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Sample records for mossy fiber synapses

  1. Extracellular proteolysis in structural and functional plasticity of mossy fiber synapses in hippocampus

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    Grzegorz eWiera

    2015-11-01

    Full Text Available Brain is continuously altered in response to experience and environmental changes. One of the underlying mechanisms is synaptic plasticity, which is manifested by modification of synapse structure and function. It is becoming clear that regulated extracellular proteolysis plays a pivotal role in the structural and functional remodeling of synapses during brain development, learning and memory formation. Clearly, plasticity mechanisms may substantially differ between projections. Mossy fiber synapses onto CA3 pyramidal cells display several unique functional features, including pronounced short-term facilitation, a presynaptically expressed LTP that is independent of NMDAR activation, and NMDA-dependent metaplasticity. Moreover, structural plasticity at mossy fiber synapses ranges from the reorganization of projection topology after hippocampus-dependent learning, through intrinsically different dynamic properties of synaptic boutons to pre- and postsynaptic structural changes accompanying LTP induction. Although concomitant functional and structural plasticity in this pathway strongly suggests a role of extracellular proteolysis, its impact only starts to be investigated in this projection. In the present report, we review the role of extracellular proteolysis in various aspects of synaptic plasticity in hippocampal mossy fiber synapses. A growing body of evidence demonstrates that among perisynaptic proteases, tPA/plasmin system, β-site amyloid precursor protein-cleaving enzyme 1 (BACE1 and metalloproteinases play a crucial role in shaping plastic changes in this projection. We discuss recent advances and emerging hypotheses on the roles of proteases in mechanisms underlying mossy fiber target specific synaptic plasticity and memory formation.

  2. Stability and Function of Hippocampal Mossy Fiber Synapses Depend on Bcl11b/Ctip2

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    Elodie De Bruyckere

    2018-04-01

    Full Text Available Structural and functional plasticity of synapses are critical neuronal mechanisms underlying learning and memory. While activity-dependent regulation of synaptic strength has been extensively studied, much less is known about the transcriptional control of synapse maintenance and plasticity. Hippocampal mossy fiber (MF synapses connect dentate granule cells to CA3 pyramidal neurons and are important for spatial memory formation and consolidation. The transcription factor Bcl11b/Ctip2 is expressed in dentate granule cells and required for postnatal hippocampal development. Ablation of Bcl11b/Ctip2 in the adult hippocampus results in impaired adult neurogenesis and spatial memory. The molecular mechanisms underlying the behavioral impairment remained unclear. Here we show that selective deletion of Bcl11b/Ctip2 in the adult mouse hippocampus leads to a rapid loss of excitatory synapses in CA3 as well as reduced ultrastructural complexity of remaining mossy fiber boutons (MFBs. Moreover, a dramatic decline of long-term potentiation (LTP of the dentate gyrus-CA3 (DG-CA3 projection is caused by adult loss of Bcl11b/Ctip2. Differential transcriptomics revealed the deregulation of genes associated with synaptic transmission in mutants. Together, our data suggest Bcl11b/Ctip2 to regulate maintenance and function of MF synapses in the adult hippocampus.

  3. NeuroD2 regulates the development of hippocampal mossy fiber synapses

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    Wilke Scott A

    2012-02-01

    Full Text Available Abstract Background The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF synapse. Results Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice. Conclusion These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.

  4. Specific Disruption of Hippocampal Mossy Fiber Synapses in a Mouse Model of Familial Alzheimer's Disease

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    Wilke, Scott A.; Raam, Tara; Antonios, Joseph K.; Bushong, Eric A.; Koo, Edward H.; Ellisman, Mark H.; Ghosh, Anirvan

    2014-01-01

    The earliest stages of Alzheimer's disease (AD) are characterized by deficits in memory and cognition indicating hippocampal pathology. While it is now recognized that synapse dysfunction precedes the hallmark pathological findings of AD, it is unclear if specific hippocampal synapses are particularly vulnerable. Since the mossy fiber (MF) synapse between dentate gyrus (DG) and CA3 regions underlies critical functions disrupted in AD, we utilized serial block-face electron microscopy (SBEM) to analyze MF microcircuitry in a mouse model of familial Alzheimer's disease (FAD). FAD mutant MF terminal complexes were severely disrupted compared to control – they were smaller, contacted fewer postsynaptic spines and had greater numbers of presynaptic filopodial processes. Multi-headed CA3 dendritic spines in the FAD mutant condition were reduced in complexity and had significantly smaller sites of synaptic contact. Significantly, there was no change in the volume of classical dendritic spines at neighboring inputs to CA3 neurons suggesting input-specific defects in the early course of AD related pathology. These data indicate a specific vulnerability of the DG-CA3 network in AD pathogenesis and demonstrate the utility of SBEM to assess circuit specific alterations in mouse models of human disease. PMID:24454724

  5. Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells.

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    Villanueva-Castillo, Cindy; Tecuatl, Carolina; Herrera-López, Gabriel; Galván, Emilio J

    2017-01-01

    The network interaction between the dentate gyrus and area CA3 of the hippocampus is responsible for pattern separation, a process that underlies the formation of new memories, and which is naturally diminished in the aged brain. At the cellular level, aging is accompanied by a progression of biochemical modifications that ultimately affects its ability to generate and consolidate long-term potentiation. Although the synapse between dentate gyrus via the mossy fibers (MFs) onto CA3 neurons has been subject of extensive studies, the question of how aging affects the MF-CA3 synapse is still unsolved. Extracellular and whole-cell recordings from acute hippocampal slices of aged Wistar rats (34 ± 2 months old) show that aging is accompanied by a reduction in the interneuron-mediated inhibitory mechanisms of area CA3. Several MF-mediated forms of short-term plasticity, MF long-term potentiation and at least one of the critical signaling cascades necessary for potentiation are also compromised in the aged brain. An analysis of the spontaneous glutamatergic and gamma-aminobutyric acid-mediated currents on CA3 cells reveal a dramatic alteration in amplitude and frequency of the nonevoked events. CA3 cells also exhibited increased intrinsic excitability. Together, these results demonstrate that aging is accompanied by a decrease in the GABAergic inhibition, reduced expression of short- and long-term forms of synaptic plasticity, and increased intrinsic excitability. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The dentate mossy fibers

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    Blaabjerg, Morten; Zimmer, Jens

    2007-01-01

    Hippocampal mossy fibers are the axons of the dentate granule cells and project to hippocampal CA3 pyramidal cells and mossy cells of the dentate hilus (CA4) as well as a number of interneurons in the two areas. Besides their role in hippocampal function, studies of which are still evolving...

  7. Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse.

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    Huang, Yang Z; Pan, Enhui; Xiong, Zhi-Qi; McNamara, James O

    2008-02-28

    The receptor tyrosine kinase, TrkB, is critical to diverse functions of the mammalian nervous system in health and disease. Evidence of TrkB activation during epileptogenesis in vivo despite genetic deletion of its prototypic neurotrophin ligands led us to hypothesize that a non-neurotrophin, the divalent cation zinc, can transactivate TrkB. We found that zinc activates TrkB through increasing Src family kinase activity by an activity-regulated mechanism independent of neurotrophins. One subcellular locale at which zinc activates TrkB is the postsynaptic density of excitatory synapses. Exogenous zinc potentiates the efficacy of the hippocampal mossy fiber (mf)-CA3 pyramid synapse by a TrkB-requiring mechanism. Long-term potentiation of this synapse is impaired by deletion of TrkB, inhibition of TrkB kinase activity, and by CaEDTA, a selective chelator of zinc. The activity-dependent activation of synaptic TrkB in a neurotrophin-independent manner provides a mechanism by which this receptor can regulate synaptic plasticity.

  8. β-Secretase BACE1 Promotes Surface Expression and Function of Kv3.4 at Hippocampal Mossy Fiber Synapses.

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    Hartmann, Stephanie; Zheng, Fang; Kyncl, Michele C; Karch, Sandra; Voelkl, Kerstin; Zott, Benedikt; D'Avanzo, Carla; Lomoio, Selene; Tesco, Giuseppina; Kim, Doo Y; Alzheimer, Christian; Huth, Tobias

    2018-04-04

    The β-secretase β-site APP-cleaving enzyme 1 (BACE1) is deemed a major culprit in Alzheimer's disease, but accumulating evidence indicates that there is more to the enzyme than driving the amyloidogenic processing of the amyloid precursor protein. For example, BACE1 has emerged as an important regulator of neuronal activity through proteolytic and, most unexpectedly, also through nonproteolytic interactions with several ion channels. Here, we identify and characterize the voltage-gated K + channel 3.4 (Kv3.4) as a new and functionally relevant interaction partner of BACE1. Kv3.4 gives rise to A-type current with fast activating and inactivating kinetics and serves to repolarize the presynaptic action potential. We found that BACE1 and Kv3.4 are highly enriched and remarkably colocalized in hippocampal mossy fibers (MFs). In BACE1 -/- mice of either sex, Kv3.4 surface expression was significantly reduced in the hippocampus and, in synaptic fractions thereof, Kv3.4 was specifically diminished, whereas protein levels of other presynaptic K + channels such as K Ca 1.1 and K Ca 2.3 remained unchanged. The apparent loss of presynaptic Kv3.4 affected the strength of excitatory transmission at the MF-CA3 synapse in hippocampal slices of BACE1 -/- mice when probed with the Kv3 channel blocker BDS-I. The effect of BACE1 on Kv3.4 expression and function should be bidirectional, as predicted from a heterologous expression system, in which BACE1 cotransfection produced a concomitant upregulation of Kv3.4 surface level and current based on a physical interaction between the two proteins. Our data show that, by targeting Kv3.4 to presynaptic sites, BACE1 endows the terminal with a powerful means to regulate the strength of transmitter release. SIGNIFICANCE STATEMENT The β-secretase β-site APP-cleaving enzyme 1 (BACE1) is infamous for its crucial role in the pathogenesis of Alzheimer's disease, but its physiological functions in the intact nervous system are only gradually

  9. Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation

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    Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano

    2018-01-01

    Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report...... pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling...... the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation....

  10. Adolescent mice show anxiety- and aggressive-like behavior and the reduction of long-term potentiation in mossy fiber-CA3 synapses after neonatal maternal separation.

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    Shin, S Y; Han, S H; Woo, R-S; Jang, S H; Min, S S

    2016-03-01

    Exposure to maternal separation (MS) during early life is an identified risk factor for emotional disorders such as anxiety and depression later in life. This study investigated the effects of neonatal MS on the behavior and long-term potentiation (LTP) as well as basic synaptic transmission at hippocampal CA3-CA1 and mossy fiber (MF)-CA3 synapses in adolescent mice for 19days. When mice were adolescents, we measured depression, learning, memory, anxious and aggressive behavior using the forced swimming test (FST), Y-maze, Morris water maze (MWM), elevated plus maze (EPM), three consecutive days of the open field test, the social interaction test, the tube-dominance test and the resident-intruder test. The results showed that there was no difference in FST, Y-maze, and MWM performance. However, MS mice showed more anxiety-like behavior in the EPM test and aggressive-like behavior in the tube-dominance and resident-intruder tests. In addition, the magnitude of LTP and release probability in the MF-CA3 synapses was reduced in the MS group but not in the CA3-CA1 synapse. Our results indicate that early life stress due to MS may induce anxiety- and aggressive-like behavior during adolescence, and these effects are associated with synaptic plasticity at the hippocampal MF-CA3 synapses. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation.

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    Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano; Alviña, Karina; Zhang, Yuxiang; Dushko, Margaret; Ku, Taeyun; Zemoura, Khaled; Rich, David; Garcia-Dominguez, Dario; Hung, Matthew; Yelhekar, Tushar D; Sørensen, Andreas Toft; Xu, Weifeng; Chung, Kwanghun; Castillo, Pablo E; Lin, Yingxi

    2018-03-07

    Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Response of hippocampal mossy fiber zinc to excessive glutamate release.

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    Takeda, Atsushi; Minami, Akira; Sakurada, Naomi; Nakajima, Satoko; Oku, Naoto

    2007-01-01

    The response of hippocampal mossy fiber zinc to excessive glutamate release was examined to understand the role of the zinc in excessive excitation in the hippocampus. Extracellular zinc and glutamate concentrations during excessive stimulation with high K(+) were compared between the hippocampal CA3 and CA1 by the in vivo microdialysis. Zinc concentration in the CA3 was more increased than that in the CA1, while glutamate concentration in the CA3 was less increased than that in the CA1. It is likely that more increase in extracellular zinc is linked with less increase in extracellular glutamate in the CA3. To see zinc action in mossy fiber synapses during excessive excitation, furthermore, 1mM glutamate was regionally delivered to the stratum lucidum in the presence of zinc or CaEDTA, a membrane-impermeable zinc chelator, and intracellular calcium signal was measured in the CA3 pyramidal cell layer. The persistent increase in calcium signal during stimulation with glutamate was significantly attenuated in the presence of 100 microM zinc, while significantly enhanced in the presence of 1mM CaEDTA. These results suggest that zinc released from mossy fibers attenuates the increase in intracellular calcium signal in mossy fiber synapses and postsynaptic CA3 neurons after excessive inputs to dentate granular cells.

  13. Attenuation of hippocampal mossy fiber long-term potentiation by low micromolar concentrations of zinc.

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    Takeda, Atsushi; Kanno, Shingo; Sakurada, Naomi; Ando, Masaki; Oku, Naoto

    2008-10-01

    The role of zinc in long-term potentiation (LTP) at hippocampal mossy fiber synapses is controversial because of the contrary results obtained when using zinc chelators. On the basis of the postulation that exogenous zinc enhances the action of zinc released from mossy fibers, mossy fiber LTP after tetanic stimulation (100 Hz, 1 sec) was checked in the presence of exogenous zinc at low micromolar concentrations. Mossy fiber LTP was significantly attenuated in the presence of 5-30 microM ZnCl(2), and the amplitude of field excitatory postsynaptic potentials 60 min after tetanic stimulation was decreased to almost the basal level. Mossy fiber LTP was also attenuated in the presence of 5 microM ZnCl(2) 5 min after tetanic stimulation. The present study is the first to demonstrate that low micromolar concentrations of zinc attenuate mossy fiber LTP. When mossy fiber LTP was induced in the presence of CaEDTA and ZnAF-2 DA, a membrane-impermeable and a membrane-permeable zinc chelator, respectively, extracellular and intracellular chelation of zinc enhanced a transient posttetanic potentiation (PTP) without altering LTP. It is likely that zinc released by tetanic stimulation is immediately taken up into the mossy fibers and attenuates mossy fiber PTP. These results suggest that attenuation of PTP rather than LTP at mossy fiber synapses is a more physiological role for endogenous zinc. Targeting molecules of zinc in mossy fiber LTP seem to be different between during and after LTP induction because of the differential synaptic activity between them. (c) 2008 Wiley-Liss, Inc.

  14. Dopamine D1/D5, but not D2/D3, receptor dependency of synaptic plasticity at hippocampal mossy fiber synapses that is enabled by patterned afferent stimulation, or spatial learning

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    Hardy Hagena

    2016-09-01

    Full Text Available Although the mossy fiber (MF synapses of the hippocampal CA3 region display quite distinct properties in terms of the molecular mechanisms that underlie synaptic plasticity, they nonetheless exhibit persistent (>24h synaptic plasticity that is akin to that observed at the Schaffer collateral (SCH-CA1 and perforant path (PP-dentate gyrus (DG synapses of freely behaving rats. In addition, they also respond to novel spatial learning with very enduring forms of long-term potentiation (LTP and long-term depression (LTD. These latter forms of synaptic plasticity are directly related to the learning behavior: novel exploration of generalized changes in space facilitates the expression of LTP at MF-CA3 synapses, whereas exploration of novel configurations of large environmental features facilitates the expression of LTD. In the absence of spatial novelty, synaptic plasticity is not expressed. Motivation is a potent determinant of whether learning about spatial experience effectively occurs and the neuromodulator dopamine plays a key role in motivation-based learning. Prior research on the regulation by dopamine receptors of long-term synaptic plasticity in CA1 and dentate gyrus synapses in vivo suggests that whereas D2/D3 receptors may modulate a general predisposition toward expressing plasticity, D1/D5 receptors may directly regulate the direction of change in synaptic strength that occurs during learning. Although the CA3 region is believed to play a pivotal role in many forms of learning, the role of these receptors in persistent (>24h forms of synaptic plasticity at MF-CA3 synapses is unknown. Here, we report that whereas pharmacological antagonism of D2/D3 receptors had no impact on LTP or LTD, antagonism of D1/D5 receptors significantly impaired LTP and LTD that were induced by solely by means of patterned afferent stimulation, or LTP/LTD that are typically enhanced by the conjunction of afferent stimulation and novel spatial learning. These data

  15. Enhancement of hippocampal mossy fiber activity in zinc deficiency and its influence on behavior.

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    Takeda, Atsushi; Itoh, Hiromasa; Yamada, Kohei; Tamano, Haruna; Oku, Naoto

    2008-10-01

    The extracellular concentration of glutamate in the hippocampus is increased by hippocampal perfusion with CaEDTA, a membrane-impermeable zinc chelator, suggesting that the activity of glutamatergic neurons in the hippocampus are influenced by the extracellular concentrations of zinc. In the present study, the relationship between the extracellular concentrations of zinc and mossy fiber activity in the hippocampus was examined in mice and rats fed a zinc-deficient diet for 4 weeks. Timm's stain, by which histochemically reactive zinc in the presynaptic vesicles is detected, was attenuated in the hippocampus in zinc deficiency. The extracellular signal of ZnAF-2, a membrane-impermeable zinc indicator, was also lower in the hippocampal CA3, suggesting that the basal extracellular concentrations of zinc are lower maintained in zinc deficiency. To check mossy fiber activity after 4-week zinc deprivation, the decrease in the signal of FM4-64, an indicator of presynaptic activity (exocytosis), at mossy fiber synapses was measured under the condition of spontaneous depolarization. The decrease was significantly facilitated by zinc deficiency, suggesting that the basal exocytosis at mossy fiber synapses is enhanced by zinc deficiency. On the other hand, the increase in anxiety-like behavior was observed in the open-field test after 4-week zinc deprivation. The present study demonstrates that the decrease in the basal extracellular concentrations of zinc may be linked to the enhancement of the basal mossy fiber activity in zinc deficiency. This decrease seems to be also involved in neuropsychological behavior in zinc deficiency.

  16. Facilitation of granule cell epileptiform activity by mossy fiber-released zinc in the pilocarpine model of temporal lobe epilepsy.

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    Timofeeva, Olga; Nadler, J Victor

    2006-03-17

    Recurrent mossy fiber synapses in the dentate gyrus of epileptic brain facilitate the synchronous firing of granule cells and may promote seizure propagation. Mossy fiber terminals contain and release zinc. Released zinc inhibits the activation of NMDA receptors and may therefore oppose the development of granule cell epileptiform activity. Hippocampal slices from rats that had experienced pilocarpine-induced status epilepticus and developed a recurrent mossy fiber pathway were used to investigate this possibility. Actions of released zinc were inferred from the effects of chelation with 1 mM calcium disodium EDTA (CaEDTA). When granule cell population bursts were evoked by mossy fiber stimulation in the presence of 6 mM K(+) and 30 microM bicuculline, CaEDTA slowed the rate at which evoked bursting developed, but did not change the magnitude of the bursts once they had developed fully. The effects of CaEDTA were then studied on the pharmacologically isolated NMDA receptor- and AMPA/kainate receptor-mediated components of the fully developed bursts. CaEDTA increased the magnitude of NMDA receptor-mediated bursts and reduced the magnitude of AMPA/kainate receptor-mediated bursts. CaEDTA did not affect the granule cell bursts evoked in slices from untreated rats by stimulating the perforant path in the presence of bicuculline and 6 mM K(+). These results suggest that zinc released from the recurrent mossy fibers serves mainly to facilitate the recruitment of dentate granule cells into population bursts.

  17. Activity-dependent control of NMDA receptor subunit composition at hippocampal mossy fibre synapses.

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    Carta, Mario; Srikumar, Bettadapura N; Gorlewicz, Adam; Rebola, Nelson; Mulle, Christophe

    2018-02-15

    CA3 pyramidal cells display input-specific differences in the subunit composition of synaptic NMDA receptors (NMDARs). Although at low density, GluN2B contributes significantly to NMDAR-mediated EPSCs at mossy fibre synapses. Long-term potentiation (LTP) of NMDARs triggers a modification in the subunit composition of synaptic NMDARs by insertion of GluN2B. GluN2B subunits are essential for the expression of LTP of NMDARs at mossy fibre synapses. Single neurons express NMDA receptors (NMDARs) with distinct subunit composition and biophysical properties that can be segregated in an input-specific manner. The dynamic control of the heterogeneous distribution of synaptic NMDARs is crucial to control input-dependent synaptic integration and plasticity. In hippocampal CA3 pyramidal cells from mice of both sexes, we found that mossy fibre (MF) synapses display a markedly lower proportion of GluN2B-containing NMDARs than associative/commissural synapses. The mechanism involved in such heterogeneous distribution of GluN2B subunits is not known. Here we show that long-term potentiation (LTP) of NMDARs, which is selectively expressed at MF-CA3 pyramidal cell synapses, triggers a modification in the subunit composition of synaptic NMDARs by insertion of GluN2B. This activity-dependent recruitment of GluN2B at mature MF-CA3 pyramidal cell synapses contrasts with the removal of GluN2B subunits at other glutamatergic synapses during development and in response to activity. Furthermore, although expressed at low levels, GluN2B is necessary for the expression of LTP of NMDARs at MF-CA3 pyramidal cell synapses. Altogether, we reveal a previously unknown activity-dependent regulation and function of GluN2B subunits that may contribute to the heterogeneous plasticity induction rules in CA3 pyramidal cells. © 2017 Centre Nationnal de la Recherche Scientifique. The Journal of Physiology © 2017 The Physiological Society.

  18. Inhibition of presynaptic activity by zinc released from mossy fiber terminals during tetanic stimulation.

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    Minami, Akira; Sakurada, Naomi; Fuke, Sayuri; Kikuchi, Kazuya; Nagano, Tetsuo; Oku, Naoto; Takeda, Atsushi

    2006-01-01

    Zinc exists in high densities in the giant boutons of hippocampal mossy fibers. On the basis of the evidence that zinc decreases extracellular glutamate concentration in the hippocampus, the presynaptic action of zinc released from mossy fibers during high-frequency (tetanic) stimulation was examined using hippocampal slices. The increase in zinc-specific fluorescent signals was observed in both extracellular and intracellular compartments in the mossy fiber terminals during the delivery of tetanic stimuli (100 Hz, 1 sec) to the dentate granule cell layer, suggesting that zinc released from mossy fibers is immediately retaken up by mossy fibers. When mossy fiber terminals were preferentially double-stained with zinc and calcium indicators and tetanic stimuli (100 Hz, 1 sec) were delivered to the dentate granule cell layer, the increase in calcium orange signal during the stimulation was enhanced in mossy fiber terminals by addition of CaEDTA, a membrane-impermeable zinc chelator, and was suppressed by addition of zinc. The decrease in FM4-64 signal (vesicular exocytosis) during tetanic stimulation (10 Hz, 180 sec), which induced mossy fiber long-term potentiation, was also enhanced in mossy fiber terminals by addition of CaEDTA and was suppressed by addition of zinc. The present study demonstrates that zinc released from mossy fibers may be a negative-feedback factor against presynaptic activity during tetanic stimulation.

  19. The Molecular and Cellular Mechanisms of Axon Guidance in Mossy Fiber Sprouting

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    Ryuta Koyama

    2018-05-01

    Full Text Available The question of whether mossy fiber sprouting is epileptogenic has not been resolved; both sprouting-induced recurrent excitatory and inhibitory circuit hypotheses have been experimentally (but not fully supported. Therefore, whether mossy fiber sprouting is a potential therapeutic target for epilepsy remains under debate. Moreover, the axon guidance mechanisms of mossy fiber sprouting have attracted the interest of neuroscientists. Sprouting of mossy fibers exhibits several uncommon axonal growth features in the basically non-plastic adult brain. For example, robust branching of axonal collaterals arises from pre-existing primary mossy fiber axons. Understanding the branching mechanisms in adulthood may contribute to axonal regeneration therapies in neuroregenerative medicine in which robust axonal re-growth is essential. Additionally, because granule cells are produced throughout life in the neurogenic dentate gyrus, it is interesting to examine whether the mossy fibers of newly generated granule cells follow the pre-existing trajectories of sprouted mossy fibers in the epileptic brain. Understanding these axon guidance mechanisms may contribute to neuron transplantation therapies, for which the incorporation of transplanted neurons into pre-existing neural circuits is essential. Thus, clarifying the axon guidance mechanisms of mossy fiber sprouting could lead to an understanding of central nervous system (CNS network reorganization and plasticity. Here, we review the molecular and cellular mechanisms of axon guidance in mossy fiber sprouting by discussing mainly in vitro studies.

  20. Diurnal inhibition of NMDA-EPSCs at rat hippocampal mossy fibre synapses through orexin-2 receptors

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    Perin, Martina; Longordo, Fabio; Massonnet, Christine; Welker, Egbert; Lüthi, Anita

    2014-01-01

    Diurnal release of the orexin neuropeptides orexin-A (Ox-A, hypocretin-1) and orexin-B (Ox-B, hypocretin-2) stabilises arousal, regulates energy homeostasis and contributes to cognition and learning. However, whether cellular correlates of brain plasticity are regulated through orexins, and whether they do so in a time-of-day-dependent manner, has never been assessed. Immunohistochemically we found sparse but widespread innervation of hippocampal subfields through Ox-A- and Ox-B-containing fibres in young adult rats. The actions of Ox-A were studied on NMDA receptor (NMDAR)-mediated excitatory synaptic transmission in acute hippocampal slices prepared around the trough (Zeitgeber time (ZT) 4–8, corresponding to 4–8 h into the resting phase) and peak (ZT 23) of intracerebroventricular orexin levels. At ZT 4–8, exogenous Ox-A (100 nm in bath) inhibited NMDA receptor-mediated excitatory postsynaptic currents (NMDA-EPSCs) at mossy fibre (MF)–CA3 (to 55.6 ± 6.8% of control, P = 0.0003) and at Schaffer collateral–CA1 synapses (70.8 ± 6.3%, P = 0.013), whereas it remained ineffective at non-MF excitatory synapses in CA3. Ox-A actions were mediated postsynaptically and blocked by the orexin-2 receptor (OX2R) antagonist JNJ10397049 (1 μm), but not by orexin-1 receptor inhibition (SB334867, 1 μm) or by adrenergic and cholinergic antagonists. At ZT 23, inhibitory effects of exogenous Ox-A were absent (97.6 ± 2.9%, P = 0.42), but reinstated (87.2 ± 3.3%, P = 0.002) when endogenous orexin signalling was attenuated for 5 h through i.p. injections of almorexant (100 mg kg−1), a dual orexin receptor antagonist. In conclusion, endogenous orexins modulate hippocampal NMDAR function in a time-of-day-dependent manner, suggesting that they may influence cellular plasticity and consequent variations in memory performance across the sleep–wake cycle. PMID:25085886

  1. Human limbic encephalitis serum enhances hippocampal mossy fiber-CA3 pyramidal cell synaptic transmission.

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    Lalic, Tatjana; Pettingill, Philippa; Vincent, Angela; Capogna, Marco

    2011-01-01

    Limbic encephalitis (LE) is a central nervous system (CNS) disease characterized by subacute onset of memory loss and epileptic seizures. A well-recognized form of LE is associated with voltage-gated potassium channel complex antibodies (VGKC-Abs) in the patients' sera. We aimed to test the hypothesis that purified immunoglobulin G (IgG) from a VGKC-Ab LE serum would excite hippocampal CA3 pyramidal cells by reducing VGKC function at mossy-fiber (MF)-CA3 pyramidal cell synapses. We compared the effects of LE and healthy control IgG by whole-cell patch-clamp and extracellular recordings from CA3 pyramidal cells of rat hippocampal acute slices. We found that the LE IgG induced epileptiform activity at a population level, since synaptic stimulation elicited multiple population spikes extracellularly recorded in the CA3 area. Moreover, the LE IgG increased the rate of tonic firing and strengthened the MF-evoked synaptic responses. The synaptic failure of evoked excitatory postsynaptic currents (EPSCs) was significantly lower in the presence of the LE IgG compared to the control IgG. This suggests that the LE IgG increased the release probability on MF-CA3 pyramidal cell synapses compared to the control IgG. Interestingly, α-dendrotoxin (120 nm), a selective Kv1.1, 1.2, and 1.6 subunit antagonist of VGKC, mimicked the LE IgG-mediated effects. This is the first functional demonstration that LE IgGs reduce VGKC function at CNS synapses and increase cell excitability. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  2. Spatial, contextual and working memory are not affected by the absence of mossy fiber long-term potentiation and depression

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    Hensbroek, R.A.; Kamal, A.; Baars, A.M.; Verhage, M.; Spruijt, B.M.

    2003-01-01

    The mossy fibers of the hippocampus display NMDA-receptor independent long-term plasticity. A number of studies addressed the role of mossy fiber long-term plasticity in memory, but have provided contrasting results. Here, we have exploited a genetic model, the rab3A null-mutant, which is

  3. Distribution of hippocampal mossy fibers in the rat. An experimental study with silver impregnation methods

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    Blackstad, T W; Brink, K; Hem, J

    1970-01-01

    dentata and the layer of mossy fibers in the rat form a curved and twisted structure extending from the level of the posterior aspect of the septum to the temporal tip. The horizontal serial sections used for this study were, therefore, in part interpreted by means of three‐dimensional reconstructions...... inferior. The bands of degenerated mossy fibers produced by lesions in the fascia dentata were largely oriented in the transverse direction (slightly in a temporal direction) and were somewhat wider distally than at the origin from the hilus. Very narrow bands were seen in a few animals with particularly...

  4. A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in Mossy Fiber Synaptic Plasticity

    Directory of Open Access Journals (Sweden)

    Yoav Ben-Simon

    2015-07-01

    Full Text Available Neurotransmitter release probability (Pr largely determines the dynamic properties of synapses. While much is known about the role of presynaptic proteins in transmitter release, their specific contribution to synaptic plasticity is unclear. One such protein, tomosyn, is believed to reduce Pr by interfering with the SNARE complex formation. Tomosyn is enriched at hippocampal mossy fiber-to-CA3 pyramidal cell synapses (MF-CA3, which characteristically exhibit low Pr, strong synaptic facilitation, and pre-synaptic protein kinase A (PKA-dependent long-term potentiation (LTP. To evaluate tomosyn’s role in MF-CA3 function, we used a combined knockdown (KD-optogenetic strategy whereby presynaptic neurons with reduced tomosyn levels were selectively activated by light. Using this approach in mouse hippocampal slices, we found that facilitation, LTP, and PKA-induced potentiation were significantly impaired at tomosyn-deficient synapses. These findings not only indicate that tomosyn is a key regulator of MF-CA3 plasticity but also highlight the power of a combined KD-optogenetic approach to determine the role of presynaptic proteins.

  5. Subcellular fractionation on Percoll gradient of mossy fiber synaptosomes: morphological and biochemical characterization in control and degranulated rat hippocampus.

    Science.gov (United States)

    Taupin, P; Zini, S; Cesselin, F; Ben-Ari, Y; Roisin, M P

    1994-04-01

    A method for preparation of hippocampal mossy fiber synaptosomes directly from the postnuclear pellet is presented. This method represents an adaptation of that previously described for the isolation of synaptosomes by centrifugation through Percoll gradients directly from the supernatant fraction. We have characterized by electron microscopy two fractions, PII and PIII, enriched in mossy fiber synaptosomes; fraction PIII had 75% mossy fiber synaptosomes with well-preserved morphology (large size 3 microns, complex morphology, high synaptic vesicle density, multisynapses), whereas fraction PII contained 12%. These fractions were enriched in lactate dehydrogenase activity indicating that the integrity of synaptosomes was preserved. Compared with the other synaptosomal fractions, these fractions showed greater levels of dynorphin A (1-8) immunoreactivity and endogenous zinc, which are particularly concentrated in hippocampal mossy fiber terminals. Furthermore, we prepared synaptosomes from adult hippocampus after neonatal irradiation, which destroys the majority of granule cells and associated mossy fibers. The levels of dynorphin and zinc decreased by 88 and 70% in fraction PII and by 95 and 90%, respectively, in PIII. These results suggest that the rapid Percoll procedure is convenient for the purification of mossy fiber synaptosomes.

  6. PTEN deletion from adult-generated dentate granule cells disrupts granule cell mossy fiber axon structure.

    Science.gov (United States)

    LaSarge, Candi L; Santos, Victor R; Danzer, Steve C

    2015-03-01

    Dysregulation of the mTOR-signaling pathway is implicated in the development of temporal lobe epilepsy. In mice, deletion of PTEN from hippocampal dentate granule cells leads to mTOR hyperactivation and promotes the rapid onset of spontaneous seizures. The mechanism by which these abnormal cells initiate epileptogenesis, however, is unclear. PTEN-knockout granule cells develop abnormally, exhibiting morphological features indicative of increased excitatory input. If these cells are directly responsible for seizure genesis, it follows that they should also possess increased output. To test this prediction, dentate granule cell axon morphology was quantified in control and PTEN-knockout mice. Unexpectedly, PTEN deletion increased giant mossy fiber bouton spacing along the axon length, suggesting reduced innervation of CA3. Increased width of the mossy fiber axon pathway in stratum lucidum, however, which likely reflects an unusual increase in mossy fiber axon collateralization in this region, offsets the reduction in boutons per axon length. These morphological changes predict a net increase in granule cell innervation of CA3. Increased diameter of axons from PTEN-knockout cells would further enhance granule cell communication with CA3. Altogether, these findings suggest that amplified information flow through the hippocampal circuit contributes to seizure occurrence in the PTEN-knockout mouse model of temporal lobe epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Loss of protohaem IX farnesyltransferase in mature dentate granule cells impairs short-term facilitation at mossy fibre to CA3 pyramidal cell synapses.

    Science.gov (United States)

    Booker, Sam A; Campbell, Graham R; Mysiak, Karolina S; Brophy, Peter J; Kind, Peter C; Mahad, Don J; Wyllie, David J A

    2017-03-15

    Neurodegenerative disorders can exhibit dysfunctional mitochondrial respiratory chain complex IV activity. Conditional deletion of cytochrome c oxidase, the terminal enzyme in the respiratory electron transport chain of mitochondria, from hippocampal dentate granule cells in mice does not affect low-frequency dentate to CA3 glutamatergic synaptic transmission. High-frequency dentate to CA3 glutamatergic synaptic transmission and feedforward inhibition are significantly attenuated in cytochrome c oxidase-deficient mice. Intact presynaptic mitochondrial function is critical for the short-term dynamics of mossy fibre to CA3 synaptic function. Neurodegenerative disorders are characterized by peripheral and central symptoms including cognitive impairments which have been associated with reduced mitochondrial function, in particular mitochondrial respiratory chain complex IV or cytochrome c oxidase activity. In the present study we conditionally removed a key component of complex IV, protohaem IX farnesyltransferase encoded by the COX10 gene, in granule cells of the adult dentate gyrus. Utilizing whole-cell patch-clamp recordings from morphologically identified CA3 pyramidal cells from control and complex IV-deficient mice, we found that reduced mitochondrial function did not result in overt deficits in basal glutamatergic synaptic transmission at the mossy-fibre synapse because the amplitude, input-output relationship and 50 ms paired-pulse facilitation were unchanged following COX10 removal from dentate granule cells. However, trains of stimuli given at high frequency (> 20 Hz) resulted in dramatic reductions in short-term facilitation and, at the highest frequencies (> 50 Hz), also reduced paired-pulse facilitation, suggesting a requirement for adequate mitochondrial function to maintain glutamate release during physiologically relevant activity patterns. Interestingly, local inhibition was reduced, suggesting the effect observed was not restricted to synapses

  8. Subcellular fractionation on Percoll gradient of mossy fiber synaptosomes: evoked release of glutamate, GABA, aspartate and glutamate decarboxylase activity in control and degranulated rat hippocampus.

    Science.gov (United States)

    Taupin, P; Ben-Ari, Y; Roisin, M P

    1994-05-02

    Using discontinuous density gradient centrifugation in isotonic Percoll sucrose, we have characterized two subcellular fractions (PII and PIII) enriched in mossy fiber synaptosomes and two others (SII and SIII) enriched in small synaptosomes. These synaptosomal fractions were compared with those obtained from adult hippocampus irradiated at neonatal stage to destroy granule cells and their mossy fibers. Synaptosomes were viable as judged by their ability to release aspartate, glutamate and GABA upon K+ depolarization. After irradiation, compared to the control values, the release of glutamate and GABA was decreased by 57 and 74% in the PIII fraction, but not in the other fractions and the content of glutamate, aspartate and GABA was also decreased in PIII fraction by 62, 44 and 52% respectively. These results suggest that mossy fiber (MF) synaptosomes contain and release glutamate and GABA. Measurement of the GABA synthesizing enzyme, glutamate decarboxylase, exhibited no significant difference after irradiation, suggesting that GABA is not synthesized by this enzyme in mossy fibers.

  9. High-pass filtering and dynamic gain regulation enhance vertical bursts transmission along the mossy fiber pathway of cerebellum

    Directory of Open Access Journals (Sweden)

    Jonathan Mapelli

    2010-05-01

    Full Text Available Signal elaboration in the cerebellum mossy fiber input pathway presents controversial aspects, especially concerning gain regulation and the spot-like (rather than beam-like appearance of granular-to-molecular layer transmission. By using voltage-sensitive dye (VSD imaging in rat cerebellar slices (Mapelli et al., 2010, we found that mossy fiber bursts optimally excited the granular layer above ~50 Hz and the overlaying molecular layer above ~100 Hz, thus generating a cascade of high-pass filters. NMDA receptors enhanced transmission in the granular, while GABA-A receptors depressed transmission in both the granular and molecular layer. Burst transmission gain was controlled through a dynamic frequency-dependent involvement of these receptors. Moreover, while high-frequency transmission was enhanced along vertical lines connecting the granular to molecular layer, no high-frequency enhancement was observed along the parallel fiber axis in the molecular layer. This was probably due to the stronger effect of Purkinje cell GABA-A receptor-mediated inhibition occurring along the parallel fibers than along the granule cell axon ascending branch. The consequent amplification of burst responses along vertical transmission lines could explain the spot-like activation of Purkinje cells observed following punctuate stimulation in vivo .

  10. Dietary Supplementation of Hericium erinaceus Increases Mossy Fiber-CA3 Hippocampal Neurotransmission and Recognition Memory in Wild-Type Mice

    Directory of Open Access Journals (Sweden)

    Federico Brandalise

    2017-01-01

    Full Text Available Hericium erinaceus (Bull. Pers. is a medicinal mushroom capable of inducing a large number of modulatory effects on human physiology ranging from the strengthening of the immune system to the improvement of cognitive functions. In mice, dietary supplementation with H. erinaceus prevents the impairment of spatial short-term and visual recognition memory in an Alzheimer model. Intriguingly other neurobiological effects have recently been reported like the effect on neurite outgrowth and differentiation in PC12 cells. Until now no investigations have been conducted to assess the impact of this dietary supplementation on brain function in healthy subjects. Therefore, we have faced the problem by considering the effect on cognitive skills and on hippocampal neurotransmission in wild-type mice. In wild-type mice the oral supplementation with H. erinaceus induces, in behaviour test, a significant improvement in the recognition memory and, in hippocampal slices, an increase in spontaneous and evoked excitatory synaptic current in mossy fiber-CA3 synapse. In conclusion, we have produced a series of findings in support of the concept that H. erinaceus induces a boost effect onto neuronal functions also in nonpathological conditions.

  11. Dietary Supplementation of Hericium erinaceus Increases Mossy Fiber-CA3 Hippocampal Neurotransmission and Recognition Memory in Wild-Type Mice.

    Science.gov (United States)

    Brandalise, Federico; Cesaroni, Valentina; Gregori, Andrej; Repetti, Margherita; Romano, Chiara; Orrù, Germano; Botta, Laura; Girometta, Carolina; Guglielminetti, Maria Lidia; Savino, Elena; Rossi, Paola

    2017-01-01

    Hericium erinaceus (Bull.) Pers. is a medicinal mushroom capable of inducing a large number of modulatory effects on human physiology ranging from the strengthening of the immune system to the improvement of cognitive functions. In mice, dietary supplementation with H. erinaceus prevents the impairment of spatial short-term and visual recognition memory in an Alzheimer model. Intriguingly other neurobiological effects have recently been reported like the effect on neurite outgrowth and differentiation in PC12 cells. Until now no investigations have been conducted to assess the impact of this dietary supplementation on brain function in healthy subjects. Therefore, we have faced the problem by considering the effect on cognitive skills and on hippocampal neurotransmission in wild-type mice. In wild-type mice the oral supplementation with H. erinaceus induces, in behaviour test, a significant improvement in the recognition memory and, in hippocampal slices, an increase in spontaneous and evoked excitatory synaptic current in mossy fiber-CA3 synapse. In conclusion, we have produced a series of findings in support of the concept that H. erinaceus induces a boost effect onto neuronal functions also in nonpathological conditions.

  12. Transient downregulation of Sema3A mRNA in a rat model for temporal lobe epilepsy. A novel molecular event potentially contributing to mossy fiber sprouting

    NARCIS (Netherlands)

    Holtmaat, Anthony J D G; Gorter, Jan A; de Wit, Joris; Tolner, Else A; Spijker, Sabine; Giger, Roman J; Lopes da Silva, Fernando H; Verhaagen, J.

    Mossy fiber sprouting (MFS) in the hippocampal dentate gyrus is thought to play a critical role in the hyperexcitability of the hippocampus in temporal lobe epilepsy patients. The composition of molecular signals that is needed to direct this sprouting response has not yet been elucidated to a great

  13. The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses

    DEFF Research Database (Denmark)

    Guetg, Nicole; Seddik, Riad; Vigot, Réjan

    2009-01-01

    )) receptors mediate heterosynaptic depression of MF transmission, a physiological phenomenon involving transsynaptic inhibition of glutamate release via presynaptic GABA(B) receptors. Our data demonstrate that the difference in GABA(B1a) and GABA(B1b) protein levels at MF terminals is sufficient to produce...... a strictly GABA(B1a)-specific effect under physiological conditions. This consolidates that the differential subcellular localization of the GABA(B1a) and GABA(B1b) proteins is of regulatory relevance.......GABA(B) receptor subtypes are based on the subunit isoforms GABA(B1a) and GABA(B1b), which associate with GABA(B2) subunits to form pharmacologically indistinguishable GABA(B(1a,2)) and GABA(B(1b,2)) receptors. Studies with mice selectively expressing GABA(B1a) or GABA(B1b) subunits revealed...

  14. Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression.

    Science.gov (United States)

    Liu, Chung-Hsiang; Lin, Yi-Wen; Tang, Nou-Ying; Liu, Hsu-Jan; Hsieh, Ching-Liang

    2012-01-01

    Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABA(A)) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus.

  15. Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

    Directory of Open Access Journals (Sweden)

    Chung-Hsiang Liu

    2012-01-01

    Full Text Available Uncaria rhynchophylla (UR, which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA- induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus

  16. Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

    OpenAIRE

    Chung-Hsiang Liu; Yi-Wen Lin; Nou-Ying Tang; Hsu-Jan Liu; Ching-Liang Hsieh

    2012-01-01

    Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treat...

  17. Alpha-Bungarotoxin labeling and acetylcholinesterase localization at the Mauthner fiber giant synapse in the hatchetfish

    International Nuclear Information System (INIS)

    Day, J.W.; Hall, D.H.; Hall, L.M.; Bennett, M.V.

