selective stimulation. Here we evaluated the possibility of using type-specific neurotrophins to preferentially entice the regeneration of defined axonal populations from transected peripheral nerves into separate compartments. Segregation of mixed sensory fibers from dorsal root ganglion neurons was evaluated in vitro by compartmentalized diffusion delivery of nerve growth factor (NGF and neurotrophin-3 (NT-3, to preferentially entice the growth of TrkA+ nociceptive and TrkC+ proprioceptive subsets of sensory neurons, respectively. The average axon length in the NGF channel increased 2.5 fold compared to that in saline or NT-3, whereas the number of branches increased 3 fold in the NT-3 channels. These results were confirmed using a 3-D “Y”-shaped in vitro assay showing that the arm containing NGF was able to entice a 5-fold increase in axonal length of unbranched fibers. To address if such segregation can be enticed in vivo, a “Y”-shaped tubing was used to allow regeneration of the transected adult rat sciatic nerve into separate compartments filled with either NFG or NT-3. A significant increase in the number of CGRP+ pain fibers were attracted towards the sural nerve, while N-52+ large diameter axons were observed in the tibial and NT-3 compartments. This study demonstrates the guided enrichment of sensory axons in specific regenerative chambers, and supports the notion that neurotrophic factors can be used to segregate sensory and perhaps motor axons in separate peripheral interfaces.

  6. Trafifc lights for axon growth:proteoglycans and their neuronal receptors

    Institute of Scientific and Technical Information of China (English)

    Yingjie Shen

    2014-01-01

    Axon growth is a central event in the development and post-injury plasticity of the nervous system. Growing axons encounter a wide variety of environmental instructions. Much like trafifc lights in controlling the migrating axons, chondroitin sulfate proteoglycans (CSPGs) and hepa-ran sulfate proteoglycans (HSPGs) often lead to“stop”and“go”growth responses in the axons, respectively. Recently, the LAR family and NgR family molecules were identified as neuronal receptors for CSPGs and HSPGs. These discoveries provided molecular tools for further study of mechanisms underlying axon growth regulation. More importantly, the identiifcation of these proteoglycan receptors offered potential therapeutic targets for promoting post-injury axon re-generation.

  7. Negative regulation of glial engulfment activity by Draper terminates glial responses to axon injury

    OpenAIRE

    Logan, Mary A.; Hackett, Rachel; Doherty, Johnna; Sheehan, Amy; Speese, Sean D.; Freeman, Marc R

    2012-01-01

    Neuronal injury elicits potent cellular responses from glia, but molecular pathways modulating glial activation, phagocytic function, and termination of reactive responses remain poorly defined. Here we show that positive or negative regulation of glial reponses to axon injury are molecularly encoded by unique isoforms of the Drosophila engulfment receptor Draper. Draper-I promotes engulfment of axonal debris through an immunoreceptor tyrosine-based activation motif (ITAM). In contrast, Drape...

  8. Brain gangliosides in axon-myelin stability and axon regeneration

    OpenAIRE

    Schnaar, Ronald L.

    2009-01-01

    Gangliosides, sialic acid-bearing glycosphingolipids, are expressed at high abundance and complexity in the brain. Altered ganglioside expression results in neural disorders, including seizures and axon degeneration. Brain gangliosides function, in part, by interacting with a ganglioside-binding lectin, myelin-associated glycoprotein (MAG). MAG, on the innermost wrap of the myelin sheath, binds to gangliosides GD1a and GT1b on axons. MAG-ganglioside binding ensures optimal axon-myelin cell-ce...

  9. Ludic Elicitation: Using Games for Knowledge Elicitation

    Science.gov (United States)

    Cao, Yan

    2014-01-01

    Knowledge elicitation from human beings is important for many fields, such as decision support systems, risk communication, and customer preference studying. Traditional approaches include observations, questionnaires, structured and semi-structured interviews, and group discussions. Many publications have been studying different techniques for a…

  10. Microfluidic control of axonal guidance

    Science.gov (United States)

    Gu, Ling; Black, Bryan; Ordonez, Simon; Mondal, Argha; Jain, Ankur; Mohanty, Samarendra

    2014-10-01

    The precision of axonal pathfinding and the accurate formation of functional neural circuitry are crucial for an organism during development as well as during adult central and peripheral nerve regeneration. While chemical cues are believed to be primarily responsible for axonal pathfinding, we hypothesize that forces due to localized fluid flow may directly affect neuronal guidance during early organ development. Here, we report direct evidence of fluid flow influencing axonal migration, producing turning angles of up to 90°. Microfluidic flow simulations indicate that an axon may experience significant bending force due to cross-flow, which may contribute to the observed axonal turning. This method of flow-based guidance was successfully used to fasciculate one advancing axon onto another, showcasing the potential of this technique to be used for the formation of in vitro neuronal circuits.

  11. [A case of acute motor sensory axonal polyneuropathy after Haemophilus influenzae infection].

    Science.gov (United States)

    Oda, M; Udaka, F; Kubori, T; Oka, N; Kameyama, M

    2000-08-01

    A 47-year-old woman developed consciousness disturbance, and experienced hallucinations while traveling abroad, and then went into critical condition. She was placed in the critical care unit, and had flaccid tetraparesis requiring mechanical ventilation. Haemophilus influenzae was cultured from the sputum. The level of protein of the cerebrospinal fluid was elevated to 114 mg/dl, nerve conduction study showed findings of pure axonal damage, and the sural nerve biopsy revealed severe axonal degeneration. She improved gradually by plasma exchange. The diagnosis of acute motor sensory axonal polyneuropathy (AMSAN) based on autoimmune mechanism was made. We speculate that H. influenzae infection may have elicited AMSAN in this case. PMID:11218707

  12. Belief Elicitation in Experiments

    DEFF Research Database (Denmark)

    Blanco, Mariana; Engelmann, Dirk; Koch, Alexander;

    in the experiment. This raises two questions: (i) can we trust the existing belief elicitation results, (ii) can we avoid potential hedging confounds? Our results instill confidence regarding both issues. We propose an experimental design that eliminates hedging opportunities, and use this to test...... for the empirical relevance of hedging effects in the lab. We find no evidence for hedging, comparing the standard 'hedging-prone' belief elicitation treatment to a 'hedging-proof' design in a sequential prisoners' dilemma game. Our findings are strengthened by the absence of hedging even in an...... additional non-belief elicitation treatment using a financial investment frame, where hedging arguably would be most natural....

  13. Thiazolidinediones promote axonal growth through the activation of the JNK pathway.

    Directory of Open Access Journals (Sweden)

    Rodrigo A Quintanilla

    Full Text Available The axon is a neuronal process involved in protein transport, synaptic plasticity, and neural regeneration. It has been suggested that their structure and function are profoundly impaired in neurodegenerative diseases. Previous evidence suggest that Peroxisome Proliferator-Activated Receptors-γ (PPARγ promote neuronal differentiation on various neuronal cell types. In addition, we demonstrated that activation of PPARγby thiazolidinediones (TZDs drugs that selectively activate PPARγ prevent neurite loss and axonal damage induced by amyloid-β (Aβ. However, the potential role of TZDs in axonal elongation and neuronal polarity has not been explored. We report here that the activation of PPARγ by TZDs promoted axon elongation in primary hippocampal neurons. Treatments with different TZDs significantly increased axonal growth and branching area, but no significant effects were observed in neurite elongation compared to untreated neurons. Treatment with PPARγ antagonist (GW 9662 prevented TZDs-induced axonal growth. Recently, it has been suggested that the c-Jun N-terminal kinase (JNK plays an important role regulating axonal growth and neuronal polarity. Interestingly, in our studies, treatment with TZDs induced activation of the JNK pathway, and the pharmacological blockage of this pathway prevented axon elongation induced by TZDs. Altogether, these results indicate that activation of JNK induced by PPARγactivators stimulates axonal growth and accelerates neuronal polarity. These novel findings may contribute to the understanding of the effects of PPARγ on neuronal differentiation and validate the use of PPARγ activators as therapeutic agents in neurodegenerative diseases.

  14. The genetics of axonal transport and axonal transport disorders.

    Directory of Open Access Journals (Sweden)

    Jason E Duncan

    2006-09-01

    Full Text Available Neurons are specialized cells with a complex architecture that includes elaborate dendritic branches and a long, narrow axon that extends from the cell body to the synaptic terminal. The organized transport of essential biological materials throughout the neuron is required to support its growth, function, and viability. In this review, we focus on insights that have emerged from the genetic analysis of long-distance axonal transport between the cell body and the synaptic terminal. We also discuss recent genetic evidence that supports the hypothesis that disruptions in axonal transport may cause or dramatically contribute to neurodegenerative diseases.

  15. Voluntary exercise increases axonal regeneration from sensory neurons

    OpenAIRE

    Molteni, Raffaella; Zheng, Jun-Qi; Ying, Zhe; Gómez-Pinilla, Fernando; Twiss, Jeffery L

    2004-01-01

    Recent advances in understanding the role of neurotrophins on activity-dependent plasticity have provided insight into how behavior can affect specific aspects of neuronal biology. We present evidence that voluntary exercise can prime adult dorsal root ganglion neurons for increased axonal regeneration through a neurotrophin-dependent mechanism. Dorsal root ganglion neurons showed an increase in neurite outgrowth when cultured from animals that had undergone 3 or 7 days of exercise compared w...

  16. Local protein synthesis in neuronal axons: why and how we study

    OpenAIRE

    Kim, Eunjin; Jung, Hosung

    2015-01-01

    Adaptive brain function and synaptic plasticity rely on dynamic regulation of local proteome. One way for the neuron to introduce new proteins to the axon terminal is to transport those from the cell body, which had long been thought as the only source of axonal proteins. Another way, which is the topic of this review, is synthesizing proteins on site by local mRNA translation. Recent evidence indicates that the axon stores a reservoir of translationally silent mRNAs and regulates their expre...

  17. Axonal tubulin and axonal microtubules: biochemical evidence for cold stability

    OpenAIRE

    1984-01-01

    Nerve extracts containing tubulin labeled by axonal transport were analyzed by electrophoresis and differential extraction. We found that a substantial fraction of the tubulin in the axons of the retinal ganglion cell of guinea pigs is not solubilized by conventional methods for preparation of microtubules from whole brain. In two-dimensional polyacrylamide gel electrophoresis this cold-insoluble tubulin was biochemically distinct from tubulin obtained from whole brain microtubules prepared b...

  18. Neurofilament Polymer Transport in Axons

    OpenAIRE

    Yan, Yanping; Brown, Anthony

    2005-01-01

    Neurofilament proteins are known to be transported along axons by slow axonal transport, but the form in which they move is controversial. In previous studies on cultured rat sympathetic neurons, we found that green fluorescent protein-tagged neurofilament proteins move predominantly in the form of filamentous structures, and we proposed that these structures are single neurofilament polymers. In the present study, we have tested this hypothesis by using a rapid perfusion technique to capture...

  19. Local translation and directional steering in axons

    OpenAIRE

    Lin, Andrew C; Holt, Christine E.

    2007-01-01

    The assembly of functional neural circuits in the developing brain requires neurons to extend axons to the correct targets. This in turn requires the navigating tips of axons to respond appropriately to guidance cues present along the axonal pathway, despite being cellular ‘outposts' far from the soma. Work over the past few years has demonstrated a critical role for local translation within the axon in this process in vitro, making axon guidance another process that requires spatially locali...

  20. Flexibility in the nervous system: Regulation of axonal spike initiation in a sensory neuron fine-tunes signal integration

    OpenAIRE

    Städele, Carola

    2016-01-01

    Generating appropriate behavioral responses to sensory inputs is a pivotal function of the nervous system. Changes in internal conditions or the environment elicit action potentials that travel along the axon of sensory neurons to inform the central nervous system of the occurred changes. My work shows for the first time that neurons in the central nervous system feed back to the sensory system and regulate action potential initiation in the sensory axon. This regulation increases the activit...

  1. Automated Preferences Elicitation

    Czech Academy of Sciences Publication Activity Database

    Kárný, Miroslav; Guy, Tatiana Valentine

    Prague : Institute of Information Theory and Automation, 2011, s. 20-25. ISBN 978-80-903834-6-3. [The 2nd International Workshop od Decision Making with Multiple Imperfect Decision Makers. Held in Conjunction with the 25th Annual Conference on Neural Information Processing Systems (NIPS 2011). Sierra Nevada (ES), 16.12.2011-16.12.2011] R&D Projects: GA MŠk 1M0572; GA ČR GA102/08/0567 Institutional research plan: CEZ:AV0Z10750506 Keywords : elicitation * decision making * Bayesian decision making * fully probabilistic design Subject RIV: BB - Applied Statistics, Operational Research http://library.utia.cas.cz/separaty/2011/AS/karny-automated preferences elicitation.pdf

  2. Axon density and axon orientation dispersion in children born preterm

    NARCIS (Netherlands)

    Kelly, Claire E.; Thompson, Deanne K.; Chen, Jian; Leemans, Alexander; Adamson, Christopher L.; Inder, Terrie E.; Cheong, Jeanie L Y; Doyle, Lex W.; Anderson, Peter J.

    2016-01-01

    Background Very preterm birth (VPT, <32 weeks' gestation) is associated with altered white matter fractional anisotropy (FA), the biological basis of which is uncertain but may relate to changes in axon density and/or dispersion, which can be measured using Neurite Orientation Dispersion and Density

  3. Outsourcing CREB translation to axons to survive

    OpenAIRE

    Lin, Andrew C; Holt, Christine E.

    2008-01-01

    Nerve growth factor induces sensory neuron survival via retrograde signalling from the axon to the cell body. Local translation of the transcription factor CREB in the axon, followed by its transport to the nucleus, is involved in this process.

  4. Axon damage and repair in multiple sclerosis.

    OpenAIRE

    Perry, V.H.; Anthony, D. C.

    1999-01-01

    It is well known that within long-standing multiple sclerosis (MS) lesions there is axonal loss but whether it is an early or late event has been more difficult to establish. The use of immunocytochemical methods that reveal axonal end-bulbs is a valuable approach to investigating acute axonal injury in human pathological material. The application of these techniques to multiple sclerosis tissue reveals evidence of axonal injury in acute lesions; the distribution of the end-bulbs in acute and...

  5. Physiological role for amyloid precursor protein in adult experience-dependent plasticity.

    Science.gov (United States)

    Marik, Sally A; Olsen, Olav; Tessier-Lavigne, Marc; Gilbert, Charles D

    2016-07-12

    Changes in neural circuits after experience-dependent plasticity are brought about by the formation of new circuits via axonal growth and pruning. Here, using a combination of electrophysiology, adeno-associated virus-delivered fluorescent proteins, analysis of mutant mice, and two-photon microscopy, we follow long-range horizontally projecting axons in primary somatosensory cortex before and after selective whisker plucking. Whisker plucking induces axonal growth and pruning of horizontal projecting axons from neurons located in the surrounding intact whisker representations. We report that amyloid precursor protein is crucial for axonal pruning and contributes in a cell autonomous way. PMID:27354516

  6. Human intraretinal myelination: Axon diameters and axon/myelin thickness ratios

    Science.gov (United States)

    FitzGibbon, Thomas; Nestorovski, Zoran

    2013-01-01

    Purpose: Human intraretinal myelination of ganglion cell axons occurs in about 1% of the population. We examined myelin thickness and axon diameter in human retinal specimens containing myelinated retinal ganglion cell axons. Materials and Methods: Two eyes containing myelinated patches were prepared for electron microscopy. Two areas were examined in one retina and five in the second retina. Measurements were compared to normal retinal and optic nerve samples and the rabbit retina, which normally contains myelinated axons. Measurements were made using a graphics tablet. Results: Mean axon diameter of myelinated axons at all locations were significantly larger than unmyelinated axons (P ≤ 0.01). Myelinated axons within the patches were significantly larger than axons within the optic nerve (P < 0.01). The relationship between axon diameter/fiber diameter (the G-ratio) seen in the retinal sites differed from that in the nerve. G-ratios were higher and myelin thickness was positively correlated to axon diameter (P < 0.01) in the retina but negatively correlated to axon diameter in the nerve (P < 0.001). Conclusion: Intraretinally myelinated axons are larger than non-myelinated axons from the same population and suggests that glial cells can induce diameter changes in retinal axons that are not normally myelinated. This effect is more dramatic on intraretinal axons compared with the normal transition zone as axons enter the optic nerve and these changes are abnormal. Whether intraretinal myelin alters axonal conduction velocity or blocks axonal conduction remains to be clarified and these issues may have different clinical outcomes. PMID:24212308

  7. Generalized plasticity

    CERN Document Server

    Yu, Mao-Hong

    2006-01-01

    Dealing with the plasticity of materials and structures, this book is an expansion of the "Unified Strength Theory to Plasticity Theory", leading to a unified treatment of metal plasticity and plasticity of geomaterials. It includes the metal plasticity for Tresca materials, Huber-von-Mises materials and twin-shear materials.

  8. Developmental Axon Stretch Stimulates Neuron Growth While Maintaining Normal Electrical Activity, Intracellular Calcium Flux, and Somatic Morphology

    Directory of Open Access Journals (Sweden)

    Joseph R Loverde

    2015-08-01

    Full Text Available Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18 % applied over 5 minutes. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25 % strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury.

  9. EEG functional connectivity, axon delays and white matter disease

    Science.gov (United States)

    Nunez, Paul L.; Srinivasan, Ramesh; Fields, R. Douglas

    2016-01-01

    Objective Both structural and functional brain connectivities are closely linked to white matter disease. We discuss several such links of potential interest to neurologists, neurosurgeons, radiologists, and non-clinical neuroscientists. Methods Treatment of brains as genuine complex systems suggests major emphasis on the multi-scale nature of brain connectivity and dynamic behavior. Cross-scale interactions of local, regional, and global networks are apparently responsible for much of EEG's oscillatory behaviors. Finite axon propagation speed, often assumed to be infinite in local network models, is central to our conceptual framework. Results Myelin controls axon speed, and the synchrony of impulse traffic between distant cortical regions appears to be critical for optimal mental performance and learning. Results Several experiments suggest that axon conduction speed is plastic, thereby altering the regional and global white matter connections that facilitate binding of remote local networks. Conclusions Combined EEG and high resolution EEG can provide distinct multi-scale estimates of functional connectivity in both healthy and diseased brains with measures like frequency and phase spectra, covariance, and coherence. Significance White matter disease may profoundly disrupt normal EEG coherence patterns, but currently these kinds of studies are rare in scientific labs and essentially missing from clinical environments. PMID:24815984

  10. Isolation and analyses of axonal ribonucleoprotein complexes.

    Science.gov (United States)

    Doron-Mandel, Ella; Alber, Stefanie; Oses, Juan A; Medzihradszky, Katalin F; Burlingame, Alma L; Fainzilber, Mike; Twiss, Jeffery L; Lee, Seung Joon

    2016-01-01

    Cytoskeleton-dependent RNA transport and local translation in axons are gaining increased attention as key processes in the maintenance and functioning of neurons. Specific axonal transcripts have been found to play roles in many aspects of axonal physiology including axon guidance, axon survival, axon to soma communication, injury response and regeneration. This axonal transcriptome requires long-range transport that is achieved by motor proteins carrying transcripts as messenger ribonucleoprotein (mRNP) complexes along microtubules. Other than transport, the mRNP complex plays a major role in the generation, maintenance, and regulation of the axonal transcriptome. Identification of axonal RNA-binding proteins (RBPs) and analyses of the dynamics of their mRNPs are of high interest to the field. Here, we describe methods for the study of interactions between RNA and proteins in axons. First, we describe a protocol for identifying binding proteins for an RNA of interest by using RNA affinity chromatography. Subsequently, we discuss immunoprecipitation (IP) methods allowing the dissection of protein-RNA and protein-protein interactions in mRNPs under various physiological conditions. PMID:26794529

  11. Plastic Surgery

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Plastic Surgery KidsHealth > For Teens > Plastic Surgery Print A ... her forehead lightened with a laser? What Is Plastic Surgery? Just because the name includes the word " ...

  12. Sorting of Dendritic and Axonal Vesicles at the Pre-axonal Exclusion Zone

    Directory of Open Access Journals (Sweden)

    Ginny G. Farías

    2015-11-01

    Full Text Available Polarized sorting of newly synthesized proteins to the somatodendritic and axonal domains of neurons occurs by selective incorporation into distinct populations of vesicular transport carriers. An unresolved issue is how the vesicles themselves are sorted to their corresponding neuronal domains. Previous studies concluded that the axon initial segment (AIS is an actin-based filter that selectively prevents passage of somatodendritic vesicles into the axon. We find, however, that most somatodendritic vesicles fail to enter the axon at a more proximal region in the axon hillock, herein referred to as the pre-axonal exclusion zone (PAEZ. Forced coupling of a somatodendritic cargo protein to an axonally directed kinesin is sufficient to drive transport of whole somatodendritic vesicles through the PAEZ toward the distal axon. Based on these findings, we propose that polarized sorting of transport vesicles occurs at the PAEZ and depends on the ability of the vesicles to acquire an appropriately directed microtubule motor.

  13. Coordinating gene expression and axon assembly to control axon growth: potential role of GSK3 signaling

    Directory of Open Access Journals (Sweden)

    Fengquan Zhou

    2012-02-01

    Full Text Available Axon growth requires coordinated regulation of gene expression in the neuronal soma, anterograde transport of synthesized raw materials along the axon, and assembly of cytoskeleton and membranes in the nerve growth cone. Glycogen synthase kinase 3 (GSK3 signaling has recently been shown to play key roles in regulation of axonal transport and cytoskeletal assembly during axon growth. GSK3 signaling is also known to regulate gene expression via controlling the functions of many transcription factors, suggesting that GSK3 may be an important regulator of gene transcription supporting axon growth. Here we will review signaling pathways that control local axon assembly at the growth cone and gene expression in the soma during developmental or regenerative axon growth and discuss the potential involvement of GSK3 signaling in these processes, with a particular focus on how GSK3 signaling modulates the function of axon growth-associated transcription factors.

  14. Mitochondrial Transport and Docking in Axons

    OpenAIRE

    Cai, Qian; Sheng, Zu-Hang

    2009-01-01

    Proper transport and distribution of mitochondria in axons and at synapses are critical for the normal physiology of neurons. Mitochondria in axons display distinct motility patterns and undergo saltatory and bidirectional movement, where mitochondria frequently stop, start moving again, and change direction. While approximately one-third of axonal mitochondria are mobile in mature neurons, a large proportion remains stationary. Their net movement is significantly influenced by recruitment to...

  15. 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.

  16. AxonSeg: Open Source Software for Axon and Myelin Segmentation and Morphometric Analysis.

    Science.gov (United States)

    Zaimi, Aldo; Duval, Tanguy; Gasecka, Alicja; Côté, Daniel; Stikov, Nikola; Cohen-Adad, Julien

    2016-01-01

    Segmenting axon and myelin from microscopic images is relevant for studying the peripheral and central nervous system and for validating new MRI techniques that aim at quantifying tissue microstructure. While several software packages have been proposed, their interface is sometimes limited and/or they are designed to work with a specific modality (e.g., scanning electron microscopy (SEM) only). Here we introduce AxonSeg, which allows to perform automatic axon and myelin segmentation on histology images, and to extract relevant morphometric information, such as axon diameter distribution, axon density and the myelin g-ratio. AxonSeg includes a simple and intuitive MATLAB-based graphical user interface (GUI) and can easily be adapted to a variety of imaging modalities. The main steps of AxonSeg consist of: (i) image pre-processing; (ii) pre-segmentation of axons over a cropped image and discriminant analysis (DA) to select the best parameters based on axon shape and intensity information; (iii) automatic axon and myelin segmentation over the full image; and (iv) atlas-based statistics to extract morphometric information. Segmentation results from standard optical microscopy (OM), SEM and coherent anti-Stokes Raman scattering (CARS) microscopy are presented, along with validation against manual segmentations. Being fully-automatic after a quick manual intervention on a cropped image, we believe AxonSeg will be useful to researchers interested in large throughput histology. AxonSeg is open source and freely available at: https://github.com/neuropoly/axonseg. PMID:27594833

  17. Axonal regeneration through arterial grafts.

    OpenAIRE

    Anderson, P. N.; Turmaine, M.

    1986-01-01

    The left common peroneal nerves of adult inbred mice were severed and allowed to regenerate through the lumina of Y-shaped tubes comprising grafts of abdominal aorta and its bifurcation. Very little regeneration took place within the grafts unless the distal nerve stump was inserted into one limb of the Y-tube. Using syngeneic grafts virtually all the axons regenerating through the lumen grew down the limb of the Y-tube containing the distal nerve. Using non-syngeneic grafts, however, a subst...

  18. Plasticity theory

    CERN Document Server

    Lubliner, Jacob

    2008-01-01

    The aim of Plasticity Theory is to provide a comprehensive introduction to the contemporary state of knowledge in basic plasticity theory and to its applications. It treats several areas not commonly found between the covers of a single book: the physics of plasticity, constitutive theory, dynamic plasticity, large-deformation plasticity, and numerical methods, in addition to a representative survey of problems treated by classical methods, such as elastic-plastic problems, plane plastic flow, and limit analysis; the problem discussed come from areas of interest to mechanical, structural, and

  19. Axonal interferon responses and alphaherpesvirus neuroinvasion

    Science.gov (United States)

    Song, Ren

    Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at a peripheral epithelial surface and continues into the peripheral nervous system (PNS) that innervates this tissue. Inflammatory responses are induced at the infected peripheral site prior to viral invasion of the PNS. PNS neurons are highly polarized cells with long axonal processes that connect to distant targets. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which include type I interferon (e.g. IFNbeta) and type II interferon (i.e. IFNgamma). IFNbeta can be produced by all types of cells, while IFNgamma is secreted by some specific types of immune cells. And both types of IFN induce antiviral responses in surrounding cells that express the IFN receptors. The fundamental question is how do PNS neurons respond to the inflammatory milieu experienced only by their axons. Axons must act as potential front-line barriers to prevent PNS infection and damage. Using compartmented cultures that physically separate neuron axons from cell bodies, I found that pretreating isolated axons with IFNbeta or IFNgamma significantly diminished the number of HSV-1 and PRV particles moving from axons to the cell bodies in an IFN receptor-dependent manner. Furthermore, I found the responses in axons are activated differentially by the two types of IFNs. The response to IFNbeta is a rapid, axon-only response, while the response to IFNgamma involves long distance signaling to the PNS cell body. For example, exposing axons to IFNbeta induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFNgamma induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated IFNgamma-, but not IFNbeta-mediated antiviral effects. Proteomic analysis of IFNbeta- or IFNgamma-treated axons identified several differentially regulated proteins. Therefore

  20. Neurofilament spacing, phosphorylation, and axon diameter in regenerating and uninjured lamprey axons.

    Science.gov (United States)

    Pijak, D S; Hall, G F; Tenicki, P J; Boulos, A S; Lurie, D I; Selzer, M E

    1996-05-13

    It has been postulated that phosphorylation of the carboxy terminus sidearms of neurofilaments (NFs) increases axon diameter through repulsive electrostatic forces that increase sidearm extension and interfilament spacing. To evaluate this hypothesis, the relationships among NF phosphorylation, NF spacing, and axon diameter were examined in uninjured and spinal cord-transected larval sea lampreys (Petromyzon marinus). In untransected animals, axon diameters in the spinal cord varied from 0.5 to 50 microns. Antibodies specific for highly phosphorylated NFs labeled only large axons (> 10 microns), whereas antibodies for lightly phosphorylated NFs labeled medium-sized and small axons more darkly than large axons. For most axons in untransected animals, diameter was inversely related to NF packing density, but the interfilament distances of the largest axons were only 1.5 times those of the smallest axons. In addition, the lightly phosphorylated NFs of the small axons in the dorsal columns were widely spaced, suggesting that phosphorylation of NFs does not rigidly determine their spacing and that NF spacing does not rigidly determine axon diameter. Regenerating neurites of giant reticulospinal axons (GRAs) have diameters only 5-10% of those of their parent axons. If axon caliber is controlled by NF phosphorylation via mutual electrostatic repulsion, then NFs in the slender regenerating neurites should be lightly phosphorylated and densely packed (similar to NFs in uninjured small caliber axons), whereas NFs in the parent GRAs should be highly phosphorylated and loosely packed. However, although linear density of NFs (the number of NFs per micrometer) in these slender regenerating neurites was twice that in their parent axons, they were highly phosphorylated. Following sectioning of these same axons close to the cell body, axon-like neurites regenerated ectopically from dendritic tips. These ectopically regenerating neurites had NF linear densities 2.5 times those of

  1. A neonatal mouse spinal cord injury model for assessing post-injury adaptive plasticity and human stem cell integration.

    Directory of Open Access Journals (Sweden)

    Jean-Luc Boulland

    Full Text Available Despite limited regeneration capacity, partial injuries to the adult mammalian spinal cord can elicit variable degrees of functional recovery, mediated at least in part by reorganization of neuronal circuitry. Underlying mechanisms are believed to include synaptic plasticity and collateral sprouting of spared axons. Because plasticity is higher in young animals, we developed a spinal cord compression (SCC injury model in the neonatal mouse to gain insight into the potential for reorganization during early life. The model provides a platform for high-throughput assessment of functional synaptic connectivity that is also suitable for testing the functional integration of human stem and progenitor cell-derived neurons being considered for clinical cell replacement strategies. SCC was generated at T9-T11 and functional recovery was assessed using an integrated approach including video kinematics, histology, tract tracing, electrophysiology, and high-throughput optical recording of descending inputs to identified spinal neurons. Dramatic degeneration of axons and synaptic contacts was evident within 24 hours of SCC, and loss of neurons in the injured segment was evident for at least a month thereafter. Initial hindlimb paralysis was paralleled by a loss of descending inputs to lumbar motoneurons. Within 4 days of SCC and progressively thereafter, hindlimb motility began to be restored and descending inputs reappeared, but with examples of atypical synaptic connections indicating a reorganization of circuitry. One to two weeks after SCC, hindlimb motility approached sham control levels, and weight-bearing locomotion was virtually indistinguishable in SCC and sham control mice. Genetically labeled human fetal neural progenitor cells injected into the injured spinal cord survived for at least a month, integrated into the host tissue and began to differentiate morphologically. This integrative neonatal mouse model provides opportunities to explore early

  2. Axon reflexes in human cold exposed fingers

    NARCIS (Netherlands)

    Daanen, H.A.M.; Ducharme, M.B.

    2000-01-01

    Exposure of fingers to severe cold induces cold induced vasodilation (CIVD). The mechanism of CIVD is still debated. The original theory states that an axon reflex causes CIVD. To test this hypothesis, axon reflexes were evoked by electrical stimulation of the middle fingers of hands immersed in wat

  3. Cable energy function of cortical axons.

    Science.gov (United States)

    Ju, Huiwen; Hines, Michael L; Yu, Yuguo

    2016-01-01

    Accurate estimation of action potential (AP)-related metabolic cost is essential for understanding energetic constraints on brain connections and signaling processes. Most previous energy estimates of the AP were obtained using the Na(+)-counting method, which seriously limits accurate assessment of metabolic cost of ionic currents that underlie AP conduction along the axon. Here, we first derive a full cable energy function for cortical axons based on classic Hodgkin-Huxley (HH) neuronal equations and then apply the cable energy function to precisely estimate the energy consumption of AP conduction along axons with different geometric shapes. Our analytical approach predicts an inhomogeneous distribution of metabolic cost along an axon with either uniformly or nonuniformly distributed ion channels. The results show that the Na(+)-counting method severely underestimates energy cost in the cable model by 20-70%. AP propagation along axons that differ in length may require over 15% more energy per unit of axon area than that required by a point model. However, actual energy cost can vary greatly depending on axonal branching complexity, ion channel density distributions, and AP conduction states. We also infer that the metabolic rate (i.e. energy consumption rate) of cortical axonal branches as a function of spatial volume exhibits a 3/4 power law relationship. PMID:27439954

  4. Cable energy function of cortical axons

    Science.gov (United States)

    Ju, Huiwen; Hines, Michael L.; Yu, Yuguo

    2016-01-01

    Accurate estimation of action potential (AP)-related metabolic cost is essential for understanding energetic constraints on brain connections and signaling processes. Most previous energy estimates of the AP were obtained using the Na+-counting method, which seriously limits accurate assessment of metabolic cost of ionic currents that underlie AP conduction along the axon. Here, we first derive a full cable energy function for cortical axons based on classic Hodgkin-Huxley (HH) neuronal equations and then apply the cable energy function to precisely estimate the energy consumption of AP conduction along axons with different geometric shapes. Our analytical approach predicts an inhomogeneous distribution of metabolic cost along an axon with either uniformly or nonuniformly distributed ion channels. The results show that the Na+-counting method severely underestimates energy cost in the cable model by 20–70%. AP propagation along axons that differ in length may require over 15% more energy per unit of axon area than that required by a point model. However, actual energy cost can vary greatly depending on axonal branching complexity, ion channel density distributions, and AP conduction states. We also infer that the metabolic rate (i.e. energy consumption rate) of cortical axonal branches as a function of spatial volume exhibits a 3/4 power law relationship. PMID:27439954

  5. Neuronal Development: SAD Kinases Make Happy Axons

    OpenAIRE

    Xing, Lei; Newbern, Jason M.; Snider, William D

    2013-01-01

    The polarity proteins LKB1 and SAD-A/B are key regulators of axon specification in the developing cerebral cortex. Recent studies now show that this mechanism cannot be generalized to other classes of neurons: instead, SAD-A/B functions downstream of neurotrophin signaling in sensory neurons to mediate a later stage of axon development — arborization in the target field.

  6. Dynamics of mitochondrial transport in axons

    Directory of Open Access Journals (Sweden)

    Robert Francis Niescier

    2016-05-01

    Full Text Available The polarized structure and long neurites of neurons pose a unique challenge for proper mitochondrial distribution. It is widely accepted that mitochondria move from the cell body to axon ends and vice versa; however, we have found that mitochondria originating from the axon ends moving in the retrograde direction never reach to the cell body, and only a limited number of mitochondria moving in the anterograde direction from the cell body arrive at the axon ends of mouse hippocampal neurons. Furthermore, we have derived a mathematical formula using the Fokker-Planck equation to characterize features of mitochondrial transport, and the equation could determine altered mitochondrial transport in axons overexpressing parkin. Our analysis will provide new insights into the dynamics of mitochondrial transport in axons of normal and unhealthy neurons.

  7. Dynamics of Mitochondrial Transport in Axons.

    Science.gov (United States)

    Niescier, Robert F; Kwak, Sang Kyu; Joo, Se Hun; Chang, Karen T; Min, Kyung-Tai

    2016-01-01

    The polarized structure and long neurites of neurons pose a unique challenge for proper mitochondrial distribution. It is widely accepted that mitochondria move from the cell body to axon ends and vice versa; however, we have found that mitochondria originating from the axon ends moving in the retrograde direction never reach to the cell body, and only a limited number of mitochondria moving in the anterograde direction from the cell body arrive at the axon ends of mouse hippocampal neurons. Furthermore, we have derived a mathematical formula using the Fokker-Planck equation to characterize features of mitochondrial transport, and the equation could determine altered mitochondrial transport in axons overexpressing parkin. Our analysis will provide new insights into the dynamics of mitochondrial transport in axons of normal and unhealthy neurons. PMID:27242435

  8. Early events in axon/dendrite polarization.

    Science.gov (United States)

    Cheng, Pei-lin; Poo, Mu-ming

    2012-01-01

    Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure. PMID:22715881

  9. A multi-component model of the developing retinocollicular pathway incorporating axonal and synaptic growth.

    Directory of Open Access Journals (Sweden)

    Keith B Godfrey

    2009-12-01

    Full Text Available During development, neurons extend axons to different brain areas and produce stereotypical patterns of connections. The mechanisms underlying this process have been intensively studied in the visual system, where retinal neurons form retinotopic maps in the thalamus and superior colliculus. The mechanisms active in map formation include molecular guidance cues, trophic factor release, spontaneous neural activity, spike-timing dependent plasticity (STDP, synapse creation and retraction, and axon growth, branching and retraction. To investigate how these mechanisms interact, a multi-component model of the developing retinocollicular pathway was produced based on phenomenological approximations of each of these mechanisms. Core assumptions of the model were that the probabilities of axonal branching and synaptic growth are highest where the combined influences of chemoaffinity and trophic factor cues are highest, and that activity-dependent release of trophic factors acts to stabilize synapses. Based on these behaviors, model axons produced morphologically realistic growth patterns and projected to retinotopically correct locations in the colliculus. Findings of the model include that STDP, gradient detection by axonal growth cones and lateral connectivity among collicular neurons were not necessary for refinement, and that the instructive cues for axonal growth appear to be mediated first by molecular guidance and then by neural activity. Although complex, the model appears to be insensitive to variations in how the component developmental mechanisms are implemented. Activity, molecular guidance and the growth and retraction of axons and synapses are common features of neural development, and the findings of this study may have relevance beyond organization in the retinocollicular pathway.

  10. Genetics Home Reference: giant axonal neuropathy

    Science.gov (United States)

    ... in giant axonal neuropathy: new insights into disease mechanisms. Muscle Nerve. 2012 Aug;46(2):246-56. ... with a qualified healthcare professional . About Genetics Home Reference Site Map Contact Us Selection Criteria for Links ...

  11. Axonal Transmission in the Retina Introduces a Small Dispersion of Relative Timing in the Ganglion Cell Population Response

    OpenAIRE

    Zeck, G; Lambacher, A.; Fromherz, P

    2011-01-01

    Background: Visual stimuli elicit action potentials in tens of different retinal ganglion cells. Each ganglion cell type responds with a different latency to a given stimulus, thus transforming the high-dimensional input into a temporal neural code. The timing of the first spikes between different retinal projection neurons cells may further change along axonal transmission. The purpose of this study is to investigate if intraretinal conduction velocity leads to a synchronization or dispersio...

  12. Elicitation of ostomy pouch preferences

    DEFF Research Database (Denmark)

    Bonnichsen, Ole

    2011-01-01

    stoma care would affect patients and, to the author's knowledge, the present study is the first to elicit preferences for potential improvements in ostomy pouches in the form of monetary values. Objective: This article examines and measures Swedish patients' preferences for potential improvements in...... the utility that patients would obtain from a potential improvement in their ostomy pouch. This provides information as to how treatment options in terms of stoma management can be structured so as to maximize the benefits for patients....

  13. Survey Based Reviewof Elicitation Problems

    OpenAIRE

    Sidra Arshad

    2016-01-01

    Any software development process is the combination of multiple development activities and each activity has a vital role in the software development cycle. Requirement Engineering is the main and basic branch of Software Engineering, it has many phases but the most initial phase is Requirement Elicitation. In this phase requirements are gathered for system development. This paper provides a literature review of the requirements engineering processes performed in traditional and ...

  14. Plastic Bronchitis

    OpenAIRE

    Quysner, Annie; Surani, Salim; Roberts, Daniel

    2011-01-01

    Plastic bronchitis is not yet well understood. There have been less than 500 reported cases in adults worldwide. This patient presented with a one month history of productive sputum consisting of bronchial casts resulting in a diagnosis of plastic bronchitis. [West J Emerg Med. 2011;12(1):118-119.

  15. Protein phosphorylation: Localization in regenerating optic axons

    International Nuclear Information System (INIS)

    A number of axonal proteins display changes in phosphorylation during goldfish optic nerve regeneration. (1) To determine whether the phosphorylation of these proteins was closely linked to their synthesis in the retinal ganglion cell body, cycloheximide was injected intraocularly into goldfish whose optic nerves had been regenerating for 3 weeks. Cycloheximide reduced the incorporation of [3H]proline and 32P orthophosphate into total nerve protein by 84% and 46%, respectively. Of the 20 individual proteins examined, 17 contained less than 15% of the [3H]proline label measured in corresponding controls, whereas 18 proteins contained 50% or more of the 32P label, suggesting that phosphorylation was largely independent of synthesis. (2) To determine whether the proteins were phosphorylated in the ganglion cell axons, axonal transport of proteins was blocked by intraocular injection of vincristine. Vincristine reduced [3H]proline labeling of total protein by 88% and 32P labeling by 49%. Among the individual proteins [3H]proline labeling was reduced by 90% or more in 18 cases but 32P labeling was reduced only by 50% or less. (3) When 32P was injected into the cranial cavity near the ends of the optic axons, all of the phosphoproteins were labeled more intensely in the optic tract than in the optic nerve. These results suggest that most of the major phosphoproteins that undergo changes in phosphorylation in the course of regeneration are phosphorylated in the optic axons

  16. Calpain activity promotes the sealing of severed giant axons

    OpenAIRE

    Godell, Christopher M.; Smyers, Mark E.; Eddleman, Christopher S.; Ballinger, Martis L.; Fishman, Harvey M.; Bittner, George D.

    1997-01-01

    A barrier (seal) must form at the cut ends of a severed axon if a neuron is to survive and eventually regenerate. Following severance of crayfish medial giant axons in physiological saline, vesicles accumulate at the cut end and form a barrier (seal) to ion and dye diffusion. In contrast, squid giant axons do not seal, even though injury-induced vesicles form after axonal transection and accumulate at cut axonal ends. Neither axon seals in Ca2+-free salines. The addition of calpain to the bat...

  17. Eliciting expert knowledge in conservation science.

    Science.gov (United States)

    Martin, Tara G; Burgman, Mark A; Fidler, Fiona; Kuhnert, Petra M; Low-Choy, Samantha; McBride, Marissa; Mengersen, Kerrie

    2012-02-01

    Expert knowledge is used widely in the science and practice of conservation because of the complexity of problems, relative lack of data, and the imminent nature of many conservation decisions. Expert knowledge is substantive information on a particular topic that is not widely known by others. An expert is someone who holds this knowledge and who is often deferred to in its interpretation. We refer to predictions by experts of what may happen in a particular context as expert judgments. In general, an expert-elicitation approach consists of five steps: deciding how information will be used, determining what to elicit, designing the elicitation process, performing the elicitation, and translating the elicited information into quantitative statements that can be used in a model or directly to make decisions. This last step is known as encoding. Some of the considerations in eliciting expert knowledge include determining how to work with multiple experts and how to combine multiple judgments, minimizing bias in the elicited information, and verifying the accuracy of expert information. We highlight structured elicitation techniques that, if adopted, will improve the accuracy and information content of expert judgment and ensure uncertainty is captured accurately. We suggest four aspects of an expert elicitation exercise be examined to determine its comprehensiveness and effectiveness: study design and context, elicitation design, elicitation method, and elicitation output. Just as the reliability of empirical data depends on the rigor with which it was acquired so too does that of expert knowledge. PMID:22280323

  18. Microfluidic device for unidirectional axon growth

    Science.gov (United States)

    Malishev, E.; Pimashkin, A.; Gladkov, A.; Pigareva, Y.; Bukatin, A.; Kazantsev, V.; Mukhina, I.; Dubina, M.

    2015-11-01

    In order to better understand the communication and connectivity development of neuron networks, we designed microfluidic devices with several chambers for growing dissociated neuronal cultures from mice fetal hippocampus (E18). The chambers were connected with microchannels providing unidirectional axonal growth between “Source” and “Target” neural sub-networks. Experiments were performed in a hippocampal cultures plated in a poly-dimethylsiloxane (PDMS) microfluidic chip, aligned with a 60 microelectrode array (MEA). Axonal growth through microchannels was observed with brightfield, phase-contrast and fluorescence microscopy, and after 7 days in vitro electrical activity was recorded. Visual inspection and spike propagation analysis showed the predominant axonal growth in microchannels in a direction from “Source” to “Target”.

  19. Diverse modes of axon elaboration in the developing neocortex.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available The development of axonal arbors is a critical step in the establishment of precise neural circuits, but relatively little is known about the mechanisms of axonal elaboration in the neocortex. We used in vivo two-photon time-lapse microscopy to image axons in the neocortex of green fluorescent protein-transgenic mice over the first 3 wk of postnatal development. This period spans the elaboration of thalamocortical (TC and Cajal-Retzius (CR axons and cortical synaptogenesis. Layer 1 collaterals of TC and CR axons were imaged repeatedly over time scales ranging from minutes up to days, and their growth and pruning were analyzed. The structure and dynamics of TC and CR axons differed profoundly. Branches of TC axons terminated in small, bulbous growth cones, while CR axon branch tips had large growth cones with numerous long filopodia. TC axons grew rapidly in straight paths, with frequent interstitial branch additions, while CR axons grew more slowly along tortuous paths. For both types of axon, new branches appeared at interstitial sites along the axon shaft and did not involve growth cone splitting. Pruning occurred via retraction of small axon branches (tens of microns, at both CR and TC axons or degeneration of large portions of the arbor (hundreds of microns, for TC axons only. The balance between growth and retraction favored overall growth, but only by a slight margin. Given the identical layer 1 territory upon which CR and TC axons grow, the differences in their structure and dynamics likely reflect distinct intrinsic growth programs for axons of long projection neurons versus local interneurons.

  20. Automated Axon Counting in Rodent Optic Nerve Sections with AxonJ

    Science.gov (United States)

    Zarei, Kasra; Scheetz, Todd E.; Christopher, Mark; Miller, Kathy; Hedberg-Buenz, Adam; Tandon, Anamika; Anderson, Michael G.; Fingert, John H.; Abràmoff, Michael David

    2016-01-01

    We have developed a publicly available tool, AxonJ, which quantifies the axons in optic nerve sections of rodents stained with paraphenylenediamine (PPD). In this study, we compare AxonJ’s performance to human experts on 100x and 40x images of optic nerve sections obtained from multiple strains of mice, including mice with defects relevant to glaucoma. AxonJ produced reliable axon counts with high sensitivity of 0.959 and high precision of 0.907, high repeatability of 0.95 when compared to a gold-standard of manual assessments and high correlation of 0.882 to the glaucoma damage staging of a previously published dataset. AxonJ allows analyses that are quantitative, consistent, fully-automated, parameter-free, and rapid on whole optic nerve sections at 40x. As a freely available ImageJ plugin that requires no highly specialized equipment to utilize, AxonJ represents a powerful new community resource augmenting studies of the optic nerve using mice. PMID:27226405

  1. Axonal transport of ribonucleoprotein particles (vaults).

    Science.gov (United States)

    Li, J Y; Volknandt, W; Dahlstrom, A; Herrmann, C; Blasi, J; Das, B; Zimmermann, H

    1999-01-01

    RNA was previously shown to be transported into both dendritic and axonal compartments of nerve cells, presumably involving a ribonucleoprotein particle. In order to reveal potential mechanisms of transport we investigated the axonal transport of the major vault protein of the electric ray Torpedo marmorata. This protein is the major protein component of a ribonucleoprotein particle (vault) carrying a non-translatable RNA and has a wide distribution in the animal kingdom. It is highly enriched in the cholinergic electromotor neurons and similar in size to synaptic vesicles. The axonal transport of vaults was investigated by immunofluorescence, using the anti-vault protein antibody as marker, and cytofluorimetric scanning, and was compared to that of the synaptic vesicle membrane protein SV2 and of the beta-subunit of the F1-ATPase as a marker for mitochondria. Following a crush significant axonal accumulation of SV2 proximal to the crush could first be observed after 1 h, that of mitochondria after 3 h and that of vaults after 6 h, although weekly fluorescent traces of accumulations of vault protein were observed in the confocal microscope as early as 3 h. Within the time-period investigated (up to 72 h) the accumulation of all markers increased continuously. Retrograde accumulations also occurred, and the immunofluorescence for the retrograde component, indicating recycling, was weaker than that for the anterograde component, suggesting that more than half of the vaults are degraded within the nerve terminal. High resolution immunofluorescence revealed a granular structure-in accordance with the biochemical characteristics of vaults. Of interest was the observation that the increase of vault immunoreactivity proximal to the crush accelerated with time after crushing, while that of SV2-containing particles appeared to decelerate, indicating that the crush procedure with time may have induced perikaryal alterations in the production and subsequent export to the axon

  2. MSC p43 required for axonal development in motor neurons

    Science.gov (United States)

    Zhu, Xiaodong; Liu, Yang; Yin, Yanqing; Shao, Aiyun; Zhang, Bo; Kim, Sunghoon; Zhou, Jiawei

    2009-01-01

    Neuron connectivity and correct neural function largely depend on axonal integrity. Neurofilaments (NFs) constitute the main cytoskeletal network maintaining the structural integrity of neurons and exhibit dynamic changes during axonal and dendritic growth. However, the mechanisms underlying axonal development and maintenance remain poorly understood. Here, we identify that multisynthetase complex p43 (MSC p43) is essential for NF assembly and axon maintenance. The MSC p43 protein was predominantly expressed in central neurons and interacted with NF light subunit in vivo. Mice lacking MSC p43 exhibited axon degeneration in motor neurons, defective neuromuscular junctions, muscular atrophy, and motor dysfunction. Furthermore, MSC p43 depletion in mice caused disorganization of the axonal NF network. Mechanistically, MSC p43 is required for maintaining normal phosphorylation levels of NFs. Thus, MSC p43 is indispensable in maintaining axonal integrity. Its dysfunction may underlie the NF disorganization and axon degeneration associated with motor neuron degenerative diseases. PMID:19717447

  3. Eliciting Spill: A methodological note

    Directory of Open Access Journals (Sweden)

    Alvita Nathaniel, Ph.D.

    2008-03-01

    Full Text Available Classic grounded theory is an inductive process that focuses on the experiences and perceptions of research participants (Glaser, 1978, 1998. Although grounded theorists may utilize other types of data, most are likely to gather information through qualitative interviews. The theorist seeks to understand what is going on as people resolve their main concern in a given substantive area. People know what is important to them and most want to tell their stories. They feel encouraged to talk when they recognize that their stories are valued. Once the informant realizes that he or she is being heard, the story flows. This is what Glaser refers to as “spill.” When this occurs, the theorist becomes a vessel to receive the story. As Glaser describes it, “The researcher will become a ‘big ear’ to pour into incessantly” (1998, p. 124. But, as easy as this seems, the researcher must overcome certain positivist tendencies to allow this to happen. Rather than asking a list of pre-planned questions, the grounded theorist will try to develop one question that will trigger the telling of a story. Eliciting spill requires a deliberate process that employs a deep understanding of the fundamentals of classic grounded theory. Derived from Glaser’s writings, the following are suggestions intended to help the novice grounded theorist to elicit spill.

  4. Plastic Fishes

    CERN Multimedia

    Trettnak, Wolfgang

    2015-01-01

    In terms of weight, the plastic pollution in the world’s oceans is estimated to be around 300,000 tonnes. This plastic comes from both land-based and ocean-based sources. A lecture at CERN by chemist Wolfgang Trettnak addressed this issue and highlighted the role of art in raising people’s awareness. The slideshow below gives you a taste of the artworks by Wolfgang Trettnak and Margarita Cimadevila.

  5. Functions of axon guidance molecules in synapse formation

    OpenAIRE

    Chen, Shih-Yu; Cheng, Hwai-Jong

    2009-01-01

    Axon guidance and synapse formation are important developmental events for establishing a functional neuronal circuitry. These two related cellular processes occur in a coordinated fashion but previous studies from multiple model organisms seemed to suggest that axon guidance and synapse formation are mediated by distinct molecular cues. Thus, axon guidance molecules are responsible for guiding the navigating axon toward its target area, while other adhesion or ligand-receptor molecules speci...

  6. Impaired Axonal Na(+) Current by Hindlimb Unloading: Implication for Disuse Neuromuscular Atrophy.

    Science.gov (United States)

    Banzrai, Chimeglkham; Nodera, Hiroyuki; Kawarai, Toshitaka; Higashi, Saki; Okada, Ryo; Mori, Atsuko; Shimatani, Yoshimitsu; Osaki, Yusuke; Kaji, Ryuji

    2016-01-01

    This study aimed to characterize the excitability changes in peripheral motor axons caused by hindlimb unloading (HLU), which is a model of disuse neuromuscular atrophy. HLU was performed in normal 8-week-old male mice by fixing the proximal tail by a clip connected to the top of the animal's cage for 3 weeks. Axonal excitability studies were performed by stimulating the sciatic nerve at the ankle and recording the compound muscle action potential (CMAP) from the foot. The amplitudes of the motor responses of the unloading group were 51% of the control amplitudes [2.2 ± 1.3 mV (HLU) vs. 4.3 ± 1.2 mV (Control), P = 0.03]. Multiple axonal excitability analysis showed that the unloading group had a smaller strength-duration time constant (SDTC) and late subexcitability (recovery cycle) than the controls [0.075 ± 0.01 (HLU) vs. 0.12 ± 0.01 (Control), P < 0.01; 5.4 ± 1.0 (HLU) vs. 10.0 ± 1.3 % (Control), P = 0.01, respectively]. Three weeks after releasing from HLU, the SDTC became comparable to the control range. Using a modeling study, the observed differences in the waveforms could be explained by reduced persistent Na(+) currents along with parameters related to current leakage. Quantification of RNA of a SCA1A gene coding a voltage-gated Na(+) channel tended to be decreased in the sciatic nerve in HLU. The present study suggested that axonal ion currents are altered in vivo by HLU. It is still undetermined whether the dysfunctional axonal ion currents have any pathogenicity on neuromuscular atrophy or are the results of neural plasticity by atrophy. PMID:26909041

  7. Depletion of endogenous noradrenaline does not prevent spinal cord plasticity following peripheral nerve injury

    OpenAIRE

    Hayashida, Ken-ichiro; Peters, Christopher M.; Gutierrez, Silvia; Eisenach, James C.

    2011-01-01

    The present study examined the role of endogenous noradrenaline on glial and neuronal plasticity in the spinal cord in rats after peripheral nerve injury. An intrathecal injection of dopamine-β-hydroxylase antibody conjugated to saporin (DβH-saporin) completely depleted noradrenergic axons in the spinal cord and also reduced noradrenergic neurons in the locus coeruleus (A6) and A5 noradrenergic nucleus in the brainstem and noradrenergic axons in the paraventricular nucleus of the hypothalamus...

  8. Sugar-Dependent Modulation of Neuronal Development, Regeneration, and Plasticity by Chondroitin Sulfate Proteoglycans

    OpenAIRE

    Miller, Gregory M.; Hsieh-Wilson, Linda C.

    2015-01-01

    Chondroitin sulfate proteoglycans (CSPGs) play important roles in the developing and mature nervous system, where they guide axons, maintain stable connections, restrict synaptic plasticity, and prevent axon regeneration following CNS injury. The chondroitin sulfate glycosaminoglycan (CS GAG) chains that decorate CSPGs are essential for their functions. Through these sugar chains, CSPGs are able to bind and regulate the activity of a diverse range of proteins. CSPGs have been found both to pr...

