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Sample records for spikes regulate dendritic

  1. Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes.

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    Zagha, Edward; Manita, Satoshi; Ross, William N; Rudy, Bernardo

    2010-06-01

    Purkinje cell dendrites are excitable structures with intrinsic and synaptic conductances contributing to the generation and propagation of electrical activity. Voltage-gated potassium channel subunit Kv3.3 is expressed in the distal dendrites of Purkinje cells. However, the functional relevance of this dendritic distribution is not understood. Moreover, mutations in Kv3.3 cause movement disorders in mice and cerebellar atrophy and ataxia in humans, emphasizing the importance of understanding the role of these channels. In this study, we explore functional implications of this dendritic channel expression and compare Purkinje cell dendritic excitability in wild-type and Kv3.3 knockout mice. We demonstrate enhanced excitability of Purkinje cell dendrites in Kv3.3 knockout mice, despite normal resting membrane properties. Combined data from local application pharmacology, voltage clamp analysis of ionic currents, and assessment of dendritic Ca(2+) spike threshold in Purkinje cells suggest a role for Kv3.3 channels in opposing Ca(2+) spike initiation. To study the physiological relevance of altered dendritic excitability, we measured [Ca(2+)](i) changes throughout the dendritic tree in response to climbing fiber activation. Ca(2+) signals were specifically enhanced in distal dendrites of Kv3.3 knockout Purkinje cells, suggesting a role for dendritic Kv3.3 channels in regulating propagation of electrical activity and Ca(2+) influx in distal dendrites. These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease.

  2. RAB-10 Regulates Dendritic Branching by Balancing Dendritic Transport

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    Taylor, Caitlin A.; Yan, Jing; Howell, Audrey S.; Dong, Xintong; Shen, Kang

    2015-01-01

    The construction of a large dendritic arbor requires robust growth and the precise delivery of membrane and protein cargoes to specific subcellular regions of the developing dendrite. How the microtubule-based vesicular trafficking and sorting systems are regulated to distribute these dendritic development factors throughout the dendrite is not well understood. Here we identify the small GTPase RAB-10 and the exocyst complex as critical regulators of dendrite morphogenesis and patterning in the C. elegans sensory neuron PVD. In rab-10 mutants, PVD dendritic branches are reduced in the posterior region of the cell but are excessive in the distal anterior region of the cell. We also demonstrate that the dendritic branch distribution within PVD depends on the balance between the molecular motors kinesin-1/UNC-116 and dynein, and we propose that RAB-10 regulates dendrite morphology by balancing the activity of these motors to appropriately distribute branching factors, including the transmembrane receptor DMA-1. PMID:26633194

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

    DEFF Research Database (Denmark)

    Hounsgaard, J; Kiehn, O

    1993-01-01

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

  4. The shaping of two distinct dendritic spikes by A-type voltage-gated K+ channels

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    Sungchil eYang

    2015-12-01

    Full Text Available Dendritic ion channels have been a subject of intense research in neuroscience because active ion channels in dendrites shape input signals. Ca2+-permeable channels including NMDA receptors (NMDARs have been implicated in supralinear dendritic integration, and the IA conductance in sublinear integration. Despite their essential roles in dendritic integration, it has remained uncertain whether these conductances coordinate with, or counteract, each other in the process of dendritic integration. To address this question, experiments were designed in hippocampal CA1 neurons with a recent 3D digital holography system that has shown excellent performance for spatial photoactivation. The results demonstrated a role of IA as a key contributor to two distinct dendritic spikes, low- and high-threshold Ca2+ spikes, through a preferential action of IA on Ca2+-permeable channel-mediated currents, over fast AMPAR-mediated currents. It is likely that the rapid kinetics of IA provides feed-forward inhibition to counteract the delayed Ca2+ channel-mediated dendritic excitability. This research reveals one dynamic ionic mechanism of dendritic integration, and may contribute to a new understanding of neuronal hyperexcitability embedded in several neural diseases such as epilepsy, fragile X syndrome and Alzheimer's disease.

  5. Dendritic nonlinearities are tuned for efficient spike-based computations in cortical circuits.

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    Ujfalussy, Balázs B; Makara, Judit K; Branco, Tiago; Lengyel, Máté

    2015-12-24

    Cortical neurons integrate thousands of synaptic inputs in their dendrites in highly nonlinear ways. It is unknown how these dendritic nonlinearities in individual cells contribute to computations at the level of neural circuits. Here, we show that dendritic nonlinearities are critical for the efficient integration of synaptic inputs in circuits performing analog computations with spiking neurons. We developed a theory that formalizes how a neuron's dendritic nonlinearity that is optimal for integrating synaptic inputs depends on the statistics of its presynaptic activity patterns. Based on their in vivo preynaptic population statistics (firing rates, membrane potential fluctuations, and correlations due to ensemble dynamics), our theory accurately predicted the responses of two different types of cortical pyramidal cells to patterned stimulation by two-photon glutamate uncaging. These results reveal a new computational principle underlying dendritic integration in cortical neurons by suggesting a functional link between cellular and systems--level properties of cortical circuits.

  6. Dendritic Actin Cytoskeleton: Structure, Functions, and Regulations

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    Anja Konietzny

    2017-05-01

    Full Text Available Actin is a versatile and ubiquitous cytoskeletal protein that plays a major role in both the establishment and the maintenance of neuronal polarity. For a long time, the most prominent roles that were attributed to actin in neurons were the movement of growth cones, polarized cargo sorting at the axon initial segment, and the dynamic plasticity of dendritic spines, since those compartments contain large accumulations of actin filaments (F-actin that can be readily visualized using electron- and fluorescence microscopy. With the development of super-resolution microscopy in the past few years, previously unknown structures of the actin cytoskeleton have been uncovered: a periodic lattice consisting of actin and spectrin seems to pervade not only the whole axon, but also dendrites and even the necks of dendritic spines. Apart from that striking feature, patches of F-actin and deep actin filament bundles have been described along the lengths of neurites. So far, research has been focused on the specific roles of actin in the axon, while it is becoming more and more apparent that in the dendrite, actin is not only confined to dendritic spines, but serves many additional and important functions. In this review, we focus on recent developments regarding the role of actin in dendrite morphology, the regulation of actin dynamics by internal and external factors, and the role of F-actin in dendritic protein trafficking.

  7. Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In Vivo

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    Christina Labarrera

    2018-04-01

    Full Text Available Summary: The excitability of the apical tuft of layer 5 pyramidal neurons is thought to play a crucial role in behavioral performance and synaptic plasticity. We show that the excitability of the apical tuft is sensitive to adrenergic neuromodulation. Using two-photon dendritic Ca2+ imaging and in vivo whole-cell and extracellular recordings in awake mice, we show that application of the α2A-adrenoceptor agonist guanfacine increases the probability of dendritic Ca2+ events in the tuft and lowers the threshold for dendritic Ca2+ spikes. We further show that these effects are likely to be mediated by the dendritic current Ih. Modulation of Ih in a realistic compartmental model controlled both the generation and magnitude of dendritic calcium spikes in the apical tuft. These findings suggest that adrenergic neuromodulation may affect cognitive processes such as sensory integration, attention, and working memory by regulating the sensitivity of layer 5 pyramidal neurons to top-down inputs. : Labarrera et al. show that noradrenergic neuromodulation can be an effective way to regulate the interaction between different input streams of information processed by an individual neuron. These findings may have important implications for our understanding of how adrenergic neuromodulation affects sensory integration, attention, and working memory. Keywords: cortical layer 5 pyramidal neuron, dendrites, norepinephrine, HCN, Ih, Ca2+ spike, apical tuft, guanfacine, ADHD, somatosensory cortex

  8. Regulation of dendrite growth and maintenance by exocytosis

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    Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

    2015-01-01

    Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential req...

  9. Timed Synaptic Inhibition Shapes NMDA Spikes, Influencing Local Dendritic Processing and Global I/O Properties of Cortical Neurons

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    Michael Doron

    2017-11-01

    Full Text Available The NMDA spike is a long-lasting nonlinear phenomenon initiated locally in the dendritic branches of a variety of cortical neurons. It plays a key role in synaptic plasticity and in single-neuron computations. Combining dynamic system theory and computational approaches, we now explore how the timing of synaptic inhibition affects the NMDA spike and its associated membrane current. When impinging on its early phase, individual inhibitory synapses strongly, but transiently, dampen the NMDA spike; later inhibition prematurely terminates it. A single inhibitory synapse reduces the NMDA-mediated Ca2+ current, a key player in plasticity, by up to 45%. NMDA spikes in distal dendritic branches/spines are longer-lasting and more resilient to inhibition, enhancing synaptic plasticity at these branches. We conclude that NMDA spikes are highly sensitive to dendritic inhibition; sparse weak inhibition can finely tune synaptic plasticity both locally at the dendritic branch level and globally at the level of the neuron’s output.

  10. Regulation of dendrite growth and maintenance by exocytosis

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    Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

    2015-01-01

    ABSTRACT Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential requirements for exocytosis in the growth and maintenance of different dendritic compartments. Rop promotes dendrite growth together with the exocyst, an octameric protein complex involved in tethering vesicles to the plasma membrane, with Rop–exocyst complexes and exocytosis predominating in primary dendrites over terminal dendrites. By contrast, membrane-associated proteins readily diffuse from primary dendrites into terminals, but not in the reverse direction, suggesting that diffusion, rather than targeted exocytosis, supplies membranous material for terminal dendritic growth, revealing key differences in the distribution of materials to these expanding dendritic compartments. PMID:26483382

  11. Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell.

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    Michael J Schachter

    2010-08-01

    Full Text Available The On-Off direction-selective ganglion cell (DSGC in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell's dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within

  12. Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell.

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    Schachter, Michael J; Oesch, Nicholas; Smith, Robert G; Taylor, W Rowland

    2010-08-19

    The On-Off direction-selective ganglion cell (DSGC) in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials) are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS) in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell's dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within cortical circuitry.

  13. Epigenetic regulation of axon and dendrite growth

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    Ephraim F Trakhtenberg

    2012-03-01

    Full Text Available Neuroregenerative therapies for central nervous system (CNS injury, neurodegenerative disease, or stroke require axons of damaged neurons to grow and reinnervate their targets. However, mature mammalian CNS neurons do not regenerate their axons, limiting recovery in these diseases (Yiu and He, 2006. CNS’ regenerative failure may be attributable to the development of an inhibitory CNS environment by glial-associated inhibitory molecules (Yiu and He, 2006, and by various cell-autonomous factors (Sun and He, 2010. Intrinsic axon growth ability also declines developmentally (Li et al., 1995; Goldberg et al., 2002; Bouslama-Oueghlani et al., 2003; Blackmore and Letourneau, 2006 and is dependent on transcription (Moore et al., 2009. Although neurons’ intrinsic capacity for axon growth may depend in part on the panoply of expressed transcription factors (Moore and Goldberg, 2011, epigenetic factors such as the accessibility of DNA and organization of chromatin are required for downstream genes to be transcribed. Thus a potential approach to overcoming regenerative failure focuses on the epigenetic mechanisms regulating regenerative gene expression in the CNS. Here we review molecular mechanisms regulating the epigenetic state of DNA through chromatin modifications, their implications for regulating axon and dendrite growth, and important new directions for this field of study.

  14. Spiking Neural Classifier with Lumped Dendritic Nonlinearity and Binary Synapses: A Current Mode VLSI Implementation and Analysis.

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    Bhaduri, Aritra; Banerjee, Amitava; Roy, Subhrajit; Kar, Sougata; Basu, Arindam

    2018-03-01

    We present a neuromorphic current mode implementation of a spiking neural classifier with lumped square law dendritic nonlinearity. It has been shown previously in software simulations that such a system with binary synapses can be trained with structural plasticity algorithms to achieve comparable classification accuracy with fewer synaptic resources than conventional algorithms. We show that even in real analog systems with manufacturing imperfections (CV of 23.5% and 14.4% for dendritic branch gains and leaks respectively), this network is able to produce comparable results with fewer synaptic resources. The chip fabricated in [Formula: see text]m complementary metal oxide semiconductor has eight dendrites per cell and uses two opposing cells per class to cancel common-mode inputs. The chip can operate down to a [Formula: see text] V and dissipates 19 nW of static power per neuronal cell and [Formula: see text] 125 pJ/spike. For two-class classification problems of high-dimensional rate encoded binary patterns, the hardware achieves comparable performance as software implementation of the same with only about a 0.5% reduction in accuracy. On two UCI data sets, the IC integrated circuit has classification accuracy comparable to standard machine learners like support vector machines and extreme learning machines while using two to five times binary synapses. We also show that the system can operate on mean rate encoded spike patterns, as well as short bursts of spikes. To the best of our knowledge, this is the first attempt in hardware to perform classification exploiting dendritic properties and binary synapses.

  15. A novel role of dendritic gap junction and mechanisms underlying its interaction with thalamocortical conductance in fast spiking inhibitory neurons

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    Sun Qian-Quan

    2009-10-01

    Full Text Available Abstract Background Little is known about the roles of dendritic gap junctions (GJs of inhibitory interneurons in modulating temporal properties of sensory induced responses in sensory cortices. Electrophysiological dual patch-clamp recording and computational simulation methods were used in combination to examine a novel role of GJs in sensory mediated feed-forward inhibitory responses in barrel cortex layer IV and its underlying mechanisms. Results Under physiological conditions, excitatory post-junctional potentials (EPJPs interact with thalamocortical (TC inputs within an unprecedented few milliseconds (i.e. over 200 Hz to enhance the firing probability and synchrony of coupled fast-spiking (FS cells. Dendritic GJ coupling allows fourfold increase in synchrony and a significant enhancement in spike transmission efficacy in excitatory spiny stellate cells. The model revealed the following novel mechanisms: 1 rapid capacitive current (Icap underlies the activation of voltage-gated sodium channels; 2 there was less than 2 milliseconds in which the Icap underlying TC input and EPJP was coupled effectively; 3 cells with dendritic GJs had larger input conductance and smaller membrane response to weaker inputs; 4 synchrony in inhibitory networks by GJ coupling leads to reduced sporadic lateral inhibition and increased TC transmission efficacy. Conclusion Dendritic GJs of neocortical inhibitory networks can have very powerful effects in modulating the strength and the temporal properties of sensory induced feed-forward inhibitory and excitatory responses at a very high frequency band (>200 Hz. Rapid capacitive currents are identified as main mechanisms underlying interaction between two transient synaptic conductances.

  16. Fast Na+ spike generation in dendrites of guinea-pig substantia nigra pars compacta neurons

    DEFF Research Database (Denmark)

    Nedergaard, S; Hounsgaard, Jørn Dybkjær

    1996-01-01

    were not inhibited in the presence of glutamate receptor antagonists or during Ca2+ channel blockade. Blockers of gap junctional conductance (sodium propionate, octanol and halothane) did not affect the field-induced spikes. The spike generation was highly sensitive to changes in membrane conductance...

  17. Converging effects of Ginkgo biloba extract at the level of transmitter release, NMDA and sodium currents and dendritic spikes.

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    Szasz, Bernadett K; Lenkey, Nora; Barth, Albert M; Mike, Arpad; Somogyvari, Zsolt; Farkas, Orsolya; Lendvai, Balazs

    2008-08-01

    In this study, an attempt was made to integrate the effects of GINKGO BILOBA extract (GBE) in different experimental systems (IN VITRO cochlea, brain slice preparations and cortical cell culture) to elucidate whether these processes converge to promote neuroprotection or interfere with normal neural function. GBE increased the release of dopamine in the cochlea. NMDA-evoked currents were dose-dependently inhibited by rapid GBE application in cultured cortical cells. GBE moderately inhibited Na+ channels at depolarised holding potential in cortical cells. These inhibitory effects by GBE may sufficiently contribute to the prevention of excitotoxic damage in neurons. However, these channels also interact with memory formation at the cellular level. The lack of effect by GBE on dendritic spike initiation in neocortical layer 5 pyramidal neurons indicates that the integrative functions may remain intact during the inhibitory actions of GBE.

  18. LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive endosomes.

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    Takano, Tetsuya; Urushibara, Tomoki; Yoshioka, Nozomu; Saito, Taro; Fukuda, Mitsunori; Tomomura, Mineko; Hisanaga, Shin-Ichi

    2014-06-01

    Neurons extend two types of neurites-axons and dendrites-that differ in structure and function. Although it is well understood that the cytoskeleton plays a pivotal role in neurite differentiation and extension, the mechanisms by which membrane components are supplied to growing axons or dendrites is largely unknown. We previously reported that the membrane supply to axons is regulated by lemur kinase 1 (LMTK1) through Rab11A-positive endosomes. Here we investigate the role of LMTK1 in dendrite formation. Down-regulation of LMTK1 increases dendrite growth and branching of cerebral cortical neurons in vitro and in vivo. LMTK1 knockout significantly enhances the prevalence, velocity, and run length of anterograde movement of Rab11A-positive endosomes to levels similar to those expressing constitutively active Rab11A-Q70L. Rab11A-positive endosome dynamics also increases in the cell body and growth cone of LMTK1-deficient neurons. Moreover, a nonphosphorylatable LMTK1 mutant (Ser34Ala, a Cdk5 phosphorylation site) dramatically promotes dendrite growth. Thus LMTK1 negatively controls dendritic formation by regulating Rab11A-positive endosomal trafficking in a Cdk5-dependent manner, indicating the Cdk5-LMTK1-Rab11A pathway as a regulatory mechanism of dendrite development as well as axon outgrowth. © 2014 Takano et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  19. Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

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    Shan Meltzer

    2017-10-01

    Full Text Available Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas, which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.

  20. Dendritic cells regulate angiogenesis associated with liver fibrogenesis.

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    Blois, Sandra M; Piccioni, Flavia; Freitag, Nancy; Tirado-González, Irene; Moschansky, Petra; Lloyd, Rodrigo; Hensel-Wiegel, Karin; Rose, Matthias; Garcia, Mariana G; Alaniz, Laura D; Mazzolini, Guillermo

    2014-01-01

    During liver fibrogenesis the immune response and angiogenesis process are fine-tuned resulting in activation of hepatic stellate cells that produce an excess of extracellular matrix proteins. Dendritic cells (DC) play a central role modulating the liver immunity and have recently been implicated to favour fibrosis regression; although their ability to influence the development of fibrogenesis is unknown. Therefore, we explored whether the depletion of DC during early stages of liver injury has an impact in the development of fibrogenesis. Using the CD11c.DTR transgenic mice, DC were depleted in two experimental models of fibrosis in vivo. The effect of anti-angiogenic therapy was tested during early stages of liver fibrogenesis. DC depletion accelerates the development of fibrosis and as a consequence, the angiogenesis process is boosted. We observed up-regulation of pro-angiogenic factors together with an enhanced vascular endothelial growth factor (VEGF) bioavailability, mainly evidenced by the decrease of anti-angiogenic VEGF receptor 1 (also known as sFlt-1) levels. Interestingly, fibrogenesis process enhanced the expression of Flt-1 on hepatic DC and administration of sFlt-1 was sufficient to abrogate the acceleration of fibrogenesis upon DC depletion. Thus, DC emerge as novel players during the development of liver fibrosis regulating the angiogenesis process and thereby influencing fibrogenesis.

  1. Non-centered spike-triggered covariance analysis reveals neurotrophin-3 as a developmental regulator of receptive field properties of ON-OFF retinal ganglion cells.

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    Donald R Cantrell

    2010-10-01

    Full Text Available The functional separation of ON and OFF pathways, one of the fundamental features of the visual system, starts in the retina. During postnatal development, some retinal ganglion cells (RGCs whose dendrites arborize in both ON and OFF sublaminae of the inner plexiform layer transform into RGCs with dendrites that monostratify in either the ON or OFF sublamina, acquiring final dendritic morphology in a subtype-dependent manner. Little is known about how the receptive field (RF properties of ON, OFF, and ON-OFF RGCs mature during this time because of the lack of a reliable and efficient method to classify RGCs into these subtypes. To address this deficiency, we developed an innovative variant of Spike Triggered Covariance (STC analysis, which we term Spike Triggered Covariance - Non-Centered (STC-NC analysis. Using a multi-electrode array (MEA, we recorded the responses of a large population of mouse RGCs to a Gaussian white noise stimulus. As expected, the Spike-Triggered Average (STA fails to identify responses driven by symmetric static nonlinearities such as those that underlie ON-OFF center RGC behavior. The STC-NC technique, in contrast, provides an efficient means to identify ON-OFF responses and quantify their RF center sizes accurately. Using this new tool, we find that RGCs gradually develop sensitivity to focal stimulation after eye opening, that the percentage of ON-OFF center cells decreases with age, and that RF centers of ON and ON-OFF cells become smaller. Importantly, we demonstrate for the first time that neurotrophin-3 (NT-3 regulates the development of physiological properties of ON-OFF center RGCs. Overexpression of NT-3 leads to the precocious maturation of RGC responsiveness and accelerates the developmental decrease of RF center size in ON-OFF cells. In summary, our study introduces STC-NC analysis which successfully identifies subtype RGCs and demonstrates how RF development relates to a neurotrophic driver in the retina.

  2. Spike timing regulation on the millisecond scale by distributed synaptic plasticity at the cerebellum input stage: a simulation study

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    Jesus A Garrido

    2013-05-01

    Full Text Available The way long-term synaptic plasticity regulates neuronal spike patterns is not completely understood. This issue is especially relevant for the cerebellum, which is endowed with several forms of long-term synaptic plasticity and has been predicted to operate as a timing and a learning machine. Here we have used a computational model to simulate the impact of multiple distributed synaptic weights in the cerebellar granular layer network. In response to mossy fiber bursts, synaptic weights at multiple connections played a crucial role to regulate spike number and positioning in granule cells. The weight at mossy fiber to granule cell synapses regulated the delay of the first spike and the weight at mossy fiber and parallel fiber to Golgi cell synapses regulated the duration of the time-window during which the first-spike could be emitted. Moreover, the weights of synapses controlling Golgi cell activation regulated the intensity of granule cell inhibition and therefore the number of spikes that could be emitted. First spike timing was regulated with millisecond precision and the number of spikes ranged from 0 to 3. Interestingly, different combinations of synaptic weights optimized either first-spike timing precision or spike number, efficiently controlling transmission and filtering properties. These results predict that distributed synaptic plasticity regulates the emission of quasi-digital spike patterns on the millisecond time scale and allows the cerebellar granular layer to flexibly control burst transmission along the mossy fiber pathway.

  3. PINK1 regulates mitochondrial trafficking in dendrites of cortical neurons through mitochondrial PKA.

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    Das Banerjee, Tania; Dagda, Raul Y; Dagda, Marisela; Chu, Charleen T; Rice, Monica; Vazquez-Mayorga, Emmanuel; Dagda, Ruben K

    2017-08-01

    Mitochondrial Protein Kinase A (PKA) and PTEN-induced kinase 1 (PINK1), which is linked to Parkinson's disease, are two neuroprotective serine/threonine kinases that regulate dendrite remodeling and mitochondrial function. We have previously shown that PINK1 regulates dendrite morphology by enhancing PKA activity. Here, we show the molecular mechanisms by which PINK1 and PKA in the mitochondrion interact to regulate dendrite remodeling, mitochondrial morphology, content, and trafficking in dendrites. PINK1-deficient cortical neurons exhibit impaired mitochondrial trafficking, reduced mitochondrial content, fragmented mitochondria, and a reduction in dendrite outgrowth compared to wild-type neurons. Transient expression of wild-type, but not a PKA-binding-deficient mutant of the PKA-mitochondrial scaffold dual-specificity A Kinase Anchoring Protein 1 (D-AKAP1), restores mitochondrial trafficking, morphology, and content in dendrites of PINK1-deficient cortical neurons suggesting that recruiting PKA to the mitochondrion reverses mitochondrial pathology in dendrites induced by loss of PINK1. Mechanistically, full-length and cleaved forms of PINK1 increase the binding of the regulatory subunit β of PKA (PKA/RIIβ) to D-AKAP1 to enhance the autocatalytic-mediated phosphorylation of PKA/RIIβ and PKA activity. D-AKAP1/PKA governs mitochondrial trafficking in dendrites via the Miro-2/TRAK2 complex and by increasing the phosphorylation of Miro-2. Our study identifies a new role of D-AKAP1 in regulating mitochondrial trafficking through Miro-2, and supports a model in which PINK1 and mitochondrial PKA participate in a similar neuroprotective signaling pathway to maintain dendrite connectivity. © 2017 International Society for Neurochemistry.

  4. Dendritic branching of olfactory bulb mitral and tufted cells: regulation by TrkB.

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    Fumiaki Imamura

    2009-08-01

    Full Text Available Projection neurons of mammalian olfactory bulb (OB, mitral and tufted cells, have dendrites whose morphologies are specifically differentiated for efficient odor information processing. The apical dendrite extends radially and arborizes in single glomerulus where it receives primary input from olfactory sensory neurons that express the same odor receptor. The lateral dendrites extend horizontally in the external plexiform layer and make reciprocal dendrodendritic synapses with granule cells, which moderate mitral/tufted cell activity. The molecular mechanisms regulating dendritic development of mitral/tufted cells is one of the unsolved important problems in the olfactory system. Here, we focused on TrkB receptors to test the hypothesis that neurotrophin-mediate mechanisms contributed to dendritic differentiation of OB mitral/tufted cells.With immunohistochemical analysis, we found that the TrkB neurotrophin receptor is expressed by both apical and lateral dendrites of mitral/tufted cells and that expression is evident during the early postnatal days when these dendrites exhibit their most robust growth and differentiation. To examine the effect of TrkB activation on mitral/tufted cell dendritic development, we cultured OB neurons. When BDNF or NT4 were introduced into the cultures, there was a significant increase in the number of primary neurites and branching points among the mitral/tufted cells. Moreover, BDNF facilitated filopodial extension along the neurites of mitral/tufted cells.In this report, we show for the first time that TrkB activation stimulates the dendritic branching of mitral/tufted cells in developing OB. This suggests that arborization of the apical dendrite in a glomerulus is under the tight regulation of TrkB activation.

  5. VCP and ATL1 regulate endoplasmic reticulum and protein synthesis for dendritic spine formation.

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    Shih, Yu-Tzu; Hsueh, Yi-Ping

    2016-03-17

    Imbalanced protein homeostasis, such as excessive protein synthesis and protein aggregation, is a pathogenic hallmark of a range of neurological disorders. Here, using expression of mutant proteins, a knockdown approach and disease mutation knockin mice, we show that VCP (valosin-containing protein), together with its cofactor P47 and the endoplasmic reticulum (ER) morphology regulator ATL1 (Atlastin-1), regulates tubular ER formation and influences the efficiency of protein synthesis to control dendritic spine formation in neurons. Strengthening the significance of protein synthesis in dendritic spinogenesis, the translation blocker cyclohexamide and the mTOR inhibitor rapamycin reduce dendritic spine density, while a leucine supplement that increases protein synthesis ameliorates the dendritic spine defects caused by Vcp and Atl1 deficiencies. Because VCP and ATL1 are the causative genes of several neurodegenerative and neurodevelopmental disorders, we suggest that impaired ER formation and inefficient protein synthesis are significant in the pathogenesis of multiple neurological disorders.

  6. Estrogen levels regulate the subcellular distribution of phosphorylated Akt in hippocampal CA1 dendrites.

    Science.gov (United States)

    Znamensky, Vladimir; Akama, Keith T; McEwen, Bruce S; Milner, Teresa A

    2003-03-15

    In addition to genomic pathways, estrogens may regulate gene expression by activating specific signal transduction pathways, such as that involving phosphatidylinositol 3-kinase (PI3-K) and the subsequent phosphorylation of Akt (protein kinase B). The Akt pathway regulates various cellular events, including the initiation of protein synthesis. Our previous studies showed that synaptogenesis in hippocampal CA1 pyramidal cell dendritic spines is highest when brain estrogen levels are highest. To address the role of Akt in this process, the subcellular distribution of phosphorylated Akt immunoreactivity (pAkt-I) in the hippocampus of female rats across the estrous cycle and male rats was analyzed by light microscopy (LM) and electron microscopy (EM). By LM, the density of pAkt-I in stratum radiatum of CA1 was significantly higher in proestrus rats (or in estrogen-supplemented ovariectomized females) compared with diestrus, estrus, or male rats. By EM, pAkt-I was found throughout the shafts and in select spines of stratum radiatum dendrites. Quantitative ultrastructural analysis identifying pAkt-I with immunogold particles revealed that proestrus rats compared with diestrus, estrus, and male rats contained significantly higher pAkt-I associated with (1) dendritic spines (both cytoplasm and plasmalemma), (2) spine apparati located within 0.1 microm of dendritic spine bases, (3) endoplasmic reticula and polyribosomes in the cytoplasm of dendritic shafts, and (4) the plasmalemma of dendritic shafts. These findings suggest that estrogens may regulate spine formation in CA1 pyramidal neurons via Akt-mediated signaling events.

  7. Interleukin 20 regulates dendritic cell migration and expression of co-stimulatory molecules

    DEFF Research Database (Denmark)

    Bech, Rikke; Jalilian, Babak; Agger, Ralf

    2016-01-01

    BACKGROUND: Psoriasis is an inflammatory disease characterized by leukocyte skin infiltration. Interestingly, recent works suggest that the migration of dendritic cells (DCs) is abnormal in psoriatic skin. DCs have significant role in regulating the function of T lymphocytes, at least in part...... influenced by the local environment of cytokines. In psoriatic skin lesions the expression of IL-20 is highly up-regulated. It is unclear if this cytokine has any influence on DCs. METHODS: Here, we investigated the influence of IL-20 in monocyte-derived dendritic cell (MDDCs) in vitro. This work addressed...

  8. Intestinal dendritic cells in the regulation of mucosal immunity

    DEFF Research Database (Denmark)

    Bekiaris, Vasileios; Persson, Emma K.; Agace, William Winston

    2014-01-01

    immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive....... The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality...

  9. Histone Deacetylase Rpd3 Regulates Olfactory Projection Neuron Dendrite Targeting via the Transcription Factor Prospero

    Science.gov (United States)

    Tea, Joy S.; Chihara, Takahiro; Luo, Liqun

    2010-01-01

    Compared to the mechanisms of axon guidance, relatively little is known about the transcriptional control of dendrite guidance. The Drosophila olfactory system with its stereotyped organization provides an excellent model to study the transcriptional control of dendrite wiring specificity. Each projection neuron (PN) targets its dendrites to a specific glomerulus in the antennal lobe and its axon stereotypically to higher brain centers. Using a forward genetic screen, we identified a mutation in Rpd3 that disrupts PN targeting specificity. Rpd3 encodes a class I histone deacetylase (HDAC) homologous to mammalian HDAC1 and HDAC2. Rpd3−/− PN dendrites that normally target to a dorsolateral glomerulus mistarget to medial glomeruli in the antennal lobe, and axons exhibit a severe overbranching phenotype. These phenotypes can be rescued by postmitotic expression of Rpd3 but not HDAC3, the only other class I HDAC in Drosophila. Furthermore, disruption of the atypical homeodomain transcription factor Prospero (Pros) yields similar phenotypes, which can be rescued by Pros expression in postmitotic neurons. Strikingly, overexpression of Pros can suppress Rpd3−/− phenotypes. Our study suggests a specific function for the general chromatin remodeling factor Rpd3 in regulating dendrite targeting in neurons, largely through the postmitotic action of the Pros transcription factor. PMID:20660276

  10. Dendritic Cytoskeletal Architecture Is Modulated by Combinatorial Transcriptional Regulation in Drosophila melanogaster.

    Science.gov (United States)

    Das, Ravi; Bhattacharjee, Shatabdi; Patel, Atit A; Harris, Jenna M; Bhattacharya, Surajit; Letcher, Jamin M; Clark, Sarah G; Nanda, Sumit; Iyer, Eswar Prasad R; Ascoli, Giorgio A; Cox, Daniel N

    2017-12-01

    Transcription factors (TFs) have emerged as essential cell autonomous mediators of subtype specific dendritogenesis; however, the downstream effectors of these TFs remain largely unknown, as are the cellular events that TFs control to direct morphological change. As dendritic morphology is largely dictated by the organization of the actin and microtubule (MT) cytoskeletons, elucidating TF-mediated cytoskeletal regulatory programs is key to understanding molecular control of diverse dendritic morphologies. Previous studies in Drosophila melanogaster have demonstrated that the conserved TFs Cut and Knot exert combinatorial control over aspects of dendritic cytoskeleton development, promoting actin and MT-based arbor morphology, respectively. To investigate transcriptional targets of Cut and/or Knot regulation, we conducted systematic neurogenomic studies, coupled with in vivo genetic screens utilizing multi-fluor cytoskeletal and membrane marker reporters. These analyses identified a host of putative Cut and/or Knot effector molecules, and a subset of these putative TF targets converge on modulating dendritic cytoskeletal architecture, which are grouped into three major phenotypic categories, based upon neuromorphometric analyses: complexity enhancer, complexity shifter, and complexity suppressor. Complexity enhancer genes normally function to promote higher order dendritic growth and branching with variable effects on MT stabilization and F-actin organization, whereas complexity shifter and complexity suppressor genes normally function in regulating proximal-distal branching distribution or in restricting higher order branching complexity, respectively, with spatially restricted impacts on the dendritic cytoskeleton. Collectively, we implicate novel genes and cellular programs by which TFs distinctly and combinatorially govern dendritogenesis via cytoskeletal modulation. Copyright © 2017 by the Genetics Society of America.

  11. Sphingosine 1-phosphate as a novel immune regulator of dendritic ...

    Indian Academy of Sciences (India)

    Although originally described as an intracellular second messenger, sphingosine 1-phosphate (S1P) has recently been shown to be involved in several physiological and pathological functions as an extracellular mediator. S1P receptors are widely expressed and thought to regulate important functions in cell signalling.

  12. Suppressive effects of primed eosinophils on single epicutaneous sensitization through regulation of dermal dendritic cells.

    Science.gov (United States)

    Lin, Jing-Yi; Ta, Yng-Cun; Liu, I-Lin; Chen, Hsi-Wen; Wang, Li-Fang

    2016-07-01

    Eosinophils are multifunctional innate immune cells involved in many aspects of innate and adaptive immunity. Epicutaneous sensitization with protein allergen is an important sensitization route for atopic dermatitis. In this study, using a murine single protein-patch model, we show that eosinophils of a primed status accumulate in draining lymph nodes following single epicutaneous sensitization. Further, depletion of eosinophils results in enhancement of the induced Th1/Th2 immune responses, whereas IL-5-induced hypereosinophilia suppresses these responses. Mechanistically, primed eosinophils cause a reduction in the numbers and activation status of dermal dendritic cells in draining lymph nodes. Collectively, these results demonstrate that primed eosinophils exert suppressive effects on single epicutaneous sensitization through regulation of dermal dendritic cells. Thus, these findings highlight the critical roles of eosinophils in the pathogenesis of atopic dermatitis with important clinical implications for the prevention of allergen sensitization. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. HIV-1 tat promotes integrin-mediated HIV transmission to dendritic cells by binding Env spikes and competes neutralization by anti-HIV antibodies.

    Directory of Open Access Journals (Sweden)

    Paolo Monini

    Full Text Available Use of Env in HIV vaccine development has been disappointing. Here we show that, in the presence of a biologically active Tat subunit vaccine, a trimeric Env protein prevents in monkeys virus spread from the portal of entry to regional lymph nodes. This appears to be due to specific interactions between Tat and Env spikes that form a novel virus entry complex favoring R5 or X4 virus entry and productive infection of dendritic cells (DCs via an integrin-mediated pathway. These Tat effects do not require Tat-transactivation activity and are blocked by anti-integrin antibodies (Abs. Productive DC infection promoted by Tat is associated with a highly efficient virus transmission to T cells. In the Tat/Env complex the cysteine-rich region of Tat engages the Env V3 loop, whereas the Tat RGD sequence remains free and directs the virus to integrins present on DCs. V2 loop deletion, which unshields the CCR5 binding region of Env, increases Tat/Env complex stability. Of note, binding of Tat to Env abolishes neutralization of Env entry or infection of DCs by anti-HIV sera lacking anti-Tat Abs, which are seldom present in natural infection. This is reversed, and neutralization further enhanced, by HIV sera containing anti-Tat Abs such as those from asymptomatic or Tat-vaccinated patients, or by sera from the Tat/Env vaccinated monkeys. Thus, both anti-Tat and anti-Env Abs are required for efficient HIV neutralization. These data suggest that the Tat/Env interaction increases HIV acquisition and spreading, as a mechanism evolved by the virus to escape anti-Env neutralizing Abs. This may explain the low effectiveness of Env-based vaccines, which are also unlikely to elicit Abs against new Env epitopes exposed by the Tat/Env interaction. As Tat also binds Envs from different clades, new vaccine strategies should exploit the Tat/Env interaction for both preventative and therapeutic interventions.

  14. Activity-Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines.

    Science.gov (United States)

    Padamsey, Zahid; McGuinness, Lindsay; Bardo, Scott J; Reinhart, Marcia; Tong, Rudi; Hedegaard, Anne; Hart, Michael L; Emptage, Nigel J

    2017-01-04

    Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function as Ca 2+ stores. Here we examined the function of these stores in hippocampal pyramidal neurons. We found that back-propagating action potentials (bpAPs) could elicit Ca 2+ release from lysosomes in the dendrites. This Ca 2+ release triggered the fusion of lysosomes with the plasma membrane, resulting in the release of Cathepsin B. Cathepsin B increased the activity of matrix metalloproteinase 9 (MMP-9), an enzyme involved in extracellular matrix (ECM) remodelling and synaptic plasticity. Inhibition of either lysosomal Ca 2+ signaling or Cathepsin B release prevented the maintenance of dendritic spine growth induced by Hebbian activity. This impairment could be rescued by exogenous application of active MMP-9. Our findings suggest that activity-dependent exocytosis of Cathepsin B from lysosomes regulates the long-term structural plasticity of dendritic spines by triggering MMP-9 activation and ECM remodelling. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  15. Npas4 Regulates Mdm2 and thus Dcx in Experience-Dependent Dendritic Spine Development of Newborn Olfactory Bulb Interneurons

    Directory of Open Access Journals (Sweden)

    Sei-ichi Yoshihara

    2014-08-01

    Full Text Available Sensory experience regulates the development of various brain structures, including the cortex, hippocampus, and olfactory bulb (OB. Little is known about how sensory experience regulates the dendritic spine development of OB interneurons, such as granule cells (GCs, although it is well studied in mitral/tufted cells. Here, we identify a transcription factor, Npas4, which is expressed in OB GCs immediately after sensory input and is required for dendritic spine formation. Npas4 overexpression in OB GCs increases dendritic spine density, even under sensory deprivation, and rescues reduction of dendrite spine density in the Npas4 knockout OB. Furthermore, loss of Npas4 upregulates expression of the E3-ubiquitin ligase Mdm2, which ubiquitinates a microtubule-associated protein Dcx. This leads to reduction in the dendritic spine density of OB GCs. Together, these findings suggest that Npas4 regulates Mdm2 expression to ubiquitinate and degrade Dcx during dendritic spine development in newborn OB GCs after sensory experience.

  16. Phosphorylation of CRMP2 by Cdk5 Regulates Dendritic Spine Development of Cortical Neuron in the Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Xiaohua Jin

    2016-01-01

    Full Text Available Proper density and morphology of dendritic spines are important for higher brain functions such as learning and memory. However, our knowledge about molecular mechanisms that regulate the development and maintenance of dendritic spines is limited. We recently reported that cyclin-dependent kinase 5 (Cdk5 is required for the development and maintenance of dendritic spines of cortical neurons in the mouse brain. Previous in vitro studies have suggested the involvement of Cdk5 substrates in the formation of dendritic spines; however, their role in spine development has not been tested in vivo. Here, we demonstrate that Cdk5 phosphorylates collapsin response mediator protein 2 (CRMP2 in the dendritic spines of cultured hippocampal neurons and in vivo in the mouse brain. When we eliminated CRMP2 phosphorylation in CRMP2KI/KI mice, the densities of dendritic spines significantly decreased in hippocampal CA1 pyramidal neurons in the mouse brain. These results indicate that phosphorylation of CRMP2 by Cdk5 is important for dendritic spine development in cortical neurons in the mouse hippocampus.

  17. Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells

    OpenAIRE

    Walseng, Even; Furuta, Kazuyuki; Bosch, Berta; Weih, Karis A.; Matsuki, Yohei; Bakke, Oddmund; Ishido, Satoshi; Roche, Paul A.

    2010-01-01

    The expression and turnover of MHC class II-peptide complexes (pMHC-II) on the surface of dendritic cells (DCs) is essential for their ability to activate CD4 T cells efficiently. The half-life of surface pMHC-II is significantly greater in activated (mature) DCs than in resting (immature) DCs, but the molecular mechanism leading to this difference remains unknown. We now show that ubiquitination of pMHC-II by the E3 ubiquitin ligase membrane-associated RING-CH 1 (March-I) regulates surface e...

  18. Redox regulation of stress signals: possible roles of dendritic stellate TRX producer cells (DST cell types).

    Science.gov (United States)

    Yodoi, Junji; Nakamura, Hajime; Masutani, Hiroshi

    2002-01-01

    Thioredoxin (TRX) is a 12 kDa protein with redox-active dithiol (Cys-Gly-Pro-Cys) in the active site. TRX is induced by a variety of stresses including viral infection and inflammation. The promoter sequences of the TRX gene contain a series of stress-responsive elements including ORE, ARE, XRE, CRE and SP-1. TRX promotes DNA binding of transcription factors such as NF-kappaB, AP-1 and p53. TRX interacts with target proteins modulating the activity of those proteins. We have identified TRX binding protein-2 (TBP-2), which was identical to vitamin D3 up-regulated protein 1 (VDUP1). Potential action of TBP-2/VDUP1 as a redox-sensitive tumor suppressor will be discussed. There is accumulating evidence for the involvement of TRX in the protection against infectious and inflammatory disorders. We will discuss the role of TRX-dependent redox regulation of the host defense mechanism, in particular its relation to the emerging concept of constitutive and/or inducible TRX on special cell types with dendritic and stellate morphology in the immune, endocrine and nervous systems, which we provisionally designate as dendritic stellate TRX producer cells (DST cell types).

  19. DMPD: Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derivedinflammatory mediators. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available l) (.csml) Show Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derivedinflammatory mediator...egulation of dendritic cell-derivedinflammatory mediators. Authors Harizi H, Gualde N. Publication Cell Mol ...16978535 Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derivedinflammatory mediat...ors. Harizi H, Gualde N. Cell Mol Immunol. 2006 Aug;3(4):271-7. (.png) (.svg) (.htm

  20. Cux1 and Cux2 regulate dendritic branching, spine morphology and synapses of the upper layer neurons of the cortex

    Science.gov (United States)

    Cubelos, Beatriz; Sebastián-Serrano, Alvaro; Beccari, Leonardo; Calcagnotto, Maria Elisa; Cisneros, Elsa; Kim, Seonhee; Dopazo, Ana; Alvarez-Dolado, Manuel; Redondo, Juan Miguel; Bovolenta, Paola; Walsh, Christopher A.; Nieto, Marta

    2010-01-01

    Summary Dendrite branching and spine formation determines the function of morphologically distinct and specialized neuronal subclasses. However, little is known about the programs instructing specific branching patterns in vertebrate neurons and whether such programs influence dendritic spines and synapses. Using knockout and knockdown studies combined with morphological, molecular and electrophysiological analysis we show that the homeobox Cux1 and Cux2 are intrinsic and complementary regulators of dendrite branching, spine development and synapse formation in layer II–III neurons of the cerebral cortex. Cux genes control the number and maturation of dendritic spines partly through direct regulation of the expression of Xlr3b and Xlr4b, chromatin remodeling genes previously implicated in cognitive defects. Accordingly, abnormal dendrites and synapses in Cux2−/− mice correlate with reduced synaptic function and defects in working memory. These demonstrate critical roles of Cux in dendritogenesis and highlight novel subclass-specific mechanisms of synapse regulation that contribute to the establishment of cognitive circuits. PMID:20510857

  1. Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation

    Directory of Open Access Journals (Sweden)

    Jessberger Sebastian

    2006-11-01

    Full Text Available Abstract Background In the course of adult hippocampal neurogenesis most regulation takes place during the phase of doublecortin (DCX expression, either as pro-proliferative effect on precursor cells or as survival-promoting effect on postmitotic cells. We here obtained quantitative data about the proliferative population and the dynamics of postmitotic dendrite development during the period of DCX expression. The question was, whether any indication could be obtained that the initiation of dendrite development is timely bound to the exit from the cell cycle. Alternatively, the temporal course of morphological maturation might be subject to additional regulatory events. Results We found that (1 20% of the DCX population were precursor cells in cell cycle, whereas more than 70% were postmitotic, (2 the time span until newborn cells had reached the most mature stage associated with DCX expression varied between 3 days and several weeks, (3 positive or negative regulation of precursor cell proliferation did not alter the pattern and dynamics of dendrite development. Dendrite maturation was largely independent of close contacts to astrocytes. Conclusion These data imply that dendrite maturation of immature neurons is initiated at varying times after cell cycle exit, is variable in duration, and is controlled independently of the regulation of precursor cell proliferation. We conclude that in addition to the major regulatory events in cell proliferation and selective survival, additional micro-regulatory events influence the course of adult hippocampal neurogenesis.

  2. Synaptic convergence regulates synchronization-dependent spike transfer in feedforward neural networks.

    Science.gov (United States)

    Sailamul, Pachaya; Jang, Jaeson; Paik, Se-Bum

    2017-12-01

    Correlated neural activities such as synchronizations can significantly alter the characteristics of spike transfer between neural layers. However, it is not clear how this synchronization-dependent spike transfer can be affected by the structure of convergent feedforward wiring. To address this question, we implemented computer simulations of model neural networks: a source and a target layer connected with different types of convergent wiring rules. In the Gaussian-Gaussian (GG) model, both the connection probability and the strength are given as Gaussian distribution as a function of spatial distance. In the Uniform-Constant (UC) and Uniform-Exponential (UE) models, the connection probability density is a uniform constant within a certain range, but the connection strength is set as a constant value or an exponentially decaying function, respectively. Then we examined how the spike transfer function is modulated under these conditions, while static or synchronized input patterns were introduced to simulate different levels of feedforward spike synchronization. We observed that the synchronization-dependent modulation of the transfer function appeared noticeably different for each convergence condition. The modulation of the spike transfer function was largest in the UC model, and smallest in the UE model. Our analysis showed that this difference was induced by the different spike weight distributions that was generated from convergent synapses in each model. Our results suggest that, the structure of the feedforward convergence is a crucial factor for correlation-dependent spike control, thus must be considered important to understand the mechanism of information transfer in the brain.

  3. Regulation of granule cell excitability by a low-threshold calcium spike in turtle olfactory bulb

    DEFF Research Database (Denmark)

    Pinato, Giulietta; Midtgaard, Jens

    2003-01-01

    of the cell usually increased their amplitude so that they more easily boosted Na spike initiation. The LTS persisted in the presence of TTX but was antagonized by blockers of T-type calcium channels. The voltage dependence, kinetics, and inactivation properties of the LTS were characteristic of a low......-threshold calcium spike. The threshold of the LTS was slightly above the resting potential but well below the Na spike threshold, and the LTS was often evoked in isolation in normal medium. Tetraethylammonium (TEA) and 4-aminopyridine (4-AP) had only minimal effects on the LTS but revealed the presence of a high...

  4. Developmental shaping of dendritic arbors in Drosophila relies on tightly regulated intra-neuronal activity of protein kinase A (PKA).

    Science.gov (United States)

    Copf, Tijana

    2014-09-15

    Dendrites develop morphologies characterized by multiple levels of complexity that involve neuron type specific dendritic length and particular spatial distribution. How this is developmentally regulated and in particular which signaling molecules are crucial in the process is still not understood. Using Drosophila class IV dendritic arborization (da) neurons we test in vivo the effects of cell-autonomous dose-dependent changes in the activity levels of the cAMP-dependent Protein Kinase A (PKA) on the formation of complex dendritic arbors. We find that genetic manipulations of the PKA activity levels affect profoundly the arbor complexity with strongest impact on distal branches. Both decreasing and increasing PKA activity result in a reduced complexity of the arbors, as reflected in decreased dendritic length and number of branching points, suggesting an inverted U-shape response to PKA. The phenotypes are accompanied by changes in organelle distribution: Golgi outposts and early endosomes in distal dendritic branches are reduced in PKA mutants. By using Rab5 dominant negative we find that PKA interacts genetically with the early endosomal pathway. We test if the possible relationship between PKA and organelles may be the result of phosphorylation of the microtubule motor dynein components or Rab5. We find that Drosophila cytoplasmic dynein components are direct PKA phosphorylation targets in vitro, but not in vivo, thus pointing to a different putative in vivo target. Our data argue that tightly controlled dose-dependent intra-neuronal PKA activity levels are critical in determining the dendritic arbor complexity, one of the possible ways being through the regulation of organelle distribution. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Calcitonin gene-related peptide regulates type IV hypersensitivity through dendritic cell functions.

    Directory of Open Access Journals (Sweden)

    Norihisa Mikami

    Full Text Available Dendritic cells (DCs play essential roles in both innate and adaptive immune responses. In addition, mutual regulation of the nervous system and immune system is well studied. One of neuropeptides, calcitonin gene-related peptide (CGRP, is a potent regulator in immune responses; in particular, it has anti-inflammatory effects in innate immunity. For instance, a deficiency of the CGRP receptor component RAMP 1 (receptor activity-modifying protein 1 results in higher cytokine production in response to LPS (lipopolysaccharide. On the other hand, how CGRP affects DCs in adaptive immunity is largely unknown. In this study, we show that CGRP suppressed Th1 cell differentiation via inhibition of IL-12 production in DCs using an in vitro co-culture system and an in vivo ovalbumin-induced delayed-type hypersensitivity (DTH model. CGRP also down-regulated the expressions of chemokine receptor CCR2 and its ligands CCL2 and CCL12 in DCs. Intriguingly, the frequency of migrating CCR2(+ DCs in draining lymph nodes of RAMP1-deficient mice was higher after DTH immunization. Moreover, these CCR2(+ DCs highly expressed IL-12 and CD80, resulting in more effective induction of Th1 differentiation compared with CCR2(- DCs. These results indicate that CGRP regulates Th1 type reactions by regulating expression of cytokines, chemokines, and chemokine receptors in DCs.

  6. A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis

    NARCIS (Netherlands)

    Siegel, Gabriele; Obernosterer, Gregor; Fiore, Roberto; Oehmen, Martin; Bicker, Silvia; Christensen, Mette; Khudayberdiev, Sharof; Leuschner, Philipp F; Busch, Clara J L; Kane, Christina; Hübel, Katja; Dekker, Frank; Hedberg, Christian; Rengarajan, Balamurugan; Drepper, Carsten; Waldmann, Herbert; Kauppinen, Sakari; Greenberg, Michael E; Draguhn, Andreas; Rehmsmeier, Marc; Martinez, Javier; Schratt, Gerhard M; Dekker, Frank

    The microRNA pathway has been implicated in the regulation of synaptic protein synthesis and ultimately in dendritic spine morphogenesis, a phenomenon associated with long-lasting forms of memory. However, the particular microRNAs (miRNAs) involved are largely unknown. Here we identify specific

  7. Regulation of TGFβ in the immune system: an emerging role for integrins and dendritic cells.

    Science.gov (United States)

    Worthington, John J; Fenton, Thomas M; Czajkowska, Beata I; Klementowicz, Joanna E; Travis, Mark A

    2012-12-01

    Regulation of an immune response requires complex crosstalk between cells of the innate and adaptive immune systems, via both cell-cell contact and secretion of cytokines. An important cytokine with a broad regulatory role in the immune system is transforming growth factor-β (TGF-β). TGF-β is produced by and has effects on many different cells of the immune system, and plays fundamental roles in the regulation of immune responses during homeostasis, infection and disease. Although many cells can produce TGFβ, it is always produced as an inactive complex that must be activated to bind to the TGFβ receptor complex and promote downstream signalling. Thus, regulation of TGFβ activation is a crucial step in controlling TGFβ function. This review will discuss how TGFβ controls diverse immune responses and how TGFβ function is regulated, with a focus on recent work highlighting a critical role for the integrin αvβ8 expressed by dendritic cells in activating TGFβ. Copyright © 2012 Elsevier GmbH. All rights reserved.

  8. Wnt-5a/Frizzled9 Receptor Signaling through the Gαo-Gβγ Complex Regulates Dendritic Spine Formation*

    Science.gov (United States)

    Ramírez, Valerie T.; Ramos-Fernández, Eva; Henríquez, Juan Pablo; Lorenzo, Alfredo; Inestrosa, Nibaldo C.

    2016-01-01

    Wnt ligands play crucial roles in the development and regulation of synapse structure and function. Specifically, Wnt-5a acts as a secreted growth factor that regulates dendritic spine formation in rodent hippocampal neurons, resulting in postsynaptic development that promotes the clustering of the PSD-95 (postsynaptic density protein 95). Here, we focused on the early events occurring after the interaction between Wnt-5a and its Frizzled receptor at the neuronal cell surface. Additionally, we studied the role of heterotrimeric G proteins in Wnt-5a-dependent synaptic development. We report that FZD9 (Frizzled9), a Wnt receptor related to Williams syndrome, is localized in the postsynaptic region, where it interacts with Wnt-5a. Functionally, FZD9 is required for the Wnt-5a-mediated increase in dendritic spine density. FZD9 forms a precoupled complex with Gαo under basal conditions that dissociates after Wnt-5a stimulation. Accordingly, we found that G protein inhibition abrogates the Wnt-5a-dependent pathway in hippocampal neurons. In particular, the activation of Gαo appears to be a key factor controlling the Wnt-5a-induced dendritic spine density. In addition, we found that Gβγ is required for the Wnt-5a-mediated increase in cytosolic calcium levels and spinogenesis. Our findings reveal that FZD9 and heterotrimeric G proteins regulate Wnt-5a signaling and dendritic spines in cultured hippocampal neurons. PMID:27402827

  9. Molecular regulation of dendritic cell development and function in homeostasis, inflammation, and cancer.

    Science.gov (United States)

    Chrisikos, Taylor T; Zhou, Yifan; Slone, Natalie; Babcock, Rachel; Watowich, Stephanie S; Li, Haiyan S

    2018-03-14

    Dendritic cells (DCs) are the principal antigen-presenting cells of the immune system and play key roles in controlling immune tolerance and activation. As such, DCs are chief mediators of tumor immunity. DCs can regulate tolerogenic immune responses that facilitate unchecked tumor growth. Importantly, however, DCs also mediate immune-stimulatory activity that restrains tumor progression. For instance, emerging evidence indicates the cDC1 subset has important functions in delivering tumor antigens to lymph nodes and inducing antigen-specific lymphocyte responses to tumors. Moreover, DCs control specific therapeutic responses in cancer including those resulting from immune checkpoint blockade. DC generation and function is influenced profoundly by cytokines, as well as their intracellular signaling proteins including STAT transcription factors. Regardless, our understanding of DC regulation in the cytokine-rich tumor microenvironment is still developing and must be better defined to advance cancer treatment. Here, we review literature focused on the molecular control of DCs, with a particular emphasis on cytokine- and STAT-mediated DC regulation. In addition, we highlight recent studies that delineate the importance of DCs in anti-tumor immunity and immune therapy, with the overall goal of improving knowledge of tumor-associated factors and intrinsic DC signaling cascades that influence DC function in cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. microRNAs in the regulation of dendritic cell functions in inflammation and atherosclerosis.

    Science.gov (United States)

    Busch, Martin; Zernecke, Alma

    2012-08-01

    Atherosclerosis has been established as a chronic inflammatory disease of the vessel wall. Among the mononuclear cell types recruited to the lesions, specialized dendritic cells (DCs) have gained increasing attention, and their secretory products and interactions shape the progression of atherosclerotic plaques. The regulation of DC functions by microRNAs (miRNAs) may thus be of primary importance in disease. We here systematically summarize the biogenesis and functions of miRNAs and provide an overview of miRNAs in DCs, their targets, and potential implications for atherosclerosis, with a particular focus on the best characterized miRNAs in DCs, namely, miR-155 and miR-146. MiRNA functions in DCs range from regulation of lipid uptake to cytokine production and T cell responses with a complex picture emerging, in which miRNAs cooperate or antagonize DC behavior, thereby promoting or counterbalancing inflammatory responses. As miRNAs regulate key functions of DCs known to control atherosclerotic vascular disease, their potential as a therapeutic target holds promise and should be attended to in future research.

  11. Proteomics analysis of dendritic cell activation by contact allergens reveals possible biomarkers regulated by Nrf2

    Energy Technology Data Exchange (ETDEWEB)

    Mussotter, Franz, E-mail: franz.mussotter@bfr.bund.de [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany); Tomm, Janina Melanie [Helmholtz Centre for Environmental Research (UFZ), Department of Molecular Systems Biology, Leipzig (Germany); El Ali, Zeina; Pallardy, Marc; Kerdine-Römer, Saadia [INSERM UMR 996, Univ Paris-Sud, Université Paris-Saclay, Chátenay-Malabry (France); Götz, Mario [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany); Bergen, Martin von [Helmholtz Centre for Environmental Research (UFZ), Department of Molecular Systems Biology, Leipzig (Germany); University of Leipzig, Institute of Biochemistry, Leipzig (Germany); Aalborg University, Department of Chemistry and Bioscience, Aalborg (Denmark); Haase, Andrea; Luch, Andreas [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany)

    2016-12-15

    Allergic contact dermatitis is a widespread disease with high clinical relevance affecting approximately 20% of the general population. Typically, contact allergens are low molecular weight electrophilic compounds which can activate the Keap1/Nrf2 pathway. We performed a proteomics study to reveal possible biomarkers for dendritic cell (DC) activation by contact allergens and to further elucidate the role of Keap1/Nrf2 signaling in this process. We used bone marrow derived dendritic cells (BMDCs) of wild-type (nrf2{sup +/+}) and Nrf2 knockout (nrf2{sup −/−}) mice and studied their response against the model contact sensitizers 2,4-dinitrochlorobenzene (DNCB), cinnamaldehyde (CA) and nickel(II) sulfate by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) in combination with electrospray ionization tandem mass spectrometry (ESI-MS/MS). Sodium dodecyl sulfate (SDS, 100 μM) served as irritant control. While treatment with nickel(II) sulfate and SDS had only little effects, CA and DNCB led to significant changes in protein expression. We found 18 and 30 protein spots up-regulated in wild-type cells treated with 50 and 100 μM CA, respectively. For 5 and 10 μM DNCB, 32 and 37 spots were up-regulated, respectively. Almost all of these proteins were not differentially expressed in nrf2{sup −/−} BMDCs, indicating an Nrf2-dependent regulation. Among them proteins were detected which are involved in oxidative stress and heat shock responses, as well as in signal transduction or basic cellular pathways. The applied approach allowed us to differentiate between Nrf2-dependent and Nrf2-independent cellular biomarkers differentially regulated upon allergen-induced DC activation. The data presented might contribute to the further development of suitable in vitro testing methods for chemical-mediated sensitization. - Highlights: • Contact allergens induce proteins involved in DC maturation Nrf2-dependently. • Induction of these proteins points to a functional

  12. Separate transcriptionally regulated pathways specify distinct classes of sister dendrites in a nociceptive neuron.

    Science.gov (United States)

    O'Brien, Barbara M J; Palumbos, Sierra D; Novakovic, Michaela; Shang, Xueying; Sundararajan, Lakshmi; Miller, David M

    2017-12-15

    The dendritic processes of nociceptive neurons transduce external signals into neurochemical cues that alert the organism to potentially damaging stimuli. The receptive field for each sensory neuron is defined by its dendritic arbor, but the mechanisms that shape dendritic architecture are incompletely understood. Using the model nociceptor, the PVD neuron in C. elegans, we determined that two types of PVD lateral branches project along the dorsal/ventral axis to generate the PVD dendritic arbor: (1) Pioneer dendrites that adhere to the epidermis, and (2) Commissural dendrites that fasciculate with circumferential motor neuron processes. Previous reports have shown that the LIM homeodomain transcription factor MEC-3 is required for all higher order PVD branching and that one of its targets, the claudin-like membrane protein HPO-30, preferentially promotes outgrowth of pioneer branches. Here, we show that another MEC-3 target, the conserved TFIIA-like zinc finger transcription factor EGL-46, adopts the alternative role of specifying commissural dendrites. The known EGL-46 binding partner, the TEAD transcription factor EGL-44, is also required for PVD commissural branch outgrowth. Double mutants of hpo-30 and egl-44 show strong enhancement of the lateral branching defect with decreased numbers of both pioneer and commissural dendrites. Thus, HPO-30/Claudin and EGL-46/EGL-44 function downstream of MEC-3 and in parallel acting pathways to direct outgrowth of two distinct classes of PVD dendritic branches. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells

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    Joanna Bandoła

    2017-08-01

    Full Text Available Plasmacytoid dendritic cells (pDCs regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR by the antigen-presenting pDCs, mediated by toll-like receptor (TLR 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders.

  14. Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells.

    Science.gov (United States)

    Bandoła, Joanna; Richter, Cornelia; Ryser, Martin; Jamal, Arshad; Ashton, Michelle P; von Bonin, Malte; Kuhn, Matthias; Dorschner, Benjamin; Alexopoulou, Dimitra; Navratiel, Katrin; Roeder, Ingo; Dahl, Andreas; Hedrich, Christian M; Bonifacio, Ezio; Brenner, Sebastian; Thieme, Sebastian

    2017-01-01

    Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders.

  15. Regulation of spike timing-dependent plasticity of olfactory inputs in mitral cells in the rat olfactory bulb.

    Directory of Open Access Journals (Sweden)

    Teng-Fei Ma

    Full Text Available The recent history of activity input onto granule cells (GCs in the main olfactory bulb can affect the strength of lateral inhibition, which functions to generate contrast enhancement. However, at the plasticity level, it is unknown whether and how the prior modification of lateral inhibition modulates the subsequent induction of long-lasting changes of the excitatory olfactory nerve (ON inputs to mitral cells (MCs. Here we found that the repetitive stimulation of two distinct excitatory inputs to the GCs induced a persistent modification of lateral inhibition in MCs in opposing directions. This bidirectional modification of inhibitory inputs differentially regulated the subsequent synaptic plasticity of the excitatory ON inputs to the MCs, which was induced by the repetitive pairing of excitatory postsynaptic potentials (EPSPs with postsynaptic bursts. The regulation of spike timing-dependent plasticity (STDP was achieved by the regulation of the inter-spike-interval (ISI of the postsynaptic bursts. This novel form of inhibition-dependent regulation of plasticity may contribute to the encoding or processing of olfactory information in the olfactory bulb.

  16. miR-132 Regulates Dendritic Spine Structure by Direct Targeting of Matrix Metalloproteinase 9 mRNA.

    Science.gov (United States)

    Jasińska, Magdalena; Miłek, Jacek; Cymerman, Iwona A; Łęski, Szymon; Kaczmarek, Leszek; Dziembowska, Magdalena

    2016-09-01

    Mir-132 is a neuronal activity-regulated microRNA that controls the morphology of dendritic spines and neuronal transmission. Similar activities have recently been attributed to matrix metalloproteinase-9 (MMP-9), an extrasynaptic protease. In the present study, we provide evidence that miR-132 directly regulates MMP-9 mRNA in neurons to modulate synaptic plasticity. With the use of luciferase reporter system, we show that miR-132 binds to the 3'UTR of MMP-9 mRNA to regulate its expression in neurons. The overexpression of miR-132 in neurons reduces the level of endogenous MMP-9 protein secretion. In synaptoneurosomes, metabotropic glutamate receptor (mGluR)-induced signaling stimulates the dissociation of miR-132 from polyribosomal fractions and shifts it towards the messenger ribonucleoprotein (mRNP)-containing fraction. Furthermore, we demonstrate that the overexpression of miR-132 in the cultured hippocampal neurons from Fmr1 KO mice that have increased synaptic MMP-9 level provokes enlargement of the dendritic spine heads, a process previously implicated in enhanced synaptic plasticity. We propose that activity-dependent miR-132 regulates structural plasticity of dendritic spines through matrix metalloproteinase 9.

  17. Chemoresistance of human monocyte-derived dendritic cells is regulated by IL-17A.

    Directory of Open Access Journals (Sweden)

    Selma Olsson Åkefeldt

    Full Text Available Dendritic cells initiate adaptive immune responses, leading either to control cancer by effector T cells or to exacerbate cancer by regulatory T cells that inhibit IFN-γ-mediated Th1-type response. Dendritic cells can also induce Th17-type immunity, mediated by IL-17A. However, the controversial role of this cytokine in cancer requires further investigations. We generated dendritic cells from peripheral blood monocytes to investigate lifespan, phenotype and chemoresistance of dendritic cells, treated with IL-17A with or without IFN-γ. Studying the expression of Bcl-2 family members, we demonstrated that dendritic cells constitutively express one pro-survival Bcl-2 member: MCL1. Immature dendritic cells were CD40(lowHLADR(low CD1a(+ MCL1(+, did not express CD14, CD68 or BCL2A1, and displayed a short 2-day lifespan. IL-17A-treated DC exhibited a semi-mature (CD40(high HLADR(low pre-M2 (CCL22(+ CD206(+ CD163(+ IL1RN(+ IL-10(- CXCL10(- IL-12(- mixed (CD1a(+ CD14+ CD68(+ macrophage-dendritic cell phenotype. They efficiently exerted mannose receptor-mediated endocytosis and did not produce superoxide anions, in the absence of TLR engagement. Interestingly, IL-17A promoted a long-term survival of dendritic cells, beyond 12 days, that correlated to BCL2A1 induction, a pro-survival Bcl-2 family member. BCL2A1 transcription was activated by NF-κB, downstream of IL-17A transduction. Thus, immature dendritic cells only express MCL1, whereas IL-17A-treated dendritic cells concomitantly expressed two pro-survival Bcl-2 family members: MCL1 and BCL2A1. These latter developed chemoresistance to 11 of the 17 chemotherapy agents tested. However, high doses of either vinblastine or cytarabine decreased MCL1 expression and induced dendritic cell death. When IL-17A is produced in vivo, administration of anti-IL-17A biotherapy may impair dendritic cell survival by targeting BCL2A1 expression. Consequently, depending on the effector or regulatory role of dendritic

  18. Spiking sychronization regulated by noise in three types of Hodgkin—Huxley neuronal networks

    International Nuclear Information System (INIS)

    Zhang Zheng-Zhen; Zeng Shang-You; Tang Wen-Yan; Hu Jin-Lin; Zeng Shao-Wen; Ning Wei-Lian; Qiu Yi; Wu Hui-Si

    2012-01-01

    In this paper, we study spiking synchronization in three different types of Hodgkin—Huxley neuronal networks, which are the small-world, regular, and random neuronal networks. All the neurons are subjected to subthreshold stimulus and external noise. It is found that in each of all the neuronal networks there is an optimal strength of noise to induce the maximal spiking synchronization. We further demonstrate that in each of the neuronal networks there is a range of synaptic conductance to induce the effect that an optimal strength of noise maximizes the spiking synchronization. Only when the magnitude of the synaptic conductance is moderate, will the effect be considerable. However, if the synaptic conductance is small or large, the effect vanishes. As the connections between neurons increase, the synaptic conductance to maximize the effect decreases. Therefore, we show quantitatively that the noise-induced maximal synchronization in the Hodgkin—Huxley neuronal network is a general effect, regardless of the specific type of neuronal network

  19. D1 receptors regulate dendritic morphology in normal and stressed prelimbic cortex.

    Science.gov (United States)

    Lin, Grant L; Borders, Candace B; Lundewall, Leslie J; Wellman, Cara L

    2015-01-01

    Both stress and dysfunction of prefrontal cortex are linked to psychological disorders, and structure and function of medial prefrontal cortex (mPFC) are altered by stress. Chronic restraint stress causes dendritic retraction in the prelimbic region (PL) of mPFC in rats. Dopamine release in mPFC increases during stress, and chronic administration of dopaminergic agonists results in dendritic remodeling. Thus, stress-induced alterations in dopaminergic transmission in PL may contribute to dendritic remodeling. We examined the effects of dopamine D1 receptor (D1R) blockade in PL during daily restraint stress on dendritic morphology in PL. Rats either underwent daily restraint stress (3h/day, 10 days) or remained unstressed. In each group, rats received daily infusions of either the D1R antagonist SCH23390 or vehicle into PL prior to restraint; unstressed and stressed rats that had not undergone surgery were also examined. On the final day of restraint, rats were euthanized and brains were processed for Golgi histology. Pyramidal neurons in PL were reconstructed and dendritic morphology was quantified. Vehicle-infused stressed rats demonstrated dendritic retraction compared to unstressed rats, and D1R blockade in PL prevented this effect. Moreover, in unstressed rats, D1R blockade produced dendritic retraction. These effects were not due to attenuation of the HPA axis response to acute stress: plasma corticosterone levels in a separate group of rats that underwent acute restraint stress with or without D1R blockade were not significantly different. These findings indicate that dopaminergic transmission in mPFC during stress contributes directly to the stress-induced retraction of apical dendrites, while dopamine transmission in the absence of stress is important in maintaining normal dendritic morphology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Eosinophils Regulate Interferon Alpha Production in Plasmacytoid Dendritic Cells Stimulated with Components of Neutrophil Extracellular Traps.