    1983-01-01

    Autoradiographic and histochemical techniques have been used to characterize further the pharmacology of transmission at the Mauthner fiber giant synapse of the South American hatchetfish. [ 125 I]alpha-Bungarotoxin was applied to hatchetfish medullae and a standard autoradiographic procedure was carried out on 3- to 4-microns sections of glutaraldehyde-fixed tissue. All Mauthner fiber giant synapses, as identified by light microscopic criteria, had closely associated silver grains. Labeling was blocked by d-tubocurarine. Glutaraldehyde-fixed slices of hatchetfish medulla were stained histochemically for acetylcholinesterase; all giant synapses that could be identified in the light microscope showed heavy deposits of reaction product. Staining was blocked by diisopropyl-fluorophosphate, which inhibits both pseudocholinesterase and acetylcholinesterase, but was not blocked by tetraisopropylpyrophosphoramide, a specific pseudocholinesterase inhibitor. This evidence strongly supports the suggestion that the Mauthner fiber giant synapse is nicotinic cholinergic

  18. alpha-Bungarotoxin labeling and acetylcholinesterase localization at the Mauthner fiber giant synapse in the hatchetfish

    International Nuclear Information System (INIS)

    Day, J.W.; Hall, D.H.; Hall, L.M.; Bennett, M.V.

    1983-01-01

    Autoradiographic and histochemical techniques have been used to characterize further the pharmacology of transmission at the Mauthner fiber giant synapse of the South American hatchetfish. [ 125 I]alpha-Bungarotoxin was applied to hatchetfish medullae and a standard autoradiographic procedure was carried out on 3- to 4-microns sections of glutaraldehyde-fixed tissue. All Mauthner fiber giant synapses, as identified by light microscopic criteria, had closely associated silver grains. Labeling was blocked by d-tubocurarine. Glutaraldehyde-fixed slices of hatchetfish medulla were stained histochemically for acetylcholinesterase; all giant synapses that could be identified in the light microscope showed heavy deposits of reaction product. Staining was blocked by diisopropyl-fluorophosphate, which inhibits both pseudocholinesterase and acetylcholinesterase, but was not blocked by tetraisopropylpyrophosphoramide, a specific pseudocholinesterase inhibitor. This evidence strongly supports the suggestion that the Mauthner fiber giant synapse is nicotinic cholinergic

  19. Alpha-Bungarotoxin labeling and acetylcholinesterase localization at the Mauthner fiber giant synapse in the hatchetfish

    Energy Technology Data Exchange (ETDEWEB)

    Day, J.W.; Hall, D.H.; Hall, L.M.; Bennett, M.V.

    1983-02-01

    Autoradiographic and histochemical techniques have been used to characterize further the pharmacology of transmission at the Mauthner fiber giant synapse of the South American hatchetfish. (/sup 125/I)alpha-Bungarotoxin was applied to hatchetfish medullae and a standard autoradiographic procedure was carried out on 3- to 4-microns sections of glutaraldehyde-fixed tissue. All Mauthner fiber giant synapses, as identified by light microscopic criteria, had closely associated silver grains. Labeling was blocked by d-tubocurarine. Glutaraldehyde-fixed slices of hatchetfish medulla were stained histochemically for acetylcholinesterase; all giant synapses that could be identified in the light microscope showed heavy deposits of reaction product. Staining was blocked by diisopropyl-fluorophosphate, which inhibits both pseudocholinesterase and acetylcholinesterase, but was not blocked by tetraisopropylpyrophosphoramide, a specific pseudocholinesterase inhibitor. This evidence strongly supports the suggestion that the Mauthner fiber giant synapse is nicotinic cholinergic.

  20. alpha-Bungarotoxin labeling and acetylcholinesterase localization at the Mauthner fiber giant synapse in the hatchetfish

    Energy Technology Data Exchange (ETDEWEB)

    Day, J.W.; Hall, D.H.; Hall, L.M.; Bennett, M.V.

    1983-02-01

    Autoradiographic and histochemical techniques have been used to characterize further the pharmacology of transmission at the Mauthner fiber giant synapse of the South American hatchetfish. (/sup 125/I)alpha-Bungarotoxin was applied to hatchetfish medullae and a standard autoradiographic procedure was carried out on 3- to 4-microns sections of glutaraldehyde-fixed tissue. All Mauthner fiber giant synapses, as identified by light microscopic criteria, had closely associated silver grains. Labeling was blocked by d-tubocurarine. Glutaraldehyde-fixed slices of hatchetfish medulla were stained histochemically for acetylcholinesterase; all giant synapses that could be identified in the light microscope showed heavy deposits of reaction product. Staining was blocked by diisopropyl-fluorophosphate, which inhibits both pseudocholinesterase and acetylcholinesterase, but was not blocked by tetraisopropylpyrophosphoramide, a specific pseudocholinesterase inhibitor. This evidence strongly supports the suggestion that the Mauthner fiber giant synapse is nicotinic cholinergic.

  1. Resistance of neurofilaments to degradation, and lack of neuronal death and mossy fiber sprouting after kainic acid-induced status epilepticus in the developing rat hippocampus.

    Science.gov (United States)

    Lopez-Picon, Francisco; Puustinen, Niina; Kukko-Lukjanov, Tiina-Kaisa; Holopainen, Irma E

    2004-12-01

    Neurofilament (NF) proteins, the major constituent of intermediate filaments in neurons, have an important role in cellular stability and plasticity. We have now studied the short-term (hours) and long-term (up to 1 week) effects of kainic acid (KA)-induced status epilepticus (SE) on the reactivity of NF proteins, and mossy fiber (MF) sprouting and neuronal death up to 4 weeks in 9-day-old rats. In Western blotting, the expression of the phosphorylation-independent epitopes of NF-L, NF-M, and NF-H rapidly but transiently increased after the treatment, whereas the phosphorylated NF-M remained elevated for 7 days. However, the treatment did not change the immunoreactivity of NF proteins, and no neuronal death or mossy fiber sprouting was detected at any time point. Our findings indicate seizure-induced reactivity of NF proteins but their resistance to degradation, which could be of importance in neuronal survival and may also prevent MF sprouting in the developing hippocampus.

  2. Combined role of seizure-induced dendritic morphology alterations and spine loss in newborn granule cells with mossy fiber sprouting on the hyperexcitability of a computer model of the dentate gyrus.

    Science.gov (United States)

    Tejada, Julian; Garcia-Cairasco, Norberto; Roque, Antonio C

    2014-05-01

    Temporal lobe epilepsy strongly affects hippocampal dentate gyrus granule cells morphology. These cells exhibit seizure-induced anatomical alterations including mossy fiber sprouting, changes in the apical and basal dendritic tree and suffer substantial dendritic spine loss. The effect of some of these changes on the hyperexcitability of the dentate gyrus has been widely studied. For example, mossy fiber sprouting increases the excitability of the circuit while dendritic spine loss may have the opposite effect. However, the effect of the interplay of these different morphological alterations on the hyperexcitability of the dentate gyrus is still unknown. Here we adapted an existing computational model of the dentate gyrus by replacing the reduced granule cell models with morphologically detailed models coming from three-dimensional reconstructions of mature cells. The model simulates a network with 10% of the mossy fiber sprouting observed in the pilocarpine (PILO) model of epilepsy. Different fractions of the mature granule cell models were replaced by morphologically reconstructed models of newborn dentate granule cells from animals with PILO-induced Status Epilepticus, which have apical dendritic alterations and spine loss, and control animals, which do not have these alterations. This complex arrangement of cells and processes allowed us to study the combined effect of mossy fiber sprouting, altered apical dendritic tree and dendritic spine loss in newborn granule cells on the excitability of the dentate gyrus model. Our simulations suggest that alterations in the apical dendritic tree and dendritic spine loss in newborn granule cells have opposing effects on the excitability of the dentate gyrus after Status Epilepticus. Apical dendritic alterations potentiate the increase of excitability provoked by mossy fiber sprouting while spine loss curtails this increase.

  3. Modulation, plasticity and pathophysiology of the parallel fiber-Purkinje cell synapse

    Directory of Open Access Journals (Sweden)

    Eriola Hoxha

    2016-11-01

    Full Text Available The parallel fiber-Purkinje cell synapse represents the point of maximal signal divergence in the cerebellar cortex with an estimated number of about 60 billion synaptic contacts in the rat and 100,000 billions in humans. At the same time, the Purkinje cell dendritic tree is a site of remarkable convergence of more than 100,000 parallel fiber synapses. Parallel fibers activity generates fast postsynaptic currents via AMPA receptors, and slower signals, mediated by mGlu1 receptors, resulting in Purkinje cell depolarization accompanied by sharp calcium elevation within dendritic regions. Long-term depression and long-term potentiation have been widely described for the parallel fiber-Purkinje cell synapse and have been proposed as mechanisms for motor learning. The mechanisms of induction for LTP and LTD involve different signaling mechanisms within the presynaptic terminal and/or at the postsynaptic site, promoting enduring modification in the neurotransmitter release and change in responsiveness to the neurotransmitter. The parallel fiber-Purkinje cell synapse is finely modulated by several neurotransmitters, including serotonin, noradrenaline, and acetylcholine. The ability of these neuromodulators to gate LTP and LTD at the parallel fiber-Purkinje cell synapse could, at least in part, explain their effect on cerebellar-dependent learning and memory paradigms. Overall, these findings have important implications for understanding the cerebellar involvement in a series of pathological conditions, ranging from ataxia to autism. For example, parallel fiber-Purkinje cell synapse dysfunctions have been identified in several murine models of spinocerebellar ataxia (SCA types 1, 3, 5 and 27. In some cases, the defect is specific for the AMPA receptor signaling (SCA27, while in others the mGlu1 pathway is affected (SCA1, 3, 5. Interestingly, the parallel fiber-Purkinje cell synapse has been shown to be hyper-functional in a mutant mouse model of autism

  4. Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse

    Directory of Open Access Journals (Sweden)

    Bertholet Jean-Yves

    2005-04-01

    Full Text Available Abstract Background The aim of this study was to investigate the effects of prenatal alcohol exposure on radial-maze learning and hippocampal neuroanatomy, particularly the sizes of the intra- and infrapyramidal mossy fiber (IIPMF terminal fields, in three inbred strains of mice (C57BL/6J, BALB/cJ, and DBA/2J. Results Although we anticipated a modification of both learning and IIPMF sizes, no such effects were detected. Prenatal alcohol exposure did, however, interfere with reproduction in C57BL/6J animals and decrease body and brain weight (in interaction with the genotype at adult age. Conclusion Prenatal alcohol exposure influenced neither radial maze performance nor the sizes of the IIPMF terminal fields. We believe that future research should be pointed either at different targets when using mouse models for Fetal Alcohol Syndrome (e.g. more complicated behavioral paradigms, different hippocampal substructures, or other brain structures or involve different animal models.

  5. Spontaneous release from mossy fiber terminals inhibits Ni2+-sensitive T-type Ca2+ channels of CA3 pyramidal neurons in the rat organotypic hippocampal slice.

    Science.gov (United States)

    Reid, Christopher A; Xu, Shenghong; Williams, David A

    2008-01-01

    Mossy fibers (axons arising from dentate granule cells) form large synaptic contacts exclusively onto the proximal apical dendrites of CA3 pyramidal neurons. They can generate large synaptic currents that occur in close proximity to the soma. These properties mean that active conductance in the proximal apical dendrite could have a disproportionate influence on CA3 pyramidal neuron excitability. Ni(2+)-sensitive T-type Ca(2+) channels are important modulators of dendritic excitability. Here, we use an optical approach to determine the contribution of Ni(2+) (100 microM)-sensitive Ca(2+) channels to action potential (AP) elicited Ca(2+) flux in the soma, proximal apical and distal apical dendrites. At resting membrane potentials Ni(2+)-sensitive Ca(2+) channels do not contribute to the Ca(2+) signal in the proximal apical dendrite, but do contribute in the other cell regions. Spontaneous release from mossy fiber terminals acting on 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive postsynaptic channels underlies a tonic inhibition of Ni(2+)-sensitive channels. Chelating Zn(2+) with CaEDTA blocks CNQX-sensitive changes in Ca(2+) flux implicating a mechanistic role of this ion in T-type Ca(2+) channel block. To test if this inhibition influenced excitability, progressively larger depolarizing pulses were delivered to CA3 pyramidal neurons. CNQX significantly reduced the size of the depolarizing step required to generate APs and increased the absolute number of APs per depolarizing step. This change in AP firing was completely reversed by the addition of Ni(2+). This mechanism may reduce the impact of T-type Ca(2+) channels in a region where large synaptic events are common.

  6. Hilar Mossy Cell Degeneration Causes Transient Dentate Granule Cell Hyperexcitability and Impaired Pattern Separation

    Science.gov (United States)

    Jinde, Seiichiro; Zsiros, Veronika; Jiang, Zhihong; Nakao, Kazuhito; Pickel, James; Kohno, Kenji; Belforte, Juan E.; Nakazawa, Kazu

    2012-01-01

    Summary Although excitatory mossy cells of the hippocampal hilar region are known to project both to dentate granule cells and to interneurons, it is as yet unclear whether mossy cell activity’s net effect on granule cells is excitatory or inhibitory. To explore their influence on dentate excitability and hippocampal function, we generated a conditional transgenic mouse line, using the Cre/loxP system, in which diphtheria toxin receptor was selectively expressed in mossy cells. One week after injecting toxin into this line, mossy cells throughout the longitudinal axis were degenerated extensively, theta wave power of dentate local field potentials increased during exploration, and deficits occurred in contextual discrimination. By contrast, we detected no epileptiform activity, spontaneous behavioral seizures, or mossy-fiber sprouting 5–6 weeks after mossy cell degeneration. These results indicate that the net effect of mossy cell excitation is to inhibit granule cell activity and enable dentate pattern separation. PMID:23259953

  7. Response of cat cerebellar vermis induced by sound. II. The role of the mossy and climbing fibers in acoustic transmission to the cerebellar cortex and influence of stimuli parameters.

    Science.gov (United States)

    Jastreboff, P J; Tarnecki, R

    1975-01-01

    Experiments were performed on cats under Chloralose or Nembutal anesthesia. The parameters of the acoustic click stimuli were found to have a strong influence on the responses registered from both the surface of the cerebellar vermis lobuli V up VII as well as from single units. It was shown that a stimulus frequency rate not greater than 1/2 s should be used, since higher frequencies caused strong attenuation of the response. The type of anesthesia did not change the latencies of reactions of both evoked potentials and single units. However, decreasing the strength of the click resulted in increased response latencies, in the case of single unit reactions. A very strong influence of weak visual stimuli on units was also observed. It is suggested that mossy fibers are the most important fibers in the transmission of acoustic information to the cerebellar cortex.

  8. Non-synaptic signaling from cerebellar climbing fibers modulates Golgi cell activity.

    Science.gov (United States)

    Nietz, Angela K; Vaden, Jada H; Coddington, Luke T; Overstreet-Wadiche, Linda; Wadiche, Jacques I

    2017-10-13

    Golgi cells are the principal inhibitory neurons at the input stage of the cerebellum, providing feedforward and feedback inhibition through mossy fiber and parallel fiber synapses. In vivo studies have shown that Golgi cell activity is regulated by climbing fiber stimulation, yet there is little functional or anatomical evidence for synapses between climbing fibers and Golgi cells. Here, we show that glutamate released from climbing fibers activates ionotropic and metabotropic receptors on Golgi cells through spillover-mediated transmission. The interplay of excitatory and inhibitory conductances provides flexible control over Golgi cell spiking, allowing either excitation or a biphasic sequence of excitation and inhibition following single climbing fiber stimulation. Together with prior studies of spillover transmission to molecular layer interneurons, these results reveal that climbing fibers exert control over inhibition at both the input and output layers of the cerebellar cortex.

  9. The organization of plasticity in the cerebellar cortex: from synapses to control.

    Science.gov (United States)

    D'Angelo, Egidio

    2014-01-01

    The cerebellum is thought to play a critical role in procedural learning, but the relationship between this function and the underlying cellular and synaptic mechanisms remains largely speculative. At present, at least nine forms of long-term synaptic and nonsynaptic plasticity (some of which are bidirectional) have been reported in the cerebellar cortex and deep cerebellar nuclei. These include long-term potentiation (LTP) and long-term depression at the mossy fiber-granule cell synapse, at the synapses formed by parallel fibers, climbing fibers, and molecular layer interneurons on Purkinje cells, and at the synapses formed by mossy fibers and Purkinje cells on deep cerebellar nuclear cells, as well as LTP of intrinsic excitability in granule cells, Purkinje cells, and deep cerebellar nuclear cells. It is suggested that the complex properties of cerebellar learning would emerge from the distribution of plasticity in the network and from its dynamic remodeling during the different phases of learning. Intrinsic and extrinsic factors may hold the key to explain how the different forms of plasticity cooperate to select specific transmission channels and to regulate the signal-to-noise ratio through the cerebellar cortex. These factors include regulation of neuronal excitation by local inhibitory networks, engagement of specific molecular mechanisms by spike bursts and theta-frequency oscillations, and gating by external neuromodulators. Therefore, a new and more complex view of cerebellar plasticity is emerging with respect to that predicted by the original "Motor Learning Theory," opening issues that will require experimental and computational testing. © 2014 Elsevier B.V. All rights reserved.

  10. 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

  11. Differences in kainate receptor involvement in hippocampal mossy fibre long-term potentiation depending on slice orientation.

    Science.gov (United States)

    Sherwood, John L; Amici, Mascia; Dargan, Sheila L; Culley, Georgia R; Fitzjohn, Stephen M; Jane, David E; Collingridge, Graham L; Lodge, David; Bortolotto, Zuner A

    2012-09-01

    Long-term potentiation (LTP) is a well-established experimental model used to investigate the synaptic basis of learning and memory. LTP at mossy fibre - CA3 synapses in the hippocampus is unusual because it is normally N-methyl-d-aspartate (NMDA) receptor-independent. Instead it seems that the trigger for mossy fibre LTP involves kainate receptors (KARs). Although it is generally accepted that pre-synaptic KARs play an essential role in frequency facilitation and LTP, their subunit composition remains a matter of significant controversy. We have reported previously that both frequency facilitation and LTP can be blocked by selective antagonism of GluK1 (formerly GluR5/Glu(K5))-containing KARs, but other groups have failed to reproduce this effect. Moreover, data from receptor knockout and mRNA expression studies argue against a major role of GluK1, supporting a more central role for GluK2 (formerly GluR6/Glu(K6)). A potential reason underlying the controversy in the pharmacological experiments may reside in differences in the preparations used. Here we show differences in pharmacological sensitivity of synaptic plasticity at mossy fibre - CA3 synapses depend critically on slice orientation. In transverse slices, LTP of fEPSPs was invariably resistant to GluK1-selective antagonists whereas in parasagittal slices LTP was consistently blocked by GluK1-selective antagonists. In addition, there were pronounced differences in the magnitude of frequency facilitation and the sensitivity to the mGlu2/3 receptor agonist DCG-IV. Using anterograde labelling of granule cells we show that slices of both orientations possess intact mossy fibres and both large and small presynaptic boutons. Transverse slices have denser fibre tracts but a smaller proportion of giant mossy fibre boutons. These results further demonstrate a considerable heterogeneity in the functional properties of the mossy fibre projection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Mixed electrical-chemical synapses in adult rat hippocampus are primarily glutamatergic and coupled by connexin-36

    Directory of Open Access Journals (Sweden)

    Farid eHamzei-Sichani

    2012-05-01

    Full Text Available Dendrodendritic electrical signaling via gap junctions is now an accepted feature of neuronal communication in the mammalian brain, whereas axodendritic and axosomatic gap junctions have rarely been described. We present ultrastructural, immunocytochemical, and dye-coupling evidence for mixed (electrical/chemical synapses in adult rat hippocampus on both principal cells and interneurons. Thin-section electron microscopic images of small gap junction-like appositions were found at mossy fiber (MF terminals on thorny excrescences of CA3 pyramidal neurons (CA3pyr, apparently forming glutamatergic mixed synapses. Lucifer Yellow injected into four weakly-fixed CA3pyr was detected in MF axons that contacted the injected CA3pyr, supporting gap junction-mediated coupling between those two types of principal cells. Freeze-fracture replica immunogold-labeling revealed diverse sizes and morphologies of connexin36-containing gap junctions throughout hippocampus. Of 20 immunogold-labeled gap junctions, seven were large (328-1140 connexons, three of which were consistent with electrical synapses between interneurons; but nine were at axon terminal synapses, three of which were immediately adjacent to distinctive glutamate receptor-containing postsynaptic densities, forming mixed glutamatergic synapses. Four others were adjacent to small clusters of immunogold-labeled 10-nm E-face intramembrane particles, apparently representing extrasynaptic glutamate receptor particles. Gap junctions also were on spines in stratum lucidum, stratum oriens, dentate gyrus, and hilus, on both interneurons and unidentified neurons. In addition, one putative GABAergic mixed synapse was found in thin section images of a CA3pyr, but none found by immunogold-labeling were at GABAergic mixed synapses, suggesting their rarity. Cx36-containing gap junctions throughout hippocampus suggest the possibility of reciprocal modulation of electrical and chemical signals in diverse hippocampal

  13. Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit

    NARCIS (Netherlands)

    Zampini, Valeria; Liu, Jian K; Diana, Marco A; Maldonado, Paloma P; Brunel, Nicolas; Dieudonné, Stéphane

    2016-01-01

    Synaptic currents display a large degree of heterogeneity of their temporal characteristics, but the functional role of such heterogeneities remains unknown. We investigated in rat cerebellar slices synaptic currents in Unipolar Brush Cells (UBCs), which generate intrinsic mossy fibers relaying

  14. Hilar mossy cell circuitry controlling dentate granule cell excitability

    Directory of Open Access Journals (Sweden)

    Seiichiro eJinde

    2013-02-01

    Full Text Available Glutamatergic hilar mossy cells of the dentate gyrus can either excite or inhibit distant granule cells, depending on whether their direct excitatory projections to granule cells or their projections to local inhibitory interneurons dominate. However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition. Clarifying this controversy has particular relevance to temporal lobe epilepsy, which is marked by dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. Two diametrically opposed hypotheses have been advanced to explain this granule cell hyperexcitability – the dormant basket cell and the irritable mossy cell hypotheses. The dormant basket cell hypothesis proposes that mossy cells normally exert a net inhibitory effect on granule cells and therefore their loss causes dentate granule cell hyperexcitability. The irritable mossy cell hypothesis takes the opposite view that mossy cells normally excite granule cells and that the surviving mossy cells in epilepsy increase their activity, causing granule cell excitation. The inability to eliminate mossy cells selectively has made it difficult to test these two opposing hypotheses. To this end, we developed a transgenic toxin-mediated, mossy cell-ablation mouse line. Using these mutants, we demonstrated that the extensive elimination of hilar mossy cells causes granule cell hyperexcitability, although the mossy cell loss observed appeared insufficient to cause clinical epilepsy. In this review, we focus on this topic and also suggest that different interneuron populations may mediate mossy cell-induced translamellar lateral inhibition and intralamellar recurrent inhibition. These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.

  15. Presynaptic calcium signalling in cerebellar mossy fibres

    DEFF Research Database (Denmark)

    Thomsen, Louiza Bohn; Jörntell, Henrik; Midtgaard, Jens

    2010-01-01

    Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX......)-sensitive fast Na(+) spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers....... Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon...

  16. Mossy cells in epilepsy: rigor mortis or vigor mortis?

    Science.gov (United States)

    Ratzliff, Annad d H; Santhakumar, Vijayalakshmi; Howard, Allyson; Soltesz, Ivan

    2002-03-01

    Mossy cells are bi-directionally connected through a positive feedback loop to granule cells, the principal cells of the dentate gyrus. This recurrent circuit is strategically placed between the entorhinal cortex and the hippocampal CA3 region. In spite of their potentially pro-convulsive arrangement with granule cells, mossy cells have not been seriously considered to promote seizures, because mossy cells, allegedly one of the most vulnerable cell types in the entire mammalian brain, have long been 'known' to die en masse in epilepsy. However, new data suggest that rumors of the rapid demise of the mossy cells might have been greatly exaggerated.

  17. Hilar mossy cells of the dentate gyrus: a historical perspective

    Science.gov (United States)

    Scharfman, Helen E.; Myers, Catherine E.

    2013-01-01

    The circuitry of the dentate gyrus (DG) of the hippocampus is unique compared to other hippocampal subfields because there are two glutamatergic principal cells instead of one: granule cells, which are the vast majority of the cells in the DG, and the so-called “mossy cells.” The distinctive appearance of mossy cells, the extensive divergence of their axons, and their vulnerability to excitotoxicity relative to granule cells has led to a great deal of interest in mossy cells. Nevertheless, there is no consensus about the normal functions of mossy cells and the implications of their vulnerability. There even seems to be some ambiguity about exactly what mossy cells are. Here we review initial studies of mossy cells, characteristics that define them, and suggest a practical definition to allow investigators to distinguish mossy cells from other hilar neurons even if all morphological and physiological information is unavailable due to technical limitations of their experiments. In addition, hypotheses are discussed about the role of mossy cells in the DG network, reasons for their vulnerability and their implications for disease. PMID:23420672

  18. Hilar mossy cells of the dentate gyrus: a historical perspective

    Directory of Open Access Journals (Sweden)

    Helen E Scharfman

    2013-01-01

    Full Text Available The circuitry of the dentate gyrus of the hippocampus is unique compared to other hippocampal subfields because there are two glutamatergic principal cells instead of one: granule cells, which are the vast majority of the cells in the dentate gyrus, and the so-called ‘mossy cells.’ The distinctive appearance of mossy cells, the extensive divergence of their axons, and their vulnerability to excitotoxicity relative to granule cells has led to a great deal of interest in mossy cells. Nevertheless, there is no consensus about the normal functions of mossy cells and the implications of their vulnerability. There even seems to be some ambiguity about exactly what mossy cells are. Here we review initial studies of mossy cells, characteristics that define them, and suggest a practical definition to allow investigators to distinguish mossy cells from other hilar neurons even if all morphological and physiological information is unavailable due to technical limitations of their experiments. In addition, hypotheses are discussed about the role of mossy cells in the dentate gyrus network, reasons for their vulnerability and their implications for disease.

  19. Calcium microdomains near R-type calcium channels control the induction of presynaptic LTP at parallel fiber to Purkinje cell synapses

    Science.gov (United States)

    Myoga, Michael H.; Regehr, Wade G.

    2011-01-01

    R-type calcium channels in postsynaptic spines signal through functional calcium microdomains to regulate a calcium-calmodulin sensitive potassium channel that in turn regulates postsynaptic hippocampal LTP. Here we ask whether R-type calcium channels in presynaptic terminals also signal through calcium microdomains to control presynaptic LTP. We focus on presynaptic LTP at parallel fiber to Purkinje cell synapses in the cerebellum (PF-LTP), which is mediated by calcium/calmodulin-stimulated adenylyl cyclases. Although most presynaptic calcium influx is through N-type and P/Q-type calcium channels, blocking these channels does not disrupt PF-LTP, but blocking R-type calcium channels does. Moreover, global calcium signaling cannot account for the calcium dependence of PF-LTP because R-type channels contribute modestly to overall calcium entry. These findings indicate that within presynaptic terminals, R-type calcium channels produce calcium microdomains that evoke presynaptic LTP at moderate frequencies that do not greatly increase global calcium levels,. PMID:21471358

  20. The immunological synapse

    DEFF Research Database (Denmark)

    Klemmensen, Thomas; Pedersen, Lars Ostergaard; Geisler, Carsten

    2003-01-01

    . A distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure has been termed the "immunological synapse" (IS). Here, we review molecular aspects concerning...

  1. A fraction enriched in rat hippocampal mossy fibre synaptosomes contains trophic activities.

    Science.gov (United States)

    Taupin, P; Roisin, M P; Ben-Ari, Y; Barbin, G

    1994-06-27

    Subcellular fractions prepared from the rat hippocampus, were assessed for the presence of trophic activities. The cytosol of synaptosomal fractions induced mitotic reinitiation of confluent 3T3 fibroblasts. The synaptosomal fraction, enriched in mossy fibre terminals, contained the highest mitotic activity. The mitogenic activity was heat and trypsin sensitive, suggesting that polypeptides are involved. The cytosol of the mossy fibre synaptosomal fraction promoted neuritic outgrowth of PC 12 cells and embryonic hippocampal neurones in primary cultures. These results suggest that mossy fibres contain both mitogenic and neurotrophic activities. These factors could participate in mossy fibre sprouting that occur following brief seizures or experimental lesions.

  2. Local and Long-Range Circuit Connections to Hilar Mossy Cells in the Dentate Gyrus

    Science.gov (United States)

    Sun, Yanjun; Grieco, Steven F.; Holmes, Todd C.

    2017-01-01

    Abstract Hilar mossy cells are the prominent glutamatergic cell type in the dentate hilus of the dentate gyrus (DG); they have been proposed to have critical roles in the DG network. To better understand how mossy cells contribute to DG function, we have applied new viral genetic and functional circuit mapping approaches to quantitatively map and compare local and long-range circuit connections of mossy cells and dentate granule cells in the mouse. The great majority of inputs to mossy cells consist of two parallel inputs from within the DG: an excitatory input pathway from dentate granule cells and an inhibitory input pathway from local DG inhibitory neurons. Mossy cells also receive a moderate degree of excitatory and inhibitory CA3 input from proximal CA3 subfields. Long range inputs to mossy cells are numerically sparse, and they are only identified readily from the medial septum and the septofimbrial nucleus. In comparison, dentate granule cells receive most of their inputs from the entorhinal cortex. The granule cells receive significant synaptic inputs from the hilus and the medial septum, and they also receive direct inputs from both distal and proximal CA3 subfields, which has been underdescribed in the existing literature. Our slice-based physiological mapping studies further supported the identified circuit connections of mossy cells and granule cells. Together, our data suggest that hilar mossy cells are major local circuit integrators and they exert modulation of the activity of dentate granule cells as well as the CA3 region through “back-projection” pathways. PMID:28451637

  3. Survival of mossy cells of the hippocampal dentate gyrus in humans with mesial temporal lobe epilepsy.

    Science.gov (United States)

    Seress, László; Abrahám, Hajnalka; Horváth, Zsolt; Dóczi, Tamás; Janszky, József; Klemm, Joyce; Byrne, Richard; Bakay, Roy A E

    2009-12-01

    Hippocampal sclerosis can be identified in most patients with mesial temporal lobe epilepsy (TLE). Surgical removal of the sclerotic hippocampus is widely performed to treat patients with drug-resistant mesial TLE. In general, both epilepsy-prone and epilepsy-resistant neurons are believed to be in the hippocampal formation. The hilar mossy cells of the hippocampal dentate gyrus are usually considered one of the most vulnerable types of neurons. The aim of this study was to clarify the fate of mossy cells in the hippocampus in epileptic humans. Of the 19 patients included in this study, 15 underwent temporal lobe resection because of drug-resistant TLE. Four patients were used as controls because they harbored tumors that had not invaded the hippocampus and they had experienced no seizures. Histological evaluation of resected hippocampal tissues was performed using immunohistochemistry. Mossy cells were identified in the control as well as the epileptic hippocampi by using cocaine- and amphetamine-regulated transcript peptide immunohistochemistry. In most cases the number of mossy cells was reduced and thorny excrescences were smaller in the epileptic hippocampi than in controls; however, there was a significant loss of pyramidal cells and a partial loss of granule cells in the same epileptic hippocampi in which mossy cell loss was apparent. The loss of mossy cells could be correlated with the extent of hippocampal sclerosis, patient age at seizure onset, duration of epilepsy, and frequency of seizures. In many cases large numbers of mossy cells were present in the hilus of the dentate gyrus when most pyramidal neurons of the CA1 and CA3 areas of the Ammon's horn were lost, suggesting that mossy cells may not be more vulnerable to epileptic seizures than the hippocampal pyramidal neurons.

  4. On-chip photonic synapse.

    Science.gov (United States)

    Cheng, Zengguang; Ríos, Carlos; Pernice, Wolfram H P; Wright, C David; Bhaskaran, Harish

    2017-09-01

    The search for new "neuromorphic computing" architectures that mimic the brain's approach to simultaneous processing and storage of information is intense. Because, in real brains, neuronal synapses outnumber neurons by many orders of magnitude, the realization of hardware devices mimicking the functionality of a synapse is a first and essential step in such a search. We report the development of such a hardware synapse, implemented entirely in the optical domain via a photonic integrated-circuit approach. Using purely optical means brings the benefits of ultrafast operation speed, virtually unlimited bandwidth, and no electrical interconnect power losses. Our synapse uses phase-change materials combined with integrated silicon nitride waveguides. Crucially, we can randomly set the synaptic weight simply by varying the number of optical pulses sent down the waveguide, delivering an incredibly simple yet powerful approach that heralds systems with a continuously variable synaptic plasticity resembling the true analog nature of biological synapses.

  5. The sticky synapse

    DEFF Research Database (Denmark)

    Owczarek, Sylwia Elzbieta; Kristiansen, Lars Villiam; Hortsch, Michael

    NCAM-type proteins modulate multiple neuronal functions, including the outgrowth and guidance of neurites, the formation, maturation, and plasticity of synapses, and the induction of both long-term potentiation and long-term depression. The ectodomains of NCAM proteins have a basic structure...... mediate cell-cell adhesion through homophilic interactions and bind to growth factors, growth factor receptors, glutamate receptors, other CAMs, and components of the extracellular matrix. Intracellularly, NCAM-type proteins interact with various cytoskeletal proteins and regulators of intracellular...... signal transduction. A central feature of the synaptic function of NCAM proteins is the regulation of their extracellular interactions by adhesion-modulating glycoepitopes, their removal from the cell surface by endocytosis, and the elimination of their adhesion-mediating interactions by the proteolytic...

  6. Recurrent synapses and circuits in the CA3 region of the hippocampus: an associative network.

    Directory of Open Access Journals (Sweden)

    Richard eMiles

    2014-01-01

    Full Text Available In the CA3 region of the hippocampus, pyramidal cells excite other pyramidal cells and interneurons. The axons of CA3 pyramidal cells spread throughout most of the region to form an associative network. These connections were first drawn by Cajal and Lorente de No. Their physiological properties were explored to understand epileptiform discharges generated in the region. Synapses between pairs of pyramidal cells involve one or few release sites and are weaker than connections made by mossy fibres on CA3 pyramidal cells. Synapses with interneurons are rather effective, as needed to control unchecked excitation. We examine contributions of recurrent synapses to epileptiform synchrony, to the genesis of sharp waves in the CA3 region and to population oscillations at theta and gamma frequencies. Recurrent connections in CA3, as other associative cortices, have a lower connectivity spread over a larger area than in primary sensory cortices. This sparse, but wide-ranging connectivity serves the functions of an associative network, including acquisition of neuronal representations as activity in groups of CA3 cells and completion involving the recall from partial cues of these ensemble firing patterns.

  7. Zinc at glutamatergic synapses.

    Science.gov (United States)

    Paoletti, P; Vergnano, A M; Barbour, B; Casado, M

    2009-01-12

    It has long been known that the mammalian forebrain contains a subset of glutamatergic neurons that sequester zinc in their synaptic vesicles. This zinc may be released into the synaptic cleft upon neuronal activity. Extracellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate receptors and transporters. Among these targets, NMDA receptors appear particularly interesting because certain NMDA receptor subtypes (those containing the NR2A subunit) contain allosteric sites exquisitely sensitive to extracellular zinc. The existence of these high-affinity zinc binding sites raises the possibility that zinc may act both in a phasic and tonic mode. Changes in zinc concentration and subcellular zinc distribution have also been described in several pathological conditions linked to glutamatergic transmission dysfunctions. However, despite intense investigation, the functional significance of vesicular zinc remains largely a mystery. In this review, we present the anatomy and the physiology of the glutamatergic zinc-containing synapse. Particular emphasis is put on the molecular and cellular mechanisms underlying the putative roles of zinc as a messenger involved in excitatory synaptic transmission and plasticity. We also highlight the many controversial issues and unanswered questions. Finally, we present and compare two widely used zinc chelators, CaEDTA and tricine, and show why tricine should be preferred to CaEDTA when studying fast transient zinc elevations as may occur during synaptic activity.

  8. Fiber

    Science.gov (United States)

    ... meals instead of white rice. Add beans (kidney, black, navy, and pinto) to rice dishes for even more fiber. Spice up salads with berries and almonds, chickpeas, cooked artichokes, and beans (kidney, black, navy, or pinto). Use whole-grain (corn or ...

  9. Synapse Pathology in Psychiatric and Neurologic Disease

    NARCIS (Netherlands)

    M. van Spronsen (Myrrhe); C.C. Hoogenraad (Casper)

    2010-01-01

    textabstractInhibitory and excitatory synapses play a fundamental role in information processing in the brain. Excitatory synapses usually are situated on dendritic spines, small membrane protrusions that harbor glutamate receptors and postsynaptic density components and help transmit electrical

  10. Prevention of Noise Damage to Cochlear Synapses

    Science.gov (United States)

    2017-10-01

    Assessment of synapse regeneration : Twelve week old CBA/CaJ mice are exposed to a moderate noise that destroys synapses on inner hair cells (IHCs) but spares...result of excitotoxic trauma to cochlear synapses due to glutamate released from the hair cells . Excitotoxic trauma damages the postsynaptic cell by...components ............................................. 12 d) Quantitative analysis of effects of neurotrophic factors on synapse regeneration in vitro

  11. The balancing act of GABAergic synapse organizers.

    Science.gov (United States)

    Ko, Jaewon; Choii, Gayoung; Um, Ji Won

    2015-04-01

    GABA (γ-aminobutyric acid) is the main neurotransmitter at inhibitory synapses in the mammalian brain. It is essential for maintaining the excitation and inhibition (E/I) ratio, whose imbalance underlies various brain diseases. Emerging information about inhibitory synapse organizers provides a novel molecular framework for understanding E/I balance at the synapse, circuit, and systems levels. This review highlights recent advances in deciphering these components of the inhibitory synapse and their roles in the development, transmission, and circuit properties of inhibitory synapses. We also discuss how their dysfunction may lead to a variety of brain disorders, suggesting new therapeutic strategies based on balancing the E/I ratio.

  12. A grading system for hippocampal sclerosis based on the degree of hippocampal mossy fiber sprouting

    NARCIS (Netherlands)

    Gispen, W.H.; Proper, E.A.; Jansen, G.H.; Veelen, C.W. van; Rijen, P.C. van; Graan, P.N.E. de

    2001-01-01

    Abstract. In patients suffering from temporal lobe epilepsy (TLE) a highly variable degree of hippocampal sclerosis (HS) can be observed. For standard neuropathological evaluation after hippocampal resection, neuronal cell loss in the hippocampal subareas is assessed (Wyler score 0-4) [Wyler et al.

  13. Organization of central synapses by adhesion molecules

    OpenAIRE

    Tallafuss, Alexandra; Constable, John R.L.; Washbourne, Philip

    2010-01-01

    Synapses are the primary means for transmitting information from one neuron to the next. They are formed during development of the nervous system, and formation of appropriate synapses is crucial for establishment of neuronal circuits that underlie behavior and cognition. Understanding how synapses form and are maintained will allow us to address developmental disorders such as autism, mental retardation and possibly also psychological disorders. A number of biochemical and proteomic studies ...

  14. Mammalian Cochlear Hair Cell Regeneration and Ribbon Synapse Reformation

    Directory of Open Access Journals (Sweden)

    Xiaoling Lu

    2016-01-01

    Full Text Available Hair cells (HCs are the sensory preceptor cells in the inner ear, which play an important role in hearing and balance. The HCs of organ of Corti are susceptible to noise, ototoxic drugs, and infections, thus resulting in permanent hearing loss. Recent approaches of HCs regeneration provide new directions for finding the treatment of sensor neural deafness. To have normal hearing function, the regenerated HCs must be reinnervated by nerve fibers and reform ribbon synapse with the dendrite of spiral ganglion neuron through nerve regeneration. In this review, we discuss the research progress in HC regeneration, the synaptic plasticity, and the reinnervation of new regenerated HCs in mammalian inner ear.

  15. Face classification using electronic synapses

    Science.gov (United States)

    Yao, Peng; Wu, Huaqiang; Gao, Bin; Eryilmaz, Sukru Burc; Huang, Xueyao; Zhang, Wenqiang; Zhang, Qingtian; Deng, Ning; Shi, Luping; Wong, H.-S. Philip; Qian, He

    2017-05-01

    Conventional hardware platforms consume huge amount of energy for cognitive learning due to the data movement between the processor and the off-chip memory. Brain-inspired device technologies using analogue weight storage allow to complete cognitive tasks more efficiently. Here we present an analogue non-volatile resistive memory (an electronic synapse) with foundry friendly materials. The device shows bidirectional continuous weight modulation behaviour. Grey-scale face classification is experimentally demonstrated using an integrated 1024-cell array with parallel online training. The energy consumption within the analogue synapses for each iteration is 1,000 × (20 ×) lower compared to an implementation using Intel Xeon Phi processor with off-chip memory (with hypothetical on-chip digital resistive random access memory). The accuracy on test sets is close to the result using a central processing unit. These experimental results consolidate the feasibility of analogue synaptic array and pave the way toward building an energy efficient and large-scale neuromorphic system.

  16. Presynaptic proteoglycans: sweet organizers of synapse development.

    Science.gov (United States)

    Song, Yoo Sung; Kim, Eunjoon

    2013-08-21

    Synaptic adhesion molecules control neuronal synapse development. In this issue of Neuron, Siddiqui et al. (2013) and de Wit et al. (2013) demonstrate that LRRTM4, a postsynaptic adhesion molecule, trans-synaptically interacts with presynaptic heparan sulfate proteoglycans (HSPGs) to promote synapse development. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Organization of central synapses by adhesion molecules.

    Science.gov (United States)

    Tallafuss, Alexandra; Constable, John R L; Washbourne, Philip

    2010-07-01

    Synapses are the primary means for transmitting information from one neuron to the next. They are formed during the development of the nervous system, and the formation of appropriate synapses is crucial for the establishment of neuronal circuits that underlie behavior and cognition. Understanding how synapses form and are maintained will allow us to address developmental disorders such as autism, mental retardation and possibly also psychological disorders. A number of biochemical and proteomic studies have revealed a diverse and vast assortment of molecules that are present at the synapse. It is now important to untangle this large array of proteins and determine how it assembles into a functioning unit. Here we focus on recent reports describing how synaptic cell adhesion molecules interact with and organize the presynaptic and postsynaptic specializations of both excitatory and inhibitory central synapses. © The Authors (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  18. Organizers of inhibitory synapses come of age.

    Science.gov (United States)

    Krueger-Burg, Dilja; Papadopoulos, Theofilos; Brose, Nils

    2017-08-01

    While the postsynaptic density of excitatory synapses is known to encompass a highly complex molecular machinery, the equivalent organizational structure of inhibitory synapses has long remained largely undefined. In recent years, however, substantial progress has been made towards identifying the full complement of organizational proteins present at inhibitory synapses, including submembranous scaffolds, intracellular signaling proteins, transsynaptic adhesion proteins, and secreted factors. Here, we summarize these findings and discuss future challenges in assigning synapse-specific functions to the newly discovered catalog of proteins, an endeavor that will depend heavily on newly developed technologies such as proximity biotinylation. Further advances are made all the more essential by growing evidence that links inhibitory synapses to psychiatric and neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory.

    Science.gov (United States)

    Bui, Anh D; Nguyen, Theresa M; Limouse, Charles; Kim, Hannah K; Szabo, Gergely G; Felong, Sylwia; Maroso, Mattia; Soltesz, Ivan

    2018-02-16

    Temporal lobe epilepsy (TLE) is characterized by debilitating, recurring seizures and an increased risk for cognitive deficits. Mossy cells (MCs) are key neurons in the hippocampal excitatory circuit, and the partial loss of MCs is a major hallmark of TLE. We investigated how MCs contribute to spontaneous ictal activity and to spatial contextual memory in a mouse model of TLE with hippocampal sclerosis, using a combination of optogenetic, electrophysiological, and behavioral approaches. In chronically epileptic mice, real-time optogenetic modulation of MCs during spontaneous hippocampal seizures controlled the progression of activity from an electrographic to convulsive seizure. Decreased MC activity is sufficient to impede encoding of spatial context, recapitulating observed cognitive deficits in chronically epileptic mice. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  20. A new measure for the strength of electrical synapses

    Directory of Open Access Journals (Sweden)

    Julie S Haas

    2015-09-01

    Full Text Available Electrical synapses, like chemical synapses, mediate intraneuronal communication. Electrical synapses are typically quantified by subthreshold measurements of coupling, which fall short in describing their impact on spiking activity in coupled neighbors. Here we describe a novel measurement for electrical synapse strength that directly evaluates the effect of synaptically transmitted activity on spike timing. This method, also applicable to neurotransmitter-based synapses, communicates the considerable strength of electrical synapses. For electrical synapses measured in rodent slices of the thalamic reticular nucleus, spike timing is modulated by tens of ms by activity in a coupled neighbor.

