Sample records for axon initial segment

  1. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy. (United States)

    Kole, Maarten H P; Letzkus, Johannes J; Stuart, Greg J


    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 microm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits.

  2. Action potentials initiate in the axon initial segment and propagate through axon collaterals reliably in cerebellar Purkinje neurons. (United States)

    Foust, Amanda; Popovic, Marko; Zecevic, Dejan; McCormick, David A


    Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By using a recent improvement in voltage-sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission.

  3. Fast and reliable identification of axons, axon initial segments and dendrites with local field potential recording

    DEFF Research Database (Denmark)

    Petersen, Anders V.; Johansen, Emil O.; Perrier, Jean-Francois


    The axon initial segment (AIS) is an essential neuronal compartment. It is usually where action potentials are initiated. Recent studies demonstrated that the AIS is a plastic structure that can be regulated by neuronal activity and by the activation of metabotropic receptors. Studying the AIS...... of neurons, we can detect sinks caused by inward currents flowing across the membrane. We determine the location of the AIS by comparing the timing of these events with the action potential. We demonstrate that this method allows the unequivocal identification of the AIS of different types of neurons from...

  4. Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons. (United States)

    Colbert, C M; Johnston, D


    A long-standing hypothesis is that action potentials initiate first in the axon hillock/initial segment (AH-IS) region because of a locally high density of Na+ channels. We tested this idea in subicular pyramidal neurons by using patch-clamp recordings in hippocampal slices. Simultaneous recordings from the soma and IS confirmed that orthodromic action potentials initiated in the axon and then invaded the soma. However, blocking Na+ channels in the AH-IS with locally applied tetrodotoxin (TTX) did not raise the somatic threshold membrane potential for orthodromic spikes. TTX applied to the axon beyond the AH-IS (30-60 microm from the soma) raised the apparent somatic threshold by approximately 8 mV. We estimated the Na+ current density in the AH-IS and somatic membranes by using cell-attached patch-clamp recordings and found similar magnitudes (3-4 pA/microm2). Thus, the present results suggest that orthodromic action potentials initiate in the axon beyond the AH-IS and that the minimum threshold for spike initiation of the neuron is not determined by a high density of Na+ channels in the AH-IS region.

  5. Kinesin I transports tetramerized Kv3 channels through the axon initial segment via direct binding. (United States)

    Xu, Mingxuan; Gu, Yuanzheng; Barry, Joshua; Gu, Chen


    Precise targeting of various voltage-gated ion channels to proper membrane domains is crucial for their distinct roles in neuronal excitability and synaptic transmission. How each channel protein is transported within the cytoplasm is poorly understood. Here, we report that KIF5/kinesin I transports Kv3.1 voltage-gated K(+) (Kv) channels through the axon initial segment (AIS) via direct binding. First, we have identified a novel interaction between Kv3.1 and KIF5, confirmed by immunoprecipitation from mouse brain lysates and by pull-down assays with exogenously expressed proteins. The interaction is mediated by a direct binding between the Kv3.1 N-terminal T1 domain and a conserved region in KIF5 tail domains, in which proper T1 tetramerization is crucial. Overexpression of this region of KIF5B markedly reduces axonal levels of Kv3.1bHA. In mature hippocampal neurons, endogenous Kv3.1b and KIF5 colocalize. Suppressing the endogenous KIF5B level by RNA interference significantly reduces the Kv3.1b axonal level. Furthermore, mutating the Zn(2+)-binding site within T1 markedly decreases channel axonal targeting and forward trafficking, likely through disrupting T1 tetramerization and hence eliminating the binding to KIF5 tail. The mutation also alters channel activity. Interestingly, coexpression of the YFP (yellow fluorescent protein)-tagged KIF5B assists dendritic Kv3.1a and even mutants with a faulty axonal targeting motif to penetrate the AIS. Finally, fluorescently tagged Kv3.1 channels colocalize and comove with KIF5B along axons revealed by two-color time-lapse imaging. Our findings suggest that the binding to KIF5 ensures properly assembled and functioning Kv3.1 channels to be transported into axons.

  6. Nanoscale Architecture of the Axon Initial Segment Reveals an Organized and Robust Scaffold

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    Christophe Leterrier


    Full Text Available The axon initial segment (AIS, located within the first 30 μm of the axon, has two essential roles in generating action potentials and maintaining axonal identity. AIS assembly depends on a ßIV-spectrin/ankyrin G scaffold, but its macromolecular arrangement is not well understood. Here, we quantitatively determined the AIS nanoscale architecture by using stochastic optical reconstruction microscopy (STORM. First, we directly demonstrate that the 190-nm periodicity of the AIS submembrane lattice results from longitudinal, head-to-head ßIV-spectrin molecules connecting actin rings. Using multicolor 3D-STORM, we resolve the nanoscale organization of ankyrin G: its amino terminus associates with the submembrane lattice, whereas the C terminus radially extends (∼32 nm on average toward the cytosol. This AIS nano-architecture is highly resistant to cytoskeletal perturbations, indicating its role in structural stabilization. Our findings provide a comprehensive view of AIS molecular architecture and will help reveal the crucial physiological functions of this compartment.

  7. Developmental Expression of Kv Potassium Channels at the Axon Initial Segment of Cultured Hippocampal Neurons (United States)

    Sánchez-Ponce, Diana; DeFelipe, Javier; Garrido, Juan José; Muñoz, Alberto


    Axonal outgrowth and the formation of the axon initial segment (AIS) are early events in the acquisition of neuronal polarity. The AIS is characterized by a high concentration of voltage-dependent sodium and potassium channels. However, the specific ion channel subunits present and their precise localization in this axonal subdomain vary both during development and among the types of neurons, probably determining their firing characteristics in response to stimulation. Here, we characterize the developmental expression of different subfamilies of voltage-gated potassium channels in the AISs of cultured mouse hippocampal neurons, including subunits Kv1.2, Kv2.2 and Kv7.2. In contrast to the early appearance of voltage-gated sodium channels and the Kv7.2 subunit at the AIS, Kv1.2 and Kv2.2 subunits were tethered at the AIS only after 10 days in vitro. Interestingly, we observed different patterns of Kv1.2 and Kv2.2 subunit expression, with each confined to distinct neuronal populations. The accumulation of Kv1.2 and Kv2.2 subunits at the AIS was dependent on ankyrin G tethering, it was not affected by disruption of the actin cytoskeleton and it was resistant to detergent extraction, as described previously for other AIS proteins. This distribution of potassium channels in the AIS further emphasizes the heterogeneity of this structure in different neuronal populations, as proposed previously, and suggests corresponding differences in action potential regulation. PMID:23119056

  8. β-Arrestin-Dependent Dopaminergic Regulation of Calcium Channel Activity in the Axon Initial Segment. (United States)

    Yang, Sungchil; Ben-Shalom, Roy; Ahn, Misol; Liptak, Alayna T; van Rijn, Richard M; Whistler, Jennifer L; Bender, Kevin J


    G-protein-coupled receptors (GPCRs) initiate a variety of signaling cascades, depending on effector coupling. β-arrestins, which were initially characterized by their ability to "arrest" GPCR signaling by uncoupling receptor and G protein, have recently emerged as important signaling effectors for GPCRs. β-arrestins engage signaling pathways that are distinct from those mediated by G protein. As such, arrestin-dependent signaling can play a unique role in regulating cell function, but whether neuromodulatory GPCRs utilize β-arrestin-dependent signaling to regulate neuronal excitability remains unclear. Here, we find that D3 dopamine receptors (D3R) regulate axon initial segment (AIS) excitability through β-arrestin-dependent signaling, modifying CaV3 voltage dependence to suppress high-frequency action potential generation. This non-canonical D3R signaling thereby gates AIS excitability via pathways distinct from classical GPCR signaling pathways.

  9. ATP-P2X7 Receptor Modulates Axon Initial Segment Composition and Function in Physiological Conditions and Brain Injury


    Puerto del Pino, Ana del; Fronzaroli-Molinieres, Laure; Pérez-Álvarez, María José; Giraud, Pierre; Carlier, Edmond; Wandosell, Francisco; Debanne, Dominique; Garrido, Juan José


    © 2014 The Author. All rights reserved. Axon properties, including action potential initiation and modulation, depend on both AIS integrity and the regulation of ion channel expression in the AIS. Alteration of the axon initial segment (AIS) has been implicated in neurodegenerative, psychiatric, and brain trauma diseases, thus identification of the physiological mechanisms that regulate the AIS is required to understand and circumvent AIS alterations in pathological conditions. Here, we show ...

  10. Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment

    DEFF Research Database (Denmark)

    Rasmussen, Hanne B; Frøkjaer-Jensen, Christian; Jensen, Camilla Stampe;


    The potassium channel subunits KCNQ2 and KCNQ3 are believed to underlie the M current of hippocampal neurons. The M-type potassium current plays a key role in the regulation of neuronal excitability; however, the subcellular location of the ion channels underlying this regulation has been...... controversial. We report here that KCNQ2 and KCNQ3 subunits are localized to the axon initial segment of pyramidal neurons of adult rat hippocampus and in cultured hippocampal neurons. We demonstrate that the localization of the KCNQ2/3 channel complex to the axon initial segment is favored by co......-expression of the two channel subunits. Deletion of the ankyrin-G-binding motif in both the KCNQ2 and KCNQ3 C-terminals leads to the disappearance of the complex from the axon initial segment, albeit the channel complex remains functional and still reaches the plasma membrane. We further show that although heteromeric...

  11. Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment (United States)

    Tapia, Mónica; Dominguez, Ana; Zhang, Wei; del Puerto, Ana; Ciorraga, María; Benitez, María José; Guaza, Carmen; Garrido, Juan José


    Neuronal polarization underlies the ability of neurons to integrate and transmit information. This process begins early in development with axon outgrowth, followed by dendritic growth and subsequent maturation. In between these two steps, the axon initial segment (AIS), a subcellular domain crucial for generating action potentials (APs) and maintaining the morphological and functional polarization, starts to develop. However, the cellular/molecular mechanisms and receptors involved in AIS initial development and maturation are mostly unknown. In this study, we have focused on the role of the type-1 cannabinoid receptor (CB1R), a highly abundant G-protein coupled receptor (GPCR) in the nervous system largely involved in different phases of neuronal development and differentiation. Although CB1R activity modulation has been related to changes in axons or dendrites, its possible role as a modulator of AIS development has not been yet explored. Here we analyzed the potential role of CB1R on neuronal morphology and AIS development using pharmacological and RNA interference approaches in cultured hippocampal neurons. CB1R inhibition, at a very early developmental stage, has no effect on axonal growth, yet CB1R activation can promote it. By contrast, subsequent dendritic growth is impaired by CB1R inhibition, which also reduces ankyrinG density at the AIS. Moreover, our data show a significant correlation between early dendritic growth and ankyrinG density. However, CB1R inhibition in later developmental stages after dendrites are formed only reduces ankyrinG accumulation at the AIS. In conclusion, our data suggest that neuronal CB1R basal activity plays a role in initial development of dendrites and indirectly in AIS proteins accumulation. Based on the lack of CB1R expression at the AIS, we hypothesize that CB1R mediated modulation of dendritic arbor size during early development indirectly determines the accumulation of ankyrinG and AIS development. Further studies

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

    DEFF Research Database (Denmark)

    Cotel, Florence; Exley, Richard; Cragg, Stephanie


    --as during motor exercise--activated 5-HT1A receptors that decreased motoneuronal excitability. Electrophysiological tests combined with pharmacology showed that focal activation of 5-HT1A receptors at the axon initial segment (AIS), but not on other motoneuronal compartments, inhibited the action potential...... adequately independently of the muscle physiology. Indirect evidence indicates that central fatigue is caused by serotonin (5-HT), but the cellular mechanisms are unknown. In a slice preparation from the spinal cord of the adult turtle, we found that prolonged stimulation of the raphe-spinal pathway...

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

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    Annika eGutzmann


    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

  14. Ion channel clustering at the axon initial segment and node of Ranvier evolved sequentially in early chordates.

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    Alexis S Hill


    Full Text Available In many mammalian neurons, dense clusters of ion channels at the axonal initial segment and nodes of Ranvier underlie action potential generation and rapid conduction. Axonal clustering of mammalian voltage-gated sodium and KCNQ (Kv7 potassium channels is based on linkage to the actin-spectrin cytoskeleton, which is mediated by the adaptor protein ankyrin-G. We identified key steps in the evolution of this axonal channel clustering. The anchor motif for sodium channel clustering evolved early in the chordate lineage before the divergence of the wormlike cephalochordate, amphioxus. Axons of the lamprey, a very primitive vertebrate, exhibited some invertebrate features (lack of myelin, use of giant diameter to hasten conduction, but possessed narrow initial segments bearing sodium channel clusters like in more recently evolved vertebrates. The KCNQ potassium channel anchor motif evolved after the divergence of lampreys from other vertebrates, in a common ancestor of shark and humans. Thus, clustering of voltage-gated sodium channels was a pivotal early innovation of the chordates. Sodium channel clusters at the axon initial segment serving the generation of action potentials evolved long before the node of Ranvier. KCNQ channels acquired anchors allowing their integration into pre-existing sodium channel complexes at about the same time that ancient vertebrates acquired myelin, saltatory conduction, and hinged jaws. The early chordate refinements in action potential mechanisms we have elucidated appear essential to the complex neural signaling, active behavior, and evolutionary success of vertebrates.

  15. Preferential targeting of Nav1.6 voltage-gated Na+ Channels to the axon initial segment during development.

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    Elizabeth J Akin

    Full Text Available During axonal maturation, voltage-gated sodium (Nav channels accumulate at the axon initial segment (AIS at high concentrations. This localization is necessary for the efficient initiation of action potentials. The mechanisms underlying channel trafficking to the AIS during axonal development have remained elusive due to a lack of Nav reagents suitable for high resolution imaging of channels located specifically on the cell surface. Using an optical pulse-chase approach in combination with a novel Nav1.6 construct containing an extracellular biotinylation domain we demonstrate that Nav1.6 channels are preferentially inserted into the AIS membrane during neuronal development via direct vesicular trafficking. Single-molecule tracking illustrates that axonal channels are immediately immobilized following delivery, while channels delivered to the soma are often mobile. Neither a Nav1.6 channel lacking the ankyrin-binding motif nor a chimeric Kv2.1 channel containing the Nav ankyrinG-binding domain show preferential AIS insertion. Together these data support a model where ankyrinG-binding is required for preferential Nav1.6 insertion into the AIS plasma membrane. In contrast, ankyrinG-binding alone does not confer the preferential delivery of proteins to the AIS.

  16. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation (United States)

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


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

  17. Bilaterian Giant Ankyrins Have a Common Evolutionary Origin and Play a Conserved Role in Patterning the Axon Initial Segment (United States)

    Jegla, Timothy; Nguyen, Michelle M.; Feng, Chengye; Goetschius, Daniel J.; van Rossum, Damian B.; Pisupati, Aditya; Milner, Elliott S.


    In vertebrate neurons, the axon initial segment (AIS) is specialized for action potential initiation. It is organized by a giant 480 Kd variant of ankyrin G (AnkG) that serves as an anchor for ion channels and is required for a plasma membrane diffusion barrier that excludes somatodendritic proteins from the axon. An unusually long exon required to encode this 480Kd variant is thought to have been inserted only recently during vertebrate evolution, so the giant ankyrin-based AIS scaffold has been viewed as a vertebrate adaptation for fast, precise signaling. We re-examined AIS evolution through phylogenomic analysis of ankyrins and by testing the role of ankyrins in proximal axon organization in a model multipolar Drosophila neuron (ddaE). We find giant isoforms of ankyrin in all major bilaterian phyla, and present evidence in favor of a single common origin for giant ankyrins and the corresponding long exon in a bilaterian ancestor. This finding raises the question of whether giant ankyrin isoforms play a conserved role in AIS organization throughout the Bilateria. We examined this possibility by looking for conserved ankyrin-dependent AIS features in Drosophila ddaE neurons via live imaging. We found that ddaE neurons have an axonal diffusion barrier proximal to the cell body that requires a giant isoform of the neuronal ankyrin Ank2. Furthermore, the potassium channel shal concentrates in the proximal axon in an Ank2-dependent manner. Our results indicate that the giant ankyrin-based cytoskeleton of the AIS may have evolved prior to the radiation of extant bilaterian lineages, much earlier than previously thought. PMID:27911898

  18. The Kv2.1 K+ channel targets to the axon initial segment of hippocampal and cortical neurons in culture and in situ

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    Tamkun Michael M


    Full Text Available Abstract Background The Kv2.1 delayed-rectifier K+ channel regulates membrane excitability in hippocampal neurons where it targets to dynamic cell surface clusters on the soma and proximal dendrites. In the past, Kv2.1 has been assumed to be absent from the axon initial segment. Results Transfected and endogenous Kv2.1 is now demonstrated to preferentially accumulate within the axon initial segment (AIS over other neurite processes; 87% of 14 DIV hippocampal neurons show endogenous channel concentrated at the AIS relative to the soma and proximal dendrites. In contrast to the localization observed in pyramidal cells, GAD positive inhibitory neurons within the hippocampal cultures did not show AIS targeting. Photoactivable-GFP-Kv2.1-containing clusters at the AIS were stable, moving μm/hr with no channel turnover. Photobleach studies indicated individual channels within the cluster perimeter were highly mobile (FRAP τ = 10.4 ± 4.8 sec, supporting our model that Kv2.1 clusters are formed by the retention of mobile channels behind a diffusion-limiting perimeter. Demonstrating that the AIS targeting is not a tissue culture artifact, Kv2.1 was found in axon initial segments within both the adult rat hippocampal CA1, CA2, and CA3 layers and cortex. Conclusion In summary, Kv2.1 is associated with the axon initial segment both in vitro and in vivo where it may modulate action potential frequency and back propagation. Since transfected Kv2.1 initially localizes to the AIS before appearing on the soma, it is likely multiple mechanisms regulate Kv2.1 trafficking to the cell surface.

  19. Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice. (United States)

    Herde, Michel K; Herbison, Allan E


    GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

  20. Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures. (United States)

    Dinocourt, Celine; Petanjek, Zdravko; Freund, Tamas F; Ben-Ari, Yezekiel; Esclapez, Monique


    In the pilocarpine model of chronic limbic seizures, vulnerability of GABAergic interneurons to excitotoxic damage has been reported in the hippocampal CA1 region. However, little is known about the specific types of interneurons that degenerate in this region. In order to characterize these interneurons, we performed quantitative analyses of the different populations of GABAergic neurons labeled for their peptide or calcium-binding protein content. Our data demonstrate that the decrease in the number of GAD mRNA-containing neurons in the stratum oriens of CA1 in pilocarpine-treated rats involved two subpopulations of GABAergic interneurons: interneurons labeled for somatostatin only (O-LM and bistratified cells) and interneurons labeled for parvalbumin only (basket and axo-axonic cells). Stratum oriens interneurons labeled for somatostatin/calbindin or somatostatin/parvalbumin were preserved. The decrease in number of somatostatin- and parvalbumin-containing neurons was observed as early as 72 hours after the sustained seizures induced by pilocarpine injection. Many degenerating cell bodies in the stratum oriens and degenerating axon terminals in the stratum lacunosum-moleculare were observed at 1 and 2 weeks after injection. In addition, the synaptic coverage of the axon initial segment of CA1 pyramidal cells was significantly decreased in pilocarpine-treated animals. These results indicate that the loss of somatostatin-containing neurons corresponds preferentially to the degeneration of interneurons with an axon projecting to stratum lacunosum-moleculare (O-LM cells) and suggest that the death of these neurons is mainly responsible for the deficit of dendritic inhibition reported in this region. We demonstrate that the loss of parvalbumin-containing neurons corresponds to the death of axo-axonic cells, suggesting that perisomatic inhibition and mechanisms controlling action potential generation are also impaired in this model.

  1. Distinct Kv channel subtypes contribute to differences in spike signaling properties in the axon initial segment and presynaptic boutons of cerebellar interneurons. (United States)

    Rowan, Matthew J M; Tranquil, Elizabeth; Christie, Jason M


    The discrete arrangement of voltage-gated K(+) (Kv) channels in axons may impart functional advantages in action potential (AP) signaling yet, in compact cell types, the organization of Kv channels is poorly understood. We find that in cerebellar stellate cell interneurons of mice, the composition and influence of Kv channels populating the axon is diverse and depends on location allowing axonal compartments to differentially control APs in a local manner. Kv1 channels determine AP repolarization at the spike initiation site but not at more distal sites, limiting the expression of use-dependent spike broadening to the most proximal axon region, likely a key attribute informing spiking phenotype. Local control of AP repolarization at presynaptic boutons depends on Kv3 channels keeping APs brief, thus limiting Ca(2+) influx and synaptic strength. These observations suggest that AP repolarization is tuned by the local influence of distinct Kv channel types, and this organization enhances the functional segregation of axonal compartments.

  2. 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:

  3. Live Imaging of Kv7.2/7.3 Cell Surface Dynamics at the Axon Initial Segment: High Steady-State Stability and Calpain-Dependent Excitotoxic Downregulation Revealed

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Christensen, Rasmus Kordt; Denti, Federico;


    The voltage-gated K(+) channels Kv7.2 and Kv7.3 are located at the axon initial segment (AIS) and exert strong control over action potential generation. Therefore, changes in their localization or cell surface numbers are likely to influence neuronal signaling. However, nothing is known about......7.3. This seven transmembrane chimera, named super ecliptic phluorin (SEP)-TAC-7.3, functions and traffics as a wild-type (WT) channel. We expressed SEP-TAC-7.3 in dissociated rat hippocampal neurons to examine the lateral mobility, surface numbers, and localization of AIS Kv7.2/7.3 heteromers using...... STATEMENT: The voltage-gated K(+) channels Kv7.2 and Kv7.3 exert strong control over action potential generation, but little is known about their cell surface dynamics. Using a novel phluorin-based approach, we here show that these channels are highly stable at steady state and different types of neuronal...

  4. Initiation and blocking of the action potential in the axon in a weak ultrasonic field

    CERN Document Server

    Shneider, M N


    It is shown that the longitudinal standing ultrasonic wave of low intensity leads to the lateral drift and to redistribution of the transmembrane ion channels in the initial segment of the myelinated axon of a neuron. The analysis is based on the Hodgkin - Huxley model of an axon. Redistribution of the density of transmembrane sodium channels, caused by ultrasound, may reduce the threshold of the action potential, up to its spontaneous initiation. At significant redistribution of sodium channels in membrane, the zones of rarefaction of the transmembrane channels density are formed blocking the propagation of the action potential. After switching the ultrasound off, the unperturbed uniform distribution of transmembrane channels in the axon recovers due to lateral diffusion. The blocking effect of the action potential can be used in anesthesia.

  5. Compliance with Segment Disclosure Initiatives

    DEFF Research Database (Denmark)

    Arya, Anil; Frimor, Hans; Mittendorf, Brian


    Regulatory oversight of capital markets has intensified in recent years, with a particular emphasis on expanding financial transparency. A notable instance is efforts by the Financial Accounting Standards Board that push firms to identify and report performance of individual business units...... (segments). This paper seeks to address short-run and long-run consequences of stringent enforcement of and uniform compliance with these segment disclosure standards. To do so, we develop a parsimonious model wherein a regulatory agency promulgates disclosure standards and either permits voluntary...... compliance or mandates strict compliance from firms. Under voluntary compliance, a firm is able to credibly withhold individual segment information from its competitors by disclosing data only at the aggregate firm level. Consistent with regulatory hopes, we show that mandatory compliance enhances welfare...

  6. Network structure implied by initial axon outgrowth in rodent cortex: empirical measurement and models. (United States)

    Cahalane, Diarmuid J; Clancy, Barbara; Kingsbury, Marcy A; Graf, Ethan; Sporns, Olaf; Finlay, Barbara L


    The developmental mechanisms by which the network organization of the adult cortex is established are incompletely understood. Here we report on empirical data on the development of connections in hamster isocortex and use these data to parameterize a network model of early cortical connectivity. Using anterograde tracers at a series of postnatal ages, we investigate the growth of connections in the early cortical sheet and systematically map initial axon extension from sites in anterior (motor), middle (somatosensory) and posterior (visual) cortex. As a general rule, developing axons extend from all sites to cover relatively large portions of the cortical field that include multiple cortical areas. From all sites, outgrowth is anisotropic, covering a greater distance along the medial/lateral axis than along the anterior/posterior axis. These observations are summarized as 2-dimensional probability distributions of axon terminal sites over the cortical sheet. Our network model consists of nodes, representing parcels of cortex, embedded in 2-dimensional space. Network nodes are connected via directed edges, representing axons, drawn according to the empirically derived anisotropic probability distribution. The networks generated are described by a number of graph theoretic measurements including graph efficiency, node betweenness centrality and average shortest path length. To determine if connectional anisotropy helps reduce the total volume occupied by axons, we define and measure a simple metric for the extra volume required by axons crossing. We investigate the impact of different levels of anisotropy on network structure and volume. The empirically observed level of anisotropy suggests a good trade-off between volume reduction and maintenance of both network efficiency and robustness. Future work will test the model's predictions for connectivity in larger cortices to gain insight into how the regulation of axonal outgrowth may have evolved to achieve efficient

  7. Mechanisms of axon degeneration: from development to disease. (United States)

    Saxena, Smita; Caroni, Pico


    Axon degeneration is an active, tightly controlled and versatile process of axon segment self-destruction. Although not involving cell death, it resembles apoptosis in its logics. It involves three distinct steps: induction of competence in specific neurons, triggering of degeneration at defined axon segments of competent neurons, and rapid fragmentation and removal of the segments. The mechanisms that initiate degeneration are specific to individual settings, but the final pathway of pruning is shared; it involves microtubule disassembly, axon swellings, axon fragmentation, and removal of the remnants by locally recruited phagocytes. The tight regulatory properties of axon degeneration distinguish it from passive loss phenomena, and confer significance to processes that involve it. Axon degeneration has prominent roles in development, upon lesions and in disease. In development, it couples the progressive specification of neurons and circuits to the removal of defined axon branches. Competence might involve transcriptional switches, and local triggering can involve axon guidance molecules and synaptic activity patterns. Lesion-induced Wallerian degeneration is inhibited in the presence of Wld(S) fusion protein in neurons; it involves early local, and later, distal degeneration. It has recently become clear that like in other settings, axon degeneration in disease is a rapid and specific process, which should not be confused with a variety of disease-related pathologies. Elucidating the specific mechanisms that initiate axon degeneration should open up new avenues to investigate principles of circuit assembly and plasticity, to uncover mechanisms of disease progression, and to identify ways of protecting synapses and axons in disease.

  8. Molecular composition of the node of Ranvier: identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain-) and NrCAM at nodal axon segments. (United States)

    Davis, J Q; Lambert, S; Bennett, V


    Neurofascin, NrCAM, L1, and NgCAM are a family of Ig/FNIII cell adhesion molecules that share ankyrin-binding activity in their cytoplasmic domains, and are candidates to form membrane-spanning complexes with members of the ankyrin family of spectrin-binding proteins in a variety of cellular contexts in the nervous system. Specialized forms of ankyrin, 270 kD and/or 480 kD ankyrinG are components of the membrane undercoat of axons at the node of Ranvier. This paper focuses on definition of the isoforms of ankyrin-binding cell adhesion molecules localized with ankyrinG at the nodal axon segment. The exon usage of two major forms of neurofascin was determined by isolation of full-length cDNAs and used to prepare isoform-specific antibodies. An isoform of neurofascin containing a mucin-like domain and lacking the third FNIII domain was concentrated at axon initial segments and colocalized at nodes of Ranvier with ankyrinG and the voltage-dependent sodium channel. An alternative form of neurofascin lacking the mucin-like domain and containing the third FNIII domain was present in unmyelinated axons. The antibody initially raised against neurofascin was used to screen a rat brain cDNA expression library. In addition to neurofascin, this screen yielded a clone with 80% sequence identity to NrCAM from chicken. The sequences of two full-length cDNAs are presented. NrCAM is most closely related to neurofascin among the other members of the L1/neurofascin/NgCAM family, with over 70% identity between cytoplasmic domains. NrCAM, visualized with antibodies specific for the ecto-domain, also was found to be coexpressed with neurofascin at nodes of Ranvier and at axon initial segments. This is the first characterization of defined neuronal cell adhesion molecules localized to axonal membranes at the node of Ranvier of myelinated axons.

  9. Mixed Initiative in Dialogue An Investigation into Discourse Segmentation

    CERN Document Server

    Walker, M; Walker, Marilyn; Whittaker, Steve


    Conversation between two people is usually of mixed-initiative, with control over the conversation being transferred from one person to another. We apply a set of rules for the transfer of control to 4 sets of dialogues consisting of a total of 1862 turns. The application of the control rules lets us derive domain-independent discourse structures. The derived structures indicate that initiative plays a role in the structuring of discourse. In order to explore the relationship of control and initiative to discourse processes like centering, we analyze the distribution of four different classes of anaphora for two data sets. This distribution indicates that some control segments are hierarchically related to others. The analysis suggests that discourse participants often mutually agree to a change of topic. We also compared initiative in Task Oriented and Advice Giving dialogues and found that both allocation of control and the manner in which control is transferred is radically different for the two dialogue t...

  10. Estimation of Initial Position Using Line Segment Matching in Maps

    Directory of Open Access Journals (Sweden)

    Chongyang Wei


    Full Text Available While navigating in a typical traffic scene, with a drastic drift or sudden jump in its Global Positioning System (GPS position, the localization based on such an initial position is unable to extract precise overlapping data from the prior map in order to match the current data, thus rendering the localization as unfeasible. In this paper, we first propose a new method to estimate an initial position by matching the infrared reflectivity maps. The maps consist of a highly precise prior map, built with the offline simultaneous localization and mapping (SLAM technique, and a smooth current map, built with the integral over velocities. Considering the attributes of the maps, we first propose to exploit the stable, rich line segments to match the lidar maps. To evaluate the consistency of the candidate line pairs in both maps, we propose to adopt the local appearance, pairwise geometric attribute and structural likelihood to construct an affinity graph, as well as employ a spectral algorithm to solve the graph efficiently. The initial position is obtained according to the relationship between the vehicle’s current position and matched lines. Experiments on the campus with a GPS error of dozens of metres show that our algorithm can provide an accurate initial value with average longitudinal and lateral errors being 1.68m and 1.04m, respectively.

  11. Segmental mode of neural patterning in sipuncula

    DEFF Research Database (Denmark)

    Kristof, Alen; Wollesen, Tim; Wanninger, Andreas


    sipunculan, Phascolosoma agassizii, we found that neurogenesis initially follows a segmental pattern similar to that of annelids. Starting out with paired FMRFamidergic and serotonergic axons, four pairs of associated serotonergic perikarya and interconnecting commissures form one after another...

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


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


    Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle adequately independently of the muscle physiology. Indirect evidence indicates that central fatigue is caused by serotonin (5-HT), but the cellular mechanisms are unknown. In a slice preparation from the spi...

  13. Initial Object Segmentation for Video Object Plane GenerationUsing Cellular Neural Networks

    Institute of Scientific and Technical Information of China (English)

    王慧; 杨高波; 张兆杨


    MPEG-4 is a basic tool for interactivity and manipulation of video sequences. Video object segmentation is a key issue in defining the content of any video sequence, which is often divided into two steps: initial object segmentation and object tracking. In this paper, an initial object segmentation method for video object plane(VOP) generation using color information is proposed. Based on 3 by 3 linear templates, a cellular neural network (CNN) is used to implemented object segmentation. The Experimental results arepresented to verify the efficiency and robustness of this approach.

  14. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons

    NARCIS (Netherlands)

    Battefeld, A.; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P


    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axon

  15. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons

    NARCIS (Netherlands)

    Battefeld, A.; Tran, B.T.; Gavrilis, J.; Cooper, E.C.; Kole, Maarten


    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of Kv7 potassium channels and voltage-gated sodium (Nav ) channels in the axonal

  16. Loss of Saltation and Presynaptic Action Potential Failure in Demyelinated Axons (United States)

    Hamada, Mustafa S.; Popovic, Marko A.; Kole, Maarten H. P.


    In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood. Here, using the cuprizone demyelination model, we performed optical voltage-sensitive dye (VSD) imaging from control and demyelinated layer 5 pyramidal neuron axons. In the main axon, we find that myelin loss switches the modality of AP propagation from rapid saltation towards a slow continuous wave. The duration of single AP waveforms at BPs or nodes was, however, only slightly briefer. In contrast, by using two-photon microscopy-guided loose-seal patch recordings from axon collaterals we revealed a presynaptic AP broadening in combination with a reduced velocity and frequency-dependent failure. Finally, internodal myelin loss was also associated with de novo sprouting of axon collaterals starting from the primary (demyelinated) axon. Thus, the loss of oligodendrocytes and myelin sheaths bears functional consequences beyond the main axon, impeding the temporal fidelity of presynaptic APs and affecting the functional and structural organization of synaptic connectivity within the neocortex.

  17. Role of calpains in the injury-induced dysfunction and degeneration of the mammalian axon. (United States)

    Ma, Marek


    Axonal injury and degeneration, whether primary or secondary, contribute to the morbidity and mortality seen in many acquired and inherited central nervous system (CNS) and peripheral nervous system (PNS) disorders, such as traumatic brain injury, spinal cord injury, cerebral ischemia, neurodegenerative diseases, and peripheral neuropathies. The calpain family of proteases has been mechanistically linked to the dysfunction and degeneration of axons. While the direct mechanisms by which transection, mechanical strain, ischemia, or complement activation trigger intra-axonal calpain activity are likely different, the downstream effects of unregulated calpain activity may be similar in seemingly disparate diseases. In this review, a brief examination of axonal structure is followed by a focused overview of the calpain family. Finally, the mechanisms by which calpains may disrupt the axonal cytoskeleton, transport, and specialized domains (axon initial segment, nodes, and terminals) are discussed.

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

    Directory of Open Access Journals (Sweden)

    Pietro eBalbi


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

  19. Synchrony dynamics during initiation, failure, and rescue of the segmentation clock. (United States)

    Riedel-Kruse, Ingmar H; Müller, Claudia; Oates, Andrew C


    The "segmentation clock" is thought to coordinate sequential segmentation of the body axis in vertebrate embryos. This clock comprises a multicellular genetic network of synchronized oscillators, coupled by intercellular Delta-Notch signaling. How this synchrony is established and how its loss determines the position of segmentation defects in Delta and Notch mutants are unknown. We analyzed the clock's synchrony dynamics by varying strength and timing of Notch coupling in zebra-fish embryos with techniques for quantitative perturbation of gene function. We developed a physical theory based on coupled phase oscillators explaining the observed onset and rescue of segmentation defects, the clock's robustness against developmental noise, and a critical point beyond which synchrony decays. We conclude that synchrony among these genetic oscillators can be established by simultaneous initiation and self-organization and that the segmentation defect position is determined by the difference between coupling strength and noise.

  20. Myelin loss and axonal ion channel adaptations associated with gray matter neuronal hyperexcitability

    NARCIS (Netherlands)

    Hamada, Mustafa S; Kole, Maarten H P


    Myelination and voltage-gated ion channel clustering at the nodes of Ranvier are essential for the rapid saltatory conduction of action potentials. Whether myelination influences the structural organization of the axon initial segment (AIS) and action potential initiation is poorly understood. Using

  1. Liver segmentation with new supervised method to create initial curve for active contour. (United States)

    Zareei, Abouzar; Karimi, Abbas


    The liver performs a critical task in the human body; therefore, detecting liver diseases and preparing a robust plan for treating them are both crucial. Liver diseases kill nearly 25,000 Americans every year. A variety of image segmentation methods are available to determine the liver's position and to detect possible liver tumors. Among these is the Active Contour Model (ACM), a framework which has proven very sensitive to initial contour delineation and control parameters. In the proposed method based on image energy, we attempted to obtain an initial segmentation close to the liver's boundary, and then implemented an ACM to improve the initial segmentation. The ACM used in this work incorporates gradient vector flow (GVF) and balloon energy in order to overcome ACM limitations, such as local minima entrapment and initial contour dependency. Additionally, in order to adjust active contour control parameters, we applied a genetic algorithm to produce a proper parameter set close to the optimal solution. The pre-processing method has a better ability to segment the liver tissue during a short time with respect to other mentioned methods in this paper. The proposed method was performed using Sliver CT image datasets. The results show high accuracy, precision, sensitivity, specificity and low overlap error, MSD and runtime with few ACM iterations.

  2. Polarized axonal surface expression of neuronal KCNQ potassium channels is regulated by calmodulin interaction with KCNQ2 subunit.

    Directory of Open Access Journals (Sweden)

    John P Cavaretta

    Full Text Available KCNQ potassium channels composed of KCNQ2 and KCNQ3 subunits give rise to the M-current, a slow-activating and non-inactivating voltage-dependent potassium current that limits repetitive firing of action potentials. KCNQ channels are enriched at the surface of axons and axonal initial segments, the sites for action potential generation and modulation. Their enrichment at the axonal surface is impaired by mutations in KCNQ2 carboxy-terminal tail that cause benign familial neonatal convulsion and myokymia, suggesting that their correct surface distribution and density at the axon is crucial for control of neuronal excitability. However, the molecular mechanisms responsible for regulating enrichment of KCNQ channels at the neuronal axon remain elusive. Here, we show that enrichment of KCNQ channels at the axonal surface of dissociated rat hippocampal cultured neurons is regulated by ubiquitous calcium sensor calmodulin. Using immunocytochemistry and the cluster of differentiation 4 (CD4 membrane protein as a trafficking reporter, we demonstrate that fusion of KCNQ2 carboxy-terminal tail is sufficient to target CD4 protein to the axonal surface whereas inhibition of calmodulin binding to KCNQ2 abolishes axonal surface expression of CD4 fusion proteins by retaining them in the endoplasmic reticulum. Disruption of calmodulin binding to KCNQ2 also impairs enrichment of heteromeric KCNQ2/KCNQ3 channels at the axonal surface by blocking their trafficking from the endoplasmic reticulum to the axon. Consistently, hippocampal neuronal excitability is dampened by transient expression of wild-type KCNQ2 but not mutant KCNQ2 deficient in calmodulin binding. Furthermore, coexpression of mutant calmodulin, which can interact with KCNQ2/KCNQ3 channels but not calcium, reduces but does not abolish their enrichment at the axonal surface, suggesting that apo calmodulin but not calcium-bound calmodulin is necessary for their preferential targeting to the axonal

  3. Motor axon excitability during Wallerian degeneration

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez, Susana; Krarup, Christian


    , action potential propagation and structural integrity of the distal segment are maintained. The aim of this study was to investigate in vivo the changes in membrane function of motor axons during the 'latent' phase of Wallerian degeneration. Multiple indices of axonal excitability of the tibial nerve...

  4. Action-potential modulation during axonal conduction. (United States)

    Sasaki, Takuya; Matsuki, Norio; Ikegaya, Yuji


    Once initiated near the soma, an action potential (AP) is thought to propagate autoregeneratively and distribute uniformly over axonal arbors. We challenge this classic view by showing that APs are subject to waveform modulation while they travel down axons. Using fluorescent patch-clamp pipettes, we recorded APs from axon branches of hippocampal CA3 pyramidal neurons ex vivo. The waveforms of axonal APs increased in width in response to the local application of glutamate and an adenosine A(1) receptor antagonist to the axon shafts, but not to other unrelated axon branches. Uncaging of calcium in periaxonal astrocytes caused AP broadening through ionotropic glutamate receptor activation. The broadened APs triggered larger calcium elevations in presynaptic boutons and facilitated synaptic transmission to postsynaptic neurons. This local AP modification may enable axonal computation through the geometry of axon wiring.

  5. Dendrite-derived supernumerary axons on adult axotomized motor neurons possess proteins that are essential for the initiation and propagation of action potentials and synaptic vesicle release

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; MacDermid, Victoria E; Montague, Steven J;


    . This study extends this definition to determine whether, more importantly, these processes possess the prerequisite molecular machinery to function as axons. Using a combination of intracellular labeling and immunohistochemistry, we demonstrate that the distribution of voltage-gated sodium channels...

  6. Fully automatic prostate segmentation from transrectal ultrasound images based on radial bas-relief initialization and slice-based propagation. (United States)

    Yu, Yanyan; Chen, Yimin; Chiu, Bernard


    Prostate segmentation from transrectal ultrasound (TRUS) images plays an important role in the diagnosis and treatment planning of prostate cancer. In this paper, a fully automatic slice-based segmentation method was developed to segment TRUS prostate images. The initial prostate contour was determined using a novel method based on the radial bas-relief (RBR) method, and a false edge removal algorithm proposed here in. 2D slice-based propagation was used in which the contour on each image slice was deformed using a level-set evolution model, which was driven by edge-based and region-based energy fields generated by dyadic wavelet transform. The optimized contour on an image slice propagated to the adjacent slice, and subsequently deformed using the level-set model. The propagation continued until all image slices were segmented. To determine the initial slice where the propagation began, the initial prostate contour was deformed individually on each transverse image. A method was developed to self-assess the accuracy of the deformed contour based on the average image intensity inside and outside of the contour. The transverse image on which highest accuracy was attained was chosen to be the initial slice for the propagation process. Evaluation was performed for 336 transverse images from 15 prostates that include images acquired at mid-gland, base and apex regions of the prostates. The average mean absolute difference (MAD) between algorithm and manual segmentations was 0.79±0.26mm, which is comparable to results produced by previously published semi-automatic segmentation methods. Statistical evaluation shows that accurate segmentation was not only obtained at the mid-gland, but also at the base and apex regions.

  7. Action potential generation in an anatomically constrained model of medial superior olive axons. (United States)

    Lehnert, Simon; Ford, Marc C; Alexandrova, Olga; Hellmundt, Franziska; Felmy, Felix; Grothe, Benedikt; Leibold, Christian


    Neurons in the medial superior olive (MSO) encode interaural time differences (ITDs) with sustained firing rates of >100 Hz. They are able to generate such high firing rates for several hundred milliseconds despite their extremely low-input resistances of only few megaohms and high synaptic conductances in vivo. The biophysical mechanisms by which these leaky neurons maintain their excitability are not understood. Since action potentials (APs) are usually assumed to be generated in the axon initial segment (AIS), we analyzed anatomical data of proximal MSO axons in Mongolian gerbils and found that the axon diameter is <1 μm and the internode length is ∼100 μm. Using a morphologically constrained computational model of the MSO axon, we show that these thin axons facilitate the excitability of the AIS. However, for ongoing high rates of synaptic inputs the model generates a substantial fraction of APs in its nodes of Ranvier. These distally initiated APs are mediated by a spatial gradient of sodium channel inactivation and a strong somatic current sink. The model also predicts that distal AP initiation increases the dynamic range of the rate code for ITDs.

  8. Laser-based single-axon transection for high-content axon injury and regeneration studies.

    Directory of Open Access Journals (Sweden)

    Darío Kunik

    Full Text Available The investigation of the regenerative response of the neurons to axonal injury is essential to the development of new axoprotective therapies. Here we study the retinal neuronal RGC-5 cell line after laser transection, demonstrating that the ability of these cells to initiate a regenerative response correlates with axon length and cell motility after injury. We show that low energy picosecond laser pulses can achieve transection of unlabeled single axons in vitro and precisely induce damage with micron precision. We established the conditions to achieve axon transection, and characterized RGC-5 axon regeneration and cell body response using time-lapse microscopy. We developed an algorithm to analyze cell trajectories and established correlations between cell motility after injury, axon length, and the initiation of the regeneration response. The characterization of the motile response of axotomized RGC-5 cells showed that cells that were capable of repair or regrowth of damaged axons migrated more slowly than cells that could not. Moreover, we established that RGC-5 cells with long axons could not recover their injured axons, and such cells were much more motile. The platform we describe allows highly controlled axonal damage with subcellular resolution and the performance of high-content screening in cell cultures.

  9. 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.

  10. Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation. (United States)

    Saga, Y; Hata, N; Koseki, H; Taketo, M M


    We isolated a novel bHLH protein gene Mesp2 (for mesoderm posterior 2) that cross-hybridizes with Mesp1 expressed in the early mouse mesoderm. Mesp2 is expressed in the rostral presomitic mesoderm, but down-regulated immediately after the formation of the segmented somites. To determine the function of MesP2 protein (MesP2) in somitogenesis, we generated Mesp2-deficient mice by gene targeting. The homozygous Mesp2 (-/-) mice died shortly after birth and had fused vertebral columns and dorsal root ganglia, with impaired sclerotomal polarity. The earliest defect in the homozygous embryos was a lack of segmented somites. Their disruption of the metameric features, altered expression of Mox-1, Pax-1, and Dll1, and lack of expression of Notch1, Notch2, and FGFR1 suggested that MesP2 controls sclerotomal polarity by regulating the signaling systems mediated by notch-delta and FGF, which are essential for segmentation.

  11. The cytoskeleton-associated protein SCHIP1 is involved in axon guidance, and is required for piriform cortex and anterior commissure development. (United States)

    Klingler, Esther; Martin, Pierre-Marie; Garcia, Marta; Moreau-Fauvarque, Caroline; Falk, Julien; Chareyre, Fabrice; Giovannini, Marco; Chédotal, Alain; Girault, Jean-Antoine; Goutebroze, Laurence


    SCHIP1 is a cytoplasmic partner of cortical cytoskeleton ankyrins. The IQCJ-SCHIP1 isoform is a component of axon initial segments and nodes of Ranvier of mature axons in peripheral and central nervous systems, where it associates with membrane complexes comprising cell adhesion molecules. SCHIP1 is also expressed in the mouse developing central nervous system during embryonic stages of active axonogenesis. Here, we identify a new and early role for SCHIP1 during axon development and establishment of the anterior commissure (AC). The AC is composed of axons from the piriform cortex, the anterior olfactory nucleus and the amygdala. Schip1 mutant mice displayed early defects in AC development that might result from impaired axon growth and guidance. In addition, mutant mice presented a reduced thickness of the piriform cortex, which affected projection neurons in layers 2/3 and was likely to result from cell death rather than from impairment of neuron generation or migration. Piriform cortex neurons from E14.5 mutant embryos displayed axon initiation/outgrowth delay and guidance defects in vitro. The sensitivity of growth cones to semaphorin 3F and Eph receptor B2, two repulsive guidance cues crucial for AC development, was increased, providing a possible basis for certain fiber tract alterations. Thus, our results reveal new evidence for the involvement of cortical cytoskeleton-associated proteins in the regulation of axon development and their importance for the formation of neuronal circuits.

  12. Rapid Automated Target Segmentation and Tracking on 4D Data without Initial Contours

    Directory of Open Access Journals (Sweden)

    Venkata V. Chebrolu


    Full Text Available Purpose. To achieve rapid automated delineation of gross target volume (GTV and to quantify changes in volume/position of the target for radiotherapy planning using four-dimensional (4D CT. Methods and Materials. Novel morphological processing and successive localization (MPSL algorithms were designed and implemented for achieving autosegmentation. Contours automatically generated using MPSL method were compared with contours generated using state-of-the-art deformable registration methods (using Elastix© and MIMVista software. Metrics such as the Dice similarity coefficient, sensitivity, and positive predictive value (PPV were analyzed. The target motion tracked using the centroid of the GTV estimated using MPSL method was compared with motion tracked using deformable registration methods. Results. MPSL algorithm segmented the GTV in 4DCT images in 27.0±11.1 seconds per phase (512×512 resolution as compared to 142.3±11.3 seconds per phase for deformable registration based methods in 9 cases. Dice coefficients between MPSL generated GTV contours and manual contours (considered as ground-truth were 0.865±0.037. In comparison, the Dice coefficients between ground-truth and contours generated using deformable registration based methods were 0.909 ± 0.051. Conclusions. The MPSL method achieved similar segmentation accuracy as compared to state-of-the-art deformable registration based segmentation methods, but with significant reduction in time required for GTV segmentation.

  13. Axon diversity of lamina I local-circuit neurons in the lumbar spinal cord. (United States)

    Szucs, Peter; Luz, Liliana L; Pinho, Raquel; Aguiar, Paulo; Antal, Zsófia; Tiong, Sheena Y X; Todd, Andrew J; Safronov, Boris V


    Spinal lamina I is a key area for relaying and integrating information from nociceptive primary afferents with various other sources of inputs. Although lamina I projection neurons have been intensively studied, much less attention has been given to local-circuit neurons (LCNs), which form the majority of the lamina I neuronal population. In this work the infrared light-emitting diode oblique illumination technique was used to visualize and label LCNs, allowing reconstruction and analysis of their dendritic and extensive axonal trees. We show that the majority of lamina I neurons with locally branching axons fall into the multipolar (with ventrally protruding dendrites) and flattened (dendrites limited to lamina I) somatodendritic categories. Analysis of their axons revealed that the initial myelinated part gives rise to several unmyelinated small-diameter branches that have a high number of densely packed, large varicosities and an extensive rostrocaudal (two or three segments), mediolateral, and dorsoventral (reaching laminae III-IV) distribution. The extent of the axon and the occasional presence of long, solitary branches suggest that LCNs may also form short and long propriospinal connections. We also found that the distribution of axon varicosities and terminal field locations show substantial heterogeneity and that a substantial portion of LCNs is inhibitory. Our observations indicate that LCNs of lamina I form intersegmental as well as interlaminar connections and may govern large numbers of neurons, providing anatomical substrate for rostrocaudal "processing units" in the dorsal horn.

  14. Early ambulance initiation versus in-hospital initiation of high dose clopidogrel in ST-segment elevation myocardial infarction

    NARCIS (Netherlands)

    Postma, S.; Dambrink, J.H.; Ottervanger, J.P.; Gosselink, A.T.M.; Koopmans, P.C.; Berg, J.M. van den; Suryapranata, H.; Hof, A.W. van 't


    Pre-hospital infarct diagnosis gives the opportunity to start anti-platelet and anti-thrombotic agents before arrival at the PCI centre. However, more evidence is necessary to demonstrate whether high dose (HD) clopidogrel (600 mg) administered in the ambulance is associated with improved initial pa

  15. Characterization of axo-axonic synapses in the piriform cortex of Mus musculus. (United States)

    Wang, Xinjun; Sun, Qian-Quan


    Previous anatomical and physiological studies have established major glutamatergic and GABAergic neuronal subtypes within the piriform cortical circuits. However, quantitative information regarding axo-axonic inhibitory synapses mediated by chandelier cells across major cortical subdivisions of piriform cortex is lacking. Therefore, we examined the properties of these synapses across the entire piriform cortex. Our results show the following. 1) γ-Aminobutyric acid membrane transporter 1-positive varicosities, whose appearance resembles chandelier cartridges, are found around the initial segments of axons of glutamatergic cells across layers II and III. 2) Both the density of axo-axonic cartridges and the degree of γ-aminobutyric acid membrane transporter 1 innervation in each axo-axonic synapse are significantly higher in the piriform cortex than in the neocortex. 3) Glutamate decarboxylase 67, vesicular GABA transporter, and parvalbumin, but not calbindin, are colocalized with the presynaptic varicosities, whereas gephyrin, Na-K-2Cl cotransporter 1, and GABA(A) receptor α1 subunit, but not K-Cl cotransporter 2, are colocalized at the presumed postsynaptic sites. 4) The axo-axonic cartridges innervate the majority of excitatory neurons and are distributed more frequently in putative centrifugal cells and posterior piriform cortex. We further describe the morphology of chandelier cells by using parvalbumin-immunoreactivity and single-cell labeling. In summary, our results demonstrate that a small population of chandelier cells mediates abundant axo-axonic synapses across the entire piriform cortex. Because of the critical location of these inhibitory synapses in relation to action potential regulation, our results highlight a critical role of axo-axonic synapses in regulating information flow and olfactory-related oscillations within the piriform cortex in vivo.

  16. Breast segmentation in MRI using Poisson surface reconstruction initialized with random forest edge detection (United States)

    Martel, Anne L.; Gallego-Ortiz, Cristina; Lu, YingLi


    Segmentation of breast tissue in MRI images is an important pre-processing step for many applications. We present a new method that uses a random forest classifier to identify candidate edges in the image and then applies a Poisson reconstruction step to define a 3D surface based on the detected edge points. Using a leave one patient out cross validation we achieve a Dice overlap score of 0.96 +/- 0.02 for T1 weighted non-fat suppressed images in 8 patients. In a second dataset of 332 images acquired using a Dixon sequence, which was not used in training the random classifier, the mean Dice score was 0.90 +/- 0.03. Using this approach we have achieved accurate, robust segmentation results using a very small training set.

  17. Network state-dependent inhibition of identified hippocampal CA3 axo-axonic cells in vivo. (United States)

    Viney, Tim J; Lasztoczi, Balint; Katona, Linda; Crump, Michael G; Tukker, John J; Klausberger, Thomas; Somogyi, Peter


    Hippocampal sharp waves are population discharges initiated by an unknown mechanism in pyramidal cell networks of CA3. Axo-axonic cells (AACs) regulate action potential generation through GABAergic synapses on the axon initial segment. We found that CA3 AACs in anesthetized rats and AACs in freely moving rats stopped firing during sharp waves, when pyramidal cells fire most. AACs fired strongly and rhythmically around the peak of theta oscillations, when pyramidal cells fire at low probability. Distinguishing AACs from other parvalbumin-expressing interneurons by their lack of detectable SATB1 transcription factor immunoreactivity, we discovered a somatic GABAergic input originating from the medial septum that preferentially targets AACs. We recorded septo-hippocampal GABAergic cells that were activated during hippocampal sharp waves and projected to CA3. We hypothesize that inhibition of AACs, and the resulting subcellular redistribution of inhibition from the axon initial segment to other pyramidal cell domains, is a necessary condition for the emergence of sharp waves promoting memory consolidation.

  18. Geomorphic Segmentation, Hydraulic Geometry, and Hydraulic Microhabitats of the Niobrara River, Nebraska - Methods and Initial Results (United States)

    Alexander, Jason S.; Zelt, Ronald B.; Schaepe, Nathaniel J.


    The Niobrara River of Nebraska is a geologically, ecologically, and economically significant resource. The State of Nebraska has recognized the need to better manage the surface- and ground-water resources of the Niobrara River so they are sustainable in the long term. In cooperation with the Nebraska Game and Parks Commission, the U.S. Geological Survey is investigating the hydrogeomorphic settings and hydraulic geometry of the Niobrara River to assist in characterizing the types of broad-scale physical habitat attributes that may be of importance to the ecological resources of the river system. This report includes an inventory of surface-water and ground-water hydrology data, surface water-quality data, a longitudinal geomorphic segmentation and characterization of the main channel and its valley, and hydraulic geometry relations for the 330-mile section of the Niobrara River from Dunlap Diversion Dam in western Nebraska to the Missouri River confluence. Hydraulic microhabitats also were analyzed using available data from discharge measurements to demonstrate the potential application of these data and analysis methods. The main channel of the Niobrara was partitioned into three distinct fluvial geomorphic provinces: an upper province characterized by open valleys and a sinuous, equiwidth channel; a central province characterized by mixed valley and channel settings, including several entrenched canyon reaches; and a lower province where the valley is wide, yet restricted, but the river also is wide and persistently braided. Within the three fluvial geomorphic provinces, 36 geomorphic segments were identified using a customized, process-orientated classification scheme, which described the basic physical characteristics of the Niobrara River and its valley. Analysis of the longitudinal slope characteristics indicated that the Niobrara River longitudinal profile may be largely bedrock-controlled, with slope inflections co-located at changes in bedrock type at

  19. Distinct interneuron types express m2 muscarinic receptor immunoreactivity on their dendrites or axon terminals in the hippocampus. (United States)

    Hájos, N; Papp, E C; Acsády, L; Levey, A I; Freund, T F


    In previous studies m2 muscarinic acetylcholine receptor-immunoreactive interneurons and various types of m2-positive axon terminals have been described in the hippocampal formation. The aim of the present study was to identify the types of interneurons expressing m2 receptor and to examine whether the somadendritic and axonal m2 immunostaining labels the same or distinct cell populations. In the CA1 subfield, neurons immunoreactive for m2 have horizontal dendrites, they are located at the stratum oriens/alveus border and have an axon that project to the dendritic region of pyramidal cells. In the CA3 subfield and the hilus, m2-positive neurons are multipolar and are scattered in all layers except stratum lacunosum-moleculare. In stratum pyramidale of the CA1 and CA3 regions, striking axon terminal staining for m2 was observed, surrounding the somata and axon initial segments of pyramidal cells in a basket-like manner. The co-localization of m2 with neurochemical markers and GABA was studied using the "mirror" technique and fluorescent double-immunostaining at the light microscopic level and with double-labelling using colloidal gold-conjugated antisera and immunoperoxidase reaction (diaminobenzidine) at the electron microscopic level. GABA was shown to be present in the somata of most m2-immunoreactive interneurons, as well as in the majority of m2-positive terminals in all layers. The calcium-binding protein parvalbumin was absent from practically all m2-immunoreactive cell bodies and dendrites. In contrast, many of the terminals synapsing on pyramidal cell somata and axon initial segments co-localized parvalbumin and m2, suggesting a differential distribution of m2 receptor immunoreactivity on the axonal and somadendritic membrane of parvalbumin-containing basket and axo-axonic cells. The co-existence of m2 receptors with the calcium-binding protein calbindin and the neuropeptides cholecystokinin and vasoactive intestinal polypeptide was rare throughout the

  20. Motor and dorsal root ganglion axons serve as choice points for the ipsilateral turning of dI3 axons. (United States)

    Avraham, Oshri; Hadas, Yoav; Vald, Lilach; Hong, Seulgi; Song, Mi-Ryoung; Klar, Avihu


    The axons of the spinal intersegmental interneurons are projected longitudinally along various funiculi arrayed along the dorsal-ventral axis of the spinal cord. The roof plate and the floor plate have a profound role in patterning their initial axonal trajectory. However, other positional cues may guide the final architecture of interneuron tracks in the spinal cord. To gain more insight into the organization of specific axonal tracks in the spinal cord, we focused on the trajectory pattern of a genetically defined neuronal population, dI3 neurons, in the chick spinal cord. Exploitation of newly characterized enhancer elements allowed specific labeling of dI3 neurons and axons. dI3 axons are projected ipsilaterally along two longitudinal fascicules at the ventral lateral funiculus (VLF) and the dorsal funiculus (DF). dI3 axons change their trajectory plane from the transverse to the longitudinal axis at two novel checkpoints. The axons that elongate at the DF turn at the dorsal root entry zone, along the axons of the dorsal root ganglion (DRG) neurons, and the axons that elongate at the VLF turn along the axons of motor neurons. Loss and gain of function of the Lim-HD protein Isl1 demonstrate that Isl1 is not required for dI3 cell fate. However, Isl1 is sufficient to impose ipsilateral turning along the motor axons when expressed ectopically in the commissural dI1 neurons. The axonal patterning of dI3 neurons, revealed in this study, highlights the role of established axonal cues-the DRG and motor axons-as intermediate guidepost cues for dI3 axons.