  9. Morphometry of Axons in Optic Nerves of Siamese's Twins

    Institute of Scientific and Technical Information of China (English)

    Xinzu Gu; Zhenping Zhang; Qi Lin; Jiongji Liang; Wenyu Lu; Xiulan Ye; A A Sadun

    2002-01-01

    Purpose: To observe the development of optic nerve, we examined four optic nerves from Siameses Twins by absolute counts of axons.Methods: Mean axon diameter, mean axon density, totally axonal population and optic nerve area were noted for each optic nerve. The mean axon diameter and the mean axon density were compared between paraxial (inner sectors)and cortical (outer sectors)areas of the nerves.Results: More myelinated axons were seen in the inner sectors as compared to the outer sectors(average 11 axons/1 000 μm2 in inner sectors and 34 axons/l 000 μm2 in outer sectors( P=0. 036) . The myelinated fibers were also smaller(63 microns) in the outer sectors as compared to the inner sectors(72 microns) ( P = 0. 001 ). The average cross sectors area for the four 40 week stage optical nerves of Siamese Twins was 3.32 × 103 as compared to 1 million axons for 32-week-old normals.Conclusion: Our finding of fewer axonal number and small myelinated fibers in the Siamese Twins suggests hypoplasia. Myelination was more abnormal in the paraxial optic nerve than that in the peripheral sectors, suggesting anomalous development of optic nerve peripherally and delayed developnent centrally. Axonal density is higher in inner sectors than that in outer sectors, suggesting delayed development of the outer nerve sector.

  10. Electrokinetic confinement of axonal growth for dynamically configurable neural networks.

    Science.gov (United States)

    Honegger, Thibault; Scott, Mark A; Yanik, Mehmet F; Voldman, Joel

    2013-02-21

    Axons in the developing nervous system are directed via guidance cues, whose expression varies both spatially and temporally, to create functional neural circuits. Existing methods to create patterns of neural connectivity in vitro use only static geometries, and are unable to dynamically alter the guidance cues imparted on the cells. We introduce the use of AC electrokinetics to dynamically control axonal growth in cultured rat hippocampal neurons. We find that the application of modest voltages at frequencies on the order of 10(5) Hz can cause developing axons to be stopped adjacent to the electrodes while axons away from the electric fields exhibit uninhibited growth. By switching electrodes on or off, we can reversibly inhibit or permit axon passage across the electrodes. Our models suggest that dielectrophoresis is the causative AC electrokinetic effect. We make use of our dynamic control over axon elongation to create an axon-diode via an axon-lock system that consists of a pair of electrode 'gates' that either permit or prevent axons from passing through. Finally, we developed a neural circuit consisting of three populations of neurons, separated by three axon-locks to demonstrate the assembly of a functional, engineered neural network. Action potential recordings demonstrate that the AC electrokinetic effect does not harm axons, and Ca(2+) imaging demonstrated the unidirectional nature of the synaptic connections. AC electrokinetic confinement of axonal growth has potential for creating configurable, directional neural networks. PMID:23314575

  11. Spatial temperature gradients guide axonal outgrowth

    Science.gov (United States)

    Black, Bryan; Vishwakarma, Vivek; Dhakal, Kamal; Bhattarai, Samik; Pradhan, Prabhakar; Jain, Ankur; Kim, Young-Tae; Mohanty, Samarendra

    2016-07-01

    Formation of neural networks during development and regeneration after injury depends on accuracy of axonal pathfinding, which is primarily believed to be influenced by chemical cues. Recently, there is growing evidence that physical cues can play crucial role in axonal guidance. However, detailed mechanism involved in such guidance cues is lacking. By using weakly-focused near-infrared continuous wave (CW) laser microbeam in the path of an advancing axon, we discovered that the beam acts as a repulsive guidance cue. Here, we report that this highly-effective at-a-distance guidance is the result of a temperature field produced by the near-infrared laser light absorption. Since light absorption by extracellular medium increases when the laser wavelength was red shifted, the threshold laser power for reliable guidance was significantly lower in the near-infrared as compared to the visible spectrum. The spatial temperature gradient caused by the near-infrared laser beam at-a-distance was found to activate temperature-sensitive membrane receptors, resulting in an influx of calcium. The repulsive guidance effect was significantly reduced when extracellular calcium was depleted or in the presence of TRPV1-antagonist. Further, direct heating using micro-heater confirmed that the axonal guidance is caused by shallow temperature-gradient, eliminating the role of any non-photothermal effects.

  12. Axonal PPARγ promotes neuronal regeneration after injury.

    Science.gov (United States)

    Lezana, Juan Pablo; Dagan, Shachar Y; Robinson, Ari; Goldstein, Ronald S; Fainzilber, Mike; Bronfman, Francisca C; Bronfman, Miguel

    2016-06-01

    PPARγ is a ligand-activated nuclear receptor best known for its involvement in adipogenesis and glucose homeostasis. PPARγ activity has also been associated with neuroprotection in different neurological disorders, but the mechanisms involved in PPARγ effects in the nervous system are still unknown. Here we describe a new functional role for PPARγ in neuronal responses to injury. We found both PPAR transcripts and protein within sensory axons and observed an increase in PPARγ protein levels after sciatic nerve crush. This was correlated with increased retrograde transport of PPARγ after injury, increased association of PPARγ with the molecular motor dynein, and increased nuclear accumulation of PPARγ in cell bodies of sensory neurons. Furthermore, PPARγ antagonists attenuated the response of sensory neurons to sciatic nerve injury, and inhibited axonal growth of both sensory and cortical neurons in culture. Thus, axonal PPARγ is involved in neuronal injury responses required for axonal regeneration. Since PPARγ is a major molecular target of the thiazolidinedione (TZD) class of drugs used in the treatment of type II diabetes, several pharmaceutical agents with acceptable safety profiles in humans are available. Our findings provide motivation and rationale for the evaluation of such agents for efficacy in central and peripheral nerve injuries. PMID:26446277

  13. Early cellular signaling responses to axonal injury

    Directory of Open Access Journals (Sweden)

    Wang Ai

    2009-03-01

    Full Text Available Abstract Background We have used optic nerve injury as a model to study early signaling events in neuronal tissue following axonal injury. Optic nerve injury results in the selective death of retinal ganglion cells (RGCs. The time course of cell death takes place over a period of days with the earliest detection of RGC death at about 48 hr post injury. We hypothesized that in the period immediately following axonal injury, there are changes in the soma that signal surrounding glia and neurons and that start programmed cell death. In the current study, we investigated early changes in cellular signaling and gene expression that occur within the first 6 hrs post optic nerve injury. Results We found evidence of cell to cell signaling within 30 min of axonal injury. We detected differences in phosphoproteins and gene expression within the 6 hrs time period. Activation of TNFα and glutamate receptors, two pathways that can initiate cell death, begins in RGCs within 6 hrs following axonal injury. Differential gene expression at 6 hrs post injury included genes involved in cytokine, neurotrophic factor signaling (Socs3 and apoptosis (Bax. Conclusion We interpret our studies to indicate that both neurons and glia in the retina have been signaled within 30 min after optic nerve injury. The signals are probably initiated by the RGC soma. In addition, signals activating cellular death pathways occur within 6 hrs of injury, which likely lead to RGC degeneration.

  14. Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-Convergence on axonal guidance

    DEFF Research Database (Denmark)

    Kaalund, Sanne Simone; Venø, Morten T; Bak, Mads;

    2014-01-01

    . Moreover, miR-204 and miR-218 showed strong changes in expression during fetal development of the hippocampus in pigs, and we identified four target genes, involved in axonal guidance and synaptic plasticity, ROBO1, GRM1, SLC1A2, and GNAI2, as bona fide targets of miR-218. GRM1 was also shown to be a...

  15. Patterns of growth, axonal extension and axonal arborization of neuronal lineages in the developing Drosophila brain

    OpenAIRE

    Larsen, Camilla; Shy, Diana; Spindler, Shana R; Fung, Siaumin; Pereanu, Wayne; Younossi -Hartenstein, Amelia; Hartenstein, Volker

    2009-01-01

    The Drosophila central brain is composed of approximately 100 paired lineages, with most lineages comprising 100–150 neurons. Most lineages have a number of important characteristics in common. Typically, neurons of a lineage stay together as a coherent cluster and project their axons into a coherent bundle visible from late embryo to adult. Neurons born during the embryonic period form the primary axon tracts (PATs) that follow stereotyped pathways in the neuropile. Apoptotic cell death remo...

  16. White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis

    Science.gov (United States)

    Cambron, Melissa; D'Haeseleer, Miguel; Laureys, Guy; Clinckers, Ralph; Debruyne, Jan; De Keyser, Jacques

    2012-01-01

    In patients with multiple sclerosis (MS), a diffuse axonal degeneration occurring throughout the white matter of the central nervous system causes progressive neurologic disability. The underlying mechanism is unclear. This review describes a number of pathways by which dysfunctional astrocytes in MS might lead to axonal degeneration. White-matter astrocytes in MS show a reduced metabolism of adenosine triphosphate-generating phosphocreatine, which may impair the astrocytic sodium potassium pump and lead to a reduced sodium-dependent glutamate uptake. Astrocytes in MS white matter appear to be deficient in β2 adrenergic receptors, which are involved in stimulating glycogenolysis and suppressing inducible nitric oxide synthase (NOS2). Glutamate toxicity, reduced astrocytic glycogenolysis leading to reduced lactate and glutamine production, and enhanced nitric oxide (NO) levels may all impair axonal mitochondrial metabolism, leading to axonal degeneration. In addition, glutamate-mediated oligodendrocyte damage and impaired myelination caused by a decreased production of N-acetylaspartate by axonal mitochondria might also contribute to axonal loss. White-matter astrocytes may be considered as a potential target for neuroprotective MS therapies. PMID:22214904

  17. Mislocalization of neuronal mitochondria reveals regulation of Wallerian degeneration and NMNAT/WLDS-mediated axon protection independent of axonal mitochondria

    OpenAIRE

    Kitay, Brandon M.; McCormack, Ryan; Wang, Yunfang; Tsoulfas, Pantelis; Zhai, R. Grace

    2013-01-01

    Axon degeneration is a common and often early feature of neurodegeneration that correlates with the clinical manifestations and progression of neurological disease. Nicotinamide mononucleotide adenylytransferase (NMNAT) is a neuroprotective factor that delays axon degeneration following injury and in models of neurodegenerative diseases suggesting a converging molecular pathway of axon self-destruction. The underlying mechanisms have been under intense investigation and recent reports suggest...

  18. AxonQuant: A Microfluidic Chamber Culture-Coupled Algorithm That Allows High-Throughput Quantification of Axonal Damage

    Directory of Open Access Journals (Sweden)

    Yang Li

    2014-02-01

    Full Text Available Published methods for imaging and quantitatively analyzing morphological changes in neuronal axons have serious limitations because of their small sample sizes, and their time-consuming and nonobjective nature. Here we present an improved microfluidic chamber design suitable for fast and high-throughput imaging of neuronal axons. We developed the AxonQuant algorithm, which is suitable for automatic processing of axonal imaging data. This microfluidic chamber-coupled algorithm allows calculation of an ‘axonal continuity index' that quantitatively measures axonal health status in a manner independent of neuronal or axonal density. This method allows quantitative analysis of axonal morphology in an automatic and nonbiased manner. Our method will facilitate large-scale high-throughput screening for genes or therapeutic compounds for neurodegenerative diseases involving axonal damage. When combined with imaging technologies utilizing different gene markers, this method will provide new insights into the mechanistic basis for axon degeneration. Our microfluidic chamber culture-coupled AxonQuant algorithm will be widely useful for studying axonal biology and neurodegenerative disorders. © 2014 S. Karger AG, Basel

  19. A Novel and Efficient Gene Transfer Strategy Reduces Glial Reactivity and Improves Neuronal Survival and Axonal Growth In Vitro

    OpenAIRE

    Mathieu Desclaux; Marisa Teigell; Lahouari Amar; Roland Vogel; Minerva Gimenez Y Ribotta; Alain Privat; Jacques Mallet

    2009-01-01

    Background: The lack of axonal regeneration in the central nervous system is attributed among other factors to the formation of a glial scar. This cellular structure is mainly composed of reactive astrocytes that overexpress two intermediate filament proteins, the glial fibrillary acidic protein (GFAP) and vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin were shown to be the substrate for increased neuronal plasticity. Moreover, double knockout mice lacking both G...

  20. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

    Science.gov (United States)

    Crago, Patrick E.; Makowski, Nathaniel S.

    2014-10-01

    Objective. Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main results. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic

  1. Oxidative stress inhibits axonal transport: implications for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Fang Cheng

    2012-06-01

    Full Text Available Abstract Background Reactive oxygen species (ROS released by microglia and other inflammatory cells can cause axonal degeneration. A reduction in axonal transport has also been implicated as a cause of axonal dystrophies and neurodegeneration, but there is a paucity of experimental data concerning the effects of ROS on axonal transport. We used live cell imaging to examine the effects of hydrogen peroxide on the axonal transport of mitochondria and Golgi-derived vesicles in cultured rat hippocampal neurons. Results Hydrogen peroxide rapidly inhibited axonal transport, hours before any detectable changes in mitochondrial morphology or signs of axonal degeneration. Mitochondrial transport was affected earlier and was more severely inhibited than the transport of Golgi-derived vesicles. Anterograde vesicle transport was more susceptible to peroxide inhibition than retrograde transport. Axonal transport partially recovered following removal of hydrogen peroxide and local application of hydrogen peroxide inhibited transport, suggesting that the effects were not simply a result of nerve cell death. Sodium azide, an ATP synthesis blocker, had similar effects on axonal transport, suggesting that ATP depletion may contribute to the transport inhibition due to hydrogen peroxide. Conclusions These results indicate that inhibition of axonal transport is an early consequence of exposure to ROS and may contribute to subsequent axonal degeneration.

  2. Axon Membrane Skeleton Structure is Optimized for Coordinated Sodium Propagation

    CERN Document Server

    Zhang, Yihao; Li, He; Tzingounis, Anastasios V; Lykotrafitis, George

    2016-01-01

    Axons transmit action potentials with high fidelity and minimal jitter. This unique capability is likely the result of the spatiotemporal arrangement of sodium channels along the axon. Super-resolution microscopy recently revealed that the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under entropic tension. Sodium channels also exhibit a periodic distribution pattern, as they bind to ankyrin G, which associates with spectrin. Here, we elucidate the relationship between the axon membrane skeleton structure and the function of the axon. By combining cytoskeletal dynamics and continuum diffusion modeling, we show that spectrin filaments under tension minimize the thermal fluctuations of sodium channels and prevent overlap of neighboring channel trajectories. Importantly, this axon skeletal arrangement allows for a highly reproducible band-like activation of sodium channels leading to coordinated sodium propagation along the axon.

  3. Axon position within the corpus callosum determines contralateral cortical projection.

    Science.gov (United States)

    Zhou, Jing; Wen, Yunqing; She, Liang; Sui, Ya-Nan; Liu, Lu; Richards, Linda J; Poo, Mu-Ming

    2013-07-16

    How developing axons in the corpus callosum (CC) achieve their homotopic projection to the contralateral cortex remains unclear. We found that axonal position within the CC plays a critical role in this projection. Labeling of nearby callosal axons in mice showed that callosal axons were segregated in an orderly fashion, with those from more medial cerebral cortex located more dorsally and subsequently projecting to more medial contralateral cortical regions. The normal axonal order within the CC was grossly disturbed when semaphorin3A/neuropilin-1 signaling was disrupted. However, the order in which axons were positioned within the CC still determined their contralateral projection, causing a severe disruption of the homotopic contralateral projection that persisted at postnatal day 30, when the normal developmental refinement of contralateral projections is completed in wild-type (WT) mice. Thus, the orderly positioning of axons within the CC is a primary determinant of how homotopic interhemispheric projections form in the contralateral cortex. PMID:23812756

  4. Mixed plastics recycling technology

    CERN Document Server

    Hegberg, Bruce

    1995-01-01

    Presents an overview of mixed plastics recycling technology. In addition, it characterizes mixed plastics wastes and describes collection methods, costs, and markets for reprocessed plastics products.

  5. Cosmetic Plastic Surgery Statistics

    Science.gov (United States)

    2014 Cosmetic Plastic Surgery Statistics Cosmetic Procedure Trends 2014 Plastic Surgery Statistics Report Please credit the AMERICAN SOCIETY OF PLASTIC SURGEONS when citing statistical data or using ...

  6. Plastic fish

    CERN Multimedia

    Antonella Del Rosso

    2015-01-01

    In terms of weight, the plastic pollution in the world’s oceans is estimated to be around 300,000 tonnes. This plastic comes from both land-based and ocean-based sources. A lecture at CERN by chemist Wolfgang Trettnak addressed this issue and highlighted the role of art in raising people’s awareness.   Artwork by Wolfgang Trettnak. Packaging materials, consumer goods (shoes, kids’ toys, etc.), leftovers from fishing and aquaculture activities… our oceans and beaches are full of plastic litter. Most of the debris from beaches is plastic bottles. “PET bottles have high durability and stability,” explains Wolfgang Trettnak, a chemist by education and artist from Austria, who gave a lecture on this topic organised by the Staff Association at CERN on 26 May. “PET degrades very slowly and the estimated lifetime of a bottle is 450 years.” In addition to the beach litter accumulated from human use, rivers bring several ki...

  7. Synaptic Democracy and Vesicular Transport in Axons

    Science.gov (United States)

    Bressloff, Paul C.; Levien, Ethan

    2015-04-01

    Synaptic democracy concerns the general problem of how regions of an axon or dendrite far from the cell body (soma) of a neuron can play an effective role in neuronal function. For example, stimulated synapses far from the soma are unlikely to influence the firing of a neuron unless some sort of active dendritic processing occurs. Analogously, the motor-driven transport of newly synthesized proteins from the soma to presynaptic targets along the axon tends to favor the delivery of resources to proximal synapses. Both of these phenomena reflect fundamental limitations of transport processes based on a localized source. In this Letter, we show that a more democratic distribution of proteins along an axon can be achieved by making the transport process less efficient. This involves two components: bidirectional or "stop-and-go" motor transport (which can be modeled in terms of advection-diffusion), and reversible interactions between motor-cargo complexes and synaptic targets. Both of these features have recently been observed experimentally. Our model suggests that, just as in human societies, there needs to be a balance between "efficiency" and "equality".

  8. Mesencephalic stimulation elicits inhibition of phrenic nerve activity in cat.

    Science.gov (United States)

    Gallman, E A; Lawing, W L; Millhorn, D E

    1991-05-01

    1. Previous work from this laboratory has indicated that the mesencephalon is the anatomical substrate for a mechanism capable of inhibiting central respiratory drive in glomectomized cats for periods of up to 1 h or more following brief exposure to systemic hypoxia; phrenic nerve activity was used as an index of central respiratory drive. 2. The present study was undertaken to further localize the region responsible for the observed post-hypoxic inhibition of respiratory drive. We studied the phrenic nerve response to stimulations of the mesencephalon in anaesthetized, paralysed peripherally chemo-denervated cats with end-expired PCO2 and body temperature servo-controlled. 3. Stimulations of two types were employed. Electrical stimulation allowed rapid determination of sites from which phrenic inhibition could be elicited. Microinjections of excitatory amino acids were used subsequently in order to confine excitation to neuronal cell bodies and not axons of passage. 4. Stimulation of discrete regions of the ventromedial aspect of the mesencephalon in the vicinity of the red nucleus produced substantial inhibition of phrenic activity which lasted up to 45 min. Stimulation of other areas of the mesencephalon either produced no phrenic inhibition or resulted in a slight stimulation of phrenic activity. 5. The results are discussed in the context of the central respiratory response to hypoxia. PMID:1676420

  9. Requirements Elicitation Problems: A Literature Analysis

    Directory of Open Access Journals (Sweden)

    Bill Davey

    2015-06-01

    Full Text Available Requirements elicitation is the process through which analysts determine the software requirements of stakeholders. Requirements elicitation is seldom well done, and an inaccurate or incomplete understanding of user requirements has led to the downfall of many software projects. This paper proposes a classification of problem types that occur in requirements elicitation. The classification has been derived from a literature analysis. Papers reporting on techniques for improving requirements elicitation practice were examined for the problem the technique was designed to address. In each classification the most recent or prominent techniques for ameliorating the problems are presented. The classification allows the requirements engineer to be sensitive to problems as they arise and the educator to structure delivery of requirements elicitation training.

  10. Plastic bronchitis

    Directory of Open Access Journals (Sweden)

    Anil Kumar Singhi

    2015-01-01

    Full Text Available Plastic bronchitis, a rare but serious clinical condition, commonly seen after Fontan surgeries in children, may be a manifestation of suboptimal adaptation to the cavopulmonary circulation with unfavorable hemodynamics. They are ominous with poor prognosis. Sometimes, infection or airway reactivity may provoke cast bronchitis as a two-step insult on a vulnerable vascular bed. In such instances, aggressive management leads to longer survival. This report of cast bronchitis discusses its current understanding.

  11. Plastic bronchitis

    OpenAIRE

    Anil Kumar Singhi; Bharathi Vinoth; Sarah Kuruvilla; Kothandam Sivakumar

    2015-01-01

    Plastic bronchitis, a rare but serious clinical condition, commonly seen after Fontan surgeries in children, may be a manifestation of suboptimal adaptation to the cavopulmonary circulation with unfavorable hemodynamics. They are ominous with poor prognosis. Sometimes, infection or airway reactivity may provoke cast bronchitis as a two-step insult on a vulnerable vascular bed. In such instances, aggressive management leads to longer survival. This report of cast bronchitis discusses its curre...

  12. Focal axonal swellings and associated ultrastructural changes attenuate conduction velocity in central nervous system axons: a computer modeling study.

    Science.gov (United States)

    Kolaric, Katarina V; Thomson, Gemma; Edgar, Julia M; Brown, Angus M

    2013-08-01

    The constancy of action potential conduction in the central nervous system (CNS) relies on uniform axon diameter coupled with fidelity of the overlying myelin providing high-resistance, low capacitance insulation. Whereas the effects of demyelination on conduction have been extensively studied/modeled, equivalent studies on the repercussions for conduction of axon swelling, a common early pathological feature of (potentially reversible) axonal injury, are lacking. The recent description of experimentally acquired morphological and electrical properties of small CNS axons and oligodendrocytes prompted us to incorporate these data into a computer model, with the aim of simulating the effects of focal axon swelling on action potential conduction. A single swelling on an otherwise intact axon, as occurs in optic nerve axons of Cnp1 null mice caused a small decrease in conduction velocity. The presence of single swellings on multiple contiguous internodal regions (INR), as likely occurs in advanced disease, caused qualitatively similar results, except the dimensions of the swellings required to produce equivalent attenuation of conduction were significantly decreased. Our simulations of the consequences of metabolic insult to axons, namely, the appearance of multiple swollen regions, accompanied by perturbation of overlying myelin and increased axolemmal permeability, contained within a single INR, revealed that conduction block occurred when the dimensions of the simulated swellings were within the limits of those measured experimentally, suggesting that multiple swellings on a single axon could contribute to axonal dysfunction, and that increased axolemmal permeability is the decisive factor that promotes conduction block. PMID:24303138

  13. Early ultrastructural defects of axons and axon-glia junctions in mice lacking expression of Cnp1.

    Science.gov (United States)

    Edgar, Julia M; McLaughlin, Mark; Werner, Hauke B; McCulloch, Mailis C; Barrie, Jennifer A; Brown, Angus; Faichney, Andrew Blyth; Snaidero, Nicolas; Nave, Klaus-Armin; Griffiths, Ian R

    2009-12-01

    Most axons in the central nervous system (CNS) are surrounded by a multilayered myelin sheath that promotes fast, saltatory conduction of electrical impulses. By insulating the axon, myelin also shields the axoplasm from the extracellular milieu. In the CNS, oligodendrocytes provide support for the long-term maintenance of myelinated axons, independent of the myelin sheath. Here, we use electron microscopy and morphometric analyses to examine the evolution of axonal and oligodendroglial changes in mice deficient in 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and in mice deficient in both CNP and proteolipid protein (PLP/DM20). We show that CNP is necessary for the formation of a normal inner tongue process of oligodendrocytes that myelinate small diameter axons. We also show that axonal degeneration in Cnp1 null mice is present very early in postnatal life. Importantly, compact myelin formed by transplanted Cnp1 null oligodendrocytes induces the same degenerative changes in shiverer axons that normally are dysmyelinated but structurally intact. Mice deficient in both CNP and PLP develop a more severe axonal phenotype than either single mutant, indicating that the two oligodendroglial proteins serve distinct functions in supporting the myelinated axon. These observations support a model in which the trophic functions of oligodendrocytes serve to offset the physical shielding of axons by myelin membranes. PMID:19459211

  14. A comparative quantitative assessment of axonal and dendritic mRNA transport in maturing hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Gunja K Pathak

    Full Text Available Translation of mRNA in axons and dendrites enables a rapid supply of proteins to specific sites of localization within the neuron. Distinct mRNA-containing cargoes, including granules and mitochondrial mRNA, are transported within neuronal projections. The distributions of these cargoes appear to change during neuronal development, but details on the dynamics of mRNA transport during these transitions remain to be elucidated. For this study, we have developed imaging and image processing methods to quantify several transport parameters that can define the dynamics of RNA transport and localization. Using these methods, we characterized the transport of mitochondrial and non-mitochondrial mRNA in differentiated axons and dendrites of cultured hippocampal neurons varying in developmental maturity. Our results suggest differences in the transport profiles of mitochondrial and non-mitochondrial mRNA, and differences in transport parameters at different time points, and between axons and dendrites. Furthermore, within the non-mitochondrial mRNA pool, we observed two distinct populations that differed in their fluorescence intensity and velocity. The net axonal velocity of the brighter pool was highest at day 7 (0.002±0.001 µm/s, mean ± SEM, raising the possibility of a presynaptic requirement for mRNA during early stages of synapse formation. In contrast, the net dendritic velocity of the brighter pool increased steadily as neurons matured, with a significant difference between day 12 (0.0013±0.0006 µm/s and day 4 (-0.003±0.001 µm/s suggesting a postsynaptic role for mRNAs in more mature neurons. The dim population showed similar trends, though velocities were two orders of magnitude higher than of the bright particles. This study provides a baseline for further studies on mRNA transport, and has important implications for the regulation of neuronal plasticity during neuronal development and in response to neuronal injury.

  15. Dynamics of axon fasciculation in the presence of neuronal turnover

    CERN Document Server

    Chaudhuri, Debasish; Mohanty, P K; Zapotocky, Martin

    2008-01-01

    We formulate and characterize a model aiming to describe the formation of fascicles of axons mediated by contact axon-axon interactions. The growing axons are represented as interacting directed random walks in two spatial dimensions. To mimic axonal turnover in the mammalian olfactory system, the random walkers are injected and removed at specified rates. In the dynamical steady state, the position-dependent distribution of fascicle sizes obeys a scaling law. We identify several distinct time scales that emerge from the dynamics, are sensitive functions of the microscopic parameters of the model, and can exceed the average axonal lifetime by orders of magnitude. We discuss our findings in terms of an analytically tractable, effective model of fascicle dynamics.

  16. Axonal Protein Synthesis and the Regulation of Local Mitochondrial Function

    OpenAIRE

    2009-01-01

    Axons and presynaptic nerve terminals of both invertebrate and mammalian SCG neurons contain a heterogeneous population of nuclear-encoded mitochondrial mRNAs and a local cytosolic protein synthetic system. Nearly one quarter of the total protein synthesized in these structural/functional domains of the neuron is destined for mitochondria. Acute inhibition of axonal protein synthesis markedly reduces the functional activity of mitochondria. The blockade of axonal protein into mitochondria had...

  17. Axonal protein synthesis and the regulation of local mitochondrial function

    OpenAIRE

    Kaplan, B.B.; Gioio, A.E.; Hillefors, M.; Aschrafi, A.

    2009-01-01

    Axons and presynaptic nerve terminals of both invertebrate and mammalian SCG neurons contain a heterogeneous population of nuclear-encoded mitochondrial mRNAs and a local cytosolic protein synthetic system. Nearly one quarter of the total protein synthesized in these structural/functional domains of the neuron is destined for mitochondria. Acute inhibition of axonal protein synthesis markedly reduces the functional activity of mitochondria. The blockade of axonal protein into mitochondria had...

  18. Action potentials reliably invade axonal arbors of rat neocortical neurons

    OpenAIRE

    Cox, Charles L.; Denk, Winfried; Tank, David W.; Svoboda, Karel

    2000-01-01

    Neocortical pyramidal neurons have extensive axonal arborizations that make thousands of synapses. Action potentials can invade these arbors and cause calcium influx that is required for neurotransmitter release and excitation of postsynaptic targets. Thus, the regulation of action potential invasion in axonal branches might shape the spread of excitation in cortical neural networks. To measure the reliability and extent of action potential invasion into axonal arbors, we have used two-photon...

  19. Axon diameter mapping in crossing fibers with diffusion MRI

    DEFF Research Database (Denmark)

    Zhang, Hui; Dyrby, Tim B; Alexander, Daniel C

    2011-01-01

    tissue than measures derived from diffusion tensor imaging. Most existing techniques for axon diameter mapping assume a single axon orientation in the tissue model, which limits their application to only the most coherently oriented brain white matter, such as the corpus callosum, where the single...... technique by establishing reasonable axon diameter indices in the crossing region at the interface of the cingulum and the corpus callosum....

  20. Axon target matching in the developing visual system

    OpenAIRE

    Osterhout, Jessica A.

    2015-01-01

    The central nervous system (CNS) is made up of trillions of connections between specific sets of highly specialized neurons. How each individual neuron finds and connects to the correct synaptic partner remains an important and unresolved issue in neuroscience. Using the mouse visual system as a model I probed the cellular and molecular mechanisms that govern one of the key steps leading to CNS development: axon target matching. Axon target matching is the process by which axons to find and i...

  1. Axon Regeneration in the Peripheral and Central Nervous Systems

    OpenAIRE

    Huebner, Eric A.; Strittmatter, Stephen M

    2009-01-01

    Axon regeneration in the mature mammalian central nervous system (CNS) is extremely limited after injury. Consequently, functional deficits persist after spinal cord injury (SCI), traumatic brain injury, stroke, and related conditions that involve axonal disconnection. This situation differs from that in the mammalian peripheral nervous system (PNS), where long- distance axon regeneration and substantial functional recovery can occur in the adult. Both extracellular molecules and the intrinsi...

  2. Myelin sheath survival after guanethidine-induced axonal degeneration

    OpenAIRE

    1992-01-01

    Membrane-membrane interactions between axons and Schwann cells are required for initial myelin formation in the peripheral nervous system. However, recent studies of double myelination in sympathetic nerve have indicated that myelin sheaths continue to exist after complete loss of axonal contact (Kidd, G. J., and J. W. Heath. 1988. J. Neurocytol. 17:245-261). This suggests that myelin maintenance may be regulated either by diffusible axonal factors or by nonaxonal mechanisms. To test these hy...

  3. Axonal autophagy during regeneration of the rat sciatic nerve

    Institute of Scientific and Technical Information of China (English)

    Kangrong Lu; Zhongxian Piao; Zhenxi Liu; Weiwang Gu; Wanshan Wang; Nngjie Piao

    2008-01-01

    BACKGROUND: The removal of degenerated axonal debris during Wallerian degeneration is very important for nerve regeneration. However, the mechanism by which debris is removed is not been completely understood. Considerable controversy remains as to the clearance pathway and cells that are involved. OBJECTIVE: To investigate axonal autophagy during removal of degenerated axonal debris by transecting the sciatic nerve in a rat Wallerian degeneration model.DESIGN, TIME AND SETTING: Experimental neuropathological analysis. The experiment was conducted at the Laboratory Animal Service Center of the Southern Medical University between January and June 2005. MATERIALS: Fifty-four adult, Wistar rats of either sex, weighing 180-250 g, were obtained from the Laboratory Animal Service Center of the Southern Medical University. Animals were randomly divided into nine groups of six rats. METHODS: Wallerian degeneration was induced by transecting the rat sciatic nerve, and tissue samples from the distal stump were obtained 0.2, 0.4, 1, 2, 3, 4, 7, 10, and 15 days post-transection. Ultrathin sections were prepared for electron microscopy to study ultrastructure and enzyme cytochemistry staining. MAIN OUTCOME MEASURES: Ultrastructure (axon body, autophagic body, and cystoskeleton) of axons and myelin sheaths observed with electron microscopy; acidic phosphatase activity detected by Gomori staining using electron microscopy. RESULTS: The major changes of degenerating axons after transection were axoplasm swelling and separation of axons from their myelin sheath between five hours and two days post-transection. At four days post-transection, the axoplasm condensed and axons were completely separated from the myelin sheath, forming dissociative axon bodies. Vacuoles of different sizes formed in axons during the early phase after lesion. Larger dissociative axon bodies were formed when the axons were completely separated from the myelin sheath during a late phase. The axolemma

  4. Localization of Axonal Motor Molecules Machinery in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Fulvio Florenzano

    2012-04-01

    Full Text Available Axonal transport and neuronal survival depend critically on active transport and axon integrity both for supplying materials and communication to different domains of the cell body. All these actions are executed through cytoskeleton, transport and regulatory elements that appear to be disrupted in neurodegenerative diseases. Motor-driven transport both supplies and clears distal cellular portions with proteins and organelles. This transport is especially relevant in projection and motor neurons, which have long axons to reach the farthest nerve endings. Thus, any disturbance of axonal transport may have severe consequences for neuronal function and survival. A growing body of literature indicates the presence of alterations to the motor molecules machinery, not only in expression levels and phosphorylation, but also in their subcellular distribution within populations of neurons, which are selectively affected in the course of neurodegenerative diseases. The implications of this altered subcellular localization and how this affects axon survival and neuronal death still remain poorly understood, although several hypotheses have been suggested. Furthermore, cytoskeleton and transport element localization can be selectively disrupted in some disorders suggesting that specific loss of the axonal functionality could be a primary hallmark of the disorder. This can lead to axon degeneration and neuronal death either directly, through the functional absence of essential axonal proteins, or indirectly, through failures in communication among different cellular domains. This review compares the localization of cytoskeleton and transport elements in some neurodegenerative disorders to ask what aspects may be essential for axon survival and neuronal death.

  5. Studies in the development of a bridging device for guiding regenerating axons

    Science.gov (United States)

    Wen, Xuejun

    At present there is no clinically effective treatment for injuries or pathological processes that disrupt the continuity of axons in the mature central nervous system. However, a number of studies suggest that a tremendous potential exists for developing therapies. In particular biomaterials in the form of bridging substrates been shown to support at least some level of axonal regeneration across the lesion site, but display a limited capacity for directing axons toward their targets. To influence the directionality of the regeneration process filaments and tubes appear promising but the technology is far from optimized. As a step toward optimization, we investigated various components of a tissue-engineered bridging device consisting of numerous filaments surrounded by a semipermeable biodegradable hollow fiber membrane (HFM). In the first part of the thesis, we studied the influence of filament diameter and various extracellular matrix coatings on neuron regeneration suing a dorsal root ganglion explant model. We found that laminin surface treated filaments that approached the size of spinal axons support significantly longer regenerative outgrowth than similarly treated filaments of larger diameter, and exceed outgrowth distance on similarly sized filaments treated with fibronectin. Such substrates also consistently supported the attachment and alignment of glial cells and directed the outgrowth of regenerating axons along the long axis of the filaments. In the last part of the thesis, biodegradable hollow fiber membranes were fabricated and their physical, chemical and degradation properties were analyzed. We found that it is possible to use phase inversion methods to fabricate hollow fiber membranes of widely varying properties that degrade of the course of several months. We then evaluated the biocompatibility of the new materials after implantation in the CNS using an adult rat model. We found that the implants were well tolerated and elicited a reaction

  6. Focal axonal swellings and associated ultrastructural changes attenuate conduction velocity in central nervous system axons: a computer modeling study

    OpenAIRE

    Kolaric, Katarina V; Thomson, Gemma; Edgar, Julia M; Brown, Angus M.

    2013-01-01

    The constancy of action potential conduction in the central nervous system (CNS) relies on uniform axon diameter coupled with fidelity of the overlying myelin providing high-resistance, low capacitance insulation. Whereas the effects of demyelination on conduction have been extensively studied/modeled, equivalent studies on the repercussions for conduction of axon swelling, a common early pathological feature of (potentially reversible) axonal injury, are lacking. The recent description of ex...

  7. Patterns of growth, axonal extension and axonal arborization of neuronal lineages in the developing Drosophila brain.

    Science.gov (United States)

    Larsen, Camilla; Shy, Diana; Spindler, Shana R; Fung, Siaumin; Pereanu, Wayne; Younossi-Hartenstein, Amelia; Hartenstein, Volker

    2009-11-15

    The Drosophila central brain is composed of approximately 100 paired lineages, with most lineages comprising 100-150 neurons. Most lineages have a number of important characteristics in common. Typically, neurons of a lineage stay together as a coherent cluster and project their axons into a coherent bundle visible from late embryo to adult. Neurons born during the embryonic period form the primary axon tracts (PATs) that follow stereotyped pathways in the neuropile. Apoptotic cell death removes an average of 30-40% of primary neurons around the time of hatching. Secondary neurons generated during the larval period form secondary axon tracts (SATs) that typically fasciculate with their corresponding primary axon tract. SATs develop into the long fascicles that interconnect the different compartments of the adult brain. Structurally, we distinguish between three types of lineages: PD lineages, characterized by distinct, spatially separate proximal and distal arborizations; C lineages with arborizations distributed continuously along the entire length of their tract; D lineages that lack proximal arborizations. Arborizations of many lineages, in particular those of the PD type, are restricted to distinct neuropile compartments. We propose that compartments are "scaffolded" by individual lineages, or small groups thereof. Thereby, the relatively small number of primary neurons of each primary lineage set up the compartment map in the late embryo. Compartments grow during the larval period simply by an increase in arbor volume of primary neurons. Arbors of secondary neurons form within or adjacent to the larval compartments, resulting in smaller compartment subdivisions and additional, adult specific compartments. PMID:19538956

  8. Requirement Elicitation for Requirement in Software Engineering

    OpenAIRE

    Swathine.K*; Dr. J.KomalaLakshmi

    2014-01-01

    Requirement Elicitation is also called as Requirement Gathering, in which requirements are collected from User, Stakeholders, and Customer to build the system. Requirements elicitation practices include interviews, questionnaires, task analysis, domain analysis, user observation, workshops, brainstorming, use cases, role playing and prototyping by using this practices quality of the requirements are satisfied. A wide variety of tools exist that have been developed and used to supp...

  9. Neurofilament gene expression: a major determinant of axonal caliber

    International Nuclear Information System (INIS)

    Within the wide spectrum of axonal diameters occurring in mammalian nerve fibers, each class of neurons has a relatively restricted range of axonal calibers. The control of caliber has functional significance because diameter is the principal determinant of conduction velocity in myelinated nerve fibers. Previous observations support the hypothesis that neurofilaments (NF) are major intrinsic determinants of axonal caliber in large myelinated nerve fibers. Following interruption of axons (axotomy) by crushing or cutting a peripheral nerve, caliber is reduced in the proximal axonal stumps, which extend from the cell bodies to the site of axotomy. This reduction in axonal caliber in the proximal stumps is associated with a selective diminution in the amount of NF protein undergoing slow axonal transport in these axons, with a decrease in axonal NF content, and with reduced conduction velocity. The present report demonstrates that changes in axonal caliber after axotomy correlate with a selective alteration in NF gene expression. Hybridization with specific cDNAs was used to measure levels of mRNA encoding the 68-kDa neurofilament protein (NF68), β-tubulin, and actin in lumbar sensory neurons of rat at various times after crushing the sciatic nerve. Between 4 and 42 days after axotomy by nerve crush, the levels of NF68 mRNA were reduced 2- to 3-fold. At the same times, the levels of tubulin and actin mRNAs were increased several-fold. These findings support the hypothesis that the expression of a single set of neuron-specific genes (encoding NF) directly determines axonal caliber, a feature neuronal morphology with important consequences for physiology and behavior

  10. New insights into mRNA trafficking in axons

    NARCIS (Netherlands)

    Gumy, Laura; Katrukha, Eugene; Kapitein, Lukas; Hoogenraad, Casper

    2014-01-01

    In recent years, it has been demonstrated that mRNAs localize to axons of young and mature central and peripheral nervous system neurons in culture and in vivo. Increasing evidence is supporting a fundamental role for the local translation of these mRNAs in neuronal function by regulating axon growt

  11. Restoration of Visual Function by Enhancing Conduction in Regenerated Axons.

    Science.gov (United States)

    Bei, Fengfeng; Lee, Henry Hing Cheong; Liu, Xuefeng; Gunner, Georgia; Jin, Hai; Ma, Long; Wang, Chen; Hou, Lijun; Hensch, Takao K; Frank, Eric; Sanes, Joshua R; Chen, Chinfei; Fagiolini, Michela; He, Zhigang

    2016-01-14

    Although a number of repair strategies have been shown to promote axon outgrowth following neuronal injury in the mammalian CNS, it remains unclear whether regenerated axons establish functional synapses and support behavior. Here, in both juvenile and adult mice, we show that either PTEN and SOCS3 co-deletion, or co-overexpression of osteopontin (OPN)/insulin-like growth factor 1 (IGF1)/ciliary neurotrophic factor (CNTF), induces regrowth of retinal axons and formation of functional synapses in the superior colliculus (SC) but not significant recovery of visual function. Further analyses suggest that regenerated axons fail to conduct action potentials from the eye to the SC due to lack of myelination. Consistent with this idea, administration of voltage-gated potassium channel blockers restores conduction and results in increased visual acuity. Thus, enhancing both regeneration and conduction effectively improves function after retinal axon injury. PMID:26771493

  12. Receptor Tyrosine Kinases: Molecular Switches Regulating CNS Axon Regeneration

    Directory of Open Access Journals (Sweden)

    Vasanthy Vigneswara

    2012-01-01

    Full Text Available The poor or lack of injured adult central nervous system (CNS axon regeneration results in devastating consequences and poor functional recovery. The interplay between the intrinsic and extrinsic factors contributes to robust inhibition of axon regeneration of injured CNS neurons. The insufficient or lack of trophic support for injured neurons is considered as one of the major obstacles contributing to their failure to survive and regrow their axons after injury. In the CNS, many of the signalling pathways associated with neuronal survival and axon regeneration are regulated by several classes of receptor tyrosine kinases (RTK that respond to a variety of ligands. This paper highlights and summarises the most relevant recent findings pertinent to different classes of the RTK family of molecules, with a particular focus on elucidating their role in CNS axon regeneration.

  13. SnoN facilitates axonal regeneration after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Jiun L Do

    Full Text Available Adult CNS neurons exhibit a reduced capacity for growth compared to developing neurons, due in part to downregulation of growth-associated genes as development is completed. We tested the hypothesis that SnoN, an embryonically regulated transcription factor that specifies growth of the axonal compartment, can enhance growth in injured adult neurons. In vitro, SnoN overexpression in dissociated adult DRG neuronal cultures significantly enhanced neurite outgrowth. Moreover, TGF-β1, a negative regulator of SnoN, inhibited neurite outgrowth, and SnoN over-expression overcame this inhibition. We then examined whether SnoN influenced axonal regeneration in vivo: indeed, expression of a mutant form of SnoN resistant to degradation significantly enhanced axonal regeneration following cervical spinal cord injury, despite peri-lesional upregulation of TGF-β1. Thus, a developmental mechanism that specifies extension of the axonal compartment also promotes axonal regeneration after adult CNS injury.

  14. Brain injury tolerance limit based on computation of axonal strain.

    Science.gov (United States)

    Sahoo, Debasis; Deck, Caroline; Willinger, Rémy

    2016-07-01

    Traumatic brain injury (TBI) is the leading cause of death and permanent impairment over the last decades. In both the severe and mild TBIs, diffuse axonal injury (DAI) is the most common pathology and leads to axonal degeneration. Computation of axonal strain by using finite element head model in numerical simulation can enlighten the DAI mechanism and help to establish advanced head injury criteria. The main objective of this study is to develop a brain injury criterion based on computation of axonal strain. To achieve the objective a state-of-the-art finite element head model with enhanced brain and skull material laws, was used for numerical computation of real world head trauma. The implementation of new medical imaging data such as, fractional anisotropy and axonal fiber orientation from Diffusion Tensor Imaging (DTI) of 12 healthy patients into the finite element brain model was performed to improve the brain constitutive material law with more efficient heterogeneous anisotropic visco hyper-elastic material law. The brain behavior has been validated in terms of brain deformation against Hardy et al. (2001), Hardy et al. (2007), and in terms of brain pressure against Nahum et al. (1977) and Trosseille et al. (1992) experiments. Verification of model stability has been conducted as well. Further, 109 well-documented TBI cases were simulated and axonal strain computed to derive brain injury tolerance curve. Based on an in-depth statistical analysis of different intra-cerebral parameters (brain axonal strain rate, axonal strain, first principal strain, Von Mises strain, first principal stress, Von Mises stress, CSDM (0.10), CSDM (0.15) and CSDM (0.25)), it was shown that axonal strain was the most appropriate candidate parameter to predict DAI. The proposed brain injury tolerance limit for a 50% risk of DAI has been established at 14.65% of axonal strain. This study provides a key step for a realistic novel injury metric for DAI. PMID:27038501

  15. Overcoming maladaptive plasticity through plastic compensation

    Institute of Scientific and Technical Information of China (English)

    Matthew R.J.MORRIS; Sean M.ROGERS

    2013-01-01

    Most species evolve within fluctuating environments,and have developed adaptations to meet the challenges posed by environmental heterogeneity.One such adaptation is phenotypic plasticity,or the ability of a single genotype to produce multiple environmentally-induced phenotypes.Yet,not all plasticity is adaptive.Despite the renewed interest in adaptive phenotypic plasticity and its consequences for evolution,much less is known about maladaptive plasticity.However,maladaptive plasticity is likely an important driver of phenotypic similarity among populations living in different environments.This paper traces four strategies for overcoming maladaptive plasticity that result in phenotypic similarity,two of which involve genetic changes (standing genetic variation,genetic compensation) and two of which do not (standing epigenetic variation,plastic compensation).Plastic compensation is defined as adaptive plasticity overcoming maladaptive plasticity.In particular,plastic compensation may increase the likelihood of genetic compensation by facilitating population persistence.We provide key terms to disentangle these aspects of phenotypic plasticity and introduce examples to reinforce the potential importance of plastic compensation for understanding evolutionary change.

  16. 4S RNA is transported axonally in normal and regenerating axons of the sciatic nerves of rats

    International Nuclear Information System (INIS)

    Experiments were designed to determine if following injection of [3H]uridine into the lumbar spinal cord of the rat, [3H]RNA could be demonstrated within axons of the sciatic nerve, and if 4S RNA is the predominant predominant RNA species present in these axons. (Auth.)

  17. Stereoscopy Amplifies Emotions Elicited by Facial Expressions.

    Science.gov (United States)

    Hakala, Jussi; Kätsyri, Jari; Häkkinen, Jukka

    2015-12-01

    Mediated facial expressions do not elicit emotions as strongly as real-life facial expressions, possibly due to the low fidelity of pictorial presentations in typical mediation technologies. In the present study, we investigated the extent to which stereoscopy amplifies emotions elicited by images of neutral, angry, and happy facial expressions. The emotional self-reports of positive and negative valence (which were evaluated separately) and arousal of 40 participants were recorded. The magnitude of perceived depth in the stereoscopic images was manipulated by varying the camera base at 15, 40, 65, 90, and 115 mm. The analyses controlled for participants' gender, gender match, emotional empathy, and trait alexithymia. The results indicated that stereoscopy significantly amplified the negative valence and arousal elicited by angry expressions at the most natural (65 mm) camera base, whereas stereoscopy amplified the positive valence elicited by happy expressions in both the narrowed and most natural (15-65 mm) base conditions. Overall, the results indicate that stereoscopy amplifies the emotions elicited by mediated emotional facial expressions when the depth geometry is close to natural. The findings highlight the sensitivity of the visual system to depth and its effect on emotions. PMID:27551358

  18. Overcoming maladaptive plasticity through plastic compensation

    OpenAIRE

    Matthew R.J. MORRIS, Sean M. ROGERS

    2013-01-01

    Most species evolve within fluctuating environments, and have developed adaptations to meet the challenges posed by environmental heterogeneity. One such adaptation is phenotypic plasticity, or the ability of a single genotype to produce multiple environmentally-induced phenotypes. Yet, not all plasticity is adaptive. Despite the renewed interest in adaptive phenotypic plasticity and its consequences for evolution, much less is known about maladaptive plasticity. However, maladaptive plastici...

  19. Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons

    Czech Academy of Sciences Publication Activity Database

    Balaštík, Martin; Zhou, X.Z.; Alberich-Jorda, Meritxell; Weissová, Romana; Žiak, Jakub; Pazyra-Murphy, M.F.; Cosker, K.E.; Machoňová, Olga; Kozmiková, Iryna; Chen, CH.; Pastorino, L.; Asara, J.M.; Cole, A.; Sutherland, C.; Segal, R. A.; Lu, K.P.

    2015-01-01

    Roč. 13, č. 4 (2015), s. 812-828. ISSN 2211-1247 R&D Projects: GA MŠk(CZ) LK11213; GA MŠk LK21307; GA ČR GA15-03796S; GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : Pin1 * axon guidance * Semaphorin 3A Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.358, year: 2014

  20. Clinical features of diffuse axonal injury

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To analyze the mechanism of diffuse axonal injury (DAI) and study the relationship between DAI and brain concussion, brain contusion, and primary brain stem injury.Methods: The clinical data and iconographic characteristics of 56 patients with DAI were analyzed retrospectively.Results: Traffic accidents were the main cause of DAI. Among the 56 cases, 34 were injured for at least twice, and 71.43% of the patients were complicated with contusion.Conclusions: It is considered that DAI is a common pattern of primary brain injury, which is often underestimated. And DAI includes cerebral concussion and primary brain injury, and is often complicated by cerebral cortex contusion. Therefore, it is very simple and practical to divide primary brain injuries into local and diffuse injuries.

  1. Rational elicitation of cold-sensitive phenotypes.

    Science.gov (United States)

    Baliga, Chetana; Majhi, Sandipan; Mondal, Kajari; Bhattacharjee, Antara; VijayRaghavan, K; Varadarajan, Raghavan

    2016-05-01

    Cold-sensitive phenotypes have helped us understand macromolecular assembly and biological phenomena, yet few attempts have been made to understand the basis of cold sensitivity or to elicit it by design. We report a method for rational design of cold-sensitive phenotypes. The method involves generation of partial loss-of-function mutants, at either buried or functional sites, coupled with selective overexpression strategies. The only essential input is amino acid sequence, although available structural information can be used as well. The method has been used to elicit cold-sensitive mutants of a variety of proteins, both monomeric and dimeric, and in multiple organisms, namely Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster This simple, yet effective technique of inducing cold sensitivity eliminates the need for complex mutations and provides a plausible molecular mechanism for eliciting cold-sensitive phenotypes. PMID:27091994

  2. Membrane turnover and receptor trafficking in regenerating axons.

    Science.gov (United States)

    Hausott, Barbara; Klimaschewski, Lars

    2016-02-01

    Peripheral axonal regeneration requires surface-expanding membrane addition. The continuous incorporation of new membranes into the axolemma allows the pushing force of elongating microtubules to drive axonal growth cones forwards. Hence, a constant supply of membranes and cytoskeletal building blocks is required, often for many weeks. In human peripheral nerves, axonal tips may be more than 1 m away from the neuronal cell body. Therefore, in the initial phase of regeneration, membranes are derived from pre-existing vesicles or synthesised locally. Only later stages of axonal regeneration are supported by membranes and proteins synthesised in neuronal cell bodies, considering that the fastest anterograde transport mechanisms deliver cargo at 20 cm/day. Whereas endocytosis and exocytosis of membrane vesicles are balanced in intact axons, membrane incorporation exceeds membrane retrieval during regeneration to compensate for the loss of membranes distal to the lesion site. Physiological membrane turnover rates will not be established before the completion of target reinnervation. In this review, the current knowledge on membrane traffic in axonal outgrowth is summarised, with a focus on endosomal vesicles as the providers of membranes and carriers of growth factor receptors required for initiating signalling pathways to promote the elongation and branching of regenerating axons in lesioned peripheral nerves. PMID:26222895

  3. Astrocyte scar formation aids central nervous system axon regeneration.

    Science.gov (United States)

    Anderson, Mark A; Burda, Joshua E; Ren, Yilong; Ao, Yan; O'Shea, Timothy M; Kawaguchi, Riki; Coppola, Giovanni; Khakh, Baljit S; Deming, Timothy J; Sofroniew, Michael V

    2016-04-14

    Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration. PMID:27027288

  4. Eliciting Subjective Probabilities with Binary Lotteries

    DEFF Research Database (Denmark)

    Harrison, Glenn W.; Martínez-Correa, Jimmy; Swarthout, J. Todd

    2014-01-01

    We evaluate a binary lottery procedure for inducing risk neutral behavior in a subjective belief elicitation task. Prior research has shown this procedure to robustly induce risk neutrality when subjects are given a single risk task defined over objective probabilities. Drawing a sample from the...... same subject population, we find evidence that the binary lottery procedure also induces linear utility in a subjective probability elicitation task using the Quadratic Scoring Rule. We also show that the binary lottery procedure can induce direct revelation of subjective probabilities in subjects with...

  5. A Discussion of Usefulness and Pitfall of Elicitation and Introspection

    Institute of Scientific and Technical Information of China (English)

    陈燕娜

    2013-01-01

    Nowadays, many scholars would like to use evidence derived from elicitation and introspection in their research. Both elicitation and introspection are common methods of data collection. The essay discusses the usefulness and pitfall of elicitation and introspection. It finds out that both elicitation and introspection have their own advantages and disadvantages.

  6. Axonal transmission in the retina introduces a small dispersion of relative timing in the ganglion cell population response.