    Science.gov (United States)

    Skrzeczynska-Moncznik, Joanna; Zabieglo, Katarzyna; Bossowski, Jozef P; Osiecka, Oktawia; Wlodarczyk, Agnieszka; Kapinska-Mrowiecka, Monika; Kwitniewski, Mateusz; Majewski, Pawel; Dubin, Adam; Cichy, Joanna

    2017-03-01

    Eosinophils constitute an important component of helminth immunity and are not only associated with various allergies but are also linked to autoinflammatory disorders, including the skin disease psoriasis. Here we demonstrate the functional relationship between eosinophils and plasmacytoid dendritic cells (pDCs) as related to skin diseases. We previously showed that pDCs colocalize with neutrophil extracellular traps (NETs) in psoriatic skin. Here we demonstrate that eosinophils are found in psoriatic skin near neutrophils and NETs, suggesting that pDC responses can be regulated by eosinophils. Eosinophils inhibited pDC function in vitro through a mechanism that did not involve cell contact but depended on soluble factors. In pDCs stimulated by specific NET components, eosinophil-conditioned media attenuated the production of interferon α (IFNα) but did not affect the maturation of pDCs as evidenced by the unaltered expression of the costimulatory molecules CD80 and CD86. As pDCs and IFNα play a key role in autoimmune skin inflammation, these data suggest that eosinophils may influence autoinflammatory responses through their impact on the production of IFNα by pDCs.

  1. Overexpression of cypin alters dendrite morphology, single neuron activity, and network properties via distinct mechanisms

    Science.gov (United States)

    Rodríguez, Ana R.; O'Neill, Kate M.; Swiatkowski, Przemyslaw; Patel, Mihir V.; Firestein, Bonnie L.

    2018-02-01

    Objective. This study investigates the effect that overexpression of cytosolic PSD-95 interactor (cypin), a regulator of synaptic PSD-95 protein localization and a core regulator of dendrite branching, exerts on the electrical activity of rat hippocampal neurons and networks. Approach. We cultured rat hippocampal neurons and used lipid-mediated transfection and lentiviral gene transfer to achieve high levels of cypin or cypin mutant (cypinΔPDZ PSD-95 non-binding) expression cellularly and network-wide, respectively. Main results. Our analysis revealed that although overexpression of cypin and cypinΔPDZ increase dendrite numbers and decrease spine density, cypin and cypinΔPDZ distinctly regulate neuronal activity. At the single cell level, cypin promotes decreases in bursting activity while cypinΔPDZ reduces sEPSC frequency and further decreases bursting compared to cypin. At the network level, by using the Fano factor as a measure of spike count variability, cypin overexpression results in an increase in variability of spike count, and this effect is abolished when cypin cannot bind PSD-95. This variability is also dependent on baseline activity levels and on mean spike rate over time. Finally, our spike sorting data show that overexpression of cypin results in a more complex distribution of spike waveforms and that binding to PSD-95 is essential for this complexity. Significance. Our data suggest that dendrite morphology does not play a major role in cypin action on electrical activity.

  2. Unsaturated compounds induce up-regulation of CD86 on dendritic cells in the in vitro sensitization assay LCSA.

    Science.gov (United States)

    Frohwein, Thomas Armin; Sonnenburg, Anna; Zuberbier, Torsten; Stahlmann, Ralf; Schreiner, Maximilian

    2016-04-01

    Unsaturated compounds are known to cause false-positive reactions in the local lymph node assay (LLNA) but not in the guinea pig maximization test. We have tested a panel of substances (succinic acid, undecylenic acid, 1-octyn-3-ol, fumaric acid, maleic acid, linoleic acid, oleic acid, alpha-linolenic acid, squalene, and arachidonic acid) in the loose-fit coculture-based sensitization assay (LCSA) to evaluate whether unspecific activation of dendritic cells is a confounder for sensitization testing in vitro. Eight out of 10 tested substances caused significant up-regulation of CD86 on dendritic cells cocultured with keratinocytes and would have been classified as sensitizers; only succinic acid was tested negative, and squalene had to be excluded from data analysis due to poor solubility in cell culture medium. Based on human data, only undecylenic acid can be considered a true sensitizer. The true sensitizing potential of 1-octyn-3-ol is uncertain. Fumaric acid and its isomer maleic acid are not known as sensitizers, but their esters are contact allergens. A group of 18- to 20-carbon chain unsaturated fatty acids (linoleic acid, oleic acid, alpha-linolenic acid, and arachidonic acid) elicited the strongest reaction in vitro. This is possibly due to the formation of pro-inflammatory lipid mediators in the cell culture causing nonspecific activation of dendritic cells. In conclusion, both the LLNA and the LCSA seem to provide false-positive results for unsaturated fatty acids. The inclusion of T cells in dendritic cell-based in vitro sensitization assays may help to eliminate false-positive results due to nonspecific dendritic cell activation. This would lead to more accurate prediction of sensitizers, which is paramount for consumer health protection and occupational safety.

  3. Specific and Novel microRNAs Are Regulated as Response to Fungal Infection in Human Dendritic Cells

    Science.gov (United States)

    Dix, Andreas; Czakai, Kristin; Leonhardt, Ines; Schäferhoff, Karin; Bonin, Michael; Guthke, Reinhard; Einsele, Hermann; Kurzai, Oliver; Löffler, Jürgen; Linde, Jörg

    2017-01-01

    Within the last two decades, the incidence of invasive fungal infections has been significantly increased. They are characterized by high mortality rates and are often caused by Candida albicans and Aspergillus fumigatus. The increasing number of infections underlines the necessity for additional anti-fungal therapies, which require extended knowledge of gene regulations during fungal infection. MicroRNAs are regulators of important cellular processes, including the immune response. By analyzing their regulation and impact on target genes, novel therapeutic and diagnostic approaches may be developed. Here, we examine the role of microRNAs in human dendritic cells during fungal infection. Dendritic cells represent the bridge between the innate and the adaptive immune systems. Therefore, analysis of gene regulation of dendritic cells is of particular significance. By applying next-generation sequencing of small RNAs, we quantify microRNA expression in monocyte-derived dendritic cells after 6 and 12 h of infection with C. albicans and A. fumigatus as well as treatment with lipopolysaccharides (LPS). We identified 26 microRNAs that are differentially regulated after infection by the fungi or LPS. Three and five of them are specific for fungal infections after 6 and 12 h, respectively. We further validated interactions of miR-132-5p and miR-212-5p with immunological relevant target genes, such as FKBP1B, KLF4, and SPN, on both RNA and protein level. Our results indicate that these microRNAs fine-tune the expression of immune-related target genes during fungal infection. Beyond that, we identified previously undiscovered microRNAs. We validated three novel microRNAs via qRT-PCR. A comparison with known microRNAs revealed possible relations with the miR-378 family and miR-1260a/b for two of them, while the third one features a unique sequence with no resemblance to known microRNAs. In summary, this study analyzes the effect of known microRNAs in dendritic cells during

  4. L-Type Voltage-Gated Ca2+ Channels Regulate Synaptic-Activity-Triggered Recycling Endosome Fusion in Neuronal Dendrites

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    Brian G. Hiester

    2017-11-01

    Full Text Available The repertoire and abundance of proteins displayed on the surface of neuronal dendrites are tuned by regulated fusion of recycling endosomes (REs with the dendritic plasma membrane. While this process is critical for neuronal function and plasticity, how synaptic activity drives RE fusion remains unexplored. We demonstrate a multistep fusion mechanism that requires Ca2+ from distinct sources. NMDA receptor Ca2+ initiates RE fusion with the plasma membrane, while L-type voltage-gated Ca2+ channels (L-VGCCs regulate whether fused REs collapse into the membrane or reform without transferring their cargo to the cell surface. Accordingly, NMDA receptor activation triggered AMPA-type glutamate receptor trafficking to the dendritic surface in an L-VGCC-dependent manner. Conversely, potentiating L-VGCCs enhanced AMPA receptor surface expression only when NMDA receptors were also active. Thus L-VGCCs play a role in tuning activity-triggered surface expression of key synaptic proteins by gating the mode of RE fusion.

  5. Adaptive Regulation of Osteopontin Production by Dendritic Cells Through the Bidirectional Interaction With Mesenchymal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Sara Scutera

    2018-06-01

    Full Text Available Mesenchymal stromal cells (MSCs exert immunosuppressive effects on immune cells including dendritic cells (DCs. However, many details of the bidirectional interaction of MSCs with DCs are still unsolved and information on key molecules by which DCs can modulate MSC functions is limited. Here, we report that osteopontin (OPN, a cytokine involved in homeostatic and pathophysiologic responses, is constitutively expressed by DCs and regulated in the DC/MSC cocultures depending on the activation state of MSCs. Resting MSCs promoted OPN production, whereas the production of OPN was suppressed when MSCs were activated by proinflammatory cytokines (i.e., TNF-α, IL-6, and IL-1β. OPN induction required cell-to-cell contact, mediated at least in part, by β1 integrin (CD29. Conversely, activated MSCs inhibited the release of OPN via the production of soluble factors with a major role played by Prostaglandin E2 (PGE2. Accordingly, pretreatment with indomethacin significantly abrogated the MSC-mediated suppression of OPN while the direct addition of exogenous PGE2 inhibited OPN production by DCs. Furthermore, DC-conditioned medium promoted osteogenic differentiation of MSCs with a concomitant inhibition of adipogenesis. These effects were paralleled by the repression of the adipogenic markers PPARγ, adiponectin, and FABP4, and induction of the osteogenic markers alkaline phosphatase, RUNX2, and of the bone-anabolic chemokine CCL5. Notably, blocking OPN activity with RGD peptides or with an antibody against CD29, one of the OPN receptors, prevented the effects of DC-conditioned medium on MSC differentiation and CCL5 induction. Because MSCs have a key role in maintenance of bone marrow (BM hematopoietic stem cell niche through reciprocal regulation with immune cells, we investigated the possible MSC/DC interaction in human BM by immunohistochemistry. Although DCs (CD1c+ are a small percentage of BM cells, we demonstrated colocalization of CD271+ MSCs with

  6. Gal-3 regulates the capacity of dendritic cells to promote NKT-cell-induced liver injury.

    Science.gov (United States)

    Volarevic, Vladislav; Markovic, Bojana Simovic; Bojic, Sanja; Stojanovic, Maja; Nilsson, Ulf; Leffler, Hakon; Besra, Gurdyal S; Arsenijevic, Nebojsa; Paunovic, Verica; Trajkovic, Vladimir; Lukic, Miodrag L

    2015-02-01

    Galectin-3 (Gal-3), an endogenous lectin, exhibits pro- and anti-inflammatory effects in various disease conditions. In order to explore the role of Gal-3 in NKT-cell-dependent pathology, we induced hepatitis in C57BL/6 WT and Gal-3-deficient mice by using specific ligand for NKT cells: α-galactosylceramide, glycolipid Ag presented by CD1d. The injection of α-galactosylceramide significantly enhanced expression of Gal-3 in liver NKT and dendritic cells (DCs). Genetic deletion or selective inhibition of Gal-3 (induced by Gal-3-inhibitor TD139) abrogated the susceptibility to NKT-cell-dependent hepatitis. Blood levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-12) and their production by liver DCs and NKT cells were also downregulated. Genetic deletion or selective inhibition of Gal-3 alleviated influx of inflammatory CD11c(+) CD11b(+) DCs in the liver and favored tolerogenic phenotype and IL-10 production of liver NKT and DCs. Deletion of Gal-3 attenuated the capacity of DCs to support liver damage in the passive transfer experiments and to produce pro-inflammatory cytokines in vitro. Gal-3-deficient DCs failed to optimally stimulate production of pro-inflammatory cytokines in NKT cells, in vitro and in vivo. In conclusion, Gal-3 regulates the capacity of DCs to support NKT-cell-mediated liver injury, playing an important pro-inflammatory role in acute liver injury. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Ion channel density regulates switches between regular and fast spiking in soma but not in axons.

    Directory of Open Access Journals (Sweden)

    Hugo Zeberg

    2010-04-01

    Full Text Available The threshold firing frequency of a neuron is a characterizing feature of its dynamical behaviour, in turn determining its role in the oscillatory activity of the brain. Two main types of dynamics have been identified in brain neurons. Type 1 dynamics (regular spiking shows a continuous relationship between frequency and stimulation current (f-I(stim and, thus, an arbitrarily low frequency at threshold current; Type 2 (fast spiking shows a discontinuous f-I(stim relationship and a minimum threshold frequency. In a previous study of a hippocampal neuron model, we demonstrated that its dynamics could be of both Type 1 and Type 2, depending on ion channel density. In the present study we analyse the effect of varying channel density on threshold firing frequency on two well-studied axon membranes, namely the frog myelinated axon and the squid giant axon. Moreover, we analyse the hippocampal neuron model in more detail. The models are all based on voltage-clamp studies, thus comprising experimentally measurable parameters. The choice of analysing effects of channel density modifications is due to their physiological and pharmacological relevance. We show, using bifurcation analysis, that both axon models display exclusively Type 2 dynamics, independently of ion channel density. Nevertheless, both models have a region in the channel-density plane characterized by an N-shaped steady-state current-voltage relationship (a prerequisite for Type 1 dynamics and associated with this type of dynamics in the hippocampal model. In summary, our results suggest that the hippocampal soma and the two axon membranes represent two distinct kinds of membranes; membranes with a channel-density dependent switching between Type 1 and 2 dynamics, and membranes with a channel-density independent dynamics. The difference between the two membrane types suggests functional differences, compatible with a more flexible role of the soma membrane than that of the axon membrane.

  8. Collagen I-induced dendritic cells activation is regulated by TNF-α ...

    Indian Academy of Sciences (India)

    2015-02-04

    Feb 4, 2015 ... tion factor IRF4, when compared to collagen I only treated cells. Collectively, our ... and multiple scelerosis, use of TNF-α inhibitors is an important treatment ..... sclerosis complex 1 in dendritic cell activation of CD4 T cells by.

  9. Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in mice.

    Science.gov (United States)

    Huo, Feifei; Li, Dongbei; Zhao, Bo; Luo, Yadong; Zhao, Bingjie; Zou, Xueyang; Li, Yi; Yang, Wei

    2018-02-01

    As a transcription factor, autoimmune regulator (Aire) participates in thymic negative selection and maintains immune tolerance mainly by regulating the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). Aire is also expressed in dendritic cells (DCs). DCs are professional antigen-presenting cells (APCs) that affect the differentiation of T cells toward distinct subpopulations and participate in the immune response and tolerance, thereby playing an important role in maintaining homeostasis. To determine the role of Aire in maintaining immune tolerance by bone marrow-derived dendritic cells (BMDCs), in the present study we utilized Aire-knockout mice to examine the changes of maturation status and TRAs expression on BMDCs, additionally investigate the differentiation of CD4 + T cells. The results showed that expression of costimulatory molecule and major histocompatibility complex class II (MHC-II) molecule was increased and expression of various TRAs was decreased in BMDCs from Aire-knockout mice. Aire deficiency reduced the differentiation of naïve CD4 + T cells into type 2T helper (Th2) cells and regulatory T cells (Tregs) but enhanced the differentiation of naïve CD4 + T cells into Th1 cells, Th17 cells, and follicular helper T (Tfh) cells. The results demonstrate that Aire expressed by BMDCs plays an important role in the maintenance of homeostasis by regulating TRA expression and the differentiation of T cell subsets.

  10. MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2

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    Yunjia Zhang

    2016-06-01

    Full Text Available ABSTRACT MicroRNAs (miRNAs are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function mutations in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Furthermore, expression of the wild-type MeCP2, but not a loss-of-function mutant, rescues the miR-130a-induced phenotype. Our study uncovers the MECP2 gene as a previous unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by regulating MeCP2. Together with data from other groups, our work suggests that a feedback regulatory mechanism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development.

  11. Sensory Neuron Fates Are Distinguished by a Transcriptional Switch that Regulates Dendrite Branch Stabilization

    Science.gov (United States)

    Smith, Cody J.; O’Brien, Timothy; Chatzigeorgiou, Marios; Spencer, W. Clay; Feingold-Link, Elana; Husson, Steven J.; Hori, Sayaka; Mitani, Shohei; Gottschalk, Alexander; Schafer, William R.; Miller, David M.

    2013-01-01

    SUMMARY Sensory neurons adopt distinct morphologies and functional modalities to mediate responses to specific stimuli. Transcription factors and their downstream effectors orchestrate this outcome but are incompletely defined. Here, we show that different classes of mechanosensory neurons in C. elegans are distinguished by the combined action of the transcription factors MEC-3, AHR-1, and ZAG-1. Low levels of MEC-3 specify the elaborate branching pattern of PVD nociceptors, whereas high MEC-3 is correlated with the simple morphology of AVM and PVM touch neurons. AHR-1 specifies AVM touch neuron fate by elevating MEC-3 while simultaneously blocking expression of nociceptive genes such as the MEC-3 target, the claudin-like membrane protein HPO-30, that promotes the complex dendritic branching pattern of PVD. ZAG-1 exercises a parallel role to prevent PVM from adopting the PVD fate. The conserved dendritic branching function of the Drosophila AHR-1 homolog, Spineless, argues for similar pathways in mammals. PMID:23889932

  12. The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Giulia Chiaruttini

    2016-03-01

    Full Text Available Interleukin-12 (IL-12, produced by dendritic cells in response to activation, is central to pathogen eradication and tumor rejection. The trafficking pathways controlling spatial distribution and intracellular transport of IL-12 vesicles to the cell surface are still unknown. Here, we show that intracellular IL-12 localizes in late endocytic vesicles marked by the SNARE VAMP7. Dendritic cells (DCs from VAMP7-deficient mice are partially impaired in the multidirectional release of IL-12. Upon encounter with antigen-specific T cells, IL-12-containing vesicles rapidly redistribute at the immune synapse and release IL-12 in a process entirely dependent on VAMP7 expression. Consistently, acquisition of effector functions is reduced in T cells stimulated by VAMP7-null DCs. These results provide insights into IL-12 intracellular trafficking pathways and show that VAMP7-mediated release of IL-12 at the immune synapse is a mechanism to transmit innate signals to T cells.

  13. C. elegans bicd-1, homolog of the Drosophila dynein accessory factor Bicaudal D, regulates the branching of PVD sensory neuron dendrites.

    Science.gov (United States)

    Aguirre-Chen, Cristina; Bülow, Hannes E; Kaprielian, Zaven

    2011-02-01

    The establishment of cell type-specific dendritic arborization patterns is a key phase in the assembly of neuronal circuitry that facilitates the integration and processing of synaptic and sensory input. Although studies in Drosophila and vertebrate systems have identified a variety of factors that regulate dendrite branch formation, the molecular mechanisms that control this process remain poorly defined. Here, we introduce the use of the Caenorhabditis elegans PVD neurons, a pair of putative nociceptors that elaborate complex dendritic arbors, as a tractable model for conducting high-throughput RNAi screens aimed at identifying key regulators of dendritic branch formation. By carrying out two separate RNAi screens, a small-scale candidate-based screen and a large-scale screen of the ~3000 genes on chromosome IV, we retrieved 11 genes that either promote or suppress the formation of PVD-associated dendrites. We present a detailed functional characterization of one of the genes, bicd-1, which encodes a microtubule-associated protein previously shown to modulate the transport of mRNAs and organelles in a variety of organisms. Specifically, we describe a novel role for bicd-1 in regulating dendrite branch formation and show that bicd-1 is likely to be expressed, and primarily required, in PVD neurons to control dendritic branching. We also present evidence that bicd-1 operates in a conserved pathway with dhc-1 and unc-116, components of the dynein minus-end-directed and kinesin-1 plus-end-directed microtubule-based motor complexes, respectively, and interacts genetically with the repulsive guidance receptor unc-5.

  14. Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses

    DEFF Research Database (Denmark)

    Litjens, Nicolle H R; Rademaker, Mirjam; Ravensbergen, Bep

    2004-01-01

    Psoriasis vulgaris, a type-1 cytokine-mediated chronic skin disease, can be treated successfully with fumaric acid esters (FAE). Beneficial effects of this medication coincided with decreased production of IFN-gamma. Since dendritic cells (DC) regulate the differentiation of T helper (Th) cells......% of that by the respective Th cells cocultured with control DC. IL-4 production by primed, but not naive Th cells cocultured with MMF-DC was decreased as compared to cocultures with control DC. IL-10 production by naive and primed Th cells cocultured with MMF-DC and control DC did not differ. In addition, MMF inhibited LPS......-induced NF-kappaB activation in DC. Together, beneficial effects of FAE in psoriasis involve modulation of DC polarization by MMF such that these cells down-regulate IFN-gamma production by Th cells....

  15. Differential regulation of the excitability of prefrontal cortical fast-spiking interneurons and pyramidal neurons by serotonin and fluoxetine.

    Directory of Open Access Journals (Sweden)

    Ping Zhong

    2011-02-01

    Full Text Available Serotonin exerts a powerful influence on neuronal excitability. In this study, we investigated the effects of serotonin on different neuronal populations in prefrontal cortex (PFC, a major area controlling emotion and cognition. Using whole-cell recordings in PFC slices, we found that bath application of 5-HT dose-dependently increased the firing of FS (fast spiking interneurons, and decreased the firing of pyramidal neurons. The enhancing effect of 5-HT in FS interneurons was mediated by 5-HT₂ receptors, while the reducing effect of 5-HT in pyramidal neurons was mediated by 5-HT₁ receptors. Fluoxetine, the selective serotonin reuptake inhibitor, also induced a concentration-dependent increase in the excitability of FS interneurons, but had little effect on pyramidal neurons. In rats with chronic fluoxetine treatment, the excitability of FS interneurons was significantly increased, while pyramidal neurons remained unchanged. Fluoxetine injection largely occluded the enhancing effect of 5-HT in FS interneurons, but did not alter the reducing effect of 5-HT in pyramidal neurons. These data suggest that the excitability of PFC interneurons and pyramidal neurons is regulated by exogenous 5-HT in an opposing manner, and FS interneurons are the major target of Fluoxetine. It provides a framework for understanding the action of 5-HT and antidepressants in altering PFC network activity.

  16. From neurodevelopment to neurodegeneration: the interaction of neurofibromin and valosin-containing protein/p97 in regulation of dendritic spine formation

    Directory of Open Access Journals (Sweden)

    Hsueh Yi-Ping

    2012-03-01

    Full Text Available Abstract Both Neurofibromatosis type I (NF1 and inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD are autosomal dominant genetic disorders. These two diseases are fully penetrant but with high heterogeneity in phenotypes, suggesting the involvement of genetic modifiers in modulating patients' phenotypes. Although NF1 is recognized as a developmental disorder and IBMPFD is associated with degeneration of multiple tissues, a recent study discovered the direct protein interaction between neurofibromin, the protein product of the NF1 gene, and VCP/p97, encoded by the causative gene of IBMPFD. Both NF1 and VCP/p97 are critical for dendritic spine formation, which provides the cellular mechanism explaining the cognitive deficits and dementia found in patients. Moreover, disruption of the interaction between neurofibromin and VCP impairs dendritic spinogenesis. Neurofibromin likely influences multiple downstream pathways to control dendritic spinogenesis. One is to activate the protein kinase A pathway to initiate dendritic spine formation; another is to regulate the synaptic distribution of VCP and control the activity of VCP in dendritic spinogenesis. Since neurofibromin and VCP/p97 also regulate cell growth and bone metabolism, the understanding of neurofibromin and VCP/p97 in neurons may be applied to study of cancer and bone. Statin treatment rescues the spine defects caused by VCP deficiency, suggesting the potential role of statin in clinical treatment for these two diseases.

  17. From neurodevelopment to neurodegeneration: the interaction of neurofibromin and valosin-containing protein/p97 in regulation of dendritic spine formation.

    Science.gov (United States)

    Hsueh, Yi-Ping

    2012-03-26

    Both Neurofibromatosis type I (NF1) and inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) are autosomal dominant genetic disorders. These two diseases are fully penetrant but with high heterogeneity in phenotypes, suggesting the involvement of genetic modifiers in modulating patients' phenotypes. Although NF1 is recognized as a developmental disorder and IBMPFD is associated with degeneration of multiple tissues, a recent study discovered the direct protein interaction between neurofibromin, the protein product of the NF1 gene, and VCP/p97, encoded by the causative gene of IBMPFD. Both NF1 and VCP/p97 are critical for dendritic spine formation, which provides the cellular mechanism explaining the cognitive deficits and dementia found in patients. Moreover, disruption of the interaction between neurofibromin and VCP impairs dendritic spinogenesis. Neurofibromin likely influences multiple downstream pathways to control dendritic spinogenesis. One is to activate the protein kinase A pathway to initiate dendritic spine formation; another is to regulate the synaptic distribution of VCP and control the activity of VCP in dendritic spinogenesis. Since neurofibromin and VCP/p97 also regulate cell growth and bone metabolism, the understanding of neurofibromin and VCP/p97 in neurons may be applied to study of cancer and bone. Statin treatment rescues the spine defects caused by VCP deficiency, suggesting the potential role of statin in clinical treatment for these two diseases.

  18. Cortical Regulation of Striatal Medium Spiny Neuron Dendritic Remodeling in Parkinsonism: Modulation of Glutamate Release Reverses Dopamine Depletion–Induced Dendritic Spine Loss

    OpenAIRE

    Garcia, Bonnie G.; Neely, M. Diana; Deutch, Ariel Y.

    2010-01-01

    Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if dec...

  19. Regulated Assembly of Vacuolar ATPase Is Increased during Cluster Disruption-induced Maturation of Dendritic Cells through a Phosphatidylinositol 3-Kinase/mTOR-dependent Pathway*

    Science.gov (United States)

    Liberman, Rachel; Bond, Sarah; Shainheit, Mara G.; Stadecker, Miguel J.; Forgac, Michael

    2014-01-01

    The vacuolar (H+)-ATPases (V-ATPases) are ATP-driven proton pumps composed of a peripheral V1 domain and a membrane-embedded V0 domain. Regulated assembly of V1 and V0 represents an important regulatory mechanism for controlling V-ATPase activity in vivo. Previous work has shown that V-ATPase assembly increases during maturation of bone marrow-derived dendritic cells induced by activation of Toll-like receptors. This increased assembly is essential for antigen processing, which is dependent upon an acidic lysosomal pH. Cluster disruption of dendritic cells induces a semi-mature phenotype associated with immune tolerance. Thus, semi-mature dendritic cells are able to process and present self-peptides to suppress autoimmune responses. We have investigated V-ATPase assembly in bone marrow-derived, murine dendritic cells and observed an increase in assembly following cluster disruption. This increased assembly is not dependent upon new protein synthesis and is associated with an increase in concanamycin A-sensitive proton transport in FITC-loaded lysosomes. Inhibition of phosphatidylinositol 3-kinase with wortmannin or mTORC1 with rapamycin effectively inhibits the increased assembly observed upon cluster disruption. These results suggest that the phosphatidylinositol 3-kinase/mTOR pathway is involved in controlling V-ATPase assembly during dendritic cell maturation. PMID:24273170

  20. Regeneration of Drosophila sensory neuron axons and dendrites is regulated by the Akt pathway involving Pten and microRNA bantam

    Science.gov (United States)

    Song, Yuanquan; Ori-McKenney, Kassandra M.; Zheng, Yi; Han, Chun; Jan, Lily Yeh; Jan, Yuh Nung

    2012-01-01

    Both cell-intrinsic and extrinsic pathways govern axon regeneration, but only a limited number of factors have been identified and it is not clear to what extent axon regeneration is evolutionarily conserved. Whether dendrites also regenerate is unknown. Here we report that, like the axons of mammalian sensory neurons, the axons of certain Drosophila dendritic arborization (da) neurons are capable of substantial regeneration in the periphery but not in the CNS, and activating the Akt pathway enhances axon regeneration in the CNS. Moreover, those da neurons capable of axon regeneration also display dendrite regeneration, which is cell type-specific, developmentally regulated, and associated with microtubule polarity reversal. Dendrite regeneration is restrained via inhibition of the Akt pathway in da neurons by the epithelial cell-derived microRNA bantam but is facilitated by cell-autonomous activation of the Akt pathway. Our study begins to reveal mechanisms for dendrite regeneration, which depends on both extrinsic and intrinsic factors, including the PTEN–Akt pathway that is also important for axon regeneration. We thus established an important new model system—the fly da neuron regeneration model that resembles the mammalian injury model—with which to study and gain novel insights into the regeneration machinery. PMID:22759636

  1. Decoding spatiotemporal spike sequences via the finite state automata dynamics of spiking neural networks

    International Nuclear Information System (INIS)

    Jin, Dezhe Z

    2008-01-01

    Temporally complex stimuli are encoded into spatiotemporal spike sequences of neurons in many sensory areas. Here, we describe how downstream neurons with dendritic bistable plateau potentials can be connected to decode such spike sequences. Driven by feedforward inputs from the sensory neurons and controlled by feedforward inhibition and lateral excitation, the neurons transit between UP and DOWN states of the membrane potentials. The neurons spike only in the UP states. A decoding neuron spikes at the end of an input to signal the recognition of specific spike sequences. The transition dynamics is equivalent to that of a finite state automaton. A connection rule for the networks guarantees that any finite state automaton can be mapped into the transition dynamics, demonstrating the equivalence in computational power between the networks and finite state automata. The decoding mechanism is capable of recognizing an arbitrary number of spatiotemporal spike sequences, and is insensitive to the variations of the spike timings in the sequences

  2. Dendritic spine changes in the development of alcohol addiction regulated by α-calcium/calmodulin-dependent protein kinase II

    Directory of Open Access Journals (Sweden)

    Zofia Mijakowska

    2014-03-01

    Full Text Available Introduction Alcohol has many adverse effects on the brain. Among them are dendritic spine morphology alterations, which are believed to be the basis of alcohol addiction. Autophosphorylation of α-calcium/calmodulin-dependent protein kinase II (αCaMKII has been shown to regulate spine morphology in vitro. Here we show that αCaMKII can also regulate addiction related behaviour and dendritic spine morphology changes caused by alcohol consumption in vivo. Method 12 αCaMKII-autophosphorylation deficient female mice (T286A and 12 wild type littermates were used in the study. T286A strain was created by Giese et al. (1998. Mice were housed and tested in two IntelliCages from NewBehavior (www.newbehavior.com. IntelliCage is an automated learning system. After 95 days of alcohol drinking interrupted by tests for motivation, persistence in alcohol seeking and probability of relapse, mice were ascribed to ‘high’ or ‘low’ drinkers group according to their performance in the tests. Additional criterion was the amount of alcohol consumed during the whole experiment. Result of each test was evaluated separately. 1/3 of the mice that scored highest in each criterion were considered ‘positive’ for this trait. ‘Positive’ animals were given 1 point, negative 0 points. Mice that were positive in at least 2 criteria were ascribed to ‘high’ drinkers (‘+’ group. Remaining mice – to ‘low’ drinkers (‘–‘. This method of behavioral phenotyping, developed by Radwanska and Kaczmarek (2012, is inspired by DSM-IV. Since the results of this evaluation are discrete (i.e. by definition all the animals score between 0 to +4, we developed also a continuous method of addiction rating, which we call ‘addiction index’. The result of the second method is a sum of the standardized (z-score results of the above mentioned tests. We use it to examine the correlations between addiction-like behavior and spine parameters. Control group (12 WT, 8

  3. The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity.

    Science.gov (United States)

    Xiao, Yichuan; Zou, Qiang; Xie, Xiaoping; Liu, Ting; Li, Haiyan S; Jie, Zuliang; Jin, Jin; Hu, Hongbo; Manyam, Ganiraju; Zhang, Li; Cheng, Xuhong; Wang, Hui; Marie, Isabelle; Levy, David E; Watowich, Stephanie S; Sun, Shao-Cong

    2017-05-01

    Dendritic cells (DCs) are crucial for mediating immune responses but, when deregulated, also contribute to immunological disorders, such as autoimmunity. The molecular mechanism underlying the function of DCs is incompletely understood. In this study, we have identified TANK-binding kinase 1 (TBK1), a master innate immune kinase, as an important regulator of DC function. DC-specific deletion of Tbk1 causes T cell activation and autoimmune symptoms and also enhances antitumor immunity in animal models of cancer immunotherapy. The TBK1-deficient DCs have up-regulated expression of co-stimulatory molecules and increased T cell-priming activity. We further demonstrate that TBK1 negatively regulates the induction of a subset of genes by type I interferon receptor (IFNAR). Deletion of IFNAR1 could largely prevent aberrant T cell activation and autoimmunity in DC-conditional Tbk1 knockout mice. These findings identify a DC-specific function of TBK1 in the maintenance of immune homeostasis and tolerance. © 2017 Xiao et al.

  4. Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy.

    Science.gov (United States)

    van de Laar, Lianne; Coffer, Paul J; Woltman, Andrea M

    2012-04-12

    Dendritic cells (DCs) represent a small and heterogeneous fraction of the hematopoietic system, specialized in antigen capture, processing, and presentation. The different DC subsets act as sentinels throughout the body and perform a key role in the induction of immunogenic as well as tolerogenic immune responses. Because of their limited lifespan, continuous replenishment of DC is required. Whereas the importance of GM-CSF in regulating DC homeostasis has long been underestimated, this cytokine is currently considered a critical factor for DC development under both steady-state and inflammatory conditions. Regulation of cellular actions by GM-CSF depends on the activation of intracellular signaling modules, including JAK/STAT, MAPK, PI3K, and canonical NF-κB. By directing the activity of transcription factors and other cellular effector proteins, these pathways influence differentiation, survival and/or proliferation of uncommitted hematopoietic progenitors, and DC subset-specific precursors, thereby contributing to specific aspects of DC subset development. The specific intracellular events resulting from GM-CSF-induced signaling provide a molecular explanation for GM-CSF-dependent subset distribution as well as clues to the specific characteristics and functions of GM-CSF-differentiated DCs compared with DCs generated by fms-related tyrosine kinase 3 ligand. This knowledge can be used to identify therapeutic targets to improve GM-CSF-dependent DC-based strategies to regulate immunity.

  5. The microRNA bantam regulates a developmental transition in epithelial cells that restricts sensory dendrite growth

    OpenAIRE

    Jiang, Nan; Soba, Peter; Parker, Edward; Kim, Charles C.; Parrish, Jay Z.

    2014-01-01

    As animals grow, many early born structures grow by cell expansion rather than cell addition; thus growth of distinct structures must be coordinated to maintain proportionality. This phenomenon is particularly widespread in the nervous system, with dendrite arbors of many neurons expanding in concert with their substrate to sustain connectivity and maintain receptive field coverage as animals grow. After rapidly growing to establish body wall coverage, dendrites of Drosophila class IV dendrit...

  6. Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC

    Science.gov (United States)

    Tai, Lee-Hwa; Goulet, Marie-Line; Belanger, Simon; Toyama-Sorimachi, Noriko; Fodil-Cornu, Nassima; Vidal, Silvia M.; Troke, Angela D.; McVicar, Daniel W.; Makrigiannis, Andrew P.

    2008-01-01

    Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2Kb. Conversely, CpG-ODN–dependent IFN-α production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2Kb ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo. PMID:19075287

  7. Palmitoylation-dependent CDKL5–PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development

    Science.gov (United States)

    Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

    2013-01-01

    The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5–PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation-dependent CDKL5–PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutations may be implicated in the pathogenesis of CDKL5-related disorders. PMID:23671101

  8. Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development.

    Science.gov (United States)

    Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

    2013-05-28

    The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5-PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation-dependent CDKL5-PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutations may be implicated in the pathogenesis of CDKL5-related disorders.

  9. TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning

    Directory of Open Access Journals (Sweden)

    Sarah X. Luo

    2016-12-01

    Full Text Available Neural circuits involving midbrain dopaminergic (DA neurons regulate reward and goal-directed behaviors. Although local GABAergic input is known to modulate DA circuits, the mechanism that controls excitatory/inhibitory synaptic balance in DA neurons remains unclear. Here, we show that DA neurons use autocrine transforming growth factor β (TGF-β signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-β type II receptor in DA neurons also disrupts the balance in TGF-β1 expression in DA neurons and neighboring GABAergic neurons, which increases inhibitory input, reduces excitatory synaptic input, and alters phasic firing patterns in DA neurons. Mice lacking TGF-β signaling in DA neurons are hyperactive and exhibit inflexibility in relinquishing learned behaviors and re-establishing new stimulus-reward associations. These results support a role for TGF-β in regulating the delicate balance of excitatory/inhibitory synaptic input in local microcircuits involving DA and GABAergic neurons and its potential contributions to neuropsychiatric disorders.

  10. Donor lung derived myeloid and plasmacytoid dendritic cells differentially regulate T cell proliferation and cytokine production

    Directory of Open Access Journals (Sweden)

    Benson Heather L

    2012-03-01

    Full Text Available Abstract Background Direct allorecognition, i.e., donor lung-derived dendritic cells (DCs stimulating recipient-derived T lymphocytes, is believed to be the key mechanism of lung allograft rejection. Myeloid (cDCs and plasmacytoid (pDCs are believed to have differential effects on T cell activation. However, the roles of each DC type on T cell activation and rejection pathology post lung transplantation are unknown. Methods Using transgenic mice and antibody depletion techniques, either or both cell types were depleted in lungs of donor BALB/c mice (H-2d prior to transplanting into C57BL/6 mice (H-2b, followed by an assessment of rejection pathology, and pDC or cDC-induced proliferation and cytokine production in C57BL/6-derived mediastinal lymph node T cells (CD3+. Results Depleting either DC type had modest effect on rejection pathology and T cell proliferation. In contrast, T cells from mice that received grafts depleted of both DCs did not proliferate and this was associated with significantly reduced acute rejection scores compared to all other groups. cDCs were potent inducers of IFNγ, whereas both cDCs and pDCs induced IL-10. Both cell types had variable effects on IL-17A production. Conclusion Collectively, the data show that direct allorecognition by donor lung pDCs and cDCs have differential effects on T cell proliferation and cytokine production. Depletion of both donor lung cDC and pDC could prevent the severity of acute rejection episodes.

  11. Mucolipin 1 positively regulates TLR7 responses in dendritic cells by facilitating RNA transportation to lysosomes.

    Science.gov (United States)

    Li, Xiaobing; Saitoh, Shin-Ichiroh; Shibata, Takuma; Tanimura, Natsuko; Fukui, Ryutaro; Miyake, Kensuke

    2015-02-01

    Toll-like receptor 7 (TLR7) and TLR9 sense microbial single-stranded RNA (ssRNA) and ssDNA in endolysosomes. Nucleic acid (NA)-sensing in endolysosomes is thought to be important for avoiding TLR7/9 responses to self-derived NAs. Aberrant self-derived NA transportation to endolysosomes predisposes to autoimmune diseases. To restrict NA-sensing in endolysosomes, TLR7/9 trafficking is tightly controlled by a multiple transmembrane protein Unc93B1. In contrast to TLR7/9 trafficking, little is known about a mechanism underlying NA transportation. We here show that Mucolipin 1 (Mcoln1), a member of the transient receptor potential (TRP) cation channel gene family, has an important role in ssRNA trafficking into lysosomes. Mcoln1(-/-) dendritic cells (DCs) showed impaired TLR7 responses to ssRNA. A mucolipin agonist specifically enhanced TLR7 responses to ssRNAs. The channel activity of Mcoln1 is activated by a phospholipid phosphatidylinositol (3,5) bisphosphate (PtdIns(3,5)P2), which is generated by a class III lipid kinase PIKfyve. A PIKfyve inhibitor completely inhibited TLR7 responses to ssRNA in DCs. Confocal analyses showed that ssRNA transportation to lysosomes in DCs was impaired by PIKfyve inhibitor as well as by the lack of Mcoln1. Transportation of TLR9 ligands was also impaired by the PIKfyve inhibitor. These results demonstrate that the PtdIns(3,5)P2-Mcoln1 axis has an important role in ssRNA transportation into lysosomes in DCs. © The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Influence of the cystic fibrosis transmembrane conductance regulator on expression of lipid metabolism-related genes in dendritic cells

    Directory of Open Access Journals (Sweden)

    Quadri Luis EN

    2009-04-01

    Full Text Available Abstract Background Cystic fibrosis (CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR gene. Infections of the respiratory tract are a hallmark in CF. The host immune responses in CF are not adequate to eradicate pathogens, such as P. aeruginosa. Dendritic cells (DC are crucial in initiation and regulation of immune responses. Changes in DC function could contribute to abnormal immune responses on multiple levels. The role of DC in CF lung disease remains unknown. Methods This study investigated the expression of CFTR gene in bone marrow-derived DC. We compared the differentiation and maturation profile of DC from CF and wild type (WT mice. We analyzed the gene expression levels in DC from naive CF and WT mice or following P. aeruginosa infection. Results CFTR is expressed in DC with lower level compared to lung tissue. DC from CF mice showed a delayed in the early phase of differentiation. Gene expression analysis in DC generated from naive CF and WT mice revealed decreased expression of Caveolin-1 (Cav1, a membrane lipid raft protein, in the CF DC compared to WT DC. Consistently, protein and activity levels of the sterol regulatory element binding protein (SREBP, a negative regulator of Cav1 expression, were increased in CF DC. Following exposure to P. aeruginosa, expression of 3β-hydroxysterol-Δ7 reductase (Dhcr7 and stearoyl-CoA desaturase 2 (Scd2, two enzymes involved in the lipid metabolism that are also regulated by SREBP, was less decreased in the CF DC compared to WT DC. Conclusion These results suggest that CFTR dysfunction in DC affects factors involved in membrane structure and lipid-metabolism, which may contribute to the abnormal inflammatory and immune response characteristic of CF.

  13. Spiking Neurons for Analysis of Patterns

    Science.gov (United States)

    Huntsberger, Terrance

    2008-01-01

    Artificial neural networks comprising spiking neurons of a novel type have been conceived as improved pattern-analysis and pattern-recognition computational systems. These neurons are represented by a mathematical model denoted the state-variable model (SVM), which among other things, exploits a computational parallelism inherent in spiking-neuron geometry. Networks of SVM neurons offer advantages of speed and computational efficiency, relative to traditional artificial neural networks. The SVM also overcomes some of the limitations of prior spiking-neuron models. There are numerous potential pattern-recognition, tracking, and data-reduction (data preprocessing) applications for these SVM neural networks on Earth and in exploration of remote planets. Spiking neurons imitate biological neurons more closely than do the neurons of traditional artificial neural networks. A spiking neuron includes a central cell body (soma) surrounded by a tree-like interconnection network (dendrites). Spiking neurons are so named because they generate trains of output pulses (spikes) in response to inputs received from sensors or from other neurons. They gain their speed advantage over traditional neural networks by using the timing of individual spikes for computation, whereas traditional artificial neurons use averages of activity levels over time. Moreover, spiking neurons use the delays inherent in dendritic processing in order to efficiently encode the information content of incoming signals. Because traditional artificial neurons fail to capture this encoding, they have less processing capability, and so it is necessary to use more gates when implementing traditional artificial neurons in electronic circuitry. Such higher-order functions as dynamic tasking are effected by use of pools (collections) of spiking neurons interconnected by spike-transmitting fibers. The SVM includes adaptive thresholds and submodels of transport of ions (in imitation of such transport in biological

  14. Regulation of TGFβ in the immune system: An emerging role for integrins and dendritic cells

    OpenAIRE

    Worthington, John J.; Fenton, Thomas M.; Czajkowska, Beata I.; Klementowicz, Joanna E.; Travis, Mark A.

    2012-01-01

    Regulation of an immune response requires complex crosstalk between cells of the innate and adaptive immune systems, via both cell?cell contact and secretion of cytokines. An important cytokine with a broad regulatory role in the immune system is transforming growth factor-? (TGF-?). TGF-? is produced by and has effects on many different cells of the immune system, and plays fundamental roles in the regulation of immune responses during homeostasis, infection and disease. Although many cells ...

  15. Notch-ligand expression by NALT dendritic cells regulates mucosal Th1- and Th2-type responses

    International Nuclear Information System (INIS)

    Fukuyama, Yoshiko; Tokuhara, Daisuke; Sekine, Shinichi; Kataoka, Kosuke; Markham, Jonathan D.; Irwin, Allyson R.; Moon, Grace H.; Tokuhara, Yuka; Fujihashi, Keiko; Davydova, Julia; Yamamoto, Masato; Gilbert, Rebekah S.; Fujihashi, Kohtaro

    2012-01-01

    Highlights: ► Nasal Ad-FL effectively up-regulates APC function by CD11c + DCs in mucosal tissues. ► Nasal Ad-FL induces Notch ligand (L)-expressing CD11c + DCs. ► Notch L-expressing DCs support the induction of Th1- and Th2-type cytokine responses. -- Abstract: Our previous studies showed that an adenovirus (Ad) serotype 5 vector expressing Flt3 ligand (Ad-FL) as nasal adjuvant activates CD11c + dendritic cells (DCs) for the enhancement of antigen (Ag)-specific IgA antibody (Ab) responses. In this study, we examined the molecular mechanism for activation of CD11c + DCs and their roles in induction of Ag-specific Th1- and Th2-cell responses. Ad-FL activated CD11c + DCs expressed increased levels of the Notch ligand (L)-expression and specific mRNA. When CD11c + DCs from various mucosal and systemic lymphoid tissues of mice given nasal OVA plus Ad-FL were cultured with CD4 + T cells isolated from non-immunized OVA TCR-transgenic (OT II) mice, significantly increased levels of T cell proliferative responses were noted. Furthermore, Ad-FL activated DCs induced IFN-γ, IL-2 and IL-4 producing CD4 + T cells. Of importance, these APC functions by Ad-FL activated DCs were down-regulated by blocking Notch–Notch-L pathway. These results show that Ad-FL induces CD11c + DCs to the express Notch-ligands and these activated DCs regulate the induction of Ag-specific Th1- and Th2-type cytokine responses.

  16. Dual Role of the Tyrosine Kinase Syk in Regulation of Toll-Like Receptor Signaling in Plasmacytoid Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Besma Aouar

    Full Text Available Crosslinking of regulatory immunoreceptors (RR, such as BDCA-2 (CD303 or ILT7 (CD85g, of plasmacytoid dendritic cells (pDCs efficiently suppresses production of type-I interferon (IFN-α/β and other cytokines in response to Toll-like receptor (TLR 7/9 ligands. This cytokine-inhibitory pathway is mediated by spleen tyrosine kinase (Syk associated with the ITAM-containing adapter of RR. Here we demonstrate by pharmacological targeting of Syk that in addition to the negative regulation of TLR7/9 signaling via RR, Syk also positively regulates the TLR7/9 pathway in human pDCs. Novel highly specific Syk inhibitor AB8779 suppressed IFN-α, TNF-α and IL-6 production induced by TLR7/9 agonists in primary pDCs and in the pDC cell line GEN2.2. Triggering of TLR9 or RR signaling induced a differential kinetics of phosphorylation at Y352 and Y525/526 of Syk and a differential sensitivity to AB8779. Consistent with the different roles of Syk in TLR7/9 and RR signaling, a concentration of AB8779 insufficient to block TLR7/9 signaling still released the block of IFN-α production triggered via the RR pathway, including that induced by hepatitis B and C viruses. Thus, pharmacological targeting of Syk partially restored the main pDC function-IFN-α production. Opposing roles of Syk in TLR7/9 and RR pathways may regulate the innate immune response to weaken inflammation reaction.

  17. Notch-ligand expression by NALT dendritic cells regulates mucosal Th1- and Th2-type responses

    Energy Technology Data Exchange (ETDEWEB)

    Fukuyama, Yoshiko; Tokuhara, Daisuke [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States); Division of Mucosal Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan); Sekine, Shinichi [Department of Preventive Dentistry, Graduate School of Dentistry, Osaka University, Osaka 565-0871 (Japan); Kataoka, Kosuke [Department of Preventive Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Markham, Jonathan D.; Irwin, Allyson R.; Moon, Grace H.; Tokuhara, Yuka; Fujihashi, Keiko [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States); Davydova, Julia; Yamamoto, Masato [Department of Surgery, University of Minnesota, Minneapolis, MN 55455 (United States); Gilbert, Rebekah S. [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States); Fujihashi, Kohtaro, E-mail: kohtarof@uab.edu [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Nasal Ad-FL effectively up-regulates APC function by CD11c{sup +} DCs in mucosal tissues. Black-Right-Pointing-Pointer Nasal Ad-FL induces Notch ligand (L)-expressing CD11c{sup +} DCs. Black-Right-Pointing-Pointer Notch L-expressing DCs support the induction of Th1- and Th2-type cytokine responses. -- Abstract: Our previous studies showed that an adenovirus (Ad) serotype 5 vector expressing Flt3 ligand (Ad-FL) as nasal adjuvant activates CD11c{sup +} dendritic cells (DCs) for the enhancement of antigen (Ag)-specific IgA antibody (Ab) responses. In this study, we examined the molecular mechanism for activation of CD11c{sup +} DCs and their roles in induction of Ag-specific Th1- and Th2-cell responses. Ad-FL activated CD11c{sup +} DCs expressed increased levels of the Notch ligand (L)-expression and specific mRNA. When CD11c{sup +} DCs from various mucosal and systemic lymphoid tissues of mice given nasal OVA plus Ad-FL were cultured with CD4{sup +} T cells isolated from non-immunized OVA TCR-transgenic (OT II) mice, significantly increased levels of T cell proliferative responses were noted. Furthermore, Ad-FL activated DCs induced IFN-{gamma}, IL-2 and IL-4 producing CD4{sup +} T cells. Of importance, these APC functions by Ad-FL activated DCs were down-regulated by blocking Notch-Notch-L pathway. These results show that Ad-FL induces CD11c{sup +} DCs to the express Notch-ligands and these activated DCs regulate the induction of Ag-specific Th1- and Th2-type cytokine responses.

  18. The role of dendritic non-linearities in single neuron computation

    Directory of Open Access Journals (Sweden)

    Boris Gutkin

    2014-05-01

    Full Text Available Experiment has demonstrated that summation of excitatory post-synaptic protientials (EPSPs in dendrites is non-linear. The sum of multiple EPSPs can be larger than their arithmetic sum, a superlinear summation due to the opening of voltage-gated channels and similar to somatic spiking. The so-called dendritic spike. The sum of multiple of EPSPs can also be smaller than their arithmetic sum, because the synaptic current necessarily saturates at some point. While these observations are well-explained by biophysical models the impact of dendritic spikes on computation remains a matter of debate. One reason is that dendritic spikes may fail to make the neuron spike; similarly, dendritic saturations are sometime presented as a glitch which should be corrected by dendritic spikes. We will provide solid arguments against this claim and show that dendritic saturations as well as dendritic spikes enhance single neuron computation, even when they cannot directly make the neuron fire. To explore the computational impact of dendritic spikes and saturations, we are using a binary neuron model in conjunction with Boolean algebra. We demonstrate using these tools that a single dendritic non-linearity, either spiking or saturating, combined with somatic non-linearity, enables a neuron to compute linearly non-separable Boolean functions (lnBfs. These functions are impossible to compute when summation is linear and the exclusive OR is a famous example of lnBfs. Importantly, the implementation of these functions does not require the dendritic non-linearity to make the neuron spike. Next, We show that reduced and realistic biophysical models of the neuron are capable of computing lnBfs. Within these models and contrary to the binary model, the dendritic and somatic non-linearity are tightly coupled. Yet we show that these neuron models are capable of linearly non-separable computations.

  19. Conditional ablation of CD205+ conventional dendritic cells impacts the regulation of T-cell immunity and homeostasis in vivo.

    Science.gov (United States)

    Fukaya, Tomohiro; Murakami, Ryuichi; Takagi, Hideaki; Sato, Kaori; Sato, Yumiko; Otsuka, Haruna; Ohno, Michiko; Hijikata, Atsushi; Ohara, Osamu; Hikida, Masaki; Malissen, Bernard; Sato, Katsuaki

    2012-07-10

    Dendritic cells (DCs) are composed of multiple subsets that play a dual role in inducing immunity and tolerance. However, it is unclear how CD205(+) conventional DCs (cDCs) control immune responses in vivo. Here we generated knock-in mice with the selective conditional ablation of CD205(+) cDCs. CD205(+) cDCs contributed to antigen-specific priming of CD4(+) T cells under steady-state conditions, whereas they were dispensable for antigen-specific CD4(+) T-cell responses under inflammatory conditions. In contrast, CD205(+) cDCs were required for antigen-specific priming of CD8(+) T cells to generate cytotoxic T lymphocytes (CTLs) mediated through cross-presentation. Although CD205(+) cDCs were involved in the thymic generation of CD4(+) regulatory T cells (Tregs), they maintained the homeostasis of CD4(+) Tregs and CD4(+) effector T cells in peripheral and mucosal tissues. On the other hand, CD205(+) cDCs were involved in the inflammation triggered by Toll-like receptor ligand as well as bacterial and viral infections. Upon microbial infections, CD205(+) cDCs contributed to the cross-priming of CD8(+) T cells for generating antimicrobial CTLs to efficiently eliminate pathogens, whereas they suppressed antimicrobial CD4(+) T-cell responses. Thus, these findings reveal a critical role for CD205(+) cDCs in the regulation of T-cell immunity and homeostasis in vivo.

  20. Homeostatic NF-κB Signaling in Steady-State Migratory Dendritic Cells Regulates Immune Homeostasis and Tolerance.

    Science.gov (United States)

    Baratin, Myriam; Foray, Chloe; Demaria, Olivier; Habbeddine, Mohamed; Pollet, Emeline; Maurizio, Julien; Verthuy, Christophe; Davanture, Suzel; Azukizawa, Hiroaki; Flores-Langarica, Adriana; Dalod, Marc; Lawrence, Toby

    2015-04-21

    Migratory non-lymphoid tissue dendritic cells (NLT-DCs) transport antigens to lymph nodes (LNs) and are required for protective immune responses in the context of inflammation and to promote tolerance to self-antigens in steady-state. However, the molecular mechanisms that elicit steady-state NLT-DC maturation and migration are unknown. By comparing the transcriptome of NLT-DCs in the skin with their migratory counterparts in draining LNs, we have identified a novel NF-κB-regulated gene network specific to migratory DCs. We show that targeted deletion of IKKβ in DCs, a major activator of NF-κB, prevents NLT-DC accumulation in LNs and compromises regulatory T cell conversion in vivo. This was associated with impaired tolerance and autoimmunity. NF-κB is generally considered the prototypical pro-inflammatory transcription factor, but this study describes a role for NF-κB signaling in DCs for immune homeostasis and tolerance that could have implications in autoimmune diseases and immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production

    Directory of Open Access Journals (Sweden)

    Matthew J. Elder

    2017-07-01

    Full Text Available Dectin-1/CLEC7A is a pattern recognition receptor that recognizes β-1,3 glucans, and its stimulation initiates signaling events characterized by the production of inflammatory cytokines from human dendritic cells (DCs required for antifungal immunity. β-glucans differ greatly in size, structure, and ability to activate effector immune responses from DC; as such, small particulate β-glucans are thought to be poor activators of innate immunity. We show that β-glucan particle size is a critical factor contributing to the secretion of cytokines from human DC; large β-glucan-stimulated DC generate significantly more IL-1β, IL-6, and IL-23 compared to those stimulated with the smaller β-glucans. In marked contrast, the secretion of TSLP and CCL22 were found to be insensitive to β-glucan particle size. Furthermore, we show that the capacity to induce phagocytosis, and the relative IL-1β production determined by β-glucan size, regulates the composition of the cytokine milieu generated from DC. This suggests that β-glucan particle size is critically important in orchestrating the nature of the immune response to fungi.

  2. CD4+ T‐cell activation is differentially modulated by bacteria‐primed dendritic cells, but is generally down‐regulated by n‐3 polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Pedersen, Susanne Brix; Lund, Pia; Kjær, Tanja

    2010-01-01

    provided by dendritic cells (DCs). Upon interaction with DCs primed by different concentrations and species of gut bacteria, CD4+ T cells were activated according to the type of DC stimulus. The levels of CD80 were found to correlate to the levels of expression of CD28 and to the proliferation of CD4+ T......, thereby affecting and shaping activation of acquired immunity by differential regulation of proliferation and costimulatory molecule expression in CD4+ T cells....

  3. Complement C1q regulates LPS-induced cytokine production in bone marrow-derived dendritic cells.

    Science.gov (United States)

    Yamada, Masahide; Oritani, Kenji; Kaisho, Tsuneyasu; Ishikawa, Jun; Yoshida, Hitoshi; Takahashi, Isao; Kawamoto, Shinichirou; Ishida, Naoko; Ujiie, Hidetoshi; Masaie, Hiroaki; Botto, Marina; Tomiyama, Yoshiaki; Matsuzawa, Yuji

    2004-01-01

    We show here that C1q suppresses IL-12p40 production in LPS-stimulated murine bone marrow-derived dendritic cells (BMDC). Serum IL-12p40 concentration of C1q-deficient mice was higher than that of wild-type mice after intraperitoneal LPS-injection. Because neither globular head of C1q (gC1q) nor collagen-like region of C1q (cC1q) failed to suppress LPS-induced IL-12p40 production, both gC1q and cC1q, and/or some specialized conformation of native C1q may be required for the inhibition. While C1q did not affect mRNA expression of Toll-like receptor 4 (TLR4), MD-2, and myeloid differentiation factor 88 (MyD88), BMDC treated with C1q showed the reduced activity of NF-kappaB and the delayed phosphorylation of p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase after LPS-stimulation. CpG oligodeoxynucleotide-induced IL-12p40 and TNF-alpha production, another MyD88-dependent TLR-mediated signal, was also suppressed by C1q treatment. Therefore, C1q is likely to suppress MyD88-dependent pathway in TLR-mediated signals. In contrast, C1q failed to suppress colony formation of B cells responding to LPS or LPS-induced CD40 and CD86 expression on BMDC in MyD88-deficient mice, indicating that inhibitory effects of C1q on MyD88-independent pathways may be limited. Taken together, C1q may regulate innate and adaptive immune systems via modification of signals mediated by interactions between invading pathogens and TLR.

  4. Regulation of dendritic cell function by insulin/IGF-1/PI3K/Akt signaling through klotho expression.

    Science.gov (United States)

    Xuan, Nguyen Thi; Hoang, Nguyen Huy; Nhung, Vu Phuong; Duong, Nguyen Thuy; Ha, Nguyen Hai; Hai, Nong Van

    2017-06-01

    Insulin or insulin-like growth factor 1 (IGF-1) promotes the activation of phosphoinositide 3 kinase (PI3K)/Akt signaling in immune cells including dendritic cells (DCs), the most potent professional antigen-presenting cells for naive T cells. Klotho, an anti-aging protein, participates in the regulation of the PI3K/Akt signaling, thus the Ca 2+ -dependent migration is reduced in klotho-deficient DCs. The present study explored the effects of insulin/IGF-1 on DC function through klotho expression. To this end, the mouse bone marrow cells were isolated and cultured with GM-CSF to attain bone marrow-derived DCs (BMDCs). Cells were treated with insulin or IGF-1 and followed by stimulating with lipopolysaccharides (LPS). Tumor necrosis factor (TNF)-α formation was examined by enzyme-linked immunosorbent assay (ELISA). Phagocytosis was analyzed by FITC-dextran uptake assay. The expression of klotho was determined by quantitative PCR, immunoprecipitation and western blotting. As a result, treatment of the cells with insulin/IGF-1 resulted in reducing the klotho expression as well as LPS-stimulated TNF-α release and increasing the FITC-dextran uptake but unaltering reactive oxygen species (ROS) production in BMDCs. The effects were abolished by using pharmacological inhibition of PI3K/Akt with LY294002 and paralleled by transfecting DCs with klotho siRNA. In conclusion, the regulation of klotho sensitive DC function by IGF-1 or insulin is mediated through PI3K/Akt signaling pathway in BMDCs.

  5. Functional Impairment of Myeloid Dendritic Cells during Advanced Stage of HIV-1 Infection: Role of Factors Regulating Cytokine Signaling.

    Directory of Open Access Journals (Sweden)

    Meenakshi Sachdeva

    Full Text Available Severely immunocompromised state during advanced stage of HIV-1 infection has been linked to functionally defective antigen presentation by dendritic cells (DCs. The molecular mechanisms behind DC impairment are still obscure. We investigated changes in DC function and association of key regulators of cytokine signaling during different stages of HIV-1 infection and following antiretroviral therapy (ART.Phenotypic and functional characteristics of circulating myeloid DCs (mDCs in 56 ART-naive patients (23 in early and 33 in advanced stage of disease, 36 on ART and 24 healthy controls were evaluated. Sixteen patients were studied longitudinally prior-to and 6 months after the start of ART. For functional studies, monocyte-derived DCs (Mo-DCs were evaluated for endocytosis, allo-stimulation and cytokine secretion. The expression of suppressor of cytokine signaling (SOCS-1 and other regulators of cytokine signaling was evaluated by real-time RT-PCR.The ability to respond to an antigenic stimulation was severely impaired in patients in advanced HIV-1 disease which showed partial recovery in the treated group. Mo-DCs from patients with advanced HIV-disease remained immature with low allo-stimulation and reduced cytokine secretion even after TLR-4 mediated stimulation ex-vivo. The cells had an increased expression of negative regulatory factors like SOCS-1, SOCS-3, SH2-containing phosphatase (SHP-1 and a reduced expression of positive regulators like Janus kinase (JAK2 and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB1. A functional recovery after siRNA mediated silencing of SOCS-1 in these mo-DCs confirms the role of negative regulatory factors in functional impairment of these cells.Functionally defective DCs in advanced stage of HIV-1 infection seems to be due to imbalanced state of negative and positive regulatory gene expression. Whether this is a cause or effect of increased viral replication at this stage of disease

  6. A novel CARD containing splice-isoform of CIITA regulates nitric oxide synthesis in dendritic cells.

    Science.gov (United States)

    Huang, Dachuan; Lim, Sylvia; Chua, Rong Yuan Ray; Shi, Hong; Ng, Mah Lee; Wong, Siew Heng

    2010-03-01

    MHC class II expression is controlled mainly at transcriptional level by class II transactivator (CIITA), which is a non-DNA binding coactivator and serves as a master control factor for MHC class II genes expression. Here, we describe the function of a novel splice-isoform of CIITA, DC-expressed caspase inhibitory isoform of CIITA (or DC-CASPIC), and we show that the expression of DCCASPIC in DC is upregulated upon lipopolysaccharides (LPS) induction. DC-CASPIC localizes to mitochondria, and protein-protein interaction study demonstrates that DC-CASPIC interacts with caspases and inhibits its activity in DC. Consistently, DC-CASPIC suppresses caspases-induced degradation of nitric oxide synthase-2 (NOS2) and subsequently promotes the synthesis of nitric oxide (NO). NO is an essential regulatory molecule that modulates the capability of DC in stimulating T cell proliferation/activation in vitro; hence, overexpression of DC-CASPIC in DC enhances this stimulation. Collectively, our findings reveal that DC-CASPIC is a key molecule that regulates caspases activity and NO synthesis in DC.

  7. Learning Universal Computations with Spikes

    Science.gov (United States)

    Thalmeier, Dominik; Uhlmann, Marvin; Kappen, Hilbert J.; Memmesheimer, Raoul-Martin

    2016-01-01

    Providing the neurobiological basis of information processing in higher animals, spiking neural networks must be able to learn a variety of complicated computations, including the generation of appropriate, possibly delayed reactions to inputs and the self-sustained generation of complex activity patterns, e.g. for locomotion. Many such computations require previous building of intrinsic world models. Here we show how spiking neural networks may solve these different tasks. Firstly, we derive constraints under which classes of spiking neural networks lend themselves to substrates of powerful general purpose computing. The networks contain dendritic or synaptic nonlinearities and have a constrained connectivity. We then combine such networks with learning rules for outputs or recurrent connections. We show that this allows to learn even difficult benchmark tasks such as the self-sustained generation of desired low-dimensional chaotic dynamics or memory-dependent computations. Furthermore, we show how spiking networks can build models of external world systems and use the acquired knowledge to control them. PMID:27309381

  8. Dynein and EFF-1 control dendrite morphology by regulating the localization pattern of SAX-7 in epidermal cells.

    Science.gov (United States)

    Zhu, Ting; Liang, Xing; Wang, Xiang-Ming; Shen, Kang

    2017-12-01

    Our previous work showed that the cell adhesion molecule SAX-7 forms an elaborate pattern in Caenorhabditis elegans epidermal cells, which instructs PVD dendrite branching. However, the molecular mechanism forming the SAX-7 pattern in the epidermis is not fully understood. Here, we report that the dynein light intermediate chain DLI-1 and the fusogen EFF-1 are required in epidermal cells to pattern SAX-7. While previous reports suggest that these two molecules act cell-autonomously in the PVD, our results show that the disorganized PVD dendritic arbors in these mutants are due to the abnormal SAX-7 localization patterns in epidermal cells. Three lines of evidence support this notion. First, the epidermal SAX-7 pattern was severely affected in dli-1 and eff-1 mutants. Second, the abnormal SAX-7 pattern was predictive of the ectopic PVD dendrites. Third, expression of DLI-1 or EFF-1 in the epidermis rescued both the SAX-7 pattern and the disorganized PVD dendrite phenotypes, whereas expression of these molecules in the PVD did not. We also show that DLI-1 functions cell-autonomously in the PVD to promote distal branch formation. These results demonstrate the unexpected roles of DLI-1 and EFF-1 in the epidermis in the control of PVD dendrite morphogenesis. © 2017. Published by The Company of Biologists Ltd.