  1. Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures.


    Dinocourt, Celine; Petanjek, Zdravko; Freund, Tamas,; Ben-Ari, Yezekiel; Esclapez, Monique


    International audience; In the pilocarpine model of chronic limbic seizures, vulnerability of GABAergic interneurons to excitotoxic damage has been reported in the hippocampal CA1 region. However, little is known about the specific types of interneurons that degenerate in this region. In order to characterize these interneurons, we performed quantitative analyses of the different populations of GABAergic neurons labeled for their peptide or calcium-binding protein content. Our data demonstrat...

  2. Physiological properties of anatomically identified axo-axonic cells in the rat hippocampus. (United States)

    Buhl, E H; Han, Z S; Lörinczi, Z; Stezhka, V V; Karnup, S V; Somogyi, P


    1. The properties of a well-defined type of GABAergic local circuit neuron, the axo-axonic cell (n = 17), were investigated in rat hippocampal slice preparations. During intracellular recording we injected axo-axonic cells with biocytin and subsequently identified them with correlated light and electron microscopy. Employing an immunogold-silver intensification technique we showed that one of the physiologically characterized cells was immunoreactive for gamma-aminobutyric acid (GABA). 2. Axo-axonic cells were encountered in the dentate gyrus (n = 5) as well as subfields CA3 (n = 2) and CA1 (n = 10). They generally had smooth, beaded dendrites that extended throughout all hippocampal layers. Their axons ramified densely in the cell body layers and in the subjacent stratum oriens or hilus, respectively. Tested with electron microscopy, labeled terminals (n = 53) established synapses exclusively with the axon initial segment of principal cells in strata oriens and pyramidale and rarely in lower radiatum. Within a 400-microns slice a single CA1 axo-axonic cell was estimated to be in synaptic contact with 686 pyramidal cells. 3. Axo-axonic cells (n = 14) had a mean resting membrane potential of -65.1 mV, an average input resistance of 73.9 M omega, and a mean time constant of 7.7 ms. Action potentials were of short duration (389-microseconds width at half-amplitude) and had a mean amplitude of 64.1 mV. 4. Nine of 10 tested cells showed a varying degree of spike frequency adaptation in response to depolarizing current injection. Current-evoked action potentials were usually curtailed by a deep (10.2 mV) short-latency afterhyperpolarization (AHP) with a mean duration of 28.1 ms. 5. Cells with strong spike frequency accommodation (n = 5) had a characteristic firing pattern with numerous spike doublets. These appeared to be triggered by an underlying depolarizing afterpotential. In the same cells, prolonged bursts of action potentials were followed by a prominent long

  3. Axonal GABAA receptors. (United States)

    Trigo, Federico F; Marty, Alain; Stell, Brandon M


    Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.

  4. 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.

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



    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 specialized glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarization followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is...

  6. Axons take a dive (United States)

    Tong, Cheuk Ka; Cebrián-Silla, Arantxa; Paredes, Mercedes F; Huang, Eric J; García-Verdugo, Jose Manuel; Alvarez-Buylla, Arturo


    In the walls of the lateral ventricles of the adult mammalian brain, neural stem cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular–subventricular zone (V–SVZ). In a recent article, we show that supraependymal serotonergic (5HT) axons originating from the raphe nuclei in mice form an extensive plexus on the walls of the lateral ventricles where they contact E1 cells and NSCs. Here we further characterize the contacts between 5HT supraependymal axons and E1 cells in mice, and show that suprependymal axons tightly associated to E1 cells are also present in the walls of the human lateral ventricles. These observations raise interesting questions about the function of supraependymal axons in the regulation of E1 cells. PMID:26413556

  7. Axonal bleb recording

    Institute of Scientific and Technical Information of China (English)

    Wenqin Hu; Yousheng Shu


    Patch-clamp recording requires direct accessibility of the cell membrane to patch pipettes and allows the investigation of ion channel properties and functions in specific cellular compartments.The cell body and relatively thick dendrites are the most accessible compartments of a neuron,due to their large diameters and therefore great membrane surface areas.However,axons are normally inaccessible to patch pipettes because of their thin structure; thus studies of axon physiology have long been hampered by the lack of axon recording methods.Recently,a new method of patchclamp recording has been developed,enabling direct and tight-seal recording from cortical axons.These recordings are performed at the enlarged structure (axonal bleb) formed at the cut end of an axon after slicing procedures.This method has facilitated studies of the mechanisms underlying the generation and propagation of the main output signal,the action potential,and led to the finding that cortical neurons communicate not only in action potential-mediated digital mode but also in membrane potential-dependent analog mode.

  8. Simultaneous 3D segmentation of three bone compartments on high resolution knee MR images from osteoarthritis initiative (OAI) using graph cuts (United States)

    Shim, Hackjoon; Kwoh, C. Kent; Yun, Il Dong; Lee, Sang Uk; Bae, Kyongtae


    Osteoarthritis (OA) is associated with degradation of cartilage and related changes in the underlying bone. Quantitative measurement of those changes from MR images is an important biomarker to study the progression of OA and it requires a reliable segmentation of knee bone and cartilage. As the most popular method, manual segmentation of knee joint structures by boundary delineation is highly laborious and subject to user-variation. To overcome these difficulties, we have developed a semi-automated method for segmentation of knee bones, which consisted of two steps: placement of seeds and computation of segmentation. In the first step, seeds were placed by the user on a number of slices and then were propagated automatically to neighboring images. The seed placement could be performed on any of sagittal, coronal, and axial planes. The second step, computation of segmentation, was based on a graph-cuts algorithm where the optimal segmentation is the one that minimizes a cost function, which integrated the seeds specified by the user and both the regional and boundary properties of the regions to be segmented. The algorithm also allows simultaneous segmentation of three compartments of the knee bone (femur, tibia, patella). Our method was tested on the knee MR images of six subjects from the osteoarthritis initiative (OAI). The segmentation processing time (mean+/-SD) was (22+/-4)min, which is much shorter than that by the manual boundary delineation method (typically several hours). With this improved efficiency, our segmentation method will facilitate the quantitative morphologic analysis of changes in knee bones associated with osteoarthritis.

  9. Molecular analysis of axon repulsion by the notochord. (United States)

    Anderson, Christopher N G; Ohta, Kunimasa; Quick, Marie M; Fleming, Angeleen; Keynes, Roger; Tannahill, David


    During development of the amniote peripheral nervous system, the initial trajectory of primary sensory axons is determined largely by the action of axon repellents. We have shown previously that tissues flanking dorsal root ganglia, the notochord lying medially and the dermamyotomes lying laterally, are sources of secreted molecules that prevent axons from entering inappropriate territories. Although there is evidence suggesting that SEMA3A contributes to the repellent activity of the dermamyotome, the nature of the activity secreted by the notochord remains undetermined. We have employed an expression cloning strategy to search for axon repellents secreted by the notochord, and have identified SEMA3A as a candidate repellent. Moreover, using a spectrum of different axon populations to assay the notochord activity, together with neuropilin/Fc receptor reagents to block semaphorin activity in collagen gel assays, we show that SEMA3A probably contributes to notochord-mediated repulsion. Sympathetic axons that normally avoid the midline in vivo are also repelled, in part, by a semaphorin-based notochord activity. Although our results implicate semaphorin signalling in mediating repulsion by the notochord, repulsion of early dorsal root ganglion axons is only partially blocked when using neuropilin/Fc reagents. Moreover, retinal axons, which are insensitive to SEMA3A, are also repelled by the notochord. We conclude that multiple factors act in concert to guide axons in this system, and that further notochord repellents remain to be identified.

  10. Impact of Pretreatment With Clopidogrel on Initial Patency and Outcome in Patients Treated With Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction A Systematic Review

    NARCIS (Netherlands)

    Vlaar, Pieter J.; Svilaas, Tone; Damman, Kevin; de Smet, Bart J. G. L.; Tijssen, Jan G. P.; Hillege, Hans L.; Zijlstra, Felix


    Background-The main goal of the initial treatment of ST-segment elevation myocardial infarction is prompt reperfusion of the infarct-related artery. The value of pretreatment with clopidogrel before primary percutaneous coronary intervention is currently unclear. Methods and Results-Studies were ret

  11. Semi-automatic lung segmentation of DCE-MRI data sets of 2-year old children after congenital diaphragmatic hernia repair: Initial results. (United States)

    Zöllner, Frank G; Daab, Markus; Weidner, Meike; Sommer, Verena; Zahn, Katrin; Schaible, Thomas; Weisser, Gerald; Schoenberg, Stefan O; Neff, K Wolfgang; Schad, Lothar R


    In congenital diaphragmatic hernia (CDH), lung hypoplasia and secondary pulmonary hypertension are the major causes of death and severe disability. Based on new therapeutic strategies survival rates could be improved to up to 80%. However, after surgical repair of CDH, long-term follow-up of these pediatric patients is necessary. In this, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) provides insights into the pulmonary microcirculation and might become a tool within the routine follow-up program of CDH patients. However, whole lung segmentation from DCE-MRI scans is tedious and automated procedures are warranted. Therefore, in this study, an approach to semi-automated lung segmentation is presented. Segmentation of the lung is obtained by calculating the cross correlation and the area under curve between all voxels in the data set and a reference region-of-interest (ROI), here the arterial input function (AIF). By applying an upper and lower threshold to the obtained maps and intersecting these, a final segmentation is reached. This approach was tested on twelve DCE-MRI data sets of 2-year old children after CDH repair. Segmentation accuracy was evaluated by comparing obtained automatic segmentations to manual delineations using the Dice overlap measure. Optimal thresholds for the cross correlation were 0.5/0.95 and 0.1/0.5 for the area under curve, respectively. The ipsilateral (left) lung showed reduced segmentation accuracy compared to the contralateral (right) lung. Average processing time was about 1.4s per data set. Average Dice score was 0.7±0.1 for the whole lung. In conclusion, initial results are promising. By our approach, whole lung segmentation is possible and a rapid evaluation of whole lung perfusion becomes possible. This might allow for a more detailed analysis of lung hypoplasia of children after CDH.

  12. Glia to axon RNA transfer. (United States)

    Sotelo, José Roberto; Canclini, Lucía; Kun, Alejandra; Sotelo-Silveira, José Roberto; Calliari, Aldo; Cal, Karina; Bresque, Mariana; Dipaolo, Andrés; Farias, Joaquina; Mercer, John A


    The existence of RNA in axons has been a matter of dispute for decades. Evidence for RNA and ribosomes has now accumulated to a point at which it is difficult to question, much of the disputes turned to the origin of these axonal RNAs. In this review, we focus on studies addressing the origin of axonal RNAs and ribosomes. The neuronal soma as the source of most axonal RNAs has been demonstrated and is indisputable. However, the surrounding glial cells may be a supplemental source of axonal RNAs, a matter scarcely investigated in the literature. Here, we review the few papers that have demonstrated that glial-to-axon RNA transfer is not only feasible, but likely. We describe this process in both invertebrate axons and vertebrate axons. Schwann cell to axon ribosomes transfer was conclusively demonstrated (Court et al. [2008]: J. Neurosci 28:11024-11029; Court et al. [2011]: Glia 59:1529-1539). However, mRNA transfer still remains to be demonstrated in a conclusive way. The intercellular transport of mRNA has interesting implications, particularly with respect to the integration of glial and axonal function. This evolving field is likely to impact our understanding of the cell biology of the axon in both normal and pathological conditions. Most importantly, if the synthesis of proteins in the axon can be controlled by interacting glia, the possibilities for clinical interventions in injury and neurodegeneration are greatly increased.

  13. Segment coupling and coordination variability analyses of the roundhouse kick in taekwondo relative to the initial stance position. (United States)

    Estevan, Isaac; Freedman Silvernail, Julia; Jandacka, Daniel; Falco, Coral


    The initial stance position (ISP) has been observed as a factor affecting the execution technique during taekwondo kicks. In the present study, authors aimed to analyse a roundhouse kick to the chest by measuring movement coordination and the variability of coordination and comparing this across the different ISP (0°, 45° and 90°). Eight experienced taekwondo athletes performed consecutive kicking trials in random order from every of the three relative positions. The execution was divided into three phases (stance, first swing and second swing phase). A motion capture system was used to measure athletes' angular displacement of pelvis and thigh. A modified vector coding technique was used to quantify the coordination of the segments which contributed to the overall movement. The variability of this coordination (CV) for each ISP was also calculated. Comparative analysis showed that during the stance phase in the transverse plane, athletes coordinated movement of the trunk and thigh with a higher frequency of in-phase and lower frequency of exclusive thigh rotation in the 0° stance than the 90° stance position (P < 0.05). CV was also influenced by the different ISP. During the first swing and the majority of the second swing phase, predominant in-phase coordination of the pelvis and thigh was observed. Including exercises that require in-phase movement could not only help athletes to acquire coordination stability but also efficiency. The existence of a constraint such as ISP implies an increase of the variability when the athletes have to kick from ISP they are not used to adopt (i.e., 0° and 90° ISP) as an evidence of adaptability in the athletes' execution technique.

  14. The importance of axonal undulation in diffusion MR measurements: a Monte Carlo simulation study. (United States)

    Nilsson, Markus; Lätt, Jimmy; Ståhlberg, Freddy; van Westen, Danielle; Hagslätt, Håkan


    Many axons follow wave-like undulating courses. This is a general feature of extracranial nerve segments, but is also found in some intracranial nervous tissue. The importance of axonal undulation has previously been considered, for example, in the context of biomechanics, where it has been shown that posture affects undulation properties. However, the importance of axonal undulation in the context of diffusion MR measurements has not been investigated. Using an analytical model and Monte Carlo simulations of water diffusion, this study compared undulating and straight axons in terms of diffusion propagators, diffusion-weighted signal intensities and parameters derived from diffusion tensor imaging, such as the mean diffusivity (MD), the eigenvalues and the fractional anisotropy (FA). All parameters were strongly affected by the presence of undulation. The diffusivity perpendicular to the undulating axons increased with the undulation amplitude, thus resembling that of straight axons with larger diameters. Consequently, models assuming straight axons for the estimation of the axon diameter from diffusion MR measurements might overestimate the diameter if undulation is present. FA decreased from approximately 0.7 to 0.5 when axonal undulation was introduced into the simulation model structure. Our results indicate that axonal undulation may play a role in diffusion measurements when investigating, for example, the optic and sciatic nerves and the spinal cord. The simulations also demonstrate that the stretching or compression of neuronal tissue comprising undulating axons alters the observed water diffusivity, suggesting that posture may be of importance for the outcome of diffusion MRI measurements.

  15. The axon-dendrite targeting of Kv3 (Shaw) channels is determined by a targeting motif that associates with the T1 domain and ankyrin G. (United States)

    Xu, Mingxuan; Cao, Ruifeng; Xiao, Rui; Zhu, Michael X; Gu, Chen


    Kv3 (Shaw) channels regulate rapid spiking, transmitter release and dendritic integration of many central neurons. Crucial to functional diversity are the complex targeting patterns of channel proteins. However, the targeting mechanisms are not known. Here we report that the axon-dendrite targeting of Kv3.1 is controlled by a conditional interaction of a C-terminal axonal targeting motif (ATM) with the N-terminal T1 domain and adaptor protein ankyrin G. In cultured hippocampal neurons, although the two splice variants of Kv3.1, Kv3.1a and Kv3.1b, are differentially targeted to the somatodendritic and axonal membrane, respectively, the lysine-rich ATM is surprisingly common for both splice variants. The ATM not only directly binds to the T1 domain in a Zn2+-dependent manner, but also associates with the ankyrin-repeat domain of ankyrin G. However, the full-length channel proteins of Kv3.1b display stronger association to ankyrin G than those of Kv3.1a, suggesting that the unique splice domain at Kv3.1b C terminus influences ATM binding to T1 and ankyrin G. Because ankyrin G mainly resides at the axon initial segment, we propose that it may function as a barrier for axon-dendrite targeting of Kv3.1 channels. In support of this idea, disrupting ankyrin G function either by over-expressing a dominant-negative mutant or by siRNA knockdown decreases polarized axon-dendrite targeting of both Kv3.1a and Kv3.1b. We conclude that the conditional ATM masked by the T1 domain in Kv3.1a is exposed by the splice domain in Kv3.1b, and is subsequently recognized by ankyrin G to target Kv3.1b into the axon.

  16. Evidence for the Role of MAP1B in Axon Formation (United States)

    Gonzalez-Billault, Christian; Avila, Jesus; Cáceres, Alfredo


    Cultured neurons obtained from a hypomorphous MAP1B mutant mouse line display a selective and significant inhibition of axon formation that reflects a delay in axon outgrowth and a reduced rate of elongation. This phenomenon is paralleled by decreased microtubule formation and dynamics, which is dramatic at the distal axonal segment, as well as in growth cones, where the more recently assembled microtubule polymer normally predominates. These neurons also have aberrant growth cone formation and increased actin-based protrusive activity. Taken together, this study provides direct evidence showing that by promoting microtubule dynamics and regulating cytoskeletal organization MAP1B has a crucial role in axon formation. PMID:11452005

  17. Action potential initiation in neocortical inhibitory interneurons.

    Directory of Open Access Journals (Sweden)

    Tun Li


    Full Text Available Action potential (AP generation in inhibitory interneurons is critical for cortical excitation-inhibition balance and information processing. However, it remains unclear what determines AP initiation in different interneurons. We focused on two predominant interneuron types in neocortex: parvalbumin (PV- and somatostatin (SST-expressing neurons. Patch-clamp recording from mouse prefrontal cortical slices showed that axonal but not somatic Na+ channels exhibit different voltage-dependent properties. The minimal activation voltage of axonal channels in SST was substantially higher (∼7 mV than in PV cells, consistent with differences in AP thresholds. A more mixed distribution of high- and low-threshold channel subtypes at the axon initial segment (AIS of SST cells may lead to these differences. Surprisingly, NaV1.2 was found accumulated at AIS of SST but not PV cells; reducing NaV1.2-mediated currents in interneurons promoted recurrent network activity. Together, our results reveal the molecular identity of axonal Na+ channels in interneurons and their contribution to AP generation and regulation of network activity.

  18. Improved Fuzzy C-Means based Particle Swarm Optimization (PSO) initialization and outlier rejection with level set methods for MR brain image segmentation. (United States)

    Mekhmoukh, Abdenour; Mokrani, Karim


    In this paper, a new image segmentation method based on Particle Swarm Optimization (PSO) and outlier rejection combined with level set is proposed. A traditional approach to the segmentation of Magnetic Resonance (MR) images is the Fuzzy C-Means (FCM) clustering algorithm. The membership function of this conventional algorithm is sensitive to the outlier and does not integrate the spatial information in the image. The algorithm is very sensitive to noise and in-homogeneities in the image, moreover, it depends on cluster centers initialization. To improve the outlier rejection and to reduce the noise sensitivity of conventional FCM clustering algorithm, a novel extended FCM algorithm for image segmentation is presented. In general, in the FCM algorithm the initial cluster centers are chosen randomly, with the help of PSO algorithm the clusters centers are chosen optimally. Our algorithm takes also into consideration the spatial neighborhood information. These a priori are used in the cost function to be optimized. For MR images, the resulting fuzzy clustering is used to set the initial level set contour. The results confirm the effectiveness of the proposed algorithm.

  19. Calpain Inhibition Reduces Axolemmal Leakage in Traumatic Axonal Injury

    Directory of Open Access Journals (Sweden)

    János Sándor


    Full Text Available Calcium-induced, calpain-mediated proteolysis (CMSP has recently been implicated to the pathogenesis of diffuse (traumatic axonal injury (TAI. Some studies suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP alterations observed in TAI. Seeking direct evidence for this premise we investigated whether subaxolemmal CMSP may contribute to axolemmal permeability alterations (APA and pre-injury calpain-inhibition could reduce AP in a rat model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons with APA was administered one hour prior to injury into the lateral ventricle; 30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a calpain inhibitor or its vehicle was applied in Wistar rats exposed to impact acceleration brain injury. Histological detection of traumatically injured axonal segments accumulating HRP and statistical analysis revealed that pre-injury administration of the calpain inhibitor MDL-28170 significantly reduced the average length of HRP-labeled axonal segments. The axono-protective effect of pre-injury calpain inhibition recently demonstrated with classical immunohistochemical markers of TAI was further corroborated in this experiment; significant reduction of the length of labeled axons in the drug-treated rats implicate CMSP in the progression of altered AP in TAI.

  20. The spatio-temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study. (United States)

    Popovic, Marko A; Foust, Amanda J; McCormick, David A; Zecevic, Dejan


    The spatial pattern of Na(+) channel clustering in the axon initial segment (AIS) plays a critical role in tuning neuronal computations, and changes in Na(+) channel distribution have been shown to mediate novel forms of neuronal plasticity in the axon. However, immunocytochemical data on channel distribution may not directly predict spatio-temporal characteristics of action potential initiation, and prior electrophysiological measures are either indirect (extracellular) or lack sufficient spatial resolution (intracellular) to directly characterize the spike trigger zone (TZ). We took advantage of a critical methodological improvement in the high sensitivity membrane potential imaging (V(m) imaging) technique to directly determine the location and length of the spike TZ as defined in functional terms. The results show that in mature axons of mouse cortical layer 5 pyramidal cells, action potentials initiate in a region ∼20 μm in length centred between 20 and 40 μm from the soma. From this region, the AP depolarizing wave invades initial nodes of Ranvier within a fraction of a millisecond and propagates in a saltatory fashion into axonal collaterals without failure at all physiologically relevant frequencies. We further demonstrate that, in contrast to the saltatory conduction in mature axons, AP propagation is non-saltatory (monotonic) in immature axons prior to myelination.

  1. Initial Object Segmentation for Video Object Plane Generation Using Cellular Neural Networks%在视频对象平面生成中使用细胞神经网络进行初始对象的分割

    Institute of Scientific and Technical Information of China (English)

    王慧; 杨高波; 张兆扬


    MPEG-4 is a basic tool for interactivity and manipulation of video sequences. Video object segmentation is a key issue indefining the content of any video sequence, which is often divided into two steps: initial object segmentation and object tracking. Inthis paper, an initial object segmentation method for video object plane(VOP) generation using color information is proposed. Based on3 by 3 linear templates, a cellular neural network (CNN) is used to implemented object segmentation, The Experimental results arepresented to verify the efficiency and robustness of this approach.

  2. Segmentation of pulmonary nodules in computed tomography using a regression neural network approach and its application to the Lung Image Database Consortium and Image Database Resource Initiative dataset. (United States)

    Messay, Temesguen; Hardie, Russell C; Tuinstra, Timothy R


    We present new pulmonary nodule segmentation algorithms for computed tomography (CT). These include a fully-automated (FA) system, a semi-automated (SA) system, and a hybrid system. Like most traditional systems, the new FA system requires only a single user-supplied cue point. On the other hand, the SA system represents a new algorithm class requiring 8 user-supplied control points. This does increase the burden on the user, but we show that the resulting system is highly robust and can handle a variety of challenging cases. The proposed hybrid system starts with the FA system. If improved segmentation results are needed, the SA system is then deployed. The FA segmentation engine has 2 free parameters, and the SA system has 3. These parameters are adaptively determined for each nodule in a search process guided by a regression neural network (RNN). The RNN uses a number of features computed for each candidate segmentation. We train and test our systems using the new Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) data. To the best of our knowledge, this is one of the first nodule-specific performance benchmarks using the new LIDC-IDRI dataset. We also compare the performance of the proposed methods with several previously reported results on the same data used by those other methods. Our results suggest that the proposed FA system improves upon the state-of-the-art, and the SA system offers a considerable boost over the FA system.

  3. Morphology of axonal transport abnormalities in primate eyes. (United States)

    Radius, R L; Anderson, D R


    The ultrastructure of the retina and optic nerve head was studied in primate eyes after central retinal artery occlusion. Within 2 hours of the vascular occlusion the inner retinal layers undergo watery (isosmotic) swelling. This watery swelling of axons and astroglia extends into the nerve head as far back as the anterior boundary of the scleral lamina cribrosa. The swelling is increased 4 hours after the occlusion, and by 24 hours disintegration has occurred. At the optic nerve head mitochondria and vesicles of smooth endoplasmic reticulum begin to accumulate within 2 hours. The accumulation increases at 4 hours and persists to 24 hours. The watery swelling seems characteristic of ischaemic axons. Membranous organelles accumulate at the boundary of an ischaemic zone when material carried by axonal transport is brought via the healthy axon segment to the boundary, but they cannot proceed further into the ischaemic zone. Such accumulation is typical of locations where rapid orthograde axonal transport or retrograde axonal transport is blocked. In contrast, when slow axonal flow is impaired, the swelling is characterised by an excess of cytoplasmic gel without a marked accumulation of organelles. Rapid orthograde transport and retrograde transport seem to be closely related to one another, while slow axoplasmic flow seems fundamentally different. From morphological findings we suspect that, in experimental glaucoma, intraocular pressure first affects the intracellular physiological process of rapid orthograde and retrograde axonal transport. Watery swelling may not occur unless the ischaemic injury to cell metabolism is more advanced. In contrast, in experimental papilloedema, the swelling results predominantly from impaired slow axoplasmic flow.

  4. Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons. (United States)

    del Castillo, Urko; Winding, Michael; Lu, Wen; Gelfand, Vladimir I


    In this study, we investigated how microtubule motors organize microtubules in Drosophila neurons. We showed that, during the initial stages of axon outgrowth, microtubules display mixed polarity and minus-end-out microtubules push the tip of the axon, consistent with kinesin-1 driving outgrowth by sliding antiparallel microtubules. At later stages, the microtubule orientation in the axon switches from mixed to uniform polarity with plus-end-out. Dynein knockdown prevents this rearrangement and results in microtubules of mixed orientation in axons and accumulation of microtubule minus-ends at axon tips. Microtubule reorganization requires recruitment of dynein to the actin cortex, as actin depolymerization phenocopies dynein depletion, and direct recruitment of dynein to the membrane bypasses the actin requirement. Our results show that cortical dynein slides 'minus-end-out' microtubules from the axon, generating uniform microtubule arrays. We speculate that differences in microtubule orientation between axons and dendrites could be dictated by differential activity of cortical dynein.

  5. Magnetic resonance image segmentation using semi-automated software for quantification of knee articular cartilage - initial evaluation of a technique for paired scans

    Energy Technology Data Exchange (ETDEWEB)

    Brem, M.H. [Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Friedrich-Alexander-University Erlangen Nurenberg, Division of Orthopaedic and Trauma Surgery, Department of Surgery, Erlangen (Germany); Lang, P.K.; Neumann, G.; Schlechtweg, P.M.; Yoshioka, H.; Pappas, G.; Duryea, J. [Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Schneider, E. [LLC, SciTrials, Rocky River, OH (United States); Cleveland Clinic, Imaging Institute, Cleveland, OH (United States); Jackson, R.; Yu, J. [Ohio State University, Diabetes and Metabolism and Radiology, Department of Endocrinology, Columbus, OH (United States); Eaton, C.B. [Center for Primary Care and Prevention and the Warren Alpert Medical School of Brown University, Memorial Hospital of Rhode Island, Providence, RI (United States); Hennig, F.F. [Friedrich-Alexander-University Erlangen Nurenberg, Division of Orthopaedic and Trauma Surgery, Department of Surgery, Erlangen (Germany)


    Software-based image analysis is important for studies of cartilage changes in knee osteoarthritis (OA). This study describes an evaluation of a semi-automated cartilage segmentation software tool capable of quantifying paired images for potential use in longitudinal studies of knee OA. We describe the methodology behind the analysis and demonstrate its use by determination of test-retest analysis precision of duplicate knee magnetic resonance imaging (MRI) data sets. Test-retest knee MR images of 12 subjects with a range of knee health were evaluated from the Osteoarthritis Initiative (OAI) pilot MR study. Each subject was removed from the magnet between the two scans. The 3D DESS (sagittal, 0.456 mm x 0.365 mm, 0.7 mm slice thickness, TR 16.5 ms, TE 4.7 ms) images were obtained on a 3-T Siemens Trio MR system with a USA Instruments quadrature transmit-receive extremity coil. Segmentation of one 3D-image series was first performed and then the corresponding retest series was segmented by viewing both image series concurrently in two adjacent windows. After manual registration of the series, the first segmentation cartilage outline served as an initial estimate for the second segmentation. We evaluated morphometric measures of the bone and cartilage surface area (tAB and AC), cartilage volume (VC), and mean thickness ( for medial/lateral tibia (MT/LT), total femur (F) and patella (P). Test-retest reproducibility was assessed using the root-mean square coefficient of variation (RMS CV%). For the paired analyses, RMS CV % ranged from 0.9% to 1.2% for VC, from 0.3% to 0.7% for AC, from 0.6% to 2.7% for tAB and 0.8% to 1.5% for Paired image analysis improved the measurement precision of cartilage segmentation. Our results are in agreement with other publications supporting the use of paired analysis for longitudinal studies of knee OA. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Rosa-Eva Huettl


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

  7. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb. (United States)

    Huettl, Rosa-Eva; Soellner, Heidi; Bianchi, Elisa; Novitch, Bennett G; Huber, Andrea B


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

  8. 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.

  9. Segmented crystalline scintillators: an initial investigation of high quantum efficiency detectors for megavoltage x-ray imaging. (United States)

    Sawant, Amit; Antonuk, Larry E; El-Mohri, Youcef; Zhao, Qihua; Li, Yixin; Su, Zhong; Wang, Yi; Yamamoto, Jin; Du, Hong; Cunningham, Ian; Klugerman, Misha; Shah, Kanai


    Electronic portal imaging devices (EPIDs) based on indirect detection, active matrix flat panel imagers (AMFPIs) have become the technology of choice for geometric verification of patient localization and dose delivery in external beam radiotherapy. However, current AMFPI EPIDs, which are based on powdered-phosphor screens, make use of only approximately 2% of the incident radiation, thus severely limiting their imaging performance as quantified by the detective quantum efficiency (DQE) (approximately 1%, compared to approximately 75% for kilovoltage AMFPIs). With the rapidly increasing adoption of image-guided techniques in virtually every aspect of radiotherapy, there exist strong incentives to develop high-DQE megavoltage x-ray imagers, capable of providing soft-tissue contrast at very low doses in megavoltage tomographic and, potentially, projection imaging. In this work we present a systematic theoretical and preliminary empirical evaluation of a promising, high-quantum-efficiency, megavoltage x-ray detector design based on a two-dimensional matrix of thick, optically isolated, crystalline scintillator elements. The detector is coupled with an indirect detection-based active matrix array, with the center-to-center spacing of the crystalline elements chosen to match the pitch of the underlying array pixels. Such a design enables the utilization of a significantly larger fraction of the incident radiation (up to 80% for a 6 MV beam), through increases in the thickness of the crystalline elements, without loss of spatial resolution due to the spread of optical photons. Radiation damage studies were performed on test samples of two candidate scintillator materials, CsI(Tl) and BGO, under conditions relevant to radiotherapy imaging. A detailed Monte Carlo-based study was performed in order to examine the signal, spatial spreading, and noise properties of the absorbed energy for several segmented detector configurations. Parameters studied included scintillator

  10. Axon-glia interaction and membrane traffic in myelin formation. (United States)

    White, Robin; Krämer-Albers, Eva-Maria


    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 specialized glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarization 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 emphasizing the central role of the Src-family kinase Fyn during central nervous system (CNS) myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of proteolipid protein (PLP) transport by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases.

  11. 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.

  12. Intra-axonal protein synthesis - a new target for neural repair?

    Directory of Open Access Journals (Sweden)

    Jeffery L Twiss


    Full Text Available Although initially argued to be a feature of immature neurons with incomplete polarization, there is clear evidence that neurons in the peripheral nervous system retain the capacity for intra-axonal protein synthesis well into adulthood. This localized protein synthesis has been shown to contribute to injury signaling and axon regeneration in peripheral nerves. Recent works point to potential for protein synthesis in axons of the vertebrate central nervous system. mRNAs and protein synthesis machinery have now been documented in lamprey, mouse, and rat spinal cord axons. Intra-axonal protein synthesis appears to be activated in adult vertebrate spinal cord axons when they are regeneration-competent. Rat spinal cord axons regenerating into a peripheral nerve graft contain mRNAs and markers of activated translational machinery. Indeed, levels of some growth-associated mRNAs in these spinal cord axons are comparable to the regenerating sciatic nerve. Markers of active translation tend to decrease when these axons stop growing, but can be reactivated by a second axotomy. These emerging observations raise the possibility that mRNA transport into and translation within axons could be targeted to facilitate regeneration in both the peripheral and central nervous systems.

  13. Intra-axonal protein synthesis - a new target for neural repair? (United States)

    Twiss, Jeffery L; Kalinski, Ashley L; Sachdeva, Rahul; Houle, John D


    Although initially argued to be a feature of immature neurons with incomplete polarization, there is clear evidence that neurons in the peripheral nervous system retain the capacity for intra-axonal protein synthesis well into adulthood. This localized protein synthesis has been shown to contribute to injury signaling and axon regeneration in peripheral nerves. Recent works point to potential for protein synthesis in axons of the vertebrate central nervous system. mRNAs and protein synthesis machinery have now been documented in lamprey, mouse, and rat spinal cord axons. Intra-axonal protein synthesis appears to be activated in adult vertebrate spinal cord axons when they are regeneration-competent. Rat spinal cord axons regenerating into a peripheral nerve graft contain mRNAs and markers of activated translational machinery. Indeed, levels of some growth-associated mRNAs in these spinal cord axons are comparable to the regenerating sciatic nerve. Markers of active translation tend to decrease when these axons stop growing, but can be reactivated by a second axotomy. These emerging observations raise the possibility that mRNA transport into and translation within axons could be targeted to facilitate regeneration in both the peripheral and central nervous systems.

  14. Intra-axonal protein synthesis - a new target for neural repair?

    Institute of Scientific and Technical Information of China (English)

    Jeffery L Twiss; Ashley L Kalinski; Rahul Sachdeva; John D Houle


    Although initially argued to be a feature of immature neurons with incomplete polarization, there is clear evidence that neurons in the peripheral nervous system retain the capacity for intra-axonal protein synthe-sis well into adulthood. This localized protein synthesis has been shown to contribute to injury signaling and axon regeneration in peripheral nerves. Recent works point to potential for protein synthesis in axons of the vertebrate central nervous system. mRNAs and protein synthesis machinery have now been docu-mented in lamprey, mouse, and rat spinal cord axons. Intra-axonal protein synthesis appears to be activated in adult vertebrate spinal cord axons when they are regeneration-competent. Rat spinal cord axons regen-erating into a peripheral nerve graft contain mRNAs and markers of activated translational machinery. Indeed, levels of some growth-associated mRNAs in these spinal cord axons are comparable to the regen-erating sciatic nerve. Markers of active translation tend to decrease when these axons stop growing, but can be reactivated by a second axotomy. These emerging observations raise the possibility that mRNA transport into and translation within axons could be targeted to facilitate regeneration in both the peripheral and central nervous systems.

  15. Quantitative ultrastructural analysis of basket and axo-axonic cell terminals in the mouse hippocampus. (United States)

    Takács, Virág T; Szőnyi, András; Freund, Tamás F; Nyiri, Gábor; Gulyás, Attila I


    Three functionally different populations of perisomatic interneurons establish GABAergic synapses on hippocampal pyramidal cells: parvalbumin (PV)-containing basket cells, type 1 cannabinoid receptor (CB1)-positive basket cells both of which target somata, and PV-positive axo-axonic cells that innervate axon initial segments. Using electron microscopic reconstructions, we estimated that a pyramidal cell body receives synapses from about 60 and 140 synaptic terminals in the CA1 and CA3 area, respectively. About 60 % of these terminals were PV positive, whereas 35-40 % of them were CB1 positive. Only about 1 % (CA1) and 4 % (CA3) of the somatic boutons were negative for both markers. Using fluorescent labeling, we showed that most of the CB1-positive terminals expressed vesicular glutamate transporter 3. Reconstruction of somatic boutons revealed that although their volumes are similar, CB1-positive boutons are more flat and the total volume of their mitochondria was smaller than that of PV-positive boutons. Both types of boutons contain dense-core vesicles and frequently formed multiple release sites on their targets and innervated an additional soma or dendrite as well. PV-positive boutons possessed small, macular synapses; whereas the total synaptic area of CB1-positive boutons was larger and formed multiple irregular-shaped synapses. Axo-axonic boutons were smaller than somatic boutons, had only one synapse and their ultrastructural parameters were closer to those of PV-positive somatic boutons. Our results represent the first quantitative measurement-using a highly reliable method-of the contribution of different cell types to the perisomatic innervation of pyramidal neurons, and may help to explain functional differences in their output properties.

  16. Trajectory and terminal distribution of single centrifugal axons from olfactory cortical areas in the rat olfactory bulb. (United States)

    Matsutani, S


    The olfactory bulb receives a large number of centrifugal fibers whose functions remain unclear. To gain insight into the function of the bulbar centrifugal system, the morphology of individual centrifugal axons from olfactory cortical areas was examined in detail. An anterograde tracer, Phaseolus vulgaris leucoagglutinin, was injected into rat olfactory cortical areas, including the pars lateralis of the anterior olfactory nucleus (lAON) and the anterior part of the piriform cortex (aPC). Reconstruction from serial sections revealed that the extrabulbar segments of centrifugal axons from the lAON and those from the aPC had distinct trajectories: the former tended to innervate the pars externa of the AON before entering the olfactory bulb, while the latter had extrabulbar collaterals that extended to a variety of targets. In contrast to the extrabulbar segments, no clear differences were found between the intrabulbar segments of axons from the lAON and from the aPC. The intrabulbar segments of centrifugal axons were mainly found in the granule cell layer but a few axons extended into the external plexiform and glomerular layer. Approximately 40% of centrifugal axons innervated both the medial and lateral aspects of the olfactory bulb. The number of boutons found on single intrabulbar segments was typically less than 1000. Boutons tended to aggregate and form complex terminal tufts with short axonal branches. Terminal tufts, no more than 10 in single axons from ipsilateral cortical areas, were localized to the granule cell layer with varying intervals; some tufts formed patchy clusters and others were scattered over areas that extended for a few millimeters. The patchy, widespread distribution of terminals suggests that the centrifugal axons are able to couple the activity of specific subsets of bulbar neurons even when the subsets are spatially separated.

  17. Transcellular degradation of axonal mitochondria. (United States)

    Davis, Chung-ha O; Kim, Keun-Young; Bushong, Eric A; Mills, Elizabeth A; Boassa, Daniela; Shih, Tiffany; Kinebuchi, Mira; Phan, Sebastien; Zhou, Yi; Bihlmeyer, Nathan A; Nguyen, Judy V; Jin, Yunju; Ellisman, Mark H; Marsh-Armstrong, Nicholas


    It is generally accepted that healthy cells degrade their own mitochondria. Here, we report that retinal ganglion cell axons of WT mice shed mitochondria at the optic nerve head (ONH), and that these mitochondria are internalized and degraded by adjacent astrocytes. EM demonstrates that mitochondria are shed through formation of large protrusions that originate from otherwise healthy axons. A virally introduced tandem fluorophore protein reporter of acidified mitochondria reveals that acidified axonal mitochondria originating from the retinal ganglion cell are associated with lysosomes within columns of astrocytes in the ONH. According to this reporter, a greater proportion of retinal ganglion cell mitochondria are degraded at the ONH than in the ganglion cell soma. Consistently, analyses of degrading DNA reveal extensive mtDNA degradation within the optic nerve astrocytes, some of which comes from retinal ganglion cell axons. Together, these results demonstrate that surprisingly large proportions of retinal ganglion cell axonal mitochondria are normally degraded by the astrocytes of the ONH. This transcellular degradation of mitochondria, or transmitophagy, likely occurs elsewhere in the CNS, because structurally similar accumulations of degrading mitochondria are also found along neurites in superficial layers of the cerebral cortex. Thus, the general assumption that neurons or other cells necessarily degrade their own mitochondria should be reconsidered.

  18. Axonal and Schwann cell BACE1 is equally required for remyelination of peripheral nerves. (United States)

    Hu, Xiangyou; Hu, Jinxuan; Dai, Lu; Trapp, Bruce; Yan, Riqiang


    Inhibition of β-site APP cleaving enzyme 1 (BACE1) is being pursued as a therapeutic target for treating patients with Alzheimer's disease because BACE1 is the sole β-secretase for generating β-amyloid peptide. Knowledge regarding the other cellular functions of BACE1 is therefore critical for the safe use of BACE1 inhibitors in human patients. BACE1 deficiency in mice causes hypomyelination during development and impairs remyelination in injured sciatic nerves. Since BACE1 is expected to be ubiquitously expressed, we asked whether axonal or Schwann cell BACE1 is required for optimal remyelination. By swapping sciatic nerve segments from BACE1-null mice with the corresponding wild-type nerve segments or vice versa, we tested how a deficiency of BACE1 in Schwann cells or axons affects remyelination. Our results show that BACE1 in axons and Schwann cells is similarly important for remyelination of regenerated axons. Nerve injury induces BACE1 transcription and protein levels are elevated in Schwann cells. Expression of type I neuregulin 1 (Nrg1), rather than type III Nrg1, was induced by Schwann cells, and the abolished Nrg1 cleavage in BACE1-null Schwann cells contributed to decreased remyelination of regenerated axons. Hence, this study is the first to demonstrate the equal importance of axonal and Schwann cell BACE1 for remyelination of injured nerves.

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

    Directory of Open Access Journals (Sweden)

    Katherine Olsson-Carter


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

  20. Coexpression of high-voltage-activated ion channels Kv3.4 and Cav1.2 in pioneer axons during pathfinding in the developing rat forebrain. (United States)

    Huang, Chia-Yi; Chu, Dachen; Hwang, Wei-Chao; Tsaur, Meei-Ling


    Precise axon pathfinding is crucial for establishment of the initial neuronal network during development. Pioneer axons navigate without the help of preexisting axons and pave the way for follower axons that project later. Voltage-gated ion channels make up the intrinsic electrical activity of pioneer axons and regulate axon pathfinding. To elucidate which channel molecules are present in pioneer axons, immunohistochemical analysis was performed to examine 14 voltage-gated ion channels (Kv1.1-Kv1.3, Kv3.1-Kv3.4, Kv4.3, Cav1.2, Cav1.3, Cav2.2, Nav1.2, Nav1.6, and Nav1.9) in nine axonal tracts in the developing rat forebrain, including the optic nerve, corpus callosum, corticofugal fibers, thalamocortical axons, lateral olfactory tract, hippocamposeptal projection, anterior commissure, hippocampal commissure, and medial longitudinal fasciculus. We found A-type K⁺ channel Kv3.4 in both pioneer axons and early follower axons and L-type Ca²⁺ channel Cav1.2 in pioneer axons and early and late follower axons. Spatially, Kv3.4 and Cav1.2 were colocalized with markers of pioneer neurons and pioneer axons, such as deleted in colorectal cancer (DCC), in most fiber tracts examined. Temporally, Kv3.4 and Cav1.2 were expressed abundantly in most fiber tracts during axon pathfinding but were downregulated beginning in synaptogenesis. By contrast, delayed rectifier Kv channels (e.g., Kv1.1) and Nav channels (e.g., Nav1.2) were absent from these fiber tracts (except for the corpus callosum) during pathfinding of pioneer axons. These data suggest that Kv3.4 and Cav1.2, two high-voltage-activated ion channels, may act together to control Ca²⁺ -dependent electrical activity of pioneer axons and play important roles during axon pathfinding.

  1. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial

    DEFF Research Database (Denmark)

    Cannon, Christopher P; Husted, Steen; Harrington, Robert A;


    OBJECTIVES: Our goal was to compare the safety and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, with clopidogrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). BACKGROUND: AZD6140 achieves higher mean levels of p...

  2. NF-Protocadherin Regulates Retinal Ganglion Cell Axon Behaviour in the Developing Visual System.

    Directory of Open Access Journals (Sweden)

    Louis C Leung

    Full Text Available Cell adhesion molecules play a central role in mediating axonal tract development within the nascent nervous system. NF-protocadherin (NFPC, a member of the non-clustered protocadherin family, has been shown to regulate retinal ganglion cell (RGC axon and dendrite initiation, as well as influencing axonal navigation within the mid-optic tract. However, whether NFPC mediates RGC axonal behaviour at other positions within the optic pathway remains unclear. Here we report that NFPC plays an important role in RGC axonogenesis, but not in intraretinal guidance. Moreover, axons with reduced NFPC levels exhibit insensitivity to Netrin-1, an attractive guidance cue expressed at the optic nerve head. Netrin-1 induces rapid turnover of NFPC localized to RGC growth cones, suggesting that the regulation of NFPC protein levels may underlie Netrin-1-mediated entry of RGC axons into the optic nerve head. At the tectum, we further reveal a function for NFPC in controlling RGC axonal entry into the final target area. Collectively, our results expand our understanding of the role of NFPC in RGC guidance and illustrate that this adhesion molecule contributes to axon behaviour at multiple points in the optic pathway.

  3. 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.

  4. Axonal recovery after severe traumatic brain injury demonstrated in vivo by 1H MR spectroscopy

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    Danielsen, E.R.; Thomsen, C. [Department of Neuroradiology, Section 3023, Rigshospitalet, Copenhagen (Denmark); Christensen, P.B. [Hammel Neurocentre, Department of Neurology, Aarhus University Hospital (Denmark); Arlien-Soeborg, P. [Department of Neurology, Rigshospitalet, Copenhagen (Denmark)


    Proton magnetic resonance spectroscopy (MRS) suggested almost complete axonal recovery 21 months after trauma in a patient with severe diffuse axonal injury. MRS while the patient was comatose showed evidence of severe diffuse axonal injury in occipitoparietal white matter, but occipital grey matter was relatively spared. At 21 months N-acetylaspartate was normal. At 33 months examination showed a Functional Independence Measure of 83 and a Rancho Los Amigos Scale of Cognitive Function of 7-8, a remarkable improvement considering all the initial findings, except those of MRS. (orig.)

  5. Axonal regeneration through the fibrous scar in lesioned goldfish spinal cord. (United States)

    Takeda, A; Atobe, Y; Kadota, T; Goris, R C; Funakoshi, K


    Spontaneous nerve regeneration beyond the scar frequently occurs in fish after spinal cord lesions, in contrast to mammals. Here we examined the spatiotemporal relationship between the fibrous scar and axonal regeneration in the goldfish. Within 1 week after hemisection of the spinal cord, the open wound was closed by a fibrous scar that was demarcated from the surrounding nervous tissue by the glia limitans, which was immunoreactive for laminin. Within 1 week after hemisection, regenerating axons entered the fibrous scar, and were surrounded by laminin-coated tubular structures continuous with the glia limitans. Regenerating axons that initially entered the fibrous scar were usually accompanied by glial processes. Within 2-3 weeks after hemisection, the tubular structures became enlarged, and the regenerating axons increased in number, fasciculating in the tubules. Glial processes immunoreactive for glial fibrillary acid protein and 5-hydroxytryptamine neurons then entered the tubular structures to associate with the regenerating axons. The tubular structures developed further, creating tunnels that penetrated the fibrous scar, through which the regenerating axons passed. At 6-12 weeks after hemisection, the fibrous scar was smaller and the enlarged tunnels contained many glial processes and several axons. The findings of present study demonstrated that, following spinal lesions in goldfish, regenerating axons enter and pass the scar tissue. The regenerating axons first enter the fibrous scar with glial elements and then grow through laminin-coated tubular structures within the fibrous scar. Invasion by glial processes and neuronal elements into the tubular structures reduces the fibrous scar area and allows for more regenerating axons to pass beyond the fibrous scar.

  6. Axonal abnormalities in cerebellar Purkinje cells of the Ts65Dn mouse. (United States)

    Necchi, Daniela; Lomoio, Selene; Scherini, Elda


    Ts65Dn mice are a genetic model for Down syndrome. Among others, these mice have cerebellar pathology features which parallel those seen in Down syndrome patients. Both individuals with Down syndrome and Ts65Dn mice have reduced cerebellar volume and numbers of granule and Purkinje cells. In this report, we describe morphological abnormalities of axons of Purkinje cells in the cerebellum of Ts65Dn mice, by using anti-calbindin immunocytochemistry. A consistent number of Purkinje cells shows axons bearing giant varicosities along their transit through the granular layer. The cerebellar arbor vitae made by fasciculated Purkinje cell axons has a patchy appearance, some tracks being devoid of calbindin staining. The infraganglionic plexus, formed by recurrent collaterals of Purkinje cell axons, has enormously increased density, which is evidence for a compensatory reaction to degeneration of distal segments of axons. These alterations are accompanied by strong glial reaction as evidenced by GFAP immunocytochemistry. Moreover, the alterations are more consistent in the anterior lobules of the vermis and intermediate cortex. The axonal pathology of Purkinje cells may explain the impairment in cerebellar functions observed in Ts65Dn mice at the adulthood.

  7. Axon-myelin sheath relations of oligodendrocyte unit phenotypes in the adult rat anterior medullary velum. (United States)

    Butt, A M; Ibrahim, M; Berry, M


    Axon-oligodendrocyte relations of Rip-immunolabelled and dye-injected oligodendrocyte units are characterised in the adult rat anterior medullary velum (AMV). Each oligodendrocyte unit comprised the oligodendrocyte cell body, processes and the internodal myelin segments they support. Oligodendrocyte units corresponded to classically described type I/II or type III/IV unit phenotypes which respectively myelinated discrete populations of small and large diameter axons, delineated by a myelinated fire diameter of 2-4 microns (diameter of the axon plus its myelin sheath). Within units, mean fibre diameter was directly related to mean internodal length and inversely related to the number of myelin sheaths in the unit. The relationship between fibre diameter and internodal length was retained in units which myelinated axons of different diameters, indicating that axon diameter was an important determinant of the longitudinal dimensions of myelin sheaths. We also show that type III/IV units maintained a far greater volume of myelin than type I/II units. It was concluded that type I/II and III/IV oligodendrocytes represent two functionally and morphologically distinct phenotypes whose distribution densities were determined by the diameter and spatial dispersion of axons.

  8. Regenerative Responses and Axon Pathfinding of Retinal Ganglion Cells in Chronically Injured Mice (United States)

    Yungher, Benjamin J.; Ribeiro, Márcio; Park, Kevin K.


    Purpose Enhanced regeneration of retinal ganglion cell (RGC) axons can be achieved by modification of numerous neuronal-intrinsic factors. However, axon growth initiation and the pathfinding behavior of these axons after traumatic injury remain poorly understood outside of acute injury paradigms, despite the clinical relevance of more chronic settings. We therefore examined RGC axon regeneration following therapeutic delivery that is postponed until 2 months after optic nerve crush injury. Methods Optic nerve regeneration was induced by virally mediated (adeno-associated virus) ciliary neurotrophic factor (AAV-CNTF) administered either immediately or 56 days after optic nerve crush in wild-type or Bax knockout (KO) mice. Retinal ganglion nerve axon regeneration was assessed 21 and 56 days after viral injection. Immunohistochemical analysis of RGC injury signals and extrinsic factors in the optic nerve were also examined at 5 and 56 days post crush. Results In addition to sustained expression of injury response proteins in surviving RGCs, we observe axon regrowth in wild-type and apoptosis-deficient Bax KO mice following AAV-CNTF treatment. Fewer instances of aberrant axon growth are seen, at least in the area near the lesion site, in animals given treatment 56 days after crush injury compared to the animals given treatment immediately after injury. We also find evidence of long distance growth into a visual target in Bax KO mice despite postponed initiation of this regenerative program. Conclusions These studies provide evidence against an intrinsic critical period for RGC axon regeneration or degradation of injury signals. Regeneration results from Bax KO mice imply highly sustained regenerative capacity in RGCs, highlighting the importance of long-lasting neuroprotective strategies as well as of RGC axon guidance research in chronically injured animals. PMID:28324115

  9. Midbrain dopaminergic axons are guided longitudinally through the diencephalon by Slit/Robo signals. (United States)

    Dugan, James P; Stratton, Andrea; Riley, Hilary P; Farmer, W Todd; Mastick, Grant S


    Dopaminergic neurons from the ventral mesencephalon/diencephalon (mesodiencephalon) form vital pathways constituting the majority of the brain's dopamine systems. Mesodiencephalic dopaminergic (mdDA) neurons extend longitudinal projections anteriorly through the diencephalon, ascending toward forebrain targets. The mechanisms by which mdDA axons initially navigate through the diencephalon are poorly understood. Recently the Slit family of secreted axon guidance proteins, and their Robo receptors, have been identified as important guides for descending longitudinal axons. To test the potential roles of Slit/Robo guidance in ascending trajectories, we examined tyrosine hydroxylase-positive (TH+) projections from mdDA neurons in mutant mouse embryos. We found that mdDA axons grow out of and parallel to Slit-positive ventral regions within the diencephalon, and that subsets of the mdDA axons likely express Robo1 and possibly also Robo2. Slit2 was able to directly inhibit TH axon outgrowth in explant co-culture assays. The mdDA axons made significant pathfinding errors in Slit1/2 and Robo1/2 knockout mice, including spreading out in the diencephalon to form a wider tract. The wider tract resulted from a combination of invasion of the ventral midline, consistent with Slit repulsion, but also axons wandering dorsally, away from the ventral midline. Aberrant dorsal trajectories were prominent in Robo1 and Robo1/2 knockout mice, suggesting that an aspect of Robo receptor function is Slit-independent. These results indicate that Slit/Robo signaling is critical during the initial establishment of dopaminergic pathways, with roles in the dorsoventral positioning and precise pathfinding of these ascending longitudinal axons.

  10. Somite polarity and segmental patterning of the peripheral nervous system. (United States)

    Kuan, C-Y Kelly; Tannahill, David; Cook, Geoffrey M W; Keynes, Roger J


    The analysis of the outgrowth pattern of spinal axons in the chick embryo has shown that somites are polarized into anterior and posterior halves. This polarity dictates the segmental development of the peripheral nervous system: migrating neural crest cells and outgrowing spinal axons traverse exclusively the anterior halves of the somite-derived sclerotomes, ensuring a proper register between spinal axons, their ganglia and the segmented vertebral column. Much progress has been made recently in understanding the molecular basis for somite polarization, and its linkage with Notch/Delta, Wnt and Fgf signalling. Contact-repulsive molecules expressed by posterior half-sclerotome cells provide critical guidance cues for axons and neural crest cells along the anterior-posterior axis. Diffusible repellents from surrounding tissues, particularly the dermomyotome and notochord, orient outgrowing spinal axons in the dorso-ventral axis ('surround repulsion'). Repulsive forces therefore guide axons in three dimensions. Although several molecular systems have been identified that may guide neural crest cells and axons in the sclerotome, it remains unclear whether these operate together with considerable overall redundancy, or whether any one system predominates in vivo.