  1. Neurobeachin regulates neurotransmitter receptor trafficking to synapses

    NARCIS (Netherlands)

    Nair, R.; Lauks, J.; Jung, S; Cooke, N.E.; de Wit, H.; Brose, N.; Kilimann, M.W.; Verhage, M.; Rhee, J.

    2013-01-01

    The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found

  2. The Diversity of Cortical Inhibitory Synapses

    Directory of Open Access Journals (Sweden)

    Yoshiyuki eKubota

    2016-04-01

    Full Text Available The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their IPSP size is not uniform. Thus cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit.

  3. Comparative anatomy of phagocytic and immunological synapses

    Directory of Open Access Journals (Sweden)

    Florence eNiedergang

    2016-01-01

    Full Text Available The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all critical features to build functional phagosomes and immunological synapses. Interestingly, both phagocytic cups and immunological synapses display particular spatial and temporal patterns of receptors and signaling molecules, leading to the notion of phagocytic synapse. Here we discuss both types of structures, their organization and the mechanisms by which they are generated and regulated.

  4. The biochemical anatomy of cortical inhibitory synapses.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Heller

    Full Text Available Classical electron microscopic studies of the mammalian brain revealed two major classes of synapses, distinguished by the presence of a large postsynaptic density (PSD exclusively at type 1, excitatory synapses. Biochemical studies of the PSD have established the paradigm of the synapse as a complex signal-processing machine that controls synaptic plasticity. We report here the results of a proteomic analysis of type 2, inhibitory synaptic complexes isolated by affinity purification from the cerebral cortex. We show that these synaptic complexes contain a variety of neurotransmitter receptors, neural cell-scaffolding and adhesion molecules, but that they are entirely lacking in cell signaling proteins. This fundamental distinction between the functions of type 1 and type 2 synapses in the nervous system has far reaching implications for models of synaptic plasticity, rapid adaptations in neural circuits, and homeostatic mechanisms controlling the balance of excitation and inhibition in the mature brain.

  5. Memory Synapses Are Defined by Distinct Molecular Complexes: A Proposal.

    Science.gov (United States)

    Sossin, Wayne S

    2018-01-01

    Synapses are diverse in form and function. While there are strong evidential and theoretical reasons for believing that memories are stored at synapses, the concept of a specialized "memory synapse" is rarely discussed. Here, we review the evidence that memories are stored at the synapse and consider the opposing possibilities. We argue that if memories are stored in an active fashion at synapses, then these memory synapses must have distinct molecular complexes that distinguish them from other synapses. In particular, examples from Aplysia sensory-motor neuron synapses and synapses on defined engram neurons in rodent models are discussed. Specific hypotheses for molecular complexes that define memory synapses are presented, including persistently active kinases, transmitter receptor complexes and trans-synaptic adhesion proteins.

  6. Defects of the Glycinergic Synapse in Zebrafish

    OpenAIRE

    Ogino, Kazutoyo; Hirata, Hiromi

    2016-01-01

    Glycine mediates fast inhibitory synaptic transmission. Physiological importance of the glycinergic synapse is well established in the brainstem and the spinal cord. In humans, the loss of glycinergic function in the spinal cord and brainstem leads to hyperekplexia, which is characterized by an excess startle reflex to sudden acoustic or tactile stimulation. In addition, glycinergic synapses in this region are also involved in the regulation of respiration and locomotion, and in the nocicepti...

  7. Communication, the centrosome and the immunological synapse.

    Science.gov (United States)

    Stinchcombe, Jane C; Griffiths, Gillian M

    2014-09-05

    Recent findings on the behaviour of the centrosome at the immunological synapse suggest a critical role for centrosome polarization in controlling the communication between immune cells required to generate an effective immune response. The features observed at the immunological synapse show parallels to centrosome (basal body) polarization seen in cilia and flagella, and the cellular communication that is now known to occur at all of these sites.

  8. Diversity in immunological synapse structure

    Science.gov (United States)

    Thauland, Timothy J; Parker, David C

    2010-01-01

    Immunological synapses (ISs) are formed at the T cell–antigen-presenting cell (APC) interface during antigen recognition, and play a central role in T-cell activation and in the delivery of effector functions. ISs were originally described as a peripheral ring of adhesion molecules surrounding a central accumulation of T-cell receptor (TCR)–peptide major histocompatibility complex (pMHC) interactions. Although the structure of these ‘classical’ ISs has been the subject of intense study, non-classical ISs have also been observed under a variety of conditions. Multifocal ISs, characterized by adhesion molecules dispersed among numerous small accumulations of TCR–pMHC, and motile ‘immunological kinapses’ have both been described. In this review, we discuss the conditions under which non-classical ISs are formed. Specifically, we explore the profound effect that the phenotypes of both T cells and APCs have on IS structure. We also comment on the role that IS structure may play in T-cell function. PMID:21039474

  9. Synapse formation and maintenance by C1q family proteins: a new class of secreted synapse organizers.

    Science.gov (United States)

    Yuzaki, Michisuke

    2010-07-01

    Several C1q family members, especially the Cbln and C1q-like subfamilies, are highly and predominantly expressed in the central nervous system. Cbln1, a member of the Cbln subfamily, plays two unique roles at parallel fiber (PF)-Purkinje cell synapses in the cerebellum: the formation and stabilization of synaptic contact, and the control of functional synaptic plasticity by regulating the postsynaptic endocytotic pathway. The delta2 glutamate receptor (GluD2), which is predominantly expressed in Purkinje cells, plays similar critical roles in the cerebellum. In addition, viral expression of GluD2 or the application of recombinant Cbln1 induces PF-Purkinje cell synaptogenesis in vitro and in vivo. Antigen-unmasking methods were necessary to reveal the immunoreactivities for endogenous Cbln1 and GluD2 at the synaptic junction of PF synapses. We propose that Cbln1 and GluD2 are located at the synaptic cleft, where various proteins undergo intricate molecular interactions with each other, and serve as a bidirectional synaptic organizer. © The Author (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  10. Glutamate synapses in human cognitive disorders.

    Science.gov (United States)

    Volk, Lenora; Chiu, Shu-Ling; Sharma, Kamal; Huganir, Richard L

    2015-07-08

    Accumulating data, including those from large genetic association studies, indicate that alterations in glutamatergic synapse structure and function represent a common underlying pathology in many symptomatically distinct cognitive disorders. In this review, we discuss evidence from human genetic studies and data from animal models supporting a role for aberrant glutamatergic synapse function in the etiology of intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ), neurodevelopmental disorders that comprise a significant proportion of human cognitive disease and exact a substantial financial and social burden. The varied manifestations of impaired perceptual processing, executive function, social interaction, communication, and/or intellectual ability in ID, ASD, and SCZ appear to emerge from altered neural microstructure, function, and/or wiring rather than gross changes in neuron number or morphology. Here, we review evidence that these disorders may share a common underlying neuropathy: altered excitatory synapse function. We focus on the most promising candidate genes affecting glutamatergic synapse function, highlighting the likely disease-relevant functional consequences of each. We first present a brief overview of glutamatergic synapses and then explore the genetic and phenotypic evidence for altered glutamate signaling in ID, ASD, and SCZ.

  11. Pursuit of Neurotransmitter Functions: Being Attracted with Fascination of the Synapse.

    Science.gov (United States)

    Konishi, Shiro

    2017-01-01

    In the beginning of the 1970s, only two chemical substances, acetylcholine and γ-aminobutyric acid (GABA), had been definitely established as neurotransmitters. Under such circumstances, I started my scientific career in Professor Masanori Otsuka's lab searching for the transmitter of primary sensory neurons. Until 1976, lines of evidence had accumulated indicating that the undecapeptide substance P could be released as a transmitter from primary afferent fibers into spinal synapses, although the substance P-mediated synaptic response had yet to be identified. Peripheral synapses could serve as a good model and thus, it was demonstrated in the prevertebral sympathetic ganglia by1985 that substance P released from axon collaterals of primary sensory neurons acts as the transmitter mediating non-cholinergic slow excitatory postsynaptic potential (EPSP). At that time, we also found that autonomic synapses were useful to uncover the transmitter role of the opioid peptide enkephalins, whose functions had been unknown since their discovery in 1975. Accordingly, enkephalins were found to serve a transmitter role in mediating presynaptic inhibition of cholinergic fast and non-cholinergic slow transmission in the prevertebral sympathetic ganglia. In 1990s, we attempted to devise a combined technique of brain slices and patch-clamp recordings. We applied it to study the regulatory mechanisms that operate around cerebellar GABAergic inhibitory synapses, because most of the studies then had centered on excitatory synapses and because inhibitory synapses are crucially involved in brain functions and disorders. Consequently, we discovered novel forms of heterosynaptic interactions, dual actions of a single transmitter, and receptor crosstalk, the details of which are described in this review.

  12. Shaping Synapses by the Neural Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Maura Ferrer-Ferrer

    2018-05-01

    Full Text Available Accumulating data support the importance of interactions between pre- and postsynaptic neuronal elements with astroglial processes and extracellular matrix (ECM for formation and plasticity of chemical synapses, and thus validate the concept of a tetrapartite synapse. Here we outline the major mechanisms driving: (i synaptogenesis by secreted extracellular scaffolding molecules, like thrombospondins (TSPs, neuronal pentraxins (NPs and cerebellins, which respectively promote presynaptic, postsynaptic differentiation or both; (ii maturation of synapses via reelin and integrin ligands-mediated signaling; and (iii regulation of synaptic plasticity by ECM-dependent control of induction and consolidation of new synaptic configurations. Particularly, we focused on potential importance of activity-dependent concerted activation of multiple extracellular proteases, such as ADAMTS4/5/15, MMP9 and neurotrypsin, for permissive and instructive events in synaptic remodeling through localized degradation of perisynaptic ECM and generation of proteolytic fragments as inducers of synaptic plasticity.

  13. Cell Biology of Astrocyte-Synapse Interactions.

    Science.gov (United States)

    Allen, Nicola J; Eroglu, Cagla

    2017-11-01

    Astrocytes, the most abundant glial cells in the mammalian brain, are critical regulators of brain development and physiology through dynamic and often bidirectional interactions with neuronal synapses. Despite the clear importance of astrocytes for the establishment and maintenance of proper synaptic connectivity, our understanding of their role in brain function is still in its infancy. We propose that this is at least in part due to large gaps in our knowledge of the cell biology of astrocytes and the mechanisms they use to interact with synapses. In this review, we summarize some of the seminal findings that yield important insight into the cellular and molecular basis of astrocyte-neuron communication, focusing on the role of astrocytes in the development and remodeling of synapses. Furthermore, we pose some pressing questions that need to be addressed to advance our mechanistic understanding of the role of astrocytes in regulating synaptic development. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Reciprocal synapses between outer hair cells and their afferent terminals: evidence for a local neural network in the mammalian cochlea.

    Science.gov (United States)

    Thiers, Fabio A; Nadol, Joseph B; Liberman, M Charles

    2008-12-01

    Cochlear outer hair cells (OHCs) serve both as sensory receptors and biological motors. Their sensory function is poorly understood because their afferent innervation, the type-II spiral ganglion cell, has small unmyelinated axons and constitutes only 5% of the cochlear nerve. Reciprocal synapses between OHCs and their type-II terminals, consisting of paired afferent and efferent specialization, have been described in the primate cochlea. Here, we use serial and semi-serial-section transmission electron microscopy to quantify the nature and number of synaptic interactions in the OHC area of adult cats. Reciprocal synapses were found in all OHC rows and all cochlear frequency regions. They were more common among third-row OHCs and in the apical half of the cochlea, where 86% of synapses were reciprocal. The relative frequency of reciprocal synapses was unchanged following surgical transection of the olivocochlear bundle in one cat, confirming that reciprocal synapses were not formed by efferent fibers. In the normal ear, axo-dendritic synapses between olivocochlear terminals and type-II terminals and/or dendrites were as common as synapses between olivocochlear terminals and OHCs, especially in the first row, where, on average, almost 30 such synapses were seen in the region under a single OHC. The results suggest that a complex local neuronal circuitry in the OHC area, formed by the dendrites of type-II neurons and modulated by the olivocochlear system, may be a fundamental property of the mammalian cochlea, rather than a curiosity of the primate ear. This network may mediate local feedback control of, and bidirectional communication among, OHCs throughout the cochlear spiral.

  15. Studies on the development of mossy zinc electrodeposits from flowing alkaline electrolytes

    Energy Technology Data Exchange (ETDEWEB)

    Mc Vay, L.

    1991-07-01

    The initiation and characteristics of mossy zinc electrodeposits have been investigated. Batteries with zinc electrodes are candidates for electric vehicle applications; however, this electrode is prone to form non-compact deposits that contribute to capacity loss and battery failure. Moss is deposited when the current density is far from the limiting current. This morphology first appears only after the bulk deposit is approximately 1 {mu}m thick. In this investigation, the effects of flow rate (Re=0--4000), current density (0--50 mA/cm{sup 2}), concentration of the electroactive species (0.25 and 0.5 M), and the concentration of supporting electrolyte (3, 6, and 12 M) on the initiation of moss were examined. The rotating concentric cylinder electrode was employed for most of the experiments; and a flow channel was used to study the development of morphology. After the experiment, the deposit was characterized using microscopic, x-ray diffraction, and profilometric techniques. 94 refs., 72 figs.

  16. Wireless synapses in bio-inspired neural networks

    Science.gov (United States)

    Jannson, Tomasz; Forrester, Thomas; Degrood, Kevin

    2009-05-01

    Wireless (virtual) synapses represent a novel approach to bio-inspired neural networks that follow the infrastructure of the biological brain, except that biological (physical) synapses are replaced by virtual ones based on cellular telephony modeling. Such synapses are of two types: intracluster synapses are based on IR wireless ones, while intercluster synapses are based on RF wireless ones. Such synapses have three unique features, atypical of conventional artificial ones: very high parallelism (close to that of the human brain), very high reconfigurability (easy to kill and to create), and very high plasticity (easy to modify or upgrade). In this paper we analyze the general concept of wireless synapses with special emphasis on RF wireless synapses. Also, biological mammalian (vertebrate) neural models are discussed for comparison, and a novel neural lensing effect is discussed in detail.

  17. Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development.

    Science.gov (United States)

    Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó, Anna; Cilleros, Víctor

    2017-01-01

    During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ) are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR), adenosine autoreceptors (AR) and trophic factor receptors (TFR, for neurotrophins and trophic cytokines) during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

  18. Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development

    Directory of Open Access Journals (Sweden)

    Josep Tomàs

    2017-05-01

    Full Text Available During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR, adenosine autoreceptors (AR and trophic factor receptors (TFR, for neurotrophins and trophic cytokines during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

  19. Otanps synapse linear relation multiplier circuit

    International Nuclear Information System (INIS)

    Chible, H.

    2008-01-01

    In this paper, a four quadrant VLSI analog multiplier will be proposed, in order to be used in the implementation of the neurons and synapses modules of the artificial neural networks. The main characteristics of this multiplier are the small silicon area and the low power consumption and the high value of the weight input voltage. (author)

  20. Intercellular protein-protein interactions at synapses.

    Science.gov (United States)

    Yang, Xiaofei; Hou, Dongmei; Jiang, Wei; Zhang, Chen

    2014-06-01

    Chemical synapses are asymmetric intercellular junctions through which neurons send nerve impulses to communicate with other neurons or excitable cells. The appropriate formation of synapses, both spatially and temporally, is essential for brain function and depends on the intercellular protein-protein interactions of cell adhesion molecules (CAMs) at synaptic clefts. The CAM proteins link pre- and post-synaptic sites, and play essential roles in promoting synapse formation and maturation, maintaining synapse number and type, accumulating neurotransmitter receptors and ion channels, controlling neuronal differentiation, and even regulating synaptic plasticity directly. Alteration of the interactions of CAMs leads to structural and functional impairments, which results in many neurological disorders, such as autism, Alzheimer's disease and schizophrenia. Therefore, it is crucial to understand the functions of CAMs during development and in the mature neural system, as well as in the pathogenesis of some neurological disorders. Here, we review the function of the major classes of CAMs, and how dysfunction of CAMs relates to several neurological disorders.

  1. Localization of mineralocorticoid receptors at mammalian synapses.

    Directory of Open Access Journals (Sweden)

    Eric M Prager

    Full Text Available In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids.

  2. Silent synapses in neuromuscular junction development.

    Science.gov (United States)

    Tomàs, Josep; Santafé, Manel M; Lanuza, Maria A; García, Neus; Besalduch, Nuria; Tomàs, Marta

    2011-01-01

    In the last few years, evidence has been found to suggest that some synaptic contacts become silent but can be functionally recruited before they completely retract during postnatal synapse elimination in muscle. The physiological mechanism of developmental synapse elimination may be better understood by studying this synapse recruitment. This Mini-Review collects previously published data and new results to propose a molecular mechanism for axonal disconnection. The mechanism is based on protein kinase C (PKC)-dependent inhibition of acetylcholine (ACh) release. PKC activity may be stimulated by a methoctramine-sensitive M2-type muscarinic receptor and by calcium inflow though P/Q- and L-type voltage-dependent calcium channels. In addition, tropomyosin-related tyrosine kinase B (trkB) receptor-mediated brain-derived neurotrophic factor (BDNF) activity may oppose the PKC-mediated ACh release depression. Thus, a balance between trkB and muscarinic pathways may contribute to the final functional suppression of some neuromuscular synapses during development. © 2010 Wiley-Liss, Inc.

  3. Neural Activity During The Formation Of A Giant Auditory Synapse

    NARCIS (Netherlands)

    M.C. Sierksma (Martijn)

    2018-01-01

    markdownabstractThe formation of synapses is a critical step in the development of the brain. During this developmental stage neural activity propagates across the brain from synapse to synapse. This activity is thought to instruct the precise, topological connectivity found in the sensory central

  4. Defects of the Glycinergic Synapse in Zebrafish

    Science.gov (United States)

    Ogino, Kazutoyo; Hirata, Hiromi

    2016-01-01

    Glycine mediates fast inhibitory synaptic transmission. Physiological importance of the glycinergic synapse is well established in the brainstem and the spinal cord. In humans, the loss of glycinergic function in the spinal cord and brainstem leads to hyperekplexia, which is characterized by an excess startle reflex to sudden acoustic or tactile stimulation. In addition, glycinergic synapses in this region are also involved in the regulation of respiration and locomotion, and in the nociceptive processing. The importance of the glycinergic synapse is conserved across vertebrate species. A teleost fish, the zebrafish, offers several advantages as a vertebrate model for research of glycinergic synapse. Mutagenesis screens in zebrafish have isolated two motor defective mutants that have pathogenic mutations in glycinergic synaptic transmission: bandoneon (beo) and shocked (sho). Beo mutants have a loss-of-function mutation of glycine receptor (GlyR) β-subunit b, alternatively, sho mutant is a glycinergic transporter 1 (GlyT1) defective mutant. These mutants are useful animal models for understanding of glycinergic synaptic transmission and for identification of novel therapeutic agents for human diseases arising from defect in glycinergic transmission, such as hyperekplexia or glycine encephalopathy. Recent advances in techniques for genome editing and for imaging and manipulating of a molecule or a physiological process make zebrafish more attractive model. In this review, we describe the glycinergic defective zebrafish mutants and the technical advances in both forward and reverse genetic approaches as well as in vivo visualization and manipulation approaches for the study of the glycinergic synapse in zebrafish. PMID:27445686

  5. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

    Science.gov (United States)

    Chung, Won-Suk; Clarke, Laura E.; Wang, Gordon X.; Stafford, Benjamin K.; Sher, Alexander; Chakraborty, Chandrani; Joung, Julia; Foo, Lynette C.; Thompson, Andrew; Chen, Chinfei; Smith, Stephen J.; Barres, Ben A.

    2013-12-01

    To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodelling. Recently, microglial cells have been shown to be responsible for a portion of synaptic pruning, but the remaining mechanisms remain unknown. Here we report a new role for astrocytes in actively engulfing central nervous system synapses. This process helps to mediate synapse elimination, requires the MEGF10 and MERTK phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to refine their retinogeniculate connections normally and retain excess functional synapses. Finally, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify MEGF10 and MERTK as critical proteins in the synapse remodelling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes.

  6. Mitochondria and Neurotransmission: Evacuating the Synapse

    OpenAIRE

    Hollenbeck, Peter J.

    2005-01-01

    An abundance of mitochondria has been the hallmark of synapses since their first ultrastructural description 50 years ago. Mitochondria have been shown to be essential for synaptic form and function in many systems, but until recently it has not been clear exactly what role(s) they play in neurotransmission. Now, evidence from the nervous system of Drosophila identifies the specific subcellular events that are most dependent upon nearby mitochondria.

  7. Ca(2+) influx and neurotransmitter release at ribbon synapses.

    Science.gov (United States)

    Cho, Soyoun; von Gersdorff, Henrique

    2012-01-01

    Ca(2+) influx through voltage-gated Ca(2+) channels triggers the release of neurotransmitters at presynaptic terminals. Some sensory receptor cells in the peripheral auditory and visual systems have specialized synapses that express an electron-dense organelle called a synaptic ribbon. Like conventional synapses, ribbon synapses exhibit SNARE-mediated exocytosis, clathrin-mediated endocytosis, and short-term plasticity. However, unlike non-ribbon synapses, voltage-gated L-type Ca(2+) channel opening at ribbon synapses triggers a form of multiquantal release that can be highly synchronous. Furthermore, ribbon synapses appear to be specialized for fast and high throughput exocytosis controlled by graded membrane potential changes. Here we will discuss some of the basic aspects of synaptic transmission at different types of ribbon synapses, and we will emphasize recent evidence that auditory and retinal ribbon synapses have marked differences. This will lead us to suggest that ribbon synapses are specialized for particular operating ranges and frequencies of stimulation. We propose that different types of ribbon synapses transfer diverse rates of sensory information by expressing a particular repertoire of critical components, and by placing them at precise and strategic locations, so that a continuous supply of primed vesicles and Ca(2+) influx leads to fast, accurate, and ongoing exocytosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Energy-efficient neuron, synapse and STDP integrated circuits.

    Science.gov (United States)

    Cruz-Albrecht, Jose M; Yung, Michael W; Srinivasa, Narayan

    2012-06-01

    Ultra-low energy biologically-inspired neuron and synapse integrated circuits are presented. The synapse includes a spike timing dependent plasticity (STDP) learning rule circuit. These circuits have been designed, fabricated and tested using a 90 nm CMOS process. Experimental measurements demonstrate proper operation. The neuron and the synapse with STDP circuits have an energy consumption of around 0.4 pJ per spike and synaptic operation respectively.

  9. Communication Breakdown: The Impact of Ageing on Synapse Structure

    Science.gov (United States)

    Petralia, Ronald S.; Mattson, Mark P.; Yao, Pamela J.

    2014-01-01

    Impaired synaptic plasticity is implicated in the functional decline of the nervous system associated with ageing. Understanding the structure of ageing synapses is essential to understanding the functions of these synapses and their role in the ageing nervous system. In this review, we summarize studies on ageing synapses in vertebrates and invertebrates, focusing on changes in morphology and ultrastructure. We cover different parts of the nervous system, including the brain, the retina, the cochlea, and the neuromuscular junction. The morphological characteristics of aged synapses could shed light on the underlying molecular changes and their functional consequences. PMID:24495392

  10. How synapses can enhance sensibility of a neural network

    Science.gov (United States)

    Protachevicz, P. R.; Borges, F. S.; Iarosz, K. C.; Caldas, I. L.; Baptista, M. S.; Viana, R. L.; Lameu, E. L.; Macau, E. E. N.; Batista, A. M.

    2018-02-01

    In this work, we study the dynamic range in a neural network modelled by cellular automaton. We consider deterministic and non-deterministic rules to simulate electrical and chemical synapses. Chemical synapses have an intrinsic time-delay and are susceptible to parameter variations guided by learning Hebbian rules of behaviour. The learning rules are related to neuroplasticity that describes change to the neural connections in the brain. Our results show that chemical synapses can abruptly enhance sensibility of the neural network, a manifestation that can become even more predominant if learning rules of evolution are applied to the chemical synapses.

  11. Retrograde Signaling from Progranulin to Sort1 Counteracts Synapse Elimination in the Developing Cerebellum.

    Science.gov (United States)

    Uesaka, Naofumi; Abe, Manabu; Konno, Kohtarou; Yamazaki, Maya; Sakoori, Kazuto; Watanabe, Takaki; Kao, Tzu-Huei; Mikuni, Takayasu; Watanabe, Masahiko; Sakimura, Kenji; Kano, Masanobu

    2018-02-21

    Elimination of redundant synapses formed early in development and strengthening of necessary connections are crucial for shaping functional neural circuits. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs) with similar strengths. A single CF is strengthened whereas the other CFs are eliminated in each PC during postnatal development. The underlying mechanisms, particularly for the strengthening of single CFs, are poorly understood. Here we report that progranulin, a multi-functional growth factor implicated in the pathogenesis of frontotemporal dementia, strengthens developing CF synaptic inputs and counteracts their elimination from postnatal day 11 to 16. Progranulin derived from PCs acts retrogradely onto its putative receptor Sort1 on CFs. This effect is independent of semaphorin 3A, another retrograde signaling molecule that counteracts CF synapse elimination. We propose that progranulin-Sort1 signaling strengthens and maintains developing CF inputs, and may contribute to selection of single "winner" CFs that survive synapse elimination. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Cadmium action in synapses in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto [Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka (Japan)

    2001-05-01

    Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of {sup 109}CdCl{sub 2} into the amygdala of rats, {sup 109}Cd release into the extracellular space was facilitated by stimulation with high K{sup +}, suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 {mu}M CdCl{sub 2}. The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and {gamma}-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

  13. Cadmium action in synapses in the brain

    International Nuclear Information System (INIS)

    Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto

    2001-01-01

    Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of 109 CdCl 2 into the amygdala of rats, 109 Cd release into the extracellular space was facilitated by stimulation with high K + , suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 μM CdCl 2 . The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and γ-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

  14. Cell adhesion and matricellular support by astrocytes of the tripartite synapse

    NARCIS (Netherlands)

    Hillen, Anne E J; Burbach, J Peter H; Hol, Elly M

    2018-01-01

    Astrocytes contribute to the formation, function, and plasticity of synapses. Their processes enwrap the neuronal components of the tripartite synapse, and due to this close interaction they are perfectly positioned to modulate neuronal communication. The interaction between astrocytes and synapses

  15. Rhythmic changes in synapse numbers in Drosophila melanogaster motor terminals.

    Directory of Open Access Journals (Sweden)

    Santiago Ruiz

    Full Text Available Previous studies have shown that the morphology of the neuromuscular junction of the flight motor neuron MN5 in Drosophila melanogaster undergoes daily rhythmical changes, with smaller synaptic boutons during the night, when the fly is resting, than during the day, when the fly is active. With electron microscopy and laser confocal microscopy, we searched for a rhythmic change in synapse numbers in this neuron, both under light:darkness (LD cycles and constant darkness (DD. We expected the number of synapses to increase during the morning, when the fly has an intense phase of locomotion activity under LD and DD. Surprisingly, only our DD data were consistent with this hypothesis. In LD, we found more synapses at midnight than at midday. We propose that under LD conditions, there is a daily rhythm of formation of new synapses in the dark phase, when the fly is resting, and disassembly over the light phase, when the fly is active. Several parameters appeared to be light dependent, since they were affected differently under LD or DD. The great majority of boutons containing synapses had only one and very few had either two or more, with a 70∶25∶5 ratio (one, two and three or more synapses in LD and 75∶20∶5 in DD. Given the maintenance of this proportion even when both bouton and synapse numbers changed with time, we suggest that there is a homeostatic mechanism regulating synapse distribution among MN5 boutons.

  16. IR wireless cluster synapses of HYDRA very large neural networks

    Science.gov (United States)

    Jannson, Tomasz; Forrester, Thomas

    2008-04-01

    RF/IR wireless (virtual) synapses are critical components of HYDRA (Hyper-Distributed Robotic Autonomy) neural networks, already discussed in two earlier papers. The HYDRA network has the potential to be very large, up to 10 11-neurons and 10 18-synapses, based on already established technologies (cellular RF telephony and IR-wireless LANs). It is organized into almost fully connected IR-wireless clusters. The HYDRA neurons and synapses are very flexible, simple, and low-cost. They can be modified into a broad variety of biologically-inspired brain-like computing capabilities. In this third paper, we focus on neural hardware in general, and on IR-wireless synapses in particular. Such synapses, based on LED/LD-connections, dominate the HYDRA neural cluster.

  17. Coding deficits in noise-induced hidden hearing loss may stem from incomplete repair of ribbon synapses in the cochlea

    Directory of Open Access Journals (Sweden)

    Lijuan eShi

    2016-05-01

    Full Text Available Recent evidence has shown that noise-induced damage to the synapse between inner hair cells (IHCs and type I afferent auditory nerve fibers (ANFs may occur in the absence of permanent threshold shift (PTS, and that synapses connecting IHCs with low spontaneous rate (SR ANFs are disproportionately affected. Due to the functional importance of low-SR ANF units for temporal processing and signal coding in noisy backgrounds, deficits in cochlear coding associated with noise-induced damage may result in significant difficulties with temporal processing and hearing in noise (i.e., hidden hearing loss. However, significant noise-induced coding deficits have not been reported at the single unit level following the loss of low-SR units. We have found evidence to suggest that some aspects of neural coding are not significantly changed with the initial loss of low-SR ANFs, and that further coding deficits arise in association with the subsequent reestablishment of the synapses. This suggests that synaptopathy in hidden hearing loss may be the result of insufficient repair of disrupted synapses, and not simply due to the loss of low-SR units. These coding deficits include decreases in driven spike rate for intensity coding as well as several aspects of temporal coding: spike latency, peak-to-sustained spike ratio and the recovery of spike rate as a function of click-interval.

  18. Recruitment of activation receptors at inhibitory NK cell immune synapses.

    Directory of Open Access Journals (Sweden)

    Nicolas Schleinitz

    2008-09-01

    Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

  19. A shared synapse architecture for efficient FPGA implementation of autoencoders.

    Science.gov (United States)

    Suzuki, Akihiro; Morie, Takashi; Tamukoh, Hakaru

    2018-01-01

    This paper proposes a shared synapse architecture for autoencoders (AEs), and implements an AE with the proposed architecture as a digital circuit on a field-programmable gate array (FPGA). In the proposed architecture, the values of the synapse weights are shared between the synapses of an input and a hidden layer, and between the synapses of a hidden and an output layer. This architecture utilizes less of the limited resources of an FPGA than an architecture which does not share the synapse weights, and reduces the amount of synapse modules used by half. For the proposed circuit to be implemented into various types of AEs, it utilizes three kinds of parameters; one to change the number of layers' units, one to change the bit width of an internal value, and a learning rate. By altering a network configuration using these parameters, the proposed architecture can be used to construct a stacked AE. The proposed circuits are logically synthesized, and the number of their resources is determined. Our experimental results show that single and stacked AE circuits utilizing the proposed shared synapse architecture operate as regular AEs and as regular stacked AEs. The scalability of the proposed circuit and the relationship between the bit widths and the learning results are also determined. The clock cycles of the proposed circuits are formulated, and this formula is used to estimate the theoretical performance of the circuit when the circuit is used to construct arbitrary networks.

  20. Evidence for presynaptically silent synapses in the immature hippocampus

    International Nuclear Information System (INIS)

    Yoon, Jae Young; Choi, Sukwoo

    2017-01-01

    Silent synapses show NMDA receptor (NMDAR)-mediated synaptic responses, but not AMPAR-mediated synaptic responses. A prevailing hypothesis states that silent synapses contain NMDARs, but not AMPARs. However, alternative presynaptic hypotheses, according to which AMPARs are present at silent synapses, have been proposed; silent synapses show slow glutamate release via a fusion pore, and glutamate spillover from the neighboring synaptic terminals. Consistent with these presynaptic hypotheses, the peak glutamate concentrations at silent synapses have been estimated to be ≪170 μM, much lower than those seen at functional synapses. Glutamate transients predicted based on the two presynaptic mechanisms have been shown to activate only high-affinity NMDARs, but not low-affinity AMPARs. Interestingly, a previous study has developed a new approach to distinguish between the two presynaptic mechanisms using dextran, an inert macromolecule that reduces the diffusivity of released glutamate: postsynaptic responses through the fusion pore mechanism, but not through the spillover mechanism, are potentiated by reduced glutamate diffusivity. Therefore, we reasoned that if the fusion pore mechanism underlies silent synapses, dextran application would reveal AMPAR-mediated synaptic responses at silent synapses. In the present study, we recorded AMPAR-mediated synaptic responses at the CA3-CA1 synapses in neonatal rats in the presence of blockers for NMDARs and GABAARs. Bath application of dextran revealed synaptic responses at silent synapses. GYKI53655, a selective AMPAR-antagonist, completely inhibited the unsilenced synaptic responses, indicating that the unsilenced synaptic responses are mediated by AMPARs. The dextran-mediated reduction in glutamate diffusivity would also lead to the activation of metabotropic glutamate receptors (mGluRs), which might induce unsilencing via the activation of unknown intracellular signaling. Hence, we determined whether mGluR-blockers alter

  1. The immunological synapse: a focal point for endocytosis and exocytosis.

    Science.gov (United States)

    Griffiths, Gillian M; Tsun, Andy; Stinchcombe, Jane C

    2010-05-03

    There are many different cells in the immune system. To mount an effective immune response, they need to communicate with each other. One way in which this is done is by the formation of immunological synapses between cells. Recent developments show that the immune synapse serves as a focal point for exocytosis and endocytosis, directed by centrosomal docking at the plasma membrane. In this respect, formation of the immunological synapse bears striking similarities to cilia formation and cytokinesis. These intriguing observations suggest that the centrosome may play a conserved role in designating a specialized area of membrane for localized endocytosis and exocytosis.

  2. The cytotoxic T lymphocyte immune synapse at a glance.

    Science.gov (United States)

    Dieckmann, Nele M G; Frazer, Gordon L; Asano, Yukako; Stinchcombe, Jane C; Griffiths, Gillian M

    2016-08-01

    The immune synapse provides an important structure for communication with immune cells. Studies on immune synapses formed by cytotoxic T lymphocytes (CTLs) highlight the dynamic changes and specialised mechanisms required to facilitate focal signalling and polarised secretion in immune cells. In this Cell Science at a Glance article and the accompanying poster, we illustrate the different steps that reveal the specialised mechanisms used to focus secretion at the CTL immune synapse and allow CTLs to be such efficient and precise serial killers. © 2016. Published by The Company of Biologists Ltd.

  3. Replacement of asymmetric synaptic profiles in the molecular layer of dentate gyrus following cycloheximide in the pilocarpine model in rats.

    Directory of Open Access Journals (Sweden)

    Simone eBittencourt

    2015-11-01

    Full Text Available Mossy fiber sprouting is among the best-studied forms of post-lesional synaptic plasticity and is regarded by many as contributory to seizures in both humans and animal models of epilepsy. It is not known whether mossy fiber sprouting increases the number of synapses in the molecular layer or merely replaces lost contacts. Using the pilocarpine model of status epilepticus to induce mossy fiber sprouting, and cycloheximide to block this sprouting, we evaluated at the ultrastructural level the number and type of asymmetric synaptic contacts in the molecular layer of the dentate gyrus. As expected, whereas pilocarpine-treated rats had dense silver grain deposits in the inner molecular layer (reflecting mossy fiber sprouting, pilocarpine+cycloheximide-treated animals did not differ from controls. Both groups of treated rats (Pilo group and CHX+Pilo group had reduced density of asymmetric synaptic profiles (putative excitatory synaptic contacts, which was greater for cycloheximide-treated animals. For both treated groups the loss of excitatory synaptic contacts was even greater in the outer molecular layer than in the best studied inner molecular layer (in which mossy fiber sprouting occurs. These results indicate that mossy fiber sprouting tends to replace lost synaptic contacts rather than increase the absolute number of contacts. We speculate that the overall result is more consistent with restored rather than with increased excitability.

  4. Advances in synapse formation: forging connections in the worm.

    Science.gov (United States)

    Cherra, Salvatore J; Jin, Yishi

    2015-01-01

    Synapse formation is the quintessential process by which neurons form specific connections with their targets to enable the development of functional circuits. Over the past few decades, intense research efforts have identified thousands of proteins that localize to the pre- and postsynaptic compartments. Genetic dissection has provided important insights into the nexus of the molecular and cellular network, and has greatly advanced our knowledge about how synapses form and function physiologically. Moreover, recent studies have highlighted the complex regulation of synapse formation with the identification of novel mechanisms involving cell interactions from non-neuronal sources. In this review, we cover the conserved pathways required for synaptogenesis and place specific focus on new themes of synapse modulation arising from studies in Caenorhabditis elegans. For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article. © 2014 Wiley Periodicals, Inc.

  5. Silent Synapse-Based Circuitry Remodeling in Drug Addiction.

    Science.gov (United States)

    Dong, Yan

    2016-05-01

    Exposure to cocaine, and likely other drugs of abuse, generates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-silent glutamatergic synapses in the nucleus accumbens. These immature synaptic contacts evolve after drug withdrawal to redefine the neurocircuital properties. These results raise at least three critical questions: (1) what are the molecular and cellular mechanisms that mediate drug-induced generation of silent synapses; (2) how are neurocircuits remodeled upon generation and evolution of drug-generated silent synapses; and (3) what behavioral consequences are produced by silent synapse-based circuitry remodeling? This short review analyzes related experimental results, and extends them to some speculations. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  6. Changes in rat hippocampal CA1 synapses following imipramine treatment

    DEFF Research Database (Denmark)

    Chen, Fenghua; Madsen, Torsten M; Wegener, Gregers

    2008-01-01

    Neuronal plasticity in hippocampus is hypothesized to play an important role in both the pathophysiology of depressive disorders and the treatment. In this study, we investigated the consequences of imipramine treatment on neuroplasticity (including neurogenesis, synaptogenesis, and remodelling...... and number of neurons of hippocampal subregions following imipramine treatment were found. However, the number and percentage of CA1 asymmetric spine synapses increased significantly and, conversely, the percentage of asymmetric shaft synapses significantly decreased in the imipramine treated group. Our...

  7. When is an Inhibitory Synapse Effective?

    Science.gov (United States)

    Qian, Ning; Sejnowski, Terrence J.

    1990-10-01

    Interactions between excitatory and inhibitory synaptic inputs on dendrites determine the level of activity in neurons. Models based on the cable equation predict that silent shunting inhibition can strongly veto the effect of an excitatory input. The cable model assumes that ionic concentrations do not change during the electrical activity, which may not be a valid assumption, especially for small structures such as dendritic spines. We present here an analysis and computer simulations to show that for large Cl^- conductance changes, the more general Nernst-Planck electrodiffusion model predicts that shunting inhibition on spines should be much less effective than that predicted by the cable model. This is a consequence of the large changes in the intracellular ionic concentration of Cl^- that can occur in small structures, which would alter the reversal potential and reduce the driving force for Cl^-. Shunting inhibition should therefore not be effective on spines, but it could be significantly more effective on the dendritic shaft at the base of the spine. In contrast to shunting inhibition, hyperpolarizing synaptic inhibition mediated by K^+ currents can be very effective in reducing the excitatory synaptic potentials on the same spine if the excitatory conductance change is less than 10 nS. We predict that if the inhibitory synapses found on cortical spines are to be effective, then they should be mediated by K^+ through GABA_B receptors.

  8. Calcium channel-dependent molecular maturation of photoreceptor synapses.

    Directory of Open Access Journals (Sweden)

    Nawal Zabouri

    Full Text Available Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V1.4(α(1F knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V1.4(α(1F knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

  9. Calcium channel-dependent molecular maturation of photoreceptor synapses.

    Science.gov (United States)

    Zabouri, Nawal; Haverkamp, Silke

    2013-01-01

    Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V)1.4(α(1F)) knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V)1.4(α(1F)) knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V)1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V)1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V)1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

  10. Transmitter release in the neuromuscular synapse of the protein kinase C theta-deficient adult mouse.

    Science.gov (United States)

    Besalduch, Núria; Santafé, Manel M; Garcia, Neus; Gonzalez, Carmen; Tomás, Marta; Tomás, Josep; Lanuza, Maria A

    2011-04-01

    We studied structural and functional features of the neuromuscular junction in adult mice (P30) genetically deficient in the protein kinase C (PKC) theta isoform. Confocal and electron microscopy shows that there are no differences in the general morphology of the endplates between PKC theta-deficient and wild-type (WT) mice. Specifically, there is no difference in the density of the synaptic vesicles. However, the myelin sheath is not as thick in the intramuscular nerve fibers of the PKC theta-deficient mice. We found a significant reduction in the size of evoked endplate potentials and in the frequency of spontaneous, asynchronous, miniature endplate potentials in the PKC theta-deficient neuromuscular preparations in comparison with the WT, but the mean amplitude of the spontaneous potentials is not different. These changes indicate that PKC theta has a presynaptic role in the function of adult neuromuscular synapses. Copyright © 2010 Wiley-Liss, Inc.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Stabilization of memory States by stochastic facilitating synapses.

    Science.gov (United States)

    Miller, Paul

    2013-12-06

    Bistability within a small neural circuit can arise through an appropriate strength of excitatory recurrent feedback. The stability of a state of neural activity, measured by the mean dwelling time before a noise-induced transition to another state, depends on the neural firing-rate curves, the net strength of excitatory feedback, the statistics of spike times, and increases exponentially with the number of equivalent neurons in the circuit. Here, we show that such stability is greatly enhanced by synaptic facilitation and reduced by synaptic depression. We take into account the alteration in times of synaptic vesicle release, by calculating distributions of inter-release intervals of a synapse, which differ from the distribution of its incoming interspike intervals when the synapse is dynamic. In particular, release intervals produced by a Poisson spike train have a coefficient of variation greater than one when synapses are probabilistic and facilitating, whereas the coefficient of variation is less than one when synapses are depressing. However, in spite of the increased variability in postsynaptic input produced by facilitating synapses, their dominant effect is reduced synaptic efficacy at low input rates compared to high rates, which increases the curvature of neural input-output functions, leading to wider regions of bistability in parameter space and enhanced lifetimes of memory states. Our results are based on analytic methods with approximate formulae and bolstered by simulations of both Poisson processes and of circuits of noisy spiking model neurons.

  13. Efficacité comparée de deux méthodes de maîtrise de la reproduction de la brebis Djalonké, variété 'Mossi'

    Directory of Open Access Journals (Sweden)

    Boly, H.

    2000-01-01

    Full Text Available Estrous Synchronisation in Djalonke, var. 'Mossi' Ewes : Comparison of Hormonal Treatment and Ram Effect. Zootechnical (ram effect and hormonal (Fluoro Gestone Acetate or FGA, and Pregnant Mare Serum Gonodotropin or PMSG methods on estrous and parturition synchronisation were tested on 24 Djalonke var. 'Mossi' ewes. The use of ram jumping combined with plasma progesterone assay showed that the zootechnical method using male effect provides better estrous synchronisation (4.8 + 2.2 days for estrous delay and better gathering of parturition (within 8 days. The hormonal method by FGA + PMSG provide good estrous synchronisation (3.1 + 20days but lead to a weak lam-bing gathering (within 21 days. After hormonal induction of estrous, a lower fertility was observed and seems to be related to the doses of FGA and PMSG with were relatively high for these small format of Djalonke var. 'Mossi' breed.

  14. Fiber webs

    Science.gov (United States)

    Roger M. Rowell; James S. Han; Von L. Byrd

    2005-01-01

    Wood fibers can be used to produce a wide variety of low-density three-dimensional webs, mats, and fiber-molded products. Short wood fibers blended with long fibers can be formed into flexible fiber mats, which can be made by physical entanglement, nonwoven needling, or thermoplastic fiber melt matrix technologies. The most common types of flexible mats are carded, air...

  15. Oxytocin Depolarizes Fast-Spiking Hilar Interneurons and Induces GABA Release onto Mossy Cells of the Rat Dentate Gyrus

    Science.gov (United States)

    Harden, Scott W.; Frazier, Charles J.