  9. Dynamic Hebbian Cross-Correlation Learning Resolves the Spike Timing Dependent Plasticity Conundrum

    Directory of Open Access Journals (Sweden)

    Tjeerd V. olde Scheper

    2018-01-01

    Full Text Available Spike Timing-Dependent Plasticity has been found to assume many different forms. The classic STDP curve, with one potentiating and one depressing window, is only one of many possible curves that describe synaptic learning using the STDP mechanism. It has been shown experimentally that STDP curves may contain multiple LTP and LTD windows of variable width, and even inverted windows. The underlying STDP mechanism that is capable of producing such an extensive, and apparently incompatible, range of learning curves is still under investigation. In this paper, it is shown that STDP originates from a combination of two dynamic Hebbian cross-correlations of local activity at the synapse. The correlation of the presynaptic activity with the local postsynaptic activity is a robust and reliable indicator of the discrepancy between the presynaptic neuron and the postsynaptic neuron's activity. The second correlation is between the local postsynaptic activity with dendritic activity which is a good indicator of matching local synaptic and dendritic activity. We show that this simple time-independent learning rule can give rise to many forms of the STDP learning curve. The rule regulates synaptic strength without the need for spike matching or other supervisory learning mechanisms. Local differences in dendritic activity at the synapse greatly affect the cross-correlation difference which determines the relative contributions of different neural activity sources. Dendritic activity due to nearby synapses, action potentials, both forward and back-propagating, as well as inhibitory synapses will dynamically modify the local activity at the synapse, and the resulting STDP learning rule. The dynamic Hebbian learning rule ensures furthermore, that the resulting synaptic strength is dynamically stable, and that interactions between synapses do not result in local instabilities. The rule clearly demonstrates that synapses function as independent localized

  10. Clonorchis sinensis adult-derived proteins elicit Th2 immune responses by regulating dendritic cells via mannose receptor.

    Directory of Open Access Journals (Sweden)

    Lu Zhao

    2018-03-01

    Full Text Available Clonorchis sinensis (C. sinensis is the most widespread human liver fluke in East Asia including China and Korea. Clonorchiasis as a neglected tropical zoonosis, leads to serious economic and public health burden in China. There are considerable evidences for an etiological relation between chronic clonorchiasis and liver fibrosis in human beings. Liver fibrosis is a highly conserved and over-protected response to hepatic tissue injury. Immune cells including CD4+ T cell as well as dendritic cell (DC, and pro-fibrogenic cytokines like interleukin 4 (IL-4, IL-13 have been identified as vital manipulators in liver fibrogenesis. Our previous studies had a mere glimpse of T helper type 2 (Th2 dominant immune responses as key players in liver fibrosis induced by C. sinensis infection, but little is known about the involved mechanisms in this pathological process.By flow cytometry (FACS, adult-derived total proteins of C. sinensis (CsTPs down-regulated the expression of surface markers CD80, CD86 and major histocompatibility complex class II (MHC-II on lipopolysaccharide (LPS induced DC. ELISA results demonstrated that CsTPs inhibited IL-12p70 release from LPS-treated bone marrow-derived dendritic cells (BMDC. IL-10 level increased in a time-dependent manner in LPS-treated BMDCs after incubation with CsTPs. CD4+ T cells incubated with LPS-treated BMDCs plus CsTPs could significantly elevate IL-4 level by ELISA. Meanwhile, elevated expression of pro-fibrogenic mediators including IL-13 and IL-4 were detected in a co-culture system of LPS-activated BMDCs and naive T cells containing CsTPs. In vivo, CsTPs-immunized mice enhanced expression of type 2 cytokines IL-13, IL-10 and IL-4 in both splenocytes and hepatic tissue. Exposure of BMDCs to CsTPs activated expression of mannose receptor (MR but not toll like receptor 2 (TLR2, TLR4, C-type lectin receptor DC-SIGN and Dectin-2 on the cell surface by RT-PCR and FACS. Blockade of MR almost completely

  11. Large-conductance calcium-dependent potassium channels prevent dendritic excitability in neocortical pyramidal neurons.

    Science.gov (United States)

    Benhassine, Narimane; Berger, Thomas

    2009-03-01

    Large-conductance calcium-dependent potassium channels (BK channels) are homogeneously distributed along the somatodendritic axis of layer 5 pyramidal neurons of the rat somatosensory cortex. The relevance of this conductance for dendritic calcium electrogenesis was studied in acute brain slices using somatodendritic patch clamp recordings and calcium imaging. BK channel activation reduces the occurrence of dendritic calcium spikes. This is reflected in an increased critical frequency of somatic spikes necessary to activate the distal initiation zone. Whilst BK channels repolarise the somatic spike, they dampen it only in the distal dendrite. Their activation reduces dendritic calcium influx via glutamate receptors. Furthermore, they prevent dendritic calcium electrogenesis and subsequent somatic burst discharges. However, the time window for coincident somatic action potential and dendritic input to elicit dendritic calcium events is not influenced by BK channels. Thus, BK channel activation in layer 5 pyramidal neurons affects cellular excitability primarily by establishing a high threshold at the distal action potential initiation zone.

  12. The Mechanisms of Repetitive Spike Generation in an Axonless Retinal Interneuron

    Directory of Open Access Journals (Sweden)

    Mark S. Cembrowski

    2012-02-01

    Full Text Available Several types of retinal interneurons exhibit spikes but lack axons. One such neuron is the AII amacrine cell, in which spikes recorded at the soma exhibit small amplitudes (5 ms. Here, we used electrophysiological recordings and computational analysis to examine the mechanisms underlying this atypical spiking. We found that somatic spikes likely represent large, brief action potential-like events initiated in a single, electrotonically distal dendritic compartment. In this same compartment, spiking undergoes slow modulation, likely by an M-type K conductance. The structural correlate of this compartment is a thin neurite that extends from the primary dendritic tree: local application of TTX to this neurite, or excision of it, eliminates spiking. Thus, the physiology of the axonless AII is much more complex than would be anticipated from morphological descriptions and somatic recordings; in particular, the AII possesses a single dendritic structure that controls its firing pattern.

  13. Regulation of dendritic cell development by GM-CSF: Molecular control and implications for immune homeostasis and therapy

    NARCIS (Netherlands)

    L. van de Laar (Lianne); P.J. Coffer (Paul); A.M. Woltman (Andrea)

    2012-01-01

    textabstractDendritic cells (DCs) represent a small and heterogeneous fraction of the hematopoietic system, specialized in antigen capture, processing, and presentation. The different DC subsets act as sentinels throughout the body and perform a key role in the induction of immunogenic as well as

  14. Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation.

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Szepesi

    Full Text Available Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs, a family of extracellularly acting and Zn(2+-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.

  15. Microtubule nucleation and organization in dendrites

    Science.gov (United States)

    Delandre, Caroline; Amikura, Reiko; Moore, Adrian W.

    2016-01-01

    ABSTRACT Dendrite branching is an essential process for building complex nervous systems. It determines the number, distribution and integration of inputs into a neuron, and is regulated to create the diverse dendrite arbor branching patterns characteristic of different neuron types. The microtubule cytoskeleton is critical to provide structure and exert force during dendrite branching. It also supports the functional requirements of dendrites, reflected by differential microtubule architectural organization between neuron types, illustrated here for sensory neurons. Both anterograde and retrograde microtubule polymerization occur within growing dendrites, and recent studies indicate that branching is enhanced by anterograde microtubule polymerization events in nascent branches. The polarities of microtubule polymerization events are regulated by the position and orientation of microtubule nucleation events in the dendrite arbor. Golgi outposts are a primary microtubule nucleation center in dendrites and share common nucleation machinery with the centrosome. In addition, pre-existing dendrite microtubules may act as nucleation sites. We discuss how balancing the activities of distinct nucleation machineries within the growing dendrite can alter microtubule polymerization polarity and dendrite branching, and how regulating this balance can generate neuron type-specific morphologies. PMID:27097122

  16. Hypocretin (orexin) regulates glutamate input to fast-spiking interneurons in layer V of the Fr2 region of the murine prefrontal cortex.

    Science.gov (United States)

    Aracri, Patrizia; Banfi, Daniele; Pasini, Maria Enrica; Amadeo, Alida; Becchetti, Andrea

    2015-05-01

    We studied the effect of hypocretin 1 (orexin A) in the frontal area 2 (Fr2) of the murine neocortex, implicated in the motivation-dependent goal-directed tasks. In layer V, hypocretin stimulated the spontaneous excitatory postsynaptic currents (EPSCs) on fast-spiking (FS) interneurons. The effect was accompanied by increased frequency of miniature EPSCs, indicating that hypocretin can target the glutamatergic terminals. Moreover, hypocretin stimulated the spontaneous inhibitory postsynaptic currents (IPSCs) on pyramidal neurons, with no effect on miniature IPSCs. This action was prevented by blocking 1) the ionotropic glutamatergic receptors; 2) the hypocretin receptor type 1 (HCRTR-1), with SB-334867. Finally, hypocretin increased the firing frequency in FS cells, and the effect was blocked when the ionotropic glutamate transmission was inhibited. Immunolocalization confirmed that HCRTR-1 is highly expressed in Fr2, particularly in layer V-VI. Conspicuous labeling was observed in pyramidal neuron somata and in VGLUT1+ glutamatergic terminals, but not in VGLUT2+ fibers (mainly thalamocortical afferents). The expression of HCRTR-1 in GABAergic structures was scarce. We conclude that 1) hypocretin regulates glutamate release in Fr2; 2) the effect presents a presynaptic component; 3) the peptide control of FS cells is indirect, and probably mediated by the regulation of glutamatergic input onto these cells. © The Author 2013. Published by Oxford University Press.

  17. 1Autoreactive pre-plasma cells break tolerance in the absence of regulation by dendritic cells and macrophages

    OpenAIRE

    Gilbert, Mileka R.; Wagner, Nikki J.; Jones, Shannon Z.; Wisz, Amanda B.; Roques, Jose R.; Krum, Kristen N.; Lee, Sang-Ryul; Nickeleit, Volker; Hulbert, Chrys; Thomas, James W.; Gauld, Stephen B.; Vilen, Barbara J.

    2012-01-01

    The ability to induce antibody responses to pathogens while maintaining the quiescence of autoreactive cells is an important aspect of immune tolerance. During activation of Toll-like receptor-4 (TLR4), dendritic cells (DCs) and macrophages (MFs) repress autoantibody production through their secretion of IL-6 and soluble CD40L (sCD40L). These soluble mediators selectively repress B cells chronically exposed to antigen, but not naïve cells, suggesting a means to maintain tolerance during TLR4 ...

  18. Spiking in auditory cortex following thalamic stimulation is dominated by cortical network activity

    Science.gov (United States)

    Krause, Bryan M.; Raz, Aeyal; Uhlrich, Daniel J.; Smith, Philip H.; Banks, Matthew I.

    2014-01-01

    The state of the sensory cortical network can have a profound impact on neural responses and perception. In rodent auditory cortex, sensory responses are reported to occur in the context of network events, similar to brief UP states, that produce “packets” of spikes and are associated with synchronized synaptic input (Bathellier et al., 2012; Hromadka et al., 2013; Luczak et al., 2013). However, traditional models based on data from visual and somatosensory cortex predict that ascending sensory thalamocortical (TC) pathways sequentially activate cells in layers 4 (L4), L2/3, and L5. The relationship between these two spatio-temporal activity patterns is unclear. Here, we used calcium imaging and electrophysiological recordings in murine auditory TC brain slices to investigate the laminar response pattern to stimulation of TC afferents. We show that although monosynaptically driven spiking in response to TC afferents occurs, the vast majority of spikes fired following TC stimulation occurs during brief UP states and outside the context of the L4>L2/3>L5 activation sequence. Specifically, monosynaptic subthreshold TC responses with similar latencies were observed throughout layers 2–6, presumably via synapses onto dendritic processes located in L3 and L4. However, monosynaptic spiking was rare, and occurred primarily in L4 and L5 non-pyramidal cells. By contrast, during brief, TC-induced UP states, spiking was dense and occurred primarily in pyramidal cells. These network events always involved infragranular layers, whereas involvement of supragranular layers was variable. During UP states, spike latencies were comparable between infragranular and supragranular cells. These data are consistent with a model in which activation of auditory cortex, especially supragranular layers, depends on internally generated network events that represent a non-linear amplification process, are initiated by infragranular cells and tightly regulated by feed-forward inhibitory

  19. Deep Spiking Networks

    NARCIS (Netherlands)

    O'Connor, P.; Welling, M.

    2016-01-01

    We introduce an algorithm to do backpropagation on a spiking network. Our network is "spiking" in the sense that our neurons accumulate their activation into a potential over time, and only send out a signal (a "spike") when this potential crosses a threshold and the neuron is reset. Neurons only

  20. Flt3/Flt3L Participates in the Process of Regulating Dendritic Cells and Regulatory T Cells in DSS-Induced Colitis

    Directory of Open Access Journals (Sweden)

    Jing-Wei Mao

    2014-01-01

    Full Text Available The immunoregulation between dendritic cells (DCs and regulatory T cells (T-regs plays an important role in the pathogenesis of ulcerative colitis (UC. Recent research showed that Fms-like tyrosine kinase 3 (Flt3 and Flt3 ligand (Flt3L were involved in the process of DCs regulating T-regs. The DSS-induced colitis model is widely used because of its simplicity and many similarities with human UC. In this study, we observe the disease activity index (DAI and histological scoring, detect the amounts of DCs and T-regs and expression of Flt3/Flt3L, and investigate Flt3/Flt3L participating in the process of DCs regulating T-regs in DSS-induced colitis. Our findings suggest that the reduction of Flt3 and Flt3L expression may possibly induce colonic immunoregulatory imbalance between CD103+MHCII+DCs and CD4+CD25+FoxP3+T-regs in DSS-induced colitis. Flt3/Flt3L participates in the process of regulating DCS and T-regs in the pathogenesis of UC, at least, in the acute stage of this disease.

  1. PKB/SGK-dependent GSK3-phosphorylation in the regulation of LPS-induced Ca2+ increase in mouse dendritic cells.

    Science.gov (United States)

    Russo, Antonella; Schmid, Evi; Nurbaeva, Meerim K; Yang, Wenting; Yan, Jing; Bhandaru, Madhuri; Faggio, Caterina; Shumilina, Ekaterina; Lang, Florian

    2013-08-02

    The function of dendritic cells (DCs) is modified by glycogen synthase kinase GSK3 and GSK3 inhibitors have been shown to protect against inflammatory disease. Regulators of GSK3 include the phosphoinositide 3 kinase (PI3K) pathway leading to activation of protein kinase B (PKB/Akt) and serum and glucocorticoid inducible kinase (SGK) isoforms, which in turn phosphorylate and thus inhibit GSK3. The present study explored, whether PKB/SGK-dependent inhibition of GSK3 contributes to the regulation of cytosolic Ca(2+) concentration following stimulation with bacterial lipopolysaccharides (LPS). To this end DCs from mutant mice, in which PKB/SGK-dependent GSK3α,β regulation was disrupted by replacement of the serine residues in the respective SGK/PKB-phosphorylation consensus sequence by alanine (gsk3(KI)), were compared to DCs from respective wild type mice (gsk3(WT)). According to Western blotting, GSK3 phosphorylation was indeed absent in gsk3(KI) DCs. According to flow cytometry, expression of antigen-presenting molecule major histocompatibility complex II (MHCII) and costimulatory molecule CD86, was similar in unstimulated and LPS (1μg/ml, 24h)-stimulated gsk3(WT) and gsk3(KI) DCs. Moreover, production of cytokines IL-6, IL-10, IL-12 and TNFα was not significantly different in gsk3(KI) and gsk3(WT) DCs. In gsk3(WT) DCs, stimulation with LPS (1μg/ml) within 10min led to transient phosphorylation of GSK3. According to Fura2 fluorescence, LPS (1μg/ml) increased cytosolic Ca(2+) concentration, an effect significantly more pronounced in gsk3(KI) DCs than in gsk3(WT) DCs. Conversely, GSK3 inhibitor SB216763 (3-[2,4-Dichlorophenyl]-4-[1-methyl-1H-indol-3-yl]-1H-pyrrole-2,5-dione, 10μM, 30min) significantly blunted the increase of cytosolic Ca(2+) concentration following LPS exposure. In conclusion, PKB/SGK-dependent GSK3α,β activity participates in the regulation of Ca(2+) signaling in dendritic cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. 1Autoreactive pre-plasma cells break tolerance in the absence of regulation by dendritic cells and macrophages

    Science.gov (United States)

    Gilbert, Mileka R.; Wagner, Nikki J.; Jones, Shannon Z.; Wisz, Amanda B.; Roques, Jose R.; Krum, Kristen N.; Lee, Sang-Ryul; Nickeleit, Volker; Hulbert, Chrys; Thomas, James W.; Gauld, Stephen B.; Vilen, Barbara J.

    2012-01-01

    The ability to induce antibody responses to pathogens while maintaining the quiescence of autoreactive cells is an important aspect of immune tolerance. During activation of Toll-like receptor-4 (TLR4), dendritic cells (DCs) and macrophages (MFs) repress autoantibody production through their secretion of IL-6 and soluble CD40L (sCD40L). These soluble mediators selectively repress B cells chronically exposed to antigen, but not naïve cells, suggesting a means to maintain tolerance during TLR4 stimulation, yet allow immunity. In this study, we identify TNFα as a third repressive factor, which together with IL-6 and CD40L, account for nearly all the repression conferred by DCs and MFs. Like IL-6 and sCD40L, TNFα did not alter B cell proliferation or survival. Rather, it reduced the number of antibody secreting cells. To address whether the soluble mediators secreted by DCs and MFs functioned in vivo, we generated mice lacking IL-6, CD40L and TNFα. Compared to wildtype mice, these mice showed prolonged anti-nuclear antibody responses following TLR4 stimulation. Further, adoptive transfer of autoreactive B cells into chimeric IL-6-/- × CD40L-/- × TNFα-/- mice showed that pre-plasma cells secreted autoantibodies independent of germinal center formation or extrafollicular foci. These data indicate that in the absence of genetic predisposition to autoimmunity, loss of endogenous IL-6, CD40L, and TNFα promotes autoantibody secretion during TLR4 stimulation. PMID:22675201

  3. Layer-specific high-frequency spiking in the prefrontal cortex of awake rats

    Directory of Open Access Journals (Sweden)

    Zimbo Saroeni Raymond Maria Boudewijns

    2013-06-01

    Full Text Available Cortical pyramidal neurons show irregular in vivo action potential (AP spiking with high frequency bursts occurring on sparse background activity. Somatic APs can backpropagate from soma into basal and apical dendrites and locally generate dendritic calcium spikes. The critical AP frequency for generation of such dendritic calcium spikes can be very different depending on cell-type or brain area involved. Previously, it was shown in vitro that calcium electrogenesis can also be induced in L(ayer 5 pyramidal neurons of prefrontal cortex (PFC. It remains an open question whether somatic burst spiking and resulting dendritic calcium electrogenesis also occur in morphologically more compact L2/3 pyramidal neurons. Furthermore, it is not known whether critical frequencies that trigger dendritic calcium electrogenesis occur in PFC under awake conditions in vivo. Here, we addressed these issues and found that pyramidal neurons in both PFC L2/3 and L5 in awake rats spike APs in short bursts, but with different probabilities. The critical frequency for calcium electrogenesis in vitro was layer-specific and lower in L5 neurons compared to L2/3. Taking the in vitro critical frequency as predictive measure for dendritic electrogenesis during in vivo spontaneous activity, supracritical bursts in vivo were observed in a larger fraction of L5 neurons compared to L2/3 neurons but with similar incidence within these subpopulations. Together, these results show that in PFC of awake rats, AP spiking occurs at frequencies that are relevant for dendritic calcium electrogenesis and suggest that in awake rat PFC, dendritic calcium electrogenesis may be involved in neuronal computation.

  4. 1,25-dihydroxyvitamin D3 is an autonomous regulator of the transcriptional changes leading to a tolerogenic dendritic cell phenotype.

    Science.gov (United States)

    Széles, Lajos; Keresztes, Gábor; Töröcsik, Dániel; Balajthy, Zoltán; Krenács, László; Póliska, Szilárd; Steinmeyer, Andreas; Zuegel, Ulrich; Pruenster, Monika; Rot, Antal; Nagy, László

    2009-02-15

    Activation of vitamin D receptor (VDR) by 1,25-dihydroxyvitamin D(3) (1,25-vitD) reprograms dendritic cells (DC) to become tolerogenic. Previous studies suggested that 1,25-vitD could inhibit the changes brought about by differentiation and maturation of DCs. Underpinning the described phenotypic and functional alterations, there must be 1,25-vitD-coordinated transcriptional events. However, this transcriptional program has not been systematically investigated, particularly not in a developmental context. Hence, it has not been explored how 1,25-vitD-regulated genes, particularly the ones bringing about the tolerogenic phenotype, are connected to differentiation. We conducted global gene expression analysis followed by comprehensive quantitative PCR validation to clarify the interrelationship between 1,25-vitD and differentiation-driven gene expression patterns in developing human monocyte-derived and blood myeloid DCs. In this study we show that 1,25-vitD regulates a large set of genes that are not affected by differentiation. Interestingly, several genes, impacted both by the ligand and by differentiation, appear to be regulated by 1,25-vitD independently of the developmental context. We have also characterized the kinetics of generation of 1,25-vitD by using three early and robustly regulated genes, the chemokine CCL22, the inhibitory receptors CD300LF and CYP24A1. We found that monocyte-derived DCs are able to turn on 1,25-vitD sensitive genes in early phases of differentiation if the precursor is present. Our data collectively suggest that exogenous or endogenously generated 1,25-vitD regulates a large set of its targets autonomously and not via inhibition of differentiation and maturation, leading to the previously characterized tolerogenic state.

  5. Decoding spikes in a spiking neuronal network

    Energy Technology Data Exchange (ETDEWEB)

    Feng Jianfeng [Department of Informatics, University of Sussex, Brighton BN1 9QH (United Kingdom); Ding, Mingzhou [Department of Mathematics, Florida Atlantic University, Boca Raton, FL 33431 (United States)

    2004-06-04

    We investigate how to reliably decode the input information from the output of a spiking neuronal network. A maximum likelihood estimator of the input signal, together with its Fisher information, is rigorously calculated. The advantage of the maximum likelihood estimation over the 'brute-force rate coding' estimate is clearly demonstrated. It is pointed out that the ergodic assumption in neuroscience, i.e. a temporal average is equivalent to an ensemble average, is in general not true. Averaging over an ensemble of neurons usually gives a biased estimate of the input information. A method on how to compensate for the bias is proposed. Reconstruction of dynamical input signals with a group of spiking neurons is extensively studied and our results show that less than a spike is sufficient to accurately decode dynamical inputs.

  6. Decoding spikes in a spiking neuronal network

    International Nuclear Information System (INIS)

    Feng Jianfeng; Ding, Mingzhou

    2004-01-01

    We investigate how to reliably decode the input information from the output of a spiking neuronal network. A maximum likelihood estimator of the input signal, together with its Fisher information, is rigorously calculated. The advantage of the maximum likelihood estimation over the 'brute-force rate coding' estimate is clearly demonstrated. It is pointed out that the ergodic assumption in neuroscience, i.e. a temporal average is equivalent to an ensemble average, is in general not true. Averaging over an ensemble of neurons usually gives a biased estimate of the input information. A method on how to compensate for the bias is proposed. Reconstruction of dynamical input signals with a group of spiking neurons is extensively studied and our results show that less than a spike is sufficient to accurately decode dynamical inputs

  7. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    Science.gov (United States)

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling.

    Directory of Open Access Journals (Sweden)

    Helen M Lazear

    2013-01-01

    Full Text Available Although the transcription factors IRF-3 and IRF-7 are considered master regulators of type I interferon (IFN induction and IFN stimulated gene (ISG expression, Irf3(-/-×Irf7(-/- double knockout (DKO myeloid dendritic cells (mDC produce relatively normal levels of IFN-β after viral infection. We generated Irf3(-/-×Irf5(-/-×Irf7(-/- triple knockout (TKO mice to test whether IRF-5 was the source of the residual induction of IFN-β and ISGs in mDCs. In pathogenesis studies with two unrelated positive-sense RNA viruses (West Nile virus (WNV and murine norovirus, TKO mice succumbed at rates greater than DKO mice and equal to or approaching those of mice lacking the type I IFN receptor (Ifnar(-/-. In ex vivo studies, after WNV infection or exposure to Toll-like receptor agonists, TKO mDCs failed to produce IFN-β or express ISGs. In contrast, this response was sustained in TKO macrophages following WNV infection. To define IRF-regulated gene signatures, we performed microarray analysis on WNV-infected mDC from wild type (WT, DKO, TKO, or Ifnar(-/- mice, as well as from mice lacking the RIG-I like receptor adaptor protein MAVS. Whereas the gene induction pattern in DKO mDC was similar to WT cells, remarkably, almost no ISG induction was detected in TKO or Mavs(-/- mDC. The relative equivalence of TKO and Mavs(-/- responses suggested that MAVS dominantly regulates ISG induction in mDC. Moreover, we showed that MAVS-dependent induction of ISGs can occur through an IRF-5-dependent yet IRF-3 and IRF-7-independent pathway. Our results establish IRF-3, -5, and -7 as the key transcription factors responsible for mediating the type I IFN and ISG response in mDC during WNV infection and suggest a novel signaling link between MAVS and IRF-5.

  9. Automatic EEG spike detection.

    Science.gov (United States)

    Harner, Richard

    2009-10-01

    Since the 1970s advances in science and technology during each succeeding decade have renewed the expectation of efficient, reliable automatic epileptiform spike detection (AESD). But even when reinforced with better, faster tools, clinically reliable unsupervised spike detection remains beyond our reach. Expert-selected spike parameters were the first and still most widely used for AESD. Thresholds for amplitude, duration, sharpness, rise-time, fall-time, after-coming slow waves, background frequency, and more have been used. It is still unclear which of these wave parameters are essential, beyond peak-peak amplitude and duration. Wavelet parameters are very appropriate to AESD but need to be combined with other parameters to achieve desired levels of spike detection efficiency. Artificial Neural Network (ANN) and expert-system methods may have reached peak efficiency. Support Vector Machine (SVM) technology focuses on outliers rather than centroids of spike and nonspike data clusters and should improve AESD efficiency. An exemplary spike/nonspike database is suggested as a tool for assessing parameters and methods for AESD and is available in CSV or Matlab formats from the author at brainvue@gmail.com. Exploratory Data Analysis (EDA) is presented as a graphic method for finding better spike parameters and for the step-wise evaluation of the spike detection process.

  10. A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis

    DEFF Research Database (Denmark)

    Siegel, Gabriele; Obernosterer, Gregor; Fiore, Roberto

    2009-01-01

    of acyl protein thioesterase 1 (APT1), an enzyme regulating the palmitoylation status of proteins that are known to function at the synapse, including the alpha(13) subunits of G proteins (Galpha(13)). RNA-interference-mediated knockdown of APT1 and the expression of membrane-localized Galpha(13) both...... suppress spine enlargement caused by inhibition of miR-138, suggesting that APT1-regulated depalmitoylation of Galpha(13) might be an important downstream event of miR-138 function. Our results uncover a previously unknown miRNA-dependent mechanism in neurons and demonstrate a previously unrecognized...

  11. HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation

    Science.gov (United States)

    Granelli-Piperno, Angela; Golebiowska, Angelika; Trumpfheller, Christine; Siegal, Frederick P.; Steinman, Ralph M.

    2004-05-01

    Dendritic cells (DCs) undergo maturation during virus infection and thereby become potent stimulators of cell-mediated immunity. HIV-1 replicates in immature DCs, but we now find that infection is not accompanied by many components of maturation in either infected cells or uninfected bystanders. The infected cultures do not develop potent stimulating activity for the mixed leukocyte reaction (MLR), and the DCs producing HIV-1 gag p24 do not express CD83 and DC-lysosome-associated membrane protein maturation markers. If different maturation stimuli are applied to DCs infected with HIV-1, the infected cells selectively fail to mature. When DCs from HIV-1-infected patients are infected and cultured with autologous T cells, IL-10 was produced in 6 of 10 patients. These DC-T cell cocultures could suppress another immune response, the MLR. The regulation was partially IL-10-dependent and correlated in extent with the level of IL-10 produced. Suppressor cells only developed from infected patients, rather than healthy controls, and the DCs had to be exposed to live virus rather than HIV-1 gag peptides or protein. These results indicate that HIV-1-infected DCs have two previously unrecognized means to evade immune responses: maturation can be blocked reducing the efficacy of antigen presentation from infected cells, and T cell-dependent suppression can be induced.

  12. Addition of interferon-alpha to a standard maturation cocktail induces CD38 up-regulation and increases dendritic cell function

    DEFF Research Database (Denmark)

    Trepiakas, Redas; Pedersen, Anders Elm; Met, Ozcan

    2009-01-01

    Monocyte-derived dendritic cells (DCs) are used as adjuvant cells in cancer immunotherapy and have shown promising results. In order to obtain full functional capacity, these DCs need to be maturated, and the current "gold standard" for this process is maturation with TNF-alpha, IL-1beta, IL-6...... a functional relationship between CD38, IFN-alpha and TLR3. Thus, CD38 appear to be a relevant marker for activation by TLR3 or IFN-alpha. Addition of IFN-alpha to the sDC cocktail results in up-regulation of both CD38 and CD83 and improved capacity for induction of autologous T-cell responses despite few...... other changes in DC phenotype and cytokine secretion. Our observations suggest that IFN-alpha could be included in maturation protocols for clinical grade DCs used for immunotherapy against cancer and should be included if DCs are used for CD8+ T-cell stimulation in vitro....

  13. CC chemokine receptor 4 is required for experimental autoimmune encephalomyelitis by regulating GM-CSF and IL-23 production in dendritic cells

    Science.gov (United States)

    Poppensieker, Karola; Otte, David-Marian; Schürmann, Britta; Limmer, Andreas; Dresing, Philipp; Drews, Eva; Schumak, Beatrix; Klotz, Luisa; Raasch, Jennifer; Mildner, Alexander; Waisman, Ari; Scheu, Stefanie; Knolle, Percy; Förster, Irmgard; Prinz, Marco; Maier, Wolfgang; Zimmer, Andreas; Alferink, Judith

    2012-01-01

    Dendritic cells (DCs) are pivotal for the development of experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which they control disease remain to be determined. This study demonstrates that expression of CC chemokine receptor 4 (CCR4) by DCs is required for EAE induction. CCR4−/− mice presented enhanced resistance to EAE associated with a reduction in IL-23 and GM-CSF expression in the CNS. Restoring CCR4 on myeloid cells in bone marrow chimeras or intracerebral microinjection of CCR4-competent DCs, but not macrophages, restored EAE in CCR4−/− mice, indicating that CCR4+ DCs are cellular mediators of EAE development. Mechanistically, CCR4−/− DCs were less efficient in GM-CSF and IL-23 production and also TH-17 maintenance. Intraspinal IL-23 reconstitution restored EAE in CCR4−/− mice, whereas intracerebral inoculation using IL-23−/− DCs or GM-CSF−/− DCs failed to induce disease. Thus, CCR4-dependent GM-CSF production in DCs required for IL-23 release in these cells is a major component in the development of EAE. Our study identified a unique role for CCR4 in regulating DC function in EAE, harboring therapeutic potential for the treatment of CNS autoimmunity by targeting CCR4 on this specific cell type. PMID:22355103

  14. Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25.

    Science.gov (United States)

    Li, Ying; Sheng, Kangliang; Chen, Jingyu; Wu, Yujing; Zhang, Feng; Chang, Yan; Wu, Huaxun; Fu, Jingjing; Zhang, Lingling; Wei, Wei

    2015-12-15

    This study was to investigate PGE2 and TNF-alpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells (DCs) and the effect of CP-25. Bone marrow DCs were isolated and stimulated by PGE2 and TNF-alpha respectively. The markers of maturation and activation expressed on DCs, such as CD40, CD80, CD83, CD86, MHC-II, and the ability of antigen uptake of DCs were analyzed by flow cytometry. The proliferation of T cells co-cultured with DCs, the signaling pathways of PGE2-EP4-cAMP and TNF-alpha-TRADD-TRAF2-NF-κB in DCs were analyzed. The results showed that both PGE2 and TNF-alpha up-regulated the expressions of CD40, CD80, CD83, CD86, and MHC-II, decreased the antigen uptake of DCs, and DCs stimulated by PGE2 or TNF-alpha could increase T cell proliferation. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased significantly the expressions of CD40, CD80, CD83, CD86 and MHC-II, increased the antigen uptake of DCs, and suppressed T cell proliferation induced by DCs. PGE2 increased the expressions of EP4, NF-κB and down-regulated cAMP level of DCs. TNF-alpha could also up-regulate TNFR1, TRADD, TRAF2, and NF-κB expression of DCs. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased the expressions of EP4 and NF-κB, increased cAMP level in DCs stimulated by PGE2. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) also could down-regulate significantly TNFR1, TRADD, TRAF2, and NF-κB expression in DCs stimulated by TNF-alpha. These results demonstrate that PGE2 and TNF-alpha could enhance DCs functions by mediating PGE2-EP4-cAMP pathway, TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathway respectively. CP-25 might inhibit the function of DCs through regulating PGE2-EP4-cAMP and TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Palmitoylation-dependent CDKL5–PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development

    OpenAIRE

    Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

    2013-01-01

    The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD...

  16. CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation.

    Science.gov (United States)

    Kim, Jin Hyoung; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Patil, Ajit Mahadev; Han, Young Woo; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

    2015-12-02

    Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.

  17. βIII Spectrin Is Necessary for Formation of the Constricted Neck of Dendritic Spines and Regulation of Synaptic Activity in Neurons.

    Science.gov (United States)

    Efimova, Nadia; Korobova, Farida; Stankewich, Michael C; Moberly, Andrew H; Stolz, Donna B; Wang, Junling; Kashina, Anna; Ma, Minghong; Svitkina, Tatyana

    2017-07-05

    Dendritic spines are postsynaptic structures in neurons often having a mushroom-like shape. Physiological significance and cytoskeletal mechanisms that maintain this shape are poorly understood. The spectrin-based membrane skeleton maintains the biconcave shape of erythrocytes, but whether spectrins also determine the shape of nonerythroid cells is less clear. We show that βIII spectrin in hippocampal and cortical neurons from rodent embryos of both sexes is distributed throughout the somatodendritic compartment but is particularly enriched in the neck and base of dendritic spines and largely absent from spine heads. Electron microscopy revealed that βIII spectrin forms a detergent-resistant cytoskeletal network at these sites. Knockdown of βIII spectrin results in a significant decrease in the density of dendritic spines. Surprisingly, the density of presynaptic terminals is not affected by βIII spectrin knockdown. However, instead of making normal spiny synapses, the presynaptic structures in βIII spectrin-depleted neurons make shaft synapses that exhibit increased amplitudes of miniature EPSCs indicative of excessive postsynaptic excitation. Thus, βIII spectrin is necessary for formation of the constricted shape of the spine neck, which in turn controls communication between the synapse and the parent dendrite to prevent excessive excitation. Notably, mutations of SPTNB2 encoding βIII spectrin are associated with neurodegenerative syndromes, spinocerebellar ataxia Type 5, and spectrin-associated autosomal recessive cerebellar ataxia Type 1, but molecular mechanisms linking βIII spectrin functions to neuronal pathologies remain unresolved. Our data suggest that spinocerebellar ataxia Type 5 and spectrin-associated autosomal recessive cerebellar ataxia Type 1 pathology likely arises from poorly controlled synaptic activity that leads to excitotoxicity and neurodegeneration. SIGNIFICANCE STATEMENT Dendritic spines are small protrusions from neuronal

  18. A critical evaluation of the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1 ’s putative role in regulating dendritic plasticity, cognitive processes, and mood in animal models of depression.

    Directory of Open Access Journals (Sweden)

    Yan eLi

    2015-08-01

    Full Text Available Major depressive disorder (MDD is primarily conceptualized as a mood disorder but cognitive dysfunction is also prevalent, and may limit the daily function of MDD patients. Current theories on MDD highlight disturbances in dendritic plasticity in its pathophysiology, which could conceivably play a role in the production of both MDD-related mood and cognitive symptoms. This paper attempts to review the accumulated knowledge on the basic biology of the activity-regulated cytoskeleton-associated protein (Arc or Arg3.1, its effects on neural plasticity, and how these may be related to mood or cognitive dysfunction in animal models of MDD. On a cellular level, Arc is found to play an important role in modulating dendritic spine density and remodeling. Arc is also found to have a close, bidirectional relationship with postsynaptic glutamate neurotransmission, since it is stimulated by multiple glutamatergic receptor mechanisms but also modulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor internalization. The effects on AMPA receptor trafficking are likely related to Arc’s ability to modulate phenomena such as long-term potentiation, long-term depression, and synaptic scaling, each of which are important for maintaining proper cognitive function. Animal studies of chronic stress models of MDD show suppressed Arc expression in the frontal cortex but elevation in the amygdala. Interestingly, cognitive tasks depending on the frontal cortex are generally impaired by chronic stress, while those depending on the amygdala are enhanced, and antidepressant treatments stimulate cortical Arc expression with a timeline that is reminiscent of the treatment efficacy lag observed in the clinic or in preclinical models. However, pharmacological treatments that stimulate regional Arc expression do not universally improve relevant cognitive functions, and this highlights a need to further refine our understanding of Arc on a subcellular and

  19. Dendritic cells and anergic type I NKT cells play a crucial role in sulfatide-mediated immune regulation in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Maricic, Igor; Halder, Ramesh; Bischof, Felix; Kumar, Vipin

    2014-08-01

    CD1d-restricted NKT cells can be divided into two groups: type I NKT cells use a semi-invariant TCR, whereas type II express a relatively diverse set of TCRs. A major subset of type II NKT cells recognizes myelin-derived sulfatides and is selectively enriched in the CNS tissue during experimental autoimmune encephalomyelitis (EAE). We have shown that activation of sulfatide-reactive type II NKT cells by sulfatide prevents induction of EAE. In this article, we have addressed the mechanism of regulation, as well as whether a single immunodominant form of synthetic sulfatide can treat ongoing chronic and relapsing EAE in SJL/J mice. We have shown that the activation of sulfatide-reactive type II NKT cells leads to a significant reduction in the frequency and effector function of myelin proteolipid proteins 139-151/I-A(s)-tetramer(+) cells in lymphoid and CNS tissues. In addition, type I NKT cells and dendritic cells (DCs) in the periphery, as well as CNS-resident microglia, are inactivated after sulfatide administration, and mice deficient in type I NKT cells are not protected from disease. Moreover, tolerized DCs from sulfatide-treated animals can adoptively transfer protection into naive mice. Treatment of SJL/J mice with a synthetic cis-tetracosenoyl sulfatide, but not α-galactosylceramide, reverses ongoing chronic and relapsing EAE. Our data highlight a novel immune-regulatory pathway involving NKT subset interactions leading to inactivation of type I NKT cells, DCs, and microglial cells in suppression of autoimmunity. Because CD1 molecules are nonpolymorphic, the sulfatide-mediated immune-regulatory pathway can be targeted for development of non-HLA-dependent therapeutic approaches to T cell-mediated autoimmune diseases. Copyright © 2014 by The American Association of Immunologists, Inc.

  20. RAB-10-Dependent Membrane Transport Is Required for Dendrite Arborization

    Science.gov (United States)

    Zou, Wei; Yadav, Smita; DeVault, Laura; Jan, Yuh Nung; Sherwood, David R.

    2015-01-01

    Formation of elaborately branched dendrites is necessary for the proper input and connectivity of many sensory neurons. Previous studies have revealed that dendritic growth relies heavily on ER-to-Golgi transport, Golgi outposts and endocytic recycling. How new membrane and associated cargo is delivered from the secretory and endosomal compartments to sites of active dendritic growth, however, remains unknown. Using a candidate-based genetic screen in C. elegans, we have identified the small GTPase RAB-10 as a key regulator of membrane trafficking during dendrite morphogenesis. Loss of rab-10 severely reduced proximal dendritic arborization in the multi-dendritic PVD neuron. RAB-10 acts cell-autonomously in the PVD neuron and localizes to the Golgi and early endosomes. Loss of function mutations of the exocyst complex components exoc-8 and sec-8, which regulate tethering, docking and fusion of transport vesicles at the plasma membrane, also caused proximal dendritic arborization defects and led to the accumulation of intracellular RAB-10 vesicles. In rab-10 and exoc-8 mutants, the trans-membrane proteins DMA-1 and HPO-30, which promote PVD dendrite stabilization and branching, no longer localized strongly to the proximal dendritic membranes and instead were sequestered within intracellular vesicles. Together these results suggest a crucial role for the Rab10 GTPase and the exocyst complex in controlling membrane transport from the secretory and/or endosomal compartments that is required for dendritic growth. PMID:26394140

  1. Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons.

    Science.gov (United States)

    Connelly, William M; Crunelli, Vincenzo; Errington, Adam C

    2017-05-24

    Backpropagating action potentials (bAPs) are indispensable in dendritic signaling. Conflicting Ca 2+ -imaging data and an absence of dendritic recording data means that the extent of backpropagation in thalamocortical (TC) and thalamic reticular nucleus (TRN) neurons remains unknown. Because TRN neurons signal electrically through dendrodendritic gap junctions and possibly via chemical dendritic GABAergic synapses, as well as classical axonal GABA release, this lack of knowledge is problematic. To address this issue, we made two-photon targeted patch-clamp recordings from rat TC and TRN neuron dendrites to measure bAPs directly. These recordings reveal that "tonic"' and low-threshold-spike (LTS) "burst" APs in both cell types are always recorded first at the soma before backpropagating into the dendrites while undergoing substantial distance-dependent dendritic amplitude attenuation. In TC neurons, bAP attenuation strength varies according to firing mode. During LTS bursts, somatic AP half-width increases progressively with increasing spike number, allowing late-burst spikes to propagate more efficiently into the dendritic tree compared with spikes occurring at burst onset. Tonic spikes have similar somatic half-widths to late burst spikes and undergo similar dendritic attenuation. In contrast, in TRN neurons, AP properties are unchanged between LTS bursts and tonic firing and, as a result, distance-dependent dendritic attenuation remains consistent across different firing modes. Therefore, unlike LTS-associated global electrical and calcium signals, the spatial influence of bAP signaling in TC and TRN neurons is more restricted, with potentially important behavioral-state-dependent consequences for synaptic integration and plasticity in thalamic neurons. SIGNIFICANCE STATEMENT In most neurons, action potentials (APs) initiate in the axosomatic region and propagate into the dendritic tree to provide a retrograde signal that conveys information about the level of

  2. Dendritic cell vaccines.

    Science.gov (United States)

    Mosca, Paul J; Lyerly, H Kim; Clay, Timothy M; Morse, Michael A; Lyerly, H Kim

    2007-05-01

    Dendritic cells are antigen-presenting cells that have been shown to stimulate tumor antigen-specific T cell responses in preclinical studies. Consequently, there has been intense interest in developing dendritic cell based cancer vaccines. A variety of methods for generating dendritic cells, loading them with tumor antigens, and administering them to patients have been described. In recent years, a number of early phase clinical trials have been performed and have demonstrated the safety and feasibility of dendritic cell immunotherapies. A number of these trials have generated valuable preliminary data regarding the clinical and immunologic response to DC-based immunotherapy. The emphasis of dendritic cell immunotherapy research is increasingly shifting toward the development of strategies to increase the potency of dendritic cell vaccine preparations.

  3. Familiar Taste Induces Higher Dendritic Levels of Activity-Regulated Cytoskeleton-Associated Protein in the Insular Cortex than a Novel One

    Science.gov (United States)

    Morin, Jean-Pascal; Quiroz, Cesar; Mendoza-Viveros, Lucia; Ramirez-Amaya, Victor; Bermudez-Rattoni, Federico

    2011-01-01

    The immediate early gene (IEG) "Arc" is known to play an important role in synaptic plasticity; its protein is locally translated in the dendrites where it has been involved in several types of plasticity mechanisms. Because of its tight coupling with neuronal activity, "Arc" has been widely used as a tool to tag behaviorally activated networks.…

  4. Spike timing-dependent plasticity as the origin of the formation of clustered synaptic efficacy engrams

    Directory of Open Access Journals (Sweden)

    Nicolangelo L Iannella

    2010-07-01

    Full Text Available Synapse location, dendritic active properties and synaptic plasticity are all known to play some role in shaping the different input streams impinging onto a neuron. It remains unclear however, how the magnitude and spatial distribution of synaptic efficacies emerge from this interplay. Here, we investigate this interplay using a biophysically detailed neuron model of a reconstructed layer 2/3 pyramidal cell and spike timing-dependent plasticity (STDP. Specifically, we focus on the issue of how the efficacy of synapses contributed by different input streams are spatially represented in dendrites after STDP learning. We construct a simple feed forward network where a detailed model neuron receives synaptic inputs independently from multiple yet equally sized groups of afferent fibres with correlated activity, mimicking the spike activity from different neuronal populations encoding, for example, different sensory modalities. Interestingly, ensuing STDP learning, we observe that for all afferent groups, STDP leads to synaptic efficacies arranged into spatially segregated clusters effectively partitioning the dendritic tree. These segregated clusters possess a characteristic global organisation in space, where they form a tessellation in which each group dominates mutually exclusive regions of the dendrite.Put simply, the dendritic imprint from different input streams left after STDP learning effectively forms what we term a dendritic efficacy mosaic. Furthermore, we show how variations of the inputs and STDP rule affect such an organization. Our model suggests that STDP may be an important mechanism for creating a clustered plasticity engram, which shapes how different input streams are spatially represented in dendrite.

  5. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    DEFF Research Database (Denmark)

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

    2002-01-01

    recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

  6. Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.

    Directory of Open Access Journals (Sweden)

    Bardia F Behabadi

    Full Text Available Neocortical pyramidal neurons (PNs receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.

  7. The variational spiked oscillator

    International Nuclear Information System (INIS)

    Aguilera-Navarro, V.C.; Ullah, N.

    1992-08-01

    A variational analysis of the spiked harmonic oscillator Hamiltonian -d 2 / d x 2 + x 2 + δ/ x 5/2 , δ > 0, is reported in this work. A trial function satisfying Dirichlet boundary conditions is suggested. The results are excellent for a large range of values of the coupling parameter. (author)

  8. Synaptic Control of Secretory Trafficking in Dendrites

    Directory of Open Access Journals (Sweden)

    Cyril Hanus

    2014-06-01

    Full Text Available Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo in dendrites exits the endoplasmic reticulum (ER from local zones of ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized membrane proteins can be processed locally, the mechanisms that control the spatial range of secretory cargo transport in dendritic segments are unknown. Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER compartments under regimes of low or increased neuronal activity. In response to activity blockade, post-ER carriers are highly mobile and are transported over long distances. Conversely, increasing synaptic activity dramatically restricts the spatial scale of post-ER trafficking along dendrites. This activity-induced confinement of secretory cargo requires site-specific phosphorylation of the kinesin motor KIF17 by Ca2+/calmodulin-dependent protein kinases (CaMK. Thus, the length scales of early secretory trafficking in dendrites are tuned by activity-dependent regulation of microtubule-dependent transport.

  9. Spiking neural network for recognizing spatiotemporal sequences of spikes

    International Nuclear Information System (INIS)

    Jin, Dezhe Z.

    2004-01-01

    Sensory neurons in many brain areas spike with precise timing to stimuli with temporal structures, and encode temporally complex stimuli into spatiotemporal spikes. How the downstream neurons read out such neural code is an important unsolved problem. In this paper, we describe a decoding scheme using a spiking recurrent neural network. The network consists of excitatory neurons that form a synfire chain, and two globally inhibitory interneurons of different types that provide delayed feedforward and fast feedback inhibition, respectively. The network signals recognition of a specific spatiotemporal sequence when the last excitatory neuron down the synfire chain spikes, which happens if and only if that sequence was present in the input spike stream. The recognition scheme is invariant to variations in the intervals between input spikes within some range. The computation of the network can be mapped into that of a finite state machine. Our network provides a simple way to decode spatiotemporal spikes with diverse types of neurons

  10. Marginal Iodine Deficiency Affects Dendritic Spine Development by Disturbing the Function of Rac1 Signaling Pathway on Cytoskeleton.

    Science.gov (United States)

    Min, Hui; Dong, Jing; Wang, Yi; Wang, Yuan; Yu, Ye; Shan, Zhongyan; Xi, Qi; Teng, Weiping; Chen, Jie

    2017-01-01

    Iodine deficiency (ID)-induced thyroid hormone (TH) insufficient during development leads to impairments of brain function, such as learning and memory. Marginal ID has been defined as subtle insufficiency of TH, characterized as low thyroxine (T 4 ) levels, whether marginal ID potentially had adverse effects on the development of hippocampus and the underlying mechanisms remain unclear. Thus, in the present study, we established Wistar rat models with ID diet during pregnancy and lactation. The effects of marginal ID on long-term potentiation (LTP) were investigated in the hippocampal CA1 region. To study the development of dendritic spines in pyramidal cells, Golgi-Cox staining was conducted on postnatal day (PN) 7, PN14, PN21, and PN28. The activation of Rac1 signaling pathway, which is essential for dendritic spine development by regulating actin cytoskeleton, was also investigated. Our results showed that marginal ID slightly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Besides, the density of dendritic spines during the critical period of rat postnatal development was mildly decreased, and we found no significant change of spine morphology in marginal ID group. We also observed decreased activation of the Rac1 signaling pathway in pups subjected to maternal marginal ID. Our study may support the hypothesis that decreased T 4 induced by marginal ID results in slight impairments of LTP and leads to mild damage of dendritic spine development, which may be due to abnormal regulation of Rac1 signaling pathway on cytoskeleton.

  11. A Novel Forward Genetic Screen for Identifying Mutations Affecting Larval Neuronal Dendrite Development in Drosophila melanogaster

    OpenAIRE

    Medina, Paul Mark B.; Swick, Lance L.; Andersen, Ryan; Blalock, Zachary; Brenman, Jay E.

    2006-01-01

    Vertebrate and invertebrate dendrites are information-processing compartments that can be found on both central and peripheral neurons. Elucidating the molecular underpinnings of information processing in the nervous system ultimately requires an understanding of the genetic pathways that regulate dendrite formation and maintenance. Despite the importance of dendrite development, few forward genetic approaches have been used to analyze the latest stages of dendrite development, including the ...

  12. Inorganic proton conducting electrolyte coupled oxide-based dendritic transistors for synaptic electronics.

    Science.gov (United States)

    Wan, Chang Jin; Zhu, Li Qiang; Zhou, Ju Mei; Shi, Yi; Wan, Qing

    2014-05-07

    Ionic/electronic hybrid devices with synaptic functions are considered to be the essential building blocks for neuromorphic systems and brain-inspired computing. Here, artificial synapses based on indium-zinc-oxide (IZO) transistors gated by nanogranular SiO2 proton-conducting electrolyte films are fabricated on glass substrates. Spike-timing dependent plasticity and paired-pulse facilitation are successfully mimicked in an individual bottom-gate transistor. Most importantly, dynamic logic and dendritic integration established by spatiotemporally correlated spikes are also mimicked in dendritic transistors with two in-plane gates as the presynaptic input terminals.

  13. Spike timing precision of neuronal circuits.

    Science.gov (United States)

    Kilinc, Deniz; Demir, Alper

    2018-04-17

    Spike timing is believed to be a key factor in sensory information encoding and computations performed by the neurons and neuronal circuits. However, the considerable noise and variability, arising from the inherently stochastic mechanisms that exist in the neurons and the synapses, degrade spike timing precision. Computational modeling can help decipher the mechanisms utilized by the neuronal circuits in order to regulate timing precision. In this paper, we utilize semi-analytical techniques, which were adapted from previously developed methods for electronic circuits, for the stochastic characterization of neuronal circuits. These techniques, which are orders of magnitude faster than traditional Monte Carlo type simulations, can be used to directly compute the spike timing jitter variance, power spectral densities, correlation functions, and other stochastic characterizations of neuronal circuit operation. We consider three distinct neuronal circuit motifs: Feedback inhibition, synaptic integration, and synaptic coupling. First, we show that both the spike timing precision and the energy efficiency of a spiking neuron are improved with feedback inhibition. We unveil the underlying mechanism through which this is achieved. Then, we demonstrate that a neuron can improve on the timing precision of its synaptic inputs, coming from multiple sources, via synaptic integration: The phase of the output spikes of the integrator neuron has the same variance as that of the sample average of the phases of its inputs. Finally, we reveal that weak synaptic coupling among neurons, in a fully connected network, enables them to behave like a single neuron with a larger membrane area, resulting in an improvement in the timing precision through cooperation.

  14. SuperSpike: Supervised Learning in Multilayer Spiking Neural Networks.

    Science.gov (United States)

    Zenke, Friedemann; Ganguli, Surya

    2018-04-13

    A vast majority of computation in the brain is performed by spiking neural networks. Despite the ubiquity of such spiking, we currently lack an understanding of how biological spiking neural circuits learn and compute in vivo, as well as how we can instantiate such capabilities in artificial spiking circuits in silico. Here we revisit the problem of supervised learning in temporally coding multilayer spiking neural networks. First, by using a surrogate gradient approach, we derive SuperSpike, a nonlinear voltage-based three-factor learning rule capable of training multilayer networks of deterministic integrate-and-fire neurons to perform nonlinear computations on spatiotemporal spike patterns. Second, inspired by recent results on feedback alignment, we compare the performance of our learning rule under different credit assignment strategies for propagating output errors to hidden units. Specifically, we test uniform, symmetric, and random feedback, finding that simpler tasks can be solved with any type of feedback, while more complex tasks require symmetric feedback. In summary, our results open the door to obtaining a better scientific understanding of learning and computation in spiking neural networks by advancing our ability to train them to solve nonlinear problems involving transformations between different spatiotemporal spike time patterns.

  15. Activity-dependent trafficking of lysosomes in dendrites and dendritic spines.

    Science.gov (United States)

    Goo, Marisa S; Sancho, Laura; Slepak, Natalia; Boassa, Daniela; Deerinck, Thomas J; Ellisman, Mark H; Bloodgood, Brenda L; Patrick, Gentry N

    2017-08-07

    In neurons, lysosomes, which degrade membrane and cytoplasmic components, are thought to primarily reside in somatic and axonal compartments, but there is little understanding of their distribution and function in dendrites. Here, we used conventional and two-photon imaging and electron microscopy to show that lysosomes traffic bidirectionally in dendrites and are present in dendritic spines. We find that lysosome inhibition alters their mobility and also decreases dendritic spine number. Furthermore, perturbing microtubule and actin cytoskeletal dynamics has an inverse relationship on the distribution and motility of lysosomes in dendrites. We also find trafficking of lysosomes is correlated with synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors. Strikingly, lysosomes traffic to dendritic spines in an activity-dependent manner and can be recruited to individual spines in response to local activation. These data indicate the position of lysosomes is regulated by synaptic activity and thus plays an instructive role in the turnover of synaptic membrane proteins. © 2017 Goo et al.

  16. Entorhinal-CA3 Dual-Input Control of Spike Timing in the Hippocampus by Theta-Gamma Coupling.

    Science.gov (United States)

    Fernández-Ruiz, Antonio; Oliva, Azahara; Nagy, Gergő A; Maurer, Andrew P; Berényi, Antal; Buzsáki, György

    2017-03-08

    Theta-gamma phase coupling and spike timing within theta oscillations are prominent features of the hippocampus and are often related to navigation and memory. However, the mechanisms that give rise to these relationships are not well understood. Using high spatial resolution electrophysiology, we investigated the influence of CA3 and entorhinal inputs on the timing of CA1 neurons. The theta-phase preference and excitatory strength of the afferent CA3 and entorhinal inputs effectively timed the principal neuron activity, as well as regulated distinct CA1 interneuron populations in multiple tasks and behavioral states. Feedback potentiation of distal dendritic inhibition by CA1 place cells attenuated the excitatory entorhinal input at place field entry, coupled with feedback depression of proximal dendritic and perisomatic inhibition, allowing the CA3 input to gain control toward the exit. Thus, upstream inputs interact with local mechanisms to determine theta-phase timing of hippocampal neurons to support memory and spatial navigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites

    Directory of Open Access Journals (Sweden)

    Guillermo López-Doménech

    2016-10-01

    Full Text Available Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration.

  18. Dendritic excitability modulates dendritic information processing in a purkinje cell model.

    Science.gov (United States)

    Coop, Allan D; Cornelis, Hugo; Santamaria, Fidel

    2010-01-01

    Using an electrophysiological compartmental model of a Purkinje cell we quantified the contribution of individual active dendritic currents to processing of synaptic activity from granule cells. We used mutual information as a measure to quantify the information from the total excitatory input current (I(Glu)) encoded in each dendritic current. In this context, each active current was considered an information channel. Our analyses showed that most of the information was encoded by the calcium (I(CaP)) and calcium activated potassium (I(Kc)) currents. Mutual information between I(Glu) and I(CaP) and I(Kc) was sensitive to different levels of excitatory and inhibitory synaptic activity that, at the same time, resulted in the same firing rate at the soma. Since dendritic excitability could be a mechanism to regulate information processing in neurons we quantified the changes in mutual information between I(Glu) and all Purkinje cell currents as a function of the density of dendritic Ca (g(CaP)) and Kca (g(Kc)) conductances. We extended our analysis to determine the window of temporal integration of I(Glu) by I(CaP) and I(Kc) as a function of channel density and synaptic activity. The window of information integration has a stronger dependence on increasing values of g(Kc) than on g(CaP), but at high levels of synaptic stimulation information integration is reduced to a few milliseconds. Overall, our results show that different dendritic conductances differentially encode synaptic activity and that dendritic excitability and the level of synaptic activity regulate the flow of information in dendrites.

  19. Dendritic cell neoplasms: an overview.

    Science.gov (United States)

    Kairouz, Sebastien; Hashash, Jana; Kabbara, Wadih; McHayleh, Wassim; Tabbara, Imad A

    2007-10-01

    Dendritic cell neoplasms are rare tumors that are being recognized with increasing frequency. They were previously classified as lymphomas, sarcomas, or histiocytic neoplasms. The World Health Organization (WHO) classifies dendritic cell neoplasms into five groups: Langerhans' cell histiocytosis, Langerhans' cell sarcoma, Interdigitating dendritic cell sarcoma/tumor, Follicular dendritic cell sarcoma/tumor, and Dendritic cell sarcoma, not specified otherwise (Jaffe, World Health Organization classification of tumors 2001; 273-289). Recently, Pileri et al. provided a comprehensive immunohistochemical classification of histiocytic and dendritic cell tumors (Pileri et al., Histopathology 2002;59:161-167). In this article, a concise overview regarding the pathological, clinical, and therapeutic aspects of follicular dendritic, interdigitating dendritic, and Langerhans' cell tumors is presented.

  20. Coronavirus spike-receptor interactions

    NARCIS (Netherlands)

    Mou, H.

    2015-01-01

    Coronaviruses cause important diseases in humans and animals. Coronavirus infection starts with the virus binding with its spike proteins to molecules present on the surface of host cells that act as receptors. This spike-receptor interaction is highly specific and determines the virus’ cell, tissue

  1. Probabilistic inference in general graphical models through sampling in stochastic networks of spiking neurons.

    Science.gov (United States)

    Pecevski, Dejan; Buesing, Lars; Maass, Wolfgang

    2011-12-01

    An important open problem of computational neuroscience is the generic organization of computations in networks of neurons in the brain. We show here through rigorous theoretical analysis that inherent stochastic features of spiking neurons, in combination with simple nonlinear computational operations in specific network motifs and dendritic arbors, enable networks of spiking neurons to carry out probabilistic inference through sampling in general graphical models. In particular, it enables them to carry out probabilistic inference in Bayesian networks with converging arrows ("explaining away") and with undirected loops, that occur in many real-world tasks. Ubiquitous stochastic features of networks of spiking neurons, such as trial-to-trial variability and spontaneous activity, are necessary ingredients of the underlying computational organization. We demonstrate through computer simulations that this approach can be scaled up to neural emulations of probabilistic inference in fairly large graphical models, yielding some of the most complex computations that have been carried out so far in networks of spiking neurons.

  2. Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons.

    Science.gov (United States)

    Díez-García, Andrea; Barros-Zulaica, Natali; Núñez, Ángel; Buño, Washington; Fernández de Sevilla, David

    2017-01-01

    According to Hebb's original hypothesis (Hebb, 1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic input causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol. Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca 2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca 2+ spike and Ca 2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor information.

  3. Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons

    Science.gov (United States)

    Díez-García, Andrea; Barros-Zulaica, Natali; Núñez, Ángel; Buño, Washington; Fernández de Sevilla, David

    2017-01-01

    According to Hebb's original hypothesis (Hebb, 1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic input causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol. Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca2+ spike and Ca2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor information. PMID:28203145

  4. Mapping spikes to sensations

    Directory of Open Access Journals (Sweden)

    Maik Christopher Stüttgen

    2011-11-01

    Full Text Available Single-unit recordings conducted during perceptual decision-making tasks have yielded tremendous insights into the neural coding of sensory stimuli. In such experiments, detection or discrimination behavior (the psychometric data is observed in parallel with spike trains in sensory neurons (the neurometric data. Frequently, candidate neural codes for information read-out are pitted against each other by transforming the neurometric data in some way and asking which code’s performance most closely approximates the psychometric performance. The code that matches the psychometric performance best is retained as a viable candidate and the others are rejected. In following this strategy, psychometric data is often considered to provide an unbiased measure of perceptual sensitivity. It is rarely acknowledged that psychometric data result from a complex interplay of sensory and non-sensory processes and that neglect of these processes may result in misestimating psychophysical sensitivity. This again may lead to erroneous conclusions regarding the adequacy of neural candidate codes. In this review, we first discuss requirements on the neural data for a subsequent neurometric-psychometric comparison. We then focus on different psychophysical tasks for the assessment of detection and discrimination performance and the cognitive processes that may underlie their execution. We discuss further factors that may compromise psychometric performance and how they can be detected or avoided. We believe that these considerations point to shortcomings in our understanding of the processes underlying perceptual decisions, and therefore offer potential for future research.

  5. NLRP10 Enhances CD4+ T-Cell-Mediated IFNγ Response via Regulation of Dendritic Cell-Derived IL-12 Release

    Directory of Open Access Journals (Sweden)

    Maurizio Vacca

    2017-11-01

    Full Text Available NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10−/− mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10−/− dendritic cells (DCs elicited sub-optimal IFNγ production by antigen-specific CD4+ T cells compared to wild-type (WT DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10−/− DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. Upon Mycobacterium tuberculosis (Mtb infection, Nlrp10−/− mice displayed diminished T helper 1-cell responses and increased bacterial growth compared to WT mice. These data indicate that NLRP10-mediated IL-12 production by DCs is critical for IFNγ induction in T cells and contributes to promote the host defense against Mtb.

  6. MyD88 Signaling Regulates Steady-State Migration of Intestinal CD103+ Dendritic Cells Independently of TNF-α and the Gut Microbiota

    DEFF Research Database (Denmark)

    Hägerbrand, Karin; Westlund, Jessica; Yrlid, Ulf

    2015-01-01

    Intestinal homeostasis and induction of systemic tolerance to fed Ags (i.e., oral tolerance) rely on the steady-state migration of smallintestinal lamina propria dendritic cells (DCs) into draining mesenteric lymph nodes (MLN). The majority of these migratory DCs express the α integrin chain CD103......, and in this study we demonstrate that the steady-state mobilization of CD103+ DCs into the MLN is in part governed by the IL-1R family/TLR signaling adaptor molecule MyD88. Similar to mice with complete MyD88 deficiency, specific deletion of MyD88 in DCs resulted in a 50–60% reduction in short-term accumulation......, the proportion and phenotypic composition of DCs were similar in mesentericlymph from germ-free and conventionally housed mice. Although TNF-α was required for CD103+ DC migration to the MLN after oral administration of the TLR7 agonist R848, it was not required for the steady-state migration of these cells...

  7. The ATP-binding cassette transporter A1 regulates phosphoantigen release and Vγ9Vδ2 T cell activation by dendritic cells

    Science.gov (United States)

    Castella, Barbara; Kopecka, Joanna; Sciancalepore, Patrizia; Mandili, Giorgia; Foglietta, Myriam; Mitro, Nico; Caruso, Donatella; Novelli, Francesco; Riganti, Chiara; Massaia, Massimo

    2017-01-01

    Vγ9Vδ2 T cells are activated by phosphoantigens, such as isopentenyl pyrophosphate (IPP), which is generated in the mevalonate pathway of antigen-presenting cells. IPP is released in the extracellular microenvironment via unknown mechanisms. Here we show that the ATP-binding cassette transporter A1 (ABCA1) mediates extracellular IPP release from dendritic cells (DC) in cooperation with apolipoprotein A-I (apoA-I) and butyrophilin-3A1. IPP concentrations in the supernatants are sufficient to induce Vγ9Vδ2 T cell proliferation after DC mevalonate pathway inhibition with zoledronic acid (ZA). ZA treatment increases ABCA1 and apoA-I expression via IPP-dependent LXRα nuclear translocation and PI3K/Akt/mTOR pathway inhibition. These results close the mechanistic gap in our understanding of extracellular IPP release from DC and provide a framework to fine-tune Vγ9Vδ2 T cell activation via mevalonate and PI3K/Akt/mTOR pathway modulation. PMID:28580927

  8. Allogeneic Adipose-Derived Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Regulating Self-Reactive T Cell Responses and Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Per Anderson

    2017-01-01

    Full Text Available Multipotent mesenchymal stromal cells (MSCs have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS. Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS and cyclooxygenase- (COX- 1/2 activities. mASCs also prevented the lipopolysaccharide- (LPS- induced maturation of dendritic cells (DCs in vitro. The addition of the COX-1/2 inhibitor indomethacin, but not the iNOS inhibitor L-NAME, reversed the block in DC maturation implicating prostaglandin (PG E2 in this process. In vivo, early administration of murine and human ASCs (hASCs ameliorated myelin oligodendrocyte protein- (MOG35-55- induced EAE in C57Bl/6 mice. Mechanistic studies showed that mASCs suppressed the function of autoantigen-specific T cells and also decreased the frequency of activated (CD11c+CD40high and CD11c+TNF-α+ DCs in draining lymph nodes (DLNs. In summary, these data suggest that mASCs reduce EAE severity, in part, through the impairment of DC and T cell function.