    Directory of Open Access Journals (Sweden)

    Günther Zeck

    Full Text Available BACKGROUND: Visual stimuli elicit action potentials in tens of different retinal ganglion cells. Each ganglion cell type responds with a different latency to a given stimulus, thus transforming the high-dimensional input into a temporal neural code. The timing of the first spikes between different retinal projection neurons cells may further change along axonal transmission. The purpose of this study is to investigate if intraretinal conduction velocity leads to a synchronization or dispersion of the population signal leaving the eye. METHODOLOGY/PRINCIPAL FINDINGS: We 'imaged' the initiation and transmission of light-evoked action potentials along individual axons in the rabbit retina at micron-scale resolution using a high-density multi-transistor array. We measured unimodal conduction velocity distributions (1.3±0.3 m/sec, mean ± SD for axonal populations at all retinal eccentricities with the exception of the central part that contains myelinated axons. The velocity variance within each piece of retina is caused by ganglion cell types that show narrower and slightly different average velocity tuning. Ganglion cells of the same type respond with similar latency to spatially homogenous stimuli and conduct with similar velocity. For ganglion cells of different type intraretinal conduction velocity and response latency to flashed stimuli are negatively correlated, indicating that differences in first spike timing increase (up to 10 msec. Similarly, the analysis of pair-wise correlated activity in response to white-noise stimuli reveals that conduction velocity and response latency are negatively correlated. CONCLUSION/SIGNIFICANCE: Intraretinal conduction does not change the relative spike timing between ganglion cells of the same type but increases spike timing differences among ganglion cells of different type. The fastest retinal ganglion cells therefore act as indicators of new stimuli for postsynaptic neurons. The intraretinal dispersion

  7. Intra-axonal myosin and actin in nerve regeneration.

    Science.gov (United States)

    McQuarrie, Irvine G; Lund, Linda M

    2009-10-01

    A focused review of sciatic nerve regeneration in the rat model, based on research conducted by the authors, is presented. We examine structural proteins carried distally in the axon by energy-requiring motor enzymes, using protein chemistry and molecular biology techniques in combination with immunohistochemistry. Relevant findings from other laboratories are cited and discussed. The general conclusion is that relatively large amounts of actin and tubulin are required to construct a regenerating axon and that these materials mainly originate in the parent axon. The motor enzymes that carry these proteins forward as macromolecules include kinesin and dynein but probably also include myosin. PMID:19927086

  8. Axon guidance and neuronal migration research in China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Proper migration of neuronal somas and axonal growth cones to designated locations in the developing brain is essential for the assembly of functional neuronal circuits.Rapid progress in research of axon guidance and neuronal migration has been made in the last twenty years.Chinese researchers began their exploration in this field ten years ago and have made significant contributions in clarifying the signal transduction of axon guidance and neuronal migration.Several unique experimental approaches,including the migration assay of single isolated neurons in response to locally delivered guidance cues,have been developed by Chinese neuroscientists to investigate the molecular machinery underlying these guidance events.

  9. Eliciting Subjective Probabilities with Binary Lotteries

    DEFF Research Database (Denmark)

    Harrison, Glenn W.; Martínez-Correa, Jimmy; Swarthout, J. Todd

    We evaluate the binary lottery procedure for inducing risk neutral behavior in a subjective belief elicitation task. Harrison, Martínez-Correa and Swarthout [2013] found that the binary lottery procedure works robustly to induce risk neutrality when subjects are given one risk task defined over o...

  10. Affective multimodal mirror: sensing and eliciting laughter

    NARCIS (Netherlands)

    Melder, W.A.; Truong, K.P.; Uyl, M. den; Leeuwen, D.A. van; Neerincx, M.A.; Loos, L.R.; Stock Plum, B.

    2007-01-01

    In this paper, we present a multimodal affective mirror that senses and elicits laughter. Currently, the mirror contains a vocal and a facial affect-sensing module, a component that fuses the output of these two modules to achieve a user-state assessment, a user state transition model, and a compone

  11. Convergent differential regulation of SLIT-ROBO axon guidance genes in the brains of vocal learners.

    Science.gov (United States)

    Wang, Rui; Chen, Chun-Chun; Hara, Erina; Rivas, Miriam V; Roulhac, Petra L; Howard, Jason T; Chakraborty, Mukta; Audet, Jean-Nicolas; Jarvis, Erich D

    2015-04-15

    Only a few distantly related mammals and birds have the trait of complex vocal learning, which is the ability to imitate novel sounds. This ability is critical for speech acquisition and production in humans, and is attributed to specialized forebrain vocal control circuits that have several unique connections relative to adjacent brain circuits. As a result, it has been hypothesized that there could exist convergent changes in genes involved in neural connectivity of vocal learning circuits. In support of this hypothesis, expanding on our related study (Pfenning et al. [2014] Science 346: 1256846), here we show that the forebrain part of this circuit that makes a relatively rare direct connection to brainstem vocal motor neurons in independent lineages of vocal learning birds (songbird, parrot, and hummingbird) has specialized regulation of axon guidance genes from the SLIT-ROBO molecular pathway. The SLIT1 ligand was differentially downregulated in the motor song output nucleus that makes the direct projection, whereas its receptor ROBO1 was developmentally upregulated during critical periods for vocal learning. Vocal nonlearning bird species and male mice, which have much more limited vocal plasticity and associated circuits, did not show comparable specialized regulation of SLIT-ROBO genes in their nonvocal motor cortical regions. These findings are consistent with SLIT and ROBO gene dysfunctions associated with autism, dyslexia, and speech sound language disorders and suggest that convergent evolution of vocal learning was associated with convergent changes in the SLIT-ROBO axon guidance pathway. PMID:25424606

  12. Transcriptional changes in sensory ganglia associated with primary afferent axon collateral sprouting in spared dermatome model

    Directory of Open Access Journals (Sweden)

    Benjamin J. Harrison

    2015-12-01

    Full Text Available Primary afferent collateral sprouting is a process whereby non-injured primary afferent neurons respond to some stimulus and extend new branches from existing axons. Neurons of both the central and peripheral nervous systems undergo this process, which contributes to both adaptive and maladaptive plasticity (e.g., [1–9]. In the model used here (the “spared dermatome” model, the intact sensory neurons respond to the denervation of adjacent areas of skin by sprouting new axon branches into that adjacent denervated territory. Investigations of gene expression changes associated with collateral sprouting can provide a better understanding of the molecular mechanisms controlling this process. Consequently, it can be used to develop treatments to promote functional recovery for spinal cord injury and other similar conditions. This report includes raw gene expression data files from microarray experiments in order to study the gene regulation in spared sensory ganglia in the initiation (7 days and maintenance (14 days phases of the spared dermatome model relative to intact (“naïve” sensory ganglia. Data has been deposited into GEO (GSE72551.

  13. Recycling of Plastic

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Fruergaard, Thilde

    2011-01-01

    Plastic is produced from fossil oil. Plastic is used for many different products. Some plastic products like, for example, wrapping foil, bags and disposable containers for food and beverage have very short lifetimes and thus constitute a major fraction of most waste. Other plastic products like...

  14. Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration.

    Science.gov (United States)

    Painter, Michio W; Brosius Lutz, Amanda; Cheng, Yung-Chih; Latremoliere, Alban; Duong, Kelly; Miller, Christine M; Posada, Sean; Cobos, Enrique J; Zhang, Alice X; Wagers, Amy J; Havton, Leif A; Barres, Ben; Omura, Takao; Woolf, Clifford J

    2014-07-16

    The regenerative capacity of the peripheral nervous system declines with age. Why this occurs, however, is unknown. We demonstrate that 24-month-old mice exhibit an impairment of functional recovery after nerve injury compared to 2-month-old animals. We find no difference in the intrinsic growth capacity between aged and young sensory neurons in vitro or in their ability to activate growth-associated transcriptional programs after injury. Instead, using age-mismatched nerve transplants in vivo, we show that the extent of functional recovery depends on the age of the nerve graft, and not the age of the host. Molecular interrogation of the sciatic nerve reveals that aged Schwann cells (SCs) fail to rapidly activate a transcriptional repair program after injury. Functionally, aged SCs exhibit impaired dedifferentiation, myelin clearance, and macrophage recruitment. These results suggest that the age-associated decline in axonal regeneration results from diminished Schwann cell plasticity, leading to slower myelin clearance. PMID:25033179

  15. Genetics Home Reference: autosomal recessive axonal neuropathy with neuromyotonia

    Science.gov (United States)

    ... neuromyotonia is a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles ... caused by damage to a particular part of peripheral nerves called axons , which are the extensions of nerve ...

  16. Internodal function in normal and regenerated mammalian axons

    DEFF Research Database (Denmark)

    Moldovan, M; Krarup, C

    2007-01-01

    AIM: Following Wallerian degeneration, peripheral myelinated axons have the ability to regenerate and, given a proper pathway, establish functional connections with targets. In spite of this capacity, the clinical outcome of nerve regeneration remains unsatisfactory. Early studies have found that...

  17. Syndecan Promotes Axon Regeneration by Stabilizing Growth Cone Migration

    Directory of Open Access Journals (Sweden)

    Tyson J. Edwards

    2014-07-01

    Full Text Available Growth cones facilitate the repair of nervous system damage by providing the driving force for axon regeneration. Using single-neuron laser axotomy and in vivo time-lapse imaging, we show that syndecan, a heparan sulfate (HS proteoglycan, is required for growth cone function during axon regeneration in C. elegans. In the absence of syndecan, regenerating growth cones form but are unstable and collapse, decreasing the effective growth rate and impeding regrowth to target cells. We provide evidence that syndecan has two distinct functions during axon regeneration: (1 a canonical function in axon guidance that requires expression outside the nervous system and depends on HS chains and (2 an intrinsic function in growth cone stabilization that is mediated by the syndecan core protein, independently of HS. Thus, syndecan is a regulator of a critical choke point in nervous system repair.

  18. Treadmill Training Promotes Axon Regeneration in Injured Peripheral Nerves

    OpenAIRE

    Sabatier, Manning J.; Redmon, Natalie; Schwartz, Gail; English, Arthur W.

    2008-01-01

    Physical activity after spinal cord injury promotes improvements in motor function, but its effects following peripheral nerve injury are less clear. Although axons in peripheral nerves are known to regenerate better than those in the CNS, methods of accelerating regeneration are needed due to the slow overall rate of growth. Therefore we studied the effect of two weeks of treadmill locomotion on the growth of regenerating axons in peripheral nerves following injury. The common fibular nerves...

  19. Fcγ receptor-mediated inflammation inhibits axon regeneration.

    Directory of Open Access Journals (Sweden)

    Gang Zhang

    Full Text Available Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

  20. Axonal integrity predicts cortical reorganisation following cervical injury

    OpenAIRE

    Freund, P.; Wheeler-Kingshott, C.A.; Nagy, Z.; Gorgoraptis, N.; N. Weiskopf; Friston, K.; Thompson, A J; Hutton, C.

    2012-01-01

    Background Traumatic spinal cord injury (SCI) leads to disruption of axonal architecture and macroscopic tissue loss with impaired information flow between the brain and spinal cord—the presumed basis of ensuing clinical impairment. Objective The authors used a clinically viable, multimodal MRI protocol to quantify the axonal integrity of the cranial corticospinal tract (CST) and to establish how microstructural white matter changes in the CST are related to cross-sectional spinal cord area a...

  1. Axonal neuropathy associated with monoclonal gammopathy of undetermined significance

    OpenAIRE

    GORSON, K.; Ropper, A.

    1997-01-01

    OBJECTIVE—The neuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) is typically a predominantly demyelinating process that may have additional features of axonal degeneration. Sixteen patients with MGUS and a pure or predominantly axonal neuropathy are reported and compared with 20 consecutive patients with demyelinating neuropathy and MGUS who were seen during the same period.
METHODS—Retrospective review of a consecutive series of patients w...

  2. Changes in prefrontal axons may disrupt the network in autism

    OpenAIRE

    Zikopoulos, Basilis; Barbas, Helen

    2010-01-01

    Neural communication is disrupted in autism by unknown mechanisms. Here we examined whether in autism there are changes in axons, which are the conduit for neural communication. We investigated single axons and their ultrastructure in the white matter of post-mortem human brain tissue below the anterior cingulate cortex (ACC), orbitofrontal (OFC), and lateral (LPFC) prefrontal cortices, which are associated with attention, social interactions, and emotions and have been consistently implicate...

  3. Axonal maintenance, glia, exosomes, and heat shock proteins

    OpenAIRE

    Michael Tytell; Lasek, Raymond J.; Harold Gainer

    2016-01-01

    Of all cellular specializations, the axon is especially distinctive because it is a narrow cylinder of specialized cytoplasm called axoplasm with a length that may be orders of magnitude greater than the diameter of the cell body from which it originates. Thus, the volume of axoplasm can be much greater than the cytoplasm in the cell body. This fact raises a logistical problem with regard to axonal maintenance. Many of the components of axoplasm, such as soluble proteins and cytoskeleton, are...

  4. THEORETICAL PRINCIPLES UNDERLYING OPTICAL STIMULATION OF MYELINATED AXONS EXPRESSING CHANNELRHODOPSIN-2

    OpenAIRE

    ARLOW, R. L.; FOUTZ, T. J.; MCINTYRE, C. C.

    2013-01-01

    Numerous clinical conditions can be treated by neuromodulation of the peripheral nervous system (PNS). Typical electrical PNS therapies activate large diameter axons at lower electrical stimulus thresholds than small diameter axons. However, recent animal experiments with peripheral optogenetic neural stimulation (PONS) of myelinated axons expressing channelrhodopsin-2 (ChR2) have shown that this technique activates small diameter axons at lower irradiances than large diameter axons. We hypot...

  5. Spinal irradiation does not inhibit distal axonal sprouting

    International Nuclear Information System (INIS)

    In an attempt to determine the relative importance of the nerve cell body and of the axon in initiating and controlling axonal regeneration, nerve cell bodies were irradiated and the ability of the distal axon to sprout was examined. Mice were subjected to either 25 or 50 Gray (Gy) of x-irradiation localized to the lumbar spinal cord. After times varying from 1 day to 6 months after irradiation, a sublethal dose of botulinum toxin (BoTx) was injected into the calf muscles of one leg. The soleus muscle was examined histologically after times varying from 1 week to 6 months after injection, and BoTx-induced ultraterminal axonal sprouting was assessed by the number of motor endplates showing sprouts, the length of the sprouts, and the long term endplate morphology. Apart from some irradiated subgroups having slightly shorter sprout lengths, no significant differences were found between irradiated and nonirradiated groups. The results suggest either that the processes in the nerve cell body responsible for initiating and supporting axonal growth are resistant to large doses of irradiation, or that growth regulatory mechanisms in the distal axon are under local control

  6. Dynamics of signal propagation and collision in axons

    Science.gov (United States)

    Follmann, Rosangela; Rosa, Epaminondas; Stein, Wolfgang

    2015-09-01

    Long-range communication in the nervous system is usually carried out with the propagation of action potentials along the axon of nerve cells. While typically thought of as being unidirectional, it is not uncommon for axonal propagation of action potentials to happen in both directions. This is the case because action potentials can be initiated at multiple "ectopic" positions along the axon. Two ectopic action potentials generated at distinct sites, and traveling toward each other, will collide. As neuronal information is encoded in the frequency of action potentials, action potential collision and annihilation may affect the way in which neuronal information is received, processed, and transmitted. We investigate action potential propagation and collision using an axonal multicompartment model based on the Hodgkin-Huxley equations. We characterize propagation speed, refractory period, excitability, and action potential collision for slow (type I) and fast (type II) axons. In addition, our studies include experimental measurements of action potential propagation in axons of two biological systems. Both computational and experimental results unequivocally indicate that colliding action potentials do not pass each other; they are reciprocally annihilated.

  7. Axon-glia interaction and membrane traffic in myelin formation

    Directory of Open Access Journals (Sweden)

    Robin eWhite

    2014-01-01

    Full Text Available In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialised glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarisation followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is established. Continuous communication between neurons and glial cells is essential for myelin maintenance and axonal integrity. A diverse group of diseases, from multiple sclerosis to schizophrenia, have been linked to malfunction of myelinating cells reflecting the physiological importance of the axon-glial unit. This review describes the mechanisms of axonal signal integration by oligodendrocytes emphasising the central role of the Src-family kinase Fyn during CNS myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of PLP (proteolipid protein transport by SNARE proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases.

  8. A comparison of five elicitation techniques for elicitation of attributes of low involvement products

    DEFF Research Database (Denmark)

    Bech-Larsen, Tino; Nielsen, Niels Asger

    1999-01-01

    dimensions directed from theories of consumer buying behaviour. Although a number of differences between the techniques are identified in the study, the main findings are that the robustness of the different techniques for attribute elicitation is considerable Udgivelsesdato: JUN...

  9. Plasticity in the Human Visual Cortex: An Ophthalmology-Based Perspective

    Directory of Open Access Journals (Sweden)

    Andreia Martins Rosa

    2013-01-01

    Full Text Available Neuroplasticity refers to the ability of the brain to reorganize the function and structure of its connections in response to changes in the environment. Adult human visual cortex shows several manifestations of plasticity, such as perceptual learning and adaptation, working under the top-down influence of attention. Plasticity results from the interplay of several mechanisms, including the GABAergic system, epigenetic factors, mitochondrial activity, and structural remodeling of synaptic connectivity. There is also a downside of plasticity, that is, maladaptive plasticity, in which there are behavioral losses resulting from plasticity changes in the human brain. Understanding plasticity mechanisms could have major implications in the diagnosis and treatment of ocular diseases, such as retinal disorders, cataract and refractive surgery, amblyopia, and in the evaluation of surgical materials and techniques. Furthermore, eliciting plasticity could open new perspectives in the development of strategies that trigger plasticity for better medical and surgical outcomes.

  10. Ultrastructural observation of effect of moderate hypothermia on axonal damage in an animal model of diffuse axonal injury

    Institute of Scientific and Technical Information of China (English)

    孙晓川; 唐文渊; 郑履平

    2002-01-01

    Objective: To investigate the effect of moderate hypothermia on responses of axonal cytoskeleton to axonal injury in the acute stage of injury. Methods: Of fifteen adult guinea pigs, twelve animals were subjected to stretch injury to the right optic nerves and divided into the normothermic group (n=6) in which the animal's core temperature was maintained at 36.0-37.5℃ and the hypothermia group (n=6) in which the core temperature was reduced to 32.0-32.5℃ after stretch injury. Remaining three animals sustained no injury to the right optic nerves and served as control group. Half of injured animals (n=3) of either normothermic group or hypothermic group were killed at either 2 hours or 4 hours after injury. The ultrastructural changes of axonal cytoskeleton of the right optic nerve fibers from the animals were examined under a transmission electron microscope and analyzed by quantitative analysis with a computer image analysis system. Results: At 2 hours after stretch injury, there was a significant reduction in the mean number of microtubules (P<0.001), and a significant increase in the mean intermicrotubule spacing (P<0.05 or P<0.01) in axons of all sizes in normothermic animals. The mean number of neurofilaments also decreased statistically (P<0.01) in large and medium subgroups of axons in the same experimental group at 2 hours. By 4 hours, the large subgroup of axons in normothermic animals still demonstrated a significant decline in the mean number of microtubules (P<0.01) and an increase in the mean intermicrotubule spacing (P<0.05), while the medium and small subgroups of axons displayed a significant increase in the mean number of neurofilaments (P<0.05) and reduction in the mean interneurofilament spacing (P<0.05). On the contrary, either the mean number of microtubules and the mean intermicrotubule spacing, or the mean number of neurofilaments and interneurofilament spacing in axons of all sizes in hypothermic stretch-injured animals was not

  11. Regeneration of motor axons in the rat sciatic nerve studied by labeling with axonally transported radioactive proteins

    International Nuclear Information System (INIS)

    Labeling regenerating axons with axonally transported radioactive proteins provides information about the location of the entire range of axons from the fastest growing ones to those which are trapped in the scar. This technique has been used to study the regeneration of motor axons in the rat sciatic nerve after a crush lesion. From 2 to 14 days after the crush the lumbar spinal cord was exposed by laminectomy and multiple injections of [3H]proline were made stereotactically in the ventral horn. Twenty-four hours later the nerves were removed and the distribution of radioactivity along the nerve was measured by liquid scintillation counting. There was a peak of radioactivity in the regenerating axons distal to the crush due to an accumulation of label in the tips of these axons. After a delay of 3.2 +- 0.2 (S.E.) days, this peak advanced down the nerve at a rate of 3.0 +- 0.1 (S.E.) mm/day. The leading edge of this peak, which marks the location of the endings of the most rapidly growing labeled fibers, moved down the nerve at a rate of 4.4 +- 0.2 mm/day after a delay of 2.1 +- 0.2 days; this is the same time course as that of the most rapidly regenerating sensory axons in the rat sciatic nerve, measured by the pinch test. Another peak of radioactivity at the crush site, presumed to represent the ends of unregenerated axons or misdirected sprouts, declined rapidly during the first week, and more slowly thereafter. (Auth.)

  12. Can packaging elements elicit consumers’ emotional responses?

    DEFF Research Database (Denmark)

    Liao, Lewis; Corsi, Armando; Lockshin, Larry;

    Emotion has been an important concept in many areas of consumer research such as judgment, decision-making and advertising. Little research has been done on emotion in packaging adopting the physiological measures used in other areas. This paper draws on past studies in advertising that measure...... emotional responses toward image, colour and font, and apply them to packaging research. The study tests the extent at which packaging can elicit consumers’ spontaneous emotional response for each of those three elements, by using skin conductance, facial electromyography (EMG) and selfassessment scales....... The results show that packaging can elicit an emotional response via different elements. The paper also raises concerns about the accuracy of using selfreport measures of emotional responses to packaging research....

  13. Eliciting taxpayer preferences increases tax compliance

    OpenAIRE

    De Neve, Jan-Emmanuel; Lamberton, Cait; Norton, Michael I.

    2014-01-01

    Two experiments show that eliciting taxpayer preferences on government spending—providing taxpayer agency--increases tax compliance. We first create an income and taxation environment in a laboratory setting to test for compliance with a lab tax. Allowing a treatment group to express nonbinding preferences over tax spending priorities, leads to a 16% increase in tax compliance. A followup online study tests this treatment with a simulation of paying US federal taxes. Allowing taxpayers to sig...

  14. Unstructured Direct Elicitation of Decision Rules

    OpenAIRE

    Ding, Min; John R. Hauser; Dong, Songting; Dzyabura, Daria; Yang, Zhilin; Su, Chenting; Gaskin, Steven

    2010-01-01

    We investigate the feasibility of unstructured direct-elicitation (UDE) of decision rules consumers use to form consideration sets. With incentives to think hard and answer truthfully, tested formats ask respondents to state non-compensatory, compensatory, or mixed rules for agents who will select a product for the respondents. In a mobile-phone study two validation tasks (one delayed 3 weeks) ask respondents to indicate which of 32 mobile phones they would consider from a fractional 4[supers...

  15. Elicitation of secondary metabolism in actinomycetes

    OpenAIRE

    Abdelmohsen, Usama Ramadan; Grkovic, Tanja; Balasubramanian, Srikkanth; Kamel, Mohamed Salah; Quinn, Ronald J.; Hentschel, Ute

    2015-01-01

    Genomic sequence data have revealed the presence of a large fraction of putatively silent biosynthetic gene clusters in the genomes of actinomycetes that encode for secondary metabolites, which are not detected under standard fermentation conditions. This review focuses on the effects of biological (co-cultivation), chemical, as well as molecular elicitation on secondary metabolism in actinomycetes. Our review covers the literature until June 2014 and exemplifies the diversity of natural prod...

  16. A Paradigm for Eliciting Story Variation

    OpenAIRE

    Fisseni, Bernhard; Lawrence, Faith

    2013-01-01

    The understanding of story variation, whether motivated by cultural currents or other factors, is important for applications of formal models of narrative such as story generation or story retrieval. We present the first stage of an experiment to elicit natural narrative variation data suitable for evaluation with respect to story similarity, to qualitative and quantitative analysis of story variation, and also for data processing. We also present few prelimary results from the first stage of...

  17. Essays on probability elicitation scoring rules

    Science.gov (United States)

    Firmino, Paulo Renato A.; dos Santos Neto, Ademir B.

    2012-10-01

    In probability elicitation exercises it has been usual to considerer scoring rules (SRs) to measure the performance of experts when inferring about a given unknown, Θ, for which the true value, θ*, is (or will shortly be) known to the experimenter. Mathematically, SRs quantify the discrepancy between f(θ) (the distribution reflecting the expert's uncertainty about Θ) and d(θ), a zero-one indicator function of the observation θ*. Thus, a remarkable characteristic of SRs is to contrast expert's beliefs with the observation θ*. The present work aims at extending SRs concepts and formulas for the cases where Θ is aleatory, highlighting advantages of goodness-of-fit and entropy-like measures. Conceptually, it is argued that besides of evaluating the personal performance of the expert, SRs may also play a role when comparing the elicitation processes adopted to obtain f(θ). Mathematically, it is proposed to replace d(θ) by g(θ), the distribution that model the randomness of Θ, and do also considerer goodness-of-fit and entropylike metrics, leading to SRs that measure the adherence of f(θ) to g(θ). The implications of this alternative perspective are discussed and illustrated by means of case studies based on the simulation of controlled experiments. The usefulness of the proposed approach for evaluating the performance of experts and elicitation processes is investigated.

  18. Axonal synapses utilize multiple synaptic ribbons in the mammalian retina.

    Directory of Open Access Journals (Sweden)

    Hong-Lim Kim

    Full Text Available In the mammalian retina, bipolar cells and ganglion cells which stratify in sublamina a of the inner plexiform layer (IPL show OFF responses to light stimuli while those that stratify in sublamina b show ON responses. This functional relationship between anatomy and physiology is a key principle of retinal organization. However, there are at least three types of retinal neurons, including intrinsically photosensitive retinal ganglion cells (ipRGCs and dopaminergic amacrine cells, which violate this principle. These cell types have light-driven ON responses, but their dendrites mainly stratify in sublamina a of the IPL, the OFF sublayer. Recent anatomical studies suggested that certain ON cone bipolar cells make axonal or ectopic synapses as they descend through sublamina a, thus providing ON input to cells which stratify in the OFF sublayer. Using immunoelectron microscopy with 3-dimensional reconstruction, we have identified axonal synapses of ON cone bipolar cells in the rabbit retina. Ten calbindin ON cone bipolar axons made en passant ribbon synapses onto amacrine or ganglion dendrites in sublamina a of the IPL. Compared to the ribbon synapses made by bipolar terminals, these axonal ribbon synapses were characterized by a broad postsynaptic element that appeared as a monad and by the presence of multiple short synaptic ribbons. These findings confirm that certain ON cone bipolar cells can provide ON input to amacrine and ganglion cells whose dendrites stratify in the OFF sublayer via axonal synapses. The monadic synapse with multiple ribbons may be a diagnostic feature of the ON cone bipolar axonal synapse in sublamina a. The presence of multiple ribbons and a broad postsynaptic density suggest these structures may be very efficient synapses. We also identified axonal inputs to ipRGCs with the architecture described above.

  19. Neuroinflammation triggered by β-glucan/dectin-1 signaling enables CNS axon regeneration.

    Science.gov (United States)

    Baldwin, Katherine T; Carbajal, Kevin S; Segal, Benjamin M; Giger, Roman J

    2015-02-24

    Innate immunity can facilitate nervous system regeneration, yet the underlying cellular and molecular mechanisms are not well understood. Here we show that intraocular injection of lipopolysaccharide (LPS), a bacterial cell wall component, or the fungal cell wall extract zymosan both lead to rapid and comparable intravitreal accumulation of blood-derived myeloid cells. However, when combined with retro-orbital optic nerve crush injury, lengthy growth of severed retinal ganglion cell (RGC) axons occurs only in zymosan-injected mice, and not in LPS-injected mice. In mice deficient for the pattern recognition receptor dectin-1 but not Toll-like receptor-2 (TLR2), zymosan-mediated RGC regeneration is greatly reduced. The combined loss of dectin-1 and TLR2 completely blocks the proregenerative effects of zymosan. In the retina, dectin-1 is expressed by microglia and dendritic cells, but not by RGCs. Dectin-1 is also present on blood-derived myeloid cells that accumulate in the vitreous. Intraocular injection of the dectin-1 ligand curdlan [a particulate form of β(1, 3)-glucan] promotes optic nerve regeneration comparable to zymosan in WT mice, but not in dectin-1(-/-) mice. Particulate β(1, 3)-glucan leads to increased Erk1/2 MAP-kinase signaling and cAMP response element-binding protein (CREB) activation in myeloid cells in vivo. Loss of the dectin-1 downstream effector caspase recruitment domain 9 (CARD9) blocks CREB activation and attenuates the axon-regenerative effects of β(1, 3)-glucan. Studies with dectin-1(-/-)/WT reciprocal bone marrow chimeric mice revealed a requirement for dectin-1 in both retina-resident immune cells and bone marrow-derived cells for β(1, 3)-glucan-elicited optic nerve regeneration. Collectively, these studies identify a molecular framework of how innate immunity enables repair of injured central nervous system neurons. PMID:25675510

  20. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

    Science.gov (United States)

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

    1998-01-01

    Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

  1. In vivo imaging of axonal transport using MRI: aging and Alzheimer's disease

    International Nuclear Information System (INIS)

    MRI using manganese as a trans-synaptic axonal tracing agent can unveil dynamics of axonal transport in living subjects. We use this technology to test the hypotheses if impaired axonal transport is a significant pathophysiological process in aging and early Alzheimer's disease (AD) and in part accounting for ''selective vulnerability'' of projection neurons in AD. To allow quantitative assessment of axonal transport in vivo, we developed voxel-based statistical mapping technology as well as a tracer kinetic modeling method based on mass transport for manganese-enhanced MRI to estimate axonal transport rates in aging rats and AD transgenic mice. These techniques demonstrated manganese-enhanced signal changes in axonal projections of the olfactory tract and decreased axonal transport rates in rodent models of aging and AD. Altered axonal transport may be a critical pathophysiological process in aging and AD. Manganese-enhanced MRI provides exciting opportunities for the investigations of altered axonal transport in AD and related disorders. (orig.)

  2. Regulation of Microtubule Dynamics in Axon Regeneration: Insights from C. elegans [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Ngang Heok Tang

    2016-04-01

    Full Text Available The capacity of an axon to regenerate is regulated by its external environment and by cell-intrinsic factors. Studies in a variety of organisms suggest that alterations in axonal microtubule (MT dynamics have potent effects on axon regeneration. We review recent findings on the regulation of MT dynamics during axon regeneration, focusing on the nematode Caenorhabditis elegans. In C. elegans the dual leucine zipper kinase (DLK promotes axon regeneration, whereas the exchange factor for Arf6 (EFA-6 inhibits axon regeneration. Both DLK and EFA-6 respond to injury and control axon regeneration in part via MT dynamics. How the DLK and EFA-6 pathways are related is a topic of active investigation, as is the mechanism by which EFA-6 responds to axonal injury. We evaluate potential candidates, such as the MT affinity-regulating kinase PAR-1/MARK, in regulation of EFA-6 and axonal MT dynamics in regeneration.

  3. Plasticity and Geotechnics

    Science.gov (United States)

    Yu, Hai-Sui

    Plasticity and Geotechnics is the first attempt to summarize and present, in one volume, the major developments achieved to date in the field of plasticity theory for geotechnical materials and its applications to geotechnical analysis and design.

  4. Functional complexity of the axonal growth cone: a proteomic analysis.

    Directory of Open Access Journals (Sweden)

    Adriana Estrada-Bernal

    Full Text Available The growth cone, the tip of the emerging neurite, plays a crucial role in establishing the wiring of the developing nervous system. We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at ≥ 99% confidence level. Using informatics, including functional annotation cluster and KEGG pathway analysis, we found great diversity of proteins involved in axonal pathfinding, cytoskeletal remodeling, vesicular traffic and carbohydrate metabolism, as expected. We also found a large and complex array of proteins involved in translation, protein folding, posttranslational processing, and proteasome/ubiquitination-dependent degradation. Immunofluorescence studies performed on hippocampal neurons in culture confirmed the presence in the axonal growth cone of proteins representative of these processes. These analyses also provide evidence for rough endoplasmic reticulum and reveal a reticular structure equipped with Golgi-like functions in the axonal growth cone. Furthermore, Western blot revealed the growth cone enrichment, relative to fetal brain homogenate, of some of the proteins involved in protein synthesis, folding and catabolism. Our study provides a resource for further research and amplifies the relatively recently developed concept that the axonal growth cone is equipped with proteins capable of performing a highly diverse range of functions.

  5. A novel technique using hydrophilic polymers to promote axonal fusion

    Institute of Scientific and Technical Information of China (English)

    Ravinder Bamba; D Colton Riley; Nathaniel D Kelm; Mark D Does; Richard D Dortch; Wesley P hTayer

    2016-01-01

    The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury, outcomes of surgical intervention have been unpredictable. The inability to manipulate the pathophysiology of nerve injury (i.e., Wallerian degeneration) has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration (~1 mm/day). When axons are severed, the endings undergo calcium-mediated plasmalemmal sealing, which limits the ability of the axon to be primarily re-paired. Polythethylene glycol (PEG) in combination with a bioengineered process overcomes the inability to fuse axons. The mechanism for PEG axonal fusion is not clearly understood, but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion. The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur. This review highlights PEG fusion, its past and current studies, and future directions in PEG fusion.

  6. Highly effective photonic cue for repulsive axonal guidance.

    Directory of Open Access Journals (Sweden)

    Bryan J Black

    Full Text Available In vivo nerve repair requires not only the ability to regenerate damaged axons, but most importantly, the ability to guide developing or regenerating axons along paths that will result in functional connections. Furthermore, basic studies in neuroscience and neuro-electronic interface design require the ability to construct in vitro neural circuitry. Both these applications require the development of a noninvasive, highly effective tool for axonal growth-cone guidance. To date, a myriad of technologies have been introduced based on chemical, electrical, mechanical, and hybrid approaches (such as electro-chemical, optofluidic flow and photo-chemical methods. These methods are either lacking in desired spatial and temporal selectivity or require the introduction of invasive external factors. Within the last fifteen years however, several attractive guidance cues have been developed using purely light based cues to achieve axonal guidance. Here, we report a novel, purely optical repulsive guidance technique that uses low power, near infrared light, and demonstrates the guidance of primary goldfish retinal ganglion cell axons through turns of up to 120 degrees and over distances of ∼90 µm.

  7. Subtypes of GABAergic neurons project axons in the neocortex

    Directory of Open Access Journals (Sweden)

    Shigeyoshi Higo

    2009-11-01

    Full Text Available γ-aminobutyric acid (GABAergic neurons in the neocortex have been regarded as interneurons and speculated to modulate the activity of neurons locally. Recently, however, several experiments revealed that neuronal nitric oxide synthase (nNOS-positive GABAergic neurons project cortico-cortically with long axons. In this study, we illustrate Golgi-like images of the nNOS-positive GABAergic neurons using a nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d reaction and follow the emanating axon branches in cat brain sections. These axon branches projected cortico-cortically with other non-labeled arcuate fibers, contra-laterally via the corpus callosum and anterior commissure. The labeled fibers were not limited to the neocortex but found also in the fimbria of the hippocampus. In order to have additional information on these GABAergic neuron projections, we investigated green fluorescent protein (GFP-labeled GABAergic neurons in GAD67-Cre knock-in / GFP Cre-reporter mice. GFP-labeled axons emanate densely, especially in the fimbria, a small number in the anterior commissure, and very sparsely in the corpus callosum. These two different approaches confirm that not only nNOS-positive GABAergic neurons but also other subtypes of GABAergic neurons project long axons in the cerebral cortex and are in a position to be involved in information processing.

  8. Plastic value chains

    DEFF Research Database (Denmark)

    Baxter, John; Wahlstrom, Margareta; Zu Castell-Rüdenhausen, Malin;

    2014-01-01

    Optimizing plastic value chains is regarded as an important measure in order to increase recycling of plastics in an efficient way. This can also lead to improved awareness of the hazardous substances contained in plastic waste, and how to avoid that these substances are recycled. As an example...

  9. STUDY OF PLASTIC SURGERY

    OpenAIRE

    Shrutika Sarangi

    2015-01-01

    Plastic surgery is a therapeutic system with the motivation behind modification or restoring the body's type. In spite of the fact that corrective or stylish surgery is the most surely understood sort of plastic surgery, plastic surgery itself is not inexorably considered cosmetic; and incorporates numerous sorts of reconstructive surgery, craniofacial surgery, hand surgery, microsurgery, and the treatment of smolders.

  10. Chemical Recycle of Plastics

    Directory of Open Access Journals (Sweden)

    Sara Fatima

    2014-11-01

    Full Text Available Various chemical processes currently prevalent in the chemical industry for plastics recycling have been discussed. Possible future scenarios in chemical recycling have also been discussed. Also analyzed are the effects on the environment, the risks, costs and benefits of PVC recycling. Also listed are the various types of plastics and which plastics are safe to use and which not after rcycle

  11. Automated Preference Elicitation for Decision Making

    Czech Academy of Sciences Publication Activity Database

    Kárný, Miroslav

    Vol. 3. Berlin: Springer, 2013, s. 65-99. (Studies in Computational Intelligence. 474). ISBN 978-3-642-36405-1 R&D Projects: GA ČR GA13-13502S; GA ČR GA102/08/0567 Institutional research plan: CEZ:AV0Z1075907 Institutional support: RVO:67985556 Keywords : Bayesian decision making * fully probabilistic design * DM preference elicitation * support of imperfect participants Subject RIV: BC - Control Systems Theory http://library.utia.cas.cz/separaty/2013/AS/karny-0389631.pdf

  12. DESIGNERS’ KNOWLEDGE IN PLASTICS

    DEFF Research Database (Denmark)

    Eriksen, Kaare

    2013-01-01

    The Industrial designers’ knowledge in plastics materials and manufacturing principles of polymer products is very important for the innovative strength of the industry, according to a group of Danish plastics manufacturers, design students and practicing industrial designers. These three groups...... answered the first Danish national survey, PD13[1], investigating the importance of industrial designers’ knowledge in plastics and the collaboration between designers and the polymer industry. The plastics industry and the industrial designers collaborate well, but both groups frequently experience that...... designing plastic products....

  13. Journal of CHINA PLASTICS

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Journal of CHINA PLASTICS was authorized and approved by The State Committee of Science and Technology of China and The Bureau of News Press of China, and published by The China Plastics Processing Industry Association,Beijing Technology and Business University and The Institute of Plastics Processing and Application of Light Industry, distributed worldwide. Since its birth in 1987, CHINA PLASTICS has become a leading magazine in plastics industry in China, a national Chinese core journal and journal of Chinese scientific and technological article statistics. It is covered by CA.

  14. Biodegradability of Plastics

    Directory of Open Access Journals (Sweden)

    Yutaka Tokiwa

    2009-08-01

    Full Text Available Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.. In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed.

  15. Involvement of SARA in Axon and Dendrite Growth.

    Science.gov (United States)

    Arias, Cristina Isabel; Siri, Sebastián Omar; Conde, Cecilia

    2015-01-01

    SARA (Smad Anchor for Receptor Activation) plays a crucial role in Rab5-mediated endocytosis in cell lines localizing to early endosomes where it regulates morphology and function. Here, we analyzed the role of SARA during neuronal development and tested whether it functions as a regulator of endocytic trafficking of selected axonal and membrane proteins. Suppression of SARA perturbs the appearance of juxtanuclear endocytic recycling compartments and the neurons show long axons with large growth cones. Furthermore, surface distribution of the cell adhesion molecule L1 in axons and the fusion of vesicles containing transferring receptor (TfR) in dendrites were increased in neurons where SARA was silenced. Conversely, SARA overexpression generated large early endosomes and reduced neurite outgrowth. Taken together, our findings suggest a significant contribution of SARA to key aspects of neuronal development, including neurite formation. PMID:26405814

  16. Neurofilament proteins in axonal regeneration and neurodegenerative diseases

    Institute of Scientific and Technical Information of China (English)

    Haitao Wang; Minfei Wu; Chuanjun Zhan; Enyuan Ma; Maoguang Yang; Xiaoyu Yang; Yingpu Li

    2012-01-01

    Neurofilament protein is a component of the mature neuronal cytoskeleton, and it interacts with the zygosome, which is mediated by neurofilament-related proteins. Neurofilament protein regulates enzyme function and the structure of linker proteins. In addition, neurofilament gene expression plays an important role in nervous system development. Previous studies have shown that neurofilament gene transcriptional regulation is crucial for neurofilament protein expression, especially in axonal regeneration and degenerative diseases. Post-transcriptional regulation increased neurofilament protein gene transcription during axonal regeneration, ultimately resulting in a pattern of neurofilament protein expression. An expression imbalance of post-transcriptional regulatory proteins and other disorders could lead to amyotrophic lateral sclerosis or other neurodegenerative diseases. These findings indicated that after transcription, neurofilament protein regulated expression of related proteins and promoted regeneration of damaged axons, suggesting that regulation disorders could lead to neurodegenerative diseases.

  17. 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.

  18. [A clinical and pathological study of diffuse axonal injury].

    Science.gov (United States)

    Nakazawa, S; Kobayashi, S; Yokota, H; Shimura, T

    1989-03-01

    There is increasing evidence from human and experimental studies that the most important factor governing the outcome in head injury is the severity of diffuse axonal injuries. The authors have experienced 18 cases of severe diffuse axonal injury which showed post-traumatic coma for more than 24 hours and CT findings resembling those of shearing injuries of the cerebral white matter such as have been presented by Zimmerman et al. (1978). The consciousness levels on admission were 6 or less on the Glasgow Coma Scale and all cases were shown clinically to have primary brain stem injury. The main type of head trauma resulted from road traffic accidents (83%). Skull fractures were found in only 5 cases (28%). These findings suggested that acceleration/deceleration injury produce in the patients severe diffuse axonal injury. Initial ICP was below 20 mmHg in 11 cases out of 13 (85%). Parenchymal small hemorrhagic lesions of initial CT were basal ganglia (7 cases), corpus callosum (4 cases), pons (4 cases), midbrain (3 cases) and thalamus (2 cases). Extraparenchymal hemorrhagic lesions included intraventricular hemorrhage (6 cases) and subarachnoid hemorrhage (6 cases). Two autopsied cases of severe diffuse axonal injury (acute case and chronic case) showed remarkable congestion and edema in the deep part of the frontal white matter. Microscopic examination revealed marked axonal degeneration including axonal retraction ball in the corpus callosum, in the internal capsule and in the white matter of the brain stem. Glasgow Outcome Scale of the 18 patients at 3 months after the trauma made us concerned that no patients indicated good recovery or even only moderate disability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2770962

  19. Challenges in plastics recycling

    DEFF Research Database (Denmark)

    Pivnenko, Kostyantyn; Jakobsen, L. G.; Eriksen, Marie Kampmann;

    2015-01-01

    undertaken to investigate the factors affecting quality in plastics recycling. The preliminary results showed factors primarily influencing quality of plastics recycling to be polymer cross contamination, presence of additives, non-polymer impurities, and polymer degradation. Deprivation of plastics quality......Recycling of waste plastics still remains a challenging area in the waste management sector. The current and potential goals proposed on EU or regional levels are difficult to achieve, and even to partially fullfil them the improvements in collection and sorting should be considerable. A study was......, with respect to recycling, has been shown to happen throughout the plastics value chain, but steps where improvements may happen have been preliminary identified. Example of Cr in plastic samples analysed showed potential spreading and accumulation of chemicals ending up in the waste plastics. In order...

  20. Glassy metallic plastics

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This paper reports a class of bulk metallic glass including Ce-, LaCe-, CaLi-, Yb-, and Sr-based metallic glasses, which are regarded as glassy metallic plastics because they combine some unique properties of both plastics and metallic alloys. These glassy metallic plastics have very low glass transition temperature (Tg~25oC to 150oC) and low Young’s modulus (~20 GPa to 35 GPa). Similar to glassy plastics, these metallic plastics show excellent plastic-like deformability on macro-, micro- and even nano-scale in their supercooled liquid range and can be processed, such as elongated, compressed, bent, and imprinted at low temperatures, in hot water for instance. Under ambient conditions, they display such metallic properties as high thermal and electric conductivities and excellent mechanical properties and other unique properties. The metallic plastics have potential applications and are also a model system for studying issues in glass physics.

  1. Pushing the Limits: Cognitive, Affective, and Neural Plasticity Revealed by an Intensive Multifaceted Intervention

    OpenAIRE

    Mrazek, Michael D.; Mooneyham, Benjamin W.; Mrazek, Kaita L.; Schooler, Jonathan W.

    2016-01-01

    Scientific understanding of how much the adult brain can be shaped by experience requires examination of how multiple influences combine to elicit cognitive, affective, and neural plasticity. Using an intensive multifaceted intervention, we discovered that substantial and enduring improvements can occur in parallel across multiple cognitive and neuroimaging measures in healthy young adults. The intervention elicited substantial improvements in physical health, working memory, standardized tes...

  2. Isolated sleep paralysis elicited by sleep interruption.

    Science.gov (United States)

    Takeuchi, T; Miyasita, A; Sasaki, Y; Inugami, M; Fukuda, K

    1992-06-01

    We elicited isolated sleep paralysis (ISP) from normal subjects by a nocturnal sleep interruption schedule. On four experimental nights, 16 subjects had their sleep interrupted for 60 minutes by forced awakening at the time when 40 minutes of nonrapid eye movement (NREM) sleep had elapsed from the termination of rapid eye movement (REM) sleep in the first or third sleep cycle. This schedule produced a sleep onset REM period (SOREMP) after the interruption at a high rate of 71.9%. We succeeded in eliciting six episodes of ISP in the sleep interruptions performed (9.4%). All episodes of ISP except one occurred from SOREMP, indicating a close correlation between ISP and SOREMP. We recorded verbal reports about ISP experiences and recorded the polysomnogram (PSG) during ISP. All of the subjects with ISP experienced inability to move and were simultaneously aware of lying in the laboratory. All but one reported auditory/visual hallucinations and unpleasant emotions. PSG recordings during ISP were characterized by a REM/W stage dissociated state, i.e. abundant alpha electroencephalographs and persistence of muscle atonia shown by the tonic electromyogram. Judging from the PSG recordings, ISP differs from other dissociated states such as lucid dreaming, nocturnal panic attacks and REM sleep behavior disorders. We compare some of the sleep variables between ISP and non-ISP nights. We also discuss the similarities and differences between ISP and sleep paralysis in narcolepsy. PMID:1621022

  3. Axon-glial interactions in the central nervous system

    OpenAIRE

    Butt, Arthur; Bay, Virginia

    2011-01-01

    Axon-glial interactions are critical for brain information transmission and processing. In the CNS, this is a function of the major types of glia – astrocytes, oligodendrocytes and novel NG2-glia. This special issue of the Journal of Anatomy comprises contributions arising from a symposium entitled ‘Axon-glial interactions in the CNS’, held at the University of Portsmouth, UK in July 2010. The aim of the special issue is to bring together an international group of experts to demonstrate the c...

  4. A chloride channel in rat and human axons

    OpenAIRE

    Strupp, Michael; Grafe, Peter

    1991-01-01

    Current recordings from single chloride channels were obtained from excised and cell-attached patches of rat and human axons. In rat axons the channels showed an outwardly rectifying current-voltage relationship with a slope conductance of 33 pS at negative membrane potentials and 65 pS at positive potentials (symmetrical 150 mM CsCl). They were measurably for cations (PNa/PCs/PCl=0.1/0.2/1). Channel currents were independent of cytoplasmatic calcium concentration. Inactivation was not observ...

  5. Tuning the orchestra: transcriptional pathways controlling axon regeneration

    Directory of Open Access Journals (Sweden)

    Andrea Tedeschi

    2012-01-01

    Full Text Available Trauma in the adult mammalian central nervous system leads to irreversible structural and functional impairment due to failed regeneration attempts. In contrast, neurons in the peripheral nervous system exhibit a greater regenerative ability. It has been proposed that an orchestrated sequence of transcriptional events controlling the expression of specific sets of genes may be the underlying basis of an early cell-autonomous regenerative response. Understanding whether transcriptional fine tuning, in parallel with strategies aimed at counteracting extrinsic impediments promotes axon re-growth following central nervous system injuries represents an exciting challenge for future studies. Transcriptional pathways controlling axon regeneration are presented and discussed in this review.

  6. Networks of Polarized Actin Filaments in the Axon Initial Segment Provide a Mechanism for Sorting Axonal and Dendritic Proteins

    Directory of Open Access Journals (Sweden)

    Kaori Watanabe

    2012-12-01

    Full Text Available Trafficking of proteins specifically to the axonal or somatodendritic membrane allows neurons to establish and maintain polarized compartments with distinct morphology and function. Diverse evidence suggests that an actin-dependent vesicle filter within the axon initial segment (AIS plays a critical role in polarized trafficking; however, no distinctive actin-based structures capable of comprising such a filter have been found within the AIS. Here, using correlative light and scanning electron microscopy, we visualized networks of actin filaments several microns wide within the AIS of cortical neurons in culture. Individual filaments within these patches are predominantly oriented with their plus ends facing toward the cell body, consistent with models of filter selectivity. Vesicles carrying dendritic proteins are much more likely to stop in regions occupied by the actin patches than in other regions, indicating that the patches likely prevent movement of dendritic proteins to the axon and thereby act as a vesicle filter.

  7. Membrane potential dynamics of axons in cultured hippocampal neurons probed by second-harmonic-generation imaging

    Science.gov (United States)

    Nuriya, Mutsuo; Yasui, Masato

    2010-03-01

    The electrical properties of axons critically influence the nature of communication between neurons. However, due to their small size, direct measurement of membrane potential dynamics in intact and complex mammalian axons has been a challenge. Furthermore, quantitative optical measurements of axonal membrane potential dynamics have not been available. To characterize the basic principles of somatic voltage signal propagation in intact axonal arbors, second-harmonic-generation (SHG) imaging is applied to cultured mouse hippocampal neurons. When FM4-64 is applied extracellularly to dissociated neurons, whole axonal arbors are visualized by SHG imaging. Upon action potential generation by somatic current injection, nonattenuating action potentials are recorded in intact axonal arbors. Interestingly, however, both current- and voltage-clamp recordings suggest that nonregenerative subthreshold somatic voltage changes at the soma are poorly conveyed to these axonal sites. These results reveal the nature of membrane potential dynamics of cultured hippocampal neurons, and further show the possibility of SHG imaging in physiological investigations of axons.

  8. Axon diameter and intra-axonal volume fraction of the corticospinal tract in idiopathic normal pressure hydrocephalus measured by q-space imaging.

    Directory of Open Access Journals (Sweden)

    Kouhei Kamiya

    Full Text Available PURPOSE: Previous studies suggest that compression and stretching of the corticospinal tract (CST potentially cause treatable gait disturbance in patients with idiopathic normal pressure hydrocephalus (iNPH. Measurement of axon diameter with diffusion MRI has recently been used to investigate microstructural alterations in neurological diseases. In this study, we investigated alterations in the axon diameter and intra-axonal fraction of the CST in iNPH by q-space imaging (QSI analysis. METHODS: Nineteen patients with iNPH and 10 age-matched controls were recruited. QSI data were obtained with a 3-T system by using a single-shot echo planar imaging sequence with the diffusion gradient applied parallel to the antero-posterior axis. By using a two-component low-q fit model, the root mean square displacements of intra-axonal space ( =  axon diameter and intra-axonal volume fraction of the CST were calculated at the levels of the internal capsule and body of the lateral ventricle, respectively. RESULTS: Wilcoxon's rank-sum test revealed a significant increase in CST intra-axonal volume fraction at the paraventricular level in patients (p<0.001, whereas no significant difference was observed in the axon diameter. At the level of the internal capsule, neither axon diameter nor intra-axonal volume fraction differed significantly between the two groups. CONCLUSION: Our results suggest that in patients with iNPH, the CST does not undergo irreversible axonal damage but is rather compressed and/or stretched owing to pressure from the enlarged ventricle. These analyses of axon diameter and intra-axonal fraction yield insights into microstructural alterations of the CST in iNPH.

  9. Synapses formed by identified retinogeniculate axons during the segregation of eye input.

    OpenAIRE

    Campbell, G; Shatz, C J

    1992-01-01

    The synaptic organization of identified retinogeniculate axons was studied during the prenatal development of eye-specific layers in the LGN of the cat. During this period, retinogeniculate axons undergo stereotyped morphological changes. Retinogeniculate axons originating from one eye and passing through LGN territory destined to be solely innervated by the other eye (inappropriate territory) initially give rise to many side branches. As the eye-specific layers emerge, these axons elaborate ...

  10. Correlates of Post-Stroke Brain Plasticity, Relationship to Pathophysiological Settings and Implications for Human Proof-of-Concept Studies.

    Science.gov (United States)

    Sanchez-Mendoza, Eduardo H; Hermann, Dirk Matthias

    2016-01-01

    The promotion of neurological recovery by enhancing neuroplasticity has recently obtained strong attention in the stroke field. Experimental studies support the hypothesis that stroke recovery can be improved by therapeutic interventions that augment neuronal sprouting. However plasticity responses of neurons are highly complex, involving the growth and differentiation of axons, dendrites, dendritic spines and synapses, which depend on the pathophysiological setting and are tightly controlled by extracellular and intracellular signals. Thorough mechanistic insights are needed into how neuronal plasticity is influenced by plasticity-promoting therapies in order not to risk the success of future clinical proof-of-concept studies. PMID:27547178

  11. Brief environmental enrichment elicits metaplasticity of hippocampal synaptic potentiation in vivo

    Directory of Open Access Journals (Sweden)

    Denise Manahan-Vaughan

    2012-12-01

    We assessed whether short-term EE elicits alterations in hippocampal synaptic plasticity and if social context may play a role. Adult mice were exposed to EE for 14 consecutive days. We found that robust late-LTP (>24h and short-term depression (<2h at Schaffer-collateral-CA1 synapses in freely behaving mice were unaltered, whereas early-LTP (E-LTP, <2h was significantly enhanced by EE. Effects were transient: E-LTP returned to control levels 1 week after cessation of EE. Six weeks later animals were re-exposed to EE for 14d. Under these conditions, E-LTP was facilitated into L-LTP (>24h, suggesting that metaplasticity was induced during the first EE experience and that EE-mediated modifications are cumulative. Effects were absent in mice that underwent solitary enrichment or were group-housed without EE. These data suggest that EE in naïve animals strengthens E-LTP, and also promotes L-LTP in animals that underwent EE in the past. This indicates that brief exposure to EE, particularly under social conditions can elicit lasting positive effects on synaptic strength that may have beneficial consequences for cognition that depends on synaptic plasticity.