  11. 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

  12. Calpain-mediated cleavage of collapsin response mediator protein-2 drives acute axonal degeneration (United States)

    Zhang, Jian-Nan; Michel, Uwe; Lenz, Christof; Friedel, Caroline C.; Köster, Sarah; d’Hedouville, Zara; Tönges, Lars; Urlaub, Henning; Bähr, Mathias; Lingor, Paul; Koch, Jan C.


    Axonal degeneration is a key initiating event in many neurological diseases. Focal lesions to axons result in a rapid disintegration of the perilesional axon by acute axonal degeneration (AAD) within several hours. However, the underlying molecular mechanisms of AAD are only incompletely understood. Here, we studied AAD in vivo through live-imaging of the rat optic nerve and in vitro in primary rat cortical neurons in microfluidic chambers. We found that calpain is activated early during AAD of the optic nerve and that calpain inhibition completely inhibits axonal fragmentation on the proximal side of the crush while it attenuates AAD on the distal side. A screening of calpain targets revealed that collapsin response mediator protein-2 (CRMP2) is a main downstream target of calpain activation in AAD. CRMP2-overexpression delayed bulb formation and rescued impairment of axonal mitochondrial transport after axotomy in vitro. In vivo, CRMP2-overexpression effectively protected the proximal axon from fragmentation within 6 hours after crush. Finally, a proteomic analysis of the optic nerve was performed at 6 hours after crush, which identified further proteins regulated during AAD, including several interactors of CRMP2. These findings reveal CRMP2 as an important mediator of AAD and define it as a putative therapeutic target. PMID:27845394

  13. 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.

  14. Commissural axons of the mouse cochlear nucleus. (United States)

    Brown, M Christian; Drottar, Marie; Benson, Thane E; Darrow, Keith


    The axons of commissural neurons that project from one cochlear nucleus to the other were studied after labeling with anterograde tracer. Injections were made into the dorsal subdivision of the cochlear nucleus in order to restrict labeling only to the group of commissural neurons that gave off collaterals to, or were located in, this subdivision. The number of labeled commissural axons in each injection was correlated with the number of labeled radiate multipolar neurons, suggesting radiate neurons as the predominant origin of the axons. The radiate commissural axons are thick and myelinated, and they exit the dorsal acoustic stria of the injected cochlear nucleus to cross the brainstem in the dorsal half, near the crossing position of the olivocochlear bundle. They enter the opposite cochlear nucleus via the dorsal and ventral acoustic stria and at its medial border. Reconstructions of single axons demonstrate that terminations are mostly in the core and typically within a single subdivision of the cochlear nucleus. Extents of termination range from narrow to broad along both the dorsoventral (i.e., tonotopic) and the rostrocaudal dimensions. In the electron microscope, labeled swellings form synapses that are symmetric (in that there is little postsynaptic density), a characteristic of inhibitory synapses. Our labeled axons do not appear to include excitatory commissural axons that end in edge regions of the nucleus. Radiate commissural axons could mediate the broadband inhibition observed in responses to contralateral sound, and they may balance input from the two ears with a quick time course.

  15. Ascending Midbrain Dopaminergic Axons Require Descending GAD65 Axon Fascicles for Normal Pathfinding

    Directory of Open Access Journals (Sweden)

    Claudia Marcela Garcia-Peña


    Full Text Available The Nigrostriatal pathway (NSP is formed by dopaminergic axons that project from the ventral midbrain to the dorsolateral striatum as part of the medial forebrain bundle. Previous studies have implicated chemotropic proteins in the formation of the NSP during development but little is known of the role of substrate-anchored signals in this process. We observed in mouse and rat embryos that midbrain dopaminergic axons ascend in close apposition to descending GAD65-positive axon bundles throughout their trajectory to the striatum. To test whether such interaction is important for dopaminergic axon pathfinding, we analyzed transgenic mouse embryos in which the GAD65 axon bundle was reduced by the conditional expression of the diphtheria toxin. In these embryos we observed dopaminergic misprojection into the hypothalamic region and abnormal projection in the striatum. In addition, analysis of Robo1/2 and Slit1/2 knockout embryos revealed that the previously described dopaminergic misprojection in these embryos is accompanied by severe alterations in the GAD65 axon scaffold. Additional studies with cultured dopaminergic neurons and whole embryos suggest that NCAM and Robo proteins are involved in the interaction of GAD65 and dopaminergic axons. These results indicate that the fasciculation between descending GAD65 axon bundles and ascending dopaminergic axons is required for the stereotypical NSP formation during brain development and that known guidance cues may determine this projection indirectly by instructing the pathfinding of the axons that are part of the GAD65 axon scaffold.

  16. 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.

  17. 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.

  18. 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.

  19. Myosin-Va-dependent cell-to-cell transfer of RNA from Schwann cells to axons. (United States)

    Sotelo, José R; Canclini, Lucía; Kun, Alejandra; Sotelo-Silveira, José R; Xu, Lei; Wallrabe, Horst; Calliari, Aldo; Rosso, Gonzalo; Cal, Karina; Mercer, John A


    To better understand the role of protein synthesis in axons, we have identified the source of a portion of axonal RNA. We show that proximal segments of transected sciatic nerves accumulate newly-synthesized RNA in axons. This RNA is synthesized in Schwann cells because the RNA was labeled in the complete absence of neuronal cell bodies both in vitro and in vivo. We also demonstrate that the transfer is prevented by disruption of actin and that it fails to occur in the absence of myosin-Va. Our results demonstrate cell-to-cell transfer of RNA and identify part of the mechanism required for transfer. The induction of cell-to-cell RNA transfer by injury suggests that interventions following injury or degeneration, particularly gene therapy, may be accomplished by applying them to nearby glial cells (or implanted stem cells) at the site of injury to promote regeneration.

  20. A Variational Level Set Method of Image Segmentation Based on Thresholding Initial Contour%一种基于阈值初始化的变分水平集牙菌斑图像分割方法

    Institute of Scientific and Technical Information of China (English)

    兰红; 陈凌; 张璐


    将变分水平集和图像阀值化两种图像分割方法相结合,在分析灰度图像直方图分布的基础上提出利用图像阈值设定C-V模型的初始化轮廓的新方法,改变了原有C-V模型的初始轮廓线设置中存在的不足.新方法应用于牙菌斑图像分割中能够较好的识别牙齿图像边缘信息,为下一步对牙菌斑进行量化分析提供了良好的数据基础.%Variational level set method is a quite hot research point in image processing. C-V model is a classic approach to segment image based on variational level set. It is especially helpful for medical images analysis ,which has complex topology constructions, strong noises and lower contrast. But C-V model depends on initial contour. Image thresholding is also a simple and popular image segmentation method, which separates an image into two parts, and gets the target sub-image from background image. In the article, these two methods are integrated together. By analyzing the distribution of image gray level histogram , the authors propose a new method which initializes contour using threshold. It solves the shortages about how to set initial contours in C-V model . The novel C-V model used in dental plaque image segmentation and experiments illustrates that the method proposed can help segment images. It provides a preliminary work to further analyze dental plaque.

  1. Segmentation: Identification of consumer segments

    DEFF Research Database (Denmark)

    Høg, Esben


    origin in other sciences as for example biology, anthropology etc. From an economic point of view, it is called segmentation when specific scientific techniques are used to classify consumers to different characteristic groupings. What is the purpose of segmentation? For example, to be able to obtain...... a basic understanding of grouping people. Advertising agencies may use segmentation totarget advertisements, while food companies may usesegmentation to develop products to various groups of consumers. MAPP has for example investigated the positioning of fish in relation to other food products...... and analysed possible segments in the market. Results show that the statistical model used identified two segments - a segment of so-called "fish lovers" and another segment called "traditionalists". The "fish lovers" are very fond of eating fish and they actually prefer fish to other dishes...

  2. Efficient simulations of tubulin-driven axonal growth. (United States)

    Diehl, Stefan; Henningsson, Erik; Heyden, Anders


    This work concerns efficient and reliable numerical simulations of the dynamic behaviour of a moving-boundary model for tubulin-driven axonal growth. The model is nonlinear and consists of a coupled set of a partial differential equation (PDE) and two ordinary differential equations. The PDE is defined on a computational domain with a moving boundary, which is part of the solution. Numerical simulations based on standard explicit time-stepping methods are too time consuming due to the small time steps required for numerical stability. On the other hand standard implicit schemes are too complex due to the nonlinear equations that needs to be solved in each step. Instead, we propose to use the Peaceman-Rachford splitting scheme combined with temporal and spatial scalings of the model. Simulations based on this scheme have shown to be efficient, accurate, and reliable which makes it possible to evaluate the model, e.g. its dependency on biological and physical model parameters. These evaluations show among other things that the initial axon growth is very fast, that the active transport is the dominant reason over diffusion for the growth velocity, and that the polymerization rate in the growth cone does not affect the final axon length.

  3. The Highwire ubiquitin ligase promotes axonal degeneration by tuning levels of Nmnat protein.

    Directory of Open Access Journals (Sweden)

    Xin Xiong

    Full Text Available Axonal degeneration is a hallmark of many neuropathies, neurodegenerative diseases, and injuries. Here, using a Drosophila injury model, we have identified a highly conserved E3 ubiquitin ligase, Highwire (Hiw, as an important regulator of axonal and synaptic degeneration. Mutations in hiw strongly inhibit Wallerian degeneration in multiple neuron types and developmental stages. This new phenotype is mediated by a new downstream target of Hiw: the NAD+ biosynthetic enzyme nicotinamide mononucleotide adenyltransferase (Nmnat, which acts in parallel to a previously known target of Hiw, the Wallenda dileucine zipper kinase (Wnd/DLK MAPKKK. Hiw promotes a rapid disappearance of Nmnat protein in the distal stump after injury. An increased level of Nmnat protein in hiw mutants is both required and sufficient to inhibit degeneration. Ectopically expressed mouse Nmnat2 is also subject to regulation by Hiw in distal axons and synapses. These findings implicate an important role for endogenous Nmnat and its regulation, via a conserved mechanism, in the initiation of axonal degeneration. Through independent regulation of Wnd/DLK, whose function is required for proximal axons to regenerate, Hiw plays a central role in coordinating both regenerative and degenerative responses to axonal injury.

  4. Plum, an immunoglobulin superfamily protein, regulates axon pruning by facilitating TGF-β signaling. (United States)

    Yu, Xiaomeng M; Gutman, Itai; Mosca, Timothy J; Iram, Tal; Ozkan, Engin; Garcia, K Christopher; Luo, Liqun; Schuldiner, Oren


    Axon pruning during development is essential for proper wiring of the mature nervous system, but its regulation remains poorly understood. We have identified an immunoglobulin superfamily (IgSF) transmembrane protein, Plum, that is cell autonomously required for axon pruning of mushroom body (MB) γ neurons and for ectopic synapse refinement at the developing neuromuscular junction in Drosophila. Plum promotes MB γ neuron axon pruning by regulating the expression of Ecdysone Receptor-B1, a key initiator of axon pruning. Genetic analyses indicate that Plum acts to facilitate signaling of Myoglianin, a glial-derived TGF-β, on MB γ neurons upstream of the type-I TGF-β receptor Baboon. Myoglianin, Baboon, and Ecdysone Receptor-B1 are also required for neuromuscular junction ectopic synapse refinement. Our study highlights both IgSF proteins and TGF-β facilitation as key promoters of developmental axon elimination and demonstrates a mechanistic conservation between MB axon pruning during metamorphosis and the refinement of ectopic larval neuromuscular connections.

  5. Genetics Home Reference: giant axonal neuropathy (United States)

    ... R. Proteomic analysis in giant axonal neuropathy: new insights into disease mechanisms. Muscle Nerve. 2012 Aug;46( ... healthcare professional . About Genetics Home Reference Site Map Customer Support Selection Criteria for Links Copyright ...

  6. Genetic dissection of myelinated axons in zebrafish



    In the vertebrate nervous system, the myelin sheath allows for rapid and efficient conduction of action potentials along axons. Despite the essential function of myelin, many questions remain unanswered about the mechanisms that govern the development of myelinated axons. The fundamental properties of myelin are widely shared among vertebrates, and the zebrafish has emerged as a powerful system to study myelination in vivo. This review will highlight recent advances from genetic screens in ze...

  7. Crossing axons in the third nerve nucleus. (United States)

    Bienfang, D C


    The research presented in this paper studied the pathway taken by the crossed fibers of the third nerve nucleus in an animal whose nucleus has been well mapped and found to correlate well with higher mammals and man. Autoradiography using tritiated amino acid labeled the cell bodies an axons of the left side of the oculomotor nucleus of the cat. Axons so labeled could be seen emerging from the ventral portion of the left nucleus through the median longitudinal fasciculus (mlf) to join the left oculomotor nerve. Labeled axons were also seen to emerge from the medial border of the caudal left nucleus, cross the midline, and pass through the right nucleus and the right mlf to join the right oculomotor nerve. These latter axons must be the crossed axons of the superior rectus and levator palpebrae subnuclei. Since the path of these crossed axons is through the caudal portion of the nucleus of the opposite side, the destruction of one lateral half of the oculomotor nucleus would result in a bilateral palsy of the crossed subnuclei. Bilateral palsy of the superior rectus and bilateral assymetrical palsy of the levator palpebrae muscles would result.

  8. Medical image segmentation by MDP model (United States)

    Lu, Yisu; Chen, Wufan


    MDP (Dirichlet Process Mixtures) model is applied to segment medical images in this paper. Segmentation can been automatically done without initializing segmentation class numbers. The MDP model segmentation algorithm is used to segment natural images and MR (Magnetic Resonance) images in the paper. To demonstrate the accuracy of the MDP model segmentation algorithm, many compared experiments, such as EM (Expectation Maximization) image segmentation algorithm, K-means image segmentation algorithm and MRF (Markov Field) image segmentation algorithm, have been done to segment medical MR images. All the methods are also analyzed quantitatively by using DSC (Dice Similarity Coefficients). The experiments results show that DSC of MDP model segmentation algorithm of all slices exceed 90%, which show that the proposed method is robust and accurate.

  9. Astrocytes phagocytose focal dystrophies from shortening myelin segments in the optic nerve of Xenopus laevis at metamorphosis. (United States)

    Mills, Elizabeth A; Davis, Chung-ha O; Bushong, Eric A; Boassa, Daniela; Kim, Keun-Young; Ellisman, Mark H; Marsh-Armstrong, Nicholas


    Oligodendrocytes can adapt to increases in axon diameter through the addition of membrane wraps to myelin segments. Here, we report that myelin segments can also decrease their length in response to optic nerve (ON) shortening during Xenopus laevis metamorphic remodeling. EM-based analyses revealed that myelin segment shortening is accomplished by focal myelin-axon detachments and protrusions from otherwise intact myelin segments. Astrocyte processes remove these focal myelin dystrophies using known phagocytic machinery, including the opsonin milk fat globule-EGF factor 8 (Mfge8) and the downstream effector ras-related C3 botulinum toxin substrate 1 (Rac1). By the end of metamorphic nerve shortening, one-quarter of all myelin in the ON is enwrapped or internalized by astrocytes. As opposed to the removal of degenerating myelin by macrophages, which is usually associated with axonal pathologies, astrocytes selectively remove large amounts of myelin without damaging axons during this developmental remodeling event.

  10. Fingerprint Segmentation


    Jomaa, Diala


    In this thesis, a new algorithm has been proposed to segment the foreground of the fingerprint from the image under consideration. The algorithm uses three features, mean, variance and coherence. Based on these features, a rule system is built to help the algorithm to efficiently segment the image. In addition, the proposed algorithm combine split and merge with modified Otsu. Both enhancements techniques such as Gaussian filter and histogram equalization are applied to enhance and improve th...

  11. The L1-type cell adhesion molecule Neuroglian is necessary for maintenance of sensory axon advance in the Drosophila embryo

    Directory of Open Access Journals (Sweden)

    Martin Veronica


    Full Text Available Abstract Background Cell adhesion molecules have long been implicated in the regulation of axon growth, but the precise cellular roles played by individual cell adhesion molecules and the molecular basis for their action are still not well understood. We have used the sensory system of the Drosophila embryo to shed light on the mechanism by which the L1-type cell adhesion molecule Neuroglian regulates axon growth. Results We have found a highly penetrant sensory axon stalling phenotype in neuroglian mutant embryos. Axons stalled at a variety of positions along their normal trajectory, but most commonly in the periphery some distance along the peripheral nerve. All lateral and dorsal cluster sensory neurons examined, except for the dorsal cluster neuron dbd, showed stalling. Sensory axons were never seen to project along inappropriate pathways in neuroglian mutants and stalled axons showed normal patterns of fasciculation within nerves. The growth cones of stalled axons possessed a simple morphology, similar to their appearance in wild-type embryos when advancing along nerves. Driving expression of the wild-type form of Neuroglian in sensory neurons alone rescued the neuroglian mutant phenotype of both pioneering and follower neurons. A partial rescue was achieved by expressing the Neuroglian extracellular domain. Over/mis-expression of Neuroglian in all neurons, oenocytes or trachea had no apparent effect on sensory axon growth. Conclusion We conclude that Neuroglian is necessary to maintain axon advance along axonal substrates, but is not required for initiation of axon outgrowth, axon fasciculation or recognition of correct growth substrates. Expression of Neuroglian in sensory neurons alone is sufficient to promote axon advance and the intracellular region of the molecule is largely dispensable for this function. It is unlikely, therefore, that Nrg acts as a molecular 'clutch' to couple adhesion of F-actin within the growth cone to the

  12. Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase. (United States)

    Chen, Lizhen; Chuang, Marian; Koorman, Thijs; Boxem, Mike; Jin, Yishi; Chisholm, Andrew D


    Axon injury triggers a series of changes in the axonal cytoskeleton that are prerequisites for effective axon regeneration. In Caenorhabditis elegans the signaling protein Exchange Factor for ARF-6 (EFA-6) is a potent intrinsic inhibitor of axon regrowth. Here we show that axon injury triggers rapid EFA-6-dependent inhibition of axonal microtubule (MT) dynamics, concomitant with relocalization of EFA-6. EFA-6 relocalization and axon regrowth inhibition require a conserved 18-aa motif in its otherwise intrinsically disordered N-terminal domain. The EFA-6 N-terminus binds the MT-associated proteins TAC-1/Transforming-Acidic-Coiled-Coil, and ZYG-8/Doublecortin-Like-Kinase, both of which are required for regenerative growth cone formation, and which act downstream of EFA-6. After injury TAC-1 and EFA-6 transiently relocalize to sites marked by the MT minus end binding protein PTRN-1/Patronin. We propose that EFA-6 acts as a bifunctional injury-responsive regulator of axonal MT dynamics, acting at the cell cortex in the steady state and at MT minus ends after injury.

  13. GABA increases electrical excitability in a subset of human unmyelinated peripheral axons.

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    Richard W Carr

    Full Text Available BACKGROUND: A proportion of small diameter primary sensory neurones innervating human skin are chemosensitive. They respond in a receptor dependent manner to chemical mediators of inflammation as well as naturally occurring algogens, thermogens and pruritogens. The neurotransmitter GABA is interesting in this respect because in animal models of neuropathic pain GABA pre-synaptically regulates nociceptive input to the spinal cord. However, the effect of GABA on human peripheral unmyelinated axons has not been established. METHODOLOGY/PRINCIPAL FINDINGS: Electrical stimulation was used to assess the effect of GABA on the electrical excitability of unmyelinated axons in isolated fascicles of human sural nerve. GABA (0.1-100 microM increased electrical excitability in a subset (ca. 40% of C-fibres in human sural nerve fascicles suggesting that axonal GABA sensitivity is selectively restricted to a sub-population of human unmyelinated axons. The effects of GABA were mediated by GABA(A receptors, being mimicked by bath application of the GABA(A agonist muscimol (0.1-30 microM while the GABA(B agonist baclofen (10-30 microM was without effect. Increases in excitability produced by GABA (10-30 microM were blocked by the GABA(A antagonists gabazine (10-20 microM, bicuculline (10-20 microM and picrotoxin (10-20 microM. CONCLUSIONS/SIGNIFICANCE: Functional GABA(A receptors are present on a subset of unmyelinated primary afferents in humans and their activation depolarizes these axons, an effect likely due to an elevated intra-axonal chloride concentration. GABA(A receptor modulation may therefore regulate segmental and peripheral components of nociception.

  14. Optimal myelin elongation relies on YAP activation by axonal growth and inhibition by Crb3/Hippo pathway (United States)

    Fernando, Ruani N.; Cotter, Laurent; Perrin-Tricaud, Claire; Berthelot, Jade; Bartolami, Sylvain; Pereira, Jorge A.; Gonzalez, Sergio; Suter, Ueli; Tricaud, Nicolas


    Fast nerve conduction relies on successive myelin segments that electrically isolate axons. Segment geometry—diameter and length—is critical for the optimization of nerve conduction and the molecular mechanisms allowing this optimized geometry are partially known. We show here that peripheral myelin elongation is dynamically regulated by stimulation of YAP (Yes-associated protein) transcription cofactor activity during axonal elongation and limited by inhibition of YAP activity via the Hippo pathway. YAP promotes myelin and non-myelin genes transcription while the polarity protein Crb3, localized at the tips of the myelin sheath, activates the Hippo pathway to temper YAP activity, therefore allowing for optimal myelin growth. Dystrophic Dy2j/2j mice mimicking human peripheral neuropathy with reduced internodal lengths have decreased nuclear YAP which, when corrected, leads to longer internodes. These data show a novel mechanism controlling myelin growth and nerve conduction, and provide a molecular ground for disease with short myelin segments. PMID:27435623

  15. 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.

  16. Protein phosphorylation: Localization in regenerating optic axons

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    Larrivee, D. (Cornell Univ. Medical College, New York, NY (USA))


    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.

  17. The clinical utility of reduced-distortion readout-segmented echo-planar imaging in the head and neck region: initial experience

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    Koyasu, Sho; Iima, Mami; Umeoka, Shigeaki; Morisawa, Nobuko; Togashi, Kaori [Kyoto University, Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Sakyo-Ku, Kyoto (Japan); Porter, David A. [Siemens AG, MED MR PLM AW Neurology, Allee am Roethelheimpark 2, Erlangen (Germany); Ito, Juichi [Kyoto University, Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Sakyo-Ku, Kyoto (Japan); Le Bihan, Denis [Kyoto University, Human Brain Research Center, Graduate School of Medicine, Sakyo-Ku, Kyoto (Japan); Neurospin, CEA-Saclay Center, Gif-sur-Yvette Cedex (France)


    To evaluate whether readout-segmented echo-planar imaging (RS-EPI) diffusion weighted image (DWI) can diminish image distortion in the head and neck area, compared with single-shot (SS)-EPI DWI. We conducted phantom and patient studies using 3 T magnetic resonance imaging (MRI) with a 16-channel coil. For the phantom study, we evaluated distortion and signal homogeneity in gel phantoms. For the patient study, 29 consecutive patients with clinically suspicious parotid lesions were prospectively enrolled. RS-EPI and SS-EPI DWI were evaluated by two independent readers for identification of organ/lesion and distortion, using semiquantitative scales and quantitative scores. Apparent diffusion coefficient (ADC) values and contrast-noise ratios of parotid tumours (if present; n = 15) were also compared. The phantom experiments showed that RS-EPI provided less distorted and more homogeneous ADC maps than SS-EPI. In the patient study, RS-EPI was found to provide significantly less distortion in almost all organs/lesions (p < 0.05), according to both semiquantitative scales and quantitative scores. There was no significant difference in ADC values and contrast-noise ratios between the two DWI techniques. The distortion in DWI was significantly reduced with RS-EPI in both phantom and patient studies. The RS-EPI technique provided more homogenous images than SS-EPI, and can potentially offer higher image quality in the head and neck area. (orig.)

  18. Sustained maximal voluntary contraction produces independent changes in human motor axons and the muscle they innervate.

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    David A Milder

    Full Text Available The repetitive discharges required to produce a sustained muscle contraction results in activity-dependent hyperpolarization of the motor axons and a reduction in the force-generating capacity of the muscle. We investigated the relationship between these changes in the adductor pollicis muscle and the motor axons of its ulnar nerve supply, and the reproducibility of these changes. Ten subjects performed a 1-min maximal voluntary contraction. Activity-dependent changes in axonal excitability were measured using threshold tracking with electrical stimulation at the wrist; changes in the muscle were assessed as evoked and voluntary electromyography (EMG and isometric force. Separate components of axonal excitability and muscle properties were tested at 5 min intervals after the sustained contraction in 5 separate sessions. The current threshold required to produce the target muscle action potential increased immediately after the contraction by 14.8% (p<0.05, reflecting decreased axonal excitability secondary to hyperpolarization. This was not correlated with the decline in amplitude of muscle force or evoked EMG. A late reversal in threshold current after the initial recovery from hyperpolarization peaked at -5.9% at ∼35 min (p<0.05. This pattern was mirrored by other indices of axonal excitability revealing a previously unreported depolarization of motor axons in the late recovery period. Measures of axonal excitability were relatively stable at rest but less so after sustained activity. The coefficient of variation (CoV for threshold current increase was higher after activity (CoV 0.54, p<0.05 whereas changes in voluntary (CoV 0.12 and evoked twitch (CoV 0.15 force were relatively stable. These results demonstrate that activity-dependent changes in motor axon excitability are unlikely to contribute to concomitant changes in the muscle after sustained activity in healthy people. The variability in axonal excitability after sustained activity

  19. Comparison of electrical responses of terminals, axons, and somata of a peptidergic neurosecretory system. (United States)

    Nagano, M; Cooke, I M


    Spontaneous and evoked electrical activity was recorded intracellularly from somata, axons, and terminal dilatations of an isolated peptidergic neurosecretory system, the X-organ-sinus gland, of the crabs Cardisoma carnifex and Podophthalmus vigil in order to compare their electrical characteristics. Spontaneous impulse activity was present in most penetrations and included irregular and pacemaker-like firing, as well as patterned activity (bursting). Extracellular recording showed that spontaneous impulses and bursting originate in a proximal region of the axon tract. Somata vary from being electrically nonresponsive to having overshooting impulses with a relatively slow rate of rise. Overshooting impulses were consistently recorded from axons and terminals. Regional differences include (1) a longer action potential duration in terminals, (2) ability of axons and terminals but not somata to sustain repetitive firing, (3) presence of depolarizing afterpotentials in axons but of hyperpolarizing afterpotentials in somata and terminals, and (4) occurrence of impulse broadening during repetitive firing in some terminals but not in axons or somata. Somata and terminals sustained reduced and slowed, but regenerative impulses in nominally Na-free saline and showed alterations of waveform in nominally Ca-free salines, while axons showed no regenerative responses in Na-free saline and no change of impulse form in Ca-free saline. Terminal responses in the presence of tetraethylammonium chloride (TEA) (50 mM) or Ba (50 mM) exhibited long depolarized plateaus, while impulses of somata were much less prolonged. Bursts often took the form of impulses superimposed on a depolarized plateau. Bursts could be evoked by single stimuli applied to the axon tract but not by current passed intracellularly. After addition of TTX, axon tract stimulation evoked plateaus without superimposed impulses. Terminals exhibit specialization of their electrical responses by comparison to axons and


    Physicochemical and analytical studies of the fibrous protein and other constituents of the axoplasm of the giant fibers of the large squid Dosidicus ... gigas were made. Axon material was dissected from a large number of squid and stock piled for future analysis. Initial experiments were made in an

  1. Rescuing axons from degeneration does not affect retinal ganglion cell death

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    S. de Lima


    Full Text Available After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD, an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18 treated with an exogenous calpain inhibitor (20 mM administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05 and an increase in the number of preserved fibers (P<0.05 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage.

  2. Dopaminergic and glutamatergic microdomains in a subset of rodent mesoaccumbens axons. (United States)

    Zhang, Shiliang; Qi, Jia; Li, Xueping; Wang, Hui-Ling; Britt, Jonathan P; Hoffman, Alexander F; Bonci, Antonello; Lupica, Carl R; Morales, Marisela


    Mesoaccumbens fibers are thought to co-release dopamine and glutamate. However, the mechanism is unclear, and co-release by mesoaccumbens fibers has not been documented. Using electron microcopy, we found that some mesoaccumbens fibers have vesicular transporters for dopamine (VMAT2) in axon segments that are continuous with axon terminals that lack VMAT2, but contain vesicular glutamate transporters type 2 (VGluT2). In vivo overexpression of VMAT2 did not change the segregation of the two vesicular types, suggesting the existence of highly regulated mechanisms for maintaining this segregation. The mesoaccumbens axon terminals containing VGluT2 vesicles make asymmetric synapses, commonly associated with excitatory signaling. Using optogenetics, we found that dopamine and glutamate were released from the same mesoaccumbens fibers. These findings reveal a complex type of signaling by mesoaccumbens fibers in which dopamine and glutamate can be released from the same axons, but are not normally released at the same site or from the same synaptic vesicles.

  3. 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.

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

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    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.

  5. Axon-glial relationships in the anterior medullary velum of the adult rat. (United States)

    Berry, M; Ibrahim, M; Carlile, J; Ruge, F; Duncan, A; Butt, A M


    The anterior medullary velum is a thin sheet of CNS tissue which roofs the rostral part of the IVth ventricle and contains fascicles of myelinated fibres which, in part, arise from the nucleus of the IVth cranial nerve. This study used histochemical, immunohistochemical, and intracellular dye-injection techniques to describe cellular interrelationships in the velum in whole-mounts and in sections. Rip antibody-stained whole mounts provided a unique description of both oligodendrocyte units (defined as an oligodendrocyte and the complement of myelinated internodal segments it forms), and consecutive myelin sheaths along the same axon. A broad range of unit morphologies was categorised into four arbitrary groups, according to classical criteria, which comprised small cells supporting the short, thin myelin sheaths of 15-30 small diameter axons (Type I), through intermediate types (II & III), to the largest cells forming the long, thick myelin sheaths of 1-3 large diameter axons. Rip antibody and ferric ion-ferrocyanide staining, together with intracellular dye injection, revealed oligodendrocyte process branching patterns and their mode of engagement of myelin sheaths, nodes of Ranvier, and the spatial disposition of the outer cytoplasmic rims of myelin sheaths. The latter formed a conspicuous spiral ridge on the exterior surface of myelin sheaths which connected with the paranodal loops at each heminode. Large bundles of axons decussated through the velum, the bulk of which were IVth nerve fibres which constituted the IVth nerve rootlet. The PNS/CNS transitional zone of the IVth nerve was located 0.25-0.50 mm along the root, where astrocytic end-feet defined an abrupt margin, convex towards the periphery, where the heminodes of central and peripheral myelin were apposed, and where the basal lamina tubes of the Schwann cell units were discontinued. The basal processes of ependymal cells lining the ventricular wall of the velum, passed between axon bundles before

  6. Neural Progenitor Cells Promote Axonal Growth and Alter Axonal mRNA Localization in Adult Neurons (United States)

    Merianda, Tanuja T.; Jin, Ying


    Abstract The inhibitory environment of the spinal cord and the intrinsic properties of neurons prevent regeneration of axons following CNS injury. However, both ascending and descending axons of the injured spinal cord have been shown to regenerate into grafts of embryonic neural progenitor cells (NPCs). Previous studies have shown that grafts composed of glial-restricted progenitors (GRPs) and neural-restricted progenitors (NRPs) can provide a permissive microenvironment for axon growth. We have used cocultures of adult rat dorsal root ganglion (DRG) neurons together with NPCs, which have shown significant enhancement of axon growth by embryonic rat GRP and GRPs/NRPs, both in coculture conditions and when DRGs are exposed to conditioned medium from the NPC cultures. This growth-promoting effect of NPC-conditioned medium was also seen in injury-conditioned neurons. DRGs cocultured with GRPs/NRPs showed altered expression of regeneration-associated genes at transcriptional and post-transcriptional levels. We found that levels of GAP-43 mRNA increased in DRG cell bodies and axons. However, hepcidin antimicrobial peptide (HAMP) mRNA decreased in the cell bodies of DRGs cocultured with GRPs/NRPs, which is distinct from the increase in cell body HAMP mRNA levels seen in DRGs after injury conditioning. Endogenous GAP-43 and β-actin mRNAs as well as reporter RNAs carrying axonally localizing 3'UTRs of these transcripts showed significantly increased levels in distal axons in the DRGs cocultured with GRPs/NRPs. These results indicate that axon growth promoted by NPCs is associated not only with enhanced transcription of growth-associated genes but also can increase localization of some mRNAs into growing axons. PMID:28197547

  7. Axonal degeneration in association with carpal tunnel syndrome Degeneração axonal na síndrome do túnel do carpo

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    Marcelo Ribeiro Caetano


    Full Text Available Median nerve entrapment in the palm to wrist segment is known as carpal tunnel syndrome (CTS. Electromyography is the best evaluation test to confirm the disease, as it shows a median reduced conduction velocity and/or conduction block; however, the usual CTS electrodiagnostic tests do not separate segmental demyelination alone from segmental demyelination plus secondary axonal degeneration. We studied 100 hands from CTS patients (classified as mild, moderate, and severe, and 50 hands from normal subjects. The median palmar sensory nerve action potential (SNAP amplitude was measured and compared between the two groups. It would be expected that SNAP was normal if no axonal degeneration had occurred. The results showed that in mild CTS group and part of moderate CTS group SNAP amplitude was normal, whereas in severe CTS group, and part of moderate group SNAP amplitude was reduced, proving that axonal degeneration was involved. As it is well stated that axonal lesions have worse prognosis than segmental demyelinating ones, this simple test may help to preditic the CTS outcome and treatment.A compressão do nervo mediano no segmento punho-palma produz uma entidade clínica conhecida como síndrome do túnel do carpo (STC. A eletroneuromiografia é o exame de escolha para o diagnóstico da STC, através da identificação de diminuição de velocidade e/ou bloqueio de condução quando estudamos a neurocondução do nervo mediano, no trecho do punho. Entretanto, as técnicas comumente usadas não conseguem separar a lesão em mielínica focal com ou sem degeneração axonal secundária. Avaliamos 100 mãos de pacientes com STC e comparamos com 50 mãos de um grupo controle. Medimos a amplitude do potencial de ação do nervo sensitivo do mediano, com estímulo na palma e captação no dedo, e comparamos entre os grupos controle e de pacientes (o grupo de STC foi subdividido em leve, moderado e grave. Era esperado que a amplitude do potencial

  8. Tracking Quantum-Dot labeled neurotropic factors transport along primary neuronal axons in compartmental microfluidic chambers. (United States)

    Gluska, Shani; Chein, Michael; Rotem, Nimrod; Ionescu, Ariel; Perlson, Eran


    Neurons are highly polarized cells, with very long axons. Neurotrophic factors like the neuronal growth factor (NGF) are secreted from neuronal targets to promote neuron survival and proper function. These neurotrophic factors must undergo retrograde axonal transport towards the cell body, wherein they initiate signaling pathways important for neurons' various functions and overall health. This process of long-distance axonal signaling is conducted by the dynein motor protein, which transmits signaling endosomes of ligand-receptor complexes retrogradely along microtubule tracks. Here we describe step by step the use of polydimethylsiloxane (PDMS) compartmentalized microfluidic chambers for tracking axonal transport of trophic factors, with a focus on labeled NGF. We describe in detail how to fabricate the molds, assemble the PDMS platform, plate neurons and image, as well as analyze NGF transport along the axon. This method is useful for studying molecular communication mechanisms within the neuron's different compartments as well as between the neuron and its diverse microenvironments, both in health and under pathological conditions.

  9. Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

    Institute of Scientific and Technical Information of China (English)

    Wen-Liang Lei; Shi-Ge Xing; Cai-Yun Deng; Xiang-Chun Ju; Xing-Yu Jiang; Zhen-Ge Luo


    Axon specification during neuronal polarization is closely associated with increased microtubule stabilization in one of the neurites of unpolarized neuron,but how this increased microtubule stability is achieved is unclear.Here,we show that extracellular matrix (ECM) component laminin promotes neuronal polarization via regulating directional microtubule assembly through β1 integrin (Itgb1).Contact with laminin coated on culture substrate or polystyrene beads was sufficient for axon specification of undifferentiated neurites in cultured hippocampal neurons and cortical slices.Active Itgb1 was found to be concentrated in laminin-contacting neurites.Axon formation was promoted and abolished by enhancing and attenuating Itgbl signaling,respectively.Interestingly,laminin contact promoted plus-end microtubule assembly in a manner that required Itgbl.Moreover,stabilizing microtubules partially prevented polarization defects caused by ltgbl downregulation.Finally,genetic ablation of ltgbl in dorsal telencephalic progenitors caused deficits in axon development of cortical pyramidal neurons.Thus,laminin/Itgb1 signaling plays an instructive role in axon initiation and growth,both in vitro and in vivo,through the regulation of microtubule assembly.This study has established a linkage between an extrinsic factor and intrinsic cytoskeletai dynamics during neuronal polarization.

  10. Myelin-associated glycoprotein and its axonal receptors. (United States)

    Schnaar, Ronald L; Lopez, Pablo H H


    Myelin-associated glycoprotein (MAG) is expressed on the innermost myelin membrane wrap, directly apposed to the axon surface. Although it is not required for myelination, MAG enhances long-term axon-myelin stability, helps to structure nodes of Ranvier, and regulates the axon cytoskeleton. In addition to its role in axon-myelin stabilization, MAG inhibits axon regeneration after injury; MAG and a discrete set of other molecules on residual myelin membranes at injury sites actively signal axons to halt elongation. Both the stabilizing and the axon outgrowth inhibitory effects of MAG are mediated by complementary MAG receptors on the axon surface. Two MAG receptor families have been described, sialoglycans (specifically gangliosides GD1a and GT1b) and Nogo receptors (NgRs). Controversies remain about which receptor(s) mediates which of MAG's biological effects. Here we review the findings and challenges in associating MAG's biological effects with specific receptors.

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

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    Jan Jessen Krut

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

  12. Arrest of myelination and reduced axon growth when Schwann cells lack mTOR. (United States)

    Sherman, Diane L; Krols, Michiel; Wu, Lai-Man N; Grove, Matthew; Nave, Klaus-Armin; Gangloff, Yann-Gaël; Brophy, Peter J


    In developing peripheral nerves, differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. In recent years, there has been an increased understanding of the extracellular and intracellular factors that initiate and stimulate Schwann cell myelination, together with a growing appreciation of some of the signaling pathways involved. However, our knowledge of how Schwann cell growth is regulated during myelination is still incomplete. The mammalian target of rapamycin (mTOR) is a core kinase in two major complexes, mTORC1 and mTORC2, that regulate cell growth and differentiation in a variety of mammalian cells. Here we show that elimination of mTOR from murine Schwann cells prevented neither radial sorting nor the initiation of myelination. However, normal postnatal growth of myelinating Schwann cells, both radially and longitudinally, was highly retarded. The myelin sheath in the mutant was much thinner than normal; nevertheless, sheath thickness relative to axon diameter (g-ratio) remained constant in both wild-type and mutant nerves from P14 to P90. Although axon diameters were normal in the mutant at the initiation of myelination, further growth as myelination proceeded was retarded, and this was associated with reduced phosphorylation of neurofilaments. Consistent with thinner axonal diameters and internodal lengths, conduction velocities in mutant quadriceps nerves were also reduced. These data establish a critical role for mTOR signaling in both the longitudinal and radial growth of the myelinating Schwann cell.

  13. The pathophysiology of axonal transport in alzheimer’s disease


    Vicario Orri, Elena; Opazo, Carlos; Muñoz López, Francisco José, 1964-


    Neurons communicate in the nervous system by carrying out information along the length of their axons to finally transmit it at the synapse. Proper function of axons and axon terminals relies on the transport of proteins, organelles, vesicles, and other elements from the site of synthesis in the cell body. Conversely, neurotrophins secreted from axonal targets and other components at nerve terminals need to travel toward the cell body for clearance. Molecular motors, namely kinesins and dynei...

  14. The developmentally regulated expression of Menkes protein ATP7A suggests a role in axon extension and synaptogenesis. (United States)

    El Meskini, Rajaâ; Cline, Laura B; Eipper, Betty A; Ronnett, Gabriele V


    Menkes disease (MD) is a neurodegenerative disorder caused by mutation of the copper transporter ATP7A. While several enzymes expressed in mature neurons require copper, MD neurodegenerative changes cannot be explained by known requirements for ATP7A in neuronal development. To investigate additional roles for ATP7A during development, we characterized its pattern of expression using the olfactory system as a neurodevelopmental model. ATP7A expression in neurons was developmentally regulated rather than constitutively. Initially expressed in the cell bodies of developing neurons, ATP7A protein later shifted to extending axons, peaking prior to synaptogenesis. Similarly, after injury-stimulated neurogenesis, ATP7A expression increased in neurons and axons preceding synaptogenesis. Interestingly, copper-transport-deficient ATP7A still exhibits axonal localization. These results support a role for ATP7A in axon extension, which may contribute to the severe neurodegeneration characteristic of MD.

  15. Modeling molecular mechanisms in the axon (United States)

    de Rooij, R.; Miller, K. E.; Kuhl, E.


    Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena—both in isolation and in interaction—to explore emergent cellular-level features under physiological and pathological conditions.

  16. A Microfluidics Approach to Investigate Axon Guidance (United States)


    coat the substrate with PLL. The cells of one dissociated embryonic spinal cord was re-suspended in 3 µl of freshly-prepared Modified Frog Ringer’s...Surround repulsion of spinal sensory axons in higher vertebrate embryos . Neuron 18, 889-897 (1997). 8. Colamarino, S. & Tessier-Lavigne, M. The

  17. 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.

  18. MAPK signaling promotes axonal degeneration by speeding the turnover of the axonal maintenance factor NMNAT2 (United States)

    Walker, Lauren J; Summers, Daniel W; Sasaki, Yo; Brace, EJ; Milbrandt, Jeffrey; DiAntonio, Aaron


    Injury-induced (Wallerian) axonal degeneration is regulated via the opposing actions of pro-degenerative factors such as SARM1 and a MAPK signal and pro-survival factors, the most important of which is the NAD+ biosynthetic enzyme NMNAT2 that inhibits activation of the SARM1 pathway. Here we investigate the mechanism by which MAPK signaling facilitates axonal degeneration. We show that MAPK signaling promotes the turnover of the axonal survival factor NMNAT2 in cultured mammalian neurons as well as the Drosophila ortholog dNMNAT in motoneurons. The increased levels of NMNAT2 are required for the axonal protection caused by loss of MAPK signaling. Regulation of NMNAT2 by MAPK signaling does not require SARM1, and so cannot be downstream of SARM1. Hence, pro-degenerative MAPK signaling functions upstream of SARM1 by limiting the levels of the essential axonal survival factor NMNAT2 to promote injury-dependent SARM1 activation. These findings are consistent with a linear molecular pathway for the axonal degeneration program. DOI: PMID:28095293

  19. Primary mirror segment fabrication for CELT (United States)

    Mast, Terry S.; Nelson, Jerry E.; Sommargren, Gary E.


    The primary mirror of the proposed California Extremely Large Telescope is a 30-meter diameter mosaic of hexagonal segments. An initial design calls for about a thousand segments with a hexagon side length of 0.5 meters, a primary-mirror focal ratio of 1.5, and a segment surface quality of about 20 nanometers rms. We describe concepts for fabricating these segments.

  20. [Segmental neurofibromatosis]. (United States)

    Zulaica, A; Peteiro, C; Pereiro, M; Pereiro Ferreiros, M; Quintas, C; Toribio, J


    Four cases of segmental neurofibromatosis (SNF) are reported. It is a rare entity considered to be a localized variant of neurofibromatosis (NF)-Riccardi's type V. Two cases are male and two female. The lesions are located to the head in a patient and the other three cases in the trunk. No family history nor transmission to progeny were manifested. The rest of the organs are undamaged.

  1. Spider silk constructs enhance axonal regeneration and remyelination in long nerve defects in sheep.

    Directory of Open Access Journals (Sweden)

    Christine Radtke

    Full Text Available BACKGROUND: Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. METHODOLOGY/PRINCIPAL FINDINGS: The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6 was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6 staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery.

  2. Axonal diameter and density estimated with 7-Tesla hybrid diffusion imaging in transgenic Alzheimer rats (United States)

    Daianu, Madelaine; Jacobs, Russell E.; Town, Terrence; Thompson, Paul M.


    Diffusion-weighted MR imaging (DWI) is a powerful tool to study brain tissue microstructure. DWI is sensitive to subtle changes in the white matter (WM), and can provide insight into abnormal brain changes in diseases such as Alzheimer's disease (AD). In this study, we used 7-Tesla hybrid diffusion imaging (HYDI) to scan 3 transgenic rats (line TgF344-AD; that model the full clinico-pathological spectrum of the human disease) ex vivo at 10, 15 and 24 months. We acquired 300 DWI volumes across 5 q-sampling shells (b=1000, 3000, 4000, 8000, 12000 s/mm2). From the top three b-value shells with highest signal-to-noise ratios, we reconstructed markers of WM disease, including indices of axon density and diameter in the corpus callosum (CC) - directly quantifying processes that occur in AD. As expected, apparent anisotropy progressively decreased with age; there were also decreases in the intra- and extra-axonal MR signal along axons. Axonal diameters were larger in segments of the CC (splenium and body, but not genu), possibly indicating neuritic dystrophy - characterized by enlarged axons and dendrites as previously observed at the ultrastructural level (see Cohen et al., J. Neurosci. 2013). This was further supported by increases in MR signals trapped in glial cells, CSF and possibly other small compartments in WM structures. Finally, tractography detected fewer fibers in the CC at 10 versus 24 months of age. These novel findings offer great potential to provide technical and scientific insight into the biology of brain disease.

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Christopher Nelson Hansen


    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

  5. Sparing of Descending Axons Rescues Interneuron Plasticity in the Lumbar Cord to Allow Adaptive Learning After Thoracic Spinal Cord Injury. (United States)

    Hansen, Christopher N; Faw, Timothy D; White, Susan; Buford, John A; Grau, James W; Basso, D Michele


    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 (ILP). 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 7 days, 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 spared

  6. Polyethylene glycol rapidly restores axonal integrity and improves the rate of motor behavior recovery after sciatic nerve crush injury. (United States)

    Britt, Joshua M; Kane, Jacqueline R; Spaeth, Christopher S; Zuzek, Aleksej; Robinson, Garrett L; Gbanaglo, Melengor Y; Estler, Cody J; Boydston, Elaine A; Schallert, Timothy; Bittner, George D


    The inability to rapidly (within minutes to hours) improve behavioral function after severance of peripheral nervous system axons is an ongoing clinical problem. We have previously reported that polyethylene glycol (PEG) can rapidly restore axonal integrity (PEG-fusion) between proximal and distal segments of cut- and crush-severed rat axons in vitro and in vivo. We now report that PEG-fusion not only reestablishes the integrity of crush-severed rat sciatic axons as measured by the restored conduction of compound action potentials (CAPs) and the intraaxonal diffusion of fluorescent dye across the lesion site, but also produces more rapid recovery of appropriate hindlimb motor behaviors. Improvement in recovery occurred during the first few postoperative weeks for the foot fault (FF) asymmetry test and between week 2 and week 3 for the Sciatic Functional Index (SFI) based on analysis of footprints. That is, the FF test was the more sensitive indicator of early behavioral recovery, showing significant postoperative improvement of motor behavior in PEG-treated animals at 24-48 h. In contrast, the SFI more sensitively measured longer-term postoperative behavioral recovery and deficits at 4-8 wk, perhaps reflecting the development of fine (distal) motor control. These and other data show that PEG-fusion not only rapidly restores physiological and morphological axonal continuity, but also more quickly improves behavioral recovery.

  7. 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.

  8. 4-Hydroxy-2-nonenal induces mitochondrial dysfunction and aberrant axonal outgrowth in adult sensory neurons that mimics features of diabetic neuropathy. (United States)

    Akude, Eli; Zherebitskaya, Elena; Roy Chowdhury, Subir K; Girling, Kimberly; Fernyhough, Paul


    Modification of proteins by 4-hydroxy-2-nonenal (4-HNE) has been proposed to cause neurotoxicity in a number of neurodegenerative diseases, including distal axonopathy in diabetic sensory neuropathy. We tested the hypothesis that exposure of cultured adult rat sensory neurons to 4-HNE would result in the formation of amino acid adducts on mitochondrial proteins and that this process would be associated with impaired mitochondrial function and axonal regeneration. In addition, we compared 4-HNE-induced axon pathology with that exhibited by neurons isolated from diabetic rats. Cultured adult rat dorsal root ganglion (DRG) sensory neurons were incubated with varying concentrations of 4-HNE. Cell survival, axonal morphology, and level of axon outgrowth were assessed. In addition, video microscopy of live cells, western blot, and immunofluorescent staining were utilized to detect protein adduct formation by 4-HNE and to localize actively respiring mitochondria. 4-HNE induced formation of protein adducts on cytoskeletal and mitochondrial proteins, and impaired axon regeneration by approximately 50% at 3 microM while having no effect on neuronal survival. 4-HNE initiated formation of aberrant axonal structures and caused the accumulation of mitochondria in these dystrophic structures. Neurons treated with 4-HNE exhibited a distal loss of active mitochondria. Finally, the distal axonopathy and the associated aberrant axonal structures generated by 4-HNE treatment mimicked axon pathology observed in DRG sensory neurons isolated from diabetic rats and replicated aspects of neurodegeneration observed in human diabetic sensory neuropathy.

  9. T-cell- and macrophage-mediated axon damage in the absence of a CNS-specific immune response: involvement of metalloproteinases. (United States)

    Newman, T A; Woolley, S T; Hughes, P M; Sibson, N R; Anthony, D C; Perry, V H


    Recent evidence has highlighted the fact that axon injury is an important component of multiple sclerosis pathology. The issue of whether a CNS antigen-specific immune response is required to produce axon injury remains unresolved. We investigated the extent and time course of axon injury in a rodent model of a delayed-type hypersensitivity (DTH) reaction directed against the mycobacterium bacille Calmette-Guérin (BCG). Using MRI, we determined whether the ongoing axon injury is restricted to the period during which the blood-brain barrier is compromised. DTH lesions were initiated in adult rats by intracerebral injection of heat-killed BCG followed by a peripheral challenge with BCG. Our findings demonstrate that a DTH reaction to a non-CNS antigen within a CNS white matter tract leads to axon injury. Ongoing axon injury persisted throughout the 3-month period studied and was not restricted to the period of blood-brain barrier breakdown, as detected by MRI enhancing lesions. We have previously demonstrated that matrix metalloproteinases (MMPs) are upregulated in multiple sclerosis plaques and DTH lesions. In this study we demonstrated that microinjection of activated MMPs into the cortical white matter results in axon injury. Our results show that axon injury, possibly mediated by MMPs, is immunologically non-specific and may continue behind an intact blood-brain barrier.

  10. Schwann cells-axon interaction in myelination. (United States)

    Taveggia, Carla


    The remarkable interaction between glial cells and axons is crucial for nervous system development and homeostasis. Alterations in this continuous communication can cause severe pathologies that can compromise the integrity of the nervous system. The most dramatic consequence of this interaction is the generation of the myelin sheath, made by myelinating glial cells: Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. In this review I will focus on signals coming from axons in the first part and then on those from Schwann cells that promote the formation and the maintenance of peripheral myelin. I will discuss their inter-relationship together with seminal and important advances recently made.

  11. Multifunctional Silk Nerve Guides for Axon Outgrowth (United States)

    Tupaj, Marie C.

    Peripheral nerve regeneration is a critical issue as 2.8% of trauma patients present with this type of injury, estimating a total of 200,000 nerve repair procedures yearly in the United States. While the peripheral nervous system exhibits slow regeneration, at a rate of 0.5 mm -- 9 mm/day following trauma, this regenerative ability is only possible under certain conditions. Clinical repairs have changed slightly in the last 30 years and standard methods of treatment include suturing damaged nerve ends, allografting, and autografting, with the autograft the gold standard of these approaches. Unfortunately, the use of autografts requires a second surgery and there is a shortage of nerves available for grafting. Allografts are a second option however allografts have lower success rates and are accompanied by the need of immunosuppressant drugs. Recently there has been a focus on developing nerve guides as an "off the shelf" approach. Although some natural and synthetic guidance channels have been approved by the FDA, these nerve guides are unfunctionalized and repair only short gaps, less than 3 cm in length. The goal of this project was to identify strategies for functionalizing peripheral nerve conduits for the outgrowth of neuron axons in vitro . To accomplish this, two strategies (bioelectrical and biophysical) were indentified for increasing axon outgrowth and promoting axon guidance. Bioelectrical strategies exploited electrical stimulation for increasing neurite outgrowth. Biophysical strategies tested a range of surface topographies for axon guidance. Novel methods were developed for integrating electrical and biophysical strategies into silk films in 2D. Finally, a functionalized nerve conduit system was developed that integrated all strategies for the purpose of attaching, elongating, and guiding nervous tissue in vitro. Future directions of this work include silk conduit translation into a rat sciatic nerve model in vivo for the purpose of repairing long

  12. Interspecies variation in axon-myelin relationships. (United States)

    Fraher, J P; O'Sullivan, A W


    The primary objective of this paper was to determine the extent and nature of interspecies differences in axon calibre and myelin sheath thickness and in the various relationships between these. Morphometric analysis of the axon perimeter-myelin sheath thickness relationship was performed on an equivalent nerve fibre population in a mammal, the rat, a bird, the chicken, an amphibian, the frog, a bony fish, the trout, and a cartilaginous fish, the dogfish. The abducent nerve was studied. It is especially suitable for this purpose because its fibres are closely similar in type and in peripheral distribution across the species studied. The relationship differed substantially between species. Differences were present in its setting, as described by the positions of the scatterplots, in the g ratio and in the regression and correlation data relating the parameters. Both parameters were markedly larger in the fish species than in all of the others. In addition, in rat, chicken, frog and trout, where large and small fibre classes could be differentiated clearly, the setting of the relationship between the two parameters was different for the two classes. In the main, variation in each of the parameters was greater between than within species. The larger fibres in the fish species were closely similar in axon perimeter and sheath thickness despite their long evolutionary separation. From this study and from others in the series, it may be concluded that there is no fixed or constant relationship between axon calibre and the thickness of the surrounding myelin sheath. Each nerve tends to have its own particular relationship and this differs between species.

  13. Role of sensory-motor cortex activity in postnatal development of corticospinal axon terminals in the cat. (United States)

    Friel, Kathleen M; Martin, John H


    The initial pattern of corticospinal (CS) terminations, as axons grow into the spinal gray matter, bears little resemblance to the pattern later in development and in maturity. This is because of extensive axon pruning and local axon terminal growth during early postnatal development. Pruning is driven by activity-dependent competition between the CS systems on each side during postnatal weeks (PW) 3-7. It is not known whether CS axon terminal growth and final topography are activity dependent. We examined the activity dependence of CS axon terminal growth and topography at different postnatal times. We inactivated sensory-motor cortex by infusion of the gamma-aminobutyric acid type A (GABA(A)) agonist muscimol and traced CS axons from the inactivated side. Inactivation between PW5 and PW7 produced permanent changes in projection topography, reduced local axon branching, and prevented development of dense clusters of presynaptic sites, which are normally characteristic of CS terminals. Inactivation at younger (PW3-5) and older (PW8-12) ages did not affect projection topography but impeded development of local axon branching and presynaptic site clusters. These effects were not due to increased cortical cell death during inactivation. Neural activity plays an important role in determining the morphology of CS terminals during the entire period of development, but, for the projection topography, the role of activity is exercised during a very brief period. This points to a complex, and possibly independent, regulation of termination topography and terminal morphology. Surprisingly, when a CS neuron's activity is blocked during early development, it does not recover lost connections later in development once activity resumes.

  14. Retinoic acid signaling in axonal regeneration

    Directory of Open Access Journals (Sweden)

    Radhika ePuttagunta


    Full Text Available Following an acute central nervous system injury, axonal regeneration and functional recovery are extremely limited. This is due to an extrinsic inhibitory growth environment and the lack of intrinsic growth competence. Retinoic acid (RA signaling, essential in developmental dorsoventral patterning and specification of spinal motor neurons, has been shown through its receptor, the transcription factor RA receptor β2 (RARß2, to induce axonal regeneration following spinal cord injury (SCI. Recently, it has been shown that in dorsal root ganglia neurons, cAMP levels were greatly increased by lentiviral RARβ2 expression and contributed to neurite outgrowth. Moreover, RARβ agonists, in cerebellar granule neurons and in the brain in vivo, induced phosphoinositide 3-kinase dependent phosphorylation of AKT that was involved in RARβ-dependent neurite outgrowth. More recently, RA-RARß pathways were shown to directly transcriptionally repress a member of the inhibitory Nogo receptor complex, Lingo-1, under an axonal growth inhibitory environment in vitro as well as following spinal injury in vivo. This perspective focuses on these newly discovered molecular mechanisms and future directions in the field.