  9. Modification of dendritic development.

    Science.gov (United States)

    Feria-Velasco, Alfredo; del Angel, Alma Rosa; Gonzalez-Burgos, Ignacio

    2002-01-01

    Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the

  10. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis

    Directory of Open Access Journals (Sweden)

    Mala Misra

    2016-08-01

    Full Text Available Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling.

  11. The influence of single bursts vs. single spikes at excitatory dendrodendritic synapses

    Science.gov (United States)

    Masurkar, Arjun V.; Chen, Wei R.

    2015-01-01

    The synchronization of neuronal activity is thought to enhance information processing. There is much evidence supporting rhythmically bursting external tufted cells (ETCs) of the rodent olfactory bulb glomeruli coordinating the activation of glomerular interneurons and mitral cells via dendrodendritic excitation. However, as bursting has variable significance at axodendritic cortical synapses, it is not clear if ETC bursting imparts a specific functional advantage over the preliminary spike in dendrodendritic synaptic networks. To answer this question, we investigated the influence of single ETC bursts and spikes with the in-vitro rat olfactory bulb preparation at different levels of processing, via calcium imaging of presynaptic ETC dendrites, dual electrical recording of ETC–interneuron synaptic pairs, and multicellular calcium imaging of ETC-induced population activity. Our findings supported single ETC bursts, vs. single spikes, driving robust presynaptic calcium signaling, which in turn was associated with profound extension of the initial monosynaptic spike-driven dendrodendritic excitatory postsynaptic potential. This extension could be driven by either the spike-dependent or spike-independent components of the burst. At the population level, burst-induced excitation was more widespread and reliable compared with single spikes. This further supports the ETC network, in part due to a functional advantage of bursting at excitatory dendrodendritic synapses, coordinating synchronous activity at behaviorally relevant frequencies related to odor processing in vivo. PMID:22277089

  12. The influence of single bursts versus single spikes at excitatory dendrodendritic synapses.

    Science.gov (United States)

    Masurkar, Arjun V; Chen, Wei R

    2012-02-01

    The synchronization of neuronal activity is thought to enhance information processing. There is much evidence supporting rhythmically bursting external tufted cells (ETCs) of the rodent olfactory bulb glomeruli coordinating the activation of glomerular interneurons and mitral cells via dendrodendritic excitation. However, as bursting has variable significance at axodendritic cortical synapses, it is not clear if ETC bursting imparts a specific functional advantage over the preliminary spike in dendrodendritic synaptic networks. To answer this question, we investigated the influence of single ETC bursts and spikes with the in vitro rat olfactory bulb preparation at different levels of processing, via calcium imaging of presynaptic ETC dendrites, dual electrical recording of ETC -interneuron synaptic pairs, and multicellular calcium imaging of ETC-induced population activity. Our findings supported single ETC bursts, versus single spikes, driving robust presynaptic calcium signaling, which in turn was associated with profound extension of the initial monosynaptic spike-driven dendrodendritic excitatory postsynaptic potential. This extension could be driven by either the spike-dependent or spike-independent components of the burst. At the population level, burst-induced excitation was more widespread and reliable compared with single spikes. This further supports the ETC network, in part due to a functional advantage of bursting at excitatory dendrodendritic synapses, coordinating synchronous activity at behaviorally relevant frequencies related to odor processing in vivo. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  13. Biophysical properties and computational modeling of calcium spikes in serotonergic neurons of the dorsal raphe nucleus.

    Science.gov (United States)

    Tuckwell, Henry C

    2013-06-01

    Serotonergic neurons of the dorsal raphe nuclei, with their extensive innervation of nearly the whole brain have important modulatory effects on many cognitive and physiological processes. They play important roles in clinical depression and other psychiatric disorders. In order to quantify the effects of serotonergic transmission on target cells it is desirable to construct computational models and to this end these it is necessary to have details of the biophysical and spike properties of the serotonergic neurons. Here several basic properties are reviewed with data from several studies since the 1960s to the present. The quantities included are input resistance, resting membrane potential, membrane time constant, firing rate, spike duration, spike and afterhyperpolarization (AHP) amplitude, spike threshold, cell capacitance, soma and somadendritic areas. The action potentials of these cells are normally triggered by a combination of sodium and calcium currents which may result in autonomous pacemaker activity. We here analyse the mechanisms of high-threshold calcium spikes which have been demonstrated in these cells the presence of TTX (tetrodotoxin). The parameters for calcium dynamics required to give calcium spikes are quite different from those for regular spiking which suggests the involvement of restricted parts of the soma-dendritic surface as has been found, for example, in hippocampal neurons. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Wavelet analysis of epileptic spikes

    Science.gov (United States)

    Latka, Miroslaw; Was, Ziemowit; Kozik, Andrzej; West, Bruce J.

    2003-05-01

    Interictal spikes and sharp waves in human EEG are characteristic signatures of epilepsy. These potentials originate as a result of synchronous pathological discharge of many neurons. The reliable detection of such potentials has been the long standing problem in EEG analysis, especially after long-term monitoring became common in investigation of epileptic patients. The traditional definition of a spike is based on its amplitude, duration, sharpness, and emergence from its background. However, spike detection systems built solely around this definition are not reliable due to the presence of numerous transients and artifacts. We use wavelet transform to analyze the properties of EEG manifestations of epilepsy. We demonstrate that the behavior of wavelet transform of epileptic spikes across scales can constitute the foundation of a relatively simple yet effective detection algorithm.

  15. Wavelet analysis of epileptic spikes

    CERN Document Server

    Latka, M; Kozik, A; West, B J; Latka, Miroslaw; Was, Ziemowit; Kozik, Andrzej; West, Bruce J.

    2003-01-01

    Interictal spikes and sharp waves in human EEG are characteristic signatures of epilepsy. These potentials originate as a result of synchronous, pathological discharge of many neurons. The reliable detection of such potentials has been the long standing problem in EEG analysis, especially after long-term monitoring became common in investigation of epileptic patients. The traditional definition of a spike is based on its amplitude, duration, sharpness, and emergence from its background. However, spike detection systems built solely around this definition are not reliable due to the presence of numerous transients and artifacts. We use wavelet transform to analyze the properties of EEG manifestations of epilepsy. We demonstrate that the behavior of wavelet transform of epileptic spikes across scales can constitute the foundation of a relatively simple yet effective detection algorithm.

  16. Role of Dendritic Cells in Immune Dysfunction

    Science.gov (United States)

    Savary, Cherylyn A.

    1997-01-01

    Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

  17. Dendritic cells in Barrett's esophagus and esophageal adenocarcinoma.

    Science.gov (United States)

    Bobryshev, Yuri V; Tran, Dinh; Killingsworth, Murray C; Buckland, Michael; Lord, Reginald V N

    2009-01-01

    Like other premalignant conditions that develop in the presence of chronic inflammation, the development and progression of Barrett's esophagus is associated with the development of an immune response, but how this immune response is regulated is poorly understood. A comprehensive literature search failed to find any report of the presence of dendritic cells in Barrett's intestinal metaplasia and esophageal adenocarcinoma and this prompted our study. We used immunohistochemical staining and electron microscopy to examine whether dendritic cells are present in Barrett's esophagus and esophageal adenocarcinoma. Immunohistochemical staining with CD83, a specific marker for dendritic cells, was performed on paraffin-embedded sections of Barrett's intestinal metaplasia (IM, n = 12), dysplasia (n = 11) and adenocarcinoma (n = 14). CD83+ cells were identified in the lamina propria surrounding intestinal type glands in Barrett's IM, dysplasia, and cancer tissues. Computerized quantitative analysis showed that the numbers of dendritic cells were significantly higher in cancer tissues. Double immunostaining with CD83, CD20, and CD3, and electron microscopy demonstrated that dendritic cells are present in Barrett's esophagus and form clusters with T cells and B cells directly within the lamina propria. These findings demonstrate that dendritic cells are present in Barrett's tissues, with a significant increase in density in adenocarcinoma compared to benign Barrett's esophagus. Dendritic cells may have a role in the pathogenesis and immunotherapy treatment of Barrett's esophagus and adenocarcinoma.

  18. Conserved RNA-Binding Proteins Required for Dendrite Morphogenesis in Caenorhabditis elegans Sensory Neurons

    Science.gov (United States)

    Antonacci, Simona; Forand, Daniel; Wolf, Margaret; Tyus, Courtney; Barney, Julia; Kellogg, Leah; Simon, Margo A.; Kerr, Genevieve; Wells, Kristen L.; Younes, Serena; Mortimer, Nathan T.; Olesnicky, Eugenia C.; Killian, Darrell J.

    2015-01-01

    The regulation of dendritic branching is critical for sensory reception, cell−cell communication within the nervous system, learning, memory, and behavior. Defects in dendrite morphology are associated with several neurologic disorders; thus, an understanding of the molecular mechanisms that govern dendrite morphogenesis is important. Recent investigations of dendrite morphogenesis have highlighted the importance of gene regulation at the posttranscriptional level. Because RNA-binding proteins mediate many posttranscriptional mechanisms, we decided to investigate the extent to which conserved RNA-binding proteins contribute to dendrite morphogenesis across phyla. Here we identify a core set of RNA-binding proteins that are important for dendrite morphogenesis in the PVD multidendritic sensory neuron in Caenorhabditis elegans. Homologs of each of these genes were previously identified as important in the Drosophila melanogaster dendritic arborization sensory neurons. Our results suggest that RNA processing, mRNA localization, mRNA stability, and translational control are all important mechanisms that contribute to dendrite morphogenesis, and we present a conserved set of RNA-binding proteins that regulate these processes in diverse animal species. Furthermore, homologs of these genes are expressed in the human brain, suggesting that these RNA-binding proteins are candidate regulators of dendrite development in humans. PMID:25673135

  19. Sleeping dendrites: fiber-optic measurements of dendritic calcium activity in freely moving and sleeping animals

    Directory of Open Access Journals (Sweden)

    Julie Seibt

    2014-03-01

    Full Text Available Dendrites are the post-synaptic sites of most excitatory and inhibitory synapses in the brain, making them the main location of cortical information processing and synaptic plasticity. Although current hypotheses suggest a central role for sleep in proper cognitive function and brain plasticity, virtually nothing is known about changes in dendritic activity across the sleep-wake cycle and how waking experience modifies this activity. To start addressing these questions, we developed a method that allows long-term recordings of EEGs/EMG combined with in vivo cortical calcium (Ca2+ activity in freely moving and sleeping rats. We measured Ca2+ activity from populations of dendrites of layer (L 5 pyramidal neurons (n = 13 rats that we compared with Ca2+ activity from populations of neurons in L2/3 (n = 11 rats. L5 and L2/3 neurons were labelled using bolus injection of OGB1-AM or GCaMP6 (1. Ca2+ signals were detected using a fiber-optic system (cannula diameter = 400µm, transmitting the changes in fluorescence to a photodiode. Ca2+ fluctuations could then be correlated with ongoing changes in brain oscillatory activity during 5 major brain states: active wake [AW], quiet wake [QW], NREM, REM and NREM-REM transition (or intermediate state, [IS]. Our Ca2+ recordings show large transients in L5 dendrites and L2/3 neurons that oscillate predominantly at frequencies In summary, we show that this technique is successful in monitoring fluctuations in ongoing dendritic Ca2+ activity during natural brain states and allows, in principle, to combine behavioral measurement with imaging from various brain regions (e.g. deep structures in freely behaving animals. Using this method, we show that Ca2+ transients from populations of L2/3 neurons and L5 dendrites are deferentially regulated across the sleep/wake cycle, with dendritic activity being the highest during the IS sleep. Our correlation analysis suggests that specific sleep EEG activity during NREM and IS

  20. Stochastic models for spike trains of single neurons

    CERN Document Server

    Sampath, G

    1977-01-01

    1 Some basic neurophysiology 4 The neuron 1. 1 4 1. 1. 1 The axon 7 1. 1. 2 The synapse 9 12 1. 1. 3 The soma 1. 1. 4 The dendrites 13 13 1. 2 Types of neurons 2 Signals in the nervous system 14 2. 1 Action potentials as point events - point processes in the nervous system 15 18 2. 2 Spontaneous activi~ in neurons 3 Stochastic modelling of single neuron spike trains 19 3. 1 Characteristics of a neuron spike train 19 3. 2 The mathematical neuron 23 4 Superposition models 26 4. 1 superposition of renewal processes 26 4. 2 Superposition of stationary point processe- limiting behaviour 34 4. 2. 1 Palm functions 35 4. 2. 2 Asymptotic behaviour of n stationary point processes superposed 36 4. 3 Superposition models of neuron spike trains 37 4. 3. 1 Model 4. 1 39 4. 3. 2 Model 4. 2 - A superposition model with 40 two input channels 40 4. 3. 3 Model 4. 3 4. 4 Discussion 41 43 5 Deletion models 5. 1 Deletion models with 1nd~endent interaction of excitatory and inhibitory sequences 44 VI 5. 1. 1 Model 5. 1 The basic de...

  1. Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft rejection

    International Nuclear Information System (INIS)

    Zheng, De-Hua; Dou, Li-Ping; Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong; Shi, Bing-Yi

    2010-01-01

    Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-γ by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4 + CD25 high Foxp3 + regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

  2. Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells and down-regulates cardiac allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, De-Hua [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Dou, Li-Ping [Department of Hematology, Chinese PLA General Hospital, No. 28 Fu-Xing Road, Beijing 100853 (China); Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Shi, Bing-Yi, E-mail: shibingyi@medmail.com.cn [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China)

    2010-05-14

    Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-{gamma} by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4{sup +}CD25{sup high}Foxp3{sup +} regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

  3. Dendritic protein synthesis in the normal and diseased brain

    Science.gov (United States)

    Swanger, Sharon A.; Bassell, Gary J.

    2015-01-01

    Synaptic activity is a spatially-limited process that requires a precise, yet dynamic, complement of proteins within the synaptic micro-domain. The maintenance and regulation of these synaptic proteins is regulated, in part, by local mRNA translation in dendrites. Protein synthesis within the postsynaptic compartment allows neurons tight spatial and temporal control of synaptic protein expression, which is critical for proper functioning of synapses and neural circuits. In this review, we discuss the identity of proteins synthesized within dendrites, the receptor-mediated mechanisms regulating their synthesis, and the possible roles for these locally synthesized proteins. We also explore how our current understanding of dendritic protein synthesis in the hippocampus can be applied to new brain regions and to understanding the pathological mechanisms underlying varied neurological diseases. PMID:23262237

  4. Training spiking neural networks to associate spatio-temporal input-output spike patterns

    OpenAIRE

    Mohemmed, A; Schliebs, S; Matsuda, S; Kasabov, N

    2013-01-01

    In a previous work (Mohemmed et al., Method for training a spiking neuron to associate input–output spike trains) [1] we have proposed a supervised learning algorithm based on temporal coding to train a spiking neuron to associate input spatiotemporal spike patterns to desired output spike patterns. The algorithm is based on the conversion of spike trains into analogue signals and the application of the Widrow–Hoff learning rule. In this paper we present a mathematical formulation of the prop...

  5. Computational modeling of distinct neocortical oscillations driven by cell-type selective optogenetic drive: Separable resonant circuits controlled by low-threshold spiking and fast-spiking interneurons

    Directory of Open Access Journals (Sweden)

    Dorea Vierling-Claassen

    2010-11-01

    Full Text Available Selective optogenetic drive of fast spiking interneurons (FS leads to enhanced local field potential (LFP power across the traditional gamma frequency band (20-80Hz; Cardin et al., 2009. In contrast, drive to regular-spiking pyramidal cells (RS enhances power at lower frequencies, with a peak at 8 Hz. The first result is consistent with previous computational studies emphasizing the role of FS and the time constant of GABAA synaptic inhibition in gamma rhythmicity. However, the same theoretical models do not typically predict low-frequency LFP enhancement with RS drive. To develop hypotheses as to how the same network can support these contrasting behaviors, we constructed a biophysically principled network model of primary somatosensory neocortex containing FS, RS and low-threshold-spiking (LTS interneurons. Cells were modeled with detailed cell anatomy and physiology, multiple dendritic compartments, and included active somatic and dendritic ionic currents. Consistent with prior studies, the model demonstrated gamma resonance during FS drive, dependent on the time-constant of GABAA inhibition induced by synchronous FS activity. Lower frequency enhancement during RS drive was replicated only on inclusion of an inhibitory LTS population, whose activation was critically dependent on RS synchrony and evoked longer-lasting inhibition. Our results predict that differential recruitment of FS and LTS inhibitory populations is essential to the observed cortical dynamics and may provide a means for amplifying the natural expression of distinct oscillations in normal cortical processing.

  6. Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes

    Science.gov (United States)

    2012-01-01

    Action potentials at the neurons and graded signals at the synapses are primary codes in the brain. In terms of their functional interaction, the studies were focused on the influence of presynaptic spike patterns on synaptic activities. How the synapse dynamics quantitatively regulates the encoding of postsynaptic digital spikes remains unclear. We investigated this question at unitary glutamatergic synapses on cortical GABAergic neurons, especially the quantitative influences of release probability on synapse dynamics and neuronal encoding. Glutamate release probability and synaptic strength are proportionally upregulated by presynaptic sequential spikes. The upregulation of release probability and the efficiency of probability-driven synaptic facilitation are strengthened by elevating presynaptic spike frequency and Ca2+. The upregulation of release probability improves spike capacity and timing precision at postsynaptic neuron. These results suggest that the upregulation of presynaptic glutamate release facilitates a conversion of synaptic analogue signals into digital spikes in postsynaptic neurons, i.e., a functional compatibility between presynaptic and postsynaptic partners. PMID:22852823

  7. Computing with Spiking Neuron Networks

    NARCIS (Netherlands)

    H. Paugam-Moisy; S.M. Bohte (Sander); G. Rozenberg; T.H.W. Baeck (Thomas); J.N. Kok (Joost)

    2012-01-01

    htmlabstractAbstract Spiking Neuron Networks (SNNs) are often referred to as the 3rd gener- ation of neural networks. Highly inspired from natural computing in the brain and recent advances in neurosciences, they derive their strength and interest from an ac- curate modeling of synaptic interactions

  8. Neuroelectric Tuning of Cortical Oscillations by Apical Dendrites in Loop Circuits

    Directory of Open Access Journals (Sweden)

    David LaBerge

    2017-06-01

    Full Text Available Bundles of relatively long apical dendrites dominate the neurons that make up the thickness of the cerebral cortex. It is proposed that a major function of the apical dendrite is to produce sustained oscillations at a specific frequency that can serve as a common timing unit for the processing of information in circuits connected to that apical dendrite. Many layer 5 and 6 pyramidal neurons are connected to thalamic neurons in loop circuits. A model of the apical dendrites of these pyramidal neurons has been used to simulate the electric activity of the apical dendrite. The results of that simulation demonstrated that subthreshold electric pulses in these apical dendrites can be tuned to specific frequencies and also can be fine-tuned to narrow bandwidths of less than one Hertz (1 Hz. Synchronous pulse outputs from the circuit loops containing apical dendrites can tune subthreshold membrane oscillations of neurons they contact. When the pulse outputs are finely tuned, they function as a local “clock,” which enables the contacted neurons to synchronously communicate with each other. Thus, a shared tuning frequency can select neurons for membership in a circuit. Unlike layer 6 apical dendrites, layer 5 apical dendrites can produce burst firing in many of their neurons, which increases the amplitude of signals in the neurons they contact. This difference in amplitude of signals serves as basis of selecting a sub-circuit for specialized processing (e.g., sustained attention within the typically larger layer 6-based circuit. After examining the sustaining of oscillations in loop circuits and the processing of spikes in network circuits, we propose that cortical functioning can be globally viewed as two systems: a loop system and a network system. The loop system oscillations influence the network system’s timing and amplitude of pulse signals, both of which can select circuits that are momentarily dominant in cortical activity.

  9. Automatic spike sorting using tuning information.

    Science.gov (United States)

    Ventura, Valérie

    2009-09-01

    Current spike sorting methods focus on clustering neurons' characteristic spike waveforms. The resulting spike-sorted data are typically used to estimate how covariates of interest modulate the firing rates of neurons. However, when these covariates do modulate the firing rates, they provide information about spikes' identities, which thus far have been ignored for the purpose of spike sorting. This letter describes a novel approach to spike sorting, which incorporates both waveform information and tuning information obtained from the modulation of firing rates. Because it efficiently uses all the available information, this spike sorter yields lower spike misclassification rates than traditional automatic spike sorters. This theoretical result is verified empirically on several examples. The proposed method does not require additional assumptions; only its implementation is different. It essentially consists of performing spike sorting and tuning estimation simultaneously rather than sequentially, as is currently done. We used an expectation-maximization maximum likelihood algorithm to implement the new spike sorter. We present the general form of this algorithm and provide a detailed implementable version under the assumptions that neurons are independent and spike according to Poisson processes. Finally, we uncover a systematic flaw of spike sorting based on waveform information only.

  10. A Simulation Study on the Effects of Dendritic Morphology on Layer V Prefontal Pyramidal Cell Firing Behavior

    Directory of Open Access Journals (Sweden)

    Maria ePsarrou

    2014-09-01

    Full Text Available Pyramidal cells, the most abundant neurons in neocortex, exhibit significant structural variability across different brain areas and layers in different species. Moreover, in response to a somatic step current, these cells display a range of firing behaviors, the most common being (1 repetitive action potentials (Regular Spiking - RS, and (2 an initial cluster of 2-5 action potentials with short ISIs followed by single spikes (Intrinsic Bursting - IB. A correlation between firing behavior and dendritic morphology has recently been reported. In this work we use computational modeling to investigate quantitatively the effects of the basal dendritic tree morphology on the firing behavior of 112 three-dimensional reconstructions of layer V PFC rat pyramidal cells. Particularly, we focus on how different morphological (diameter, total length, volume and branch number and passive (Mean Electrotonic Path length features of basal dendritic trees shape somatic firing when the spatial distribution of ionic mechanisms in the basal dendritic trees is uniform or non-uniform. Our results suggest that total length, volume and branch number are the best morphological parameters to discriminate the cells as RS or IB, regardless of the distribution of ionic mechanisms in basal trees. The discriminatory power of total length, volume and branch number remains high in the presence of different apical dendrites. These results suggest that morphological variations in the basal dendritic trees of layer V pyramidal neurons in the PFC influence their firing patterns in a predictive manner and may in turn influence the information processing capabilities of these neurons.

  11. Calcium transient prevalence across the dendritic arbour predicts place field properties.

    Science.gov (United States)

    Sheffield, Mark E J; Dombeck, Daniel A

    2015-01-08

    Establishing the hippocampal cellular ensemble that represents an animal's environment involves the emergence and disappearance of place fields in specific CA1 pyramidal neurons, and the acquisition of different spatial firing properties across the active population. While such firing flexibility and diversity have been linked to spatial memory, attention and task performance, the cellular and network origin of these place cell features is unknown. Basic integrate-and-fire models of place firing propose that such features result solely from varying inputs to place cells, but recent studies suggest instead that place cells themselves may play an active role through regenerative dendritic events. However, owing to the difficulty of performing functional recordings from place cell dendrites, no direct evidence of regenerative dendritic events exists, leaving any possible connection to place coding unknown. Using multi-plane two-photon calcium imaging of CA1 place cell somata, axons and dendrites in mice navigating a virtual environment, here we show that regenerative dendritic events do exist in place cells of behaving mice, and, surprisingly, their prevalence throughout the arbour is highly spatiotemporally variable. Furthermore, we show that the prevalence of such events predicts the spatial precision and persistence or disappearance of place fields. This suggests that the dynamics of spiking throughout the dendritic arbour may play a key role in forming the hippocampal representation of space.

  12. Advantages and limitations of the use of optogenetic approach in studying fast-scale spike encoding.

    Directory of Open Access Journals (Sweden)

    Aleksey Malyshev

    Full Text Available Understanding single-neuron computations and encoding performed by spike-generation mechanisms of cortical neurons is one of the central challenges for cell electrophysiology and computational neuroscience. An established paradigm to study spike encoding in controlled conditions in vitro uses intracellular injection of a mixture of signals with fluctuating currents that mimic in vivo-like background activity. However this technique has two serious limitations: it uses current injection, while synaptic activation leads to changes of conductance, and current injection is technically most feasible in the soma, while the vast majority of synaptic inputs are located on the dendrites. Recent progress in optogenetics provides an opportunity to circumvent these limitations. Transgenic expression of light-activated ionic channels, such as Channelrhodopsin2 (ChR2, allows induction of controlled conductance changes even in thin distant dendrites. Here we show that photostimulation provides a useful extension of the tools to study neuronal encoding, but it has its own limitations. Optically induced fluctuating currents have a low cutoff (~70 Hz, thus limiting the dynamic range of frequency response of cortical neurons. This leads to severe underestimation of the ability of neurons to phase-lock their firing to high frequency components of the input. This limitation could be worked around by using short (2 ms light stimuli which produce membrane potential responses resembling EPSPs by their fast onset and prolonged decay kinetics. We show that combining application of short light stimuli to different parts of dendritic tree for mimicking distant EPSCs with somatic injection of fluctuating current that mimics fluctuations of membrane potential in vivo, allowed us to study fast encoding of artificial EPSPs photoinduced at different distances from the soma. We conclude that dendritic photostimulation of ChR2 with short light pulses provides a powerful tool to

  13. Epileptiform spike detection via convolutional neural networks

    DEFF Research Database (Denmark)

    Johansen, Alexander Rosenberg; Jin, Jing; Maszczyk, Tomasz

    2016-01-01

    The EEG of epileptic patients often contains sharp waveforms called "spikes", occurring between seizures. Detecting such spikes is crucial for diagnosing epilepsy. In this paper, we develop a convolutional neural network (CNN) for detecting spikes in EEG of epileptic patients in an automated...

  14. Dendrite Injury Triggers DLK-Independent Regeneration

    Directory of Open Access Journals (Sweden)

    Michelle C. Stone

    2014-01-01

    Full Text Available Axon injury triggers regeneration through activation of a conserved kinase cascade, which includes the dual leucine zipper kinase (DLK. Although dendrites are damaged during stroke, traumatic brain injury, and seizure, it is not known whether mature neurons monitor dendrite injury and initiate regeneration. We probed the response to dendrite damage using model Drosophila neurons. Two larval neuron types regrew dendrites in distinct ways after all dendrites were removed. Dendrite regeneration was also triggered by injury in adults. Next, we tested whether dendrite injury was initiated with the same machinery as axon injury. Surprisingly, DLK, JNK, and fos were dispensable for dendrite regeneration. Moreover, this MAP kinase pathway was not activated by injury to dendrites. Thus, neurons respond to dendrite damage and initiate regeneration without using the conserved DLK cascade that triggers axon regeneration.

  15. Neuronal coding and spiking randomness

    Czech Academy of Sciences Publication Activity Database

    Košťál, Lubomír; Lánský, Petr; Rospars, J. P.

    2007-01-01

    Roč. 26, č. 10 (2007), s. 2693-2988 ISSN 0953-816X R&D Projects: GA MŠk(CZ) LC554; GA AV ČR(CZ) 1ET400110401; GA AV ČR(CZ) KJB100110701 Grant - others:ECO-NET(FR) 112644PF Institutional research plan: CEZ:AV0Z50110509 Keywords : spike train * variability * neurovědy Subject RIV: FH - Neurology Impact factor: 3.673, year: 2007

  16. iSpike: a spiking neural interface for the iCub robot

    International Nuclear Information System (INIS)

    Gamez, D; Fidjeland, A K; Lazdins, E

    2012-01-01

    This paper presents iSpike: a C++ library that interfaces between spiking neural network simulators and the iCub humanoid robot. It uses a biologically inspired approach to convert the robot’s sensory information into spikes that are passed to the neural network simulator, and it decodes output spikes from the network into motor signals that are sent to control the robot. Applications of iSpike range from embodied models of the brain to the development of intelligent robots using biologically inspired spiking neural networks. iSpike is an open source library that is available for free download under the terms of the GPL. (paper)

  17. Delay selection by spike-timing-dependent plasticity in recurrent networks of spiking neurons receiving oscillatory inputs.

    Directory of Open Access Journals (Sweden)

    Robert R Kerr

    Full Text Available Learning rules, such as spike-timing-dependent plasticity (STDP, change the structure of networks of neurons based on the firing activity. A network level understanding of these mechanisms can help infer how the brain learns patterns and processes information. Previous studies have shown that STDP selectively potentiates feed-forward connections that have specific axonal delays, and that this underlies behavioral functions such as sound localization in the auditory brainstem of the barn owl. In this study, we investigate how STDP leads to the selective potentiation of recurrent connections with different axonal and dendritic delays during oscillatory activity. We develop analytical models of learning with additive STDP in recurrent networks driven by oscillatory inputs, and support the results using simulations with leaky integrate-and-fire neurons. Our results show selective potentiation of connections with specific axonal delays, which depended on the input frequency. In addition, we demonstrate how this can lead to a network becoming selective in the amplitude of its oscillatory response to this frequency. We extend this model of axonal delay selection within a single recurrent network in two ways. First, we show the selective potentiation of connections with a range of both axonal and dendritic delays. Second, we show axonal delay selection between multiple groups receiving out-of-phase, oscillatory inputs. We discuss the application of these models to the formation and activation of neuronal ensembles or cell assemblies in the cortex, and also to missing fundamental pitch perception in the auditory brainstem.

  18. Circulating dendritic cells in pediatric patients with nephrotic syndrome

    African Journals Online (AJOL)

    Background: Dendritic cells (DCs) represent one of the most extensively studied topics in immunology, because of their central role in the induction and regulation of adaptive immunity, and because of their therapeutic potential for manipulating immune responses. Objectives: To evaluate circulating DC levels in pediatric ...

  19. Information transmission with spiking Bayesian neurons

    International Nuclear Information System (INIS)

    Lochmann, Timm; Deneve, Sophie

    2008-01-01

    Spike trains of cortical neurons resulting from repeatedpresentations of a stimulus are variable and exhibit Poisson-like statistics. Many models of neural coding therefore assumed that sensory information is contained in instantaneous firing rates, not spike times. Here, we ask how much information about time-varying stimuli can be transmitted by spiking neurons with such input and output variability. In particular, does this variability imply spike generation to be intrinsically stochastic? We consider a model neuron that estimates optimally the current state of a time-varying binary variable (e.g. presence of a stimulus) by integrating incoming spikes. The unit signals its current estimate to other units with spikes whenever the estimate increased by a fixed amount. As shown previously, this computation results in integrate and fire dynamics with Poisson-like output spike trains. This output variability is entirely due to the stochastic input rather than noisy spike generation. As a result such a deterministic neuron can transmit most of the information about the time varying stimulus. This contrasts with a standard model of sensory neurons, the linear-nonlinear Poisson (LNP) model which assumes that most variability in output spike trains is due to stochastic spike generation. Although it yields the same firing statistics, we found that such noisy firing results in the loss of most information. Finally, we use this framework to compare potential effects of top-down attention versus bottom-up saliency on information transfer with spiking neurons

  20. Geometry sensing by dendritic cells dictates spatial organization and PGE(2)-induced dissolution of podosomes.

    NARCIS (Netherlands)

    Dries, K. van den; Helden, S.F.G. van; Riet, J.T. te; Diez-Ahedo, R.; Manzo, C.; Oud, M.M.; Leeuwen, F.N. van; Brock, R.E.; Garcia-Parajo, M.F.; Cambi, A.; Figdor, C.G.

    2012-01-01

    Assembly and disassembly of adhesion structures such as focal adhesions (FAs) and podosomes regulate cell adhesion and differentiation. On antigen-presenting dendritic cells (DCs), acquisition of a migratory and immunostimulatory phenotype depends on podosome dissolution by prostaglandin E(2)

  1. Racing to learn: statistical inference and learning in a single spiking neuron with adaptive kernels.

    Science.gov (United States)

    Afshar, Saeed; George, Libin; Tapson, Jonathan; van Schaik, André; Hamilton, Tara J

    2014-01-01

    This paper describes the Synapto-dendritic Kernel Adapting Neuron (SKAN), a simple spiking neuron model that performs statistical inference and unsupervised learning of spatiotemporal spike patterns. SKAN is the first proposed neuron model to investigate the effects of dynamic synapto-dendritic kernels and demonstrate their computational power even at the single neuron scale. The rule-set defining the neuron is simple: there are no complex mathematical operations such as normalization, exponentiation or even multiplication. The functionalities of SKAN emerge from the real-time interaction of simple additive and binary processes. Like a biological neuron, SKAN is robust to signal and parameter noise, and can utilize both in its operations. At the network scale neurons are locked in a race with each other with the fastest neuron to spike effectively "hiding" its learnt pattern from its neighbors. The robustness to noise, high speed, and simple building blocks not only make SKAN an interesting neuron model in computational neuroscience, but also make it ideal for implementation in digital and analog neuromorphic systems which is demonstrated through an implementation in a Field Programmable Gate Array (FPGA). Matlab, Python, and Verilog implementations of SKAN are available at: http://www.uws.edu.au/bioelectronics_neuroscience/bens/reproducible_research.

  2. Derp1-modified dendritic cells attenuate allergic inflammation by regulating the development of T helper type1(Th1)/Th2 cells and regulatory T cells in a murine model of allergic rhinitis.

    Science.gov (United States)

    Yu, Shaoqing; Han, Bing; Liu, Shuangxi; Wang, Hong; Zhuang, Wenjie; Huang, Yu; Zhang, Ruxin

    2017-10-01

    The CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) are known to regulate Th2-induced allergic rhinitis (AR). In this study, we evaluated the efficacy of Derp1-modified dendritic cells (DCs) in AR immunotherapy. Derp1 was synthesized and transfected into DCs to generate Derp1-modified DCs. Phenotypes of Derp1-modified DCs were analyzed with flow cytometry using antibodies against DC markers CD11c, CD11b, CD59, CD103 and Toll-like receptor 1(TLR1). Four groups of subject mice were formed; the controls were treated with immature DCs, while the AR mice models were sensitized with Derp1(AR) and treated with DCs(DC-AR) or Derp1-modified DCs (Derp1DC-AR). The frequency of sneezing and scratching, eosinophil cell count, and Th1/Th2 ratio in the spleen were measured for all groups. The percentage of CD4 + CD25 + Foxp3 + Tregs in peripheral blood mononuclear cells was measured using flow cytometry; serum IgE, IgG1, and histamine were measured using enzyme-linked immunosorbent assay; expression levels of transcription factors T-bet, GATA3, Foxp3+ and IL-10 were analyzed using reverse transcription-polymerase chain reaction, and Western blot used in analyzed expression of Foxp3+ and IL-10 in nasal mucosa. Treatment with Derp1-modified DCs ameliorated the allergic response. The Derp1DC-AR group had significantly lower eosinophil cell count and the IgE, IgG1, and histamine levels than the AR and DC-AR groups, and higher mRNA levels of Th1 transcription factors T-bet, IL-10 and Foxp3 in nasal mucosa than DC-AR mice, but Th2 transcription factors GATA3 mRNA expression level has the opposite results. Furthermore, the Th1/Th2 ratio and percentage of CD4 + CD25 + Foxp3 + Tregs was significantly lower in the AR group (pTh1/Th2, showing an immunotherapeutic effect against AR. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes.

    Science.gov (United States)

    Burroughs, Amelia; Wise, Andrew K; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen Y; Lang, Eric J; Apps, Richard; Cerminara, Nadia L

    2017-01-01

    Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes. Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets. The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear. We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number. This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition

  4. DIXDC1 Phosphorylation and Control of Dendritic Morphology Are Impaired by Rare Genetic Variants

    Directory of Open Access Journals (Sweden)

    Vickie Kwan

    2016-11-01

    Full Text Available The development of neural connectivity is essential for brain function, and disruption of this process is associated with autism spectrum disorders (ASDs. DIX domain containing 1 (DIXDC1 has previously been implicated in neurodevelopmental disorders, but its role in postnatal brain function remains unknown. Using a knockout mouse model, we determined that DIXDC1 is a regulator of excitatory neuron dendrite development and synapse function in the cortex. We discovered that MARK1, previously linked to ASDs, phosphorylates DIXDC1 to regulate dendrite and spine development through modulation of the cytoskeletal network in an isoform-specific manner. Finally, rare missense variants in DIXDC1 were identified in ASD patient cohorts via genetic sequencing. Interestingly, the variants inhibit DIXDC1 isoform 1 phosphorylation, causing impairment to dendrite and spine growth. These data reveal that DIXDC1 is a regulator of cortical dendrite and synaptic development and provide mechanistic insight into morphological defects associated with neurodevelopmental disorders.

  5. Motor control by precisely timed spike patterns

    DEFF Research Database (Denmark)

    Srivastava, Kyle H; Holmes, Caroline M; Vellema, Michiel

    2017-01-01

    whether the information in spike timing actually plays a role in brain function. By examining the activity of individual motor units (the muscle fibers innervated by a single motor neuron) and manipulating patterns of activation of these neurons, we provide both correlative and causal evidence......A fundamental problem in neuroscience is understanding how sequences of action potentials ("spikes") encode information about sensory signals and motor outputs. Although traditional theories assume that this information is conveyed by the total number of spikes fired within a specified time...... interval (spike rate), recent studies have shown that additional information is carried by the millisecond-scale timing patterns of action potentials (spike timing). However, it is unknown whether or how subtle differences in spike timing drive differences in perception or behavior, leaving it unclear...

  6. Coding and decoding with dendrites.

    Science.gov (United States)

    Papoutsi, Athanasia; Kastellakis, George; Psarrou, Maria; Anastasakis, Stelios; Poirazi, Panayiota

    2014-02-01

    Since the discovery of complex, voltage dependent mechanisms in the dendrites of multiple neuron types, great effort has been devoted in search of a direct link between dendritic properties and specific neuronal functions. Over the last few years, new experimental techniques have allowed the visualization and probing of dendritic anatomy, plasticity and integrative schemes with unprecedented detail. This vast amount of information has caused a paradigm shift in the study of memory, one of the most important pursuits in Neuroscience, and calls for the development of novel theories and models that will unify the available data according to some basic principles. Traditional models of memory considered neural cells as the fundamental processing units in the brain. Recent studies however are proposing new theories in which memory is not only formed by modifying the synaptic connections between neurons, but also by modifications of intrinsic and anatomical dendritic properties as well as fine tuning of the wiring diagram. In this review paper we present previous studies along with recent findings from our group that support a key role of dendrites in information processing, including the encoding and decoding of new memories, both at the single cell and the network level. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Development of on-off spiking in superior paraolivary nucleus neurons of the mouse

    Science.gov (United States)

    Felix, Richard A.; Vonderschen, Katrin; Berrebi, Albert S.

    2013-01-01

    The superior paraolivary nucleus (SPON) is a prominent cell group in the auditory brain stem that has been increasingly implicated in representing temporal sound structure. Although SPON neurons selectively respond to acoustic signals important for sound periodicity, the underlying physiological specializations enabling these responses are poorly understood. We used in vitro and in vivo recordings to investigate how SPON neurons develop intrinsic cellular properties that make them well suited for encoding temporal sound features. In addition to their hallmark rebound spiking at the stimulus offset, SPON neurons were characterized by spiking patterns termed onset, adapting, and burst in response to depolarizing stimuli in vitro. Cells with burst spiking had some morphological differences compared with other SPON neurons and were localized to the dorsolateral region of the nucleus. Both membrane and spiking properties underwent strong developmental regulation, becoming more temporally precise with age for both onset and offset spiking. Single-unit recordings obtained in young mice demonstrated that SPON neurons respond with temporally precise onset spiking upon tone stimulation in vivo, in addition to the typical offset spiking. Taken together, the results of the present study demonstrate that SPON neurons develop sharp on-off spiking, which may confer sensitivity to sound amplitude modulations or abrupt sound transients. These findings are consistent with the proposed involvement of the SPON in the processing of temporal sound structure, relevant for encoding communication cues. PMID:23515791

  8. Multineuronal Spike Sequences Repeat with Millisecond Precision

    Directory of Open Access Journals (Sweden)

    Koki eMatsumoto

    2013-06-01

    Full Text Available Cortical microcircuits are nonrandomly wired by neurons. As a natural consequence, spikes emitted by microcircuits are also nonrandomly patterned in time and space. One of the prominent spike organizations is a repetition of fixed patterns of spike series across multiple neurons. However, several questions remain unsolved, including how precisely spike sequences repeat, how the sequences are spatially organized, how many neurons participate in sequences, and how different sequences are functionally linked. To address these questions, we monitored spontaneous spikes of hippocampal CA3 neurons ex vivo using a high-speed functional multineuron calcium imaging technique that allowed us to monitor spikes with millisecond resolution and to record the location of spiking and nonspiking neurons. Multineuronal spike sequences were overrepresented in spontaneous activity compared to the statistical chance level. Approximately 75% of neurons participated in at least one sequence during our observation period. The participants were sparsely dispersed and did not show specific spatial organization. The number of sequences relative to the chance level decreased when larger time frames were used to detect sequences. Thus, sequences were precise at the millisecond level. Sequences often shared common spikes with other sequences; parts of sequences were subsequently relayed by following sequences, generating complex chains of multiple sequences.

  9. The Second Spiking Threshold: Dynamics of Laminar Network Spiking in the Visual Cortex

    DEFF Research Database (Denmark)

    Forsberg, Lars E.; Bonde, Lars H.; Harvey, Michael A.

    2016-01-01

    and moving visual stimuli from the spontaneous ongoing spiking state, in all layers and zones of areas 17 and 18 indicating that the second threshold is a property of the network. Spontaneous and evoked spiking, thus can easily be distinguished. In addition, the trajectories of spontaneous ongoing states......Most neurons have a threshold separating the silent non-spiking state and the state of producing temporal sequences of spikes. But neurons in vivo also have a second threshold, found recently in granular layer neurons of the primary visual cortex, separating spontaneous ongoing spiking from...... visually evoked spiking driven by sharp transients. Here we examine whether this second threshold exists outside the granular layer and examine details of transitions between spiking states in ferrets exposed to moving objects. We found the second threshold, separating spiking states evoked by stationary...

  10. Divergent Effects of Dendritic Cells on Pancreatitis

    Science.gov (United States)

    2015-09-01

    role of dendritic cells in pancreatitis. Dendritic cells are professional antigen presenting cells which initiate innate and adaptive immune... Lymphoid -tissue-specific homing of bone- marrow-derived dendritic cells . Blood. 113:6638–6647. http://dx.doi .org/10.1182/blood-2009-02-204321 Dapito...Award Number: W81XWH-12-1-0313 TITLE: Divergent Effects of Dendritic Cells on Pancreatitis PRINCIPAL INVESTIGATOR: Dr. George Miller

  11. An inverse approach for elucidating dendritic function

    Directory of Open Access Journals (Sweden)

    Benjamin Torben-Nielsen

    2010-09-01

    Full Text Available We outline an inverse approach for investigating dendritic function-structure relationships by optimizing dendritic trees for a-priori chosen computational functions. The inverse approach can be applied in two different ways. First, we can use it as a `hypothesis generator' in which we optimize dendrites for a function of general interest. The optimization yields an artificial dendrite that is subsequently compared to real neurons. This comparison potentially allows us to propose hypotheses about the function of real neurons. In this way, we investigated dendrites that optimally perform input-order detection. Second, we can use it as a `function confirmation' by optimizing dendrites for functions hypothesized to be performed by classes of neurons. If the optimized, artificial, dendrites resemble the dendrites of real neurons the artificial dendrites corroborate the hypothesized function of the real neuron. Moreover, properties of the artificial dendrites can lead to predictions about yet unmeasured properties. In this way, we investigated wide-field motion integration performed by the VS cells of the fly visual system. In outlining the inverse approach and two applications, we also elaborate on the nature of dendritic function. We furthermore discuss the role of optimality in assigning functions to dendrites and point out interesting future directions.

  12. Probabilistic Inference in General Graphical Models through Sampling in Stochastic Networks of Spiking Neurons

    Science.gov (United States)

    Pecevski, Dejan; Buesing, Lars; Maass, Wolfgang

    2011-01-01

    An important open problem of computational neuroscience is the generic organization of computations in networks of neurons in the brain. We show here through rigorous theoretical analysis that inherent stochastic features of spiking neurons, in combination with simple nonlinear computational operations in specific network motifs and dendritic arbors, enable networks of spiking neurons to carry out probabilistic inference through sampling in general graphical models. In particular, it enables them to carry out probabilistic inference in Bayesian networks with converging arrows (“explaining away”) and with undirected loops, that occur in many real-world tasks. Ubiquitous stochastic features of networks of spiking neurons, such as trial-to-trial variability and spontaneous activity, are necessary ingredients of the underlying computational organization. We demonstrate through computer simulations that this approach can be scaled up to neural emulations of probabilistic inference in fairly large graphical models, yielding some of the most complex computations that have been carried out so far in networks of spiking neurons. PMID:22219717

  13. Does spike-timing-dependent synaptic plasticity couple or decouple neurons firing in synchrony?

    Directory of Open Access Journals (Sweden)

    Andreas eKnoblauch

    2012-08-01

    Full Text Available Spike synchronization is thought to have a constructive role for feature integration, attention, associativelearning, and the formation of bidirectionally connected Hebbian cell assemblies. By contrast, theoreticalstudies on spike-timing-dependent plasticity (STDP report an inherently decoupling influence of spikesynchronization on synaptic connections of coactivated neurons. For example, bidirectional synapticconnections as found in cortical areas could be reproduced only by assuming realistic models of STDP andrate coding. We resolve this conflict by theoretical analysis and simulation of various simple and realisticSTDP models that provide a more complete characterization of conditions when STDP leads to eithercoupling or decoupling of neurons firing in synchrony. In particular, we show that STDP consistentlycouples synchronized neurons if key model parameters are matched to physiological data: First, synapticpotentiation must be significantly stronger than synaptic depression for small (positive or negative timelags between presynaptic and postsynaptic spikes. Second, spike synchronization must be sufficientlyimprecise, for example, within a time window of 5-10msec instead of 1msec. Third, axonal propagationdelays should not be much larger than dendritic delays. Under these assumptions synchronized neuronswill be strongly coupled leading to a dominance of bidirectional synaptic connections even for simpleSTDP models and low mean firing rates at the level of spontaneous activity.

  14. Probabilistic inference in general graphical models through sampling in stochastic networks of spiking neurons.

    Directory of Open Access Journals (Sweden)

    Dejan Pecevski

    2011-12-01

    Full Text Available An important open problem of computational neuroscience is the generic organization of computations in networks of neurons in the brain. We show here through rigorous theoretical analysis that inherent stochastic features of spiking neurons, in combination with simple nonlinear computational operations in specific network motifs and dendritic arbors, enable networks of spiking neurons to carry out probabilistic inference through sampling in general graphical models. In particular, it enables them to carry out probabilistic inference in Bayesian networks with converging arrows ("explaining away" and with undirected loops, that occur in many real-world tasks. Ubiquitous stochastic features of networks of spiking neurons, such as trial-to-trial variability and spontaneous activity, are necessary ingredients of the underlying computational organization. We demonstrate through computer simulations that this approach can be scaled up to neural emulations of probabilistic inference in fairly large graphical models, yielding some of the most complex computations that have been carried out so far in networks of spiking neurons.

  15. Spike voltage topography in temporal lobe epilepsy.

    Science.gov (United States)

    Asadi-Pooya, Ali A; Asadollahi, Marjan; Shimamoto, Shoichi; Lorenzo, Matthew; Sperling, Michael R

    2016-07-15

    We investigated the voltage topography of interictal spikes in patients with temporal lobe epilepsy (TLE) to see whether topography was related to etiology for TLE. Adults with TLE, who had epilepsy surgery for drug-resistant seizures from 2011 until 2014 at Jefferson Comprehensive Epilepsy Center were selected. Two groups of patients were studied: patients with mesial temporal sclerosis (MTS) on MRI and those with other MRI findings. The voltage topography maps of the interictal spikes at the peak were created using BESA software. We classified the interictal spikes as polar, basal, lateral, or others. Thirty-four patients were studied, from which the characteristics of 340 spikes were investigated. The most common type of spike orientation was others (186 spikes; 54.7%), followed by lateral (146; 42.9%), polar (5; 1.5%), and basal (3; 0.9%). Characteristics of the voltage topography maps of the spikes between the two groups of patients were somewhat different. Five spikes in patients with MTS had polar orientation, but none of the spikes in patients with other MRI findings had polar orientation (odds ratio=6.98, 95% confidence interval=0.38 to 127.38; p=0.07). Scalp topographic mapping of interictal spikes has the potential to offer different information than visual inspection alone. The present results do not allow an immediate clinical application of our findings; however, detecting a polar spike in a patient with TLE may increase the possibility of mesial temporal sclerosis as the underlying etiology. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells

    Directory of Open Access Journals (Sweden)

    Wu Kong-Yan

    2010-06-01

    Full Text Available Abstract Background During cerebellar development, Purkinje cells (PCs form the most elaborate dendritic trees among neurons in the brain, but the mechanism regulating PC arborization remains largely unknown. Geranylgeranyltransferase I (GGT is a prenyltransferase that is responsible for lipid modification of several signaling proteins, such as Rho family small GTPase Rac1, which has been shown to be involved in neuronal morphogenesis. Here we show that GGT plays an important role in dendritic development of PCs. Results We found that GGT was abundantly expressed in the developing rat cerebellum, in particular molecular layer (ML, the region enriched with PC dendrites. Inhibition or down-regulation of GGT using small interference RNA (siRNA inhibited dendritic development of PCs. In contrast, up-regulation of GGT promoted dendritic arborization of PCs. Furthermore, neuronal depolarization induced by high K+ or treatment with brain-derived neurotrophic factor (BDNF promoted membrane association of Rac1 and dendritic development of PCs in cultured cerebellar slices. The effect of BDNF or high K+ was inhibited by inhibition or down-regulation of GGT. Conclusion Our results indicate that GGT plays an important role in Purkinje cell development, and suggest a novel role of GGT in neuronal morphogenesis in vivo.

  17. Modulation of Dendritic Cell Responses by Parasites: A Common Strategy to Survive

    Directory of Open Access Journals (Sweden)

    César A. Terrazas

    2010-01-01

    Full Text Available Parasitic infections are one of the most important causes of morbidity and mortality in our planet and the immune responses triggered by these organisms are critical to determine their outcome. Dendritic cells are key elements for the development of immunity against parasites; they control the responses required to eliminate these pathogens while maintaining host homeostasis. However, there is evidence showing that parasites can influence and regulate dendritic cell function in order to promote a more permissive environment for their survival. In this review we will focus on the strategies protozoan and helminth parasites have developed to interfere with dendritic cell activities as well as in the possible mechanisms involved.

  18. Organization and dynamics of the actin cytoskeleton during dendritic spine morphological remodeling.

    Science.gov (United States)

    Chazeau, Anaël; Giannone, Grégory

    2016-08-01

    In the central nervous system, most excitatory post-synapses are small subcellular structures called dendritic spines. Their structure and morphological remodeling are tightly coupled to changes in synaptic transmission. The F-actin cytoskeleton is the main driving force of dendritic spine remodeling and sustains synaptic plasticity. It is therefore essential to understand how changes in synaptic transmission can regulate the organization and dynamics of actin binding proteins (ABPs). In this review, we will provide a detailed description of the organization and dynamics of F-actin and ABPs in dendritic spines and will discuss the current models explaining how the actin cytoskeleton sustains both structural and functional synaptic plasticity.

  19. Bayesian population decoding of spiking neurons.

    Science.gov (United States)

    Gerwinn, Sebastian; Macke, Jakob; Bethge, Matthias

    2009-01-01

    The timing of action potentials in spiking neurons depends on the temporal dynamics of their inputs and contains information about temporal fluctuations in the stimulus. Leaky integrate-and-fire neurons constitute a popular class of encoding models, in which spike times depend directly on the temporal structure of the inputs. However, optimal decoding rules for these models have only been studied explicitly in the noiseless case. Here, we study decoding rules for probabilistic inference of a continuous stimulus from the spike times of a population of leaky integrate-and-fire neurons with threshold noise. We derive three algorithms for approximating the posterior distribution over stimuli as a function of the observed spike trains. In addition to a reconstruction of the stimulus we thus obtain an estimate of the uncertainty as well. Furthermore, we derive a 'spike-by-spike' online decoding scheme that recursively updates the posterior with the arrival of each new spike. We use these decoding rules to reconstruct time-varying stimuli represented by a Gaussian process from spike trains of single neurons as well as neural populations.

  20. Bayesian population decoding of spiking neurons

    Directory of Open Access Journals (Sweden)

    Sebastian Gerwinn

    2009-10-01

    Full Text Available The timing of action potentials in spiking neurons depends on the temporal dynamics of their inputs and contains information about temporal fluctuations in the stimulus. Leaky integrate-and-fire neurons constitute a popular class of encoding models, in which spike times depend directly on the temporal structure of the inputs. However, optimal decoding rules for these models have only been studied explicitly in the noiseless case. Here, we study decoding rules for probabilistic inference of a continuous stimulus from the spike times of a population of leaky integrate-and-fire neurons with threshold noise. We derive three algorithms for approximating the posterior distribution over stimuli as a function of the observed spike trains. In addition to a reconstruction of the stimulus we thus obtain an estimate of the uncertainty as well. Furthermore, we derive a `spike-by-spike' online decoding scheme that recursively updates the posterior with the arrival of each new spike. We use these decoding rules to reconstruct time-varying stimuli represented by a Gaussian process from spike trains of single neurons as well as neural populations.

  1. Statistical properties of superimposed stationary spike trains.

    Science.gov (United States)

    Deger, Moritz; Helias, Moritz; Boucsein, Clemens; Rotter, Stefan

    2012-06-01

    The Poisson process is an often employed model for the activity of neuronal populations. It is known, though, that superpositions of realistic, non- Poisson spike trains are not in general Poisson processes, not even for large numbers of superimposed processes. Here we construct superimposed spike trains from intracellular in vivo recordings from rat neocortex neurons and compare their statistics to specific point process models. The constructed superimposed spike trains reveal strong deviations from the Poisson model. We find that superpositions of model spike trains that take the effective refractoriness of the neurons into account yield a much better description. A minimal model of this kind is the Poisson process with dead-time (PPD). For this process, and for superpositions thereof, we obtain analytical expressions for some second-order statistical quantities-like the count variability, inter-spike interval (ISI) variability and ISI correlations-and demonstrate the match with the in vivo data. We conclude that effective refractoriness is the key property that shapes the statistical properties of the superposition spike trains. We present new, efficient algorithms to generate superpositions of PPDs and of gamma processes that can be used to provide more realistic background input in simulations of networks of spiking neurons. Using these generators, we show in simulations that neurons which receive superimposed spike trains as input are highly sensitive for the statistical effects induced by neuronal refractoriness.

  2. Linking investment spikes and productivity growth

    NARCIS (Netherlands)

    Geylani, P.C.; Stefanou, S.E.

    2013-01-01

    We investigate the relationship between productivity growth and investment spikes using Census Bureau’s plant-level dataset for the U.S. food manufacturing industry. There are differences in productivity growth and investment spike patterns across different sub-industries and food manufacturing

  3. Mimickers of generalized spike and wave discharges.

    Science.gov (United States)

    Azzam, Raed; Bhatt, Amar B

    2014-06-01

    Overinterpretation of benign EEG variants is a common problem that can lead to the misdiagnosis of epilepsy. We review four normal patterns that mimic generalized spike and wave discharges: phantom spike-and-wave, hyperventilation hypersynchrony, hypnagogic/ hypnopompic hypersynchrony, and mitten patterns.

  4. Enhancement of the 1985 Browns Ferry exercise through the use of spiked samples

    International Nuclear Information System (INIS)

    McNees, J.L.

    1987-01-01

    The use of spiked environmental samples has proven to be a beneficial part of nuclear power plant exercises. Milk, soil, and air sampling cartridges can easily be spiked with realistic concentrations of radionuclide without violating Nuclear Regulatory Commission regulations or policy and with no significant radiation hazard to exercise participants. Analysis and reporting of data from realistic samples significantly improves motivation, attitude, moral, and overall preparedness of the individuals participating in that phase of the exercise

  5. Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    LENUS (Irish Health Repository)

    Michielsen, Adriana J

    2011-01-01

    Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

  6. Neuronal gain modulability is determined by dendritic morphology: A computational optogenetic study.

    Science.gov (United States)

    Jarvis, Sarah; Nikolic, Konstantin; Schultz, Simon R

    2018-03-01

    The mechanisms by which the gain of the neuronal input-output function may be modulated have been the subject of much investigation. However, little is known of the role of dendrites in neuronal gain control. New optogenetic experimental paradigms based on spatial profiles or patterns of light stimulation offer the prospect of elucidating many aspects of single cell function, including the role of dendrites in gain control. We thus developed a model to investigate how competing excitatory and inhibitory input within the dendritic arbor alters neuronal gain, incorporating kinetic models of opsins into our modeling to ensure it is experimentally testable. To investigate how different topologies of the neuronal dendritic tree affect the neuron's input-output characteristics we generate branching geometries which replicate morphological features of most common neurons, but keep the number of branches and overall area of dendrites approximately constant. We found a relationship between a neuron's gain modulability and its dendritic morphology, with neurons with bipolar dendrites with a moderate degree of branching being most receptive to control of the gain of their input-output relationship. The theory was then tested and confirmed on two examples of realistic neurons: 1) layer V pyramidal cells-confirming their role in neural circuits as a regulator of the gain in the circuit in addition to acting as the primary excitatory neurons, and 2) stellate cells. In addition to providing testable predictions and a novel application of dual-opsins, our model suggests that innervation of all dendritic subdomains is required for full gain modulation, revealing the importance of dendritic targeting in the generation of neuronal gain control and the functions that it subserves. Finally, our study also demonstrates that neurophysiological investigations which use direct current injection into the soma and bypass the dendrites may miss some important neuronal functions, such as gain

  7. Neutrophils, dendritic cells and Toxoplasma.

    Science.gov (United States)

    Denkers, Eric Y; Butcher, Barbara A; Del Rio, Laura; Bennouna, Soumaya

    2004-03-09

    Toxoplasma gondii rapidly elicits strong Type 1 cytokine-based immunity. The necessity for this response is well illustrated by the example of IFN-gamma and IL-12 gene knockout mice that rapidly succumb to the effects of acute infection. The parasite itself is skilled at sparking complex interactions in the innate immune system that lead to protective immunity. Neutrophils are one of the first cell types to arrive at the site of infection, and the cells release several proinflammatory cytokines and chemokines in response to Toxoplasma. Dendritic cells are an important source of IL-12 during infection with T. gondii and other microbial pathogens, and they are also specialized for high-level antigen presentation to T lymphocytes. Tachyzoites express at least two types of molecules that trigger innate immune cell cytokine production. One of these involves Toll-like receptor/MyD88 pathways common to many microbial pathogens. The second pathway is less conventional and involves molecular mimicry between a parasite cyclophilin and host CC chemokine receptor 5-binding ligands. Neutrophils, dendritic cells and Toxoplasma work together to elicit the immune response required for host survival. Cytokine and chemokine cross-talk between parasite-triggered neutrophils and dendritic cells results in recruitment, maturation and activation of the latter. Neutrophil-empowered dendritic cells possess properties expected of highly potent antigen presenting cells that drive T helper 1 generation.

  8. Advanced dendritic web growth development

    Science.gov (United States)

    Hopkins, R. H.

    1985-01-01

    A program to develop the technology of the silicon dendritic web ribbon growth process is examined. The effort is being concentrated on the area rate and quality requirements necessary to meet the JPL/DOE goals for terrestrial PV applications. Closed loop web growth system development and stress reduction for high area rate growth is considered.

  9. Stochastic Variational Learning in Recurrent Spiking Networks

    Directory of Open Access Journals (Sweden)

    Danilo eJimenez Rezende

    2014-04-01

    Full Text Available The ability to learn and perform statistical inference with biologically plausible recurrent network of spiking neurons is an important step towards understanding perception and reasoning. Here we derive and investigate a new learning rule for recurrent spiking networks with hidden neurons, combining principles from variational learning and reinforcement learning. Our network defines a generative model over spike train histories and the derived learning rule has the form of a local Spike Timing Dependent Plasticity rule modulated by global factors (neuromodulators conveying information about ``novelty on a statistically rigorous ground.Simulations show that our model is able to learn bothstationary and non-stationary patterns of spike trains.We also propose one experiment that could potentially be performed with animals in order to test the dynamics of the predicted novelty signal.

  10. Spiking neural P systems with multiple channels.

    Science.gov (United States)

    Peng, Hong; Yang, Jinyu; Wang, Jun; Wang, Tao; Sun, Zhang; Song, Xiaoxiao; Luo, Xiaohui; Huang, Xiangnian

    2017-11-01

    Spiking neural P systems (SNP systems, in short) are a class of distributed parallel computing systems inspired from the neurophysiological behavior of biological spiking neurons. In this paper, we investigate a new variant of SNP systems in which each neuron has one or more synaptic channels, called spiking neural P systems with multiple channels (SNP-MC systems, in short). The spiking rules with channel label are introduced to handle the firing mechanism of neurons, where the channel labels indicate synaptic channels of transmitting the generated spikes. The computation power of SNP-MC systems is investigated. Specifically, we prove that SNP-MC systems are Turing universal as both number generating and number accepting devices. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Stochastic variational learning in recurrent spiking networks.

    Science.gov (United States)

    Jimenez Rezende, Danilo; Gerstner, Wulfram

    2014-01-01

    The ability to learn and perform statistical inference with biologically plausible recurrent networks of spiking neurons is an important step toward understanding perception and reasoning. Here we derive and investigate a new learning rule for recurrent spiking networks with hidden neurons, combining principles from variational learning and reinforcement learning. Our network defines a generative model over spike train histories and the derived learning rule has the form of a local Spike Timing Dependent Plasticity rule modulated by global factors (neuromodulators) conveying information about "novelty" on a statistically rigorous ground. Simulations show that our model is able to learn both stationary and non-stationary patterns of spike trains. We also propose one experiment that could potentially be performed with animals in order to test the dynamics of the predicted novelty signal.

  12. Application of cross-correlated delay shift rule in spiking neural networks for interictal spike detection.

    Science.gov (United States)

    Lilin Guo; Zhenzhong Wang; Cabrerizo, Mercedes; Adjouadi, Malek

    2016-08-01

    This study proposes a Cross-Correlated Delay Shift (CCDS) supervised learning rule to train neurons with associated spatiotemporal patterns to classify spike patterns. The objective of this study was to evaluate the feasibility of using the CCDS rule to automate the detection of interictal spikes in electroencephalogram (EEG) data on patients with epilepsy. Encoding is the initial yet essential step for spiking neurons to process EEG patterns. A new encoding method is utilized to convert the EEG signal into spike patterns. The simulation results show that the proposed algorithm identified 69 spikes out of 82 spikes, or 84% detection rate, which is quite high considering the subtleties of interictal spikes and the tediousness of monitoring long EEG records. This CCDS rule is also benchmarked by ReSuMe on the same task.

  13. Distribution and function of HCN channels in the apical dendritic tuft of neocortical pyramidal neurons.

    Science.gov (United States)

    Harnett, Mark T; Magee, Jeffrey C; Williams, Stephen R

    2015-01-21

    The apical tuft is the most remote area of the dendritic tree of neocortical pyramidal neurons. Despite its distal location, the apical dendritic tuft of layer 5 pyramidal neurons receives substantial excitatory synaptic drive and actively processes corticocortical input during behavior. The properties of the voltage-activated ion channels that regulate synaptic integration in tuft dendrites have, however, not been thoroughly investigated. Here, we use electrophysiological and optical approaches to examine the subcellular distribution and function of hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels in rat layer 5B pyramidal neurons. Outside-out patch recordings demonstrated that the amplitude and properties of ensemble HCN channel activity were uniform in patches excised from distal apical dendritic trunk and tuft sites. Simultaneous apical dendritic tuft and trunk whole-cell current-clamp recordings revealed that the pharmacological blockade of HCN channels decreased voltage compartmentalization and enhanced the generation and spread of apical dendritic tuft and trunk regenerative activity. Furthermore, multisite two-photon glutamate uncaging demonstrated that HCN channels control the amplitude and duration of synaptically evoked regenerative activity in the distal apical dendritic tuft. In contrast, at proximal apical dendritic trunk and somatic recording sites, the blockade of HCN channels decreased excitability. Dynamic-clamp experiments revealed that these compartment-specific actions of HCN channels were heavily influenced by the local and distributed impact of the high density of HCN channels in the distal apical dendritic arbor. The properties and subcellular distribution pattern of HCN channels are therefore tuned to regulate the interaction between integration compartments in layer 5B pyramidal neurons. Copyright © 2015 the authors 0270-6474/15/351024-14$15.00/0.

  14. Serial Spike Time Correlations Affect Probability Distribution of Joint Spike Events.

    Science.gov (United States)

    Shahi, Mina; van Vreeswijk, Carl; Pipa, Gordon

    2016-01-01

    Detecting the existence of temporally coordinated spiking activity, and its role in information processing in the cortex, has remained a major challenge for neuroscience research. Different methods and approaches have been suggested to test whether the observed synchronized events are significantly different from those expected by chance. To analyze the simultaneous spike trains for precise spike correlation, these methods typically model the spike trains as a Poisson process implying that the generation of each spike is independent of all the other spikes. However, studies have shown that neural spike trains exhibit dependence among spike sequences, such as the absolute and relative refractory periods which govern the spike probability of the oncoming action potential based on the time of the last spike, or the bursting behavior, which is characterized by short epochs of rapid action potentials, followed by longer episodes of silence. Here we investigate non-renewal processes with the inter-spike interval distribution model that incorporates spike-history dependence of individual neurons. For that, we use the Monte Carlo method to estimate the full shape of the coincidence count distribution and to generate false positives for coincidence detection. The results show that compared to the distributions based on homogeneous Poisson processes, and also non-Poisson processes, the width of the distribution of joint spike events changes. Non-renewal processes can lead to both heavy tailed or narrow coincidence distribution. We conclude that small differences in the exact autostructure of the point process can cause large differences in the width of a coincidence distribution. Therefore, manipulations of the autostructure for the estimation of significance of joint spike events seem to be inadequate.

  15. Reliability of MEG source imaging of anterior temporal spikes: analysis of an intracranially characterized spike focus.