  12. In vivo two-photon imaging of climbing fibers plasticity after laser axotomy

    Science.gov (United States)

    Allegra Mascaro, A. L.; Cesare, P.; Sacconi, L.; Grasselli, G.; Mandolesi, G.; Maco, B.; Knott, G. W.; De Paola, V.; Strata, P.; Pavone, F. S.

    2013-06-01

    In the adult nervous system, different neuronal classes show different regenerative behavior. Although previous studies demonstrated that olivocerebellar fibers are capable of axonal regeneration in a suitable environment as a response to injury, we have hitherto no details about the real dynamics of fiber regeneration. We set up a model of singularly axotomized climbing fibers (CF) to investigate their reparative properties in the adult central nervous system (CNS) in vivo. Here we describe the approach followed to characterize the reactive plasticity after injury.

  13. Differential Axonal Projection of Mitral and Tufted Cells in the Mouse Main Olfactory System

    Directory of Open Access Journals (Sweden)

    Shin Nagayama

    2010-09-01

    Full Text Available In the past decade, much has been elucidated regarding the functional organization of the axonal connection of olfactory sensory neurons to olfactory bulb (OB glomeruli. However, the manner in which projection neurons of the OB process odorant input and send this information to higher brain centers remains unclear. Here, we report long-range, large-scale tracing of the axonal projection patterns of OB neurons using two-photon microscopy. Tracer injection into a single glomerulus demonstrated widely distributed mitral/tufted cell axonal projections on the lateroventral surface of the mouse brain, including the anterior/posterior piriform cortex (PC and olfactory tubercle (OT. We noted two distinct groups of labeled axons: PC-orienting axons and OT-orienting axons. Each group occupied distinct parts of the lateral olfactory tract. PC-orienting axons projected axon collaterals to a wide area of the PC but only a few collaterals to the OT. OT-orienting axons densely projected axon collaterals primarily to the anterolateral OT (alOT. Different colored dye injections into the superficial and deep portions of the OB external plexiform layer revealed that the PC-orienting axon populations originated in presumed mitral cells and the OT-orienting axons in presumed tufted cells. These data suggest that although mitral and tufted cells receive similar odor signals from a shared glomerulus, they process the odor information in different ways and send their output to different higher brain centers via the PC and alOT.

  14. Needs Elicitation for Novel Pervasive Healthcare Technology

    DEFF Research Database (Denmark)

    Thorpe, Julia Rosemary; Forchhammer, B. H.; Maier, Anja

    2016-01-01

    inform designers about patients’ support needs and healthcare providers’ information needs.H ealthcare professionals offer a wealth of knowledge based on a clinical understanding of the condition as well as experience listening to patients' problems. Especially where patients are in denial about their......, and they are able to comment on trends, scale or proportions .We therefore explore how users' needs can be elicited by observing activities in which information is already being shared and discussed in the care process, and from the extensive knowledge of healthcare professionals. This is particularly...... include the large number of users required to represent the entire population. Failure to do so may lead to a solution that is over specialised to fit the needs of only a small subset of users. Both challenges are common in healthcare applications in which the end-user is also care recipient (or patient...

  15. Augmenting Usability: Cultural Elicitation in HCI

    Science.gov (United States)

    Camara, Souleymane Boundaouda; Oyugi, Cecilia; Abdelnour-Nocera, José; Smith, Andy

    This paper offers context and culture elicitation in an inter-cultural and multi-disciplinary setting of ICT design. Localised usability evaluation (LUE) is augmented with a socio-technical evaluation tool (STEM) as a methodological approach to expose and address issues in a collaborative ICT design within the Village e-Science for Life (VeSeL) project in rural Kenya. The paper argues that designers need to locally identify context and culture in situ and further explicate their implications through the design process and at the global level. Stakeholders' context, culture, decisions, agendas, expectations, disciplines and requirements need to be locally identified and globally evaluated to ensure a fit for purpose solution.

  16. Quantifying mechanical force in axonal growth and guidance

    Directory of Open Access Journals (Sweden)

    Ahmad Ibrahim Mahmoud Athamneh

    2015-09-01

    Full Text Available Mechanical force plays a fundamental role in neuronal development, physiology, and regeneration. In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections. However, much of the details about the exact role of force in these fundamental processes remain unknown. In this review, we highlight (1 standing questions concerning the role of mechanical force in axonal growth and guidance and (2 different experimental techniques used to quantify forces in axons and growth cones. We believe that satisfying answers to these questions will require quantitative information about the relationship between elongation, forces, cytoskeletal dynamics, axonal transport, signaling, substrate adhesion, and stiffness contributing to directional growth advance. Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics. We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.

  17. Traction Force and Tension Fluctuations During Axon Growth

    Directory of Open Access Journals (Sweden)

    Jamison ePolackwich

    2015-10-01

    Full Text Available Actively generated mechanical forces play a central role in axon growthand guidance, but the mechanisms that underly force generation andregulation in growing axons remain poorly understood. We reportmeasurements of the dynamics of traction stresses from growth cones ofactively advancing axons from postnatal rat DRG neurons. By tracking themovement of the growth cone and analyzing the traction stress field froma reference frame that moves with it, we are able to show that there isa clear and consistent average stress field that underlies the complexspatial stresses present at any one time. The average stress field hasstrong maxima on the sides of the growth cone, directed inward towardthe growth cone neck. This pattern represents a contractile stresscontained within the growth cone, and a net force that is balanced bythe axon tension. Using high time-resolution measurements of the growthcone traction stresses, we show that the stress field is composed offluctuating local stress peaks, with a large number peaks that live fora short time, a population of peaks whose lifetime distribution followsan exponential decay, and a small number of very long-lived peaks. Weshow that the high time-resolution data also reveal that the tensionappears to vary randomly over short time scales, roughly consistent withthe lifetime of the stress peaks, suggesting that the tensionfluctuations originate from stochastic adhesion dynamics.

  18. Model of fasciculation and sorting in mixed populations of axons

    Czech Academy of Sciences Publication Activity Database

    Chaudhuri, D.; Borowski, P.; Zápotocký, Martin

    2011-01-01

    Roč. 84, č. 2 (2011), e021908. ISSN 1539-3755 R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : axon guidance * neurogenesis * mathematical model Subject RIV: FH - Neurology Impact factor: 2.255, year: 2011

  19. Spectrins in axonal cytoskeletons: Dynamics revealed by extensions and fluctuations

    Science.gov (United States)

    Lai, Lipeng; Cao, Jianshu

    2014-07-01

    The macroscopic properties, the properties of individual components, and how those components interact with each other are three important aspects of a composited structure. An understanding of the interplay between them is essential in the study of complex systems. Using axonal cytoskeleton as an example system, here we perform a theoretical study of slender structures that can be coarse-grained as a simple smooth three-dimensional curve. We first present a generic model for such systems based on the fundamental theorem of curves. We use this generic model to demonstrate the applicability of the well-known worm-like chain (WLC) model to the network level and investigate the situation when the system is stretched by strong forces (weakly bending limit). We specifically studied recent experimental observations that revealed the hitherto unknown periodic cytoskeleton structure of axons and measured the longitudinal fluctuations. Instead of focusing on single molecules, we apply analytical results from the WLC model to both single molecule and network levels and focus on the relations between extensions and fluctuations. We show how this approach introduces constraints to possible local dynamics of the spectrin tetramers in the axonal cytoskeleton and finally suggests simple but self-consistent dynamics of spectrins in which the spectrins in one spatial period of axons fluctuate in-sync.

  20. PTEN inhibition and axon regeneration and neural repair

    Institute of Scientific and Technical Information of China (English)

    Yosuke Ohtake; Umar Hayat; Shuxin Li

    2015-01-01

    The intrinsic growth ability of all the neurons declines during development although some may grow better than others. Numerous intracellular signaling proteins and transcription factors have been shown to regulate the intrinsic growth capacity in mature neurons. Among them, PI3 kinase/Akt pathway is important for controlling axon elongation. As a negative regulator of this pathway, the tumor suppressor phosphatase and tensin homolog (PTEN) appears critical to con-trol the regenerative ability of young and adult neurons. This review will focus on recent research progress in axon regeneration and neural repair by PTEN inhibition and therapeutic potential of blocking this phosphatase for neurological disorders. Inhibition of PTEN by deletion in con-ditional knockout mice, knockdown by short-hairpin RNA, or blockade by pharmacological approaches, including administration of selective PTEN antagonist peptides, stimulates various degrees of axon regrowth in juvenile or adult rodents with central nervous system injuries. Im-portantly, post-injury PTEN suppression could enhance axonal growth and functional recovery in adult central nervous system after injury.

  1. Handbook of Plastic Welding

    DEFF Research Database (Denmark)

    Islam, Aminul

    The purpose of this document is to summarize the information about the laser welding of plastic. Laser welding is a matured process nevertheless laser welding of micro dimensional plastic parts is still a big challenge. This report collects the latest information about the laser welding of plastic...... materials and provides an extensive knowhow on the industrial plastic welding process. The objectives of the report include: - Provide the general knowhow of laser welding for the beginners - Summarize the state-of-the-art information on the laser welding of plastics - Find the technological limits in terms...... of design, materials and process - Find the best technology, process and machines adaptive to Sonion’s components - Provide the skills to Sonion’s Design Engineers for successful design of the of the plastic components suitable for the laser welding The ultimate goal of this report is to serve as a...

  2. Plasticized phenolphthalein polycarbonate

    Science.gov (United States)

    Harrison, E. S.

    1976-01-01

    Phenolphthalein polycarbonate was successfully plasticized with polychlorinated biphenyls (e.g., Aroclor 1231) or tricresyl phosphate and cast from tetrahydrofuran to give clear films without loss of fire resistance. At loadings of 20 to 30 percent plasticizer the Tg was lowered to approximately 100 C which would render phenolphthalein polycarbonate easily moldable. Although these materials had some mechanical integrity as shown by their film forming ability, the room temperature toughness of the plasticized polymer was not significantly improved over unmodified polymer.

  3. Development of plastic surgery

    OpenAIRE

    Pećanac Marija Đ.

    2015-01-01

    Introduction. Plastic surgery is a medical specialty dealing with corrections of defects, improvements in appearance and restoration of lost function. Ancient Times. The first recorded account of reconstructive plastic surgery was found in ancient Indian Sanskrit texts, which described reconstructive surgeries of the nose and ears. In ancient Greece and Rome, many medicine men performed simple plastic cosmetic surgeries to repair damaged parts of the body c...

  4. Plastic Pollution from Ships

    OpenAIRE

    ČULIN, Jelena; Bielić, Toni

    2016-01-01

    The environmental impact of shipping on marine environment includes discharge of garbage. Plastic litter is of particular concern due to abundance, resistance to degradation and detrimental effect on marine biota. According to recently published studies, a further research is required to assess human health risk. Monitoring data indicate that despite banning plastic disposal at sea, shipping is still a source of plastic pollution. Some of the measures to combat the problem are discussed.

  5. β₂-adrenergic receptors protect axons during energetic stress but do not influence basal glio-axonal lactate shuttling in mouse white matter.

    Science.gov (United States)

    Laureys, G; Valentino, M; Demol, F; Zammit, C; Muscat, R; Cambron, M; Kooijman, R; De Keyser, J

    2014-09-26

    In vitro studies have demonstrated that β2-adrenergic receptor activation stimulates glycogen degradation in astrocytes, generating lactate as a potential energy source for neurons. Using in vivo microdialysis in mouse cerebellar white matter we demonstrate continuous axonal lactate uptake and glial-axonal metabolic coupling of glutamate/lactate exchange. However, this physiological lactate production was not influenced by activation (clenbuterol) or blocking (ICI 118551) of β2-adrenergic receptors. In two-photon imaging experiments on ex vivo mouse corpus callosum subjected to aglycemia, β2-adrenergic activation rescued axons, whereas inhibition of axonal lactate uptake by α-cyano-4-hydroxycinnamic acid (4-CIN) was associated with severe axonal loss. Our results suggest that axonal protective effects of glial β2-adrenergic receptor activation are not mediated by enhanced lactate production. PMID:25064060

  6. Analysis of the potential-dependent changes in optical retardation in the squid giant axon.

    Science.gov (United States)

    Cohen, L B; Hille, B; Keynes, R D; Landowne, D; Rojas, E

    1971-10-01

    1. An analysis has been made of the change in optical retradation of the membrane elicited by the application of voltage-clamp pulses in squid giant axons.2. The retardation response consists of three separate voltage-dependent components. For freshly mounted axons, defined as being in state 1, hyperpolarizing pulses give a rapid increase in the light intensity measured with crossed polarizers which has been termed the fast phase. This is followed by a rather slow return towards the base line termed the rebound. On treatment of the axon with certain agents that include tetrodotoxin, high calcium and terbium, the rebound disappears and the fast phase slows down, increases in size, and has a new slow component added to it. This transition from state 1 to a second state, 2, appears to be irreversible.3. In state 1, the time constant of the fast phase is 20-40 musec at 13 degrees C; it has a very large negative temperature coefficient (Q(10) = Ca.(1/8)). The size of the retardation change is independent of temperature and varies as the square of the applied voltage, but the voltage-retardation curve is symmetrical about a point well beyond zero membrane potential, at an internal potential of around + 70 mV. In state 2, the time constant is about five times larger, and varies much less markedly with temperature; the apex of the voltage-retardation curve is shifted to + 200 mV.4. The rebound has a time constant of the order of 20 msec at 13 degrees C. A 10 degrees rise in temperature more than halves the time constant and roughly doubles the amplitude of the rebound. The voltage dependence of the rebound differed from that of the fast phase.5. The slow component of state 2 has a time constant of about 2 msec which does not change noticeably between 10 and 25 degrees C. The size of this component seems to be linearly dependent on the applied voltage, rather than obeying a square law.6. A tenfold increase in external calcium concentration had no discernible effect on the

  7. Synaptic Plasticity and Nociception

    Institute of Scientific and Technical Information of China (English)

    ChenJianguo

    2004-01-01

    Synaptic plasticity is one of the fields that progresses rapidly and has a lot of success in neuroscience. The two major types of synaptie plasticity: long-term potentiation ( LTP and long-term depression (LTD are thought to be the cellular mochanisms of learning and memory. Recently, accumulating evidence suggests that, besides serving as a cellular model for learning and memory, the synaptic plasticity involves in other physiological or pathophysiological processes, such as the perception of pain and the regulation of cardiovascular system. This minireview will focus on the relationship between synaptic plasticity and nociception.

  8. Astrocytes: Orchestrating synaptic plasticity?

    Science.gov (United States)

    De Pittà, M; Brunel, N; Volterra, A

    2016-05-26

    Synaptic plasticity is the capacity of a preexisting connection between two neurons to change in strength as a function of neural activity. Because synaptic plasticity is the major candidate mechanism for learning and memory, the elucidation of its constituting mechanisms is of crucial importance in many aspects of normal and pathological brain function. In particular, a prominent aspect that remains debated is how the plasticity mechanisms, that encompass a broad spectrum of temporal and spatial scales, come to play together in a concerted fashion. Here we review and discuss evidence that pinpoints to a possible non-neuronal, glial candidate for such orchestration: the regulation of synaptic plasticity by astrocytes. PMID:25862587

  9. Plastics and health risks.

    Science.gov (United States)

    Halden, Rolf U

    2010-01-01

    By 2010, the worldwide annual production of plastics will surpass 300 million tons. Plastics are indispensable materials in modern society, and many products manufactured from plastics are a boon to public health (e.g., disposable syringes, intravenous bags). However, plastics also pose health risks. Of principal concern are endocrine-disrupting properties, as triggered for example by bisphenol A and di-(2-ethylhexyl) phthalate (DEHP). Opinions on the safety of plastics vary widely, and despite more than five decades of research, scientific consensus on product safety is still elusive. This literature review summarizes information from more than 120 peer-reviewed publications on health effects of plastics and plasticizers in lab animals and humans. It examines problematic exposures of susceptible populations and also briefly summarizes adverse environmental impacts from plastic pollution. Ongoing efforts to steer human society toward resource conservation and sustainable consumption are discussed, including the concept of the 5 Rs--i.e., reduce, reuse, recycle, rethink, restrain--for minimizing pre- and postnatal exposures to potentially harmful components of plastics. PMID:20070188

  10. IH activity is increased in populations of slow versus fast motor axons of the rat.

    Directory of Open Access Journals (Sweden)

    Chad eLorenz

    2014-09-01

    Full Text Available Much is known about the electrophysiological variation in motoneuron somata across different motor units. However comparatively less is known about electrophysiological variation in motor axons and how this could impact function or electrodiagnosis in healthy or diseased states. We performed nerve excitability testing on two groups of motor axons in Sprague-Dawley rats that are known to differ significantly in their chronic daily activity patterns and in the relative proportion of motor unit types: one group innervating the soleus (slow motor axons and the other group innervating the tibialis anterior (fast motor axons muscles. We found that slow motor axons have significantly larger accommodation compared to fast motor axons upon application of a 100 ms hyperpolarizing conditioning stimulus that is 40% of axon threshold (Z = 3.24, p = 0.001 or 20% of axon threshold (Z = 2.67, p = 0.008. Slow motor axons had larger accommodation to hyperpolarizing currents in the current-threshold measurement (-80% Z = 3.07, p = 0.002; -90% Z = 2.98, p = 0.003. In addition, we found that slow motor axons have a significantly smaller rheobase than fast motor axons (Z = -1.99, p = 0.047 accompanied by a lower threshold in stimulus-response curves. The results provide evidence that slow motor axons have greater activity of the hyperpolarization-activated inwardly rectifying cation conductance (IH than fast motor axons. It is possible that this difference between fast and slow axons is caused by an adaptation to their chronic differences in daily activity patterns, and that this adaptation might have a functional effect on the motor unit. Moreover, these findings indicate that slow and fast motor axons may react differently to pathological conditions.

  11. White matter involvement after TBI: Clues to axon and myelin repair capacity.

    Science.gov (United States)

    Armstrong, Regina C; Mierzwa, Amanda J; Marion, Christina M; Sullivan, Genevieve M

    2016-01-01

    Impact-acceleration forces to the head cause traumatic brain injury (TBI) with damage in white matter tracts comprised of long axons traversing the brain. White matter injury after TBI involves both traumatic axonal injury (TAI) and myelin pathology that evolves throughout the post-injury time course. The axon response to initial mechanical forces and secondary insults follows the process of Wallerian degeneration, which initiates as a potentially reversible phase of intra-axonal damage and proceeds to an irreversible phase of axon fragmentation. Distal to sites of axon disconnection, myelin sheaths remain for prolonged periods, which may activate neuroinflammation and inhibit axon regeneration. In addition to TAI, TBI can cause demyelination of intact axons. These evolving features of axon and myelin pathology also represent opportunities for repair. In experimental TBI, demyelinated axons exhibit remyelination, which can serve to both protect axons and facilitate recovery of function. Myelin remodeling may also contribute to neuroplasticity. Efficient clearance of myelin debris is a potential target to attenuate the progression of chronic pathology. During the early phase of Wallerian degeneration, interventions that prevent the transition from reversible damage to axon disconnection warrant the highest priority, based on the poor regenerative capacity of axons in the CNS. Clinical evaluation of TBI will need to address the challenge of accurately detecting the extent and stage of axon damage. Distinguishing the complex white matter changes associated with axons and myelin is necessary for interpreting advanced neuroimaging approaches and for identifying a broader range of therapeutic opportunities to improve outcome after TBI. PMID:25697845

  12. Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy

    DEFF Research Database (Denmark)

    Fenrich, Keith K; Skelton, Nicole; MacDermid, Victoria E;

    2007-01-01

    Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injur...

  13. Plastic Surgeon Expertise in Predicting Breast Reconstruction Outcomes for Patient Decision Analysis

    Directory of Open Access Journals (Sweden)

    Clement S. Sun, MS

    2013-11-01

    Conclusions: The use of individual plastic surgeon–elicited probability information is not encouraged unless the individual’s prediction skill has been evaluated. In the absence of this information, a group consensus on the probability of outcomes is preferred. Without a large evidence base for calculating probabilities, estimates assessed from a group of plastic surgeons may be acceptable for purposes of breast reconstruction decision analysis.

  14. Investigating the Use of Audiovisual Elicitation on the Creative Enterprise

    OpenAIRE

    Flatt, Nicholas

    2014-01-01

    Elicitation methods have been explored extensively in social science research, and in business contexts, to uncover unarticulated informant knowledge. This qualitative study investigates the use of an audiovisual elicitation interviewing technique, developed by a UKbased creative multimedia production social enterprise; Fifth Planet Productions CIC. The method employs a system of using audiovisual stimulus to elicit participant responses in the interview setting. This study, conducted in t...

  15. Expert Elicitation of Population-Level Effects of Disturbance.

    Science.gov (United States)

    Fleishman, Erica; Burgman, Mark; Runge, Michael C; Schick, Robert S; Kraus, Scott

    2016-01-01

    Expert elicitation is a rigorous method for synthesizing expert knowledge to inform decision making and is reliable and practical when field data are limited. We evaluated the feasibility of applying expert elicitation to estimate population-level effects of disturbance on marine mammals. Diverse experts estimated parameters related to mortality and sublethal injury of North Atlantic right whales (Eubalaena glacialis). We are now eliciting expert knowledge on the movement of right whales among geographic regions to parameterize a spatial model of health. Expert elicitation complements methods such as simulation models or extrapolations from other species, sometimes with greater accuracy and less uncertainty. PMID:26610972

  16. Alterations of mitochondrial dynamics allow retrograde propagation of locally initiated axonal insults.

    Science.gov (United States)

    Lassus, Benjamin; Magifico, Sebastien; Pignon, Sandra; Belenguer, Pascale; Miquel, Marie-Christine; Peyrin, Jean-Michel

    2016-01-01

    In chronic neurodegenerative syndromes, neurons progressively die through a generalized retraction pattern triggering retrograde axonal degeneration toward the cell bodies, which molecular mechanisms remain elusive. Recent observations suggest that direct activation of pro-apoptotic signaling in axons triggers local degenerative events associated with early alteration of axonal mitochondrial dynamics. This raises the question of the role of mitochondrial dynamics on both axonal vulnerability stress and their implication in the spreading of damages toward unchallenged parts of the neuron. Here, using microfluidic chambers, we assessed the consequences of interfering with OPA1 and DRP1 proteins on axonal degeneration induced by local application of rotenone. We found that pharmacological inhibition of mitochondrial fission prevented axonal damage induced by rotenone, in low glucose conditions. While alteration of mitochondrial dynamics per se did not lead to spontaneous axonal degeneration, it dramatically enhanced axonal vulnerability to rotenone, which had no effect in normal glucose conditions, and promoted retrograde spreading of axonal degeneration toward the cell body. Altogether, our results suggest a mitochondrial priming effect in axons as a key process of axonal degeneration. In the context of neurodegenerative diseases, like Parkinson's and Alzheimer's, mitochondria fragmentation could hasten neuronal death and initiate spatial dispersion of locally induced degenerative events. PMID:27604820

  17. Detecting plastics in seedcotton

    Science.gov (United States)

    To increase global market share and value the US cotton industry needs to supply cotton lint that is free of contamination. Removing plastic contamination first requires developing a means to detect plastics in seedcotton. This study was conducted to validate a custom Ion Mobility Spectrometer (IM...

  18. Halos of Plastic

    Institute of Scientific and Technical Information of China (English)

    Maya Reid

    2012-01-01

    The halos that span South Africa's coastline are anything but angelic. Fanning out around four major urban centers-Cape Town, Port Elizabeth, East London and Durban-they are made up of innumerable bits and pieces of plastic. As a form of pollution, their shelflife is unfathomable. Plastic is essentially chemically inactive. It's designed to never break down.

  19. Laser processing of plastics

    Science.gov (United States)

    Atanasov, Peter A.

    1995-03-01

    CO2-laser processing of plastics has been studied experimentally and theoretically. Welding of cylindrical parts made from polycarbonate and polypropylene, cutting of polymethyl-methacrylate plates, and drilling holes in polypropylene are presented as examples. A good coincidence between theoretical and experimental results in case of laser welding has been found. Some practical aspects of laser processing of plastics has been given.

  20. The role of T-cadherin in axonal pathway formation in neocortical circuits.

    Science.gov (United States)

    Hayano, Yuki; Zhao, Hong; Kobayashi, Hiroaki; Takeuchi, Kosei; Norioka, Shigemi; Yamamoto, Nobuhiko

    2014-12-01

    Cortical efferent and afferent fibers are arranged in a stereotyped pattern in the intermediate zone (IZ). Here, we studied the mechanism of axonal pathway formation by identifying a molecule that is expressed in a subset of cortical axons in the rat. We found that T-cadherin (T-cad), a member of the cadherin family, is expressed in deep-layer cell axons projecting to subcortical structures, but not in upper layer callosal axons projecting to the contralateral cortex. Ectopic expression of T-cad in upper layer cells induced axons to project toward subcortical structures via the upper part of the IZ. Moreover, the axons of deep-layer cells in which T-cad expression was suppressed by RNAi projected towards the contralateral cortex via an aberrant route. These results suggest that T-cad is involved in axonal pathway formation in the developing cortex. PMID:25468941

  1. Acting green elicits a literal warm glow

    Science.gov (United States)

    Taufik, Danny; Bolderdijk, Jan Willem; Steg, Linda

    2015-01-01

    Environmental policies are often based on the assumption that people only act environmentally friendly if some extrinsic reward is implicated, usually money. We argue that people might also be motivated by intrinsic rewards: doing the right thing (such as acting environmentally friendly) elicits psychological rewards in the form of positive feelings, a phenomenon known as warm glow. Given the fact that people's psychological state may affect their thermal state, we expected that this warm glow could express itself quite literally: people who act environmentally friendly may perceive the temperature to be higher. In two studies, we found that people who learned they acted environmentally friendly perceived a higher temperature than people who learned they acted environmentally unfriendly. The underlying psychological mechanism pertains to the self-concept: learning you acted environmentally friendly signals to yourself that you are a good person. Together, our studies show that acting environmentally friendly can be psychologically rewarding, suggesting that appealing to intrinsic rewards can be an alternative way to encourage pro-environmental actions.

  2. Environment and brain plasticity: towards an endogenous pharmacotherapy.

    Science.gov (United States)

    Sale, Alessandro; Berardi, Nicoletta; Maffei, Lamberto

    2014-01-01

    Brain plasticity refers to the remarkable property of cerebral neurons to change their structure and function in response to experience, a fundamental theoretical theme in the field of basic research and a major focus for neural rehabilitation following brain disease. While much of the early work on this topic was based on deprivation approaches relying on sensory experience reduction procedures, major advances have been recently obtained using the conceptually opposite paradigm of environmental enrichment, whereby an enhanced stimulation is provided at multiple cognitive, sensory, social, and motor levels. In this survey, we aim to review past and recent work concerning the influence exerted by the environment on brain plasticity processes, with special emphasis on the underlying cellular and molecular mechanisms and starting from experimental work on animal models to move to highly relevant work performed in humans. We will initiate introducing the concept of brain plasticity and describing classic paradigmatic examples to illustrate how changes at the level of neuronal properties can ultimately affect and direct key perceptual and behavioral outputs. Then, we describe the remarkable effects elicited by early stressful conditions, maternal care, and preweaning enrichment on central nervous system development, with a separate section focusing on neurodevelopmental disorders. A specific section is dedicated to the striking ability of environmental enrichment and physical exercise to empower adult brain plasticity. Finally, we analyze in the last section the ever-increasing available knowledge on the effects elicited by enriched living conditions on physiological and pathological aging brain processes. PMID:24382886

  3. American Society of Plastic Surgeons

    Science.gov (United States)

    ... doctor who is a member of the American Society of Plastic Surgeons (ASPS®), you can rest assured ... ASPS The Plastic Surgery Foundation Copyright © 2016 American Society of Plastic Surgeons | Privacy Policy | Sitemap | Terms and ...

  4. Introducing Forum Theatre to Elicit and Advocate Children's Views

    Science.gov (United States)

    Hammond, Nick

    2013-01-01

    Eliciting and advocating the voice of the child remains at the heart of international political agenda and also remains a central role for educational psychologists (EPs). Previous research indicates that EPs tend to use language-based methods for eliciting and advocating views of children. However, these approaches are often limited. Taking a…

  5. Elicited Emotions and Cognitive Functioning in Preschool Children

    Science.gov (United States)

    Blau, Rivka; Klein, Pnina S.

    2010-01-01

    In this study, the effects of eliciting positive and negative emotions on various cognitive functions of four- to five-year-old preschool children were examined. Emotions were elicited through presentations of "happy" and "sad" video clips, before the children performed the cognitive tasks. Behavioural (facial expressions) and physiological (heart…

  6. Belief elicitation in experiments: Is there a hedging problem?

    DEFF Research Database (Denmark)

    Blanco, Mariana; Engelmann, Dirk; Koch, Alexander;

    2010-01-01

    Belief-elicitation experiments usually reward accuracy of stated beliefs in addition to payments for other decisions. But this allows risk-averse subjects to hedge with their stated beliefs against adverse outcomes of the other decisions. So can we trust the existing belief-elicitation results? A...

  7. Science Teachers' Elicitation Practices: Insights for Formative Assessment

    Science.gov (United States)

    Ateh, Comfort M.

    2015-01-01

    In evaluating teachers' instructional decisions during instruction, it is clear that the nature of their elicitation is crucial for student learning. When instructional decisions are informed by information about students' conceptual understanding, significant learning is possible. This article examined the elicitation practices of two high school…

  8. Axonal degeneration affects muscle density in older men and women.

    Science.gov (United States)

    Lauretani, Fulvio; Bandinelli, Stefania; Bartali, Benedetta; Di Iorio, Angelo; Giacomini, Vittoria; Corsi, Anna Maria; Guralnik, Jack M; Ferrucci, Luigi

    2006-08-01

    Using data from InCHIANTI, a prospective population-based survey of older persons, we examined the relationship of peroneal nerve conduction velocity (NCV, a measure of nerve myelination) and compound muscle action potential (CMAP, a measure of axonal degeneration) with calf muscle mass and density, two complementary measures of sarcopenia. NCV and CMAP were assessed by surface electroneurography of the right peroneal nerve conducted in 1162 participants, 515 men and 647 women, age 21-96 years, free of major neurological diseases. Cross-sectional muscle area and calf muscle density were measured using peripheral quantitative computerized tomography (pQCT). Both nerve and muscle parameters declined with age although in most cases the decline was not linear. In both sexes, CMAP, but not NCV, was independently and significantly associated with calf muscle density. These findings suggest that intrinsic changes in the muscle tissue are partially caused by a reduction in the number of motor axons. PMID:16085338

  9. Missed connections: photoreceptor axon seeks target neuron for synaptogenesis.

    Science.gov (United States)

    Astigarraga, Sergio; Hofmeyer, Kerstin; Treisman, Jessica E

    2010-08-01

    Extending axons must choose the appropriate synaptic target cells in order to assemble functional neural circuitry. The axons of the Drosophila color-sensitive photoreceptors R7 and R8 project as a single fascicle from each ommatidium, but their terminals are segregated into distinct layers within their target region. Recent studies have begun to reveal the molecular mechanisms that establish this projection pattern. Both homophilic adhesion molecules and specific ligand-receptor interactions make important contributions to stabilizing R7 and R8 terminals in the appropriate target layers. These cell recognition molecules are regulated by the same transcription factors that control R7 and R8 cell fates. Autocrine and repulsive signaling mechanisms prevent photoreceptor terminals from encroaching on their neighbors, preserving the spatial resolution of visual information. PMID:20434326

  10. Bazooka mediates secondary axon morphology in Drosophila brain lineages

    OpenAIRE

    Hartenstein Volker; Spindler Shana R

    2011-01-01

    Abstract In the Drosophila brain, neural lineages project bundled axon tracts into a central neuropile. Each lineage exhibits a stereotypical branching pattern and trajectory, which distinguish it from other lineages. In this study, we used a multilineage approach to explore the neural function of the Par-complex member Par3/Bazooka in vivo. Drosophila bazooka is expressed in post-mitotic neurons of the larval brain and localizes within neurons in a lineage-dependent manner. The fact that mul...

  11. Giant axonal neuropathy: observations on a further patient.

    OpenAIRE

    Donaghy, M; Brett, E M; Ormerod, I E; King, R H; Thomas, P. K.

    1988-01-01

    A further child with giant axonal neuropathy (GAN), abnormally curly hair and consanguineous parents is described. Of the 19 patients with GAN so far reported in the literature, six, including the present patient, have resulted from consanguineous marriages. This makes autosomal recessive inheritance of GAN highly probable. Our patient also exhibited cerebellar ataxia and signs of pyramidal tract damage; magnetic resonance brain imaging demonstrated abnormalities within the cerebellar and cer...

  12. Craniocerebral trauma. Magnetic resonance imaging of diffuse axonal injury

    International Nuclear Information System (INIS)

    Acceleration-deceleration rotational brain trauma is a common cause of disability or death in young adults and often leads to a focal destruction of axons. The resulting pathology, axonal shear injury is referred to as diffuse axonal injury (DAI). The DAI-associated lesions occur bilaterally, are widely dispersed and have been observed in the surface and deep white matter. They are found near to and far from the impact site. When DAI is clinically suspected, magnetic resonance imaging (MRI) is the method of choice for further clarification, especially in patients where cranial computed tomography (CT) is inconspicuous. To investigate the presence of DAI after traumatic brain injury (TBI), a multimodal MRI approach is applied including the common structural and also functional imaging sequences. For structural MRI, fluid-attenuated inversion recovery (FLAIR) weighted and susceptibility contrast imaging (SWI) are the sequences mainly used. The SWI technique is extremely sensitive to blood breakdown products, which appear as small signal voids at three locations, at the gray-white interface, in the corpus callosum and in the brain stem. Functional MRI comprises a group of constantly developing techniques that have great potential in optimal evaluation of the white matter in patients after craniocerebral trauma. These imaging techniques allow the visualization of changes associated with shear injuries, such as functional impairment of axons and decreased blood flow and abnormal metabolic activity of the brain parts affected. The multimodal MRI approach in patients with DAI results in a more detailed and differentiated representation of the underlying pathophysiological changes of the injured nerve tracts and helps to improve the diagnostic and prognostic accuracy of MRI. When DAI is suspected multimodal MRI should be performed as soon as possible after craniocerebral injury. (orig.)

  13. Estimating neuronal connectivity from axonal and dendritic density fields

    Directory of Open Access Journals (Sweden)

    Jaap evan Pelt

    2013-11-01

    Full Text Available Neurons innervate space by extending axonal and dendritic arborizations. When axons and dendrites come in close proximity of each other, synapses between neurons can be formed. Neurons vary greatly in their morphologies and synaptic connections with other neurons. The size and shape of the arborizations determine the way neurons innervate space. A neuron may therefore be characterized by the spatial distribution of its axonal and dendritic 'mass'. A population mean 'mass' density field of a particular neuron type can be obtained by averaging over the individual variations in neuron geometries. Connectivity in terms of candidate synaptic contacts between neurons can be determined directly on the basis of their arborizations but also indirectly on the basis of their density fields. To decide when a candidate synapse can be formed, we previously developed a criterion defining that axonal and dendritic line pieces should cross in 3D and have an orthogonal distance less than a threshold value. In this paper, we developed new methodology for applying this criterion to density fields. We show that estimates of the number of contacts between neuron pairs calculated from their density fields are fully consistent with the number of contacts calculated from the actual arborizations. However, the estimation of the connection probability and the expected number of contacts per connection cannot be calculated directly from density fields, because density fields do not carry anymore the correlative structure in the spatial distribution of synaptic contacts. Alternatively, these two connectivity measures can be estimated from the expected number of contacts by using empirical mapping functions. The neurons used for the validation studies were generated by our neuron simulator NETMORPH. An example is given of the estimation of average connectivity and Euclidean pre- and postsynaptic distance distributions in a network of neurons represented by their population

  14. Tau phosphorylation affects its axonal transport and degradation

    OpenAIRE

    Rodríguez-Martín, Teresa; Cuchillo-Ibáñez, Inmaculada; Noble, Wendy; Nyenya, Fanon; Anderton, Brian H; Hanger, Diane P.

    2013-01-01

    Phosphorylated forms of microtubule-associated protein tau accumulate in neurofibrillary tangles in Alzheimer's disease. To investigate the effects of specific phosphorylated tau residues on its function, wild type or phosphomutant tau was expressed in cells. Elevated tau phosphorylation decreased its microtubule binding and bundling, and increased the number of motile tau particles, without affecting axonal transport kinetics. In contrast, reducing tau phosphorylation enhanced the amount of ...

  15. Abnormal Corticospinal Excitability in Traumatic Diffuse Axonal Brain Injury

    OpenAIRE

    Bernabeu, Montse; Demirtas-Tatlidede, Asli; Opisso, Eloy; Lopez, Raquel; Tormos, Jose Mª; Pascual-Leone, Alvaro

    2009-01-01

    This study aimed to investigate the cortical motor excitability characteristics in diffuse axonal injury (DAI) due to severe traumatic brain injury (TBI). A variety of excitatory and inhibitory transcranial magnetic stimulation (TMS) paradigms were applied to primary motor cortices of 17 patients and 11 healthy controls. The parameters of testing included resting motor threshold (MT), motor evoked potential (MEP) area under the curve, input-output curves, MEP variability, and silent period (S...

  16. Slowing of the axonal transport of neurofilament proteins during development

    International Nuclear Information System (INIS)

    We examined age-dependent changes in neurofilament transport in motor axons of the rat sciatic nerve. SDS-PAGE and gel fluorography confirmed that the distribution of labeled neurofilament triplet protein coincides with the major slow component a (SCa) wave in these neurons. The velocity of neurofilament transport was calculated on the basis of the location of the 50th percentile of radioactivity in this wave 33 days after motor neurons were labeled by the intraspinal administration of [3H]leucine and [3H]lysine. Overall, the velocity fell from 1.95 mm/day at 3 weeks of age to 1.12 mm/day at 20 weeks. Between 3 and 10 weeks, it fell at a 6-fold higher rate (0.096 mm/day/week) than between 10 and 20 weeks (0.016 mm/day/week). We also found a marked change in the shape of the slow component wave during development. It appeared to consist of several overlapping peaks moving at slightly different velocities in animals 10 weeks of age or less as compared to a single slower moving peak at 20 weeks. We propose that the velocity of slow axonal transport reflects the level of maturation of the neuron, and that the presence of several overlapping peaks of transported radioactivity in the sciatic nerve of younger animals reflects the presence of several populations of motor axons at different stages of development. We also discuss the relationship between changes in the velocity of neurofilament transport and alterations in the composition of the cytoskeleton that occur as the axon grows in caliber during postnatal development

  17. Adult motor axons preferentially reinnervate predegenerated muscle nerve

    OpenAIRE

    M. Abdullah; O'Daly, A.; A Vyas; Rohde, C.; Brushart, T.M.

    2013-01-01

    Preferential motor reinnervation (PMR) is the tendency for motor axons regenerating after repair of mixed nerve to reinnervate muscle nerve and/or muscle rather than cutaneous nerve or skin. PMR may occur in response to the peripheral nerve pathway alone in juvenile rats (Brushart, 1993; Redett et al., 2005), yet the ability to identify and respond to specific pathway markers is reportedly lost in adults (Uschold et al., 2007). The experiments reported here evaluate the relative roles of path...

  18. White matter microstructure from nonparametric axon diameter distribution mapping.

    Science.gov (United States)

    Benjamini, Dan; Komlosh, Michal E; Holtzclaw, Lynne A; Nevo, Uri; Basser, Peter J

    2016-07-15

    We report the development of a double diffusion encoding (DDE) MRI method to estimate and map the axon diameter distribution (ADD) within an imaging volume. A variety of biological processes, ranging from development to disease and trauma, may lead to changes in the ADD in the central and peripheral nervous systems. Unlike previously proposed methods, this ADD experimental design and estimation framework employs a more general, nonparametric approach, without a priori assumptions about the underlying form of the ADD, making it suitable to analyze abnormal tissue. In the current study, this framework was used on an ex vivo ferret spinal cord, while emphasizing the way in which the ADD can be weighted by either the number or the volume of the axons. The different weightings, which result in different spatial contrasts, were considered throughout this work. DDE data were analyzed to derive spatially resolved maps of average axon diameter, ADD variance, and extra-axonal volume fraction, along with a novel sub-micron restricted structures map. The morphological information contained in these maps was then used to segment white matter into distinct domains by using a proposed k-means clustering algorithm with spatial contiguity and left-right symmetry constraints, resulting in identifiable white matter tracks. The method was validated by comparing histological measures to the estimated ADDs using a quantitative similarity metric, resulting in good agreement. With further acquisition acceleration and experimental parameters adjustments, this ADD estimation framework could be first used preclinically, and eventually clinically, enabling a wide range of neuroimaging applications for improved understanding of neurodegenerative pathologies and assessing microstructural changes resulting from trauma. PMID:27126002

  19. Structural Plasticity, Effectual Connectivity, and Memory in Cortex.

    Science.gov (United States)

    Knoblauch, Andreas; Sommer, Friedrich T

    2016-01-01

    Learning and memory is commonly attributed to the modification of synaptic strengths in neuronal networks. More recent experiments have also revealed a major role of structural plasticity including elimination and regeneration of synapses, growth and retraction of dendritic spines, and remodeling of axons and dendrites. Here we work out the idea that one likely function of structural plasticity is to increase "effectual connectivity" in order to improve the capacity of sparsely connected networks to store Hebbian cell assemblies that are supposed to represent memories. For this we define effectual connectivity as the fraction of synaptically linked neuron pairs within a cell assembly representing a memory. We show by theory and numerical simulation the close links between effectual connectivity and both information storage capacity of neural networks and effective connectivity as commonly employed in functional brain imaging and connectome analysis. Then, by applying our model to a recently proposed memory model, we can give improved estimates on the number of cell assemblies that can be stored in a cortical macrocolumn assuming realistic connectivity. Finally, we derive a simplified model of structural plasticity to enable large scale simulation of memory phenomena, and apply our model to link ongoing adult structural plasticity to recent behavioral data on the spacing effect of learning. PMID:27378861

  20. Axonal Transport Impairment in Chemotherapy-Induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Gabriella Nicolini

    2015-08-01

    Full Text Available Chemotherapy-Induced Peripheral Neuropathy (CIPN is a dose-limiting side effect of several antineoplastic drugs which significantly reduces patients’ quality of life. Although different molecular mechanisms have been investigated, CIPN pathobiology has not been clarified yet. It has largely been recognized that Dorsal Root Ganglia are the main targets of chemotherapy and that the longest nerves are the most damaged, together with fast axonal transport. Indeed, this bidirectional cargo-specific transport has a pivotal role in neuronal function and its impairment is involved in several neurodegenerative and neurodevelopmental diseases. Literature data demonstrate that, despite different mechanisms of action, all antineoplastic agents impair the axonal trafficking to some extent and the severity of the neuropathy correlates with the degree of damage on this bidirectional transport. In this paper, we will examine the effect of the main old and new chemotherapeutic drug categories on axonal transport, with the aim of clarifying their potential mechanisms of action, and, if possible, of identifying neuroprotective strategies, based on the knowledge of the alterations induced by each drugs.

  1. Retinal glia promote dorsal root ganglion axon regeneration.

    Directory of Open Access Journals (Sweden)

    Barbara Lorber

    Full Text Available Axon regeneration in the adult central nervous system (CNS is limited by several factors including a lack of neurotrophic support. Recent studies have shown that glia from the adult rat CNS, specifically retinal astrocytes and Müller glia, can promote regeneration of retinal ganglion cell axons. In the present study we investigated whether retinal glia also exert a growth promoting effect outside the visual system. We found that retinal glial conditioned medium significantly enhanced neurite growth and branching of adult rat dorsal root ganglion neurons (DRG in culture. Furthermore, transplantation of retinal glia significantly enhanced regeneration of DRG axons past the dorsal root entry zone after root crush in adult rats. To identify the factors that mediate the growth promoting effects of retinal glia, mass spectrometric analysis of retinal glial conditioned medium was performed. Apolipoprotein E and secreted protein acidic and rich in cysteine (SPARC were found to be present in high abundance, a finding further confirmed by western blotting. Inhibition of Apolipoprotein E and SPARC significantly reduced the neuritogenic effects of retinal glial conditioned medium on DRG in culture, suggesting that Apolipoprotein E and SPARC are the major mediators of this regenerative response.

  2. Dysregulated axonal RNA translation in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Yasuda, Kyota; Mili, Stavroula

    2016-09-01

    Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease that has been associated with a diverse array of genetic changes. Prominent among these are mutations in RNA-binding proteins (RBPs) or repeat expansions that give rise to toxic RNA species. RBPs are additionally central components of pathologic aggregates that constitute a disease hallmark, suggesting that dysregulation of RNA metabolism underlies disease progression. In the context of neuronal physiology, transport of RNAs and localized RNA translation in axons are fundamental to neuronal survival and function. Several lines of evidence suggest that axonal RNA translation is a central process perturbed by various pathogenic events associated with ALS. Dysregulated translation of specific RNA groups could underlie feedback effects that connect and reinforce disease manifestations. Among such candidates are RNAs encoding proteins involved in the regulation of microtubule dynamics. Further understanding of axonally dysregulated RNA targets and of the feedback mechanisms they induce could provide useful therapeutic insights. WIREs RNA 2016, 7:589-603. doi: 10.1002/wrna.1352 For further resources related to this article, please visit the WIREs website. PMID:27038103

  3. Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis.

    Directory of Open Access Journals (Sweden)

    Yuta Iwai

    Full Text Available Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS, suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP amplitude (index of motor neuronal loss and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44, ALS patients (n = 140 had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p 5mV. Regression analyses showed that SDTC (R = -0.22 and depolarizing threshold electrotonus (R = -0.22 increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS.

  4. Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Iwai, Yuta; Shibuya, Kazumoto; Misawa, Sonoko; Sekiguchi, Yukari; Watanabe, Keisuke; Amino, Hiroshi; Kuwabara, Satoshi

    2016-01-01

    Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS), suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP) amplitude (index of motor neuronal loss) and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44), ALS patients (n = 140) had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p CMAP (> 5mV). Regression analyses showed that SDTC (R = -0.22) and depolarizing threshold electrotonus (R = -0.22) increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS. PMID:27383069

  5. Sensory axon-derived neuregulin-1 is required for axoglial signaling and normal sensory function but not for long-term axon maintenance

    DEFF Research Database (Denmark)

    Fricker, F.R.; Zhu, N.; Tsantoulas, C.;

    2009-01-01

    " pockets. The total number of axons in the sural nerve was unchanged, but a greater proportion was unmyelinated. In addition, we observed large-diameter axons that were in a 1:1 relationship with Schwann cells, surrounded by a basal lamina but not myelinated. There was no evidence of DRG or Schwann cell...

  6. Map formation in the olfactory bulb by axon guidance of olfactory neurons

    Directory of Open Access Journals (Sweden)

    Benjamin Auffarth

    2011-10-01

    Full Text Available The organization of representations in the brain has been observed to locally reflect subspaces of inputsthat are relevant to behavioral or perceptual feature combinations, such as in areas receptiveto lower and higher-order features in the visual system. The early olfactory system developedhighly plastic mechanisms and convergent evidence indicates that projections from primaryneurons converge onto the glomerular level of the olfactory bulb (OB to form a code composed ofcontinuous spatial zones that are differentially active for particular physico–-chemical featurecombinations, some of which are known to trigger behavioral responses. In a model study of theearly human olfactory system, we derive a glomerular organization based on a set of real-world,biologically-relevant stimuli, a distribution of receptors that respond each to a set ofodorants of similar ranges of molecular properties, and a mechanism of axon guidance basedon activity. Apart from demonstrating activity-dependent glomeruli formation and reproducing therelationship of glomerular recruitment with concentration, it is shown that glomerular responsesreflect similarities of human odor category perceptions and that further, a spatial code providesa better correlation than a distributed population code. These results are consistent with evidenceof functional compartmentalization in the OB and could suggest a function for the bulb inencoding of perceptual dimensions.

  7. Exosomes mediate cell contact-independent ephrin-Eph signaling during axon guidance.

    Science.gov (United States)

    Gong, Jingyi; Körner, Roman; Gaitanos, Louise; Klein, Rüdiger

    2016-07-01

    The cellular release of membranous vesicles known as extracellular vesicles (EVs) or exosomes represents a novel mode of intercellular communication. Eph receptor tyrosine kinases and their membrane-tethered ephrin ligands have very important roles in such biologically diverse processes as neuronal development, plasticity, and pathological diseases. Until now, it was thought that ephrin-Eph signaling requires direct cell contact. Although the biological functions of ephrin-Eph signaling are well understood, our mechanistic understanding remains modest. Here we report the release of EVs containing Ephs and ephrins by different cell types, a process requiring endosomal sorting complex required for transport (ESCRT) activity and regulated by neuronal activity. Treatment of cells with purified EphB2(+) EVs induces ephrinB1 reverse signaling and causes neuronal axon repulsion. These results indicate a novel mechanism of ephrin-Eph signaling independent of direct cell contact and proteolytic cleavage and suggest the participation of EphB2(+) EVs in neural development and synapse physiology. PMID:27354374

  8. Axon Degeneration Gated by Retrograde Activation of Somatic Pro-apoptotic Signaling.

    Science.gov (United States)

    Simon, David J; Pitts, Jason; Hertz, Nicholas T; Yang, Jing; Yamagishi, Yuya; Olsen, Olav; Tešić Mark, Milica; Molina, Henrik; Tessier-Lavigne, Marc

    2016-02-25

    During development, sensory axons compete for limiting neurotrophic support, and local neurotrophin insufficiency triggers caspase-dependent axon degeneration. The signaling driving axon degeneration upon local deprivation is proposed to reside within axons. Our results instead support a model in which, despite the apoptotic machinery being present in axons, the cell body is an active participant in gating axonal caspase activation and axon degeneration. Loss of trophic support in axons initiates retrograde activation of a somatic pro-apoptotic pathway, which, in turn, is required for distal axon degeneration via an anterograde pro-degenerative factor. At a molecular level, the cell body is the convergence point of two signaling pathways whose integrated action drives upregulation of pro-apoptotic Puma, which, unexpectedly, is confined to the cell body. Puma then overcomes inhibition by pro-survival Bcl-xL and Bcl-w and initiates the anterograde pro-degenerative program, highlighting the role of the cell body as an arbiter of large-scale axon removal. PMID:26898330

  9. Regulation of action potential waveforms by axonal GABAA receptors in cortical pyramidal neurons.

    Directory of Open Access Journals (Sweden)

    Yang Xia

    Full Text Available GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb of the main axon trunk of layer -5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors.

  10. Irregular geometries in normal unmyelinated axons: a 3D serial EM analysis.

    Science.gov (United States)

    Greenberg, M M; Leitao, C; Trogadis, J; Stevens, J K

    1990-12-01

    Axons have generally been represented as straight cylinders. It is not at all uncommon for anatomists to take single cross-sections of an axonal bundle, and from the axonal diameter compute expected conduction velocities. This assumes that each cross-section represents a slice through a perfect cylinder. We have examined the three-dimensional geometry of 98 central and peripheral unmyelinated axons, using computer-assisted serial electron microscopy. These reconstructions reveal that virtually all unmyelinated axons have highly irregular axial shapes consisting of periodic varicosities. The varicosities were, without exception, filled with membranous organelles frequently including mitochondria, and have obligatory volumes similar to that described in other neurites. The mitochondria make contact with microtubules, while the other membraneous organelles were frequently found free floating in the cytoplasm. We conclude that unmyelinated axons are fundamentally varicose structures created by the presence of organelles, and that an axon's calibre is dynamic in both space and time. These irregular axonal geometries raise serious doubts about standard two dimensional morphometric analysis and suggest that electrical properties may be more heterogeneous than expected from single section data. These results also suggest that the total number of microtubules contained in an axon, rather than its single section diameter, may prove to be a more accurate predictor of properties such as conduction velocity. Finally, these results offer an explanation for a number of pathological changes that have been described in unmyelinated axons. PMID:2292722

  11. Soluble axoplasm enriched from injured CNS axons reveals the early modulation of the actin cytoskeleton.

    Directory of Open Access Journals (Sweden)

    Patrick Garland

    Full Text Available Axon injury and degeneration is a common consequence of diverse neurological conditions including multiple sclerosis, traumatic brain injury and spinal cord injury. The molecular events underlying axon degeneration are poorly understood. We have developed a novel method to enrich for axoplasm from rodent optic nerve and characterised the early events in Wallerian degeneration using an unbiased proteomics screen. Our detergent-free method draws axoplasm into a dehydrated hydrogel of the polymer poly(2-hydroxyethyl methacrylate, which is then recovered using centrifugation. This technique is able to recover axonal proteins and significantly deplete glial contamination as confirmed by immunoblotting. We have used iTRAQ to compare axoplasm-enriched samples from naïve vs injured optic nerves, which has revealed a pronounced modulation of proteins associated with the actin cytoskeleton. To confirm the modulation of the actin cytoskeleton in injured axons we focused on the RhoA pathway. Western blotting revealed an augmentation of RhoA and phosphorylated cofilin in axoplasm-enriched samples from injured optic nerve. To investigate the localisation of these components of the RhoA pathway in injured axons we transected axons of primary hippocampal neurons in vitro. We observed an early modulation of filamentous actin with a concomitant redistribution of phosphorylated cofilin in injured axons. At later time-points, RhoA is found to accumulate in axonal swellings and also colocalises with filamentous actin. The actin cytoskeleton is a known sensor of cell viability across multiple eukaryotes, and our results suggest a similar role for the actin cytoskeleton following axon injury. In agreement with other reports, our data also highlights the role of the RhoA pathway in axon degeneration. These findings highlight a previously unexplored area of axon biology, which may open novel avenues to prevent axon degeneration. Our method for isolating CNS axoplasm

  12. A Plastic Menagerie

    Science.gov (United States)

    Hadley, Mary Jane

    2010-01-01

    Bobble heads had become quite popular, depicting all sorts of sports figures, animals, and even presidents. In this article, the author describes how her fourth graders made bobble head sculptures out of empty plastic drink bottles. (Contains 1 online resource.)