  15. 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".

  16. MRI of the diffuse axonal injury

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Yang Gu; Woo, Young Hoon; Suh, Soo Jhi [Keimyung University School of Medicine, Daegu (Korea, Republic of)


    CT has facilitated early recognition and treatment of focal brain injuries in patients with head trauma. However, CT shows relatively low sensitivity in identifying non hemorrhage contusion and injuries of white matter. MR is known to be superior to CT in detection of white matter injuries, such as diffuse axonal injury. MR imaging in 14 cases of diffuse axonal injury on 2.0T was studied. The corpus callosum, especially the body portion, was the most commonly involved site. The lesions ranged from 5 to 20mm in size with ovoid to elliptical shape. T2WI was the most sensitive pulse sequence in detecting lesions such as white matter degeneration, hemorrhagic and non hemorrhagic contusion. The lesions were nonspecific as high and low signal intensities on T2WI and T1WI respectively. CT showed white matter abnormality in only 1 case of 14 cases. We propose MR imaging as the primary imaging procedure for the detection of diffuse axonal injury because of its multiplanar capabilities and higher sensitivity.

  17. Where does slow axonal transport go? (United States)

    Terada, Sumio


    Axonal transport is the specialized and well-developed intracellular transport system for regulated and/or long-distance transport based on generalized cellular machineries. Among them, slow axonal transport conveys cytoplasmic proteins. The motor molecule, the nature of transporting complex and the transport regulation mechanism for slow transport are still unclarified. There has been a dispute regarding the nature of transporting complex of cytoskeletal proteins, polymer-sliding hypothesis versus subunit-transport theory. Recent data supporting the hypothesis of polymer sliding in cultured neurons only reconfirm the previously reported structure and this inference suffers from the lack of ultrastructural evidence and the direct relevance to the physiological slow transport phenomenon in vivo. Observation of the moving cytoskeletal proteins in vivo using transgenic mice or squid giant axons revealed that subunits do move in a microtubule-dependent manner, strongly indicating the involvement of microtubule-based motor kinesin. If the slow transport rate reflects the intermittent fast transport dependent on kinesin motor, we have to investigate the molecular constituents of the transporting complex in more detail and evaluate why the motor and cargo interaction is so unstable. This kind of weak and fluctuating interaction between various molecular pairs could not be detected by conventional techniques, thus necessitating the establishment of a new experimental system before approaching the molecular regulation problem.

  18. Shh goes multidirectional in axon guidance

    Institute of Scientific and Technical Information of China (English)

    Paola Bovolenta; Luisa Sanchez-Arrones


    Shh and Wnts,secreted by the floor and roof plate of the spinal cord,direct longitudinal growth of the axons from the adjacent ventral funiculus and cortico-spinal tract.Whether these midline cues influencethe directionality of axons elongating in more lateral positions of the spinal cord is unexplored.Song and colleagues investigate this possibility and demonstrate that the location of descending raphe-spinal tract in the ventrolateral spinal cord is dictated by the simultaneous repellent activity of Shh gradients in both the anteriorto-posterior (A-P) and medial-tolateral (M-L) axis. The spinal cord is the main pathway for exchange of information between the brain and the rest of the body.Sensory information collected in the body periphery is conveyed to the brain by axonal tracts that ascend along the spinal cord whereas motor information travels from the brain to the periphery in descending tracts.Precise spatial organization of these fiber tracts is thus essential for animal behavior and survival.

  19. Axon-glial relations during regeneration of axons in the adult rat anterior medullary velum. (United States)

    Berry, M; Hunter, A S; Duncan, A; Lordan, J; Kirvell, S; Tsang, W L; Butt, A M


    The anterior medullary velum (AMV) of adult Wistar rats was lesioned in the midsagittal plane, transecting all decussating axons including those of the central projection of the IVth nerve. At selected times up to 200 days after transection, the degenerative and regenerative responses of axons and glia were analyzed using transmission and scanning electron microscopy and immunohistochemistry. In particular, both the capacity of oligodendrocytes to remyelinate regenerated fibers and the stability of the CNS/PNS junctional zone of the IVth nerve rootlet were documented. Transected central AMV axons exhibited four patterns of fiber regeneration in which fibers grew: rostrocaudally in the reactive paralesion neuropil (Group 1); randomly within the AMV (Group 2); into the ipsilateral IVth nerve rootlet, after turning at the lesion edge and growing recurrently through the old degenerated contralateral central trochlear nerve trajectory (Group 3); and ectopically through paralesion tears in the ependyma onto the surface of the IVth ventricle (Group 4). Group 1-3 axons regenerated unperturbed through degenerating central myelin, reactive astrocytes, oligodendrocytes, microglia, and large accumulations of hematogenous macrophages. Only Group 3 axons survived long term in significant numbers, and all became myelinated by oligodendrocytes, ultimately establishing thin sheaths with relatively normal nodal gaps and intersegmental myelin sheath lengths. Schwann cells at the CNS/PNS junction of the IVth nerve rootlet did not invade the CNS, but astrocyte processes grew across the junction into the PNS portion of the IVth nerve. The basal lamina of the junctional glia limitans remained stable throughout the experimental period.

  20. Segmentation of moving images by the human visual system. (United States)

    Chantelau, K


    New segments appearing in an image sequence or spontaneously accelerated segments are band limited by the visual system due to a nonperfect tracking of these segments by eye movements. In spite of this band limitation and acceleration of segments, a coarse segmentation (initial segmentation phase) can be performed by the visual system. This is interesting for the development of purely automatic segmentation algorithms for multimedia applications. In this paper the segmentation of the visual system is modelled and used in an automatic coarse initial segmentation. A suitable model for motion processing based on a spectral representation is presented and applied to the segmentation of synthetic and real image sequences with band limited and accelerated moving foreground and background segments.

  1. Myelin-based inhibitors of oligodendrocyte myelination: clues from axonal growth and regeneration

    Institute of Scientific and Technical Information of China (English)

    Feng Mei; S.Y.Christin Chong; Jonah R.Chan


    The differentiation of and myelination by oligodendrocytes (OLs) are exquisitely regulated by a series of intrinsic and extrinsic mechanisms.As each OL can make differing numbers of myelin segments with variable lengths along similar axon tracts,myelination can be viewed as a graded process shaped by inhibitory/inductive cues during development.Myelination by OLs is a prime example of an adaptive process determined by the microenvironment and architecture of the central nervous system (CNS).In this review,we discuss how myelin formation by OLs may be controlled by the heterogeneous microenvironment of the CNS.Then we address recent findings demonstrating that neighboring OLs may compete for available axon space,and highlight our current understanding of myelin-based inhibitors of axonal regeneration that are potentially responsible for the reciprocal dialogue between OLs and determine the numbers and lengths of myelin internodes.Understanding the mechanisms that control the spatiotemporal regulation of myelinogenic potential during development may provide valuable insight into therapeutic strategies for promoting remyelination in an inhibitory microenvironment.

  2. Myelin-based inhibitors of oligodendrocyte myelination: clues from axonal growth and regeneration. (United States)

    Mei, Feng; Christin Chong, S Y; Chan, Jonah R


    The differentiation of and myelination by oligodendrocytes (OLs) are exquisitely regulated by a series of intrinsic and extrinsic mechanisms. As each OL can make differing numbers of myelin segments with variable lengths along similar axon tracts, myelination can be viewed as a graded process shaped by inhibitory/inductive cues during development. Myelination by OLs is a prime example of an adaptive process determined by the microenvironment and architecture of the central nervous system (CNS). in this review, we discuss how myelin formation by OLs may be controlled by the heterogeneous microenvironment of the CNS. Then we address recent findings demonstrating that neighboring OLs may compete for available axon space, and highlight our current understanding of myelin-based inhibitors of axonal regeneration that are potentially responsible for the reciprocal dialogue between OLs and determine the numbers and lengths of myelin internodes. Understanding the mechanisms that control the spatiotemporal regulation of myelinogenic potential during development may provide valuable insight into therapeutic strategies for promoting remyelination in an inhibitory microenvironment.

  3. 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.

  4. Quantitative analysis of axon bouton distribution of subthalamic nucleus neurons in the rat by single neuron visualization with a viral vector. (United States)

    Koshimizu, Yoshinori; Fujiyama, Fumino; Nakamura, Kouichi C; Furuta, Takahiro; Kaneko, Takeshi


    The subthalamic nucleus (STN) of the basal ganglia plays a key role in motor control, and STN efferents are known to mainly target the external segment of the globus pallidus (GPe), entopeduncular nucleus (Ep), and substantia nigra (SN) with some axon collaterals to the other regions. However, it remains to be clarified how each STN neuron projects axon fibers and collaterals to those target nuclei of the STN. Here we visualized the whole axonal arborization of single STN neurons in the rat brain by using a viral vector expressing membrane-targeted green fluorescent protein, and examined the distribution of axon boutons in those target nuclei. The vast majority (8-9) of 10 reconstructed STN neurons projected to the GPe, SN, caudate-putamen (CPu), and Ep, which received, on average ± SD, 457 ± 425, 400 ± 347, 126 ± 143, and 106 ± 100 axon boutons per STN neuron, respectively. Furthermore, the density of axon boutons in the GPe was highest among these nuclei. Although these target nuclei were divided into calbindin-rich and -poor portions, STN projection showed no exclusive preference for those portions. Since STN neurons mainly projected not only to the GPe, SN, and Ep but also to the CPu, the subthalamostriatal projection might serve as a positive feedback path for the striato-GPe-subthalamic disinhibitory pathway, or work as another route of cortical inputs to the striatum through the corticosubthalamostriatal disynaptic excitatory pathway.

  5. Chlorpyrifos-Oxon Disrupts Zebrafish Axonal Growth and Motor Behavior


    Yang, Dongren; Lauridsen, Holly; Buels, Kalmia; Chi, Lai-Har; La Du, Jane; Bruun, Donald A.; Olson, James R.; Tanguay, Robert L.; Lein, Pamela J.


    Axonal morphology is a critical determinant of neuronal connectivity, and perturbation of the rate or extent of axonal growth during development has been linked to neurobehavioral deficits in animal models and humans. We previously demonstrated that the organophosphorus pesticide (OP) chlorpyrifos (CPF) inhibits axonal growth in cultured neurons. In this study, we used a zebrafish model to determine whether CPF, its oxon metabolite (CPFO), or the excreted metabolite trichloro-2-pyridinol (TCP...

  6. A unified cell biological perspective on axon-myelin injury


    Simons, Mikael; Misgeld, Thomas; Kerschensteiner, Martin


    Demyelination and axon loss are pathological hallmarks of the neuroinflammatory disorder multiple sclerosis (MS). Although we have an increasingly detailed understanding of how immune cells can damage axons and myelin individually, we lack a unified view of how the axon–myelin unit as a whole is affected by immune-mediated attack. In this review, we propose that as a result of the tight cell biological interconnection of axons and myelin, damage to either can spread, which might convert a loc...

  7. Arrest of Myelination and Reduced Axon Growth when Schwann Cells Lack mTOR


    Sherman, Diane L; Krols, Michiel; Wu, Lai-Man N; Grove, Matthew; Nave, Klaus-Armin; Gangloff, Yann-Gaël; Brophy, Peter J.


    In developing peripheral nerves differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. In recent years there has been an increasing understanding of the extracellular and intracellular factors that initiate and stimulate Schwann cell myelination together with a growing appreciation of some of the signalling pathways involved. However, our knowledge of how Schwann cell growth is regulated during myelination is still incomplete....

  8. Axonal BACE1 dynamics and targeting in hippocampal neurons: a role for Rab11 GTPase


    Buggia-Prévot, Virginie; Fernandez, Celia G; Riordan, Sean; Vetrivel, Kulandaivelu S.; Roseman, Jelita; Waters, Jack; Bindokas, Vytautas P.; Vassar, Robert; Thinakaran, Gopal


    Background BACE1 is one of the two enzymes that cleave amyloid precursor protein to generate Alzheimer's disease (AD) beta amyloid peptides. It is widely believed that BACE1 initiates APP processing in endosomes, and in the brain this cleavage is known to occur during axonal transport of APP. In addition, BACE1 accumulates in dystrophic neurites surrounding brain senile plaques in individuals with AD, suggesting that abnormal accumulation of BACE1 at presynaptic terminals contributes to patho...

  9. Corticostriatal combinatorics: the implications of corticostriatal axonal arborizations. (United States)

    Zheng, T; Wilson, C J


    The complete striatal axonal arborizations of 16 juxtacellularly stained cortical pyramidal cells were analyzed. Corticostriatal neurons were located in the medial agranular or anterior cingulate cortex of rats. All axons were of the extended type and formed synaptic contacts in both the striosomal and matrix compartments as determined by counterstaining for the mu-opiate receptor. Six axonal arborizations were from collaterals of brain stem-projecting cells and the other 10 from bilaterally projecting cells with no brain stem projections. The distribution of synaptic boutons along the axons were convolved with the average dendritic tree volume of spiny projection neurons to obtain an axonal innervation volume and innervation density map for each axon. Innervation volumes varied widely, with single axons occupying between 0.4 and 14.2% of the striatum (average = 4%). The total number of boutons formed by individual axons ranged from 25 to 2,900 (average = 879). Within the innervation volume, the density of innervation was extremely sparse but inhomogeneous. The pattern of innervation resembled matrisomes, as defined by bulk labeling and functional mapping experiments, superimposed on a low background innervation. Using this sample as representative of all corticostriatal axons, the total number of corticostriatal neurons was estimated to be 17 million, about 10 times the number of striatal projection neurons.

  10. Differences in excitability properties of FDI and ADM motor axons. (United States)

    Bae, Jong Seok; Sawai, Setsu; Misawa, Sonoko; Kanai, Kazuaki; Isose, Sagiri; Kuwabara, Satoshi


    The first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles are innervated by the same ulnar nerve, but studies have shown that the former is much more severely affected in amyotrophic lateral sclerosis. In this study, threshold tracking was used to investigate whether membrane properties differ between FDI and ADM motor axons. In 12 normal subjects, compound muscle action potentials were recorded from FDI and ADM after ulnar nerve stimulation at the wrist. The strength-duration time constant was significantly longer in the FDI axons than in the ADM axons, and latent addition studies showed greater threshold changes at the conditioning-test stimulus of 0.2 ms in FDI than in ADM axons. These findings suggest that nodal persistent sodium conductances are more prominent in FDI axons than in ADM axons, and therefore excitability is physiologically higher in FDI axons. Even in the same nerve at the same sites, membrane properties of FDI and ADM motor axons differ significantly, and thus their axonal/neuronal responses to disease may also differ.

  11. Fast axonal transport in early experimental disc edema. (United States)

    Radius, R L; Anderson, D R


    Previous work has documented impairment of slow axonal transport in papilledema, but the abnormalities in rapid transport were less certain. Therefore fast axonal transport was studied in 19 primate eyes subjected to ocular hypotony for 6 to 72 hr following surgical fistulization of the anterior chamber. Mild, irregular alterations in fast axonal transport were detected only after nerve head swelling was apparent. These changes in fast transport mechanisms in cases of nerve head edema occur after, and may be secondary to, impaired slow axoplasmic flow and the resultant axonal swelling. Furthermore, since prolonged complete interruption of axonal transport is theoretically inconsistent with the continued normal neuron function characteristic of papilledema and, moreover, since previous data shows a "slowdown" rather than complete blockade of axonal transport in papilledema, it is likely that in eyes with papilledema there does not exist a complete flock of axonal transport. Therefore we hypothesize that the swelling results when slow axoplasmic flow is locally slowed down but not totally stopped, with the axon distention producing secondary mild, irregular changes in fast axonal transport.

  12. 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

  13. Crossing the Border: Molecular Control of Motor Axon Exit

    Directory of Open Access Journals (Sweden)

    Arlene Bravo-Ambrosio


    Full Text Available Living organisms heavily rely on the function of motor circuits for their survival and for adapting to ever-changing environments. Unique among central nervous system (CNS neurons, motor neurons (MNs project their axons out of the CNS. Once in the periphery, motor axons navigate along highly stereotyped trajectories, often at considerable distances from their cell bodies, to innervate appropriate muscle targets. A key decision made by pathfinding motor axons is whether to exit the CNS through dorsal or ventral motor exit points (MEPs. In contrast to the major advances made in understanding the mechanisms that regulate the specification of MN subtypes and the innervation of limb muscles, remarkably little is known about how MN axons project out of the CNS. Nevertheless, a limited number of studies, mainly in Drosophila, have identified transcription factors, and in some cases candidate downstream effector molecules, that are required for motor axons to exit the spinal cord. Notably, specialized neural crest cell derivatives, referred to as Boundary Cap (BC cells, pre-figure and demarcate MEPs in vertebrates. Surprisingly, however, BC cells are not required for MN axon exit, but rather restrict MN cell bodies from ectopically migrating along their axons out of the CNS. Here, we describe the small set of studies that have addressed motor axon exit in Drosophila and vertebrates, and discuss our fragmentary knowledge of the mechanisms, which guide motor axons out of the CNS.

  14. A unified cell biological perspective on axon-myelin injury. (United States)

    Simons, Mikael; Misgeld, Thomas; Kerschensteiner, Martin


    Demyelination and axon loss are pathological hallmarks of the neuroinflammatory disorder multiple sclerosis (MS). Although we have an increasingly detailed understanding of how immune cells can damage axons and myelin individually, we lack a unified view of how the axon-myelin unit as a whole is affected by immune-mediated attack. In this review, we propose that as a result of the tight cell biological interconnection of axons and myelin, damage to either can spread, which might convert a local inflammatory disease process early in MS into the global progressive disorder seen during later stages. This mode of spreading could also apply to other neurological disorders.

  15. Present status of studies on diffuse axonal injury

    Institute of Scientific and Technical Information of China (English)

    Jie Ma; Chonggong Zhang; Yi Li


    OBJECTIVE: To explain the present status of study on diffuse axonal injury,investigate its pathogenesis and pathophysiological changes ,and suggest principles for the diagnosis and treatment.DATA SOURCES: Articles about diffuse axonal injury published in English from January 1994 to October 2006 were searched in Pubmed database using the keywords of "diffuse axonal injury,pathogenesis,therapy".STUDY SELECTION: The collected articles were primarily screened to select those associated with diffuse axonal injury,the obviously irrelated articles were excluded,and the rest ones were retrieved manually,and the full-texes were searched.DATA EXTRACTION: Totally 98 articles were collected,41 of them were involved.and the other 57 were excluded.DATA SYNTHESIS: Diffuse axonal injury is mainly caused by acceleratory or deceleratory injury,and its pathophysiological change is a progressive duration,local axonal injury finally develops to axonal breakage,mainly includes inactivation of natrium channel,intracellular Ca2+ overloading,activation of calcium protease,caspase etc.,and mitochondrial injury.At present,there is still lack of effective therapeutic methods for diffuse axonal injury,so we should actively explore more effective methods to relieve the pain of patients and improve their prognosis.CONCLUSION: At present,diffuse axonal injury has not attracted enough attentions in China,the mechanisms for its diagnosis and attack are still unclear,and the treatments are mainly aiming at the symptoms.

  16. Dopaminergic axon guidance: which makes what?

    Directory of Open Access Journals (Sweden)

    Laetitia ePrestoz


    Full Text Available Mesotelencephalic pathways in the adult central nervous system have been studied in great detail because of their implication in major physiological functions as well as in psychiatric, neurological and neurodegenerative diseases. However, the ontogeny of these pathways and the molecular mechanisms that guide dopaminergic axons during embryogenesis have been only recently studied. This line of research is of crucial interest for the repair of lesioned circuits in adulthood following neurodegenerative diseases or common traumatic injuries. For instance, in the adult, the anatomic and functional repair of the nigrostriatal pathway following dopaminergic embryonic neuron transplantation suggests that specific guidance cues exist which govern embryonic fibers outgrowth, and suggests that axons from transplanted embryonic cells are able to respond to theses cues, which then guide them to their final targets. In this review, we first synthesize the work that has been performed in the last few years on developing mesotelencephalic pathways, and summarize the current knowledge on the identity of cellular and molecular signals thought to be involved in establishing mesotelencephalic dopaminergic neuronal connectivity during embryogenesis in the central nervous system of rodents. Then, we review the modulation of expression of these molecular signals in the lesioned adult brain and discuss their potential role in remodeling the mesotelencephalic dopaminergic circuitry, with a particular focus on Parkinson’s disease. Identifying guidance molecules involved in the connection of grafted cells may be useful for cellular therapy in Parkinsonian patients, as these molecules may help direct axons from grafted cells along the long distance they have to travel from the substantia nigra to the striatum.

  17. 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


    at 4-5 weeks post injury. The somata of axotomized CINs were identified by the presence of immunoreactivity for the axonal growth-associated protein-43 (GAP-43). Nearly half of the CINs had de novo axons that emerged from distal dendrites. These axons lacked immunoreactivity for the dendritic protein......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 injury......, develop de novo axons. Our goal was to determine whether spinal commissural interneurons (CINs), axotomized by 3-4-mm midsagittal transection at C3, form de novo axons from distal dendrites. All experiments were performed on adult cats. CINs in C3 were stained with extracellular injections of Neurobiotin...

  18. IMP2 axonal localization, RNA interactome, and function in the development of axon trajectories

    DEFF Research Database (Denmark)

    Preitner, Nicolas; Quan, Jie; Li, Xinmin


    RNA-based regulatory mechanisms play important roles in the development and plasticity of neural circuits and neurological disease. Developing axons provide a model well suited to the study of RNA-based regulation, and contain specific subsets of mRNAs that are locally translated and have roles i...

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

    NARCIS (Netherlands)

    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 M

  20. AxonPacking: An Open-Source Software to Simulate Arrangements of Axons in White Matter. (United States)

    Mingasson, Tom; Duval, Tanguy; Stikov, Nikola; Cohen-Adad, Julien


    HIGHLIGHTS AxonPacking: Open-source software for simulating white matter microstructure.Validation on a theoretical disk packing problem.Reproducible and stable for various densities and diameter distributions.Can be used to study interplay between myelin/fiber density and restricted fraction. Quantitative Magnetic Resonance Imaging (MRI) can provide parameters that describe white matter microstructure, such as the fiber volume fraction (FVF), the myelin volume fraction (MVF) or the axon volume fraction (AVF) via the fraction of restricted water (fr). While already being used for clinical application, the complex interplay between these parameters requires thorough validation via simulations. These simulations required a realistic, controlled and adaptable model of the white matter axons with the surrounding myelin sheath. While there already exist useful algorithms to perform this task, none of them combine optimisation of axon packing, presence of myelin sheath and availability as free and open source software. Here, we introduce a novel disk packing algorithm that addresses these issues. The performance of the algorithm is tested in term of reproducibility over 50 runs, resulting density, and stability over iterations. This tool was then used to derive multiple values of FVF and to study the impact of this parameter on fr and MVF in light of the known microstructure based on histology sample. The standard deviation of the axon density over runs was lower than 10(-3) and the expected hexagonal packing for monodisperse disks was obtained with a density close to the optimal density (obtained: 0.892, theoretical: 0.907). Using an FVF ranging within [0.58, 0.82] and a mean inter-axon gap ranging within [0.1, 1.1] μm, MVF ranged within [0.32, 0.44] and fr ranged within [0.39, 0.71], which is consistent with the histology. The proposed algorithm is implemented in the open-source software AxonPacking ( and can be useful for

  1. Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease. (United States)

    Sevilla, Teresa; Lupo, Vincenzo; Martínez-Rubio, Dolores; Sancho, Paula; Sivera, Rafael; Chumillas, María J; García-Romero, Mar; Pascual-Pascual, Samuel I; Muelas, Nuria; Dopazo, Joaquín; Vílchez, Juan J; Palau, Francesc; Espinós, Carmen


    Charcot-Marie-Tooth disease (CMT) is a complex disorder with wide genetic heterogeneity. Here we present a new axonal Charcot-Marie-Tooth disease form, associated with the gene microrchidia family CW-type zinc finger 2 (MORC2). Whole-exome sequencing in a family with autosomal dominant segregation identified the novel MORC2 p.R190W change in four patients. Further mutational screening in our axonal Charcot-Marie-Tooth disease clinical series detected two additional sporadic cases, one patient who also carried the same MORC2 p.R190W mutation and another patient that harboured a MORC2 p.S25L mutation. Genetic and in silico studies strongly supported the pathogenicity of these sequence variants. The phenotype was variable and included patients with congenital or infantile onset, as well as others whose symptoms started in the second decade. The patients with early onset developed a spinal muscular atrophy-like picture, whereas in the later onset cases, the initial symptoms were cramps, distal weakness and sensory impairment. Weakness and atrophy progressed in a random and asymmetric fashion and involved limb girdle muscles, leading to a severe incapacity in adulthood. Sensory loss was always prominent and proportional to disease severity. Electrophysiological studies were consistent with an asymmetric axonal motor and sensory neuropathy, while fasciculations and myokymia were recorded rather frequently by needle electromyography. Sural nerve biopsy revealed pronounced multifocal depletion of myelinated fibres with some regenerative clusters and occasional small onion bulbs. Morc2 is expressed in both axons and Schwann cells of mouse peripheral nerve. Different roles in biological processes have been described for MORC2. As the silencing of Charcot-Marie-Tooth disease genes have been associated with DNA damage response, it is tempting to speculate that a deregulation of this pathway may be linked to the axonal degeneration observed in MORC2 neuropathy, thus adding a

  2. Fasciculation and guidance of spinal motor axons in the absence of FGFR2 signaling.

    Directory of Open Access Journals (Sweden)

    Rosa-Eva Huettl

    Full Text Available During development, fibroblast growth factors (FGF are essential for early patterning events along the anterior-posterior axis, conferring positional identity to spinal motor neurons by activation of different Hox codes. In the periphery, signaling through one of four fibroblast growth factor receptors supports the development of the skeleton, as well as induction and maintenance of extremities. In previous studies, FGF receptor 2 (FGFR2 was found to interact with axon bound molecules involved in axon fasciculation and extension, thus rendering this receptor an interesting candidate for the promotion of proper peripheral innervation. However, while the involvement of FGFR2 in limb bud induction has been extensively studied, its role during axon elongation and formation of distinct nervous projections has not been addressed so far. We show here that motor neurons in the spinal cord express FGFR2 and other family members during the establishment of motor connections to the forelimb and axial musculature. Employing a conditional genetic approach to selectively ablate FGFR2 from motor neurons we found that the patterning of motor columns and the expression patterns of other FGF receptors and Sema3A in the motor columns of mutant embryos are not altered. In the absence of FGFR2 signaling, pathfinding of motor axons is intact, and also fasciculation, distal advancement of motor nerves and gross morphology and positioning of axonal projections are not altered. Our findings therefore show that FGFR2 is not required cell-autonomously in motor neurons during the formation of initial motor projections towards limb and axial musculature.

  3. The relationship between developing oligodendrocyte units and maturing axons during myelinogenesis in the anterior medullary velum of neonatal rats. (United States)

    Butt, A M; Ibrahim, M; Berry, M


    Myelinogenesis was investigated in whole-mounted anterior medullary vela from rats aged postnatal day (P) 10-12, using double immunofluorescence labelling with Rip and anti-neurofilament 200 (NF200) antibodies, to identify oligodendrocytes and axons, respectively. A number of discrete phases of maturation of oligodendrocyte units were recognised. (1) Promyelinating oligodendrocytes co-expressed Rip and Myelin basic Protein and formed axonal associations, prior to ensheathment. (2) Transitional oligodendrocytes contained both ensheathing and non-ensheating processes. (3) Myelinating oligodendrocytes were established after a period of remodelling (in which non-ensheathing processes were lost), appearing as oligodendrocyte unit morphological phenotypes with a definitive number of incipient myelin sheaths. (4) Maturation of myelinating oligodendrocytes was defined as the establishment of internodal sheath lengths and the redistrubution of myelin basic protein from the cell somata and radial processes into the myelin sheaths only. Myelination was probably related to the maturational state of the axons, since it was initiated when the latter had attained a critical diameter of between approximately 0.2 and 0.4 micron, coincident with the expression of NF200. Oligodendrocyte differentiation and myelination of the AMV were asynchronous and multifocal, and at P10: (1) axons which were destined to be of the largest calibre in the adult AMV were already myelinated by early developing oligodendrocytes, whilst those which were destined to be the smallest calibre in the adult were unmyelinated, but ultimately became ensheathed by late developing oligoendrocytes; (2) axons were sequentially ensheathed by early developing myelinating oligodendrocytes and late developing promyelinating oligodendrocytes; (3) all axons were small calibre; (4) oligodendrocyte units exhibited polymorphism. Thus, the development of oligodendrocyte morphological phenotypes was not related solely to

  4. Differential extraction of axonally transported proteoglycans

    Energy Technology Data Exchange (ETDEWEB)

    Elam, J.S. (Florida State Univ., Tallahassee (USA))


    Axonally transported proteoglycans were differentially solubilized by a sequence of extractions designed to infer their relationship to nerve terminal membranes. Groups of goldfish were injected unilaterally with 35SO4 and contralateral optic tecta containing axonally transported molecules were removed 16 h later. Tecta were homogenized in isotonic buffer and centrifuged at 100,000 g for 60 min to create a total supernatant fraction. Subsequent homogenizations followed by recentrifugation were with hypotonic buffer (lysis extract), 1 M NaCl, Triton X-100 or alternatively Triton-1 M NaCl. Populations of proteoglycans in each extract were isolated on DEAE ion exchange columns and evaluated for content of glycosaminoglycans (GAGs). Results show the distribution of transported proteoglycans to be 26.3% total soluble, 13.7% lysis extract, 13.8% NaCl extract, 12.2% Triton extract, and 46.2% Triton-NaCl extract. Proteoglycans from all fractions contained heparan sulfate as the predominant GAG, with lesser amounts of chondroitin (4 or 6) sulfate. The possible localizations of transported proteoglycans suggested by the extraction results are discussed.

  5. Image Series Segmentation and Improved MC Algorithm

    Institute of Scientific and Technical Information of China (English)

    WAN Wei-bing; SHI Peng-fei


    A semiautomatic segmentation method based on active contour is proposed for computed tomog-raphy (CT) image series. First, to get initial contour, one image slice was segmented exactly by C-V method based on Mumford-Shah model. Next, the computer will segment the nearby slice automatically using the snake model one by one. During segmenting of image slices, former slice boundary, as next slice initial con-tour, may cross over next slice real boundary and never return to right position. To avoid contour skipping over, the distance variance between two slices is evaluated by an threshold, which decides whether to initiate again. Moreover, a new improved marching cubes (MC) algorithm based on 2D images series segmentation boundary is given for 3D image reconstruction. Compared with the standard method, the proposed algorithm reduces detecting time and needs less storing memory. The effectiveness and capabilities of the algorithm were illustrated by experimental results.

  6. Neuronal Logistics : Axonal Transport in Development and Disease

    NARCIS (Netherlands)

    R. van den Berg (Robert)


    markdownabstractBrain cells are uniquely shaped among the many cell types of the body. While most cells are more or less rounded or square-shaped, neurons grow one or more long axons that can reach lengths of a meter or more. To keep these axons alive and functional, neurons are dependent on an intr

  7. Molecular Determinants Fundamental to Axon Regeneration after SCI (United States)


    TITLE: Molecular Determinants Fundamental to Axon Regeneration after SCI PRINCIPAL INVESTIGATOR: Jeffrey Alan Plunkett, Ph.D. Martin...TYPE FINAL 3. DATES COVERED (From - To) 1 Sept 2011 - 1 Sept 2014 4. TITLE AND SUBTITLE Molecular Determinants Fundamental to Axon Regeneration...available that restore motor impairments resulting fromspinal cord injury (SCI). Soldiers with SCI are permanently paralyzed and in needof lifelong care

  8. Molecular Determinants Fundamental to Axon Regeneration after SCI (United States)


    currently employed to investigate the evolution of the scar and the time course of axon regeneration after spinal cord injury. The data from these...Medicine, Pittsburgh, PA. It has been established in amphibians and fish that neurons can successfully regenerate their axons in the damaged central

  9. Spontaneous axonal regeneration in rodent spinal cord after ischemic injury

    DEFF Research Database (Denmark)

    von Euler, Mia; Janson, A M; Larsen, Jytte Overgaard;


    Here we present evidence for spontaneous and long-lasting regeneration of CNS axons after spinal cord lesions in adult rats. The length of 200 kD neurofilament (NF)-immunolabeled axons was estimated after photochemically induced ischemic spinal cord lesions using a stereological tool. The total l...

  10. Inhibiting poly(ADP-ribosylation) improves axon regeneration (United States)

    Byrne, Alexandra B; McWhirter, Rebecca D; Sekine, Yuichi; Strittmatter, Stephen M; Miller, David M; Hammarlund, Marc


    The ability of a neuron to regenerate its axon after injury depends in part on its intrinsic regenerative potential. Here, we identify novel intrinsic regulators of axon regeneration: poly(ADP-ribose) glycohodrolases (PARGs) and poly(ADP-ribose) polymerases (PARPs). PARGs, which remove poly(ADP-ribose) from proteins, act in injured C. elegans GABA motor neurons to enhance axon regeneration. PARG expression is regulated by DLK signaling, and PARGs mediate DLK function in enhancing axon regeneration. Conversely, PARPs, which add poly(ADP-ribose) to proteins, inhibit axon regeneration of both C. elegans GABA neurons and mammalian cortical neurons. Furthermore, chemical PARP inhibitors improve axon regeneration when administered after injury. Our results indicate that regulation of poly(ADP-ribose) levels is a critical function of the DLK regeneration pathway, that poly-(ADP ribosylation) inhibits axon regeneration across species, and that chemical inhibition of PARPs can elicit axon regeneration. DOI:

  11. Axon guidance of rat cortical neurons by microcontact printed gradients. (United States)

    Fricke, Rita; Zentis, Peter D; Rajappa, Lionel T; Hofmann, Boris; Banzet, Marko; Offenhäusser, Andreas; Meffert, Simone H


    Substrate-bound gradients expressed in numerous spatio-temporal patterns play a crucial role during the development of complex neural circuits. A deeper understanding of the axon guidance mechanism is provided by studying the effect of a defined substrate-bound cue on a confined neural network. In this study, we constructed a discontinuous substrate-bound gradient to control neuronal cell position, the path of neurite growth, and axon directionality. A variety of gradient patterns, with slight changes in slope, width, and length were designed and fabricated by microcontact printing using laminin/poly-l-lysine (PLL) or PLL alone. The gradients were tested for neurite growth and their impact on axon guidance of embryonic rat cortical neurons. The neurite length was determined and the axon was evaluated by Tau-1 immunostaining. We found that the microgradients of laminin/PLL and PLL directed neurons' adhesion, differentially controlled the neurite growth, and guided up to 84% of the axons. The effect of the protein micropattern on axon guidance and neurite growth depended on the protein and geometric parameters used. Our approach proved to be very successful in guiding axons of single multipolar neurons with very high efficiency. It could thereby be useful to engineer defined neural networks for analyzing signal processing of functional circuits, as well as to unravel fundamental questions of the axon guidance mechanism.

  12. Increased Human Wildtype Tau Attenuates Axonal Transport Deficits Caused by Loss of APP in Mouse Models


    Smith, Karen D.B.; Erica Peethumnongsin; Han Lin; Hui Zheng; Pautler, Robia G.


    Amyloid precursor protein (APP) is implicated in axonal elongation, synaptic plasticity, and axonal transport. However, the role of APP on axonal transport in conjunction with the microtubule associated protein tau continues to be debated. Here we measured in vivo axonal transport in APP knockout mice with Manganese Enhanced MRI (MEMRI) to determine whether APP is necessary for maintaining normal axonal transport. We also tested how overexpression and mutations of tau affect axonal transport ...

  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. 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 regenerated internodes remain persistently short though this abnormality did not seem to influence recovery in conduction. It remains unclear to which extent abnormalities in axonal function itself may contribute to the poor outcome of nerve regeneration. METHODS: We review experimental evidence indicating...... that internodes play an active role in axonal function. RESULTS: By investigating internodal contribution to axonal excitability we have found evidence that axonal function may be permanently compromised in regenerated nerves. Furthermore, we illustrate that internodal function is also abnormal in regenerated...

  15. Signaling mechanisms in cortical axon growth, guidance and branching

    Directory of Open Access Journals (Sweden)

    Katherine eKalil


    Full Text Available Precise wiring of cortical circuits during development depends upon axon extension, guidance and branching to appropriate targets. Motile growth cones at axon tips navigate through the nervous system by responding to molecular cues, which modulate signaling pathways within axonal growth cones. Intracellular calcium signaling has emerged as a major transducer of guidance cues but exactly how calcium signaling pathways modify the actin and microtubule cytoskeleton to evoke growth cone behaviors and axon branching is still mysterious. Axons must often pause in their outgrowth while their branches extend into targets. Some evidence suggests a competition between growth of axons and branches but the mechanisms are poorly understood. Since it is difficult to study growing axons deep within the mammalian brain, much of what we know about signaling pathways and cytoskeletal dynamics has come from studies of axonal growth cones, in many cases from non-mammalian species, growing in tissue culture. Consequently it is not well understood how guidance cues relevant to mammalian neural development in vivo signal to the growth cone cytoskeleton during axon outgrowth and guidance. In this review we describe our recent work in dissociated cultures of developing rodent sensorimotor cortex in the context of the current literature on molecular guidance cues, calcium signaling pathways and cytoskeletal dynamics that regulate growth cone behaviors. A major challenge is to relate findings in tissue culture to mechanisms of cortical development in vivo. Toward this goal, we describe our recent work in cortical slices, which preserve the complex cellular and molecular environment of the mammalian brain but allow direct visualization of growth cone behaviors and calcium signaling. Findings from this work suggest that mechanisms regulating axon growth and guidance in dissociated culture neurons also underlie development of cortical connectivity in vivo.

  16. Segmentation of MRI Volume Data Based on Clustering Method

    Directory of Open Access Journals (Sweden)

    Ji Dongsheng


    Full Text Available Here we analyze the difficulties of segmentation without tag line of left ventricle MR images, and propose an algorithm for automatic segmentation of left ventricle (LV internal and external profiles. Herein, we propose an Incomplete K-means and Category Optimization (IKCO method. Initially, using Hough transformation to automatically locate initial contour of the LV, the algorithm uses a simple approach to complete data subsampling and initial center determination. Next, according to the clustering rules, the proposed algorithm finishes MR image segmentation. Finally, the algorithm uses a category optimization method to improve segmentation results. Experiments show that the algorithm provides good segmentation results.

  17. 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.

  18. Pontine reticulospinal projections in the neonatal mouse: Internal organization and axon trajectories. (United States)

    Sivertsen, Magne S; Perreault, Marie-Claude; Glover, Joel C


    We recently characterized physiologically a pontine reticulospinal (pRS) projection in the neonatal mouse that mediates synaptic effects on spinal motoneurons via parallel uncrossed and crossed pathways (Sivertsen et al. [2014] J Neurophysiol 112:1628-1643). Here we characterize the origins, anatomical organization, and supraspinal axon trajectories of these pathways via retrograde tracing from the high cervical spinal cord. The two pathways derive from segregated populations of ipsilaterally and contralaterally projecting pRS neurons with characteristic locations within the pontine reticular formation (PRF). We obtained estimates of relative neuron numbers by counting from sections, digitally generated neuron position maps, and 3D reconstructions. Ipsilateral pRS neurons outnumber contralateral pRS neurons by threefold and are distributed about equally in rostral and caudal regions of the PRF, whereas contralateral pRS neurons are concentrated in the rostral PRF. Ipsilateral pRS neuron somata are on average larger than contralateral. No pRS neurons are positive in transgenic mice that report the expression of GAD, suggesting that they are predominantly excitatory. Putative GABAergic interneurons are interspersed among the pRS neurons, however. Ipsilateral and contralateral pRS axons have distinctly different trajectories within the brainstem. Their initial spinal funicular trajectories also differ, with ipsilateral and contralateral pRS axons more highly concentrated medially and laterally, respectively. The larger size and greater number of ipsilateral vs. contralateral pRS neurons is compatible with our previous finding that the uncrossed projection transmits more reliably to spinal motoneurons. The information about supraspinal and initial spinal pRS axon trajectories should facilitate future physiological assessment of synaptic connections between pRS neurons and spinal neurons.

  19. Segmentation Similarity and Agreement

    CERN Document Server

    Fournier, Chris


    We propose a new segmentation evaluation metric, called segmentation similarity (S), that quantifies the similarity between two segmentations as the proportion of boundaries that are not transformed when comparing them using edit distance, essentially using edit distance as a penalty function and scaling penalties by segmentation size. We propose several adapted inter-annotator agreement coefficients which use S that are suitable for segmentation. We show that S is configurable enough to suit a wide variety of segmentation evaluations, and is an improvement upon the state of the art. We also propose using inter-annotator agreement coefficients to evaluate automatic segmenters in terms of human performance.

  20. Calpains mediate axonal cytoskeleton disintegration during Wallerian degeneration. (United States)

    Ma, Marek; Ferguson, Toby A; Schoch, Kathleen M; Li, Jian; Qian, Yaping; Shofer, Frances S; Saatman, Kathryn E; Neumar, Robert W


    In both the central nervous system (CNS) and peripheral nervous system (PNS), transected axons undergo Wallerian degeneration. Even though Augustus Waller first described this process after transection of axons in 1850, the molecular mechanisms may be shared, at least in part, by many human diseases. Early pathology includes failure of synaptic transmission, target denervation, and granular disintegration of the axonal cytoskeleton (GDC). The Ca(2+)-dependent protease calpains have been implicated in GDC but causality has not been established. To test the hypothesis that calpains play a causal role in axonal and synaptic degeneration in vivo, we studied transgenic mice that express human calpastatin (hCAST), the endogenous calpain inhibitor, in optic and sciatic nerve axons. Five days after optic nerve transection and 48 h after sciatic nerve transection, robust neurofilament proteolysis observed in wild-type controls was reduced in hCAST transgenic mice. Protection of the axonal cytoskeleton in sciatic nerves of hCAST mice was nearly complete 48 h post-transection. In addition, hCAST expression preserved the morphological integrity of neuromuscular junctions. However, compound muscle action potential amplitudes after nerve transection were similar in wild-type and hCAST mice. These results, in total, provide direct evidence that calpains are responsible for the morphological degeneration of the axon and synapse during Wallerian degeneration.

  1. Local erythropoietin signaling enhances regeneration in peripheral axons. (United States)

    Toth, C; Martinez, J A; Liu, W Q; Diggle, J; Guo, G F; Ramji, N; Mi, R; Hoke, A; Zochodne, D W


    Erythropoietin (EPO) and its receptor (EPO-R), mediate neuroprotection from axonopathy and apoptosis in the peripheral nervous system (PNS). We examined the impact and potential mechanisms of local EPO signaling on regenerating PNS axons in vivo and in vitro. As a consequence of injury, peripheral nerve axons and DRG neurons have a marked increase in the expression of EPO and EPO-R. Local delivery of EPO via conduit over 2 weeks to rat sciatic nerve following crush injury increased the density and maturity of regenerating myelinated axons growing distally from the crush site. In addition, EPO also rescued retrograde degeneration and atrophy of axons. EPO substantially increased the density and intensity of calcitonin gene-related peptide (CGRP) expression within outgrowing axons. Behavioral improvements in sensorimotor function also occurred in rats exposed to near nerve EPO delivery. EPO delivery led to decreased nuclear factor kappaB (NFkB) activation but increased phosphorylation of Akt and STAT3 within nerve and dorsal root ganglia neurons indicating rescue from an injury phenotype. Spinal cord explant studies also demonstrated a similar dose-dependent effect of EPO upon motor axonal outgrowth. Local EPO signaling enhances regenerating peripheral nervous system axons in addition to its known neuroprotection. Exogenous EPO may have a therapeutic role in a large number of peripheral nerve diseases through its impact on regeneration.

  2. A Novel Iris Segmentation Scheme

    Directory of Open Access Journals (Sweden)

    Chen-Chung Liu


    Full Text Available One of the key steps in the iris recognition system is the accurate iris segmentation from its surrounding noises including pupil, sclera, eyelashes, and eyebrows of a captured eye-image. This paper presents a novel iris segmentation scheme which utilizes the orientation matching transform to outline the outer and inner iris boundaries initially. It then employs Delogne-Kåsa circle fitting (instead of the traditional Hough transform to further eliminate the outlier points to extract a more precise iris area from an eye-image. In the extracted iris region, the proposed scheme further utilizes the differences in the intensity and positional characteristics of the iris, eyelid, and eyelashes to detect and delete these noises. The scheme is then applied on iris image database, UBIRIS.v1. The experimental results show that the presented scheme provides a more effective and efficient iris segmentation than other conventional methods.

  3. Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons (United States)

    Alavi, Maryam; Song, Minmin; Gillis, Taylor; Bousum, Adam; Miller, Amanda; Kidd, Thomas


    The Slit protein is a major midline repellent for central nervous system (CNS) axons. In vivo, Slit is proteolytically cleaved into N- and C-terminal fragments, but the biological significance of this is unknown. Analysis in the Drosophila ventral nerve cord of a slit allele (slit-UC) that cannot be cleaved revealed that midline repulsion is still present but longitudinal axon guidance is disrupted, particularly across segment boundaries. Double mutants for the Slit receptors Dscam1 and robo1 strongly resemble the slit-UC phenotype, suggesting they cooperate in longitudinal axon guidance, and through biochemical approaches, we found that Dscam1 and Robo1 form a complex dependent on Slit-N. In contrast, Robo1 binding alone shows a preference for full-length Slit, whereas Dscam1 only binds Slit-N. Using a variety of transgenes, we demonstrated that Dscam1 appears to modify the output of Robo/Slit complexes so that signaling is no longer repulsive. Our data suggest that the complex is promoting longitudinal axon growth across the segment boundary. The ability of Dscam1 to modify the output of other receptors in a ligand-dependent fashion may be a general principle for Dscam proteins. PMID:27654876

  4. GeoSegmenter: A statistically learned Chinese word segmenter for the geoscience domain (United States)

    Huang, Lan; Du, Youfu; Chen, Gongyang


    Unlike English, the Chinese language has no space between words. Segmenting texts into words, known as the Chinese word segmentation (CWS) problem, thus becomes a fundamental issue for processing Chinese documents and the first step in many text mining applications, including information retrieval, machine translation and knowledge acquisition. However, for the geoscience subject domain, the CWS problem remains unsolved. Although a generic segmenter can be applied to process geoscience documents, they lack the domain specific knowledge and consequently their segmentation accuracy drops dramatically. This motivated us to develop a segmenter specifically for the geoscience subject domain: the GeoSegmenter. We first proposed a generic two-step framework for domain specific CWS. Following this framework, we built GeoSegmenter using conditional random fields, a principled statistical framework for sequence learning. Specifically, GeoSegmenter first identifies general terms by using a generic baseline segmenter. Then it recognises geoscience terms by learning and applying a model that can transform the initial segmentation into the goal segmentation. Empirical experimental results on geoscience documents and benchmark datasets showed that GeoSegmenter could effectively recognise both geoscience terms and general terms.

  5. 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.

  6. Excitatory cortical neurons with multipolar shape establish neuronal polarity by forming a tangentially oriented axon in the intermediate zone. (United States)

    Hatanaka, Yumiko; Yamauchi, Kenta


    The formation of axon-dendrite polarity is crucial for neuron to make the proper information flow within the brain. Although the processes of neuronal polarity formation have been extensively studied using neurons in dissociated culture, the corresponding developmental processes in vivo are still unclear. Here, we illuminate the initial steps of morphological polarization of excitatory cortical neurons in situ, by sparsely labeling their neuroepithelial progenitors using in utero electroporation and then examining their neuronal progeny in brain sections and in slice cultures. Morphological analysis showed that an axon-like long tangential process formed in progeny cells in the intermediate zone (IZ). Time-lapse imaging analysis using slice culture revealed that progeny cells with multipolar shape, after alternately extending and retracting their short processes for several hours, suddenly elongated a long process tangentially. These cells then transformed into a bipolar shape, extending a pia-directed leading process, and migrated radially leaving the tangential process behind, which gave rise to an "L-shaped" axon. Our findings suggest that neuronal polarity in these cells is established de novo from a nonpolarized stage in vivo and indicate that excitatory cortical neurons with multipolar shape in the IZ initiate axon outgrowth before radial migration into the cortical plate.

  7. Pituitary Adenoma Segmentation

    CERN Document Server

    Egger, Jan; Kuhnt, Daniela; Freisleben, Bernd; Nimsky, Christopher


    Sellar tumors are approximately 10-15% among all intracranial neoplasms. The most common sellar lesion is the pituitary adenoma. Manual segmentation is a time-consuming process that can be shortened by using adequate algorithms. In this contribution, we present a segmentation method for pituitary adenoma. The method is based on an algorithm we developed recently in previous work where the novel segmentation scheme was successfully used for segmentation of glioblastoma multiforme and provided an average Dice Similarity Coefficient (DSC) of 77%. This scheme is used for automatic adenoma segmentation. In our experimental evaluation, neurosurgeons with strong experiences in the treatment of pituitary adenoma performed manual slice-by-slice segmentation of 10 magnetic resonance imaging (MRI) cases. Afterwards, the segmentations were compared with the segmentation results of the proposed method via the DSC. The average DSC for all data sets was 77.49% +/- 4.52%. Compared with a manual segmentation that took, on the...

  8. The importance of combinatorial gene expression in early mammalian thalamic patterning and thalamocortical axonal guidance

    Directory of Open Access Journals (Sweden)

    David J Price


    Full Text Available The thalamus is essential for sensory perception. In mammals, work on the mouse has taught us most of what we know about how it develops and connects to the cortex. The mature thalamus of all mammalian species comprises numerous anatomically distinct collections of neurons called nuclei that differ in function, connectivity and molecular constitution. At the time of its initial appearance as a distinct structure following neural tube closure, the thalamus is already patterned by the regional expression of numerous regulatory genes. This patterning, which lays down the blueprint for later development of thalamic nuclei, predates the development of thalamocortical projections. In this review we apply novel analytical methods to gene expression data available in the Allen Developing Mouse Brain Atlas to highlight the complex organized molecular heterogeneity already present among cells in the thalamus from the earliest stages at which it contains differentiating neurons. This early patterning is likely to invest in axons growing from different parts of the thalamus the ability to navigate in an ordered way to their appropriate area in the cerebral cortex. We review the mechanisms and cues that thalamic axons use, encounter and interpret to attain the cortex. Mechanisms include guidance by previously-generated guidepost cells, such as those in the subpallium that maintain thalamic axonal order and direction, and axons such as those of reciprocal projections from intermediate structures or from the cortex itself back towards the thalamus. We show how thalamocortical pathfinding involves numerous guidance cues operating at a series of steps along their route. We stress the importance of the combinatorial actions of multiple genes for the development of the numerous specific identities and functions of cells in this exquisitely complex system and their orderly innervation of the cortex.

  9. The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK-JNK Signaling Pathway in Axon Regeneration. (United States)

    Hisamoto, Naoki; Nagamori, Yuki; Shimizu, Tatsuhiro; Pastuhov, Strahil I; Matsumoto, Kunihiro


    The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. However, the signaling pathways that orchestrate axon regeneration are not well understood. In Caenorhabditis elegans, initiation of axon regeneration is positively regulated by SVH-2 Met-like growth factor receptor tyrosine kinase (RTK) signaling through the JNK MAPK pathway. Here we show that SVH-4/DDR-2, an RTK containing a discoidin domain that is activated by collagen, and EMB-9 collagen type IV regulate the regeneration of neurons following axon injury. The scaffold protein SHC-1 interacts with both DDR-2 and SVH-2. Furthermore, we demonstrate that overexpression of svh-2 and shc-1 suppresses the delay in axon regeneration observed in ddr-2 mutants, suggesting that DDR-2 functions upstream of SVH-2 and SHC-1. These results suggest that DDR-2 modulates the SVH-2-JNK pathway via SHC-1. We thus identify two different RTK signaling networks that play coordinated roles in the regulation of axonal regeneration.

  10. The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration (United States)

    Shimizu, Tatsuhiro; Matsumoto, Kunihiro


    The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. However, the signaling pathways that orchestrate axon regeneration are not well understood. In Caenorhabditis elegans, initiation of axon regeneration is positively regulated by SVH-2 Met-like growth factor receptor tyrosine kinase (RTK) signaling through the JNK MAPK pathway. Here we show that SVH-4/DDR-2, an RTK containing a discoidin domain that is activated by collagen, and EMB-9 collagen type IV regulate the regeneration of neurons following axon injury. The scaffold protein SHC-1 interacts with both DDR-2 and SVH-2. Furthermore, we demonstrate that overexpression of svh-2 and shc-1 suppresses the delay in axon regeneration observed in ddr-2 mutants, suggesting that DDR-2 functions upstream of SVH-2 and SHC-1. These results suggest that DDR-2 modulates the SVH-2–JNK pathway via SHC-1. We thus identify two different RTK signaling networks that play coordinated roles in the regulation of axonal regeneration. PMID:27984580

  11. Structural plasticity of axon terminals in the adult. (United States)

    Gogolla, Nadine; Galimberti, Ivan; Caroni, Pico


    There is now conclusive evidence for widespread ongoing structural plasticity of presynaptic boutons and axon side-branches in the adult brain. The plasticity complements that of postsynaptic spines, but axonal plasticity samples larger volumes of neuropil, and has a larger impact on circuit remodeling. Axons from distinct neurons exhibit unique ratios of stable (t1/2>9 months) and dynamic (t1/2 5-20 days) boutons, which persist as spatially intermingled subgroups along terminal arbors. In addition, phases of side-branch dynamics mediate larger scale remodeling guided by synaptogenesis. The plasticity is most pronounced during critical periods; its patterns and outcome are controlled by Hebbian mechanisms and intrinsic neuronal factors. Novel experience, skill learning, life-style, and age can persistently modify local circuit structure through axonal structural plasticity.

  12. Sodium Channels, Mitochondria, and Axonal Degeneration in Peripheral Neuropathy. (United States)

    Persson, Anna-Karin; Hoeijmakers, Janneke G J; Estacion, Mark; Black, Joel A; Waxman, Stephen G


    Peripheral neuropathy results from damage to peripheral nerves and is often accompanied by pain in affected limbs. Treatment represents an unmet medical need and a thorough understanding of the mechanisms underlying axonal injury is needed. Longer nerve fibers tend to degenerate first (length-dependence), and patients carrying pathogenic mutations throughout life usually become symptomatic in mid- or late-life (time-dependence). The activity of voltage-gated sodium channels can contribute to axonal injury and sodium channel gain-of-function mutations have been linked to peripheral neuropathy. Recent studies have implicated sodium channel activity, mitochondrial compromise, and reverse-mode Na(+)/Ca(2+) exchange in time- and length-dependent axonal injury. Elucidation of molecular mechanisms underlying axonal injury in peripheral neuropathy may provide new therapeutic strategies for this painful and debilitating condition.

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

    Directory of Open Access Journals (Sweden)

    Parisa eLotfi


    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.

  14. Electrophysiology of a nonmyelinated glutamatergic axon in rat hippocampus


    Alle, Henrik


    The common theme of the presented work on the nonmyelinated hippocampal mossy fiber (the axon of the granule cell in the dentate gyrus) is the generation of subthreshold and suprathreshold electrical signals. Subthreshold depolarizations in the axon can occur due to passive propagation of excitatory postsynaptic potentials, which are generated in the somato-dendritic domain. The remote passive propagation of these comparatively slow but transient signals is due to a space constant...

  15. 6-Sulphated chondroitins have a positive influence on axonal regeneration.