    Science.gov (United States)

    Wennberg, Richard; Cheyne, Douglas

    2014-05-01

    To assess the reliability of MEG source imaging (MSI) of anterior temporal spikes through detailed analysis of the localization and orientation of source solutions obtained for a large number of spikes that were separately confirmed by intracranial EEG to be focally generated within a single, well-characterized spike focus. MSI was performed on 64 identical right anterior temporal spikes from an anterolateral temporal neocortical spike focus. The effects of different volume conductors (sphere and realistic head model), removal of noise with low frequency filters (LFFs) and averaging multiple spikes were assessed in terms of the reliability of the source solutions. MSI of single spikes resulted in scattered dipole source solutions that showed reasonable reliability for localization at the lobar level, but only for solutions with a goodness-of-fit exceeding 80% using a LFF of 3 Hz. Reliability at a finer level of intralobar localization was limited. Spike averaging significantly improved the reliability of source solutions and averaging 8 or more spikes reduced dependency on goodness-of-fit and data filtering. MSI performed on topographically identical individual spikes from an intracranially defined classical anterior temporal lobe spike focus was limited by low reliability (i.e., scattered source solutions) in terms of fine, sublobar localization within the ipsilateral temporal lobe. Spike averaging significantly improved reliability. MSI performed on individual anterior temporal spikes is limited by low reliability. Reduction of background noise through spike averaging significantly improves the reliability of MSI solutions. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Modeling spiking behavior of neurons with time-dependent Poisson processes.

    Science.gov (United States)

    Shinomoto, S; Tsubo, Y

    2001-10-01

    Three kinds of interval statistics, as represented by the coefficient of variation, the skewness coefficient, and the correlation coefficient of consecutive intervals, are evaluated for three kinds of time-dependent Poisson processes: pulse regulated, sinusoidally regulated, and doubly stochastic. Among these three processes, the sinusoidally regulated and doubly stochastic Poisson processes, in the case when the spike rate varies slowly compared with the mean interval between spikes, are found to be consistent with the three statistical coefficients exhibited by data recorded from neurons in the prefrontal cortex of monkeys.

  17. Visually Evoked Spiking Evolves While Spontaneous Ongoing Dynamics Persist

    DEFF Research Database (Denmark)

    Huys, Raoul; Jirsa, Viktor K; Darokhan, Ziauddin

    2016-01-01

    attractor. Its existence guarantees that evoked spiking return to the spontaneous state. However, the spontaneous ongoing spiking state and the visual evoked spiking states are qualitatively different and are separated by a threshold (separatrix). The functional advantage of this organization...

  18. Memristors Empower Spiking Neurons With Stochasticity

    KAUST Repository

    Al-Shedivat, Maruan

    2015-06-01

    Recent theoretical studies have shown that probabilistic spiking can be interpreted as learning and inference in cortical microcircuits. This interpretation creates new opportunities for building neuromorphic systems driven by probabilistic learning algorithms. However, such systems must have two crucial features: 1) the neurons should follow a specific behavioral model, and 2) stochastic spiking should be implemented efficiently for it to be scalable. This paper proposes a memristor-based stochastically spiking neuron that fulfills these requirements. First, the analytical model of the memristor is enhanced so it can capture the behavioral stochasticity consistent with experimentally observed phenomena. The switching behavior of the memristor model is demonstrated to be akin to the firing of the stochastic spike response neuron model, the primary building block for probabilistic algorithms in spiking neural networks. Furthermore, the paper proposes a neural soma circuit that utilizes the intrinsic nondeterminism of memristive switching for efficient spike generation. The simulations and analysis of the behavior of a single stochastic neuron and a winner-take-all network built of such neurons and trained on handwritten digits confirm that the circuit can be used for building probabilistic sampling and pattern adaptation machinery in spiking networks. The findings constitute an important step towards scalable and efficient probabilistic neuromorphic platforms. © 2011 IEEE.

  19. Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation

    OpenAIRE

    Thomson, Angus W.; Zahorchak, Alan F.; Ezzelarab, Mohamed B.; Butterfield, Lisa H.; Lakkis, Fadi G.; Metes, Diana M.

    2016-01-01

    Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering...

  20. Quantification of dendritic and axonal growth after injury to the auditory system of the adult cricket Gryllus bimaculatus

    Directory of Open Access Journals (Sweden)

    Alexandra ePfister

    2013-08-01

    Full Text Available Dendrite and axon growth and branching during development are regulated by a complex set of intracellular and external signals. However, the cues that maintain or influence adult neuronal morphology are less well understood. Injury and deafferentation tend to have negative effects on adult nervous systems. An interesting example of injury-induced compensatory growth is seen in the cricket, Gryllus bimaculatus. After unilateral loss of an ear in the adult cricket, auditory neurons within the central nervous system sprout to compensate for the injury. Specifically, after being deafferented, ascending neurons (AN-1 and AN-2 send dendrites across the midline of the prothoracic ganglion where they receive input from auditory afferents that project through the contralateral auditory nerve (N5. Deafferentation also triggers contralateral N5 axonal growth. In this study, we quantified AN dendritic and N5 axonal growth at 30 hours, as well as at 3, 5, 7, 14 and 20 days after deafferentation in adult crickets. Significant differences in the rates of dendritic growth between males and females were noted. In females, dendritic growth rates were non-linear; a rapid burst of dendritic extension in the first few days was followed by a plateau reached at 3 days after deafferentation. In males, however, dendritic growth rates were linear, with dendrites growing steadily over time and reaching lengths, on average, twice as long as in females. On the other hand, rates of N5 axonal growth showed no significant sexual dimorphism and were linear. Within each animal, the growth rates of dendrites and axons were not correlated, indicating that independent factors likely influence dendritic and axonal growth in response to injury in this system. Our findings provide a basis for future study of the cellular features that allow differing dendrite and axon growth patterns as well as sexually dimorphic dendritic growth in response to deafferentation.

  1. Spike Bursts from an Excitable Optical System

    Science.gov (United States)

    Rios Leite, Jose R.; Rosero, Edison J.; Barbosa, Wendson A. S.; Tredicce, Jorge R.

    Diode Lasers with double optical feedback are shown to present power drop spikes with statistical distribution controllable by the ratio of the two feedback times. The average time between spikes and the variance within long time series are studied. The system is shown to be excitable and present bursting of spikes created with specific feedback time ratios and strength. A rate equation model, extending the Lang-Kobayashi single feedback for semiconductor lasers proves to match the experimental observations. Potential applications to construct network to mimic neural systems having controlled bursting properties in each unit will be discussed. Brazilian Agency CNPQ.

  2. The Second Spiking Threshold: Dynamics of Laminar Network Spiking in the Visual Cortex

    Science.gov (United States)

    Forsberg, Lars E.; Bonde, Lars H.; Harvey, Michael A.; Roland, Per E.

    2016-01-01

    Most neurons have a threshold separating the silent non-spiking state and the state of producing temporal sequences of spikes. But neurons in vivo also have a second threshold, found recently in granular layer neurons of the primary visual cortex, separating spontaneous ongoing spiking from visually evoked spiking driven by sharp transients. Here we examine whether this second threshold exists outside the granular layer and examine details of transitions between spiking states in ferrets exposed to moving objects. We found the second threshold, separating spiking states evoked by stationary and moving visual stimuli from the spontaneous ongoing spiking state, in all layers and zones of areas 17 and 18 indicating that the second threshold is a property of the network. Spontaneous and evoked spiking, thus can easily be distinguished. In addition, the trajectories of spontaneous ongoing states were slow, frequently changing direction. In single trials, sharp as well as smooth and slow transients transform the trajectories to be outward directed, fast and crossing the threshold to become evoked. Although the speeds of the evolution of the evoked states differ, the same domain of the state space is explored indicating uniformity of the evoked states. All evoked states return to the spontaneous evoked spiking state as in a typical mono-stable dynamical system. In single trials, neither the original spiking rates, nor the temporal evolution in state space could distinguish simple visual scenes. PMID:27582693

  3. Phase field modeling of dendritic coarsening during isothermal

    Directory of Open Access Journals (Sweden)

    Zhang Yutuo

    2011-08-01

    Full Text Available Dendritic coarsening in Al-2mol%Si alloy during isothermal solidification at 880K was investigated by phase field modeling. Three coarsening mechanisms operate in the alloy: (a melting of small dendrite arms; (b coalescence of dendrites near the tips leading to the entrapment of liquid droplets; (c smoothing of dendrites. Dendrite melting is found to be dominant in the stage of dendritic growth, whereas coalescence of dendrites and smoothing of dendrites are dominant during isothermal holding. The simulated results provide a better understanding of dendrite coarsening during isothermal solidification.

  4. Spike persistence and normalization in benign epilepsy with centrotemporal spikes - Implications for management.

    Science.gov (United States)

    Kim, Hunmin; Kim, Soo Yeon; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Dlugos, Dennis J

    2018-05-10

    This study was performed 1) to determine the timing of spike normalization in patients with benign epilepsy with centrotemporal spikes (BECTS); 2) to identify relationships between age of seizure onset, age of spike normalization, years of spike persistence and treatment; and 3) to assess final outcomes between groups of patients with or without spikes at the time of medication tapering. Retrospective analysis of BECTS patients confirmed by clinical data, including age of onset, seizure semiology and serial electroencephalography (EEG) from diagnosis to remission. Age at spike normalization, years of spike persistence, and time of treatment onset to spike normalization were assessed. Final seizure and EEG outcome were compared between the groups with or without spikes at the time of AED tapering. One hundred and thirty-four patients were included. Mean age at seizure onset was 7.52 ± 2.11 years. Mean age at spike normalization was 11.89 ± 2.11 (range: 6.3-16.8) years. Mean time of treatment onset to spike normalization was 4.11 ± 2.13 (range: 0.24-10.08) years. Younger age of seizure onset was correlated with longer duration of spike persistence (r = -0.41, p < 0.001). In treated patients, spikes persisted for 4.1 ± 1.95 years, compared with 2.9 ± 1.97 years in untreated patients. No patients had recurrent seizures after AED was discontinued, regardless of the presence/absence of spikes at time of AED tapering. Years of spike persistence was longer in early onset BECTS patients. Treatment with AEDs did not shorten years of spike persistence. Persistence of spikes at time of treatment withdrawal was not associated with seizure recurrence. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  5. Memristors Empower Spiking Neurons With Stochasticity

    KAUST Repository

    Al-Shedivat, Maruan; Naous, Rawan; Cauwenberghs, Gert; Salama, Khaled N.

    2015-01-01

    Recent theoretical studies have shown that probabilistic spiking can be interpreted as learning and inference in cortical microcircuits. This interpretation creates new opportunities for building neuromorphic systems driven by probabilistic learning

  6. Fitting neuron models to spike trains

    Directory of Open Access Journals (Sweden)

    Cyrille eRossant

    2011-02-01

    Full Text Available Computational modeling is increasingly used to understand the function of neural circuitsin systems neuroscience.These studies require models of individual neurons with realisticinput-output properties.Recently, it was found that spiking models can accurately predict theprecisely timed spike trains produced by cortical neurons in response tosomatically injected currents,if properly fitted. This requires fitting techniques that are efficientand flexible enough to easily test different candidate models.We present a generic solution, based on the Brian simulator(a neural network simulator in Python, which allowsthe user to define and fit arbitrary neuron models to electrophysiological recordings.It relies on vectorization and parallel computing techniques toachieve efficiency.We demonstrate its use on neural recordings in the barrel cortex andin the auditory brainstem, and confirm that simple adaptive spiking modelscan accurately predict the response of cortical neurons. Finally, we show how a complexmulticompartmental model can be reduced to a simple effective spiking model.

  7. Frequency of Rolandic Spikes in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-10-01

    Full Text Available The frequency of rolandic spikes in nonepileptic children with attention deficit hyperactivity disorder (ADHD was compared with a control group of normal school-aged children in a study at the University of Frankfurt, Germany.

  8. THE POLITICAL CRITIQUE OF SPIKE Lee's Bamboozled

    African Journals Online (AJOL)

    Admin

    CONTEMPORARY AMERICAN MEDIA: THE POLITICAL. CRITIQUE OF SPIKE ... KEYWORDS: Blackface Minstrelsy, Racist Stereotypes and American Media. INTRODUCTION ..... of a difference that is itself a process of disavowal.” In this ...

  9. Thermosolutal convection during dendritic solidification

    Science.gov (United States)

    Heinrich, J. C.; Nandapurkar, P.; Poirier, D. R.; Felicelli, S.

    1989-01-01

    This paper presents a mathematical model for directional solidification of a binary alloy including a dendritic region underlying an all-liquid region. It is assumed initially that there exists a nonconvecting state with planar isotherms and isoconcentrates solidifying at a constant velocity. The stability of this system has been analyzed and nonlinear calculations are performed that show the effect of convection in the solidification process when the system is unstable. Results of calculations for various cases defined by the initial temperature gradient at the dendrite tips and varying strength of the gravitational field are presented for systems involving lead-tin alloys. The results show that the systems are stable for a gravitational constant of 0.0001 g(0) and that convection can be suppressed by appropriate choice of the container's size for higher values of the gravitational constant. It is also concluded that for the lead-tin systems considered, convection in the mushy zone is not significant below the upper 20 percent of the dendritic zone, if al all.

  10. Spatial distribution of excitatory synapses on the dendrites of ganglion cells in the mouse retina.

    Directory of Open Access Journals (Sweden)

    Yin-Peng Chen

    Full Text Available Excitatory glutamatergic inputs from bipolar cells affect the physiological properties of ganglion cells in the mammalian retina. The spatial distribution of these excitatory synapses on the dendrites of retinal ganglion cells thus may shape their distinct functions. To visualize the spatial pattern of excitatory glutamatergic input into the ganglion cells in the mouse retina, particle-mediated gene transfer of plasmids expressing postsynaptic density 95-green fluorescent fusion protein (PSD95-GFP was used to label the excitatory synapses. Despite wide variation in the size and morphology of the retinal ganglion cells, the expression of PSD95 puncta was found to follow two general rules. Firstly, the PSD95 puncta are regularly spaced, at 1-2 µm intervals, along the dendrites, whereby the presence of an excitatory synapse creates an exclusion zone that rules out the presence of other glutamatergic synaptic inputs. Secondly, the spatial distribution of PSD95 puncta on the dendrites of diverse retinal ganglion cells are similar in that the number of excitatory synapses appears to be less on primary dendrites and to increase to a plateau on higher branch order dendrites. These observations suggest that synaptogenesis is spatially regulated along the dendritic segments and that the number of synaptic contacts is relatively constant beyond the primary dendrites. Interestingly, we also found that the linear puncta density is slightly higher in large cells than in small cells. This may suggest that retinal ganglion cells with a large dendritic field tend to show an increased connectivity of excitatory synapses that makes up for their reduced dendrite density. Mapping the spatial distribution pattern of the excitatory synapses on retinal ganglion cells thus provides explicit structural information that is essential for our understanding of how excitatory glutamatergic inputs shape neuronal responses.

  11. A Reinforcement Learning Framework for Spiking Networks with Dynamic Synapses

    Directory of Open Access Journals (Sweden)

    Karim El-Laithy

    2011-01-01

    Full Text Available An integration of both the Hebbian-based and reinforcement learning (RL rules is presented for dynamic synapses. The proposed framework permits the Hebbian rule to update the hidden synaptic model parameters regulating the synaptic response rather than the synaptic weights. This is performed using both the value and the sign of the temporal difference in the reward signal after each trial. Applying this framework, a spiking network with spike-timing-dependent synapses is tested to learn the exclusive-OR computation on a temporally coded basis. Reward values are calculated with the distance between the output spike train of the network and a reference target one. Results show that the network is able to capture the required dynamics and that the proposed framework can reveal indeed an integrated version of Hebbian and RL. The proposed framework is tractable and less computationally expensive. The framework is applicable to a wide class of synaptic models and is not restricted to the used neural representation. This generality, along with the reported results, supports adopting the introduced approach to benefit from the biologically plausible synaptic models in a wide range of intuitive signal processing.

  12. Enhanced polychronisation in a spiking network with metaplasticity

    Directory of Open Access Journals (Sweden)

    Mira eGuise

    2015-02-01

    Full Text Available Computational models of metaplasticity have usually focused on the modeling of single synapses (Shouval et al., 2002. In this paper we study the effect of metaplasticity on network behavior. Our guiding assumption is that the primary purpose of metaplasticity is to regulate synaptic plasticity, by increasing it when input is low and decreasing it when input is high. For our experiments we adopt a model of metaplasticity that demonstrably has this effect for a single synapse; our primary interest is in how metaplasticity thus defined affects network-level phenomena. We focus on a network-level phenomenon called polychronicity, that has a potential role in representation and memory. A network with polychronicity has the ability to produce non-synchronous but precisely timed sequences of neural firing events that can arise from strongly connected groups of neurons called polychronous neural groups (Izhikevich et al., 2004; Izhikevich, 2006a. Polychronous groups (PNGs develop readily when spiking networks are exposed to repeated spatio-temporal stimuli under the influence of spike-timing-dependent plasticity (STDP, but are sensitive to changes in synaptic weight distribution. We use a technique we have recently developed called Response Fingerprinting to show that PNGs formed in the presence of metaplasticity are significantly larger than those with no metaplasticity. A potential mechanism for this enhancement is proposed that links an inherent property of integrator type neurons called spike latency to an increase in the tolerance of PNG neurons to jitter in their inputs.

  13. Inferring oscillatory modulation in neural spike trains.

    Science.gov (United States)

    Arai, Kensuke; Kass, Robert E

    2017-10-01

    Oscillations are observed at various frequency bands in continuous-valued neural recordings like the electroencephalogram (EEG) and local field potential (LFP) in bulk brain matter, and analysis of spike-field coherence reveals that spiking of single neurons often occurs at certain phases of the global oscillation. Oscillatory modulation has been examined in relation to continuous-valued oscillatory signals, and independently from the spike train alone, but behavior or stimulus triggered firing-rate modulation, spiking sparseness, presence of slow modulation not locked to stimuli and irregular oscillations with large variability in oscillatory periods, present challenges to searching for temporal structures present in the spike train. In order to study oscillatory modulation in real data collected under a variety of experimental conditions, we describe a flexible point-process framework we call the Latent Oscillatory Spike Train (LOST) model to decompose the instantaneous firing rate in biologically and behaviorally relevant factors: spiking refractoriness, event-locked firing rate non-stationarity, and trial-to-trial variability accounted for by baseline offset and a stochastic oscillatory modulation. We also extend the LOST model to accommodate changes in the modulatory structure over the duration of the experiment, and thereby discover trial-to-trial variability in the spike-field coherence of a rat primary motor cortical neuron to the LFP theta rhythm. Because LOST incorporates a latent stochastic auto-regressive term, LOST is able to detect oscillations when the firing rate is low, the modulation is weak, and when the modulating oscillation has a broad spectral peak.

  14. Anticipating Activity in Social Media Spikes

    OpenAIRE

    Higham, Desmond J.; Grindrod, Peter; Mantzaris, Alexander V.; Otley, Amanda; Laflin, Peter

    2014-01-01

    We propose a novel mathematical model for the activity of microbloggers during an external, event-driven spike. The model leads to a testable prediction of who would become most active if a spike were to take place. This type of information is of great interest to commercial organisations, governments and charities, as it identifies key players who can be targeted with information in real time when the network is most receptive. The model takes account of the fact that dynamic interactions ev...

  15. Building functional networks of spiking model neurons.

    Science.gov (United States)

    Abbott, L F; DePasquale, Brian; Memmesheimer, Raoul-Martin

    2016-03-01

    Most of the networks used by computer scientists and many of those studied by modelers in neuroscience represent unit activities as continuous variables. Neurons, however, communicate primarily through discontinuous spiking. We review methods for transferring our ability to construct interesting networks that perform relevant tasks from the artificial continuous domain to more realistic spiking network models. These methods raise a number of issues that warrant further theoretical and experimental study.

  16. Preferential control of basal dendritic protrusions by EphB2.

    Directory of Open Access Journals (Sweden)

    Matthew S Kayser

    2011-02-01

    Full Text Available The flow of information between neurons in many neural circuits is controlled by a highly specialized site of cell-cell contact known as a synapse. A number of molecules have been identified that are involved in central nervous system synapse development, but knowledge is limited regarding whether these cues direct organization of specific synapse types or on particular regions of individual neurons. Glutamate is the primary excitatory neurotransmitter in the brain, and the majority of glutamatergic synapses occur on mushroom-shaped protrusions called dendritic spines. Changes in the morphology of these structures are associated with long-lasting modulation of synaptic strength thought to underlie learning and memory, and can be abnormal in neuropsychiatric disease. Here, we use rat cortical slice cultures to examine how a previously-described synaptogenic molecule, the EphB2 receptor tyrosine kinase, regulates dendritic protrusion morphology in specific regions of the dendritic arbor in cortical pyramidal neurons. We find that alterations in EphB2 signaling can bidirectionally control protrusion length, and knockdown of EphB2 expression levels reduces the number of dendritic spines and filopodia. Expression of wild-type or dominant negative EphB2 reveals that EphB2 preferentially regulates dendritic protrusion structure in basal dendrites. Our findings suggest that EphB2 may act to specify synapse formation in a particular subcellular region of cortical pyramidal neurons.

  17. Training Deep Spiking Neural Networks Using Backpropagation.

    Science.gov (United States)

    Lee, Jun Haeng; Delbruck, Tobi; Pfeiffer, Michael

    2016-01-01

    Deep spiking neural networks (SNNs) hold the potential for improving the latency and energy efficiency of deep neural networks through data-driven event-based computation. However, training such networks is difficult due to the non-differentiable nature of spike events. In this paper, we introduce a novel technique, which treats the membrane potentials of spiking neurons as differentiable signals, where discontinuities at spike times are considered as noise. This enables an error backpropagation mechanism for deep SNNs that follows the same principles as in conventional deep networks, but works directly on spike signals and membrane potentials. Compared with previous methods relying on indirect training and conversion, our technique has the potential to capture the statistics of spikes more precisely. We evaluate the proposed framework on artificially generated events from the original MNIST handwritten digit benchmark, and also on the N-MNIST benchmark recorded with an event-based dynamic vision sensor, in which the proposed method reduces the error rate by a factor of more than three compared to the best previous SNN, and also achieves a higher accuracy than a conventional convolutional neural network (CNN) trained and tested on the same data. We demonstrate in the context of the MNIST task that thanks to their event-driven operation, deep SNNs (both fully connected and convolutional) trained with our method achieve accuracy equivalent with conventional neural networks. In the N-MNIST example, equivalent accuracy is achieved with about five times fewer computational operations.

  18. Dendritic cells in chronic myelomonocytic leukaemia.

    Science.gov (United States)

    Vuckovic, S; Fearnley, D B; Gunningham, S; Spearing, R L; Patton, W N; Hart, D N

    1999-06-01

    Blood dendritic cells (DC) differentiate in vitro via two separate pathways: either directly from blood DC precursors (DCp) or from CD14+ monocytes. In chronic myelomonocytic leukaemia (CMML) abnormal bone marrow precursors contribute to blood monocyte development but DC development has not been studied previously. Monocytes comprised 60% of blood MNC in 15 CMML patients studied, compared with 20% in 16 age-matched controls. The increase in blood monocytes was accompanied by a reciprocal decrease in mean blood DC percentage (from 0.42% of MNC in normal individuals to 0.16% of MNC in CMML patients). Absolute blood DC numbers showed a minimal (non-significant) reduction from 9.8 x 10(6)/l in normal individuals to 7.5 x 10(6)/l in CMML patients. The CD14(low) WCD16+ monocyte subpopulation was not found in CMML patients. After culture in GM-CSF/IL-4, CMML CD14+ monocytes acquired the phenotype of immature monocyte derived DC (Mo-DC) with similar yields to normal blood Mo-DC generation. Addition of TNF-alpha or LPS induced both normal and CMML Mo-DC to express prominent dendritic processes, the CMRF44+ and CD83+ antigens and high levels of HLA-DR, CD80 and CD86. Treatment either with TNF-alpha or LPS increased the allostimulatory activity of normal Mo-DC, but had little effect on the allostimulatory activity of CMML Mo-DC, perhaps reflecting the underlying neoplastic changes in monocyte precursors. We conclude that the blood DC numbers are relatively unaffected in CMML, suggesting discrete regulation of monocyte and DC production.

  19. Orientations of dendritic growth during solidification

    Science.gov (United States)

    Lee, Dong Nyung

    2017-03-01

    Dendrites are crystalline forms which grow far from the limit of stability of the plane front and adopt an orientation which is as close as possible to the heat flux direction. Dendritic growth orientations for cubic metals, bct Sn, and hcp Zn, can be controlled by thermal conductivity, Young's modulus, and surface energy. The control factors have been elaborated. Since the dendrite is a single crystal, its properties such as thermal conductivity that influences the heat flux direction, the minimum Young's modulus direction that influences the strain energy minimization, and the minimum surface energy plane that influences the crystal/liquid interface energy minimization have been proved to control the dendritic growth direction. The dendritic growth directions of cubic metals are determined by the minimum Young's modulus direction and/or axis direction of symmetry of the minimum crystal surface energy plane. The dendritic growth direction of bct Sn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction. The primary dendritic growth direction of hcp Zn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction and the secondary dendrite arm direction of hcp Zn is normal to the primary dendritic growth direction.

  20. Dendritic cell fate is determined by BCL11A

    Science.gov (United States)

    Ippolito, Gregory C.; Dekker, Joseph D.; Wang, Yui-Hsi; Lee, Bum-Kyu; Shaffer, Arthur L.; Lin, Jian; Wall, Jason K.; Lee, Baeck-Seung; Staudt, Louis M.; Liu, Yong-Jun; Iyer, Vishwanath R.; Tucker, Haley O.

    2014-01-01

    The plasmacytoid dendritic cell (pDC) is vital to the coordinated action of innate and adaptive immunity. pDC development has not been unequivocally traced, nor has its transcriptional regulatory network been fully clarified. Here we confirm an essential requirement for the BCL11A transcription factor in fetal pDC development, and demonstrate this lineage-specific requirement in the adult organism. Furthermore, we identify BCL11A gene targets and provide a molecular mechanism for its action in pDC commitment. Embryonic germ-line deletion of Bcl11a revealed an absolute cellular, molecular, and functional absence of pDCs in fetal mice. In adults, deletion of Bcl11a in hematopoietic stem cells resulted in perturbed yet continued generation of progenitors, loss of downstream pDC and B-cell lineages, and persisting myeloid, conventional dendritic, and T-cell lineages. Challenge with virus resulted in a marked reduction of antiviral response in conditionally deleted adults. Genome-wide analyses of BCL11A DNA binding and expression revealed that BCL11A regulates transcription of E2-2 and other pDC differentiation modulators, including ID2 and MTG16. Our results identify BCL11A as an essential, lineage-specific factor that regulates pDC development, supporting a model wherein differentiation into pDCs represents a primed “default” pathway for common dendritic cell progenitors. PMID:24591644

  1. CD1d-restricted IFN-γ-secreting NKT cells promote immune complex-induced acute lung injury by regulating macrophage-inflammatory protein-1α production and activation of macrophages and dendritic cells.

    Science.gov (United States)

    Kim, Ji Hyung; Chung, Doo Hyun

    2011-02-01

    Immune complex-induced acute lung injury (IC-ALI) has been implicated in various pulmonary disease states. However, the role of NKT cells in IC-ALI remains unknown. Therefore, we explored NKT cell functions in IC-ALI using chicken egg albumin and anti-chicken egg albumin IgG. The bronchoalveolar lavage fluid of CD1d(-/-) and Jα18(-/-) mice contained few Ly6G(+)CD11b(+) granulocytes, whereas levels in B6 mice were greater and were increased further by α-galactosyl ceramide. IFN-γ and MIP-1α production in the lungs was greater in B6 than CD1d(-/-) mice. Adoptive transfer of wild type (WT) but not IFN-γ-, MIP-1α-, or FcγR-deficient NKT cells into CD1d(-/-) mice caused recruitment of inflammatory cells to the lungs. Moreover, adoptive transfer of IFN-γR-deficient NKT cells enhanced MIP-1α production and cell recruitment in the lungs of CD1d(-/-) or CD1d(-/-)IFN-γ(-/-) mice, but to a lesser extent than WT NKT cells. This suggests that IFN-γ-producing NKT cells enhance MIP-1α production in both an autocrine and a paracrine manner. IFN-γ-deficient NKT cells induced less IL-1β and TNF-α production by alveolar macrophages and dendritic cells in CD1d(-/-) mice than did WT NKT cells. Taken together, these data suggest that CD1d-restricted IFN-γ-producing NKT cells promote IC-ALI by producing MIP-1α and enhancing proinflammatory cytokine production by alveolar macrophages and dendritic cells.

  2. Visually Evoked Spiking Evolves While Spontaneous Ongoing Dynamics Persist

    Science.gov (United States)

    Huys, Raoul; Jirsa, Viktor K.; Darokhan, Ziauddin; Valentiniene, Sonata; Roland, Per E.

    2016-01-01

    Neurons in the primary visual cortex spontaneously spike even when there are no visual stimuli. It is unknown whether the spiking evoked by visual stimuli is just a modification of the spontaneous ongoing cortical spiking dynamics or whether the spontaneous spiking state disappears and is replaced by evoked spiking. This study of laminar recordings of spontaneous spiking and visually evoked spiking of neurons in the ferret primary visual cortex shows that the spiking dynamics does not change: the spontaneous spiking as well as evoked spiking is controlled by a stable and persisting fixed point attractor. Its existence guarantees that evoked spiking return to the spontaneous state. However, the spontaneous ongoing spiking state and the visual evoked spiking states are qualitatively different and are separated by a threshold (separatrix). The functional advantage of this organization is that it avoids the need for a system reorganization following visual stimulation, and impedes the transition of spontaneous spiking to evoked spiking and the propagation of spontaneous spiking from layer 4 to layers 2–3. PMID:26778982

  3. Non-orthogonally transitive G2 spike solution

    International Nuclear Information System (INIS)

    Lim, Woei Chet

    2015-01-01

    We generalize the orthogonally transitive (OT) G 2 spike solution to the non-OT G 2 case. This is achieved by applying Geroch’s transformation on a Kasner seed. The new solution contains two more parameters than the OT G 2 spike solution. Unlike the OT G 2 spike solution, the new solution always resolves its spike. (fast track communication)

  4. Spike timing rigidity is maintained in bursting neurons under pentobarbital-induced anesthetic conditions

    Directory of Open Access Journals (Sweden)

    Risako Kato

    2016-11-01

    Full Text Available Pentobarbital potentiates γ-aminobutyric acid (GABA-mediated inhibitory synaptic transmission by prolonging the open time of GABAA receptors. However, it is unknown how pentobarbital regulates cortical neuronal activities via local circuits in vivo. To examine this question, we performed extracellular unit recording in rat insular cortex under awake and anesthetic conditions. Not a few studies apply time-rescaling theorem to detect the features of repetitive spike firing. Similar to these methods, we define an average spike interval locally in time using random matrix theory (RMT, which enables us to compare different activity states on a universal scale. Neurons with high spontaneous firing frequency (> 5 Hz and bursting were classified as HFB neurons (n = 10, and those with low spontaneous firing frequency (< 10 Hz and without bursting were classified as non-HFB neurons (n = 48. Pentobarbital injection (30 mg/kg reduced firing frequency in all HFB neurons and in 78% of non-HFB neurons. RMT analysis demonstrated that pentobarbital increased in the number of neurons with repulsion in both HFB and non-HFB neurons, suggesting that there is a correlation between spikes within a short interspike interval. Under awake conditions, in 50% of HFB and 40% of non-HFB neurons, the decay phase of normalized histograms of spontaneous firing were fitted to an exponential function, which indicated that the first spike had no correlation with subsequent spikes. In contrast, under pentobarbital-induced anesthesia conditions, the number of non-HFB neurons that were fitted to an exponential function increased to 80%, but almost no change in HFB neurons was observed. These results suggest that under both awake and pentobarbital-induced anesthetized conditions, spike firing in HFB neurons is more robustly regulated by preceding spikes than by non-HFB neurons, which may reflect the GABAA receptor-mediated regulation of cortical activities. Whole-cell patch

  5. Spindle-F Is the Central Mediator of Ik2 Kinase-Dependent Dendrite Pruning in Drosophila Sensory Neurons.

    Directory of Open Access Journals (Sweden)

    Tzu Lin

    2015-11-01

    Full Text Available During development, certain Drosophila sensory neurons undergo dendrite pruning that selectively eliminates their dendrites but leaves the axons intact. How these neurons regulate pruning activity in the dendrites remains unknown. Here, we identify a coiled-coil protein Spindle-F (Spn-F that is required for dendrite pruning in Drosophila sensory neurons. Spn-F acts downstream of IKK-related kinase Ik2 in the same pathway for dendrite pruning. Spn-F exhibits a punctate pattern in larval neurons, whereas these Spn-F puncta become redistributed in pupal neurons, a step that is essential for dendrite pruning. The redistribution of Spn-F from puncta in pupal neurons requires the phosphorylation of Spn-F by Ik2 kinase to decrease Spn-F self-association, and depends on the function of microtubule motor dynein complex. Spn-F is a key component to link Ik2 kinase to dynein motor complex, and the formation of Ik2/Spn-F/dynein complex is critical for Spn-F redistribution and for dendrite pruning. Our findings reveal a novel regulatory mechanism for dendrite pruning achieved by temporal activation of Ik2 kinase and dynein-mediated redistribution of Ik2/Spn-F complex in neurons.

  6. Axonal propagation of simple and complex spikes in cerebellar Purkinje neurons.

    Science.gov (United States)

    Khaliq, Zayd M; Raman, Indira M

    2005-01-12

    In cerebellar Purkinje neurons, the reliability of propagation of high-frequency simple spikes and spikelets of complex spikes is likely to regulate inhibition of Purkinje target neurons. To test the extent to which a one-to-one correspondence exists between somatic and axonal spikes, we made dual somatic and axonal recordings from Purkinje neurons in mouse cerebellar slices. Somatic action potentials were recorded with a whole-cell pipette, and the corresponding axonal signals were recorded extracellularly with a loose-patch pipette. Propagation of spontaneous and evoked simple spikes was highly reliable. At somatic firing rates of approximately 200 spikes/sec, 375 Hz during somatic hyperpolarizations that silenced spontaneous firing to approximately 150 Hz during spontaneous activity. The probability of propagation of individual spikelets could be described quantitatively as a saturating function of spikelet amplitude, rate of rise, or preceding interspike interval. The results suggest that ion channels of Purkinje axons are adapted to produce extremely short refractory periods and that brief bursts of forward-propagating action potentials generated by complex spikes may contribute transiently to inhibition of postsynaptic neurons.

  7. Spiking Neural Networks Based on OxRAM Synapses for Real-Time Unsupervised Spike Sorting.

    Science.gov (United States)

    Werner, Thilo; Vianello, Elisa; Bichler, Olivier; Garbin, Daniele; Cattaert, Daniel; Yvert, Blaise; De Salvo, Barbara; Perniola, Luca

    2016-01-01

    In this paper, we present an alternative approach to perform spike sorting of complex brain signals based on spiking neural networks (SNN). The proposed architecture is suitable for hardware implementation by using resistive random access memory (RRAM) technology for the implementation of synapses whose low latency (spike sorting. This offers promising advantages to conventional spike sorting techniques for brain-computer interfaces (BCI) and neural prosthesis applications. Moreover, the ultra-low power consumption of the RRAM synapses of the spiking neural network (nW range) may enable the design of autonomous implantable devices for rehabilitation purposes. We demonstrate an original methodology to use Oxide based RRAM (OxRAM) as easy to program and low energy (Spike Timing Dependent Plasticity. Real spiking data have been recorded both intra- and extracellularly from an in-vitro preparation of the Crayfish sensory-motor system and used for validation of the proposed OxRAM based SNN. This artificial SNN is able to identify, learn, recognize and distinguish between different spike shapes in the input signal with a recognition rate about 90% without any supervision.

  8. Spike rate and spike timing contributions to coding taste quality information in rat periphery

    Directory of Open Access Journals (Sweden)

    Vernon eLawhern

    2011-05-01

    Full Text Available There is emerging evidence that individual sensory neurons in the rodent brain rely on temporal features of the discharge pattern to code differences in taste quality information. In contrast, in-vestigations of individual sensory neurons in the periphery have focused on analysis of spike rate and mostly disregarded spike timing as a taste quality coding mechanism. The purpose of this work was to determine the contribution of spike timing to taste quality coding by rat geniculate ganglion neurons using computational methods that have been applied successfully in other sys-tems. We recorded the discharge patterns of narrowly-tuned and broadly-tuned neurons in the rat geniculate ganglion to representatives of the five basic taste qualities. We used mutual in-formation to determine significant responses and the van Rossum metric to characterize their temporal features. While our findings show that spike timing contributes a significant part of the message, spike rate contributes the largest portion of the message relayed by afferent neurons from rat fungiform taste buds to the brain. Thus, spike rate and spike timing together are more effective than spike rate alone in coding stimulus quality information to a single basic taste in the periphery for both narrowly-tuned specialist and broadly-tuned generalist neurons.

  9. Spike Code Flow in Cultured Neuronal Networks.

    Science.gov (United States)

    Tamura, Shinichi; Nishitani, Yoshi; Hosokawa, Chie; Miyoshi, Tomomitsu; Sawai, Hajime; Kamimura, Takuya; Yagi, Yasushi; Mizuno-Matsumoto, Yuko; Chen, Yen-Wei

    2016-01-01

    We observed spike trains produced by one-shot electrical stimulation with 8 × 8 multielectrodes in cultured neuronal networks. Each electrode accepted spikes from several neurons. We extracted the short codes from spike trains and obtained a code spectrum with a nominal time accuracy of 1%. We then constructed code flow maps as movies of the electrode array to observe the code flow of "1101" and "1011," which are typical pseudorandom sequence such as that we often encountered in a literature and our experiments. They seemed to flow from one electrode to the neighboring one and maintained their shape to some extent. To quantify the flow, we calculated the "maximum cross-correlations" among neighboring electrodes, to find the direction of maximum flow of the codes with lengths less than 8. Normalized maximum cross-correlations were almost constant irrespective of code. Furthermore, if the spike trains were shuffled in interval orders or in electrodes, they became significantly small. Thus, the analysis suggested that local codes of approximately constant shape propagated and conveyed information across the network. Hence, the codes can serve as visible and trackable marks of propagating spike waves as well as evaluating information flow in the neuronal network.

  10. Spike Code Flow in Cultured Neuronal Networks

    Directory of Open Access Journals (Sweden)

    Shinichi Tamura

    2016-01-01

    Full Text Available We observed spike trains produced by one-shot electrical stimulation with 8 × 8 multielectrodes in cultured neuronal networks. Each electrode accepted spikes from several neurons. We extracted the short codes from spike trains and obtained a code spectrum with a nominal time accuracy of 1%. We then constructed code flow maps as movies of the electrode array to observe the code flow of “1101” and “1011,” which are typical pseudorandom sequence such as that we often encountered in a literature and our experiments. They seemed to flow from one electrode to the neighboring one and maintained their shape to some extent. To quantify the flow, we calculated the “maximum cross-correlations” among neighboring electrodes, to find the direction of maximum flow of the codes with lengths less than 8. Normalized maximum cross-correlations were almost constant irrespective of code. Furthermore, if the spike trains were shuffled in interval orders or in electrodes, they became significantly small. Thus, the analysis suggested that local codes of approximately constant shape propagated and conveyed information across the network. Hence, the codes can serve as visible and trackable marks of propagating spike waves as well as evaluating information flow in the neuronal network.

  11. Effects of active conductance distribution over dendrites on the synaptic integration in an identified nonspiking interneuron.

    Directory of Open Access Journals (Sweden)

    Akira Takashima

    Full Text Available The synaptic integration in individual central neuron is critically affected by how active conductances are distributed over dendrites. It has been well known that the dendrites of central neurons are richly endowed with voltage- and ligand-regulated ion conductances. Nonspiking interneurons (NSIs, almost exclusively characteristic to arthropod central nervous systems, do not generate action potentials and hence lack voltage-regulated sodium channels, yet having a variety of voltage-regulated potassium conductances on their dendritic membrane including the one similar to the delayed-rectifier type potassium conductance. It remains unknown, however, how the active conductances are distributed over dendrites and how the synaptic integration is affected by those conductances in NSIs and other invertebrate neurons where the cell body is not included in the signal pathway from input synapses to output sites. In the present study, we quantitatively investigated the functional significance of active conductance distribution pattern in the spatio-temporal spread of synaptic potentials over dendrites of an identified NSI in the crayfish central nervous system by computer simulation. We systematically changed the distribution pattern of active conductances in the neuron's multicompartment model and examined how the synaptic potential waveform was affected by each distribution pattern. It was revealed that specific patterns of nonuniform distribution of potassium conductances were consistent, while other patterns were not, with the waveform of compound synaptic potentials recorded physiologically in the major input-output pathway of the cell, suggesting that the possibility of nonuniform distribution of potassium conductances over the dendrite cannot be excluded as well as the possibility of uniform distribution. Local synaptic circuits involving input and output synapses on the same branch or on the same side were found to be potentially affected under

  12. Active Dendrites and Differential Distribution of Calcium Channels Enable Functional Compartmentalization of Golgi Cells.

    Science.gov (United States)

    Rudolph, Stephanie; Hull, Court; Regehr, Wade G

    2015-11-25

    Interneurons are essential to controlling excitability, timing, and synaptic integration in neuronal networks. Golgi cells (GoCs) serve these roles at the input layer of the cerebellar cortex by releasing GABA to inhibit granule cells (grcs). GoCs are excited by mossy fibers (MFs) and grcs and provide feedforward and feedback inhibition to grcs. Here we investigate two important aspects of GoC physiology: the properties of GoC dendrites and the role of calcium signaling in regulating GoC spontaneous activity. Although GoC dendrites are extensive, previous studies concluded they are devoid of voltage-gated ion channels. Hence, the current view holds that somatic voltage signals decay passively within GoC dendrites, and grc synapses onto distal dendrites are not amplified and are therefore ineffective at firing GoCs because of strong passive attenuation. Using whole-cell recording and calcium imaging in rat slices, we find that dendritic voltage-gated sodium channels allow somatic action potentials to activate voltage-gated calcium channels (VGCCs) along the entire dendritic length, with R-type and T-type VGCCs preferentially located distally. We show that R- and T-type VGCCs located in the dendrites can boost distal synaptic inputs and promote burst firing. Active dendrites are thus critical to the regulation of GoC activity, and consequently, to the processing of input to the cerebellar cortex. In contrast, we find that N-type channels are preferentially located near the soma, and control the frequency and pattern of spontaneous firing through their close association with calcium-activated potassium (KCa) channels. Thus, VGCC types are differentially distributed and serve specialized functions within GoCs. Interneurons are essential to neural processing because they modulate excitability, timing, and synaptic integration within circuits. At the input layer of the cerebellar cortex, a single type of interneuron, the Golgi cell (GoC), carries these functions. The

  13. Recrystallization phenomena of solution grown paraffin dendrites

    NARCIS (Netherlands)

    Hollander, F.F.A.; Hollander, F.; Stasse, O.; van Suchtelen, J.; van Enckevort, W.J.P.

    2001-01-01

    Paraffin crystals were grown from decane solutions using a micro-Bridgman set up for in-situ observation of the morphology at the growth front. It is shown that for large imposed velocities, dendrites are obtained. After dendritic growth, aging or recrystallization processes set in rather quickly,

  14. Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons

    Directory of Open Access Journals (Sweden)

    Chang Geon Chung

    2017-07-01

    Full Text Available Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs and a decreased supply of plasma membrane (PM in Drosophila class IV dendritic arborization (da (C4 da neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis. Transcription factor enrichment analysis identified CREB3L1/CrebA, which regulates COPII gene expression. CrebA overexpression in C4 da neurons restores the dysregulation of COPII genes, GOP synthesis, and PM supply. Chromatin immunoprecipitation (ChIP-PCR revealed that CrebA expression is regulated by CREB-binding protein (CBP, which is sequestered by polyQ proteins. Furthermore, co-overexpression of CrebA and Rac1 synergistically restores the polyQ-induced dendrite pathology. Collectively, our results suggest that GOPs impaired by polyQ proteins contribute to dendrite pathology through the CBP-CrebA-COPII pathway.

  15. Age-Based Comparison of Human Dendritic Spine Structure Using Complete Three-Dimensional Reconstructions

    Science.gov (United States)

    Benavides-Piccione, Ruth; Fernaud-Espinosa, Isabel; Robles, Victor; Yuste, Rafael; DeFelipe, Javier

    2013-01-01

    Dendritic spines of pyramidal neurons are targets of most excitatory synapses in the cerebral cortex. Recent evidence suggests that the morphology of the dendritic spine could determine its synaptic strength and learning rules. However, unfortunately, there are scant data available regarding the detailed morphology of these structures for the human cerebral cortex. In the present study, we analyzed over 8900 individual dendritic spines that were completely 3D reconstructed along the length of apical and basal dendrites of layer III pyramidal neurons in the cingulate cortex of 2 male humans (aged 40 and 85 years old), using intracellular injections of Lucifer Yellow in fixed tissue. We assembled a large, quantitative database, which revealed a major reduction in spine densities in the aged case. Specifically, small and short spines of basal dendrites and long spines of apical dendrites were lost, regardless of the distance from the soma. Given the age difference between the cases, our results suggest selective alterations in spines with aging in humans and indicate that the spine volume and length are regulated by different biological mechanisms. PMID:22710613

  16. Vertical solidification of dendritic binary alloys

    Science.gov (United States)

    Heinrich, J. C.; Felicelli, S.; Poirier, D. R.

    1991-01-01

    Three numerical techniques are employed to analyze the influence of thermosolutal convection on defect formation in directionally solidified (DS) alloys. The finite-element models are based on the Boussinesq approximation and include the plane-front model and two plane-front models incorporating special dendritic regions. In the second model the dendritic region has a time-independent volume fraction of liquid, and in the last model the dendritic region evolves as local conditions dictate. The finite-element models permit the description of nonlinear thermosolutal convection by treating the dendritic regions as porous media with variable porosities. The models are applied to lead-tin alloys including DS alloys, and severe segregation phenomena such as freckles and channels are found to develop in the DS alloys. The present calculations and the permeability functions selected are shown to predict behavior in the dendritic regions that qualitatively matches that observed experimentally.

  17. The electric potential of tripolar spikes

    Energy Technology Data Exchange (ETDEWEB)

    Nocera, L. [Theoretical Plasma Physics, IPCF-CNR, Via Moruzzi 1, I-56124 Pisa (Italy)

    2010-02-22

    We present an analytical formula for the waveform of the electric potential associated with a tripolar spike in a plasma. This formula is based on the construction and on the subsequent solution of a differential equation for the waveform. We work out this equation as a direct consequence of the morphological and functional properties of the observed waveform, without making any reference to the velocity distributions of the electrons and of the ions which sustain the spike. In the approximation of small potential amplitudes, we solve this equation by quadrature. In particular, in the second order approximation, the solution of this equation is given in terms of elementary functions. This analytical solution is able to reproduce the potential waveforms associated with electron holes, ion holes, monotonic and nonmonotonic double layers and tripolar spikes, in excellent agreement with observations.

  18. The electric potential of tripolar spikes

    International Nuclear Information System (INIS)

    Nocera, L.

    2010-01-01

    We present an analytical formula for the waveform of the electric potential associated with a tripolar spike in a plasma. This formula is based on the construction and on the subsequent solution of a differential equation for the waveform. We work out this equation as a direct consequence of the morphological and functional properties of the observed waveform, without making any reference to the velocity distributions of the electrons and of the ions which sustain the spike. In the approximation of small potential amplitudes, we solve this equation by quadrature. In particular, in the second order approximation, the solution of this equation is given in terms of elementary functions. This analytical solution is able to reproduce the potential waveforms associated with electron holes, ion holes, monotonic and nonmonotonic double layers and tripolar spikes, in excellent agreement with observations.

  19. Trace element ink spiking for signature authentication

    International Nuclear Information System (INIS)

    Hatzistavros, V.S.; Kallithrakas-Kontos, N.G.

    2008-01-01

    Signature authentication is a critical question in forensic document examination. Last years the evolution of personal computers made signature copying a quite easy task, so the development of new ways for signature authentication is crucial. In the present work a commercial ink was spiked with many trace elements in various concentrations. Inorganic and organometallic ink soluble compounds were used as spiking agents, whilst ink retained its initial properties. The spiked inks were used for paper writing and the documents were analyzed by a non destructive method, the energy dispersive X-ray fluorescence. The thin target model was proved right for quantitative analysis and a very good linear relationship of the intensity (X-ray signal) against concentration was estimated for all used elements. Intensity ratios between different elements in the same ink gave very stable results, independent on the writing alterations. The impact of time both to written document and prepared inks was also investigated. (author)

  20. A Novel and Simple Spike Sorting Implementation.

    Science.gov (United States)

    Petrantonakis, Panagiotis C; Poirazi, Panayiota

    2017-04-01

    Monitoring the activity of multiple, individual neurons that fire spikes in the vicinity of an electrode, namely perform a Spike Sorting (SS) procedure, comprises one of the most important tools for contemporary neuroscience in order to reverse-engineer the brain. As recording electrodes' technology rabidly evolves by integrating thousands of electrodes in a confined spatial setting, the algorithms that are used to monitor individual neurons from recorded signals have to become even more reliable and computationally efficient. In this work, we propose a novel framework of the SS approach in which a single-step processing of the raw (unfiltered) extracellular signal is sufficient for both the detection and sorting of the activity of individual neurons. Despite its simplicity, the proposed approach exhibits comparable performance with state-of-the-art approaches, especially for spike detection in noisy signals, and paves the way for a new family of SS algorithms with the potential for multi-recording, fast, on-chip implementations.

  1. Evoking prescribed spike times in stochastic neurons

    Science.gov (United States)

    Doose, Jens; Lindner, Benjamin

    2017-09-01

    Single cell stimulation in vivo is a powerful tool to investigate the properties of single neurons and their functionality in neural networks. We present a method to determine a cell-specific stimulus that reliably evokes a prescribed spike train with high temporal precision of action potentials. We test the performance of this stimulus in simulations for two different stochastic neuron models. For a broad range of parameters and a neuron firing with intermediate firing rates (20-40 Hz) the reliability in evoking the prescribed spike train is close to its theoretical maximum that is mainly determined by the level of intrinsic noise.

  2. Temporal Correlations and Neural Spike Train Entropy

    International Nuclear Information System (INIS)

    Schultz, Simon R.; Panzeri, Stefano

    2001-01-01

    Sampling considerations limit the experimental conditions under which information theoretic analyses of neurophysiological data yield reliable results. We develop a procedure for computing the full temporal entropy and information of ensembles of neural spike trains, which performs reliably for limited samples of data. This approach also yields insight to the role of correlations between spikes in temporal coding mechanisms. The method, when applied to recordings from complex cells of the monkey primary visual cortex, results in lower rms error information estimates in comparison to a 'brute force' approach

  3. Implementing Signature Neural Networks with Spiking Neurons.

    Science.gov (United States)

    Carrillo-Medina, José Luis; Latorre, Roberto

    2016-01-01

    Spiking Neural Networks constitute the most promising approach to develop realistic Artificial Neural Networks (ANNs). Unlike traditional firing rate-based paradigms, information coding in spiking models is based on the precise timing of individual spikes. It has been demonstrated that spiking ANNs can be successfully and efficiently applied to multiple realistic problems solvable with traditional strategies (e.g., data classification or pattern recognition). In recent years, major breakthroughs in neuroscience research have discovered new relevant computational principles in different living neural systems. Could ANNs benefit from some of these recent findings providing novel elements of inspiration? This is an intriguing question for the research community and the development of spiking ANNs including novel bio-inspired information coding and processing strategies is gaining attention. From this perspective, in this work, we adapt the core concepts of the recently proposed Signature Neural Network paradigm-i.e., neural signatures to identify each unit in the network, local information contextualization during the processing, and multicoding strategies for information propagation regarding the origin and the content of the data-to be employed in a spiking neural network. To the best of our knowledge, none of these mechanisms have been used yet in the context of ANNs of spiking neurons. This paper provides a proof-of-concept for their applicability in such networks. Computer simulations show that a simple network model like the discussed here exhibits complex self-organizing properties. The combination of multiple simultaneous encoding schemes allows the network to generate coexisting spatio-temporal patterns of activity encoding information in different spatio-temporal spaces. As a function of the network and/or intra-unit parameters shaping the corresponding encoding modality, different forms of competition among the evoked patterns can emerge even in the absence

  4. Improved SpikeProp for Using Particle Swarm Optimization

    Directory of Open Access Journals (Sweden)

    Falah Y. H. Ahmed

    2013-01-01

    Full Text Available A spiking neurons network encodes information in the timing of individual spike times. A novel supervised learning rule for SpikeProp is derived to overcome the discontinuities introduced by the spiking thresholding. This algorithm is based on an error-backpropagation learning rule suited for supervised learning of spiking neurons that use exact spike time coding. The SpikeProp is able to demonstrate the spiking neurons that can perform complex nonlinear classification in fast temporal coding. This study proposes enhancements of SpikeProp learning algorithm for supervised training of spiking networks which can deal with complex patterns. The proposed methods include the SpikeProp particle swarm optimization (PSO and angle driven dependency learning rate. These methods are presented to SpikeProp network for multilayer learning enhancement and weights optimization. Input and output patterns are encoded as spike trains of precisely timed spikes, and the network learns to transform the input trains into target output trains. With these enhancements, our proposed methods outperformed other conventional neural network architectures.

  5. Span: spike pattern association neuron for learning spatio-temporal spike patterns.

    Science.gov (United States)

    Mohemmed, Ammar; Schliebs, Stefan; Matsuda, Satoshi; Kasabov, Nikola

    2012-08-01

    Spiking Neural Networks (SNN) were shown to be suitable tools for the processing of spatio-temporal information. However, due to their inherent complexity, the formulation of efficient supervised learning algorithms for SNN is difficult and remains an important problem in the research area. This article presents SPAN - a spiking neuron that is able to learn associations of arbitrary spike trains in a supervised fashion allowing the processing of spatio-temporal information encoded in the precise timing of spikes. The idea of the proposed algorithm is to transform spike trains during the learning phase into analog signals so that common mathematical operations can be performed on them. Using this conversion, it is possible to apply the well-known Widrow-Hoff rule directly to the transformed spike trains in order to adjust the synaptic weights and to achieve a desired input/output spike behavior of the neuron. In the presented experimental analysis, the proposed learning algorithm is evaluated regarding its learning capabilities, its memory capacity, its robustness to noisy stimuli and its classification performance. Differences and similarities of SPAN regarding two related algorithms, ReSuMe and Chronotron, are discussed.

  6. Essential Roles for ARID1B in Dendritic Arborization and Spine Morphology of Developing Pyramidal Neurons

    Science.gov (United States)

    Ka, Minhan; Chopra, Divyan A.; Dravid, Shashank M.

    2016-01-01

    De novo truncating mutations in ARID1B, a chromatin-remodeling gene, cause Coffin–Siris syndrome, a developmental disorder characterized by intellectual disability and speech impairment; however, how the genetic elimination leads to cognitive dysfunction remains unknown. Thus, we investigated the neural functions of ARID1B during brain development. Here, we show that ARID1B regulates dendritic differentiation in the developing mouse brain. We knocked down ARID1B expression in mouse pyramidal neurons using in utero gene delivery methodologies. ARID1B knockdown suppressed dendritic arborization of cortical and hippocampal pyramidal neurons in mice. The abnormal development of dendrites accompanied a decrease in dendritic outgrowth into layer I. Furthermore, knockdown of ARID1B resulted in aberrant dendritic spines and synaptic transmission. Finally, ARID1B deficiency led to altered expression of c-Fos and Arc, and overexpression of these factors rescued abnormal differentiation induced by ARID1B knockdown. Our results demonstrate a novel role for ARID1B in neuronal differentiation and provide new insights into the origin of cognitive dysfunction associated with developmental intellectual disability. SIGNIFICANCE STATEMENT Haploinsufficiency of ARID1B, a component of chromatin remodeling complex, causes intellectual disability. However, the role of ARID1B in brain development is unknown. Here, we demonstrate that ARID1B is required for neuronal differentiation in the developing brain, such as in dendritic arborization and synapse formation. Our findings suggest that ARID1B plays a critical role in the establishment of cognitive circuitry by regulating dendritic complexity. Thus, ARID1B deficiency may cause intellectual disability via abnormal brain wiring induced by the defective differentiation of cortical neurons. PMID:26937011

  7. Distinguishing linear vs. nonlinear integration in CA1 radial oblique dendrites: it’s about time

    Directory of Open Access Journals (Sweden)

    José Francisco eGómez González

    2011-11-01

    Full Text Available It was recently shown that multiple excitatory inputs to CA1 pyramidal neuron dendrites must be activated nearly simultaneously to generate local dendritic spikes and superlinear responses at the soma; even slight input desynchronization prevented local spike initiation (Gasparini, 2006;Losonczy, 2006. This led to the conjecture that CA1 pyramidal neurons may only express their nonlinear integrative capabilities during the highly synchronized sharp waves and ripples that occur during slow wave sleep and resting/consummatory behavior, whereas during active exploration and REM sleep (theta rhythm, inadequate synchronization of excitation would lead CA1 pyramidal cells to function as essentially linear devices. Using a detailed single neuron model, we replicated the experimentally observed synchronization effect for brief inputs mimicking single synaptic release events. When synapses were driven instead by double pulses, more representative of the bursty inputs that occur in vivo, we found that the tolerance for input desynchronization was increased by more than an order of magnitude. The effect depended mainly on paired pulse facilitation of NMDA receptor-mediated responses at Schaffer collateral synapses. Our results suggest that CA1 pyramidal cells could function as nonlinear integrative units in all major hippocampal states.

  8. Physics of volleyball: Spiking with a purpose

    Science.gov (United States)

    Behroozi, F.

    1998-05-01

    A few weeks ago our volleyball coach telephoned me with a problem: How high should a player jump to "spike" a "set" ball so it would clear the net and land at a known distance on the other side of the net?

  9. An Unsupervised Online Spike-Sorting Framework.

    Science.gov (United States)

    Knieling, Simeon; Sridharan, Kousik S; Belardinelli, Paolo; Naros, Georgios; Weiss, Daniel; Mormann, Florian; Gharabaghi, Alireza

    2016-08-01

    Extracellular neuronal microelectrode recordings can include action potentials from multiple neurons. To separate spikes from different neurons, they can be sorted according to their shape, a procedure referred to as spike-sorting. Several algorithms have been reported to solve this task. However, when clustering outcomes are unsatisfactory, most of them are difficult to adjust to achieve the desired results. We present an online spike-sorting framework that uses feature normalization and weighting to maximize the distinctiveness between different spike shapes. Furthermore, multiple criteria are applied to either facilitate or prevent cluster fusion, thereby enabling experimenters to fine-tune the sorting process. We compare our method to established unsupervised offline (Wave_Clus (WC)) and online (OSort (OS)) algorithms by examining their performance in sorting various test datasets using two different scoring systems (AMI and the Adamos metric). Furthermore, we evaluate sorting capabilities on intra-operative recordings using established quality metrics. Compared to WC and OS, our algorithm achieved comparable or higher scores on average and produced more convincing sorting results for intra-operative datasets. Thus, the presented framework is suitable for both online and offline analysis and could substantially improve the quality of microelectrode-based data evaluation for research and clinical application.

  10. Spike-timing theory of working memory.

    Directory of Open Access Journals (Sweden)

    Botond Szatmáry

    Full Text Available Working memory (WM is the part of the brain's memory system that provides temporary storage and manipulation of information necessary for cognition. Although WM has limited capacity at any given time, it has vast memory content in the sense that it acts on the brain's nearly infinite repertoire of lifetime long-term memories. Using simulations, we show that large memory content and WM functionality emerge spontaneously if we take the spike-timing nature of neuronal processing into account. Here, memories are represented by extensively overlapping groups of neurons that exhibit stereotypical time-locked spatiotemporal spike-timing patterns, called polychronous patterns; and synapses forming such polychronous neuronal groups (PNGs are subject to associative synaptic plasticity in the form of both long-term and short-term spike-timing dependent plasticity. While long-term potentiation is essential in PNG formation, we show how short-term plasticity can temporarily strengthen the synapses of selected PNGs and lead to an increase in the spontaneous reactivation rate of these PNGs. This increased reactivation rate, consistent with in vivo recordings during WM tasks, results in high interspike interval variability and irregular, yet systematically changing, elevated firing rate profiles within the neurons of the selected PNGs. Additionally, our theory explains the relationship between such slowly changing firing rates and precisely timed spikes, and it reveals a novel relationship between WM and the perception of time on the order of seconds.

  11. Crosstalk between T lymphocytes and dendritic cells.

    Science.gov (United States)

    Hivroz, Claire; Chemin, Karine; Tourret, Marie; Bohineust, Armelle

    2012-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique property of inducing priming and differentiation of naïve CD4+ and CD8+ T cells into helper and cytotoxic effectors. Their efficiency is due to their unique ability to process antigen, express costimulatory molecules, secrete cytokines, and migrate to tissues or lymphoid organs to prime T cells. DCs also play an important role in T-cell peripheral tolerance. There is ample evidence that the DC ability to present antigens is regulated by CD4+ helper T cells. Indeed, interactions between surface receptors and ligands expressed respectively by T cells and DCs, as well as T-cell-derived cytokines modify DC functions. This T-cell-induced modification of DCs has been called "education" or "licensing." This intimate crosstalk between DCs and T lymphocytes is key in establishing appropriate adaptive immune responses. It requires cognate interactions between T lymphocytes and DCs, which are organized in time and space by structures called immunological synapses. Here we discuss the particular aspects of immunological synapses formed between T cells and DCs and the role these organized interactions have in T-cell-DC crosstalk.

  12. Spike-timing dependent plasticity in the striatum

    Directory of Open Access Journals (Sweden)

    Elodie Fino

    2010-06-01

    Full Text Available The striatum is the major input nucleus of basal ganglia, an ensemble of interconnected sub-cortical nuclei associated with fundamental processes of action-selection and procedural learning and memory. The striatum receives afferents from the cerebral cortex and the thalamus. In turn, it relays the integrated information towards the basal ganglia output nuclei through which it operates a selected activation of behavioral effectors. The striatal output neurons, the GABAergic medium-sized spiny neurons (MSNs, are in charge of the detection and integration of behaviorally relevant information. This property confers to the striatum the ability to extract relevant information from the background noise and select cognitive-motor sequences adapted to environmental stimuli. As long-term synaptic efficacy changes are believed to underlie learning and memory, the corticostriatal long-term plasticity provides a fundamental mechanism for the function of the basal ganglia in procedural learning. Here, we reviewed the different forms of spike-timing dependent plasticity (STDP occurring at corticostriatal synapses. Most of the studies have focused on MSNs and their ability to develop long-term plasticity. Nevertheless, the striatal interneurons (the fast-spiking GABAergic, the NO synthase and cholinergic interneurons also receive monosynaptic afferents from the cortex and tightly regulated corticostriatal information processing. Therefore, it is important to take into account the variety of striatal neurons to fully understand the ability of striatum to develop long-term plasticity. Corticostriatal STDP with various spike-timing dependence have been observed depending on the neuronal sub-populations and experimental conditions. This complexity highlights the extraordinary potentiality in term of plasticity of the corticostriatal pathway.

  13. Spiking Neural P Systems with Communication on Request.

    Science.gov (United States)

    Pan, Linqiang; Păun, Gheorghe; Zhang, Gexiang; Neri, Ferrante

    2017-12-01

    Spiking Neural [Formula: see text] Systems are Neural System models characterized by the fact that each neuron mimics a biological cell and the communication between neurons is based on spikes. In the Spiking Neural [Formula: see text] systems investigated so far, the application of evolution rules depends on the contents of a neuron (checked by means of a regular expression). In these [Formula: see text] systems, a specified number of spikes are consumed and a specified number of spikes are produced, and then sent to each of the neurons linked by a synapse to the evolving neuron. [Formula: see text]In the present work, a novel communication strategy among neurons of Spiking Neural [Formula: see text] Systems is proposed. In the resulting models, called Spiking Neural [Formula: see text] Systems with Communication on Request, the spikes are requested from neighboring neurons, depending on the contents of the neuron (still checked by means of a regular expression). Unlike the traditional Spiking Neural [Formula: see text] systems, no spikes are consumed or created: the spikes are only moved along synapses and replicated (when two or more neurons request the contents of the same neuron). [Formula: see text]The Spiking Neural [Formula: see text] Systems with Communication on Request are proved to be computationally universal, that is, equivalent with Turing machines as long as two types of spikes are used. Following this work, further research questions are listed to be open problems.

  14. Statistical characteristics of climbing fiber spikes necessary for efficient cerebellar learning.

    Science.gov (United States)

    Kuroda, S; Yamamoto, K; Miyamoto, H; Doya, K; Kawat, M

    2001-03-01

    Mean firing rates (MFRs), with analogue values, have thus far been used as information carriers of neurons in most brain theories of learning. However, the neurons transmit the signal by spikes, which are discrete events. The climbing fibers (CFs), which are known to be essential for cerebellar motor learning, fire at the ultra-low firing rates (around 1 Hz), and it is not yet understood theoretically how high-frequency information can be conveyed and how learning of smooth and fast movements can be achieved. Here we address whether cerebellar learning can be achieved by CF spikes instead of conventional MFR in an eye movement task, such as the ocular following response (OFR), and an arm movement task. There are two major afferents into cerebellar Purkinje cells: parallel fiber (PF) and CF, and the synaptic weights between PFs and Purkinje cells have been shown to be modulated by the stimulation of both types of fiber. The modulation of the synaptic weights is regulated by the cerebellar synaptic plasticity. In this study we simulated cerebellar learning using CF signals as spikes instead of conventional MFR. To generate the spikes we used the following four spike generation models: (1) a Poisson model in which the spike interval probability follows a Poisson distribution, (2) a gamma model in which the spike interval probability follows the gamma distribution, (3) a max model in which a spike is generated when a synaptic input reaches maximum, and (4) a threshold model in which a spike is generated when the input crosses a certain small threshold. We found that, in an OFR task with a constant visual velocity, learning was successful with stochastic models, such as Poisson and gamma models, but not in the deterministic models, such as max and threshold models. In an OFR with a stepwise velocity change and an arm movement task, learning could be achieved only in the Poisson model. In addition, for efficient cerebellar learning, the distribution of CF spike

  15. Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC-induced dendritic tree complexity.