    2016-01-01

    Delivery of exogenous oxytocin (OXT) to central oxytocin receptors (OXT-Rs) is currently being investigated as a potential treatment for conditions such as post-traumatic stress disorder (PTSD), depression, social anxiety, and autism spectrum disorder (ASD). Despite significant research implicating central OXT signaling in modulation of mood, affect, social behavior, and stress response, relatively little is known about the cellular and synaptic mechanisms underlying these complex actions, particularly in brain regions which express the OXT-R but lie outside of the hypothalamus (where OXT-synthesizing neurons reside). We report that bath application of low concentrations of the selective OXT-R agonist Thr4,Gly7-OXT (TGOT) reliably and robustly drives GABA release in the dentate gyrus in an action potential dependent manner. Additional experiments led to identification of a small subset of small hilar interneurons that are directly depolarized by acute application of TGOT. From a physiological perspective, TGOT-responsive hilar interneurons have high input resistance, rapid repolarization velocity during an action potential, and a robust afterhyperpolarization. Further, they fire irregularly (or stutter) in response to moderate depolarization, and fire quickly with minimal spike frequency accommodation in response to large current injections. From an anatomical perspective, TGOT responsive hilar interneurons have dense axonal arborizations in the hilus that were found close proximity with mossy cell somata and/or proximal dendrites, and also invade the granule cell layer. Further, they have primary dendrites that always extend into the granule cell layer, and sometimes have clear arborizations in the molecular layer. Overall, these data reveal a novel site of action for OXT in an important limbic circuit, and represent a significant step towards better understanding how endogenous OXT may modulate flow of information in hippocampal networks. PMID:27068005

  16. Acute restraint stress decreases c-fos immunoreactivity in hilar mossy cells of the adult dentate gyrus

    Science.gov (United States)

    Moretto, Jillian N.; Duffy, Áine M.

    2017-01-01

    Although a great deal of information is available about the circuitry of the mossy cells (MCs) of the dentate gyrus (DG) hilus, their activity in vivo is not clear. The immediate early gene c-fos can be used to gain insight into the activity of MCs in vivo, because c-fos protein expression reflects increased neuronal activity. In prior work, it was identified that control rats that were perfusion-fixed after removal from their home cage exhibited c-fos immunoreactivity (ir) in the DG in a spatially stereotyped pattern: ventral MCs and dorsal granule cells (GCs) expressed c-fos protein (Duffy et al., Hippocampus 23:649–655, 2013). In this study, we hypothesized that restraint stress would alter c-fos-ir, because MCs express glucocorticoid type 2 receptors and the DG is considered to be involved in behaviors related to stress or anxiety. We show that acute restraint using a transparent nose cone for just 10 min led to reduced c-fos-ir in ventral MCs compared to control rats. In these comparisons, c-fos-ir was evaluated 30 min after the 10 min-long period of restraint, and if evaluation was later than 30 min c-fos-ir was no longer suppressed. Granule cells (GCs) also showed suppressed c-fos-ir after acute restraint, but it was different than MCs, because the suppression persisted for over 30 min after the restraint. We conclude that c-fos protein expression is rapidly and transiently reduced in ventral hilar MCs after a brief period of restraint, and suppressed longer in dorsal GCs. PMID:28190104

  17. Estradiol pretreatment ameliorates impaired synaptic plasticity at synapses of insulted CA1 neurons after transient global ischemia

    Science.gov (United States)

    Takeuchi, Koichi; Yang, Yupeng; Takayasu, Yukihiro; Gertner, Michael; Hwang, Jee-Yeon; Aromolaran, Kelly; Bennett, Michael V.L.; Zukin, R. Suzanne

    2015-01-01

    Global ischemia in humans or induced experimentally in animals causes selective and delayed neuronal death in pyramidal neurons of the hippocampal CA1. The ovarian hormone estradiol administered before or immediately after insult affords histological protection in experimental models of focal and global ischemia and ameliorates the cognitive deficits associated with ischemic cell death. However, the impact of estradiol on the functional integrity of Schaffer collateral to CA1 (Sch-CA1) pyramidal cell synapses following global ischemia is not clear. Here we show that long term estradiol treatment initiated 14 days prior to global ischemia in ovariectomized female rats acts via the IGF-1 receptor to protect the functional integrity of CA1 neurons. Global ischemia impairs basal synaptic transmission, assessed by the input/output relation at Sch-CA1 synapses, and NMDA receptor (NMDAR)-dependent long term potentiation (LTP), assessed at 3 days after surgery. Presynaptic function, assessed by fiber volley and paired pulse facilitation, is unchanged. To our knowledge, our results are the first to demonstrate that estradiol at near physiological concentrations enhances basal excitatory synaptic transmission and ameliorates deficits in LTP at synapses onto CA1 neurons in a clinically-relevant model of global ischemia. Estradiol-induced rescue of LTP requires the IGF-1 receptor, but not the classical estrogen receptors (ER)-α or β. These findings support a model whereby estradiol acts via the IGF-1 receptor to maintain the functional integrity of hippocampal CA1 synapses in the face of global ischemia. PMID:25463028

  18. Spatially restricted actin-regulatory signaling contributes to synapse morphology

    Science.gov (United States)

    Nicholson, Daniel A.; Cahill, Michael E.; Tulisiak, Christopher T.; Geinisman, Yuri; Penzes, Peter

    2012-01-01

    The actin cytoskeleton in dendritic spines is organized into microdomains, but how signaling molecules that regulate actin are spatially governed is incompletely understood. Here we examine how the localization of the RacGEF kalirin-7, a well-characterized regulator of actin in spines, varies as a function of postsynaptic density (PSD) area and spine volume. Using serial section electron microscopy (EM), we find that extrasynaptic, but not synaptic, expression of kalirin-7 varies directly with synapse size and spine volume. Moreover, we find that overall expression levels of kalirin-7 differ in spines bearing perforated and non-perforated synapses, due primarily to extrasynaptic pools of kalirin-7 expression in the former. Overall, our findings indicate that kalirin-7 is differentially compartmentalized in spines as a function of both synapse morphology and spine size. PMID:22458534

  19. Dynamic mobility of functional GABAA receptors at inhibitory synapses.

    Science.gov (United States)

    Thomas, Philip; Mortensen, Martin; Hosie, Alastair M; Smart, Trevor G

    2005-07-01

    Importing functional GABAA receptors into synapses is fundamental for establishing and maintaining inhibitory transmission and for controlling neuronal excitability. By introducing a binding site for an irreversible inhibitor into the GABAA receptor alpha1 subunit channel lining region that can be accessed only when the receptor is activated, we have determined the dynamics of receptor mobility between synaptic and extrasynaptic locations in hippocampal pyramidal neurons. We demonstrate that the cell surface GABAA receptor population shows no fast recovery after irreversible inhibition. In contrast, after selective inhibition, the synaptic receptor population rapidly recovers by the import of new functional entities within minutes. The trafficking pathways that promote rapid importation of synaptic receptors do not involve insertion from intracellular pools, but reflect receptor diffusion within the plane of the membrane. This process offers the synapse a rapid mechanism to replenish functional GABAA receptors at inhibitory synapses and a means to control synaptic efficacy.

  20. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  1. Neuromorphic function learning with carbon nanotube based synapses

    International Nuclear Information System (INIS)

    Gacem, Karim; Filoramo, Arianna; Derycke, Vincent; Retrouvey, Jean-Marie; Chabi, Djaafar; Zhao, Weisheng; Klein, Jacques-Olivier

    2013-01-01

    The principle of using nanoscale memory devices as artificial synapses in neuromorphic circuits is recognized as a promising way to build ground-breaking circuit architectures tolerant to defects and variability. Yet, actual experimental demonstrations of the neural network type of circuits based on non-conventional/non-CMOS memory devices and displaying function learning capabilities remain very scarce. We show here that carbon-nanotube-based memory elements can be used as artificial synapses, combined with conventional neurons and trained to perform functions through the application of a supervised learning algorithm. The same ensemble of eight devices can notably be trained multiple times to code successively any three-input linearly separable Boolean logic function despite device-to-device variability. This work thus represents one of the very few demonstrations of actual function learning with synapses based on nanoscale building blocks. The potential of such an approach for the parallel learning of multiple and more complex functions is also evaluated. (paper)

  2. Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Rosa M Villalba

    2011-08-01

    Full Text Available Striatal dopamine denervation is the pathological hallmark of Parkinson’s disease (PD. Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastructural features of the neuronal synaptic elements at the remaining corticostriatal and thalamostriatal glutamatergic axo-spinous synapses undergo complex ultrastructural remodeling consistent with increased synaptic activity (Villalba et al., 2011. The concept of tripartite synapses (TS was introduced a decade ago, according to which astrocytes process and exchange information with neuronal synaptic elements at glutamatergic synapses (Araque et al., 1999a. Although there has been compelling evidence that astrocytes are integral functional elements of tripartite glutamatergic synaptic complexes in the cerebral cortex and hippocampus, their exact functional role, degree of plasticity and preponderance in other CNS regions remain poorly understood. In this review, we discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We also present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia-neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD

  3. Dynamic Information Encoding With Dynamic Synapses in Neural Adaptation

    Science.gov (United States)

    Li, Luozheng; Mi, Yuanyuan; Zhang, Wenhao; Wang, Da-Hui; Wu, Si

    2018-01-01

    Adaptation refers to the general phenomenon that the neural system dynamically adjusts its response property according to the statistics of external inputs. In response to an invariant stimulation, neuronal firing rates first increase dramatically and then decrease gradually to a low level close to the background activity. This prompts a question: during the adaptation, how does the neural system encode the repeated stimulation with attenuated firing rates? It has been suggested that the neural system may employ a dynamical encoding strategy during the adaptation, the information of stimulus is mainly encoded by the strong independent spiking of neurons at the early stage of the adaptation; while the weak but synchronized activity of neurons encodes the stimulus information at the later stage of the adaptation. The previous study demonstrated that short-term facilitation (STF) of electrical synapses, which increases the synchronization between neurons, can provide a mechanism to realize dynamical encoding. In the present study, we further explore whether short-term plasticity (STP) of chemical synapses, an interaction form more common than electrical synapse in the cortex, can support dynamical encoding. We build a large-size network with chemical synapses between neurons. Notably, facilitation of chemical synapses only enhances pair-wise correlations between neurons mildly, but its effect on increasing synchronization of the network can be significant, and hence it can serve as a mechanism to convey the stimulus information. To read-out the stimulus information, we consider that a downstream neuron receives balanced excitatory and inhibitory inputs from the network, so that the downstream neuron only responds to synchronized firings of the network. Therefore, the response of the downstream neuron indicates the presence of the repeated stimulation. Overall, our study demonstrates that STP of chemical synapse can serve as a mechanism to realize dynamical neural

  4. Distinct transmitter release properties determine differences in short-term plasticity at functional and silent synapses.

    Science.gov (United States)

    Cabezas, Carolina; Buño, Washington

    2006-05-01

    Recent evidence suggests that functional and silent synapses are not only postsynaptically different but also presynaptically distinct. The presynaptic differences may be of functional importance in memory formation because a proposed mechanism for long-term potentiation is the conversion of silent synapses into functional ones. However, there is little direct experimentally evidence of these differences. We have investigated the transmitter release properties of functional and silent Schaffer collateral synapses and show that on the average functional synapses displayed a lower percentage of failures and higher excitatory postsynaptic current (EPSC) amplitudes than silent synapses at +60 mV. Moreover, functional but not silent synapses show paired-pulse facilitation (PPF) at +60 mV and thus presynaptic short-term plasticity will be distinct in the two types of synapse. We examined whether intraterminal endoplasmic reticulum Ca2+ stores influenced the release properties of these synapses. Ryanodine (100 microM) and thapsigargin (1 microM) increased the percentage of failures and decreased both the EPSC amplitude and PPF in functional synapses. Caffeine (10 mM) had the opposite effects. In contrast, silent synapses were insensitive to both ryanodine and caffeine. Hence we have identified differences in the release properties of functional and silent synapses, suggesting that synaptic terminals of functional synapses express regulatory molecular mechanisms that are absent in silent synapses.

  5. Ultralow power artificial synapses using nanotextured magnetic Josephson junctions

    Science.gov (United States)

    Schneider, Michael L.; Donnelly, Christine A.; Russek, Stephen E.; Baek, Burm; Pufall, Matthew R.; Hopkins, Peter F.; Dresselhaus, Paul D.; Benz, Samuel P.; Rippard, William H.

    2018-01-01

    Neuromorphic computing promises to markedly improve the efficiency of certain computational tasks, such as perception and decision-making. Although software and specialized hardware implementations of neural networks have made tremendous accomplishments, both implementations are still many orders of magnitude less energy efficient than the human brain. We demonstrate a new form of artificial synapse based on dynamically reconfigurable superconducting Josephson junctions with magnetic nanoclusters in the barrier. The spiking energy per pulse varies with the magnetic configuration, but in our demonstration devices, the spiking energy is always less than 1 aJ. This compares very favorably with the roughly 10 fJ per synaptic event in the human brain. Each artificial synapse is composed of a Si barrier containing Mn nanoclusters with superconducting Nb electrodes. The critical current of each synapse junction, which is analogous to the synaptic weight, can be tuned using input voltage spikes that change the spin alignment of Mn nanoclusters. We demonstrate synaptic weight training with electrical pulses as small as 3 aJ. Further, the Josephson plasma frequencies of the devices, which determine the dynamical time scales, all exceed 100 GHz. These new artificial synapses provide a significant step toward a neuromorphic platform that is faster, more energy-efficient, and thus can attain far greater complexity than has been demonstrated with other technologies. PMID:29387787

  6. Sleep: The hebbian reinforcement of the local inhibitory synapses.

    Science.gov (United States)

    Touzet, Claude

    2015-09-01

    Sleep is ubiquitous among the animal realm, and represents about 30% of our lives. Despite numerous efforts, the reason behind our need for sleep is still unknown. The Theory of neuronal Cognition (TnC) proposes that sleep is the period of time during which the local inhibitory synapses (in particular the cortical ones) are replenished. Indeed, as long as the active brain stays awake, hebbian learning guarantees that efficient inhibitory synapses lose their efficiency – just because they are efficient at avoiding the activation of the targeted neurons. Since hebbian learning is the only known mechanism of synapse modification, it follows that to replenish the inhibitory synapses' efficiency, source and targeted neurons must be activated together. This is achieved by a local depolarization that may travel (wave). The period of time during which such slow waves are experienced has been named the "slow-wave sleep" (SWS). It is cut into several pieces by shorter periods of paradoxical sleep (REM) which activity resembles that of the awake state. Indeed, SWS – because it only allows local neural activation – decreases the excitatory long distance connections strength. To avoid losing the associations built during the awake state, these long distance activations are played again during the REM sleep. REM and SWS sleeps act together to guarantee that when the subject awakes again, his inhibitory synaptic efficiency is restored and his (excitatory) long distance associations are still there. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. A Neuron- and a Synapse Chip for Artificial Neural Networks

    DEFF Research Database (Denmark)

    Lansner, John; Lehmann, Torsten

    1992-01-01

    A cascadable, analog, CMOS chip set has been developed for hardware implementations of artificial neural networks (ANN's):I) a neuron chip containing an array of neurons with hyperbolic tangent activation functions and adjustable gains, and II) a synapse chip (or a matrix-vector multiplier) where...

  8. Short-term ionic plasticity at GABAergic synapses

    Directory of Open Access Journals (Sweden)

    Joseph Valentino Raimondo

    2012-10-01

    Full Text Available Fast synaptic inhibition in the brain is mediated by the pre-synaptic release of the neurotransmitter γ-Aminobutyric acid (GABA and the post-synaptic activation of GABA-sensitive ionotropic receptors. As with excitatory synapses, it is being increasinly appreciated that a variety of plastic processes occur at inhibitory synapses, which operate over a range of timescales. Here we examine a form of activity-dependent plasticity that is somewhat unique to GABAergic transmission. This involves short-lasting changes to the ionic driving force for the postsynaptic receptors, a process referred to as short-term ionic plasticity. These changes are directly related to the history of activity at inhibitory synapses and are influenced by a variety of factors including the location of the synapse and the post-synaptic cell’s ion regulation mechanisms. We explore the processes underlying this form of plasticity, when and where it can occur, and how it is likely to impact network activity.

  9. Shaping inhibition: activity dependent structural plasticity of GABAergic synapses

    Directory of Open Access Journals (Sweden)

    Carmen E Flores

    2014-10-01

    Full Text Available Inhibitory transmission through the neurotransmitter Ɣ-aminobutyric acid (GABA shapes network activity in the mammalian cerebral cortex by filtering synaptic incoming information and dictating the activity of principal cells. The incredibly diverse population of cortical neurons that use GABA as neurotransmitter shows an equally diverse range of mechanisms that regulate changes in the strength of GABAergic synaptic transmission and allow them to dynamically follow and command the activity of neuronal ensembles. Similarly to glutamatergic synaptic transmission, activity-dependent functional changes in inhibitory neurotransmission are accompanied by alterations in GABAergic synapse structure that range from morphological reorganization of postsynaptic density to de novo formation and elimination of inhibitory contacts. Here we review several aspects of structural plasticity of inhibitory synapses, including its induction by different forms of neuronal activity, behavioral and sensory experience and the molecular mechanisms and signaling pathways involved. We discuss the functional consequences of GABAergic synapse structural plasticity for information processing and memory formation in view of the heterogenous nature of the structural plasticity phenomena affecting inhibitory synapses impinging on somatic and dendritic compartments of cortical and hippocampal neurons.

  10. Cell Adhesion, the Backbone of the Synapse: “Vertebrate” and “Invertebrate” Perspectives

    OpenAIRE

    Giagtzoglou, Nikolaos; Ly, Cindy V.; Bellen, Hugo J.

    2009-01-01

    Synapses are asymmetric intercellular junctions that mediate neuronal communication. The number, type, and connectivity patterns of synapses determine the formation, maintenance, and function of neural circuitries. The complexity and specificity of synaptogenesis relies upon modulation of adhesive properties, which regulate contact initiation, synapse formation, maturation, and functional plasticity. Disruption of adhesion may result in structural and functional imbalance that may lead to neu...

  11. Analog memristive synapse in spiking networks implementing unsupervised learning

    Directory of Open Access Journals (Sweden)

    Erika Covi

    2016-10-01

    Full Text Available Emerging brain-inspired architectures call for devices that can emulate the functionality of biological synapses in order to implement new efficient computational schemes able to solve ill-posed problems. Various devices and solutions are still under investigation and, in this respect, a challenge is opened to the researchers in the field. Indeed, the optimal candidate is a device able to reproduce the complete functionality of a synapse, i.e. the typical synaptic process underlying learning in biological systems (activity-dependent synaptic plasticity. This implies a device able to change its resistance (synaptic strength, or weight upon proper electrical stimuli (synaptic activity and showing several stable resistive states throughout its dynamic range (analog behavior. Moreover, it should be able to perform spike timing dependent plasticity (STDP, an associative homosynaptic plasticity learning rule based on the delay time between the two firing neurons the synapse is connected to. This rule is a fundamental learning protocol in state-of-art networks, because it allows unsupervised learning. Notwithstanding this fact, STDP-based unsupervised learning has been proposed several times mainly for binary synapses rather than multilevel synapses composed of many binary memristors. This paper proposes an HfO2-based analog memristor as a synaptic element which performs STDP within a small spiking neuromorphic network operating unsupervised learning for character recognition. The trained network is able to recognize five characters even in case incomplete or noisy characters are displayed and it is robust to a device-to-device variability of up to +/-30%.

  12. Analog Memristive Synapse in Spiking Networks Implementing Unsupervised Learning.

    Science.gov (United States)

    Covi, Erika; Brivio, Stefano; Serb, Alexander; Prodromakis, Themis; Fanciulli, Marco; Spiga, Sabina

    2016-01-01

    Emerging brain-inspired architectures call for devices that can emulate the functionality of biological synapses in order to implement new efficient computational schemes able to solve ill-posed problems. Various devices and solutions are still under investigation and, in this respect, a challenge is opened to the researchers in the field. Indeed, the optimal candidate is a device able to reproduce the complete functionality of a synapse, i.e., the typical synaptic process underlying learning in biological systems (activity-dependent synaptic plasticity). This implies a device able to change its resistance (synaptic strength, or weight) upon proper electrical stimuli (synaptic activity) and showing several stable resistive states throughout its dynamic range (analog behavior). Moreover, it should be able to perform spike timing dependent plasticity (STDP), an associative homosynaptic plasticity learning rule based on the delay time between the two firing neurons the synapse is connected to. This rule is a fundamental learning protocol in state-of-art networks, because it allows unsupervised learning. Notwithstanding this fact, STDP-based unsupervised learning has been proposed several times mainly for binary synapses rather than multilevel synapses composed of many binary memristors. This paper proposes an HfO 2 -based analog memristor as a synaptic element which performs STDP within a small spiking neuromorphic network operating unsupervised learning for character recognition. The trained network is able to recognize five characters even in case incomplete or noisy images are displayed and it is robust to a device-to-device variability of up to ±30%.

  13. Photorefractive Fibers

    National Research Council Canada - National Science Library

    Kuzyk, Mark G

    2003-01-01

    ... scope of the project. In addition to our work in optical limiting fibers, spillover results included making fiber-based light-sources, writing holograms in fibers, and developing the theory of the limits of the nonlinear...

  14. Molecular Mechanisms of Synaptic Specificity: Spotlight on Hippocampal and Cerebellar Synapse Organizers.

    Science.gov (United States)

    Park, Dongseok; Bae, Sungwon; Yoon, Taek Han; Ko, Jaewon

    2018-04-18

    Synapses and neural circuits form with exquisite specificity during brain development to allow the precise and appropriate flow of neural information. Although this property of synapses and neural circuits has been extensively investigated for more than a century, molecular mechanisms underlying this property are only recently being unveiled. Recent studies highlight several classes of cell-surface proteins as organizing hubs in building structural and functional architectures of specific synapses and neural circuits. In the present minireview, we discuss recent findings on various synapse organizers that confer the distinct properties of specific synapse types and neural circuit architectures in mammalian brains, with a particular focus on the hippocampus and cerebellum.

  15. Making of a Synapse: Recurrent Roles of Drebrin A at Excitatory Synapses Throughout Life.

    Science.gov (United States)

    Aoki, Chiye; Sherpa, Ang D

    2017-01-01

    Mature excitatory synapses are composed of more than 1500 proteins postsynaptically and hundreds more that operate presynaptically. Among them, drebrin is an F-actin-binding protein that increases noticeably during juvenile synaptogenesis. Electron microscopic analysis reveals that drebrin is highly enriched specifically on the postsynaptic side of excitatory synapses. Since dendritic spines are structures specialized for excitatory synaptic transmission, the function of drebrin was probed by analyzing the ultrastructural characteristics of dendritic spines of animals with genetic deletion of drebrin A (DAKO), the adult isoform of drebrin. Electron microscopic analyses revealed that these brains are surprisingly intact, in that axo-spinous synaptic junctions are well-formed and not significantly altered in number. This normal ultrastructure may be because drebrin E, the alternate embryonic isoform, compensates for the genetic deletion of drebrin A. However, DAKO results in the loss of homeostatic plasticity of N-methyl-D-aspartate receptors (NMDARs). The NMDAR activation-dependent trafficking of the NR2A subunit-containing NMDARs from dendritic shafts into spine head cytoplasm is greatly diminished within brains of DAKO. Conversely, within brains of wild-type rodents, spines respond to NMDAR blockade with influx of F-actin, drebrin A, and NR2A subunits of NMDARs. These observations indicate that drebrin A facilitates the trafficking of NMDAR cargos in an F-actin-dependent manner to mediate homeostatic plasticity. Analysis of the brains of transgenic mice used as models of Alzheimer's disease (AD) reveals that the loss of drebrin from dendritic spines predates the emergence of synaptic dysfunction and cognitive impairment, suggesting that this form of homeostatic plasticity contributes toward cognition. Two studies suggest that the nature of drebrin's interaction with NMDARs is dependent on the receptor's subunit composition. Drebrin A can be found co

  16. Influence of oculomotor nerve afferents on central endings of primary trigeminal fibers.

    Science.gov (United States)

    Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E; Draicchio, F

    1987-12-01

    Painful fibers running in the third nerve and originating from the ophthalmic trigeminal area send their central projections at level of substantia gelatinosa of nucleus caudalis trigemini. The central endings of these fibers form axoaxonic synapses with trigeminal fibers entering the brain stem through the trigeminal root. The effect of electrical stimulation of the third nerve central stump on the central endings of trigeminal afferent fibers consists in an increased excitability, possibly resulting in a presynaptic inhibition. This inhibitory influence is due to both direct and indirect connections of the third nerve afferent fibers with the trigeminal ones.

  17. Emergent Synapse Organizers: LAR-RPTPs and Their Companions.

    Science.gov (United States)

    Han, K A; Jeon, S; Um, J W; Ko, J

    2016-01-01

    Leukocyte common antigen-related receptor tyrosine phosphatases (LAR-RPTPs) have emerged as key players that organize various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. Recent research has highlighted the roles of LAR-RPTPs at neuronal synapses in mediating distinct synaptic adhesion pathways through interactions with a host of extracellular ligands and in governing a variety of intracellular signaling cascades through binding to various scaffolds and signaling proteins. In this chapter, we review and update current research progress on the extracellular ligands of LAR-RPTPs, regulation of their extracellular interactions by alternative splicing and heparan sulfates, and their intracellular signaling machineries. In particular, we review structural insights on complexes of LAR-RPTPs with their various ligands. These studies lend support to general molecular mechanisms underlying LAR-RPTP-mediated synaptic adhesion and signaling pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Autaptic effects on synchrony of neurons coupled by electrical synapses

    Science.gov (United States)

    Kim, Youngtae

    2017-07-01

    In this paper, we numerically study the effects of a special synapse known as autapse on synchronization of population of Morris-Lecar (ML) neurons coupled by electrical synapses. Several configurations of the ML neuronal populations such as a pair or a ring or a globally coupled network with and without autapses are examined. While most of the papers on the autaptic effects on synchronization have used networks of neurons of same spiking rate, we use the network of neurons of different spiking rates. We find that the optimal autaptic coupling strength and the autaptic time delay enhance synchronization in our neural networks. We use the phase response curve analysis to explain the enhanced synchronization by autapses. Our findings reveal the important relationship between the intraneuronal feedback loop and the interneuronal coupling.

  19. Neural circuit rewiring: insights from DD synapse remodeling.

    Science.gov (United States)

    Kurup, Naina; Jin, Yishi

    2016-01-01

    Nervous systems exhibit many forms of neuronal plasticity during growth, learning and memory consolidation, as well as in response to injury. Such plasticity can occur across entire nervous systems as with the case of insect metamorphosis, in individual classes of neurons, or even at the level of a single neuron. A striking example of neuronal plasticity in C. elegans is the synaptic rewiring of the GABAergic Dorsal D-type motor neurons during larval development, termed DD remodeling. DD remodeling entails multi-step coordination to concurrently eliminate pre-existing synapses and form new synapses on different neurites, without changing the overall morphology of the neuron. This mini-review focuses on recent advances in understanding the cellular and molecular mechanisms driving DD remodeling.

  20. Microorganism and filamentous fungi drive evolution of plant synapses.

    Science.gov (United States)

    Baluška, František; Mancuso, Stefano

    2013-01-01

    In the course of plant evolution, there is an obvious trend toward an increased complexity of plant bodies, as well as an increased sophistication of plant behavior and communication. Phenotypic plasticity of plants is based on the polar auxin transport machinery that is directly linked with plant sensory systems impinging on plant behavior and adaptive responses. Similar to the emergence and evolution of eukaryotic cells, evolution of land plants was also shaped and driven by infective and symbiotic microorganisms. These microorganisms are the driving force behind the evolution of plant synapses and other neuronal aspects of higher plants; this is especially pronounced in the root apices. Plant synapses allow synaptic cell-cell communication and coordination in plants, as well as sensory-motor integration in root apices searching for water and mineral nutrition. These neuronal aspects of higher plants are closely linked with their unique ability to adapt to environmental changes.

  1. The mossy north

    DEFF Research Database (Denmark)

    Mateo, Ruben G.; Broennimann, Olivier; Normand, Signe

    2016-01-01

    , as predicted by theory, and whether the assembly mechanisms differ among taxonomic groups. SR increases towards the south in spermatophytes, but towards the north in ferns and bryophytes. SR patterns in spermatophytes are consistent with their patterns of beta diversity, with high levels of nestedness...... and turnover in the north and in the south, respectively, indicating species exclusion towards the north and increased opportunities for speciation in the south. Liverworts exhibit the highest levels of nestedness, suggesting that they represent the most sensitive group to the impact of past climate change...

  2. The State of Synapses in Fragile X Syndrome

    OpenAIRE

    Pfeiffer, Brad E.; Huber, Kimberly M.

    2009-01-01

    Fragile X Syndrome is the most common inherited form of mental retardation and a leading genetic cause of autism. There is increasing evidence in both FXS and other forms of autism that alterations in synapse number, structure and function are associated and contribute to these prevalent diseases. FXS is caused by loss of function of the Fmr1 gene which encodes the RNA binding protein, FMRP. Therefore, FXS is a tractable model to understand synaptic dysfunction in cognitive disorders. FMRP is...

  3. Storage capacity of attractor neural networks with depressing synapses

    International Nuclear Information System (INIS)

    Torres, Joaquin J.; Pantic, Lovorka; Kappen, Hilbert J.

    2002-01-01

    We compute the capacity of a binary neural network with dynamic depressing synapses to store and retrieve an infinite number of patterns. We use a biologically motivated model of synaptic depression and a standard mean-field approach. We find that at T=0 the critical storage capacity decreases with the degree of the depression. We confirm the validity of our main mean-field results with numerical simulations

  4. Process for forming synapses in neural networks and resistor therefor

    Science.gov (United States)

    Fu, Chi Y.

    1996-01-01

    Customizable neural network in which one or more resistors form each synapse. All the resistors in the synaptic array are identical, thus simplifying the processing issues. Highly doped, amorphous silicon is used as the resistor material, to create extremely high resistances occupying very small spaces. Connected in series with each resistor in the array is at least one severable conductor whose uppermost layer has a lower reflectivity of laser energy than typical metal conductors at a desired laser wavelength.

  5. Fiber dielectrophoresis

    International Nuclear Information System (INIS)

    Lipowicz, P.J.; Yeh, H.C.

    1988-01-01

    Dielectrophoresis is the motion of uncharged particles in nonuniform electric fields. We find that the theoretical dielectrophoretic velocity of a conducting fiber in an insulating medium is proportional to the square of the fiber length, and is virtually independent of fiber diameter. This prediction has been verified experimentally. The results point to the development of a fiber length classifier based on dielectrophoresis. (author)

  6. TFH-derived dopamine accelerates productive synapses in germinal centres.

    Science.gov (United States)

    Papa, Ilenia; Saliba, David; Ponzoni, Maurilio; Bustamante, Sonia; Canete, Pablo F; Gonzalez-Figueroa, Paula; McNamara, Hayley A; Valvo, Salvatore; Grimbaldeston, Michele; Sweet, Rebecca A; Vohra, Harpreet; Cockburn, Ian A; Meyer-Hermann, Michael; Dustin, Michael L; Doglioni, Claudio; Vinuesa, Carola G

    2017-07-20

    Protective high-affinity antibody responses depend on competitive selection of B cells carrying somatically mutated B-cell receptors by follicular helper T (T FH ) cells in germinal centres. The rapid T-B-cell interactions that occur during this process are reminiscent of neural synaptic transmission pathways. Here we show that a proportion of human T FH cells contain dense-core granules marked by chromogranin B, which are normally found in neuronal presynaptic terminals storing catecholamines such as dopamine. T FH cells produce high amounts of dopamine and release it upon cognate interaction with B cells. Dopamine causes rapid translocation of intracellular ICOSL (inducible T-cell co-stimulator ligand, also known as ICOSLG) to the B-cell surface, which enhances accumulation of CD40L and chromogranin B granules at the human T FH cell synapse and increases the synapse area. Mathematical modelling suggests that faster dopamine-induced T-B-cell interactions increase total germinal centre output and accelerate it by days. Delivery of neurotransmitters across the T-B-cell synapse may be advantageous in the face of infection.

  7. The space where aging acts: focus on the GABAergic synapse.

    Science.gov (United States)

    Rozycka, Aleksandra; Liguz-Lecznar, Monika

    2017-08-01

    As it was established that aging is not associated with massive neuronal loss, as was believed in the mid-20th Century, scientific interest has addressed the influence of aging on particular neuronal subpopulations and their synaptic contacts, which constitute the substrate for neural plasticity. Inhibitory neurons represent the most complex and diverse group of neurons, showing distinct molecular and physiological characteristics and possessing a compelling ability to control the physiology of neural circuits. This review focuses on the aging of GABAergic neurons and synapses. Understanding how aging affects synapses of particular neuronal subpopulations may help explain the heterogeneity of aging-related effects. We reviewed the literature concerning the effects of aging on the numbers of GABAergic neurons and synapses as well as aging-related alterations in their presynaptic and postsynaptic components. Finally, we discussed the influence of those changes on the plasticity of the GABAergic system, highlighting our results concerning aging in mouse somatosensory cortex and linking them to plasticity impairments and brain disorders. We posit that aging-induced impairments of the GABAergic system lead to an inhibitory/excitatory imbalance, thereby decreasing neuron's ability to respond with plastic changes to environmental and cellular challenges, leaving the brain more vulnerable to cognitive decline and damage by synaptopathic diseases. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  8. Synapse geometry and receptor dynamics modulate synaptic strength.

    Directory of Open Access Journals (Sweden)

    Dominik Freche

    Full Text Available Synaptic transmission relies on several processes, such as the location of a released vesicle, the number and type of receptors, trafficking between the postsynaptic density (PSD and extrasynaptic compartment, as well as the synapse organization. To study the impact of these parameters on excitatory synaptic transmission, we present a computational model for the fast AMPA-receptor mediated synaptic current. We show that in addition to the vesicular release probability, due to variations in their release locations and the AMPAR distribution, the postsynaptic current amplitude has a large variance, making a synapse an intrinsic unreliable device. We use our model to examine our experimental data recorded from CA1 mice hippocampal slices to study the differences between mEPSC and evoked EPSC variance. The synaptic current but not the coefficient of variation is maximal when the active zone where vesicles are released is apposed to the PSD. Moreover, we find that for certain type of synapses, receptor trafficking can affect the magnitude of synaptic depression. Finally, we demonstrate that perisynaptic microdomains located outside the PSD impacts synaptic transmission by regulating the number of desensitized receptors and their trafficking to the PSD. We conclude that geometrical modifications, reorganization of the PSD or perisynaptic microdomains modulate synaptic strength, as the mechanisms underlying long-term plasticity.

  9. Synapse-specific astrocyte gating of amygdala-related behavior.

    Science.gov (United States)

    Martin-Fernandez, Mario; Jamison, Stephanie; Robin, Laurie M; Zhao, Zhe; Martin, Eduardo D; Aguilar, Juan; Benneyworth, Michael A; Marsicano, Giovanni; Araque, Alfonso

    2017-11-01

    The amygdala plays key roles in fear and anxiety. Studies of the amygdala have largely focused on neuronal function and connectivity. Astrocytes functionally interact with neurons, but their role in the amygdala remains largely unknown. We show that astrocytes in the medial subdivision of the central amygdala (CeM) determine the synaptic and behavioral outputs of amygdala circuits. To investigate the role of astrocytes in amygdala-related behavior and identify the underlying synaptic mechanisms, we used exogenous or endogenous signaling to selectively activate CeM astrocytes. Astrocytes depressed excitatory synapses from basolateral amygdala via A 1 adenosine receptor activation and enhanced inhibitory synapses from the lateral subdivision of the central amygdala via A 2A receptor activation. Furthermore, astrocytic activation decreased the firing rate of CeM neurons and reduced fear expression in a fear-conditioning paradigm. Therefore, we conclude that astrocyte activity determines fear responses by selectively regulating specific synapses, which indicates that animal behavior results from the coordinated activity of neurons and astrocytes.

  10. Memory-Relevant Mushroom Body Output Synapses Are Cholinergic.

    Science.gov (United States)

    Barnstedt, Oliver; Owald, David; Felsenberg, Johannes; Brain, Ruth; Moszynski, John-Paul; Talbot, Clifford B; Perrat, Paola N; Waddell, Scott

    2016-03-16

    Memories are stored in the fan-out fan-in neural architectures of the mammalian cerebellum and hippocampus and the insect mushroom bodies. However, whereas key plasticity occurs at glutamatergic synapses in mammals, the neurochemistry of the memory-storing mushroom body Kenyon cell output synapses is unknown. Here we demonstrate a role for acetylcholine (ACh) in Drosophila. Kenyon cells express the ACh-processing proteins ChAT and VAChT, and reducing their expression impairs learned olfactory-driven behavior. Local ACh application, or direct Kenyon cell activation, evokes activity in mushroom body output neurons (MBONs). MBON activation depends on VAChT expression in Kenyon cells and is blocked by ACh receptor antagonism. Furthermore, reducing nicotinic ACh receptor subunit expression in MBONs compromises odor-evoked activation and redirects odor-driven behavior. Lastly, peptidergic corelease enhances ACh-evoked responses in MBONs, suggesting an interaction between the fast- and slow-acting transmitters. Therefore, olfactory memories in Drosophila are likely stored as plasticity of cholinergic synapses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Natural killer cell signal integration balances synapse symmetry and migration.

    Directory of Open Access Journals (Sweden)

    Fiona J Culley

    2009-07-01

    Full Text Available Natural killer (NK cells discern the health of other cells by recognising the balance of activating and inhibitory ligands expressed by each target cell. However, how the integration of activating and inhibitory signals relates to formation of the NK cell immune synapse remains a central question in our understanding of NK cell recognition. Here we report that ligation of LFA-1 on NK cells induced asymmetrical cell spreading and migration. In contrast, ligation of the activating receptor NKG2D induced symmetrical spreading of ruffled lamellipodia encompassing a dynamic ring of f-actin, concurrent with polarization towards a target cell and a "stop" signal. Ligation of both LFA-1 and NKG2D together resulted in symmetrical spreading but co-ligation of inhibitory receptors reverted NK cells to an asymmetrical migratory configuration leading to inhibitory synapses being smaller and more rapidly disassembled. Using micropatterned activating and inhibitory ligands, signals were found to be continuously and locally integrated during spreading. Together, these data demonstrate that NK cells spread to form large, stable, symmetrical synapses if activating signals dominate, whereas asymmetrical migratory "kinapses" are favoured if inhibitory signals dominate. This clarifies how the integration of activating and inhibitory receptor signals is translated to an appropriate NK cell response.

  12. The 'disector' a tool for quantitative assessment of synaptic plasticity an example on hippocampal synapses and synapse-perforations in ageing rats

    NARCIS (Netherlands)

    Groot, D.M.G. de; Bierman, E.P.B.; Bruijnzeel, P.L.B.; Woutersen, R.A.

    1995-01-01

    The 'disector' method was used to estimate number and size of simple non-perforated and complex 'perforated' synapses and their 'perforations' in the hippocampal CA3 area of 3, 12, 24 and 30 months old rats. A decrease with age from 3 to 24 months of age in the number of non-perforated synapses per

  13. Fiber Amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten

    2017-01-01

    The chapter provides a discussion of optical fiber amplifiers and through three sections provides a detailed treatment of three types of optical fiber amplifiers, erbium doped fiber amplifiers (EDFA), Raman amplifiers, and parametric amplifiers. Each section comprises the fundamentals including...... the basic physics and relevant in-depth theoretical modeling, amplifiers characteristics and performance data as a function of specific operation parameters. Typical applications in fiber optic communication systems and the improvement achievable through the use of fiber amplifiers are illustrated....

  14. Stochastic resonance in small-world neuronal networks with hybrid electrical–chemical synapses

    International Nuclear Information System (INIS)

    Wang, Jiang; Guo, Xinmeng; Yu, Haitao; Liu, Chen; Deng, Bin; Wei, Xile; Chen, Yingyuan

    2014-01-01

    Highlights: •We study stochastic resonance in small-world neural networks with hybrid synapses. •The resonance effect depends largely on the probability of chemical synapse. •An optimal chemical synapse probability exists to evoke network resonance. •Network topology affects the stochastic resonance in hybrid neuronal networks. - Abstract: The dependence of stochastic resonance in small-world neuronal networks with hybrid electrical–chemical synapses on the probability of chemical synapse and the rewiring probability is investigated. A subthreshold periodic signal is imposed on one single neuron within the neuronal network as a pacemaker. It is shown that, irrespective of the probability of chemical synapse, there exists a moderate intensity of external noise optimizing the response of neuronal networks to the pacemaker. Moreover, the effect of pacemaker driven stochastic resonance of the system depends largely on the probability of chemical synapse. A high probability of chemical synapse will need lower noise intensity to evoke the phenomenon of stochastic resonance in the networked neuronal systems. In addition, for fixed noise intensity, there is an optimal chemical synapse probability, which can promote the propagation of the localized subthreshold pacemaker across neural networks. And the optimal chemical synapses probability turns even larger as the coupling strength decreases. Furthermore, the small-world topology has a significant impact on the stochastic resonance in hybrid neuronal networks. It is found that increasing the rewiring probability can always enhance the stochastic resonance until it approaches the random network limit

  15. The urodelean Mauthner cell. Morphology of the afferent synapses to the M-cell of larval Salamandra salamandra

    Energy Technology Data Exchange (ETDEWEB)

    Cioni, C; De Palma, F; De Vito, L; Stefanelli, A [Rome, Univ. (Italy). Dipt. di Biologia Animale e dell` Uomo

    1998-12-31

    In the present work the fine morphology and the distribution of the afferent synapses to the Mauthner cell of larval Salamandra salamandra are described. The aim of the study is to characterize the synaptic bed in the larvae of this terrestrial salamander in order to compare it with that of larval axolotl and larval anurans. Four main types of afferent endings have been identified: myelinated club endings, round-vesicle end bulbs, flattened-vesicle end bulbs and spiral fibers endings. The M-cell afferent synaptology of larval stages of terrestrial amphibians is quite similar to that previously observed in larval stages of aquatic species. This fact can be related to the fundamental similarities between the larval lifestyles.

  16. The urodelean Mauthner cell. Morphology of the afferent synapses to the M-cell of larval Salamandra salamandra

    Energy Technology Data Exchange (ETDEWEB)

    Cioni, C.; De Palma, F.; De Vito, L.; Stefanelli, A. [Rome, Univ. (Italy). Dipt. di Biologia Animale e dell`Uomo

    1997-12-31

    In the present work the fine morphology and the distribution of the afferent synapses to the Mauthner cell of larval Salamandra salamandra are described. The aim of the study is to characterize the synaptic bed in the larvae of this terrestrial salamander in order to compare it with that of larval axolotl and larval anurans. Four main types of afferent endings have been identified: myelinated club endings, round-vesicle end bulbs, flattened-vesicle end bulbs and spiral fibers endings. The M-cell afferent synaptology of larval stages of terrestrial amphibians is quite similar to that previously observed in larval stages of aquatic species. This fact can be related to the fundamental similarities between the larval lifestyles.

  17. Alterations in the properties of neonatal thalamocortical synapses with time in in vitro slices.

    Directory of Open Access Journals (Sweden)

    Liliana L Luz

    Full Text Available New synapses are constantly being generated and lost in the living brain with only a subset of these being stabilized to form an enduring component of neuronal circuitry. The properties of synaptic transmission have primarily been established in a variety of in vitro neuronal preparations. It is not clear, however, if newly-formed and persistent synapses contribute to the results of these studies consistently throughout the lifespan of these preparations. In neonatal somatosensory, barrel, cortex we have previously hypothesized that a population of thalamocortical synapses displaying unusually slow kinetics represent newly-formed, default-transient synapses. This clear phenotype would provide an ideal tool to investigate if such newly formed synapses consistently contribute to synaptic transmission throughout a normal experimental protocol. We show that the proportion of synapses recorded in vitro displaying slow kinetics decreases with time after brain slice preparation. However, slow synapses persist in vitro in the presence of either minocycline, an inhibitor of microglia-mediated synapse elimination, or the TrkB agonist 7,8-dihydroxyflavone a promoter of synapse formation. These findings show that the observed properties of synaptic transmission may systematically change with time in vitro in a standard brain slice preparation.