    Directory of Open Access Journals (Sweden)

    Rachel Lin

    Full Text Available Chondroitin sulphate proteoglycans (CSPGs upregulated in the glial scar inhibit axon regeneration via their sulphated glycosaminoglycans (GAGs. Chondroitin 6-sulphotransferase-1 (C6ST-1 is upregulated after injury leading to an increase in 6-sulphated GAG. In this study, we ask if this increase in 6-sulphated GAG is responsible for the increased inhibition within the glial scar, or whether it represents a partial reversion to the permissive embryonic state dominated by 6-sulphated glycosaminoglycans (GAGs. Using C6ST-1 knockout mice (KO, we studied post-injury changes in chondroitin sulphotransferase (CSST expression and the effect of chondroitin 6-sulphates on both central and peripheral axon regeneration. After CNS injury, wild-type animals (WT showed an increase in mRNA for C6ST-1, C6ST-2 and C4ST-1, but KO did not upregulate any CSSTs. After PNS injury, while WT upregulated C6ST-1, KO showed an upregulation of C6ST-2. We examined regeneration of nigrostriatal axons, which demonstrate mild spontaneous axon regeneration in the WT. KO showed many fewer regenerating axons and more axonal retraction than WT. However, in the PNS, repair of the median and ulnar nerves led to similar and normal levels of axon regeneration in both WT and KO. Functional tests on plasticity after the repair also showed no evidence of enhanced plasticity in the KO. Our results suggest that the upregulation of 6-sulphated GAG after injury makes the extracellular matrix more permissive for axon regeneration, and that the balance of different CSs in the microenvironment around the lesion site is an important factor in determining the outcome of nervous system injury.

  16. Axon morphology at the lamina cribrosa in monkey eyes. (United States)

    Radius, R L; Klewin, K M


    The eyes of 8 monkeys (Aotus trivirgatus) were studied. The mean cross-section area and the least diameter of axon cylinders were calculated from measurements made by computer assisted planimetry of electron photomicrographs of sections through the optic nerve head at the level of the lamina cribrosa. The density of intrabundle connective tissue and glial cell elements in nerve fiber bundles was also calculated. The mean cross-section area and minimum diameter of axons in the temporal part were less than in the nasal part of the nerve. The values for axons in the superior and inferior parts of the nerve were intermediate. A similar pattern of increasing dimensions was seen in axons from the more axial nerve compared to neurons in the more circumferential nerve sectors. The density of the intrabundle, nonaxonal tissue elements did not differ significantly across the nerve. Although axon dimensions may play some role in defining the vulnerability of neuronal tissue to a pressure insult, the results of this anatomic investigation do not support the hypothesis that differences in axonal distribution by size across the nerve section define the regional vulnerability of the nerve head to elevated intraocular pressure.

  17. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy. (United States)

    Sung, Jia-Ying; Tani, Jowy; Chang, Tsui-San; Lin, Cindy Shin-Yi


    This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (Pmotor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (Pdevelopment of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

  18. GPS Control Segment (United States)


    Luke J. Schaub Chief, GPS Control Segment Division 29 Apr 15 GPS Control Segment Report Documentation Page Form ApprovedOMB No. 0704-0188...00-2015 4. TITLE AND SUBTITLE GPS Control Segment 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Center, GPS Control Segment Division,Los Angeles AFB, El Segundo,CA,90245 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S

  19. 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

  20. Automatic Melody Segmentation

    NARCIS (Netherlands)

    Rodríguez López, Marcelo


    The work presented in this dissertation investigates music segmentation. In the field of Musicology, segmentation refers to a score analysis technique, whereby notated pieces or passages of these pieces are divided into “units” referred to as sections, periods, phrases, and so on. Segmentation analy

  1. Combining comparative proteomics and molecular genetics uncovers regulators of synaptic and axonal stability and degeneration in vivo.

    Directory of Open Access Journals (Sweden)

    Thomas M Wishart

    Full Text Available Degeneration of synaptic and axonal compartments of neurons is an early event contributing to the pathogenesis of many neurodegenerative diseases, but the underlying molecular mechanisms remain unclear. Here, we demonstrate the effectiveness of a novel "top-down" approach for identifying proteins and functional pathways regulating neurodegeneration in distal compartments of neurons. A series of comparative quantitative proteomic screens on synapse-enriched fractions isolated from the mouse brain following injury identified dynamic perturbations occurring within the proteome during both initiation and onset phases of degeneration. In silico analyses highlighted significant clustering of proteins contributing to functional pathways regulating synaptic transmission and neurite development. Molecular markers of degeneration were conserved in injury and disease, with comparable responses observed in synapse-enriched fractions isolated from mouse models of Huntington's disease (HD and spinocerebellar ataxia type 5. An initial screen targeting thirteen degeneration-associated proteins using mutant Drosophila lines revealed six potential regulators of synaptic and axonal degeneration in vivo. Mutations in CALB2, ROCK2, DNAJC5/CSP, and HIBCH partially delayed injury-induced neurodegeneration. Conversely, mutations in DNAJC6 and ALDHA1 led to spontaneous degeneration of distal axons and synapses. A more detailed genetic analysis of DNAJC5/CSP mutants confirmed that loss of DNAJC5/CSP was neuroprotective, robustly delaying degeneration in axonal and synaptic compartments. Our study has identified conserved molecular responses occurring within synapse-enriched fractions of the mouse brain during the early stages of neurodegeneration, focused on functional networks modulating synaptic transmission and incorporating molecular chaperones, cytoskeletal modifiers, and calcium-binding proteins. We propose that the proteins and functional pathways identified in

  2. X-ray scattering study of pike olfactory nerve: elastic, thermodynamic and physiological properties of the axonal membrane. (United States)

    Luzzati, Vittorio; Benoit, Evelyne; Charpentier, Gilles; Vachette, Patrice


    The effects of several agents, sugars, isotonic KCl, and a variety of drugs, on the structure of the axonal membranes of unmyelinated pike olfactory nerve have been studied by synchrotron radiation X-ray scattering experiments. The main effects of the sugars are: (i) to increase the electron density of the extra-axonal space and thereby yield the absolute scale of the electron density profile; (ii) to osmotically stress the membrane and thus yield its elastic modulus of area compressibility, since the related strain, thickness dilation, is directly determined by the X-ray scattering experiments. Exposure to isotonic KCl, a depolarizing agent, induces membrane thickness to increase. The energy liberated in this process is a function of the amplitude of the dilation and of the elastic modulus of the membrane. This energy turns out to be close to the thermal energy liberated by the pike olfactory nerve during the initial phase of action potential that has previously been measured by others. Electrical depolarization thus seems to be accompanied by a thickness dilation of the axonal membrane. Another effect of isotonic KCl is to induce a large fraction of the membranes to pair by tight apposition of their extra-axonal faces. Local anaesthetics and some drugs have the effect of altering membrane thickness. All these observations are interpreted in terms of a modulation of the conformational disorder of the hydrocarbon chains of the lipid molecules.

  3. Atomic Force Microscopy Reveals Important Differences in Axonal Resistance to Injury (United States)

    Magdesian, Margaret H.; Sanchez, Fernando S.; Lopez, Monserratt; Thostrup, Peter; Durisic, Nela; Belkaid, Wiam; Liazoghli, Dalinda; Grütter, Peter; Colman, David R.


    Axonal degeneration after traumatic brain injury and nerve compression is considered a common underlying cause of temporary as well as permanent disability. Because a proper functioning of neural network requires phase coherence of all components, even subtle changes in circuitry may lead to network failure. However, it is still not possible to determine which axons will recover or degenerate after injury. Several groups have studied the pressure threshold for axonal injury within a nerve, but difficulty accessing the injured region; insufficient imaging methods and the extremely small dimensions involved have prevented the evaluation of the response of individual axons to injury. We combined microfluidics with atomic force microscopy and in vivo imaging to estimate the threshold force required to 1), uncouple axonal transport without impairing axonal survival, and 2), compromise axonal survival in both individual and bundled axons. We found that rat hippocampal axons completely recover axonal transport with no detectable axonal loss when compressed with pressures up to 65 ± 30 Pa for 10 min, while dorsal root ganglia axons can resist to pressures up to 540 ± 220 Pa. We investigated the reasons for the differential susceptibility of hippocampal and DRG axons to mechanical injury and estimated the elasticity of live axons. We found that dorsal root ganglia axons have a 20% lower elastic modulus than hippocampal axons. Our results emphasize the importance of the integrity of the axonal cytoskeleton in deciding the axonal fate after damage and open up new avenues to improve injury diagnosis and to identify ways to protect axons. PMID:22947856

  4. What is a segment? (United States)

    Hannibal, Roberta L; Patel, Nipam H


    Animals have been described as segmented for more than 2,000 years, yet a precise definition of segmentation remains elusive. Here we give the history of the definition of segmentation, followed by a discussion on current controversies in defining a segment. While there is a general consensus that segmentation involves the repetition of units along the anterior-posterior (a-p) axis, long-running debates exist over whether a segment can be composed of only one tissue layer, whether the most anterior region of the arthropod head is considered segmented, and whether and how the vertebrate head is segmented. Additionally, we discuss whether a segment can be composed of a single cell in a column of cells, or a single row of cells within a grid of cells. We suggest that 'segmentation' be used in its more general sense, the repetition of units with a-p polarity along the a-p axis, to prevent artificial classification of animals. We further suggest that this general definition be combined with an exact description of what is being studied, as well as a clearly stated hypothesis concerning the specific nature of the potential homology of structures. These suggestions should facilitate dialogue among scientists who study vastly differing segmental structures.

  5. 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.

  6. Robust shape regression for supervised vessel segmentation and its application to coronary segmentation in CTA

    DEFF Research Database (Denmark)

    Schaap, Michiel; van Walsum, Theo; Neefjes, Lisan;


    This paper presents a vessel segmentation method which learns the geometry and appearance of vessels in medical images from annotated data and uses this knowledge to segment vessels in unseen images. Vessels are segmented in a coarse-to-fine fashion. First, the vessel boundaries are estimated...... with multivariate linear regression using image intensities sampled in a region of interest around an initialization curve. Subsequently, the position of the vessel boundary is refined with a robust nonlinear regression technique using intensity profiles sampled across the boundary of the rough segmentation...... and using information about plausible cross-sectional vessel shapes. The method was evaluated by quantitatively comparing segmentation results to manual annotations of 229 coronary arteries. On average the difference between the automatically obtained segmentations and manual contours was smaller than...

  7. Automatic segmentation of vertebrae from radiographs

    DEFF Research Database (Denmark)

    Mysling, Peter; Petersen, Peter Kersten; Nielsen, Mads


    Segmentation of vertebral contours is an essential task in the design of automatic tools for vertebral fracture assessment. In this paper, we propose a novel segmentation technique which does not require operator interaction. The proposed technique solves the segmentation problem in a hierarchical...... manner. In a first phase, a coarse estimate of the overall spine alignment and the vertebra locations is computed using a shape model sampling scheme. These samples are used to initialize a second phase of active shape model search, under a nonlinear model of vertebra appearance. The search...

  8. 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.

  9. Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. (United States)

    Lopez-Verrilli, María Alejandra; Picou, Frederic; Court, Felipe A


    Axonal regeneration in the peripheral nervous system is greatly supported by Schwann cells (SCs). After nerve injury, SCs dedifferentiate to a progenitor-like state and efficiently guide axons to their original target tissues. Contact and soluble factors participate in the crosstalk between SCs and axons during axonal regeneration. Here we show that dedifferentiated SCs secrete nano-vesicles known as exosomes which are specifically internalized by axons. Surprisingly, SC-derived exosomes markedly increase axonal regeneration in vitro and enhance regeneration after sciatic nerve injury in vivo. Exosomes shift the growth cone morphology to a pro-regenerating phenotype and decrease the activity of the GTPase RhoA, involved in growth cone collapse and axon retraction. Altogether, our work identifies a novel mechanism by which SCs communicate with neighboring axons during regenerative processes. We propose that SC exosomes represent an important mechanism by which these cells locally support axonal maintenance and regeneration after nerve damage.

  10. A novel role for MuSK and non-canonical Wnt signaling during segmental neural crest cell migration. (United States)

    Banerjee, Santanu; Gordon, Laura; Donn, Thomas M; Berti, Caterina; Moens, Cecilia B; Burden, Steven J; Granato, Michael


    Trunk neural crest cells delaminate from the dorsal neural tube as an uninterrupted sheet; however, they convert into segmentally organized streams before migrating through the somitic territory. These neural crest cell streams join the segmental trajectories of pathfinding spinal motor axons, suggesting that interactions between these two cell types might be important for neural crest cell migration. Here, we show that in the zebrafish embryo migration of both neural crest cells and motor axons is temporally synchronized and spatially restricted to the center of the somite, but that motor axons are dispensable for segmental neural crest cell migration. Instead, we find that muscle-specific receptor kinase (MuSK) and its putative ligand Wnt11r are crucial for restricting neural crest cell migration to the center of each somite. Moreover, we find that blocking planar cell polarity (PCP) signaling in somitic muscle cells also results in non-segmental neural crest cell migration. Using an F-actin biosensor we show that in the absence of MuSK neural crest cells fail to retract non-productive leading edges, resulting in non-segmental migration. Finally, we show that MuSK knockout mice display similar neural crest cell migration defects, suggesting a novel, evolutionarily conserved role for MuSK in neural crest migration. We propose that a Wnt11r-MuSK dependent, PCP-like pathway restricts neural crest cells to their segmental path.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Ravinder Bamba


    Full Text Available 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 repaired. 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.

  13. 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.

  14. 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.

  15. Keypoint Transfer Segmentation


    Wachinger, C.; Toews, M.; Langs, G.; Wells, W.; Golland, P.


    We present an image segmentation method that transfers label maps of entire organs from the training images to the novel image to be segmented. The transfer is based on sparse correspondences between keypoints that represent automatically identified distinctive image locations. Our segmentation algorithm consists of three steps: (i) keypoint matching, (ii) voting-based keypoint labeling, and (iii) keypoint-based probabilistic transfer of organ label maps. We introduce generative models for th...

  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. Pili canaliculi as manifestation of giant axonal neuropathy* (United States)

    de Almeida Jr., Hiram Larangeira; Garcias, Gilberto; Silva, Ricardo Marques e; Batista, Stela Laner; Pasetto, Fernanda


    Giant axonal neuropathy is a rare autosomal recessive neurodegenerative disease. The condition is characterized by neurons with abnormally large axons due to intracellular filament accumulation. The swollen axons affect both the peripheral and central nervous system. A 6-year old female patient had been referred to a geneticist reporting problems with walking and hypotonia. At the age of 10, she became wheelchair dependent. Scanning electron microscopy of a curly hair classified it as pili canaliculi. GAN gene sequencing demonstrated mutation c.1456G>A (p.GLU486LYS). At the age of 12, the patient died due to respiratory complications. Dermatologists should be aware of this entity since hair changes are considered suggestive of GAN.

  18. Using quantum filters to process images of diffuse axonal injury (United States)

    Pineda Osorio, Mateo


    Some images corresponding to a diffuse axonal injury (DAI) are processed using several quantum filters such as Hermite Weibull and Morse. Diffuse axonal injury is a particular, common and severe case of traumatic brain injury (TBI). DAI involves global damage on microscopic scale of brain tissue and causes serious neurologic abnormalities. New imaging techniques provide excellent images showing cellular damages related to DAI. Said images can be processed with quantum filters, which accomplish high resolutions of dendritic and axonal structures both in normal and pathological state. Using the Laplacian operators from the new quantum filters, excellent edge detectors for neurofiber resolution are obtained. Image quantum processing of DAI images is made using computer algebra, specifically Maple. Quantum filter plugins construction is proposed as a future research line, which can incorporated to the ImageJ software package, making its use simpler for medical personnel.

  19. Universal Numeric Segmented Display

    CERN Document Server

    Azad, Md Abul kalam; Kamruzzaman, S M


    Segmentation display plays a vital role to display numerals. But in today's world matrix display is also used in displaying numerals. Because numerals has lots of curve edges which is better supported by matrix display. But as matrix display is costly and complex to implement and also needs more memory, segment display is generally used to display numerals. But as there is yet no proposed compact display architecture to display multiple language numerals at a time, this paper proposes uniform display architecture to display multiple language digits and general mathematical expressions with higher accuracy and simplicity by using a 18-segment display, which is an improvement over the 16 segment display.

  20. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy (United States)

    Sung, Jia-Ying; Tani, Jowy; Chang, Tsui-San; Lin, Cindy Shin-Yi


    This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05), shortened strength-duration time constant (P<0.01), increased superexcitability (P<0.01), decreased subexcitability (P<0.05), decreased accommodation to depolarizing current (P<0.01), and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1–8) and G2+3 (TNSr 9–24) groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01) in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches. PMID:28182728

  1. 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.

  2. Giant Axonal Neuropathy Among Two Siblings - A Case Report

    Directory of Open Access Journals (Sweden)

    John Jhon. K


    Full Text Available Giant axonal neuropathy is a rate disorder with an autosomal recessive inheritance. It should be differentiated from toxic neuropathies, and hereditary degenerative disorders of nervous system like Friedreich′s ataxia and HMSN. Thick curly hair, though may not be present always is a useful clinical clue to identify cases. Prognosis is generally poor though course of the illness is variable. We report here a clinically and hisopathologically characteristic familial case of giant axonal neuropathy, which occurred in a 17-year-old boy, and his 21-year-old sister.

  3. Resurgent Na+ current in pyramidal neurones of rat perirhinal cortex: axonal location of channels and contribution to depolarizing drive during repetitive firing (United States)

    Castelli, Loretta; Biella, Gerardo; Toselli, Mauro; Magistretti, Jacopo


    processes are lost, we carried out experiments of focal tetrodotoxin (TTX) application in slices to verify whether the channels responsible for INaR are located in compartment(s) different from the soma. We found that TTX preferentially inhibited INaR when applied close to the site of axon emergence from soma, whereas application to the apical pole of the soma had a significantly smaller effect on INaR. Our results indicate that in area 35 pyramidal cells INaR is largely generated in the axon initial segment, where it may participate in setting the coding properties of these neurones. PMID:17525112

  4. Overexpression of Pax6 results in microphthalmia, retinal dysplasia and defective retinal ganglion cell axon guidance

    Directory of Open Access Journals (Sweden)

    Jeffery Glen


    contralateral optic tracts at the optic chiasm vary differently with gene dosage. Increasing dosage increases the proportion projecting ipsilaterally regardless of the size of the total projection. Conclusion Pax6 overexpression does not obviously impair the initial formation of the eye and its major cell-types but prevents normal development of the retina from about E14.5, leading eventually to severe retinal degeneration in postnatal life. This sequence is different to that underlying microphthalmia in Pax6+/- heterozygotes, which is due primarily to defects in the initial stages of lens formation. Before the onset of severe retinal dysplasia, Pax6 overexpression causes defects of retinal axons, preventing their normal growth and navigation through the optic chiasm.

  5. Tumor necrosis factor and its p55 and p75 receptors are not required for axonal lesion-induced microgliosis in mouse fascia dentata

    DEFF Research Database (Denmark)

    Fenger, Christina; Drojdahl, Nina; Wirenfeldt, Martin


    and terminal degeneration in mice, we studied the effect of TNF and its p55 and p75 receptors on axonal lesion-induced microglial activation in fascia dentata following transection of the perforant path (PP) projection. Unexpectedly, cell counting showed that the axonal lesion-induced microglial response...... maximum. However, in spite of the induction of TNF mRNA, TNF protein level remained at base-line in fascia dentata using immunohistochemistry and ELISA. In conclusion, the results showed a lower than expected lesion-induced increase in TNF protein, and that neither TNF nor its receptors were required...... for the axonal lesion-induced microglial morphological transformation and proliferation or for the initial clearance of degenerated myelin in the PP-deafferented fascia dentata....

  6. Segmentation, advertising and prices

    NARCIS (Netherlands)

    Galeotti, Andrea; Moraga González, José


    This paper explores the implications of market segmentation on firm competitiveness. In contrast to earlier work, here market segmentation is minimal in the sense that it is based on consumer attributes that are completely unrelated to tastes. We show that when the market is comprised by two consume

  7. Hospital benefit segmentation. (United States)

    Finn, D W; Lamb, C W


    Market segmentation is an important topic to both health care practitioners and researchers. The authors explore the relative importance that health care consumers attach to various benefits available in a major metropolitan area hospital. The purposes of the study are to test, and provide data to illustrate, the efficacy of one approach to hospital benefit segmentation analysis.

  8. From interpretation to segmentation

    NARCIS (Netherlands)

    Koning, A.R.; Lier, R.J. van


    In visual perception, part segmentation of an object is considered to be guided by image-based properties, such as occurrences of deep concavities in the outer contour. However, object-based properties can also provide information regarding segmentation. In this study, outer contours and interpretat

  9. Regulation of Axonal Midline Guidance by Prolyl 4-Hydroxylation in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Torpe, Nanna; Pocock, Roger David John


    Neuronal wiring during development requires that the growth cones of axons and dendrites are correctly guided to their appropriate targets. As in other animals, axon growth cones in Caenorhabditis elegans integrate information in their extracellular environment via interactions among transiently...

  10. Rapid axonal transport in primate optic nerve. Distribution of pressure-induced interruption. (United States)

    Radius, R L; Anderson, D R


    Six primate eyes were studied after four hours of elevated intraocular pressure. Tissue specimens from the region of the lamina cribrosa were examined in cross section by transmission electron microscopy. Interruption in fast orthograde and retrograde axonal transport was identified in individual axons by noting accumulation of membraneous microorganelles, such as mitochondria and microvesicles within axon cylinders. Although organelle accumulation varied from bundle to bundle, involvement of individual axons was diffuse across the extent of a specific axon bundle. This observation contradicts the apparent association of axonal transport block with crosswise-oriented trabecular beams at the level of the lamina cribrosa as seen in tissue specimens examined in longitudinal section. It also fails to support the notion that blocked axonal transport with elevated pressure is produced by kinking of axons at the lamina.

  11. 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.

  12. Computational Analysis of Axonal Transport: A Novel Assessment of Neurotoxicity, Neuronal Development and Functions

    Directory of Open Access Journals (Sweden)

    Toshiyuki Gotoh


    Full Text Available Axonal transport plays a crucial role in neuronal morphogenesis, survival and function. Despite its importance, however, the molecular mechanisms of axonal transport remain mostly unknown because a simple and quantitative assay system for monitoring this cellular process has been lacking. In order to better characterize the mechanisms involved in axonal transport, we formulate a novel computer-assisted monitoring system of axonal transport. Potential uses of this system and implications for future studies will be discussed.

  13. IFNgamma enhances microglial reactions to hippocampal axonal degeneration

    DEFF Research Database (Denmark)

    Jensen, M B; Hegelund, I V; Lomholt, N D;


    periods. Message for the immune cytokine interferon-gamma (IFNgamma) was undetectable, and glial reactivity to axonal lesions occurred as normal in IFNgamma-deficient mice. Microglial responses to lesion-induced neuronal injury were markedly enhanced in myelin basic protein promoter-driven transgenic mice...

  14. 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.

  15. Life-or-death decisions upon axonal damage. (United States)

    Roselli, Francesco; Caroni, Pico


    In this issue of Neuron, Hu et al. (2012) report that upon axonal damage, CHOP and XBP1 unfolded protein response pathways are not recruited equally and have opposite effects on neuronal survival. XBP1 pathway boosting may represent a valuable neuroprotective strategy.

  16. Drosophila Ryks and their roles in axon and muscle guidance

    NARCIS (Netherlands)

    Lahaye, Liza Lucia


    In the last decade it has become clear that a number of the molecular mechanisms that are required for proper navigation of axons in complex nervous systems are also employed to guide muscles to their appropriate attachment sites. Among the gene families that mediate these diverse processes is the R

  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. Unravelling the incidence and etiology of chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Visser, N.A.


    Chronic idiopathic axonal polyneuropathy (CIAP) is a sensory or sensorimotor polyneuropathy that has a slowly progressive course without severe disability. CIAP is diagnosed in a significant proportion of patients with polyneuropathy, but precise figures on the incidence of polyneuropathy and CIAP w

  19. Axon diameter mapping in crossing fibers with diffusion MRI

    DEFF Research Database (Denmark)

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


    This paper proposes a technique for a previously unaddressed problem, namely, mapping axon diameter in crossing fiber regions, using diffusion MRI. Direct measurement of tissue microstructure of this kind using diffusion MRI offers a new class of biomarkers that give more specific information abo...

  20. Axonal dynamics of excitatory and inhibitory neurons in somatosensory cortex.

    Directory of Open Access Journals (Sweden)

    Sally A Marik

    Full Text Available Cortical topography can be remapped as a consequence of sensory deprivation, suggesting that cortical circuits are continually modified by experience. To see the effect of altered sensory experience on specific components of cortical circuits, we imaged neurons, labeled with a genetically modified adeno-associated virus, in the intact mouse somatosensory cortex before and after whisker plucking. Following whisker plucking we observed massive and rapid reorganization of the axons of both excitatory and inhibitory neurons, accompanied by a transient increase in bouton density. For horizontally projecting axons of excitatory neurons there was a net increase in axonal projections from the non-deprived whisker barrel columns into the deprived barrel columns. The axon collaterals of inhibitory neurons located in the deprived whisker barrel columns retracted in the vicinity of their somata and sprouted long-range projections beyond their normal reach towards the non-deprived whisker barrel columns. These results suggest that alterations in the balance of excitation and inhibition in deprived and non-deprived barrel columns underlie the topographic remapping associated with sensory deprivation.

  1. Chronic excitotoxin-induced axon degeneration in a compartmented neuronal culture model

    Directory of Open Access Journals (Sweden)

    Katherine A Hosie


    Full Text Available Glutamate excitotoxicity is a major pathogenic process implicated in many neurodegenerative conditions, including AD (Alzheimer's disease and following traumatic brain injury. Occurring predominantly from over-stimulation of ionotropic glutamate receptors located along dendrites, excitotoxic axonal degeneration may also occur in white matter tracts. Recent identification of axonal glutamate receptor subunits within axonal nanocomplexes raises the possibility of direct excitotoxic effects on axons. Individual neuronal responses to excitotoxicity are highly dependent on the complement of glutamate receptors expressed by the cell, and the localization of the functional receptors. To enable isolation of distal axons and targeted excitotoxicity, murine cortical neuron cultures were prepared in compartmented microfluidic devices, such that distal axons were isolated from neuronal cell bodies. Within the compartmented culture system, cortical neurons developed to relative maturity at 11 DIV (days in vitro as demonstrated by the formation of dendritic spines and clustering of the presynaptic protein synaptophysin. The isolated distal axons retained growth cone structures in the absence of synaptic targets, and expressed glutamate receptor subunits. Glutamate treatment (100 μM to the cell body chamber resulted in widespread degeneration within this chamber and degeneration of distal axons in the other chamber. Glutamate application to the distal axon chamber triggered a lesser degree of axonal degeneration without degenerative changes in the untreated somal chamber. These data indicate that in addition to current mechanisms of indirect axonal excitotoxicity, the distal axon may be a primary target for excitotoxicity in neurodegenerative conditions.

  2. 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.

  3. Wnt-induced calcium signaling mediates axon growth and guidance in the developing corpus callosum. (United States)

    Hutchins, B Ian; Li, Li; Kalil, Katherine


    Wnt5a gradients guide callosal axons by repulsion through Ryk receptors in vivo. We recently found that Wnt5a repels cortical axons and promotes axon outgrowth through calcium signaling in vitro. Here, using cortical slices, we show that Wnt5a signals through Ryk to guide and promote outgrowth of callosal axons after they cross the midline. Calcium transient frequencies in callosal growth cones positively correlate with axon outgrowth rates in vitro. In cortical slices, calcium release through inositol 1,4,5-trisphosphate (IP(3)) receptors and calcium entry through transient receptor potential channels modulate axon growth and guidance. Knocking down Ryk inhibits calcium signaling in cortical axons, reduces rates of axon outgrowth subsequent to midline crossing, and causes axon guidance defects. Calcium- and calmodulin-dependent protein kinase II (CaMKII) is required downstream of Wnt-induced calcium signaling for postcrossing callosal axon growth and guidance. Taken together, these results suggest that growth and guidance of postcrossing callosal axons by Wnt-Ryk-calcium signaling involves axon repulsion through CaMKII.

  4. Segmentation of consumer's markets and evaluation of market's segments


    ŠVECOVÁ, Iveta


    The goal of this bachelor thesis was to explain a possibly segmentation of consumer´s markets for a chosen company, and to present a suitable goods offer, so it would be suitable to the needs of selected segments. The work is divided into theoretical and practical part. First part describes marketing, segmentation, segmentation of consumer's markets, consumer's market, market's segments a other terms. Second part describes an evaluation of questionnaire survey, discovering of market's segment...

  5. Nicotine elicits prolonged calcium signaling along ventral hippocampal axons. (United States)

    Zhong, Chongbo; Talmage, David A; Role, Lorna W


    Presynaptic nicotinic acetylcholine receptors (nAChRs) have long been implicated in the modulation of CNS circuits. We previously reported that brief exposure to low concentrations of nicotine induced sustained potentiation of glutamatergic transmission at ventral hippocampal (vHipp)-striatal synapses. Here, we exploited nAChR subtype-selective antagonists and agonists and α7*nAChR knockout mutant mice (α7-/-) to elucidate the signaling mechanisms underlying nAChR-mediated modulation of synaptic transmission. Using a combination of micro-slices culture from WT and α7-/-mice, calcium imaging, and immuno-histochemical techniques, we found that nicotine elicits localized and oscillatory increases in intracellular Ca(2+) along vHipp axons that persists for up to 30 minutes. The sustained phase of the nicotine-induced Ca(2+) response was blocked by α-BgTx but not by DHβE and was mimicked by α7*nAChR agonists but not by non-α7*nAChR agonists. In vHipp slices from α7-/- mice, nicotine elicited only transient increases of axonal Ca(2+) signals and did not activate CaMKII. The sustained phase of the nicotine-induced Ca(2+) response required localized activation of CaMKII, phospholipase C, and IP3 receptor mediated Ca(2+)-induced Ca(2+) release (CICR). In conclusion, activation of presynaptic nAChRs by nicotine elicits Ca(2+) influx into the presynaptic axons, the sustained phase of the nicotine-induced Ca(2+) response requires that axonal α7*nAChR activate a downstream signaling network in the vHipp axons.

  6. Unsupervised fuzzy segmentation of 3D magnetic resonance brain images (United States)

    Velthuizen, Robert P.; Hall, Lawrence O.; Clarke, Laurence P.; Bensaid, Amine M.; Arrington, J. A.; Silbiger, Martin L.


    Unsupervised fuzzy methods are proposed for segmentation of 3D Magnetic Resonance images of the brain. Fuzzy c-means (FCM) has shown promising results for segmentation of single slices. FCM has been investigated for volume segmentations, both by combining results of single slices and by segmenting the full volume. Different strategies and initializations have been tried. In particular, two approaches have been used: (1) a method by which, iteratively, the furthest sample is split off to form a new cluster center, and (2) the traditional FCM in which the membership grade matrix is initialized in some way. Results have been compared with volume segmentations by k-means and with two supervised methods, k-nearest neighbors and region growing. Results of individual segmentations are presented as well as comparisons on the application of the different methods to a number of tumor patient data sets.

  7. Keypoint Transfer Segmentation. (United States)

    Wachinger, C; Toews, M; Langs, G; Wells, W; Golland, P


    We present an image segmentation method that transfers label maps of entire organs from the training images to the novel image to be segmented. The transfer is based on sparse correspondences between keypoints that represent automatically identified distinctive image locations. Our segmentation algorithm consists of three steps: (i) keypoint matching, (ii) voting-based keypoint labeling, and (iii) keypoint-based probabilistic transfer of organ label maps. We introduce generative models for the inference of keypoint labels and for image segmentation, where keypoint matches are treated as a latent random variable and are marginalized out as part of the algorithm. We report segmentation results for abdominal organs in whole-body CT and in contrast-enhanced CT images. The accuracy of our method compares favorably to common multi-atlas segmentation while offering a speed-up of about three orders of magnitude. Furthermore, keypoint transfer requires no training phase or registration to an atlas. The algorithm's robustness enables the segmentation of scans with highly variable field-of-view.

  8. Pancreas and cyst segmentation (United States)

    Dmitriev, Konstantin; Gutenko, Ievgeniia; Nadeem, Saad; Kaufman, Arie


    Accurate segmentation of abdominal organs from medical images is an essential part of surgical planning and computer-aided disease diagnosis. Many existing algorithms are specialized for the segmentation of healthy organs. Cystic pancreas segmentation is especially challenging due to its low contrast boundaries, variability in shape, location and the stage of the pancreatic cancer. We present a semi-automatic segmentation algorithm for pancreata with cysts. In contrast to existing automatic segmentation approaches for healthy pancreas segmentation which are amenable to atlas/statistical shape approaches, a pancreas with cysts can have even higher variability with respect to the shape of the pancreas due to the size and shape of the cyst(s). Hence, fine results are better attained with semi-automatic steerable approaches. We use a novel combination of random walker and region growing approaches to delineate the boundaries of the pancreas and cysts with respective best Dice coefficients of 85.1% and 86.7%, and respective best volumetric overlap errors of 26.0% and 23.5%. Results show that the proposed algorithm for pancreas and pancreatic cyst segmentation is accurate and stable.

  9. ALS Along the Axons – Expression of Coding and Noncoding RNA Differs in Axons of ALS models (United States)

    Rotem, Nimrod; Magen, Iddo; Ionescu, Ariel; Gershoni-Emek, Noga; Altman, Topaz; Costa, Christopher J.; Gradus, Tal; Pasmanik-Chor, Metsada; Willis, Dianna E.; Ben-Dov, Iddo Z.; Hornstein, Eran; Perlson, Eran


    Amyotrophic lateral sclerosis (ALS) is a multifactorial lethal motor neuron disease with no known treatment. Although the basic mechanism of its degenerative pathogenesis remains poorly understood, a subcellular spatial alteration in RNA metabolism is thought to play a key role. The nature of these RNAs remains elusive, and a comprehensive characterization of the axonal RNAs involved in maintaining neuronal health has yet to be described. Here, using cultured spinal cord (SC) neurons grown using a compartmented platform followed by next-generation sequencing (NGS) technology, we find that RNA expression differs between the somatic and axonal compartments of the neuron, for both mRNA and microRNA (miRNA). Further, the introduction of SOD1G93A and TDP43A315T, established ALS-related mutations, changed the subcellular expression and localization of RNAs within the neurons, showing a spatial specificity to either the soma or the axon. Altogether, we provide here the first combined inclusive profile of mRNA and miRNA expression in two ALS models at the subcellular level. These data provide an important resource for studies on the roles of local protein synthesis and axon degeneration in ALS and can serve as a possible target pool for ALS treatment. PMID:28300211

  10. Axonal transport and neurodegenerative disease: vesicle-motor complex formation and their regulation

    Directory of Open Access Journals (Sweden)

    Anderson EN


    Full Text Available Eric N Anderson,* Joseph A White II,* Shermali GunawardenaDepartment of Biological Sciences, The State University of New York at Buffalo, Buffalo, NY, USA *These authors contributed equally to this work Abstract: The process of axonal transport serves to move components over very long distances on microtubule tracks in order to maintain neuronal viability. Molecular motors – kinesin and dynein – are essential for the movement of neuronal cargoes along these tracks; defects in this pathway have been implicated in the initiation or progression of some neurodegenerative diseases, suggesting that this process may be a key contributor in neuronal dysfunction. Recent work has led to the identification of some of the motor-cargo complexes, adaptor proteins, and their regulatory elements in the context of disease proteins. In this review, we focus on the assembly of the amyloid precursor protein, huntingtin, mitochondria, and the RNA-motor complexes and discuss how these may be regulated during long-distance transport in the context of neurodegenerative disease. As knowledge of these motor-cargo complexes and their involvement in axonal transport expands, insight into how defects in this pathway contribute to the development of neurodegenerative diseases becomes evident. Therefore, a better understanding of how this pathway normally functions has important implications for early diagnosis and treatment of diseases before the onset of disease pathology or behavior. Keywords: kinesin, dynein, amyloid precursor protein, huntingtin, microtubules

  11. ENA/VASP downregulation triggers cell death by impairing axonal maintenance in hippocampal neurons. (United States)

    Franco, D Lorena; Rezával, Carolina; Cáceres, Alfredo; Schinder, Alejandro F; Ceriani, M Fernanda


    Neurodegenerative diseases encompass a broad variety of motor and cognitive disorders that are accompanied by death of specific neuronal populations or brain regions. Cellular and molecular mechanisms underlying these complex disorders remain largely unknown. In a previous work we searched for novel Drosophila genes relevant for neurodegeneration and singled out enabled (ena), which encodes a protein involved in cytoskeleton remodeling. To extend our understanding on the mechanisms of ENA-triggered degeneration we now investigated the effect of silencing ena ortholog genes in mouse hippocampal neurons. We found that ENA/VASP downregulation led to neurite retraction and concomitant neuronal cell death through an apoptotic pathway. Remarkably, this retraction initially affected the axonal structure, showing no effect on dendrites. Reduction in ENA/VASP levels blocked the neuritogenic effect of a specific RhoA kinase (ROCK) inhibitor, thus suggesting that these proteins could participate in the Rho-signaling pathway. Altogether these observations demonstrate that ENA/VASP proteins are implicated in the establishment and maintenance of the axonal structure and that a change on their expression levels triggers neuronal degeneration.

  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. Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets. (United States)

    Oyanagi, Kiyomitsu; Kinoshita, Michiaki; Suzuki-Kouyama, Emi; Inoue, Teruhiko; Nakahara, Asa; Tokiwai, Mika; Arai, Nobutaka; Satoh, Jun-Ichi; Aoki, Naoya; Jinnai, Kenji; Yazawa, Ikuru; Arai, Kimihito; Ishihara, Kenji; Kawamura, Mitsuru; Ishizawa, Keisuke; Hasegawa, Kazuko; Yagisita, Saburo; Amano, Naoji; Yoshida, Kunihiro; Terada, Seishi; Yoshida, Mari; Akiyama, Haruhiko; Mitsuyama, Yoshio; Ikeda, Shu-Ichi


    The brains of 10 Japanese patients with adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD) and eight Japanese patients with Nasu-Hakola disease (N-HD) and five age-matched Japanese controls were examined neuropathologically with special reference to lesion staging and dynamic changes of microglial subsets. In both diseases, the pathognomonic neuropathological features included spherically swollen axons (spheroids and globules), axon loss and changes of microglia in the white matter. In ALSP, four lesion stages based on the degree of axon loss were discernible: Stage I, patchy axon loss in the cerebral white matter without atrophy; Stage II, large patchy areas of axon loss with slight atrophy of the cerebral white matter and slight dilatation of the lateral ventricles; Stage III, extensive axon loss in the cerebral white matter and dilatation of the lateral and third ventricles without remarkable axon loss in the brainstem and cerebellum; Stage IV, devastated cerebral white matter with marked dilatation of the ventricles and axon loss in the brainstem and/or cerebellum. Internal capsule and pontine base were relatively well preserved in the N-HD, even at Stage IV, and the swollen axons were larger with a higher density in the ALSP. Microglial cells immunopositive for CD68, CD163 or CD204 were far more obvious in ALSP, than in N-HD, and the shape and density of the cells changed in each stage. With progression of the stage, clinical symptoms became worse to apathetic state, and epilepsy was frequently observed in patients at Stages III and IV in both diseases. From these findings, it is concluded that (i) shape, density and subsets of microglia change dynamically along the passage of stages and (ii) increase of IBA-1-, CD68-, CD163- and CD204-immunopositive cells precedes loss of axons in ALSP.

  14. 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.

  15. Segmentation of antiperspirants and deodorants


    KRÁL, Tomáš


    The goal of Master's Thesis on topic Segmentation of antiperspirants and deodorants is to discover differences in consumer's behaviour, determinate and describe segments of consumers based on these differences and propose marketing strategy for the most attractive segments. Theoretical part describes market segmentation in general, process of segmentation and segmentation criteria. Analytic part characterizes Czech market of antiperspirants and deodorants, analyzes ACNielsen market data and d...

  16. An electromagnetic shashlik calorimeter with longitudinal segmentation

    CERN Document Server

    Benvenuti, Alberto C; Camporesi, T; Checchia, P; Fenyuk, A; Hedberg, V; Lishin, V A; Margoni, M; Mazzucato, M; Obraztsov, V F; Paganoni, M; Polyakov, V A; Simonetto, F; Terranova, F; Vlasov, E


    A novel technique for longitudinal segmentation of shashlik calorimeters has been tested in the CERN West Area beam facility. A 25 tower e.m. calorimeter has been built with vacuum photodiodes inserted in the first 8 radiation lengths to sample the initial development of the shower. Results concerning energy resolution, impact point reconstruction and $e/\\pi$ separation are reported.

  17. A Fully Automated Penumbra Segmentation Tool

    DEFF Research Database (Denmark)

    Nagenthiraja, Kartheeban; Ribe, Lars Riisgaard; Hougaard, Kristina Dupont


    salavageable tissue, quickly and accurately. We present a fully Automated Penumbra Segmentation (APS) algorithm using PWI and DWI images. We compare automatically generated PWI-DWI mismatch mask to mask outlined manually by experts, in 168 patients. Method: The algorithm initially identifies PWI lesions...

  18. Adjacent segment disease. (United States)

    Virk, Sohrab S; Niedermeier, Steven; Yu, Elizabeth; Khan, Safdar N


    EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Understand the forces that predispose adjacent cervical segments to degeneration. 2. Understand the challenges of radiographic evaluation in the diagnosis of cervical and lumbar adjacent segment disease. 3. Describe the changes in biomechanical forces applied to adjacent segments of lumbar vertebrae with fusion. 4. Know the risk factors for adjacent segment disease in spinal fusion. Adjacent segment disease (ASD) is a broad term encompassing many complications of spinal fusion, including listhesis, instability, herniated nucleus pulposus, stenosis, hypertrophic facet arthritis, scoliosis, and vertebral compression fracture. The area of the cervical spine where most fusions occur (C3-C7) is adjacent to a highly mobile upper cervical region, and this contributes to the biomechanical stress put on the adjacent cervical segments postfusion. Studies have shown that after fusion surgery, there is increased load on adjacent segments. Definitive treatment of ASD is a topic of continuing research, but in general, treatment choices are dictated by patient age and degree of debilitation. Investigators have also studied the risk factors associated with spinal fusion that may predispose certain patients to ASD postfusion, and these data are invaluable for properly counseling patients considering spinal fusion surgery. Biomechanical studies have confirmed the added stress on adjacent segments in the cervical and lumbar spine. The diagnosis of cervical ASD is complicated given the imprecise correlation of radiographic and clinical findings. Although radiological and clinical diagnoses do not always correlate, radiographs and clinical examination dictate how a patient with prolonged pain is treated. Options for both cervical and lumbar spine ASD include fusion and/or decompression. Current studies are encouraging regarding the adoption of arthroplasty in spinal surgery, but more long

  19. Dictionary Based Image Segmentation

    DEFF Research Database (Denmark)

    Dahl, Anders Bjorholm; Dahl, Vedrana Andersen


    We propose a method for weakly supervised segmentation of natural images, which may contain both textured or non-textured regions. Our texture representation is based on a dictionary of image patches. To divide an image into separated regions with similar texture we use an implicit level sets...... in an efficient implementation of our segmentation method. We experimentally validated our approach on a number of natural as well as composed images....

  20. Skin Images Segmentation

    Directory of Open Access Journals (Sweden)

    Ali E. Zaart


    Full Text Available Problem statement: Image segmentation is a fundamental step in many applications of image processing. Skin cancer has been the most common of all new cancers detected each year. At early stage detection of skin cancer, simple and economic treatment can cure it mostly. An accurate segmentation of skin images can help the diagnosis to define well the region of the cancer. The principal approach of segmentation is based on thresholding (classification that is lied to the problem of the thresholds estimation. Approach: The objective of this study is to develop a method to segment the skin images based on a mixture of Beta distributions. We assume that the data in skin images can be modeled by a mixture of Beta distributions. We used an unsupervised learning technique with Beta distribution to estimate the statistical parameters of the data in skin image and then estimate the thresholds for segmentation. Results: The proposed method of skin images segmentation was implemented and tested on different skin images. We obtained very good results in comparing with the same techniques with Gamma distribution. Conclusion: The experiment showed that the proposed method obtained very good results but it requires more testing on different types of skin images.

  1. The Pathomorphological Change of the Initial Segment of Vertebral Artery Related with Cervical Vertigo%颈性眩晕的椎动脉起始段(V1段)血管形态病理学改变

    Institute of Scientific and Technical Information of China (English)

    范炳华; 许丽; 林敏; 李伟; 汪芳俊; 徐泉珍


    [目的]探索颈性眩晕的椎动脉起始段(V1段)血管形态病理学改变。[方法]回顾1999年至2011年以头晕为主症,符合寰枕痛、恶心(呕吐)、耳鸣(耳塞)、视物模糊(视物旋转)4项症状中2项以上,经颅多普勒检测有椎-基底动脉血流速增快或减慢患者1680例,分析这些患者的椎-基底动脉CT血管造影三维重建技术(3D-CTA)的血管形态影像资料,观察椎动脉V1段血管形态病理学改变情况。[结果]颈性眩晕患者椎动脉V1段血管形态病理学有椎动脉纤细、椎动脉痉挛、椎动脉穿孔位置异常、椎动脉走行迂曲、椎动脉起始源异常、椎动脉瘤(或伴钙化)6种改变。[结论]颈性眩晕的椎动脉V1段存在6种血管形态病理学改变,根据这些病理改变,有助于在临床上判断预后,选择不同手法进行针对性地治疗,并指导患者在生活中的注意事项。%Objective] To explore the pathomorphological change of the initial segment of vertebral artery(V1 part) related with cervical vertigo. [Method] Review 1680 cases who had vertigo as primary symptom, associated with either 2 or more symptoms as fol ows: neck pain, nausea(or vomit), tinnitus(or ear stuffiness), blurred vision(or rotation). Al the cases had TCD examination which showed over fast or too slow blood flow speed, and 3D-CTA examination(Three-Dimensional Computed Tomography Angiography). The pathomorphological change of the initial segment of vertebral artery was observed through 3D-CTA technology. [Results] There were 6 kinds of pathomorphological changes in the initial segment of vertebral artery. They were tenuous vertebral artery, spasm vertebral artery, abnormal position of vertebral artery entering cervical transverse foramen, circuitous vertebral artery, abnormal initiating terminal, vertebral artery aneurysm(or associated with calcification).[Conclusion]There are 6 kinds of pathomorphological changes in the

  2. Changes in microtubule stability and density in myelin-deficient shiverer mouse CNS axons (United States)

    Kirkpatrick, L. L.; Witt, A. S.; Payne, H. R.; Shine, H. D.; Brady, S. T.


    Altered axon-Schwann cell interactions in PNS myelin-deficient Trembler mice result in changed axonal transport rates, neurofilament and microtubule-associated protein phosphorylation, neurofilament density, and microtubule stability. To determine whether PNS and CNS myelination have equivalent effects on axons, neurofilaments, and microtubules in CNS, myelin-deficient shiverer axons were examined. The genetic defect in shiverer is a deletion in the myelin basic protein (MBP) gene, an essential component of CNS myelin. As a result, shiverer mice have little or no compact CNS myelin. Slow axonal transport rates in shiverer CNS axons were significantly increased, in contrast to the slowing in demyelinated PNS nerves. Even more striking were substantial changes in the composition and properties of microtubules in shiverer CNS axons. The density of axonal microtubules is increased, reflecting increased expression of tubulin in shiverer, and the stability of microtubules is drastically reduced in shiverer axons. Shiverer transgenic mice with two copies of a wild-type myelin basic protein transgene have an intermediate level of compact myelin, making it possible to determine whether the actual level of compact myelin is an important regulator of axonal microtubules. Both increased microtubule density and reduced microtubule stability were still observed in transgenic mouse nerves, indicating that signals beyond synaptogenesis and the mere presence of compact myelin are required for normal regulation of the axonal microtubule cytoskeleton.

  3. Neuroinflammation by cytotoxic T-lymphocytes impairs retrograde axonal transport in an oligodendrocyte mutant mouse.

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    Chi Wang Ip

    Full Text Available Mice overexpressing proteolipid protein (PLP develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow transfer from wildtype mice, but not from perforin- or granzyme B-deficient mutants, into lymphocyte-deficient PLP mutant mice led again to impaired axonal transport and the formation of axonal swellings, which are predominantly located at the juxtaparanodal region. This demonstrates that the adaptive immune system, including cytotoxic T-lymphocytes which release perforin and granzyme B, are necessary to perturb axonal integrity in the PLP-transgenic disease model. Based on our observations, so far not attended molecular and cellular players belonging to the immune system should be considered to understand pathogenesis in inherited myelin disorders with progressive axonal damage.

  4. Eph:ephrin-B1 forward signaling controls fasciculation of sensory and motor axons. (United States)

    Luxey, Maëva; Jungas, Thomas; Laussu, Julien; Audouard, Christophe; Garces, Alain; Davy, Alice


    Axon fasciculation is one of the processes controlling topographic innervation during embryonic development. While axon guidance steers extending axons in the accurate direction, axon fasciculation allows sets of co-extending axons to grow in tight bundles. The Eph:ephrin family has been involved both in axon guidance and fasciculation, yet it remains unclear how these two distinct types of responses are elicited. Herein we have characterized the role of ephrin-B1, a member of the ephrinB family in sensory and motor innervation of the limb. We show that ephrin-B1 is expressed in sensory axons and in the limb bud mesenchyme while EphB2 is expressed in motor and sensory axons. Loss of ephrin-B1 had no impact on the accurate dorso-ventral innervation of the limb by motor axons, yet EfnB1 mutants exhibited decreased fasciculation of peripheral motor and sensory nerves. Using tissue-specific excision of EfnB1 and in vitro experiments, we demonstrate that ephrin-B1 controls fasciculation of axons via a surround repulsion mechanism involving growth cone collapse of EphB2-expressing axons. Altogether, our results highlight the complex role of Eph:ephrin signaling in the development of the sensory-motor circuit innervating the limb.

  5. The corpus callosum in primates: processing speed of axons and the evolution of hemispheric asymmetry (United States)

    Phillips, Kimberley A.; Stimpson, Cheryl D.; Smaers, Jeroen B.; Raghanti, Mary Ann; Jacobs, Bob; Popratiloff, Anastas; Hof, Patrick R.; Sherwood, Chet C.


    Interhemispheric communication may be constrained as brain size increases because of transmission delays in action potentials over the length of axons. Although one might expect larger brains to have progressively thicker axons to compensate, spatial packing is a limiting factor. Axon size distributions within the primate corpus callosum (CC) may provide insights into how these demands affect conduction velocity. We used electron microscopy to explore phylogenetic variation in myelinated axon density and diameter of the CC from 14 different anthropoid primate species, including humans. The majority of axons were less than 1 µm in diameter across all species, indicating that conduction velocity for most interhemispheric communication is relatively constant regardless of brain size. The largest axons within the upper 95th percentile scaled with a progressively higher exponent than the median axons towards the posterior region of the CC. While brain mass among the primates in our analysis varied by 97-fold, estimates of the fastest cross-brain conduction times, as conveyed by axons at the 95th percentile, varied within a relatively narrow range between 3 and 9 ms across species, whereas cross-brain conduction times for the median axon diameters differed more substantially between 11 and 38 ms. Nonetheless, for both size classes of axons, an increase in diameter does not entirely compensate for the delay in interhemispheric transmission time that accompanies larger brain size. Such biophysical constraints on the processing speed of axons conveyed by the CC may play an important role in the evolution of hemispheric asymmetry. PMID:26511047

  6. Effect of vesicle traps on traffic jam formation in fast axonal transport. (United States)

    Kuznetsov, A V


    The purpose of this paper is to develop a model for simulation of the formation of organelle traps in fast axonal transport. Such traps may form in the regions of microtubule polar mismatching. Depending on the orientation of microtubules pointing toward the trap region, these traps can accumulate either plus-end or minus-end oriented vesicles. The model predicts that the maximum concentrations of organelles occur at the boundaries of the trap regions; the overall concentration of organelles in the axon with traps is greatly increased compared to that in a healthy axon, which is expected to contribute to mechanical damages of the axon. The organelle traps induce hindrance to organelle transport down the axon; the total organelle flux down the axon with traps is found to be significantly reduced compared to that in a healthy axon.

  7. Regulation of neuronal axon specification by glia-neuron gap junctions in C. elegans (United States)

    Meng, Lingfeng; Zhang, Albert; Jin, Yishi; Yan, Dong


    Axon specification is a critical step in neuronal development, and the function of glial cells in this process is not fully understood. Here, we show that C. elegans GLR glial cells regulate axon specification of their nearby GABAergic RME neurons through GLR-RME gap junctions. Disruption of GLR-RME gap junctions causes misaccumulation of axonal markers in non-axonal neurites of RME neurons and converts microtubules in those neurites to form an axon-like assembly. We further uncover that GLR-RME gap junctions regulate RME axon specification through activation of the CDK-5 pathway in a calcium-dependent manner, involving a calpain clp-4. Therefore, our study reveals the function of glia-neuron gap junctions in neuronal axon specification and shows that calcium originated from glial cells can regulate neuronal intracellular pathways through gap junctions. DOI: PMID:27767956

  8. Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation. (United States)

    del Puerto, Ana; Díaz-Hernández, Juan-Ignacio; Tapia, Mónica; Gomez-Villafuertes, Rosa; Benitez, María José; Zhang, Jin; Miras-Portugal, María Teresa; Wandosell, Francisco; Díaz-Hernández, Miguel; Garrido, Juan José


    In adult brains, ionotropic or metabotropic purinergic receptors are widely expressed in neurons and glial cells. They play an essential role in inflammation and neurotransmission in response to purines secreted to the extracellular medium. Recent studies have demonstrated a role for purinergic receptors in proliferation and differentiation of neural stem cells although little is known about their role in regulating the initial neuronal development and axon elongation. The objective of our study was to investigate the role of some different types of purinergic receptors, P2Y1, P2Y13 and P2X7, which are activated by ADP or ATP. To study the role and crosstalk of P2Y1, P2Y13 and P2X7 purinergic receptors in axonal elongation, we treated neurons with specific agonists and antagonists, and we nucleofected neurons with expression or shRNA plasmids. ADP and P2Y1-GFP expression improved axonal elongation; conversely, P2Y13 and ATP-gated P2X7 receptors halted axonal elongation. Signaling through each of these receptor types was coordinated by adenylate cyclase 5. In neurons nucleofected with a cAMP FRET biosensor (ICUE3), addition of ADP or Blue Brilliant G, a P2X7 antagonist, increased cAMP levels in the distal region of the axon. Adenylate cyclase 5 inhibition or suppression impaired these cAMP increments. In conclusion, our results demonstrate a crosstalk between two metabotropic and one ionotropic purinergic receptor that regulates cAMP levels through adenylate cyclase 5 and modulates axonal elongation triggered by neurotropic factors and the PI3K-Akt-GSK3 pathway.

  9. BW Trained HMM based Aerial Image Segmentation

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    R Rajasree


    Full Text Available Image segmentation is an essential preprocessing tread in a complicated and composite image dealing out algorithm. In segmenting arial image the expenditure of misclassification could depend on the factual group of pupils. In this paper, aggravated by modern advances in contraption erudition conjecture, I introduce a modus operandi to make light of the misclassification expenditure with class-dependent expenditure. The procedure assumes the hidden Markov model (HMM which has been popularly used for image segmentation in recent years. We represent all feasible HMM based segmenters (or classifiers as a set of points in the beneficiary operating characteristic (ROC space. optimizing HMM parameters is still an important and challenging work in automatic image segmentation research area. Usually the Baum-Welch (B-W Algorithm is used to calculate the HMM model parameters. However, the B-W algorithm uses an initial random guess of the parameters, therefore after convergence the output tends to be close to this initial value of the algorithm, which is not necessarily the global optimum of the model parameters. In this project, a Adaptive Baum-Welch (GA-BW is proposed.

  10. Squid Giant Axon Contains Neurofilament Protein mRNA but does not Synthesize Neurofilament Proteins. (United States)

    Gainer, Harold; House, Shirley; Kim, Dong Sun; Chin, Hemin; Pant, Harish C


    When isolated squid giant axons are incubated in radioactive amino acids, abundant newly synthesized proteins are found in the axoplasm. These proteins are translated in the adaxonal Schwann cells and subsequently transferred into the giant axon. The question as to whether any de novo protein synthesis occurs in the giant axon itself is difficult to resolve because the small contribution of the proteins possibly synthesized intra-axonally is not easily distinguished from the large amounts of the proteins being supplied from the Schwann cells. In this paper, we reexamine this issue by studying the synthesis of endogenous neurofilament (NF) proteins in the axon. Our laboratory previously showed that NF mRNA and protein are present in the squid giant axon, but not in the surrounding adaxonal glia. Therefore, if the isolated squid axon could be shown to contain newly synthesized NF protein de novo, it could not arise from the adaxonal glia. The results of experiments in this paper show that abundant 3H-labeled NF protein is synthesized in the squid giant fiber lobe containing the giant axon's neuronal cell bodies, but despite the presence of NF mRNA in the giant axon no labeled NF protein is detected in the giant axon. This lends support to the glia-axon protein transfer hypothesis which posits that the squid giant axon obtains newly synthesized protein by Schwann cell transfer and not through intra-axonal protein synthesis, and further suggests that the NF mRNA in the axon is in a translationally repressed state.