    Science.gov (United States)

    Schulz, Jana; Franke, Kristin; Frick, Manfred; Schumacher, Stefan

    2016-10-01

    Rho GTPases play prominent roles in the regulation of cytoskeletal reorganization. Many aspects have been elaborated concerning the individual functions of Rho GTPases in distinct signaling pathways leading to cytoskeletal rearrangements. However, major questions have yet to be answered regarding the integration and the signaling hierarchy of different Rho GTPases in regulating the cytoskeleton in fundamental physiological events like neuronal process differentiation. Here, we investigate the roles of the small GTPases Rac1, Cdc42, and RhoG in defining dendritic tree complexity stimulated by the transmembrane epidermal growth factor family member CALEB/NGC. Combining gain-of-function and loss-of-function analysis in primary hippocampal neurons, we find that Rac1 is essential for CALEB/NGC-mediated dendritic branching. Cdc42 reduces the complexity of dendritic trees. Interestingly, we identify the palmitoylated isoform of Cdc42 to adversely affect dendritic outgrowth and dendritic branching, whereas the prenylated Cdc42 isoform does not. In contrast to Rac1, CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic tree complexity. Unlike Rac1, the Rac1-related GTPase RhoG reduces the complexity of dendritic trees by acting upstream of CALEB/NGC. Mechanistically, CALEB/NGC activates Rac1, and RhoG reduces the amount of CALEB/NGC that is located at the right site for Rac1 activation at the cell membrane. Thus, Rac1, Cdc42, and RhoG perform very specific and non-redundant functions at different levels of hierarchy in regulating dendritic tree complexity induced by CALEB/NGC. Rho GTPases play a prominent role in dendritic branching. CALEB/NGC is a transmembrane member of the epidermal growth factor (EGF) family that mediates dendritic branching, dependent on Rac1. CALEB/NGC stimulates Rac1 activity. RhoG inhibits CALEB/NGC-mediated dendritic branching by decreasing the amount of CALEB/NGC at the plasma membrane. Palmitoylated, but not prenylated form

  16. Regulatory dendritic cell therapy: from rodents to clinical application

    OpenAIRE

    Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W.

    2013-01-01

    Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or “tolerogenic” DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant...

  17. Impact of spike train autostructure on probability distribution of joint spike events.

    Science.gov (United States)

    Pipa, Gordon; Grün, Sonja; van Vreeswijk, Carl

    2013-05-01

    The discussion whether temporally coordinated spiking activity really exists and whether it is relevant has been heated over the past few years. To investigate this issue, several approaches have been taken to determine whether synchronized events occur significantly above chance, that is, whether they occur more often than expected if the neurons fire independently. Most investigations ignore or destroy the autostructure of the spiking activity of individual cells or assume Poissonian spiking as a model. Such methods that ignore the autostructure can significantly bias the coincidence statistics. Here, we study the influence of the autostructure on the probability distribution of coincident spiking events between tuples of mutually independent non-Poisson renewal processes. In particular, we consider two types of renewal processes that were suggested as appropriate models of experimental spike trains: a gamma and a log-normal process. For a gamma process, we characterize the shape of the distribution analytically with the Fano factor (FFc). In addition, we perform Monte Carlo estimations to derive the full shape of the distribution and the probability for false positives if a different process type is assumed as was actually present. We also determine how manipulations of such spike trains, here dithering, used for the generation of surrogate data change the distribution of coincident events and influence the significance estimation. We find, first, that the width of the coincidence count distribution and its FFc depend critically and in a nontrivial way on the detailed properties of the structure of the spike trains as characterized by the coefficient of variation CV. Second, the dependence of the FFc on the CV is complex and mostly nonmonotonic. Third, spike dithering, even if as small as a fraction of the interspike interval, can falsify the inference on coordinated firing.

  18. Detection of bursts in neuronal spike trains by the mean inter-spike interval method

    Institute of Scientific and Technical Information of China (English)

    Lin Chen; Yong Deng; Weihua Luo; Zhen Wang; Shaoqun Zeng

    2009-01-01

    Bursts are electrical spikes firing with a high frequency, which are the most important property in synaptic plasticity and information processing in the central nervous system. However, bursts are difficult to identify because bursting activities or patterns vary with phys-iological conditions or external stimuli. In this paper, a simple method automatically to detect bursts in spike trains is described. This method auto-adaptively sets a parameter (mean inter-spike interval) according to intrinsic properties of the detected burst spike trains, without any arbitrary choices or any operator judgrnent. When the mean value of several successive inter-spike intervals is not larger than the parameter, a burst is identified. By this method, bursts can be automatically extracted from different bursting patterns of cultured neurons on multi-electrode arrays, as accurately as by visual inspection. Furthermore, significant changes of burst variables caused by electrical stimulus have been found in spontaneous activity of neuronal network. These suggest that the mean inter-spike interval method is robust for detecting changes in burst patterns and characteristics induced by environmental alterations.

  19. Memory CD8+ T cells protect dendritic cells from CTL killing

    NARCIS (Netherlands)

    Watchmaker, Payal B.; Urban, Julie A.; Berk, Erik; Nakamura, Yutaro; Mailliard, Robbie B.; Watkins, Simon C.; van Ham, S. Marieke; Kalinski, Pawel

    2008-01-01

    CD8(+) T cells have been shown to be capable of either suppressing or promoting immune responses. To reconcile these contrasting regulatory functions, we compared the ability of human effector and memory CD8(+) T cells to regulate survival and functions of dendritic cells (DC). We report that, in

  20. Single Ih channels in pyramidal neuron dendrites: properties, distribution, and impact on action potential output

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Hallermann, Stefan; Stuart, Greg J.

    2006-01-01

    The hyperpolarization-activated cation current (Ih) plays an important role in regulating neuronal excitability, yet its native single-channel properties in the brain are essentially unknown. Here we use variance-mean analysis to study the properties of single Ih channels in the apical dendrites of

  1. Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells

    DEFF Research Database (Denmark)

    Schulz, Anna M; Stutte, Susanne; Hogl, Sebastian

    2015-01-01

    Cell division cycle 42 (Cdc42) is a member of the Rho guanosine triphosphatase family and has pivotal functions in actin organization, cell migration, and proliferation. To further study the molecular mechanisms of dendritic cell (DC) regulation by Cdc42, we used Cdc42-deficient DCs. Cdc42 defici...

  2. Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells

    NARCIS (Netherlands)

    Bunin, A.; Sisirak, V.; Ghosh, H.S.; Grajkowska, L.T.; Hou, Z.E.; Miron, M.; Yang, C.; Ceribelli, M.; Uetani, N.; Chaperot, L.; Plumas, J.; Hendriks, W.J.; Tremblay, M.L.; Hacker, H.; Staudt, L.M.; Green, P.H.; Bhagat, G.; Reizis, B.

    2015-01-01

    Plasmacytoid dendritic cells (pDCs) are primary producers of type I interferon (IFN) in response to viruses. The IFN-producing capacity of pDCs is regulated by specific inhibitory receptors, yet none of the known receptors are conserved in evolution. We report that within the human immune system,

  3. Dendritic ion channelopathy in acquired epilepsy

    Science.gov (United States)

    Poolos, Nicholas P.; Johnston, Daniel

    2012-01-01

    Summary Ion channel dysfunction or “channelopathy” is a proven cause of epilepsy in the relatively uncommon genetic epilepsies with Mendelian inheritance. But numerous examples of acquired channelopathy in experimental animal models of epilepsy following brain injury have also been demonstrated. Our understanding of channelopathy has grown due to advances in electrophysiology techniques that have allowed the study of ion channels in the dendrites of pyramidal neurons in cortex and hippocampus. The apical dendrites of pyramidal neurons comprise the vast majority of neuronal surface membrane area, and thus the majority of the neuronal ion channel population. Investigation of dendritic ion channels has demonstrated remarkable plasticity in ion channel localization and biophysical properties in epilepsy, many of which produce hyperexcitability and may contribute to the development and maintenance of the epileptic state. Here we review recent advances in dendritic physiology and cell biology, and their relevance to epilepsy. PMID:23216577

  4. Sequence learning in differentially activated dendrites

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2003-01-01

    . It is proposed that the neural machinery required in such a learning/retrieval mechanism could involve the NMDA receptor, in conjunction with the ability of dendrites to maintain differentially activated regions. In particular, it is suggested that such a parcellation of the dendrite allows the neuron......Differentially activated areas of a dendrite permit the existence of zones with distinct rates of synaptic modification, and such areas can be individually accessed using a reference signal which localizes synaptic plasticity and memory trace retrieval to certain subregions of the dendrite...... to participate in multiple sequences, which can be learned without suffering from the 'wash-out' of synaptic efficacy associated with superimposition of training patterns. This is a biologically plausible solution to the stability-plasticity dilemma of learning in neural networks....

  5. Con-nectin axons and dendrites.

    Science.gov (United States)

    Beaudoin, Gerard M J

    2006-07-03

    Unlike adherens junctions, synapses are asymmetric connections, usually between axons and dendrites, that rely on various cell adhesion molecules for structural stability and function. Two cell types of adhesion molecules found at adherens junctions, cadherins and nectins, are thought to mediate homophilic interaction between neighboring cells. In this issue, Togashi et al. (see p. 141) demonstrate that the differential localization of two heterophilic interacting nectins mediates the selective attraction of axons and dendrites in cooperation with cadherins.

  6. Dendritic growth forms of borax crystals

    International Nuclear Information System (INIS)

    Takoo, R.K.; Patel, B.R.; Joshi, M.S.

    1983-01-01

    A variety of dendritic forms of borax grown from solutions by the film formation method is given. The changing growth morphology is followed as a function of concentration and temperature. The initial, intermediate and final growth morphologies are described and discussed. Influence of evaporation rate and supersaturation on the mechanism of growth is assessed. It is suggested that under all crystallization conditions, borax crystals have dendritic form in the initial stages of growth. (author)

  7. Co-operative suppression of inflammatory responses in human dendritic cells by plant proanthocyanidins and products from the parasitic nematode Trichuris suis

    DEFF Research Database (Denmark)

    Williams, Andrew R; Klaver, Elsenoor J; Laan, Lisa C

    2017-01-01

    Interactions between dendritic cells (DCs) and environmental, dietary and pathogen antigens play a key role in immune homeostasis and regulation of inflammation. Dietary polyphenols such as proanthocyanidins (PAC) may reduce inflammation, and we therefore hypothesized that PAC may suppress lipopo...

  8. Grain price spikes and beggar-thy-neighbor policy responses

    DEFF Research Database (Denmark)

    Jensen, Hans Grinsted; Anderson, Kym

    2017-01-01

    When prices spike in international grain markets, national governments often reduce the extent to which that spike affects their domestic food markets. Those actions exacerbate the price spike and international welfare transfer associated with that terms of trade change. Several recent analyses...

  9. Barbed micro-spikes for micro-scale biopsy

    Science.gov (United States)

    Byun, Sangwon; Lim, Jung-Min; Paik, Seung-Joon; Lee, Ahra; Koo, Kyo-in; Park, Sunkil; Park, Jaehong; Choi, Byoung-Doo; Seo, Jong Mo; Kim, Kyung-ah; Chung, Hum; Song, Si Young; Jeon, Doyoung; Cho, Dongil

    2005-06-01

    Single-crystal silicon planar micro-spikes with protruding barbs are developed for micro-scale biopsy and the feasibility of using the micro-spike as a micro-scale biopsy tool is evaluated for the first time. The fabrication process utilizes a deep silicon etch to define the micro-spike outline, resulting in protruding barbs of various shapes. Shanks of the fabricated micro-spikes are 3 mm long, 100 µm thick and 250 µm wide. Barbs protruding from micro-spike shanks facilitate the biopsy procedure by tearing off and retaining samples from target tissues. Micro-spikes with barbs successfully extracted tissue samples from the small intestines of the anesthetized pig, whereas micro-spikes without barbs failed to obtain a biopsy sample. Parylene coating can be applied to improve the biocompatibility of the micro-spike without deteriorating the biopsy function of the micro-spike. In addition, to show that the biopsy with the micro-spike can be applied to tissue analysis, samples obtained by micro-spikes were examined using immunofluorescent staining. Nuclei and F-actin of cells which are extracted by the micro-spike from a transwell were clearly visualized by immunofluorescent staining.

  10. The Mutation Frequency in Different Spike Categories in Barley

    DEFF Research Database (Denmark)

    Frydenberg, O.; Doll, Hans; Sandfær, J.

    1964-01-01

    After gamma irradiation of barley seeds, a comparison has been made between the chlorophyll-mutant frequencies in X1 spikes that had multicellular bud meristems in the seeds at the time of treatment (denoted as pre-formed spikes) and X1 spikes having no recognizable meristems at the time...

  11. Error-backpropagation in temporally encoded networks of spiking neurons

    NARCIS (Netherlands)

    S.M. Bohte (Sander); J.A. La Poutré (Han); J.N. Kok (Joost)

    2000-01-01

    textabstractFor a network of spiking neurons that encodes information in the timing of individual spike-times, we derive a supervised learning rule, emph{SpikeProp, akin to traditional error-backpropagation and show how to overcome the discontinuities introduced by thresholding. With this algorithm,

  12. Hardware implementation of stochastic spiking neural networks.

    Science.gov (United States)

    Rosselló, Josep L; Canals, Vincent; Morro, Antoni; Oliver, Antoni

    2012-08-01

    Spiking Neural Networks, the last generation of Artificial Neural Networks, are characterized by its bio-inspired nature and by a higher computational capacity with respect to other neural models. In real biological neurons, stochastic processes represent an important mechanism of neural behavior and are responsible of its special arithmetic capabilities. In this work we present a simple hardware implementation of spiking neurons that considers this probabilistic nature. The advantage of the proposed implementation is that it is fully digital and therefore can be massively implemented in Field Programmable Gate Arrays. The high computational capabilities of the proposed model are demonstrated by the study of both feed-forward and recurrent networks that are able to implement high-speed signal filtering and to solve complex systems of linear equations.

  13. Evolving spiking networks with variable resistive memories.

    Science.gov (United States)

    Howard, Gerard; Bull, Larry; de Lacy Costello, Ben; Gale, Ella; Adamatzky, Andrew

    2014-01-01

    Neuromorphic computing is a brainlike information processing paradigm that requires adaptive learning mechanisms. A spiking neuro-evolutionary system is used for this purpose; plastic resistive memories are implemented as synapses in spiking neural networks. The evolutionary design process exploits parameter self-adaptation and allows the topology and synaptic weights to be evolved for each network in an autonomous manner. Variable resistive memories are the focus of this research; each synapse has its own conductance profile which modifies the plastic behaviour of the device and may be altered during evolution. These variable resistive networks are evaluated on a noisy robotic dynamic-reward scenario against two static resistive memories and a system containing standard connections only. The results indicate that the extra behavioural degrees of freedom available to the networks incorporating variable resistive memories enable them to outperform the comparative synapse types.

  14. Visualizing spikes in source-space

    DEFF Research Database (Denmark)

    Beniczky, Sándor; Duez, Lene; Scherg, Michael

    2016-01-01

    OBJECTIVE: Reviewing magnetoencephalography (MEG) recordings is time-consuming: signals from the 306 MEG-sensors are typically reviewed divided into six arrays of 51 sensors each, thus browsing each recording six times in order to evaluate all signals. A novel method of reconstructing the MEG...... signals in source-space was developed using a source-montage of 29 brain-regions and two spatial components to remove magnetocardiographic (MKG) artefacts. Our objective was to evaluate the accuracy of reviewing MEG in source-space. METHODS: In 60 consecutive patients with epilepsy, we prospectively...... evaluated the accuracy of reviewing the MEG signals in source-space as compared to the classical method of reviewing them in sensor-space. RESULTS: All 46 spike-clusters identified in sensor-space were also identified in source-space. Two additional spike-clusters were identified in source-space. As 29...

  15. Spiked instantons from intersecting D-branes

    Directory of Open Access Journals (Sweden)

    Nikita Nekrasov

    2017-01-01

    Full Text Available The moduli space of spiked instantons that arises in the context of the BPS/CFT correspondence [22] is realised as the moduli space of classical vacua, i.e. low-energy open string field configurations, of a certain stack of intersecting D1-branes and D5-branes in Type IIB string theory. The presence of a constant B-field induces an interesting dynamics involving the tachyon condensation.

  16. Stochastic synchronization in finite size spiking networks

    Science.gov (United States)

    Doiron, Brent; Rinzel, John; Reyes, Alex

    2006-09-01

    We study a stochastic synchronization of spiking activity in feedforward networks of integrate-and-fire model neurons. A stochastic mean field analysis shows that synchronization occurs only when the network size is sufficiently small. This gives evidence that the dynamics, and hence processing, of finite size populations can be drastically different from that observed in the infinite size limit. Our results agree with experimentally observed synchrony in cortical networks, and further strengthen the link between synchrony and propagation in cortical systems.

  17. Non-singular spiked harmonic oscillator

    International Nuclear Information System (INIS)

    Aguilera-Navarro, V.C.; Guardiola, R.

    1990-01-01

    A perturbative study of a class of non-singular spiked harmonic oscillators defined by the hamiltonian H = d sup(2)/dr sup(2) + r sup(2) + λ/r sup(α) in the domain [0,∞] is carried out, in the two extremes of a weak coupling and a strong coupling regimes. A path has been found to connect both expansions for α near 2. (author)

  18. On the sample complexity of learning for networks of spiking neurons with nonlinear synaptic interactions.

    Science.gov (United States)

    Schmitt, Michael

    2004-09-01

    We study networks of spiking neurons that use the timing of pulses to encode information. Nonlinear interactions model the spatial groupings of synapses on the neural dendrites and describe the computations performed at local branches. Within a theoretical framework of learning we analyze the question of how many training examples these networks must receive to be able to generalize well. Bounds for this sample complexity of learning can be obtained in terms of a combinatorial parameter known as the pseudodimension. This dimension characterizes the computational richness of a neural network and is given in terms of the number of network parameters. Two types of feedforward architectures are considered: constant-depth networks and networks of unconstrained depth. We derive asymptotically tight bounds for each of these network types. Constant depth networks are shown to have an almost linear pseudodimension, whereas the pseudodimension of general networks is quadratic. Networks of spiking neurons that use temporal coding are becoming increasingly more important in practical tasks such as computer vision, speech recognition, and motor control. The question of how well these networks generalize from a given set of training examples is a central issue for their successful application as adaptive systems. The results show that, although coding and computation in these networks is quite different and in many cases more powerful, their generalization capabilities are at least as good as those of traditional neural network models.

  19. A Fully Automated Approach to Spike Sorting.

    Science.gov (United States)

    Chung, Jason E; Magland, Jeremy F; Barnett, Alex H; Tolosa, Vanessa M; Tooker, Angela C; Lee, Kye Y; Shah, Kedar G; Felix, Sarah H; Frank, Loren M; Greengard, Leslie F

    2017-09-13

    Understanding the detailed dynamics of neuronal networks will require the simultaneous measurement of spike trains from hundreds of neurons (or more). Currently, approaches to extracting spike times and labels from raw data are time consuming, lack standardization, and involve manual intervention, making it difficult to maintain data provenance and assess the quality of scientific results. Here, we describe an automated clustering approach and associated software package that addresses these problems and provides novel cluster quality metrics. We show that our approach has accuracy comparable to or exceeding that achieved using manual or semi-manual techniques with desktop central processing unit (CPU) runtimes faster than acquisition time for up to hundreds of electrodes. Moreover, a single choice of parameters in the algorithm is effective for a variety of electrode geometries and across multiple brain regions. This algorithm has the potential to enable reproducible and automated spike sorting of larger scale recordings than is currently possible. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The transfer function of neuron spike.

    Science.gov (United States)

    Palmieri, Igor; Monteiro, Luiz H A; Miranda, Maria D

    2015-08-01

    The mathematical modeling of neuronal signals is a relevant problem in neuroscience. The complexity of the neuron behavior, however, makes this problem a particularly difficult task. Here, we propose a discrete-time linear time-invariant (LTI) model with a rational function in order to represent the neuronal spike detected by an electrode located in the surroundings of the nerve cell. The model is presented as a cascade association of two subsystems: one that generates an action potential from an input stimulus, and one that represents the medium between the cell and the electrode. The suggested approach employs system identification and signal processing concepts, and is dissociated from any considerations about the biophysical processes of the neuronal cell, providing a low-complexity alternative to model the neuronal spike. The model is validated by using in vivo experimental readings of intracellular and extracellular signals. A computational simulation of the model is presented in order to assess its proximity to the neuronal signal and to observe the variability of the estimated parameters. The implications of the results are discussed in the context of spike sorting. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Basalt FRP Spike Repairing of Wood Beams

    Directory of Open Access Journals (Sweden)

    Luca Righetti

    2015-08-01

    Full Text Available This article describes aspects within an experimental program aimed at improving the structural performance of cracked solid fir-wood beams repaired with Basalt Fiber Reinforced Polymer (BFRP spikes. Fir wood is characterized by its low density, low compression strength, and high level of defects, and it is likely to distort when dried and tends to fail under tension due to the presence of cracks, knots, or grain deviation. The proposed repair technique consists of the insertion of BFRP spikes into timber beams to restore the continuity of cracked sections. The experimental efforts deal with the evaluation of the bending strength and deformation properties of 24 timber beams. An artificially simulated cracking was produced by cutting the wood beams in half or notching. The obtained results for the repaired beams were compared with those of solid undamaged and damaged beams, and increases of beam capacity, bending strength and of modulus of elasticity, and analysis of failure modes was discussed. For notched beams, the application of the BFRP spikes was able to restore the original bending capacity of undamaged beams, while only a small part of the original capacity was recovered for beams that were cut in half.

  2. Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites

    Science.gov (United States)

    Colgan, Lesley A.; Cavolo, Samantha L.; Commons, Kathryn G.; Levitan, Edwin S.

    2012-01-01

    Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here three-photon (3P) microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence and immuno-gold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca2+ channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines and NMDA receptor antagonists. PMID:23136413

  3. Mechanical coupling between transsynaptic N-cadherin adhesions and actin flow stabilizes dendritic spines

    Science.gov (United States)

    Chazeau, Anaël; Garcia, Mikael; Czöndör, Katalin; Perrais, David; Tessier, Béatrice; Giannone, Grégory; Thoumine, Olivier

    2015-01-01

    The morphology of neuronal dendritic spines is a critical indicator of synaptic function. It is regulated by several factors, including the intracellular actin/myosin cytoskeleton and transcellular N-cadherin adhesions. To examine the mechanical relationship between these molecular components, we performed quantitative live-imaging experiments in primary hippocampal neurons. We found that actin turnover and structural motility were lower in dendritic spines than in immature filopodia and increased upon expression of a nonadhesive N-cadherin mutant, resulting in an inverse relationship between spine motility and actin enrichment. Furthermore, the pharmacological stimulation of myosin II induced the rearward motion of actin structures in spines, showing that myosin II exerts tension on the actin network. Strikingly, the formation of stable, spine-like structures enriched in actin was induced at contacts between dendritic filopodia and N-cadherin–coated beads or micropatterns. Finally, computer simulations of actin dynamics mimicked various experimental conditions, pointing to the actin flow rate as an important parameter controlling actin enrichment in dendritic spines. Together these data demonstrate that a clutch-like mechanism between N-cadherin adhesions and the actin flow underlies the stabilization of dendritic filopodia into mature spines, a mechanism that may have important implications in synapse initiation, maturation, and plasticity in the developing brain. PMID:25568337

  4. Lateral Information Processing by Spiking Neurons: A Theoretical Model of the Neural Correlate of Consciousness

    Directory of Open Access Journals (Sweden)

    Marc Ebner

    2011-01-01

    Full Text Available Cognitive brain functions, for example, sensory perception, motor control and learning, are understood as computation by axonal-dendritic chemical synapses in networks of integrate-and-fire neurons. Cognitive brain functions may occur either consciously or nonconsciously (on “autopilot”. Conscious cognition is marked by gamma synchrony EEG, mediated largely by dendritic-dendritic gap junctions, sideways connections in input/integration layers. Gap-junction-connected neurons define a sub-network within a larger neural network. A theoretical model (the “conscious pilot” suggests that as gap junctions open and close, a gamma-synchronized subnetwork, or zone moves through the brain as an executive agent, converting nonconscious “auto-pilot” cognition to consciousness, and enhancing computation by coherent processing and collective integration. In this study we implemented sideways “gap junctions” in a single-layer artificial neural network to perform figure/ground separation. The set of neurons connected through gap junctions form a reconfigurable resistive grid or sub-network zone. In the model, outgoing spikes are temporally integrated and spatially averaged using the fixed resistive grid set up by neurons of similar function which are connected through gap-junctions. This spatial average, essentially a feedback signal from the neuron's output, determines whether particular gap junctions between neurons will open or close. Neurons connected through open gap junctions synchronize their output spikes. We have tested our gap-junction-defined sub-network in a one-layer neural network on artificial retinal inputs using real-world images. Our system is able to perform figure/ground separation where the laterally connected sub-network of neurons represents a perceived object. Even though we only show results for visual stimuli, our approach should generalize to other modalities. The system demonstrates a moving sub-network zone of

  5. Dendritic cell-based immunotherapy.

    Science.gov (United States)

    Osada, Takuya; Clay, Timothy M; Woo, Christopher Y; Morse, Michael A; Lyerly, H Kim

    2006-01-01

    Dendritic cells (DCs) play a crucial role in the induction of antigen-specific T-cell responses, and therefore their use for the active immunotherapy of malignancies has been studied with considerable interest. More than a decade has passed since the publication of the first clinical data of DC-based vaccines, and through this and subsequent studies, a number of important developmental insights have been gleaned. These include the ideal source and type of DCs, the discovery of novel antigens and methods of loading DCs, the role of DC maturation, and the most efficient route of immunization. The generation of immune responses against tumor antigens after DC immunization has been demonstrated, and favorable clinical responses have been reported in some patients; however, it is difficult to pool the results as a whole, and thus the body of data remains inconclusive, in part because of varying DC preparation and vaccination protocols, the use of different forms of antigens, and, most importantly, a lack of rigorous criteria for defining clinical responses. As such, the standardization of clinical and immunologic criteria utilized, as well as DC preparations employed, will allow for the comparison of results across multiple clinical studies and is required in order for future trials to measure the true value and role of this treatment modality. In addition, issues regarding the optimal dose and clinical setting for the application of DC vaccines remain to be resolved, and recent clinical studies have been designed to begin to address these questions.

  6. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons

    Science.gov (United States)

    Murphy, Diane D.; Cole, Nelson B.; Segal, Menahem

    1998-01-01

    Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density. Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons. PMID:9736750

  7. The Multiple Faces of Prostaglandin E2 G-Protein Coupled Receptor Signaling during the Dendritic Cell Life Cycle

    NARCIS (Netherlands)

    de Keijzer, Sandra; Meddens, Marjolein B.M.; Torensma, Ruurd; Cambi, A.

    2013-01-01

    Many processes regulating immune responses are initiated by G-protein coupled receptors (GPCRs) and report biochemical changes in the microenvironment. Dendritic cells (DCs) are the most potent antigen-presenting cells and crucial for the regulation of innate and adaptive immune responses. The lipid

  8. A Septin-Dependent Diffusion Barrier at Dendritic Spine Necks.

    Directory of Open Access Journals (Sweden)

    Helge Ewers

    Full Text Available Excitatory glutamatergic synapses at dendritic spines exchange and modulate their receptor content via lateral membrane diffusion. Several studies have shown that the thin spine neck impedes the access of membrane and solute molecules to the spine head. However, it is unclear whether the spine neck geometry alone restricts access to dendritic spines or if a physical barrier to the diffusion of molecules exists. Here, we investigated whether a complex of septin cytoskeletal GTPases localized at the base of the spine neck regulates diffusion across the spine neck. We found that, during development, a marker of the septin complex, Septin7 (Sept7, becomes localized to the spine neck where it forms a stable structure underneath the plasma membrane. We show that diffusion of receptors and bulk membrane, but not cytoplasmic proteins, is slower in spines bearing Sept7 at their neck. Finally, when Sept7 expression was suppressed by RNA interference, membrane molecules explored larger membrane areas. Our findings indicate that Sept7 regulates membrane protein access to spines.

  9. Precise-spike-driven synaptic plasticity: learning hetero-association of spatiotemporal spike patterns.

    Directory of Open Access Journals (Sweden)

    Qiang Yu

    Full Text Available A new learning rule (Precise-Spike-Driven (PSD Synaptic Plasticity is proposed for processing and memorizing spatiotemporal patterns. PSD is a supervised learning rule that is analytically derived from the traditional Widrow-Hoff rule and can be used to train neurons to associate an input spatiotemporal spike pattern with a desired spike train. Synaptic adaptation is driven by the error between the desired and the actual output spikes, with positive errors causing long-term potentiation and negative errors causing long-term depression. The amount of modification is proportional to an eligibility trace that is triggered by afferent spikes. The PSD rule is both computationally efficient and biologically plausible. The properties of this learning rule are investigated extensively through experimental simulations, including its learning performance, its generality to different neuron models, its robustness against noisy conditions, its memory capacity, and the effects of its learning parameters. Experimental results show that the PSD rule is capable of spatiotemporal pattern classification, and can even outperform a well studied benchmark algorithm with the proposed relative confidence criterion. The PSD rule is further validated on a practical example of an optical character recognition problem. The results again show that it can achieve a good recognition performance with a proper encoding. Finally, a detailed discussion is provided about the PSD rule and several related algorithms including tempotron, SPAN, Chronotron and ReSuMe.

  10. Precise-spike-driven synaptic plasticity: learning hetero-association of spatiotemporal spike patterns.

    Science.gov (United States)

    Yu, Qiang; Tang, Huajin; Tan, Kay Chen; Li, Haizhou

    2013-01-01

    A new learning rule (Precise-Spike-Driven (PSD) Synaptic Plasticity) is proposed for processing and memorizing spatiotemporal patterns. PSD is a supervised learning rule that is analytically derived from the traditional Widrow-Hoff rule and can be used to train neurons to associate an input spatiotemporal spike pattern with a desired spike train. Synaptic adaptation is driven by the error between the desired and the actual output spikes, with positive errors causing long-term potentiation and negative errors causing long-term depression. The amount of modification is proportional to an eligibility trace that is triggered by afferent spikes. The PSD rule is both computationally efficient and biologically plausible. The properties of this learning rule are investigated extensively through experimental simulations, including its learning performance, its generality to different neuron models, its robustness against noisy conditions, its memory capacity, and the effects of its learning parameters. Experimental results show that the PSD rule is capable of spatiotemporal pattern classification, and can even outperform a well studied benchmark algorithm with the proposed relative confidence criterion. The PSD rule is further validated on a practical example of an optical character recognition problem. The results again show that it can achieve a good recognition performance with a proper encoding. Finally, a detailed discussion is provided about the PSD rule and several related algorithms including tempotron, SPAN, Chronotron and ReSuMe.

  11. Nicotine-Mediated ADP to Spike Transition: Double Spiking in Septal Neurons.

    Science.gov (United States)

    Kodirov, Sodikdjon A; Wehrmeister, Michael; Colom, Luis

    2016-04-01

    The majority of neurons in lateral septum (LS) are electrically silent at resting membrane potential. Nicotine transiently excites a subset of neurons and occasionally leads to long lasting bursting activity upon longer applications. We have observed simultaneous changes in frequencies and amplitudes of spontaneous action potentials (AP) in the presence of nicotine. During the prolonged exposure, nicotine increased numbers of spikes within a burst. One of the hallmarks of nicotine effects was the occurrences of double spikes (known also as bursting). Alignment of 51 spontaneous spikes, triggered upon continuous application of nicotine, revealed that the slope of after-depolarizing potential gradually increased (1.4 vs. 3 mV/ms) and neuron fired the second AP, termed as double spiking. A transition from a single AP to double spikes increased the amplitude of after-hyperpolarizing potential. The amplitude of the second (premature) AP was smaller compared to the first one, and this correlation persisted in regard to their duration (half-width). A similar bursting activity in the presence of nicotine, to our knowledge, has not been reported previously in the septal structure in general and in LS in particular.

  12. Supervised Learning Based on Temporal Coding in Spiking Neural Networks.

    Science.gov (United States)

    Mostafa, Hesham

    2017-08-01

    Gradient descent training techniques are remarkably successful in training analog-valued artificial neural networks (ANNs). Such training techniques, however, do not transfer easily to spiking networks due to the spike generation hard nonlinearity and the discrete nature of spike communication. We show that in a feedforward spiking network that uses a temporal coding scheme where information is encoded in spike times instead of spike rates, the network input-output relation is differentiable almost everywhere. Moreover, this relation is piecewise linear after a transformation of variables. Methods for training ANNs thus carry directly to the training of such spiking networks as we show when training on the permutation invariant MNIST task. In contrast to rate-based spiking networks that are often used to approximate the behavior of ANNs, the networks we present spike much more sparsely and their behavior cannot be directly approximated by conventional ANNs. Our results highlight a new approach for controlling the behavior of spiking networks with realistic temporal dynamics, opening up the potential for using these networks to process spike patterns with complex temporal information.

  13. Spikes and matter inhomogeneities in massless scalar field models

    International Nuclear Information System (INIS)

    Coley, A A; Lim, W C

    2016-01-01

    We shall discuss the general relativistic generation of spikes in a massless scalar field or stiff perfect fluid model. We first investigate orthogonally transitive (OT) G 2 stiff fluid spike models both heuristically and numerically, and give a new exact OT G 2 stiff fluid spike solution. We then present a new two-parameter family of non-OT G 2 stiff fluid spike solutions, obtained by the generalization of non-OT G 2 vacuum spike solutions to the stiff fluid case by applying Geroch’s transformation on a Jacobs seed. The dynamics of these new stiff fluid spike solutions is qualitatively different from that of the vacuum spike solutions in that the matter (stiff fluid) feels the spike directly and the stiff fluid spike solution can end up with a permanent spike. We then derive the evolution equations of non-OT G 2 stiff fluid models, including a second perfect fluid, in full generality, and briefly discuss some of their qualitative properties and their potential numerical analysis. Finally, we discuss how a fluid, and especially a stiff fluid or massless scalar field, affects the physics of the generation of spikes. (paper)

  14. Predictive features of persistent activity emergence in regular spiking and intrinsic bursting model neurons.

    Directory of Open Access Journals (Sweden)

    Kyriaki Sidiropoulou

    Full Text Available Proper functioning of working memory involves the expression of stimulus-selective persistent activity in pyramidal neurons of the prefrontal cortex (PFC, which refers to neural activity that persists for seconds beyond the end of the stimulus. The mechanisms which PFC pyramidal neurons use to discriminate between preferred vs. neutral inputs at the cellular level are largely unknown. Moreover, the presence of pyramidal cell subtypes with different firing patterns, such as regular spiking and intrinsic bursting, raises the question as to what their distinct role might be in persistent firing in the PFC. Here, we use a compartmental modeling approach to search for discriminatory features in the properties of incoming stimuli to a PFC pyramidal neuron and/or its response that signal which of these stimuli will result in persistent activity emergence. Furthermore, we use our modeling approach to study cell-type specific differences in persistent activity properties, via implementing a regular spiking (RS and an intrinsic bursting (IB model neuron. We identify synaptic location within the basal dendrites as a feature of stimulus selectivity. Specifically, persistent activity-inducing stimuli consist of activated synapses that are located more distally from the soma compared to non-inducing stimuli, in both model cells. In addition, the action potential (AP latency and the first few inter-spike-intervals of the neuronal response can be used to reliably detect inducing vs. non-inducing inputs, suggesting a potential mechanism by which downstream neurons can rapidly decode the upcoming emergence of persistent activity. While the two model neurons did not differ in the coding features of persistent activity emergence, the properties of persistent activity, such as the firing pattern and the duration of temporally-restricted persistent activity were distinct. Collectively, our results pinpoint to specific features of the neuronal response to a given

  15. Introduction to spiking neural networks: Information processing, learning and applications.

    Science.gov (United States)

    Ponulak, Filip; Kasinski, Andrzej

    2011-01-01

    The concept that neural information is encoded in the firing rate of neurons has been the dominant paradigm in neurobiology for many years. This paradigm has also been adopted by the theory of artificial neural networks. Recent physiological experiments demonstrate, however, that in many parts of the nervous system, neural code is founded on the timing of individual action potentials. This finding has given rise to the emergence of a new class of neural models, called spiking neural networks. In this paper we summarize basic properties of spiking neurons and spiking networks. Our focus is, specifically, on models of spike-based information coding, synaptic plasticity and learning. We also survey real-life applications of spiking models. The paper is meant to be an introduction to spiking neural networks for scientists from various disciplines interested in spike-based neural processing.

  16. SpikeTemp: An Enhanced Rank-Order-Based Learning Approach for Spiking Neural Networks With Adaptive Structure.

    Science.gov (United States)

    Wang, Jinling; Belatreche, Ammar; Maguire, Liam P; McGinnity, Thomas Martin

    2017-01-01

    This paper presents an enhanced rank-order-based learning algorithm, called SpikeTemp, for spiking neural networks (SNNs) with a dynamically adaptive structure. The trained feed-forward SNN consists of two layers of spiking neurons: 1) an encoding layer which temporally encodes real-valued features into spatio-temporal spike patterns and 2) an output layer of dynamically grown neurons which perform spatio-temporal classification. Both Gaussian receptive fields and square cosine population encoding schemes are employed to encode real-valued features into spatio-temporal spike patterns. Unlike the rank-order-based learning approach, SpikeTemp uses the precise times of the incoming spikes for adjusting the synaptic weights such that early spikes result in a large weight change and late spikes lead to a smaller weight change. This removes the need to rank all the incoming spikes and, thus, reduces the computational cost of SpikeTemp. The proposed SpikeTemp algorithm is demonstrated on several benchmark data sets and on an image recognition task. The results show that SpikeTemp can achieve better classification performance and is much faster than the existing rank-order-based learning approach. In addition, the number of output neurons is much smaller when the square cosine encoding scheme is employed. Furthermore, SpikeTemp is benchmarked against a selection of existing machine learning algorithms, and the results demonstrate the ability of SpikeTemp to classify different data sets after just one presentation of the training samples with comparable classification performance.

  17. Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells

    Directory of Open Access Journals (Sweden)

    Giorgio Grasselli

    2016-03-01

    Full Text Available The plasticity of intrinsic excitability has been described in several types of neurons, but the significance of non-synaptic mechanisms in brain plasticity and learning remains elusive. Cerebellar Purkinje cells are inhibitory neurons that spontaneously fire action potentials at high frequencies and regulate activity in their target cells in the cerebellar nuclei by generating a characteristic spike burst-pause sequence upon synaptic activation. Using patch-clamp recordings from mouse Purkinje cells, we find that depolarization-triggered intrinsic plasticity enhances spike firing and shortens the duration of spike pauses. Pause plasticity is absent from mice lacking SK2-type potassium channels (SK2−/− mice and in occlusion experiments using the SK channel blocker apamin, while apamin wash-in mimics pause reduction. Our findings demonstrate that spike pauses can be regulated through an activity-dependent, exclusively non-synaptic, SK2 channel-dependent mechanism and suggest that pause plasticity—by altering the Purkinje cell output—may be crucial to cerebellar information storage and learning.

  18. Comparison of electrodialytic removal of Cu from spiked kaolinite, spiked soil and industrially polluted soil

    DEFF Research Database (Denmark)

    Ottosen, Lisbeth M.; Lepkova, Katarina; Kubal, Martin

    2006-01-01

    Electrokinetic remediation methods for removal of heavy metals from polluted soils have been subjected for quite intense research during the past years since these methods are well suitable for fine-grained soils where other remediation methods fail. Electrodialytic remediation is an electrokinetic...... remediation method which is based on applying an electric DC field and the use of ion exchange membranes that ensures the main transport of heavy metals to be out of the pollutes soil. An experimental investigation was made with electrodialytic removal of Cu from spiked kaolinite, spiked soil and industrially...... polluted soil under the same operational conditions (constant current density 0.2 mA/cm2 and duration 28 days). The results of the present paper show that caution must be taken when generalising results obtained in spiked kaolinite to remediation of industrially polluted soils, as it was shown...

  19. Synchronous spikes are necessary but not sufficient for a synchrony code in populations of spiking neurons.

    Science.gov (United States)

    Grewe, Jan; Kruscha, Alexandra; Lindner, Benjamin; Benda, Jan

    2017-03-07

    Synchronous activity in populations of neurons potentially encodes special stimulus features. Selective readout of either synchronous or asynchronous activity allows formation of two streams of information processing. Theoretical work predicts that such a synchrony code is a fundamental feature of populations of spiking neurons if they operate in specific noise and stimulus regimes. Here we experimentally test the theoretical predictions by quantifying and comparing neuronal response properties in tuberous and ampullary electroreceptor afferents of the weakly electric fish Apteronotus leptorhynchus These related systems show similar levels of synchronous activity, but only in the more irregularly firing tuberous afferents a synchrony code is established, whereas in the more regularly firing ampullary afferents it is not. The mere existence of synchronous activity is thus not sufficient for a synchrony code. Single-cell features such as the irregularity of spiking and the frequency dependence of the neuron's transfer function determine whether synchronous spikes possess a distinct meaning for the encoding of time-dependent signals.

  20. The Early Dendritic Cell Signaling Induced by Virulent Francisella tularensis Strain Occurs in Phases and Involves the Activation of Extracellular Signal-Regulated Kinases (ERKs) and p38 In the Later Stage

    Czech Academy of Sciences Publication Activity Database

    Fabrik, I.; Link, M.; Putzova, D.; Plzakova, L.; Lubovska, Zuzana; Philimonenko, Vlada; Pavkova, I.; Řehulka, P.; Krocová, Z.; Hozák, Pavel; Santic, M.; Stulík, J.

    2018-01-01

    Roč. 17, č. 1 (2018), s. 95-108 ISSN 1535-9476 R&D Projects: GA MŠk(CZ) LM2015062 Institutional support: RVO:68378050 Keywords : factor-alpha production * live vaccine strain * phosphorylation sites * negative regulator * innate immunity * lvs infection * pathway * identification * reveals * mapk Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 6.540, year: 2016

  1. The Complete Reconfiguration of Dendritic Gold

    Science.gov (United States)

    Paneru, Govind; Flanders, Bret

    2014-03-01

    Reconfigurability-by-design is an important strategy in modern materials science, as materials with this capability could potentially be used to confer hydrophobic, lipophobic, or anti-corrosive character to substrates in a regenerative manner. The present work extends the directed electrochemical nanowire assembly (DENA) methodology, which is a technique that employs alternating voltages to grow single crystalline metallic nanowires and nano-dendrites from simple salt solutions, to enable the complete dissolution of macroscopic arrays of metallic dendrites following their growth. Our main finding is that structural reconfiguration of dendritic gold is induced by changes in the MHz-level frequencies of voltages that are applied to the dendrites. Cyclic voltammetry and micro-Raman spectroscopy have been used to show that dendritic gold grows and dissolves by the same chemical mechanisms as bulk gold. Hence, the redox chemistry that occurs at the crystal-solution interface is no different than the established electrochemistry of gold. What differs in this process and allows for reconfiguration to occur is the diffusive behavior of the gold chloride molecules in the solution adjacent to the interface. We will present a simple model that captures the physics of this behavior.

  2. Solving constraint satisfaction problems with networks of spiking neurons

    Directory of Open Access Journals (Sweden)

    Zeno eJonke

    2016-03-01

    Full Text Available Network of neurons in the brain apply – unlike processors in our current generation ofcomputer hardware – an event-based processing strategy, where short pulses (spikes areemitted sparsely by neurons to signal the occurrence of an event at a particular point intime. Such spike-based computations promise to be substantially more power-efficient thantraditional clocked processing schemes. However it turned out to be surprisingly difficult todesign networks of spiking neurons that can solve difficult computational problems on the levelof single spikes (rather than rates of spikes. We present here a new method for designingnetworks of spiking neurons via an energy function. Furthermore we show how the energyfunction of a network of stochastically firing neurons can be shaped in a quite transparentmanner by composing the networks of simple stereotypical network motifs. We show that thisdesign approach enables networks of spiking neurons to produce approximate solutions todifficult (NP-hard constraint satisfaction problems from the domains of planning/optimizationand verification/logical inference. The resulting networks employ noise as a computationalresource. Nevertheless the timing of spikes (rather than just spike rates plays an essential rolein their computations. Furthermore, networks of spiking neurons carry out for the Traveling Salesman Problem a more efficient stochastic search for good solutions compared with stochastic artificial neural networks (Boltzmann machines and Gibbs sampling.

  3. Spike-based population coding and working memory.

    Directory of Open Access Journals (Sweden)

    Martin Boerlin

    2011-02-01

    Full Text Available Compelling behavioral evidence suggests that humans can make optimal decisions despite the uncertainty inherent in perceptual or motor tasks. A key question in neuroscience is how populations of spiking neurons can implement such probabilistic computations. In this article, we develop a comprehensive framework for optimal, spike-based sensory integration and working memory in a dynamic environment. We propose that probability distributions are inferred spike-per-spike in recurrently connected networks of integrate-and-fire neurons. As a result, these networks can combine sensory cues optimally, track the state of a time-varying stimulus and memorize accumulated evidence over periods much longer than the time constant of single neurons. Importantly, we propose that population responses and persistent working memory states represent entire probability distributions and not only single stimulus values. These memories are reflected by sustained, asynchronous patterns of activity which make relevant information available to downstream neurons within their short time window of integration. Model neurons act as predictive encoders, only firing spikes which account for new information that has not yet been signaled. Thus, spike times signal deterministically a prediction error, contrary to rate codes in which spike times are considered to be random samples of an underlying firing rate. As a consequence of this coding scheme, a multitude of spike patterns can reliably encode the same information. This results in weakly correlated, Poisson-like spike trains that are sensitive to initial conditions but robust to even high levels of external neural noise. This spike train variability reproduces the one observed in cortical sensory spike trains, but cannot be equated to noise. On the contrary, it is a consequence of optimal spike-based inference. In contrast, we show that rate-based models perform poorly when implemented with stochastically spiking neurons.

  4. Consensus-Based Sorting of Neuronal Spike Waveforms.

    Science.gov (United States)

    Fournier, Julien; Mueller, Christian M; Shein-Idelson, Mark; Hemberger, Mike; Laurent, Gilles

    2016-01-01

    Optimizing spike-sorting algorithms is difficult because sorted clusters can rarely be checked against independently obtained "ground truth" data. In most spike-sorting algorithms in use today, the optimality of a clustering solution is assessed relative to some assumption on the distribution of the spike shapes associated with a particular single unit (e.g., Gaussianity) and by visual inspection of the clustering solution followed by manual validation. When the spatiotemporal waveforms of spikes from different cells overlap, the decision as to whether two spikes should be assigned to the same source can be quite subjective, if it is not based on reliable quantitative measures. We propose a new approach, whereby spike clusters are identified from the most consensual partition across an ensemble of clustering solutions. Using the variability of the clustering solutions across successive iterations of the same clustering algorithm (template matching based on K-means clusters), we estimate the probability of spikes being clustered together and identify groups of spikes that are not statistically distinguishable from one another. Thus, we identify spikes that are most likely to be clustered together and therefore correspond to consistent spike clusters. This method has the potential advantage that it does not rely on any model of the spike shapes. It also provides estimates of the proportion of misclassified spikes for each of the identified clusters. We tested our algorithm on several datasets for which there exists a ground truth (simultaneous intracellular data), and show that it performs close to the optimum reached by a support vector machine trained on the ground truth. We also show that the estimated rate of misclassification matches the proportion of misclassified spikes measured from the ground truth data.

  5. Stress-driven lithium dendrite growth mechanism and dendrite mitigation by electroplating on soft substrates

    Science.gov (United States)

    Wang, Xu; Zeng, Wei; Hong, Liang; Xu, Wenwen; Yang, Haokai; Wang, Fan; Duan, Huigao; Tang, Ming; Jiang, Hanqing

    2018-03-01

    Problems related to dendrite growth on lithium-metal anodes such as capacity loss and short circuit present major barriers to next-generation high-energy-density batteries. The development of successful lithium dendrite mitigation strategies is impeded by an incomplete understanding of the Li dendrite growth mechanisms, and in particular, Li-plating-induced internal stress in Li metal and its effect on Li growth morphology are not well addressed. Here, we reveal the enabling role of plating residual stress in dendrite formation through depositing Li on soft substrates and a stress-driven dendrite growth model. We show that dendrite growth is mitigated on such soft substrates through surface-wrinkling-induced stress relaxation in the deposited Li film. We demonstrate that this dendrite mitigation mechanism can be utilized synergistically with other existing approaches in the form of three-dimensional soft scaffolds for Li plating, which achieves higher coulombic efficiency and better capacity retention than that for conventional copper substrates.

  6. Dendritic calcium channels and their activation by synaptic signals in auditory coincidence detector neurons.

    Science.gov (United States)

    Blackmer, Trillium; Kuo, Sidney P; Bender, Kevin J; Apostolides, Pierre F; Trussell, Laurence O

    2009-08-01

    The avian nucleus laminaris (NL) encodes the azimuthal location of low-frequency sound sources by detecting the coincidence of binaural signals. Accurate coincidence detection requires precise developmental regulation of the lengths of the fine, bitufted dendrites that characterize neurons in NL. Such regulation has been suggested to be driven by local, synaptically mediated, dendritic signals such as Ca(2+). We examined Ca(2+) signaling through patch clamp and ion imaging experiments in slices containing nucleus laminaris from embryonic chicks. Voltage-clamp recordings of neurons located in the NL showed the presence of large Ca(2+) currents of two types, a low voltage-activated, fast inactivating Ni(2+) sensitive channel resembling mammalian T-type channels, and a high voltage-activated, slowly inactivating Cd(2+) sensitive channel. Two-photon Ca(2+) imaging showed that both channel types were concentrated on dendrites, even at their distal tips. Single action potentials triggered synaptically or by somatic current injection immediately elevated Ca(2+) throughout the entire cell. Ca(2+) signals triggered by subthreshold synaptic activity were highly localized. Thus when electrical activity is suprathreshold, Ca(2+) channels ensure that Ca(2+) rises in all dendrites, even those that are synaptically inactive.

  7. Motor learning induces plastic changes in Purkinje cell dendritic spines in the rat cerebellum.

    Science.gov (United States)

    González-Tapia, D; González-Ramírez, M M; Vázquez-Hernández, N; González-Burgos, I

    2017-12-14

    The paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. Adult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method. The learning curve reflected a considerable decrease in the number of errors made by rats as the training period progressed. We observed more dendritic spines on days 2 and 6, particularly more thin spines on days 1, 3, and 6, fewer mushroom spines on day 3, fewer stubby spines on day 1, and more thick spines on days 4 and 6. The initial stage of motor learning may be associated with fast processing of the underlying synaptic information combined with an apparent "silencing" of memory consolidation processes, based on the regulation of the neuronal excitability. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Apparatus for growing a dendritic web

    International Nuclear Information System (INIS)

    Duncan, C.S.; Mchugh, J.P.; Piotrowski, P.A.; Skutch, M.E.

    1983-01-01

    A melt system including a susceptor-crucible assembly having improved gradient control when melt replenishment is used during dendritic web growth. The improvement lies in the formation of a thermal barrier in the base of the receptor which is in the form of a vertical slot in the region of the susceptor underlying the crucible at the location of a compartmental separator dividing the crucible into a growth compartment and a melt replenishment compartment. The result achieved is a step change in temperature gradient in the melt thereby providing a more uniform temperature in the growth compartment from which the dendritic web is drawn

  9. Dendrite tungsten liquation in molybdenum alloys

    International Nuclear Information System (INIS)

    Kantor, M.M.; Ageeva, E.N.; Kolotinskij, V.N.

    1992-01-01

    A study was made on primary crystallization structure of ingots of Mo-W-B system alloys with electron microscopy were used to establish, that cells and cellular dendrites were the main elements of primary crystallization structure. Method of local X-ray spectral analysis enabled to establish, that intracrystallite liquation at cellular growth developed more intensively, as compared to the case of cellular dendrite formation. Change of boron content in alloys didn't practically affect the degree of development of intracrystallite W liquation in Mo

  10. Transient potentials in dendritic systems of arbitrary geometry.

    Science.gov (United States)

    Butz, E G; Cowan, J D

    1974-09-01

    A simple graphical calculus is developed that generates analytic solutions for membrane potential transforms at any point on the dendritic tree of neurons with arbitrary dendritic geometries, in response to synaptic "current" inputs. Such solutions permit the computation of transients in neurons with arbitrary geometry and may facilitate analysis of the role of dendrites in such cells.

  11. Eliminating thermal violin spikes from LIGO noise

    Energy Technology Data Exchange (ETDEWEB)

    Santamore, D. H.; Levin, Yuri

    2001-08-15

    We have developed a scheme for reducing LIGO suspension thermal noise close to violin-mode resonances. The idea is to monitor directly the thermally induced motion of a small portion of (a 'point' on) each suspension fiber, thereby recording the random forces driving the test-mass motion close to each violin-mode frequency. One can then suppress the thermal noise by optimally subtracting the recorded fiber motions from the measured motion of the test mass, i.e., from the LIGO output. The proposed method is a modification of an analogous but more technically difficult scheme by Braginsky, Levin and Vyatchanin for reducing broad-band suspension thermal noise. The efficiency of our method is limited by the sensitivity of the sensor used to monitor the fiber motion. If the sensor has no intrinsic noise (i.e. has unlimited sensitivity), then our method allows, in principle, a complete removal of violin spikes from the thermal-noise spectrum. We find that in LIGO-II interferometers, in order to suppress violin spikes below the shot-noise level, the intrinsic noise of the sensor must be less than {approx}2 x 10{sup -13} cm/Hz. This sensitivity is two orders of magnitude greater than that of currently available sensors.

  12. Eliminating thermal violin spikes from LIGO noise

    International Nuclear Information System (INIS)

    Santamore, D. H.; Levin, Yuri

    2001-01-01

    We have developed a scheme for reducing LIGO suspension thermal noise close to violin-mode resonances. The idea is to monitor directly the thermally induced motion of a small portion of (a 'point' on) each suspension fiber, thereby recording the random forces driving the test-mass motion close to each violin-mode frequency. One can then suppress the thermal noise by optimally subtracting the recorded fiber motions from the measured motion of the test mass, i.e., from the LIGO output. The proposed method is a modification of an analogous but more technically difficult scheme by Braginsky, Levin and Vyatchanin for reducing broad-band suspension thermal noise. The efficiency of our method is limited by the sensitivity of the sensor used to monitor the fiber motion. If the sensor has no intrinsic noise (i.e. has unlimited sensitivity), then our method allows, in principle, a complete removal of violin spikes from the thermal-noise spectrum. We find that in LIGO-II interferometers, in order to suppress violin spikes below the shot-noise level, the intrinsic noise of the sensor must be less than ∼2 x 10 -13 cm/Hz. This sensitivity is two orders of magnitude greater than that of currently available sensors

  13. Phase Diagram of Spiking Neural Networks

    Directory of Open Access Journals (Sweden)

    Hamed eSeyed-Allaei

    2015-03-01

    Full Text Available In computer simulations of spiking neural networks, often it is assumed that every two neurons of the network are connected by a probablilty of 2%, 20% of neurons are inhibitory and 80% are excitatory. These common values are based on experiments, observations. but here, I take a different perspective, inspired by evolution. I simulate many networks, each with a different set of parameters, and then I try to figure out what makes the common values desirable by nature. Networks which are configured according to the common values, have the best dynamic range in response to an impulse and their dynamic range is more robust in respect to synaptic weights. In fact, evolution has favored networks of best dynamic range. I present a phase diagram that shows the dynamic ranges of different networks of different parameteres. This phase diagram gives an insight into the space of parameters -- excitatory to inhibitory ratio, sparseness of connections and synaptic weights. It may serve as a guideline to decide about the values of parameters in a simulation of spiking neural network.

  14. Communication through resonance in spiking neuronal networks.

    Science.gov (United States)

    Hahn, Gerald; Bujan, Alejandro F; Frégnac, Yves; Aertsen, Ad; Kumar, Arvind

    2014-08-01

    The cortex processes stimuli through a distributed network of specialized brain areas. This processing requires mechanisms that can route neuronal activity across weakly connected cortical regions. Routing models proposed thus far are either limited to propagation of spiking activity across strongly connected networks or require distinct mechanisms that create local oscillations and establish their coherence between distant cortical areas. Here, we propose a novel mechanism which explains how synchronous spiking activity propagates across weakly connected brain areas supported by oscillations. In our model, oscillatory activity unleashes network resonance that amplifies feeble synchronous signals and promotes their propagation along weak connections ("communication through resonance"). The emergence of coherent oscillations is a natural consequence of synchronous activity propagation and therefore the assumption of different mechanisms that create oscillations and provide coherence is not necessary. Moreover, the phase-locking of oscillations is a side effect of communication rather than its requirement. Finally, we show how the state of ongoing activity could affect the communication through resonance and propose that modulations of the ongoing activity state could influence information processing in distributed cortical networks.

  15. Spike Pattern Recognition for Automatic Collimation Alignment

    CERN Document Server

    Azzopardi, Gabriella; Salvachua Ferrando, Belen Maria; Mereghetti, Alessio; Redaelli, Stefano; CERN. Geneva. ATS Department

    2017-01-01

    The LHC makes use of a collimation system to protect its sensitive equipment by intercepting potentially dangerous beam halo particles. The appropriate collimator settings to protect the machine against beam losses relies on a very precise alignment of all the collimators with respect to the beam. The beam center at each collimator is then found by touching the beam halo using an alignment procedure. Until now, in order to determine whether a collimator is aligned with the beam or not, a user is required to follow the collimator’s BLM loss data and detect spikes. A machine learning (ML) model was trained in order to automatically recognize spikes when a collimator is aligned. The model was loosely integrated with the alignment implementation to determine the classification performance and reliability, without effecting the alignment process itself. The model was tested on a number of collimators during this MD and the machine learning was able to output the classifications in real-time.

  16. Dendritic slow dynamics enables localized cortical activity to switch between mobile and immobile modes with noisy background input.

    Directory of Open Access Journals (Sweden)

    Hiroki Kurashige

    Full Text Available Mounting lines of evidence suggest the significant computational ability of a single neuron empowered by active dendritic dynamics. This motivates us to study what functionality can be acquired by a network of such neurons. The present paper studies how such rich single-neuron dendritic dynamics affects the network dynamics, a question which has scarcely been specifically studied to date. We simulate neurons with active dendrites networked locally like cortical pyramidal neurons, and find that naturally arising localized activity--called a bump--can be in two distinct modes, mobile or immobile. The mode can be switched back and forth by transient input to the cortical network. Interestingly, this functionality arises only if each neuron is equipped with the observed slow dendritic dynamics and with in vivo-like noisy background input. If the bump activity is considered to indicate a point of attention in the sensory areas or to indicate a representation of memory in the storage areas of the cortex, this would imply that the flexible mode switching would be of great potential use for the brain as an information processing device. We derive these conclusions using a natural extension of the conventional field model, which is defined by combining two distinct fields, one representing the somatic population and the other representing the dendritic population. With this tool, we analyze the spatial distribution of the degree of after-spike adaptation and explain how we can understand the presence of the two distinct modes and switching between the modes. We also discuss the possible functional impact of this mode-switching ability.

  17. A spiking neuron circuit based on a carbon nanotube transistor

    International Nuclear Information System (INIS)

    Chen, C-L; Kim, K; Truong, Q; Shen, A; Li, Z; Chen, Y

    2012-01-01

    A spiking neuron circuit based on a carbon nanotube (CNT) transistor is presented in this paper. The spiking neuron circuit has a crossbar architecture in which the transistor gates are connected to its row electrodes and the transistor sources are connected to its column electrodes. An electrochemical cell is incorporated in the gate of the transistor by sandwiching a hydrogen-doped poly(ethylene glycol)methyl ether (PEG) electrolyte between the CNT channel and the top gate electrode. An input spike applied to the gate triggers a dynamic drift of the hydrogen ions in the PEG electrolyte, resulting in a post-synaptic current (PSC) through the CNT channel. Spikes input into the rows trigger PSCs through multiple CNT transistors, and PSCs cumulate in the columns and integrate into a ‘soma’ circuit to trigger output spikes based on an integrate-and-fire mechanism. The spiking neuron circuit can potentially emulate biological neuron networks and their intelligent functions. (paper)

  18. The local field potential reflects surplus spike synchrony

    DEFF Research Database (Denmark)

    Denker, Michael; Roux, Sébastien; Lindén, Henrik

    2011-01-01

    While oscillations of the local field potential (LFP) are commonly attributed to the synchronization of neuronal firing rate on the same time scale, their relationship to coincident spiking in the millisecond range is unknown. Here, we present experimental evidence to reconcile the notions...... of synchrony at the level of spiking and at the mesoscopic scale. We demonstrate that only in time intervals of significant spike synchrony that cannot be explained on the basis of firing rates, coincident spikes are better phase locked to the LFP than predicted by the locking of the individual spikes....... This effect is enhanced in periods of large LFP amplitudes. A quantitative model explains the LFP dynamics by the orchestrated spiking activity in neuronal groups that contribute the observed surplus synchrony. From the correlation analysis, we infer that neurons participate in different constellations...

  19. An Overview of Bayesian Methods for Neural Spike Train Analysis

    Directory of Open Access Journals (Sweden)

    Zhe Chen

    2013-01-01

    Full Text Available Neural spike train analysis is an important task in computational neuroscience which aims to understand neural mechanisms and gain insights into neural circuits. With the advancement of multielectrode recording and imaging technologies, it has become increasingly demanding to develop statistical tools for analyzing large neuronal ensemble spike activity. Here we present a tutorial overview of Bayesian methods and their representative applications in neural spike train analysis, at both single neuron and population levels. On the theoretical side, we focus on various approximate Bayesian inference techniques as applied to latent state and parameter estimation. On the application side, the topics include spike sorting, tuning curve estimation, neural encoding and decoding, deconvolution of spike trains from calcium imaging signals, and inference of neuronal functional connectivity and synchrony. Some research challenges and opportunities for neural spike train analysis are discussed.

  20. A new supervised learning algorithm for spiking neurons.

    Science.gov (United States)

    Xu, Yan; Zeng, Xiaoqin; Zhong, Shuiming

    2013-06-01

    The purpose of supervised learning with temporal encoding for spiking neurons is to make the neurons emit a specific spike train encoded by the precise firing times of spikes. If only running time is considered, the supervised learning for a spiking neuron is equivalent to distinguishing the times of desired output spikes and the other time during the running process of the neuron through adjusting synaptic weights, which can be regarded as a classification problem. Based on this idea, this letter proposes a new supervised learning method for spiking neurons with temporal encoding; it first transforms the supervised learning into a classification problem and then solves the problem by using the perceptron learning rule. The experiment results show that the proposed method has higher learning accuracy and efficiency over the existing learning methods, so it is more powerful for solving complex and real-time problems.

  1. Dendritic spine morphology and dynamics in health and disease

    Directory of Open Access Journals (Sweden)

    Lee S

    2015-06-01

    Full Text Available Stacey Lee,1 Huaye Zhang,2 Donna J Webb1,3,4 1Department of Biological Sciences, Vanderbilt University, Nashville, TN, 2Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, 3Department of Cancer Biology, 4Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA Abstract: Dendritic spines are actin-rich structures that form the postsynaptic terminals of excitatory synapses in the brain. The development and plasticity of spines are essential for cognitive processes, such as learning and memory, and defects in their density, morphology, and size underlie a number of neurological disorders. In this review, we discuss the contribution and regulation of the actin cytoskeleton in spine formation and plasticity as well as learning and memory. We also highlight the role of key receptors and intracellular signaling pathways in modulating the development and morphology of spines and cognitive function. Moreover, we provide insight into spine/synapse defects associated with several neurological disorders and the molecular mechanisms that underlie these spine defects. Keywords: dendritic spines, synapses, synaptic plasticity, actin cytoskeleton, glutamate receptors, neurological disorders

  2. Effects of Spike Anticipation on the Spiking Dynamics of Neural Networks.

    Science.gov (United States)

    de Santos-Sierra, Daniel; Sanchez-Jimenez, Abel; Garcia-Vellisca, Mariano A; Navas, Adrian; Villacorta-Atienza, Jose A

    2015-01-01

    Synchronization is one of the central phenomena involved in information processing in living systems. It is known that the nervous system requires the coordinated activity of both local and distant neural populations. Such an interplay allows to merge different information modalities in a whole processing supporting high-level mental skills as understanding, memory, abstraction, etc. Though, the biological processes underlying synchronization in the brain are not fully understood there have been reported a variety of mechanisms supporting different types of synchronization both at theoretical and experimental level. One of the more intriguing of these phenomena is the anticipating synchronization, which has been recently reported in a pair of unidirectionally coupled artificial neurons under simple conditions (Pyragiene and Pyragas, 2013), where the slave neuron is able to anticipate in time the behavior of the master one. In this paper, we explore the effect of spike anticipation over the information processing performed by a neural network at functional and structural level. We show that the introduction of intermediary neurons in the network enhances spike anticipation and analyse how these variations in spike anticipation can significantly change the firing regime of the neural network according to its functional and structural properties. In addition we show that the interspike interval (ISI), one of the main features of the neural response associated with the information coding, can be closely related to spike anticipation by each spike, and how synaptic plasticity can be modulated through that relationship. This study has been performed through numerical simulation of a coupled system of Hindmarsh-Rose neurons.

  3. Effects of Spike Anticipation on the Spiking Dynamics of Neural Networks

    Directory of Open Access Journals (Sweden)

    Daniel ede Santos-Sierra

    2015-11-01

    Full Text Available Synchronization is one of the central phenomena involved in information processing in living systems. It is known that the nervous system requires the coordinated activity of both local and distant neural populations. Such an interplay allows to merge different information modalities in a whole processing supporting high-level mental skills as understanding, memory, abstraction, etc. Though the biological processes underlying synchronization in the brain are not fully understood there have been reported a variety of mechanisms supporting different types of synchronization both at theoretical and experimental level. One of the more intriguing of these phenomena is the anticipating synchronization, which has been recently reported in a pair of unidirectionally coupled artificial neurons under simple conditions cite{Pyragas}, where the slave neuron is able to anticipate in time the behaviour of the master one. In this paper we explore the effect of spike anticipation over the information processing performed by a neural network at functional and structural level. We show that the introduction of intermediary neurons in the network enhances spike anticipation and analyse how these variations in spike anticipation can significantly change the firing regime of the neural network according to its functional and structural properties. In addition we show that the interspike interval (ISI, one of the main features of the neural response associated to the information coding, can be closely related to spike anticipation by each spike, and how synaptic plasticity can be modulated through that relationship. This study has been performed through numerical simulation of a coupled system of Hindmarsh-Rose neurons.

  4. Multimodal imaging of spike propagation: a technical case report.

    Science.gov (United States)

    Tanaka, N; Grant, P E; Suzuki, N; Madsen, J R; Bergin, A M; Hämäläinen, M S; Stufflebeam, S M

    2012-06-01

    We report an 11-year-old boy with intractable epilepsy, who had cortical dysplasia in the right superior frontal gyrus. Spatiotemporal source analysis of MEG and EEG spikes demonstrated a similar time course of spike propagation from the superior to inferior frontal gyri, as observed on intracranial EEG. The tractography reconstructed from DTI showed a fiber connection between these areas. Our multimodal approach demonstrates spike propagation and a white matter tract guiding the propagation.