  13. Dreaming in plastic

    Science.gov (United States)

    Korzhov, Marianna; Andelman, David; Shikler, Rafi

    2008-07-01

    Plastic is one of the most versatile materials available. It is cheap, flexible and easy to process, and as a result it is all around us - from our computer keyboards to the soles of our shoes. One of its most common applications is as an insulating coating for electric wires; indeed, plastic is well known for its insulating characteristics. It came as something of a surprise, therefore, when in the late 1970s a new generation of plastics was discovered that displayed exactly the opposite behaviour - the ability to conduct electricity. In fact, plastics can be made with a whole range of conductivities - there are polymer materials that behave like semiconductors and there are those that can conduct as well as metals. This discovery sparked a revolution in the electronics community, and three decades of research effort is now yielding a range of stunning new applications for this ubiquitous material.

  14. Synaptic plasticity and phosphorylation

    OpenAIRE

    Lee, Hey-Kyoung

    2006-01-01

    A number of neuronal functions, including synaptic plasticity, depend on proper regulation of synaptic proteins, many of which can be rapidly regulated by phosphorylation. Neuronal activity controls the function of these synaptic proteins by exquisitely regulating the balance of various protein kinase and protein phosphatase activity. Recent understanding of synaptic plasticity mechanisms underscores important roles that these synaptic phosphoproteins play in regulating both pre- and post-syn...

  15. Extruded Plastic Scintillation Detectors

    CERN Document Server

    Pla-Dalmau, A; Mellott, K L; Pla-Dalmau, Anna; Bross, Alan D.; Mellott, Kerry L.

    1999-01-01

    As a way to lower the cost of plastic scintillation detectors, commercially available polystyrene pellets have been used in the production of scintillating materials that can be extruded into different profiles. The selection of raw materials is discussed. Two techniques to add wavelength shifting dopants to polystyrene pellets and to extrude plastic scintillating strips are described. Data on light yield and transmittance measurements are presented.

  16. Development of plastic surgery

    Directory of Open Access Journals (Sweden)

    Pećanac Marija Đ.

    2015-01-01

    Full Text Available Introduction. Plastic surgery is a medical specialty dealing with corrections of defects, improvements in appearance and restoration of lost function. Ancient Times. The first recorded account of reconstructive plastic surgery was found in ancient Indian Sanskrit texts, which described reconstructive surgeries of the nose and ears. In ancient Greece and Rome, many medicine men performed simple plastic cosmetic surgeries to repair damaged parts of the body caused by war mutilation, punishment or humiliation. In the Middle Ages, the development of all medical braches, including plastic surgery was hindered. New age. The interest in surgical reconstruction of mutilated body parts was renewed in the XVIII century by a great number of enthusiastic and charismatic surgeons, who mastered surgical disciplines and became true artists that created new forms. Modern Era. In the XX century, plastic surgery developed as a modern branch in medicine including many types of reconstructive surgery, hand, head and neck surgery, microsurgery and replantation, treatment of burns and their sequelae, and esthetic surgery. Contemporary and future plastic surgery will continue to evolve and improve with regenerative medicine and tissue engineering resulting in a lot of benefits to be gained by patients in reconstruction after body trauma, oncology amputation, and for congenital disfigurement and dysfunction.

  17. Sorting Plastic Waste in Hydrocyclone

    Directory of Open Access Journals (Sweden)

    Ernestas Šutinys

    2011-02-01

    Full Text Available The article presents material about sorting plastic waste in hydrocyclone. The tests on sorting plastic waste were carried out. Also, the findings received from the performed experiment on the technology of sorting plastic waste are interpreted applying an experimental model of the equipment used for sorting plastics of different density.Article in Lithuanian

  18. Coculture of elongated neuron axon with poly (D, L-lactide-co-glycolide) biomembrane in vitro

    Institute of Scientific and Technical Information of China (English)

    程飚; 陈峥嵘

    2004-01-01

    Objective: To elongate human nerve axon in culture and search for suitable support matrices for peripheral nervous system transplantation.Methods: Human embryo cortical neuronal cells,seeded on poly ( D, L-lactide-co-glycolide ) ( PLGA )membrane scaffolds, were elongated with a self-made neuro-axon extending device. The growth and morphological changes of neuron axons were observed to measure axolemmal permeability after elongation.Neurofilament protein was stained by immunohistochemical technique.Results: Human embryo neuron axon could be elongated and cultured on the PLGA membrane and retain their normal form and function.Conclusions: Three dimensional scaffolds with elongated neuron axon have the basic characteristics of artificial nerves, indicating a fundemental theory of nerve repair with elongated neuron axon.

  19. Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination.

    Science.gov (United States)

    Lappe-Siefke, Corinna; Goebbels, Sandra; Gravel, Michel; Nicksch, Eva; Lee, John; Braun, Peter E; Griffiths, Ian R; Nave, Klaus-Armin

    2003-03-01

    Myelination of axons by oligodendrocytes enables rapid impulse propagation in the central nervous system. But long-term interactions between axons and their myelin sheaths are poorly understood. Here we show that Cnp1, which encodes 2',3'-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly. In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death. But, in contrast to previously studied myelin mutants, the ultrastructure, periodicity and physical stability of myelin were not altered in these mice. Genetically, the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss. PMID:12590258

  20. X11/Mint Genes Control Polarized Localization of Axonal Membrane Proteins in Vivo

    OpenAIRE

    Garrett G Gross; Lone, G. Mohiddin; Leung, Lok Kwan; Hartenstein, Volker; Guo, Ming

    2013-01-01

    Mislocalization of axonal proteins can result in misassembly and/or miswiring of neural circuits, causing disease. To date, only a handful of genes that control polarized localization of axonal membrane proteins have been identified. Here we report that Drosophila X11/Mint proteins are required for targeting several proteins, including human amyloid precursor protein (APP) and Drosophila APP-like protein (APPL), to axonal membranes and for their exclusion from dendrites of the mushroom body i...

  1. Actin turnover is required to prevent axon retraction driven by endogenous actomyosin contractility

    OpenAIRE

    Gallo, Gianluca; Yee, Hal F.; Letourneau, Paul C.

    2002-01-01

    Growth cone motility and guidance depend on the dynamic reorganization of filamentous actin (F-actin). In the growth cone, F-actin undergoes turnover, which is the exchange of actin subunits from existing filaments. However, the function of F-actin turnover is not clear. We used jasplakinolide (jasp), a cell-permeable macrocyclic peptide that inhibits F-actin turnover, to study the role of F-actin turnover in axon extension. Treatment with jasp caused axon retraction, demonstrating that axon ...

  2. Directional specificity and patterning of sensory axons in trigeminal ganglion–whisker pad cocultures

    OpenAIRE

    Gunhan-Agar, Emine; Haeberle, Adam; Erzurumlu, Reha S.

    2000-01-01

    In the rodent trigeminal pathway, trigeminal axons invade the developing whisker pad from a caudal to rostral direction. We investigated directional specificity of embryonic day (E). 15 rat trigeminal axons within this peripheral target field using explant cocultures. E15 trigeminal axons readily grow into the same age whisker pad explants and form follicle-related patterns along a caudal to rostral direction. They also can grow into this target from its lateral aspects. In contrast, they are...

  3. Differential Effects of NGF and NT-3 on Embryonic Trigeminal Axon Growth Patterns

    OpenAIRE

    Ulupinar, Emel; Jacquin, Mark F.; Erzurumlu, Reha S.

    2000-01-01

    We examined the effects of neurotrophins nerve growth factor (NGF) and neurotrophin-3 (NT-3) on trigeminal axon growth patterns. Embryonic (E13–15) wholemount explants of the rat trigeminal pathway including the whisker pads, trigeminal ganglia, and brainstem were cultured in serum-free medium (SFM) or SFM supplemented with NGF or NT-3 for 3 days. Trigeminal axon growth patterns were analyzed with the use of lipophilic tracer DiI. In wholemount cultures grown in SFM, trigeminal axon projectio...

  4. Axonal Transport Proteomics Reveals Mobilization of Translation Machinery to the Lesion Site in Injured Sciatic Nerve*

    OpenAIRE

    Michaelevski, Izhak; Medzihradszky, Katalin F.; Lynn, Aenoch; Burlingame, Alma L.; Fainzilber, Mike

    2009-01-01

    Investigations of the molecular mechanisms underlying responses to nerve injury have highlighted the importance of axonal transport systems. To obtain a comprehensive view of the protein ensembles associated with axonal transport in injured axons, we analyzed the protein compositions of axoplasm concentrated at ligatures following crush injury of rat sciatic nerve. LC-MS/MS analyses of iTRAQ-labeled peptides from axoplasm distal and proximal to the ligation sites revealed protein ensembles tr...

  5. RNA Sequence Reveals Mouse Retinal Transcriptome Changes Early after Axonal Injury

    OpenAIRE

    Yasuda, Masayuki; Tanaka, Yuji; Ryu, Morin; Tsuda, Satoru; Nakazawa, Toru

    2014-01-01

    Glaucoma is an ocular disease characterized by progressive retinal ganglion cell (RGC) death caused by axonal injury. However, the underlying mechanisms involved in RGC death remain unclear. In this study, we investigated changes in the transcriptome profile following axonal injury in mice (C57BL/6) with RNA sequencing (RNA-seq) technology. The experiment group underwent an optic nerve crush (ONC) procedure to induce axonal injury in the right eye, and the control group underwent a sham proce...

  6. Roles of NAD in Protection of Axon against Degeneration via SIRT1 Pathways.

    Science.gov (United States)

    Zhang, Jing; Guo, Wei-Hua; Qi, Xiao-Xia; Li, Gui-Bao; Hu, Yan-Lai; Wu, Qi; Ding, Zhao-Xi; Li, Hong-Yu; Hao, Jing; Sun, Jin-Hao

    2016-04-30

    Axonal degeneration is a common pathological change of neurogenical disease which often arises before the neuron death. But it had not found any effective method to protect axon from degeneration. In this study we intended to confirm the protective effect of nicotinamide adenine dinucleotide (NAD), investigate the optimal administration dosage and time of NAD, and identify the relationship between silence signal regulating factor 1 (SIRT1) and axonal degeneration. An axonal degeneration model was established using dorsal root ganglion (DRG) neurons injured by vincristine to observe the protective effects of NAD to the injured axons. In addition, the potential contribution of the SIRT1 in axonal degeneration was also investigated. Through the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunochemistry staining, axons counting and length measuring, transmission electron microscope (TEM) observation, we demonstrated that NAD played an important role in preventing axonal degeneration. Further study revealed that the expression of SIRT1 and phosphorylated Akt1 (p-Akt1) was up-regulated when NAD was added into the culturing medium. Taking together, our results demonstrated that NAD might delay the axonal degeneration through SIRT1/Akt1 pathways. PMID:27080463

  7. In vivo imaging of axonal transport using MRI: aging and Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Minoshima, Satoshi [University of Washington, Departments of Radiology and Bioengineering, 1959 N.E. Pacific Street, RR215, Box 357115, Seattle, WA (United States); Cross, Donna [University of Washington, Department of Radiology, 1959 N.E. Pacific Street, RR215, Box 357115, Seattle, WA (United States)

    2008-03-15

    MRI using manganese as a trans-synaptic axonal tracing agent can unveil dynamics of axonal transport in living subjects. We use this technology to test the hypotheses if impaired axonal transport is a significant pathophysiological process in aging and early Alzheimer's disease (AD) and in part accounting for ''selective vulnerability'' of projection neurons in AD. To allow quantitative assessment of axonal transport in vivo, we developed voxel-based statistical mapping technology as well as a tracer kinetic modeling method based on mass transport for manganese-enhanced MRI to estimate axonal transport rates in aging rats and AD transgenic mice. These techniques demonstrated manganese-enhanced signal changes in axonal projections of the olfactory tract and decreased axonal transport rates in rodent models of aging and AD. Altered axonal transport may be a critical pathophysiological process in aging and AD. Manganese-enhanced MRI provides exciting opportunities for the investigations of altered axonal transport in AD and related disorders. (orig.)

  8. MicroRNA-210 promotes sensory axon regeneration of adult mice in vivo and in vitro.

    Science.gov (United States)

    Hu, Yi-Wen; Jiang, Jing-Jing; Yan-Gao; Wang, Rui-Ying; Tu, Guan-Jun

    2016-05-27

    Axon regeneration as a critical step in nerve repairing and remodeling after peripheral nerve injury relies on regulation of gene expression. MicroRNAs are emerging to be important epigenetic regulators of gene expression to control axon regeneration. Here we used a novel in vivo electroporation approach to transfect microRNA-210 (miR-210) or siRNAs to adult mice dorsal root ganglion (DRG) neurons, measured the axon length 3days after sciatic nerve crush or dissociated DRG cultures in vitro to detect the effect of miR-210 in sensory axon regeneration. Importantly, we found that miR-210 overexpression could promote sensory axon regeneration and inhibit apoptsosis by ephrin-A3 (EFNA3). In addition, inhibition of endogenous miR-210 in DRG neurons impaired axon regeneration in vitro and in vivo, the regulatory effect of miR-210 was mediated by increased expression of EFNA3 because downregulation of EFNA3 fully rescued axon regeneration. We thus demonstrate that miR-210 is a new physiological regulator of sensory axon regeneration, and EFNA3 may be the functional target of miR-210. We conclude that miR-210 may play an important role in sensory axon regeneration. PMID:27102143

  9. N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic nerve injury

    Institute of Scientific and Technical Information of China (English)

    Christian Witzel; Werner Reutter; G Bjrn Stark; Georgios Koulaxouzidis

    2015-01-01

    Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modiifed in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp) increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the inlfuence of systemic ManNProp application using a speciifc in vivo mouse model. Using mice expressing axonal lfuorescent proteins, we quantiifed the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow lfuorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg) or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection). ManNProp signiifcantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm;P<0.005) and the number of arborizing axons (21%vs. 16%;P=0.008) 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoen-gineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration.

  10. N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Christian Witzel

    2015-01-01

    Full Text Available Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modified in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the influence of systemic ManNProp application using a specific in vivo mouse model. Using mice expressing axonal fluorescent proteins, we quantified the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow fluorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection. ManNProp significantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm; P < 0.005 and the number of arborizing axons (21% vs. 16% P = 0.008 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoengineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration.

  11. Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay

    DEFF Research Database (Denmark)

    Colak, Dilek; Ji, Sheng-Jian; Porse, Bo T; Jaffrey, Samie R

    2013-01-01

    show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor-plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay...... (NMD) pathway. We find that NMD regulates Robo3.2 synthesis by inducing the degradation of Robo3.2 transcripts in axons that encounter the floor plate. Commissural neurons deficient in NMD proteins exhibit aberrant axonal trajectories after crossing the midline, consistent with misregulation of Robo3...

  12. Permissive Schwann cell graft/spinal cord interfaces for axon regeneration.

    Science.gov (United States)

    Williams, Ryan R; Henao, Martha; Pearse, Damien D; Bunge, Mary Bartlett

    2015-01-01

    The transplantation of autologous Schwann cells (SCs) to repair the injured spinal cord is currently being evaluated in a clinical trial. In support, this study determined properties of spinal cord/SC bridge interfaces that enabled regenerated brainstem axons to cross them, possibly leading to improvement in rat hindlimb movement. Fluid bridges of SCs and Matrigel were placed in complete spinal cord transections. Compared to pregelled bridges of SCs and Matrigel, they improved regeneration of brainstem axons across the rostral interface. The regenerating brainstem axons formed synaptophysin(+) bouton-like terminals and contacted MAP2A(+) dendrites at the caudal interface. Brainstem axon regeneration was directly associated with glial fibrillary acidic protein (GFAP(+)) astrocyte processes that elongated into the SC bridge. Electron microscopy revealed that axons, SCs, and astrocytes were enclosed together within tunnels bounded by a continuous basal lamina. Neuroglycan (NG2) expression was associated with these tunnels. One week after injury, the GFAP(+) processes coexpressed nestin and brain lipid-binding protein, and the tips of GFAP(+)/NG2(+) processes extended into the bridges together with the regenerating brainstem axons. Both brainstem axon regeneration and number of GFAP(+) processes in the bridges correlated with improvement in hindlimb locomotion. Following SCI, astrocytes may enter a reactive state that prohibits axon regeneration. Elongation of astrocyte processes into SC bridges, however, and formation of NG2(+) tunnels enable brainstem axon regeneration and improvement in function. It is important for spinal cord repair to define conditions that favor elongation of astrocytes into lesions/transplants. PMID:24152553

  13. Studying Axonal Regeneration by Laser Microsurgery and High-Resolution Videomicroscopy.

    Science.gov (United States)

    Xiao, Yan; López-Schier, Hernán

    2016-01-01

    Heterogeneous and unpredictable environmental insult, disease, or trauma can affect the integrity and function of neuronal circuits, leading to irreversible neural dysfunction. The peripheral nervous system can robustly regenerate axons after damage to recover the capacity to transmit sensory information to the brain. The mechanisms that allow axonal repair remain incompletely understood. Here we present a preparation in zebrafish that combines laser microsurgery of sensory axons and videomicroscopy of neurons in multicolor transgenic specimens. This simple protocol allows controlled damage of axons and dynamic high-resolution visualization and quantification of repair. PMID:27464814

  14. Intermittent Hypoxia Does not Elicit Memory Impairment in Spinal Cord Injury Patients.

    Science.gov (United States)

    Navarrete-Opazo, Angela; Alcayaga, Julio; Testa, Denisse; Quinteros, Ana Luisa

    2016-06-01

    There is a critical need for new therapeutic strategies to restore motor function in patients with spinal cord injuries (SCIs), without unwanted effects. Intermittent hypoxia (IH) induces plasticity in spared synaptic pathways to motor neurons below the level of injury, which can be harnessed to elicit motor recovery in incomplete SCI patients. However, there is conflicting evidence regarding the effects of IH on memory function. The aim of this study was to assess episodic verbal and visual memory function with the Complutense verbal learning test (TAVEC) and the Rey-Osterrieth Complex Figure Test (ROCF), respectively, before and after a 4-week protocol of repetitive IH combined with body weight-supported treadmill training (BWSTT) in incomplete ASIA C and D SCI subjects. Subjects received either IH (cycling 9%/21% FiO2 every 1.5 min, 15 cycles per day) or continued normoxia (Nx, 21% FiO2) combined with 45 min of BWSTT for 5 consecutive days, followed by 3 times per week IH and BWSTT for 3 additional weeks. ROCF Z scores between IH plus BWSTT and Nx plus BWSTT were not significantly different (p = .43). Compared with baseline, IH and BWSTT group showed a significantly greater (p .05). Our results suggest that a 4-week protocol of moderate IH does not elicit visual or verbal memory impairment. Thus, repetitive IH may be a safe therapeutic approach to incomplete spinal cord injury patients, without deleterious cognitive effects. PMID:27084733

  15. CCSI Risk Estimation: An Application of Expert Elicitation

    Energy Technology Data Exchange (ETDEWEB)

    Engel, David W.; Dalton, Angela C.

    2012-10-01

    The Carbon Capture Simulation Initiative (CCSI) is a multi-laboratory simulation-driven effort to develop carbon capture technologies with the goal of accelerating commercialization and adoption in the near future. One of the key CCSI technical challenges is representing and quantifying the inherent uncertainty and risks associated with developing, testing, and deploying the technology in simulated and real operational settings. To address this challenge, the CCSI Element 7 team developed a holistic risk analysis and decision-making framework. The purpose of this report is to document the CCSI Element 7 structured systematic expert elicitation to identify additional risk factors. We review the significance of and established approaches to expert elicitation, describe the CCSI risk elicitation plan and implementation strategies, and conclude by discussing the next steps and highlighting the contribution of risk elicitation toward the achievement of the overarching CCSI objectives.

  16. Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. II. Evidence from selective inactivation of cell bodies and axon initial segments.

    Science.gov (United States)

    Nowak, L G; Bullier, J

    1998-02-01

    The results presented in the companion paper showed that extracellular electrical stimulation of the gray matter directly activates axons, but not cell bodies. The second set of experiments presented here was designed to separate the contribution of the axon initial segments and cell bodies from that of the axonal branches to the pool of presynaptic neuronal elements activated by electrical stimulation. For that purpose, N-methyl-D-aspartate (NMDA) iontophoresis was used to induce a selective inactivation of the cell body and of the adjoining portion of the axon by depolarization block, without affecting axonal branches that lack NMDA receptors. After NMDA iontophoresis, the neurons located near the iontophoresis electrode became unable to generate action potentials in an irreversible manner. When the NMDA-induced depolarization block was performed at the site of electrical stimulation, an unexpected increase in the amplitude of the orthodromic responses was observed. Several control experiments suggested that the field potential increase was due to changes of the local environment in the vicinity of the iontophoresis pipette, which led to an increased excitability of the axons. After the period of superexcitability, the orthodromic responses displayed an amplitude that was 15-20% lower than that observed before the NMDA-induced depolarization block, even though cell bodies and axon initial segment at the site of stimulation could not be activated by electrical stimulation. This result shows a low contribution for axon initial segments to the pool of neuronal elements activated by the electrical stimulation. Altogether, these experiments demonstrate that the postsynaptic responses obtained after electrical stimulation of the cortical gray matter result almost exclusively from the activation of axonal branches. Since the neocortex is organised as a network of local and long-range reciprocal connections, great attention must be paid to the interpretation of data

  17. Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.

    Directory of Open Access Journals (Sweden)

    Jan Jessen Krut

    Full Text Available Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL in CSF with a novel, sensitive method.With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL (marker of neuronal injury, neopterin (intrathecal immunoactivation and CSF/Plasma albumin ratio (blood-brain barrier integrity were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200, HIV-associated dementia (HAD (n = 14 and on combinations antiretroviral treatment (cART (n = 85, and healthy controls (n = 204. 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation.While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups.Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further

  18. Hyperactivated Stat3 boosts axon regeneration in the CNS.

    Science.gov (United States)

    Mehta, Saloni T; Luo, Xueting; Park, Kevin K; Bixby, John L; Lemmon, Vance P

    2016-06-01

    Axonal regeneration after spinal cord injury (SCI) is intrinsically and extrinsically inhibited by multiple factors. One major factor contributing to intrinsic regeneration failure is the inability of mature neurons in the central nervous system (CNS) to activate regeneration-associated transcription factors (TFs) post-injury. A prior study identified TFs overexpressed in neurons of the peripheral nervous system (PNS) compared to the CNS; some of these could be involved in the ability of PNS neurons to regenerate. Of these, signal transducer and activator of transcription 3 (STAT3), as well its downstream regeneration-associated targets, showed a significant upregulation in PNS neurons relative to CNS neurons, and a constitutively active variant of Stat3 (Stat3CA) promoted neurite growth when expressed in cerebellar neurons (Lerch et al., 2012; Smith et al., 2011). To further enhance STAT3's neurite outgrowth enhancing activity, Stat3CA was fused with a viral activation domain (VP16). VP16 hyperactivates TFs by recruiting transcriptional co-factors to the DNA binding domain (Hirai et al., 2010). Overexpression of this VP16-Stat3CA chimera in primary cortical neurons led to a significant increase of neurite outgrowth as well as Stat3 transcriptional activity in vitro. Furthermore, in vivo transduction of retinal ganglion cells (RGCs) with AAV constructs expressing VP16-Stat3CA resulted in regeneration of optic nerve axons after injury, to a greater degree than for those expressing Stat3CA alone. These findings confirm and extend the concept that overexpression of hyperactivated transcription factors identified as functioning in PNS regeneration can promote axon regeneration in the CNS. PMID:27060489

  19. Utilizing online serious games to facilitate distributed requirements elicitation

    OpenAIRE

    Ghanbari, Hadi; Similä, Jouni; Markkula, Jouni

    2015-01-01

    Requirements elicitation is one of the most important and challenging activities in software development projects. A variety of challenges related to requirements elicitation are reported in the literature, of which the lack of proper communication and knowledge transfer between software stakeholders are among the most important. Communication and knowledge transfer are becoming even bigger challenges with the current increase in globally distributed software development projects due to the t...

  20. Elicitation of normative and fairness judgments: Do incentives matter?

    OpenAIRE

    Štěpán Veselý

    2015-01-01

    Krupka and Weber (2013) introduce an incentive-compatible coordination game as an alternative method for elicitation of normative judgments. I show, however, that people provide virtually the same responses in incentivized and non-incentivized versions of the Krupka-Weber game. Besides ratings of social appropriateness, I also elicit ratings of fairness of all possible offers in an ultimatum game. Ratings of social appropriateness and fairness are similar for low offers (bel...

  1. The new vaccines: building viruses that elicit antitumor immunity

    OpenAIRE

    Restifo, Nicholas P

    1996-01-01

    Whereas cancer cells are poor immunogens, some viruses are capable of eliciting powerful and lifelong immunity. Recombinant viruses and plasmid DNA encoding tumor-associated antigens can elicit powerful and specific immune responses that can be enhanced by the use of cytokines and costimulatory molecules. These immune responses have destroyed growing tumor cells in experimental animal models. For the first time, immunotherapeutic strategies that employ recombinant viruses are being tested in ...

  2. Elicitation of preferences for improvements in ostomy pouches

    DEFF Research Database (Denmark)

    Bonnichsen, Ole

    This paper attempts to examine and measure ostomates’ preferences for improvements in ostomy pouches. Described are the study design, elicitation procedure and resulting preference structure of the Swedish ostomate sample. The method used to elicit the preferences is a Discrete Choice Experiment ......, emphasis should be placed on this attribute when decisions are made as to the allocation of scarce health care resources within research and development aimed at improving ostomy pouches....

  3. Structured Language Requirement Elicitation Using Case Base Reasoning

    OpenAIRE

    Marryam Murtaza; Jamal Hussain Shah; Aisha Azeem; Wasif Nisar; Maria Masood

    2013-01-01

    Requirement elicitation is very difficult process in highly challenging and business based software as well as in real time software. Common problems associated with these types of software are rapidly changing the requirements and understanding the language of the layman person. In this study, a framework for requirement elicitation by using knowledge based system is proposed, which is very helpful for knowledge documentation, intelligent decision support, self-learning and more specifically...

  4. Improvement of cobalt-transport in axons by complexing agents.

    Science.gov (United States)

    Gallyas, F; Lénárd, L; Lázár, G

    1978-09-01

    The use of the cobalt technique is limited by the fact that cobaltous ions travel within axons for a shorter distance than do other intracellular markers. In the present experiments different organic cobaltous complexes were tested in the rat's sciatic nerve. Cobaltous complexes containing ornithine, threonine, lysine or Girard's reagent travelled two or three times further than did the cobaltous ions alone. Using the lysine complex in the frog's visual system, very fine terminals were observed which have never been demonstrated with other techniques. The possible use of other metal complexes as intracellular markers are also discussed. PMID:19605220

  5. Mechanisms of hyperpolarization in regenerated mature motor axons in cat

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Krarup, Christian

    2004-01-01

    We found persistent abnormalities in the recovery of membrane excitability in long-term regenerated motor nerve fibres in the cat as indicated in the companion paper. These abnormalities could partly be explained by membrane hyperpolarization. To further investigate this possibility, we compared...... the changes in excitability in control nerves and long-term regenerated cat nerves (3-5 years after tibial nerve crush) during manoeuvres known to alter axonal membrane Na(+)-K(+) pump function: polarization, cooling to 20 degrees C, reperfusion after 10 min ischaemia, and up to 60 s of repetitive stimulation...

  6. NVC Based Model for Selecting Effective Requirement Elicitation Technique

    Directory of Open Access Journals (Sweden)

    Md. Rizwan Beg

    2012-10-01

    Full Text Available Requirement Engineering process starts from gathering of requirements i.e.; requirements elicitation. Requirementselicitation (RE is the base building block for a software project and has very high impact onsubsequent design and builds phases as well. Accurately capturing system requirements is the major factorin the failure of most of software projects. Due to the criticality and impact of this phase, it is very importantto perform the requirements elicitation in no less than a perfect manner. One of the most difficult jobsfor elicitor is to select appropriate technique for eliciting the requirement. Interviewing and Interactingstakeholder during Elicitation process is a communication intensive activity involves Verbal and Nonverbalcommunication (NVC. Elicitor should give emphasis to Non-verbal communication along with verbalcommunication so that requirements recorded more efficiently and effectively. In this paper we proposea model in which stakeholders are classified by observing non-verbal communication and use it as a basefor elicitation technique selection. We also propose an efficient plan for requirements elicitation which intendsto overcome on the constraints, faced by elicitor.

  7. Time dependent integration of matrix metalloproteinases and their targeted substrates directs axonal sprouting and synaptogenesis following central nervous system injury

    Institute of Scientific and Technical Information of China (English)

    Linda L. Phillips; Julie L. Chan; Adele E. Doperalski; Thomas M. Reeves

    2014-01-01

    Over the past two decades, many investigators have reported how extracellular matrix molecules act to regulate neuroplasticity. The majority of these studies involve proteins which are targets of matrix metalloproteinases. Importantly, these enzyme/substrate interactions can regulate degenerative and regenerative phases of synaptic plasticity, directing axonal and dendritic re-organization after brain insult. The present review ifrst summarizes literature support for the prominent role of matrix metalloproteinases during neuroregeneration, followed by a discussion of data contrasting adaptive and maladaptive neuroplasticity that reveals time-dependent metal-loproteinase/substrate regulation of postinjury synaptic recovery. The potential for these enzymes to serve as therapeutic targets for enhanced neuroplasticity after brain injury is illustrated with experiments demonstrating that metalloproteinase inhibitors can alter adaptive and maladaptive outcome. Finally, the complexity of metalloproteinase role in reactive synaptogenesis is revealed in new studies showing how these enzymes interact with immune molecules to mediate cellu-lar response in the local regenerative environment, and are regulated by novel binding partners in the brain extracellular matrix. Together, these different examples show the complexity with which metalloproteinases are integrated into the process of neuroregeneration, and point to a promising new angle for future studies exploring how to facilitate brain plasticity.

  8. Consciousness and neural plasticity

    DEFF Research Database (Denmark)

    consciousness is related to neural processes it seems, at least prima facie, that the ability of the neural structures to change should be reflected in a theory of this relationship "Neural plasticity" refers to the fact that the brain can change due to its own activity. The brain is not static but rather a...... relation between consciousness and brain functions. If consciousness is connected to specific brain structures (as a function or in identity) what happens to consciousness when those specific underlying structures change? It is therefore possible that the understanding and theories of neural plasticity can......, something that is stable over time. Considering neural plasticity, this is not necessarily so. The NCC might change and hence literally change the way a person is conscious. What it is about the NCC that can and might change is, even though it can be relevant for the relation between the brain and...

  9. Matrix metalloproteinases as promising regulators of axonal regrowth in the injured adult zebrafish retinotectal system.

    Science.gov (United States)

    Lemmens, Kim; Bollaerts, Ilse; Bhumika, Stitipragyan; de Groef, Lies; Van Houcke, Jessie; Darras, Veerle M; Van Hove, Inge; Moons, Lieve

    2016-05-01

    Overcoming the failure of axon regeneration in the mammalian central nervous system (CNS) after injury remains a major challenge, which makes the search for proregenerative molecules essential. Matrix metalloproteinases (MMPs) have been implicated in axonal outgrowth during CNS development and show increased expression levels during vertebrate CNS repair. In mammals, MMPs are believed to alter the suppressive extracellular matrix to become more permissive for axon regrowth. We investigated the role of MMPs in axonal regeneration following optic nerve crush (ONC) in adult zebrafish, which fully recover from such injuries due to a high intrinsic axon growth capacity and a less inhibitory environment. Lowering general retinal MMP activity through intravitreal injections of GM6001 after ONC strongly reduced retinal ganglion cell (RGC) axonal regrowth, without influencing RGC survival. Based on a recently performed transcriptome profiling study, the expression pattern of four MMPs after ONC was determined via combined use of western blotting and immunostainings. Mmp-2 and -13a were increasingly present in RGC somata during axonal regrowth. Moreover, Mmp-2 and -9 became upregulated in regrowing RGC axons and inner plexiform layer (IPL) synapses, respectively. In contrast, after an initial rise in IPL neurites and RGC axons during the injury response, Mmp-14 expression decreased during regeneration. Altogether, a phase-dependent expression pattern for each specific MMP was observed, implicating them in axonal regrowth and inner retina remodeling after injury. In conclusion, these data suggest a novel, neuron-intrinsic function for multiple MMPs in axon regrowth that is distinct from breaking down environmental barriers. J. Comp. Neurol. 524:1472-1493, 2016. © 2015 Wiley Periodicals, Inc. PMID:26509469

  10. Gogo receptor contributes to retinotopic map formation and prevents R1-6 photoreceptor axon bundling.

    Directory of Open Access Journals (Sweden)

    Irina Hein

    Full Text Available BACKGROUND: Topographic maps form the basis of neural processing in sensory systems of both vertebrate and invertebrate species. In the Drosophila visual system, neighboring R1-R6 photoreceptor axons innervate adjacent positions in the first optic ganglion, the lamina, and thereby represent visual space as a continuous map in the brain. The mechanisms responsible for the establishment of retinotopic maps remain incompletely understood. RESULTS: Here, we show that the receptor Golden goal (Gogo is required for R axon lamina targeting and cartridge elongation in a partially redundant fashion with local guidance cues provided by neighboring axons. Loss of function of Gogo in large clones of R axons results in aberrant R1-R6 fascicle spacing. Gogo affects target cartridge selection only indirectly as a consequence of the disordered lamina map. Interestingly, small clones of gogo deficient R axons perfectly integrate into a proper retinotopic map suggesting that surrounding R axons of the same or neighboring fascicles provide complementary spatial guidance. Using single photoreceptor type rescue, we show that Gogo expression exclusively in R8 cells is sufficient to mediate targeting of all photoreceptor types in the lamina. Upon lamina targeting and cartridge selection, R axons elongate within their individual cartridges. Interestingly, here Gogo prevents bundling of extending R1-6 axons. CONCLUSION: Taken together, we propose that Gogo contributes to retinotopic map formation in the Drosophila lamina by controlling the distribution of R1-R6 axon fascicles. In a later developmental step, the regular position of R1-R6 axons along the lamina plexus is crucial for target cartridge selection. During cartridge elongation, Gogo allows R1-R6 axons to extend centrally in the lamina cartridge.

  11. Joining by plastic deformation

    DEFF Research Database (Denmark)

    Mori, Ken-ichiro; Bay, Niels; Fratini, Livan;

    2013-01-01

    As the scale and complexity of products such as aircraft and cars increase, demand for new functional processes to join mechanical parts grows. The use of plastic deformation for joining parts potentially offers improved accuracy, reliability and environmental safety as well as creating opportuni......As the scale and complexity of products such as aircraft and cars increase, demand for new functional processes to join mechanical parts grows. The use of plastic deformation for joining parts potentially offers improved accuracy, reliability and environmental safety as well as creating...

  12. An ex vivo laser-induced spinal cord injury model to assess mechanisms of axonal degeneration in real-time.

    Science.gov (United States)

    Okada, Starlyn L M; Stivers, Nicole S; Stys, Peter K; Stirling, David P

    2014-01-01

    Injured CNS axons fail to regenerate and often retract away from the injury site. Axons spared from the initial injury may later undergo secondary axonal degeneration. Lack of growth cone formation, regeneration, and loss of additional myelinated axonal projections within the spinal cord greatly limits neurological recovery following injury. To assess how central myelinated axons of the spinal cord respond to injury, we developed an ex vivo living spinal cord model utilizing transgenic mice that express yellow fluorescent protein in axons and a focal and highly reproducible laser-induced spinal cord injury to document the fate of axons and myelin (lipophilic fluorescent dye Nile Red) over time using two-photon excitation time-lapse microscopy. Dynamic processes such as acute axonal injury, axonal retraction, and myelin degeneration are best studied in real-time. However, the non-focal nature of contusion-based injuries and movement artifacts encountered during in vivo spinal cord imaging make differentiating primary and secondary axonal injury responses using high resolution microscopy challenging. The ex vivo spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time. Major advantages of this model are excellent spatiotemporal resolution that allows differentiation between the primary insult that directly injures axons and secondary injury mechanisms; controlled infusion of reagents directly to the perfusate bathing the cord; precise alterations of the environmental milieu (e.g., calcium, sodium ions, known contributors to axonal injury, but near impossible to manipulate in vivo); and murine models also offer an advantage as they provide an opportunity to visualize and manipulate genetically identified cell populations and subcellular

  13. CREB-BDNF Pathway Influences Alcohol Cue-Elicited Hyperactivation in Drinkers

    Science.gov (United States)

    Chen, Jiayu; Hutchison, Kent E.; Calhoun, Vince D.; Claus, Eric; Turner, Jessica A.; Sui, Jing; Liu, Jingyu

    2016-01-01

    Alcohol dependence (AD) is suggested to have polygenic risk factors and also exhibits neurological complications, strongly encouraging a translational study to explore the associations between aggregates of genetic variants and brain function alterations related to alcohol use. In this study, we used a semiblind multivariate approach, parallel independent component analysis with multiple references (pICA-MR) to investigate relationships of genome-wide single nucleotide polymorphisms (SNPs) with alcohol cue elicited brain activations in 326 healthy drinkers. The genetic component derived from the CREB-BDNF pathway reference was significantly associated (r = −0.36, p = 2.98×10−11) with an imaging component reflecting hyperactivation in precuneus, superior parietal lobule, and posterior cingulate for drinkers with more severe AD scores. The highlighted brain regions participate in many cognitive processes and have been robustly implicated in craving-related studies. The genetic factor highlighted the CREB and BDNF references, as well as other genes including GRM5, GRM7, GRID1, GRIN2A, PRKCA and PRKCB. Ingenuity Pathway Analysis indicated that the genetic component was enriched in synaptic plasticity, GABA and protein kinase A signaling. In summary, our findings suggest genetic variations in various neural plasticity and signaling pathways partially explain the variance of precuneus reactivity to alcohol cue which appears to be associated with AD severity. PMID:25939814

  14. Bazooka mediates secondary axon morphology in Drosophila brain lineages

    Directory of Open Access Journals (Sweden)

    Hartenstein Volker

    2011-04-01

    Full Text Available Abstract In the Drosophila brain, neural lineages project bundled axon tracts into a central neuropile. Each lineage exhibits a stereotypical branching pattern and trajectory, which distinguish it from other lineages. In this study, we used a multilineage approach to explore the neural function of the Par-complex member Par3/Bazooka in vivo. Drosophila bazooka is expressed in post-mitotic neurons of the larval brain and localizes within neurons in a lineage-dependent manner. The fact that multiple GAL4 drivers have been mapped to several lineages of the Drosophila brain enables investigation of the role of Bazooka from larval to adult stages Bazooka loss-of-function (LOF clones had abnormal morphologies, including aberrant pathway choice of ventral projection neurons in the BAla1 lineage, ectopic branching in the DALv2 and BAmv1 lineages, and excess BLD5 lineage axon projections in the optic medulla. Exogenous expression of Bazooka protein in BAla1 neurons rescued defective guidance, supporting an intrinsic requirement for Bazooka in the post-mitotic neuron. Elimination of the Par-complex member Par6 recapitulated Bazooka phenotypes in some but not all lineages, suggesting that the Par complex functions in a lineage-dependent manner, and that Bazooka may act independently in some lineages. Importantly, this study highlights the potential of using a multilineage approach when studying gene function during neural development in Drosophila.

  15. Bazooka mediates secondary axon morphology in Drosophila brain lineages.

    Science.gov (United States)

    Spindler, Shana R; Hartenstein, Volker

    2011-01-01

    In the Drosophila brain, neural lineages project bundled axon tracts into a central neuropile. Each lineage exhibits a stereotypical branching pattern and trajectory, which distinguish it from other lineages. In this study, we used a multilineage approach to explore the neural function of the Par-complex member Par3/Bazooka in vivo. Drosophila bazooka is expressed in post-mitotic neurons of the larval brain and localizes within neurons in a lineage-dependent manner. The fact that multiple GAL4 drivers have been mapped to several lineages of the Drosophila brain enables investigation of the role of Bazooka from larval to adult stages Bazooka loss-of-function (LOF) clones had abnormal morphologies, including aberrant pathway choice of ventral projection neurons in the BAla1 lineage, ectopic branching in the DALv2 and BAmv1 lineages, and excess BLD5 lineage axon projections in the optic medulla. Exogenous expression of Bazooka protein in BAla1 neurons rescued defective guidance, supporting an intrinsic requirement for Bazooka in the post-mitotic neuron. Elimination of the Par-complex member Par6 recapitulated Bazooka phenotypes in some but not all lineages, suggesting that the Par complex functions in a lineage-dependent manner, and that Bazooka may act independently in some lineages. Importantly, this study highlights the potential of using a multilineage approach when studying gene function during neural development in Drosophila. PMID:21524279

  16. Bushen Yisui Capsule ameliorates axonal injury in experimental autoimmune encephalomyelitis

    Institute of Scientific and Technical Information of China (English)

    Ling Fang; Lei Wang; Qi Zheng; Tao Yang; Hui Zhao; Qiuxia Zhang; Kangning Li; Li Zhou; Haiyang Gong; Yongping Fan

    2013-01-01

    A preliminary clinical study by our group demonstrated Bushen Yisui Capsule (formerly cal ed Er-huang Formula) in combination with conventional therapy is an effective prescription for the treat-ment of multiple sclerosis. However, its effect on axonal injury during early multiple sclerosis re-mains unclear. In this study, a MOG 35-55-immunized C57BL/6 mouse model of experimental au-toimmune encephalomyelitis was intragastrical y administered Bushen Yisui Capsule. The results showed that Bushen Yisui Capsule effectively improved clinical symptoms and neurological function of experimental autoimmune encephalomyelitis. In addition, amyloid precursor protein expression was down-regulated and microtubule-associated protein 2 was up-regulated. Experimental findings indicate that the disease-preventive mechanism of Bushen Yisui Capsule in experimental autoim-mune encephalomyelitis was mediated by amelioration of axonal damage and promotion of rege-neration. But the effects of the high-dose Bushen Yisui Capsule group was not better than that of the medium-dose and low-dose Bushen Yisui Capsule group in preventing neurological dysfunction.

  17. Automated kymograph analysis for profiling axonal transport of secretory granules.

    Science.gov (United States)

    Mukherjee, Amit; Jenkins, Brian; Fang, Cheng; Radke, Richard J; Banker, Gary; Roysam, Badrinath

    2011-06-01

    This paper describes an automated method to profile the velocity patterns of small organelles (BDNF granules) being transported along a selected section of axon of a cultured neuron imaged by time-lapse fluorescence microscopy. Instead of directly detecting the granules as in conventional tracking, the proposed method starts by generating a two-dimensional spatio-temporal map (kymograph) of the granule traffic along an axon segment. Temporal sharpening during the kymograph creation helps to highlight granule movements while suppressing clutter due to stationary granules. A voting algorithm defined over orientation distribution functions is used to refine the locations and velocities of the granules. The refined kymograph is analyzed using an algorithm inspired from the minimum set cover framework to generate multiple motion trajectories of granule transport paths. The proposed method is computationally efficient, robust to significant levels of noise and clutter, and can be used to capture and quantify trends in transport patterns quickly and accurately. When evaluated on a collection of image sequences, the proposed method was found to detect granule movement events with 94% recall rate and 82% precision compared to a time-consuming manual analysis. Further, we present a study to evaluate the efficacy of velocity profiling by analyzing the impact of oxidative stress on granule transport in which the fully automated analysis correctly reproduced the biological conclusion generated by manual analysis. PMID:21330183

  18. N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes growth of cortical axons

    Directory of Open Access Journals (Sweden)

    Giorgi Kharebava

    2015-12-01

    Full Text Available Axonogenesis, a process for the establishment of neuron connectivity, is central to brain function. The role of metabolites derived from docosahexaenoic acid (DHA, 22:6n-3 that is specifically enriched in the brain, has not been addressed in axon development. In this study, we tested if synaptamide (N-docosahexaenoylethanolamine, an endogenous metabolite of DHA, affects axon growth in cultured cortical neurons. We found that synaptamide increased the average axon length, inhibited GLI family zinc finger 1 (GLI1 transcription and sonic hedgehog (Shh target gene expression while inducing cAMP elevation. Similar effects were produced by cyclopamine, a regulator of the Shh pathway. Conversely, Shh antagonized elevation of cAMP and blocked synaptamide-mediated increase in axon length. Activation of Shh pathway by a smoothened (SMO agonist (SAG or overexpression of SMO did not inhibit axon growth mediated by synaptamide or cyclopamine. Instead, adenylate cyclase inhibitor SQ22536 abolished synaptamide-mediated axon growth indicating requirement of cAMP elevation for this process. Our findings establish that synaptamide promotes axon growth while Shh antagonizes synaptamide-mediated cAMP elevation and axon growth by a SMO-independent, non-canonical pathway.

  19. Fast and simplified mapping of mean axon diameter using temporal diffusion spectroscopy.

    Science.gov (United States)

    Xu, Junzhon; Li, Hua; Li, Ke; Harkins, Kevin D; Jiang, Xiaoyu; Xie, Jingping; Kang, Hakmook; Dortch, Richard D; Anderson, Adam W; Does, Mark D

    2016-04-01

    Mapping axon diameter is of interest for the potential diagnosis and monitoring of various neuronal pathologies. Advanced diffusion-weighted MRI methods have been developed to measure mean axon diameters non-invasively, but suffer major drawbacks that prevent their direct translation into clinical practice, such as complex non-linear data fitting and, more importantly, long scanning times that are usually not tolerable for most human subjects. In the current study, temporal diffusion spectroscopy using oscillating diffusion gradients was used to measure mean axon diameters with high sensitivity to small axons in the central nervous system. Axon diameters have been found to be correlated with a novel metric, DDR⊥ (the rate of dispersion of the perpendicular diffusion coefficient with gradient frequency), which is a model-free quantity that does not require complex data analyses and can be obtained from two diffusion coefficient measurements in clinically relevant times with conventional MRI machines. A comprehensive investigation including computer simulations and animal experiments ex vivo showed that measurements of DDR⊥ agree closely with histological data. In humans in vivo, DDR⊥ was also found to correlate well with reported mean axon diameters in human corpus callosum, and the total scan time was only about 8 min. In conclusion, DDR⊥ may have potential to serve as a fast, simple and model-free approach to map the mean axon diameter of white matter in clinics for assessing axon diameter changes. PMID:27077155

  20. DIRECT MEASUREMENT OF FAST AXONAL ORGANELLE TRANSPORT IN THE SCIATIC NERVE OF RATS TREATED WITH ACRYLAMIDE

    Science.gov (United States)

    The effects of acrylamide on fast axonal transport have been measured primarily using the indirect methods of isotope or enzyme accumulation. e report the first direct evaluation of the effects of sub-chronic acrylamide dosing (150, 300 or 500 mg/kg total dose) on the fast axonal...

  1. CD8+ T cells cause disability and axon loss in a mouse model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Chandra Deb

    Full Text Available BACKGROUND: The objective of this study was to test the hypothesis that CD8+ T cells directly mediate motor disability and axon injury in the demyelinated central nervous system. We have previously observed that genetic deletion of the CD8+ T cell effector molecule perforin leads to preservation of motor function and preservation of spinal axons in chronically demyelinated mice. METHODOLOGY/PRINCIPAL FINDINGS: To determine if CD8+ T cells are necessary and sufficient to directly injure demyelinated axons, we adoptively transferred purified perforin-competent CD8+ spinal cord-infiltrating T cells into profoundly demyelinated but functionally preserved perforin-deficient host mice. Transfer of CD8+ spinal cord-infiltrating T cells rapidly and irreversibly impaired motor function, disrupted spinal cord motor conduction, and reduced the number of medium- and large-caliber spinal axons. Likewise, immunodepletion of CD8+ T cells from chronically demyelinated wildtype mice preserved motor function and limited axon loss without altering other disease parameters. CONCLUSIONS/SIGNIFICANCE: In multiple sclerosis patients, CD8+ T cells outnumber CD4+ T cells in active lesions and the number of CD8+ T cells correlates with the extent of ongoing axon injury and functional disability. Our findings suggest that CD8+ T cells may directly injure demyelinated axons and are therefore a viable therapeutic target to protect axons and motor function in patients with multiple sclerosis.

  2. A model of fasciculation and sorting in mixed populations of axons

    CERN Document Server

    Chaudhuri, Debasish; Zapotocky, Martin

    2010-01-01

    We extend a recently proposed model (Chaudhuri et al., EPL 87, 20003 (2009)), aiming to describe the formation of fascicles of axons during neural development. The growing axons are represented as paths of interacting directed random walkers in two spatial dimensions. To mimic turnover of axons, whole paths are removed and new walkers are injected with specified rates. In the simplest version of the model, we use strongly adhesive inter-axon interactions that are identical for all pairs of axons. We generalize the model to interactions of finite strengths and to multiple types of axons with type-specific interactions. The dynamic steady state is characterized by the position-dependent distribution of fascicle sizes. With distance in the direction of axon growth, the mean fascicle size and emergent time scales grow monotonically, while the degree of sorting of fascicles by axon type has a maximum at a finite distance. To understand the emergence of slow time scales, we develop an analytical framework to analyz...

  3. Blast overpressure induced axonal injury changes in rat brainstem and spinal cord

    Directory of Open Access Journals (Sweden)

    Srinivasu Kallakuri

    2015-01-01

    Full Text Available Introduction: Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s of blast overpressure (OP induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM tracts of cervical spinal cord are limited. Objective: The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP. Materials and Methods: Sagittal brainstem sections and horizontal cervical spinal cord sections from blast and sham animals were stained by neurofilament light (NF-L chain and beta amyloid precursor protein immunocytochemistry and observed for axonal injury changes. Results: Observations from this preliminary study demonstrate axonal injury changes in the form of prominent swellings, retraction bulbs, and putative signs of membrane disruptions in the brainstem and cervical spinal cord WM tracts of rats subjected to blast OP. Conclusions: Prominent axonal injury changes following the blast OP exposure in brainstem and cervical spinal WM tracts underscores the need for careful evaluation of blast induced injury changes and associated symptoms. NF-L immunocytochemistry can be considered as an additional tool to assess the blast OP induced axonal injury.

  4. 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.

  5. A developmental timing switch promotes axon outgrowth independent of known guidance receptors.

    Directory of Open Access Journals (Sweden)

    Katherine Olsson-Carter

    2010-08-01

    Full Text Available To form functional neuronal connections, axon outgrowth and guidance must be tightly regulated across space as well as time. While a number of genes and pathways have been shown to control spatial features of axon development, very little is known about the in vivo mechanisms that direct the timing of axon initiation and elongation. The Caenorhabditis elegans hermaphrodite specific motor neurons (HSNs extend a single axon ventrally and then anteriorly during the L4 larval stage. Here we show the lin-4 microRNA promotes HSN axon initiation after cell cycle withdrawal. Axons fail to form in lin-4 mutants, while they grow prematurely in lin-4-overexpressing animals. lin-4 is required to down-regulate two inhibitors of HSN differentiation--the transcriptional regulator LIN-14 and the "stemness" factor LIN-28--and it likely does so through a cell-autonomous mechanism. This developmental switch depends neither on the UNC-40/DCC and SAX-3/Robo receptors nor on the direction of axon growth, demonstrating that it acts independently of ventral guidance signals to control the timing of HSN axon elongation.

  6. C. elegans: a new model organism for studies of axon regeneration

    OpenAIRE

    Ghosh-Roy, Anindya; Chisholm, Andrew D.

    2010-01-01

    Axonal regeneration in C. elegans was first reported five years ago. Individual GFP-labeled axons can be severed using laser microsurgery and their regrowth followed in vivo. Several neuron types display robust regrowth after injury, including motor and sensory neurons. The small size and transparency of C. elegans make possible large-scale genetic and pharmacological screens for regeneration phenotypes.

  7. Inhibition of kinesin-5 improves regeneration of injured axons by a novel microtubule-based mechanism

    Institute of Scientific and Technical Information of China (English)

    Peter W. Baas; Andrew J. Matamoros

    2015-01-01

    Microtubules have been identiifed as a powerful target for augmenting regeneration of injured adult axons in the central nervous system. Drugs that stabilize microtubules have shown some promise, but there are concerns that abnormally stabilizing microtubules may have only limited beneifts for regeneration, while at the same time may be detrimental to the normal work that microtubules perform for the axon. Kinesin-5 (also called kif11 or Eg5), a molecular motor protein best known for its crucial role in mitosis, acts as a brake on microtubule movements by other motor proteins in the axon. Drugs that inhibit kinesin-5, originally developed to treat cancer, result in greater mobility of microtubules in the axon and an overall shift in the forces on the microtubule array. As a result, the axon grows faster, retracts less, and more readily enters environments that are inhibitory to axonal regeneration. Thus, drugs that inhibit kinesin-5 offer a novel microtubule-based means to boost axonal regeneration without the concerns that ac-company abnormal stabilization of the microtubule array. Even so, inhibiting kinesin-5 is not without its own caveats, such as potential problems with navigation of the regenerating axon to its target, as well as morphological effects on dendrites that could affect learning and memory if the drugs reach the brain.

  8. Individual differences in behavioural plasticities.

    Science.gov (United States)

    Stamps, Judy A

    2016-05-01

    Interest in individual differences in animal behavioural plasticities has surged in recent years, but research in this area has been hampered by semantic confusion as different investigators use the same terms (e.g. plasticity, flexibility, responsiveness) to refer to different phenomena. The first goal of this review is to suggest a framework for categorizing the many different types of behavioural plasticities, describe examples of each, and indicate why using reversibility as a criterion for categorizing behavioural plasticities is problematic. This framework is then used to address a number of timely questions about individual differences in behavioural plasticities. One set of questions concerns the experimental designs that can be used to study individual differences in various types of behavioural plasticities. Although within-individual designs are the default option for empirical studies of many types of behavioural plasticities, in some situations (e.g. when experience at an early age affects the behaviour expressed at subsequent ages), 'replicate individual' designs can provide useful insights into individual differences in behavioural plasticities. To date, researchers using within-individual and replicate individual designs have documented individual differences in all of the major categories of behavioural plasticities described herein. Another important question is whether and how different types of behavioural plasticities are related to one another. Currently there is empirical evidence that many behavioural plasticities [e.g. contextual plasticity, learning rates, IIV (intra-individual variability), endogenous plasticities, ontogenetic plasticities) can themselves vary as a function of experiences earlier in life, that is, many types of behavioural plasticity are themselves developmentally plastic. These findings support the assumption that differences among individuals in prior experiences may contribute to individual differences in behavioural

  9. Stages in axon formation: observations of growth of Aplysia axons in culture using video-enhanced contrast-differential interference contrast microscopy

    OpenAIRE

    1986-01-01

    The regenerative growth in culture of the axons of two giant identified neurons from the central nervous system of Aplysia californica was observed using video-enhanced contrast-differential interference contrast microscopy. This technique allowed the visualization in living cells of the membranous organelles of the growth cone. Elongation of axonal branches always occurred through the same sequence of events: A flat organelle-free veil protruded from the front of the growth cone, gradually f...