  11. Segmentation of Color Images Based on Different Segmentation Techniques

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    Purnashti Bhosale


    Full Text Available In this paper, we propose an Color image segmentation algorithm based on different segmentation techniques. We recognize the background objects such as the sky, ground, and trees etc based on the color and texture information using various methods of segmentation. The study of segmentation techniques by using different threshold methods such as global and local techniques and they are compared with one another so as to choose the best technique for threshold segmentation. Further segmentation is done by using clustering method and Graph cut method to improve the results of segmentation.

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

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    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

  13. Enhanced noradrenergic axon regeneration into schwann cell-filled PVDF-TrFE conduits after complete spinal cord transection. (United States)

    Lee, Yee-Shuan; Wu, Siliang; Arinzeh, Treena Livingston; Bunge, Mary Bartlett


    Schwann cell (SC) transplantation has been utilized for spinal cord repair and demonstrated to be a promising therapeutic strategy. In this study, we investigated the feasibility of combining SC transplantation with novel conduits to bridge the completely transected adult rat spinal cord. This is the first and initial study to evaluate the potential of using a fibrous piezoelectric polyvinylidene fluoride trifluoroethylene (PVDF-TrFE) conduit with SCs for spinal cord repair. PVDF-TrFE has been shown to enhance neurite growth in vitro and peripheral nerve repair in vivo. In this study, SCs adhered and proliferated when seeded onto PVDF-TrFE scaffolds in vitro. SCs and PVDF-TrFE conduits, consisting of random or aligned fibrous inner walls, were transplanted into transected rat spinal cords for 3 weeks to examine early repair. Glial fibrillary acidic protein (GFAP)(+) astrocyte processes and GFP (green fluorescent protein)-SCs were interdigitated at both rostral and caudal spinal cord/SC transplant interfaces in both types of conduits, indicative of permissivity to axon growth. More noradrenergic/DβH(+) (dopamine-beta-hydroxylase) brainstem axons regenerated across the transplant when greater numbers of GFAP(+) astrocyte processes were present. Aligned conduits promoted extension of DβH(+) axons and GFAP(+) processes farther into the transplant than random conduits. Sensory CGRP(+) (calcitonin gene-related peptide) axons were present at the caudal interface. Blood vessels formed throughout the transplant in both conduits. This study demonstrates that PVDF-TrFE conduits harboring SCs are promising for spinal cord repair and deserve further investigation. Biotechnol. Bioeng. 2017;114: 444-456. © 2016 Wiley Periodicals, Inc.

  14. Axon and muscle spindle hyperplasia in the myostatin null mouse. (United States)

    Elashry, Mohamed I; Otto, Anthony; Matsakas, Antonios; El-Morsy, Salah E; Jones, Lisa; Anderson, Bethan; Patel, Ketan


    Germline deletion of the myostatin gene results in hyperplasia and hypertrophy of the tension-generating (extrafusal) fibres in skeletal muscle. As this gene is expressed predominantly in myogenic tissues it offers an excellent model with which to investigate the quantitative relationship between muscle and axonal development. Here we show that skeletal muscle hyperplasia in myostatin null mouse is accompanied by an increase in nerve fibres in major nerves of both the fore- and hindlimbs. We show that axons within these nerves undergo hypertrophy. Furthermore, we provide evidence that the age-related neural atrophic process is delayed in the absence of myostatin. Finally, we show that skeletal muscle hyperplasia in the myostatin null mouse is accompanied by an increase in the number of muscle spindles (also called stretch receptors or proprioceptors). However, our work demonstrates that the mechanisms regulating intrafusal fibre hyperplasia and hypertrophy differ from those that control the aetiology of extrafusal fibres.

  15. Coevolution of axon guidance molecule Slit and its receptor Robo. (United States)

    Yu, Qi; Li, Xiao-Tong; Zhao, Xiao; Liu, Xun-Li; Ikeo, Kazuho; Gojobori, Takashi; Liu, Qing-Xin


    Coevolution is important for the maintenance of the interaction between a ligand and its receptor during evolution. The interaction between axon guidance molecule Slit and its receptor Robo is critical for the axon repulsion in neural tissues, which is evolutionarily conserved from planarians to humans. However, the mechanism of coevolution between Slit and Robo remains unclear. In this study, we found that coordinated amino acid changes took place at interacting sites of Slit and Robo by comparing the amino acids at these sites among different organisms. In addition, the high level correlation between evolutionary rate of Slit and Robo was identified in vertebrates. Furthermore, the sites under positive selection of slit and robo were detected in the same lineage such as mosquito and teleost. Overall, our results provide evidence for the coevolution between Slit and Robo.

  16. Antiretroviral Therapy-Associated Acute Motor and Sensory Axonal Neuropathy

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    Kimberly N. Capers


    Full Text Available Guillain-Barré syndrome (GBS has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome.

  17. Coevolution of axon guidance molecule Slit and its receptor Robo.

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    Qi Yu

    Full Text Available Coevolution is important for the maintenance of the interaction between a ligand and its receptor during evolution. The interaction between axon guidance molecule Slit and its receptor Robo is critical for the axon repulsion in neural tissues, which is evolutionarily conserved from planarians to humans. However, the mechanism of coevolution between Slit and Robo remains unclear. In this study, we found that coordinated amino acid changes took place at interacting sites of Slit and Robo by comparing the amino acids at these sites among different organisms. In addition, the high level correlation between evolutionary rate of Slit and Robo was identified in vertebrates. Furthermore, the sites under positive selection of slit and robo were detected in the same lineage such as mosquito and teleost. Overall, our results provide evidence for the coevolution between Slit and Robo.

  18. Rediscovering market segmentation. (United States)

    Yankelovich, Daniel; Meer, David


    In 1964, Daniel Yankelovich introduced in the pages of HBR the concept of nondemographic segmentation, by which he meant the classification of consumers according to criteria other than age, residence, income, and such. The predictive power of marketing studies based on demographics was no longer strong enough to serve as a basis for marketing strategy, he argued. Buying patterns had become far better guides to consumers' future purchases. In addition, properly constructed nondemographic segmentations could help companies determine which products to develop, which distribution channels to sell them in, how much to charge for them, and how to advertise them. But more than 40 years later, nondemographic segmentation has become just as unenlightening as demographic segmentation had been. Today, the technique is used almost exclusively to fulfill the needs of advertising, which it serves mainly by populating commercials with characters that viewers can identify with. It is true that psychographic types like "High-Tech Harry" and "Joe Six-Pack" may capture some truth about real people's lifestyles, attitudes, self-image, and aspirations. But they are no better than demographics at predicting purchase behavior. Thus they give corporate decision makers very little idea of how to keep customers or capture new ones. Now, Daniel Yankelovich returns to these pages, with consultant David Meer, to argue the case for a broad view of nondemographic segmentation. They describe the elements of a smart segmentation strategy, explaining how segmentations meant to strengthen brand identity differ from those capable of telling a company which markets it should enter and what goods to make. And they introduce their "gravity of decision spectrum", a tool that focuses on the form of consumer behavior that should be of the greatest interest to marketers--the importance that consumers place on a product or product category.

  19. Neural development in Onychophora (velvet worms) suggests a step-wise evolution of segmentation in the nervous system of Panarthropoda. (United States)

    Mayer, Georg; Whitington, Paul M


    A fundamental question in biology is how animal segmentation arose during evolution. One particular challenge is to clarify whether segmental ganglia of the nervous system evolved once, twice, or several times within the Bilateria. As close relatives of arthropods, Onychophora play an important role in this debate since their nervous system displays a mixture of both segmental and non-segmental features. We present evidence that the onychophoran "ventral organs," previously interpreted as segmental anlagen of the nervous system, do not contribute to nerve cord formation and therefore cannot be regarded as vestiges of segmental ganglia. The early axonal pathways in the central nervous system arise by an anterior-to-posterior cascade of axonogenesis from neuronal cell bodies, which are distributed irregularly along each presumptive ventral cord. This pattern contrasts with the strictly segmental neuromeres present in arthropod embryos and makes the assumption of a secondary loss of segmentation in the nervous system during the evolution of the Onychophora less plausible. We discuss the implications of these findings for the evolution of neural segmentation in the Panarthropoda (Arthropoda+Onychophora+Tardigrada). Our data best support the hypothesis that the ancestral panarthropod had only a partially segmented nervous system, which evolved progressively into the segmental chain of ganglia seen in extant tardigrades and arthropods.

  20. Morphology of axonal transport abnormalities in primate eyes.


    Radius, R L; Anderson, D. R.


    The ultrastructure of the retina and optic nerve head was studied in primate eyes after central retinal artery occlusion. Within 2 hours of the vascular occlusion the inner retinal layers undergo watery (isosmotic) swelling. This watery swelling of axons and astroglia extends into the nerve head as far back as the anterior boundary of the scleral lamina cribrosa. The swelling is increased 4 hours after the occlusion, and by 24 hours disintegration has occurred. At the optic nerve head mitocho...

  1. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties


    Casale, Amanda E.; Foust, Amanda J.; Bal, Thierry; McCormick, David A.


    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two o...

  2. Self-assembling segmented coiled tubing

    Energy Technology Data Exchange (ETDEWEB)

    Raymond, David W.


    Self-assembling segmented coiled tubing is a concept that allows the strength of thick-wall rigid pipe, and the flexibility of thin-wall tubing, to be realized in a single design. The primary use is for a drillstring tubular, but it has potential for other applications requiring transmission of mechanical loads (forces and torques) through an initially coiled tubular. The concept uses a spring-loaded spherical `ball-and-socket` type joint to interconnect two or more short, rigid segments of pipe. Use of an optional snap ring allows the joint to be permanently made, in a `self-assembling` manner.

  3. GrabCut-based human segmentation in video sequences. (United States)

    Hernández-Vela, Antonio; Reyes, Miguel; Ponce, Víctor; Escalera, Sergio


    In this paper, we present a fully-automatic Spatio-Temporal GrabCut human segmentation methodology that combines tracking and segmentation. GrabCut initialization is performed by a HOG-based subject detection, face detection, and skin color model. Spatial information is included by Mean Shift clustering whereas temporal coherence is considered by the historical of Gaussian Mixture Models. Moreover, full face and pose recovery is obtained by combining human segmentation with Active Appearance Models and Conditional Random Fields. Results over public datasets and in a new Human Limb dataset show a robust segmentation and recovery of both face and pose using the presented methodology.

  4. GrabCut-Based Human Segmentation in Video Sequences

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    Sergio Escalera


    Full Text Available In this paper, we present a fully-automatic Spatio-Temporal GrabCut human segmentation methodology that combines tracking and segmentation. GrabCut initialization is performed by a HOG-based subject detection, face detection, and skin color model. Spatial information is included by Mean Shift clustering whereas temporal coherence is considered by the historical of Gaussian Mixture Models. Moreover, full face and pose recovery is obtained by combining human segmentation with Active Appearance Models and Conditional Random Fields. Results over public datasets and in a new Human Limb dataset show a robust segmentation and recovery of both face and pose using the presented methodology.

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

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    Yuta Iwai

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

  6. Axon clinical chemistry analyzer evaluated according to ECCLS protocol. (United States)

    Brenna, S; Prencipe, L


    We assessed the analytical performance of the Axon system (Bayer Diagnostici), according to the European Committee for Clinical Laboratory Standards guidelines, for assay of 12 analytes: cholesterol, creatinine, glucose, total protein, urea, uric acid, alkaline phosphatase, alpha-amylase, aspartate aminotransferase, creatine kinase, sodium, and potassium. The field evaluation lasted approximately 5 months and involved the collection of approximately 10,000 data points with the Axon. The following results were obtained: The highest CVs for controls and human sera at different concentration/activity values were 2.2% for within-run imprecision (n = 60; 3 days, pooled estimate) and 3.5% for the between-day imprecision (n = 20 days). Close correlation was found with results for patients' specimens assayed with comparative instruments (Hitachi 717 for substrates and enzymes, Beckman Synchron EL/E4A for electrolytes). No drift was observed during 8 h of operation. The linearity range was broad, sometimes exceeding the manufacturer's claims. No sample-, reagent-, or cuvette-related carryover was found. Measurement of control sera gave results within +/- 5% of the assigned values. We conclude that good reliability and practicability make the Axon system suitable for laboratories with various needs.

  7. Acute axonal polyneuropathy with predominant proximal involvement: an uncommon neurological complication of bariatric surgery

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    Machado Flavia Costa Nunes


    Full Text Available Bariatric surgery is frequently indicated in the treatment of morbid obesity. Previously unreported complications have been associated to this surgery; among them, neurological complications have gained attention. We report the case of a 25-year-old man submitted to gastric surgery for treatment of morbid obesity who developed, two months after surgery, acute proximal weakness in lower limbs. The electroneuromyography revealed axonal peripheral polyneuropathy with predominant proximal involvement. After treatment with immunoglobulin and vitamin supplementation, rapid clinical and neurophysiologic recovery was observed. We describe the clinical and electroneuromyographic features of this case, stressing the difficulty of initial diagnosis, particularly in the differential diagnosis with Guillain-Barré syndrome. We discuss the importance of nutritional follow-up and the eventual indication of routine vitamin supplementation in these patients.

  8. Acute axonal polyneuropathy with predominant proximal involvement: an uncommon neurological complication of bariatric surgery. (United States)

    Machado, Flavia Costa Nunes; Valério, Berenice Cataldo Oliveira; Morgulis, Roberto Naun Franco; Nunes, Karlo Faria; Mazzali-Verst, Sílvia


    Bariatric surgery is frequently indicated in the treatment of morbid obesity. Previously unreported complications have been associated to this surgery; among them, neurological complications have gained attention. We report the case of a 25-year-old man submitted to gastric surgery for treatment of morbid obesity who developed, two months after surgery, acute proximal weakness in lower limbs. The electroneuromyography revealed axonal peripheral polyneuropathy with predominant proximal involvement. After treatment with immunoglobulin and vitamin supplementation, rapid clinical and neurophysiologic recovery was observed. We describe the clinical and electroneuromyographic features of this case, stressing the difficulty of initial diagnosis, particularly in the differential diagnosis with Guillain-Barré syndrome. We discuss the importance of nutritional follow-up and the eventual indication of routine vitamin supplementation in these patients.

  9. Segmented heterochromia in scalp hair. (United States)

    Yoon, Kyeong Han; Kim, Daehwan; Sohn, Seonghyang; Lee, Won Soo


    Segmented heterochromia of scalp hair is characterized by the irregularly alternating segmentation of hair into dark and light bands and is known to be associated with iron deficiency anemia. The authors report the case of an 11-year-old boy with segmented heterochromia associated with iron deficiency anemia. After 11 months of iron replacement, the boy's segmented heterochromic hair recovered completely.

  10. Changes in Synapses and Axons Demonstrated by Synaptophysin Immunohistochemistry Following Spinal Cord Compression Trauma in the Rat and Mouse

    Institute of Scientific and Technical Information of China (English)



    and methods To evaluate synaptic changes using synaptophysin immunohistochemstry in rat and mouse, which spinal cords were subjected to graded compression trauma at the level of Th8-9. Results Normal animals showed numerous fine dots of synaptophysin immunoreactivity in the gray matter. An increase in synaptophysin immunoreactivity was observed in the neuropil and synapses at the surface of motor neurons of the anterior horns in the Th8-9 segments lost immunoreactivity at 4-hour point after trauma. The immunoreactive synapses reappeared around motor neurons at 9-day point. Unexpected accumulation of synaptophysin immunoreactivity occurred in injured axons of the white matter of the compressed spinal cord. Conclusion Synaptic changes were important components of secondary injuries in spinal cord trauma. Loss of synapses on motor neurons may be one of the factors causing motor dysfunction of hind limbs and formation of new synapses may play an important role in recovery of motor function. Synaptophysin immunohistochemistry is also a good tool for studies of axonal swellings in spinal cord injuries.

  11. Scorpion image segmentation system (United States)

    Joseph, E.; Aibinu, A. M.; Sadiq, B. A.; Bello Salau, H.; Salami, M. J. E.


    Death as a result of scorpion sting has been a major public health problem in developing countries. Despite the high rate of death as a result of scorpion sting, little report exists in literature of intelligent device and system for automatic detection of scorpion. This paper proposed a digital image processing approach based on the floresencing characteristics of Scorpion under Ultra-violet (UV) light for automatic detection and identification of scorpion. The acquired UV-based images undergo pre-processing to equalize uneven illumination and colour space channel separation. The extracted channels are then segmented into two non-overlapping classes. It has been observed that simple thresholding of the green channel of the acquired RGB UV-based image is sufficient for segmenting Scorpion from other background components in the acquired image. Two approaches to image segmentation have also been proposed in this work, namely, the simple average segmentation technique and K-means image segmentation. The proposed algorithm has been tested on over 40 UV scorpion images obtained from different part of the world and results obtained show an average accuracy of 97.7% in correctly classifying the pixel into two non-overlapping clusters. The proposed 1system will eliminate the problem associated with some of the existing manual approaches presently in use for scorpion detection.

  12. Segmented conjugated polymers

    Indian Academy of Sciences (India)

    G Padmanaban; S Ramakrishnan


    Segmented conjugated polymers, wherein the conjugation is randomly truncated by varying lengths of non-conjugated segments, form an interesting class of polymers as they not only represent systems of varying stiffness, but also ones where the backbone can be construed as being made up of chromophores of varying excitation energies. The latter feature, especially when the chromophores are fluorescent, like in MEHPPV, makes these systems particularly interesting from the photophysics point of view. Segmented MEHPPV- samples, where x represents the mole fraction of conjugated segments, were prepared by a novel approach that utilizes a suitable precursor wherein selective elimination of one of the two eliminatable groups is affected; the uneliminated units serve as conjugation truncations. Control of the composition x of the precursor therefore permits one to prepare segmented MEHPPV- samples with varying levels of conjugation (elimination). Using fluorescence spectroscopy, we have seen that even in single isolated polymer chains, energy migration from the shorter (higher energy) chromophores to longer (lower energy) ones occurs – the extent of which depends on the level of conjugation. Further, by varying the solvent composition, it is seen that the extent of energy transfer and the formation of poorly emissive inter-chromophore excitons are greatly enhanced with increasing amounts of non-solvent. A typical S-shaped curve represents the variation of emission yields as a function of composition suggestive of a cooperative collapse of the polymer coil, reminiscent of conformational transitions seen in biological macromolecules.

  13. Pupil segmentation using active contour with shape prior (United States)

    Ukpai, Charles O.; Dlay, Satnam S.; Woo, Wai L.


    Iris segmentation is the process of defining the valid part of the eye image used for further processing (feature extraction, matching and decision making). Segmentation of the iris mostly starts with pupil boundary segmentation. Most pupil segmentation techniques are based on the assumption that the pupil is circular shape. In this paper, we propose a new pupil segmentation technique which combines shape, location and spatial information for accurate and efficient segmentation of the pupil. Initially, the pupil's position and radius is estimated using a statistical approach and circular Hough transform. In order to segment the irregular boundary of the pupil, an active contour model is initialized close to the estimated boundary using information from the first step and segmentation is achieved using energy minimization based active contour. Pre-processing and post-processing were carried out to remove noise and occlusions respectively. Experimental results on CASIA V1.0 and 4.0 shows that the proposed method is highly effective at segmenting irregular boundaries of the pupil.

  14. Segmentation of complex document

    Directory of Open Access Journals (Sweden)

    Souad Oudjemia


    Full Text Available In this paper we present a method for segmentation of documents image with complex structure. This technique based on GLCM (Grey Level Co-occurrence Matrix used to segment this type of document in three regions namely, 'graphics', 'background' and 'text'. Very briefly, this method is to divide the document image, in block size chosen after a series of tests and then applying the co-occurrence matrix to each block in order to extract five textural parameters which are energy, entropy, the sum entropy, difference entropy and standard deviation. These parameters are then used to classify the image into three regions using the k-means algorithm; the last step of segmentation is obtained by grouping connected pixels. Two performance measurements are performed for both graphics and text zones; we have obtained a classification rate of 98.3% and a Misclassification rate of 1.79%.

  15. Optimally segmented magnetic structures

    DEFF Research Database (Denmark)

    Insinga, Andrea Roberto; Bahl, Christian; Bjørk, Rasmus;

    ], or are applicable only to analytically solvable geometries[4]. In addition, some questions remained fundamentally unanswered, such as how to segment a given design into N uniformly magnetized pieces.Our method calculates the globally optimal shape and magnetization direction of each segment inside a certain......We present a semi-analytical algorithm for magnet design problems, which calculates the optimal way to subdivide a given design region into uniformly magnetized segments.The availability of powerful rare-earth magnetic materials such as Nd-Fe-B has broadened the range of applications of permanent...... designarea with an optional constraint on the total amount of magnetic material. The method can be applied to any objective functional which is linear respect to the field, and with any combination of linear materials. Being based on an analytical-optimization approach, the algorithm is not computationally...

  16. Microscopic Halftone Image Segmentation

    Institute of Scientific and Technical Information of China (English)

    WANG Yong-gang; YANG Jie; DING Yong-sheng


    Microscopic halftone image recognition and analysis can provide quantitative evidence for printing quality control and fault diagnosis of printing devices, while halftone image segmentation is one of the significant steps during the procedure. Automatic segmentation on microscopic dots by the aid of the Fuzzy C-Means (FCM) method that takes account of the fuzziness of halftone image and utilizes its color information adequately is realized. Then some examples show the technique effective and simple with better performance of noise immunity than some usual methods. In addition, the segmentation results obtained by the FCM in different color spaces are compared, which indicates that the method using the FCM in the f1f2f3 color space is superior to the rest.

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

    Directory of Open Access Journals (Sweden)

    Yang Xia

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

  18. Statistical Images Segmentation

    Directory of Open Access Journals (Sweden)

    Corina Curilă


    Full Text Available This paper deals with fuzzy statistical imagesegmentation. We introduce a new hierarchicalMarkovian fuzzy hidden field model, which extends to thefuzzy case the classical Pérez and Heitz hard model. Twofuzzy statistical segmentation methods related with themodel proposed are defined in this paper and we show viasimulations that they are competitive with, in some casesthan, the classical Maximum Posterior Mode (MPMbased methods. Furthermore, they are faster, which willshould facilitate extensions to more than two hard classesin future work. In addition, the model proposed isapplicable to the multiscale segmentation andmultiresolution images fusion problems.

  19. GPS Control Segment Improvements (United States)


    Systems Center GPS Control Segment Improvements Mr. Tim McIntyre GPS Product Support Manager GPS Ops Support and Sustainment Division Peterson...DATE 29 APR 2015 2. REPORT TYPE 3. DATES COVERED 00-00-2015 to 00-00-2015 4. TITLE AND SUBTITLE GPS Control Segment Improvements 5a. CONTRACT...ORGANIZATION NAME(S) AND ADDRESS(ES) Air Force Space Command,Space and Missile Systems Center, GPS Ops Support and Sustainment Division,Peterson AFB,CO,80916 8

  20. ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS. (United States)

    Koch, J C; Tönges, L; Barski, E; Michel, U; Bähr, M; Lingor, P


    The Rho/ROCK/LIMK pathway is central for the mediation of repulsive environmental signals in the central nervous system. Several studies using pharmacological Rho-associated protein kinase (ROCK) inhibitors have shown positive effects on neurite regeneration and suggest additional pro-survival effects in neurons. However, as none of these drugs is completely target specific, it remains unclear how these effects are mediated and whether ROCK is really the most relevant target of the pathway. To answer these questions, we generated adeno-associated viral vectors to specifically downregulate ROCK2 and LIM domain kinase (LIMK)-1 in rat retinal ganglion cells (RGCs) in vitro and in vivo. We show here that specific knockdown of ROCK2 and LIMK1 equally enhanced neurite outgrowth of RGCs on inhibitory substrates and both induced substantial neuronal regeneration over distances of more than 5 mm after rat optic nerve crush (ONC) in vivo. However, only knockdown of ROCK2 but not LIMK1 increased survival of RGCs after optic nerve axotomy. Moreover, knockdown of ROCK2 attenuated axonal degeneration of the proximal axon after ONC assessed by in vivo live imaging. Mechanistically, we demonstrate here that knockdown of ROCK2 resulted in decreased intraneuronal activity of calpain and caspase 3, whereas levels of pAkt and collapsin response mediator protein 2 and autophagic flux were increased. Taken together, our data characterize ROCK2 as a specific therapeutic target in neurodegenerative diseases and demonstrate new downstream effects of ROCK2 including axonal degeneration, apoptosis and autophagy.

  1. Proprioceptive feedback modulates coordinating information in a system of segmentally distributed microcircuits. (United States)

    Mulloney, Brian; Smarandache-Wellmann, Carmen; Weller, Cynthia; Hall, Wendy M; DiCaprio, Ralph A


    The system of modular neural circuits that controls crustacean swimmerets drives a metachronal sequence of power-stroke (PS, retraction) and return-stroke (RS, protraction) movements that propels the animal forward efficiently. These neural modules are synchronized by an intersegmental coordinating circuit that imposes characteristic phase differences between these modules. Using a semi-intact preparation that left one swimmeret attached to an otherwise isolated central nervous system (CNS) of the crayfish, Pacifastacus leniusculus, we investigated how the rhythmic activity of this system responded to imposed movements. We recorded extracellularly from the PS and RS nerves that innervated the attached limb and from coordinating axons that encode efference copies of the periodic bursts in PS and RS axons. Simultaneously, we recorded from homologous nerves in more anterior and posterior segments. Maintained retractions did not affect cycle period but promptly weakened PS bursts, strengthened RS bursts, and caused corresponding changes in the strength and timing of efference copies in the module's coordinating axons. Changes in these efference copies then caused changes in the phase and duration, but not the strength, of PS bursts in modules controlling neighboring swimmerets. These changes were promptly reversed when the limb was released. Each swimmeret is innervated by two nonspiking stretch receptors (NSSRs) that depolarize when the limb is retracted. Voltage clamp of an NSSR changed the durations and strengths of bursts in PS and RS axons innervating the same limb and caused corresponding changes in the efference copies of this motor output.

  2. Coupled Shape Model Segmentation in Pig Carcasses

    DEFF Research Database (Denmark)

    Hansen, Mads Fogtmann; Larsen, Rasmus; Ersbøll, Bjarne Kjær;


    In this paper we are concerned with multi-object segmentation. For each object we will train a level set function based shape prior from a sample set of outlines. The outlines are aligned in a multi-resolution scheme wrt. an Euclidean similarity transformation in order to maximize the overlap...... levels inside the outline as well as in a narrow band outside the outline. The maximum a posteriori estimate of the outline is found by gradient descent optimization. In order to segment a group of mutually dependent objects we propose 2 procedures, 1) the objects are found sequentially by conditioning...... the initialization of the next search from already found objects; 2) all objects are found simultaneously and a repelling force is introduced in order to avoid overlap between outlines in the solution. The methods are applied to segmentation of cross sections of muscles in slices of CT scans of pig backs for quality...

  3. An experimental study of retrograde axonal plasmatic flow in the peripheral nerves of rats. (United States)

    Sanguinetti, C; Tranquilli Leali, P; Grispigni, C


    Retrograde axonal flow (R.A.F.) in the sciatic nerve of Sprague Dowley rats was studied by injecting horseradish peroxidase (H.R.P.) peripherally and identifying its appearance in the related segment of the spinal cord. This called for a precise identification of the vertebro-medullary topography, the afferant root levels of the sciatic nerve, and the transport velocity of the H.R.P. Our study revealed a clear difference of neuromuscular end plate permeability as between new-born and adult animals. The vertebral column of the rat consists of 8 cervical metameres, 13 dorsal, 6 lumbar, 4 sacral, and 3 coccygeal. The sciatic nerve is derived principally from the roots L4, L5, L6 and in part from L3 and S1. The injection of H.R.P. in the sural triceps of the new-born rat produced granules in the anterior horn cells as early as 12 hours later. In similar experiments with adult rats H.R.P. in the motorneurons was never detected. In our experimental model the transport velocity of H.R.P. from the point of injection to the anterior horn cells was approximately 68 mm per day. These findings provide a foundation on which to base future studies of retrograde flows in conditions of induced pathology.

  4. Voltage-clamp predictions by gompertz kinetics model relating squid-axon Na+-gating and ionic currents. (United States)

    Easton, Dexter M


    Gompertz kinetics is a simple, realistic, accurate, and computationally parsimonious alternative for prediction of macroscopic changes in Na+ conductance during voltage clamp. Conductance delay and time course depend on initial amplitudes and decay rates of surrogates for the macroscopic gating currents. The model is tested by the fit to published data of other authors. The proposed physical basis for the model is that membrane potential perturbation triggers motion of charged "gating" components of the axon membrane at rapid (activating) and at slow (inactivating) rates. The resulting distortion increases and more slowly diminishes the probability that conduction channels will be open.

  5. The unique axon trajectory of the accessory nerve is determined by intrinsic properties of the neural tube in the avian embryo. (United States)

    Bai, Zhongtian; Pu, Qin; Haque, Ziaul; Wang, Jianlin; Huang, Ruijin


    The accessory nerve is a cranial nerve, composed of only motor axons, which control neck muscles. Its axons ascend many segments along the lateral surface of the cervical spinal cord and hindbrain. At the level of the first somite, they pass ventrally through the somitic mesoderm into the periphery. The factors governing the unique root trajectory are unknown. Ablation experiments at the accessory nerve outlet points have shown that somites do not regulate the trajectory of the accessory nerve fibres. Factors from the neural tube that may control the longitudinal pathfinding of the accessory nerve fibres were tested by heterotopic transplantations of an occipital neural tube to the cervical and thoracic level. These transplantations resulted in a typical accessory nerve trajectory in the cervical and thoracic spinal cord. In contrast, cervical neural tube grafts were unable to give rise to the typical accessory nerve root pattern when transplanted to occipital level. Our results show that the formation of the unique axon root pattern of the accessory nerve is an intrinsic property of the neural tube.

  6. The mTORC1 effectors S6K1 and 4E-BP play different roles in CNS axon regeneration. (United States)

    Yang, Liu; Miao, Linqing; Liang, Feisi; Huang, Haoliang; Teng, Xiuyin; Li, Shaohua; Nuriddinov, Jaloliddin; Selzer, Michael E; Hu, Yang


    Using mouse optic nerve (ON) crush as a CNS injury model, we and others have found that activation of the mammalian target of rapamycin complex 1 (mTORC1) in mature retinal ganglion cells by deletion of the negative regulators, phosphatase and tensin homologue (PTEN), and tuberous sclerosis 1 promotes ON regeneration. mTORC1 activation inhibits eukaryotic translation initiation factor 4E-binding protein (4E-BP) and activates ribosomal protein S6 kinase 1 (S6K1), both of which stimulate translation. We reasoned that mTORC1's regeneration-promoting effects might be separable from its deleterious effects by differential manipulation of its downstream effectors. Here we show that S6K1 activation, but not 4E-BP inhibition, is sufficient to promote axon regeneration. However, inhibition of 4E-BP is required for PTEN deletion-induced axon regeneration. Both activation and inhibition of S6K1 decrease the effect of PTEN deletion on axon regeneration, implicating a dual role of S6K1 in regulating axon growth.

  7. Sipunculans and segmentation

    DEFF Research Database (Denmark)

    Wanninger, Andreas; Kristof, Alen; Brinkmann, Nora


    Comparative molecular, developmental and morphogenetic analyses show that the three major segmented animal groups- Lophotrochozoa, Ecdysozoa and Vertebrata-use a wide range of ontogenetic pathways to establish metameric body organization. Even in the life history of a single specimen, different m...

  8. [Segmental testicular infarction]. (United States)

    Ripa Saldías, L; Guarch Troyas, R; Hualde Alfaro, A; de Pablo Cárdenas, A; Ruiz Ramo, M; Pinós Paul, M


    We report the case of a 47 years old man previously diagnosed of left hidrocele. After having a recent mild left testicular pain, an ultrasonografic study revealed a solid hipoecoic testicular lesion rounded by a big hidrocele, suggesting a testicular neoplasm. Radical inguinal orchiectomy was made and pathologic study showed segmental testicular infarction. No malignancy was found. We review the literature of the topic.

  9. Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo.

    Directory of Open Access Journals (Sweden)

    Fabián Muñoz

    Full Text Available Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.

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

    Institute of Scientific and Technical Information of China (English)

    程飚; 陈峥嵘


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

  11. JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling

    DEFF Research Database (Denmark)

    Riveiro, Alba; Mariani, Luca; Malmberg, Kim Emily


    . Here, we show that the catalytic activity of a PHF8 homolog in Caenorhabditis elegans, JMJD-1.2, is required non-cell-autonomously for proper axon guidance. Loss of JMJD-1.2 dysregulates transcription of the Hedgehog-related genes wrt-8 and grl-16, the overexpression of which is sufficient to induce...... the axonal defects. Deficiency of either wrt-8 or grl-16, or reduced expression of homologs of genes promoting Hedgehog signaling, restores correct axon guidance in jmjd-1.2 mutants. Genetic and overexpression data indicate that Hedgehog-related genes act on axon guidance through actin remodelers. Thus, our...... study highlights a novel function of jmjd-1.2 in axon guidance that might be relevant for the onset of X-linked mental retardation and provides compelling evidence of a conserved function of the Hedgehog pathway in C. elegans axon migration....

  12. Sonic hedgehog regulates its own receptor on postcrossing commissural axons in a glypican1-dependent manner. (United States)

    Wilson, Nicole H; Stoeckli, Esther T


    Upon reaching their intermediate target, the floorplate, commissural axons acquire responsiveness to repulsive guidance cues, allowing the axons to exit the midline and adopt a contralateral, longitudinal trajectory. The molecular mechanisms that regulate this switch from attraction to repulsion remain poorly defined. Here, we show that the heparan sulfate proteoglycan Glypican1 (GPC1) is required as a coreceptor for the Shh-dependent induction of Hedgehog-interacting protein (Hhip) in commissural neurons. In turn, Hhip is required for postcrossing axons to respond to a repulsive anteroposterior Shh gradient. Thus, Shh is a cue with dual function. In precrossing axons it acts as an attractive guidance molecule in a transcription-independent manner. At the same time, Shh binds to GPC1 to induce the expression of its own receptor, Hhip, which mediates the repulsive response of postcrossing axons to Shh. Our study characterizes a molecular mechanism by which navigating axons switch their responsiveness at intermediate targets.

  13. 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.

  14. Automatic segmentation of bladder in CT images

    Institute of Scientific and Technical Information of China (English)

    Feng SHI; Jie YANG; Yue-min ZHU


    Segmentation of the bladder in computerized tomography (CT) images is an important step in radiation therapy planning of prostate cancer. We present a new segmentation scheme to automatically delineate the bladder contour in CT images with three major steps. First, we use the mean shift algorithm to obtain a clustered image containing the rough contour of the bladder, which is then extracted in the second step by applying a region-growing algorithm with the initial seed point selected from a line-by-line scanning process. The third step is to refine the bladder contour more accurately using the rolling-ball algorithm. These steps are then extended to segment the bladder volume in a slice-by-slice manner. The obtained results were compared to manual segmentation by radiation oncologists. The average values of sensitivity, specificity, positive predictive value, negative predictive value, and Hausdorff distance are 86.5%, 96.3%, 90.5%, 96.5%, and 2.8 pixels, respectively. The results show that the bladder can be accurately segmented.

  15. Edge Segment-Based Automatic Video Surveillance

    Directory of Open Access Journals (Sweden)

    Oksam Chae


    Full Text Available This paper presents a moving-object segmentation algorithm using edge information as segment. The proposed method is developed to address challenges due to variations in ambient lighting and background contents. We investigated the suitability of the proposed algorithm in comparison with the traditional-intensity-based as well as edge-pixel-based detection methods. In our method, edges are extracted from video frames and are represented as segments using an efficiently designed edge class. This representation helps to obtain the geometric information of edge in the case of edge matching and moving-object segmentation; and facilitates incorporating knowledge into edge segment during background modeling and motion tracking. An efficient approach for background initialization and robust method of edge matching is presented, to effectively reduce the risk of false alarm due to illumination change and camera motion while maintaining the high sensitivity to the presence of moving object. Detected moving edges are utilized along with watershed algorithm for extracting video object plane (VOP with more accurate boundary. Experiment results with real image sequence reflect that the proposed method is suitable for automated video surveillance applications in various monitoring systems.

  16. Early syllabic segmentation of fluent speech by infants acquiring French.

    Directory of Open Access Journals (Sweden)

    Louise Goyet

    Full Text Available Word form segmentation abilities emerge during the first year of life, and it has been proposed that infants initially rely on two types of cues to extract words from fluent speech: Transitional Probabilities (TPs and rhythmic units. The main goal of the present study was to use the behavioral method of the Headturn Preference Procedure (HPP to investigate again rhythmic segmentation of syllabic units by French-learning infants at the onset of segmentation abilities (around 8 months given repeated failure to find syllabic segmentation at such a young age. The second goal was to explore the interaction between the use of TPs and syllabic units for segmentation by French-learning infants. The rationale was that decreasing TP cues around target syllables embedded in bisyllabic words would block bisyllabic word segmentation and facilitate the observation of syllabic segmentation. In Experiments 1 and 2, infants were tested in a condition of moderate TP decrease; no evidence of either syllabic or bisyllabic word segmentation was found. In Experiment 3, infants were tested in a condition of more marked TP decrease, and a novelty syllabic segmentation effect was observed. Therefore, the present study first establishes early syllabic segmentation in French-learning infants, bringing support from a syllable-based language to the proposal that rhythmic units are used at the onset of segmentation abilities. Second, it confirms that French-learning infants are sensitive to TP cues. Third, it demonstrates that they are sensitive to the relative weight of TP and rhythmic cues, explaining why effects of syllabic segmentation are not observed in context of high TPs. These findings are discussed in relation to theories of word segmentation bootstrapping, and the larger debate about statistically- versus prosodically-based accounts of early language acquisition.

  17. Early syllabic segmentation of fluent speech by infants acquiring French. (United States)

    Goyet, Louise; Nishibayashi, Léo-Lyuki; Nazzi, Thierry


    Word form segmentation abilities emerge during the first year of life, and it has been proposed that infants initially rely on two types of cues to extract words from fluent speech: Transitional Probabilities (TPs) and rhythmic units. The main goal of the present study was to use the behavioral method of the Headturn Preference Procedure (HPP) to investigate again rhythmic segmentation of syllabic units by French-learning infants at the onset of segmentation abilities (around 8 months) given repeated failure to find syllabic segmentation at such a young age. The second goal was to explore the interaction between the use of TPs and syllabic units for segmentation by French-learning infants. The rationale was that decreasing TP cues around target syllables embedded in bisyllabic words would block bisyllabic word segmentation and facilitate the observation of syllabic segmentation. In Experiments 1 and 2, infants were tested in a condition of moderate TP decrease; no evidence of either syllabic or bisyllabic word segmentation was found. In Experiment 3, infants were tested in a condition of more marked TP decrease, and a novelty syllabic segmentation effect was observed. Therefore, the present study first establishes early syllabic segmentation in French-learning infants, bringing support from a syllable-based language to the proposal that rhythmic units are used at the onset of segmentation abilities. Second, it confirms that French-learning infants are sensitive to TP cues. Third, it demonstrates that they are sensitive to the relative weight of TP and rhythmic cues, explaining why effects of syllabic segmentation are not observed in context of high TPs. These findings are discussed in relation to theories of word segmentation bootstrapping, and the larger debate about statistically- versus prosodically-based accounts of early language acquisition.

  18. Educational Systems, Intergenerational Mobility and Social Segmentation

    Directory of Open Access Journals (Sweden)

    Nathalie Chusseau


    Full Text Available We show that the very characteristics of educational systems generate social segmentation. A stylised educational framework is constructed in which everyone receives a compulsory basic education and can subsequently choose between direct working, vocational studies and university. There is a selection for entering the university which consists of a minimum human capital level at the end of basic education. In the model, an individual's human capital depends (i on her/his parents' human capital, (ii on her/his schooling time, and (iii on public expenditure for education. There are three education functions corresponding to each type of study (basic, vocational, university. Divergences in total educational expenditure, in its distribution between the three studies and in the selection severity, combined with the initial distribution of human capital across individuals, can result in very different social segmentations and generate under education traps (situations in which certain dynasties remain unskilled from generation to generation at the steady state. We finally implement a series of simulations that illustrate these findings in the cases of egalitarian and elitist educational systems. Assuming the same initial distribution of human capital between individuals, we find that the first system results in two-segment stratification, quasi income equality and no under education trap whereas the elitist system generates three segments, significant inequality and a large under education trap

  19. Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway



    The failure of axons to regenerate is a major obstacle for functional recovery after central nervous system (CNS) injury. Removing extracellular inhibitory molecules results in limited axon regeneration in vivo. To test for the role of intrinsic impediments to axon regrowth, we analyzed cell growth control genes using a virus-assisted in vivo conditional knockout approach. Deletion of PTEN (phosphatase and tensin homolog), a negative regulator of the mammalian target of rapamycin (mTOR) pathw...

  20. ATP7A (Menkes Protein) functions in Axonal Targeting and Synaptogenesis


    Meskini, Rajaâ El; Crabtree, Kelli L.; Cline, Laura B.; Mains, Richard E.; Eipper, Betty A.; Ronnett, Gabriele V.


    Menkes Disease (MD) is a neurodegenerative disorder caused by mutations in the copper transporter, ATP7A, a P-type ATPase. We previously used the olfactory system to demonstrate that ATP7A expression is developmentally, not constitutive, regulated, peaking during synaptogenesis when it is highly expressed in extending axons in a copper-independent manner. Although not known to be associated with axonal functions, we explored the possibility that the inability of mutant ATP7A to support axon o...

  1. Cyclophilin D Deficiency Rescues Axonal Mitochondrial Transport in Alzheimer’s Neurons


    Lan Guo; Heng Du; Shiqiang Yan; Xiaoping Wu; Guy M. McKhann; John Xi Chen; Shirley ShiDu Yan


    Normal axonal mitochondrial transport and function is essential for the maintenance of synaptic function. Abnormal mitochondrial motility and mitochondrial dysfunction within axons are critical for amyloid β (Aβ)-induced synaptic stress and the loss of synapses relevant to the pathogenesis of Alzheimer's disease (AD). However, the mechanisms controlling axonal mitochondrial function and transport alterations in AD remain elusive. Here, we report an unexplored role of cyclophilin D (CypD)-depe...

  2. Segmentation in Tardigrada and diversification of segmental patterns in Panarthropoda. (United States)

    Smith, Frank W; Goldstein, Bob


    The origin and diversification of segmented metazoan body plans has fascinated biologists for over a century. The superphylum Panarthropoda includes three phyla of segmented animals-Euarthropoda, Onychophora, and Tardigrada. This superphylum includes representatives with relatively simple and representatives with relatively complex segmented body plans. At one extreme of this continuum, euarthropods exhibit an incredible diversity of serially homologous segments. Furthermore, distinct tagmosis patterns are exhibited by different classes of euarthropods. At the other extreme, all tardigrades share a simple segmented body plan that consists of a head and four leg-bearing segments. The modular body plans of panarthropods make them a tractable model for understanding diversification of animal body plans more generally. Here we review results of recent morphological and developmental studies of tardigrade segmentation. These results complement investigations of segmentation processes in other panarthropods and paleontological studies to illuminate the earliest steps in the evolution of panarthropod body plans.

  3. Thiazolidinediones Promote Axonal Growth through the Activation of the JNK Pathway (United States)

    Quintanilla, Rodrigo A.; Godoy, Juan A.; Alfaro, Ivan; Cabezas, Deny; von Bernhardi, Rommy; Bronfman, Miguel; Inestrosa, Nibaldo C.


    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. PMID:23741474

  4. A role for myosin VI in the localization of axonal proteins.

    Directory of Open Access Journals (Sweden)

    Tommy L Lewis


    Full Text Available In neurons polarized trafficking of vesicle-bound membrane proteins gives rise to the distinct molecular composition and functional properties of axons and dendrites. Despite their central role in shaping neuronal form and function, surprisingly little is known about the molecular processes that mediate polarized targeting of neuronal proteins. Recently, the plus-end-directed motor Myosin Va was shown to play a critical role in targeting of transmembrane proteins to dendrites; however, the role of myosin motors in axonal targeting is unknown. Here we show that Myosin VI, a minus-end-directed motor, plays a vital role in the enrichment of proteins on the surface of axons. Engineering non-neuronal proteins to interact with Myosin VI causes them to become highly concentrated at the axonal surface in dissociated rat cortical neurons. Furthermore, disruption of either Myosin VI function or expression leads to aberrant dendritic localization of axonal proteins. Myosin VI mediates the enrichment of proteins on the axonal surface at least in part by stimulating dendrite-specific endocytosis, a mechanism that has been shown to underlie the localization of many axonal proteins. In addition, a version of Channelrhodopsin 2 that was engineered to bind to Myosin VI is concentrated at the surface of the axon of cortical neurons in mice in vivo, suggesting that it could be a useful tool for probing circuit structure and function. Together, our results indicate that myosins help shape the polarized distributions of both axonal and dendritic proteins.

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

    DEFF Research Database (Denmark)

    Colak, Dilek; Ji, Sheng-Jian; Porse, Bo T


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

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

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    Christian Witzel


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

  7. Motor neuron synapse and axon defects in a C. elegans alpha-tubulin mutant.

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    Renee Baran

    Full Text Available Regulation of microtubule dynamics underlies many fundamental cellular mechanisms including cell division, cell motility, and transport. In neurons, microtubules play key roles in cell migration, axon outgrowth, control of axon and synapse growth, and the regulated transport of vesicles and structural components of synapses. Loss of synapse and axon integrity and disruption of axon transport characterize many neurodegenerative diseases. Recently, mutations that specifically alter the assembly or stability of microtubules have been found to directly cause neurodevelopmental defects or neurodegeneration in vertebrates. We report here the characterization of a missense mutation in the C-terminal domain of C. elegans alpha-tubulin, tba-1(ju89, that disrupts motor neuron synapse and axon development. Mutant ju89 animals exhibit reduction in the number and size of neuromuscular synapses, altered locomotion, and defects in axon extension. Although null mutations of tba-1 show a nearly wild-type pattern, similar axon outgrowth defects were observed in animals lacking the beta-tubulin TBB-2. Genetic analysis reveals that tba-1(ju89 affects synapse development independent of its role in axon outgrowth. tba-1(ju89 is an altered function allele that most likely perturbs interactions between TBA-1 and specific microtubule-associated proteins that control microtubule dynamics and transport of components needed for synapse and axon growth.

  8. Odorant receptors regulate the final glomerular coalescence of olfactory sensory neuron axons. (United States)

    Rodriguez-Gil, Diego J; Bartel, Dianna L; Jaspers, Austin W; Mobley, Arie S; Imamura, Fumiaki; Greer, Charles A


    Odorant receptors (OR) are strongly implicated in coalescence of olfactory sensory neuron (OSN) axons and the formation of olfactory bulb (OB) glomeruli. However, when ORs are first expressed relative to basal cell division and OSN axon extension is unknown. We developed an in vivo fate-mapping strategy that enabled us to follow OSN maturation and axon extension beginning at basal cell division. In parallel, we mapped the molecular development of OSNs beginning at basal cell division, including the onset of OR expression. Our data show that ORs are first expressed around 4 d following basal cell division, 24 h after OSN axons have reached the OB. Over the next 6+ days the OSN axons navigate the OB nerve layer and ultimately coalesce in glomeruli. These data provide a previously unidentified perspective on the role of ORs in homophilic OSN axon adhesion and lead us to propose a new model dividing axon extension into two phases. Phase I is OR-independent and accounts for up to 50% of the time during which axons approach the OB and begin navigating the olfactory nerve layer. Phase II is OR-dependent and concludes as OSN axons coalesce in glomeruli.

  9. NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion (United States)

    Sasaki, Yo; Nakagawa, Takashi; Mao, Xianrong; DiAntonio, Aaron; Milbrandt, Jeffrey


    Overexpression of the NAD+ biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD+ or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD+ metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD+ synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD+ consumption that is central to axon degeneration. DOI: PMID:27735788

  10. Effect of the Degree of Soft and Hard Segment Ordering on the Morphology and Mechanical Behavior of Semicrystalline Segmented Polyurethanes

    Energy Technology Data Exchange (ETDEWEB)

    Korley,L.; Pate, B.; Thomas, E.; Hammond, P.


    The hierarchical microstructure responsible for the unique energy-absorbing properties of natural materials, like native spider silk and wood, motivated the development of segmented polyurethanes with soft segments containing multiple levels of order. As a first step in correlating the effects of crystallinity in the soft segment phase to the hard segment phase, we chose to examine the morphology and mechanical behavior of polyurethanes containing polyether soft blocks with varying tendencies to crystallize and phase segregate and the evolution of the microstructure with deformation. A series of high molecular weight polyurethanes containing poly(ethylene oxide) (PEO) (1000 and 4600 g/mol) and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) (1900 g/mol) soft segments with varying hard segment content were synthesized using a two-step solution polymerization method. The presence of soft segment crystallinity (PEO 1000 g/mol) was shown to improve the storage modulus of the segmented polyurethanes below the T{sub m} of the soft block and to enhance toughness compared to the PEO-PPO-PEO soft segment polyurethanes. We postulate that this enhancement in mechanical behavior is the result of crystalline soft regions that serve as an additional load-bearing component during deformation. Morphological characterization also revealed that the microstructure of the segmented polyurethanes shifts from soft segment continuous to interconnected and/or hard domain continuous with increasing hard segment size, resulting in diminished ultimate elongation, but enhanced initial moduli and tensile strengths. Tuning the soft segment phase crystallinity may ultimately lead to tougher polyurethane fibers.

  11. Erbin is required for myelination in regenerated axons after injury



    Neuregulin 1 (NRG1) is an axon-derived factor that is critical for Schwann cell (SC) development and myelinogenesis in a manner dependent on transmembrane tyrosine kinases ErbB2 and ErbB3. Recent studies suggest that NRG1 signaling plays a role in remyelination of regenerated nerves after injury. In this study, we investigated the role of Erbin, a protein that interacts with ErbB2 in remyelination of injured nerves. We show that Erbin expression increased dramatically in injured nerves. Myeli...

  12. Pyridoxine neuropathy in rats: specific degeneration of sensory axons. (United States)

    Windebank, A J; Low, P A; Blexrud, M D; Schmelzer, J D; Schaumburg, H H


    When rats received pyridoxine in doses large enough to cause neuropathy in humans, the animals developed gait ataxia that subsided after the toxin was withdrawn. By using quantitative histologic techniques, we found axonal degeneration of sensory system fibers and that the fibers derived from the ventral root were spared. Although the degeneration approached the dorsal root ganglion, neurons in the ganglion did not degenerate. We found no early decrease in oxygen consumption of nerve, suggesting that impaired oxidative metabolism was not the primary event.

  13. Neuroprotective Effects of Citicoline in Diffuse Axonal Injuries


    Firooz Salehpou; Ghaffar Shokouhi; Moslem Shakeri; Mohammad Shimia; Atta Mahdkhah; Ali Baradaran; Mohammad Taghi Imani; arhad Mirzaee; Aydin Kazempour Azar; Amir Mohammad Bazzazi; Hadi Mohammad Khanli


    Citicoline is a neuroprotective agent and fundamental item of phospholipid biosynthesis in cell walls. In this study, we aimed at examining the effect of citicoline in patients suffering from traumatic brain injury with Glasgow Coma Score (GCS) ≤ 8, and diffuse axonal injury (DAI) diagnosis. Efficacy of citicoline was evaluated by measurement of malondialdehyde (MDA) plasma levels as a marker of oxidative stress. Forty patients were randomly divided into two groups of cases (treated with citi...

  14. Morphogenesis of the C. elegans Intestine Involves Axon Guidance Genes.

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    Alparsan Asan


    Full Text Available Genetic and molecular studies have provided considerable insight into how various tissue progenitors are specified in early embryogenesis, but much less is known about how those progenitors create three-dimensional tissues and organs. The C. elegans intestine provides a simple system for studying how a single progenitor, the E blastomere, builds an epithelial tube of 20 cells. As the E descendants divide, they form a primordium that transitions between different shapes over time. We used cell contours, traced from confocal optical z-stacks, to build a 3D graphic reconstruction of intestine development. The reconstruction revealed several new aspects of morphogenesis that extend and clarify previous observations. The first 8 E descendants form a plane of four right cells and four left cells; the plane arises through oriented cell divisions and VANG-1/Van Gogh-dependent repositioning of any non-planar cells. LIN-12/Notch signaling affects the left cells in the E8 primordium, and initiates later asymmetry in cell packing. The next few stages involve cell repositioning and intercalation events that shuttle cells to their final positions, like shifting blocks in a Rubik's cube. Repositioning involves breaking and replacing specific adhesive contacts, and some of these events involve EFN-4/Ephrin, MAB-20/semaphorin-2a, and SAX-3/Robo. Once cells in the primordium align along a common axis and in the correct order, cells at the anterior end rotate clockwise around the axis of the intestine. The anterior rotation appears to align segments of the developing lumen into a continuous structure, and requires the secreted ligand UNC-6/netrin, the receptor UNC-40/DCC, and an interacting protein called MADD-2. Previous studies showed that rotation requires a second round of LIN-12/Notch signaling in cells on the right side of the primordium, and we show that MADD-2-GFP appears to be downregulated in those cells.

  15. Morphogenesis of the C. elegans Intestine Involves Axon Guidance Genes. (United States)

    Asan, Alparsan; Raiders, Stephan A; Priess, James R


    Genetic and molecular studies have provided considerable insight into how various tissue progenitors are specified in early embryogenesis, but much less is known about how those progenitors create three-dimensional tissues and organs. The C. elegans intestine provides a simple system for studying how a single progenitor, the E blastomere, builds an epithelial tube of 20 cells. As the E descendants divide, they form a primordium that transitions between different shapes over time. We used cell contours, traced from confocal optical z-stacks, to build a 3D graphic reconstruction of intestine development. The reconstruction revealed several new aspects of morphogenesis that extend and clarify previous observations. The first 8 E descendants form a plane of four right cells and four left cells; the plane arises through oriented cell divisions and VANG-1/Van Gogh-dependent repositioning of any non-planar cells. LIN-12/Notch signaling affects the left cells in the E8 primordium, and initiates later asymmetry in cell packing. The next few stages involve cell repositioning and intercalation events that shuttle cells to their final positions, like shifting blocks in a Rubik's cube. Repositioning involves breaking and replacing specific adhesive contacts, and some of these events involve EFN-4/Ephrin, MAB-20/semaphorin-2a, and SAX-3/Robo. Once cells in the primordium align along a common axis and in the correct order, cells at the anterior end rotate clockwise around the axis of the intestine. The anterior rotation appears to align segments of the developing lumen into a continuous structure, and requires the secreted ligand UNC-6/netrin, the receptor UNC-40/DCC, and an interacting protein called MADD-2. Previous studies showed that rotation requires a second round of LIN-12/Notch signaling in cells on the right side of the primordium, and we show that MADD-2-GFP appears to be downregulated in those cells.

  16. Color Image Segmentation via Improved K-Means Algorithm

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    Ajay Kumar


    Full Text Available Data clustering techniques are often used to segment the real world images. Unsupervised image segmentation algorithms that are based on the clustering suffer from random initialization. There is a need for efficient and effective image segmentation algorithm, which can be used in the computer vision, object recognition, image recognition, or compression. To address these problems, the authors present a density-based initialization scheme to segment the color images. In the kernel density based clustering technique, the data sample is mapped to a high-dimensional space for the effective data classification. The Gaussian kernel is used for the density estimation and for the mapping of sample image into a high- dimensional color space. The proposed initialization scheme for the k-means clustering algorithm can homogenously segment an image into the regions of interest with the capability of avoiding the dead centre and the trapped centre by local minima phenomena. The performance of the experimental result indicates that the proposed approach is more effective, compared to the other existing clustering-based image segmentation algorithms. In the proposed approach, the Berkeley image database has been used for the comparison analysis with the recent clustering-based image segmentation algorithms like k-means++, k-medoids and k-mode.