  18. Synapse:neural network for predict power consumption: users guide

    Energy Technology Data Exchange (ETDEWEB)

    Muller, C; Mangeas, M; Perrot, N

    1994-08-01

    SYNAPSE is forecasting tool designed to predict power consumption in metropolitan France on the half hour time scale. Some characteristics distinguish this forecasting model from those which already exist. In particular, it is composed of numerous neural networks. The idea for using many neural networks arises from past tests. These tests showed us that a single neural network is not able to solve the problem correctly. From this result, we decided to perform unsupervised classification of the 24 consumption curves. From this classification, six classes appeared, linked with the weekdays: Mondays, Tuesdays, Wednesdays, Thursdays, Fridays, Saturdays, Sundays, holidays and bridge days. For each class and for each half hour, two multilayer perceptrons are built. The two of them forecast the power for one particular half hour, and for a day including one of the determined class. The input of these two network are different: the first one (short time forecasting) includes the powers for the most recent half hour and relative power of the previous day; the second (medium time forecasting) includes only the relative power of the previous day. A process connects the results of every networks and allows one to forecast more than one half-hour in advance. In this process, short time forecasting networks and medium time forecasting networks are used differently. The first kind of neural networks gives good results on the scale of one day. The second one gives good forecasts for the next predicted powers. In this note, the organization of the SYNAPSE program is detailed, and the user`s menu is described. This first version of synapse works and should allow the APC group to evaluate its utility. (authors). 6 refs., 2 appends.

  19. Neuron array with plastic synapses and programmable dendrites.

    Science.gov (United States)

    Ramakrishnan, Shubha; Wunderlich, Richard; Hasler, Jennifer; George, Suma

    2013-10-01

    We describe a novel neuromorphic chip architecture that models neurons for efficient computation. Traditional architectures of neuron array chips consist of large scale systems that are interfaced with AER for implementing intra- or inter-chip connectivity. We present a chip that uses AER for inter-chip communication but uses fast, reconfigurable FPGA-style routing with local memory for intra-chip connectivity. We model neurons with biologically realistic channel models, synapses and dendrites. This chip is suitable for small-scale network simulations and can also be used for sequence detection, utilizing directional selectivity properties of dendrites, ultimately for use in word recognition.

  20. A compound memristive synapse model for statistical learning through STDP in spiking neural networks

    Directory of Open Access Journals (Sweden)

    Johannes eBill

    2014-12-01

    Full Text Available Memristors have recently emerged as promising circuit elements to mimic the function of biological synapses in neuromorphic computing. The fabrication of reliable nanoscale memristive synapses, that feature continuous conductance changes based on the timing of pre- and postsynaptic spikes, has however turned out to be challenging. In this article, we propose an alternative approach, the compound memristive synapse, that circumvents this problem by the use of memristors with binary memristive states. A compound memristive synapse employs multiple bistable memristors in parallel to jointly form one synapse, thereby providing a spectrum of synaptic efficacies. We investigate the computational implications of synaptic plasticity in the compound synapse by integrating the recently observed phenomenon of stochastic filament formation into an abstract model of stochastic switching. Using this abstract model, we first show how standard pulsing schemes give rise to spike-timing dependent plasticity (STDP with a stabilizing weight dependence in compound synapses. In a next step, we study unsupervised learning with compound synapses in networks of spiking neurons organized in a winner-take-all architecture. Our theoretical analysis reveals that compound-synapse STDP implements generalized Expectation-Maximization in the spiking network. Specifically, the emergent synapse configuration represents the most salient features of the input distribution in a Mixture-of-Gaussians generative model. Furthermore, the network’s spike response to spiking input streams approximates a well-defined Bayesian posterior distribution. We show in computer simulations how such networks learn to represent high-dimensional distributions over images of handwritten digits with high fidelity even in presence of substantial device variations and under severe noise conditions. Therefore, the compound memristive synapse may provide a synaptic design principle for future neuromorphic

  1. A compound memristive synapse model for statistical learning through STDP in spiking neural networks.

    Science.gov (United States)

    Bill, Johannes; Legenstein, Robert

    2014-01-01

    Memristors have recently emerged as promising circuit elements to mimic the function of biological synapses in neuromorphic computing. The fabrication of reliable nanoscale memristive synapses, that feature continuous conductance changes based on the timing of pre- and postsynaptic spikes, has however turned out to be challenging. In this article, we propose an alternative approach, the compound memristive synapse, that circumvents this problem by the use of memristors with binary memristive states. A compound memristive synapse employs multiple bistable memristors in parallel to jointly form one synapse, thereby providing a spectrum of synaptic efficacies. We investigate the computational implications of synaptic plasticity in the compound synapse by integrating the recently observed phenomenon of stochastic filament formation into an abstract model of stochastic switching. Using this abstract model, we first show how standard pulsing schemes give rise to spike-timing dependent plasticity (STDP) with a stabilizing weight dependence in compound synapses. In a next step, we study unsupervised learning with compound synapses in networks of spiking neurons organized in a winner-take-all architecture. Our theoretical analysis reveals that compound-synapse STDP implements generalized Expectation-Maximization in the spiking network. Specifically, the emergent synapse configuration represents the most salient features of the input distribution in a Mixture-of-Gaussians generative model. Furthermore, the network's spike response to spiking input streams approximates a well-defined Bayesian posterior distribution. We show in computer simulations how such networks learn to represent high-dimensional distributions over images of handwritten digits with high fidelity even in presence of substantial device variations and under severe noise conditions. Therefore, the compound memristive synapse may provide a synaptic design principle for future neuromorphic architectures.

  2. GLUT4 Mobilization Supports Energetic Demands of Active Synapses.

    Science.gov (United States)

    Ashrafi, Ghazaleh; Wu, Zhuhao; Farrell, Ryan J; Ryan, Timothy A

    2017-02-08

    The brain is highly sensitive to proper fuel availability as evidenced by the rapid decline in neuronal function during ischemic attacks and acute severe hypoglycemia. We previously showed that sustained presynaptic function requires activity-driven glycolysis. Here, we provide strong evidence that during action potential (AP) firing, nerve terminals rely on the glucose transporter GLUT4 as a glycolytic regulatory system to meet the activity-driven increase in energy demands. Activity at synapses triggers insertion of GLUT4 into the axonal plasma membrane driven by activation of the metabolic sensor AMP kinase. Furthermore, we show that genetic ablation of GLUT4 leads to an arrest of synaptic vesicle recycling during sustained AP firing, similar to what is observed during acute glucose deprivation. The reliance on this biochemical regulatory system for "exercising" synapses is reminiscent of that occurring in exercising muscle to sustain cellular function and identifies nerve terminals as critical sites of proper metabolic control. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Power-law forgetting in synapses with metaplasticity

    International Nuclear Information System (INIS)

    Mehta, A; Luck, J M

    2011-01-01

    The idea of using metaplastic synapses to incorporate the separate storage of long- and short-term memories via an array of hidden states was put forward in the cascade model of Fusi et al. In this paper, we devise and investigate two models of a metaplastic synapse based on these general principles. The main difference between the two models lies in their available mechanisms of decay, when a contrarian event occurs after the build-up of a long-term memory. In one case, this leads to the conversion of the long-term memory to a short-term memory of the opposite kind, while in the other, a long-term memory of the opposite kind may be generated as a result. Appropriately enough, the response of both models to short-term events is not affected by this difference in architecture. On the contrary, the transient response of both models, after long-term memories have been created by the passage of sustained signals, is rather different. The asymptotic behaviour of both models is, however, characterised by power-law forgetting with the same universal exponent

  4. Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture

    Directory of Open Access Journals (Sweden)

    Marta Esteves da Silva

    2015-11-01

    Full Text Available Lateral diffusion in the membrane and endosomal trafficking both contribute to the addition and removal of AMPA receptors (AMPARs at postsynaptic sites. However, the spatial coordination between these mechanisms has remained unclear, because little is known about the dynamics of AMPAR-containing endosomes. In addition, how the positioning of AMPAR-containing endosomes affects synapse organization and functioning has never been directly explored. Here, we used live-cell imaging in hippocampal neuron cultures to show that intracellular AMPARs are transported in Rab11-positive recycling endosomes, which frequently enter dendritic spines and depend on the microtubule and actin cytoskeleton. By using chemically induced dimerization systems to recruit kinesin (KIF1C or myosin (MyosinV/VI motors to Rab11-positive recycling endosomes, we controlled their trafficking and found that induced removal of recycling endosomes from spines decreases surface AMPAR expression and PSD-95 clusters at synapses. Our data suggest a mechanistic link between endosome positioning and postsynaptic structure and composition.

  5. Unsupervised learning in neural networks with short range synapses

    Science.gov (United States)

    Brunnet, L. G.; Agnes, E. J.; Mizusaki, B. E. P.; Erichsen, R., Jr.

    2013-01-01

    Different areas of the brain are involved in specific aspects of the information being processed both in learning and in memory formation. For example, the hippocampus is important in the consolidation of information from short-term memory to long-term memory, while emotional memory seems to be dealt by the amygdala. On the microscopic scale the underlying structures in these areas differ in the kind of neurons involved, in their connectivity, or in their clustering degree but, at this level, learning and memory are attributed to neuronal synapses mediated by longterm potentiation and long-term depression. In this work we explore the properties of a short range synaptic connection network, a nearest neighbor lattice composed mostly by excitatory neurons and a fraction of inhibitory ones. The mechanism of synaptic modification responsible for the emergence of memory is Spike-Timing-Dependent Plasticity (STDP), a Hebbian-like rule, where potentiation/depression is acquired when causal/non-causal spikes happen in a synapse involving two neurons. The system is intended to store and recognize memories associated to spatial external inputs presented as simple geometrical forms. The synaptic modifications are continuously applied to excitatory connections, including a homeostasis rule and STDP. In this work we explore the different scenarios under which a network with short range connections can accomplish the task of storing and recognizing simple connected patterns.

  6. 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.

  7. Slack KNa Channels Influence Dorsal Horn Synapses and Nociceptive Behavior.

    Science.gov (United States)

    Evely, Katherine M; Pryce, Kerri D; Bausch, Anne E; Lukowski, Robert; Ruth, Peter; Haj-Dahmane, Samir; Bhattacharjee, Arin

    2017-01-01

    The sodium-activated potassium channel Slack (Kcnt1, Slo2.2) is highly expressed in dorsal root ganglion neurons where it regulates neuronal firing. Several studies have implicated the Slack channel in pain processing, but the precise mechanism or the levels within the sensory pathway where channels are involved remain unclear. Here, we furthered the behavioral characterization of Slack channel knockout mice and for the first time examined the role of Slack channels in the superficial, pain-processing lamina of the dorsal horn. We performed whole-cell recordings from spinal cord slices to examine the intrinsic and synaptic properties of putative inhibitory and excitatory lamina II interneurons. Slack channel deletion altered intrinsic properties and synaptic drive to favor an overall enhanced excitatory tone. We measured the amplitudes and paired pulse ratio of paired excitatory post-synaptic currents at primary afferent synapses evoked by electrical stimulation of the dorsal root entry zone. We found a substantial decrease in the paired pulse ratio at synapses in Slack deleted neurons compared to wildtype, indicating increased presynaptic release from primary afferents. Corroborating these data, plantar test showed Slack knockout mice have an enhanced nociceptive responsiveness to localized thermal stimuli compared to wildtype mice. Our findings suggest that Slack channels regulate synaptic transmission within the spinal cord dorsal horn and by doing so establishes the threshold for thermal nociception.

  8. Building blocks of temporal filters in retinal synapses.

    Directory of Open Access Journals (Sweden)

    Bongsoo Suh

    2014-10-01

    Full Text Available Sensory systems must be able to extract features of a stimulus to detect and represent properties of the world. Because sensory signals are constantly changing, a critical aspect of this transformation relates to the timing of signals and the ability to filter those signals to select dynamic properties, such as visual motion. At first assessment, one might think that the primary biophysical properties that construct a temporal filter would be dynamic mechanisms such as molecular concentration or membrane electrical properties. However, in the current issue of PLOS Biology, Baden et al. identify a mechanism of temporal filtering in the zebrafish and goldfish retina that is not dynamic but is in fact a structural building block-the physical size of a synapse itself. The authors observe that small, bipolar cell synaptic terminals are fast and highly adaptive, whereas large ones are slower and adapt less. Using a computational model, they conclude that the volume of the synaptic terminal influences the calcium concentration and the number of available vesicles. These results indicate that the size of the presynaptic terminal is an independent control for the dynamics of a synapse and may reveal aspects of synaptic function that can be inferred from anatomical structure.

  9. Alcohol impairs long-term depression at the cerebellar parallel fiber-Purkinje cell synapse

    NARCIS (Netherlands)

    A. Belmeguenai (Amor); P. Botta (Paolo); J.T. Weber (John); M. Carta (Mario); M.M. de Ruiter (Martijn); C.I. de Zeeuw (Chris); C.F. Valenzuela (Fernando); C.R.W. Hansel (Christian)

    2008-01-01

    textabstractAcute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor learning. It has previously been shown that ethanol modulates inhibitory transmission in the

  10. Autism-Associated Chromatin Regulator Brg1/SmarcA4 Is Required for Synapse Development and Myocyte Enhancer Factor 2-Mediated Synapse Remodeling.

    Science.gov (United States)

    Zhang, Zilai; Cao, Mou; Chang, Chia-Wei; Wang, Cindy; Shi, Xuanming; Zhan, Xiaoming; Birnbaum, Shari G; Bezprozvanny, Ilya; Huber, Kimberly M; Wu, Jiang I

    2016-01-01

    Synapse development requires normal neuronal activities and the precise expression of synapse-related genes. Dysregulation of synaptic genes results in neurological diseases such as autism spectrum disorders (ASD). Mutations in genes encoding chromatin-remodeling factor Brg1/SmarcA4 and its associated proteins are the genetic causes of several developmental diseases with neurological defects and autistic symptoms. Recent large-scale genomic studies predicted Brg1/SmarcA4 as one of the key nodes of the ASD gene network. We report that Brg1 deletion in early postnatal hippocampal neurons led to reduced dendritic spine density and maturation and impaired synapse activities. In developing mice, neuronal Brg1 deletion caused severe neurological defects. Gene expression analyses indicated that Brg1 regulates a significant number of genes known to be involved in synapse function and implicated in ASD. We found that Brg1 is required for dendritic spine/synapse elimination mediated by the ASD-associated transcription factor myocyte enhancer factor 2 (MEF2) and that Brg1 regulates the activity-induced expression of a specific subset of genes that overlap significantly with the targets of MEF2. Our analyses showed that Brg1 interacts with MEF2 and that MEF2 is required for Brg1 recruitment to target genes in response to neuron activation. Thus, Brg1 plays important roles in both synapse development/maturation and MEF2-mediated synapse remodeling. Our study reveals specific functions of the epigenetic regulator Brg1 in synapse development and provides insights into its role in neurological diseases such as ASD. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Remodeling of hippocampal spine synapses in the rat learned helplessness model of depression.

    Science.gov (United States)

    Hajszan, Tibor; Dow, Antonia; Warner-Schmidt, Jennifer L; Szigeti-Buck, Klara; Sallam, Nermin L; Parducz, Arpad; Leranth, Csaba; Duman, Ronald S

    2009-03-01

    Although it has been postulated for many years that depression is associated with loss of synapses, primarily in the hippocampus, and that antidepressants facilitate synapse growth, we still lack ultrastructural evidence that changes in depressive behavior are indeed correlated with structural synaptic modifications. We analyzed hippocampal spine synapses of male rats (n=127) with electron microscopic stereology in association with performance in the learned helplessness paradigm. Inescapable footshock (IES) caused an acute and persistent loss of spine synapses in each of CA1, CA3, and dentate gyrus, which was associated with a severe escape deficit in learned helplessness. On the other hand, IES elicited no significant synaptic alterations in motor cortex. A single injection of corticosterone reproduced both the hippocampal synaptic changes and the behavioral responses induced by IES. Treatment of IES-exposed animals for 6 days with desipramine reversed both the hippocampal spine synapse loss and the escape deficit in learned helplessness. We noted, however, that desipramine failed to restore the number of CA1 spine synapses to nonstressed levels, which was associated with a minor escape deficit compared with nonstressed control rats. Shorter, 1-day or 3-day desipramine treatments, however, had neither synaptic nor behavioral effects. These results indicate that changes in depressive behavior are associated with remarkable remodeling of hippocampal spine synapses at the ultrastructural level. Because spine synapse loss contributes to hippocampal dysfunction, this cellular mechanism may be an important component in the neurobiology of stress-related disorders such as depression.

  12. NKp46 clusters at the immune synapse and regulates NK cell polarization

    Directory of Open Access Journals (Sweden)

    Uzi eHadad

    2015-09-01

    Full Text Available Natural killer cells play an important role in first-line defense against tumor and virus-infected cells. The activity of NK cells is tightly regulated by a repertoire of cell-surface expressed inhibitory and activating receptors. NKp46 is a major NK cell activating receptor that is involved in the elimination of target cells. NK cells form different types of synapses that result in distinct functional outcomes: cytotoxic, inhibitory, and regulatory. Recent studies revealed that complex integration of NK receptor signaling controls cytoskeletal rearrangement and other immune synapse-related events. However the distinct nature by which NKp46 participates in NK immunological synapse formation and function remains unknown. In this study we determined that NKp46 forms microclusters structures at the immune synapse between NK cells and target cells. Over-expression of human NKp46 is correlated with increased accumulation of F-actin mesh at the immune synapse. Concordantly, knock-down of NKp46 in primary human NK cells decreased recruitment of F-actin to the synapse. Live cell imaging experiments showed a linear correlation between NKp46 expression and lytic granules polarization to the immune synapse. Taken together, our data suggest that NKp46 signaling directly regulates the NK lytic immune synapse from early formation to late function.

  13. Three-dimensional distribution of cortical synapses: a replicated point pattern-based analysis

    Science.gov (United States)

    Anton-Sanchez, Laura; Bielza, Concha; Merchán-Pérez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Larrañaga, Pedro

    2014-01-01

    The biggest problem when analyzing the brain is that its synaptic connections are extremely complex. Generally, the billions of neurons making up the brain exchange information through two types of highly specialized structures: chemical synapses (the vast majority) and so-called gap junctions (a substrate of one class of electrical synapse). Here we are interested in exploring the three-dimensional spatial distribution of chemical synapses in the cerebral cortex. Recent research has showed that the three-dimensional spatial distribution of synapses in layer III of the neocortex can be modeled by a random sequential adsorption (RSA) point process, i.e., synapses are distributed in space almost randomly, with the only constraint that they cannot overlap. In this study we hypothesize that RSA processes can also explain the distribution of synapses in all cortical layers. We also investigate whether there are differences in both the synaptic density and spatial distribution of synapses between layers. Using combined focused ion beam milling and scanning electron microscopy (FIB/SEM), we obtained three-dimensional samples from the six layers of the rat somatosensory cortex and identified and reconstructed the synaptic junctions. A total volume of tissue of approximately 4500μm3 and around 4000 synapses from three different animals were analyzed. Different samples, layers and/or animals were aggregated and compared using RSA replicated spatial point processes. The results showed no significant differences in the synaptic distribution across the different rats used in the study. We found that RSA processes described the spatial distribution of synapses in all samples of each layer. We also found that the synaptic distribution in layers II to VI conforms to a common underlying RSA process with different densities per layer. Interestingly, the results showed that synapses in layer I had a slightly different spatial distribution from the other layers. PMID:25206325

  14. Dopamine synapse is a neuroligin-2–mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures

    Science.gov (United States)

    Uchigashima, Motokazu; Ohtsuka, Toshihisa; Kobayashi, Kazuto; Watanabe, Masahiko

    2016-01-01

    Midbrain dopamine neurons project densely to the striatum and form so-called dopamine synapses on medium spiny neurons (MSNs), principal neurons in the striatum. Because dopamine receptors are widely expressed away from dopamine synapses, it remains unclear how dopamine synapses are involved in dopaminergic transmission. Here we demonstrate that dopamine synapses are contacts formed between dopaminergic presynaptic and GABAergic postsynaptic structures. The presynaptic structure expressed tyrosine hydroxylase, vesicular monoamine transporter-2, and plasmalemmal dopamine transporter, which are essential for dopamine synthesis, vesicular filling, and recycling, but was below the detection threshold for molecules involving GABA synthesis and vesicular filling or for GABA itself. In contrast, the postsynaptic structure of dopamine synapses expressed GABAergic molecules, including postsynaptic adhesion molecule neuroligin-2, postsynaptic scaffolding molecule gephyrin, and GABAA receptor α1, without any specific clustering of dopamine receptors. Of these, neuroligin-2 promoted presynaptic differentiation in axons of midbrain dopamine neurons and striatal GABAergic neurons in culture. After neuroligin-2 knockdown in the striatum, a significant decrease of dopamine synapses coupled with a reciprocal increase of GABAergic synapses was observed on MSN dendrites. This finding suggests that neuroligin-2 controls striatal synapse formation by giving competitive advantage to heterologous dopamine synapses over conventional GABAergic synapses. Considering that MSN dendrites are preferential targets of dopamine synapses and express high levels of dopamine receptors, dopamine synapse formation may serve to increase the specificity and potency of dopaminergic modulation of striatal outputs by anchoring dopamine release sites to dopamine-sensing targets. PMID:27035941

  15. Synapse-specific and compartmentalized expression of presynaptic homeostatic potentiation

    Science.gov (United States)

    Li, Xiling; Goel, Pragya; Chen, Catherine; Angajala, Varun; Chen, Xun

    2018-01-01

    Postsynaptic compartments can be specifically modulated during various forms of synaptic plasticity, but it is unclear whether this precision is shared at presynaptic terminals. Presynaptic homeostatic plasticity (PHP) stabilizes neurotransmission at the Drosophila neuromuscular junction, where a retrograde enhancement of presynaptic neurotransmitter release compensates for diminished postsynaptic receptor functionality. To test the specificity of PHP induction and expression, we have developed a genetic manipulation to reduce postsynaptic receptor expression at one of the two muscles innervated by a single motor neuron. We find that PHP can be induced and expressed at a subset of synapses, over both acute and chronic time scales, without influencing transmission at adjacent release sites. Further, homeostatic modulations to CaMKII, vesicle pools, and functional release sites are compartmentalized and do not spread to neighboring pre- or post-synaptic structures. Thus, both PHP induction and expression mechanisms are locally transmitted and restricted to specific synaptic compartments. PMID:29620520

  16. Coordinated Feeding Behavior in Trichoplax, an Animal without Synapses.

    Directory of Open Access Journals (Sweden)

    Carolyn L Smith

    Full Text Available Trichoplax is a small disk-shaped marine metazoan that adheres to substrates and locomotes by ciliary gliding. Despite having only six cell types and lacking synapses Trichoplax coordinates a complex sequence of behaviors culminating in external digestion of algae. We combine live cell imaging with electron microscopy to show how this is accomplished. When Trichoplax glides over a patch of algae, its cilia stop beating so it ceases moving. A subset of one of the cell types, lipophils, simultaneously secretes granules whose content rapidly lyses algae. This secretion is accurately targeted, as only lipophils located near algae release granules. The animal pauses while the algal content is ingested, and then resumes gliding. Global control of gliding is coordinated with precise local control of lipophil secretion suggesting the presence of mechanisms for cellular communication and integration.

  17. Synchrony detection and amplification by silicon neurons with STDP synapses.

    Science.gov (United States)

    Bofill-i-petit, Adria; Murray, Alan F

    2004-09-01

    Spike-timing dependent synaptic plasticity (STDP) is a form of plasticity driven by precise spike-timing differences between presynaptic and postsynaptic spikes. Thus, the learning rules underlying STDP are suitable for learning neuronal temporal phenomena such as spike-timing synchrony. It is well known that weight-independent STDP creates unstable learning processes resulting in balanced bimodal weight distributions. In this paper, we present a neuromorphic analog very large scale integration (VLSI) circuit that contains a feedforward network of silicon neurons with STDP synapses. The learning rule implemented can be tuned to have a moderate level of weight dependence. This helps stabilise the learning process and still generates binary weight distributions. From on-chip learning experiments we show that the chip can detect and amplify hierarchical spike-timing synchrony structures embedded in noisy spike trains. The weight distributions of the network emerging from learning are bimodal.

  18. Spin switches for compact implementation of neuron and synapse

    International Nuclear Information System (INIS)

    Quang Diep, Vinh; Sutton, Brian; Datta, Supriyo; Behin-Aein, Behtash

    2014-01-01

    Nanomagnets driven by spin currents provide a natural implementation for a neuron and a synapse: currents allow convenient summation of multiple inputs, while the magnet provides the threshold function. The objective of this paper is to explore the possibility of a hardware neural network implementation using a spin switch (SS) as its basic building block. SS is a recently proposed device based on established technology with a transistor-like gain and input-output isolation. This allows neural networks to be constructed with purely passive interconnections without intervening clocks or amplifiers. The weights for the neural network are conveniently adjusted through analog voltages that can be stored in a non-volatile manner in an underlying CMOS layer using a floating gate low dropout voltage regulator. The operation of a multi-layer SS neural network designed for character recognition is demonstrated using a standard simulation model based on coupled Landau-Lifshitz-Gilbert equations, one for each magnet in the network

  19. Spin switches for compact implementation of neuron and synapse

    Energy Technology Data Exchange (ETDEWEB)

    Quang Diep, Vinh, E-mail: vdiep@purdue.edu; Sutton, Brian; Datta, Supriyo [School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States); Behin-Aein, Behtash [GLOBALFOUNDRIES, Inc., Sunnyvale, California 94085 (United States)

    2014-06-02

    Nanomagnets driven by spin currents provide a natural implementation for a neuron and a synapse: currents allow convenient summation of multiple inputs, while the magnet provides the threshold function. The objective of this paper is to explore the possibility of a hardware neural network implementation using a spin switch (SS) as its basic building block. SS is a recently proposed device based on established technology with a transistor-like gain and input-output isolation. This allows neural networks to be constructed with purely passive interconnections without intervening clocks or amplifiers. The weights for the neural network are conveniently adjusted through analog voltages that can be stored in a non-volatile manner in an underlying CMOS layer using a floating gate low dropout voltage regulator. The operation of a multi-layer SS neural network designed for character recognition is demonstrated using a standard simulation model based on coupled Landau-Lifshitz-Gilbert equations, one for each magnet in the network.

  20. Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output.

    Science.gov (United States)

    Liu, Shaolin; Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus; Shipley, Michael T

    2015-04-08

    Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. Copyright © 2015 the authors 0270-6474/15/355680-13$15.00/0.

  1. Long-term potentiation in hilar circuitry modulates gating by the dentate gyrus.

    Science.gov (United States)

    Wright, Brandon J; Jackson, Meyer B

    2014-07-16

    The dentate gyrus serves as a gateway to the hippocampus, filtering and processing sensory inputs as an animal explores its environment. The hilus occupies a strategic position within the dentate gyrus from which it can play a pivotal role in these functions. Inputs from dentate granule cells converge on the hilus, and excitatory hilar mossy cells redistribute these signals back to granule cells to transform a pattern of cortical input into a new pattern of output to the hippocampal CA3 region. Using voltage-sensitive dye to image electrical activity in rat hippocampal slices, we explored how long-term potentiation (LTP) of different excitatory synapses modifies the flow of information. Theta burst stimulation of the perforant path potentiated responses throughout the molecular layer, but left responses in the CA3 region unchanged. By contrast, theta burst stimulation of the granule cell layer potentiated responses throughout the molecular layer, as well as in the CA3 region. Theta burst stimulation of the granule cell layer potentiated CA3 responses not only to granule cell layer stimulation but also to perforant path stimulation. Potentiation of responses in the CA3 region reflected NMDA receptor-dependent LTP of upstream synapses between granule cells and mossy cells, with no detectable contribution from NMDA receptor-independent LTP of local CA3 mossy fiber synapses. Potentiation of transmission to the CA3 region required LTP in both granule cell→mossy cell and mossy cell→granule cell synapses. This bidirectional plasticity enables hilar circuitry to regulate the flow of information through the dentate gyrus and on to the hippocampus. Copyright © 2014 the authors 0270-6474/14/349743-11$15.00/0.

  2. Two Fiber Optical Fiber Thermometry

    Science.gov (United States)

    Jones, Mathew R.; Farmer, Jeffery T.; Breeding, Shawn P.

    2000-01-01

    An optical fiber thermometer consists of an optical fiber whose sensing tip is given a metallic coating. The sensing tip of the fiber is essentially an isothermal cavity, so the emission from this cavity will be approximately equal to the emission from a blackbody. Temperature readings are obtained by measuring the spectral radiative heat flux at the end of the fiber at two wavelengths. The ratio of these measurements and Planck's Law are used to infer the temperature at the sensing tip. Optical fiber thermometers have high accuracy, excellent long-term stability and are immune to electromagnetic interference. In addition, they can be operated for extended periods without requiring re-calibration. For these reasons. it is desirable to use optical fiber thermometers in environments such as the International Space Station. However, it has recently been shown that temperature readings are corrupted by emission from the fiber when extended portions of the probe are exposed to elevated temperatures. This paper will describe several ways in which the reading from a second fiber can be used to correct the corrupted temperature measurements. The accuracy and sensitivity to measurement uncertainty will be presented for each method.

  3. Dendrites of cerebellar granule cells correctly recognize their target axons for synaptogenesis in vitro.

    Science.gov (United States)

    Ito, Shoko; Takeichi, Masatoshi

    2009-08-04

    Neural circuits are generated by precisely ordered synaptic connections among neurons, and this process is thought to rely on the ability of neurons to recognize specific partners. However, it is also known that neurons promiscuously form synapses with nonspecific partners, in particular when cultured in vitro, causing controversies about neural recognition mechanisms. Here we reexamined whether neurons can or cannot select particular partners in vitro. In the cerebellum, granule cell (GC) dendrites form synaptic connections specifically with mossy fibers, but not with climbing fibers. We cocultured GC neurons with pontine or inferior olivary axons, the major sources for mossy and climbing fibers, respectively, as well as with hippocampal axons as a control. The GC neurons formed synapses with pontine axons predominantly at the distal ends of their dendrites, reproducing the characteristic morphology of their synapses observed in vivo, whereas they failed to do so when combined with other axons. In the latter case, synaptic proteins could accumulate between axons and dendrites, but these synapses were randomly distributed throughout the contact sites, and also their synaptic vesicle recycling was anomalous. These observations suggest that GC dendrites can select their authentic partners for synaptogenesis even in vitro, forming the synapses with a GC-specific nature only with them.

  4. Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus

    Directory of Open Access Journals (Sweden)

    Miloslav eSedlacek

    2014-07-01

    Full Text Available Feedforward inhibition represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs, principal neurons of the dorsal cochlear nucleus (DCN that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and feed-forward inhibition in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven feed-forward inhibition (FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of feed-forward inhibition had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.

  5. Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus.

    Science.gov (United States)

    Sedlacek, Miloslav; Brenowitz, Stephan D

    2014-01-01

    Feed-forward inhibition (FFI) represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs), principal neurons of the dorsal cochlear nucleus (DCN) that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs) on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and FFI in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of FFI had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition, we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs) in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.

  6. On the Universality and Non-Universality of Spiking Neural P Systems With Rules on Synapses.

    Science.gov (United States)

    Song, Tao; Xu, Jinbang; Pan, Linqiang

    2015-12-01

    Spiking neural P systems with rules on synapses are a new variant of spiking neural P systems. In the systems, the neuron contains only spikes, while the spiking/forgetting rules are moved on the synapses. It was obtained that such system with 30 neurons (using extended spiking rules) or with 39 neurons (using standard spiking rules) is Turing universal. In this work, this number is improved to 6. Specifically, we construct a Turing universal spiking neural P system with rules on synapses having 6 neurons, which can generate any set of Turing computable natural numbers. As well, it is obtained that spiking neural P system with rules on synapses having less than two neurons are not Turing universal: i) such systems having one neuron can characterize the family of finite sets of natural numbers; ii) the family of sets of numbers generated by the systems having two neurons is included in the family of semi-linear sets of natural numbers.

  7. Seizures beget seizures in temporal lobe epilepsies: the boomerang effects of newly formed aberrant kainatergic synapses.

    Science.gov (United States)

    Ben-Ari, Yehezkel; Crepel, Valérie; Represa, Alfonso

    2008-01-01

    Do temporal lobe epilepsy (TLE) seizures in adults promote further seizures? Clinical and experimental data suggest that new synapses are formed after an initial episode of status epilepticus, however their contribution to the transformation of a naive network to an epileptogenic one has been debated. Recent experimental data show that newly formed aberrant excitatory synapses on the granule cells of the fascia dentate operate by means of kainate receptor-operated signals that are not present on naive granule cells. Therefore, genuine epileptic networks rely on signaling cascades that differentiate them from naive networks. Recurrent limbic seizures generated by the activation of kainate receptors and synapses in naive animals lead to the formation of novel synapses that facilitate the emergence of further seizures. This negative, vicious cycle illustrates the central role of reactive plasticity in neurological disorders.

  8. Mechanisms of input and output synaptic specificity: finding partners, building synapses, and fine-tuning communication.

    Science.gov (United States)

    Rawson, Randi L; Martin, E Anne; Williams, Megan E

    2017-08-01

    For most neurons to function properly, they need to develop synaptic specificity. This requires finding specific partner neurons, building the correct types of synapses, and fine-tuning these synapses in response to neural activity. Synaptic specificity is common at both a neuron's input and output synapses, whereby unique synapses are built depending on the partnering neuron. Neuroscientists have long appreciated the remarkable specificity of neural circuits but identifying molecular mechanisms mediating synaptic specificity has only recently accelerated. Here, we focus on recent progress in understanding input and output synaptic specificity in the mammalian brain. We review newly identified circuit examples for both and the latest research identifying molecular mediators including Kirrel3, FGFs, and DGLα. Lastly, we expect the pace of research on input and output specificity to continue to accelerate with the advent of new technologies in genomics, microscopy, and proteomics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Cytoskeletal actin dynamics shape a ramifying actin network underpinning immunological synapse formation

    DEFF Research Database (Denmark)

    Fritzsche, Marco; Fernandes, Ricardo A.; Chang, Veronica T.

    2017-01-01

    optical microscopes to analyze resting and activated T cells, we show that, following contact formation with activating surfaces, these cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse...

  10. Synapse Formation in Monosynaptic Sensory–Motor Connections Is Regulated by Presynaptic Rho GTPase Cdc42

    Science.gov (United States)

    Imai, Fumiyasu; Ladle, David R.; Leslie, Jennifer R.; Duan, Xin; Rizvi, Tilat A.; Ciraolo, Georgianne M.; Zheng, Yi

    2016-01-01

    Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in monosynaptic sensory–motor circuits in these mutants. Temporally targeted deletion of Cdc42 in sensory neurons after sensory–motor circuit establishment reveals that Cdc42 does not affect synaptic transmission. Furthermore, addition of the synaptic organizers, neuroligins, induces presynaptic differentiation of wild-type, but not Cdc42-deficient, proprioceptive sensory neurons in vitro. Together, our findings demonstrate that Cdc42 in presynaptic neurons is required for synapse formation in monosynaptic sensory–motor circuits. SIGNIFICANCE STATEMENT Group Ia proprioceptive sensory neurons form direct synapses with motor neurons, but the molecular mechanisms underlying synapse formation in these monosynaptic sensory–motor connections are unknown. We show that deleting Cdc42 in sensory neurons does not affect proprioceptive sensory axon targeting because axons reach the ventral spinal cord appropriately, but these neurons form significantly fewer presynaptic terminals on motor neurons. Electrophysiological analysis further shows that EPSPs are decreased in these mice. Finally, we demonstrate that Cdc42 is involved in neuroligin-dependent presynaptic differentiation of proprioceptive sensory neurons in vitro

  11. Poisson-Like Spiking in Circuits with Probabilistic Synapses

    Science.gov (United States)

    Moreno-Bote, Rubén

    2014-01-01

    Neuronal activity in cortex is variable both spontaneously and during stimulation, and it has the remarkable property that it is Poisson-like over broad ranges of firing rates covering from virtually zero to hundreds of spikes per second. The mechanisms underlying cortical-like spiking variability over such a broad continuum of rates are currently unknown. We show that neuronal networks endowed with probabilistic synaptic transmission, a well-documented source of variability in cortex, robustly generate Poisson-like variability over several orders of magnitude in their firing rate without fine-tuning of the network parameters. Other sources of variability, such as random synaptic delays or spike generation jittering, do not lead to Poisson-like variability at high rates because they cannot be sufficiently amplified by recurrent neuronal networks. We also show that probabilistic synapses predict Fano factor constancy of synaptic conductances. Our results suggest that synaptic noise is a robust and sufficient mechanism for the type of variability found in cortex. PMID:25032705

  12. Resolution enhancement in neural networks with dynamical synapses

    Directory of Open Access Journals (Sweden)

    C. C. Alan Fung

    2013-06-01

    Full Text Available Conventionally, information is represented by spike rates in the neural system. Here, we consider the ability of temporally modulated activities in neuronal networks to carry information extra to spike rates. These temporal modulations, commonly known as population spikes, are due to the presence of synaptic depression in a neuronal network model. We discuss its relevance to an experiment on transparent motions in macaque monkeys by Treue et al. in 2000. They found that if the moving directions of objects are too close, the firing rate profile will be very similar to that with one direction. As the difference in the moving directions of objects is large enough, the neuronal system would respond in such a way that the network enhances the resolution in the moving directions of the objects. In this paper, we propose that this behavior can be reproduced by neural networks with dynamical synapses when there are multiple external inputs. We will demonstrate how resolution enhancement can be achieved, and discuss the conditions under which temporally modulated activities are able to enhance information processing performances in general.

  13. Dysfunctional synapse in Alzheimer's disease - A focus on NMDA receptors.

    Science.gov (United States)

    Mota, Sandra I; Ferreira, Ildete L; Rego, A Cristina

    2014-01-01

    Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly. Alterations capable of causing brain circuitry dysfunctions in AD may take several years to develop. Oligomeric amyloid-beta peptide (Aβ) plays a complex role in the molecular events that lead to progressive loss of function and eventually to neurodegeneration in this devastating disease. Moreover, N-methyl-D-aspartate (NMDA) receptors (NMDARs) activation has been recently implicated in AD-related synaptic dysfunction. Thus, in this review we focus on glutamatergic neurotransmission impairment and the changes in NMDAR regulation in AD, following the description on the role and location of NMDARs at pre- and post-synaptic sites under physiological conditions. In addition, considering that there is currently no effective ways to cure AD or stop its progression, we further discuss the relevance of NMDARs antagonists to prevent AD symptomatology. This review posits additional information on the role played by Aβ in AD and the importance of targeting the tripartite glutamatergic synapse in early asymptomatic and possible reversible stages of the disease through preventive and/or disease-modifying therapeutic strategies. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Stochastic Synapses Enable Efficient Brain-Inspired Learning Machines

    Science.gov (United States)

    Neftci, Emre O.; Pedroni, Bruno U.; Joshi, Siddharth; Al-Shedivat, Maruan; Cauwenberghs, Gert

    2016-01-01

    Recent studies have shown that synaptic unreliability is a robust and sufficient mechanism for inducing the stochasticity observed in cortex. Here, we introduce Synaptic Sampling Machines (S2Ms), a class of neural network models that uses synaptic stochasticity as a means to Monte Carlo sampling and unsupervised learning. Similar to the original formulation of Boltzmann machines, these models can be viewed as a stochastic counterpart of Hopfield networks, but where stochasticity is induced by a random mask over the connections. Synaptic stochasticity plays the dual role of an efficient mechanism for sampling, and a regularizer during learning akin to DropConnect. A local synaptic plasticity rule implementing an event-driven form of contrastive divergence enables the learning of generative models in an on-line fashion. S2Ms perform equally well using discrete-timed artificial units (as in Hopfield networks) or continuous-timed leaky integrate and fire neurons. The learned representations are remarkably sparse and robust to reductions in bit precision and synapse pruning: removal of more than 75% of the weakest connections followed by cursory re-learning causes a negligible performance loss on benchmark classification tasks. The spiking neuron-based S2Ms outperform existing spike-based unsupervised learners, while potentially offering substantial advantages in terms of power and complexity, and are thus promising models for on-line learning in brain-inspired hardware. PMID:27445650

  15. Regulation of dopamine D1 receptor dynamics within the postsynaptic density of hippocampal glutamate synapses.

    Directory of Open Access Journals (Sweden)

    Laurent Ladepeche

    Full Text Available Dopamine receptor potently modulates glutamate signalling, synaptic plasticity and neuronal network adaptations in various pathophysiological processes. Although key intracellular signalling cascades have been identified, the cellular mechanism by which dopamine and glutamate receptor-mediated signalling interplay at glutamate synapse remain poorly understood. Among the cellular mechanisms proposed to aggregate D1R in glutamate synapses, the direct interaction between D1R and the scaffold protein PSD95 or the direct interaction with the glutamate NMDA receptor (NMDAR have been proposed. To tackle this question we here used high-resolution single nanoparticle imaging since it provides a powerful way to investigate at the sub-micron resolution the dynamic interaction between these partners in live synapses. We demonstrate in hippocampal neuronal networks that dopamine D1 receptors (D1R laterally diffuse within glutamate synapses, in which their diffusion is reduced. Disrupting the interaction between D1R and PSD95, through genetical manipulation and competing peptide, did not affect D1R dynamics in glutamatergic synapses. However, preventing the physical interaction between D1R and the GluN1 subunit of NMDAR abolished the synaptic stabilization of diffusing D1R. Together, these data provide direct evidence that the interaction between D1R and NMDAR in synapses participate in the building of the dopamine-receptor-mediated signalling, and most likely to the glutamate-dopamine cross-talk.

  16. Multiple synchronization transitions in scale-free neuronal networks with electrical and chemical hybrid synapses

    International Nuclear Information System (INIS)

    Liu, Chen; Wang, Jiang; Wang, Lin; Yu, Haitao; Deng, Bin; Wei, Xile; Tsang, Kaiming; Chan, Wailok

    2014-01-01

    Highlights: • Synchronization transitions in hybrid scale-free neuronal networks are investigated. • Multiple synchronization transitions can be induced by the time delay. • Effect of synchronization transitions depends on the ratio of the electrical and chemical synapses. • Coupling strength and the density of inter-neuronal links can enhance the synchronization. -- Abstract: The impacts of information transmission delay on the synchronization transitions in scale-free neuronal networks with electrical and chemical hybrid synapses are investigated. Numerical results show that multiple appearances of synchronization regions transitions can be induced by different information transmission delays. With the time delay increasing, the synchronization of neuronal activities can be enhanced or destroyed, irrespective of the probability of chemical synapses in the whole hybrid neuronal network. In particular, for larger probability of electrical synapses, the regions of synchronous activities appear broader with stronger synchronization ability of electrical synapses compared with chemical ones. Moreover, it can be found that increasing the coupling strength can promote synchronization monotonously, playing the similar role of the increasing the probability of the electrical synapses. Interestingly, the structures and parameters of the scale-free neuronal networks, especially the structural evolvement plays a more subtle role in the synchronization transitions. In the network formation process, it is found that every new vertex is attached to the more old vertices already present in the network, the more synchronous activities will be emerge

  17. Effects of Estradiol on Learned Helplessness and Associated Remodeling of Hippocampal Spine Synapses in Female Rats

    Science.gov (United States)

    Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; MacLusky, Neil J; Leranth, Csaba; Duman, Ronald S

    2009-01-01

    Background Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in females is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant, desipramine. Considering the fact that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life may influence behavioral and synaptic responses to stress and depression. Methods Using electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n=70), under different conditions of estradiol exposure. Results Stress induced an acute and persistent loss of hippocampal spine synapses, while subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either prior to stress or prior to escape testing of nonstressed animals both increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. Conclusions These findings suggest that hippocampal spine synapse remodeling may be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression. PMID:19811775

  18. A systematic random sampling scheme optimized to detect the proportion of rare synapses in the neuropil.

    Science.gov (United States)

    da Costa, Nuno Maçarico; Hepp, Klaus; Martin, Kevan A C

    2009-05-30

    Synapses can only be morphologically identified by electron microscopy and this is often a very labor-intensive and time-consuming task. When quantitative estimates are required for pathways that contribute a small proportion of synapses to the neuropil, the problems of accurate sampling are particularly severe and the total time required may become prohibitive. Here we present a sampling method devised to count the percentage of rarely occurring synapses in the neuropil using a large sample (approximately 1000 sampling sites), with the strong constraint of doing it in reasonable time. The strategy, which uses the unbiased physical disector technique, resembles that used in particle physics to detect rare events. We validated our method in the primary visual cortex of the cat, where we used biotinylated dextran amine to label thalamic afferents and measured the density of their synapses using the physical disector method. Our results show that we could obtain accurate counts of the labeled synapses, even when they represented only 0.2% of all the synapses in the neuropil.