  5. Molecular signatures of maturing dendritic cells: implications for testing the quality of dendritic cell therapies

    Directory of Open Access Journals (Sweden)

    Wang Ena

    2010-01-01

    Full Text Available Abstract Background Dendritic cells (DCs are often produced by granulocyte-macrophage colony-stimulating factor (GM-CSF and interleukin-4 (IL-4 stimulation of monocytes. To improve the effectiveness of DC adoptive immune cancer therapy, many different agents have been used to mature DCs. We analyzed the kinetics of DC maturation by lipopolysaccharide (LPS and interferon-γ (IFN-γ induction in order to characterize the usefulness of mature DCs (mDCs for immune therapy and to identify biomarkers for assessing the quality of mDCs. Methods Peripheral blood mononuclear cells were collected from 6 healthy subjects by apheresis, monocytes were isolated by elutriation, and immature DCs (iDCs were produced by 3 days of culture with GM-CSF and IL-4. The iDCs were sampled after 4, 8 and 24 hours in culture with LPS and IFN-γ and were then assessed by flow cytometry, ELISA, and global gene and microRNA (miRNA expression analysis. Results After 24 hours of LPS and IFN-γ stimulation, DC surface expression of CD80, CD83, CD86, and HLA Class II antigens were up-regulated. Th1 attractant genes such as CXCL9, CXCL10, CXCL11 and CCL5 were up-regulated during maturation but not Treg attractants such as CCL22 and CXCL12. The expression of classical mDC biomarker genes CD83, CCR7, CCL5, CCL8, SOD2, MT2A, OASL, GBP1 and HES4 were up-regulated throughout maturation while MTIB, MTIE, MTIG, MTIH, GADD45A and LAMP3 were only up-regulated late in maturation. The expression of miR-155 was up-regulated 8-fold in mDCs. Conclusion DCs, matured with LPS and IFN-γ, were characterized by increased levels of Th1 attractants as opposed to Treg attractants and may be particularly effective for adoptive immune cancer therapy.

  6. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  7. Generalized activity equations for spiking neural network dynamics

    Directory of Open Access Journals (Sweden)

    Michael A Buice

    2013-11-01

    Full Text Available Much progress has been made in uncovering the computational capabilities of spiking neural networks. However, spiking neurons will always be more expensive to simulate compared to rate neurons because of the inherent disparity in time scales - the spike duration time is much shorter than the inter-spike time, which is much shorter than any learning time scale. In numerical analysis, this is a classic stiff problem. Spiking neurons are also much more difficult to study analytically. One possible approach to making spiking networks more tractable is to augment mean field activity models with some information about spiking correlations. For example, such a generalized activity model could carry information about spiking rates and correlations between spikes self-consistently. Here, we will show how this can be accomplished by constructing a complete formal probabilistic description of the network and then expanding around a small parameter such as the inverse of the number of neurons in the network. The mean field theory of the system gives a rate-like description. The first order terms in the perturbation expansion keep track of covariances.

  8. In-reactor creep of zirconium alloys by thermal spikes

    International Nuclear Information System (INIS)

    Ibrahim, E.F.

    1975-01-01

    The size and duration of thermal spikes from fast neutrons have been calculated for zirconium alloys, showing that spikes up to 1.8 nm radius may exist for 2 x 10 -11 s at greater than melting point, at 570K ambient temperature. Creep rates have been calculated assuming that the elastic strain from the applied stress relaxes in the volume of the spikes (by preferential loop alignment or modification of an existing dislocation network). The calculated rates are consistent with strain rates observed in long term tests-in-reactor, if spike lifetimes are 2 to 2.5 x 10 -11 s. (Auth.)

  9. Solving Constraint Satisfaction Problems with Networks of Spiking Neurons.

    Science.gov (United States)

    Jonke, Zeno; Habenschuss, Stefan; Maass, Wolfgang

    2016-01-01

    Network of neurons in the brain apply-unlike processors in our current generation of computer hardware-an event-based processing strategy, where short pulses (spikes) are emitted sparsely by neurons to signal the occurrence of an event at a particular point in time. Such spike-based computations promise to be substantially more power-efficient than traditional clocked processing schemes. However, it turns out to be surprisingly difficult to design networks of spiking neurons that can solve difficult computational problems on the level of single spikes, rather than rates of spikes. We present here a new method for designing networks of spiking neurons via an energy function. Furthermore, we show how the energy function of a network of stochastically firing neurons can be shaped in a transparent manner by composing the networks of simple stereotypical network motifs. We show that this design approach enables networks of spiking neurons to produce approximate solutions to difficult (NP-hard) constraint satisfaction problems from the domains of planning/optimization and verification/logical inference. The resulting networks employ noise as a computational resource. Nevertheless, the timing of spikes plays an essential role in their computations. Furthermore, networks of spiking neurons carry out for the Traveling Salesman Problem a more efficient stochastic search for good solutions compared with stochastic artificial neural networks (Boltzmann machines) and Gibbs sampling.

  10. Surfing a spike wave down the ventral stream.

    Science.gov (United States)

    VanRullen, Rufin; Thorpe, Simon J

    2002-10-01

    Numerous theories of neural processing, often motivated by experimental observations, have explored the computational properties of neural codes based on the absolute or relative timing of spikes in spike trains. Spiking neuron models and theories however, as well as their experimental counterparts, have generally been limited to the simulation or observation of isolated neurons, isolated spike trains, or reduced neural populations. Such theories would therefore seem inappropriate to capture the properties of a neural code relying on temporal spike patterns distributed across large neuronal populations. Here we report a range of computer simulations and theoretical considerations that were designed to explore the possibilities of one such code and its relevance for visual processing. In a unified framework where the relation between stimulus saliency and spike relative timing plays the central role, we describe how the ventral stream of the visual system could process natural input scenes and extract meaningful information, both rapidly and reliably. The first wave of spikes generated in the retina in response to a visual stimulation carries information explicitly in its spatio-temporal structure: the most salient information is represented by the first spikes over the population. This spike wave, propagating through a hierarchy of visual areas, is regenerated at each processing stage, where its temporal structure can be modified by (i). the selectivity of the cortical neurons, (ii). lateral interactions and (iii). top-down attentional influences from higher order cortical areas. The resulting model could account for the remarkable efficiency and rapidity of processing observed in the primate visual system.

  11. A theory of loop formation and elimination by spike timing-dependent plasticity

    Directory of Open Access Journals (Sweden)

    James Kozloski

    2010-03-01

    Full Text Available We show that the local Spike Timing-Dependent Plasticity (STDP rule has the effect of regulating the trans-synaptic weights of loops of any length within a simulated network of neurons. We show that depending on STDP's polarity, functional loops are formed or eliminated in networks driven to normal spiking conditions by random, partially correlated inputs, where functional loops comprise synaptic weights that exceed a non-zero threshold. We further prove that STDP is a form of loop-regulating plasticity for the case of a linear network driven by noise. Thus a notable local synaptic learning rule makes a specific prediction about synapses in the brain in which standard STDP is present: that under normal spiking conditions, they should participate in predominantly feed-forward connections at all scales. Our model implies that any deviations from this prediction would require a substantial modification to the hypothesized role for standard STDP. Given its widespread occurrence in the brain, we predict that STDP could also regulate long range functional loops among individual neurons across all brain scales, up to, and including, the scale of global brain network topology.

  12. AMORE Mo-99 Spike Test Results

    Energy Technology Data Exchange (ETDEWEB)

    Youker, Amanda J. [Argonne National Lab. (ANL), Argonne, IL (United States); Krebs, John F. [Argonne National Lab. (ANL), Argonne, IL (United States); Quigley, Kevin J. [Argonne National Lab. (ANL), Argonne, IL (United States); Byrnes, James P. [Argonne National Lab. (ANL), Argonne, IL (United States); Rotsch, David A [Argonne National Lab. (ANL), Argonne, IL (United States); Brossard, Thomas [Argonne National Lab. (ANL), Argonne, IL (United States); Wesolowski, Kenneth [Argonne National Lab. (ANL), Argonne, IL (United States); Alford, Kurt [Argonne National Lab. (ANL), Argonne, IL (United States); Chemerisov, Sergey [Argonne National Lab. (ANL), Argonne, IL (United States); Vandegrift, George F. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2017-09-27

    With funding from the National Nuclear Security Administrations Material Management and Minimization Office, Argonne National Laboratory (Argonne) is providing technical assistance to help accelerate the U.S. production of Mo-99 using a non-highly enriched uranium (non-HEU) source. A potential Mo-99 production pathway is by accelerator-initiated fissioning in a subcritical uranyl sulfate solution containing low enriched uranium (LEU). As part of the Argonne development effort, we are undertaking the AMORE (Argonne Molybdenum Research Experiment) project, which is essentially a pilot facility for all phases of Mo-99 production, recovery, and purification. Production of Mo-99 and other fission products in the subcritical target solution is initiated by putting an electron beam on a depleted uranium (DU) target; the fast neutrons produced in the DU target are thermalized and lead to fissioning of U-235. At the end of irradiation, Mo is recovered from the target solution and separated from uranium and most of the fission products by using a titania column. The Mo is stripped from the column with an alkaline solution. After acidification of the Mo product solution from the recovery column, the Mo is concentrated (and further purified) in a second titania column. The strip solution from the concentration column is then purified with the LEU Modified Cintichem process. A full description of the process can be found elsewhere [1–3]. The initial commissioning steps for the AMORE project include performing a Mo-99 spike test with pH 1 sulfuric acid in the target vessel without a beam on the target to demonstrate the initial Mo separation-and-recovery process, followed by the concentration column process. All glovebox operations were tested with cold solutions prior to performing the Mo-99 spike tests. Two Mo-99 spike tests with pH 1 sulfuric acid have been performed to date. Figure 1 shows the flow diagram for the remotely operated Mo-recovery system for the AMORE project

  13. The actin-binding protein capulet genetically interacts with the microtubule motor kinesin to maintain neuronal dendrite homeostasis.

    Directory of Open Access Journals (Sweden)

    Paul M B Medina

    Full Text Available BACKGROUND: Neurons require precise cytoskeletal regulation within neurites, containing microtubule tracks for cargo transport in axons and dendrites or within synapses containing organized actin. Due to the unique architecture and specialized function of neurons, neurons are particularly susceptible to perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain proper cytoskeletal regulation. METHODOLOGY/PRINCIPAL FINDINGS: From a Drosophila forward genetic screen, we identified a mutation in capulet--encoding a conserved actin-binding protein--that causes abnormal aggregates of actin within dendrites. Through interaction studies, we demonstrate that simultaneous genetic inactivation of capulet and kinesin heavy chain, a microtubule motor protein, produces elongate cofilin-actin rods within dendrites but not axons. These rods resemble actin-rich structures induced in both mammalian neurodegenerative and Drosophila Alzheimer's models, but have not previously been identified by loss of function mutations in vivo. We further demonstrate that mitochondria, which are transported by Kinesin, have impaired distribution along dendrites in a capulet mutant. While Capulet and Cofilin may biochemically cooperate in certain circumstances, in neuronal dendrites they genetically antagonize each other. CONCLUSIONS/SIGNIFICANCE: The present study is the first molecularly defined loss of function demonstration of actin-cofilin rods in vivo. This study suggests that simultaneous, seemingly minor perturbations in neuronal dendrites can synergize producing severe abnormalities affecting actin, microtubules and mitochondria/energy availability in dendrites. Additionally, as >90% of Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by which multiple mutations together may contribute to neurodegeneration instead of reliance on single mutations to produce disease.

  14. Peptides and proteins in dendritic assemblies

    NARCIS (Netherlands)

    Baal, van I.

    2007-01-01

    Multiple, simultaneous interactions are often used in biology to enhance the affinity and specificity of binding, an effect referred to as multivalency. This multivalency can be mimicked by anchoring multiple peptides and proteins onto synthetic dendritic scaffolds. The aim of this research was to

  15. Targeting nanoparticles to dendritic cells for immunotherapy.

    NARCIS (Netherlands)

    Cruz, L.J.; Tacken, P.J.; Rueda, F.; Domingo, J.C.; Albericio, F.; Figdor, C.G.

    2012-01-01

    Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy for treatment of cancer and infectious diseases. Development of targeted nanodelivery systems carrying vaccine components, including antigens and adjuvants, to DCs in

  16. Antigen dynamics of follicular dendritic cells

    NARCIS (Netherlands)

    Heesters, B.A.

    2015-01-01

    Stromal-derived follicular dendritic cells (FDCs) are a major depot for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate and high-affinity antibody production takes place. Historically, FDCs have been characterized as ‘accessory’

  17. Dendritic cells: biology of the skin

    NARCIS (Netherlands)

    Toebak, M.J.; Gibbs, S.; Bruynzeel, D.P.; Scheper, R.J.; Rustemeyer, T.

    2009-01-01

    Allergic contact dermatitis results from a T-cell-mediated, delayed-type hypersensitivity immune response induced by allergens. Skin dendritic cells (DCs) play a central role in the initiation of allergic skin responses. Following encounter with an allergen, DCs become activated and undergo

  18. Thermosolutal convection and macrosegregation in dendritic alloys

    Science.gov (United States)

    Poirier, David R.; Heinrich, J. C.

    1993-01-01

    A mathematical model of solidification, that simulates the formation of channel segregates or freckles, is presented. The model simulates the entire solidification process, starting with the initial melt to the solidified cast, and the resulting segregation is predicted. Emphasis is given to the initial transient, when the dendritic zone begins to develop and the conditions for the possible nucleation of channels are established. The mechanisms that lead to the creation and eventual growth or termination of channels are explained in detail and illustrated by several numerical examples. A finite element model is used for the simulations. It uses a single system of equations to deal with the all-liquid region, the dendritic region, and the all-solid region. The dendritic region is treated as an anisotropic porous medium. The algorithm uses the bilinear isoparametric element, with a penalty function approximation and a Petrov-Galerkin formulation. The major task was to develop the solidification model. In addition, other tasks that were performed in conjunction with the modeling of dendritic solidification are briefly described.

  19. Dendritic cells in peripheral tolerance and immunity

    DEFF Research Database (Denmark)

    Gad, Monika; Claesson, Mogens Helweg; Pedersen, Anders Elm

    2003-01-01

    Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular...

  20. Dendritic cells modified by vitamin D

    DEFF Research Database (Denmark)

    Pedersen, Ayako Wakatsuki; Claesson, Mogens Helweg; Zocca, Mai-Britt

    2011-01-01

    Dendritic cells (DCs), the most potent antigen-presenting cells of the immune system, express nuclear receptors for 1,25-dihydroxyvitamin D(3) (VD3) and they are one of its main targets. In the presence of VD3, DCs differentiate into a phenotype that resembles semimature DCs, with reduced T cell ...

  1. Randomly oriented twin domains in electrodeposited silver dendrites

    Directory of Open Access Journals (Sweden)

    Ivanović Evica R.

    2015-01-01

    Full Text Available Silver dendrites were prepared by electrochemical deposition. The structures of Ag dendrites, the type of twins and their distribution were investigated by scanning electron microscopy (SEM, Z-contrast high angle annular dark field transmission electron microscopy (HAADF, and crystallografically sensitive orientation imaging microscopy (OIM. The results revealed that silver dendrites are characterized by the presence of randomly distributed 180° rotational twin domains. The broad surface of dendrites was of the {111} type. Growth directions of the main dendrite stem and all branches were of type. [Projekat Ministarstva nauke Republike Srbije, br. 172054

  2. Self-control with spiking and non-spiking neural networks playing games.

    Science.gov (United States)

    Christodoulou, Chris; Banfield, Gaye; Cleanthous, Aristodemos

    2010-01-01

    Self-control can be defined as choosing a large delayed reward over a small immediate reward, while precommitment is the making of a choice with the specific aim of denying oneself future choices. Humans recognise that they have self-control problems and attempt to overcome them by applying precommitment. Problems in exercising self-control, suggest a conflict between cognition and motivation, which has been linked to competition between higher and lower brain functions (representing the frontal lobes and the limbic system respectively). This premise of an internal process conflict, lead to a behavioural model being proposed, based on which, we implemented a computational model for studying and explaining self-control through precommitment behaviour. Our model consists of two neural networks, initially non-spiking and then spiking ones, representing the higher and lower brain systems viewed as cooperating for the benefit of the organism. The non-spiking neural networks are of simple feed forward multilayer type with reinforcement learning, one with selective bootstrap weight update rule, which is seen as myopic, representing the lower brain and the other with the temporal difference weight update rule, which is seen as far-sighted, representing the higher brain. The spiking neural networks are implemented with leaky integrate-and-fire neurons with learning based on stochastic synaptic transmission. The differentiating element between the two brain centres in this implementation is based on the memory of past actions determined by an eligibility trace time constant. As the structure of the self-control problem can be likened to the Iterated Prisoner's Dilemma (IPD) game in that cooperation is to defection what self-control is to impulsiveness or what compromising is to insisting, we implemented the neural networks as two players, learning simultaneously but independently, competing in the IPD game. With a technique resembling the precommitment effect, whereby the

  3. [Wide QRS tachycardia preceded by pacemaker spikes].

    Science.gov (United States)

    Romero, M; Aranda, A; Gómez, F J; Jurado, A

    2014-04-01

    The differential diagnosis and therapeutic management of wide QRS tachycardia preceded by pacemaker spike is presented. The pacemaker-mediated tachycardia, tachycardia fibrillo-flutter in patients with pacemakers, and runaway pacemakers, have a similar surface electrocardiogram, but respond to different therapeutic measures. The tachycardia response to the application of a magnet over the pacemaker could help in the differential diagnosis, and in some cases will be therapeutic, as in the case of a tachycardia-mediated pacemaker. Although these conditions are diagnosed and treated in hospitals with catheterization laboratories using the application programmer over the pacemaker, patients presenting in primary care clinic and emergency forced us to make a diagnosis and treat the haemodynamically unstable patient prior to referral. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  4. A propane price spike nails users

    International Nuclear Information System (INIS)

    Milke, M.

    1997-01-01

    The increase in price for propane was discussed. In 1993, propane cost about 5 cents per litre; by December 1996, the price has risen to 27 cents wholesale, while retail prices for auto propane reached 40 cents per litre. As a result, farmers and fleet operators are considering switching to an alternative energy supply. The five factors which may have played a role in the propane price spike were described. These included a cold winter which lowered inventories, a Pemex gas plant in Mexico which had been damaged by fire, forcing Mexico to import natural gas and natural gas liquids from the USA, the failure of propane distributors to restock during the summer months in the hope of lower prices, and increased cost of competing fuels in the face of increased demand. It was noted that these factors are transitory, which could mean better prices this summer

  5. Spike sorting for polytrodes: a divide and conquer approach

    Directory of Open Access Journals (Sweden)

    Nicholas V. Swindale

    2014-02-01

    Full Text Available In order to determine patterns of neural activity, spike signals recorded by extracellular electrodes have to be clustered (sorted with the aim of ensuring that each cluster represents all the spikes generated by an individual neuron. Many methods for spike sorting have been proposed but few are easily applicable to recordings from polytrodes which may have 16 or more recording sites. As with tetrodes, these are spaced sufficiently closely that signals from single neurons will usually be recorded on several adjacent sites. Although this offers a better chance of distinguishing neurons with similarly shaped spikes, sorting is difficult in such cases because of the high dimensionality of the space in which the signals must be classified. This report details a method for spike sorting based on a divide and conquer approach. Clusters are initially formed by assigning each event to the channel on which it is largest. Each channel-based cluster is then sub-divided into as many distinct clusters as possible. These are then recombined on the basis of pairwise tests into a final set of clusters. Pairwise tests are also performed to establish how distinct each cluster is from the others. A modified gradient ascent clustering (GAC algorithm is used to do the clustering. The method can sort spikes with minimal user input in times comparable to real time for recordings lasting up to 45 minutes. Our results illustrate some of the difficulties inherent in spike sorting, including changes in spike shape over time. We show that some physiologically distinct units may have very similar spike shapes. We show that RMS measures of spike shape similarity are not sensitive enough to discriminate clusters that can otherwise be separated by principal components analysis. Hence spike sorting based on least-squares matching to templates may be unreliable. Our methods should be applicable to tetrodes and scaleable to larger multi-electrode arrays (MEAs.

  6. Neuronal spike sorting based on radial basis function neural networks

    Directory of Open Access Journals (Sweden)

    Taghavi Kani M

    2011-02-01

    Full Text Available "nBackground: Studying the behavior of a society of neurons, extracting the communication mechanisms of brain with other tissues, finding treatment for some nervous system diseases and designing neuroprosthetic devices, require an algorithm to sort neuralspikes automatically. However, sorting neural spikes is a challenging task because of the low signal to noise ratio (SNR of the spikes. The main purpose of this study was to design an automatic algorithm for classifying neuronal spikes that are emitted from a specific region of the nervous system."n "nMethods: The spike sorting process usually consists of three stages: detection, feature extraction and sorting. We initially used signal statistics to detect neural spikes. Then, we chose a limited number of typical spikes as features and finally used them to train a radial basis function (RBF neural network to sort the spikes. In most spike sorting devices, these signals are not linearly discriminative. In order to solve this problem, the aforesaid RBF neural network was used."n "nResults: After the learning process, our proposed algorithm classified any arbitrary spike. The obtained results showed that even though the proposed Radial Basis Spike Sorter (RBSS reached to the same error as the previous methods, however, the computational costs were much lower compared to other algorithms. Moreover, the competitive points of the proposed algorithm were its good speed and low computational complexity."n "nConclusion: Regarding the results of this study, the proposed algorithm seems to serve the purpose of procedures that require real-time processing and spike sorting.

  7. Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.

    Directory of Open Access Journals (Sweden)

    Fabrice Ango

    2008-04-01

    Full Text Available The geometric and subcellular organization of axon arbors distributes and regulates electrical signaling in neurons and networks, but the underlying mechanisms have remained elusive. In rodent cerebellar cortex, stellate interneurons elaborate characteristic axon arbors that selectively innervate Purkinje cell dendrites and likely regulate dendritic integration. We used GFP BAC transgenic reporter mice to examine the cellular processes and molecular mechanisms underlying the development of stellate cell axons and their innervation pattern. We show that stellate axons are organized and guided towards Purkinje cell dendrites by an intermediate scaffold of Bergmann glial (BG fibers. The L1 family immunoglobulin protein Close Homologue of L1 (CHL1 is localized to apical BG fibers and stellate cells during the development of stellate axon arbors. In the absence of CHL1, stellate axons deviate from BG fibers and show aberrant branching and orientation. Furthermore, synapse formation between aberrant stellate axons and Purkinje dendrites is reduced and cannot be maintained, leading to progressive atrophy of axon terminals. These results establish BG fibers as a guiding scaffold and CHL1 a molecular signal in the organization of stellate axon arbors and in directing their dendritic innervation.

  8. Clustering predicts memory performance in networks of spiking and non-spiking neurons

    Directory of Open Access Journals (Sweden)

    Weiliang eChen

    2011-03-01

    Full Text Available The problem we address in this paper is that of finding effective and parsimonious patterns of connectivity in sparse associative memories. This problem must be addressed in real neuronal systems, so that results in artificial systems could throw light on real systems. We show that there are efficient patterns of connectivity and that these patterns are effective in models with either spiking or non-spiking neurons. This suggests that there may be some underlying general principles governing good connectivity in such networks. We also show that the clustering of the network, measured by Clustering Coefficient, has a strong linear correlation to the performance of associative memory. This result is important since a purely static measure of network connectivity appears to determine an important dynamic property of the network.

  9. An essential role for neuregulin-4 in the growth and elaboration of developing neocortical pyramidal dendrites.

    Science.gov (United States)

    Paramo, Blanca; Wyatt, Sean; Davies, Alun M

    2018-04-01

    Neuregulins, with the exception of neuregulin-4 (NRG4), have been shown to be extensively involved in many aspects of neural development and function and are implicated in several neurological disorders, including schizophrenia, depression and bipolar disorder. Here we provide the first evidence that NRG4 has a crucial function in the developing brain. We show that both the apical and basal dendrites of neocortical pyramidal neurons are markedly stunted in Nrg4 -/- neonates in vivo compared with Nrg4 +/+ littermates. Neocortical pyramidal neurons cultured from Nrg4 -/- embryos had significantly shorter and less branched neurites than those cultured from Nrg4 +/+ littermates. Recombinant NRG4 rescued the stunted phenotype of embryonic neocortical pyramidal neurons cultured from Nrg4 -/- mice. The majority of cultured wild type embryonic cortical pyramidal neurons co-expressed NRG4 and its receptor ErbB4. The difference between neocortical pyramidal dendrites of Nrg4 -/- and Nrg4 +/+ mice was less pronounced, though still significant, in juvenile mice. However, by adult stages, the pyramidal dendrite arbors of Nrg4 -/- and Nrg4 +/+ mice were similar, suggesting that compensatory changes in Nrg4 -/- mice occur with age. Our findings show that NRG4 is a major novel regulator of dendritic arborisation in the developing cerebral cortex and suggest that it exerts its effects by an autocrine/paracrine mechanism. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Living in the branches: population dynamics and ecological processes in dendritic networks

    Science.gov (United States)

    Grant, E.H.C.; Lowe, W.H.; Fagan, W.F.

    2007-01-01

    Spatial structure regulates and modifies processes at several levels of ecological organization (e.g. individual/genetic, population and community) and is thus a key component of complex systems, where knowledge at a small scale can be insufficient for understanding system behaviour at a larger scale. Recent syntheses outline potential applications of network theory to ecological systems, but do not address the implications of physical structure for network dynamics. There is a specific need to examine how dendritic habitat structure, such as that found in stream, hedgerow and cave networks, influences ecological processes. Although dendritic networks are one type of ecological network, they are distinguished by two fundamental characteristics: (1) both the branches and the nodes serve as habitat, and (2) the specific spatial arrangement and hierarchical organization of these elements interacts with a species' movement behaviour to alter patterns of population distribution and abundance, and community interactions. Here, we summarize existing theory relating to ecological dynamics in dendritic networks, review empirical studies examining the population- and community-level consequences of these networks, and suggest future research integrating spatial pattern and processes in dendritic systems.

  11. Pyramidal cell development: postnatal spinogenesis, dendritic growth, axon growth, and electrophysiology.

    Directory of Open Access Journals (Sweden)

    Guy eElston

    2014-08-01

    Full Text Available Here we review recent findings related to postnatal spinogenesis, dendritic and axon growth, pruning and electrophysiology of neocortical pyramidal cells in the developing primate brain. Pyramidal cells in sensory, association and executive cortex grow dendrites, spines and axons at different rates, and vary in the degree of pruning. Of particular note is the fact that pyramidal cells in primary visual area (V1 prune more spines than they grow during postnatal development, whereas those in inferotemporal (TEO and TE and granular prefrontal cortex (gPFC; Brodmann’s area 12 grow more than they prune. Moreover, pyramidal cells in TEO, TE and the gPFC continue to grow larger dendritic territories from birth into adulthood, replete with spines, whereas those in V1 become smaller during this time. The developmental profile of intrinsic axons also varies between cortical areas: those in V1, for example, undergo an early proliferation followed by pruning and local consolidation into adulthood, whereas those in area TE tend to establish their territory and consolidate it into adulthood with little pruning. We correlate the anatomical findings with the electrophysiological properties of cells in the different cortical areas, including membrane time constant, depolarizing sag, duration of individual action potentials, and spike-frequency adaptation. All of the electrophysiological variables ramped up before 7 months of age in V1, but continued to ramp up over a protracted period of time in area TE. These data suggest that the anatomical and electrophysiological profiles of pyramidal cells vary among cortical areas at birth, and continue to diverge into adulthood. Moreover, the data reveal that the use it or lose it notion of synaptic reinforcement may speak to only part of the story, use it but you still might lose it may be just as prevalent in the cerebral cortex.

  12. Inorganic arsenic impairs differentiation and functions of human dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Macoch, Mélinda; Morzadec, Claudie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

    2013-01-15

    Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

  13. Inorganic arsenic impairs differentiation and functions of human dendritic cells

    International Nuclear Information System (INIS)

    Macoch, Mélinda; Morzadec, Claudie; Fardel, Olivier; Vernhet, Laurent

    2013-01-01

    Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

  14. Spikes and memory in (Nord Pool) electricity price spot prices

    DEFF Research Database (Denmark)

    Proietti, Tomasso; Haldrup, Niels; Knapik, Oskar

    Electricity spot prices are subject to transitory sharp movements commonly referred to as spikes. The paper aims at assessing their effects on model based inferences and predictions, with reference to the Nord Pool power exchange. We identify a spike as a price value which deviates substantially...

  15. The Nature of Power Spikes: a regime-switch approach

    NARCIS (Netherlands)

    C.M. de Jong (Cyriel)

    2005-01-01

    textabstractDue to its non-storable nature, electricity is a commodity with probably the most volatile spot prices, exemplified by occasional spikes. Appropriate pricing, portfolio, and risk management models have to incorporate these characteristics, and the spikes in particular. We investigate the

  16. No WIMP mini-spikes in dwarf spheroidal galaxies

    NARCIS (Netherlands)

    Wanders, M.; Bertone, G.; Volonteri, M.; Weniger, C.

    2015-01-01

    The formation of black holes inevitably affects the distribution of dark and baryonic matter in their vicinity, leading to an enhancement of the dark matter density, called spike, and if dark matter is made of WIMPs, to a strong enhancement of the dark matter annihilation rate. Spikes at the center

  17. Spiking and bursting patterns of fractional-order Izhikevich model

    Science.gov (United States)

    Teka, Wondimu W.; Upadhyay, Ranjit Kumar; Mondal, Argha

    2018-03-01

    Bursting and spiking oscillations play major roles in processing and transmitting information in the brain through cortical neurons that respond differently to the same signal. These oscillations display complex dynamics that might be produced by using neuronal models and varying many model parameters. Recent studies have shown that models with fractional order can produce several types of history-dependent neuronal activities without the adjustment of several parameters. We studied the fractional-order Izhikevich model and analyzed different kinds of oscillations that emerge from the fractional dynamics. The model produces a wide range of neuronal spike responses, including regular spiking, fast spiking, intrinsic bursting, mixed mode oscillations, regular bursting and chattering, by adjusting only the fractional order. Both the active and silent phase of the burst increase when the fractional-order model further deviates from the classical model. For smaller fractional order, the model produces memory dependent spiking activity after the pulse signal turned off. This special spiking activity and other properties of the fractional-order model are caused by the memory trace that emerges from the fractional-order dynamics and integrates all the past activities of the neuron. On the network level, the response of the neuronal network shifts from random to scale-free spiking. Our results suggest that the complex dynamics of spiking and bursting can be the result of the long-term dependence and interaction of intracellular and extracellular ionic currents.

  18. Spectral components of cytosolic [Ca2+] spiking in neurons

    DEFF Research Database (Denmark)

    Kardos, J; Szilágyi, N; Juhász, G

    1998-01-01

    . Delayed complex responses of large [Ca2+]c spiking observed in cells from a different set of cultures were synthesized by a set of frequencies within the range 0.018-0.117 Hz. Differential frequency patterns are suggested as characteristics of the [Ca2+]c spiking responses of neurons under different...

  19. Accelerated spike resampling for accurate multiple testing controls.

    Science.gov (United States)

    Harrison, Matthew T

    2013-02-01

    Controlling for multiple hypothesis tests using standard spike resampling techniques often requires prohibitive amounts of computation. Importance sampling techniques can be used to accelerate the computation. The general theory is presented, along with specific examples for testing differences across conditions using permutation tests and for testing pairwise synchrony and precise lagged-correlation between many simultaneously recorded spike trains using interval jitter.

  20. Causal Inference and Explaining Away in a Spiking Network

    Science.gov (United States)

    Moreno-Bote, Rubén; Drugowitsch, Jan

    2015-01-01

    While the brain uses spiking neurons for communication, theoretical research on brain computations has mostly focused on non-spiking networks. The nature of spike-based algorithms that achieve complex computations, such as object probabilistic inference, is largely unknown. Here we demonstrate that a family of high-dimensional quadratic optimization problems with non-negativity constraints can be solved exactly and efficiently by a network of spiking neurons. The network naturally imposes the non-negativity of causal contributions that is fundamental to causal inference, and uses simple operations, such as linear synapses with realistic time constants, and neural spike generation and reset non-linearities. The network infers the set of most likely causes from an observation using explaining away, which is dynamically implemented by spike-based, tuned inhibition. The algorithm performs remarkably well even when the network intrinsically generates variable spike trains, the timing of spikes is scrambled by external sources of noise, or the network is mistuned. This type of network might underlie tasks such as odor identification and classification. PMID:26621426

  1. Cytoplasmic tail of coronavirus spike protein has intracellular

    Indian Academy of Sciences (India)

    https://www.ias.ac.in/article/fulltext/jbsc/042/02/0231-0244. Keywords. Coronavirus spike protein trafficking; cytoplasmic tail signal; endoplasmic reticulum–Golgi intermediate complex; lysosome. Abstract. Intracellular trafficking and localization studies of spike protein from SARS and OC43 showed that SARS spikeprotein is ...

  2. Prospective clinical testing of regulatory dendritic cells (DCreg) in organ transplantation

    OpenAIRE

    ANGUS W THOMSON; ALAN F ZAHORCHAK; Mohamed B. Ezzelarab; Lisa H. Butterfield; Fadi G. Lakkis; Diana M Metes

    2016-01-01

    Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering...

  3. Effector and regulatory dendritic cells display distinct patterns of miRNA expression

    OpenAIRE

    Lombardi, Vincent; Luce, Sonia; Moussu, H?l?ne; Morizur, Lise; Gueguen, Claire; Neukirch, Catherine; Chollet?Martin, Sylvie; Mascarell, Laurent; Aubier, Michel; Baron?Bodo, V?ronique; Moingeon, Philippe

    2017-01-01

    Abstract Introduction MicroRNAs (miRNAs) contribute to the regulation of dendritic cell (DC) polarization, thereby influencing the balance of adaptive immune responses. Herein, we studied the expression of miRNAs in polarized DCs and analyzed whether expression of these miRNAs could be associated with allergic rhinitis and allergen immunotherapy (AIT) outcome. Method Using specific culture conditions, we differentiated immature human monocyte?derived DCs into DC1, DC2, and DCreg subsets (supp...

  4. Pressurized water reactor iodine spiking behavior under power transient conditions

    International Nuclear Information System (INIS)

    Ho, J.C.

    1992-01-01

    The most accepted theory explaining the cause of pressurized water reactor iodine spiking is steam formation and condensation in damaged fuel rods. The phase transformation of the primary coolant from water to steam and back again is believed to cause the iodine spiking phenomenon. But due to the complex nature of the phenomenon, a comprehensive model of the behavior has not yet been successfully developed. This paper presents a new model based on an empirical approach, which gives a first-order estimation of the peak iodine spiking magnitude. Based on the proposed iodine spiking model, it is apparent that it is feasible to derive a correlation using the plant operating data base to monitor and control the peak iodine spiking magnitude

  5. Recent progress in multi-electrode spike sorting methods.

    Science.gov (United States)

    Lefebvre, Baptiste; Yger, Pierre; Marre, Olivier

    2016-11-01

    In recent years, arrays of extracellular electrodes have been developed and manufactured to record simultaneously from hundreds of electrodes packed with a high density. These recordings should allow neuroscientists to reconstruct the individual activity of the neurons spiking in the vicinity of these electrodes, with the help of signal processing algorithms. Algorithms need to solve a source separation problem, also known as spike sorting. However, these new devices challenge the classical way to do spike sorting. Here we review different methods that have been developed to sort spikes from these large-scale recordings. We describe the common properties of these algorithms, as well as their main differences. Finally, we outline the issues that remain to be solved by future spike sorting algorithms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Unsupervised spike sorting based on discriminative subspace learning.

    Science.gov (United States)

    Keshtkaran, Mohammad Reza; Yang, Zhi

    2014-01-01

    Spike sorting is a fundamental preprocessing step for many neuroscience studies which rely on the analysis of spike trains. In this paper, we present two unsupervised spike sorting algorithms based on discriminative subspace learning. The first algorithm simultaneously learns the discriminative feature subspace and performs clustering. It uses histogram of features in the most discriminative projection to detect the number of neurons. The second algorithm performs hierarchical divisive clustering that learns a discriminative 1-dimensional subspace for clustering in each level of the hierarchy until achieving almost unimodal distribution in the subspace. The algorithms are tested on synthetic and in-vivo data, and are compared against two widely used spike sorting methods. The comparative results demonstrate that our spike sorting methods can achieve substantially higher accuracy in lower dimensional feature space, and they are highly robust to noise. Moreover, they provide significantly better cluster separability in the learned subspace than in the subspace obtained by principal component analysis or wavelet transform.

  7. A supervised learning rule for classification of spatiotemporal spike patterns.

    Science.gov (United States)

    Lilin Guo; Zhenzhong Wang; Adjouadi, Malek

    2016-08-01

    This study introduces a novel supervised algorithm for spiking neurons that take into consideration synapse delays and axonal delays associated with weights. It can be utilized for both classification and association and uses several biologically influenced properties, such as axonal and synaptic delays. This algorithm also takes into consideration spike-timing-dependent plasticity as in Remote Supervised Method (ReSuMe). This paper focuses on the classification aspect alone. Spiked neurons trained according to this proposed learning rule are capable of classifying different categories by the associated sequences of precisely timed spikes. Simulation results have shown that the proposed learning method greatly improves classification accuracy when compared to the Spike Pattern Association Neuron (SPAN) and the Tempotron learning rule.

  8. GM-CSF Controls Nonlymphoid Tissue Dendritic Cell Homeostasis but Is Dispensable for the Differentiation of Inflammatory Dendritic Cells

    Science.gov (United States)

    Greter, Melanie; Helft, Julie; Chow, Andrew; Hashimoto, Daigo; Mortha, Arthur; Agudo-Cantero, Judith; Bogunovic, Milena; Gautier, Emmanuel L.; Miller, Jennifer; Leboeuf, Marylene; Lu, Geming; Aloman, Costica; Brown, Brian D.; Pollard, Jeffrey W.; Xiong, Huabao; Randolph, Gwendalyn J.; Chipuk, Jerry E.; Frenette, Paul S.; Merad, Miriam

    2012-01-01

    SUMMARY GM-CSF (Csf-2) is a critical cytokine for the in vitro generation of dendritic cells (DCs) and is thought to control the development of inflammatory DCs and resident CD103+ DCs in some tissues. Here we showed that in contrast to the current understanding, Csf-2 receptor acts in the steady state to promote the survival and homeostasis of nonlymphoid tissue-resident CD103+ and CD11b+ DCs. Absence of Csf-2 receptor on lung DCs abrogated the induction of CD8+ T cell immunity after immunization with particulate antigens. In contrast, Csf-2 receptor was dispensable for the differentiation and innate function of inflammatory DCs during acute injuries. Instead, inflammatory DCs required Csf-1 receptor for their development. Thus, Csf-2 is important in vaccine-induced CD8+ T cell immunity through the regulation of nonlymphoid tissue DC homeostasis rather than control of inflammatory DCs in vivo. PMID:22749353

  9. Feline coronavirus: Insights into viral pathogenesis based on the spike protein structure and function.

    Science.gov (United States)

    Jaimes, Javier A; Whittaker, Gary R

    2018-04-01

    Feline coronavirus (FCoV) is an etiological agent that causes a benign enteric illness and the fatal systemic disease feline infectious peritonitis (FIP). The FCoV spike (S) protein is considered the viral regulator for binding and entry to the cell. This protein is also involved in FCoV tropism and virulence, as well as in the switch from enteric disease to FIP. This regulation is carried out by spike's major functions: receptor binding and virus-cell membrane fusion. In this review, we address important aspects in FCoV genetics, replication and pathogenesis, focusing on the role of S. To better understand this, FCoV S protein models were constructed, based on the human coronavirus NL63 (HCoV-NL63) S structure. We describe the specific structural characteristics of the FCoV S, in comparison with other coronavirus spikes. We also revise the biochemical events needed for FCoV S activation and its relation to the structural features of the protein. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Theta frequency background tunes transmission but not summation of spiking responses.

    Directory of Open Access Journals (Sweden)

    Dhanya Parameshwaran

    Full Text Available Hippocampal neurons are known to fire as a function of frequency and phase of spontaneous network rhythms, associated with the animal's behaviour. This dependence is believed to give rise to precise rate and temporal codes. However, it is not well understood how these periodic membrane potential fluctuations affect the integration of synaptic inputs. Here we used sinusoidal current injection to the soma of CA1 pyramidal neurons in the rat brain slice to simulate background oscillations in the physiologically relevant theta and gamma frequency range. We used a detailed compartmental model to show that somatic current injection gave comparable results to more physiological synaptically driven theta rhythms incorporating excitatory input in the dendrites, and inhibitory input near the soma. We systematically varied the phase of synaptic inputs with respect to this background, and recorded changes in response and summation properties of CA1 neurons using whole-cell patch recordings. The response of the cell was dependent on both the phase of synaptic inputs and frequency of the background input. The probability of the cell spiking for a given synaptic input was up to 40% greater during the depolarized phases between 30-135 degrees of theta frequency current injection. Summation gain on the other hand, was not affected either by the background frequency or the phasic afferent inputs. This flat summation gain, coupled with the enhanced spiking probability during depolarized phases of the theta cycle, resulted in enhanced transmission of summed inputs during the same phase window of 30-135 degrees. Overall, our study suggests that although oscillations provide windows of opportunity to selectively boost transmission and EPSP size, summation of synaptic inputs remains unaffected during membrane oscillations.

  11. Dendritic cell-associated immune inflammation of cardiac mucosa: a possible factor in the formation of Barrett's esophagus.

    Science.gov (United States)

    Bobryshev, Yuri V; Tran, Dinh; Killingsworth, Murray C; Buckland, Michael; Lord, Reginald V N

    2009-03-01

    The development of Barrett's esophagus is poorly understood, but it has been suggested that cardiac mucosa is a precursor of intestinal type metaplasia and that inflammation of cardiac mucosa may play a role in the formation of Barrett's esophagus. The present study was undertaken to examine the presence and distribution of immune-inflammatory cells in cardiac mucosa, specifically focusing on dendritic cells because of their importance as regulators of immune reactions. Endoscopic biopsy specimens were obtained from 12 patients with cardiac mucosa without Barrett's esophagus or adenocarcinoma and from 21 patients with Barrett's esophagus without dysplasia (intestinal metaplasia). According to histology, in nine of the 21 specimens with Barrett's esophagus, areas of mucosa composed of cardiac type epithelium-lined glands were present as well. Immunohistochemical staining and electron microscopy were used to examine immune-inflammatory cells in paraffin-embedded sections. Immune-inflammatory cells, including T cells, B cells, dendritic cells, macrophages, and mast cells, were present in the connective tissue matrix that surrounded cardiac type epithelium-lined glands in all patients with cardiac mucosa. Clustering of dendritic cells with each other and with lymphocytes and the intrusion of dendritic cells between glandular mucus cells were observed. In the Barrett's esophagus specimens that contained cardiac type glands, computerized CD83 expression quantitation revealed that there were more dendritic cells in cardiac mucosa than in intestinal metaplasia. Immune-inflammatory infiltrates containing dendritic cells are consistently present in cardiac mucosa. The finding of a larger number of dendritic cells in areas of cardiac mucosa in Barrett's esophagus biopsies suggests that the immune inflammation of cardiac mucosa might play a role in modifying the local tissue environment to promote the development of specialized intestinal type metaplasia.

  12. The Proprotein Convertase KPC-1/Furin Controls Branching and Self-avoidance of Sensory Dendrites in Caenorhabditis elegans

    Science.gov (United States)

    Bülow, Hannes E.

    2014-01-01

    Animals sample their environment through sensory neurons with often elaborately branched endings named dendritic arbors. In a genetic screen for genes involved in the development of the highly arborized somatosensory PVD neuron in C. elegans, we have identified mutations in kpc-1, which encodes the homolog of the proprotein convertase furin. We show that kpc-1/furin is necessary to promote the formation of higher order dendritic branches in PVD and to ensure self-avoidance of sister branches, but is likely not required during maintenance of dendritic arbors. A reporter for kpc-1/furin is expressed in neurons (including PVD) and kpc-1/furin can function cell-autonomously in PVD neurons to control patterning of dendritic arbors. Moreover, we show that kpc-1/furin also regulates the development of other neurons in all major neuronal classes in C. elegans, including aspects of branching and extension of neurites as well as cell positioning. Our data suggest that these developmental functions require proteolytic activity of KPC-1/furin. Recently, the skin-derived MNR-1/menorin and the neural cell adhesion molecule SAX-7/L1CAM have been shown to act as a tripartite complex with the leucine rich transmembrane receptor DMA-1 on PVD mechanosensory to orchestrate the patterning of dendritic branches. Genetic analyses show that kpc-1/furin functions in a pathway with MNR-1/menorin, SAX-7/L1CAM and DMA-1 to control dendritic branch formation and extension of PVD neurons. We propose that KPC-1/furin acts in concert with the ‘menorin’ pathway to control branching and growth of somatosensory dendrites in PVD. PMID:25232734

  13. Noisy Spiking in Visual Area V2 of Amblyopic Monkeys.

    Science.gov (United States)

    Wang, Ye; Zhang, Bin; Tao, Xiaofeng; Wensveen, Janice M; Smith, Earl L; Chino, Yuzo M

    2017-01-25

    Interocular decorrelation of input signals in developing visual cortex can cause impaired binocular vision and amblyopia. Although increased intrinsic noise is thought to be responsible for a range of perceptual deficits in amblyopic humans, the neural basis for the elevated perceptual noise in amblyopic primates is not known. Here, we tested the idea that perceptual noise is linked to the neuronal spiking noise (variability) resulting from developmental alterations in cortical circuitry. To assess spiking noise, we analyzed the contrast-dependent dynamics of spike counts and spiking irregularity by calculating the square of the coefficient of variation in interspike intervals (CV 2 ) and the trial-to-trial fluctuations in spiking, or mean matched Fano factor (m-FF) in visual area V2 of monkeys reared with chronic monocular defocus. In amblyopic neurons, the contrast versus response functions and the spike count dynamics exhibited significant deviations from comparable data for normal monkeys. The CV 2 was pronounced in amblyopic neurons for high-contrast stimuli and the m-FF was abnormally high in amblyopic neurons for low-contrast gratings. The spike count, CV 2 , and m-FF of spontaneous activity were also elevated in amblyopic neurons. These contrast-dependent spiking irregularities were correlated with the level of binocular suppression in these V2 neurons and with the severity of perceptual loss for individual monkeys. Our results suggest that the developmental alterations in normalization mechanisms resulting from early binocular suppression can explain much of these contrast-dependent spiking abnormalities in V2 neurons and the perceptual performance of our amblyopic monkeys. Amblyopia is a common developmental vision disorder in humans. Despite the extensive animal studies on how amblyopia emerges, we know surprisingly little about the neural basis of amblyopia in humans and nonhuman primates. Although the vision of amblyopic humans is often described as

  14. Evaluating Local Primary Dendrite Arm Spacing Characterization Techniques Using Synthetic Directionally Solidified Dendritic Microstructures

    Science.gov (United States)

    Tschopp, Mark A.; Miller, Jonathan D.; Oppedal, Andrew L.; Solanki, Kiran N.

    2015-10-01

    Microstructure characterization continues to play an important bridge to understanding why particular processing routes or parameters affect the properties of materials. This statement certainly holds true in the case of directionally solidified dendritic microstructures, where characterizing the primary dendrite arm spacing is vital to developing the process-structure-property relationships that can lead to the design and optimization of processing routes for defined properties. In this work, four series of simulations were used to examine the capability of a few Voronoi-based techniques to capture local microstructure statistics (primary dendrite arm spacing and coordination number) in controlled (synthetically generated) microstructures. These simulations used both cubic and hexagonal microstructures with varying degrees of disorder (noise) to study the effects of length scale, base microstructure, microstructure variability, and technique parameters on the local PDAS distribution, local coordination number distribution, bulk PDAS, and bulk coordination number. The Voronoi tesselation technique with a polygon-side-length criterion correctly characterized the known synthetic microstructures. By systematically studying the different techniques for quantifying local primary dendrite arm spacings, we have evaluated their capability to capture this important microstructure feature in different dendritic microstructures, which can be an important step for experimentally correlating with both processing and properties in single crystal nickel-based superalloys.

  15. Sensitivity of Dendritic Cells to Microenvironment Signals

    Directory of Open Access Journals (Sweden)

    Juliana Maria Motta

    2016-01-01

    Full Text Available Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies.

  16. Spiking irregularity and frequency modulate the behavioral report of single-neuron stimulation.

    Science.gov (United States)

    Doron, Guy; von Heimendahl, Moritz; Schlattmann, Peter; Houweling, Arthur R; Brecht, Michael

    2014-02-05

    The action potential activity of single cortical neurons can evoke measurable sensory effects, but it is not known how spiking parameters and neuronal subtypes affect the evoked sensations. Here, we examined the effects of spike train irregularity, spike frequency, and spike number on the detectability of single-neuron stimulation in rat somatosensory cortex. For regular-spiking, putative excitatory neurons, detectability increased with spike train irregularity and decreasing spike frequencies but was not affected by spike number. Stimulation of single, fast-spiking, putative inhibitory neurons led to a larger sensory effect compared to regular-spiking neurons, and the effect size depended only on spike irregularity. An ideal-observer analysis suggests that, under our experimental conditions, rats were using integration windows of a few hundred milliseconds or more. Our data imply that the behaving animal is sensitive to single neurons' spikes and even to their temporal patterning. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Asynchronous Rate Chaos in Spiking Neuronal Circuits.

    Directory of Open Access Journals (Sweden)

    Omri Harish

    2015-07-01

    Full Text Available The brain exhibits temporally complex patterns of activity with features similar to those of chaotic systems. Theoretical studies over the last twenty years have described various computational advantages for such regimes in neuronal systems. Nevertheless, it still remains unclear whether chaos requires specific cellular properties or network architectures, or whether it is a generic property of neuronal circuits. We investigate the dynamics of networks of excitatory-inhibitory (EI spiking neurons with random sparse connectivity operating in the regime of balance of excitation and inhibition. Combining Dynamical Mean-Field Theory with numerical simulations, we show that chaotic, asynchronous firing rate fluctuations emerge generically for sufficiently strong synapses. Two different mechanisms can lead to these chaotic fluctuations. One mechanism relies on slow I-I inhibition which gives rise to slow subthreshold voltage and rate fluctuations. The decorrelation time of these fluctuations is proportional to the time constant of the inhibition. The second mechanism relies on the recurrent E-I-E feedback loop. It requires slow excitation but the inhibition can be fast. In the corresponding dynamical regime all neurons exhibit rate fluctuations on the time scale of the excitation. Another feature of this regime is that the population-averaged firing rate is substantially smaller in the excitatory population than in the inhibitory population. This is not necessarily the case in the I-I mechanism. Finally, we discuss the neurophysiological and computational significance of our results.

  18. Memory recall and spike-frequency adaptation

    Science.gov (United States)

    Roach, James P.; Sander, Leonard M.; Zochowski, Michal R.

    2016-05-01

    The brain can reproduce memories from partial data; this ability is critical for memory recall. The process of memory recall has been studied using autoassociative networks such as the Hopfield model. This kind of model reliably converges to stored patterns that contain the memory. However, it is unclear how the behavior is controlled by the brain so that after convergence to one configuration, it can proceed with recognition of another one. In the Hopfield model, this happens only through unrealistic changes of an effective global temperature that destabilizes all stored configurations. Here we show that spike-frequency adaptation (SFA), a common mechanism affecting neuron activation in the brain, can provide state-dependent control of pattern retrieval. We demonstrate this in a Hopfield network modified to include SFA, and also in a model network of biophysical neurons. In both cases, SFA allows for selective stabilization of attractors with different basins of attraction, and also for temporal dynamics of attractor switching that is not possible in standard autoassociative schemes. The dynamics of our models give a plausible account of different sorts of memory retrieval.

  19. Phase diagram of spiking neural networks.

    Science.gov (United States)

    Seyed-Allaei, Hamed

    2015-01-01

    In computer simulations of spiking neural networks, often it is assumed that every two neurons of the network are connected by a probability of 2%, 20% of neurons are inhibitory and 80% are excitatory. These common values are based on experiments, observations, and trials and errors, but here, I take a different perspective, inspired by evolution, I systematically simulate many networks, each with a different set of parameters, and then I try to figure out what makes the common values desirable. I stimulate networks with pulses and then measure their: dynamic range, dominant frequency of population activities, total duration of activities, maximum rate of population and the occurrence time of maximum rate. The results are organized in phase diagram. This phase diagram gives an insight into the space of parameters - excitatory to inhibitory ratio, sparseness of connections and synaptic weights. This phase diagram can be used to decide the parameters of a model. The phase diagrams show that networks which are configured according to the common values, have a good dynamic range in response to an impulse and their dynamic range is robust in respect to synaptic weights, and for some synaptic weights they oscillates in α or β frequencies, independent of external stimuli.

  20. Asynchronous Rate Chaos in Spiking Neuronal Circuits

    Science.gov (United States)

    Harish, Omri; Hansel, David

    2015-01-01

    The brain exhibits temporally complex patterns of activity with features similar to those of chaotic systems. Theoretical studies over the last twenty years have described various computational advantages for such regimes in neuronal systems. Nevertheless, it still remains unclear whether chaos requires specific cellular properties or network architectures, or whether it is a generic property of neuronal circuits. We investigate the dynamics of networks of excitatory-inhibitory (EI) spiking neurons with random sparse connectivity operating in the regime of balance of excitation and inhibition. Combining Dynamical Mean-Field Theory with numerical simulations, we show that chaotic, asynchronous firing rate fluctuations emerge generically for sufficiently strong synapses. Two different mechanisms can lead to these chaotic fluctuations. One mechanism relies on slow I-I inhibition which gives rise to slow subthreshold voltage and rate fluctuations. The decorrelation time of these fluctuations is proportional to the time constant of the inhibition. The second mechanism relies on the recurrent E-I-E feedback loop. It requires slow excitation but the inhibition can be fast. In the corresponding dynamical regime all neurons exhibit rate fluctuations on the time scale of the excitation. Another feature of this regime is that the population-averaged firing rate is substantially smaller in the excitatory population than in the inhibitory population. This is not necessarily the case in the I-I mechanism. Finally, we discuss the neurophysiological and computational significance of our results. PMID:26230679

  1. The Isothermal Dendritic Growth Experiment Archive

    Science.gov (United States)

    Koss, Matthew

    2009-03-01

    The growth of dendrites is governed by the interplay between two simple and familiar processes---the irreversible diffusion of energy, and the reversible work done in the formation of new surface area. To advance our understanding of these processes, NASA sponsored a project that flew on the Space Shuttle Columbia is 1994, 1996, and 1997 to record and analyze benchmark data in an apparent-microgravity ``laboratory.'' In this laboratory, energy transfer by gravity driven convection was essentially eliminated and one could test independently, for the first time, both components of dendritic growth theory. The analysis of this data shows that although the diffusion of energy can be properly accounted for, the results from interfacial physics appear to be in disagreement and alternate models should receive increased attention. Unfortunately, currently and for the foreseeable future, there is no access or financial support to develop and conduct additional experiments of this type. However, the benchmark data of 35mm photonegatives, video, and all supporting instrument data are now available at the IDGE Archive at the College of the Holy Cross. This data may still have considerable relevance to researchers working specifically with dendritic growth, and more generally those working in the synthesis, growth & processing of materials, multiscale computational modeling, pattern formation, and systems far from equilibrium.

  2. BDNF pro-peptide regulates dendritic spines via caspase-3

    OpenAIRE

    Guo, J; Ji, Y; Ding, Y; Jiang, W; Sun, Y; Lu, B; Nagappan, G

    2016-01-01

    The precursor of brain-derived neurotrophic factor (BDNF) (proBDNF) is enzymatically cleaved, by either intracellular (furin/PC1) or extracellular proteases (tPA/plasmin/MMP), to generate mature BDNF (mBDNF) and its pro-peptide (BDNF pro-peptide). Little is known about the function of BDNF pro-peptide. We have developed an antibody that specifically detects cleaved BDNF pro-peptide, but not proBDNF or mBDNF. Neuronal depolarization elicited a marked increase in extracellular BDNF pro-peptide,...

  3. Bursts generate a non-reducible spike-pattern code

    Directory of Open Access Journals (Sweden)

    Hugo G Eyherabide

    2009-05-01

    Full Text Available On the single-neuron level, precisely timed spikes can either constitute firing-rate codes or spike-pattern codes that utilize the relative timing between consecutive spikes. There has been little experimental support for the hypothesis that such temporal patterns contribute substantially to information transmission. Using grasshopper auditory receptors as a model system, we show that correlations between spikes can be used to represent behaviorally relevant stimuli. The correlations reflect the inner structure of the spike train: a succession of burst-like patterns. We demonstrate that bursts with different spike counts encode different stimulus features, such that about 20% of the transmitted information corresponds to discriminating between different features, and the remaining 80% is used to allocate these features in time. In this spike-pattern code, the "what" and the "when" of the stimuli are encoded in the duration of each burst and the time of burst onset, respectively. Given the ubiquity of burst firing, we expect similar findings also for other neural systems.

  4. A Simple Deep Learning Method for Neuronal Spike Sorting

    Science.gov (United States)

    Yang, Kai; Wu, Haifeng; Zeng, Yu

    2017-10-01

    Spike sorting is one of key technique to understand brain activity. With the development of modern electrophysiology technology, some recent multi-electrode technologies have been able to record the activity of thousands of neuronal spikes simultaneously. The spike sorting in this case will increase the computational complexity of conventional sorting algorithms. In this paper, we will focus spike sorting on how to reduce the complexity, and introduce a deep learning algorithm, principal component analysis network (PCANet) to spike sorting. The introduced method starts from a conventional model and establish a Toeplitz matrix. Through the column vectors in the matrix, we trains a PCANet, where some eigenvalue vectors of spikes could be extracted. Finally, support vector machine (SVM) is used to sort spikes. In experiments, we choose two groups of simulated data from public databases availably and compare this introduced method with conventional methods. The results indicate that the introduced method indeed has lower complexity with the same sorting errors as the conventional methods.

  5. Automated spike preparation system for Isotope Dilution Mass Spectrometry (IDMS)

    International Nuclear Information System (INIS)

    Maxwell, S.L. III; Clark, J.P.

    1990-01-01

    Isotope Dilution Mass Spectrometry (IDMS) is a method frequently employed to measure dissolved, irradiated nuclear materials. A known quantity of a unique isotope of the element to be measured (referred to as the ''spike'') is added to the solution containing the analyte. The resulting solution is chemically purified then analyzed by mass spectrometry. By measuring the magnitude of the response for each isotope and the response for the ''unique spike'' then relating this to the known quantity of the ''spike'', the quantity of the nuclear material can be determined. An automated spike preparation system was developed at the Savannah River Site (SRS) to dispense spikes for use in IDMS analytical methods. Prior to this development, technicians weighed each individual spike manually to achieve the accuracy required. This procedure was time-consuming and subjected the master stock solution to evaporation. The new system employs a high precision SMI Model 300 Unipump dispenser interfaced with an electronic balance and a portable Epson HX-20 notebook computer to automate spike preparation

  6. Predictive coding of dynamical variables in balanced spiking networks.

    Science.gov (United States)

    Boerlin, Martin; Machens, Christian K; Denève, Sophie

    2013-01-01

    Two observations about the cortex have puzzled neuroscientists for a long time. First, neural responses are highly variable. Second, the level of excitation and inhibition received by each neuron is tightly balanced at all times. Here, we demonstrate that both properties are necessary consequences of neural networks that represent information efficiently in their spikes. We illustrate this insight with spiking networks that represent dynamical variables. Our approach is based on two assumptions: We assume that information about dynamical variables can be read out linearly from neural spike trains, and we assume that neurons only fire a spike if that improves the representation of the dynamical variables. Based on these assumptions, we derive a network of leaky integrate-and-fire neurons that is able to implement arbitrary linear dynamical systems. We show that the membrane voltage of the neurons is equivalent to a prediction error about a common population-level signal. Among other things, our approach allows us to construct an integrator network of spiking neurons that is robust against many perturbations. Most importantly, neural variability in our networks cannot be equated to noise. Despite exhibiting the same single unit properties as widely used population code models (e.g. tuning curves, Poisson distributed spike trains), balanced networks are orders of magnitudes more reliable. Our approach suggests that spikes do matter when considering how the brain computes, and that the reliability of cortical representations could have been strongly underestimated.

  7. A method for decoding the neurophysiological spike-response transform.

    Science.gov (United States)

    Stern, Estee; García-Crescioni, Keyla; Miller, Mark W; Peskin, Charles S; Brezina, Vladimir

    2009-11-15

    Many physiological responses elicited by neuronal spikes-intracellular calcium transients, synaptic potentials, muscle contractions-are built up of discrete, elementary responses to each spike. However, the spikes occur in trains of arbitrary temporal complexity, and each elementary response not only sums with previous ones, but can itself be modified by the previous history of the activity. A basic goal in system identification is to characterize the spike-response transform in terms of a small number of functions-the elementary response kernel and additional kernels or functions that describe the dependence on previous history-that will predict the response to any arbitrary spike train. Here we do this by developing further and generalizing the "synaptic decoding" approach of Sen et al. (1996). Given the spike times in a train and the observed overall response, we use least-squares minimization to construct the best estimated response and at the same time best estimates of the elementary response kernel and the other functions that characterize the spike-response transform. We avoid the need for any specific initial assumptions about these functions by using techniques of mathematical analysis and linear algebra that allow us to solve simultaneously for all of the numerical function values treated as independent parameters. The functions are such that they may be interpreted mechanistically. We examine the performance of the method as applied to synthetic data. We then use the method to decode real synaptic and muscle contraction transforms.

  8. Geomagnetic spikes on the core-mantle boundary

    Science.gov (United States)

    Davies, C. J.; Constable, C.

    2017-12-01

    Extreme variations of Earth's magnetic field occurred in the Levantine region around 1000 BC, where the field intensity rose and fell by a factor of 2-3 over a short time and confined spatial region. There is presently no coherent link between this intensity spike and the generating processes in Earth's liquid core. Here we test the attribution of a surface spike to a flux patch visible on the core-mantle boundary (CMB), calculating geometric and energetic bounds on resulting surface geomagnetic features. We show that the Levantine intensity high must span at least 60 degrees in longitude. Models providing the best trade-off between matching surface spike intensity, minimizing L1 and L2 misfit to the available data and satisfying core energy constraints produce CMB spikes 8-22 degrees wide with peak values of O(100) mT. We propose that the Levantine spike grew in place before migrating northward and westward, contributing to the growth of the axial dipole field seen in Holocene field models. Estimates of Ohmic dissipation suggest that diffusive processes, which are often neglected, likely govern the ultimate decay of geomagnetic spikes. Using these results, we search for the presence of spike-like features in geodynamo simulations.

  9. Ginseng Berry Extract Promotes Maturation of Mouse Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Ginseng extract has been shown to possess certain anti-virus, anti-tumor and immune-activating effects. However, the immunostimulatory effect of ginseng berry extract (GB has been less well characterized. In this study, we investigated the effect of GB on the activation of mouse dendritic cells (DCs in vitro and in vivo. GB treatment induced up-regulation of co-stimulatory molecules in bone marrow-derived DCs (BMDCs. Interestingly, GB induced a higher degree of co-stimulatory molecule up-regulation than ginseng root extract (GR at the same concentrations. Moreover, in vivo administration of GB promoted up-regulation of CD86, MHC class I and MHC class II and production of IL-6, IL-12 and TNF-α in spleen DCs. GB also promoted the generation of Th1 and Tc1 cells. Furthermore, Toll like receptor 4 (TLR4 and myeloid differentiation primary response 88 (MyD88 signaling pathway were essential for DC activation induced by GB. In addition, GB strongly prompted the proliferation of ovalbumin (OVA-specific CD4 and CD8 T cells. Finally, GB induced DC activation in tumor-bearing mice and the combination of OVA and GB treatment inhibited B16-OVA tumor cell growth in C57BL/6 mice. These results demonstrate that GB is a novel tumor therapeutic vaccine adjuvant by promoting DC and T cell activation.

  10. Chemokines: a new dendritic cell signal for T cell activation

    Directory of Open Access Journals (Sweden)

    Christoph A Thaiss

    2011-08-01

    Full Text Available Dendritic cells (DCs are the main inducers and regulators of cytotoxic T lymphocyte (CTL responses against viruses and tumors. One checkpoint to avoid misguided CTL activation, which might damage healthy cells of the body, is the necessity for multiple activation signals, involving both antigenic as well as additional signals that reflect the presence of pathogens. DCs provide both signals when activated by ligands of pattern recognition receptors and licensed by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (classical licensing or by NKT cells (alternative licensing. Licensing regulates the DC/CTL cross-talk at multiple layers. Direct recruitment of CTLs through chemokines released by licensed DCs has recently emerged as a common theme and has a crucial impact on the efficiency of CTL responses. Here, we discuss recent advances in our understanding of DC licensing for cross-priming and implications for the temporal and spatial regulation underlying this process. Future vaccination strategies will benefit from a deeper insight into the mechanisms that govern CTL activation.

  11. Molecular identity of dendritic voltage-gated sodium channels.

    Science.gov (United States)

    Lorincz, Andrea; Nusser, Zoltan

    2010-05-14

    Active invasion of the dendritic tree by action potentials (APs) generated in the axon is essential for associative synaptic plasticity and neuronal ensemble formation. In cortical pyramidal cells (PCs), this AP back-propagation is supported by dendritic voltage-gated Na+ (Nav) channels, whose molecular identity is unknown. Using a highly sensitive electron microscopic immunogold technique, we revealed the presence of the Nav1.6 subunit in hippocampal CA1 PC proximal and distal dendrites. Here, the subunit density is lower by a factor of 35 to 80 than that found in axon initial segments. A gradual decrease in Nav1.6 density along the proximodistal axis of the dendritic tree was also detected without any labeling in dendritic spines. Our results reveal the characteristic subcellular distribution of the Nav1.6 subunit, identifying this molecule as a key substrate enabling dendritic excitability.

  12. Recruitment of Staufen2 Enhances Dendritic Localization of an Intron-Containing CaMKIIα mRNA

    Directory of Open Access Journals (Sweden)

    Raúl Ortiz

    2017-07-01

    Full Text Available Regulation of mRNA localization is a conserved cellular process observed in many types of cells and organisms. Asymmetrical mRNA distribution plays a particularly important role in the nervous system, where local translation of localized mRNA represents a key mechanism in synaptic plasticity. CaMKIIα is a very abundant mRNA detected in neurites, consistent with its crucial role at glutamatergic synapses. Here, we report the presence of CaMKIIα mRNA isoforms that contain intron i16 in dendrites, RNA granules, and synaptoneurosomes from primary neurons and brain. This subpopulation of unspliced mRNA preferentially localizes to distal dendrites in a synaptic-activity-dependent manner. Staufen2, a well-established marker of RNA transport in dendrites, interacts with intron i16 sequences and enhances its distal dendritic localization, pointing to the existence of intron-mediated mechanisms in the molecular pathways that modulate dendritic transport and localization of synaptic mRNAs.