    Institute of Scientific and Technical Information of China (English)

    纳瑟; 刘重庆


    This paper presented a method that incorporates Markov Random Field(MRF), watershed segmentation and merging techniques for performing image segmentation and edge detection tasks. MRF is used to obtain an initial estimate of x regions in the image under process where in MRF model, gray level x, at pixel location i, in an image X, depends on the gray levels of neighboring pixels. The process needs an initial segmented result. An initial segmentation is got based on K-means clustering technique and the minimum distance, then the region process in modeled by MRF to obtain an image contains different intensity regions. Starting from this we calculate the gradient values of that image and then employ a watershed technique. When using MRF method it obtains an image that has different intensity regions and has all the edge and region information, then it improves the segmentation result by superimpose closed and an accurate boundary of each region using watershed algorithm. After all pixels of the segmented regions have been processed, a map of primitive region with edges is generated. Finally, a merge process based on averaged mean values is employed. The final segmentation and edge detection result is one closed boundary per actual region in the image.

  18. Segmentation Using Symmetry Deviation

    DEFF Research Database (Denmark)

    Hollensen, Christian; Højgaard, L.; Specht, L.;


    segmentations on manual contours was evaluated using concordance index and sensitivity for the hypopharyngeal patients. The resulting concordance index and sensitivity was compared with the result of using a threshold of 3 SUV using a paired t-test. Results: The anatomical and symmetrical atlas was constructed...... and sensitivity of respectively 0.43±0.15 and 0.56±0.18 was acquired. It was compared to the concordance index of segmentation using absolute threshold of 3 SUV giving respectively 0.41±0.16 and 0.51±0.19 for concordance index and sensitivity yielding p-values of 0.33 and 0.01 for a paired t-test respectively....

  19. Market segmentation: Venezuelan ADRs

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    Urbi Garay


    Full Text Available The control on foreign exchange imposed by Venezuela in 2003 constitute a natural experiment that allows researchers to observe the effects of exchange controls on stock market segmentation. This paper provides empirical evidence that although the Venezuelan capital market as a whole was highly segmented before the controls were imposed, the shares in the firm CANTV were, through their American Depositary Receipts (ADRs, partially integrated with the global market. Following the imposition of the exchange controls this integration was lost. Research also documents the spectacular and apparently contradictory rise experienced by the Caracas Stock Exchange during the serious economic crisis of 2003. It is argued that, as it happened in Argentina in 2002, the rise in share prices occurred because the depreciation of the Bolívar in the parallel currency market increased the local price of the stocks that had associated ADRs, which were negotiated in dollars.

  20. Evaluation of k-Means and fuzzy C-means segmentation on MR images of brain


    S.Madhukumar; N. Santhiyakumari


    This paper does the qualitative comparison of Fuzzy C-means (FCM) and k-Means segmentation, with histogram guided initialization, on tumor edema complex MR images. The accuracy of any segmentation scheme depends on its ability to distinguish different tissue classes, separately. Hence, there is a serious pre-requisite to evaluate this ability before employing the segmentation scheme on medical images. This paper evaluates the ability of FCM and k-Means to segment Gray Matter (GM), White Matte...

  1. A Semantic Connected Coherence Scheme for Efficient Image Segmentation

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    Full Text Available Image processing is a comprehensively research topic with an elongated history. Segmenting an image is the most challenging and difficult task in image processing and analysis. The principal intricacy met in image segmentation is the ability of techniques to discover semantic objects efficiently from an image without any prior knowledge. One recent work presented connected coherence tree algorithm (CCTA for image segmentation (with no prior knowledge which discovered regions of semantic coherence based on neighbor coherence segmentation criteria. It deployed an adaptive spatial scale and a suitable intensity-difference scale to extract several sets of coherent neighboring pixels and maximize the probability of single image content and minimize complex backgrounds. However CCTA segmented images either consists of small, lengthy and slender objects or rigorously ruined by noise, irregular lighting, occlusion, poor illumination, and shadow.In this paper, we present a Cluster based Semantic Coherent Tree (CBSCT scheme for image segmentation. CBSCT’s initial work is on the semantic connected coherence criteria for the image segregation. Semantic coherent regions are clustered based on Bayesian nearest neighbor search of neighborhood pixels. The segmentation regions are extracted from the images based on the cluster object purity obtained through semantic coherent regions. The clustered image regions are post processed with non linear noise filters. Performance metrics used in the evaluation of CBSCT are semantic coherent pixel size, number of cluster objects, and purity levels of the cluster, segmented coherent region intensity threshold, and quality of segmented images in terms of image clarity with PSNR.

  2. Market Segmentation for Information Services. (United States)

    Halperin, Michael


    Discusses the advantages and limitations of market segmentation as strategy for the marketing of information services made available by nonprofit organizations, particularly libraries. Market segmentation is defined, a market grid for libraries is described, and the segmentation of information services is outlined. A 16-item reference list is…

  3. Segmenting the Adult Education Market. (United States)

    Aurand, Tim


    Describes market segmentation and how the principles of segmentation can be applied to the adult education market. Indicates that applying segmentation techniques to adult education programs results in programs that are educationally and financially satisfying and serve an appropriate population. (JOW)

  4. Quantitative evaluation of six graph based semi-automatic liver tumor segmentation techniques using multiple sets of reference segmentation (United States)

    Su, Zihua; Deng, Xiang; Chefd'hotel, Christophe; Grady, Leo; Fei, Jun; Zheng, Dong; Chen, Ning; Xu, Xiaodong


    Graph based semi-automatic tumor segmentation techniques have demonstrated great potential in efficiently measuring tumor size from CT images. Comprehensive and quantitative validation is essential to ensure the efficacy of graph based tumor segmentation techniques in clinical applications. In this paper, we present a quantitative validation study of six graph based 3D semi-automatic tumor segmentation techniques using multiple sets of expert segmentation. The six segmentation techniques are Random Walk (RW), Watershed based Random Walk (WRW), LazySnapping (LS), GraphCut (GHC), GrabCut (GBC), and GrowCut (GWC) algorithms. The validation was conducted using clinical CT data of 29 liver tumors and four sets of expert segmentation. The performance of the six algorithms was evaluated using accuracy and reproducibility. The accuracy was quantified using Normalized Probabilistic Rand Index (NPRI), which takes into account of the variation of multiple expert segmentations. The reproducibility was evaluated by the change of the NPRI from 10 different sets of user initializations. Our results from the accuracy test demonstrated that RW (0.63) showed the highest NPRI value, compared to WRW (0.61), GWC (0.60), GHC (0.58), LS (0.57), GBC (0.27). The results from the reproducibility test indicated that GBC is more sensitive to user initialization than the other five algorithms. Compared to previous tumor segmentation validation studies using one set of reference segmentation, our evaluation methods use multiple sets of expert segmentation to address the inter or intra rater variability issue in ground truth annotation, and provide quantitative assessment for comparing different segmentation algorithms.

  5. Abnormal morphology of myelin and axon pathology in murine models of multiple sclerosis. (United States)

    Bando, Yoshio; Nomura, Taichi; Bochimoto, Hiroki; Murakami, Koichi; Tanaka, Tatsuhide; Watanabe, Tsuyoshi; Yoshida, Shigetaka


    Demyelination and axonal damage are responsible for neurological deficits in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. However, the pathology of axonal damage in MS is not fully understood. In this study, histological analysis of morphological changes of axonal organelles during demyelination in murine models was investigated by scanning electron microscopy (SEM) using an osmium-maceration method. In cuprizone-induced demyelination, SEM showed typical morphology of demyelination in the corpus callosum of mouse brain. In contrast, SEM displayed variations in ultrastructural abnormalities of myelin structures and axonal organelles in spinal cord white matter of experimental autoimmune encephalomyelitis (EAE) mice, an animal model of MS. Myelin detachment and excessive myelin formation were observed as typical morphological myelin abnormalities in EAE. In addition, well-developed axoplasmic reticulum-like structures and accumulated mitochondria were observed in tortuous degenerating/degenerated axons and the length of mitochondria in axons of EAE spinal cord was shorter compared with naïve spinal cord. Immunohistochemistry also revealed dysfunction of mitochondrial fusion/fission machinery in EAE spinal cord axons. Moreover, the number of Y-shaped mitochondria was significantly increased in axons of the EAE spinal cord. Axonal morphologies in myelin basic protein-deficient shiverer mice were similar to those in EAE. However, shiverer mice had "tortuous" (S-curve shaped mitochondria) and larger mitochondria compared with wild-type and EAE mice. Lastly, analysis of human MS patient autopsied brains also demonstrated abnormal myelin structures in demyelinating lesions. These results indicate that morphological abnormalities of myelin and axonal organelles play important role on the pathogenesis of axonal injury in demyelinating diseases.

  6. Plexin A3 and turnout regulate motor axonal branch morphogenesis in zebrafish.

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    Rajiv Sainath

    Full Text Available During embryogenesis motor axons navigate to their target muscles, where individual motor axons develop complex branch morphologies. The mechanisms that control axonal branching morphogenesis have been studied intensively, yet it still remains unclear when branches begin to form or how branch locations are determined. Live cell imaging of individual zebrafish motor axons reveals that the first axonal branches are generated at the ventral extent of the myotome via bifurcation of the growth cone. Subsequent branches are generated by collateral branching restricted to their synaptic target field along the distal portion of the axon. This precisely timed and spatially restricted branching process is disrupted in turnout mutants we identified in a forward genetic screen. Molecular genetic mapping positioned the turnout mutation within a 300 kb region encompassing eight annotated genes, however sequence analysis of all eight open reading frames failed to unambiguously identify the turnout mutation. Chimeric analysis and single cell labeling reveal that turnout function is required cell non-autonomously for intraspinal motor axon guidance and peripheral branch formation. turnout mutant motor axons form the first branch on time via growth cone bifurcation, but unlike wild-type they form collateral branches precociously, when the growth cone is still navigating towards the ventral myotome. These precocious collateral branches emerge along the proximal region of the axon shaft typically devoid of branches, and they develop into stable, permanent branches. Furthermore, we find that null mutants of the guidance receptor plexin A3 display identical motor axon branching defects, and time lapse analysis reveals that precocious branch formation in turnout and plexin A3 mutants is due to increased stability of otherwise short-lived axonal protrusions. Thus, plexin A3 dependent intrinsic and turnout dependent extrinsic mechanisms suppress collateral branch

  7. RabGDI controls axonal midline crossing by regulating Robo1 surface expression

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    Philipp Melanie


    Full Text Available Abstract Background Axons navigate to their future synaptic targets with the help of choice points, intermediate targets that express axon guidance cues. Once they reach a choice point, axons need to switch their response from attraction to repulsion in order to move on with the next stage of their journey. The mechanisms underlying the change in axonal responsiveness are poorly understood. Commissural axons become sensitive to the repulsive activity of Slits when they cross the ventral midline of the CNS. Responsiveness to Slits depends on surface expression of Robo receptors. In Drosophila, Commissureless (Comm plays a crucial regulatory role in midline crossing by keeping Robo levels low on precommissural axons. Interestingly, to date no vertebrate homolog of comm has been identified. Robo3/Rig1 has been shown to control Slit sensitivity before the midline, but without affecting Robo1 surface expression. Results We had identified RabGDI, a gene linked to human mental retardation and an essential component of the vesicle fusion machinery, in a screen for differentially expressed floor-plate genes. Downregulation of RabGDI by in ovo RNAi caused commissural axons to stall in the floor plate, phenocopying the effect observed after downregulation of Robo1. Conversely, premature expression of RabGDI prevented commissural axons from entering the floor plate. Furthermore, RabGDI triggered Robo1 surface expression in cultured commissural neurons. Taken together, our results identify RabGDI as a component of the switching mechanism that is required for commissural axons to change their response from attraction to repulsion at the intermediate target. Conclusion RabGDI takes over the functional role of fly Comm by regulating the surface expression of Robo1 on commissural axons in vertebrates. This in turn allows commissural axons to switch from attraction to repulsion at the midline of the spinal cord.

  8. A possible role for integrin signaling in diffuse axonal injury.

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    Matthew A Hemphill

    Full Text Available Over the past decade, investigators have attempted to establish the pathophysiological mechanisms by which non-penetrating injuries damage the brain. Several studies have implicated either membrane poration or ion channel dysfunction pursuant to neuronal cell death as the primary mechanism of injury. We hypothesized that traumatic stimulation of integrins may be an important etiological contributor to mild Traumatic Brain Injury. In order to study the effects of forces at the cellular level, we utilized two hierarchical, in vitro systems to mimic traumatic injury to rat cortical neurons: a high velocity stretcher and a magnetic tweezer system. In one system, we controlled focal adhesion formation in neurons cultured on a stretchable substrate loaded with an abrupt, one dimensional strain. With the second system, we used magnetic tweezers to directly simulate the abrupt injury forces endured by a focal adhesion on the neurite. Both systems revealed variations in the rate and nature of neuronal injury as a function of focal adhesion density and direct integrin stimulation without membrane poration. Pharmacological inhibition of calpains did not mitigate the injury yet the inhibition of Rho-kinase immediately after injury reduced axonal injury. These data suggest that integrin-mediated activation of Rho may be a contributor to the diffuse axonal injury reported in mild Traumatic Brain Injury.

  9. An analysis of conductance changes in squid axon. (United States)



    The membrane of the squid axon is considered on the basis of a pore model in which the distribution of the pore sizes strongly favors K(+) transfer when there is no potential. Electrical asymmetry causes non-penetrating ions on the membrane capacitor to exert a mechanical force on both membrane surfaces and this force results in a deformation of the membrane pore system such that it assumes a distribution of sizes favoring the ions exerting mechanical force. The ions involved appear to be Ca(++) on the outside of the membrane and isethionate(-), (i(-)) on the inside; as Ca(++) is equivalent in size to Na(+), the charged membrane is potentially able to transfer Na(+), when the ions deforming the membrane pore distribution are removed. A depolarization of the membrane leads to an opening of pores that will allow Na(+) penetration and a release of the membrane from deformation. The pores revert to the zero-potential pore size distribution hence the Na permeability change is a transient. Calculation shows that the potassium conductance vs. displacement of membrane potential curve for the squid axon and the "inactivation" function, h, can be obtained directly from the assumed membrane distortion without the introduction of arbitrary parameters. The sodium conductance, because it is a transient, requires assumptions about the time constants with which ions unblock pores at the outside and the inside of the membrane.

  10. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M


    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

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

    Institute of Scientific and Technical Information of China (English)

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


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

  12. Tau phosphorylation affects its axonal transport and degradation (United States)

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


    Phosphorylated forms of microtubule-associated protein tau accumulate in neurofibrillary tangles in Alzheimer's disease. To investigate the effects of specific phosphorylated tau residues on its function, wild type or phosphomutant tau was expressed in cells. Elevated tau phosphorylation decreased its microtubule binding and bundling, and increased the number of motile tau particles, without affecting axonal transport kinetics. In contrast, reducing tau phosphorylation enhanced the amount of tau bound to microtubules and inhibited axonal transport of tau. To determine whether differential tau clearance is responsible for the increase in phosphomimic tau, we inhibited autophagy in neurons which resulted in a 3-fold accumulation of phosphomimic tau compared with wild type tau, and endogenous tau was unaffected. In autophagy-deficient mouse embryonic fibroblasts, but not in neurons, proteasomal degradation of phosphomutant tau was also reduced compared with wild type tau. Therefore, autophagic and proteasomal pathways are involved in tau degradation, with autophagy appearing to be the primary route for clearing phosphorylated tau in neurons. Defective autophagy might contribute to the accumulaton of tau in neurodegenerative diseases. PMID:23601672

  13. Selective optogenetic stimulation of cholinergic axons in neocortex. (United States)

    Kalmbach, Abigail; Hedrick, Tristan; Waters, Jack


    Acetylcholine profoundly affects neocortical function, being involved in arousal, attention, learning, memory, sensory and motor function, and plasticity. The majority of cholinergic afferents to neocortex are from neurons in nucleus basalis. Nucleus basalis also contains projecting neurons that release other transmitters, including GABA and possibly glutamate. Hence, electrical stimulation of nucleus basalis evokes the release of a mixture of neurotransmitters in neocortex, and this lack of selectivity has impeded research on cholinergic signaling in neocortex. We describe a method for the selective stimulation of cholinergic axons in neocortex. We used the Cre-lox system and a viral vector to express the light-activated protein channelrhodopsin-2 in cholinergic neurons in nucleus basalis and their axons in neocortex. Labeled neurons depolarized on illumination with blue light but were otherwise unchanged. In anesthetized mice, illumination of neocortex desynchronized the local field potential, indicating that light evoked release of ACh. This novel technique will enable many new studies of the cellular, network, and behavioral physiology of ACh in neocortex.

  14. Neuronal development and axon growth are altered by glyphosate through a WNT non-canonical signaling pathway. (United States)

    Coullery, Romina P; Ferrari, María E; Rosso, Silvana B


    The growth and morphological differentiation of neurons are critical events in the establishment of proper neuronal connectivity and functioning. The developing nervous system is highly susceptible to damage caused by exposure to environmental contaminants. Glyphosate-containing herbicides are the most used agrochemicals in the world, particularly on genetically modified plants. Previous studies have demonstrated that glyphosate induces neurotoxicity in mammals. Therefore, its action mechanism on the nervous system needs to be determined. In this study, we report about impaired neuronal development caused by glyphosate exposure. Particularly, we observed that the initial axonal differentiation and growth of cultured neurons is affected by glyphosate since most treated cells remained undifferentiated after 1 day in culture. Although they polarized at 2 days in vitro, they elicited shorter and unbranched axons and they also developed less complex dendritic arbors compared to controls. To go further, we attempted to identify the cellular mechanism by which glyphosate affected neuronal morphology. Biochemical approaches revealed that glyphosate led to a decrease in Wnt5a level, a key factor for the initial neurite development and maturation, as well as inducing a down-regulation of CaMKII activity. This data suggests that the morphological defects would likely be a consequence of the decrease in both Wnt5a expression and CaMKII activity induced by glyphosate. Additionally, these changes might be reflected in a subsequent neuronal dysfunction. Therefore, our findings highlight the importance of establishing rigorous control on the use of glyphosate-based herbicides in order to protect mammals' health.

  15. SAR Image Segmentation using Vector Quantization Technique on Entropy Images

    CERN Document Server

    Kekre, H B; Sarode, Tanuja K


    The development and application of various remote sensing platforms result in the production of huge amounts of satellite image data. Therefore, there is an increasing need for effective querying and browsing in these image databases. In order to take advantage and make good use of satellite images data, we must be able to extract meaningful information from the imagery. Hence we proposed a new algorithm for SAR image segmentation. In this paper we propose segmentation using vector quantization technique on entropy image. Initially, we obtain entropy image and in second step we use Kekre's Fast Codebook Generation (KFCG) algorithm for segmentation of the entropy image. Thereafter, a codebook of size 128 was generated for the Entropy image. These code vectors were further clustered in 8 clusters using same KFCG algorithm and converted into 8 images. These 8 images were displayed as a result. This approach does not lead to over segmentation or under segmentation. We compared these results with well known Gray L...

  16. Shank3 is localized in axons and presynaptic specializations of developing hippocampal neurons and involved in the modulation of NMDA receptor levels at axon terminals. (United States)

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


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

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

    DEFF Research Database (Denmark)

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


    death; the markers of different DRG cell populations and cutaneous innervation were unchanged. These anatomical changes were reflected in a slowing of conduction velocity at the lower end of the A-fiber conduction velocity range and a new population of more rapidly conducting C-fibers that are likely...... cells required for normal sensory function. Sensory neuronal survival and axonal maintenance, however, are not dependent on axon-derived neuregulin-1 signaling in adulthood Udgivelsesdato: 2009/6/17...

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

    Directory of Open Access Journals (Sweden)

    Giorgi Kharebava


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

  19. Axonal transport rate decreased at the onset of optic neuritis in EAE mice. (United States)

    Lin, Tsen-Hsuan; Kim, Joong Hee; Perez-Torres, Carlos; Chiang, Chia-Wen; Trinkaus, Kathryn; Cross, Anne H; Song, Sheng-Kwei


    Optic neuritis is frequently the first symptom of multiple sclerosis (MS), an inflammatory demyelinating neurodegenerative disease. Impaired axonal transport has been considered as an early event of neurodegenerative diseases. However, few studies have assessed the integrity of axonal transport in MS or its animal models. We hypothesize that axonal transport impairment occurs at the onset of optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice. In this study, we employed manganese-enhanced MRI (MEMRI) to assess axonal transport in optic nerves in EAE mice at the onset of optic neuritis. Axonal transport was assessed as (a) optic nerve Mn(2+) accumulation rate (in % signal change/h) by measuring the rate of increased total optic nerve signal enhancement, and (b) Mn(2+) transport rate (in mm/h) by measuring the rate of change in optic nerve length enhanced by Mn(2+). Compared to sham-treated healthy mice, Mn(2+) accumulation rate was significantly decreased by 19% and 38% for EAE mice with moderate and severe optic neuritis, respectively. The axonal transport rate of Mn(2+) was significantly decreased by 43% and 65% for EAE mice with moderate and severe optic neuritis, respectively. The degree of axonal transport deficit correlated with the extent of impaired visual function and diminished microtubule-associated tubulins, as well as the severity of inflammation, demyelination, and axonal injury at the onset of optic neuritis.

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

    Institute of Scientific and Technical Information of China (English)

    Peter W. Baas; Andrew J. Matamoros


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

  1. Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF. (United States)

    Pun, San; Santos, Alexandre Ferrão; Saxena, Smita; Xu, Lan; Caroni, Pico


    Neurodegenerative diseases can have long preclinical phases and insidious progression patterns, but the mechanisms of disease progression are poorly understood. Because quantitative accounts of neuronal circuitry affected by disease have been lacking, it has remained unclear whether disease progression reflects processes of stochastic loss or temporally defined selective vulnerabilities of distinct synapses or axons. Here we derive a quantitative topographic map of muscle innervation in the hindlimb. We show that in two mouse models of motoneuron disease (G93A SOD1 and G85R SOD1), axons of fast-fatiguable motoneurons are affected synchronously, long before symptoms appear. Fast-fatigue-resistant motoneuron axons are affected at symptom-onset, whereas axons of slow motoneurons are resistant. Axonal vulnerability leads to synaptic vesicle stalling and accumulation of BC12a1-a, an anti-apoptotic protein. It is alleviated by ciliary neurotrophic factor and triggers proteasome-dependent pruning of peripheral axon branches. Thus, motoneuron disease involves predictable, selective vulnerability patterns by physiological subtypes of axons, episodes of abrupt pruning in the target region and compensation by resistant axons.

  2. Bimodal control of dendritic and axonal growth by the dual leucine zipper kinase pathway.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Knowledge of the molecular and genetic mechanisms underlying the separation of dendritic and axonal compartments is not only crucial for understanding the assembly of neural circuits, but also for developing strategies to correct defective dendrites or axons in diseases with subcellular precision. Previous studies have uncovered regulators dedicated to either dendritic or axonal growth. Here we investigate a novel regulatory mechanism that differentially directs dendritic and axonal growth within the same neuron in vivo. We find that the dual leucine zipper kinase (DLK signaling pathway in Drosophila, which consists of Highwire and Wallenda and controls axonal growth, regeneration, and degeneration, is also involved in dendritic growth in vivo. Highwire, an evolutionarily conserved E3 ubiquitin ligase, restrains axonal growth but acts as a positive regulator for dendritic growth in class IV dendritic arborization neurons in the larva. While both the axonal and dendritic functions of highwire require the DLK kinase Wallenda, these two functions diverge through two downstream transcription factors, Fos and Knot, which mediate the axonal and dendritic regulation, respectively. This study not only reveals a previously unknown function of the conserved DLK pathway in controlling dendrite development, but also provides a novel paradigm for understanding how neuronal compartmentalization and the diversity of neuronal morphology are achieved.

  3. Selective control of small versus large diameter axons using infrared laser light (Conference Presentation) (United States)

    Lothet, Emilie H.; Shaw, Kendrick M.; Horn, Charles C.; Lu, Hui; Wang, Yves T.; Jansen, E. Duco; Chiel, Hillel J.; Jenkins, Michael W.


    Sensory information is conveyed to the central nervous system via small diameter unmyelinated fibers. In general, smaller diameter axons have slower conduction velocities. Selective control of such fibers could create new clinical treatments for chronic pain, nausea in response to chemo-therapeutic agents, or hypertension. Electrical stimulation can control axonal activity, but induced axonal current is proportional to cross-sectional area, so that large diameter fibers are affected first. Physiologically, however, synaptic inputs generally affect small diameter fibers before large diameter fibers (the size principle). A more physiological modality that first affected small diameter fibers could have fewer side effects (e.g., not recruiting motor axons). A novel mathematical analysis of the cable equation demonstrates that the minimum length along the axon for inducing block scales with the square root of axon diameter. This implies that the minimum length along an axon for inhibition will scale as the square root of axon diameter, so that lower radiant exposures of infrared light will selectively affect small diameter, slower conducting fibers before those of large diameter. This prediction was tested in identified neurons from the marine mollusk Aplysia californica. Radiant exposure to block a neuron with a slower conduction velocity (B43) was consistently lower than that needed to block a faster conduction velocity neuron (B3). Furthermore, in the vagus nerve of the musk shrew, lower radiant exposure blocked slow conducting fibers before blocking faster conducting fibers. Infrared light can selectively control smaller diameter fibers, suggesting many novel clinical treatments.

  4. The central role of mitochondria in axonal degeneration in multiple sclerosis. (United States)

    Campbell, Graham R; Worrall, Joseph T; Mahad, Don J


    Neurodegeneration in multiple sclerosis (MS) is related to inflammation and demyelination. In acute MS lesions and experimental autoimmune encephalomyelitis focal immune attacks damage axons by injuring axonal mitochondria. In progressive MS, however, axonal damage occurs in chronically demyelinated regions, myelinated regions and also at the active edge of slowly expanding chronic lesions. How axonal energy failure occurs in progressive MS is incompletely understood. Recent studies show that oligodendrocytes supply lactate to myelinated axons as a metabolic substrate for mitochondria to generate ATP, a process which will be altered upon demyelination. In addition, a number of studies have identified mitochondrial abnormalities within neuronal cell bodies in progressive MS, leading to a deficiency of mitochondrial respiratory chain complexes or enzymes. Here, we summarise the mitochondrial abnormalities evident within neurons and discuss how these grey matter mitochondrial abnormalities may increase the vulnerability of axons to degeneration in progressive MS. Although neuronal mitochondrial abnormalities will culminate in axonal degeneration, understanding the different contributions of mitochondria to the degeneration of myelinated and demyelinated axons is an important step towards identifying potential therapeutic targets for progressive MS.

  5. Axonal pathfinding mechanisms at the cortical midline and in the development of the corpus callosum

    Directory of Open Access Journals (Sweden)

    Richards L.J.


    Full Text Available The corpus callosum is a large fiber tract that connects neurons in the right and left cerebral hemispheres. Agenesis of the corpus callosum (ACC is associated with a large number of human syndromes but little is known about why ACC occurs. In most cases of ACC, callosal axons are able to grow toward the midline but are unable to cross it, continuing to grow into large swirls of axons known as Probst bundles. This phenotype suggests that in some cases ACC may be due to defects in axonal guidance at the midline. General guidance mechanisms that influence the development of axons include chemoattraction and chemorepulsion, presented by either membrane-bound or diffusible molecules. These molecules are not only expressed by the final target but by intermediate targets along the pathway, and by pioneering axons that act as guides for later arriving axons. Midline glial populations are important intermediate targets for commissural axons in the spinal cord and brain, including the corpus callosum. The role of midline glial populations and pioneering axons in the formation of the corpus callosum are discussed. Finally the differential guidance of the ipsilaterally projecting perforating pathway and the contralaterally projecting corpus callosum is addressed. Development of the corpus callosum involves the coordination of a number of different guidance mechanisms and the probable involvement of a large number of molecules.

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

    Directory of Open Access Journals (Sweden)

    Srinivasu Kallakuri


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

  7. Polarized targeting of L1-CAM regulates axonal and dendritic bundling in vitro. (United States)

    Barry, Joshua; Gu, Yuanzheng; Gu, Chen


    Proper axonal and dendritic bundling is essential for the establishment of neuronal connections and the synchronization of synaptic inputs, respectively. Cell adhesion molecules of the L1-CAM (L1-cell adhesion molecule) family regulate axon guidance and fasciculation, neuron migration, dendrite morphology, and synaptic plasticity. It remains unclear how these molecules play so many different roles. Here we show that polarized axon-dendrite targeting of an avian L1-CAM protein, NgCAM (neuron-glia cell adhesion molecule), can regulate the switch of bundling of the two major compartments of rat hippocampal neurons. Using a new in-vitro model for studying neurite-neurite interactions, we found that expressed axonal NgCAM induced robust axonal bundling via the trans-homophilic interaction of immunoglobulin domains. Interestingly, dendritic bundling was induced by the dendritic targeting of NgCAM, caused by either deleting its fibronectin repeats or blocking activities of protein kinases. Consistent with the NgCAM results, expression of mouse L1-CAM also induced axonal bundling and blocking kinase activities disrupted its axonal targeting. Furthermore, the trans-homophilic interaction stabilized the bundle formation, probably through recruiting NgCAM proteins to contact sites and promoting guided axon outgrowth. Taken together, our results suggest that precise localization of L1-CAM is important for establishing proper cell-cell contacts in neural circuits.

  8. Integration of shallow gradients of Shh and Netrin-1 guides commissural axons. (United States)

    Sloan, Tyler F W; Qasaimeh, Mohammad A; Juncker, David; Yam, Patricia T; Charron, Frédéric


    During nervous system development, gradients of Sonic Hedgehog (Shh) and Netrin-1 attract growth cones of commissural axons toward the floor plate of the embryonic spinal cord. Mice defective for either Shh or Netrin-1 signaling have commissural axon guidance defects, suggesting that both Shh and Netrin-1 are required for correct axon guidance. However, how Shh and Netrin-1 collaborate to guide axons is not known. We first quantified the steepness of the Shh gradient in the spinal cord and found that it is mostly very shallow. We then developed an in vitro microfluidic guidance assay to simulate these shallow gradients. We found that axons of dissociated commissural neurons respond to steep but not shallow gradients of Shh or Netrin-1. However, when we presented axons with combined Shh and Netrin-1 gradients, they had heightened sensitivity to the guidance cues, turning in response to shallower gradients that were unable to guide axons when only one cue was present. Furthermore, these shallow gradients polarized growth cone Src-family kinase (SFK) activity only when Shh and Netrin-1 were combined, indicating that SFKs can integrate the two guidance cues. Together, our results indicate that Shh and Netrin-1 synergize to enable growth cones to sense shallow gradients in regions of the spinal cord where the steepness of a single guidance cue is insufficient to guide axons, and we identify a novel type of synergy that occurs when the steepness (and not the concentration) of a guidance cue is limiting.

  9. In vivo Imaging of Mitochondrial Transport in Single-Axon Regeneration of Zebrafish Mauthner Cells (United States)

    Xu, Yang; Chen, Min; Hu, Bingbing; Huang, Rongchen; Hu, Bing


    Mitochondrial transport is essential for neuronal function, but the evidence of connections between mitochondrial transport and axon regeneration in the central nervous system (CNS) of living vertebrates remains limited. Here, we developed a novel model to explore mitochondrial transport in a single Mauthner axon (M axon) of zebrafish with non-invasive in vivo imaging. To confirm the feasibility of using this model, we treated labeled zebrafish with nocodazole and demonstrated that it could disrupt mitochondrial transport. We also used two-photon laser axotomy to precisely axotomize M axons and simultaneously recorded their regeneration and the process of mitochondrial transport in living zebrafish larvae. The findings showed that the injured axons with stronger regenerative capability maintain greater mitochondrial motility. Furthermore, to stimulate axon regeneration, treatment with dibutyryl cyclic adenosine monophosphate (db-cAMP) could also augment mitochondrial motility. Taken together, our results provide new evidence that mitochondrial motility is positively correlated with axon regeneration in the living vertebrate CNS. This promising model will be useful for further studies on the interaction between axon regeneration and mitochondrial dynamics, using various genetic and pharmacological techniques. PMID:28174522

  10. Quantifying visual pathway axonal and myelin loss in multiple sclerosis and neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    Praveena Manogaran


    Conclusions: The relationship between reductions in OCT measures of neuro-axonal health in the anterior visual pathway and MRI-based measures of myelin health in the posterior visual pathway suggests that these measures may be linked through bidirectional axonal degeneration.

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

    Directory of Open Access Journals (Sweden)

    Peter W Baas


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

  12. Correlations between Cognitive Impairments and Employment Status in Patients with Diffuse Axonal Injury (United States)

    HIROTA, Shin; INAJI, Motoki; NARIAI, Tadashi; HARA, Mutsuya; TAMAKI, Masashi; MAEHARA, Taketoshi; TOMITA, Hiroki; TONE, Osamu


    Patients with diffuse axonal injury (DAI) may initially present with prominent physical impairments, but their cognitive dysfunctions are more persistent and are attributable to later unemployment. In this study, we analyzed how the findings of early and delayed neuropsychological assessments correlated with employment outcome of patients with DAI. A total of 56 patients with DAI without motor or visual dysfunction were included in this study. The neuropsychological battery consisted of the Wechsler Adult Intelligent Scale - Revised (WAIS-R), Wechsler Memory Scale - Revised (WMS-R), Trail Making Test (TMT), Wisconsin Card Sorting Test (WCST), and Word Fluency Test (WFT). This battery of tests was administered twice in early stage after injury and in later stage. The results of all of the neuropsychological tests improved significantly (P <0.001) between the early and later assessments. All scores other than TMT part A and B improved to the normal range (Z-score ≥ 2). The patient characteristics (age, gender, initial Glasgow Coma Scale, and duration of posttraumatic amnesia) had no relationship to the outcome. The results of TMT part B, however, were significantly correlated with employment outcome in both the early and later assessments (P = 0.01, 0.04). Given that TMT evaluates visual attention, we surmise that a lack of attention may be the core symptom of the cognitive deficit and cause the re-employment failure in patients with DAI. TMT part B in both early and later assessments has the potential to accurately predict chronic functional outcome. PMID:28003570

  13. Explaining pathological changes in axonal excitability through dynamical analysis of conductance-based models (United States)

    Coggan, Jay S.; Ocker, Gabriel K.; Sejnowski, Terrence J.; Prescott, Steven A.


    Neurons rely on action potentials, or spikes, to relay information. Pathological changes in spike generation likely contribute to certain enigmatic features of neurological disease, like paroxysmal attacks of pain and muscle spasm. Paroxysmal symptoms are characterized by abrupt onset and short duration, and are associated with abnormal spiking although the exact pathophysiology remains unclear. To help decipher the biophysical basis for 'paroxysmal' spiking, we replicated afterdischarge (i.e. continued spiking after a brief stimulus) in a minimal conductance-based axon model. We then applied nonlinear dynamical analysis to explain the dynamical basis for initiation and termination of afterdischarge. A perturbation could abruptly switch the system between two (quasi-)stable attractor states: rest and repetitive spiking. This bistability was a consequence of slow positive feedback mediated by persistent inward current. Initiation of afterdischarge was explained by activation of the persistent inward current forcing the system to cross a saddle point that separates the basins of attraction associated with each attractor. Termination of afterdischarge was explained by the attractor associated with repetitive spiking being destroyed. This occurred when ultra-slow negative feedback, such as intracellular sodium accumulation, caused the saddle point and stable limit cycle to collide; in that regard, the active attractor is not truly stable when the slowest dynamics are taken into account. The model also explains other features of paroxysmal symptoms, including temporal summation and refractoriness.

  14. Segmentation and Tracking of Neural Stem Cell

    Institute of Scientific and Technical Information of China (English)

    TANG Chun-ming; ZHAO Chun-hui; Ewert Bengtsson


    In order to understand the development of stem cells into specialized mature cells it is necessary to study the growth of cells in culture. For this purpose it is very useful to have an efficient computerized cell tracking system. In this paper a prototype system for tracking neural stem cells in a sequence of images is described. In order to get reliable tracking results it is important to have good and robust segmentation of the cells. To achieve this we have implemented three levels of segmentation. The primary level, applied to all frames, is based on fuzzy threshold and watershed segmentation of a fuzzy gray weighted distance transformed image.The second level, applied to difficult frames where the first algorithm seems to have failed, is based on a fast geometric active contour model based on the level set algorithm. Finally, the automatic segmentation result on the crucial first frame can be interactively inspected and corrected. Visual inspection and correction can also be applied to other frames but this is generally not needed. For the tracking all cells are classified into inactive, active, dividing and clustered cells. Different algorithms are used to deal with the different cell categories. A special backtracking step is used to automatically correct for some common errors that appear in the initial forward tracking process.

  15. A descriptive study to characterize segmental vitiligo

    Directory of Open Access Journals (Sweden)

    Binod K Khaitan


    Full Text Available Background: Segmental vitiligo is a small but unique subset of vitiligo requiring due importance due to its lack of response to medical treatment but excellent response to surgical treatment. Characterization of the pattern of segmental vitiligo will also help to understand the pathogenesis of the disease. Aim: To characterize clinically the features of segmental vitiligo, a cross-sectional clinical study at dermatology outpatient department at AIIMS was carried out. Methods: Consecutive 188 patients were evaluated to characterize the clinical features of segmental vitiligo by detailed history, clinical examination, and photography. Frequency of each clinical feature was calculated. Results: Certain features such as early onset, initial progression of disease followed by stability, blaschkoid pattern, irregular margins, leucotrichia within and beyond the vitiligo lesion, and islands of pigmented macules within the vitiligo lesion were found to be characteristic of the disease. Conclusions: A combination of various features such as early onset of disease, blaschkoid pattern, irregular margins, leucotrichia, and islands of pigmented macules within the vitiligo lesion are helpful in diagnosis of the disease.

  16. A toolbox for multiple sclerosis lesion segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Roura, Eloy; Oliver, Arnau; Valverde, Sergi; Llado, Xavier [University of Girona, Computer Vision and Robotics Group, Girona (Spain); Cabezas, Mariano; Pareto, Deborah; Rovira, Alex [Vall d' Hebron University Hospital, Magnetic Resonance Unit, Dept. of Radiology, Barcelona (Spain); Vilanova, Joan C. [Girona Magnetic Resonance Center, Girona (Spain); Ramio-Torrenta, Lluis [Dr. Josep Trueta University Hospital, Institut d' Investigacio Biomedica de Girona, Multiple Sclerosis and Neuroimmunology Unit, Girona (Spain)


    Lesion segmentation plays an important role in the diagnosis and follow-up of multiple sclerosis (MS). This task is very time-consuming and subject to intra- and inter-rater variability. In this paper, we present a new tool for automated MS lesion segmentation using T1w and fluid-attenuated inversion recovery (FLAIR) images. Our approach is based on two main steps, initial brain tissue segmentation according to the gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) performed in T1w images, followed by a second step where the lesions are segmented as outliers to the normal apparent GM brain tissue on the FLAIR image. The tool has been validated using data from more than 100 MS patients acquired with different scanners and at different magnetic field strengths. Quantitative evaluation provided a better performance in terms of precision while maintaining similar results on sensitivity and Dice similarity measures compared with those of other approaches. Our tool is implemented as a publicly available SPM8/12 extension that can be used by both the medical and research communities. (orig.)

  17. The course of axons through the retina and optic nerve head. (United States)

    Radius, R L; Anderson, D R


    By identifying degenerating axons in tissue specimens from 22 primate eyes, it was possible to demonstrate the normal course of axon fibers. Nerve fiber bundles from a group of retinal ganglion cells travel together with little tendency to disperse laterally. In addition, axons are stratified such that processes from more central ganglion cells are successfully added to the inner strata of the retinal nerve fiber layer. Within and behind the lamina cribrosa, areas of degeneration following retinal photocoagulation were well circumscribed and confined to a group of adjacent axon bundles. This degree of retinotopic organization of axons within the nerve head and retinal fiber layer is believed to be consistent with the premise that isolated lesions within the lamina cribrosa could cause well-organized paracentral scotomas such as those characteristic of early glaucoma.

  18. BmRobo2/3 is required for axon guidance in the silkworm Bombyx mori. (United States)

    Li, Xiao-Tong; Yu, Qi; Zhou, Qi-Sheng; Zhao, Xiao; Liu, Zhao-Yang; Cui, Wei-Zheng; Liu, Qing-Xin


    Axon guidance is critical for proper wiring of the nervous system. During the neural development, the axon guidance molecules play a key role and direct axons to choose the correct way to reach the target. Robo, as the receptor of axon guidance molecule Slit, is evolutionarily conserved from planarians to humans. However, the function of Robo in the silkworm, Bombyx mori, remained unknown. In this study, we cloned robo2/3 from B. mori (Bmrobo2/3), a homologue of robo2/3 in Tribolium castaneum. Moreover, BmRobo2/3 was localized in the neuropil, and RNAi-mediated knockdown of Bmrobo2/3 resulted in the longitudinal connectives forming closer to the midline. These data demonstrate that BmRobo2/3 is required for axon guidance in the silkworm.

  19. Electromagnetic induction between axons and their schwann cell myelin-protein sheaths. (United States)

    Goodman, G; Bercovich, D


    Two concepts have long dominated vertebrate nerve electrophysiology: (a) Schwann cell-formed myelin sheaths separated by minute non-myelinated nodal gaps and spiraling around axons of peripheral motor nerves reduce current leakage during propagation of trains of axon action potentials; (b) "jumping" by action potentials between successive nodes greatly increases signal conduction velocity. Long-held and more recent assumptions and issues underlying those concepts have been obscured by research emphasis on axon-sheath biochemical symbiosis and nerve regeneration. We hypothesize: mutual electromagnetic induction in the axon-glial sheath association, is fundamental in signal conduction in peripheral and central myelinated axons, explains the g-ratio and is relevant to animal navigation.

  20. The autophagy gene Wdr45/Wipi4 regulates learning and memory function and axonal homeostasis. (United States)

    Zhao, Yan G; Sun, Le; Miao, Guangyan; Ji, Cuicui; Zhao, Hongyu; Sun, Huayu; Miao, Lin; Yoshii, Saori R; Mizushima, Noboru; Wang, Xiaoqun; Zhang, Hong


    WDR45/WIPI4, encoding a WD40 repeat-containing PtdIns(3)P binding protein, is essential for the basal autophagy pathway. Mutations in WDR45 cause the neurodegenerative disease β-propeller protein-associated neurodegeneration (BPAN), a subtype of NBIA. We generated CNS-specific Wdr45 knockout mice, which exhibit poor motor coordination, greatly impaired learning and memory, and extensive axon swelling with numerous axon spheroids. Autophagic flux is defective and SQSTM1 (sequestosome-1)/p62 and ubiquitin-positive protein aggregates accumulate in neurons and swollen axons. Nes-Wdr45(fl/Y) mice recapitulate some hallmarks of BPAN, including cognitive impairment and defective axonal homeostasis, providing a model for revealing the disease pathogenesis of BPAN and also for investigating the possible role of autophagy in axon maintenance.

  1. Exposure to 1-bromopropane causes degeneration of noradrenergic axons in the rat brain. (United States)

    Mohideen, Sahabudeen Sheik; Ichihara, Gaku; Ichihara, Sahoko; Nakamura, Shoji


    1-Bromopropane (1-BP) has been used as an alternative to ozone-depleting solvents. Previous studies showed that 1-BP is neurotoxic in animals and humans. In humans, exposure to 1-BP caused various neurological and neurobehavioral symptoms or signs including depressive or irritated mood. However, the neurobiological changes underlying the depressive symptoms induced by 1-BP remain to be determined. The depressive symptoms are thought to be associated with degeneration of axons containing noradrenaline and serotonin. Based on this hypothesis, the present study examined the effects of repeated exposure to 1-BP on serotonergic and noradrenergic axons. Exposure to 1-BP induced dose-dependent decreases in the density of noradrenergic axons in the rat prefrontal cortex, but no apparent change in the density of serotonergic axons. The results suggest that depressive symptoms in workers exposed to 1-BP are due, at least in part, to the degeneration of noradrenergic axons in the brain.

  2. PACSIN1, a Tau-interacting protein, regulates axonal elongation and branching by facilitating microtubule instability. (United States)

    Liu, Yingying; Lv, Kaosheng; Li, Zenglong; Yu, Albert C H; Chen, Jianguo; Teng, Junlin


    Tau is a major member of the neuronal microtubule-associated proteins. It promotes tubulin assembly and stabilizes axonal microtubules. Previous studies have demonstrated that Tau forms cross-bridges between microtubules, with some particles located on cross-bridges, suggesting that some proteins interact with Tau and might be involved in regulating Tau-related microtubule dynamics. This study reports that PACSIN1 interacts with Tau in axon. PACSIN1 blockade results in impaired axonal elongation and a higher number of primary axonal branches in mouse dorsal root ganglia neurons, which is induced by increasing the binding ability of Tau to microtubules. In PACSIN1-blocked dorsal root ganglia neurons, a greater amount of Tau is inclined to accumulate in the central domain of growth cones, and it promotes the stability of the microtubule network. Taken together, these results suggest that PACSIN1 is an important Tau binding partner in regulating microtubule dynamics and forming axonal plasticity.

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

    Directory of Open Access Journals (Sweden)

    María Alejandra eLopez-Verrilli


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

  4. Noncooperative Iris Segmentation

    Directory of Open Access Journals (Sweden)

    Elsayed Mostafa


    Full Text Available In noncooperative iris recognition one should deal with uncontrolled behavior of the subject as well as uncontrolled lighting conditions. That means eyelids and eyelashes occlusion, non uniform intensities, reflections, imperfect focus, and orientation among the others are to be considered. To cope with this situation a noncooperative iris segmentation algorithm based on numerically stable direct least squares fitting of ellipses model and modified Chan-Vese model (local binary fitting energy with variational level set formulation is to be proposed. The proposed algorithm is tested using CASIA-IrisV3.

  5. Signs of segmentation?

    DEFF Research Database (Denmark)

    Ilsøe, Anna


    This article addresses the contribution of decentralized collective bargaining to the development of different forms of flexicurity for different groups of employees on the Danish labour market. Based on five case studies of company-level bargaining on flexible working hours in Danish industry...... the text of the agreements. On the other hand, less flexible employees often face difficulties in meeting the demands of the agreements and may ultimately be forced to leave the company and rely on unemployment benefits and active labour market policies. In a flexicurity perspective, this development seems...... to imply a segmentation of the Danish workforce regarding hard and soft versions of flexicurity....

  6. The LOFT Ground Segment

    DEFF Research Database (Denmark)

    Bozzo, E.; Antonelli, A.; Argan, A.;


    targets per orbit (~90 minutes), providing roughly ~80 GB of proprietary data per day (the proprietary period will be 12 months). The WFM continuously monitors about 1/3 of the sky at a time and provides data for about ~100 sources a day, resulting in a total of ~20 GB of additional telemetry. The LOFT...... we summarize the planned organization of the LOFT ground segment (GS), as established in the mission Yellow Book 1 . We describe the expected GS contributions from ESA and the LOFT consortium. A review is provided of the planned LOFT data products and the details of the data flow, archiving...

  7. A new level set model for cell image segmentation (United States)

    Ma, Jing-Feng; Hou, Kai; Bao, Shang-Lian; Chen, Chun


    In this paper we first determine three phases of cell images: background, cytoplasm and nucleolus according to the general physical characteristics of cell images, and then develop a variational model, based on these characteristics, to segment nucleolus and cytoplasm from their relatively complicated backgrounds. In the meantime, the preprocessing obtained information of cell images using the OTSU algorithm is used to initialize the level set function in the model, which can speed up the segmentation and present satisfactory results in cell image processing.

  8. A new level set model for cell image segmentation

    Institute of Scientific and Technical Information of China (English)

    Ma Jing-Feng; Hou Kai; Bao Shang-Lian; Chen Chun


    In this paper we first determine three phases of cell images: background, cytoplasm and nucleolus according to the general physical characteristics of cell images, and then develop a variational model, based on these characteristics, to segment nucleolus and cytoplasm from their relatively complicated backgrounds. In the meantime, the preprocessing obtained information of cell images using the OTSU algorithm is used to initialize the level set function in the model, which can speed up the segmentation and present satisfactory results in cell image processing.

  9. Easy-interactive and quick psoriasis lesion segmentation (United States)

    Ma, Guoli; He, Bei; Yang, Wenming; Shu, Chang


    This paper proposes an interactive psoriasis lesion segmentation algorithm based on Gaussian Mixture Model (GMM). Psoriasis is an incurable skin disease and affects large population in the world. PASI (Psoriasis Area and Severity Index) is the gold standard utilized by dermatologists to monitor the severity of psoriasis. Computer aid methods of calculating PASI are more objective and accurate than human visual assessment. Psoriasis lesion segmentation is the basis of the whole calculating. This segmentation is different from the common foreground/background segmentation problems. Our algorithm is inspired by GrabCut and consists of three main stages. First, skin area is extracted from the background scene by transforming the RGB values into the YCbCr color space. Second, a rough segmentation of normal skin and psoriasis lesion is given. This is an initial segmentation given by thresholding a single gaussian model and the thresholds are adjustable, which enables user interaction. Third, two GMMs, one for the initial normal skin and one for psoriasis lesion, are built to refine the segmentation. Experimental results demonstrate the effectiveness of the proposed algorithm.

  10. Sonic Hedgehog Guides Axons via Zipcode Binding Protein 1-Mediated Local Translation. (United States)

    Lepelletier, Léa; Langlois, Sébastien D; Kent, Christopher B; Welshhans, Kristy; Morin, Steves; Bassell, Gary J; Yam, Patricia T; Charron, Frédéric


    Sonic hedgehog (Shh) attracts spinal cord commissural axons toward the floorplate. How Shh elicits changes in the growth cone cytoskeleton that drive growth cone turning is unknown. We find that the turning of rat commissural axons up a Shh gradient requires protein synthesis. In particular, Shh stimulation increases β-actin protein at the growth cone even when the cell bodies have been removed. Therefore, Shh induces the local translation of β-actin at the growth cone. We hypothesized that this requires zipcode binding protein 1 (ZBP1), an mRNA-binding protein that transports β-actin mRNA and releases it for local translation upon phosphorylation. We found that Shh stimulation increases phospho-ZBP1 levels in the growth cone. Disruption of ZBP1 phosphorylation in vitro abolished the turning of commissural axons toward a Shh gradient. Disruption of ZBP1 function in vivo in mouse and chick resulted in commissural axon guidance errors. Therefore, ZBP1 is required for Shh to guide commissural axons. This identifies ZBP1 as a new mediator of noncanonical Shh signaling in axon guidance.SIGNIFICANCE STATEMENT Sonic hedgehog (Shh) guides axons via a noncanonical signaling pathway that is distinct from the canonical Hedgehog signaling pathway that specifies cell fate and morphogenesis. Axon guidance is driven by changes in the growth cone in response to gradients of guidance molecules. Little is known about the molecular mechanism of how Shh orchestrates changes in the growth cone cytoskeleton that are required for growth cone turning. Here, we show that the guidance of axons by Shh requires protein synthesis. Zipcode binding protein 1 (ZBP1) is an mRNA-binding protein that regulates the local translation of proteins, including actin, in the growth cone. We demonstrate that ZBP1 is required for Shh-mediated axon guidance, identifying a new member of the noncanonical Shh signaling pathway.

  11. Interleukin (IL)-8 immunoreactivity of injured axons and surrounding oligodendrocytes in traumatic head injury. (United States)

    Hayashi, Takahito; Ago, Kazutoshi; Nakamae, Takuma; Higo, Eri; Ogata, Mamoru


    Interleukin (IL)-8 has been suggested to be a positive regulator of myelination in the central nervous system, in addition to its principal role as a chemokine for neutrophils. Immunostaining for beta-amyloid precursor protein (AβPP) is an effective tool for detecting traumatic axonal injury, although AβPP immunoreactivity can also indicate axonal injury due to hypoxic causes. In this study, we examined IL-8 and AβPP immunoreactivity in sections of corpus callosum obtained from deceased patients with blunt head injury and from equivalent control tissue. AβPP immunoreactivity was detected in injured axons, such as axonal bulbs and varicose axons, in 24 of 44 head injury cases. These AβPP immunoreactive cases had survived for more than 3h. The AβPP immunostaining pattern can be classified into two types: traumatic (Pattern 1) and non-traumatic (Pattern 2) axonal injuries, which we described previously [Hayashi et al. Int. J. Legal Med. 129 (2015) 1085-1090]. Three of 44 control cases also showed AβPP immunoreactive injured axons as Pattern 2. In contrast, IL-8 immunoreactivity was detected in 7 AβPP immunoreactive and in 2 non-AβPP immunoreactive head injury cases, but was not detected in any of the 44 control cases, including the 3 AβPP immunoreactive control cases. The IL-8 immunoreactive cases had survived from 3 to 24 days, whereas those cases who survived less than 3 days (n=29) and who survived 90 days (n=1) were not IL-8 immunoreactive. Moreover, IL-8 was detected as Pattern 1 axons only. In addition, double immunofluorescence analysis showed that IL-8 is expressed by oligodendrocytes surrounding injured axons. In conclusion, our results suggest that immunohistochemical detection of IL-8 may be useful as a complementary diagnostic marker of traumatic axonal injury.

  12. Shh signaling guides spatial pathfinding of raphespinal tract axons by multidirectional repulsion

    Institute of Scientific and Technical Information of China (English)

    Lijuan Song; Yuehui Liu; YangYu; Xin Duan; Shening Qi; Yaobo Liu


    Relatively little is known about the molecular mechanisms underlying spatial pathfinding in the descending serotonergic raphespinal tract (RST) in the developing spinal cord,one of the most important nerve pathways for pain,sensory and motor functions.We provide evidence that ventral floor plate-secreted Sonic hedgehog (Shh) is responsible for the establishment of decreasing gradients in both the anterior-to-posterior (A-P) and the medialto-lateral (M-L) directions in the ventral spinal cord during serotonergic RST axon projection.Downstream components of the Shh pathway,Patched 1 (Ptch1) and Smoothened (Smo),were expressed in the serotonergic caudal raphe nuclei and enriched in the descending serotonergic RST axons.Diffusible Shh repulsion of serotonergic RST axons was shown to be mediated by Shh-Ptch1 interactions and derepression of Smo.Using a co-culture assay,we showed that A-P graded repulsion mediated by Shh signaling pushed the serotonergic axons caudally through the ventral spinal cord and M-L graded repulsion mediated by Shh signaling simultaneously restricted the serotonergic axons to the ventral and ventral-lateral funiculus.Prominent pathfinding errors of serotonergic RST axons were observed in various Shh,Ptch1 and Smo mutants.We conclude that Shh signaling-mediated multidirectional repulsion is required to push descending serotonergic RST axons in the A-P direction,and to restrict these axons to the ventral and ventral-lateral funiculus in the M-L direction.This is the first demonstration that Shh signalingmediated muitidirectional repulsion of serotonergic RST axons maintains spatial axon pathfinding in the developing spinal cord.

  13. Shh signaling guides spatial pathfinding of raphespinal tract axons by multidirectional repulsion. (United States)

    Song, Lijuan; Liu, Yuehui; Yu, Yang; Duan, Xin; Qi, Shening; Liu, Yaobo


    Relatively little is known about the molecular mechanisms underlying spatial pathfinding in the descending serotonergic raphespinal tract (RST) in the developing spinal cord, one of the most important nerve pathways for pain, sensory and motor functions. We provide evidence that ventral floor plate-secreted Sonic hedgehog (Shh) is responsible for the establishment of decreasing gradients in both the anterior-to-posterior (A-P) and the medial-to-lateral (M-L) directions in the ventral spinal cord during serotonergic RST axon projection. Downstream components of the Shh pathway, Patched 1 (Ptch1) and Smoothened (Smo), were expressed in the serotonergic caudal raphe nuclei and enriched in the descending serotonergic RST axons. Diffusible Shh repulsion of serotonergic RST axons was shown to be mediated by Shh-Ptch1 interactions and derepression of Smo. Using a co-culture assay, we showed that A-P graded repulsion mediated by Shh signaling pushed the serotonergic axons caudally through the ventral spinal cord and M-L graded repulsion mediated by Shh signaling simultaneously restricted the serotonergic axons to the ventral and ventral-lateral funiculus. Prominent pathfinding errors of serotonergic RST axons were observed in various Shh, Ptch1 and Smo mutants. We conclude that Shh signaling-mediated multidirectional repulsion is required to push descending serotonergic RST axons in the A-P direction, and to restrict these axons to the ventral and ventral-lateral funiculus in the M-L direction. This is the first demonstration that Shh signaling-mediated multidirectional repulsion of serotonergic RST axons maintains spatial axon pathfinding in the developing spinal cord.