  10. Shank3 is localized in axons and presynaptic specializations of developing hippocampal neurons and involved in the modulation of NMDA receptor levels at axon terminals.

    Science.gov (United States)

    Halbedl, Sonja; Schoen, Michael; Feiler, Marisa S; Boeckers, Tobias M; Schmeisser, Michael J

    2016-04-01

    Autism-related Shank1, Shank2, and Shank3 are major postsynaptic scaffold proteins of excitatory glutamatergic synapses. A few studies, however, have already indicated that within a neuron, the presence of Shank family members is not limited to the postsynaptic density. By separating axons from dendrites of developing hippocampal neurons in microfluidic chambers, we show that RNA of all three Shank family members is present within axons. Immunostaining confirms these findings as all three Shanks are indeed found within separated axons and further co-localize with well-known proteins of the presynaptic specialization in axon terminals. Therefore, Shank proteins might not only serve as postsynaptic scaffold proteins, but also play a crucial role during axonal outgrowth and presynaptic development and function. This is supported by our findings that shRNA-mediated knockdown of Shank3 results in up-regulation of the NMDA receptor subunit GluN1 in axon terminals. Taken together, our findings will have major implications for the future analysis of neuronal Shank biology in both health and disease. Shank1, Shank2, and Shank3 are major postsynaptic scaffold proteins of excitatory glutamatergic synapses strongly related to several neuropsychiatric disorders. However, a few studies have already implicated a functional role of the Shanks beyond the postsynaptic density (PSD). We here show that all three Shanks are localized in both axons and pre-synaptic specializiations of developing hippocampal neurons in culture. We further provide evidence that Shank3 is involved in the modulation of NMDA receptor levels at axon terminals. Taken together, our study will open up novel avenues for the future analysis of neuronal Shank biology in both health and disease. PMID:26725465

  11. Persisting Plastic Addiction

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The policy on curbing plastic shopping bag use implemented three years ago has produced mixed results In a bustling farmers’market tucked in a narrow street in Xisanqi residential community in north Beijing,stalls selling vegetables,fruits and other foods line the sidewalk.

  12. Progress in neural plasticity

    Institute of Scientific and Technical Information of China (English)

    POO; Mu-Ming

    2010-01-01

    One of the properties of the nervous system is the use-dependent plasticity of neural circuits.The structure and function of neural circuits are susceptible to changes induced by prior neuronal activity,as reflected by short-and long-term modifications of synaptic efficacy and neuronal excitability.Regarded as the most attractive cellular mechanism underlying higher cognitive functions such as learning and memory,activity-dependent synaptic plasticity has been in the spotlight of modern neuroscience since 1973 when activity-induced long-term potentiation(LTP) of hippocampal synapses was first discovered.Over the last 10 years,Chinese neuroscientists have made notable contributions to the study of the cellular and molecular mechanisms of synaptic plasticity,as well as of the plasticity beyond synapses,including activity-dependent changes in intrinsic neuronal excitability,dendritic integration functions,neuron-glia signaling,and neural network activity.This work highlight some of these significant findings.

  13. Thermodynamics of perfect plasticity

    Czech Academy of Sciences Publication Activity Database

    Roubíček, Tomáš

    2013-01-01

    Roč. 6, č. 1 (2013), s. 193-214. ISSN 1937-1632 R&D Projects: GA ČR GAP201/10/0357 Institutional support: RVO:61388998 Keywords : Prandtl-Reuss plasticity * small strains * Kelvin-Voigt rheology Subject RIV: BA - General Mathematics http://aimsciences.org/journals/home.jsp?journalID=15

  14. Informative document waste plastics

    NARCIS (Netherlands)

    Nagelhout D; Sein AA; Duvoort GL

    1989-01-01

    This "Informative document waste plastics" forms part of a series of "informative documents waste materials". These documents are conducted by RIVM on the indstruction of the Directorate General for the Environment, Waste Materials Directorate, in behalf of the program of acti

  15. Music drives brain plasticity

    OpenAIRE

    Jäncke, Lutz

    2009-01-01

    Music is becoming more and more of an issue in the cognitive neurosciences. A major finding in this research area is that musical practice is associated with structural and functional plasticity of the brain. In this brief review, I will give an overview of the most recent findings of this research area.

  16. RETROGRADE AXONAL TRANSPORT OF PHOSPHOINOSITIDES AFTER INTRANEURAL INJECTION OF [3H]MYO-INOSITOL INTO THE RAT SCIATIC NERVE

    Science.gov (United States)

    Although autoradiography has demonstrated local incorporation of [3H]inositol into axonal phospholipids after intraneural injection (Gould, 1976; Gould et at., 1987b), retrograde axonal transport of phosphatidylinositol has only been demonstrated after injection of lipid precurso...

  17. Transfer of vesicles from Schwann cell to axon: a novel mechanism of communication in the peripheral nervous system

    Directory of Open Access Journals (Sweden)

    María Alejandra eLopez-Verrilli

    2012-06-01

    Full Text Available Schwann cells (SCs are the glial component of the peripheral nervous system, with essential roles during development and maintenance of axons, as well as during regenerative processes after nerve injury. SCs increase conduction velocities by myelinating axons, regulate synaptic activity at presynaptic nerve terminals and are a source of trophic factors to neurons. Thus, development and maintenance of peripheral nerves are crucially dependent on local signalling between SCs and axons. In addition to the classic mechanisms of intercellular signalling, the possibility of communication through secreted vesicles has been poorly explored to date. Interesting recent findings suggest the occurrence of lateral transfer mediated by vesicles from glial cells to axons that could have important roles in axonal growth and axonal regeneration. Here, we review the role of vesicular transfer from SCs to axons and propose the benefits of this means in supporting neuronal and axonal maintenance and regeneration after nerve damage.

  18. Disrupted axon-glia interactions at the paranode in myelinated nerves cause axonal degeneration and neuronal cell death in the aged Caspr mutant mouse shambling.

    Science.gov (United States)

    Takagishi, Yoshiko; Katanosaka, Kimiaki; Mizoguchi, Hiroyuki; Murata, Yoshiharu

    2016-07-01

    Emerging evidence suggests that axonal degeneration is a disease mechanism in various neurodegenerative diseases and that the paranodes at the nodes of Ranvier may be the initial site of pathogenesis. We investigated the pathophysiology of the disease process in the central and peripheral nervous systems of a Caspr mutant mouse, shambling (shm), which is affected by disrupted paranodal structures and impaired nerve conduction of myelinated nerves. The shm mice manifest a progressive neurological phenotype as mice age. We found extensive axonal degeneration and a loss of neurons in the central nervous system and peripheral nervous system in aged shm mice. Axonal alteration of myelinated nerves was defined by abnormal distribution and expression of neurofilaments and derangements in the status of phosphorylated and non/de-phosphorylated neurofilaments. Autophagy-related structures were also accumulated in degenerated axons and neurons. In conclusion, our results suggest that disrupted axon-glia interactions at the paranode cause the cytoskeletal alteration in myelinated axons leading to neuronal cell death, and the process involves detrimental autophagy and aging as factors that promote the pathogenesis. PMID:27255813

  19. Axone, an ethnic probiotic containing food, reduces age of sexual maturity and increases poultry production.

    Science.gov (United States)

    Singh, Bhoj Raj; Singh, R K

    2014-06-01

    Axone (Akhuni) is a homemade synbiotic (Nagamese fermented soybean product) served as side dish in North Eastern India. In this study, effects of Axone feeding on growth, weight gain, sexual maturity and egg production on Vanaraja birds (a strain of poultry bird developed at PDP Hyderabad for villages and backyard poultry) were evaluated. Axone incorporation in commercial poultry feed at the rate of 5% (W/W) significantly improved growth rate (weight gain) both in male (p 0.001) and female (p 0.05) chicks, reduced age by 13 days at first egg laying (p 0.01), increased egg production (p ≤ 0.001) and improved egg weight (p ≤ 0.01). Microbiological analysis of Axone sample revealed that the major bacteria in Axone samples were Bacillus coagulans, well known for their probiotic value. PMID:24801640

  20. RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS.

    Science.gov (United States)

    Ito, Yasushi; Ofengeim, Dimitry; Najafov, Ayaz; Das, Sudeshna; Saberi, Shahram; Li, Ying; Hitomi, Junichi; Zhu, Hong; Chen, Hongbo; Mayo, Lior; Geng, Jiefei; Amin, Palak; DeWitt, Judy Park; Mookhtiar, Adnan Kasim; Florez, Marcus; Ouchida, Amanda Tomie; Fan, Jian-bing; Pasparakis, Manolis; Kelliher, Michelle A; Ravits, John; Yuan, Junying

    2016-08-01

    Mutations in the optineurin (OPTN) gene have been implicated in both familial and sporadic amyotrophic lateral sclerosis (ALS). However, the role of this protein in the central nervous system (CNS) and how it may contribute to ALS pathology are unclear. Here, we found that optineurin actively suppressed receptor-interacting kinase 1 (RIPK1)-dependent signaling by regulating its turnover. Loss of OPTN led to progressive dysmyelination and axonal degeneration through engagement of necroptotic machinery in the CNS, including RIPK1, RIPK3, and mixed lineage kinase domain-like protein (MLKL). Furthermore, RIPK1- and RIPK3-mediated axonal pathology was commonly observed in SOD1(G93A) transgenic mice and pathological samples from human ALS patients. Thus, RIPK1 and RIPK3 play a critical role in mediating progressive axonal degeneration. Furthermore, inhibiting RIPK1 kinase may provide an axonal protective strategy for the treatment of ALS and other human degenerative diseases characterized by axonal degeneration. PMID:27493188

  1. The Drosophila immunoglobulin gene turtle encodes guidance molecules involved in axon pathfinding

    Directory of Open Access Journals (Sweden)

    Al-Anzi Bader

    2009-08-01

    Full Text Available Abstract Background Neuronal growth cones follow specific pathways over long distances in order to reach their appropriate targets. Research over the past 15 years has yielded a large body of information concerning the molecules that regulate this process. Some of these molecules, such as the evolutionarily conserved netrin and slit proteins, are expressed in the embryonic midline, an area of extreme importance for early axon pathfinding decisions. A general model has emerged in which netrin attracts commissural axons towards the midline while slit forces them out. However, a large number of commissural axons successfully cross the midline even in the complete absence of netrin signaling, indicating the presence of a yet unidentified midline attractant. Results The evolutionarily conserved Ig proteins encoded by the turtle/Dasm1 genes are found in Drosophila, Caenorhabditis elegans, and mammals. In Drosophila the turtle gene encodes five proteins, two of which are diffusible, that are expressed in many areas, including the vicinity of the midline. Using both molecular null alleles and transgenic expression of the different isoforms, we show that the turtle encoded proteins function as non-cell autonomous axonal attractants that promote midline crossing via a netrin-independent mechanism. turtle mutants also have either stalled or missing axon projections, while overexpression of the different turtle isoforms produces invasive neurons and branching axons that do not respect the histological divisions of the nervous system. Conclusion Our findings indicate that the turtle proteins function as axon guidance cues that promote midline attraction, axon branching, and axonal invasiveness. The latter two capabilities are required by migrating axons to explore densely packed targets.

  2. Excitation by Axon Terminal GABA Spillover in a Sound Localization Circuit.

    Science.gov (United States)

    Weisz, Catherine J C; Rubio, Maria E; Givens, Richard S; Kandler, Karl

    2016-01-20

    Synapses from neurons of the medial nucleus of the trapezoid body (MNTB) onto neurons of the lateral superior olive (LSO) in the auditory brainstem are glycinergic in maturity, but also GABAergic and glutamatergic in development. The role for this neurotransmitter cotransmission is poorly understood. Here we use electrophysiological recordings in brainstem slices from P3-P21 mice to demonstrate that GABA release evoked from MNTB axons can spill over to neighboring MNTB axons and cause excitation by activating GABAAR. This spillover excitation generates patterns of staggered neurotransmitter release from different MNTB axons resulting in characteristic "doublet" postsynaptic currents in LSO neurons. Postembedding immunogold labeling and electron microscopy provide evidence that GABAARs are localized at MNTB axon terminals. Photolytic uncaging of p-hydroxyphenacyl (pHP) GABA demonstrates backpropagation of GABAAR-mediated depolarizations from MNTB axon terminals to the soma, some hundreds of microns away. These somatic depolarizations enhanced somatic excitability by increasing the probability of action potential generation. GABA spillover excitation between MNTB axon terminals may entrain neighboring MNTB neurons, which may play a role in the developmental refinement of the MNTB-LSO pathway. Axonal spillover excitation persisted beyond the second postnatal week, suggesting that this mechanism may play a role in sound localization, by providing new avenues of communication between MNTB neurons via their distal axonal projections. Significance statement: In this study, a new mechanism of neuronal communication between auditory synapses in the mammalian sound localization pathway is described. Evidence is provided that the inhibitory neurotransmitter GABA can spill over between axon terminals to cause excitation of nearby synapses to further stimulate neurotransmitter release. Excitatory GABA spillover between inhibitory axon terminals may have important implications

  3. Dynamic Changes in Local Protein Synthetic Machinery in Regenerating Central Nervous System Axons after Spinal Cord Injury

    Science.gov (United States)

    Sachdeva, Rahul; Farrell, Kaitlin; McMullen, Mary-Katharine; Twiss, Jeffery L.; Houle, John D.

    2016-01-01

    Intra-axonal localization of mRNAs and protein synthesis machinery (PSM) endows neurons with the capacity to generate proteins locally, allowing precise spatiotemporal regulation of the axonal response to extracellular stimuli. A number of studies suggest that this local translation is a promising target to enhance the regenerative capacity of damaged axons. Using a model of central nervous system (CNS) axons regenerating into intraspinal peripheral nerve grafts (PNGs) we established that adult regenerating CNS axons contain several different mRNAs and protein synthetic machinery (PSM) components in vivo. After lower thoracic level spinal cord transection, ascending sensory axons regenerate into intraspinal PNGs but axon growth is stalled when they reach the distal end of the PNG (3 versus 7 weeks after grafting, resp.). By immunofluorescence with optical sectioning of axons by confocal microscopy, the total and phosphorylated forms of PSMs are significantly lower in stalled compared with actively regenerating axons. Reinjury of these stalled axons increased axonal localization of the PSM proteins, indicative of possible priming for a subcellular response to axotomy. These results suggest that axons downregulate protein synthetic capacity as they cease growing, yet they retain the ability to upregulate PSM after a second injury.

  4. Expert elicitation on the uncertainties associated with chronic wasting disease.

    Science.gov (United States)

    Tyshenko, Michael G; Oraby, Tamer; Darshan, Shalu; Westphal, Margit; Croteau, Maxine C; Aspinall, Willy; Elsaadany, Susie; Krewski, Daniel; Cashman, Neil

    2016-01-01

    A high degree of uncertainty exists for chronic wasting disease (CWD) transmission factors in farmed and wild cervids. Evaluating the factors is important as it helps to inform future risk management strategies. Expert opinion is often used to assist decision making in a number of health, science, and technology domains where data may be sparse or missing. Using the "Classical Model" of elicitation, a group of experts was asked to estimate the most likely values for several risk factors affecting CWD transmission. The formalized expert elicitation helped structure the issues and hence provide a rational basis for estimating some transmission risk factors for which evidence is lacking. Considered judgments regarding environmental transmission, latency of CWD transmission, management, and species barrier were provided by the experts. Uncertainties for many items were determined to be large, highlighting areas requiring more research. The elicited values may be used as surrogate values until research evidence becomes available. PMID:27556566

  5. Regret-based Reward Elicitation for Markov Decision Processes

    CERN Document Server

    Regan, Kevin

    2012-01-01

    The specification of aMarkov decision process (MDP) can be difficult. Reward function specification is especially problematic; in practice, it is often cognitively complex and time-consuming for users to precisely specify rewards. This work casts the problem of specifying rewards as one of preference elicitation and aims to minimize the degree of precision with which a reward function must be specified while still allowing optimal or near-optimal policies to be produced. We first discuss how robust policies can be computed for MDPs given only partial reward information using the minimax regret criterion. We then demonstrate how regret can be reduced by efficiently eliciting reward information using bound queries, using regret-reduction as a means for choosing suitable queries. Empirical results demonstrate that regret-based reward elicitation offers an effective way to produce near-optimal policies without resorting to the precise specification of the entire reward function.

  6. Introduction to Computational Plasticity

    International Nuclear Information System (INIS)

    The focus of the book on computational plasticity embodies techniques of relevance not only to academic researchers, but also of interest to industrialists engaged in the production of components using bulk or sheet forming processes. Of particular interest is the guidance on how to create modules for use with the commercial system Abaqus for specific types of material behaviour. The book is in two parts, the first of which contains six chapters, starting with microplasticity, but predominantly on continuum plasticity. The first chapter on microplasticty gives a brief description of the grain structure of metals and the existence of slip systems within the grains. This provides an introduction to the concept of incompressibility during plastic deformation, the nature of plastic yield and the importance of the critically resolved shear stress on the slip planes (Schmid's law). Some knowledge of the notation commonly used to describe slip systems is assumed, which will be familiar to students of metallurgy, but anyone with a more general engineering background may need to undertake additional reading to understand the various descriptions. Chapter two introduces one of several yield criteria, that normally attributed to von Mises (though historians of mechanics might argue over who was first to develop the theory of yielding associated with strain energy density), and its two or three-dimensional representation as a yield surface. The expansion of the yield surface during plastic deformation, its translation due to kinematic hardening and the Bauschinger effect in reversed loading are described with a direct link to the material stress-strain curve. The assumption, that the increment of strain is normal to the yield surface, the normality principle, is introduced. Uniaxial loading of an elastic-plastic material is used as an example in which to develop expressions to describe increments in stress and strain. The full presentation of numerous expressions, tensors and

  7. Preference Elicitation in Fully Probabilistic Design of Decision Strategies

    Czech Academy of Sciences Publication Activity Database

    Kárný, Miroslav; Guy, Tatiana Valentine

    Atlanta: IEEE, 2010, s. 5327-5332. ISBN 978-1-4244-7745-6. ISSN 0743-1546. [49th IEEE Conference on Decision and Control . Atlanta (US), 14.12.2010-18.12.2010] R&D Projects: GA ČR GA102/08/0567 Institutional research plan: CEZ:AV0Z10750506 Keywords : knowledge elicitation * Bayesian decision making * fullz probabilistic design Subject RIV: BB - Applied Statistics, Operational Research http://library.utia.cas.cz/separaty/2010/AS/karny-preference elicitation in fully probabilistic design of decision strategies.pdf

  8. The cholinergic ligand binding material of axonal membranes

    International Nuclear Information System (INIS)

    Choline acetyltransferase and acetylcholinesterase, the enzymes responsible for the synthesis and hydrolysis of ACh, are present in nerve fibers. In crustacean peripheral nerves, release of ACh from cut nerve fibers has been demonstrated. Previously closed membrane vesicles have been prepared from lobster walking leg nerve plasma membrane and saturable binding of cholinergic agonsist and antagonists to such membranes have been demonstrated. This paper studies this axonal cholinergic binding material, and elucidates its functions. The binding of tritium-nicotine to lobster nerve plasma membranes was antagonized by a series of cholinergic ligands as well as by a series of local anesthetics. This preparation was capable of binding I 125-alpha-bungarotoxin, a ligand widely believed to be a specific label for nicotinic ACh receptor. The labelling of 50 K petide band with tritium-MBTA following disulfide reduction is illustrated

  9. Peripheral prostaglandin E2 prolongs the sensitization of nociceptive dorsal root ganglion neurons possibly by facilitating the synthesis and anterograde axonal trafficking of EP4 receptors.

    Science.gov (United States)

    St-Jacques, Bruno; Ma, Weiya

    2014-11-01

    Prostaglandin E2 (PGE2), a well-known pain mediator enriched in inflamed tissues, plays a pivotal role in the genesis of chronic pain conditions such as inflammatory and neuropathic pain. PGE2-prolonged sensitization of nociceptive dorsal root ganglion (DRG) neurons (nociceptors) may contribute to the transition from acute to chronic pain. However, the underlying cellular mechanisms are poorly understood. In this study, we tested the hypothesis that facilitating synthesis and anterograde axonal trafficking of EP receptors contribute to PGE2-prolonged nociceptor sensitization. Intraplantar (i.pl.) injection of a stabilized PGE2 analog, 16,16 dimethyl PGE2 (dmPGE2), in a dose- and time-dependent manner, not only elicited primary tactile allodynia which lasted for 1d, but also prolonged tactile allodynia evoked by a subsequent i.pl. injection of dmPGE2 from 1d to 4d. Moreover, the duration of tactile allodynia was progressively prolonged following multiple sequential i.pl. injections of dmPGE2. Co-injection of the selective EP1 or EP4 receptor antagonist, the inhibitors of cAMP, PKA, PKC, PKCε or PLC as well as an interleukin-6 (IL-6) neutralizing antiserum differentially blocked primary tactile allodynia elicited by the 1st dmPGE2 and the prolonged tactile allodynia evoked by the 2nd dmPGE2, suggesting the involvement of these signaling events in dmPGE2-induced nociceptor activation and sensitization. Co-injection of a selective COX2 inhibitor or two EP4 antagonists prevented or shortened inflammagen-prolonged nociceptor sensitization. I.pl. injection of dmPGE2 or carrageenan time-dependently increased EP4 levels in L4-6 DRG neurons and peripheral nerves. EP4 was expressed in almost half of IB4-binding nociceptors of L4-6 DRG. Taken together, our data suggest that stimulating the synthesis and anterograde axonal trafficking to increase EP4 availability at the axonal terminals of nociceptors is likely a novel mechanism underlying PGE2-prolonged nociceptor

  10. Plasticity modeling & computation

    CERN Document Server

    Borja, Ronaldo I

    2013-01-01

    There have been many excellent books written on the subject of plastic deformation in solids, but rarely can one find a textbook on this subject. “Plasticity Modeling & Computation” is a textbook written specifically for students who want to learn the theoretical, mathematical, and computational aspects of inelastic deformation in solids. It adopts a simple narrative style that is not mathematically overbearing, and has been written to emulate a professor giving a lecture on this subject inside a classroom. Each section is written to provide a balance between the relevant equations and the explanations behind them. Where relevant, sections end with one or more exercises designed to reinforce the understanding of the “lecture.” Color figures enhance the presentation and make the book very pleasant to read. For professors planning to use this textbook for their classes, the contents are sufficient for Parts A and B that can be taught in sequence over a period of two semesters or quarters.

  11. Diffuse axonal injury at ultra-high field MRI.

    Directory of Open Access Journals (Sweden)

    Christoph Moenninghoff

    Full Text Available Diffuse axonal injury (DAI is a specific type of traumatic brain injury caused by shearing forces leading to widespread tearing of axons and small vessels. Traumatic microbleeds (TMBs are regarded as a radiological marker for DAI. This study aims to compare DAI-associated TMBs at 3 Tesla (T and 7 T susceptibility weighted imaging (SWI to evaluate possible diagnostic benefits of ultra-high field (UHF MRI.10 study participants (4 male, 6 female, age range 20-74 years with known DAI were included. All MR exams were performed with a 3 T MR system (Magnetom Skyra and a 7 T MR research system (Magnetom 7 T, Siemens AG, Healthcare Sector, Erlangen, Germany each in combination with a 32-channel-receive coil. The average time interval between trauma and imaging was 22 months. Location and count of TMBs were independently evaluated by two neuroradiologists on 3 T and 7 T SWI images with similar and additionally increased spatial resolution at 7 T. Inter- and intraobserver reliability was assessed using the interclass correlation coefficient (ICC. Count and diameter of TMB were evaluated with Wilcoxon signed rank test.Susceptibility weighted imaging revealed a total of 485 TMBs (range 1-190, median 25 at 3 T, 584 TMBs (plus 20%, range 1-262, median 30.5 at 7 T with similar spatial resolution, and 684 TMBs (plus 41%, range 1-288, median 39.5 at 7 T with 10-times higher spatial resolution. Hemorrhagic DAI appeared significantly larger at 7 T compared to 3 T (p = 0.005. Inter- and intraobserver correlation regarding the counted TMB was high and almost equal 3 T and 7 T.7 T SWI improves the depiction of small hemorrhagic DAI compared to 3 T and may be supplementary to lower field strengths for diagnostic in inconclusive or medicolegal cases.

  12. Axonal transport of proteoglycans to the goldfish optic tectum

    International Nuclear Information System (INIS)

    The study addressed the question of whether 35SO4 labeled molecules that have been delivered to the goldfish optic nerve terminals by rapid axonal transport include soluble proteoglycans. For analysis, tectal homogenates were subfractionated into a soluble fraction (soluble after centrifugation at 105,000 g), a lysis fraction (soluble after treatment with hypotonic buffer followed by centrifugation at 105,000 g) and a final 105,000 g pellet fraction. The soluble fraction contained 25.7% of incorporated radioactivity and upon DEAE chromatography was resolved into a fraction of sulfated glycoproteins eluting at 0-0.32 M NaCl and containing 39.5% of total soluble label and a fraction eluting at 0.32-0.60 M NaCl containing 53.9% of soluble label. This latter fraction was included on columns of Sepharose CL-6B with or without 4 M guanidine and after pronase digestion was found to have 51% of its radioactivity contained in the glycosaminoglycans (GAGs) heparan sulfate and chondroitin (4 or 6) sulfate in the ratio of 70% to 30%. Mobility of both intact proteoglycans and constituent GAGs on Sepharose CL-6B indicated a size distribution that is smaller than has been observed for proteoglycans and GAGs from cultured neuronal cell lines. Similar analysis of lysis fraction, containing 11.5% of incorporated 35SO4, showed a mixture of heparan sulfate and chondroitin sulfate containing proteoglycans, apparent free heparan sulfate and few, if any, sulfated glycoproteins. Overall, the results support the hypothesis that soluble proteoglycans are among the molecules axonally transported in the visual system

  13. Sustainable reverse logistics for household plastic waste

    OpenAIRE

    Bing, X.

    2014-01-01

    Summary of the thesis titled “Sustainable Reverse Logistics for Household Plastic Waste” PhD Candidate: Xiaoyun Bing Recycled plastic can be used in the manufacturing of plastic products to reduce the use of virgin plastics material. The cost of recycled plastics is usually lower than that of virgin plastics. Therefore, it is environmentally and economically beneficial to improve the plastic recycling system to ensure more plastic waste from households is properly collected and pr...

  14. Sub-nanosecond plastic scintillators

    International Nuclear Information System (INIS)

    Quenched plastic scintillators have been developed that yield much faster short decay components and greatly reduced long decay components compared to conventional plastic scintillators. The plastics are produced through the addition of selected quench agents to NE111 plastic scintillator that result in reduced total light output. Eight different agents have been studied. Benzophenone and piperidine are two of the most effective quench agents. Data are presented both for short and long decay components. The plastics are expected to make significant contributions in areas of plasma diagnostics

  15. Plastic food packaging and health

    OpenAIRE

    Raika Durusoy; Ali Osman Karababa

    2011-01-01

    Plastics have a wide usage in our daily lives. One of their uses is for food packaging and food containers. The aim of this review is to introduce different types of chemicals that can leach from food packaging plastics into foods and cause human exposure and to mention their effects on health. The types of plastics were reviewed under the 13 headings in Turkish Codex Alimentarius and plastics recycling symbols were provided to enable the recognition of the type of plastic when applicable. Ch...

  16. 77 FR 54930 - Carlyle Plastics and Resins, Formerly Known as Fortis Plastics, A Subsidiary of Plastics...

    Science.gov (United States)

    2012-09-06

    ... determination was published in the Federal Register on Monday, July 23, 2012 (77 FR 43123). ] At the request of... Employment and Training Administration Carlyle Plastics and Resins, Formerly Known as Fortis Plastics, A Subsidiary of Plastics Acquisitions Inc., Including On-Site Leased Workers From Kelly Services and...

  17. Anisotropic Plasticity and Viscoplasticity

    OpenAIRE

    Schick, David

    2004-01-01

    Plastic anisotropy effects may be described in a phenomenological model by employing in the constitutive theory a set of internal variables, which are defined suitably. These variables have to model the hardening response of the material under consideration to describe e.g. the rotation of some symmetry axes. Such axes are imagined to be related with the development of the material substructure assumed, or, correspondingly, with the state variables characterizing this development. The objecti...

  18. Psychotherapy and brain plasticity

    OpenAIRE

    Collerton, Daniel

    2013-01-01

    In this paper, I will review why psychotherapy is relevant to the question of how consciousness relates to brain plasticity. A great deal of the research and theorizing on consciousness and the brain, including my own on hallucinations for example (Collerton and Perry, 2011) has focused upon specific changes in conscious content which can be related to temporal changes in restricted brain systems. I will argue that psychotherapy, in contrast, allows only a focus on holistic aspects of conscio...

  19. Advances in Plastic Surgery

    OpenAIRE

    McDonald, Harold D.; Luis O. Vasconez

    1982-01-01

    Recent progress in plastic surgery has been rapid and many new techniques have been developed. Reconstructive procedures have been advanced by a better understanding of the anatomy of the blood supply to skin and muscle, with the subsequent development of the use of axial flaps, musculocutaneous flaps and neurosensory flaps. Burn treatment has advanced greatly, making it possible to successfully treat larger and more complicated burns. The development of microsurgery has made possible free-fl...

  20. Microelectronics plastic molded packaging

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, D.R. [Ktech Corp., Albuquerque, NM (United States); Palmer, D.W.; Peterson, D.W. [Sandia National Lab., Albuquerque, NM (United States)] [and others

    1997-02-01

    The use of commercial off-the-shelf (COTS) microelectronics for nuclear weapon applications will soon be reality rather than hearsay. The use of COTS for new technologies for uniquely military applications is being driven by the so-called Perry Initiative that requires the U.S. Department of Defense (DoD) to accept and utilize commercial standards for procurement of military systems. Based on this philosophy, coupled with several practical considerations, new weapons systems as well as future upgrades will contain plastic encapsulated microelectronics. However, a conservative Department of Energy (DOE) approach requires lifetime predictive models. Thus, the focus of the current project is on accelerated testing to advance current aging models as well as on the development of the methodology to be used during WR qualification of plastic encapsulated microelectronics. An additional focal point involves achieving awareness of commercial capabilities, materials, and processes. One of the major outcomes of the project has been the definition of proper techniques for handling and evaluation of modern surface mount parts which might be used in future systems. This program is also raising the familiarity level of plastic within the weapons complex, allowing subsystem design rules accommodating COTS to evolve. A two year program plan is presented along with test results and commercial interactions during this first year.

  1. Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila.

    Science.gov (United States)

    Oliva, Carlos; Molina-Fernandez, Claudia; Maureira, Miguel; Candia, Noemi; López, Estefanía; Hassan, Bassem; Aerts, Stein; Cánovas, José; Olguín, Patricio; Sierralta, Jimena

    2015-09-01

    During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015. PMID:25652545

  2. New perspectives in plastic biodegradation.

    Science.gov (United States)

    Sivan, Alex

    2011-06-01

    During the past 50 years new plastic materials, in various applications, have gradually replaced the traditional metal, wood, leather materials. Ironically, the most preferred property of plastics--durability--exerts also the major environmental threat. Recycling has practically failed to provide a safe solution for disposal of plastic waste (only 5% out of 1 trillion plastic bags, annually produced in the US alone, are being recycled). Since the most utilized plastic is polyethylene (PE; ca. 140 million tons/year), any reduction in the accumulation of PE waste alone would have a major impact on the overall reduction of the plastic waste in the environment. Since PE is considered to be practically inert, efforts were made to isolate unique microorganisms capable of utilizing synthetic polymers. Recent data showed that biodegradation of plastic waste with selected microbial strains became a viable solution. PMID:21356588

  3. Coordinated Eph-ephrin signaling guides migration and axon targeting in the avian auditory system

    Directory of Open Access Journals (Sweden)

    Allen-Sharpley Michelle R

    2012-08-01

    Full Text Available Abstract Background In the avian sound localization circuit, nucleus magnocellularis (NM projects bilaterally to nucleus laminaris (NL, with ipsilateral and contralateral NM axon branches directed to dorsal and ventral NL dendrites, respectively. We previously showed that the Eph receptor EphB2 is expressed in NL neuropil and NM axons during development. Here we tested whether EphB2 contributes to NM-NL circuit formation. Results We found that misexpression of EphB2 in embryonic NM precursors significantly increased the number of axon targeting errors from NM to contralateral NL in a cell-autonomous manner when forward signaling was impaired. We also tested the effects of inhibiting forward signaling of different Eph receptor subclasses by injecting soluble unclustered Fc-fusion proteins at stages when NM axons are approaching their NL target. Again we found an increase in axon targeting errors compared to controls when forward signaling was impaired, an effect that was significantly increased when both Eph receptor subclasses were inhibited together. In addition to axon targeting errors, we also observed morphological abnormalities of the auditory nuclei when EphB2 forward signaling was increased by E2 transfection, and when Eph-ephrin forward signaling was inhibited by E6-E8 injection of Eph receptor fusion proteins. Conclusions These data suggest that EphB signaling has distinct functions in axon guidance and morphogenesis. The results provide evidence that multiple Eph receptors work synergistically in the formation of precise auditory circuitry.

  4. Chemokines induce axon outgrowth downstream of Hepatocyte Growth Factor and TCF/β-catenin signaling

    Directory of Open Access Journals (Sweden)

    Judith Camats

    2013-04-01

    Full Text Available Axon morphogenesis is a complex process regulated by a variety of secreted molecules, including morphogens and growth factors, resulting in the establishment of the neuronal circuitry. Our previous work demonstrated that growth factors (Neurotrophins (NT and Hepatocyte Growth Factor (HGF signal through β-catenin during axon morphogenesis. HGF signaling promotes axon outgrowth and branching by inducing β-catenin phosphorylation at Y142 and transcriptional regulation of T-Cell Factor (TCF target genes. Here we asked which genes are regulated by HGF signaling during axon morphogenesis. An array screening indicated that HGF signaling elevates the expression of chemokines of the CC and CXC families. In line with this, CCL7, CCL20 and CXCL2 significantly increase axon outgrowth in hippocampal neurons. Experiments using blocking antibodies and chemokine receptor antagonists demonstrate that chemokines act downstream of HGF signaling during axon morphogenesis. In addition, qPCR data demonstrates that CXCL2 and CCL5 expression is stimulated by HGF through Met/b-catenin/TCF pathway. These results identify CC family members and CXCL2 chemokines as novel regulators of axon morphogenesis downstream of HGF signaling.

  5. Differential expression of axon-sorting molecules in mouse olfactory sensory neurons.

    Science.gov (United States)

    Ihara, Naoki; Nakashima, Ai; Hoshina, Naosuke; Ikegaya, Yuji; Takeuchi, Haruki

    2016-08-01

    In the mouse olfactory system, the axons of olfactory sensory neurons that express the same type of odorant receptor (OR) converge to a specific set of glomeruli in the olfactory bulb (OB). It is widely accepted that expressed OR molecules instruct glomerular segregation by regulating the expression of axon-sorting molecules. Although the relationship between the expression of axon-sorting molecules and OR types has been analyzed in detail, those between the expressions of axon-sorting molecules remain to be elucidated. Here we collected the expression profiles of four axon-sorting molecules from a large number of glomeruli in the OB. These molecules demonstrated position-independent mosaic expressions, but their patterns were not identical in the OB. Comparing their expressions identified positive and negative correlations between several pairs of genes even though they showed various expressions. Furthermore, the principal component analysis revealed that the factor loadings in the principal component 1, which explain the largest amount of variation, were most likely to reflect the degree of the cyclic nucleotide-gated (CNG) channel dependence on the expression of axon-sorting molecules. Thus, neural activity generated through the CNG channel is a major component in the generation of a wide variety of expressions of axon-sorting molecules in glomerular segregation. PMID:27207328

  6. The business acumen of Canadian plastic surgeons.

    Science.gov (United States)

    Bliss, J A; Caputy, G G

    1995-08-01

    We as plastic surgeons are engrossed and consumed by our quest to optimize patient care. In so doing, we are often distracted by that aspect of our practice which has direct bearing on patient care yet for which we are the least prepared--the business aspect. The entire population of Canadian plastic surgeons was surveyed in an effort to establish real and perceived needs of this group with respect to the business management of their practices. The survey elicited demographic information, information on business educational background, interest, and current commitment in acquiring business knowledge, and a final category of questions dealing with how well these surgeons function as business managers. Of the 315 plastic surgeons surveyed, 122 (39 percent) responded, which, in and of itself, indicates an interest in this aspect of their practices. Twelve respondents were excluded from the study for various reasons. Eighty of the 110 remaining respondents (72 percent) used a hospital-integrated facility for both emergency and elective outpatient procedures. Eighty-four of the 110 respondents (76 percent) indicated that 10 percent of their hours per week of inpatient booked operating time was canceled. Ninety-three percent of respondents felt that a business course to familiarize surgeons with common business situations and areas of personal finance would be beneficial. Few were previously educated in business, and similarly, few had great ongoing interest in business, although the majority of respondents used publications specifically dealing with financial matters (provided by the Canadian Medical Association). Twenty-three percent of respondents saw themselves in a growing role as businesspeople; 24 percent felt this dual role was enjoyable, while 29 percent felt this role was forced on them. A total of 21 percent of respondents did not see themselves as businesspeople at all. The six basic functions of a manager (planning, acquiring, organizing, actuating

  7. Interfacial interactions between plastic particles in plastics flotation.

    Science.gov (United States)

    Wang, Chong-qing; Wang, Hui; Gu, Guo-hua; Fu, Jian-gang; Lin, Qing-quan; Liu, You-nian

    2015-12-01

    Plastics flotation used for recycling of plastic wastes receives increasing attention for its industrial application. In order to study the mechanism of plastics flotation, the interfacial interactions between plastic particles in flotation system were investigated through calculation of Lifshitz-van der Waals (LW) function, Lewis acid-base (AB) Gibbs function, and the extended Derjaguin-Landau-Verwey-Overbeek potential energy profiles. The results showed that van der Waals force between plastic particles is attraction force in flotation system. The large hydrophobic attraction, caused by the AB Gibbs function, is the dominant interparticle force. Wetting agents present significant effects on the interfacial interactions between plastic particles. It is found that adsorption of wetting agents promotes dispersion of plastic particles and decreases the floatability. Pneumatic flotation may improve the recovery and purity of separated plastics through selective adsorption of wetting agents on plastic surface. The relationships between hydrophobic attraction and surface properties were also examined. It is revealed that there exists a three-order polynomial relationship between the AB Gibbs function and Lewis base component. Our finding provides some insights into mechanism of plastics flotation. PMID:26337962

  8. gamma-Diketone neuropathy: axon atrophy and the role of cytoskeletal protein adduction.

    Science.gov (United States)

    LoPachin, Richard M; DeCaprio, Anthony P

    2004-08-15

    Multifocal giant neurofilamentous axonal swellings and secondary distal degeneration have been historically considered the hallmark features of gamma-diketone neuropathy. Accordingly, research conducted over the past 25 years has been directed toward discerning mechanisms of axonal swelling. However, this neuropathological convention has been challenged by recent observations that swollen axons were an exclusive product of long-term 2.5-hexanedione (HD) intoxication at lower daily dose-rates (e.g., 175 mg/kg/day); that is, higher HD dose-rates (e.g., 400 mg/kg/day) produced neurological deficits in the absence of axonal swellings. The observation that neurological toxicity can be expressed without axonal swelling suggests that this lesion is not an important pathophysiological event. Instead, several research groups have now shown that axon atrophy is prevalent in nervous tissues of laboratory animals intoxicated over a wide range of HD dose-rates. The well-documented nerve conduction defects associated with axon atrophy, in conjunction with the temporal correspondence between this lesion and the onset of neurological deficits, strongly suggest that atrophy has pathophysiological significance. In this commentary, we present evidence that supports a pathognomonic role for axon atrophy in gamma-diketone neuropathy and suggests that the functional consequences of this lesion mediate the corresponding neurological toxicity. Previous research has demonstrated that HD interacts with proteins via formation of pyrrole adducts. We therefore discuss the possibility that this chemical process is essential to the mechanism of atrophy. Evidence presented in this review suggests that "distal axonopathy" is an inaccurate classification and future nosological schemes should be based on the apparent primacy of axon atrophy. PMID:15289087

  9. Belief elicitation in experiments: is there a hedging problem?

    Czech Academy of Sciences Publication Activity Database

    Blanco, M.; Engelmann, Dirk; Koch, A. K.; Normann, H.-T.

    2010-01-01

    Roč. 13, č. 4 (2010), s. 412-438. ISSN 1386-4157 Institutional research plan: CEZ:AV0Z70850503 Keywords : belief elicitation * hedging * experimental methodology Subject RIV: AH - Economics Impact factor: 1.868, year: 2010

  10. Eliciting Students' Beliefs about Who Is Good at Mathematics

    Science.gov (United States)

    Morge, Shelby P.

    2007-01-01

    This article highlights a series of activities designed to elicit students' mathematics-related beliefs, particularly those related to gender. As a result of the activities, females in upper-level classes rated themselves as having less confidence than males, and viewing a movie clip was sufficient for some students to modify their descriptions of…

  11. Expert Elicitation Method Selection Process and Method Comparison

    Energy Technology Data Exchange (ETDEWEB)

    Dalton, Angela C.; Brothers, Alan J.; Walsh, Stephen J.; Whitney, Paul D.

    2010-09-21

    Research on integrative modeling has gained considerable attention in recent years and expert opinion has been increasingly recognized as an important data source and modeling contributor. However, little research has systematically compared and evaluated expert elicitation methods in terms of their ability to link to computational models that capture human behavior and social phenomena. In this paper, we describe a decision-making process we used for evaluating and selecting a task specific elicitation method within the framework of integrative computational social-behavioral modeling. From the existing literature, we identified the characteristics of problems that each candidate method is well suited to address. A small-scale expert elicitation was also conducted to evaluate the comparative strength and weaknesses of the methods against a number of consensus-based decision criteria. By developing a set of explicit method evaluation criteria and a description characterizing decision problems for the candidate methods, we seek to gain a better understanding of the feasibility and cost-effectiveness of integrating elicitation methods with computational modeling techniques. This serves an important first step toward expanding our research effort and trajectory toward greater interdisciplinary modeling research of human behavior.

  12. Computational Support for Early Elicitation and Classification of Tone

    Science.gov (United States)

    Bird, Steven; Lee, Haejoong

    2014-01-01

    Investigating a tone language involves careful transcription of tone on words and phrases. This is challenging when the phonological categories--the tones or melodies--have not been identified. Effects such as coarticulation, sandhi, and phrase-level prosody appear as obstacles to early elicitation and classification of tone. This article presents…

  13. The Role of Elicited Verbal Imitation in Toddlers' Word Learning

    Science.gov (United States)

    Hodges, Rosemary; Munro, Natalie; Baker, Elise; McGregor, Karla; Docking, Kimberley; Arciuli, Joanne

    2016-01-01

    This study is about the role of elicited verbal imitation in toddler word learning. Forty-eight toddlers were taught eight nonwords linked to referents. During training, they were asked to imitate the nonwords. Naming of the referents was tested at three intervals (one minute later [uncued], five minutes, and 1-7 days later [cued]) and recognition…

  14. Classifying groupware tools to improve communication in geographically distributed elicitation

    OpenAIRE

    Martín, Adriana; Martinez, Claudia; Martínez Carod, Nadina; Aranda, Gabriela N.; Cechich, Alejandra

    2003-01-01

    In a scene where stakeholders are geographically distributed, communication presents new challenges for research areas. Considering the characteristics of interpersonal communication and the virtual area where it is carried out, the importance of applying interdisciplinary approaches, such as Cognitive Engineering, is currently increasing. Particularly, our proposal aims at improving the interaction between stakeholders by applying learning models when eliciting distributed software requireme...

  15. Conditioned craving cues elicit an automatic approach tendency

    NARCIS (Netherlands)

    D. van Gucht; D. Vansteenwegen; O. Van den Bergh; T. Beckers

    2008-01-01

    In two experiments, we used a Pavlovian differential conditioning procedure to induce craving for chocolate. As a result of repeated pairing with chocolate intake, initially neutral cues came to elicit an automatic approach tendency in a speeded stimulus-response compatibility reaction time task. Th

  16. Creating a Framework: Art Therapy Elicits the Narrative

    Science.gov (United States)

    Harber, Karen

    2011-01-01

    A case study illustrates how art therapy was used to elicit the narrative of an adolescent male student in transition from incarceration to a transfer school setting. Childhood trauma was addressed in individual sessions and within a literacy group co-led by a reading specialist. The art therapist responded to the client's needs by broadening the…

  17. Elicitation of Pharmacologically Active Substances in Intact Medical Plant

    Czech Academy of Sciences Publication Activity Database

    Kužel, S.; Vydra, J.; Tříska, Jan; Vrchotová, Naděžda; Hrubý, Martin; Cígler, P.

    2009-01-01

    Roč. 57, č. 17 (2009), s. 7907-7911. ISSN 0021-8561 Institutional research plan: CEZ:AV0Z60870520; CEZ:AV0Z40500505 Keywords : elicitation * medical plant * Echinacea purpurea * secondary metabolite * foliar application * phenolics Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.469, year: 2009

  18. A Task that Elicits Reasoning: A Dual Analysis

    Science.gov (United States)

    Yankelewitz, Dina; Mueller, Mary; Maher, Carolyn A.

    2010-01-01

    This paper reports on the forms of reasoning elicited as fourth grade students in a suburban district and sixth grade students in an urban district worked on similar tasks involving reasoning with the use of Cuisenaire rods. Analysis of the two data sets shows similarities in the reasoning used by both groups of students on specific tasks, and the…

  19. Structured Language Requirement Elicitation Using Case Base Reasoning

    Directory of Open Access Journals (Sweden)

    Marryam Murtaza

    2013-12-01

    Full Text Available Requirement elicitation is very difficult process in highly challenging and business based software as well as in real time software. Common problems associated with these types of software are rapidly changing the requirements and understanding the language of the layman person. In this study, a framework for requirement elicitation by using knowledge based system is proposed, which is very helpful for knowledge documentation, intelligent decision support, self-learning and more specifically it is very helpful for case based reasoning and explanation. Basically in this method requirements are gathered from Artificial Intelligence (AI expert system from various sources e.g., via interviews, scenarios or use cases. Then, these are converted into structured natural language using ontology and this new problem/case is put forward to Case Based Reasoning (CBR. CBR based on its previous information having similar requirements combines with new case and suggests a proposed solution. Based on this solution a prototype is developed and delivered to customer. The use of case-based reasoning in requirements elicitation process has greatly reduced the burden and saved time of requirement analyst and results in an effective solution for handling complex or vague requirements during the elicitation process.

  20. Brain-derived neurotrophic factor induces post-lesion transcommissural growth of olivary axons that develop normal climbing fibers on mature Purkinje cells.

    Science.gov (United States)

    Dixon, Kirsty J; Sherrard, Rachel M

    2006-11-01

    In the adult mammalian central nervous system, reinnervation and recovery from trauma is limited. During development, however, post-lesion plasticity may generate alternate paths providing models to investigate factors that promote reinnervation to appropriate targets. Following unilateral transection of the neonatal rat olivocerebellar pathway, axons from the remaining inferior olive reinnervate the denervated hemicerebellum and develop climbing fiber arbors on Purkinje cells. However, the capacity to recreate this accurate target reinnervation in a mature system remains unknown. In rats lesioned on day 15 (P15) or 30 and treated with intracerebellar injection of brain-derived neurotrophic factor (BDNF) or vehicle 24 h later, the morphology and organisation of transcommissural olivocerebellar reinnervation was examined using neuronal tracing and immunohistochemistry. In all animals BDNF, but not vehicle, induced transcommissural olivocerebellar axonal growth into the denervated hemicerebellum. The distribution of reinnervating climbing fibers was not confined to the injection sites but extended throughout the denervated hemivermis and, less densely, up to 3.5 mm into the hemisphere. Transcommissural olivocerebellar axons were organised into parasagittal microzones that were almost symmetrical to those in the right hemicerebellum. Reinnervating climbing fiber arbors were predominantly normal, but in the P30-lesioned group 10% were either branched within the molecular layer forming a smaller secondary arbor or were less branched, and in the P15 lesion group the reinnervating arbors extended their terminals almost to the pial surface and were larger than control arbors (P < 0.02). These results show that BDNF can induce transcommissural olivocerebellar reinnervation, which resembles developmental neuroplasticity to promote appropriate target reinnervation in a mature environment. PMID:16790241

  1. In vivo axonal transport deficits in a mouse model of fronto-temporal dementia

    Directory of Open Access Journals (Sweden)

    Tabassum Majid

    2014-01-01

    Discussion: In our study, we identified the presence of age-dependent axonal transport deficits beginning at 3 months of age in rTg4510 mice. We correlated these deficits at 3 months to the presence of hyperphosphorylated tau in the brain and the presence within the olfactory epithelium. We observed tau pathology not only in the soma of these neurons but also within the axons and processes of these neurons. Our characterization of axonal transport in this tauopathy model provides a functional time point that can be used for future therapeutic interventions.

  2. Extracellular matrix molecules play diverse roles in the growth and guidance of central nervous system axons

    Directory of Open Access Journals (Sweden)

    M.A. Pires-Neto

    1999-05-01

    Full Text Available Axon growth and guidance represent complex biological processes in which probably intervene diverse sets of molecular cues that allow for the appropriate wiring of the central nervous system (CNS. The extracellular matrix (ECM represents a major contributor of molecular signals either diffusible or membrane-bound that may regulate different stages of neural development. Some of the brain ECM molecules form tridimensional structures (tunnels and boundaries that appear during time- and space-regulated events, possibly playing relevant roles in the control of axon elongation and pathfinding. This short review focuses mainly on the recognized roles played by proteoglycans, laminin, fibronectin and tenascin in axonal development during ontogenesis.

  3. Clinical features and molecular modelling of novel MPZ mutations in demyelinating and axonal neuropathies

    OpenAIRE

    Mandich, Paola; Fossa, Paola; Capponi, Simona; Geroldi, Alessandro; Acquaviva, Massimo; Gulli, Rossella; Ciotti, Paola; MANGANELLI, FIORE; Grandis, Marina; Bellone, Emilia

    2009-01-01

    Mutations in the myelin protein zero (MPZ) gene have been associated with different Charcot–Marie–Tooth disease (CMT) phenotypes, including classical demyelinating CMT1B and the axonal form of the disease (CMT2). The MPZ role in the pathogenesis of both demyelinating and axonal inherited neuropathies was evaluated in the Italian population by screening a cohort of 214 patients with CMT1 or CMT2. A MPZ mutation frequency of 7.9% in demyelinating cases and of 4.8% in axonal cases was observed. ...

  4. Diffuse axonal injury: detection of changes in anisotropy of water diffusion by diffusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chan, J.H.M.; Tsui, E.Y.K.; Yuen, M.K. [Department of Diagnostic Radiology, Tuen Mun Hospital, Tsing Chung Koon Road, Tuen Mun, N.T., Hong Kong (China); Peh, W.C.G. [Department of Diagnostic Radiology, Singapore General Hospital (Singapore); Fong, D.; Fok, K.F.; Leung, K.M. [Department of Neurosurgery, Tuen Mun Hospital (Hong Kong); Fung, K.K.L. [Department of Optometry and Radiography, Hong Kong Polytechnic University (China)

    2003-01-01

    Myelinated axons of white matter demonstrate prominent directional differences in water diffusion. We performed diffusion-weighted imaging on ten patients with head injury to explore the feasibility of using water diffusion anisotropy for quantitating diffuse axonal injury. We showed significant decrease in diffusion anisotropy indices in areas with or without signal abnormality on T2 and T2*-weighted images. We conclude that the water diffusion anisotropy index a potentially useful, sensitive and quantitative way of diagnosing and assessing patients with diffuse axonal injury. (orig.)

  5. Diffuse axonal injury: detection of changes in anisotropy of water diffusion by diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Myelinated axons of white matter demonstrate prominent directional differences in water diffusion. We performed diffusion-weighted imaging on ten patients with head injury to explore the feasibility of using water diffusion anisotropy for quantitating diffuse axonal injury. We showed significant decrease in diffusion anisotropy indices in areas with or without signal abnormality on T2 and T2*-weighted images. We conclude that the water diffusion anisotropy index a potentially useful, sensitive and quantitative way of diagnosing and assessing patients with diffuse axonal injury. (orig.)