  13. Boobs, Boxing, and Bombs: Problematizing the Entertainment of Spike TV

    OpenAIRE

    Walton, Gerald; Potvin, L.

    2009-01-01

    Spike is the only television network in North America “for men.” Its motto, “Get more action,” is suggestive of pursuits of various forms of violence. We conceptualize Spike not as trivial entertainment, but rather as a form of pop culture that erodes the gains of feminists who have challenged the prevalence of normalized hegemonic masculinity (HM). Our paper highlights themes of Spike content, and connects those themes to the literature on HM. Moreover, we validate the identities and lives ...

  14. Investigating evolutionary conservation of dendritic cell subset identity and functions

    Directory of Open Access Journals (Sweden)

    Thien-Phong eVu Manh

    2015-06-01

    Full Text Available Dendritic cells (DC were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks and complementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types

  15. Integrated workflows for spiking neuronal network simulations

    Directory of Open Access Journals (Sweden)

    Ján eAntolík

    2013-12-01

    Full Text Available The increasing availability of computational resources is enabling more detailed, realistic modelling in computational neuroscience, resulting in a shift towards more heterogeneous models of neuronal circuits, and employment of complex experimental protocols. This poses a challenge for existing tool chains, as the set of tools involved in a typical modeller's workflow is expanding concomitantly, with growing complexity in the metadata flowing between them. For many parts of the workflow, a range of tools is available; however, numerous areas lack dedicated tools, while integration of existing tools is limited. This forces modellers to either handle the workflow manually, leading to errors, or to write substantial amounts of code to automate parts of the workflow, in both cases reducing their productivity.To address these issues, we have developed Mozaik: a workflow system for spiking neuronal network simulations written in Python. Mozaik integrates model, experiment and stimulation specification, simulation execution, data storage, data analysis and visualisation into a single automated workflow, ensuring that all relevant metadata are available to all workflow components. It is based on several existing tools, including PyNN, Neo and Matplotlib. It offers a declarative way to specify models and recording configurations using hierarchically organised configuration files. Mozaik automatically records all data together with all relevant metadata about the experimental context, allowing automation of the analysis and visualisation stages. Mozaik has a modular architecture, and the existing modules are designed to be extensible with minimal programming effort. Mozaik increases the productivity of running virtual experiments on highly structured neuronal networks by automating the entire experimental cycle, while increasing the reliability of modelling studies by relieving the user from manual handling of the flow of metadata between the individual

  16. Biophysical Insights into How Spike Threshold Depends on the Rate of Membrane Potential Depolarization in Type I and Type II Neurons.

    Directory of Open Access Journals (Sweden)

    Guo-Sheng Yi

    Full Text Available Dynamic spike threshold plays a critical role in neuronal input-output relations. In many neurons, the threshold potential depends on the rate of membrane potential depolarization (dV/dt preceding a spike. There are two basic classes of neural excitability, i.e., Type I and Type II, according to input-output properties. Although the dynamical and biophysical basis of their spike initiation has been established, the spike threshold dynamic for each cell type has not been well described. Here, we use a biophysical model to investigate how spike threshold depends on dV/dt in two types of neuron. It is observed that Type II spike threshold is more depolarized and more sensitive to dV/dt than Type I. With phase plane analysis, we show that each threshold dynamic arises from the different separatrix and K+ current kinetics. By analyzing subthreshold properties of membrane currents, we find the activation of hyperpolarizing current prior to spike initiation is a major factor that regulates the threshold dynamics. The outward K+ current in Type I neuron does not activate at the perithresholds, which makes its spike threshold insensitive to dV/dt. The Type II K+ current activates prior to spike initiation and there is a large net hyperpolarizing current at the perithresholds, which results in a depolarized threshold as well as a pronounced threshold dynamic. These predictions are further attested in several other functionally equivalent cases of neural excitability. Our study provides a fundamental description about how intrinsic biophysical properties contribute to the threshold dynamics in Type I and Type II neurons, which could decipher their significant functions in neural coding.

  17. Heterogeneity of Purkinje cell simple spike-complex spike interactions: zebrin- and non-zebrin-related variations.

    Science.gov (United States)

    Tang, Tianyu; Xiao, Jianqiang; Suh, Colleen Y; Burroughs, Amelia; Cerminara, Nadia L; Jia, Linjia; Marshall, Sarah P; Wise, Andrew K; Apps, Richard; Sugihara, Izumi; Lang, Eric J

    2017-08-01

    Cerebellar Purkinje cells (PCs) generate two types of action potentials, simple and complex spikes. Although they are generated by distinct mechanisms, interactions between the two spike types exist. Zebrin staining produces alternating positive and negative stripes of PCs across most of the cerebellar cortex. Thus, here we compared simple spike-complex spike interactions both within and across zebrin populations. Simple spike activity undergoes a complex modulation preceding and following a complex spike. The amplitudes of the pre- and post-complex spike modulation phases were correlated across PCs. On average, the modulation was larger for PCs in zebrin positive regions. Correlations between aspects of the complex spike waveform and simple spike activity were found, some of which varied between zebrin positive and negative PCs. The implications of the results are discussed with regard to hypotheses that complex spikes are triggered by rises in simple spike activity for either motor learning or homeostatic functions. Purkinje cells (PCs) generate two types of action potentials, called simple and complex spikes (SSs and CSs). We first investigated the CS-associated modulation of SS activity and its relationship to the zebrin status of the PC. The modulation pattern consisted of a pre-CS rise in SS activity, and then, following the CS, a pause, a rebound, and finally a late inhibition of SS activity for both zebrin positive (Z+) and negative (Z-) cells, though the amplitudes of the phases were larger in Z+ cells. Moreover, the amplitudes of the pre-CS rise with the late inhibitory phase of the modulation were correlated across PCs. In contrast, correlations between modulation phases across CSs of individual PCs were generally weak. Next, the relationship between CS spikelets and SS activity was investigated. The number of spikelets/CS correlated with the average SS firing rate only for Z+ cells. In contrast, correlations across CSs between spikelet numbers and the

  18. Real-time computing platform for spiking neurons (RT-spike).

    Science.gov (United States)

    Ros, Eduardo; Ortigosa, Eva M; Agís, Rodrigo; Carrillo, Richard; Arnold, Michael

    2006-07-01

    A computing platform is described for simulating arbitrary networks of spiking neurons in real time. A hybrid computing scheme is adopted that uses both software and hardware components to manage the tradeoff between flexibility and computational power; the neuron model is implemented in hardware and the network model and the learning are implemented in software. The incremental transition of the software components into hardware is supported. We focus on a spike response model (SRM) for a neuron where the synapses are modeled as input-driven conductances. The temporal dynamics of the synaptic integration process are modeled with a synaptic time constant that results in a gradual injection of charge. This type of model is computationally expensive and is not easily amenable to existing software-based event-driven approaches. As an alternative we have designed an efficient time-based computing architecture in hardware, where the different stages of the neuron model are processed in parallel. Further improvements occur by computing multiple neurons in parallel using multiple processing units. This design is tested using reconfigurable hardware and its scalability and performance evaluated. Our overall goal is to investigate biologically realistic models for the real-time control of robots operating within closed action-perception loops, and so we evaluate the performance of the system on simulating a model of the cerebellum where the emulation of the temporal dynamics of the synaptic integration process is important.

  19. Perceptron learning rule derived from spike-frequency adaptation and spike-time-dependent plasticity.

    Science.gov (United States)

    D'Souza, Prashanth; Liu, Shih-Chii; Hahnloser, Richard H R

    2010-03-09

    It is widely believed that sensory and motor processing in the brain is based on simple computational primitives rooted in cellular and synaptic physiology. However, many gaps remain in our understanding of the connections between neural computations and biophysical properties of neurons. Here, we show that synaptic spike-time-dependent plasticity (STDP) combined with spike-frequency adaptation (SFA) in a single neuron together approximate the well-known perceptron learning rule. Our calculations and integrate-and-fire simulations reveal that delayed inputs to a neuron endowed with STDP and SFA precisely instruct neural responses to earlier arriving inputs. We demonstrate this mechanism on a developmental example of auditory map formation guided by visual inputs, as observed in the external nucleus of the inferior colliculus (ICX) of barn owls. The interplay of SFA and STDP in model ICX neurons precisely transfers the tuning curve from the visual modality onto the auditory modality, demonstrating a useful computation for multimodal and sensory-guided processing.

  20. Timing intervals using population synchrony and spike timing dependent plasticity

    Directory of Open Access Journals (Sweden)

    Wei Xu

    2016-12-01

    Full Text Available We present a computational model by which ensembles of regularly spiking neurons can encode different time intervals through synchronous firing. We show that a neuron responding to a large population of convergent inputs has the potential to learn to produce an appropriately-timed output via spike-time dependent plasticity. We explain why temporal variability of this population synchrony increases with increasing time intervals. We also show that the scalar property of timing and its violation at short intervals can be explained by the spike-wise accumulation of jitter in the inter-spike intervals of timing neurons. We explore how the challenge of encoding longer time intervals can be overcome and conclude that this may involve a switch to a different population of neurons with lower firing rate, with the added effect of producing an earlier bias in response. Experimental data on human timing performance show features in agreement with the model’s output.

  1. Stochastic optimal control of single neuron spike trains

    DEFF Research Database (Denmark)

    Iolov, Alexandre; Ditlevsen, Susanne; Longtin, Andrë

    2014-01-01

    stimulation of a neuron to achieve a target spike train under the physiological constraint to not damage tissue. Approach. We pose a stochastic optimal control problem to precisely specify the spike times in a leaky integrate-and-fire (LIF) model of a neuron with noise assumed to be of intrinsic or synaptic...... origin. In particular, we allow for the noise to be of arbitrary intensity. The optimal control problem is solved using dynamic programming when the controller has access to the voltage (closed-loop control), and using a maximum principle for the transition density when the controller only has access...... to the spike times (open-loop control). Main results. We have developed a stochastic optimal control algorithm to obtain precise spike times. It is applicable in both the supra-threshold and sub-threshold regimes, under open-loop and closed-loop conditions and with an arbitrary noise intensity; the accuracy...

  2. Inherently stochastic spiking neurons for probabilistic neural computation

    KAUST Repository

    Al-Shedivat, Maruan; Naous, Rawan; Neftci, Emre; Cauwenberghs, Gert; Salama, Khaled N.

    2015-01-01

    . Our analysis and simulations show that the proposed neuron circuit satisfies a neural computability condition that enables probabilistic neural sampling and spike-based Bayesian learning and inference. Our findings constitute an important step towards

  3. A novel unsupervised spike sorting algorithm for intracranial EEG.

    Science.gov (United States)

    Yadav, R; Shah, A K; Loeb, J A; Swamy, M N S; Agarwal, R

    2011-01-01

    This paper presents a novel, unsupervised spike classification algorithm for intracranial EEG. The method combines template matching and principal component analysis (PCA) for building a dynamic patient-specific codebook without a priori knowledge of the spike waveforms. The problem of misclassification due to overlapping classes is resolved by identifying similar classes in the codebook using hierarchical clustering. Cluster quality is visually assessed by projecting inter- and intra-clusters onto a 3D plot. Intracranial EEG from 5 patients was utilized to optimize the algorithm. The resulting codebook retains 82.1% of the detected spikes in non-overlapping and disjoint clusters. Initial results suggest a definite role of this method for both rapid review and quantitation of interictal spikes that could enhance both clinical treatment and research studies on epileptic patients.

  4. Emergent dynamics of spiking neurons with fluctuating threshold

    Science.gov (United States)

    Bhattacharjee, Anindita; Das, M. K.

    2017-05-01

    Role of fluctuating threshold on neuronal dynamics is investigated. The threshold function is assumed to follow a normal probability distribution. Standard deviation of inter-spike interval of the response is computed as an indicator of irregularity in spike emission. It has been observed that, the irregularity in spiking is more if the threshold variation is more. A significant change in modal characteristics of Inter Spike Intervals (ISI) is seen to occur as a function of fluctuation parameter. Investigation is further carried out for coupled system of neurons. Cooperative dynamics of coupled neurons are discussed in view of synchronization. Total and partial synchronization regimes are depicted with the help of contour plots of synchrony measure under various conditions. Results of this investigation may provide a basis for exploring the complexities of neural communication and brain functioning.

  5. Higher Order Spike Synchrony in Prefrontal Cortex during visual memory

    Directory of Open Access Journals (Sweden)

    Gordon ePipa

    2011-06-01

    Full Text Available Precise temporal synchrony of spike firing has been postulated as an important neuronal mechanism for signal integration and the induction of plasticity in neocortex. As prefrontal cortex plays an important role in organizing memory and executive functions, the convergence of multiple visual pathways onto PFC predicts that neurons should preferentially synchronize their spiking when stimulus information is processed. Furthermore, synchronous spike firing should intensify if memory processes require the induction of neuronal plasticity, even if this is only for short-term. Here we show with multiple simultaneously recorded units in ventral prefrontal cortex that neurons participate in 3 ms precise synchronous discharges distributed across multiple sites separated by at least 500 µm. The frequency of synchronous firing is modulated by behavioral performance and is specific for the memorized visual stimuli. In particular, during the memory period in which activity is not stimulus driven, larger groups of up to 7 sites exhibit performance dependent modulation of their spike synchronization.

  6. Spatial distribution of Na+-K+-ATPase in dendritic spines dissected by nanoscale superresolution STED microscopy

    Directory of Open Access Journals (Sweden)

    Bondar Alexander

    2011-01-01

    Full Text Available Abstract Background The Na+,K+-ATPase plays an important role for ion homeostasis in virtually all mammalian cells, including neurons. Despite this, there is as yet little known about the isoform specific distribution in neurons. Results With help of superresolving stimulated emission depletion microscopy the spatial distribution of Na+,K+-ATPase in dendritic spines of cultured striatum neurons have been dissected. The found compartmentalized distribution provides a strong evidence for the confinement of neuronal Na+,K+-ATPase (α3 isoform in the postsynaptic region of the spine. Conclusions A compartmentalized distribution may have implications for the generation of local sodium gradients within the spine and for the structural and functional interaction between the sodium pump and other synaptic proteins. Superresolution microscopy has thus opened up a new perspective to elucidate the nature of the physiological function, regulation and signaling role of Na+,K+-ATPase from its topological distribution in dendritic spines.

  7. Constructing Precisely Computing Networks with Biophysical Spiking Neurons.

    Science.gov (United States)

    Schwemmer, Michael A; Fairhall, Adrienne L; Denéve, Sophie; Shea-Brown, Eric T

    2015-07-15

    While spike timing has been shown to carry detailed stimulus information at the sensory periphery, its possible role in network computation is less clear. Most models of computation by neural networks are based on population firing rates. In equivalent spiking implementations, firing is assumed to be random such that averaging across populations of neurons recovers the rate-based approach. Recently, however, Denéve and colleagues have suggested that the spiking behavior of neurons may be fundamental to how neuronal networks compute, with precise spike timing determined by each neuron's contribution to producing the desired output (Boerlin and Denéve, 2011; Boerlin et al., 2013). By postulating that each neuron fires to reduce the error in the network's output, it was demonstrated that linear computations can be performed by networks of integrate-and-fire neurons that communicate through instantaneous synapses. This left open, however, the possibility that realistic networks, with conductance-based neurons with subthreshold nonlinearity and the slower timescales of biophysical synapses, may not fit into this framework. Here, we show how the spike-based approach can be extended to biophysically plausible networks. We then show that our network reproduces a number of key features of cortical networks including irregular and Poisson-like spike times and a tight balance between excitation and inhibition. Lastly, we discuss how the behavior of our model scales with network size or with the number of neurons "recorded" from a larger computing network. These results significantly increase the biological plausibility of the spike-based approach to network computation. We derive a network of neurons with standard spike-generating currents and synapses with realistic timescales that computes based upon the principle that the precise timing of each spike is important for the computation. We then show that our network reproduces a number of key features of cortical networks

  8. Multi-layer network utilizing rewarded spike time dependent plasticity to learn a foraging task.

    Directory of Open Access Journals (Sweden)

    Pavel Sanda

    2017-09-01

    Full Text Available Neural networks with a single plastic layer employing reward modulated spike time dependent plasticity (STDP are capable of learning simple foraging tasks. Here we demonstrate advanced pattern discrimination and continuous learning in a network of spiking neurons with multiple plastic layers. The network utilized both reward modulated and non-reward modulated STDP and implemented multiple mechanisms for homeostatic regulation of synaptic efficacy, including heterosynaptic plasticity, gain control, output balancing, activity normalization of rewarded STDP and hard limits on synaptic strength. We found that addition of a hidden layer of neurons employing non-rewarded STDP created neurons that responded to the specific combinations of inputs and thus performed basic classification of the input patterns. When combined with a following layer of neurons implementing rewarded STDP, the network was able to learn, despite the absence of labeled training data, discrimination between rewarding patterns and the patterns designated as punishing. Synaptic noise allowed for trial-and-error learning that helped to identify the goal-oriented strategies which were effective in task solving. The study predicts a critical set of properties of the spiking neuronal network with STDP that was sufficient to solve a complex foraging task involving pattern classification and decision making.

  9. The London Spikes Controversy: Homelessness, Urban Securitisation and the Question of ‘Hostile Architecture’

    Directory of Open Access Journals (Sweden)

    James Petty

    2016-03-01

    Full Text Available This article examines an ostensibly new feature of the securitised urban landscape: ‘hostile architecture’. Following controversy in 2014 London over ‘anti-homeless spikes’– metal studs implanted at ground level designed to discourage the homeless from sleeping in otherwise unrestricted spaces – certain visible methods of environmental social control were temporarily subject to intense public scrutiny and debate. While contests over public and urban spaces are not new, the spikes controversy emerged in the context of broader socio-political and governmental shifts toward neoliberal arrangements. Using the spikes issue as a case study, I contextualise hostile architecture within these broader processes and in wider patterns of urban securitisation. The article then offers an explanatory framework for understanding the controversy itself. Ultimately the article questions whether the public backlash against the use of spikes indicates genuine resistance to patterns of urban securitisation or, counterintuitively, a broader public distaste for both the homeless and the mechanisms that regulate them. 

  10. A novel automated spike sorting algorithm with adaptable feature extraction.

    Science.gov (United States)

    Bestel, Robert; Daus, Andreas W; Thielemann, Christiane

    2012-10-15

    To study the electrophysiological properties of neuronal networks, in vitro studies based on microelectrode arrays have become a viable tool for analysis. Although in constant progress, a challenging task still remains in this area: the development of an efficient spike sorting algorithm that allows an accurate signal analysis at the single-cell level. Most sorting algorithms currently available only extract a specific feature type, such as the principal components or Wavelet coefficients of the measured spike signals in order to separate different spike shapes generated by different neurons. However, due to the great variety in the obtained spike shapes, the derivation of an optimal feature set is still a very complex issue that current algorithms struggle with. To address this problem, we propose a novel algorithm that (i) extracts a variety of geometric, Wavelet and principal component-based features and (ii) automatically derives a feature subset, most suitable for sorting an individual set of spike signals. Thus, there is a new approach that evaluates the probability distribution of the obtained spike features and consequently determines the candidates most suitable for the actual spike sorting. These candidates can be formed into an individually adjusted set of spike features, allowing a separation of the various shapes present in the obtained neuronal signal by a subsequent expectation maximisation clustering algorithm. Test results with simulated data files and data obtained from chick embryonic neurons cultured on microelectrode arrays showed an excellent classification result, indicating the superior performance of the described algorithm approach. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Spatiotemporal Dynamics and Reliable Computations in Recurrent Spiking Neural Networks

    Science.gov (United States)

    Pyle, Ryan; Rosenbaum, Robert

    2017-01-01

    Randomly connected networks of excitatory and inhibitory spiking neurons provide a parsimonious model of neural variability, but are notoriously unreliable for performing computations. We show that this difficulty is overcome by incorporating the well-documented dependence of connection probability on distance. Spatially extended spiking networks exhibit symmetry-breaking bifurcations and generate spatiotemporal patterns that can be trained to perform dynamical computations under a reservoir computing framework.

  12. Spatiotemporal Dynamics and Reliable Computations in Recurrent Spiking Neural Networks.

    Science.gov (United States)

    Pyle, Ryan; Rosenbaum, Robert

    2017-01-06

    Randomly connected networks of excitatory and inhibitory spiking neurons provide a parsimonious model of neural variability, but are notoriously unreliable for performing computations. We show that this difficulty is overcome by incorporating the well-documented dependence of connection probability on distance. Spatially extended spiking networks exhibit symmetry-breaking bifurcations and generate spatiotemporal patterns that can be trained to perform dynamical computations under a reservoir computing framework.

  13. SPIKY: a graphical user interface for monitoring spike train synchrony.

    Science.gov (United States)

    Kreuz, Thomas; Mulansky, Mario; Bozanic, Nebojsa

    2015-05-01

    Techniques for recording large-scale neuronal spiking activity are developing very fast. This leads to an increasing demand for algorithms capable of analyzing large amounts of experimental spike train data. One of the most crucial and demanding tasks is the identification of similarity patterns with a very high temporal resolution and across different spatial scales. To address this task, in recent years three time-resolved measures of spike train synchrony have been proposed, the ISI-distance, the SPIKE-distance, and event synchronization. The Matlab source codes for calculating and visualizing these measures have been made publicly available. However, due to the many different possible representations of the results the use of these codes is rather complicated and their application requires some basic knowledge of Matlab. Thus it became desirable to provide a more user-friendly and interactive interface. Here we address this need and present SPIKY, a graphical user interface that facilitates the application of time-resolved measures of spike train synchrony to both simulated and real data. SPIKY includes implementations of the ISI-distance, the SPIKE-distance, and the SPIKE-synchronization (an improved and simplified extension of event synchronization) that have been optimized with respect to computation speed and memory demand. It also comprises a spike train generator and an event detector that makes it capable of analyzing continuous data. Finally, the SPIKY package includes additional complementary programs aimed at the analysis of large numbers of datasets and the estimation of significance levels. Copyright © 2015 the American Physiological Society.

  14. Nonlinear evolution of single spike in Richtmyer-Meshkov instability

    International Nuclear Information System (INIS)

    Fukuda, Y.; Nishihara, K.; Wouchuk, J.G.

    2000-01-01

    Nonlinear evolution of single spike structure and vortex in the Richtmyer-Meshkov instability is investigated with the use of a two-dimensional hydrodynamic code. It is shown that singularity appears in the vorticity left by transmitted and reflected shocks at a corrugated interface. This singularity results in opposite sign of vorticity along the interface that causes double spiral structure of the spike. (authors)

  15. Coincidence Detection Using Spiking Neurons with Application to Face Recognition

    Directory of Open Access Journals (Sweden)

    Fadhlan Kamaruzaman

    2015-01-01

    Full Text Available We elucidate the practical implementation of Spiking Neural Network (SNN as local ensembles of classifiers. Synaptic time constant τs is used as learning parameter in representing the variations learned from a set of training data at classifier level. This classifier uses coincidence detection (CD strategy trained in supervised manner using a novel supervised learning method called τs Prediction which adjusts the precise timing of output spikes towards the desired spike timing through iterative adaptation of τs. This paper also discusses the approximation of spike timing in Spike Response Model (SRM for the purpose of coincidence detection. This process significantly speeds up the whole process of learning and classification. Performance evaluations with face datasets such as AR, FERET, JAFFE, and CK+ datasets show that the proposed method delivers better face classification performance than the network trained with Supervised Synaptic-Time Dependent Plasticity (STDP. We also found that the proposed method delivers better classification accuracy than k nearest neighbor, ensembles of kNN, and Support Vector Machines. Evaluation on several types of spike codings also reveals that latency coding delivers the best result for face classification as well as for classification of other multivariate datasets.

  16. Orthobunyavirus ultrastructure and the curious tripodal glycoprotein spike.

    Directory of Open Access Journals (Sweden)

    Thomas A Bowden

    Full Text Available The genus Orthobunyavirus within the family Bunyaviridae constitutes an expanding group of emerging viruses, which threaten human and animal health. Despite the medical importance, little is known about orthobunyavirus structure, a prerequisite for understanding virus assembly and entry. Here, using electron cryo-tomography, we report the ultrastructure of Bunyamwera virus, the prototypic member of this genus. Whilst Bunyamwera virions are pleomorphic in shape, they display a locally ordered lattice of glycoprotein spikes. Each spike protrudes 18 nm from the viral membrane and becomes disordered upon introduction to an acidic environment. Using sub-tomogram averaging, we derived a three-dimensional model of the trimeric pre-fusion glycoprotein spike to 3-nm resolution. The glycoprotein spike consists mainly of the putative class-II fusion glycoprotein and exhibits a unique tripod-like arrangement. Protein-protein contacts between neighbouring spikes occur at membrane-proximal regions and intra-spike contacts at membrane-distal regions. This trimeric assembly deviates from previously observed fusion glycoprotein arrangements, suggesting a greater than anticipated repertoire of viral fusion glycoprotein oligomerization. Our study provides evidence of a pH-dependent conformational change that occurs during orthobunyaviral entry into host cells and a blueprint for the structure of this group of emerging pathogens.

  17. The Omega-Infinity Limit of Single Spikes

    CERN Document Server

    Axenides, Minos; Linardopoulos, Georgios

    A new infinite-size limit of strings in RxS2 is presented. The limit is obtained from single spike strings by letting their angular velocity omega become infinite. We derive the energy-momenta relation of omega-infinity single spikes as their linear velocity v-->1 and their angular momentum J-->1. Generally, the v-->1, J-->1 limit of single spikes is singular and has to be excluded from the spectrum and be studied separately. We discover that the dispersion relation of omega-infinity single spikes contains logarithms in the limit J-->1. This result is somewhat surprising, since the logarithmic behavior in the string spectra is typically associated with their motion in non-compact spaces such as AdS. Omega-infinity single spikes seem to completely cover the surface of the 2-sphere they occupy, so that they may essentially be viewed as some sort of "brany strings". A proof of the sphere-filling property of omega-infinity single spikes is given in the appendix.

  18. Comparison of Classifier Architectures for Online Neural Spike Sorting.

    Science.gov (United States)

    Saeed, Maryam; Khan, Amir Ali; Kamboh, Awais Mehmood

    2017-04-01

    High-density, intracranial recordings from micro-electrode arrays need to undergo Spike Sorting in order to associate the recorded neuronal spikes to particular neurons. This involves spike detection, feature extraction, and classification. To reduce the data transmission and power requirements, on-chip real-time processing is becoming very popular. However, high computational resources are required for classifiers in on-chip spike-sorters, making scalability a great challenge. In this review paper, we analyze several popular classifiers to propose five new hardware architectures using the off-chip training with on-chip classification approach. These include support vector classification, fuzzy C-means classification, self-organizing maps classification, moving-centroid K-means classification, and Cosine distance classification. The performance of these architectures is analyzed in terms of accuracy and resource requirement. We establish that the neural networks based Self-Organizing Maps classifier offers the most viable solution. A spike sorter based on the Self-Organizing Maps classifier, requires only 7.83% of computational resources of the best-reported spike sorter, hierarchical adaptive means, while offering a 3% better accuracy at 7 dB SNR.

  19. Automatic fitting of spiking neuron models to electrophysiological recordings

    Directory of Open Access Journals (Sweden)

    Cyrille Rossant

    2010-03-01

    Full Text Available Spiking models can accurately predict the spike trains produced by cortical neurons in response to somatically injected currents. Since the specific characteristics of the model depend on the neuron, a computational method is required to fit models to electrophysiological recordings. The fitting procedure can be very time consuming both in terms of computer simulations and in terms of code writing. We present algorithms to fit spiking models to electrophysiological data (time-varying input and spike trains that can run in parallel on graphics processing units (GPUs. The model fitting library is interfaced with Brian, a neural network simulator in Python. If a GPU is present it uses just-in-time compilation to translate model equations into optimized code. Arbitrary models can then be defined at script level and run on the graphics card. This tool can be used to obtain empirically validated spiking models of neurons in various systems. We demonstrate its use on public data from the INCF Quantitative Single-Neuron Modeling 2009 competition by comparing the performance of a number of neuron spiking models.

  20. Absolute Ca Isotopic Measurement Using an Improved Double Spike Technique

    Directory of Open Access Journals (Sweden)

    Jason Jiun-San Shen

    2009-01-01

    Full Text Available A new vector analytical method has been developed in order to obtain the true isotopic composition of the 42Ca-48Ca double spike. This is achieved by using two different sample-spike mixtures combined with the double spike and natural Ca data. Be cause the natural sample (two mixtures and the spike should all lie on a single mixing line, we are able to con strain the true isotopic composition of our double spike using this new approach. Once the isotopic composition of the Ca double spike is established, we are able to obtain the true Ca isotopic composition of the NIST Ca standard SRM915a, 40Ca/44Ca = 46.537 ± 2 (2sm, n = 55, 42Ca/44Ca = 0.31031 ± 1, 43Ca/44Ca = 0.06474 ± 1, and 48Ca/44Ca = 0.08956 ± 1. De spite an off set of 1.3% in 40Ca/44Ca between our result and the previously re ported value (Russell et al. 1978, our data indicate an off set of 1.89__in 40Ca/44Ca between SRM915a and seawater, entirely consistent with the published results.

  1. Spike propagation through the dorsal root ganglia in an unmyelinated sensory neuron: a modeling study.

    Science.gov (United States)

    Sundt, Danielle; Gamper, Nikita; Jaffe, David B

    2015-12-01

    Unmyelinated C-fibers are a major type of sensory neurons conveying pain information. Action potential conduction is regulated by the bifurcation (T-junction) of sensory neuron axons within the dorsal root ganglia (DRG). Understanding how C-fiber signaling is influenced by the morphology of the T-junction and the local expression of ion channels is important for understanding pain signaling. In this study we used biophysical computer modeling to investigate the influence of axon morphology within the DRG and various membrane conductances on the reliability of spike propagation. As expected, calculated input impedance and the amplitude of propagating action potentials were both lowest at the T-junction. Propagation reliability for single spikes was highly sensitive to the diameter of the stem axon and the density of voltage-gated Na(+) channels. A model containing only fast voltage-gated Na(+) and delayed-rectifier K(+) channels conducted trains of spikes up to frequencies of 110 Hz. The addition of slowly activating KCNQ channels (i.e., KV7 or M-channels) to the model reduced the following frequency to 30 Hz. Hyperpolarization produced by addition of a much slower conductance, such as a Ca(2+)-dependent K(+) current, was needed to reduce the following frequency to 6 Hz. Attenuation of driving force due to ion accumulation or hyperpolarization produced by a Na(+)-K(+) pump had no effect on following frequency but could influence the reliability of spike propagation mutually with the voltage shift generated by a Ca(2+)-dependent K(+) current. These simulations suggest how specific ion channels within the DRG may contribute toward therapeutic treatments for chronic pain. Copyright © 2015 the American Physiological Society.

  2. CTLA-4 blockade during dendritic cell based booster vaccination influences dendritic cell survival and CTL expansion

    DEFF Research Database (Denmark)

    Pedersen, Anders E; Ronchese, Franca

    2007-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells and critical for the priming of CD8+ T cells. Therefore the use of these cells as adjuvant cells has been tested in a large number of experimental and clinical vaccination studies, in particular cancer vaccine studies. A number of protocols...

  3. Nanofibrous nonwovens based on dendritic-linear-dendritic poly(ethylene glycol) hybrids

    DEFF Research Database (Denmark)

    Kikionis, Stefanos; Ioannou, Efstathia; Andren, Oliver C.J.

    2017-01-01

    unsuccessful. Nevertheless, when these DLD hybrids were blended with an array of different biodegradable polymers as entanglement enhancers, nanofibrous nonwovens were successfully prepared by electrospinning. The pseudogeneration degree of the DLDs, the nature of the co-electrospun polymer and the solvent...... nanofibers. Such dendritic nanofibrous scaffolds can be promising materials for biomedical applications due to their biocompatibility, biodegradability, multifunctionality, and advanced structural architecture....

  4. Fine structure of synapses on dendritic spines

    Directory of Open Access Journals (Sweden)

    Michael eFrotscher

    2014-09-01

    Full Text Available Camillo Golgi’s Reazione Nera led to the discovery of dendritic spines, small appendages originating from dendritic shafts. With the advent of electron microscopy (EM they were identified as sites of synaptic contact. Later it was found that changes in synaptic strength were associated with changes in the shape of dendritic spines. While live-cell imaging was advantageous in monitoring the time course of such changes in spine structure, EM is still the best method for the simultaneous visualization of all cellular components, including actual synaptic contacts, at high resolution. Immunogold labeling for EM reveals the precise localization of molecules in relation to synaptic structures. Previous EM studies of spines and synapses were performed in tissue subjected to aldehyde fixation and dehydration in ethanol, which is associated with protein denaturation and tissue shrinkage. It has remained an issue to what extent fine structural details are preserved when subjecting the tissue to these procedures. In the present review, we report recent studies on the fine structure of spines and synapses using high-pressure freezing (HPF, which avoids protein denaturation by aldehydes and results in an excellent preservation of ultrastructural detail. In these studies, HPF was used to monitor subtle fine-structural changes in spine shape associated with chemically induced long-term potentiation (cLTP at identified hippocampal mossy fiber synapses. Changes in spine shape result from reorganization of the actin cytoskeleton. We report that cLTP was associated with decreased immunogold labeling for phosphorylated cofilin (p-cofilin, an actin-depolymerizing protein. Phosphorylation of cofilin renders it unable to depolymerize F-actin, which stabilizes the actin cytoskeleton. Decreased levels of p-cofilin, in turn, suggest increased actin turnover, possibly underlying the changes in spine shape associated with cLTP. The findings reviewed here establish HPF as

  5. Hippocampal Dendritic Spines Are Segregated Depending on Their Actin Polymerization.

    Science.gov (United States)

    Domínguez-Iturza, Nuria; Calvo, María; Benoist, Marion; Esteban, José Antonio; Morales, Miguel

    2016-01-01

    Dendritic spines are mushroom-shaped protrusions of the postsynaptic membrane. Spines receive the majority of glutamatergic synaptic inputs. Their morphology, dynamics, and density have been related to synaptic plasticity and learning. The main determinant of spine shape is filamentous actin. Using FRAP, we have reexamined the actin dynamics of individual spines from pyramidal hippocampal neurons, both in cultures and in hippocampal organotypic slices. Our results indicate that, in cultures, the actin mobile fraction is independently regulated at the individual spine level, and mobile fraction values do not correlate with either age or distance from the soma. The most significant factor regulating actin mobile fraction was the presence of astrocytes in the culture substrate. Spines from neurons growing in the virtual absence of astrocytes have a more stable actin cytoskeleton, while spines from neurons growing in close contact with astrocytes show a more dynamic cytoskeleton. According to their recovery time, spines were distributed into two populations with slower and faster recovery times, while spines from slice cultures were grouped into one population. Finally, employing fast lineal acquisition protocols, we confirmed the existence of loci with high polymerization rates within the spine.

  6. Regulatory dendritic cell therapy: from rodents to clinical application.

    Science.gov (United States)

    Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W

    2014-10-01

    Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or "tolerogenic" DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant rejection. There is also evidence that adoptive transfer of DCreg can regulate T cell responses in non-human primates and humans. Important insights gained from in vitro studies and animal models have led recently to the development of clinical grade human DCreg, with potential to treat autoimmune disease or enhance transplant survival while reducing patient dependency on immunosuppressive drugs. Phase I trials have been conducted in type-1 diabetes and rheumatoid arthritis, with results that emphasize the feasibility and safety of DCreg therapy. This mini-review will outline how observations made using animal models have been translated into human use, and discuss the challenges faced in further developing this form of regulatory immune cell therapy in the fields of autoimmunity and transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Dendritic cells during Epstein Barr virus infection

    Directory of Open Access Journals (Sweden)

    Christian eMunz

    2014-06-01

    Full Text Available Epstein Barr virus (EBV causes persistent infection in more than 90% of the human adult population and is associated with 2% of all tumors in humans. This -herpesvirus infects primarily human B and epithelial cells, but has been reported to be sensed by dendritic cells (DCs during primary infection. These activated DCs are thought to contribute to innate restriction of EBV infection and initiate EBV specific adaptive immune responses via cross-priming. The respective evidence and their potential importance for EBV specific vaccine development will be discussed in this review.

  8. Gliadin fragments promote migration of dendritic cells

    Czech Academy of Sciences Publication Activity Database

    Chládková, Barbara; Kamanová, Jana; Palová-Jelínková, Lenka; Cinová, Jana; Šebo, Peter; Tučková, Ludmila

    2011-01-01

    Roč. 15, č. 4 (2011), 938-948 ISSN 1582-1838 R&D Projects: GA ČR GA310/07/0414; GA ČR GD310/08/H077; GA ČR GA310/08/0447; GA AV ČR IAA500200801; GA AV ČR IAA500200914 Institutional research plan: CEZ:AV0Z50200510 Keywords : celiac disease * gliadin * dendritic cell Subject RIV: EC - Immunology Impact factor: 4.125, year: 2011

  9. Stress-Induced Impairment of a Working Memory Task: Role of Spiking Rate and Spiking History Predicted Discharge

    Science.gov (United States)

    Devilbiss, David M.; Jenison, Rick L.; Berridge, Craig W.

    2012-01-01

    Stress, pervasive in society, contributes to over half of all work place accidents a year and over time can contribute to a variety of psychiatric disorders including depression, schizophrenia, and post-traumatic stress disorder. Stress impairs higher cognitive processes, dependent on the prefrontal cortex (PFC) and that involve maintenance and integration of information over extended periods, including working memory and attention. Substantial evidence has demonstrated a relationship between patterns of PFC neuron spiking activity (action-potential discharge) and components of delayed-response tasks used to probe PFC-dependent cognitive function in rats and monkeys. During delay periods of these tasks, persistent spiking activity is posited to be essential for the maintenance of information for working memory and attention. However, the degree to which stress-induced impairment in PFC-dependent cognition involves changes in task-related spiking rates or the ability for PFC neurons to retain information over time remains unknown. In the current study, spiking activity was recorded from the medial PFC of rats performing a delayed-response task of working memory during acute noise stress (93 db). Spike history-predicted discharge (SHPD) for PFC neurons was quantified as a measure of the degree to which ongoing neuronal discharge can be predicted by past spiking activity and reflects the degree to which past information is retained by these neurons over time. We found that PFC neuron discharge is predicted by their past spiking patterns for nearly one second. Acute stress impaired SHPD, selectively during delay intervals of the task, and simultaneously impaired task performance. Despite the reduction in delay-related SHPD, stress increased delay-related spiking rates. These findings suggest that neural codes utilizing SHPD within PFC networks likely reflects an additional important neurophysiological mechanism for maintenance of past information over time. Stress

  10. Spike Pattern Structure Influences Synaptic Efficacy Variability Under STDP and Synaptic Homeostasis. II: Spike Shuffling Methods on LIF Networks

    Directory of Open Access Journals (Sweden)

    Zedong Bi

    2016-08-01

    Full Text Available Synapses may undergo variable changes during plasticity because of the variability of spike patterns such as temporal stochasticity and spatial randomness. Here, we call the variability of synaptic weight changes during plasticity to be efficacy variability. In this paper, we investigate how four aspects of spike pattern statistics (i.e., synchronous firing, burstiness/regularity, heterogeneity of rates and heterogeneity of cross-correlations influence the efficacy variability under pair-wise additive spike-timing dependent plasticity (STDP and synaptic homeostasis (the mean strength of plastic synapses into a neuron is bounded, by implementing spike shuffling methods onto spike patterns self-organized by a network of excitatory and inhibitory leaky integrate-and-fire (LIF neurons. With the increase of the decay time scale of the inhibitory synaptic currents, the LIF network undergoes a transition from asynchronous state to weak synchronous state and then to synchronous bursting state. We first shuffle these spike patterns using a variety of methods, each designed to evidently change a specific pattern statistics; and then investigate the change of efficacy variability of the synapses under STDP and synaptic homeostasis, when the neurons in the network fire according to the spike patterns before and after being treated by a shuffling method. In this way, we can understand how the change of pattern statistics may cause the change of efficacy variability. Our results are consistent with those of our previous study which implements spike-generating models on converging motifs. We also find that burstiness/regularity is important to determine the efficacy variability under asynchronous states, while heterogeneity of cross-correlations is the main factor to cause efficacy variability when the network moves into synchronous bursting states (the states observed in epilepsy.

  11. Barriers in the brain : resolving dendritic spine morphology and compartmentalization

    NARCIS (Netherlands)

    Adrian, Max; Kusters, Remy; Wierenga, Corette J; Storm, Cornelis; Hoogenraad, Casper C; Kapitein, Lukas C

    2014-01-01

    Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50-400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and

  12. Dendrites Enable a Robust Mechanism for Neuronal Stimulus Selectivity.

    Science.gov (United States)

    Cazé, Romain D; Jarvis, Sarah; Foust, Amanda J; Schultz, Simon R

    2017-09-01

    Hearing, vision, touch: underlying all of these senses is stimulus selectivity, a robust information processing operation in which cortical neurons respond more to some stimuli than to others. Previous models assume that these neurons receive the highest weighted input from an ensemble encoding the preferred stimulus, but dendrites enable other possibilities. Nonlinear dendritic processing can produce stimulus selectivity based on the spatial distribution of synapses, even if the total preferred stimulus weight does not exceed that of nonpreferred stimuli. Using a multi-subunit nonlinear model, we demonstrate that stimulus selectivity can arise from the spatial distribution of synapses. We propose this as a general mechanism for information processing by neurons possessing dendritic trees. Moreover, we show that this implementation of stimulus selectivity increases the neuron's robustness to synaptic and dendritic failure. Importantly, our model can maintain stimulus selectivity for a larger range of loss of synapses or dendrites than an equivalent linear model. We then use a layer 2/3 biophysical neuron model to show that our implementation is consistent with two recent experimental observations: (1) one can observe a mixture of selectivities in dendrites that can differ from the somatic selectivity, and (2) hyperpolarization can broaden somatic tuning without affecting dendritic tuning. Our model predicts that an initially nonselective neuron can become selective when depolarized. In addition to motivating new experiments, the model's increased robustness to synapses and dendrites loss provides a starting point for fault-resistant neuromorphic chip development.

  13. Modelling dendritic ecological networks in space: An integrated network perspective

    Science.gov (United States)

    Erin E. Peterson; Jay M. Ver Hoef; Dan J. Isaak; Jeffrey A. Falke; Marie-Josee Fortin; Chris E. Jordan; Kristina McNyset; Pascal Monestiez; Aaron S. Ruesch; Aritra Sengupta; Nicholas Som; E. Ashley Steel; David M. Theobald; Christian E. Torgersen; Seth J. Wenger

    2013-01-01

    Dendritic ecological networks (DENs) are a unique form of ecological networks that exhibit a dendritic network topology (e.g. stream and cave networks or plant architecture). DENs have a dual spatial representation; as points within the network and as points in geographical space. Consequently, some analytical methods used to quantify relationships in other types of...

  14. Dendritic Spines in Depression: What We Learned from Animal Models

    OpenAIRE

    Qiao, Hui; Li, Ming-Xing; Xu, Chang; Chen, Hui-Bin; An, Shu-Cheng; Ma, Xin-Ming

    2016-01-01

    Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have ...

  15. Unsupervised clustering with spiking neurons by sparse temporal coding and multi-layer RBF networks

    NARCIS (Netherlands)

    S.M. Bohte (Sander); J.A. La Poutré (Han); J.N. Kok (Joost)

    2000-01-01

    textabstractWe demonstrate that spiking neural networks encoding information in spike times are capable of computing and learning clusters from realistic data. We show how a spiking neural network based on spike-time coding and Hebbian learning can successfully perform unsupervised clustering on

  16. Immune monitoring using mRNA-transfected dendritic cells

    DEFF Research Database (Denmark)

    Borch, Troels Holz; Svane, Inge Marie; Met, Özcan

    2016-01-01

    Dendritic cells are known to be the most potent antigen presenting cell in the immune system and are used as cellular adjuvants in therapeutic anticancer vaccines using various tumor-associated antigens or their derivatives. One way of loading antigen into the dendritic cells is by m......RNA electroporation, ensuring presentation of antigen through major histocompatibility complex I and potentially activating T cells, enabling them to kill the tumor cells. Despite extensive research in the field, only one dendritic cell-based vaccine has been approved. There is therefore a great need to elucidate...... and understand the immunological impact of dendritic cell vaccination in order to improve clinical benefit. In this chapter, we describe a method for performing immune monitoring using peripheral blood mononuclear cells and autologous dendritic cells transfected with tumor-associated antigen-encoding mRNA....

  17. Joint Probability-Based Neuronal Spike Train Classification

    Directory of Open Access Journals (Sweden)

    Yan Chen

    2009-01-01

    Full Text Available Neuronal spike trains are used by the nervous system to encode and transmit information. Euclidean distance-based methods (EDBMs have been applied to quantify the similarity between temporally-discretized spike trains and model responses. In this study, using the same discretization procedure, we developed and applied a joint probability-based method (JPBM to classify individual spike trains of slowly adapting pulmonary stretch receptors (SARs. The activity of individual SARs was recorded in anaesthetized, paralysed adult male rabbits, which were artificially-ventilated at constant rate and one of three different volumes. Two-thirds of the responses to the 600 stimuli presented at each volume were used to construct three response models (one for each stimulus volume consisting of a series of time bins, each with spike probabilities. The remaining one-third of the responses where used as test responses to be classified into one of the three model responses. This was done by computing the joint probability of observing the same series of events (spikes or no spikes, dictated by the test response in a given model and determining which probability of the three was highest. The JPBM generally produced better classification accuracy than the EDBM, and both performed well above chance. Both methods were similarly affected by variations in discretization parameters, response epoch duration, and two different response alignment strategies. Increasing bin widths increased classification accuracy, which also improved with increased observation time, but primarily during periods of increasing lung inflation. Thus, the JPBM is a simple and effective method performing spike train classification.

  18. An Efficient Supervised Training Algorithm for Multilayer Spiking Neural Networks.

    Science.gov (United States)

    Xie, Xiurui; Qu, Hong; Liu, Guisong; Zhang, Malu; Kurths, Jürgen

    2016-01-01

    The spiking neural networks (SNNs) are the third generation of neural networks and perform remarkably well in cognitive tasks such as pattern recognition. The spike emitting and information processing mechanisms found in biological cognitive systems motivate the application of the hierarchical structure and temporal encoding mechanism in spiking neural networks, which have exhibited strong computational capability. However, the hierarchical structure and temporal encoding approach require neurons to process information serially in space and time respectively, which reduce the training efficiency significantly. For training the hierarchical SNNs, most existing methods are based on the traditional back-propagation algorithm, inheriting its drawbacks of the gradient diffusion and the sensitivity on parameters. To keep the powerful computation capability of the hierarchical structure and temporal encoding mechanism, but to overcome the low efficiency of the existing algorithms, a new training algorithm, the Normalized Spiking Error Back Propagation (NSEBP) is proposed in this paper. In the feedforward calculation, the output spike times are calculated by solving the quadratic function in the spike response model instead of detecting postsynaptic voltage states at all time points in traditional algorithms. Besides, in the feedback weight modification, the computational error is propagated to previous layers by the presynaptic spike jitter instead of the gradient decent rule, which realizes the layer-wised training. Furthermore, our algorithm investigates the mathematical relation between the weight variation and voltage error change, which makes the normalization in the weight modification applicable. Adopting these strategies, our algorithm outperforms the traditional SNN multi-layer algorithms in terms of learning efficiency and parameter sensitivity, that are also demonstrated by the comprehensive experimental results in this paper.

  19. Dual roles for spike signaling in cortical neural populations

    Directory of Open Access Journals (Sweden)

    Dana eBallard

    2011-06-01

    Full Text Available A prominent feature of signaling in cortical neurons is that of randomness in the action potential. The output of a typical pyramidal cell can be well fit with a Poisson model, and variations in the Poisson rate repeatedly have been shown to be correlated with stimuli. However while the rate provides a very useful characterization of neural spike data, it may not be the most fundamental description of the signaling code. Recent data showing γ frequency range multi-cell action potential correlations, together with spike timing dependent plasticity, are spurring a re-examination of the classical model, since precise timing codes imply that the generation of spikes is essentially deterministic. Could the observed Poisson randomness and timing determinism reflect two separate modes of communication, or do they somehow derive from a single process? We investigate in a timing-based model whether the apparent incompatibility between these probabilistic and deterministic observations may be resolved by examining how spikes could be used in the underlying neural circuits. The crucial component of this model draws on dual roles for spike signaling. In learning receptive fields from ensembles of inputs, spikes need to behave probabilistically, whereas for fast signaling of individual stimuli, the spikes need to behave deterministically. Our simulations show that this combination is possible if deterministic signals using γ latency coding are probabilistically routed through different members of a cortical cell population at different times. This model exhibits standard features characteristic of Poisson models such as orientation tuning post-stimulus histograms and exponential interval histograms. In addition it makes testable predictions that follow from the γ latency coding.

  20. Responsive linear-dendritic block copolymers.

    Science.gov (United States)

    Blasco, Eva; Piñol, Milagros; Oriol, Luis

    2014-06-01

    The combination of dendritic and linear polymeric structures in the same macromolecule opens up new possibilities for the design of block copolymers and for applications of functional polymers that have self-assembly properties. There are three main strategies for the synthesis of linear-dendritic block copolymers (LDBCs) and, in particular, the emergence of click chemistry has made the coupling of preformed blocks one of the most efficient ways of obtaining libraries of LDBCs. In these materials, the periphery of the dendron can be precisely functionalised to obtain functional LDBCs with self-assembly properties of interest in different technological areas. The incorporation of stimuli-responsive moieties gives rise to smart materials that are generally processed as self-assemblies of amphiphilic LDBCs with a morphology that can be controlled by an external stimulus. Particular emphasis is placed on light-responsive LDBCs. Furthermore, a brief review of the biomedical or materials science applications of LDBCs is presented. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Analyzing dendritic growth in a population of immature neurons in the adult dentate gyrus using laminar quantification of disjointed dendrites

    Directory of Open Access Journals (Sweden)

    Shira eRosenzweig

    2011-03-01

    Full Text Available In the dentate gyrus of the hippocampus, new granule neurons are continuously produced throughout adult life. A prerequisite for the successful synaptic integration of these neurons is the sprouting and extension of dendrites into the molecular layer of the dentate gyrus. Thus, studies aimed at investigating the developmental stages of adult neurogenesis often use dendritic growth as an important indicator of neuronal health and maturity. Based on the known topography of the dentate gyrus, characterized by distinct laminar arrangement of granule neurons and their extensions, we have developed a new method for analysis of dendritic growth in immature adult-born granule neurons. The method is comprised of laminar quantification of cell bodies, primary, secondary and tertiary dendrites separately and independently from each other. In contrast to most existing methods, laminar quantification of dendrites does not require the use of exogenous markers and does not involve arbitrary selection of individual neurons. The new method relies on immonuhistochemical detection of endogenous markers such as doublecortin to perform a comprehensive analysis of a sub-population of immature neurons. Disjointed, orphan dendrites that often appear in the thin histological sections are taken into account. Using several experimental groups of rats and mice, we demonstrate here the suitable techniques for quantifying neurons and dendrites, and explain how the ratios between the quantified values can be used in a comparative analysis to indicate variations in dendritic growth and complexity.

  2. GABAergic activities control spike timing- and frequency-dependent long-term depression at hippocampal excitatory synapses

    Directory of Open Access Journals (Sweden)

    Makoto Nishiyama

    2010-06-01

    Full Text Available GABAergic interneuronal network activities in the hippocampus control a variety of neural functions, including learning and memory, by regulating θ and γ oscillations. How these GABAergic activities at pre- and post-synaptic sites of hippocampal CA1 pyramidal cells differentially contribute to synaptic function and plasticity during their repetitive pre- and post-synaptic spiking at θ and γ oscillations is largely unknown. We show here that activities mediated by postsynaptic GABAARs and presynaptic GABABRs determine, respectively, the spike timing- and frequency-dependence of activity-induced synaptic modifications at Schaffer collateral-CA1 excitatory synapses. We demonstrate that both feedforward and feedback GABAAR-mediated inhibition in the postsynaptic cell controls the spike timing-dependent long-term depression of excitatory inputs (“e-LTD” at the θ frequency. We also show that feedback postsynaptic inhibition specifically causes e-LTD of inputs that induce small postsynaptic currents (<70 pA with LTP timing, thus enforcing the requirement of cooperativity for induction of long-term potentiation at excitatory inputs (“e-LTP”. Furthermore, under spike-timing protocols that induce e-LTP and e-LTD at excitatory synapses, we observed parallel induction of LTP and LTD at inhibitory inputs (“i-LTP” and “i-LTD” to the same postsynaptic cells. Finally, we show that presynaptic GABABR-mediated inhibition plays a major role in the induction of frequency-dependent e-LTD at α and β frequencies. These observations demonstrate the critical influence of GABAergic interneuronal network activities in regulating the spike timing and frequency dependences of long-term synaptic modifications in the hippocampus.

  3. A metric space approach to the information capacity of spike trains

    OpenAIRE

    HOUGHTON, CONOR JAMES; GILLESPIE, JAMES

    2010-01-01

    PUBLISHED Classical information theory can be either discrete or continuous, corresponding to discrete or continuous random variables. However, although spike times in a spike train are described by continuous variables, the information content is usually calculated using discrete information theory. This is because the number of spikes, and hence, the number of variables, varies from spike train to spike train, making the continuous theory difficult to apply.It is possible to avoid ...

  4. A defined network of fast-spiking interneurons in orbitofrontal cortex: responses to behavioral contingencies and ketamine administration

    Directory of Open Access Journals (Sweden)

    Michael C Quirk

    2009-11-01

    Full Text Available Orbitofrontal cortex (OFC is a region of prefrontal cortex implicated in the motivational control of behavior and in related abnormalities seen in psychosis and depression. It has been hypothesized that a critical mechanism in these disorders is the dysfunction of GABAergic interneurons that normally regulate prefrontal information processing. Here, we studied a subclass of interneurons isolated in rat OFC using extracellular waveform and spike train analysis. During performance of a goal-directed behavioral task, the firing of this class of putative fast-spiking (FS interneurons showed robust temporal correlations indicative of a functionally coherent network. FS cell activity also co-varied with behavioral response latency, a key indicator of motivational state. Systemic administration of ketamine, a drug that can mimic psychosis, preferentially inhibited this cell class. Together, these results support the idea that OFC-FS interneurons form a critical link in the regulation of motivation by prefrontal circuits during normal and abnormal brain and behavioral states.

  5. The Gαo Activator Mastoparan-7 Promotes Dendritic Spine Formation in Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Valerie T. Ramírez

    2016-01-01

    Full Text Available Mastoparan-7 (Mas-7, an analogue of the peptide mastoparan, which is derived from wasp venom, is a direct activator of Pertussis toxin- (PTX- sensitive G proteins. Mas-7 produces several biological effects in different cell types; however, little is known about how Mas-7 influences mature hippocampal neurons. We examined the specific role of Mas-7 in the development of dendritic spines, the sites of excitatory synaptic contact that are crucial for synaptic plasticity. We report here that exposure of hippocampal neurons to a low dose of Mas-7 increases dendritic spine density and spine head width in a time-dependent manner. Additionally, Mas-7 enhances postsynaptic density protein-95 (PSD-95 clustering in neurites and activates Gαo signaling, increasing the intracellular Ca2+ concentration. To define the role of signaling intermediates, we measured the levels of phosphorylated protein kinase C (PKC, c-Jun N-terminal kinase (JNK, and calcium-calmodulin dependent protein kinase IIα (CaMKIIα after Mas-7 treatment and determined that CaMKII activation is necessary for the Mas-7-dependent increase in dendritic spine density. Our results demonstrate a critical role for Gαo subunit signaling in the regulation of synapse formation.

  6. Transcriptional Changes during Naturally Acquired Zika Virus Infection Render Dendritic Cells Highly Conducive to Viral Replication.

    Science.gov (United States)

    Sun, Xiaoming; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Einkauf, Kevin; Tse, Samantha; Ard, Kevin; Ciaranello, Andrea; Yawetz, Sigal; Sax, Paul; Rosenberg, Eric S; Lichterfeld, Mathias; Yu, Xu G

    2017-12-19

    Although dendritic cells are among the human cell population best equipped for cell-intrinsic antiviral immune defense, they seem highly susceptible to infection with the Zika virus (ZIKV). Using highly purified myeloid dendritic cells isolated from individuals with naturally acquired acute infection, we here show that ZIKV induces profound perturbations of transcriptional signatures relative to healthy donors. Interestingly, we noted a remarkable downregulation of antiviral interferon-stimulated genes and innate immune sensors, suggesting that ZIKV can actively suppress interferon-dependent immune responses. In contrast, several host factors known to support ZIKV infection were strongly upregulated during natural ZIKV infection; these transcripts included AXL, the main entry receptor for ZIKV; SOCS3, a negative regulator of ISG expression; and IDO-1, a recognized inducer of regulatory T cell responses. Thus, during in vivo infection, ZIKV can transform the transcriptome of dendritic cells in favor of the virus to render these cells highly conducive to ZIKV infection. Published by Elsevier Inc.

  7. In vivo dendritic cell depletion reduces breeding efficiency, affecting implantation and early placental development in mice.

    Science.gov (United States)

    Krey, Gesa; Frank, Pierre; Shaikly, Valerie; Barrientos, Gabriela; Cordo-Russo, Rosalia; Ringel, Frauke; Moschansky, Petra; Chernukhin, Igor V; Metodiev, Metodi; Fernández, Nelson; Klapp, Burghard F; Arck, Petra C; Blois, Sandra M

    2008-09-01

    Implantation of mammalian embryos into their mother's uterus ensures optimal nourishment and protection throughout development. Complex molecular interactions characterize the implantation process, and an optimal synchronization of the components of this embryo-maternal dialogue is crucial for a successful reproductive outcome. In the present study, we investigated the role of dendritic cells (DC) during implantation process using a transgenic mouse system (DTRtg) that allows transient depletion of CD11c+ cells in vivo through administration of diphtheria toxin. We observed that DC depletion impairs the implantation process, resulting in a reduced breeding efficiency. Furthermore, the maturity of uterine natural killer cells at dendritic cell knockout (DCKO) implantation sites was affected as well; as demonstrated by decreased perforin expression and reduced numbers of periodic-acid-Schiff (PAS)-positive cells. This was accompanied by disarrangements in decidual vascular development. In the present study, we were also able to identify a novel DC-dependent protein, phosphatidylinositol transfer protein beta (PITPbeta), involved in implantation and trophoblast development using a proteomic approach. Indeed, DCKO mice exhibited substantial anomalies in placental development, including hypocellularity of the spongiotrophoblast and labyrinthine layers and reduced numbers of trophoblast giant cells. Giant cells also down-regulated their expression of two characteristic markers of trophoblast differentiation, placental lactogen 1 and proliferin. In view of these findings, dendritic cells emerge as possible modulators in the orchestration of events leading to the establishment and maintenance of pregnancy.

  8. Midkine inhibits inducible regulatory T cell differentiation by suppressing the development of tolerogenic dendritic cells.

    Science.gov (United States)

    Sonobe, Yoshifumi; Li, Hua; Jin, Shijie; Kishida, Satoshi; Kadomatsu, Kenji; Takeuchi, Hideyuki; Mizuno, Tetsuya; Suzumura, Akio

    2012-03-15

    Midkine (MK), a heparin-binding growth factor, reportedly contributes to inflammatory diseases, including Crohn's disease and rheumatoid arthritis. We previously showed that MK aggravates experimental autoimmune encephalomyelitis (EAE) by decreasing regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs), a population that regulates the development of autoimmune responses, although the precise mechanism remains uncertain. In this article, we show that MK produced in inflammatory conditions suppresses the development of tolerogenic dendritic cells (DCregs), which drive the development of inducible Treg. MK suppressed DCreg-mediated expansion of the CD4(+)CD25(+)Foxp3(+) Treg population. DCregs expressed significantly higher levels of CD45RB and produced significantly less IL-12 compared with conventional dendritic cells. However, MK downregulated CD45RB expression and induced IL-12 production by reducing phosphorylated STAT3 levels via src homology region 2 domain-containing phosphatase-2 in DCreg. Inhibiting MK activity with anti-MK RNA aptamers, which bind to the targeted protein to suppress the function of the protein, increased the numbers of CD11c(low)CD45RB(+) dendritic cells and Tregs in the draining lymph nodes and suppressed the severity of EAE, an animal model of multiple sclerosis. Our results also demonstrated that MK was produced by inflammatory cells, in particular, CD4(+) T cells under inflammatory conditions. Taken together, these results suggest that MK aggravates EAE by suppressing DCreg development, thereby impairing the Treg population. Thus, MK is a promising therapeutic target for various autoimmune diseases.

  9. Noise-enhanced coding in phasic neuron spike trains.

    Science.gov (United States)

    Ly, Cheng; Doiron, Brent

    2017-01-01

    The stochastic nature of neuronal response has lead to conjectures about the impact of input fluctuations on the neural coding. For the most part, low pass membrane integration and spike threshold dynamics have been the primary features assumed in the transfer from synaptic input to output spiking. Phasic neurons are a common, but understudied, neuron class that are characterized by a subthreshold negative feedback that suppresses spike train responses to low frequency signals. Past work has shown that when a low frequency signal is accompanied by moderate intensity broadband noise, phasic neurons spike trains are well locked to the signal. We extend these results with a simple, reduced model of phasic activity that demonstrates that a non-Markovian spike train structure caused by the negative feedback produces a noise-enhanced coding. Further, this enhancement is sensitive to the timescales, as opposed to the intensity, of a driving signal. Reduced hazard function models show that noise-enhanced phasic codes are both novel and separate from classical stochastic resonance reported in non-phasic neurons. The general features of our theory suggest that noise-enhanced codes in excitable systems with subthreshold negative feedback are a particularly rich framework to study.

  10. Spike morphology in blast-wave-driven instability experiments

    International Nuclear Information System (INIS)

    Kuranz, C. C.; Drake, R. P.; Grosskopf, M. J.; Fryxell, B.; Budde, A.; Hansen, J. F.; Miles, A. R.; Plewa, T.; Hearn, N.; Knauer, J.

    2010-01-01

    The laboratory experiments described in the present paper observe the blast-wave-driven Rayleigh-Taylor instability with three-dimensional (3D) initial conditions. About 5 kJ of energy from the Omega laser creates conditions similar to those of the He-H interface during the explosion phase of a supernova. The experimental target is a 150 μm thick plastic disk followed by a low-density foam. The plastic piece has an embedded, 3D perturbation. The basic structure of the pattern is two orthogonal sine waves where each sine wave has an amplitude of 2.5 μm and a wavelength of 71 μm. In some experiments, an additional wavelength is added to explore the interaction of modes. In experiments with 3D initial conditions the spike morphology differs from what has been observed in other Rayleigh-Taylor experiments and simulations. Under certain conditions, experimental radiographs show some mass extending from the interface to the shock front. Current simulations show neither the spike morphology nor the spike penetration observed in the experiments. The amount of mass reaching the shock front is analyzed and potential causes for the spike morphology and the spikes reaching the shock are discussed. One such hypothesis is that these phenomena may be caused by magnetic pressure, generated by an azimuthal magnetic field produced by the plasma dynamics.

  11. Financial time series prediction using spiking neural networks.

    Science.gov (United States)

    Reid, David; Hussain, Abir Jaafar; Tawfik, Hissam

    2014-01-01

    In this paper a novel application of a particular type of spiking neural network, a Polychronous Spiking Network, was used for financial time series prediction. It is argued that the inherent temporal capabilities of this type of network are suited to non-stationary data such as this. The performance of the spiking neural network was benchmarked against three systems: two "traditional", rate-encoded, neural networks; a Multi-Layer Perceptron neural network and a Dynamic Ridge Polynomial neural network, and a standard Linear Predictor Coefficients model. For this comparison three non-stationary and noisy time series were used: IBM stock data; US/Euro exchange rate data, and the price of Brent crude oil. The experiments demonstrated favourable prediction results for the Spiking Neural Network in terms of Annualised Return and prediction error for 5-Step ahead predictions. These results were also supported by other relevant metrics such as Maximum Drawdown and Signal-To-Noise ratio. This work demonstrated the applicability of the Polychronous Spiking Network to financial data forecasting and this in turn indicates the potential of using such networks over traditional systems in difficult to manage non-stationary environments.

  12. Multiplexed Spike Coding and Adaptation in the Thalamus

    Directory of Open Access Journals (Sweden)

    Rebecca A. Mease

    2017-05-01

    Full Text Available High-frequency “burst” clusters of spikes are a generic output pattern of many neurons. While bursting is a ubiquitous computational feature of different nervous systems across animal species, the encoding of synaptic inputs by bursts is not well understood. We find that bursting neurons in the rodent thalamus employ “multiplexing” to differentially encode low- and high-frequency stimulus features associated with either T-type calcium “low-threshold” or fast sodium spiking events, respectively, and these events adapt differently. Thus, thalamic bursts encode disparate information in three channels: (1 burst size, (2 burst onset time, and (3 precise spike timing within bursts. Strikingly, this latter “intraburst” encoding channel shows millisecond-level feature selectivity and adapts across statistical contexts to maintain stable information encoded per spike. Consequently, calcium events both encode low-frequency stimuli and, in parallel, gate a transient window for high-frequency, adaptive stimulus encoding by sodium spike timing, allowing bursts to efficiently convey fine-scale temporal information.

  13. Scaling of spiking and humping in keyhole welding

    Energy Technology Data Exchange (ETDEWEB)

    Wei, P S; Chuang, K C [Department of Mechanical and Electro-Mechanical Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan (China); DebRoy, T [Department of Materials Science and Engineering, The Pennsylvania State University, University Park, PA 16802 (United States); Ku, J S, E-mail: pswei@mail.nsysu.edu.tw, E-mail: cielo.zhuang@gmail.com, E-mail: rtd1@psu.edu, E-mail: jsku@mail.nsysu.edu.tw [Institute of Materials Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan (China)

    2011-06-22

    Spiking, rippling and humping seriously reduce the strength of welds. The effects of beam focusing, volatile alloying element concentration and welding velocity on spiking, coarse rippling and humping in keyhole mode electron-beam welding are examined through scale analysis. Although these defects have been studied in the past, the mechanisms for their formation are not fully understood. This work relates the average amplitudes of spikes to fusion zone depth for the welding of Al 6061, SS 304 and carbon steel, and Al 5083. The scale analysis introduces welding and melting efficiencies and an appropriate power distribution to account for the focusing effects, and the energy which is reflected and escapes through the keyhole opening to the surroundings. The frequency of humping and spiking can also be predicted from the scale analysis. The analysis also reveals the interrelation between coarse rippling and humping. The data and the mechanistic findings reported in this study are useful for understanding and preventing spiking and humping during keyhole mode electron and laser beam welding.

  14. Neural Spike Train Synchronisation Indices: Definitions, Interpretations and Applications.