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;


    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. (United States)

    Montemurro, Nicola; Herbet, Guillaume; Duffau, Hugues


    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


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


    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

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    Anne eSchuemann


    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

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    Christopher Nelson Hansen


    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. (United States)

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


    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.

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    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

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    Petra Wahle


    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. (United States)

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


    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


    Kuscha, Veronika


    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.

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    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.


    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


    [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;


    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 (United States)

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


    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: 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). (United States)

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


    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

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    Janina Neufeld


    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;


    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. (United States)

    Coulibaly, Aminata P; Isaacson, Lori G


    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


    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


    Bonanomi, Dario; Pfaff, Samuel L


    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. (United States)

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


    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


    Frisén, J


    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


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


    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.

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    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

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    Mario I Romero


    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


    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


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


    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


    Schnaar, Ronald L.


    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 (United States)

    Cao, Yan


    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 (United States)

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


    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]. (United States)

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


    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


    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


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


    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


    Kim, Eunjin; Jung, Hosung


    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



    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


    Yan, Yanping; Brown, Anthony


    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


    Lin, Andrew C; Holt, Christine E.


    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


    Städele, Carola


    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 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.


    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


    Lin, Andrew C; Holt, Christine E.


    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.


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


    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. (United States)

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


    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 (United States)

    FitzGibbon, Thomas; Nestorovski, Zoran


    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


    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


    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 (United States)

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


    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. (United States)

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


    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 (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


    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


    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


    Cai, Qian; Sheng, Zu-Hang


    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


    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. (United States)

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


    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: PMID:27594833

  17. Axonal regeneration through arterial grafts.


    Anderson, P. N.; Turmaine, M.


    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


    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 (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. (United States)

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


    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.


    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. (United States)

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


    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 (United States)

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


    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


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


    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


    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. (United States)

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


    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. (United States)

    Cheng, Pei-lin; Poo, Mu-ming


    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


    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 (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


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


    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


    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


    Sidra Arshad


    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


    Quysner, Annie; Surani, Salim; Roberts, Daniel


    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


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


    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. (United States)

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


    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 (United States)

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


    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)


    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 (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


    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). (United States)

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


    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 (United States)

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


    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.


    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


    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


    Chen, Shih-Yu; Cheng, Hwai-Jong


    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. (United States)

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


    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


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


    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


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


    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


    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. (United States)

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


    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 (United States)

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


    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. (United States)

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


    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


    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;


    . 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


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


    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 (United States)

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


    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


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


    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


    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


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


    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 (United States)

    Crago, Patrick E.; Makowski, Nathaniel S.


    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


    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


    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. (United States)

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


    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


    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 (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


    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 (United States)

    Bressloff, Paul C.; Levien, Ethan


    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. (United States)

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


    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


    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


    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


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


    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. (United States)

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


    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. (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


    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


    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



    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


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


    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


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


    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


    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


    Osterhout, Jessica A.


    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


    Huebner, Eric A.; Strittmatter, Stephen M


    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



    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


    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


    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 (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


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


    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. (United States)

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


    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


    Swathine.K*; Dr. J.KomalaLakshmi


    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


    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. (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


    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


    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. (United States)

    Sahoo, Debasis; Deck, Caroline; Willinger, Rémy


    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


    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. (United States)

    Hakala, Jussi; Kätsyri, Jari; Häkkinen, Jukka


    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


    Matthew R.J. MORRIS, Sean M. ROGERS


    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.


    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)


    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. (United States)

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


    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. (United States)

    Hausott, Barbara; Klimaschewski, Lars


    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. (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


    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


    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)



    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. (United States)

    McQuarrie, Irvine G; Lund, Linda M


    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)


    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.


    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. (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


    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


    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


    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. (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


    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 (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


    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


    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


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


    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


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


    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


    GORSON, K.; Ropper, A.


    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


    Zikopoulos, Basilis; Barbas, Helen


    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


    Michael Tytell; Lasek, Raymond J.; Harold Gainer


    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...





    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 (United States)

    Follmann, Rosangela; Rosa, Epaminondas; Stein, Wolfgang


    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


    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


    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


    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


    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


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


    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


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


    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


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


    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


    Fisseni, Bernhard; Lawrence, Faith


    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 (United States)

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


    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. (United States)

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


    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 (United States)

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


    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


    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 (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


    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


    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;


    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...



    Shrutika Sarangi


    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


    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


    DEFF Research Database (Denmark)

    Eriksen, Kaare


    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)


    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


    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. (United States)

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


    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


    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: [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)


    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]. (United States)

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


    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;


    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)


    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


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


    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. (United States)

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


    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


    Butt, Arthur; Bay, Virginia


    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


    Strupp, Michael; Grafe, Peter


    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


    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


    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 (United States)

    Nuriya, Mutsuo; Yasui, Masato


    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.


    Campbell, G; Shatz, C J


    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. (United States)

    Sanchez-Mendoza, Eduardo H; Hermann, Dirk Matthias


    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


    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 (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.


    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


    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


    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 (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


    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


    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


    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 (United States)

    Lai, Lipeng; Cao, Jianshu


    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


    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 (United States)

    Harrison, E. S.


    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


    Pećanac Marija Đ.


    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


    ČULIN, Jelena; Bielić, Toni


    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. (United States)

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


    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. (United States)

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


    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)



    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? (United States)

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


    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. (United States)

    Halden, Rolf U


    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


    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. (United States)

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


    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;


    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


    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


    Flatt, Nicholas


    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. (United States)

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


    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. (United States)

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


    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 (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


    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 (United States)

    Atanasov, Peter A.


    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. (United States)

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


    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 (United States)

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


    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. (United States)

    Sale, Alessandro; Berardi, Nicoletta; Maffei, Lamberto


    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 (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 (United States)

    Hammond, Nick


    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 (United States)

    Blau, Rivka; Klein, Pnina S.


    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;


    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 (United States)

    Ateh, Comfort M.


    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. (United States)

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


    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. (United States)

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


    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


    Hartenstein Volker; Spindler Shana R


    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...