  6. Enzyme-instructed self-assembly of taxol promotes axonal branching

    Science.gov (United States)

    Mei, Bin; Miao, Qingqing; Tang, Anming; Liang, Gaolin

    2015-09-01

    Axonal branching is important for vertebrate neuron signaling. Taxol has a biphasic effect on axonal branching (i.e., high concentration inhibits axonal growth but low concentration restores it). To the best of our knowledge, low concentration of taxol to promote axonal branching has not been reported yet. Herein, we rationally designed a taxol derivative Fmoc-Phe-Phe-Lys(taxol)-Tyr(H2PO4)-OH (1) which could be subjected to alkaline phosphatase (ALP)-catalyzed self-assembly to form taxol nanofibers. We found that, at 10 μM, 1 has a microtubule (MT) condensation effect similar to that of taxol on mammalian cells but with more chronic toxicity than taxol on the cells. At a low concentration of 10 nM, 1 not only promoted neurite elongation as taxol did but also promoted axonal branching which was not achieved by using taxol. We propose that self-assembly of 1 along the MTs prohibited their lateral contacts and thus promoted axonal branching. Our strategy of enzyme-instructed self-assembly (EISA) of a taxol derivative provides a new tool for scientists to study the morphology of neurons, as well as their behaviours.Axonal branching is important for vertebrate neuron signaling. Taxol has a biphasic effect on axonal branching (i.e., high concentration inhibits axonal growth but low concentration restores it). To the best of our knowledge, low concentration of taxol to promote axonal branching has not been reported yet. Herein, we rationally designed a taxol derivative Fmoc-Phe-Phe-Lys(taxol)-Tyr(H2PO4)-OH (1) which could be subjected to alkaline phosphatase (ALP)-catalyzed self-assembly to form taxol nanofibers. We found that, at 10 μM, 1 has a microtubule (MT) condensation effect similar to that of taxol on mammalian cells but with more chronic toxicity than taxol on the cells. At a low concentration of 10 nM, 1 not only promoted neurite elongation as taxol did but also promoted axonal branching which was not achieved by using taxol. We propose that self-assembly of 1

  7. Hsp27 and axonal growth in adult sensory neurons in vitro

    Directory of Open Access Journals (Sweden)

    Mearow Karen M

    2005-04-01

    Full Text Available Abstract Background Neurite growth can be elicited by growth factors and interactions with extracellular matrix molecules like laminin. Among the targets of the signalling pathways activated by these stimuli are cytoskeletal elements, such as actin, tubulin and neurofilaments. The cytoskeleton can also be modulated by other proteins, such as the small heat shock protein Hsp27. Hsp27 interacts with actin and tubulin in non-neuronal cells and while it has been suggested to play a role in the response of some neurons to injury, there have been no direct studies of its contribution to axonal regeneration. Results We have investigated neurite initiation and process extension using cultures of adult dorsal root ganglion (DRG sensory neurons and a laminin stimulation paradigm. Employing confocal microscopy and biochemical analyses we have examined localization of Hsp27 at early and later stages of neurite growth. Our results show that Hsp27 is colocalized with actin and tubulin in lamellopodia, filopodia, focal contacts and mature neurites and growth cones. Disruption of the actin cytoskeleton with cytochalasin D results in aberrant neurite initiation and extension, effects which may be attributable to alterations in actin polymerization states. Inhibition of Hsp27 phosphorylation in our cultures results in an atypical growth pattern that may be attributable to an effect of pHsp27 on the stability of the actin cytoskeleton. Conclusion We observed colocalization of the phosphorylated and non-phosphorylated forms of Hsp27 with actin and tubulin in both very early and later stages of neurite growth from cultured adult DRG neurons. The colocalization of Hsp27 and pHsp27 with actin in lamellopodia and focal contacts at early stages of neurite growth, and in processes, branch points and growth cones at later stages, suggests that Hsp27 may play a role in neuritogenesis and subsequent neurite extension, and potentially in the patterning of this growth. Hsp27

  8. Identifying motor and sensory myelinated axons in rabbit peripheral nerves by histochemical staining for carbonic anhydrase and cholinesterase activities

    Science.gov (United States)

    Riley, Danny A.; Sanger, James R.; Matloub, Hani S.; Yousif, N. John; Bain, James L. W.

    1988-01-01

    Carbonic anhydrase (CA) and cholinesterase (CE) histochemical staining of rabbit spinal nerve roots and dorsal root ganglia demonstrated that among the reactive myeliated axons, with minor exceptions, sensory axons were CA positive and CE negative whereas motor axons were CA negative and CE positive. The high specificity was achieved by adjusting reaction conditions to stain subpopulations of myelinated axons selectively while leaving 50 percent or so unstained. Fixation with glutaraldehyde appeared necessary for achieving selectivity. Following sciatic nerve transection, the reciprocal staining pattern persisted in damaged axons and their regenerating processes which formed neuromas within the proximal nerve stump. Within the neuromas, CA-stained sensory processes were elaborated earlier and in greater numbers than CE-stained regenerating motor processes. The present results indicate that histochemical axon typing can be exploited to reveal heterogeneous responses of motor and sensory axons to injury.

  9. Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage Precursors

    Directory of Open Access Journals (Sweden)

    Elodie Reynaud

    2015-05-01

    Full Text Available In vivo axon pathfinding mechanisms in the neuron-dense brain remain relatively poorly characterized. We study the Drosophila mushroom body (MB axons, whose α and β branches connect to different brain areas. We show that the Ryk family WNT5 receptor, DRL (derailed, which is expressed in the dorsomedial lineages, brain structure precursors adjacent to the MBs, is required for MB α branch axon guidance. DRL acts to capture and present WNT5 to MB axons rather than transduce a WNT5 signal. DRL’s ectodomain must be cleaved and shed to guide α axons. DRL-2, another Ryk, is expressed within MB axons and functions as a repulsive WNT5 signaling receptor. Finally, our biochemical data support the existence of a ternary complex composed of the cleaved DRL ectodomain, WNT5, and DRL-2. Thus, the interaction of MB-extrinsic and -intrinsic Ryks via their common ligand acts to guide MB α axons.

  10. Direct liquefaction of plastics and coprocessing of coal with plastics

    Energy Technology Data Exchange (ETDEWEB)

    Huffman, G.P.; Feng, Z.; Mahajan, V. [Univ. of Kentucky, Lexington, KY (United States)

    1995-12-31

    The objectives of this work were to optimize reaction conditions for the direct liquefaction of waste plastics and the coprocessing of coal with waste plastics. In previous work, the direct liquefaction of medium and high density polyethylene (PE), polypropylene (PPE), poly(ethylene terephthalate) (PET), and a mixed plastic waste, and the coliquefaction of these plastics with coals of three different ranks was studied. The results established that a solid acid catalyst (HZSM-5 zeolite) was highly active for the liquefaction of the plastics alone, typically giving oil yields of 80-95% and total conversions of 90-100% at temperatures of 430-450 {degrees}C. In the coliquefaction experiments, 50:50 mixtures of plastic and coal were used with a tetralin solvent (tetralin:solid = 3:2). Using approximately 1% of the HZSM-5 catalyst and a nanoscale iron catalyst, oil yields of 50-70% and total conversion of 80-90% were typical. In the current year, further investigations were conducted of the liquefaction of PE, PPE, and a commingled waste plastic obtained from the American Plastics Council (APC), and the coprocessing of PE, PPE and the APC plastic with Black Thunder subbituminous coal. Several different catalysts were used in these studies.

  11. Fabrication of plastic biochips

    International Nuclear Information System (INIS)

    A versatile surface functionalization procedure based on rf magnetron sputtering of silica was performed on poly(methylmethacrylate), polycarbonate, polypropylene, and cyclic olefin copolymers (Topas 6015). The hybrid thermoplastic surfaces were characterized by x-ray photoelectron spectrometer analysis and contact angle measurements. The authors then used these hybrid materials to perform a sandwich assay targeting an HIV-1 antibody using fluorescent detection and biotinylated peptides immobilized using the bioaffinity of biotin-neutravidin. They found a limit of detection similar to arrays on glass surfaces and believed that this plastic biochip platform may be used for the development of disposable immunosensing and diagnostic applications.

  12. Plastics pipe couplings

    International Nuclear Information System (INIS)

    A method is described of making a pipe coupling of the type comprising a plastics socket and a resilient annular sealing member secured in the mouth thereof, in which the material of at least one component of the coupling is subjected to irradiation with high energy radiation whereby the material is caused to undergo cross-linking. As examples, the coupling may comprise a polyethylene or plasticised PVC socket the material of which is subjected to irradiation, and the sealing member may be moulded from a thermoplastic elastomer which is subjected to irradiation. (U.K.)

  13. Plastic star coupler

    Science.gov (United States)

    Yuuki, Hayato; Ito, Takeharu; Sugimoto, Tetsuo

    1991-12-01

    We applied an ultrasonic welding method for the bonding of plastic fibers, and obtained many types of optical star couplers for optical communication systems. It enables the manufacturing of optical components with low loss without damaging the clad layer except for the welding surface. Therefore, they have some merits, such as low loss, small size, light weight, and low cost. The 4-ports (2 X 2) star coupler of 1000 micrometers diam APF has 0.7 dB excess loss at most, and the welding length is 20 mm.

  14. Handbook of plastic optics

    CERN Document Server

    Bäumer, Stefan

    2011-01-01

    A coherent overview of the current status of injection molded optics, describing in detail all aspects of plastic optics, from design issues to production technology and quality control. This updated second edition is supplemented by a chapter on the equipment and process of injection wells as well as a look at recent applications.The contributors, each one a leading expert in their discipline, have either a background in or strong ties to the industry, thus combining a large amount of practical experience.With its focus firmly set on practical applications, this is an indispensable re

  15. The Actin-Binding Protein α-Adducin Is Required for Maintaining Axon Diameter.

    Science.gov (United States)

    Leite, Sérgio Carvalho; Sampaio, Paula; Sousa, Vera Filipe; Nogueira-Rodrigues, Joana; Pinto-Costa, Rita; Peters, Luanne Laurel; Brites, Pedro; Sousa, Mónica Mendes

    2016-04-19

    The actin-binding protein adducin was recently identified as a component of the neuronal subcortical cytoskeleton. Here, we analyzed mice lacking adducin to uncover the function of this protein in actin rings. α-adducin knockout mice presented progressive axon enlargement in the spinal cord and optic and sciatic nerves, followed by axon degeneration and loss. Using stimulated emission depletion super-resolution microscopy, we show that a periodic subcortical actin cytoskeleton is assembled in every neuron type inspected including retinal ganglion cells and dorsal root ganglia neurons. In neurons devoid of adducin, the actin ring diameter increased, although the inter-ring periodicity was maintained. In vitro, the actin ring diameter adjusted as axons grew, suggesting the lattice is dynamic. Our data support a model in which adducin activity is not essential for actin ring assembly and periodicity but is necessary to control the diameter of both actin rings and axons and actin filament growth within rings. PMID:27068466

  16. Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules

    Directory of Open Access Journals (Sweden)

    Lanfranco Leo

    2015-09-01

    Full Text Available Individual microtubules (MTs in the axon consist of a stable domain that is highly acetylated and a labile domain that is not. Traditional MT-severing proteins preferentially cut the MT in the stable domain. In Drosophila, fidgetin behaves in this fashion, with targeted knockdown resulting in neurons with a higher fraction of acetylated (stable MT mass in their axons. Conversely, in a fidgetin knockout mouse, the fraction of MT mass that is acetylated is lower than in the control animal. When fidgetin is depleted from cultured rodent neurons, there is a 62% increase in axonal MT mass, all of which is labile. Concomitantly, there are more minor processes and a longer axon. Together with experimental data showing that vertebrate fidgetin targets unacetylated tubulin, these results indicate that vertebrate fidgetin (unlike its fly ortholog regulates neuronal development by tamping back the expansion of the labile domains of MTs.

  17. Calcium-Activated Potassium Channels at Nodes of Ranvier Secure Axonal Spike Propagation

    Directory of Open Access Journals (Sweden)

    Jan Gründemann

    2015-09-01

    Full Text Available Functional connectivity between brain regions relies on long-range signaling by myelinated axons. This is secured by saltatory action potential propagation that depends fundamentally on sodium channel availability at nodes of Ranvier. Although various potassium channel types have been anatomically localized to myelinated axons in the brain, direct evidence for their functional recruitment in maintaining node excitability is scarce. Cerebellar Purkinje cells provide continuous input to their targets in the cerebellar nuclei, reliably transmitting axonal spikes over a wide range of rates, requiring a constantly available pool of nodal sodium channels. We show that the recruitment of calcium-activated potassium channels (IK, KCa3.1 by local, activity-dependent calcium (Ca2+ influx at nodes of Ranvier via a T-type voltage-gated Ca2+ current provides a powerful mechanism that likely opposes depolarizing block at the nodes and is thus pivotal to securing continuous axonal spike propagation in spontaneously firing Purkinje cells.

  18. Calcium-dependent proteasome activation is required for axonal neurofilament degradation

    Institute of Scientific and Technical Information of China (English)

    Joo Youn Park; So Young Jang; Yoon Kyung Shin; Duk Joon Suh; Hwan Tae Park

    2013-01-01

    Even though many studies have identified roles of proteasomes in axonal degeneration, the mo-lecular mechanisms by which axonal injury regulates proteasome activity are stil unclear. In the present study, we found evidence indicating that extracellular calcium influx is an upstream regula-tor of proteasome activity during axonal degeneration in injured peripheral nerves. In degenerating axons, the increase in proteasome activity and the degradation of ubiquitinated proteins were sig-nificantly suppressed by extracellular calcium chelation. In addition, electron microscopic findings revealed selective inhibition of neurofilament degradation, but not microtubule depolymerization or mitochondrial swel ing, by the inhibition of calpain and proteasomes. Taken together, our findings suggest that calcium increase and subsequent proteasome activation are an essential initiator of neurofilament degradation in Wal erian degeneration.

  19. Calcium-dependent proteasome activation is required for axonal neurofilament degradation.

    Science.gov (United States)

    Park, Joo Youn; Jang, So Young; Shin, Yoon Kyung; Suh, Duk Joon; Park, Hwan Tae

    2013-12-25

    Even though many studies have identified roles of proteasomes in axonal degeneration, the molecular mechanisms by which axonal injury regulates proteasome activity are still unclear. In the present study, we found evidence indicating that extracellular calcium influx is an upstream regulator of proteasome activity during axonal degeneration in injured peripheral nerves. In degenerating axons, the increase in proteasome activity and the degradation of ubiquitinated proteins were significantly suppressed by extracellular calcium chelation. In addition, electron microscopic findings revealed selective inhibition of neurofilament degradation, but not microtubule depolymerization or mitochondrial swelling, by the inhibition of calpain and proteasomes. Taken together, our findings suggest that calcium increase and subsequent proteasome activation are an essential initiator of neurofilament degradation in Wallerian degeneration. PMID:25206662

  20. Mechanisms of sodium channel clustering and its influence on axonal impulse conduction.

    Science.gov (United States)

    Freeman, Sean A; Desmazières, Anne; Fricker, Desdemona; Lubetzki, Catherine; Sol-Foulon, Nathalie

    2016-02-01

    The efficient propagation of action potentials along nervous fibers is necessary for animals to interact with the environment with timeliness and precision. Myelination of axons is an essential step to ensure fast action potential propagation by saltatory conduction, a process that requires highly concentrated voltage-gated sodium channels at the nodes of Ranvier. Recent studies suggest that the clustering of sodium channels can influence axonal impulse conduction in both myelinated and unmyelinated fibers, which could have major implications in disease, particularly demyelinating pathology. This comprehensive review summarizes the mechanisms governing the clustering of sodium channels at the peripheral and central nervous system nodes and the specific roles of their clustering in influencing action potential conduction. We further highlight the classical biophysical parameters implicated in conduction timing, followed by a detailed discussion on how sodium channel clustering along unmyelinated axons can impact axonal impulse conduction in both physiological and pathological contexts. PMID:26514731

  1. Microtubule stabilization reduces scarring and causes axon regeneration after spinal cord injury

    NARCIS (Netherlands)

    F. Hellal (Farida); A. Hurtado (Andres); J. Ruschel (Jörg); K.C. Flynn (Kevin); C.J. Laskowski (Claudia); M. Umlauf (Martina); L.C. Kapitein (Lukas); D. Strikis (Dinara); V. Lemmon (Vance); J. Bixby (John); C.C. Hoogenraad (Casper); F. Bradke (Frank)

    2011-01-01

    textabstractHypertrophic scarring and poor intrinsic axon growth capacity constitute major obstacles for spinal cord repair. These processes are tightly regulated by microtubule dynamics. Here, moderate microtubule stabilization decreased scar formation after spinal cord injury in rodents through va

  2. Axonal degeneration in multiple sclerosis: defining therapeutic targets by identifying the causes of pathology.

    Science.gov (United States)

    Lee, Jae Young; Biemond, Melissa; Petratos, Steven

    2015-12-01

    Current therapeutics in multiple sclerosis (MS) target the putative inflammation and immune attack on CNS myelin. Despite their effectiveness in blunting the relapse rate in MS patients, such therapeutics do not prevent MS disease progression. Importantly, specific clinical dilemma arises through inability to predict MS progression and thereby therapeutically target axonal injury during MS, limiting permanent disability. The current review identifies immune and neurobiological principles that govern the sequelae of axonal degeneration during MS disease progression. Defining the specific disease arbiters, inflammatory and autoimmune, oligodendrocyte dystrophy and degenerative myelin, we discuss a basis for a molecular mechanism in axons that may be targeted therapeutically, in spatial and temporal manner to limit axonal degeneration and thereby halt progression of MS. PMID:26619755

  3. Axonal degeneration stimulates the formation of NG2+ cells and oligodendrocytes in the mouse

    DEFF Research Database (Denmark)

    Nielsen, Helle Hvilsted; Ladeby, Rune; Drøjdahl, Nina;

    2006-01-01

    Proliferation of the adult NG2-expressing oligodendrocyte precursor cells has traditionally been viewed as a remyelination response ensuing from destruction of myelin and oligodendrocytes, and not to the axonal pathology that is also a characteristic of demyelinating disease. To better understand...... the response of the NG2+ cells to the different components of demyelinating pathology, we investigated the response of adult NG2+ cells to axonal degeneration in the absence of primary myelin or oligodendrocyte pathology. Axonal degeneration was induced in the hippocampal dentate gyrus of adult mice...... by transection of the entorhino-dentate perforant path projection. The acutely induced degeneration of axons and terminals resulted in a prompt response of NG2+ cells, consisting of morphological transformation, cellular proliferation, and upregulation of NG2 expression days 2-3 after surgery. This was followed...

  4. Plastic food packaging and health

    Directory of Open Access Journals (Sweden)

    Raika Durusoy

    2011-02-01

    Full Text Available Plastics have a wide usage in our daily lives. One of their uses is for food packaging and food containers. The aim of this review is to introduce different types of chemicals that can leach from food packaging plastics into foods and cause human exposure and to mention their effects on health. The types of plastics were reviewed under the 13 headings in Turkish Codex Alimentarius and plastics recycling symbols were provided to enable the recognition of the type of plastic when applicable. Chemicals used during the production and that can cause health risks are investigated under the heading of the relevant type of plastic. The most important chemicals from plastic food packaging that can cause toxicity are styrene, 1,3-butadiene, melamine, formaldehyde, acrylamide, di-2-ethylhexyl phthalate, di-2-ethylhexyl adipate, vinyl chloride and bisphenol A. These chemicals have endocrine disrupting, carcinogenic and/or development disrupting effects. These chemicals may leach into foods depending on the chemical properties of the plastic or food, temperature during packaging, processing and storage, exposure to UV and duration of storage. Contact with fatty/oily or acidic foods, heating of the food inside the container, or drinking hot drinks from plastic cups, use of old and scratched plastics and some detergents increase the risk of leaching. The use of plastic containers and packaging for food and beveradges should be avoided whenever possible and when necessary, less harmful types of plastic should be preferred. [TAF Prev Med Bull 2011; 10(1.000: 87-96

  5. PLASMA GASIFICATION OF WASTE PLASTICS

    OpenAIRE

    Tadeusz Mączka; Ewa Śliwka; Mateusz Wnukowski

    2013-01-01

    The article presents the process of obtaining liquid fuels and fuel gas in the process of plasma processing of organic materials, including waste plastics. The concept of plasma pyrolysis of plastics was presented and on its basis a prototype installation was developed. The article describes a general rule of operating the installation and its elements in the process and basic operation parameters determined during its start-up. Initial results of processing plastics and the directions furthe...

  6. Imaging brain plasticity after trauma

    OpenAIRE

    Kou, Zhifeng; Iraji, Armin

    2014-01-01

    The brain is highly plastic after stroke or epilepsy; however, there is a paucity of brain plasticity investigation after traumatic brain injury (TBI). This mini review summarizes the most recent evidence of brain plasticity in human TBI patients from the perspective of advanced magnetic resonance imaging. Similar to other forms of acquired brain injury, TBI patients also demonstrated both structural reorganization as well as functional compensation by the recruitment of other brain regions. ...

  7. Some Misconceptions About Plastic Degradation

    OpenAIRE

    Raouf, Mohamed Imad N. Raouf

    1999-01-01

    In consistence with the importance of implementing best utilization of human resources towards maintaining suitable healthy environment for our next generations, concepts and fundamentals upon which most researches on degradation of plastics are based, as a solution of solid waste reduction, will be discussed. Proper understanding of plastic figures would better utilize human efforts toward useful tasks to control solid waste. Unfortunately, when plastics are made more degradable, they becom...

  8. SNTF immunostaining reveals previously undetected axonal pathology in traumatic brain injury.

    Science.gov (United States)

    Johnson, Victoria E; Stewart, William; Weber, Maura T; Cullen, D Kacy; Siman, Robert; Smith, Douglas H

    2016-01-01

    Diffuse axonal injury (DAI) is a common feature of severe traumatic brain injury (TBI) and may also be a predominant pathology in mild TBI or "concussion". The rapid deformation of white matter at the instant of trauma can lead to mechanical failure and calcium-dependent proteolysis of the axonal cytoskeleton in association with axonal transport interruption. Recently, a proteolytic fragment of alpha-II spectrin, "SNTF", was detected in serum acutely following mild TBI in patients and was prognostic for poor clinical outcome. However, direct evidence that this fragment is a marker of DAI has yet to be demonstrated in either humans following TBI or in models of mild TBI. Here, we used immunohistochemistry (IHC) to examine for SNTF in brain tissue following both severe and mild TBI. Human severe TBI cases (survival <7d; n = 18) were compared to age-matched controls (n = 16) from the Glasgow TBI archive. We also examined brains from an established model of mild TBI at 6, 48 and 72 h post-injury versus shams. IHC specific for SNTF was compared to that of amyloid precursor protein (APP), the current standard for DAI diagnosis, and other known markers of axonal pathology including non-phosphorylated neurofilament-H (SMI-32), neurofilament-68 (NF-68) and compacted neurofilament-medium (RMO-14) using double and triple immunofluorescent labeling. Supporting its use as a biomarker of DAI, SNTF immunoreactive axons were observed at all time points following both human severe TBI and in the model of mild TBI. Interestingly, SNTF revealed a subpopulation of degenerating axons, undetected by the gold-standard marker of transport interruption, APP. While there was greater axonal co-localization between SNTF and APP after severe TBI in humans, a subset of SNTF positive axons displayed no APP accumulation. Notably, some co-localization was observed between SNTF and the less abundant neurofilament subtype markers. Other SNTF positive axons, however, did not co-localize with any

  9. Surface coating of plastics

    International Nuclear Information System (INIS)

    Electron beam hardening technology has been used mainly for the cross-linking reaction of plastic materials, but recently attention has been paid to the easiness of handling due to the reduction of equipment size and as the countermeasures for preventing atmospheric pollution caused by solvent type paints, Particularly the authors notices the excellent surface properties of electron beam-hardened coatings themselves, and advanced the research and development as one means to give functions to plastic films. In this paper, the transcription foil films having hardness and blur-preventing films are reported. The transcription process for the transcription foils on which hard coating is applied beforehand is shown. The electron beam hardening hard coating was provided next to a supporting film, and its material was polymer or oligomer/polyfunctional monomer/additive. As a primer layer, acrylic polymer was used. The procedure of making transcription foils is explained, and it is important to form uniform, smooth films. If the formation of water drops on surfaces can be prevented, blur does not arise. By heightening the hydrophilicity of material surfaces with electron beam, it may be done. By the selection of the irradiation amount of electron beam and materials, the balance must be maintained. (K.I.)

  10. Americium behaviour in plastic vessels

    Energy Technology Data Exchange (ETDEWEB)

    Legarda, F.; Herranz, M. [Departamento de Ingenieria Nuclear y Mecanica de Fluidos, Escuela Tecnica Superior de Ingenieria de Bilbao, Universidad del Pais Vasco (UPV/EHU), Alameda de Urquijo s/n, 48013 Bilbao (Spain); Idoeta, R., E-mail: raquel.idoeta@ehu.e [Departamento de Ingenieria Nuclear y Mecanica de Fluidos, Escuela Tecnica Superior de Ingenieria de Bilbao, Universidad del Pais Vasco (UPV/EHU), Alameda de Urquijo s/n, 48013 Bilbao (Spain); Abelairas, A. [Departamento de Ingenieria Nuclear y Mecanica de Fluidos, Escuela Tecnica Superior de Ingenieria de Bilbao, Universidad del Pais Vasco (UPV/EHU), Alameda de Urquijo s/n, 48013 Bilbao (Spain)

    2010-07-15

    The adsorption of {sup 241}Am dissolved in water in different plastic storage vessels was determined. Three different plastics were investigated with natural and distilled waters and the retention of {sup 241}Am by these plastics was studied. The same was done by varying vessel agitation time, vessel agitation speed, surface/volume ratio of water in the vessels and water pH. Adsorptions were measured to be between 0% and 70%. The adsorption of {sup 241}Am is minimized with no water agitation, with PET or PVC plastics, and by water acidification.

  11. Americium behaviour in plastic vessels

    International Nuclear Information System (INIS)

    The adsorption of 241Am dissolved in water in different plastic storage vessels was determined. Three different plastics were investigated with natural and distilled waters and the retention of 241Am by these plastics was studied. The same was done by varying vessel agitation time, vessel agitation speed, surface/volume ratio of water in the vessels and water pH. Adsorptions were measured to be between 0% and 70%. The adsorption of 241Am is minimized with no water agitation, with PET or PVC plastics, and by water acidification.

  12. Uptake of nerve growth factor along peripheral and spinal axons of primary sensory neurons

    International Nuclear Information System (INIS)

    To investigate the distribution of nerve growth factor (NGF) receptors on peripheral and central axons, [125I]NGF was injected into the sciatic nerve or spinal cord of adult rats. Accumulation of [125I]NGF in lumbar dorsal root ganglia was monitored by gamma emission counting and radioautography. [125I]NGF, injected endoneurially in small quantities, was taken into sensory axons by a saturable process and was transported retrogradely to their cell bodies at a maximal rate of 2.5 to 7.5 mm/hr. Because very little [125I]NGF reached peripheral terminals, the results were interpreted to indicate that receptors for NGF are present on nonterminal segments of sensory axons. The specificity and high affinity of NGF uptake were illustrated by observations that negligible amounts of gamma activity accumulated in lumbar dorsal root ganglia after comparable intraneural injection of [125I] cytochrome C or [125I]oxidized NGF. Similar techniques were used to demonstrate avid internalization and retrograde transport of [125I]NGF by intraspinal axons arising from dorsal root ganglia. Following injection of [125I]NGF into lumbar or cervical regions of the spinal cord, neuronal perikarya were clearly labeled in radioautographs of lumbar dorsal root ganglia. Sites for NGF uptake on primary sensory neurons in the adult rat are not restricted to peripheral axon terminals but are extensively distributed along both peripheral and central axons. Receptors on axons provide a mechanism whereby NGF supplied by glia could influence neuronal maintenance or axonal regeneration

  13. Skin incision induces expression of axonal regeneration-related genes in adult rat spinal sensory neurons

    OpenAIRE

    Hill, Caitlin E.; Harrison, Benjamin J; Rau, Kris K.; Hougland, M. Tyler; Bunge, Mary Bartlett; Lorne M. Mendell; Petruska, Jeffrey C.

    2010-01-01

    Skin incision and nerve injury both induce painful conditions. Incisional and post-surgical pain is believed to arise primarily from inflammation of tissue and the subsequent sensitization of peripheral and central neurons. The role of axonal regeneration-related processes in development of pain has only been considered when there has been injury to the peripheral nerve itself, even though tissue damage likely induces injury of resident axons. We sought to determine if skin incision would aff...

  14. Molecular Diagnosis of Infantile Neuro axonal Dystrophy by Next Generation Sequencing

    OpenAIRE

    Goyal, Manisha; Bijarnia-Mahay, Sunita; Kingsmore, Stephen; Farrow, Emily; Saunders, Carol; Saxena, Renu; Verma, Ishwar C

    2014-01-01

    Infantile Neuro axonal Dystrophy (INAD), is a rare inherited neurological disorder which affects nerve axons causing progressive loss of mental skills, muscular control and vision. The authors present a case of 5.8-y-old girl with INAD who was diagnosed after Next Generation Sequencing (NGS). She was born to a non-consanguineous couple and presented with hypotonia, developmental delay followed by neuroregression and nystagmus after 2 years of age. On examination, bilateral horizontal nystagmu...

  15. A cortical astrocyte subpopulation inhibits axon growth in vitro and in vivo

    OpenAIRE

    Liu, Rui; Wang, Zhe; Gou, Lin; XU, HANPENG

    2015-01-01

    Astrocytes are the most heterogeneous and predominant glial cell type in the central nervous system. However, the functional significance of this heterogeneity remains to be elucidated. Following injury, damaged astrocytes inhibit axonal regeneration in vivo and in vitro. Cultured primary astrocytes are commonly considered good supportive substrates for neuron attachment and axon regeneration. However, it is not known whether different populations of cells in the heterogeneous astrocyte cultu...

  16. Wnt Signalling Promotes Actin Dynamics during Axon Remodelling through the Actin-Binding Protein Eps8.

    Directory of Open Access Journals (Sweden)

    Eleanna Stamatakou

    Full Text Available Upon arrival at their synaptic targets, axons slow down their growth and extensively remodel before the assembly of presynaptic boutons. Wnt proteins are target-derived secreted factors that promote axonal remodelling and synaptic assembly. In the developing spinal cord, Wnts secreted by motor neurons promote axonal remodelling of NT-3 responsive dorsal root ganglia neurons. Axon remodelling induced by Wnts is characterised by growth cone pausing and enlargement, processes that depend on the re-organisation of microtubules. However, the contribution of the actin cytoskeleton has remained unexplored. Here, we demonstrate that Wnt3a regulates the actin cytoskeleton by rapidly inducing F-actin accumulation in growth cones from rodent DRG neurons through the scaffold protein Dishevelled-1 (Dvl1 and the serine-threonine kinase Gsk3β. Importantly, these changes in actin cytoskeleton occurs before enlargement of the growth cones is evident. Time-lapse imaging shows that Wnt3a increases lamellar protrusion and filopodia velocity. In addition, pharmacological inhibition of actin assembly demonstrates that Wnt3a increases actin dynamics. Through a yeast-two hybrid screen, we identified the actin-binding protein Eps8 as a direct interactor of Dvl1, a scaffold protein crucial for the Wnt signalling pathway. Gain of function of Eps8 mimics Wnt-mediated axon remodelling, whereas Eps8 silencing blocks the axon remodelling activity of Wnt3a. Importantly, blockade of the Dvl1-Eps8 interaction completely abolishes Wnt3a-mediated axonal remodelling. These findings demonstrate a novel role for Wnt-Dvl1 signalling through Eps8 in the regulation of axonal remodeling.

  17. Early phenotype expression of cortical neurons: evidence that a subclass of migrating neurons have callosal axons.

    OpenAIRE

    Schwartz, M. L.; Rakic, P.; Goldman-Rakic, P. S.

    1991-01-01

    The use of [3H]thymidine labeling in combination with various axonal transport tracers has revealed that a subset of migrating neurons in the fetal monkey cerebrum issue axons to the opposite cerebral hemisphere while still migrating to their final positions in the cortical plate. Other cortical neurons with the same "birthdate" (i.e., that underwent their last round of DNA synthesis on the same day) are not retrogradely labeled by tracer injections of the opposite hemisphere. These findings ...

  18. An Analysis of Direct Hippocampal Cortical Field CA1 Axonal Projections to Diencephalon in the Rat

    OpenAIRE

    Cenquizca, Lee A.; Swanson, Larry W.

    2006-01-01

    The hippocampal formation is generally considered essential for processing episodic memory. However, the structural organization of hippocampal afferent and efferent axonal connections is still not completely understood, although such information is critical to support functional hypotheses. The full extent of axonal projections from field CA1 to the interbrain (diencephalon) is analyzed here with the Phaseolus vulgaris-leucoagglutinin (PHAL) method. The ventral pole of field CA1 establishes ...

  19. Workflow and Atlas System for Brain-Wide Mapping of Axonal Connectivity in Rat

    OpenAIRE

    2011-01-01

    Detailed knowledge about the anatomical organization of axonal connections is important for understanding normal functions of brain systems and disease-related dysfunctions. Such connectivity data are typically generated in neuroanatomical tract-tracing experiments in which specific axonal connections are visualized in histological sections. Since journal publications typically only accommodate restricted data descriptions and example images, literature search is a cumbersome way to retrieve ...

  20. The statistical mapping of cerebral metabolism for patients with severe diffuse axonal injury

    International Nuclear Information System (INIS)

    We investigated metabolic patterns in severe diffuse axonal injury patients using three-dimensional stereotactic surface projection (3D-SSP) technique. (Material and methods) Subjects was defined as the 23 diffuse axonal injury patients having a Coma Remission Scale of < 20 points on the PET examination in chronic stage. Normal volunteers were selected as normal database. For normal volunteers and patients, FDG-PET was carried out and 3D-SSP analysis was performed in group. (authors)

  1. Purkinje cell axonal anatomy: quantifying morphometric changes in essential tremor versus control brains

    OpenAIRE

    Babij, Rachel; Lee, Michelle; Cortés, Etty; Vonsattel, Jean-Paul G.; Faust, Phyllis L.; Louis, Elan D.

    2013-01-01

    Growing clinical, neuro-imaging and post-mortem data have implicated the cerebellum as playing an important role in the pathogenesis of essential tremor. Aside from a modest reduction of Purkinje cells in some post-mortem studies, Purkinje cell axonal swellings (torpedoes) are present to a greater degree in essential tremor cases than controls. Yet a detailed study of more subtle morphometric changes in the Purkinje cell axonal compartment has not been undertaken. We performed a detailed morp...

  2. Sustained axon-glial signaling induces Schwann cell hyperproliferation, Remak bundle myelination, and tumorigenesis

    OpenAIRE

    Gómez-Sánchez, José A.; López de Armentia, Mikel; Luján, Rafael; Kessaris, Nicoletta; Richardson, William D.; Cabedo, Hugo

    2009-01-01

    Type III neuregulins exposed on axon surfaces control myelination of the peripheral nervous system. It has been shown, for example, that threshold levels of type IIIβ1a neuregulin dictate not only the myelination fate of axons but also myelin thickness. Here we show that another neuregulin isoform, type III-β3, plays a distinct role in myelination. Neuronal overexpression of this isoform in mice stimulates Schwann cell proliferation and dramatically enlarges peripheral nerves and ganglia -whi...

  3. Nitric oxide as a putative retinal axon pathfinding and target recognition cue in Xenopus laevis

    OpenAIRE

    Sara Berman; Andrea Morris

    2011-01-01

    Nitric oxide (NO) is an atypical neurotransmitter synthesized by the enzyme nitric oxide synthase (NOS) during many stages of the Xenopus laevis life cycle. This research investigates whether the gas NO is involved in axon guidance, the neurodevelopmental process in which axons travel through the brain to their appropriate target locations to form functional neural circuitry. Through immunocytochemistry and direct labeling of the NO gas with a fluorescent dye, we have found that NOS expressio...

  4. Alterations in axonal transport motor proteins in sporadic and experimental Parkinson’s disease

    OpenAIRE

    Chu, Yaping; Morfini, Gerardo A.; Langhamer, Lori B.; He, Yinzhen; Brady, Scott T.; KORDOWER, JEFFREY H.

    2012-01-01

    The progressive loss of the nigrostriatal pathway is a distinguishing feature of Parkinson’s disease. As terminal field loss seems to precede cell body loss, we tested whether alterations of axonal transport motor proteins would be early features in Parkinson’s disease. There was a decline in axonal transport motor proteins in sporadic Parkinson’s disease that preceded other well-known nigral cell-related pathology such as phenotypic downregulation of dopamine. Reductions in conventional kine...

  5. Axon-Schwann cell interactions during peripheral nerve regeneration in zebrafish larvae

    OpenAIRE

    Ceci, Maria Laura; Mardones-Krsulovic, Camila; SÁNCHEZ, MARIO; Valdivia, Leonardo E.; Allende, Miguel L

    2014-01-01

    Background Peripheral nerve injuries can severely affect the way that animals perceive signals from the surrounding environment. While damage to peripheral axons generally has a better outcome than injuries to central nervous system axons, it is currently unknown how neurons re-establish their target innervations to recover function after injury, and how accessory cells contribute to this task. Here we use a simple technique to create reproducible and localized injury in the posterior lateral...

  6. Mild hypothermia for treatment of diffuse axonal injury: a quantitative analysis of diffusion tensor imaging

    OpenAIRE

    Jing, Guojie; Yao, Xiaoteng; Li, Yiyi; Xie, Yituan; Li, Wang#x2019;an; LIU, Kejun; Jing, Yingchao; Li, Baisheng; Lv, Yifan; Ma, Baoxin

    2014-01-01

    Fractional anisotropy values in diffusion tensor imaging can quantitatively reflect the consistency of nerve fibers after brain damage, where higher values generally indicate less damage to nerve fibers. Therefore, we hypothesized that diffusion tensor imaging could be used to evaluate the effect of mild hypothermia on diffuse axonal injury. A total of 102 patients with diffuse axonal injury were randomly divided into two groups: normothermic and mild hypothermic treatment groups. Patient's m...

  7. Microtubules Have Opposite Orientation in Axons and Dendrites of Drosophila Neurons

    OpenAIRE

    Stone, Michelle C.; Roegiers, Fabrice; Rolls, Melissa M

    2008-01-01

    In vertebrate neurons, axons have a uniform arrangement of microtubules with plus ends distal to the cell body (plus-end-out), and dendrites have equal numbers of plus- and minus-end-out microtubules. To determine whether microtubule orientation is a conserved feature of axons and dendrites, we analyzed microtubule orientation in invertebrate neurons. Using microtubule plus end dynamics, we mapped microtubule orientation in Drosophila sensory neurons, interneurons, and motor neurons. As expec...

  8. Quantification of Retrograde Axonal Transport in the Rat Optic Nerve by Fluorogold Spectrometry

    OpenAIRE

    van Oterendorp, Christian; Sgouris, Stavros; Bach, Michael; Martin, Gottfried; Biermann, Julia; Jordan, Jens F.; Lagrèze, Wolf A

    2012-01-01

    Purpose Disturbed axonal transport is an important pathogenic factor in many neurodegenerative diseases, such as glaucoma, an eye disease characterised by progressive atrophy of the optic nerve. Quantification of retrograde axonal transport in the optic nerve usually requires labour intensive histochemical techniques or expensive equipment for in vivo imaging. Here, we report on a robust alternative method using Fluorogold (FG) as tracer, which is spectrometrically quantified in retinal tissu...

  9. Axonal neuregulin 1 is a rate limiting but not essential factor for nerve remyelination

    OpenAIRE

    Fricker, Florence R.; Antunes-Martins, Ana; Galino, Jorge; Paramsothy, Remi; La Russa, Federica; Perkins, James; Goldberg, Rebecca; Brelstaff, Jack; Zhu, Ning; McMahon, Stephen B; Orengo, Christine; Garratt, Alistair N.; Birchmeier, Carmen; David L H Bennett

    2013-01-01

    Neuregulin 1 acts as an axonal signal that regulates multiple aspects of Schwann cell development including the survival and migration of Schwann cell precursors, the ensheathment of axons and subsequent elaboration of the myelin sheath. To examine the role of this factor in remyelination and repair following nerve injury, we ablated neuregulin 1 in the adult nervous system using a tamoxifen inducible Cre recombinase transgenic mouse system. The loss of neuregulin 1 impaired remyelination aft...

  10. Hydrogels as scaffolds and delivery systems to enhance axonal regeneration after injuries

    Directory of Open Access Journals (Sweden)

    Oscar A. Carballo-Molina

    2015-02-01

    Full Text Available Damage caused to neural tissue by disease or injury frequently produces a discontinuity in the nervous system. Such damage generates diverse alterations that are commonly permanent, due to the limited regeneration capacity of the adult nervous system, particularly the Central Nervous System (CNS. The cellular reaction to noxious stimulus leads to several events such as the formation of glial and fibrous scars, which inhibit axonal regeneration in both the CNS and the Peripheral Nervous System (PNS. Although in the PNS there is some degree of nerve regeneration, it is common that the growing axons reinnervate incorrect areas, causing mismatches. Providing a permissive substrate for axonal regeneration in combination with delivery systems for the release of molecules, which enhances axonal growth, could increase regeneration and the recovery of functions in the CNS or the PNS. Currently, there are no effective vehicles to supply growth factors or cells to the damaged/diseased nervous system. Hydrogels are polymers that are biodegradable, biocompatible and have the capacity to deliver a large range of molecules in situ. The inclusion of cultured neural cells into hydrogels forming three-dimensional structures allows the formation of synapses and neuronal survival. There is also evidence showing that hydrogels constitute an amenable substrate for axonal growth of endogenous or grafted cells, overcoming the presence of axonal regeneration inhibitory molecules, in both the central and peripheral nervous systems. Recent experiments suggest that hydrogels can carry and deliver several proteins relevant for improving neuronal survival and axonal growth. Although the use of hydrogels is appealing, its effectiveness is still a matter of discussion, and more results are needed to achieve consistent recovery using different parameters. This review also discusses areas of opportunity where hydrogels can be applied, in order to promote axonal regeneration of

  11. Fisiopatología del síndrome de Guillain Barré axonal Physiopathology of axonal acute Guillain Barré syndrome

    OpenAIRE

    Juan Guillermo Montoya Ch.; Diana P. Martínez T.; Jaime Carrizosa Moog; Beatriz Aguirre L.

    2002-01-01

    Se describe la fisiopatología del síndrome de Guillain Barré axonal. Se consideran especialmente cinco aspectos: 1) Agentes etiológicos, específicamente el Campylobacter jejuni. 2) Susceptibilidad genética humana. 3) Mimetismo molecular entre lipopolisacáridos y lipoproteínas. 4) Mecanismo de acción de los anticuerpos antigangliósidos y 5) Hallazgos patológicos. The physiopathology of axonal acute Guillain Barré syndrome is described. Five aspects are considered, namely: 1) Etiologic agents e...

  12. The clinical findings and CT diagnosis of diffuse axonal injury

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical manifestations, characteristic CT findings and pathologic mechanism of diffuse axonal injury(DAI). Methods: The clinical materials and CT images of 58 cases of DAI were analyzed. Results: The clinical findings of DAI: (1) an acceleration or deceleration and spiral injury of head; (2) immediate coma after injury; (3) abnormalities of vital sign; (4) alternated muscle tone of extremities; (5) absence of local neurological sign. The diagnostic criterions of CT images: (1) multiple hemorrhagic lesions smaller than 2cm in diameter at the cortex-medulla junction or the axial area; (2) diffuse cerebral swellings; (3) general decompression and even disappearance of ventricles and cisterns; (4)non or moderate median structures dislocation (less than 5mm); (5) coexistence of other intra-cranial trauma. Conclusion: Combining with clinical findings and CT signs, a diagnosis of DAI can be established. Diffuse brain swelling (DBS) occurred by primary hypothalamus and vasomotor center of brain stem damaged is a special type. (authors)

  13. Sodium movements in perfused squid giant axons. Passive fluxes.

    Science.gov (United States)

    Rojas, E; Canessa-Fischer, M

    1968-08-01

    Sodium movements in internally perfused giant axons from the squid Dosidicus gigas were studied with varying internal sodium concentrations and with fluoride as the internal anion. It was found that as the internal concentration of sodium was increased from 2 to 200 mM the resting sodium efflux increased from 0.09 to 34.0 pmoles/cm(2)sec and the average resting sodium influx increased from 42.9 to 64.5 pmoles/cm(2)sec but this last change was not statistically significant. When perfusing with a mixture of 500 mM K glutamate and 100 mM Na glutamate the resting efflux was 10 +/- 3 pmoles/cm(2)sec and 41 +/- 10 pmoles/cm(2)sec for sodium influx. Increasing the internal sodium concentration also increased both the extra influx and the extra efflux of sodium due to impulse propagation. At any given internal sodium concentration the net extra influx was about 5 pmoles/cm(2)impulse. This finding supports the notion that the inward current generated in a propagated action potential can be completely accounted for by movements of sodium. PMID:5672003

  14. Metabolic efficiency with fast spiking in the squid axon

    Directory of Open Access Journals (Sweden)

    Abdelmalik Moujahid

    2012-11-01

    Full Text Available Fundamentally, action potentials in the squid axon are consequence of the entrance of sodium ions during the depolarization of the rising phase of the spike mediated by the outflow of potassium ions during the hyperpolarization of the falling phase. Perfect metabolic efficiency with a minimum charge needed for the change in voltage during the action potential would confine sodium entry to the rising phase and potassium efflux to the falling phase. However, because sodium channels remain open to a significant extent during the falling phase, a certain overlap of inward and outward currents is observed. In this work we investigate the impact of ion overlap on the number of the adenosine triphosphate (ATP molecules and energy cost required per action potential as a function of the temperature in a Hodgkin-Huxley model. Based on a recent approach to computing the energy cost of neuronal AP generation not based on ion counting, we show that increased firing frequencies induced by higher temperatures imply more efficient use of sodium entry, and then a decrease in the metabolic energy cost required to restore the concentration gradients after an action potential. Also, we determine values of sodium conductance at which the hydrolysis efficiency presents a clear minimum.

  15. Bridging Physics and Biology Using Resistance and Axons

    Science.gov (United States)

    Dyer, Joshua M.

    2014-11-01

    When teaching physics, it is often difficult to get biology-oriented students to see the relevance of physics.1 A complaint often heard is that biology students are required to take physics for the Medical College Admission Test (MCAT) as part of a "weeding out" process, but that they don't feel like they need physics for biology. Despite this impression held by students, there have been calls for better physics education for future physicians and life scientists.2,3 Research is being performed to improve physics classes and labs by linking topics in biology and physics.4,5 Described here is a laboratory experiment covering the topics of resistance of materials and circuits/Kirchhoff's laws in a biology context with their direct application to neurons, axons, and electrical impulse transmission within animals. This experiment will also demonstrate the mechanism believed to cause multiple sclerosis. The apparatus was designed with low-cost and readily available materials in mind.

  16. The neural adhesion molecule TAG-1 modulates responses of sensory axons to diffusible guidance signals.

    Science.gov (United States)

    Law, Chris O; Kirby, Rebecca J; Aghamohammadzadeh, Soheil; Furley, Andrew J W

    2008-08-01

    When the axons of primary sensory neurons project into the embryonic mammalian spinal cord, they bifurcate and extend rostrocaudally before sending collaterals to specific laminae according to neuronal subclass. The specificity of this innervation has been suggested to be the result both of differential sensitivity to chemorepellants expressed in the ventral spinal cord and of the function of Ig-like neural cell adhesion molecules in the dorsal horn. The relationship between these mechanisms has not been addressed. Focussing on the pathfinding of TrkA+ NGF-dependent axons, we demonstrate for the first time that their axons project prematurely into the dorsal horn of both L1 and TAG-1 knockout mice. We show that axons lacking TAG-1, similar to those lacking L1, are insensitive to wild-type ventral spinal cord (VSC)-derived chemorepellants, indicating that adhesion molecule function is required in the axons, and that this loss of response is explained in part by loss of response to Sema3A. We present evidence that TAG-1 affects sensitivity to Sema3A by binding to L1 and modulating the endocytosis of the L1/neuropilin 1 Sema3A receptor complex. However, TAG-1 appears to affect sensitivity to other VSC-derived chemorepellants via an L1-independent mechanism. We suggest that this dependence of chemorepellant sensitivity on the functions of combinations of adhesion molecules is important to ensure that axons project via specific pathways before extending to their final targets. PMID:18550718

  17. Effects of medium flow on axon growth with or without nerve growth factor.

    Science.gov (United States)

    Kumamoto, Junichi; Kitahata, Hiroyuki; Goto, Makiko; Nagayama, Masaharu; Denda, Mitsuhiro

    2015-09-11

    Axon growth is a crucial process in regeneration of damaged nerves. On the other hand, elongation of nerve fibers in the epidermis has been observed in skin of atopic dermatitis patients. Thus, regulation of nerve fiber extension might be an effective strategy to accelerate nerve regeneration and/or to reduce itching in pruritus dermatosis. We previously demonstrated that neurons and epidermal keratinocytes similarly contain multiple receptors that are activated by various environmental factors, and in particular, keratinocytes are influenced by shear stress. Thus, in the present study, we evaluated the effects of micro-flow of the medium on axon growth in the presence or absence of nerve growth factor (NGF), using cultured dorsal-root-ganglion (DRG) cells. The apparatus, AXIS™, consists of two chambers connected by a set of microgrooves, through which signaling molecules and axons, but not living cells, can pass. When DRG cells were present in chamber 1, NGF was present in chamber 2, and micro-flow was directed from chamber 1 to chamber 2, axon growth was significantly increased compared with other conditions. Acceleration of axon growth in the direction of the micro-flow was also observed in the absence of NGF. These results suggest that local micro-flow might significantly influence axon growth. PMID:26212442

  18. Distinct roles of neuropilin 1 signaling for radial and tangential extension of callosal axons.

    Science.gov (United States)

    Hatanaka, Yumiko; Matsumoto, Tomoko; Yanagawa, Yuchio; Fujisawa, Hajime; Murakami, Fujio; Masu, Masayuki

    2009-05-20

    Cortical excitatory neurons migrate from their origin in the ventricular zone (VZ) toward the pial surface. During migration, these neurons exhibit a stellate shape in the intermediate zone (IZ), transform into bipolar cells, and then initiate radial migration, extending a trailing process, which may lead to an axon. Here we examined the role of neuropilin 1 (NRP1) in these developmental events. Both NRP1 mRNA and protein were highly expressed in the IZ, where stellate-shaped cells were located. DiI labeling experiments showed that neuronal migration occurred normally in Nrp1 mutant mice up to embryonic day (E) 14.5, the latest day to which the mutant survives, with only subtle axonal defasciculation. However, interference with Nrp1 signaling at a later stage caused pathfinding errors: when a dominant negative form of Nrp1 was electroporated into the cortical VZ cells at E12.5 or E15.5 and examined perinatally, guidance errors were found in tangential axonal extension toward the midline. In contrast, no significant effect was noted on the migration of cortical excitatory neurons. These findings indicate that NRP1 plays an important role in the guidance of callosal axons originating from cortical excitatory neurons but does not support a role in their migration. Moreover, insofar as radial axonal extension within the cortical plate was unaffected, the present findings imply that molecular mechanisms for the axonal extension of excitatory neurons within the cortical plate are distinct from those in the white matter. PMID:19296474

  19. Extra-neurohypophyseal axonal projections from individual vasopressin-containing magnocellular neurons in rat hypothalamus

    Directory of Open Access Journals (Sweden)

    Fernando Jauregui Huerta

    2015-10-01

    Full Text Available Conventional neuroanatomical, immunohistochemical techniques and electrophysiological recording, as well as in vitro labeling methods may fail to detect long range extra-neurohypophyseal-projecting axons from vasopressin (AVP-containing magnocellular neurons (magnocells in the hypothalamic paraventricular nucleus (PVN. Here, we used in vivo extracellular recording, juxtacellular labeling, post hoc anatomo-immunohistochemical analysis and camera lucida reconstruction to address this question. We demonstrate that all well-labeled AVP immunopositive neurons inside the PVN possess main axons joining the tract of Greving and multi-axon-like processes, as well as axonal collaterals branching very near to the somata, which project to extra-neurohypophyseal regions. The detected regions in this study include the medial and lateral preoptical area, suprachiasmatic nucleus, lateral habenula, medial and central amygdala and the conducting systems, such as stria medullaris, the fornix and the internal capsule. Expression of vesicular glutamate transporter 2 was observed in axon-collaterals. These results, in congruency with several previous reports in the literature, provided unequivocal evidence that AVP magnocells have an uncommon feature of possessing multiple axon-like processes emanating from somata or proximal dendrites. Furthermore, the long-range non-neurohypophyseal projections are more common than an “occasional” phenomenon as previously thought.

  20. Enzyme-instructed self-assembly of taxol promotes axonal branching.

    Science.gov (United States)

    Mei, Bin; Miao, Qingqing; Tang, Anming; Liang, Gaolin

    2015-10-14

    Axonal branching is important for vertebrate neuron signaling. Taxol has a biphasic effect on axonal branching (i.e., high concentration inhibits axonal growth but low concentration restores it). To the best of our knowledge, low concentration of taxol to promote axonal branching has not been reported yet. Herein, we rationally designed a taxol derivative Fmoc-Phe-Phe-Lys(taxol)-Tyr(H2PO4)-OH (1) which could be subjected to alkaline phosphatase (ALP)-catalyzed self-assembly to form taxol nanofibers. We found that, at 10 μM, 1 has a microtubule (MT) condensation effect similar to that of taxol on mammalian cells but with more chronic toxicity than taxol on the cells. At a low concentration of 10 nM, 1 not only promoted neurite elongation as taxol did but also promoted axonal branching which was not achieved by using taxol. We propose that self-assembly of 1 along the MTs prohibited their lateral contacts and thus promoted axonal branching. Our strategy of enzyme-instructed self-assembly (EISA) of a taxol derivative provides a new tool for scientists to study the morphology of neurons, as well as their behaviours. PMID:26359218

  1. Human bone marrow mesenchymal stem cell transplantation attenuates axonal injur y in stroke rats

    Institute of Scientific and Technical Information of China (English)

    Yi Xu; Shiwei Du; Xinguang Yu; Xiao Han; Jincai Hou; Hao Guo

    2014-01-01

    Previous studies have shown that transplantation of human bone marrow mesenchymal stem cells promotes neural functional recovery after stroke, but the neurorestorative mechanisms remain largely unknown. We hypothesized that functional recovery of myelinated axons may be one of underlying mechanisms. In this study, an ischemia/reperfusion rat model was established using the middle cerebral artery occlusion method. Rats were used to test the hypothesis that in-travenous transplantation of human bone marrow mesenchymal stem cells through the femoral vein could exert neuroprotective effects against cerebral ischemia via a mechanism associated with the ability to attenuate axonal injury. The results of behavioral tests, infarction volume analysis and immunohistochemistry showed that cerebral ischemia caused severe damage to the myelin sheath and axons. After rats were intravenously transplanted with human bone marrow mesenchymal stem cells, the levels of axon and myelin sheath-related proteins, including mi-crotubule-associated protein 2, myelin basic protein, and growth-associated protein 43, were elevated, infarct volume was decreased and neural function was improved in cerebral ischemic rats. These ifndings suggest that intravenously transplanted human bone marrow mesenchymal stem cells promote neural function. Possible mechanisms underlying these beneifcial effects in-clude resistance to demyelination after cerebral ischemia, prevention of axonal degeneration, and promotion of axonal regeneration.

  2. The use of photo-elicitation in field research

    Directory of Open Access Journals (Sweden)

    Elisa Bignante

    2010-02-01

    Full Text Available This paper examines the use of visual methods in geographical field research, and in particular photo-elicitation. The technique involves photos, videos and other forms of visual representation used in an interview, with informants asked to comment on the images. The aim is to promote more direct involvement of the informants in the research process and to encourage and stimulate the collection of quantitatively and qualitatively different information to that obtained in conventional interviews. The potential and limitations of this technique in the field are investigated, describing and discussing photo-elicitation data collection in the Maasai village of Mkuru in northern Tanzania to explore the use and preservation of natural resources. Results and methodological insights from the fieldwork are presented and discussed.