  19. A Reaction-Diffusion Model for Synapse Growth and Long-Term Memory

    Science.gov (United States)

    Liu, Kang; Lisman, John; Hagan, Michael

    Memory storage involves strengthening of synaptic transmission known as long-term potentiation (LTP). The late phase of LTP is associated with structural processes that enlarge the synapse. Yet, synapses must be stable, despite continual subunit turnover, over the lifetime of an encoded memory. These considerations suggest that synapses are variable-size stable structure (VSSS), meaning they can switch between multiple metastable structures with different sizes. The mechanisms underlying VSSS are poorly understood. While experiments and theory have suggested that the interplay between diffusion and receptor-scaffold interactions can lead to a preferred stable size for synaptic domains, such a mechanism cannot explain how synapses adopt widely different sizes. Here we develop a minimal reaction-diffusion model of VSSS for synapse growth, incorporating the recent observation from super-resolution microscopy that neural activity can build compositional heterogeneities within synaptic domains. We find that introducing such heterogeneities can change the stable domain size in a controlled manner. We discuss a potential connection between this model and experimental data on synapse sizes, and how it provides a possible mechanism to structurally encode graded long-term memory. We acknowledge the support from NSF INSPIRE Award number IOS-1526941 (KL, MFH, JL) and the Brandeis Center for Bioinspired Soft Materials, an NSF MRSEC, DMR- 1420382 (MFH).

  20. Metaplasticity at CA1 Synapses by Homeostatic Control of Presynaptic Release Dynamics

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    Cary Soares

    2017-10-01

    Full Text Available Summary: Hebbian and homeostatic forms of plasticity operate on different timescales to regulate synaptic strength. The degree of mechanistic overlap between these processes and their mutual influence are still incompletely understood. Here, we report that homeostatic synaptic strengthening induced by prolonged network inactivity compromised the ability of CA1 synapses to exhibit LTP. This effect could not be accounted for by an obvious deficit in the postsynaptic capacity for LTP expression, since neither the fraction of silent synapses nor the ability to induce LTP by two-photon glutamate uncaging were reduced by the homeostatic process. Rather, optical quantal analysis reveals that homeostatically strengthened synapses display a reduced capacity to maintain glutamate release fidelity during repetitive stimulation, ultimately impeding the induction, and thus expression, of LTP. By regulating the short-term dynamics of glutamate release, the homeostatic process thus influences key aspects of dynamic network function and exhibits features of metaplasticity. : Several forms of synaptic plasticity operating over distinct spatiotemporal scales have been described at hippocampal synapses. Whether these distinct plasticity mechanisms interact and influence one another remains incompletely understood. Here, Soares et al. show that homeostatic plasticity induced by network silencing influences short-term release dynamics and Hebbian plasticity rules at hippocampal synapses. Keywords: synapse, LTP, homeostatic plasticity, metaplasticity, iGluSNFR

  1. Distinct structural and catalytic roles for Zap70 in formation of the immunological synapse in CTL

    Science.gov (United States)

    Jenkins, Misty R; Stinchcombe, Jane C; Au-Yeung, Byron B; Asano, Yukako; Ritter, Alex T; Weiss, Arthur; Griffiths, Gillian M

    2014-01-01

    T cell receptor (TCR) activation leads to a dramatic reorganisation of both membranes and receptors as the immunological synapse forms. Using a genetic model to rapidly inhibit Zap70 catalytic activity we examined synapse formation between cytotoxic T lymphocytes and their targets. In the absence of Zap70 catalytic activity Vav-1 activation occurs and synapse formation is arrested at a stage with actin and integrin rich interdigitations forming the interface between the two cells. The membranes at the synapse are unable to flatten to provide extended contact, and Lck does not cluster to form the central supramolecular activation cluster (cSMAC). Centrosome polarisation is initiated but aborts before reaching the synapse and the granules do not polarise. Our findings reveal distinct roles for Zap70 as a structural protein regulating integrin-mediated control of actin vs its catalytic activity that regulates TCR-mediated control of actin and membrane remodelling during formation of the immunological synapse. DOI: http://dx.doi.org/10.7554/eLife.01310.001 PMID:24596147

  2. Ligand mobility modulates immunological synapse formation and T cell activation.

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    Chih-Jung Hsu

    Full Text Available T cell receptor (TCR engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70 and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76. This molecular rearrangement results in formation of the immunological synapse (IS, a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca(2+ were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses.

  3. The C1q complement family of synaptic organizers: not just complementary.

    Science.gov (United States)

    Yuzaki, Michisuke

    2017-08-01

    Molecules that regulate formation, differentiation, and maintenance of synapses are called synaptic organizers. Recently, various 'C1q family' proteins have been shown to be released from neurons, and serve as a new class of synaptic organizers. Cbln1 and C1ql1 proteins regulate the formation and maintenance of parallel fiber-Purkinje cell and climbing fiber-Purkinje cell synapses, respectively, in the cerebellum. Cbln1 also modulates the function of postsynaptic delta2 glutamate receptors to regulate synaptic plasticity. C1ql2 and C1ql3, released from mossy fibers, determine the synaptic localization of postsynaptic kainate receptors in the hippocampus. C1ql3 also regulates the formation of synapses between the basolateral amygdala and the prefrontal cortex. These findings indicate the diverse functions of C1q family proteins in various brain regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Functional hallmarks of GABAergic synapse maturation and the diverse roles of neurotrophins

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    Rosemarie eGrantyn

    2011-07-01

    Full Text Available Functional impairment of the adult brain can result from deficits in the ontogeny of GABAergic synaptic transmission. Gene defects underlying autism spectrum disorders, Rett’s syndrome or some forms of epilepsy, but also a diverse set of syndromes accompanying perinatal trauma, hormonal imbalances, intake of sleep-inducing or mood-improving drugs or, quite common, alcohol intake during pregnancy can alter GABA signaling early in life. The search for therapeutically relevant endogenous molecules or exogenous compounds able to alleviate the consequences of dysfunction of GABAergic transmission in the embryonic or postnatal brain requires a clear understanding of its site- and state-dependent development. At the level of single synapses, it is necessary to discriminate between presynaptic and postsynaptic alterations, and to define parameters that can be regarded as both suitable and accessible for the quantification of developmental changes. Here we focus on the performance of GABAergic synapses in two brain structures, the hippocampus and the superior colliculus, describe some novel aspects of neurotrophin effects during the development of GABAergic synaptic transmission and examine the applicability of the following rules: 1 Synaptic transmission starts with GABA, 2 Nascent/immature GABAergic synapses operate in a ballistic mode (multivesicular release, 3 Immature synaptic terminals release vesicles with higher probability than mature synapses, 4 Immature GABAergic synapses are prone to paired pulse and tetanic depression, 5 Synapse maturation is characterized by an increasing dominance of synchronous over asynchronous release, 6 In immature neurons GABA acts as a depolarizing transmitter, 7 Synapse maturation implies IPSC shortening due to an increase in alpha1 subunit expression, 8 Extrasynaptic (tonic conductances can inhibit the development of synaptic (phasic GABA actions.

  5. Neuroligin-1 loss is associated with reduced tenacity of excitatory synapses.

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    Adel Zeidan

    Full Text Available Neuroligins (Nlgns are postsynaptic, integral membrane cell adhesion molecules that play important roles in the formation, validation, and maturation of synapses in the mammalian central nervous system. Given their prominent roles in the life cycle of synapses, it might be expected that the loss of neuroligin family members would affect the stability of synaptic organization, and ultimately, affect the tenacity and persistence of individual synaptic junctions. Here we examined whether and to what extent the loss of Nlgn-1 affects the dynamics of several key synaptic molecules and the constancy of their contents at individual synapses over time. Fluorescently tagged versions of the postsynaptic scaffold molecule PSD-95, the AMPA-type glutamate receptor subunit GluA2 and the presynaptic vesicle molecule SV2A were expressed in primary cortical cultures from Nlgn-1 KO mice and wild-type (WT littermates, and live imaging was used to follow the constancy of their contents at individual synapses over periods of 8-12 hours. We found that the loss of Nlgn-1 was associated with larger fluctuations in the synaptic contents of these molecules and a poorer preservation of their contents at individual synapses. Furthermore, rates of synaptic turnover were somewhat greater in neurons from Nlgn-1 knockout mice. Finally, the increased GluA2 redistribution rates observed in neurons from Nlgn-1 knockout mice were negated by suppressing spontaneous network activity. These findings suggest that the loss of Nlgn-1 is associated with some use-dependent destabilization of excitatory synapse organization, and indicate that in the absence of Nlgn-1, the tenacity of excitatory synapses might be somewhat impaired.

  6. NMDA receptor content of synapses in stratum radiatum of the hippocampal CA1 area.

    Science.gov (United States)

    Racca, C; Stephenson, F A; Streit, P; Roberts, J D; Somogyi, P

    2000-04-01

    Glutamate receptors activated by NMDA (NMDARs) or AMPA (AMPARs) are clustered on dendritic spines of pyramidal cells. Both the AMPAR-mediated postsynaptic responses and the synaptic AMPAR immunoreactivity show a large intersynapse variability. Postsynaptic responses mediated by NMDARs show less variability. To assess the variability in NMDAR content and the extent of their coexistence with AMPARs in Schaffer collateral-commissural synapses of adult rat CA1 pyramidal cells, electron microscopic immunogold localization of receptors has been used. Immunoreactivity of NMDARs was detected in virtually all synapses on spines, but AMPARs were undetectable, on average, in 12% of synapses. A proportion of synapses had a very high AMPAR content relative to the mean content, resulting in a distribution more skewed toward larger values than that of NMDARs. The variability of synaptic NMDAR content [coefficient of variation (CV), 0.64-0.70] was much lower than that of the AMPAR content (CV, 1.17-1.45). Unlike the AMPAR content, the NMDAR content showed only a weak correlation with synapse size. As reported previously for AMPARs, the immunoreactivity of NMDARs was also associated with the spine apparatus within spines. The results demonstrate that the majority of the synapses made by CA3 pyramidal cells onto spines of CA1 pyramids express both NMDARs and AMPARs, but with variable ratios. A less-variable NMDAR content is accompanied by a wide variability of AMPAR content, indicating that the regulation of expression of the two receptors is not closely linked. These findings support reports that fast excitatory transmission at some of these synapses is mediated by activation mainly of NMDARs.

  7. Low-fiber diet

    Science.gov (United States)

    ... residue; Low-fiber diet; Fiber restricted diet; Crohn disease - low fiber diet; Ulcerative colitis - low fiber diet; ... them if they do not contain seeds or pulp: Yellow squash (without seeds) Spinach Pumpkin Eggplant Potatoes, ...

  8. Photovoltaic fibers

    Science.gov (United States)

    Gaudiana, Russell; Eckert, Robert; Cardone, John; Ryan, James; Montello, Alan

    2006-08-01

    It was realized early in the history of Konarka that the ability to produce fibers that generate power from solar energy could be applied to a wide variety of applications where fabrics are utilized currently. These applications include personal items such as jackets, shirts and hats, to architectural uses such as awnings, tents, large covers for cars, trucks and even doomed stadiums, to indoor furnishings such as window blinds, shades and drapes. They may also be used as small fabric patches or fiber bundles for powering or recharging batteries in small sensors. Power generating fabrics for clothing is of particular interest to the military where they would be used in uniforms and body armor where portable power is vital to field operations. In strong sunlight these power generating fabrics could be used as a primary source of energy, or they can be used in either direct sunlight or low light conditions to recharge batteries. Early in 2002, Konarka performed a series of proof-of-concept experiments to demonstrate the feasibility of building a photovoltaic cell using dye-sensitized titania and electrolyte on a metal wire core. The approach taken was based on the sequential coating processes used in making fiber optics, namely, a fiber core, e.g., a metal wire serving as the primary electrode, is passed through a series of vertically aligned coating cups. Each of the cups contains a coating fluid that has a specific function in the photocell. A second wire, used as the counter electrode, is brought into the process prior to entering the final coating cup. The latter contains a photopolymerizable, transparent cladding which hardens when passed through a UV chamber. Upon exiting the UV chamber, the finished PV fiber is spooled. Two hundred of foot lengths of PV fiber have been made using this process. When the fiber is exposed to visible radiation, it generates electrical power. The best efficiency exhibited by these fibers is 6% with an average value in the 4

  9. Elementary properties of Ca(2+) channels and their influence on multivesicular release and phase-locking at auditory hair cell ribbon synapses.

    Science.gov (United States)

    Magistretti, Jacopo; Spaiardi, Paolo; Johnson, Stuart L; Masetto, Sergio

    2015-01-01

    Voltage-gated calcium (Cav1.3) channels in mammalian inner hair cells (IHCs) open in response to sound and the resulting Ca(2+) entry triggers the release of the neurotransmitter glutamate onto afferent terminals. At low to mid sound frequencies cell depolarization follows the sound sinusoid and pulses of transmitter release from the hair cell generate excitatory postsynaptic currents (EPSCs) in the afferent fiber that translate into a phase-locked pattern of action potential activity. The present article summarizes our current understanding on the elementary properties of single IHC Ca(2+) channels, and how these could have functional implications for certain, poorly understood, features of synaptic transmission at auditory hair cell ribbon synapses.

  10. Elementary properties of Ca2+ channels and their influence on multivesicular release and phase-locking at auditory hair cell ribbon synapses

    Science.gov (United States)

    Magistretti, Jacopo; Spaiardi, Paolo; Johnson, Stuart L.; Masetto, Sergio

    2015-01-01

    Voltage-gated calcium (Cav1.3) channels in mammalian inner hair cells (IHCs) open in response to sound and the resulting Ca2+ entry triggers the release of the neurotransmitter glutamate onto afferent terminals. At low to mid sound frequencies cell depolarization follows the sound sinusoid and pulses of transmitter release from the hair cell generate excitatory postsynaptic currents (EPSCs) in the afferent fiber that translate into a phase-locked pattern of action potential activity. The present article summarizes our current understanding on the elementary properties of single IHC Ca2+ channels, and how these could have functional implications for certain, poorly understood, features of synaptic transmission at auditory hair cell ribbon synapses. PMID:25904847

  11. Cells containing aragonite crystals mediate responses to gravity in Trichoplax adhaerens (Placozoa), an animal lacking neurons and synapses.

    Science.gov (United States)

    Mayorova, Tatiana D; Smith, Carolyn L; Hammar, Katherine; Winters, Christine A; Pivovarova, Natalia B; Aronova, Maria A; Leapman, Richard D; Reese, Thomas S

    2018-01-01

    Trichoplax adhaerens has only six cell types. The function as well as the structure of crystal cells, the least numerous cell type, presented an enigma. Crystal cells are arrayed around the perimeter of the animal and each contains a birefringent crystal. Crystal cells resemble lithocytes in other animals so we looked for evidence they are gravity sensors. Confocal microscopy showed that their cup-shaped nuclei are oriented toward the edge of the animal, and that the crystal shifts downward under the influence of gravity. Some animals spontaneously lack crystal cells and these animals behaved differently upon being tilted vertically than animals with a typical number of crystal cells. EM revealed crystal cell contacts with fiber cells and epithelial cells but these contacts lacked features of synapses. EM spectroscopic analyses showed that crystals consist of the aragonite form of calcium carbonate. We thus provide behavioral evidence that Trichoplax are able to sense gravity, and that crystal cells are likely to be their gravity receptors. Moreover, because placozoans are thought to have evolved during Ediacaran or Cryogenian eras associated with aragonite seas, and their crystals are made of aragonite, they may have acquired gravity sensors during this early era.

  12. Optimal and Local Connectivity Between Neuron and Synapse Array in the Quantum Dot/Silicon Brain

    Science.gov (United States)

    Duong, Tuan A.; Assad, Christopher; Thakoor, Anikumar P.

    2010-01-01

    This innovation is used to connect between synapse and neuron arrays using nanowire in quantum dot and metal in CMOS (complementary metal oxide semiconductor) technology to enable the density of a brain-like connection in hardware. The hardware implementation combines three technologies: 1. Quantum dot and nanowire-based compact synaptic cell (50x50 sq nm) with inherently low parasitic capacitance (hence, low dynamic power approx.l0(exp -11) watts/synapse), 2. Neuron and learning circuits implemented in 50-nm CMOS technology, to be integrated with quantum dot and nanowire synapse, and 3. 3D stacking approach to achieve the overall numbers of high density O(10(exp 12)) synapses and O(10(exp 8)) neurons in the overall system. In a 1-sq cm of quantum dot layer sitting on a 50-nm CMOS layer, innovators were able to pack a 10(exp 6)-neuron and 10(exp 10)-synapse array; however, the constraint for the connection scheme is that each neuron will receive a non-identical 10(exp 4)-synapse set, including itself, via its efficacy of the connection. This is not a fully connected system where the 100x100 synapse array only has a 100-input data bus and 100-output data bus. Due to the data bus sharing, it poses a great challenge to have a complete connected system, and its constraint within the quantum dot and silicon wafer layer. For an effective connection scheme, there are three conditions to be met: 1. Local connection. 2. The nanowire should be connected locally, not globally from which it helps to maximize the data flow by sharing the same wire space location. 3. Each synapse can have an alternate summation line if needed (this option is doable based on the simple mask creation). The 10(exp 3)x10(exp 3)-neuron array was partitioned into a 10-block, 10(exp 2)x10(exp 3)-neuron array. This building block can be completely mapped within itself (10,000 synapses to a neuron).

  13. Isolation of TRPV1 independent mechanisms of spontaneous and asynchronous glutamate release at primary afferent to NTS synapses.

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    Axel J. Fenwick

    2014-01-01

    Full Text Available Cranial visceral afferents contained within the solitary tract (ST contact second-order neurons in the nucleus of the solitary tract (NTS and release the excitatory amino acid glutamate via three distinct exocytosis pathways; synchronous, asynchronous, and spontaneous release. The presence of TRPV1 in the central terminals of a majority of ST afferents conveys activity-dependent asynchronous glutamate release and provides a temperature sensitive calcium conductance which largely determines the rate of spontaneous vesicle fusion. TRPV1 is present in unmyelinated C-fiber afferents and these facilitated forms of glutamate release may underlie the relative strength of C-fibers in activating autonomic reflex pathways. However, pharmacological blockade of TRPV1 signaling eliminates only ~50% of the asynchronous profile and attenuates the temperature sensitivity of spontaneous release indicating additional thermosensitive calcium influx pathways may exist which mediate these forms of vesicle release. In the present study we isolate the contribution of TRPV1 independent forms of glutamate release at ST-NTS synapses. We found ST afferent innervation at NTS neurons and synchronous vesicle release from TRPV1 KO mice was not different to control animals; however, only half of TRPV1 KO ST afferents completely lacked asynchronous glutamate release. Further, temperature driven spontaneous rates of vesicle release were not different from 33˚ - 37˚C between control and TRPV1 KO afferents. These findings suggest additional temperature dependent mechanisms controlling asynchronous and thermosensitive spontaneous release at physiological temperatures, possibly mediated by additional thermosensitive TRP channels in primary afferent terminals.

  14. ASIC-dependent LTP at multiple glutamatergic synapses in amygdala network is required for fear memory.

    Science.gov (United States)

    Chiang, Po-Han; Chien, Ta-Chun; Chen, Chih-Cheng; Yanagawa, Yuchio; Lien, Cheng-Chang

    2015-05-19

    Genetic variants in the human ortholog of acid-sensing ion channel-1a subunit (ASIC1a) gene are associated with panic disorder and amygdala dysfunction. Both fear learning and activity-induced long-term potentiation (LTP) of cortico-basolateral amygdala (BLA) synapses are impaired in ASIC1a-null mice, suggesting a critical role of ASICs in fear memory formation. In this study, we found that ASICs were differentially expressed within the amygdala neuronal population, and the extent of LTP at various glutamatergic synapses correlated with the level of ASIC expression in postsynaptic neurons. Importantly, selective deletion of ASIC1a in GABAergic cells, including amygdala output neurons, eliminated LTP in these cells and reduced fear learning to the same extent as that found when ASIC1a was selectively abolished in BLA glutamatergic neurons. Thus, fear learning requires ASIC-dependent LTP at multiple amygdala synapses, including both cortico-BLA input synapses and intra-amygdala synapses on output neurons.

  15. Synchronization of the small-world neuronal network with unreliable synapses

    International Nuclear Information System (INIS)

    Li, Chunguang; Zheng, Qunxian

    2010-01-01

    As is well known, synchronization phenomena are ubiquitous in neuronal systems. Recently a lot of work concerning the synchronization of the neuronal network has been accomplished. In these works, the synapses are usually considered reliable, but experimental results show that, in biological neuronal networks, synapses are usually unreliable. In our previous work, we have studied the synchronization of the neuronal network with unreliable synapses; however, we have not paid attention to the effect of topology on the synchronization of the neuronal network. Several recent studies have found that biological neuronal networks have typical properties of small-world networks, characterized by a short path length and high clustering coefficient. In this work, mainly based on the small-world neuronal network (SWNN) with inhibitory neurons, we study the effect of network topology on the synchronization of the neuronal network with unreliable synapses. Together with the network topology, the effects of the GABAergic reversal potential, time delay and noise are also considered. Interestingly, we found a counter-intuitive phenomenon for the SWNN with specific shortcut adding probability, that is, the less reliable the synapses, the better the synchronization performance of the SWNN. We also consider the effects of both local noise and global noise in this work. It is shown that these two different types of noise have distinct effects on the synchronization: one is negative and the other is positive

  16. Simulations of centriole of polarized centrosome as a monopole antenna in immune and viral synapses.

    Science.gov (United States)

    Dvorak, Josef; Melichar, Bohuslav; Filipova, Alzbeta; Grimova, Jana; Grimova, Nela; Rozsypalova, Aneta; Buka, David; Voboril, Rene; Zapletal, Radek; Buchler, Tomas; Richter, Igor; Buka, David

    2018-01-01

    The immune synapse (IS) is a temporary interface between an antigen-presenting cell and an effector lymphocyte. Viral synapse is a molecularly organized cellular junction that is structurally similar to the IS. Primary cilium is considered as a functional homologue of the IS due to the morphological and functional similarities in architecture between both micotubule structures. It has been hypothesized that endogenous electromagnetic field in the cell is generated by a unique cooperating system between mitochondria and microtubules. We are extending this prior hypothesis of the endogenous electromagnetic field in the cell postulating that polarized centriole in immune and viral synapse could serve as a monopole antenna. This is an addition to our hypothesis that primary cilium could serve as a monopole antenna. We simulated the distribution of electric field of centriole of polarized centrosome as a monopole antenna in immune and viral synapse. Very weak electromagnetic field of polarized centriole of CD8+ T lymphocyte in IS can contribute to the transport of cytolytic granules into the attacked (cancer) cell. Analogically, very weak electromagnetic field of polarized centriole in viral synapse of infected CD4 cells can aid the transport of viruses (human immunodeficiency virus) to non-infected CD4 cells. We hypothesized that healthy organisms need these monopole antennas. If, during the neoplastic transformation, healthy cells lose monopole antennas in form of primary cilia, the IS aims to replace them by monopole antennas of polarized centrioles in IS to restore homeostasis.

  17. Impacts of hybrid synapses on the noise-delayed decay in scale-free neural networks

    International Nuclear Information System (INIS)

    Yilmaz, Ergin

    2014-01-01

    Highlights: • We investigate the NDD phenomenon in a hybrid scale-free network. • Electrical synapses are more impressive on the emergence of NDD. • Electrical synapses are more efficient in suppressing of the NDD. • Average degree has two opposite effects on the appearance time of the first spike. - Abstract: We study the phenomenon of noise-delayed decay in a scale-free neural network consisting of excitable FitzHugh–Nagumo neurons. In contrast to earlier works, where only electrical synapses are considered among neurons, we primarily examine the effects of hybrid synapses on the noise-delayed decay in this study. We show that the electrical synaptic coupling is more impressive than the chemical coupling in determining the appearance time of the first-spike and more efficient on the mitigation of the delay time in the detection of a suprathreshold input signal. We obtain that hybrid networks including inhibitory chemical synapses have higher signal detection capabilities than those of including excitatory ones. We also find that average degree exhibits two different effects, which are strengthening and weakening the noise-delayed decay effect depending on the noise intensity

  18. Abundance of gap junctions at glutamatergic mixed synapses in adult Mosquitofish spinal cord neurons

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    Jose L Serrano-Velez

    2014-06-01

    Full Text Available Dye-coupling, whole-mount immunohistochemistry for gap junction channel protein connexin 35 (Cx35, and freeze-fracture replica immunogold labeling (FRIL reveal an abundance of electrical synapses/gap junctions at glutamatergic mixed synapses in the 14th spinal segment that innervates the adult male gonopodium of Western Mosquitofish, Gambusia affinis (Mosquitofish.To study gap junctions’ role in fast motor behavior, we used a minimally-invasive neural-tract-tracing technique to introduce gap junction-permeant or -impermeant dyes into deep muscles controlling the gonopodium of the adult male Mosquitofish, a teleost fish that rapidly transfers (complete in 50 of the 62 gap junctions at mixed synapses are in the 14th spinal segment.Our results support and extend studies showing gap junctions at mixed synapses in spinal cord segments involved in control of genital reflexes in rodents, and they suggest a link between mixed synapses and fast motor behavior. The findings provide a basis for studies of specific roles of spinal neurons in the generation/regulation of sex-specific behavior and for studies of gap junctions’ role in regulating fast motor behavior. Finally, the CoPA IN provides a novel candidate neuron for future studies of gap junctions and neural control of fast motor behaviors.

  19. Molecular switches at the synapse emerge from receptor and kinase traffic.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Changes in the synaptic connection strengths between neurons are believed to play a role in memory formation. An important mechanism for changing synaptic strength is through movement of neurotransmitter receptors and regulatory proteins to and from the synapse. Several activity-triggered biochemical events control these movements. Here we use computer models to explore how these putative memory-related changes can be stabilised long after the initial trigger, and beyond the lifetime of synaptic molecules. We base our models on published biochemical data and experiments on the activity-dependent movement of a glutamate receptor, AMPAR, and a calcium-dependent kinase, CaMKII. We find that both of these molecules participate in distinct bistable switches. These simulated switches are effective for long periods despite molecular turnover and biochemical fluctuations arising from the small numbers of molecules in the synapse. The AMPAR switch arises from a novel self-recruitment process where the presence of sufficient receptors biases the receptor movement cycle to insert still more receptors into the synapse. The CaMKII switch arises from autophosphorylation of the kinase. The switches may function in a tightly coupled manner, or relatively independently. The latter case leads to multiple stable states of the synapse. We propose that similar self-recruitment cycles may be important for maintaining levels of many molecules that undergo regulated movement, and that these may lead to combinatorial possible stable states of systems like the synapse.

  20. Optimal recall from bounded metaplastic synapses: predicting functional adaptations in hippocampal area CA3.

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    Cristina Savin

    2014-02-01

    Full Text Available A venerable history of classical work on autoassociative memory has significantly shaped our understanding of several features of the hippocampus, and most prominently of its CA3 area, in relation to memory storage and retrieval. However, existing theories of hippocampal memory processing ignore a key biological constraint affecting memory storage in neural circuits: the bounded dynamical range of synapses. Recent treatments based on the notion of metaplasticity provide a powerful model for individual bounded synapses; however, their implications for the ability of the hippocampus to retrieve memories well and the dynamics of neurons associated with that retrieval are both unknown. Here, we develop a theoretical framework for memory storage and recall with bounded synapses. We formulate the recall of a previously stored pattern from a noisy recall cue and limited-capacity (and therefore lossy synapses as a probabilistic inference problem, and derive neural dynamics that implement approximate inference algorithms to solve this problem efficiently. In particular, for binary synapses with metaplastic states, we demonstrate for the first time that memories can be efficiently read out with biologically plausible network dynamics that are completely constrained by the synaptic plasticity rule, and the statistics of the stored patterns and of the recall cue. Our theory organises into a coherent framework a wide range of existing data about the regulation of excitability, feedback inhibition, and network oscillations in area CA3, and makes novel and directly testable predictions that can guide future experiments.

  1. Neuron-NG2 Cell Synapses: Novel Functions for Regulating NG2 Cell Proliferation and Differentiation

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    Qian-Kun Yang

    2013-01-01

    Full Text Available NG2 cells are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes, and microglia. These cells can be identified by their NG2 proteoglycan expression. NG2 cells have a highly branched morphology, with abundant processes radiating from the cell body, and express a complex set of voltage-gated channels, AMPA/kainate, and GABA receptors. Neurons notably form classical and nonclassical synapses with NG2 cells, which have varied characteristics and functions. Neuron-NG2 cell synapses could fine-tune NG2 cell activities, including the NG2 cell cycle, differentiation, migration, and myelination, and may be a novel potential therapeutic target for NG2 cell-related diseases, such as hypoxia-ischemia injury and periventricular leukomalacia. Furthermore, neuron-NG2 cell synapses may be correlated with the plasticity of CNS in adulthood with the synaptic contacts passing onto their progenies during proliferation, and synaptic contacts decrease rapidly upon NG2 cell differentiation. In this review, we highlight the characteristics of classical and nonclassical neuron-NG2 cell synapses, the potential functions, and the fate of synaptic contacts during proliferation and differentiation, with the emphasis on the regulation of the NG2 cell cycle by neuron-NG2 cell synapses and their potential underlying mechanisms.

  2. Whisker Deprivation Drives Two Phases of Inhibitory Synapse Weakening in Layer 4 of Rat Somatosensory Cortex.

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    Melanie A Gainey

    Full Text Available Inhibitory synapse development in sensory neocortex is experience-dependent, with sustained sensory deprivation yielding fewer and weaker inhibitory synapses. Whether this represents arrest of synapse maturation, or a more complex set of processes, is unclear. To test this, we measured the dynamics of inhibitory synapse development in layer 4 of rat somatosensory cortex (S1 during continuous whisker deprivation from postnatal day 7, and in age-matched controls. In deprived columns, spontaneous miniature inhibitory postsynaptic currents (mIPSCs and evoked IPSCs developed normally until P15, when IPSC amplitude transiently decreased, recovering by P16 despite ongoing deprivation. IPSCs remained normal until P22, when a second, sustained phase of weakening began. Delaying deprivation onset by 5 days prevented the P15 weakening. Both early and late phase weakening involved measurable reduction in IPSC amplitude relative to prior time points. Thus, deprivation appears to drive two distinct phases of active IPSC weakening, rather than simple arrest of synapse maturation.

  3. LRRTM3 Regulates Excitatory Synapse Development through Alternative Splicing and Neurexin Binding

    Directory of Open Access Journals (Sweden)

    Ji Won Um

    2016-02-01

    Full Text Available The four members of the LRRTM family (LRRTM1-4 are postsynaptic adhesion molecules essential for excitatory synapse development. They have also been implicated in neuropsychiatric diseases. Here, we focus on LRRTM3, showing that two distinct LRRTM3 variants generated by alternative splicing regulate LRRTM3 interaction with PSD-95, but not its excitatory synapse-promoting activity. Overexpression of either LRRTM3 variant increased excitatory synapse density in dentate gyrus (DG granule neurons, whereas LRRTM3 knockdown decreased it. LRRTM3 also controlled activity-regulated AMPA receptor surface expression in an alternative splicing-dependent manner. Furthermore, Lrrtm3-knockout mice displayed specific alterations in excitatory synapse density, excitatory synaptic transmission and excitability in DG granule neurons but not in CA1 pyramidal neurons. Lastly, LRRTM3 required only specific splice variants of presynaptic neurexins for their synaptogenic activity. Collectively, our data highlight alternative splicing and differential presynaptic ligand utilization in the regulation of LRRTMs, revealing key regulatory mechanisms for excitatory synapse development.

  4. Kalirin, a key player in synapse formation, is implicated in human diseases.

    Science.gov (United States)

    Mandela, Prashant; Ma, Xin-Ming

    2012-01-01

    Synapse formation is considered to be crucial for learning and memory. Understanding the underlying molecular mechanisms of synapse formation is a key to understanding learning and memory. Kalirin-7, a major isoform of Kalirin in adult rodent brain, is an essential component of mature excitatory synapses. Kalirin-7 interacts with multiple PDZ-domain-containing proteins including PSD95, spinophilin, and GluR1 through its PDZ-binding motif. In cultured hippocampal/cortical neurons, overexpression of Kalirin-7 increases spine density and spine size whereas reduction of endogenous Kalirin-7 expression decreases synapse number, and spine density. In Kalirin-7 knockout mice, spine length, synapse number, and postsynaptic density (PSD) size are decreased in hippocampal CA1 pyramidal neurons; these morphological alterations are accompanied by a deficiency in long-term potentiation (LTP) and a decreased spontaneous excitatory postsynaptic current (sEPSC) frequency. Human Kalirin-7, also known as Duo or Huntingtin-associated protein-interacting protein (HAPIP), is equivalent to rat Kalirin-7. Recent studies show that Kalirin is relevant to many human diseases such as Huntington's Disease, Alzheimer's Disease, ischemic stroke, schizophrenia, depression, and cocaine addiction. This paper summarizes our recent understanding of Kalirin function.

  5. Nanogranular SiO{sub 2} proton gated silicon layer transistor mimicking biological synapses

    Energy Technology Data Exchange (ETDEWEB)

    Liu, M. J.; Huang, G. S., E-mail: gshuang@fudan.edu.cn, E-mail: pfeng@nju.edu.cn; Guo, Q. L.; Tian, Z. A.; Li, G. J.; Mei, Y. F. [Department of Materials Science, Fudan University, Shanghai 200433 (China); Feng, P., E-mail: gshuang@fudan.edu.cn, E-mail: pfeng@nju.edu.cn; Shao, F.; Wan, Q. [School of Electronic Science and Engineering and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093 (China)

    2016-06-20

    Silicon on insulator (SOI)-based transistors gated by nanogranular SiO{sub 2} proton conducting electrolytes were fabricated to mimic synapse behaviors. This SOI-based device has both top proton gate and bottom buried oxide gate. Electrical transfer properties of top proton gate show hysteresis curves different from those of bottom gate, and therefore, excitatory post-synaptic current and paired pulse facilitation (PPF) behavior of biological synapses are mimicked. Moreover, we noticed that PPF index can be effectively tuned by the spike interval applied on the top proton gate. Synaptic behaviors and functions, like short-term memory, and its properties are also experimentally demonstrated in our device. Such SOI-based electronic synapses are promising for building neuromorphic systems.

  6. Long-term potentiation expands information content of hippocampal dentate gyrus synapses.

    Science.gov (United States)

    Bromer, Cailey; Bartol, Thomas M; Bowden, Jared B; Hubbard, Dusten D; Hanka, Dakota C; Gonzalez, Paola V; Kuwajima, Masaaki; Mendenhall, John M; Parker, Patrick H; Abraham, Wickliffe C; Sejnowski, Terrence J; Harris, Kristen M

    2018-03-06

    An approach combining signal detection theory and precise 3D reconstructions from serial section electron microscopy (3DEM) was used to investigate synaptic plasticity and information storage capacity at medial perforant path synapses in adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation (LTP) markedly increased the frequencies of both small and large spines measured 30 minutes later. This bidirectional expansion resulted in heterosynaptic counterbalancing of total synaptic area per unit length of granule cell dendrite. Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast, control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic precision than either control or potentiated dentate gyrus synapses. Thus, synaptic plasticity altered total capacity, yet hippocampal subregions differed dramatically in their synaptic information storage capacity, reflecting their diverse functions and activation histories.

  7. Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses

    Science.gov (United States)

    Trouche, Stéphanie; Sasaki, Jennifer M.; Tu, Tiffany; Reijmers, Leon G.

    2013-01-01

    SUMMARY A more complete understanding of how fear extinction alters neuronal activity and connectivity within fear circuits may aid in the development of strategies to treat human fear disorders. Using a c-fos based transgenic mouse, we found that contextual fear extinction silenced basal amygdala (BA) excitatory neurons that had been previously activated during fear conditioning. We hypothesized that the silencing of BA fear neurons was caused by an action of extinction on BA inhibitory synapses. In support of this hypothesis, we found extinction-induced target-specific remodeling of BA perisomatic inhibitory synapses originating from parvalbumin and cholecystokinin-positive interneurons. Interestingly, the predicted changes in the balance of perisomatic inhibition matched the silent and active states of the target BA fear neurons. These observations suggest that target-specific changes in perisomatic inhibitory synapses represent a mechanism through which experience can sculpt the activation patterns within a neural circuit. PMID:24183705

  8. Dynamic Observation of Brain-Like Learning in a Ferroelectric Synapse Device

    Science.gov (United States)

    Nishitani, Yu; Kaneko, Yukihiro; Ueda, Michihito; Fujii, Eiji; Tsujimura, Ayumu

    2013-04-01

    A brain-like learning function was implemented in an electronic synapse device using a ferroelectric-gate field effect transistor (FeFET). The FeFET was a bottom-gate type FET with a ZnO channel and a ferroelectric Pb(Zr,Ti)O3 (PZT) gate insulator. The synaptic weight, which is represented by the channel conductance of the FeFET, is updated by applying a gate voltage through a change in the ferroelectric polarization in the PZT. A learning function based on the symmetric spike-timing dependent synaptic plasticity was implemented in the synapse device using the multilevel weight update by applying a pulse gate voltage. The dynamic weighting and learning behavior in the synapse device was observed as a change in the membrane potential in a spiking neuron circuit.

  9. Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses.

    Science.gov (United States)

    Trouche, Stéphanie; Sasaki, Jennifer M; Tu, Tiffany; Reijmers, Leon G

    2013-11-20

    A more complete understanding of how fear extinction alters neuronal activity and connectivity within fear circuits may aid in the development of strategies to treat human fear disorders. Using a c-fos-based transgenic mouse, we found that contextual fear extinction silenced basal amygdala (BA) excitatory neurons that had been previously activated during fear conditioning. We hypothesized that the silencing of BA fear neurons was caused by an action of extinction on BA inhibitory synapses. In support of this hypothesis, we found extinction-induced target-specific remodeling of BA perisomatic inhibitory synapses originating from parvalbumin and cholecystokinin-positive interneurons. Interestingly, the predicted changes in the balance of perisomatic inhibition matched the silent and active states of the target BA fear neurons. These observations suggest that target-specific changes in perisomatic inhibitory synapses represent a mechanism through which experience can sculpt the activation patterns within a neural circuit. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Eph receptors and ephrins in neuron-astrocyte communication at synapses.

    Science.gov (United States)

    Murai, Keith K; Pasquale, Elena B

    2011-11-01

    Neuron-glia communication is essential for regulating the properties of synaptic connections in the brain. Astrocytes, in particular, play a critical and complex role in synapse development, maintenance, and plasticity. Likewise, neurons reciprocally influence astrocyte physiology. However, the molecular signaling events that enable astrocytes and neurons to effectively communicate with each other are only partially defined. Recent findings have revealed that Eph receptor tyrosine kinases and ephrins play an important role in contact-dependent neuron-glia communication at synapses. Upon binding, these two families of cell surface-associated proteins trigger bidirectional signaling events that regulate the structural and physiological properties of both neurons and astrocytes. This review will focus on the emerging role of Eph receptors and ephrins in neuron-astrocyte interaction at synapses and discuss implications for synaptic plasticity, behavior, and disease. Copyright © 2011 Wiley-Liss, Inc.

  11. Unsupervised learning by spike timing dependent plasticity in phase change memory (PCM synapses

    Directory of Open Access Journals (Sweden)

    Stefano eAmbrogio

    2016-03-01

    Full Text Available We present a novel one-transistor/one-resistor (1T1R synapse for neuromorphic networks, based on phase change memory (PCM technology. The synapse is capable of spike-timing dependent plasticity (STDP, where gradual potentiation relies on set transition, namely crystallization, in the PCM, while depression is achieved via reset or amorphization of a chalcogenide active volume. STDP characteristics are demonstrated by experiments under variable initial conditions and number of pulses. Finally, we support the applicability of the 1T1R synapse for learning and recognition of visual patterns by simulations of fully connected neuromorphic networks with 2 or 3 layers with high recognition efficiency. The proposed scheme provides a feasible low-power solution for on-line unsupervised machine learning in smart reconfigurable sensors.

  12. Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress.

    Science.gov (United States)

    Maras, P M; Molet, J; Chen, Y; Rice, C; Ji, S G; Solodkin, A; Baram, T Z

    2014-07-01

    The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress.

  13. 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.

  14. Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress

    Science.gov (United States)

    Maras, P M; Molet, J; Chen, Y; Rice, C; Ji, S G; Solodkin, A; Baram, T Z

    2014-01-01

    The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress. PMID:24589888

  15. Astrocyte Transforming Growth Factor Beta 1 Protects Synapses against Aβ Oligomers in Alzheimer's Disease Model.

    Science.gov (United States)

    Diniz, Luan Pereira; Tortelli, Vanessa; Matias, Isadora; Morgado, Juliana; Bérgamo Araujo, Ana Paula; Melo, Helen M; Seixas da Silva, Gisele S; Alves-Leon, Soniza V; de Souza, Jorge M; Ferreira, Sergio T; De Felice, Fernanda G; Gomes, Flávia Carvalho Alcantara

    2017-07-12

    Alzheimer's disease (AD) is characterized by progressive cognitive decline, increasingly attributed to neuronal dysfunction induced by amyloid-β oligomers (AβOs). Although the impact of AβOs on neurons has been extensively studied, only recently have the possible effects of AβOs on astrocytes begun to be investigated. Given the key roles of astrocytes in synapse formation, plasticity, and function, we sought to investigate the impact of AβOs on astrocytes, and to determine whether this impact is related to the deleterious actions of AβOs on synapses. We found that AβOs interact with astrocytes, cause astrocyte activation and trigger abnormal generation of reactive oxygen species, which is accompanied by impairment of astrocyte neuroprotective potential in vitro We further show that both murine and human astrocyte conditioned media (CM) increase synapse density, reduce AβOs binding, and prevent AβO-induced synapse loss in cultured hippocampal neurons. Both a neutralizing anti-transforming growth factor-β1 (TGF-β1) antibody and siRNA-mediated knockdown of TGF-β1, previously identified as an important synaptogenic factor secreted by astrocytes, abrogated the protective action of astrocyte CM against AβO-induced synapse loss. Notably, TGF-β1 prevented hippocampal dendritic spine loss and memory impairment in mice that received an intracerebroventricular infusion of AβOs. Results suggest that astrocyte-derived TGF-β1 is part of an endogenous mechanism that protects synapses against AβOs. By demonstrating that AβOs decrease astrocyte ability to protect synapses, our results unravel a new mechanism underlying the synaptotoxic action of AβOs in AD. SIGNIFICANCE STATEMENT Alzheimer's disease is characterized by progressive cognitive decline, mainly attributed to synaptotoxicity of the amyloid-β oligomers (AβOs). Here, we investigated the impact of AβOs in astrocytes, a less known subject. We show that astrocytes prevent synapse loss induced by A

  16. Label-free visualization of ultrastructural features of artificial synapses via cryo-EM.

    Science.gov (United States)

    Gopalakrishnan, Gopakumar; Yam, Patricia T; Madwar, Carolin; Bostina, Mihnea; Rouiller, Isabelle; Colman, David R; Lennox, R Bruce

    2011-12-21

    The ultrastructural details of presynapses formed between artificial substrates of submicrometer silica beads and hippocampal neurons are visualized via cryo-electron microscopy (cryo-EM). The silica beads are derivatized by poly-d-lysine or lipid bilayers. Molecular features known to exist at presynapses are clearly present at these artificial synapses, as visualized by cryo-EM. Key synaptic features such as the membrane contact area at synaptic junctions, the presynaptic bouton containing presynaptic vesicles, as well as microtubular structures can be identified. This is the first report of the direct, label-free observation of ultrastructural details of artificial synapses.