  14. Hardware based segmentation in iris recognition and authentication systems (United States)

    Ulis, Bradley J.; Broussard, Randy P.; Rakvic, Ryan N.; Ives, Robert W.; Steiner, Neil; Ngo, Hau


    Iris recognition algorithms depend on image processing techniques for proper segmentation of the iris. In the Ridge Energy Direction (RED) iris recognition algorithm, the initial step in the segmentation process searches for the pupil by thresholding and using binary morphology functions to rectify artifacts obfuscating the pupil. These functions take substantial processing time in software on the order of a few hundred million operations. Alternatively, a hardware version of the binary morphology functions is implemented to assist in the segmentation process. The hardware binary morphology functions have negligible hardware footprint and power consumption while achieving speed up of 200 times compared to the original software functions.

  15. The role of microtubule-associated protein 1B in axonal growth and neuronal migration in the central nervous system

    Institute of Scientific and Technical Information of China (English)

    Maoguang Yang; Xiaoyu Yang; Minfei Wu; Peng Xia; Chunxin Wang; Peng Yan; Qi Gao; Jian Liu; Haitao Wang; Xingwei Duan


    In this review, we discuss the role of microtubule-associated protein 1B (MAP1B) and its phosphorylation in axonal development and regeneration in the central nervous system. MAP1B exhibits similar functions during axonal development and regeneration. MAP1B and phosphorylated MAP1B in neurons and axons maintain a dynamic balance between cytoskeletal components, and regulate the stability and interaction of microtubules and actin to promote axonal growth, neural connectivity and regeneration in the central nervous system.

  16. Segmentation of the Infant Food Market


    Hrůzová, Daniela


    The theoretical part covers general market segmentation, namely the marketing importance of differences among consumers, the essence of market segmentation, its main conditions and the process of segmentation, which consists of four consecutive phases - defining the market, determining important criteria, uncovering segments and developing segment profiles. The segmentation criteria, segmentation approaches, methods and techniques for the process of market segmentation are also described in t...

  17. Partial differential equations-based segmentation for radiotherapy treatment planning. (United States)

    Gibou, Frederic; Levy, Doron; Cardenas, Carlos; Liu, Pingyu; Boyer, Arthur


    The purpose of this study is to develop automatic algorithms for the segmentation phase of radiotherapy treatment planning. We develop new image processing techniques that are based on solving a partial diferential equation for the evolution of the curve that identifies the segmented organ. The velocity function is based on the piecewise Mumford-Shah functional. Our method incorporates information about the target organ into classical segmentation algorithms. This information, which is given in terms of a three- dimensional wireframe representation of the organ, serves as an initial guess for the segmentation algorithm. We check the performance of the new algorithm on eight data sets of three diferent organs: rectum, bladder, and kidney. The results of the automatic segmentation were compared with a manual seg- mentation of each data set by radiation oncology faculty and residents. The quality of the automatic segmentation was measured with the k-statistics", and with a count of over- and undersegmented frames, and was shown in most cases to be very close to the manual segmentation of the same data. A typical segmentation of an organ with sixty slices takes less than ten seconds on a Pentium IV laptop.

  18. A macroscopic model of traffic jams in axons. (United States)

    Kuznetsov, A V; Avramenko, A A


    The purpose of this paper is to develop a minimal macroscopic model capable of explaining the formation of traffic jams in fast axonal transport. The model accounts for the decrease of the number density of positively (and negatively) oriented microtubules near the location of the traffic jam due to formation of microtubule swirls; the model also accounts for the reduction of the effective velocity of organelle transport in the traffic jam region due to organelles falling off microtubule tracks more often in the swirl region. The model is based on molecular-motor-assisted transport equations and the hydrodynamic model of traffic jams in highway traffic. Parametric analyses of the model's predictions for various values of viscosity of the traffic flow, variance of the velocity distribution, diffusivity of microtubule-bound and free organelles, rate constants for binding to and detachment from microtubules, relaxation time, and average motor velocities of the retrograde and anterograde transport, are carried out.

  19. Video Object Tracking in Neural Axons with Fluorescence Microscopy Images

    Directory of Open Access Journals (Sweden)

    Liang Yuan


    tracking. In this paper, we describe two automated tracking methods for analyzing neurofilament movement based on two different techniques: constrained particle filtering and tracking-by-detection. First, we introduce the constrained particle filtering approach. In this approach, the orientation and position of a particle are constrained by the axon’s shape such that fewer particles are necessary for tracking neurofilament movement than object tracking techniques based on generic particle filtering. Secondly, a tracking-by-detection approach to neurofilament tracking is presented. For this approach, the axon is decomposed into blocks, and the blocks encompassing the moving neurofilaments are detected by graph labeling using Markov random field. Finally, we compare two tracking methods by performing tracking experiments on real time-lapse image sequences of neurofilament movement, and the experimental results show that both methods demonstrate good performance in comparison with the existing approaches, and the tracking accuracy of the tracing-by-detection approach is slightly better between the two.

  20. Neural signal registration and analysis of axons grown in microchannels (United States)

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


    Registration of neuronal bioelectrical signals remains one of the main physical tools to study fundamental mechanisms of signal processing in the brain. Neurons generate spiking patterns which propagate through complex map of neural network connectivity. Extracellular recording of isolated axons grown in microchannels provides amplification of the signal for detailed study of spike propagation. In this study we used neuronal hippocampal cultures grown in microfluidic devices combined with microelectrode arrays to investigate a changes of electrical activity during neural network development. We found that after 5 days in vitro after culture plating the spiking activity appears first in microchannels and on the next 2-3 days appears on the electrodes of overall neural network. We conclude that such approach provides a convenient method to study neural signal processing and functional structure development on a single cell and network level of the neuronal culture.

  1. Axonal transport interruption and anatomy at the lamina cribrosa. (United States)

    Radius, R L; Bade, B


    Pressure-induced, focal axonal transport abnormalities were studied in 14 cat eyes by the examination of serial step-section tissue radioautogram. Although the patterns of the transport interruption at the lamina cribrosa varied from eye to eye, the temporal sectors of the nerve head were most often involved by this abnormality. The anatomy at the lamina cribrosa was studied in adjacent (6 micrometers) cross-sectional specimens. The thickness of the extra-bundle trabeculae and the nerve fiber bundle dimensions including the cross-sectional area and the number and the shape (the ratio of the major and the minor axis diameters) of the laminar pores were measured by computer-assisted perimeter analysis. There was no correlation between the location of the transport interruption and any of these anatomic measurements.

  2. Diagnosis and treatment of diffuse axonal injury in 169 patients

    Institute of Scientific and Technical Information of China (English)

    YANG Jia-yong; YANG Zhen-jiu; FENG Cheng-xuan; LI Hong-wei; LI Wei-ping; ZHANG Jun; ZHANG Hong


    Objective: To evaluate current diagnosis and therapeutic effect and outcome of diffuse axonal injury (DAI) in 169 patients.Methods: The data of 169 DAI patients treated in the Second, Sixth, Eighth and Ninth Hospitals of Shenzhen and Shekou Hospital from January 2001 to January 2005 were collected. The imaging features, classification, GCS (Glasgow coma scale), treatment and outcome of the 169patients were retrospectively analyzed.Results: The simpler the imaging features, the closer the focus of DAI to the periphery of hemisphere and the higher the GCS score, the better the prognoses of DAI patients will be.Conclusions: The prognoses of DAI patients are closely related to the imaging features and classification,GCS and clinical treatment.

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

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Krarup, Christian


    We found persistent abnormalities in the recovery of membrane excitability in long-term regenerated motor nerve fibres in the cat as indicated in the companion paper. These abnormalities could partly be explained by membrane hyperpolarization. To further investigate this possibility, we compared...... the changes in excitability in control nerves and long-term regenerated cat nerves (3-5 years after tibial nerve crush) during manoeuvres known to alter axonal membrane Na(+)-K(+) pump function: polarization, cooling to 20 degrees C, reperfusion after 10 min ischaemia, and up to 60 s of repetitive stimulation...... at 200 Hz. The abnormalities in excitability of regenerated nerves were reduced by depolarization and cooling and increased by hyperpolarization and during postischaemia. Moreover, the time course of recovery of excitability from repetitive stimulation and ischaemia was prolonged in regenerated nerves...

  4. Multimodal transition and stochastic antiresonance in squid giant axons

    CERN Document Server

    Borkowski, L S


    The experimental data of N. Takahashi, Y. Hanyu, T. Musha, R. Kubo, and G. Matsumoto, Physica D \\textbf{43}, 318 (1990), on the response of squid giant axons stimulated by periodic sequence of short current pulses is interpreted within the Hodgkin-Huxley model. The minimum of the firing rate as a function of the stimulus amplitude $I_0$ in the high-frequency regime is due to the multimodal transition. Below this singular point only odd multiples of the driving period remain and the system is highly sensitive to noise. The coefficient of variation has a maximum and the firing rate has a minimum as a function of the noise intensity which is an indication of the stochastic coherence antiresonance. The model calculations reproduce the frequency of occurrence of the most common modes in the vicinity of the transition. A linear relation of output frequency vs. $I_0$ for above the transition is also confirmed.

  5. Semantic segmentation of multispectral overhead imagery (United States)

    Prasad, Lakshman; Pope, Paul A.; Sentz, Kari


    Land cover classification uses multispectral pixel information to separate image regions into categories. Image segmentation seeks to separate image regions into objects and features based on spectral and spatial image properties. However, making sense of complex imagery typically requires identifying image regions that are often a heterogeneous mixture of categories and features that constitute functional semantic units such as industrial, residential, or commercial areas. This requires leveraging both spectral classification and spatial feature extraction synergistically to synthesize such complex but meaningful image units. We present an efficient graphical model for extracting such semantically cohesive regions. We employ an initial hierarchical segmentation of images into features represented as nodes of an attributed graph that represents feature properties as well as their adjacency relations with other features. This provides a framework to group spectrally and structurally diverse features, which are nevertheless semantically cohesive, based on user-driven identifications of features and their contextual relationships in the graph. We propose an efficient method to construct, store, and search an augmented graph that captures nonadjacent vicinity relationships of features. This graph can be used to query for semantic notional units consisting of ontologically diverse features by constraining it to specific query node types and their indicated/desired spatial interaction characteristics. User interaction with, and labeling of, initially segmented and categorized image feature graph can then be used to learn feature (node) and regional (subgraph) ontologies as constraints, and to identify other similar semantic units as connected components of the constraint-pruned augmented graph of a query image.

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

    Directory of Open Access Journals (Sweden)

    Rahul Sachdeva


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

  7. Multichannel activity propagation across an engineered axon network (United States)

    Chen, H. Isaac; Wolf, John A.; Smith, Douglas H.


    Objective. Although substantial progress has been made in mapping the connections of the brain, less is known about how this organization translates into brain function. In particular, the massive interconnectivity of the brain has made it difficult to specifically examine data transmission between two nodes of the connectome, a central component of the ‘neural code.’ Here, we investigated the propagation of multiple streams of asynchronous neuronal activity across an isolated in vitro ‘connectome unit.’ Approach. We used the novel technique of axon stretch growth to create a model of a long-range cortico-cortical network, a modular system consisting of paired nodes of cortical neurons connected by axon tracts. Using optical stimulation and multi-electrode array recording techniques, we explored how input patterns are represented by cortical networks, how these representations shift as they are transmitted between cortical nodes and perturbed by external conditions, and how well the downstream node distinguishes different patterns. Main results. Stimulus representations included direct, synaptic, and multiplexed responses that grew in complexity as the distance between the stimulation source and recorded neuron increased. These representations collapsed into patterns with lower information content at higher stimulation frequencies. With internodal activity propagation, a hierarchy of network pathways, including latent circuits, was revealed using glutamatergic blockade. As stimulus channels were added, divergent, non-linear effects were observed in local versus distant network layers. Pairwise difference analysis of neuronal responses suggested that neuronal ensembles generally outperformed individual cells in discriminating input patterns. Significance. Our data illuminate the complexity of spiking activity propagation in cortical networks in vitro, which is characterized by the transformation of an input into myriad outputs over several network layers

  8. 4D MR phase and magnitude segmentations with GPU parallel computing. (United States)

    Bergen, Robert V; Lin, Hung-Yu; Alexander, Murray E; Bidinosti, Christopher P


    The increasing size and number of data sets of large four dimensional (three spatial, one temporal) magnetic resonance (MR) cardiac images necessitates efficient segmentation algorithms. Analysis of phase-contrast MR images yields cardiac flow information which can be manipulated to produce accurate segmentations of the aorta. Phase contrast segmentation algorithms are proposed that use simple mean-based calculations and least mean squared curve fitting techniques. The initial segmentations are generated on a multi-threaded central processing unit (CPU) in 10 seconds or less, though the computational simplicity of the algorithms results in a loss of accuracy. A more complex graphics processing unit (GPU)-based algorithm fits flow data to Gaussian waveforms, and produces an initial segmentation in 0.5 seconds. Level sets are then applied to a magnitude image, where the initial conditions are given by the previous CPU and GPU algorithms. A comparison of results shows that the GPU algorithm appears to produce the most accurate segmentation.

  9. Motility initiation in active gels

    CERN Document Server

    Recho, Pierre; Truskinovsky, Lev


    Motility initiation in crawling cells requires a symmetry breaking mechanism which transforms a symmetric state into a polarized state. Experiments on keratocytes suggest that polarization is triggered by increased contractility of motor proteins. In this paper we argue that contraction can be responsible not only for the symmetry breaking transition but also for the incipient translocation of the segment of an active gel mimicking the crawling cell. Our model suggests that when the contractility increases sufficiently far beyond the motility initiation threshold, the cell can stop and re-symmetrizes. The proposed theory reproduces the motility initiation pattern in fish keratocytes and the behavior of keratocytes prior to cell division.

  10. Schizophrenia as segmental progeria (United States)

    Papanastasiou, Evangelos; Gaughran, Fiona; Smith, Shubulade


    Schizophrenia is associated with a variety of physical manifestations (i.e. metabolic, neurological) and despite psychotropic medication being blamed for some of these (in particular obesity and diabetes), there is evidence that schizophrenia itself confers an increased risk of physical disease and early death. The observation that schizophrenia and progeroid syndromes share common clinical features and molecular profiles gives rise to the hypothesis that schizophrenia could be conceptualized as a whole body disorder, namely a segmental progeria. Mammalian cells employ the mechanisms of cellular senescence and apoptosis (programmed cell death) as a means to control inevitable DNA damage and cancer. Exacerbation of those processes is associated with accelerated ageing and schizophrenia and this warrants further investigation into possible underlying biological mechanisms, such as epigenetic control of the genome. PMID:22048679

  11. Probabilistic retinal vessel segmentation (United States)

    Wu, Chang-Hua; Agam, Gady


    Optic fundus assessment is widely used for diagnosing vascular and non-vascular pathology. Inspection of the retinal vasculature may reveal hypertension, diabetes, arteriosclerosis, cardiovascular disease and stroke. Due to various imaging conditions retinal images may be degraded. Consequently, the enhancement of such images and vessels in them is an important task with direct clinical applications. We propose a novel technique for vessel enhancement in retinal images that is capable of enhancing vessel junctions in addition to linear vessel segments. This is an extension of vessel filters we have previously developed for vessel enhancement in thoracic CT scans. The proposed approach is based on probabilistic models which can discern vessels and junctions. Evaluation shows the proposed filter is better than several known techniques and is comparable to the state of the art when evaluated on a standard dataset. A ridge-based vessel tracking process is applied on the enhanced image to demonstrate the effectiveness of the enhancement filter.

  12. Segmented heat exchanger (United States)

    Baldwin, Darryl Dean; Willi, Martin Leo; Fiveland, Scott Byron; Timmons, Kristine Ann


    A segmented heat exchanger system for transferring heat energy from an exhaust fluid to a working fluid. The heat exchanger system may include a first heat exchanger for receiving incoming working fluid and the exhaust fluid. The working fluid and exhaust fluid may travel through at least a portion of the first heat exchanger in a parallel flow configuration. In addition, the heat exchanger system may include a second heat exchanger for receiving working fluid from the first heat exchanger and exhaust fluid from a third heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the second heat exchanger in a counter flow configuration. Furthermore, the heat exchanger system may include a third heat exchanger for receiving working fluid from the second heat exchanger and exhaust fluid from the first heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the third heat exchanger in a parallel flow configuration.

  13. Axon extension in the fast and slow lanes: substratum-dependent engagement of myosin II functions. (United States)

    Ketschek, Andrea R; Jones, Steven L; Gallo, Gianluca


    Axon extension involves the coordinated regulation of the neuronal cytoskeleton. Actin filaments drive protrusion of filopodia and lamellipodia while microtubules invade the growth cone, thereby providing structural support for the nascent axon. Furthermore, in order for axons to extend the growth cone must attach to the substratum. Previous work indicates that myosin II activity inhibits the advance of microtubules into the periphery of growth cones, and myosin II has also been implicated in mediating integrin-dependent cell attachment. However, it is not clear how the functions of myosin II in regulating substratum attachment and microtubule advance are integrated during axon extension. We report that inhibition of myosin II function decreases the rate of axon extension on laminin, but surprisingly promotes extension rate on polylysine. The differential effects of myosin II inhibition on axon extension rate are attributable to myosin II having the primary function of mediating substratum attachment on laminin, but not on polylysine. Conversely, on polylysine the primary function of myosin II is to inhibit microtubule advance into growth cones. Thus, the substratum determines the role of myosin II in axon extension by controlling the functions of myosin II that contribute to extension.

  14. Modeling the mechanics of axonal fiber tracts using the embedded finite element method. (United States)

    Garimella, Harsha T; Kraft, Reuben H


    A subject-specific human head finite element model with embedded axonal fiber tractography obtained from diffusion tensor imaging was developed. The axonal fiber tractography finite element model was coupled with the volumetric elements in the head model using the embedded element method. This technique enables the calculation of axonal strains and real-time tracking of the mechanical response of the axonal fiber tracts. The coupled model was then verified using pressure and relative displacement-based (between skull and brain) experimental studies and was employed to analyze a head impact, demonstrating the applicability of this method in studying axonal injury. Following this, a comparison study of different injury criteria was performed. This model was used to determine the influence of impact direction on the extent of the axonal injury. The results suggested that the lateral impact loading is more dangerous compared to loading in the sagittal plane, a finding in agreement with previous studies. Through this analysis, we demonstrated the viability of the embedded element method as an alternative numerical approach for studying axonal injury in patient-specific human head models.

  15. Gene expression of axon growth promoting factors in the deer antler.

    Directory of Open Access Journals (Sweden)

    Wolfgang Pita-Thomas

    Full Text Available The annual regeneration cycle of deer (Cervidae, Artiodactyla antlers represents a unique model of epimorphic regeneration and rapid growth in adult mammals. Regenerating antlers are innervated by trigeminal sensory axons growing through the velvet, the modified form of skin that envelopes the antler, at elongation velocities that reach one centimetre per day in the common deer (Cervus elaphus. Several axon growth promoters like NT-3, NGF or IGF-1 have been described in the antler. To increase the knowledge on the axon growth environment, we have combined different gene-expression techniques to identify and characterize the expression of promoting molecules not previously described in the antler velvet. Cross-species microarray analyses of deer samples on human arrays allowed us to build up a list of 90 extracellular or membrane molecules involved in axon growth that were potentially being expressed in the antler. Fifteen of these genes were analysed using PCR and sequencing techniques to confirm their expression in the velvet and to compare it with the expression in other antler and skin samples. Expression of 8 axon growth promoters was confirmed in the velvet, 5 of them not previously described in the antler. In conclusion, our work shows that antler velvet provides growing axons with a variety of promoters of axon growth, sharing many of them with deer's normal and pedicle skin.

  16. Effect of fetal spinal cord graft with different methods on axonal pathology after spinal cord contusion

    Institute of Scientific and Technical Information of China (English)


    Objective: To investigate the effect of fetal spinal cord (FSC) graft with different methods on axonal pathology and neurological function recovery after spinal cord injury (SCI).   Methods: Forty Wistar rats were divided into 4 groups. In Group A, the spinal cord was injured and hemisected. In Group B, fetal spinal cord (FSC) was transferred into the injured site. In Group C, after having done as Group B, the upper and lower spinal nerve roots were anastomosed. And in Group D, after having done as Group B, the pedicled omentum was transferred into the hemisection cavity. At 6 weeks after operation, light and electronic microscopes were used to examine the axonal pathology. The neurological function was assessed with inclined plane tests in the open field. The number of axons was quantitated by a computer image analysis system.   Results: A greater loss of axons was observed in Group A than that of other groups at 6 weeks. The sequence of the reduced rate of the axons was as following, Group A>Group B>Group C>Group D (P<0.05). The remaining axons were paralleled with the significant improvement in neurological function recovery of the rats.   Conclusions: It indicates that FSC and pedicled omentum grafts after SCI can protect the axons and promote the neurological function recovery of the rats.

  17. The use of proteomic analysis to study trafficking defects in axons. (United States)

    Fu, Xiaoqin; Brown, Kristy J; Rayavarapu, Sree; Nagaraju, Kanneboyina; Liu, Judy S


    Mutations in microtubule subunits and microtubule-associated proteins are the causes of many neurological disorders. These human conditions are usually associated with axonal tract defects or degeneration. The molecular mechanisms of these axonal dysfunction are still largely unknown. Conventional methods may not yield a complete analysis of downstream molecules related to axonal dysfunctions. Therefore, we devised a simple unbiased method to screen molecular motors and axonal molecules, which might be involved in axonal defects. We performed our analysis in the mouse with a targeted deletion in the doublecortin (Dcx) gene. Dcx is a microtubule-associated protein with direct effects on microtubule motors. Furthermore, the knockout of Dcx and its functionally redundant structurally similar paralog, doublecortin-like kinase 1 (Dclk1), in mouse results in thinner or absent axon tracts, including the corpus callosum and anterior commissures. We compared protein profiles of corpus callosum from Dcx knockout and wild-type mouse of P0-P2 using mass spectrometry. This strategy allowed us to identify novel candidates downstream of Dcx involved in axon transport.

  18. Discoidin domain receptors guide axons along longitudinal tracts in C. elegans. (United States)

    Unsoeld, Thomas; Park, Ja-On; Hutter, Harald


    Discoidin domain receptors are a family of receptor tyrosine kinases activated by collagens. Here we characterize the role of the two discoidin domain receptors, ddr-1 and ddr-2, of the nematode C. elegans during nervous system development. ddr-2 mutant animals exhibit axon guidance defects in major longitudinal tracts most prominently in the ventral nerve cord. ddr-1 mutants show no significant phenotype on their own but significantly enhance guidance defects of ddr-2 in double mutants. ddr-1 and ddr-2 GFP-reporter constructs are expressed in neurons with axons in all affected nerve tracts. DDR-1 and DDR-2 GFP fusion proteins localize to axons. DDR-2 is required cell-autonomously in the PVPR neuron for the guidance of the PVPR pioneer axon, which establishes the left ventral nerve cord tract and serves as substrate for later outgrowing follower axons. Our results provide the first insight on discoidin domain receptor function in invertebrates and establish a novel role for discoidin domain receptors in axon navigation and axon tract formation.

  19. Effects of axonal topology on the somatic modulation of synaptic outputs. (United States)

    Sasaki, Takuya; Matsuki, Norio; Ikegaya, Yuji


    Depolarization of the neuronal soma augments synaptic output onto postsynaptic neurons via long-range, axonal cable properties. Here, we report that the range of this somatic influence is spatially restricted by not only axonal path length but also a branching-dependent decrease in axon diameter. Cell-attached recordings of action potentials (APs) from multiple axon branches of a rat hippocampal CA3 pyramidal cell revealed that an AP was broadened following a 20 mV depolarization of the soma and reverted to a normal width during propagation down the axon. The narrowing of the AP depended on the distance traveled by the AP and on the number of axon branch points through which the AP passed. These findings were confirmed by optical imaging of AP-induced calcium elevations in presynaptic boutons, suggesting that the somatic membrane potential modifies synaptic outputs near the soma but not long-projection outputs. Consistent with this prediction, whole-cell recordings from synaptically connected neurons revealed that depolarization of presynaptic CA3 pyramidal cells facilitated synaptic transmission to nearby CA3 pyramidal cells, but not to distant pyramidal cells in CA3 or CA1. Therefore, axonal geometry enables the differential modulation of synaptic output depending on target location.

  20. Characterizing Semaphorin-Mediated Effects on Sensory and Motor Axon Pathfinding and Connectivity During Embryonic Development. (United States)

    Huettl, Rosa Eva; Huber, Andrea B


    How are precise connectivity to peripheral targets and corresponding sensory-motor networks established during developmental innervation of the vertebrate extremities? The formation of functional sensory-motor circuits requires highly appropriate temporal and spatial regulation of axon growth which is achieved through the combination of different molecular mechanisms such as communication between heterotypic fiber systems, axon-environment, or axon-glia interactions that ensure proper fasciculation and accurate pathfinding to distal targets. Family members of the class 3 semaphorins and their cognate receptors, the neuropilins, were shown to govern various events during wiring of central and peripheral circuits, with mice lacking Sema3-Npn signaling showing deficits in timing of growth, selective fasciculation, guidance fidelity, and coupling of sensory axon growth to motor axons at developmental time points. Given the accuracy with which these processes have to interact in a stepwise manner, deficiency of the smallest cog in the wheel may impact severely on the faithful establishment and functionality of peripheral circuitries, ultimately leading to behavioral impairments or even cause the death of the animal. Reliable quantitative analyses of sensory-motor fasciculation, extension, and guidance of axons to their cognate target muscles and the skin during development, but also assessment of physiological and behavioral consequences at adult age, are therefore a necessity to extend our understanding of the molecular mechanisms of peripheral circuit formation. In this chapter we provide a detailed methodology to characterize class 3 semaphorin-mediated effects on peripheral sensory and motor axon pathfinding and connectivity during embryonic development.

  1. Morphometric analysis of Mauthner axon cytoskeletal components in adult and subadult fish. (United States)

    Alfei, L; Medolago-Albani, L; Zezze, G M; Stefanelli, A


    A previous cytoskeletal analysis on trout MA during developmental stages demonstrated, during the subadult stages, neurofilaments (NF) as main components as expressed by the high values of neurofilament to microtubules (MT) ratio which was found to be of the order of 300:1. Since the MA cytoskeletal composition is not known in the adult fish, the MA cytoskeletal composition has been compared to other axons of much smaller diameter of the fasciculus longitudinalis medialis (flm) among which the MA run in the ventral spinal cord. The following parameters were measured on conventional electron microscopy in MA and flm axons cross sections micrographs by means of a computer linked graphic tablet (Apple II): axonal caliber, number of microtubules (MT), microtubular (MT/microns2) and neurofilament (NF/microns2) densities. The analysis of these parameters demonstrated that neurofilaments are the main architectural components in the adult and subadult fish MA and flm axons. However, MA cytoskeletal composition differs from the other flm axons because of its particular very high ratio of neurofilaments to microtubules. The inverse relationship of axonal caliber to microtubular density, previously found in the trout during developmental stages and suggested also for many other vertebrate species, was further confirmed for flm axons which, with calibers 10 times smaller than MA, exhibit a microtubular density 10 times larger.

  2. EFN-4 functions in LAD-2-mediated axon guidance in Caenorhabditis elegans. (United States)

    Dong, Bingyun; Moseley-Alldredge, Melinda; Schwieterman, Alicia A; Donelson, Cory J; McMurry, Jonathan L; Hudson, Martin L; Chen, Lihsia


    During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. InC. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for the C. elegans ephrin EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with the C. elegans divergent L1 cell adhesion molecule LAD-2 acting as a non-canonical ephrin receptor to EFN-4 to promote axon guidance. We also show that EFN-4 probably functions as a diffusible factor because EFN-4 engineered to be soluble can promote LAD-2-mediated axon guidance. This study thus reveals a potential additional mechanism for ephrins in regulating axon guidance and expands the repertoire of receptors by which ephrins can signal.

  3. Differential expression of axon-sorting molecules in mouse olfactory sensory neurons. (United States)

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


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

  4. Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy. (United States)

    Sasaki, Yo; Araki, Toshiyuki; Milbrandt, Jeffrey


    Axonal degeneration occurs in many neurodegenerative diseases and after traumatic injury and is a self-destructive program independent from programmed cell death. Previous studies demonstrated that overexpression of nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) or exogenous application of nicotinamide adenine dinucleotide (NAD) can protect axons of cultured dorsal root ganglion (DRG) neurons from degeneration caused by mechanical or neurotoxic injury. In mammalian cells, NAD can be synthesized from multiple precursors, including tryptophan, nicotinic acid, nicotinamide, and nicotinamide riboside (NmR), via multiple enzymatic steps. To determine whether other components of these NAD biosynthetic pathways are capable of delaying axonal degeneration, we overexpressed each of the enzymes involved in each pathway and/or exogenously administered their respective substrates in DRG cultures and assessed their capacity to protect axons after axotomy. Among the enzymes tested, Nmnat1 had the strongest protective effects, whereas nicotinamide phosphoribosyl transferase and nicotinic acid phosphoribosyl transferase showed moderate protective activity in the presence of their substrates. Strong axonal protection was also provided by Nmnat3, which is predominantly located in mitochondria, and an Nmnat1 mutant localized to the cytoplasm, indicating that the subcellular location of NAD production is not crucial for protective activity. In addition, we showed that exogenous application of the NAD precursors that are the substrates of these enzymes, including nicotinic acid mononucleotide, nicotinamide mononucleotide, and NmR, can also delay axonal degeneration. These results indicate that stimulation of NAD biosynthetic pathways via a variety of interventions may be useful in preventing or delaying axonal degeneration.

  5. Serial Section Registration of Axonal Confocal Microscopy Datasets for Long-Range Neural Circuit Reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Hogrebe, Luke; Paiva, Antonio R.; Jurrus, Elizabeth R.; Christensen, Cameron; Bridge, Michael; Dai, Li; Pfeiffer, Rebecca; Hof, Patrick; Roysam, Badrinath; Korenberg, Julie; Tasdizen, Tolga


    In the context of long-range digital neural circuit reconstruction, this paper investigates an approach for registering axons across histological serial sections. Tracing distinctly labeled axons over large distances allows neuroscientists to study very explicit relationships between the brain's complex interconnects and, for example, diseases or aberrant development. Large scale histological analysis requires, however, that the tissue be cut into sections. In immunohistochemical studies thin sections are easily distorted due to the cutting, preparation, and slide mounting processes. In this work we target the registration of thin serial sections containing axons. Sections are first traced to extract axon centerlines, and these traces are used to define registration landmarks where they intersect section boundaries. The trace data also provides distinguishing information regarding an axon's size and orientation within a section. We propose the use of these features when pairing axons across sections in addition to utilizing the spatial relationships amongst the landmarks. The global rotation and translation of an unregistered section are accounted for using a random sample consensus (RANSAC) based technique. An iterative nonrigid refinement process using B-spline warping is then used to reconnect axons and produce the sought after connectivity information.

  6. Experience-driven axon retraction in the pharmacologically inactivated visual cortex does not require synaptic transmission.

    Directory of Open Access Journals (Sweden)

    Kana Watanabe

    Full Text Available BACKGROUND: Experience during early postnatal development plays an important role in the refinement of specific neural connections in the brain. In the mammalian visual system, altered visual experiences induce plastic adaptation of visual cortical responses and guide rearrangements of afferent axons from the lateral geniculate nucleus. Previous studies using visual deprivation demonstrated that the afferents serving an open eye significantly retract when cortical neurons are pharmacologically inhibited by applying a gamma-aminobutyric acid type A receptor agonist, muscimol, whereas those serving a deprived eye are rescued from retraction, suggesting that presynaptic activity can lead to the retraction of geniculocortical axons in the absence of postsynaptic activity. Because muscimol application suppresses the spike activity of cortical neurons leaving transmitter release intact at geniculocortical synapses, local synaptic interaction may underlie the retraction of active axons in the inhibited cortex. METHOD AND FINDINGS: New studies reported here determined whether experience-driven axon retraction can occur in the visual cortex inactivated by blocking synaptic inputs. We inactivated the primary visual cortex of kittens by suppressing synaptic transmission with cortical injections of botulinum neurotoxin type E, which cleaves a synaptic protein, SNAP-25, and blocks transmitter release, and examined the geniculocortical axon morphology in the animals with normal vision and those deprived of vision binocularly. We found that afferent axons in the animals with normal vision showed a significant retraction in the inactivated cortex, as similarly observed in the muscimol-treated cortex, whereas the axons in the binocularly deprived animals were preserved. CONCLUSIONS: Therefore, the experience-driven axon retraction in the inactivated cortex can proceed in the absence of synaptic transmission. These results suggest that presynaptic mechanisms play

  7. The Microtubule Regulatory Protein Stathmin Is Required to Maintain the Integrity of Axonal Microtubules in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jason E Duncan

    Full Text Available Axonal transport, a form of long-distance, bi-directional intracellular transport that occurs between the cell body and synaptic terminal, is critical in maintaining the function and viability of neurons. We have identified a requirement for the stathmin (stai gene in the maintenance of axonal microtubules and regulation of axonal transport in Drosophila. The stai gene encodes a cytosolic phosphoprotein that regulates microtubule dynamics by partitioning tubulin dimers between pools of soluble tubulin and polymerized microtubules, and by directly binding to microtubules and promoting depolymerization. Analysis of stai function in Drosophila, which has a single stai gene, circumvents potential complications with studies performed in vertebrate systems in which mutant phenotypes may be compensated by genetic redundancy of other members of the stai gene family. This has allowed us to identify an essential function for stai in the maintenance of the integrity of axonal microtubules. In addition to the severe disruption in the abundance and architecture of microtubules in the axons of stai mutant Drosophila, we also observe additional neurological phenotypes associated with loss of stai function including a posterior paralysis and tail-flip phenotype in third instar larvae, aberrant accumulation of transported membranous organelles in stai deficient axons, a progressive bang-sensitive response to mechanical stimulation reminiscent of the class of Drosophila mutants used to model human epileptic seizures, and a reduced adult lifespan. Reductions in the levels of Kinesin-1, the primary anterograde motor in axonal transport, enhance these phenotypes. Collectively, our results indicate that stai has an important role in neuronal function, likely through the maintenance of microtubule integrity in the axons of nerves of the peripheral nervous system necessary to support and sustain long-distance axonal transport.

  8. Robust regeneration of CNS axons through a track depleted of CNS glia. (United States)

    Moon, L D; Brecknell, J E; Franklin, R J; Dunnett, S B; Fawcett, J W


    Transected CNS axons do not regenerate spontaneously but may do so if given an appropriate environment through which to grow. Since molecules associated with CNS macroglia are thought to be inhibitory to axon regeneration, we have tested the hypothesis that removing these cell types from an area of brain will leave an environment more permissive for axon regeneration. Adult rats received unilateral knife cuts of the nigrostriatal tract and ethidium bromide (EB) was used to create a lesion devoid of astrocytes, oligodendrocytes, intact myelin sheaths, and NG2 immunoreactive cells from the site of the knife cut to the ipsilateral striatum (a distance of 6 mm). The regenerative response and the EB lesion environment was examined with immunostaining and electron microscopy at different timepoints following surgery. We report that large numbers of dopaminergic nigral axons regenerated for over 4 mm through EB lesions. At 4 days postlesion dopaminergic sprouting was maximal and the axon growth front had reached the striatum, but there was no additional growth into the striatum after 7 days. Regenerating axons did not leave the EB lesion to form terminals in the striatum, there was no recovery of function, and the end of axon growth correlated with increasing glial immunoreactivity around the EB lesion. We conclude that the removal of CNS glia promotes robust axon regeneration but that this becomes limited by the reappearance of nonpermissive CNS glia. These results suggest, first, that control of the glial reaction is likely to be an important feature in brain repair and, second, that reports of axon regeneration must be interpreted with caution since extensive regeneration can occur simply as a result of a major glia-depleting lesion, rather than as the result of some other specific intervention.

  9. Automatic segmentation of pulmonary segments from volumetric chest CT scans.

    NARCIS (Netherlands)

    Rikxoort, E.M. van; Hoop, B. de; Vorst, S. van de; Prokop, M.; Ginneken, B. van


    Automated extraction of pulmonary anatomy provides a foundation for computerized analysis of computed tomography (CT) scans of the chest. A completely automatic method is presented to segment the lungs, lobes and pulmonary segments from volumetric CT chest scans. The method starts with lung segmenta

  10. Hematopoietic progenitors express myelin basic protein and ensheath axons in Shiverer brain. (United States)

    Goolsby, James; Makar, Tapas; Dhib-Jalbut, Suhayl; Bever, Christopher T; Pessac, Bernard; Trisler, David


    Oligodendroglia are cells of the central nervous system (CNS) that form myelin sheath, which insulates neuronal axons. Neuropathologies of the CNS include dysmyelination of axons in multiple sclerosis and CNS trauma. Cell replacement is a promising but largely untested therapy for dysmyelination. Shiverer mouse, a genetic mutant that does not synthesize full-length myelin basic protein (MBP), a critical prerequisite protein in CNS myelin sheath formation, provides an unequivocal model for determining the potential of stem cells to become oligodendroglia. We demonstrate that adult wild-type mouse bone marrow stem cells can express MBP and ensheath axons when transplanted into Shiverer brain.

  11. Optic nerve fast axonal transport abnormalities in primates. Occurrence after short posterior ciliary artery occlusion. (United States)

    Radius, R L


    Fast axonal transport abnormalities in primate (Aotus trivirgatus) optic nerve were studied in ten eyes at various intervals after occlusion of the lateral short posterior ciliary circulation. Evidence of focal axonal ischemia, as indicated by swelling of mitochondria and dissolution of cytoplasmic detail, was noted as early as one hour after occlusion. Accumulation of mitochondria, microvesicles, and dense bodies, indicating focal interruption of axonal transport mechanisms, was noted in eyes examined at 2, 4, and 6 hours. This accumulation of organelles was limited to the region of the lamina cribrosa. Nerve head abnormalities were not seen in two eyes studied at two weeks.

  12. Midline governs axon pathfinding by coordinating expression of two major guidance systems. (United States)

    Liu, Qing-Xin; Hiramoto, Masaki; Ueda, Hitoshi; Gojobori, Takashi; Hiromi, Yasushi; Hirose, Susumu


    Formation of the neural network requires concerted action of multiple axon guidance systems. How neurons orchestrate expression of multiple guidance genes is poorly understood. Here, we show that Drosophila T-box protein Midline controls expression of genes encoding components of two major guidance systems: Frazzled, ROBO, and Slit. In midline mutant, expression of all these molecules are reduced, resulting in severe axon guidance defects, whereas misexpression of Midline induces their expression. Midline is present on the promoter regions of these genes, indicating that Midline controls transcription directly. We propose that Midline controls axon pathfinding through coordinating the two guidance systems.

  13. Enzyme-instructed self-assembly of taxol promotes axonal branching (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Tabassum Majid


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

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

    Directory of Open Access Journals (Sweden)

    M.A. Pires-Neto


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

  16. Shape-Memory Properties of Segmented Polymers Containing Aramid Hard Segments and Polycaprolactone Soft Segments

    Directory of Open Access Journals (Sweden)

    Arno Kraft


    Full Text Available A series of segmented multiblock copolymers containing aramid hard segments and extended polycaprolactone soft segments (with an Mn of 4,200 or 8,200 g mol–1 was prepared and tested for their shape-memory properties. Chain extenders were essential to raise the hard segment concentration so that an extended rubbery plateau could be observed. Dynamic mechanical thermal analysis provided a useful guide in identifying (i the presence of a rubbery plateau, (ii the flow temperature, and (iii the temperature when samples started to deform irreversibly.

  17. An Atypical SCF-like Ubiquitin Ligase Complex Promotes Wallerian Degeneration through Regulation of Axonal Nmnat2

    Directory of Open Access Journals (Sweden)

    Yuya Yamagishi


    Full Text Available Axon degeneration is a tightly regulated, self-destructive program that is a critical feature of many neurodegenerative diseases, but the molecular mechanisms regulating this program remain poorly understood. Here, we identify S-phase kinase-associated protein 1A (Skp1a, a core component of a Skp/Cullin/F-box (SCF-type E3 ubiquitin ligase complex, as a critical regulator of axon degeneration after injury in mammalian neurons. Depletion of Skp1a prolongs survival of injured axons in vitro and in the optic nerve in vivo. We demonstrate that Skp1a regulates the protein level of the nicotinamide adenine dinucleotide (NAD+ synthesizing enzyme nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2 in axons. Loss of axonal Nmnat2 contributes to a local ATP deficit that triggers axon degeneration. Knockdown of Skp1a elevates basal levels of axonal Nmnat2, thereby delaying axon degeneration through prolonged maintenance of axonal ATP. Consistent with Skp1a functioning through regulation of Nmnat2, Skp1a knockdown fails to protect axons from Nmnat2 knockdown. These results illuminate the molecular mechanism underlying Skp1a-dependent axonal destruction.

  18. Multiple etiologies of axonal sensory motor polyneuropathy in a renal transplant recipient: a case report

    Directory of Open Access Journals (Sweden)

    Etemadi Jalal


    Full Text Available Abstract Introduction Neurological complications leading to morbidity and mortality are not frequent in renal transplant recipients. Here, we report a renal transplant recipient who presented with diminished strength in his limbs probably due to multiple etiologies of axonal sensorimotor polyneuropathy, which resolved with intravenous immunoglobulin. Case presentation A 49-year-old Iranian male renal transplant recipient with previous history of autosomal dominant polycystic kidney disease presented with diminished strength in his limbs one month after surgery. Our patient was on cyclosporine A, mycophenolate mofetil and prednisone. Although a detected hypophosphatemia was corrected with supplemental phosphate, the loss of strength was still slowly progressive and diffuse muscular atrophy was remarkable in his trunk, upper limb and pelvic girdle. Meanwhile, his cranial nerves were intact. Post-transplant diabetes mellitus was diagnosed and insulin therapy was initiated. In addition, as a high serum cyclosporine level was detected, the dose of cyclosporine was reduced. Our patient was also put on intravenous ganciclovir due to positive serum cytomegalovirus immunoglobulin M antibody. Despite the reduction of oral cyclosporine dose along with medical therapy for the cytomegalovirus infection and diabetes mellitus, his muscular weakness and atrophy did not improve. One week after administration of intravenous immunoglobulin, a significant improvement was noted in his muscular weakness. Conclusion A remarkable response to intravenous immunoglobulin is compatible with an immunological basis for the present condition (post-transplant polyneuropathy. In cases of post-transplant polyneuropathy with a high clinical suspicion of immunological origin, administration of intravenous immunoglobulin may be recommended.

  19. Electrically conductive biodegradable polymer composite for nerve regeneration: electricity-stimulated neurite outgrowth and axon regeneration. (United States)

    Zhang, Ze; Rouabhia, Mahmoud; Wang, Zhaoxu; Roberge, Christophe; Shi, Guixin; Roche, Phillippe; Li, Jiangming; Dao, Lê H


    Normal and electrically stimulated PC12 cell cultures and the implantation of nerve guidance channels were performed to evaluate newly developed electrically conductive biodegradable polymer composites. Polypyrrole (PPy) doped by butane sulfonic acid showed a significantly higher number of viable cells compared with PPy doped by polystyrenesulfonate after a 6-day culture. The PC12 cells were left to proliferate for 6 days, and the PPy-coated membranes, showing less initial cell adherence, recorded the same proliferation rate as did the noncoated membranes. Direct current electricity at various intensities was applied to the PC12 cell-cultured conductive membranes. After 7 days, the greatest number of neurites appeared on the membranes with a current intensity approximating 1.7-8.4 microA/cm. Nerve guidance channels made of conductive biodegradable composite were implanted into rats to replace 8 mm of sciatic nerve. The implants were harvested after 2 months and analyzed with immunohistochemistry and transmission electron microscopy. The regenerated nerve tissue displayed myelinated axons and Schwann cells that were similar to those in the native nerve. Electrical stimulation applied through the electrically conductive biodegradable polymers therefore enhanced neurite outgrowth in a current-dependent fashion. The conductive polymers also supported sciatic nerve regeneration in rats.

  20. Novel RNA- and FMRP-binding protein TRF2-S regulates axonal mRNA transport and presynaptic plasticity. (United States)

    Zhang, Peisu; Abdelmohsen, Kotb; Liu, Yong; Tominaga-Yamanaka, Kumiko; Yoon, Je-Hyun; Ioannis, Grammatikakis; Martindale, Jennifer L; Zhang, Yongqing; Becker, Kevin G; Yang, In Hong; Gorospe, Myriam; Mattson, Mark P


    Despite considerable evidence that RNA-binding proteins (RBPs) regulate mRNA transport and local translation in dendrites, roles for axonal RBPs are poorly understood. Here we demonstrate that a non-telomeric isoform of telomere repeat-binding factor 2 (TRF2-S) is a novel RBP that regulates axonal plasticity. TRF2-S interacts directly with target mRNAs to facilitate their axonal delivery. The process is antagonized by fragile X mental retardation protein (FMRP). Distinct from the current RNA-binding model of FMRP, we show that FMRP occupies the GAR domain of TRF2-S protein to block the assembly of TRF2-S-mRNA complexes. Overexpressing TRF2-S and silencing FMRP promotes mRNA entry to axons and enhances axonal outgrowth and neurotransmitter release from presynaptic terminals. Our findings suggest a pivotal role for TRF2-S in an axonal mRNA localization pathway that enhances axon outgrowth and neurotransmitter release.

  1. Identifying motor and sensory myelinated axons in rabbit peripheral nerves by histochemical staining for carbonic anhydrase and cholinesterase activities (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Elodie Reynaud


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

  3. The Importance of Marketing Segmentation (United States)

    Martin, Gillian


    The rationale behind marketing segmentation is to allow businesses to focus on their consumers' behaviors and purchasing patterns. If done effectively, marketing segmentation allows an organization to achieve its highest return on investment (ROI) in turn for its marketing and sales expenses. If an organization markets its products or services to…

  4. Market Segmentation: An Instructional Module. (United States)

    Wright, Peter H.

    A concept-based introduction to market segmentation is provided in this instructional module for undergraduate and graduate transportation-related courses. The material can be used in many disciplines including engineering, business, marketing, and technology. The concept of market segmentation is primarily a transportation planning technique by…

  5. Upper medium segment cooling down

    Institute of Scientific and Technical Information of China (English)


    <正>The sluggish growth of the passenger car market in top provinces was also reflected in a depression of the upper medium segment. In Jan-Apr, 2008, the top 3 upper medium models accounting for nearly 40% of this segment performed poorly, with the Passat-Lingyu and the Accord decreasing. The Camry also saw a decrease in three top provinces: Guangdong,

  6. Optimally segmented permanent magnet structures

    DEFF Research Database (Denmark)

    Insinga, Andrea Roberto; Bjørk, Rasmus; Smith, Anders


    We present an optimization approach which can be employed to calculate the globally optimal segmentation of a two-dimensional magnetic system into uniformly magnetized pieces. For each segment the algorithm calculates the optimal shape and the optimal direction of the remanent flux density vector...

  7. Dermatology case: segmental lichen aureus


    Fernandes, I.; S. Carvalho; Machado, S.; Alves,R.; Selores, M.


    ABSTRACT The authors describe a clinical case of a six-year-old boy with history of a segmental brownish maculopapular skin eruption on his left thoracic and lumbar wall, since the last four months. Based on clinical and histological findings he was diagnosed with segmental lichen aureus.

  8. Segmentation: Slicing the Urban Pie. (United States)

    Keim, William A.


    Explains market segmentation and defines undifferentiated, concentrated, and differentiated marketing strategies. Describes in detail the marketing planning process at the Metropolitan Community Colleges. Focuses on the development and implementation of an ongoing recruitment program designed for the market segment composed of business employees.…

  9. Essays in International Market Segmentation

    NARCIS (Netherlands)

    Hofstede, ter F.


    The primary objective of this thesis is to develop and validate new methodologies to improve the effectiveness of international segmentation strategies. The current status of international market segmentation research is reviewed in an introductory chapter, which provided a number of methodological

  10. Adaptive Segmentation for Scientific Databases

    NARCIS (Netherlands)

    Ivanova, M.G.; Kersten, M.L.; Nes, N.J.


    In this paper we explore database segmentation in the context of a column-store DBMS targeted at a scientific database. We present a novel hardware- and scheme-oblivious segmentation algorithm, which learns and adapts to the workload immediately. The approach taken is to capitalize on (intermediate)

  11. Adaptive segmentation for scientific databases

    NARCIS (Netherlands)

    Ivanova, M.; Kersten, M.L.; Nes, N.


    In this paper we explore database segmentation in the context of a column-store DBMS targeted at a scientific database. We present a novel hardware- and scheme-oblivious segmentation algorithm, which learns and adapts to the workload immediately. The approach taken is to capitalize on (intermediate)

  12. The effects of magnesium sulfate therapy after severe diffuse axonal injury

    Directory of Open Access Journals (Sweden)

    Zhao L


    Full Text Available Ling Zhao,1 Wei Wang,1 Jiwen Zhong,1 YaYun Li,1 YanZi Cheng,1 Zhenjiao Su,1 Wei Zheng,1 Xiang-Dong Guan2 1Department of Critical Care Medicine, Zhuhai People’s Hospital, Zhuhai, Guangdong, 2Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China Purpose: To evaluate the clinical effects of magnesium sulfate in the treatment of diffuse axonal injury (DAI.Patients and methods: This study was a randomized, double-blind, placebo-controlled trial conducted in the First Affiliated Hospital of Sun Yat-sen University, Guangzhou and Zhuhai People’s Hospital, Zhuhai, two trauma center hospitals. A total of 128 patients suffered from DAI, with initial Glasgow coma scale (GCS scores of 3–8. They were randomly divided into two groups: magnesium sulfate treatment (MST group (n=64 and control group (n=64. The MST group received 250 µmol/kg magnesium sulfate intravenously 20 minutes after admission, followed by 750 µmol/kg magnesium sulfate intravenously daily for 5 days. The control group received standard management without MST. GCS scores and serum neuron-specific enolase values were measured and recorded at admission, and on days 3 and 7 after injury. Outcomes were determined by Glasgow outcome scale scores at discharge and at 3 months’ follow-up, respectively.Results: After the 7-day treatment, patients in the MST group, compared with those in the control group, had a lower serum neuron-specific enolase level (25.40±6.66 vs 29.58±7.32, respectively, P=0.001 and higher GCS score (8.23±2.72 vs 7.05±2.64, respectively, P=0.016. Although the length of stay and mortality did not differ between the groups in the intensive care unit, Glasgow outcome scale score was significantly lower in the MST group at discharge (3.30±1.35 vs 3.90±1.10, P=0.004 and 3 months after discharge (2.95±1.48 vs 3.66±1.44, P=0.009.Conclusion: Early treatment with magnesium sulfate

  13. Reduced axonal localization of a Caps2 splice variant impairs axonal release of BDNF and causes autistic-like behavior in mice. (United States)

    Sadakata, Tetsushi; Shinoda, Yo; Oka, Megumi; Sekine, Yukiko; Sato, Yumi; Saruta, Chihiro; Miwa, Hideki; Tanaka, Mika; Itohara, Shigeyoshi; Furuichi, Teiichi


    Ca(2)(+)-dependent activator protein for secretion 2 (CAPS2 or CADPS2) potently promotes the release of brain-derived neurotrophic factor (BDNF). A rare splicing form of CAPS2 with deletion of exon3 (dex3) was identified to be overrepresented in some patients with autism. Here, we generated Caps2-dex3 mice and verified a severe impairment in axonal Caps2-dex3 localization, contributing to a reduction in BDNF release from axons. In addition, circuit connectivity, measured by spine and interneuron density, was diminished globally. The collective effect of reduced axonal BDNF release during development was a striking and selective repertoire of deficits in social- and anxiety-related behaviors. Together, these findings represent a unique mouse model of a molecular mechanism linking BDNF-mediated coordination of brain development to autism-related behaviors and patient genotype.


    Institute of Scientific and Technical Information of China (English)

    Li Yuancheng; Zhao Liujun; Jiao Runhai


    Abstract This paper proposes a novel phishing web image segmentation algorithm which based on improving spectral clustering.Firstly,we construct a set of points which are composed of spatial location pixels and gray levels from a given image.Secondly,the data is clustered in spectral space of the similar matrix of the set points,in order to avoid the drawbacks of K-means algorithm in the conventional spectral clustering method that is sensitive to initial clustering centroids and convergence to local optimal solution,we introduce the clone operator,Cauthy mutation to enlarge the scale of clustering centers,quantum-inspired evolutionary algorithm to find the global optimal clustering centroids.Compared with phishing web image segmentation based on K-means,experimental results show that the segmentation performance of our method gains much improvement.Moreover,our method can convergence to global optimal solution and is better in accuracy of phishing web segmentation.

  15. Evolution of segmented strings

    CERN Document Server

    Gubser, Steven S


    I explain how to evolve segmented strings in de Sitter and anti-de Sitter spaces of any dimension in terms of forward-directed null displacements. The evolution is described entirely in terms of discrete hops which do not require a continuum spacetime. Moreover, the evolution rule is purely algebraic, so it can be defined not only on ordinary real de Sitter and anti-de Sitter, but also on the rational points of the quadratic equations that define these spaces. For three-dimensional anti-de Sitter space, a simpler evolution rule is possible that descends from the Wess-Zumino-Witten equations of motion. In this case, one may replace three-dimensional anti-de Sitter space by a non-compact discrete subgroup of SL(2,R) whose structure is related to the Pell equation. A discrete version of the BTZ black hole can be constructed as a quotient of this subgroup. This discrete black hole avoids the firewall paradox by a curious mechanism: even for large black holes, there are no points inside the horizon until one reach...

  16. The LOFT Ground Segment

    CERN Document Server

    Bozzo, E; Argan, A; Barret, D; Binko, P; Brandt, S; Cavazzuti, E; Courvoisier, T; Herder, J W den; Feroci, M; Ferrigno, C; Giommi, P; Götz, D; Guy, L; Hernanz, M; Zand, J J M in't; Klochkov, D; Kuulkers, E; Motch, C; Lumb, D; Papitto, A; Pittori, C; Rohlfs, R; Santangelo, A; Schmid, C; Schwope, A D; Smith, P J; Webb, N A; Wilms, J; Zane, S


    LOFT, the Large Observatory For X-ray Timing, was one of the ESA M3 mission candidates that completed their assessment phase at the end of 2013. LOFT is equipped with two instruments, the Large Area Detector (LAD) and the Wide Field Monitor (WFM). The LAD performs pointed observations of several targets per orbit (~90 minutes), providing roughly ~80 GB of proprietary data per day (the proprietary period will be 12 months). The WFM continuously monitors about 1/3 of the sky at a time and provides data for about ~100 sources a day, resulting in a total of ~20 GB of additional telemetry. The LOFT Burst alert System additionally identifies on-board bright impulsive events (e.g., Gamma-ray Bursts, GRBs) and broadcasts the corresponding position and trigger time to the ground using a dedicated system of ~15 VHF receivers. All WFM data are planned to be made public immediately. In this contribution we summarize the planned organization of the LOFT ground segment (GS), as established in the mission Yellow Book 1 . We...

  17. Segment Based Camera Calibration

    Institute of Scientific and Technical Information of China (English)

    马颂德; 魏国庆; 等


    The basic idea of calibrating a camera system in previous approaches is to determine camera parmeters by using a set of known 3D points as calibration reference.In this paper,we present a method of camera calibration in whih camera parameters are determined by a set of 3D lines.A set of constraints is derived on camea parameters in terms of perspective line mapping.Form these constraints,the same perspective transformation matrix as that for point mapping can be computed linearly.The minimum number of calibration lines is 6.This result generalizes that of Liu,Huang and Faugeras[12] for camera location determination in which at least 8 line correspondences are required for linear computation of camera location.Since line segments in an image can be located easily and more accurately than points,the use of lines as calibration reference tends to ease the computation in inage preprocessing and to improve calibration accuracy.Experimental results on the calibration along with stereo reconstruction are reported.

  18. Fiber Segment-Based Degradation Methods for a Finite Element-Informed Structural Brain Network (United States)


    would initially occur between 13% and 28% strain in a guinea pig optic nerve, and suggested an optimal threshold of 18% strain at a strain rate...Noels, L.; Jaffee, M. S.; Radovitzky, R. A. Computational Biology Modeling of Primary Blast Effects on the Central Nervous System . NeuroImage 2009...Tissue-Level Thresholds for Axonal Damage in an Experimental Model of Central Nervous System White Matter Injury. Journal of Biomechanical Engineering

  19. 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 newly...... formed axonal sprouts are able to induce a protracted myelination response in adult CNS. We show that newly formed axonal sprouts, induced by lesion of the entorhino-hippocampal perforant pathway, have the ability to induce a myelination response in stratum radiatum and lucidum C