  3. Between participants, props and stage: Eliciting insights through interaction

    DEFF Research Database (Denmark)

    Cramer-Petersen, Claus Lundgaard; Marijnissen, Thomas

    2012-01-01

    How can we develop innovative concepts? The purpose of this paper is to investigate how generative prototype sessions can elicit so-called tacit and latent knowledge from participants through interaction and play. To illustrate this, a session from the design process will be described along with ...... an indiscernible blend of different types of knowledge, but that tacit and latent constitutes an important part.......How can we develop innovative concepts? The purpose of this paper is to investigate how generative prototype sessions can elicit so-called tacit and latent knowledge from participants through interaction and play. To illustrate this, a session from the design process will be described along with a...... brief take on current theories. It is discussed how practical tools and methods along with the dynamics occurring during such a session can translate actor knowledge to become useful throughout a the entire design process. The paper concludes that knowledge gained from generative prototype sessions is...

  4. An alternative approach for eliciting willingness-to-pay

    Directory of Open Access Journals (Sweden)

    Laura J. Damschroder

    2007-04-01

    Full Text Available Open-ended methods that elicit willingness-to-pay (WTP in terms of absolute dollars often result in high rates of questionable and highly skewed responses, insensitivity to changes in health state, and raise an ethical issue related to its association with personal income. We conducted a 2x2 randomized trial over the Internet to test 4 WTP formats: 1 WTP in dollars; 2 WTP as a percentage of financial resources; 3 WTP in terms of monthly payments; and 4 WTP as a single lump-sum amount. WTP as a percentage of financial resources generated fewer questionable values, had better distribution properties, greater sensitivity to severity of health states, and was not associated with income. WTP elicited on a monthly basis also showed promise.

  5. Arousal recognition system based on heartbeat dynamics during auditory elicitation.

    Science.gov (United States)

    Nardelli, Mimma; Valenza, Gaetano; Greco, Alberto; Lanata, Antonio; Scilingo, Enzo Pasquale

    2015-08-01

    This study reports on the recognition of different arousal levels, elicited by affective sounds, performed using estimates of autonomic nervous system dynamics. Specifically, as a part of the circumplex model of affect, arousal levels were recognized by properly combining information gathered from standard and nonlinear analysis of heartbeat dynamics, which was derived from the electrocardiogram (ECG). Affective sounds were gathered from the International Affective Digitized Sound System and grouped into four different levels of arousal. A group of 27 healthy volunteers underwent such elicitation while ECG signals were continuously recorded. Results showed that a quadratic discriminant classifier, as applied implementing a leave-one-subject-out procedure, achieved a recognition accuracy of 84.26%. Moreover, this study confirms the crucial role of heartbeat nonlinear dynamics for emotion recognition, hereby estimated through lagged Poincare plots. PMID:26737686

  6. Chitin elicitation of natural product production in marine bacteria

    DEFF Research Database (Denmark)

    Månsson, Maria; Wietz, Matthias; Larsen, Thomas Ostenfeld;

    glucose-based medium. The different phenotypic responses to a natural growth substrate may reflect different niche-adaptations or ecological functions of the compounds produced and it represents a fruitful approach for elicitation of natural product production in marine bacteria....... uncharacterized chemical potential of these organisms. As part of a new project on ecology-driven drug discovery at the Technical University of Denmark, we investigate the use of chitin to elicit or alter production of antibacterial compounds in marine bacteria. Within our large collection of Gram...... indicating that andrimid serves a function while growing on chitin-containing surfaces. In contrast, a Photobacterium halotolerans sustained production of all metabolites including the antibiotic holomycin. Furthermore, chitin stimulated the production of two potentially novel metabolites not observed on...

  7. Simplified Expert Elicitation Procedure for Risk Assessment of Operating Events

    Energy Technology Data Exchange (ETDEWEB)

    Ronald L. Boring; David Gertman; Jeffrey Joe; Julie Marble; William Galyean; Larry Blackwood; Harold Blackman

    2005-06-01

    This report describes a simplified, tractable, and usable procedure within the US Nuclear Regulator Commission (NRC) for seeking expert opinion and judgment. The NRC has increased efforts to document the reliability and risk of nuclear power plants (NPPs) through Probabilistic Risk Assessment (PRA) and Human Reliability Analysis (HRA) models. The Significance Determination Process (SDP) and Accident Sequence Precursor (ASP) programs at the NRC utilize expert judgment on the probability of failure, human error, and the operability of equipment in cases where otherwise insufficient operational data exist to make meaningful estimates. In the past, the SDP and ASP programs informally sought the opinion of experts inside and outside the NRC. This document represents a formal, documented procedure to take the place of informal expert elicitation. The procedures outlined in this report follow existing formal expert elicitation methodologies, but are streamlined as appropriate to the degree of accuracy required and the schedule for producing SDP and ASP analyses.

  8. Pioneer Axon Navigation Is Controlled by AEX-3, a Guanine Nucleotide Exchange Factor for RAB-3 in Caenorhabditis elegans.

    Science.gov (United States)

    Bhat, Jaffar M; Hutter, Harald

    2016-07-01

    Precise and accurate axon tract formation is an essential aspect of brain development. This is achieved by the migration of early outgrowing axons (pioneers) allowing later outgrowing axons (followers) to extend toward their targets in the embryo. In Caenorhabditis elegans the AVG neuron pioneers the right axon tract of the ventral nerve cord, the major longitudinal axon tract. AVG is essential for the guidance of follower axons and hence organization of the ventral nerve cord. In an enhancer screen for AVG axon guidance defects in a nid-1/Nidogen mutant background, we isolated an allele of aex-3 aex-3 mutant animals show highly penetrant AVG axon navigation defects. These defects are dependent on a mutation in nid-1/Nidogen, a basement membrane component. Our data suggest that AEX-3 activates RAB-3 in the context of AVG axon navigation. aex-3 genetically acts together with known players of vesicular exocytosis: unc-64/Syntaxin, unc-31/CAPS, and ida-1/IA-2. Furthermore our genetic interaction data suggest that AEX-3 and the UNC-6/Netrin receptor UNC-5 act in the same pathway, suggesting AEX-3 might regulate the trafficking and/or insertion of UNC-5 at the growth cone to mediate the proper guidance of the AVG axon. PMID:27116976

  9. Multiple Membrane Interactions and Versatile Vesicle Deformations Elicited by Melittin

    OpenAIRE

    Kingo Takiguchi; Michio Homma; Yasunori Yokoyama; Yohko Tanaka-Takiguchi; Tomoyoshi Takahashi; Fumimasa Nomura

    2013-01-01

    Melittin induces various reactions in membranes and has been widely studied as a model for membrane-interacting peptide; however, the mechanism whereby melittin elicits its effects remains unclear. Here, we observed melittin-induced changes in individual giant liposomes using direct real-time imaging by dark-field optical microscopy, and the mechanisms involved were correlated with results obtained using circular dichroism, cosedimentation, fluorescence quenching of tryptophan residues, and e...

  10. Affective monitoring: A generic mechanism for affect elicitation

    OpenAIRE

    Phaf, R. Hans; Rotteveel, Mark

    2012-01-01

    In this paper we sketch a new framework for affect elicitation, which is based on previous evolutionary and connectionist modeling and experimental work from our group. Affective monitoring is considered a local match–mismatch process within a module of the neural network. Negative affect is raised instantly by mismatches, incongruency, disfluency, novelty, incoherence, and dissonance, whereas positive affect follows from matches, congruency, fluency, familiarity, coherence, and resonance, at...

  11. UML for Early Requirements Elicitation: A Regulation based Approach

    OpenAIRE

    Regev, Gil; Wegmann, Alain

    2002-01-01

    Early requirements of information systems are often understood in terms of the elicitation of stakeholders' high-level goals to be supported by the system under discussion. Stakeholders' goals are considered as the ultimate explanation of requirements. It is assumed that the notion of a high-level goal is natural and that high-level goals need no explanation with regard to their origins. We believe that these assumptions result in the definition of inadequate goals. We propose an organization...

  12. Classical vs. crowdsourcing surveys for eliciting geographic relevance criteria

    OpenAIRE

    De Sabbata, Stefano; Alonso, Omar; Mizzaro, Stefano

    2012-01-01

    Geographic relevance aims to assess the relevance of physical entities (e.g., shops and museums) in geographic space for a mobile user in a given context, thereby shifting the focus from the digital world (the realm of classical information retrieval) to the physical world. We study the elicitation of geographic relevance criteria by means of both a classical survey and an Amazon Mechanical Turk (a crowdsourcing platform) survey. This allows us to obtain three results: first, we gather a set ...

  13. The Elicitation of Subjective Probabilities with Applications in Agricultural Economics

    OpenAIRE

    Patricia E. NORRIS; Randall A. Kramer

    1990-01-01

    Probability judgements are important components of decision making under uncertainty. In particular, economic decisions can be aided by assuring more accurate assessment of probabilities and more realistic modelling of economic problems through the inclusion of subjective probabilities. The purpose of this paper is to describe the techniques which can be used to elicit subjective probabilities and the ways in which these techniques can be incorporated into agricultural economics research. The...

  14. Gender difference in N170 elicited under oddball task

    OpenAIRE

    Choi, Damee; Egashira, Yuka; Takakura, Jun’ya; Motoi, Midori; Nishimura, Takayuki; Watanuki, Shigeki

    2015-01-01

    Background: Some studies have reported gender differences in N170, a face-selective event-related potential (ERP) component. This study investigated gender differences in N170 elicited under oddball paradigm in order to clarify the effect of task demand on gender differences in early facial processing. Findings: Twelve males and 10 females discriminated targets (emotional faces) from non-targets (emotionally neutral faces) under an oddball paradigm, pressing a button as quickly as possible in...

  15. Gender difference in N170 elicited under oddball task

    OpenAIRE

    Choi, Damee; Egashira, Yuka; Takakura, Jun’ya; Motoi, Midori; Nishimura, Takayuki; Watanuki, Shigeki

    2015-01-01

    Background Some studies have reported gender differences in N170, a face-selective event-related potential (ERP) component. This study investigated gender differences in N170 elicited under oddball paradigm in order to clarify the effect of task demand on gender differences in early facial processing. Findings Twelve males and 10 females discriminated targets (emotional faces) from non-targets (emotionally neutral faces) under an oddball paradigm, pressing a button as quickly as possible in r...

  16. Plastics recycling: challenges and opportunities.

    Science.gov (United States)

    Hopewell, Jefferson; Dvorak, Robert; Kosior, Edward

    2009-07-27

    Plastics are inexpensive, lightweight and durable materials, which can readily be moulded into a variety of products that find use in a wide range of applications. As a consequence, the production of plastics has increased markedly over the last 60 years. However, current levels of their usage and disposal generate several environmental problems. Around 4 per cent of world oil and gas production, a non-renewable resource, is used as feedstock for plastics and a further 3-4% is expended to provide energy for their manufacture. A major portion of plastic produced each year is used to make disposable items of packaging or other short-lived products that are discarded within a year of manufacture. These two observations alone indicate that our current use of plastics is not sustainable. In addition, because of the durability of the polymers involved, substantial quantities of discarded end-of-life plastics are accumulating as debris in landfills and in natural habitats worldwide. Recycling is one of the most important actions currently available to reduce these impacts and represents one of the most dynamic areas in the plastics industry today. Recycling provides opportunities to reduce oil usage, carbon dioxide emissions and the quantities of waste requiring disposal. Here, we briefly set recycling into context against other waste-reduction strategies, namely reduction in material use through downgauging or product reuse, the use of alternative biodegradable materials and energy recovery as fuel. While plastics have been recycled since the 1970s, the quantities that are recycled vary geographically, according to plastic type and application. Recycling of packaging materials has seen rapid expansion over the last decades in a number of countries. Advances in technologies and systems for the collection, sorting and reprocessing of recyclable plastics are creating new opportunities for recycling, and with the combined actions of the public, industry and governments it

  17. Eliciting Secondary Education Pupils’ Views on Euthanasia Through Argumentative Paragraphs

    Directory of Open Access Journals (Sweden)

    Melike OZER KESKIN

    2012-12-01

    Full Text Available This study aims to elicit secondary education pupils’ views on euthanasia based on a survey model and with a study group of 253 pupils in year 9 studying in the city of Ankara in the school year 2010-2011. The study makes use of a combination of qualitative and quantitative research techniques as well as a Questionnaire for Personal Particulars in order to clarify the pupils’ demographics in data collection, and scenarios based on ethical dilemmas about active and passive euthanasia in order to elicit their views on the issue.The pupils’ views were elicited through the argumentative paragraphs that they were asked to write on the situations given in the scenarios. Of the qualitative data analysis techniques, the content analysis method was selected for the analysis of the argumentative paragraphs on the scenarios. In light of the data yielded by the content analysis, the pupils’ basic ethical guidelines in their decision-making processes were studied taking into account such variables as gender, school type, and family’s income.

  18. Sustainable reverse logistics for household plastic waste

    NARCIS (Netherlands)

    Bing, X.

    2014-01-01

    Summary of the thesis titled “Sustainable Reverse Logistics for Household Plastic Waste” PhD Candidate: Xiaoyun Bing Recycled plastic can be used in the manufacturing of plastic products to reduce the use of virgin plastics material. The cost of recycled plastics is usually lower than th

  19. Plastics for corrosion inhibition

    CERN Document Server

    Goldade, Victor A; Makarevich, Anna V; Kestelman, Vladimir N

    2005-01-01

    The development of polymer composites containing inhibitors of metal corrosion is an important endeavour in modern materials science and technology. Corrosion inhibitors can be located in a polymer matrix in the solid, liquid or gaseous phase. This book details the thermodynamic principles for selecting these components, their compatibility and their effectiveness. The various mechanisms of metal protection – barrier, inhibiting and electromechanical – are considered, as are the conflicting requirements placed on the structure of the combined material. Two main classes of inhibited materials (structural and films/coatings) are described in detail. Examples are given of structural plastics used in friction units subjected to mechano-chemical wear and of polymer films/coatings for protecting metal objects against corrosion.

  20. Plastic Deformation of Metal Surfaces

    DEFF Research Database (Denmark)

    Hansen, Niels; Zhang, Xiaodan; Huang, Xiaoxu

    2013-01-01

    Plastic deformation of metal surfaces by sliding and abrasion between moving parts can be detrimental. However, when the plastic deformation is controlled for example by applying different peening techniques hard surfaces can be produced which can increase the fracture resistance and fatigue life...

  1. Computational Strain Gradient Crystal Plasticity

    DEFF Research Database (Denmark)

    Niordson, Christian Frithiof; Kysar, Jeffrey W.

    2011-01-01

    A model for strain gradient crystal visco-plasticity is formulated along the lines proposed by Fleck andWillis (2009) for isotropic plasticity. Size-effects are included in the model due to the addition of gradient terms in both the free energy as well as through a dissipation potential. A finite...

  2. Boron Doped Plastic Scintillator Efficiency

    Science.gov (United States)

    Mahl, Adam; Chouinard-Dussault, Pascale; Pecinovsky, Cory; Potter, Andrew; Remedes, Tyler; Dorgan, John; Greife, Uwe

    2013-04-01

    This talk will describe the progress made in an interdisciplinary development project aimed at cost-effective, neutron sensitive, plastic scintillator. Colorado School of Mines researchers with backgrounds in Physics, Chemistry, and Chemical Engineering have worked on the incorporation of ^10B in plastics through extrusion. First results on transparent samples using fluorescent spectroscopy and beta excitation will be presented.

  3. New Life for Old Plastics

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Recycling joint venture utilizes innovative technology to reuse plastics Recycling,despite its green connotations,can be a messy business.In China,more than 400,000 companies are engaged in plastic recycling,but 70 percent of them are family enterprises,

  4. Improved methods for fluorescence microscopy detection of macromolecules at the axon initial segment

    Directory of Open Access Journals (Sweden)

    Musaad A Alshammari

    2016-02-01

    Full Text Available The axonal initial segment (AIS is the subcellular compartment required for initiation of the action potential in neurons. Scaffolding and regulatory proteins at the AIS cluster with ion channels ensuring the integrity of electrical signaling. Interference with the configuration of this protein network can lead to profound effects on neuronal polarity, excitability, cell-to-cell connectivity and brain circuit plasticity. As such, the ability to visualize AIS components with precision provides an invaluable opportunity for parsing out key molecular determinants of neuronal function. Fluorescence-based immunolabeling is a sensitive method for morphological and molecular characterization of fine structures in neurons. Yet, even when combined with confocal microscopy, detection of AIS elements with immunofluorescence has been limited by the loss of antigenicity caused by fixative materials. This technical barrier has posed significant limitations in detecting AIS components alone or in combination with other markers. Here, we designed improved protocols targeted to confocal immunofluorescence detection of the AIS marker fibroblast growth factor 14 (FGF14 in combination with the cytoskeletal-associated protein Ankyrin-G, the scaffolding protein βIV-spectrin, voltage-gated Na+ (Nav channels (especially the Nav1.6 isoform and critical cell type-specific neuronal markers such as parvalbumin, calbindin, and NeuN in the mouse brain. Notably, we demonstrate that intracardiac perfusion of animals with a commercially available solution containing 1% formaldehyde and 0.5% methanol, followed by brief fixation with cold acetone is an optimal and sensitive protocol for FGF14 and other AIS marker detection that guarantees excellent tissue integrity. With variations in the procedure, we also significantly improved the detection of Nav1.6, a Nav isoform known for its fixative-sensitivity. Overall, this study provides an ensemble of immunohistochemical recipes that

  5. Improved Methods for Fluorescence Microscopy Detection of Macromolecules at the Axon Initial Segment.

    Science.gov (United States)

    Alshammari, Musaad A; Alshammari, Tahani K; Laezza, Fernanda

    2016-01-01

    The axonal initial segment (AIS) is the subcellular compartment required for initiation of the action potential in neurons. Scaffolding and regulatory proteins at the AIS cluster with ion channels ensuring the integrity of electrical signaling. Interference with the configuration of this protein network can lead to profound effects on neuronal polarity, excitability, cell-to-cell connectivity and brain circuit plasticity. As such, the ability to visualize AIS components with precision provides an invaluable opportunity for parsing out key molecular determinants of neuronal function. Fluorescence-based immunolabeling is a sensitive method for morphological and molecular characterization of fine structures in neurons. Yet, even when combined with confocal microscopy, detection of AIS elements with immunofluorescence has been limited by the loss of antigenicity caused by fixative materials. This technical barrier has posed significant limitations in detecting AIS components alone or in combination with other markers. Here, we designed improved protocols targeted to confocal immunofluorescence detection of the AIS marker fibroblast growth factor 14 (FGF14) in combination with the cytoskeletal-associated protein Ankyrin-G, the scaffolding protein βIV-spectrin, voltage-gated Na(+) (Nav) channels (especially the Nav1.6 isoform) and critical cell type-specific neuronal markers such as parvalbumin, calbindin, and NeuN in the mouse brain. Notably, we demonstrate that intracardiac perfusion of animals with a commercially available solution containing 1% formaldehyde and 0.5% methanol, followed by brief fixation with cold acetone is an optimal and sensitive protocol for FGF14 and other AIS marker detection that guarantees excellent tissue integrity. With variations in the procedure, we also significantly improved the detection of Nav1.6, a Nav isoform known for its fixative-sensitivity. Overall, this study provides an ensemble of immunohistochemical recipes that permit

  6. Improved Methods for Fluorescence Microscopy Detection of Macromolecules at the Axon Initial Segment

    Science.gov (United States)

    Alshammari, Musaad A.; Alshammari, Tahani K.; Laezza, Fernanda

    2016-01-01

    The axonal initial segment (AIS) is the subcellular compartment required for initiation of the action potential in neurons. Scaffolding and regulatory proteins at the AIS cluster with ion channels ensuring the integrity of electrical signaling. Interference with the configuration of this protein network can lead to profound effects on neuronal polarity, excitability, cell-to-cell connectivity and brain circuit plasticity. As such, the ability to visualize AIS components with precision provides an invaluable opportunity for parsing out key molecular determinants of neuronal function. Fluorescence-based immunolabeling is a sensitive method for morphological and molecular characterization of fine structures in neurons. Yet, even when combined with confocal microscopy, detection of AIS elements with immunofluorescence has been limited by the loss of antigenicity caused by fixative materials. This technical barrier has posed significant limitations in detecting AIS components alone or in combination with other markers. Here, we designed improved protocols targeted to confocal immunofluorescence detection of the AIS marker fibroblast growth factor 14 (FGF14) in combination with the cytoskeletal-associated protein Ankyrin-G, the scaffolding protein βIV-spectrin, voltage-gated Na+ (Nav) channels (especially the Nav1.6 isoform) and critical cell type-specific neuronal markers such as parvalbumin, calbindin, and NeuN in the mouse brain. Notably, we demonstrate that intracardiac perfusion of animals with a commercially available solution containing 1% formaldehyde and 0.5% methanol, followed by brief fixation with cold acetone is an optimal and sensitive protocol for FGF14 and other AIS marker detection that guarantees excellent tissue integrity. With variations in the procedure, we also significantly improved the detection of Nav1.6, a Nav isoform known for its fixative-sensitivity. Overall, this study provides an ensemble of immunohistochemical recipes that permit

  7. A plastic scintillation counter prototype

    International Nuclear Information System (INIS)

    A new prototype device for beta-ray measurement, a plastic scintillation counter, was assembled as an alternative device to liquid scintillation counters. This device uses plastic scintillation sheets (PS sheets) as a sample applicator without the use of a liquid scintillator. The performance was evaluated using tritium labeled compounds, and good linearity was observed between the activity and net count rate. The calculated detection limit of the device was 0.01 Bq mL−1 after 10 h measurement for 2 mL sample. - Highlights: • A new device of plastic scintillation counter was developed to measure beta emitters. • High sensitivity with low detection limit was performed for a tritium compound. • A detection limit of tritium was 0.01 Bq mL−1 for a 10 h measurement. • A plastic scintillation counter generated no radioactive organic waste fluid. • A plastic scintillation counter could analyze qualitatively and quantitatively

  8. Size effects in crystal plasticity

    DEFF Research Database (Denmark)

    Borg, Ulrik

    2007-01-01

    growth and interaction between neighboring voids, and on a comparison between the developed strain gradient crystal plasticity theory and a discrete dislocation plasticity theory. Furthermore, voids and rigid inclusions in isotropic materials have been studied using a strain gradient plasticity theory......Numerical analyses of plasticity size effects have been carried out for different problems using a developed strain gradient crystal plasticiy theory. The theory employs higher order stresses as work conjugates to slip gradients and uses higher order boundary conditions. Problems on localization...... of plastic flow in a single crystal, grain boundary effects in a bicrystal, and grain size effects in a polycrystal are studied. Single crystals containing micro-scale voids have also been analyzed at different loading conditions with focus on the stress and deformation fields around the voids, on void...

  9. Computational strain gradient crystal plasticity

    DEFF Research Database (Denmark)

    Niordson, Christian Frithiof; Kysar, Jeffrey W.

    2014-01-01

    A numerical method for viscous strain gradient crystal plasticity theory is presented, which incorporates both energetic and dissipative gradient effects. The underlying minimum principles are discussed as well as convergence properties of the proposed finite element procedure. Three problems...... of plane crystal plasticity are studied: pure shear of a single crystal between rigid platens as well as plastic deformation around cylindrical voids in hexagonal close packed and face centered cubic crystals. Effective in-plane constitutive slip parameters for plane strain deformation of specifically...... oriented face centered cubic crystals are developed in terms of the crystallographic slip parameters. The effect on geometrically necessary dislocation structures introduced by plastic deformation is investigated as a function of the ratio of void radius to plasticity length scale....

  10. Imaging brain plasticity after trauma

    Science.gov (United States)

    Kou, Zhifeng; Iraji, Armin

    2014-01-01

    The brain is highly plastic after stroke or epilepsy; however, there is a paucity of brain plasticity investigation after traumatic brain injury (TBI). This mini review summarizes the most recent evidence of brain plasticity in human TBI patients from the perspective of advanced magnetic resonance imaging. Similar to other forms of acquired brain injury, TBI patients also demonstrated both structural reorganization as well as functional compensation by the recruitment of other brain regions. However, the large scale brain network alterations after TBI are still unknown, and the field is still short of proper means on how to guide the choice of TBI rehabilitation or treatment plan to promote brain plasticity. The authors also point out the new direction of brain plasticity investigation. PMID:25206874

  11. Imaging brain plasticity after trauma

    Institute of Scientific and Technical Information of China (English)

    Zhifeng Kou; Armin Iraji

    2014-01-01

    The brain is highly plastic after stroke or epilepsy;however, there is a paucity of brain plasticity investigation after traumatic brain injury (TBI). This mini review summarizes the most recent evidence of brain plasticity in human TBI patients from the perspective of advanced magnetic resonance imaging. Similar to other forms of acquired brain injury, TBI patients also demonstrat-ed both structural reorganization as well as functional compensation by the recruitment of other brain regions. However, the large scale brain network alterations after TBI are still unknown, and the ifeld is still short of proper means on how to guide the choice of TBI rehabilitation or treat-ment plan to promote brain plasticity. The authors also point out the new direction of brain plas-ticity investigation.

  12. The future costs of nuclear power using multiple expert elicitations: effects of RD&D and elicitation design

    Science.gov (United States)

    Díaz Anadón, Laura; Nemet, Gregory; Verdolini, Elena

    2013-09-01

    Characterization of the anticipated performance of energy technologies to inform policy decisions increasingly relies on expert elicitation. Knowledge about how elicitation design factors impact the probabilistic estimates emerging from these studies is, however, scarce. We focus on nuclear power, a large-scale low-carbon power option, for which future cost estimates are important for the design of energy policies and climate change mitigation efforts. We use data from three elicitations in the USA and in Europe and assess the role of government research, development, and demonstration (RD&D) investments on expected nuclear costs in 2030. We show that controlling for expert, technology, and design characteristics increases experts’ implied public RD&D elasticity of expected costs by 25%. Public sector and industry experts’ cost expectations are 14% and 32% higher, respectively than academics. US experts are more optimistic than their EU counterparts, with median expected costs 22% lower. On average, a doubling of public RD&D is expected to result in an 8% cost reduction, but the uncertainty is large. The difference between the 90th and 10th percentile estimates is on average 58% of the experts’ median estimates. Public RD&D investments do not affect uncertainty ranges, but US experts are less confident about costs than Europeans.

  13. The future costs of nuclear power using multiple expert elicitations: effects of RD and D and elicitation design

    International Nuclear Information System (INIS)

    Characterization of the anticipated performance of energy technologies to inform policy decisions increasingly relies on expert elicitation. Knowledge about how elicitation design factors impact the probabilistic estimates emerging from these studies is, however, scarce. We focus on nuclear power, a large-scale low-carbon power option, for which future cost estimates are important for the design of energy policies and climate change mitigation efforts. We use data from three elicitations in the USA and in Europe and assess the role of government research, development, and demonstration (RD and D) investments on expected nuclear costs in 2030. We show that controlling for expert, technology, and design characteristics increases experts’ implied public RD and D elasticity of expected costs by 25%. Public sector and industry experts’ cost expectations are 14% and 32% higher, respectively than academics. US experts are more optimistic than their EU counterparts, with median expected costs 22% lower. On average, a doubling of public RD and D is expected to result in an 8% cost reduction, but the uncertainty is large. The difference between the 90th and 10th percentile estimates is on average 58% of the experts’ median estimates. Public RD and D investments do not affect uncertainty ranges, but US experts are less confident about costs than Europeans. (letter)

  14. Nano-Ceramic Coated Plastics

    Science.gov (United States)

    Cho, Junghyun

    2013-01-01

    Plastic products, due to their durability, safety, and low manufacturing cost, are now rapidly replacing cookware items traditionally made of glass and ceramics. Despite this trend, some still prefer relatively expensive and more fragile ceramic/glassware because plastics can deteriorate over time after exposure to foods, which can generate odors, bad appearance, and/or color change. Nano-ceramic coatings can eliminate these drawbacks while still retaining the advantages of the plastic, since the coating only alters the surface of the plastic. The surface coating adds functionality to the plastics such as self-cleaning and disinfectant capabilities that result from a photocatalytic effect of certain ceramic systems. These ceramic coatings can also provide non-stick surfaces and higher temperature capabilities for the base plastics without resorting to ceramic or glass materials. Titanium dioxide (TiO2) and zinc oxide (ZnO) are the candidates for a nano-ceramic coating to deposit on the plastics or plastic films used in cookware and kitchenware. Both are wide-bandgap semiconductors (3.0 to 3.2 eV for TiO2 and 3.2 to 3.3 eV for ZnO), so they exhibit a photocatalytic property under ultraviolet (UV) light. This will lead to decomposition of organic compounds. Decomposed products can be easily washed off by water, so the use of detergents will be minimal. High-crystalline film with large surface area for the reaction is essential to guarantee good photocatalytic performance of these oxides. Low-temperature processing (nano-ceramic coatings (TiO2, ZnO) on plastic materials (silicone, Teflon, PET, etc.) that can possess both photocatalytic oxide properties and flexible plastic properties. Processing cost is low and it does not require any expensive equipment investment. Processing can be scalable to current manufacturing infrastructure.

  15. Matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase co-regulate axonal outgrowth of mouse retinal ganglion cells

    DEFF Research Database (Denmark)

    Gaublomme, Djoere; Buyens, Tom; De Groef, Lies; Stakenborg, Michelle; Janssens, Els; Ingvarsen, Signe; Porse, Astrid; Behrendt, Niels; Moons, Lieve

    2014-01-01

    , but not MMP-9, are involved in this process. Furthermore, administration of a novel antibody to MT1-MMP that selectively blocks pro-MMP-2 activation revealed a functional co-involvement of these proteinases in determining RGC axon outgrowth. Subsequent immunostainings showed expression of both MMP-2......, we were able to show that broad-spectrum MMP inhibition reduces axon outgrowth of mouse retinal ganglion cells (RGCs), implicating MMPs as beneficial factors in axonal regeneration. Additional studies, using more specific MMP inhibitors and MMP-deficient mice, disclosed that both MMP-2 and MT1-MMP...... and MT1-MMP in RGC axons and glial cells. Finally, results from combined inhibition of MMP-2 and β1-integrin were suggestive for a functional interaction between these molecules. Overall, our data indicate MMP-2 and MT1-MMP as promising axonal outgrowth-promoting molecules. Axonal regeneration in the...

  16. An animal model of female adolescent cannabinoid exposure elicits a long-lasting deficit in presynaptic long-term plasticity.

    Science.gov (United States)

    Lovelace, Jonathan W; Corches, Alex; Vieira, Philip A; Hiroto, Alex S; Mackie, Ken; Korzus, Edward

    2015-12-01

    Cannabis continues to be the most accessible and popular illicit recreational drug. Whereas current data link adolescence cannabinoid exposure to increased risk for dependence on other drugs, depression, anxiety disorders and psychosis, the mechanism(s) underlying these adverse effects remains controversial. Here we show in a mouse model of female adolescent cannabinoid exposure deficient endocannabinoid (eCB)-mediated signaling and presynaptic forms of long-term depression at adult central glutamatergic synapses in the prefrontal cortex. Increasing endocannabinoid levels by blockade of monoacylglycerol lipase, the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol (2-AG), with the specific inhibitor JZL 184 ameliorates eCB-LTD deficits. The observed deficit in cortical presynaptic signaling may represent a neural maladaptation underlying network instability and abnormal cognitive functioning. Our study suggests that adolescent cannabinoid exposure may permanently impair brain functions, including the brain's intrinsic ability to appropriately adapt to external influences. PMID:25979486

  17. Patient Safety: Guide to Safe Plastic Surgery

    Science.gov (United States)

    ... and Consumer Information > Patient Safety Guide to Safe Plastic Surgery Patient Safety More Resources Choose a surgeon ... Important facts about the safety and risks of plastic surgery Questions to ask my plastic surgeon Choose ...

  18. Structured Digital Storytelling for Eliciting Software Requirements in the ICT4D Domain

    OpenAIRE

    Sinnig, Daniel; Pitula, Kristina; Becker, Richard; Radhakrishnan, T.; Forbrig, Peter

    2010-01-01

    Due to the specific challenges that ICT4D projects present, conventional requirements elicitation techniques are often inapplicable or insufficient. We address this shortcoming by introducing structured digital storytelling (SDS) as an alternative elicitation technique especially suited for the ICD4D domain. SDS is supported by our mobile elicitation tool designed around the needs and capabilities of the targeted user population. We embed SDS in a requirements elicitation and specification pr...

  19. Endoplasmic reticulum sorting and kinesin-1 command the targeting of axonal GABAB receptors.

    Directory of Open Access Journals (Sweden)

    Viviana Valdés

    Full Text Available In neuronal cells the intracellular trafficking machinery controls the availability of neurotransmitter receptors at the plasma membrane, which is a critical determinant of synaptic strength. Metabotropic γ amino-butyric acid (GABA type B receptors (GABA(BRs are neurotransmitter receptors that modulate synaptic transmission by mediating the slow and prolonged responses to GABA. GABA(BRs are obligatory heteromers constituted by two subunits, GABA(BR1 and GABA(BR2. GABA(BR1a and GABA(BR1b are the most abundant subunit variants. GABA(BR1b is located in the somatodendritic domain whereas GABA(BR1a is additionally targeted to the axon. Sushi domains located at the N-terminus of GABA(BR1a constitute the only difference between both variants and are necessary and sufficient for axonal targeting. The precise targeting machinery and the organelles involved in sorting and transport have not been described. Here we demonstrate that GABA(BRs require the Golgi apparatus for plasma membrane delivery but that axonal sorting and targeting of GABA(BR1a operate in a pre-Golgi compartment. In the axon GABA(BR1a subunits are enriched in the endoplasmic reticulum (ER, and their dynamic behavior and colocalization with other secretory organelles like the ER-to-Golgi intermediate compartment (ERGIC suggest that they employ a local secretory route. The transport of axonal GABA(BR1a is microtubule-dependent and kinesin-1, a molecular motor of the kinesin family, determines axonal localization. Considering that progression of GABA(BRs through the secretory pathway is regulated by an ER retention motif our data contribute to understand the role of the axonal ER in non-canonical sorting and targeting of neurotransmitter receptors.

  20. Filtration coefficient of the axon membrane as measured with hydrostatic and osmotic methods.

    Science.gov (United States)

    Vargas, F F

    1968-01-01

    The hydraulic conductivity of the membranes surrounding the giant axon of the squid, Dosidicus gigas, was measured. In some axons the axoplasm was partially removed by suction. Perfusion was then established by insertion of a second pipette. In other axons the axoplasm was left intact and only one pipette was inserted. In both groups hydrostatic pressure was applied by means of a water column in a capillary manometer. Displacement of the meniscus in time gave the rate of fluid flowing across the axon sheath. In both groups osmotic differences across the membrane were established by the addition of a test molecule to the external medium which was seawater. The hydraulic conductivity determined by application of hydrostatic pressure was 10.6 +/- 0.8.10(-8) cm/sec cm H(2)O in perfused axons and 3.2 +/- 0.6.10(-8) cm/sec cm H(2)O in intact axons. When the driving force was an osmotic pressure gradient the conductivity was 4.5 +/- 0.6 x 10(-10) cm/sec cm H(2)O and 4.8 +/- 0.9 x 10(-10) cm/sec cm H(2)O in perfused and intact axons, respectively. A comparable result was found when the internal solution was made hyperosmotic. The fluid flow was a linear function of the hydrostatic pressure up to 70 cm of water. Glycerol outflux and membrane conductance were increased 1.6 and 1.1 times by the application of hydrostatic pressure. These increments do not give an explanation of the difference between the filtration coefficients. Other possible explanations are suggested and discussed. PMID:5642470

  1. Rescuing axons from degeneration does not affect retinal ganglion cell death

    Directory of Open Access Journals (Sweden)

    S. de Lima

    2016-01-01

    Full Text Available After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD, an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18 treated with an exogenous calpain inhibitor (20 mM administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05 and an increase in the number of preserved fibers (P<0.05 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage.

  2. Short-term peripheral nerve stimulation ameliorates axonal dysfunction after spinal cord injury.

    Science.gov (United States)

    Lee, Michael; Kiernan, Matthew C; Macefield, Vaughan G; Lee, Bonne B; Lin, Cindy S-Y

    2015-05-01

    There is accumulating evidence that peripheral motor axons deteriorate following spinal cord injury (SCI). Secondary axonal dysfunction can exacerbate muscle atrophy, contribute to peripheral neuropathies and neuropathic pain, and lead to further functional impairment. In an attempt to ameliorate the adverse downstream effects that developed following SCI, we investigated the effects of a short-term peripheral nerve stimulation (PNS) program on motor axonal excitability in 22 SCI patients. Axonal excitability studies were undertaken in the median and common peroneal nerves (CPN) bilaterally before and after a 6-wk unilateral PNS program. PNS was delivered percutaneously over the median nerve at the wrist and CPN around the fibular head, and the compound muscle action potential (CMAP) from the abductor pollicis brevis and tibialis anterior was recorded. Stimulus intensity was above motor threshold, and pulses (450 μs) were delivered at 100 Hz with a 2-s on/off cycle for 30 min 5 days/wk. SCI patients had consistently high thresholds with a reduced CMAP consistent with axonal loss; in some patients the peripheral nerves were completely inexcitable. Nerve excitability studies revealed profound changes in membrane potential, with a "fanned-in" appearance in threshold electrotonus, consistent with membrane depolarization, and significantly reduced superexcitability during the recovery cycle. These membrane dysfunctions were ameliorated after 6 wk of PNS, which produced a significant hyperpolarizing effect. The contralateral, nonstimulated nerves remained depolarized. Short-term PNS reversed axonal dysfunction following SCI, may provide an opportunity to prevent chronic changes in axonal and muscular function, and may improve rehabilitation outcomes. PMID:25787956

  3. Protein 4.1B contributes to the organization of peripheral myelinated axons.

    Directory of Open Access Journals (Sweden)

    Carmen Cifuentes-Diaz

    Full Text Available Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. βII spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber.

  4. Primary neuron culture for nerve growth and axon guidance studies in zebrafish (Danio rerio.

    Directory of Open Access Journals (Sweden)

    Zheyan Chen

    Full Text Available Zebrafish (Danio rerio is a widely used model organism in genetics and developmental biology research. Genetic screens have proven useful for studying embryonic development of the nervous system in vivo, but in vitro studies utilizing zebrafish have been limited. Here, we introduce a robust zebrafish primary neuron culture system for functional nerve growth and guidance assays. Distinct classes of central nervous system neurons from the spinal cord, hindbrain, forebrain, and retina from wild type zebrafish, and fluorescent motor neurons from transgenic reporter zebrafish lines, were dissociated and plated onto various biological and synthetic substrates to optimize conditions for axon outgrowth. Time-lapse microscopy revealed dynamically moving growth cones at the tips of extending axons. The mean rate of axon extension in vitro was 21.4±1.2 µm hr(-1 s.e.m. for spinal cord neurons, which corresponds to the typical ∼0.5 mm day(-1 growth rate of nerves in vivo. Fluorescence labeling and confocal microscopy demonstrated that bundled microtubules project along axons to the growth cone central domain, with filamentous actin enriched in the growth cone peripheral domain. Importantly, the growth cone surface membrane expresses receptors for chemotropic factors, as detected by immunofluorescence microscopy. Live-cell functional assays of axon extension and directional guidance demonstrated mammalian brain-derived neurotrophic factor (BDNF-dependent stimulation of outgrowth and growth cone chemoattraction, whereas mammalian myelin-associated glycoprotein inhibited outgrowth. High-resolution live-cell Ca(2+-imaging revealed local elevation of cytoplasmic Ca(2+ concentration in the growth cone induced by BDNF application. Moreover, BDNF-induced axon outgrowth, but not basal outgrowth, was blocked by treatments to suppress cytoplasmic Ca(2+ signals. Thus, this primary neuron culture model system may be useful for studies of neuronal development

  5. Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

    International Nuclear Information System (INIS)

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE-/-) versus wild type (AChE+/+) mice indicated that while these OPs inhibited axonal growth in AChE+/+ DRG neurons, they had no effect on axonal growth in AChE-/- DRG neurons. However, transfection of AChE-/- DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs

  6. Time-Lapse Imaging of the Dynamics of CNS Glial-Axonal Interactions In Vitro and Ex Vivo

    OpenAIRE

    Kalliopi Ioannidou; Anderson, Kurt I; David Strachan; Edgar, Julia M.; Barnett, Susan C.

    2012-01-01

    Background Myelination is an exquisite and dynamic example of heterologous cell-cell interaction, which consists of the concentric wrapping of multiple layers of oligodendrocyte membrane around neuronal axons. Understanding the mechanism by which oligodendrocytes ensheath axons may bring us closer to designing strategies to promote remyelination in demyelinating diseases. The main aim of this study was to follow glial-axonal interactions over time both in vitro and ex vivo to visualize th...

  7. Axonal transport and incorporation of radioactivity after injection of N-[3H]acetyl-D-mannosamine into rat mesencephalon

    International Nuclear Information System (INIS)

    A study has been performed to demonstrate the possibility of incorporation of sialic acid into nerve endings of the rubrospinal tract after antegrade axonal transport. Young adult rats received injections of N-[3H]acetyl-D-mannosamine into the red nucleus and axonal transport of the tritiated compounds along the axons of afferent and efferent connections of the red nucleus was studied and the transported material was analysed. Light microscopic autoradiography and biochemical methods were used. (Auth./C.F.)

  8. Axon degeneration and PGC-1α-mediated protection in a zebrafish model of α-synuclein toxicity

    Directory of Open Access Journals (Sweden)

    Kelley C. O’Donnell

    2014-05-01

    Full Text Available α-synuclein (aSyn expression is implicated in neurodegenerative processes, including Parkinson’s disease (PD and dementia with Lewy bodies (DLB. In animal models of these diseases, axon pathology often precedes cell death, raising the question of whether aSyn has compartment-specific toxic effects that could require early and/or independent therapeutic intervention. The relevance of axonal pathology to degeneration can only be addressed through longitudinal, in vivo monitoring of different neuronal compartments. With current imaging methods, dopaminergic neurons do not readily lend themselves to such a task in any vertebrate system. We therefore expressed human wild-type aSyn in zebrafish peripheral sensory neurons, which project elaborate superficial axons that can be continuously imaged in vivo. Axonal outgrowth was normal in these neurons but, by 2 days post-fertilization (dpf, many aSyn-expressing axons became dystrophic, with focal varicosities or diffuse beading. Approximately 20% of aSyn-expressing cells died by 3 dpf. Time-lapse imaging revealed that focal axonal swelling, but not overt fragmentation, usually preceded cell death. Co-expressing aSyn with a mitochondrial reporter revealed deficits in mitochondrial transport and morphology even when axons appeared overtly normal. The axon-protective protein Wallerian degeneration slow (WldS delayed axon degeneration but not cell death caused by aSyn. By contrast, the transcriptional coactivator PGC-1α, which has roles in the regulation of mitochondrial biogenesis and reactive-oxygen-species detoxification, abrogated aSyn toxicity in both the axon and the cell body. The rapid onset of axonal pathology in this system, and the relatively moderate degree of cell death, provide a new model for the study of aSyn toxicity and protection. Moreover, the accessibility of peripheral sensory axons will allow effects of aSyn to be studied in different neuronal compartments and might have utility in

  9. Demyelination induces transport of ribosome-containing vesicles from glia to axons: evidence from animal models and MS patient brains.

    Science.gov (United States)

    Shakhbazau, Antos; Schenk, Geert J; Hay, Curtis; Kawasoe, Jean; Klaver, Roel; Yong, V Wee; Geurts, Jeroen J G; van Minnen, Jan

    2016-06-01

    Glial cells were previously proven capable of trafficking polyribosomes to injured axons. However, the occurrence of such transfer in the general pathological context, such as demyelination-related diseases, needs further evidence. Since this may be a yet unidentified universal contributor to axonal survival, we study putative glia-axonal ribosome transport in response to demyelination in animal models and patients in both peripheral and central nervous system. In the PNS we investigate whether demyelination in a rodent model has the potential to induce ribosome transfer. We also probe the glia-axonal ribosome supply by implantation of transgenic Schwann cells engineered to produce fluorescent ribosomes in the same demyelination model. We furthermore examine the presence of axonal ribosomes in mouse experimental autoimmune encephalomyelitis (EAE), a well-established model for multiple sclerosis (MS), and in human MS autopsy brain material. We provide evidence for increased axonal ribosome content in a pharmacologically demyelinated sciatic nerve, and demonstrate that at least part of these ribosomes originate in the transgenic Schwann cells. In the CNS one of the hallmarks of MS is demyelination, which is associated with severe disruption of oligodendrocyte-axon interaction. Here, we provide evidence that axons from spinal cords of EAE mice, and in the MS human brain contain an elevated amount of axonal ribosomes compared to controls. Our data provide evidence that increased axonal ribosome content in pathological axons is at least partly due to glia-to-axon transfer of ribosomes, and that demyelination in the PNS and in the CNS is one of the triggers capable to initiate this process. PMID:27115494

  10. Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic cell types

    Directory of Open Access Journals (Sweden)

    Villegas Rosario

    2012-06-01

    Full Text Available Abstract Background Understanding the cellular mechanisms regulating axon degeneration and regeneration is crucial for developing treatments for nerve injury and neurodegenerative disease. In neurons, axon degeneration is distinct from cell body death and often precedes or is associated with the onset of disease symptoms. In the peripheral nervous system of both vertebrates and invertebrates, after degeneration of detached fragments, axons can often regenerate to restore function. Many studies of axonal degeneration and regeneration have used in vitro approaches, but the influence of extrinsic cell types on these processes can only be fully addressed in live animals. Because of its simplicity and superficial location, the larval zebrafish posterior lateral line (pLL nerve is an ideal model system for live studies of axon degeneration and regeneration. Results We used laser axotomy and time-lapse imaging of pLL axons to characterize the roles of leukocytes, Schwann cells and target sensory hair cells in axon degeneration and regeneration in vivo. Immune cells were essential for efficient removal of axonal debris after axotomy. Schwann cells were required for proper fasciculation and pathfinding of regenerating axons to their target cells. Intact target hair cells were not themselves required for regeneration, but chemical ablation of neuromasts caused axons to transiently deviate from their normal paths. Conclusions Macrophages, Schwann cells, and target sensory organs are required for distinct aspects of pLL axon degeneration or regeneration in the zebrafish larva. Our work introduces a powerful vertebrate model for analyzing axonal degeneration and regeneration in the living animal and elucidating the role of extrinsic cell types in these processes.

  11. The contributions of myelin and axonal caliber to transverse relaxation time in shiverer and neurofilament-deficient mouse models

    OpenAIRE

    Dyakin, Victor V.; Chen, Yuanxin; Branch, Craig A.; Veeranna; Yuan, Aidong; Rao, Mala; Kumar, Asok; Peterhoff, Corrinne M.; Nixon, Ralph A

    2010-01-01

    White matter disorders can involve injury to myelin or axons but the respective contribution of each to clinical course is difficult to evaluate non-invasively. Here, to develop a paradigm for further investigations of axonal pathology by MRI, we compared two genetic mouse models exhibiting relatively selective axonal or myelin deficits using quantitative MRI relaxography of the transverse relaxation times (T2) in vivo and ultrastructural morphometry. In HM-DKO mice, which lack genes encoding...

  12. Ion channel clustering at the axon initial segment and node of Ranvier evolved sequentially in early chordates.

    OpenAIRE

    Hill, Alexis S.; Atsuo Nishino; Koichi Nakajo; Giuxin Zhang; Fineman, Jaime R.; Selzer, Michael E.; Yasushi Okamura; Cooper, Edward C.

    2008-01-01

    In many mammalian neurons, dense clusters of ion channels at the axonal initial segment and nodes of Ranvier underlie action potential generation and rapid conduction. Axonal clustering of mammalian voltage-gated sodium and KCNQ (Kv7) potassium channels is based on linkage to the actin–spectrin cytoskeleton, which is mediated by the adaptor protein ankyrin-G. We identified key steps in the evolution of this axonal channel clustering. The anchor motif for sodium channel clustering evolved earl...

  13. Squeezing axons out of the gray matter: a role for slit and semaphorin proteins from midline and ventral spinal cord.

    OpenAIRE

    Y. Zou; Stoeckli, E T; Chen, H.; Tessier-Lavigne, M

    2000-01-01

    Commissural axons cross the nervous system midline and then turn to grow alongside it, neither recrossing nor projecting back into ventral regions. In Drosophila, the midline repellent Slit prevents recrossing: axons cross once because they are initially unresponsive to Slit, becoming responsive only upon crossing. We show that commissural axons in mammals similarly acquire responsiveness to a midline repellent activity upon crossing. Remarkably, they also become responsive to a repellent act...

  14. A Purine-Sensitive Pathway Regulates Multiple Genes Involved in Axon Regeneration in Goldfish Retinal Ganglion Cells

    OpenAIRE

    Petrausch, Barbara; Tabibiazar, Raymond; Roser, Timo; Jing, Yun; Goldmann, Daniel; Stürmer, Claudia; Irwin, Nina; Benowitz, Larry I.

    2000-01-01

    In lower vertebrates, retinal ganglion cells (RGCs) can regenerate their axons and reestablish functional connections after optic nerve injury. We show here that in goldfish RGCs, the effects of several trophic factors converge on a purine-sensitive signaling mechanism that controls axonal outgrowth and the expression of multiple growth-associated proteins. In culture, goldfish RGCs regenerate their axons in response to two molecules secreted by optic nerve glia, axogenesis factor-1 (AF-1) an...

  15. Brain-derived neurotrophic factor gene transfection promotes neuronal repair and neurite regeneration after diffuse axonal injury

    Institute of Scientific and Technical Information of China (English)

    Yin Yu; Chao Du; Xingli Zhao; Jiajia Shao; Qiang Shen; Tao Jiang; Wei Wu; Dong Zhu; Yu Tian; Yongchuan Guo

    2011-01-01

    This study sought to assess the potential of brain-derived neurotrophic factor (BDNF) to promote neuronal repair and regeneration in rats with diffuse axonal injury, and to examine the accompanying neurobiological changes. BDNF gene transfection reduced the severity of the pathological changes associated with diffuse axonal injury in cortical neurons of the frontal lobe and increased neurofilament protein expression. These findings demonstrate that BDNF can effectively promote neuronal repair and neurite regeneration after diffuse axonal injury.

  16. The comparison of the value of ct imaging and selected MRI sequences (including DWI) in the evaluation of axonal injuries

    OpenAIRE

    Paszkowska, Emilia; Wasilewski, Grzegorz; Szalcunas-Olsztyn, Anna; Jancewicz, Patryk; Stefanowicz, Elżbieta

    2010-01-01

    Summary Background: Diffuse axonal injuries of the brain consist in the damage (overstretching or torsion) of white matter axons, as a result of the forces of energy waves, evoked in the moment of injury, together with its accelerating-retarding inertia effect. Patients with DAI are most frequently the casualties of high speed car accidents. Diffuse axonal injuries of the brain are one of the most common acute brain injuries, with lesions typically occurring in the periventricular white matte...

  17. Developing Socio-Cultural Scaffolding Model to Elicit Learners's Speech Production

    Science.gov (United States)

    Englishtina, Inti

    2015-01-01

    This study is concerned with developing scaffolding model to elicit bilingual kindergarten children's English speech production. It is aimed at describing what the teachers need in eliciting their students' speech production; how a scaffolding model should be developed to elicit the children's speech production; and how effective is the…

  18. Spinal plasticity in robot-mediated therapy for the lower limbs

    DEFF Research Database (Denmark)

    Stevenson, Andrew James Thomas; Mrachacz-Kersting, Natalie; van Asseldonk, Edwin;

    2015-01-01

    limited to the lower limbs. Body weight-supported (BWS) robotic-assisted step training of patients with spinal cord injury (SCI) or stroke patients has been shown to lead to changes in the amplitude and phase modulation of spinal reflex pathways elicited by electrical stimulation or joint rotations. Of...... neural changes in the spinal cord. Here, we review the recent literature on spinal plasticity induced by robotic-based training in humans and propose recommendations for the measurement of spinal plasticity using robotic devices. Evidence for spinal plasticity in humans following robotic training is......Robot-mediated therapy can help improve walking ability in patients following injuries to the central nervous system. However, the efficacy of this treatment varies between patients, and evidence for the mechanisms underlying functional improvements in humans is poor, particularly in terms of...

  19. Analysis of the intraspinal calcium dynamics and its implications on the plasticity of spiking neurons

    CERN Document Server

    Yeung, L C; Shouval, H Z; Yeung, Luk C.; Castellani, Gastone C.; Shouval, Harel Z.

    2004-01-01

    The influx of calcium ions into the dendritic spines through the N-metyl-D-aspartate (NMDA) channels is believed to be the primary trigger for various forms of synaptic plasticity. In this paper, the authors calculate analytically the mean values of the calcium transients elicited by a spiking neuron undergoing a simple model of ionic currents and back-propagating action potentials. The relative variability of these transients, due to the stochastic nature of synaptic transmission, is further considered using a simple Markov model of NMDA receptos. One finds that both the mean value and the variability depend on the timing between pre- and postsynaptic action-potentials. These results could have implications on the expected form of synaptic-plasticity curve and can form a basis for a unified theory of spike time-dependent, and rate based plasticity.

  20. Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.

    Directory of Open Access Journals (Sweden)

    Fabrice Ango

    2008-04-01

    Full Text Available The geometric and subcellular organization of axon arbors distributes and regulates electrical signaling in neurons and networks, but the underlying mechanisms have remained elusive. In rodent cerebellar cortex, stellate interneurons elaborate characteristic axon arbors that selectively innervate Purkinje cell dendrites and likely regulate dendritic integration. We used GFP BAC transgenic reporter mice to examine the cellular processes and molecular mechanisms underlying the development of stellate cell axons and their innervation pattern. We show that stellate axons are organized and guided towards Purkinje cell dendrites by an intermediate scaffold of Bergmann glial (BG fibers. The L1 family immunoglobulin protein Close Homologue of L1 (CHL1 is localized to apical BG fibers and stellate cells during the development of stellate axon arbors. In the absence of CHL1, stellate axons deviate from BG fibers and show aberrant branching and orientation. Furthermore, synapse formation between aberrant stellate axons and Purkinje dendrites is reduced and cannot be maintained, leading to progressive atrophy of axon terminals. These results establish BG fibers as a guiding scaffold and CHL1 a molecular signal in the organization of stellate axon arbors and in directing their dendritic innervation.