  17. Application Specific Optical Fibers

    OpenAIRE

    Pal, Bishnu P.

    2010-01-01

    In this chapter we have attempted to provide a unified summary description of the most important propagation characteristics of an optical fiber followed by discussion on several variety of special fibers for realizing fiber amplifiers, dispersion compensating fibers, microstructured optical fibers, and so on. Even though huge progress has been made on development of optical fibers for telecom application, a need for developing special fibers, not necessarily for telecom alone, has arisen. Th...

  18. The chemical component of the mixed GF-TTMn synapse in Drosophila melanogaster uses acetylcholine as its neurotransmitter.

    Science.gov (United States)

    Allen, Marcus J; Murphey, R K

    2007-07-01

    The largest central synapse in adult Drosophila is a mixed electro-chemical synapse whose gap junctions require the product of the shaking-B (shak-B) gene. Shak-B(2) mutant flies lack gap junctions at this synapse, which is between the giant fibre (GF) and the tergotrochanteral motor neuron (TTMn), but it still exhibits a long latency response upon GF stimulation. We have targeted the expression of the light chain of tetanus toxin to the GF, to block chemical transmission, in shak-B(2) flies. The long latency response in the tergotrochanteral muscle (TTM) was abolished indicating that the chemical component of the synapse mediates this response. Attenuation of GAL4-mediated labelling by a cha-GAL80 transgene, reveals the GF to be cholinergic. We have used a temperature-sensitive allele of the choline acetyltransferase gene (cha(ts2)) to block cholinergic synapses in adult flies and this also abolished the long latency response in shak-B(2) flies. Taken together the data provide evidence that both components of this mixed synapse are functional and that the chemical neurotransmitter between the GF and the TTMn is acetylcholine. Our findings show that the two components of this synapse can be separated to allow further studies into the mechanisms by which mixed synapses are built and function.

  19. The role of neurexins and neuroligins in the formation, maturation, and function of vertebrate synapses.

    Science.gov (United States)

    Krueger, Dilja D; Tuffy, Liam P; Papadopoulos, Theofilos; Brose, Nils

    2012-06-01

    Neurexins (NXs) and neuroligins (NLs) are transsynaptically interacting cell adhesion proteins that play a key role in the formation, maturation, activity-dependent validation, and maintenance of synapses. As complex alternative splicing processes in nerve cells generate a large number of NX and NLs variants, it has been proposed that a combinatorial interaction code generated by these variants may determine synapse identity and network connectivity during brain development. The functional importance of NXs and NLs is exemplified by the fact that mutations in NX and NL genes are associated with several neuropsychiatric disorders, most notably with autism. Accordingly, major research efforts have focused on the molecular mechanisms by which NXs and NLs operate at synapses. In this review, we summarize recent progress in this field and discuss emerging topics, such as the role of alternative interaction partners of NXs and NLs in synapse formation and function, and their relevance for synaptic plasticity in the mature brain. The novel findings highlight the fundamental importance of NX-NL interactions in a wide range of synaptic functions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Human synapses show a wide temporal window for spike-timing-dependent plasticity

    NARCIS (Netherlands)

    Testa-Silva, G.; Verhoog, M.B.; Goriounova, N.A.; Loebel, A.; Hjorth, J.; Baayen, J.C.; de Kock, C.P.J.; Mansvelder, H.D.

    2010-01-01

    Throughout our lifetime, activity-dependent changes in neuronal connection strength enable the brain to refine neural circuits and learn based on experience. Synapses can bi-directionally alter strength and the magnitude and sign depend on the millisecond timing of presynaptic and postsynaptic

  1. Role of perisynaptic parameters in neurotransmitter homeostasis - computational study of a general synapse

    Science.gov (United States)

    Pendyam, Sandeep; Mohan, Ashwin; Kalivas, Peter W.; Nair, Satish S.

    2015-01-01

    Extracellular neurotransmitter concentrations vary over a wide range depending on the type of neurotransmitter and location in the brain. Neurotransmitter homeostasis near a synapse is achieved by a balance of several mechanisms including vesicular release from the presynapse, diffusion, uptake by transporters, non-synaptic production, and regulation of release by autoreceptors. These mechanisms are also affected by the glia surrounding the synapse. However, the role of these mechanisms in achieving neurotransmitter homeostasis is not well understood. A biophysical modeling framework was proposed to reverse engineer glial configurations and parameters related to homeostasis for synapses that support a range of neurotransmitter gradients. Model experiments reveal that synapses with extracellular neurotransmitter concentrations in the micromolar range require non-synaptic neurotransmitter sources and tight synaptic isolation by extracellular glial formations. The model was used to identify the role of perisynaptic parameters on neurotransmitter homeostasis, and to propose glial configurations that could support different levels of extracellular neurotransmitter concentrations. Ranking the parameters based on their effect on neurotransmitter homeostasis, non-synaptic sources were found to be the most important followed by transporter concentration and diffusion coefficient. PMID:22460547

  2. The cAMP cascade modulates the neuroinformative impact of quantal release at cholinergic synapse

    Czech Academy of Sciences Publication Activity Database

    Vyskočil, František; Bukcharaeva, E.; Samigullin, D. V.; Nikolsky, E. E.

    2001-01-01

    Roč. 2, č. 2 (2001), s. 317-323 ISSN 1539-2791 R&D Projects: GA AV ČR IAA7011902 Grant - others:EU(XX) Nesting; RFBR(RU) 99-04-48286 Institutional research plan: CEZ:AV0Z5011922 Keywords : frog neuromuscular synapse * noradrenaline Subject RIV: ED - Physiology

  3. Diversity in Long-Term Synaptic Plasticity at Inhibitory Synapses of Striatal Spiny Neurons

    Science.gov (United States)

    Rueda-Orozco, Pavel E.; Mendoza, Ernesto; Hernandez, Ricardo; Aceves, Jose J.; Ibanez-Sandoval, Osvaldo; Galarraga, Elvira; Bargas, Jose

    2009-01-01

    Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term…

  4. GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction.

    Science.gov (United States)

    Saha, Rinki; Knapp, Stephanie; Chakraborty, Darpan; Horovitz, Omer; Albrecht, Anne; Kriebel, Martin; Kaphzan, Hanoch; Ehrlich, Ingrid; Volkmer, Hansjürgen; Richter-Levin, Gal

    2017-01-01

    Inhibitory synaptic transmission in the amygdala has a pivotal role in fear learning and its extinction. However, the local circuits formed by GABAergic inhibitory interneurons within the amygdala and their detailed function in shaping these behaviors are not well understood. Here we used lentiviral-mediated knockdown of the cell adhesion molecule neurofascin in the basolateral amygdala (BLA) to specifically remove inhibitory synapses at the axon initial segment (AIS) of BLA projection neurons. Quantitative analysis of GABAergic synapse markers and measurement of miniature inhibitory postsynaptic currents in BLA projection neurons after neurofascin knockdown ex vivo confirmed the loss of GABAergic input. We then studied the impact of this manipulation on anxiety-like behavior and auditory cued fear conditioning and its extinction as BLA related behavioral paradigms, as well as on long-term potentiation (LTP) in the ventral subiculum-BLA pathway in vivo. BLA knockdown of neurofascin impaired ventral subiculum-BLA-LTP. While this manipulation did not affect anxiety-like behavior and fear memory acquisition and consolidation, it specifically impaired extinction. Our findings indicate that modification of inhibitory synapses at the AIS of BLA projection neurons is sufficient to selectively impair extinction behavior. A better understanding of the role of distinct GABAergic synapses may provide novel and more specific targets for therapeutic interventions in extinction-based therapies.

  5. Synaptic heterogeneity and stimulus-induced modulation of depression in central synapses.

    Science.gov (United States)

    Hunter, J D; Milton, J G

    2001-08-01

    Short-term plasticity is a pervasive feature of synapses. Synapses exhibit many forms of plasticity operating over a range of time scales. We develop an optimization method that allows rapid characterization of synapses with multiple time scales of facilitation and depression. Investigation of paired neurons that are postsynaptic to the same identified interneuron in the buccal ganglion of Aplysia reveals that the responses of the two neurons differ in the magnitude of synaptic depression. Also, for single neurons, prolonged stimulation of the presynaptic neuron causes stimulus-induced increases in the early phase of synaptic depression. These observations can be described by a model that incorporates two availability factors, e.g., depletable vesicle pools or desensitizing receptor populations, with different time courses of recovery, and a single facilitation component. This model accurately predicts the responses to novel stimuli. The source of synaptic heterogeneity is identified with variations in the relative sizes of the two availability factors, and the stimulus-induced decrement in the early synaptic response is explained by a slowing of the recovery rate of one of the availability factors. The synaptic heterogeneity and stimulus-induced modifications in synaptic depression observed here emphasize that synaptic efficacy depends on both the individual properties of synapses and their past history.

  6. Memory and pattern storage in neural networks with activity dependent synapses

    Science.gov (United States)

    Mejias, J. F.; Torres, J. J.

    2009-01-01

    We present recently obtained results on the influence of the interplay between several activity dependent synaptic mechanisms, such as short-term depression and facilitation, on the maximum memory storage capacity in an attractor neural network [1]. In contrast with the case of synaptic depression, which drastically reduces the capacity of the network to store and retrieve activity patterns [2], synaptic facilitation is able to enhance the memory capacity in different situations. In particular, we find that a convenient balance between depression and facilitation can enhance the memory capacity, reaching maximal values similar to those obtained with static synapses, that is, without activity-dependent processes. We also argue, employing simple arguments, that this level of balance is compatible with experimental data recorded from some cortical areas, where depression and facilitation may play an important role for both memory-oriented tasks and information processing. We conclude that depressing synapses with a certain level of facilitation allow to recover the good retrieval properties of networks with static synapses while maintaining the nonlinear properties of dynamic synapses, convenient for information processing and coding.

  7. Experience-Dependent Regulation of Presynaptic NMDARs Enhances Neurotransmitter Release at Neocortical Synapses

    Science.gov (United States)

    Urban-Ciecko, Joanna; Wen, Jing A.; Parekh, Puja K.; Barth, Alison L.

    2015-01-01

    Sensory experience can selectively alter excitatory synaptic strength at neocortical synapses. The rapid increase in synaptic strength induced by selective whisker stimulation (single-row experience/SRE, where all but one row of whiskers has been removed from the mouse face) is due, at least in part, to the trafficking of AMPA receptors (AMPARs)…

  8. Super resolution imaging of genetically labelled synapses in Drosophila brain tissue

    Directory of Open Access Journals (Sweden)

    Isabelle Ayumi Spühler

    2016-05-01

    Full Text Available Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labelled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation

  9. Super Resolution Imaging of Genetically Labeled Synapses in Drosophila Brain Tissue.

    Science.gov (United States)

    Spühler, Isabelle A; Conley, Gaurasundar M; Scheffold, Frank; Sprecher, Simon G

    2016-01-01

    Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labeled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation.

  10. NMDAR-mediated calcium transients elicited by glutamate co-release at developing inhibitory synapses

    Directory of Open Access Journals (Sweden)

    Abigail Kalmbach

    2010-07-01

    Full Text Available Before hearing onset, the topographic organization of the inhibitory sound localization pathway from the medial nucleus of the trapezoid body (MNTB to the lateral superior olive (LSO is refined by means of synaptic silencing and strengthening. During this refinement period MNTB-LSO synapses not only release GABA and glycine but also release glutamate. This co-released glutamate can elicit postsynaptic currents that are predominantly mediated by NMDA receptors (NMDARs. To gain a better understanding of how glutamate contributes to synaptic signaling at developing MNTB-LSO inhibitory synapse, we investigated to what degree and under what conditions NMDARs contribute to postsynaptic calcium responses. Our results demonstrate that MNTB-LSO synapses can elicit compartmentalized calcium responses along aspiny LSO dendrites. These responses are significantly attenuated by the NMDARs antagonist APV. APV, however, has no effect on somatically recorded electrical postsynaptic responses, indicating little, if any, contribution of NMDARs to spike generation. Small NMDAR-mediated calcium responses were also observed under physiological levels of extracellular magnesium concentrations indicating that MNTB-LSO synapses activate magnesium sensitive NMDAR on immature LSO dendrites. In Fura-2 AM loaded neurons, blocking GABAA and glycine receptors decreased NMDAR contribution to somatic calcium responses suggesting that GABA and glycine, perhaps by shunting backpropagating action potentials, decrease the level of NMDAR activation under strong stimulus conditions.

  11. Astrocyte lipid metabolism is critical for synapse development and function in vivo.

    Science.gov (United States)

    van Deijk, Anne-Lieke F; Camargo, Nutabi; Timmerman, Jaap; Heistek, Tim; Brouwers, Jos F; Mogavero, Floriana; Mansvelder, Huibert D; Smit, August B; Verheijen, Mark H G

    2017-04-01

    The brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons. Accordingly, it is generally assumed that astrocyte-derived lipids are taken up by neurons to support synapse formation and function. Initial confirmation of this assumption has been obtained in cell cultures, but whether astrocyte-derived lipids support synapses in vivo is not known. Here, we address this issue and determined the role of astrocyte lipid metabolism in hippocampal synapse formation and function in vivo. Hippocampal protein expression for the sterol regulatory element-binding protein (SREBP) and its target gene fatty acid synthase (Fasn) was found in astrocytes but not in neurons. Diminishing SREBP activity in astrocytes using mice in which the SREBP cleavage-activating protein (SCAP) was deleted from GFAP-expressing cells resulted in decreased cholesterol and phospholipid secretion by astrocytes. Interestingly, SCAP mutant mice showed more immature synapses, lower presynaptic protein SNAP-25 levels as well as reduced numbers of synaptic vesicles, indicating impaired development of the presynaptic terminal. Accordingly, hippocampal short-term and long-term synaptic plasticity were defective in mutant mice. These findings establish a critical role for astrocyte lipid metabolism in presynaptic terminal development and function in vivo. GLIA 2017;65:670-682. © 2017 Wiley Periodicals, Inc.

  12. Short-term plasticity and long-term potentiation mimicked in single inorganic synapses

    Science.gov (United States)

    Ohno, Takeo; Hasegawa, Tsuyoshi; Tsuruoka, Tohru; Terabe, Kazuya; Gimzewski, James K.; Aono, Masakazu

    2011-08-01

    Memory is believed to occur in the human brain as a result of two types of synaptic plasticity: short-term plasticity (STP) and long-term potentiation (LTP; refs , , , ). In neuromorphic engineering, emulation of known neural behaviour has proven to be difficult to implement in software because of the highly complex interconnected nature of thought processes. Here we report the discovery of a Ag2S inorganic synapse, which emulates the synaptic functions of both STP and LTP characteristics through the use of input pulse repetition time. The structure known as an atomic switch, operating at critical voltages, stores information as STP with a spontaneous decay of conductance level in response to intermittent input stimuli, whereas frequent stimulation results in a transition to LTP. The Ag2S inorganic synapse has interesting characteristics with analogies to an individual biological synapse, and achieves dynamic memorization in a single device without the need of external preprogramming. A psychological model related to the process of memorizing and forgetting is also demonstrated using the inorganic synapses. Our Ag2S element indicates a breakthrough in mimicking synaptic behaviour essential for the further creation of artificial neural systems that emulate characteristics of human memory.

  13. MET receptor tyrosine kinase controls dendritic complexity, spine morphogenesis, and glutamatergic synapse maturation in the hippocampus.

    Science.gov (United States)

    Qiu, Shenfeng; Lu, Zhongming; Levitt, Pat

    2014-12-03

    The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. Copyright © 2014 the authors 0270-6474/14/3416166-14$15.00/0.

  14. Generation of functional inhibitory synapses incorporating defined combinations of GABA(A or glycine receptor subunits

    Directory of Open Access Journals (Sweden)

    Christine Laura Dixon

    2015-12-01

    Full Text Available Fast inhibitory neurotransmission in the brain is mediated by wide range of GABAA receptor (GABAAR and glycine receptor (GlyR isoforms, each with different physiological and pharmacological properties. Because multiple isoforms are expressed simultaneously in most neurons, it is difficult to define the properties of inhibitory postsynaptic currents mediated by individual isoforms in vivo. Although recombinant expression systems permit the expression of individual isoforms in isolation, they require exogenous agonist application which cannot mimic the dynamic neurotransmitter profile characteristic of native synapses. We describe a neuron-HEK293 cell co-culture technique for generating inhibitory synapses incorporating defined combinations of GABAAR or GlyR subunits. Primary neuronal cultures, prepared from embryonic rat cerebral cortex or spinal cord, are used to provide presynaptic GABAergic and glycinergic terminals, respectively. When the cultures are mature, HEK293 cells expressing the subunits of interest plus neuroligin 2A are plated onto the neurons, which rapidly form synapses onto HEK293 cells. Patch clamp electrophysiology is then used to analyze the physiological and pharmacological properties of the inhibitory postsynaptic currents mediated by the recombinant receptors. The method is suitable for investigating the kinetic properties or the effects of drugs on inhibitory postsynaptic currents mediated by defined GABAAR or GlyR isoforms of interest, the effects of hereditary disease mutations on the formation and function of both types of synapses, and synaptogenesis and synaptic clustering mechanisms. The entire cell preparation procedure takes 2 – 5 weeks.

  15. Investigation of synapse formation and function in a glutamatergic-GABAergic two-neuron microcircuit.

    Science.gov (United States)

    Chang, Chia-Ling; Trimbuch, Thorsten; Chao, Hsiao-Tuan; Jordan, Julia-Christine; Herman, Melissa A; Rosenmund, Christian

    2014-01-15

    Neural circuits are composed of mainly glutamatergic and GABAergic neurons, which communicate through synaptic connections. Many factors instruct the formation and function of these synapses; however, it is difficult to dissect the contribution of intrinsic cell programs from that of extrinsic environmental effects in an intact network. Here, we perform paired recordings from two-neuron microculture preparations of mouse hippocampal glutamatergic and GABAergic neurons to investigate how synaptic input and output of these two principal cells develop. In our reduced preparation, we found that glutamatergic neurons showed no change in synaptic output or input regardless of partner neuron cell type or neuronal activity level. In contrast, we found that glutamatergic input caused the GABAergic neuron to modify its output by way of an increase in synapse formation and a decrease in synaptic release efficiency. These findings are consistent with aspects of GABAergic synapse maturation observed in many brain regions. In addition, changes in GABAergic output are cell wide and not target-cell specific. We also found that glutamatergic neuronal activity determined the AMPA receptor properties of synapses on the partner GABAergic neuron. All modifications of GABAergic input and output required activity of the glutamatergic neuron. Because our system has reduced extrinsic factors, the changes we saw in the GABAergic neuron due to glutamatergic input may reflect initiation of maturation programs that underlie the formation and function of in vivo neural circuits.

  16. Blocking p75 (NTR) receptors alters polyinnervationz of neuromuscular synapses during development.

    Science.gov (United States)

    Garcia, Neus; Tomàs, Marta; Santafe, Manel M; Lanuza, Maria A; Besalduch, Nuria; Tomàs, Josep

    2011-09-01

    High-resolution immunohistochemistry shows that the receptor protein p75(NTR) is present in the nerve terminal, muscle cell, and glial Schwann cell at the neuromuscular junction (NMJ) of postnatal rats (P4-P6) during the synapse elimination period. Blocking the receptor with the antibody anti-p75-192-IgG (1-5 μg/ml, 1 hr) results in reduced endplate potentials (EPPs) in mono- and polyinnervated synapses ex vivo, but the mean number of functional inputs per NMJ does not change for as long as 3 hr. Incubation with exogenous brain-derived neurotrophic factor (BDNF) for 1 hr (50 nM) resulted in a significant increase in the size of the EPPs in all nerve terminals, and preincubation with anti-p75-192-IgG prevented this potentiation. Long exposure (24 hr) in vivo of the NMJs to the antibody anti-p75-192-IgG (1-2 μg/ml) results in a delay of postnatal synapse elimination and even some regrowth of previously withdrawn axons, but also in some acceleration of the morphologic maturation of the postsynaptic nicotinic acetylcholine receptor (nAChR) clusters. The results indicate that p75(NTR) is involved in both ACh release and axonal retraction during postnatal axonal competition and synapse elimination. Copyright © 2011 Wiley-Liss, Inc.

  17. New players tip the scales in the balance between excitatory and inhibitory synapses

    Directory of Open Access Journals (Sweden)

    El-Husseini Alaa

    2005-03-01

    Full Text Available Abstract Synaptogenesis is a highly controlled process, involving a vast array of players which include cell adhesion molecules, scaffolding and signaling proteins, neurotransmitter receptors and proteins associated with the synaptic vesicle machinery. These molecules cooperate in an intricate manner on both the pre- and postsynaptic sides to orchestrate the precise assembly of neuronal contacts. This is an amazing feat considering that a single neuron receives tens of thousands of synaptic inputs but virtually no mismatch between pre- and postsynaptic components occur in vivo. One crucial aspect of synapse formation is whether a nascent synapse will develop into an excitatory or inhibitory contact. The tight control of a balance between the types of synapses formed regulates the overall neuronal excitability, and is thus critical for normal brain function and plasticity. However, little is known about how this balance is achieved. This review discusses recent findings which provide clues to how neurons may control excitatory and inhibitory synapse formation, with focus on the involvement of the neuroligin family and PSD-95 in this process.

  18. Specific recycling receptors are targeted to the immune synapse by the intraflagellar transport system

    Science.gov (United States)

    Finetti, Francesca; Patrussi, Laura; Masi, Giulia; Onnis, Anna; Galgano, Donatella; Lucherini, Orso Maria; Pazour, Gregory J.; Baldari, Cosima T.

    2014-01-01

    ABSTRACT T cell activation requires sustained signaling at the immune synapse, a specialized interface with the antigen-presenting cell (APC) that assembles following T cell antigen receptor (TCR) engagement by major histocompatibility complex (MHC)-bound peptide. Central to sustained signaling is the continuous recruitment of TCRs to the immune synapse. These TCRs are partly mobilized from an endosomal pool by polarized recycling. We have identified IFT20, a component of the intraflagellar transport (IFT) system that controls ciliogenesis, as a central regulator of TCR recycling to the immune synapse. Here, we have investigated the interplay of IFT20 with the Rab GTPase network that controls recycling. We found that IFT20 forms a complex with Rab5 and the TCR on early endosomes. IFT20 knockdown (IFT20KD) resulted in a block in the recycling pathway, leading to a build-up of recycling TCRs in Rab5+ endosomes. Recycling of the transferrin receptor (TfR), but not of CXCR4, was disrupted by IFT20 deficiency. The IFT components IFT52 and IFT57 were found to act together with IFT20 to regulate TCR and TfR recycling. The results provide novel insights into the mechanisms that control TCR recycling and immune synapse assembly, and underscore the trafficking-related function of the IFT system beyond ciliogenesis. PMID:24554435

  19. Orchestrating cytoskeleton and intracellular vesicle traffic to build functional immunological synapses.

    Science.gov (United States)

    Soares, Helena; Lasserre, Rémi; Alcover, Andrés

    2013-11-01

    Immunological synapses are specialized cell-cell contacts formed between T lymphocytes and antigen-presenting cells. They are induced upon antigen recognition and are crucial for T-cell activation and effector functions. The generation and function of immunological synapses depend on an active T-cell polarization process, which results from a finely orchestrated crosstalk between the antigen receptor signal transduction machinery, the actin and microtubule cytoskeletons, and controlled vesicle traffic. Although we understand how some of these particular events are regulated, we still lack knowledge on how these multiple cellular elements are harmonized to ensure appropriate T-cell responses. We discuss here our view on how T-cell receptor signal transduction initially commands cytoskeletal and vesicle traffic polarization, which in turn sets the immunological synapse molecular design that regulates T-cell activation. We also discuss how the human immunodeficiency virus (HIV-1) hijacks some of these processes impairing immunological synapse generation and function. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Total regional and global number of synapses in the human brain neocortex

    NARCIS (Netherlands)

    Tang, Y.; Nyengaard, J.R.; Groot, D.M.G. de; Jorgen, H.; Gundersen, G.

    2001-01-01

    An estimator of the total number of synapses in neocortex of human autopsy brains based on unbiased stereological principles is described. Each randomly chosen cerebral hemisphere was stratified into the four major neocortical regions. Uniform sampling with a varying sampling fraction in each region

  1. Mixed Analog/Digital Matrix-Vector Multiplier for Neural Network Synapses

    DEFF Research Database (Denmark)

    Lehmann, Torsten; Bruun, Erik; Dietrich, Casper

    1996-01-01

    In this work we present a hardware efficient matrix-vector multiplier architecture for artificial neural networks with digitally stored synapse strengths. We present a novel technique for manipulating bipolar inputs based on an analog two's complements method and an accurate current rectifier...

  2. Impact of delays on the synchronization transitions of modular neuronal networks with hybrid synapses

    Science.gov (United States)

    Liu, Chen; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Tsang, Kaiming; Chan, Wailok

    2013-09-01

    The combined effects of the information transmission delay and the ratio of the electrical and chemical synapses on the synchronization transitions in the hybrid modular neuronal network are investigated in this paper. Numerical results show that the synchronization of neuron activities can be either promoted or destroyed as the information transmission delay increases, irrespective of the probability of electrical synapses in the hybrid-synaptic network. Interestingly, when the number of the electrical synapses exceeds a certain level, further increasing its proportion can obviously enhance the spatiotemporal synchronization transitions. Moreover, the coupling strength has a significant effect on the synchronization transition. The dominated type of the synapse always has a more profound effect on the emergency of the synchronous behaviors. Furthermore, the results of the modular neuronal network structures demonstrate that excessive partitioning of the modular network may result in the dramatic detriment of neuronal synchronization. Considering that information transmission delays are inevitable in intra- and inter-neuronal networks communication, the obtained results may have important implications for the exploration of the synchronization mechanism underlying several neural system diseases such as Parkinson's Disease.

  3. Synapse-centric mapping of cortical models to the SpiNNaker neuromorphic architecture

    Directory of Open Access Journals (Sweden)

    James Courtney Knight

    2016-09-01

    Full Text Available While the adult human brain has approximately 8.8x10^10 neurons, this number is dwarfed by its 1x10^15 synapses. From the point of view of neuromorphic engineering and neural simulation in general this makes the simulation of these synapses a particularly complex problem. SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Current solutions for simulating spiking neural networks on SpiNNaker are heavily inspired by work on distributed high-performance computing. However, while SpiNNaker shares many characteristics with such distributed systems, its component nodes have much more limited resources and, as the system lacks global synchronization, the computation performed on each node must complete within a fixed time step. We first analyze the performance of the current SpiNNaker neural simulation software and identify several problems that occur when it is used to simulate networks of the type often used to model the cortex which contain large numbers of sparsely connected synapses. We then present a new, more flexible approach for mapping the simulation of such networks to SpiNNaker which solves many of these problems. Finally we analyze the performance of our new approach using both benchmarks, designed to represent cortical connectivity, and larger, functional cortical models. In a benchmark network where neurons receive input from 8000 STDP synapses, our new approach allows more neurons to be simulated on each SpiNNaker core than has been previously possible. We also demonstrate that the largest plastic neural network previously simulated on neuromorphic hardware can be run in real time using our new approach: double the speed that was previously achieved. Additionally this network contains two types of plastic synapse which previously had to be trained separately but, using our new approach, can be trained simultaneously.

  4. P2X7 Receptors Drive Spine Synapse Plasticity in the Learned Helplessness Model of Depression.

    Science.gov (United States)

    Otrokocsi, Lilla; Kittel, Ágnes; Sperlágh, Beáta

    2017-10-01

    Major depressive disorder is characterized by structural and functional abnormalities of cortical and limbic brain areas, including a decrease in spine synapse number in the dentate gyrus of the hippocampus. Recent studies highlighted that both genetic and pharmacological invalidation of the purinergic P2X7 receptor (P2rx7) leads to antidepressant-like phenotype in animal experiments; however, the impact of P2rx7 on depression-related structural changes in the hippocampus is not clarified yet. Effects of genetic deletion of P2rx7s on depressive-like behavior and spine synapse density in the dentate gyrus were investigated using the learned helplessness mouse model of depression. We demonstrate that in wild-type animals, inescapable footshocks lead to learned helplessness behavior reflected in increased latency and number of escape failures to subsequent escapable footshocks. This behavior is accompanied with downregulation of mRNA encoding P2rx7 and decrease of spine synapse density in the dentate gyrus as determined by electron microscopic stereology. In addition, a decrease in synaptopodin but not in PSD95 and NR2B/GluN2B protein level was also observed under these conditions. Whereas the absence of P2rx7 was characterized by escape deficit, no learned helpless behavior is observed in these animals. Likewise, no decrease in spine synapse number and synaptopodin protein levels was detected in response to inescapable footshocks in P2rx7-deficient animals. Our findings suggest the endogenous activation of P2rx7s in the learned helplessness model of depression and decreased plasticity of spine synapses in P2rx7-deficient mice might explain the resistance of these animals to repeated stressful stimuli. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  5. A Machine Learning Method for the Prediction of Receptor Activation in the Simulation of Synapses

    Science.gov (United States)

    Montes, Jesus; Gomez, Elena; Merchán-Pérez, Angel; DeFelipe, Javier; Peña, Jose-Maria

    2013-01-01

    Chemical synaptic transmission involves the release of a neurotransmitter that diffuses in the extracellular space and interacts with specific receptors located on the postsynaptic membrane. Computer simulation approaches provide fundamental tools for exploring various aspects of the synaptic transmission under different conditions. In particular, Monte Carlo methods can track the stochastic movements of neurotransmitter molecules and their interactions with other discrete molecules, the receptors. However, these methods are computationally expensive, even when used with simplified models, preventing their use in large-scale and multi-scale simulations of complex neuronal systems that may involve large numbers of synaptic connections. We have developed a machine-learning based method that can accurately predict relevant aspects of the behavior of synapses, such as the percentage of open synaptic receptors as a function of time since the release of the neurotransmitter, with considerably lower computational cost compared with the conventional Monte Carlo alternative. The method is designed to learn patterns and general principles from a corpus of previously generated Monte Carlo simulations of synapses covering a wide range of structural and functional characteristics. These patterns are later used as a predictive model of the behavior of synapses under different conditions without the need for additional computationally expensive Monte Carlo simulations. This is performed in five stages: data sampling, fold creation, machine learning, validation and curve fitting. The resulting procedure is accurate, automatic, and it is general enough to predict synapse behavior under experimental conditions that are different to the ones it has been trained on. Since our method efficiently reproduces the results that can be obtained with Monte Carlo simulations at a considerably lower computational cost, it is suitable for the simulation of high numbers of synapses and it is

  6. A machine learning method for the prediction of receptor activation in the simulation of synapses.

    Directory of Open Access Journals (Sweden)

    Jesus Montes

    Full Text Available Chemical synaptic transmission involves the release of a neurotransmitter that diffuses in the extracellular space and interacts with specific receptors located on the postsynaptic membrane. Computer simulation approaches provide fundamental tools for exploring various aspects of the synaptic transmission under different conditions. In particular, Monte Carlo methods can track the stochastic movements of neurotransmitter molecules and their interactions with other discrete molecules, the receptors. However, these methods are computationally expensive, even when used with simplified models, preventing their use in large-scale and multi-scale simulations of complex neuronal systems that may involve large numbers of synaptic connections. We have developed a machine-learning based method that can accurately predict relevant aspects of the behavior of synapses, such as the percentage of open synaptic receptors as a function of time since the release of the neurotransmitter, with considerably lower computational cost compared with the conventional Monte Carlo alternative. The method is designed to learn patterns and general principles from a corpus of previously generated Monte Carlo simulations of synapses covering a wide range of structural and functional characteristics. These patterns are later used as a predictive model of the behavior of synapses under different conditions without the need for additional computationally expensive Monte Carlo simulations. This is performed in five stages: data sampling, fold creation, machine learning, validation and curve fitting. The resulting procedure is accurate, automatic, and it is general enough to predict synapse behavior under experimental conditions that are different to the ones it has been trained on. Since our method efficiently reproduces the results that can be obtained with Monte Carlo simulations at a considerably lower computational cost, it is suitable for the simulation of high numbers of

  7. Combined effect of chemical and electrical synapses in Hindmarsh-Rose neural networks on synchronization and the rate of information.

    Science.gov (United States)

    Baptista, M S; Moukam Kakmeni, F M; Grebogi, C

    2010-09-01

    In this work we studied the combined action of chemical and electrical synapses in small networks of Hindmarsh-Rose (HR) neurons on the synchronous behavior and on the rate of information produced (per time unit) by the networks. We show that if the chemical synapse is excitatory, the larger the chemical synapse strength used the smaller the electrical synapse strength needed to achieve complete synchronization, and for moderate synaptic strengths one should expect to find desynchronous behavior. Otherwise, if the chemical synapse is inhibitory, the larger the chemical synapse strength used the larger the electrical synapse strength needed to achieve complete synchronization, and for moderate synaptic strengths one should expect to find synchronous behaviors. Finally, we show how to calculate semianalytically an upper bound for the rate of information produced per time unit (Kolmogorov-Sinai entropy) in larger networks. As an application, we show that this upper bound is linearly proportional to the number of neurons in a network whose neurons are highly connected.

  8. Espina: A Tool for the Automated Segmentation and Counting of Synapses in Large Stacks of Electron Microscopy Images

    Science.gov (United States)

    Morales, Juan; Alonso-Nanclares, Lidia; Rodríguez, José-Rodrigo; DeFelipe, Javier; Rodríguez, Ángel; Merchán-Pérez, Ángel

    2011-01-01

    The synapses in the cerebral cortex can be classified into two main types, Gray's type I and type II, which correspond to asymmetric (mostly glutamatergic excitatory) and symmetric (inhibitory GABAergic) synapses, respectively. Hence, the quantification and identification of their different types and the proportions in which they are found, is extraordinarily important in terms of brain function. The ideal approach to calculate the number of synapses per unit volume is to analyze 3D samples reconstructed from serial sections. However, obtaining serial sections by transmission electron microscopy is an extremely time consuming and technically demanding task. Using focused ion beam/scanning electron microscope microscopy, we recently showed that virtually all synapses can be accurately identified as asymmetric or symmetric synapses when they are visualized, reconstructed, and quantified from large 3D tissue samples obtained in an automated manner. Nevertheless, the analysis, segmentation, and quantification of synapses is still a labor intensive procedure. Thus, novel solutions are currently necessary to deal with the large volume of data that is being generated by automated 3D electron microscopy. Accordingly, we have developed ESPINA, a software tool that performs the automated segmentation and counting of synapses in a reconstructed 3D volume of the cerebral cortex, and that greatly facilitates and accelerates these processes. PMID:21633491

  9. Despite disorganized synapse structure, Th2 cells maintain directional delivery of CD40L to antigen-presenting B cells.

    Science.gov (United States)

    Gardell, Jennifer L; Parker, David C

    2017-01-01

    Upon recognition of peptide displayed on MHC molecules, Th1 and Th2 cells form distinct immunological synapse structures. Th1 cells have a bull's eye synapse structure with TCR/ MHC-peptide interactions occurring central to a ring of adhesion molecules, while Th2 cells have a multifocal synapse with small clusters of TCR/MHC interactions throughout the area of T cell/antigen-presenting cell interaction. In this study, we investigated whether this structural difference in the immunological synapse affects delivery of T cell help. The immunological synapse is thought to ensure antigen-specific delivery of cytolytic granules and killing of target cells by NK cells and cytolytic T cells. In helper T cells, it has been proposed that the immunological synapse may direct delivery of other effector molecules including cytokines. CD40 ligand (CD40L) is a membrane-bound cytokine essential for antigen-specific T cell help for B cells in the antibody response. We incubated Th1 and Th2 cells overnight with a mixture of antigen-presenting and bystander B cells, and the delivery of CD40L to B cells and subsequent B cell responses were compared. Despite distinct immunological synapse structures, Th1 and Th2 cell do not differ in their ability to deliver CD40L and T cell help in an antigen-specific fashion, or in their susceptibility to inhibition of help by a blocking anti-CD40L antibody.

  10. Constancy and variability in cortical structure. A study on synapses and dendritic spines in hedgehog and monkey.

    Science.gov (United States)

    Schüz, A; Demianenko, G P

    1995-01-01

    Synapses and dendritic spines were investigated in the parietal cortex of the hedgehog (Erinaceus europaeus) and the monkey (Macaca mulatta). There was no significant difference in the density of synapses between the two species (14 synapses/100 microns2 in the hedgehog, 15/100 microns2 in the monkey), neither in the size of the synaptic junctions, in the proportion of Type I and Type II synapses (8-10% were of Type II in the hedgehog, 10-14% in the monkey) nor in the proportion of perforated synapses (8% in the hedgehog, 5% in the monkey). The only striking difference at the electron microscopic level concerned the frequency of synapses in which the postsynaptic profile was deeply indented into the presynaptic terminal. Such synapses were 10 times more frequent in the monkey. Dendritic spines were investigated in Golgi-preparations. The density of spines along dendrites was similar in both species. The results are discussed with regard to connectivity in the cortex of small and large brains.

  11. ESPINA: a tool for the automated segmentation and counting of synapses in large stacks of electron microscopy images

    Directory of Open Access Journals (Sweden)

    Juan eMorales

    2011-03-01

    Full Text Available The synapses in the cerebral cortex can be classified into two main types, Gray’s type I and type II, which correspond to asymmetric (mostly glutamatergic excitatory and symmetric (inhibitory GABAergic synapses, respectively. Hence, the quantification and identification of their different types and the proportions in which they are found, is extraordinarily important in terms of brain function. The ideal approach to calculate the number of synapses per unit volume is to analyze three-dimensional samples reconstructed from serial sections. However, obtaining serial sections by transmission electron microscopy is an extremely time consuming and technically demanding task. Using FIB/SEM microscopy, we recently showed that virtually all synapses can be accurately identified as asymmetric or symmetric synapses when they are visualized, reconstructed and quantified from large three-dimensional tissue samples obtained in an automated manner. Nevertheless, the analysis, segmentation and quantification of synapses is still a labor intensive procedure. Thus, novel solutions are currently necessary to deal with the large volume of data that is being generated by automated 3D electron microscopy. Accordingly, we have developed ESPINA, a software tool that performs the automated segmentation and counting of synapses in a reconstructed 3D volume of the cerebral cortex, and that greatly facilitates and accelerates these processes.

  12. Maternal dietary loads of alpha-tocopherol increase synapse density and glial synaptic coverage in the hippocampus of adult offspring

    Directory of Open Access Journals (Sweden)

    S. Salucci

    2014-05-01

    Full Text Available An increased intake of the antioxidant α-Tocopherol (vitamin E is recommended in complicated pregnancies, to prevent free radical damage to mother and fetus. However, the anti-PKC and antimitotic activity of α-Tocopherol raises concerns about its potential effects on brain development. Recently, we found that maternal dietary loads of α-Tocopherol through pregnancy and lactation cause developmental deficit in hippocampal synaptic plasticity in rat offspring. The defect persisted into adulthood, with behavioral alterations in hippocampus-dependent learning. Here, using the same rat model of maternal supplementation, ultrastructural morphometric studies were carried out to provide mechanistic interpretation to such a functional impairment in adult offspring by the occurrence of long-term changes in density and morphological features of hippocampal synapses. Higher density of axo-spinous synapses was found in CA1 stratum radiatum of α-Tocopherol-exposed rats compared to controls, pointing to a reduced synapse pruning. No morphometric changes were found in synaptic ultrastructural features, i.e., perimeter of axon terminals, length of synaptic specializations, extension of bouton-spine contact. Glia-synapse anatomical relationship was also affected. Heavier astrocytic coverage of synapses was observed in Tocopherol-treated offspring, notably surrounding axon terminals; moreover, the percentage of synapses contacted by astrocytic endfeet at bouton-spine interface (tripartite synapses was increased. These findings indicate that gestational and neonatal exposure to supranutritional tocopherol intake can result in anatomical changes of offspring hippocampus that last through adulthood. These include a surplus of axo-spinous synapses and an aberrant glia-synapse relationship, which may represent the morphological signature of previously described alterations in synaptic plasticity and hippocampus-dependent learning.

  13. Axon Termination, Pruning, and Synaptogenesis in the Giant Fiber System of Drosophila melanogaster Is Promoted by Highwire.

    Science.gov (United States)

    Borgen, Melissa; Rowland, Kimberly; Boerner, Jana; Lloyd, Brandon; Khan, Aruna; Murphey, Rodney

    2017-03-01

    The ubiquitin ligase Highwire has a conserved role in synapse formation. Here, we show that Highwire coordinates several facets of central synapse formation in the Drosophila melanogaster giant fiber system, including axon termination, axon pruning, and synaptic function. Despite the similarities to the fly neuromuscular junction, the role of Highwire and the underlying signaling pathways are distinct in the fly's giant fiber system. During development, branching of the giant fiber presynaptic terminal occurs and, normally, the transient branches are pruned away. However, in highwire mutants these ectopic branches persist, indicating that Highwire promotes axon pruning. highwire mutants also exhibit defects in synaptic function. Highwire promotes axon pruning and synaptic function cell-autonomously by attenuating a mitogen-activated protein kinase pathway including Wallenda, c-Jun N-terminal kinase/Basket, and the transcription factor Jun. We also show a novel role for Highwire in non-cell autonomous promotion of synaptic function from the midline glia. Highwire also regulates axon termination in the giant fibers, as highwire mutant axons exhibit severe overgrowth beyond the pruning defect. This excessive axon growth is increased by manipulating Fos expression in the cells surrounding the giant fiber terminal, suggesting that Fos regulates a trans -synaptic signal that promotes giant fiber axon growth. Copyright © 2017 by the Genetics Society of America.

  14. Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

    Science.gov (United States)

    Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

    2018-01-01

    Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is likely

  15. Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

    Directory of Open Access Journals (Sweden)

    Dávid Csabai

    2018-01-01

    Full Text Available Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I and symmetric (Type II synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network

  16. Fibered F-Algebra

    OpenAIRE

    Kleyn, Aleks

    2007-01-01

    The concept of F-algebra and its representation can be extended to an arbitrary bundle. We define operations of fibered F-algebra in fiber. The paper presents the representation theory of of fibered F-algebra as well as a comparison of representation of F-algebra and of representation of fibered F-algebra.

  17. Photonic crystal fibers

    DEFF Research Database (Denmark)

    Lægsgaard, Jesper; Hansen, K P; Nielsen, M D

    2003-01-01

    Photonic crystal fibers having a complex microstructure in the transverse plane constitute a new and promising class of optical fibers. Such fibers can either guide light through total internal reflection or the photonic bandgap effect, In this paper, we review the different types and applications...... of photonic crystal fibers with particular emphasis on recent advances in the field....

  18. Photonic crystal fibers -

    DEFF Research Database (Denmark)

    Libori, Stig E. Barkou

    2002-01-01

    . Such micro-structured fibers are the ones most often trated in literature concerning micro-structured fibers. These micro-structured fibers offer a whole range of novel wave guiding characteristics, including the possibility of fibers that guide only one mode irrespective of the frequency of light...

  19. Fiber optic connector

    Science.gov (United States)

    Rajic, Slobodan; Muhs, Jeffrey D.

    1996-01-01

    A fiber optic connector and method for connecting composite materials within which optical fibers are imbedded. The fiber optic connector includes a capillary tube for receiving optical fibers at opposing ends. The method involves inserting a first optical fiber into the capillary tube and imbedding the unit in the end of a softened composite material. The capillary tube is injected with a coupling medium which subsequently solidifies. The composite material is machined to a desired configuration. An external optical fiber is then inserted into the capillary tube after fluidizing the coupling medium, whereby the optical fibers are coupled.

  20. Loss of perforated synapses in the dentate gyrus: morphological substrate of memory deficit in aged rats.

    Science.gov (United States)

    Geinisman, Y; de Toledo-Morrell, L; Morrell, F

    1986-01-01

    Most, but not all, aged rats exhibit a profound deficit in spatial memory when tested in a radial maze--a task known to depend on the integrity of the hippocampal formation. In this study, animals were divided into three groups based on their spatial memory capacity: young adult rats with good memory, aged rats with impaired memory, and aged rats with good memory. Memory-impaired aged animals showed a loss of perforated axospinous synapses in the dentate gyrus of the hippocampal formation in comparison with either young adults or aged rats with good memory. This finding suggests that the loss of perforated axospinous synapses in the hippocampal formation underlies the age-related deficit in spatial memory. Images PMID:3458260

  1. Mimicking Neurotransmitter Release in Chemical Synapses via Hysteresis Engineering in MoS2 Transistors.

    Science.gov (United States)

    Arnold, Andrew J; Razavieh, Ali; Nasr, Joseph R; Schulman, Daniel S; Eichfeld, Chad M; Das, Saptarshi

    2017-03-28

    Neurotransmitter release in chemical synapses is fundamental to diverse brain functions such as motor action, learning, cognition, emotion, perception, and consciousness. Moreover, improper functioning or abnormal release of neurotransmitter is associated with numerous neurological disorders such as epilepsy, sclerosis, schizophrenia, Alzheimer's disease, and Parkinson's disease. We have utilized hysteresis engineering in a back-gated MoS 2 field effect transistor (FET) in order to mimic such neurotransmitter release dynamics in chemical synapses. All three essential features, i.e., quantal, stochastic, and excitatory or inhibitory nature of neurotransmitter release, were accurately captured in our experimental demonstration. We also mimicked an important phenomenon called long-term potentiation (LTP), which forms the basis of human memory. Finally, we demonstrated how to engineer the LTP time by operating the MoS 2 FET in different regimes. Our findings could provide a critical component toward the design of next-generation smart and intelligent human-like machines and human-machine interfaces.

  2. Retrogradely Transported TrkA Endosomes Signal Locally within Dendrites to Maintain Sympathetic Neuron Synapses

    Directory of Open Access Journals (Sweden)

    Kathryn M. Lehigh

    2017-04-01

    Full Text Available Sympathetic neurons require NGF from their target fields for survival, axonal target innervation, dendritic growth and formation, and maintenance of synaptic inputs from preganglionic neurons. Target-derived NGF signals are propagated retrogradely, from distal axons to somata of sympathetic neurons via TrkA signaling endosomes. We report that a subset of TrkA endosomes that are transported from distal axons to cell bodies translocate into dendrites, where they are signaling competent and move bidirectionally, in close proximity to synaptic protein clusters. Using a strategy for spatially confined inhibition of TrkA kinase activity, we found that distal-axon-derived TrkA signaling endosomes are necessary within sympathetic neuron dendrites for maintenance of synapses. Thus, TrkA signaling endosomes have unique functions in different cellular compartments. Moreover, target-derived NGF mediates circuit formation and synapse maintenance through TrkA endosome signaling within dendrites to promote aggregation of postsynaptic protein complexes.

  3. The interplay between neurons and glia in synapse development and plasticity.

    Science.gov (United States)

    Stogsdill, Jeff A; Eroglu, Cagla

    2017-02-01

    In the brain, the formation of complex neuronal networks amenable to experience-dependent remodeling is complicated by the diversity of neurons and synapse types. The establishment of a functional brain depends not only on neurons, but also non-neuronal glial cells. Glia are in continuous bi-directional communication with neurons to direct the formation and refinement of synaptic connectivity. This article reviews important findings, which uncovered cellular and molecular aspects of the neuron-glia cross-talk that govern the formation and remodeling of synapses and circuits. In vivo evidence demonstrating the critical interplay between neurons and glia will be the major focus. Additional attention will be given to how aberrant communication between neurons and glia may contribute to neural pathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. From synapse to nucleus and back again--communication over distance within neurons.

    Science.gov (United States)

    Fainzilber, Mike; Budnik, Vivian; Segal, Rosalind A; Kreutz, Michael R

    2011-11-09

    How do neurons integrate intracellular communication from synapse to nucleus and back? Here we briefly summarize aspects of this topic covered by a symposium at Neuroscience 2011. A rich repertoire of signaling mechanisms link both dendritic terminals and axon tips with neuronal soma and nucleus, using motor-dependent transport machineries to traverse the long intracellular distances along neuronal processes. Activation mechanisms at terminals include localized translation of dendritic or axonal RNA, proteolytic cleavage of receptors or second messengers, and differential phosphorylation of signaling moieties. Signaling complexes may be transported in endosomes, or as non-endosomal complexes associated with importins and dynein. Anterograde transport of RNA granules from the soma to neuronal processes, coupled with retrograde transport of proteins translated locally at terminals or within processes, may fuel ongoing bidirectional communication between soma and synapse to modulate synaptic plasticity as well as neuronal growth and survival decisions.

  5. Navigating barriers: the challenge of directed secretion at the natural killer cell lytic immunological synapse.

    Science.gov (United States)

    Sanborn, Keri B; Orange, Jordan S

    2010-05-01

    Natural killer (NK) cells have an inherent ability to recognize and destroy a wide array of cells rendered abnormal by stress or disease. NK cells can kill a targeted cell by forming a tight interface-the lytic immunological synapse. This represents a dynamic molecular arrangement that over time progresses through a series of steps to ultimately deliver the contents of specialized organelles known as lytic granules. In order to mediate cytotoxicity, the NK cell faces the challenge of mobilizing the lytic granules, polarizing them to the targeted cell, facilitating their approximation to the NK cell membrane, and releasing their contents. This review is focused upon the final steps in accessing function through the lytic immunological synapse.

  6. Synapses of the rat end brain in response to flight effects

    International Nuclear Information System (INIS)

    Antipov, V.V.; Tikhonchuk, V.S.; Ushakov, I.B.; Fedorov, V.P.

    1988-01-01

    Using electron microscopy, synapses of different structures of the rat end brain related to cognitive and motor acts (sensorimotor cortex, caudate nucleus) as well as memory and behavior (hippocampus) were examined. Rats were exposed to ionizing radiation, superhigh frequency, hypoxia, hyperoxia, vibration and acceleration (applied separately or in combination) which have been traditionally in the focus of space and aviation medicine. Brain internuronal junctions were found to be very sensitive to the above effects, particularly ionizing radiation and hypoxia. Conversely, synapses were shown to be highly resistant to short-term hyperoxia and electromagnetic radiation. When combined effects were used, response of interneuronal junctions depended on the irradiation dose and order of application of radiation and other flight factors

  7. A cortical attractor network with Martinotti cells driven by facilitating synapses.

    Directory of Open Access Journals (Sweden)

    Pradeep Krishnamurthy

    Full Text Available The population of pyramidal cells significantly outnumbers the inhibitory interneurons in the neocortex, while at the same time the diversity of interneuron types is much more pronounced. One acknowledged key role of inhibition is to control the rate and patterning of pyramidal cell firing via negative feedback, but most likely the diversity of inhibitory pathways is matched by a corresponding diversity of functional roles. An important distinguishing feature of cortical interneurons is the variability of the short-term plasticity properties of synapses received from pyramidal cells. The Martinotti cell type has recently come under scrutiny due to the distinctly facilitating nature of the synapses they receive from pyramidal cells. This distinguishes these neurons from basket cells and other inhibitory interneurons typically targeted by depressing synapses. A key aspect of the work reported here has been to pinpoint the role of this variability. We first set out to reproduce quantitatively based on in vitro data the di-synaptic inhibitory microcircuit connecting two pyramidal cells via one or a few Martinotti cells. In a second step, we embedded this microcircuit in a previously developed attractor memory network model of neocortical layers 2/3. This model network demonstrated that basket cells with their characteristic depressing synapses are the first to discharge when the network enters an attractor state and that Martinotti cells respond with a delay, thereby shifting the excitation-inhibition balance and acting to terminate the attractor state. A parameter sensitivity analysis suggested that Martinotti cells might, in fact, play a dominant role in setting the attractor dwell time and thus cortical speed of processing, with cellular adaptation and synaptic depression having a less prominent role than previously thought.

  8. Anatomically detailed and large-scale simulations studying synapse loss and synchrony using NeuroBox

    Directory of Open Access Journals (Sweden)

    Markus eBreit

    2016-02-01

    Full Text Available The morphology of neurons and networks plays an important role in processing electrical and biochemical signals. Based on neuronal reconstructions, which are becoming abundantly available through databases such as NeuroMorpho.org, numerical simulations of Hodgkin-Huxley-type equations, coupled to biochemical models, can be performed in order to systematically investigate the influence of cellular morphology and the connectivity pattern in networks on the underlying function. Development in the area of synthetic neural network generation and morphology reconstruction from microscopy data has brought forth the software tool NeuGen. Coupling this morphology data (either from databases, synthetic or reconstruction to the simulation platform UG 4 (which harbors a neuroscientific portfolio and VRL-Studio, has brought forth the extendible toolbox NeuroBox. NeuroBox allows users to perform numerical simulations on hybrid-dimensional morphology representations. The code basis is designed in a modular way, such that e.g. new channel or synapse types can be added to the library. Workflows can be specified through scripts or through the VRL-Studio graphical workflow representation. Third-party tools, such as ImageJ, can be added to NeuroBox workflows. In this paper, NeuroBox is used to study the electrical and biochemical effects of synapse loss vs. synchrony in neurons, to investigate large morphology data sets within detailed biophysical simulations, and used to demonstrate the capability of utilizing high-performance computing infrastructure for large scale network simulations. Using new synapse distribution methods and Finite Volume based numerical solvers for compartment-type models, our results demonstrate how an increase in synaptic synchronization can compensate synapse loss at the electrical and calcium level, and how detailed neuronal morphology can be integrated in large-scale network simulations.

  9. Three-terminal ferroelectric synapse device with concurrent learning function for artificial neural networks

    International Nuclear Information System (INIS)

    Nishitani, Y.; Kaneko, Y.; Ueda, M.; Fujii, E.; Morie, T.

    2012-01-01

    Spike-timing-dependent synaptic plasticity (STDP) is demonstrated in a synapse device based on a ferroelectric-gate field-effect transistor (FeFET). STDP is a key of the learning functions observed in human brains, where the synaptic weight changes only depending on the spike timing of the pre- and post-neurons. The FeFET is composed of the stacked oxide materials with ZnO/Pr(Zr,Ti)O 3 (PZT)/SrRuO 3 . In the FeFET, the channel conductance can be altered depending on the density of electrons induced by the polarization of PZT film, which can be controlled by applying the gate voltage in a non-volatile manner. Applying a pulse gate voltage enables the multi-valued modulation of the conductance, which is expected to be caused by a change in PZT polarization. This variation depends on the height and the duration of the pulse gate voltage. Utilizing these characteristics, symmetric and asymmetric STDP learning functions are successfully implemented in the FeFET-based synapse device by applying the non-linear pulse gate voltage generated from a set of two pulses in a sampling circuit, in which the two pulses correspond to the spikes from the pre- and post-neurons. The three-terminal structure of the synapse device enables the concurrent learning, in which the weight update can be performed without canceling signal transmission among neurons, while the neural networks using the previously reported two-terminal synapse devices need to stop signal transmission for learning.

  10. Emerging roles of the neurotrophin receptor TrkC in synapse organization.

    Science.gov (United States)

    Naito, Yusuke; Lee, Alfred Kihoon; Takahashi, Hideto

    2017-03-01

    Tropomyosin-receptor-kinase (Trk) receptors have been extensively studied for their roles in kinase-dependent signaling cascades in nervous system development. Synapse organization is coordinated by trans-synaptic interactions of various cell adhesion proteins, a representative example of which is the neurexin-neuroligin complex. Recently, a novel role for TrkC as a synapse organizing protein has been established. Post-synaptic TrkC binds to pre-synaptic type-IIa receptor-type protein tyrosine phosphatase sigma (PTPσ). TrkC-PTPσ specifically induces excitatory synapses in a kinase domain-independent manner. TrkC has distinct extracellular domains for PTPσ- and NT-3-binding and thus may bind both ligands simultaneously. Indeed, NT-3 enhances the TrkC-PTPσ interaction, thus facilitating synapse induction at the pre-synaptic side and increasing pre-synaptic vesicle recycling in a kinase-independent fashion. A crystal structure study has revealed the detailed structure of the TrkC-PTPσ complex as well as competitive modulation of TrkC-mediated synaptogenesis by heparan sulfate proteoglycans (HSPGs), which bind the same domain of TrkC as PTPσ. Thus, there is strong evidence supporting a role for the TrkC-PTPσ complex in mechanisms underlying the fine turning of neural connectivity. Furthermore, disruption of the TrkC-PTPσ complex may be the underlying cause of certain psychiatric disorders caused by mutations in the gene encoding TrkC (NTRK3), supporting its role in cognitive functions. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  11. The interplay between neurons and glia in synapse development and plasticity

    OpenAIRE

    Stogsdill, Jeff A; Eroglu, Cagla

    2016-01-01

    In the brain, the formation of complex neuronal networks amenable to experience-dependent remodeling is complicated by the diversity of neurons and synapse types. The establishment of a functional brain depends not only on neurons, but also non-neuronal glial cells. Glia are in continuous bi-directional communication with neurons to direct the formation and refinement of synaptic connectivity. This article reviews important findings, which uncovered cellular and molecular aspects of the neuro...

  12. Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear.

    Science.gov (United States)

    Mendus, Diana; Sundaresan, Srividya; Grillet, Nicolas; Wangsawihardja, Felix; Leu, Rose; Müller, Ulrich; Jones, Sherri M; Mustapha, Mirna

    2014-04-01

    Thrombospondins (TSPs) constitute a family of secreted extracellular matrix proteins that have been shown to be involved in the formation of synapses in the central nervous system. In this study, we show that TSP1 and TSP2 are expressed in the cochlea, and offer the first description of their putative roles in afferent synapse development and function in the inner ear. We examined mice with deletions of TSP1, TSP2 and both (TSP1/TSP2) for inner ear development and function. Immunostaining for synaptic markers indicated a significant decrease in the number of formed afferent synapses in the cochleae of TSP2 and TSP1/TSP2 knockout (KO) mice at postnatal day (P)29. In functional studies, TSP2 and TSP1/TSP2 KO mice showed elevated auditory brainstem response (ABR) thresholds as compared with wild-type littermates, starting at P15, with the most severe phenotype being seen for TSP1/TSP2 KO mice. TSP1/TSP2 KO mice also showed reduced wave I amplitudes of ABRs and vestibular evoked potentials, suggesting synaptic dysfunction in both the auditory and vestibular systems. Whereas ABR thresholds in TSP1 KO mice were relatively unaffected at early ages, TSP1/TSP2 KO mice showed the most severe phenotype among all of the genotypes tested, suggesting functional redundancy between the two genes. On the basis of the above results, we propose that TSPs play an important role in afferent synapse development and function of the inner ear. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Energy-efficient STDP-based learning circuits with memristor synapses

    Science.gov (United States)

    Wu, Xinyu; Saxena, Vishal; Campbell, Kristy A.

    2014-05-01

    It is now accepted that the traditional von Neumann architecture, with processor and memory separation, is ill suited to process parallel data streams which a mammalian brain can efficiently handle. Moreover, researchers now envision computing architectures which enable cognitive processing of massive amounts of data by identifying spatio-temporal relationships in real-time and solving complex pattern recognition problems. Memristor cross-point arrays, integrated with standard CMOS technology, are expected to result in massively parallel and low-power Neuromorphic computing architectures. Recently, significant progress has been made in spiking neural networks (SNN) which emulate data processing in the cortical brain. These architectures comprise of a dense network of neurons and the synapses formed between the axons and dendrites. Further, unsupervised or supervised competitive learning schemes are being investigated for global training of the network. In contrast to a software implementation, hardware realization of these networks requires massive circuit overhead for addressing and individually updating network weights. Instead, we employ bio-inspired learning rules such as the spike-timing-dependent plasticity (STDP) to efficiently update the network weights locally. To realize SNNs on a chip, we propose to use densely integrating mixed-signal integrate-andfire neurons (IFNs) and cross-point arrays of memristors in back-end-of-the-line (BEOL) of CMOS chips. Novel IFN circuits have been designed to drive memristive synapses in parallel while maintaining overall power efficiency (<1 pJ/spike/synapse), even at spike rate greater than 10 MHz. We present circuit design details and simulation results of the IFN with memristor synapses, its response to incoming spike trains and STDP learning characterization.

  14. Coexisting chaotic attractors in a single neuron model with adapting feedback synapse

    International Nuclear Information System (INIS)

    Li Chunguang; Chen Guanrong

    2005-01-01

    In this paper, we consider the nonlinear dynamical behavior of a single neuron model with adapting feedback synapse, and show that chaotic behaviors exist in this model. In some parameter domain, we observe two coexisting chaotic attractors, switching from the coexisting chaotic attractors to a connected chaotic attractor, and then switching back to the two coexisting chaotic attractors. We confirm the chaoticity by simulations with phase plots, waveform plots, and power spectra

  15. Transglial transmission at the dorsal root ganglion sandwich synapse: glial cell to postsynaptic neuron communication.

    Science.gov (United States)

    Rozanski, Gabriela M; Li, Qi; Stanley, Elise F

    2013-04-01

    The dorsal root ganglion (DRG) contains a subset of closely-apposed neuronal somata (NS) separated solely by a thin satellite glial cell (SGC) membrane septum to form an NS-glial cell-NS trimer. We recently reported that stimulation of one NS with an impulse train triggers a delayed, noisy and long-lasting response in its NS pair via a transglial signaling pathway that we term a 'sandwich synapse' (SS). Transmission could be unidirectional or bidirectional and facilitated in response to a second stimulus train. We have shown that in chick or rat SS the NS-to-SGC leg of the two-synapse pathway is purinergic via P2Y2 receptors but the second SGC-to-NS synapse mechanism remained unknown. A noisy evoked current in the target neuron, a reversal potential close to 0 mV, and insensitivity to calcium scavengers or G protein block favored an ionotropic postsynaptic receptor. Selective block by D-2-amino-5-phosphonopentanoate (AP5) implicated glutamatergic transmission via N-methyl-d-aspartate receptors. This agent also blocked NS responses evoked by puff of UTP, a P2Y2 agonist, directly onto the SGC cell, confirming its action at the second synapse of the SS transmission pathway. The N-methyl-d-aspartate receptor NR2B subunit was implicated by block of transmission with ifenprodil and by its immunocytochemical localization to the NS membrane, abutting the glial septum P2Y2 receptor. Isolated DRG cell clusters exhibited daisy-chain and branching NS-glial cell-NS contacts, suggestive of a network organization within the ganglion. The identification of the glial-to-neuron transmitter and receptor combination provides further support for transglial transmission and completes the DRG SS molecular transmission pathway. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  16. Accelerated Intoxication of GABAergic Synapses by Botulinum Neurotoxin A Disinhibits Stem Cell-Derived Neuron Networks Prior to Network Silencing

    Science.gov (United States)

    2015-04-23

    administered BoNT can lead to central nervous system intoxication is currently being debated. Recent findings in vitro and in vivo suggest that BoNT...Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Accelerated intoxication of GABAergic synapses by botulinum neurotoxin A disinhibits 5a...April 2015 Published: 23 April 2015 Citation: Beske PH, Scheeler SM, AdlerM and McNutt PM (2015) Accelerated intoxication of GABAergic synapses by

  17. Reduced cortical distribution volume of iodine-123 iomazenil in Alzheimer's disease as a measure of loss of synapses

    DEFF Research Database (Denmark)

    Soricelli, A; Postiglione, A; Grivet-Fojaja, M R

    1996-01-01

    Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABAA receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (Vd) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer's disease (AD), where synaptic loss tends indiscriminat...... simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex Vd was significantly (P...

  18. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit

    Directory of Open Access Journals (Sweden)

    Lisa eMapelli

    2015-05-01

    Full Text Available The way long-term potentiation (LTP and depression (LTD are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network , in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei and correspondingly regulate the function of their three main neurons: granule cells (GrCs, Purkinje cells (PCs and deep cerebellar nuclear (DCN cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

  19. Multiple cell adhesion molecules shaping a complex nicotinic synapse on neurons.

    Science.gov (United States)

    Triana-Baltzer, Gallen B; Liu, Zhaoping; Gounko, Natalia V; Berg, Darwin K

    2008-09-01

    Neuroligin, SynCAM, and L1-CAM are cell adhesion molecules with synaptogenic roles in glutamatergic pathways. We show here that SynCAM is expressed in the chick ciliary ganglion, embedded in a nicotinic pathway, and, as shown previously for neuroligin and L1-CAM, acts transcellularly to promote synaptic maturation on the neurons in culture. Moreover, we show that electroporation of chick embryos with dominant negative constructs disrupting any of the three molecules in vivo reduces the total amount of presynaptic SV2 overlaying the neurons expressing the constructs. Only disruption of L1-CAM and neuroligin, however, reduces the number of SV2 puncta specifically overlaying nicotinic receptor clusters. Disrupting L1-CAM and neuroligin together produces no additional decrement, indicating that they act on the same subset of synapses. SynCAM may affect synaptic maturation rather than synapse formation. The results indicate that individual neurons can express multiple synaptogenic molecules with different effects on the same class of nicotinic synapses.

  20. High resolution in situ zymography reveals matrix metalloproteinase activity at glutamatergic synapses.

    Science.gov (United States)

    Gawlak, M; Górkiewicz, T; Gorlewicz, A; Konopacki, F A; Kaczmarek, L; Wilczynski, G M

    2009-01-12

    Synaptic plasticity involves remodeling of extracellular matrix. This is mediated, in part, by enzymes of the matrix metalloproteinase (MMP) family, in particular by gelatinase MMP-9. Accordingly, there is a need of developing methods to visualize gelatinolytic activity at the level of individual synapses, especially in the context of neurotransmitters receptors. Here we present a high-resolution fluorescent in situ zymography (ISZ), performed in thin sections of the alcohol-fixed and polyester wax-embedded brain tissue of the rat (Rattus norvegicus), which is superior to the current ISZ protocols. The method allows visualization of structural details up to the resolution-limit of light microscopy, in conjunction with immunofluorescent labeling. We used this technique to visualize and quantify gelatinolytic activity at the synapses in control and seizure-affected rat brain. In particular, we demonstrated, for the first time, frequent colocalization of gelatinase(s) with synaptic N-methyl-D-aspartic acid (NMDA)- and AMPA-type glutamate receptors. We believe that our method represents a valuable tool to study extracellular proteolytic processes at the synapses, it could be used, as well, to investigate proteinase involvement in a range of physiological and pathological phenomena in the nervous system.

  1. Contextual Learning Requires Functional Diversity at Excitatory and Inhibitory Synapses onto CA1 Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Dai Mitsushima

    2015-01-01

    Full Text Available Although the hippocampus is processing temporal and spatial information in particular context, the encoding rule creating memory is completely unknown. To examine the mechanism, we trained rats on an inhibitory avoidance (IA task, a hippocampus-dependent rapid one-trial contextual learning paradigm. By combining Herpes virus-mediated in vivo gene delivery with in vitro patch-clamp recordings, I reported contextual learning drives GluR1-containing AMPA receptors into CA3-CA1 synapses. The molecular event is required for contextual memory, since bilateral expression of delivery blocker in CA1 successfully blocked IA learning. Moreover, I found a logarithmic correlation between the number of delivery blocking cells and learning performance. Considering that one all-or-none device can process 1-bit of data per clock (Nobert Wiener 1961, the logarithmic correlation may provides evidence that CA1 neurons transmit essential data of contextual information. Further, I recently reported critical role of acetylcholine as an intrinsic trigger of learning-dependent synaptic plasticity. IA training induced ACh release in CA1 that strengthened not only AMPA receptor-mediated excitatory synapses, but also GABAA receptor-mediated inhibitory synapses on each CA1 neuron. More importantly, IA-trained rats showed individually different excitatory and inhibitory synaptic inputs with wide variation on each CA1 neuron. Here I propose a new hypothesis that the diversity of synaptic inputs on CA1 neurons may depict cell-specific outputs processing experienced episodes after training.

  2. The demise of the synapse as the locus of memory: A looming paradigm shift?

    Directory of Open Access Journals (Sweden)

    Patrick C. Trettenbrein

    2016-11-01

    Full Text Available Synaptic plasticity is widely considered to be the neurobiological basis of learning and memory by neuroscientists and researchers in adjacent fields, though diverging opinions are increasingly being recognised. From the perspective of what we might call classical cognitive science it has always been understood that the mind/brain is to be considered a computational-representational system. Proponents of the information-processing approach to cognitive science have long been critical of connectionist or network approaches to (neuro-cognitive architecture, pointing to the shortcomings of the associative psychology that underlies Hebbian learning as well as to the fact that synapses are practically unfit to implement symbols. Recent work on memory has been adding fuel to the fire and current findings in neuroscience now provide first tentative neurobiological evidence for the cognitive scientists’ doubts about the synapse as the (sole locus of memory in the brain. This paper briefly considers the history and appeal of synaptic plasticity as a memory mechanism, followed by a summary of the cognitive scientists’ objections regarding these assertions. Next, a variety of tentative neuroscientific evidence that appears to substantiate questioning the idea of the synapse as the locus of memory is presented. On this basis, a novel way of thinking about the role of synaptic plasticity in learning and memory is proposed.

  3. Early Seizures Prematurely Unsilence Auditory Synapses to Disrupt Thalamocortical Critical Period Plasticity

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    Hongyu Sun

    2018-05-01

    Full Text Available Heightened neural excitability in infancy and childhood results in increased susceptibility to seizures. Such early-life seizures are associated with language deficits and autism that can result from aberrant development of the auditory cortex. Here, we show that early-life seizures disrupt a critical period (CP for tonotopic map plasticity in primary auditory cortex (A1. We show that this CP is characterized by a prevalence of “silent,” NMDA-receptor (NMDAR-only, glutamate receptor synapses in auditory cortex that become “unsilenced” due to activity-dependent AMPA receptor (AMPAR insertion. Induction of seizures prior to this CP occludes tonotopic map plasticity by prematurely unsilencing NMDAR-only synapses. Further, brief treatment with the AMPAR antagonist NBQX following seizures, prior to the CP, prevents synapse unsilencing and permits subsequent A1 plasticity. These findings reveal that early-life seizures modify CP regulators and suggest that therapeutic targets for early post-seizure treatment can rescue CP plasticity.

  4. Artificial Synapses Based on in-Plane Gate Organic Electrochemical Transistors.

    Science.gov (United States)

    Qian, Chuan; Sun, Jia; Kong, Ling-An; Gou, Guangyang; Yang, Junliang; He, Jun; Gao, Yongli; Wan, Qing

    2016-10-05

    Realization of biological synapses using electronic devices is regarded as the basic building blocks for neuromorphic engineering and artificial neural network. With the advantages of biocompatibility, low cost, flexibility, and compatible with printing and roll-to-roll processes, the artificial synapse based on organic transistor is of great interest. In this paper, the artificial synapse simulation by ion-gel gated organic field-effect transistors (FETs) with poly(3-hexylthiophene) (P3HT) active channel is demonstrated. Key features of the synaptic behaviors, such as paired-pulse facilitation (PPF), short-term plasticity (STP), self-tuning, the spike logic operation, spatiotemporal dentritic integration, and modulation are successfully mimicked. Furthermore, the interface doping processes of electrolyte ions between the active P3HT layer and ion gels is comprehensively studied for confirming the operating processes underlying the conductivity and excitatory postsynaptic current (EPSC) variations in the organic synaptic devices. This study represents an important step toward building future artificial neuromorphic systems with newly emerged ion gel gated organic synaptic devices.

  5. A reconfigurable on-line learning spiking neuromorphic processor comprising 256 neurons and 128K synapses.

    Science.gov (United States)

    Qiao, Ning; Mostafa, Hesham; Corradi, Federico; Osswald, Marc; Stefanini, Fabio; Sumislawska, Dora; Indiveri, Giacomo

    2015-01-01

    Implementing compact, low-power artificial neural processing systems with real-time on-line learning abilities is still an open challenge. In this paper we present a full-custom mixed-signal VLSI device with neuromorphic learning circuits that emulate the biophysics of real spiking neurons and dynamic synapses for exploring the properties of computational neuroscience models and for building brain-inspired computing systems. The proposed architecture allows the on-chip configuration of a wide range of network connectivities, including recurrent and deep networks, with short-term and long-term plasticity. The device comprises 128 K analog synapse and 256 neuron circuits with biologically plausible dynamics and bi-stable spike-based plasticity mechanisms that endow it with on-line learning abilities. In addition to the analog circuits, the device comprises also asynchronous digital logic circuits for setting different synapse and neuron properties as well as different network configurations. This prototype device, fabricated using a 180 nm 1P6M CMOS process, occupies an area of 51.4 mm(2), and consumes approximately 4 mW for typical experiments, for example involving attractor networks. Here we describe the details of the overall architecture and of the individual circuits and present experimental results that showcase its potential. By supporting a wide range of cortical-like computational modules comprising plasticity mechanisms, this device will enable the realization of intelligent autonomous systems with on-line learning capabilities.

  6. Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses

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    Tanaka Mika

    2013-01-01

    Full Text Available Abstract Background Neuronal activity alters calcium ion (Ca2+ dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling. Results Attenuated Ca2+ activity correlated with reduced astrocytic coverage of asymmetric synapses in the hippocampal CA1 region in these animals. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice also exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved. Conclusions Our findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.

  7. Emerging phenomena in neural networks with dynamic synapses and their computational implications

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    Joaquin J. eTorres

    2013-04-01

    Full Text Available In this paper we review our research on the effect and computational role of dynamical synapses on feed-forward and recurrent neural networks. Among others, we report on the appearance of a new class of dynamical memories which result from the destabilisation of learned memory attractors. This has important consequences for dynamic information processing allowing the system to sequentially access the information stored in the memories under changing stimuli. Although storage capacity of stable memories also decreases, our study demonstrated the positive effect of synaptic facilitation to recover maximum storage capacity and to enlarge the capacity of the system for memory recall in noisy conditions. Possibly, the new dynamical behaviour can be associated with the voltage transitions between up and down states observed in cortical areas in the brain. We investigated the conditions for which the permanence times in the up state are power-law distributed, which is a sign for criticality, and concluded that the experimentally observed large variability of permanence times could be explained as the result of noisy dynamic synapses with large recovery times. Finally, we report how short-term synaptic processes can transmit weak signals throughout more than one frequency range in noisy neural networks, displaying a kind of stochastic multi-resonance. This effect is due to competition between activity-dependent synaptic fluctuations (due to dynamic synapses and the existence of neuron firing threshold which adapts to the incoming mean synaptic input.

  8. A 2-transistor/1-resistor artificial synapse capable of communication and stochastic learning in neuromorphic systems.

    Science.gov (United States)

    Wang, Zhongqiang; Ambrogio, Stefano; Balatti, Simone; Ielmini, Daniele

    2014-01-01

    Resistive (or memristive) switching devices based on metal oxides find applications in memory, logic and neuromorphic computing systems. Their small area, low power operation, and high functionality meet the challenges of brain-inspired computing aiming at achieving a huge density of active connections (synapses) with low operation power. This work presents a new artificial synapse scheme, consisting of a memristive switch connected to 2 transistors responsible for gating the communication and learning operations. Spike timing dependent plasticity (STDP) is achieved through appropriate shaping of the pre-synaptic and the post synaptic spikes. Experiments with integrated artificial synapses demonstrate STDP with stochastic behavior due to (i) the natural variability of set/reset processes in the nanoscale switch, and (ii) the different response of the switch to a given stimulus depending on the initial state. Experimental results are confirmed by model-based simulations of the memristive switching. Finally, system-level simulations of a 2-layer neural network and a simplified STDP model show random learning and recognition of patterns.

  9. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit.

    Science.gov (United States)

    Mapelli, Lisa; Pagani, Martina; Garrido, Jesus A; D'Angelo, Egidio

    2015-01-01

    The way long-term potentiation (LTP) and depression (LTD) are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network, in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei) and correspondingly regulate the function of their three main neurons: granule cells (GrCs), Purkinje cells (PCs) and deep cerebellar nuclear (DCN) cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

  10. Low-doses of cisplatin injure hippocampal synapses: a mechanism for 'chemo' brain?

    Science.gov (United States)

    Andres, Adrienne L; Gong, Xing; Di, Kaijun; Bota, Daniela A

    2014-05-01

    Chemotherapy-related cognitive deficits are a major neurological problem, but the underlying mechanisms are unclear. The death of neural stem/precursor cell (NSC) by cisplatin has been reported as a potential cause, but this requires high doses of chemotherapeutic agents. Cisplatin is frequently used in modern oncology, and it achieves high concentrations in the patient's brain. Here we report that exposure to low concentrations of cisplatin (0.1μM) causes the loss of dendritic spines and synapses within 30min. Longer exposures injured dendritic branches and reduced dendritic complexity. At this low concentration, cisplatin did not affect NSC viability nor provoke apoptosis. However, higher cisplatin levels (1μM) led to the rapid loss of synapses and dendritic disintegration, and neuronal-but not NSC-apoptosis. In-vivo treatment with cisplatin at clinically relevant doses also caused a reduction of dendritic branches and decreased spine density in CA1 and CA3 hippocampal neurons. An acute increase in cell death was measured in the CA1 and CA3 neurons, as well as in the NSC population located in the subgranular zone of the dentate gyrus in the cisplatin treated animals. The density of dendritic spines is related to the degree of neuronal connectivity and function, and pathological changes in spine number or structure have significant consequences for brain function. Therefore, this synapse and dendritic damage might contribute to the cognitive impairment observed after cisplatin treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Astrocytic glutamate transport regulates a Drosophila CNS synapse that lacks astrocyte ensheathment.

    Science.gov (United States)

    MacNamee, Sarah E; Liu, Kendra E; Gerhard, Stephan; Tran, Cathy T; Fetter, Richard D; Cardona, Albert; Tolbert, Leslie P; Oland, Lynne A

    2016-07-01

    Anatomical, molecular, and physiological interactions between astrocytes and neuronal synapses regulate information processing in the brain. The fruit fly Drosophila melanogaster has become a valuable experimental system for genetic manipulation of the nervous system and has enormous potential for elucidating mechanisms that mediate neuron-glia interactions. Here, we show the first electrophysiological recordings from Drosophila astrocytes and characterize their spatial and physiological relationship with particular synapses. Astrocyte intrinsic properties were found to be strongly analogous to those of vertebrate astrocytes, including a passive current-voltage relationship, low membrane resistance, high capacitance, and dye-coupling to local astrocytes. Responses to optogenetic stimulation of glutamatergic premotor neurons were correlated directly with anatomy using serial electron microscopy reconstructions of homologous identified neurons and surrounding astrocytic processes. Robust bidirectional communication was present: neuronal activation triggered astrocytic glutamate transport via excitatory amino acid transporter 1 (Eaat1), and blocking Eaat1 extended glutamatergic interneuron-evoked inhibitory postsynaptic currents in motor neurons. The neuronal synapses were always located within 1 μm of an astrocytic process, but none were ensheathed by those processes. Thus, fly astrocytes can modulate fast synaptic transmission via neurotransmitter transport within these anatomical parameters. J. Comp. Neurol. 524:1979-1998, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Haowen Liu

    2018-02-01

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

  13. Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity.

    Science.gov (United States)

    Davenport, A J; Cross, R S; Watson, K A; Liao, Y; Shi, W; Prince, H M; Beavis, P A; Trapani, J A; Kershaw, M H; Ritchie, D S; Darcy, P K; Neeson, P J; Jenkins, M R

    2018-02-27

    Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell. Copyright © 2018 the Author(s). Published by PNAS.

  14. Effects of dynamic synapses on noise-delayed response latency of a single neuron

    Science.gov (United States)

    Uzuntarla, M.; Ozer, M.; Ileri, U.; Calim, A.; Torres, J. J.

    2015-12-01

    The noise-delayed decay (NDD) phenomenon emerges when the first-spike latency of a periodically forced stochastic neuron exhibits a maximum for a particular range of noise intensity. Here, we investigate the latency response dynamics of a single Hodgkin-Huxley neuron that is subject to both a suprathreshold periodic stimulus and a background activity arriving through dynamic synapses. We study the first-spike latency response as a function of the presynaptic firing rate f . This constitutes a more realistic scenario than previous works, since f provides a suitable biophysically realistic parameter to control the level of activity in actual neural systems. We first report on the emergence of classical NDD behavior as a function of f for the limit of static synapses. Second, we show that when short-term depression and facilitation mechanisms are included at the synapses, different NDD features can be found due to their modulatory effect on synaptic current fluctuations. For example, an intriguing double NDD (DNDD) behavior occurs for different sets of relevant synaptic parameters. Moreover, depending on the balance between synaptic depression and synaptic facilitation, single NDD or DNDD can prevail, in such a way that synaptic facilitation favors the emergence of DNDD whereas synaptic depression favors the existence of single NDD. Here we report the existence of the DNDD effect in the response latency dynamics of a neuron.

  15. Monoacylated Cellular Prion Proteins Reduce Amyloid-β-Induced Activation of Cytoplasmic Phospholipase A2 and Synapse Damage

    Directory of Open Access Journals (Sweden)

    Ewan West

    2015-06-01

    Full Text Available Alzheimer’s disease (AD is a progressive neurodegenerative disease characterized by the accumulation of amyloid-β (Aβ and the loss of synapses. Aggregation of the cellular prion protein (PrPC by Aβ oligomers induced synapse damage in cultured neurons. PrPC is attached to membranes via a glycosylphosphatidylinositol (GPI anchor, the composition of which affects protein targeting and cell signaling. Monoacylated PrPC incorporated into neurons bound “natural Aβ”, sequestering Aβ outside lipid rafts and preventing its accumulation at synapses. The presence of monoacylated PrPC reduced the Aβ-induced activation of cytoplasmic phospholipase A2 (cPLA2 and Aβ-induced synapse damage. This protective effect was stimulus specific, as treated neurons remained sensitive to α-synuclein, a protein associated with synapse damage in Parkinson’s disease. In synaptosomes, the aggregation of PrPC by Aβ oligomers triggered the formation of a signaling complex containing the cPLA2.a process, disrupted by monoacylated PrPC. We propose that monoacylated PrPC acts as a molecular sponge, binding Aβ oligomers at the neuronal perikarya without activating cPLA2 or triggering synapse damage.

  16. Differential regulation of polarized synaptic vesicle trafficking and synapse stability in neural circuit rewiring in Caenorhabditis elegans.

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    Naina Kurup

    2017-06-01

    Full Text Available Neural circuits are dynamic, with activity-dependent changes in synapse density and connectivity peaking during different phases of animal development. In C. elegans, young larvae form mature motor circuits through a dramatic switch in GABAergic neuron connectivity, by concomitant elimination of existing synapses and formation of new synapses that are maintained throughout adulthood. We have previously shown that an increase in microtubule dynamics during motor circuit rewiring facilitates new synapse formation. Here, we further investigate cellular control of circuit rewiring through the analysis of mutants obtained in a forward genetic screen. Using live imaging, we characterize novel mutations that alter cargo binding in the dynein motor complex and enhance anterograde synaptic vesicle movement during remodeling, providing in vivo evidence for the tug-of-war between kinesin and dynein in fast axonal transport. We also find that a casein kinase homolog, TTBK-3, inhibits stabilization of nascent synapses in their new locations, a previously unexplored facet of structural plasticity of synapses. Our study delineates temporally distinct signaling pathways that are required for effective neural circuit refinement.

  17. ProBDNF and mature BDNF as punishment and reward signals for synapse elimination at mouse neuromuscular junctions.

    Science.gov (United States)

    Je, H Shawn; Yang, Feng; Ji, Yuanyuan; Potluri, Srilatha; Fu, Xiu-Qing; Luo, Zhen-Ge; Nagappan, Guhan; Chan, Jia Pei; Hempstead, Barbara; Son, Young-Jin; Lu, Bai

    2013-06-12

    During development, mammalian neuromuscular junctions (NMJs) transit from multiple-innervation to single-innervation through axonal competition via unknown molecular mechanisms. Previously, using an in vitro model system, we demonstrated that the postsynaptic secretion of pro-brain-derived neurotrophic factor (proBDNF) stabilizes or eliminates presynaptic axon terminals, depending on its proteolytic conversion at synapses. Here, using developing mouse NMJs, we obtained in vivo evidence that proBDNF and mature BDNF (mBDNF) play roles in synapse elimination. We observed that exogenous proBDNF promoted synapse elimination, whereas mBDNF infusion substantially delayed synapse elimination. In addition, pharmacological inhibition of the proteolytic conversion of proBDNF to mBDNF accelerated synapse elimination via activation of p75 neurotrophin receptor (p75(NTR)). Furthermore, the inhibition of both p75(NTR) and sortilin signaling attenuated synapse elimination. We propose a model in which proBDNF and mBDNF serve as potential "punishment" and "reward" signals for inactive and active terminals, respectively, in vivo.

  18. Involvement of intracellular Zn2+ signaling in LTP at perforant pathway-CA1 pyramidal cell synapse.

    Science.gov (United States)

    Tamano, Haruna; Nishio, Ryusuke; Takeda, Atsushi

    2017-07-01

    Physiological significance of synaptic Zn 2+ signaling was examined at perforant pathway-CA1 pyramidal cell synapses. In vivo long-term potentiation (LTP) at perforant pathway-CA1 pyramidal cell synapses was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. Perforant pathway LTP was not attenuated under perfusion with CaEDTA (10 mM), an extracellular Zn 2+ chelator, but attenuated under perfusion with ZnAF-2DA (50 μM), an intracellular Zn 2+ chelator, suggesting that intracellular Zn 2+ signaling is required for perforant pathway LTP. Even in rat brain slices bathed in CaEDTA in ACSF, intracellular Zn 2+ level, which was measured with intracellular ZnAF-2, was increased in the stratum lacunosum-moleculare where perforant pathway-CA1 pyramidal cell synapses were contained after tetanic stimulation. These results suggest that intracellular Zn 2+ signaling, which originates in internal stores/proteins, is involved in LTP at perforant pathway-CA1 pyramidal cell synapses. Because the influx of extracellular Zn 2+ , which originates in presynaptic Zn 2+ release, is involved in LTP at Schaffer collateral-CA1 pyramidal cell synapses, synapse-dependent Zn 2+ dynamics may be involved in plasticity of postsynaptic CA1 pyramidal cells. © 2017 Wiley Periodicals, Inc.

  19. Changes in Properties of Auditory Nerve Synapses following Conductive Hearing Loss.

    Science.gov (United States)

    Zhuang, Xiaowen; Sun, Wei; Xu-Friedman, Matthew A

    2017-01-11

    Auditory activity plays an important role in the development of the auditory system. Decreased activity can result from conductive hearing loss (CHL) associated with otitis media, which may lead to long-term perceptual deficits. The effects of CHL have been mainly studied at later stages of the auditory pathway, but early stages remain less examined. However, changes in early stages could be important because they would affect how information about sounds is conveyed to higher-order areas for further processing and localization. We examined the effects of CHL at auditory nerve synapses onto bushy cells in the mouse anteroventral cochlear nucleus following occlusion of the ear canal. These synapses, called endbulbs of Held, normally show strong depression in voltage-clamp recordings in brain slices. After 1 week of CHL, endbulbs showed even greater depression, reflecting higher release probability. We observed no differences in quantal size between control and occluded mice. We confirmed these observations using mean-variance analysis and the integration method, which also revealed that the number of release sites decreased after occlusion. Consistent with this, synaptic puncta immunopositive for VGLUT1 decreased in area after occlusion. The level of depression and number of release sites both showed recovery after returning to normal conditions. Finally, bushy cells fired fewer action potentials in response to evoked synaptic activity after occlusion, likely because of increased depression and decreased input resistance. These effects appear to reflect a homeostatic, adaptive response of auditory nerve synapses to reduced activity. These effects may have important implications for perceptual changes following CHL. Normal hearing is important to everyday life, but abnormal auditory experience during development can lead to processing disorders. For example, otitis media reduces sound to the ear, which can cause long-lasting deficits in language skills and verbal

  20. Nonlinear Photonic Crystal Fibers

    DEFF Research Database (Denmark)

    Hansen, Kim Per

    2004-01-01

    Despite the general recession in the global economy and the collapse of the optical telecommunication market, research within specialty fibers is thriving. This is, more than anything else, due to the technology transition from standard all-glass fibers to photonic crystal fibers, which, instead....... The freedom to design the dispersion profile of the fibers is much larger and it is possible to create fibers, which support only a single spatial mode, regardless of wavelength. In comparison, the standard dispersion-shifted fibers are limited by a much lower index-contrast between the core and the cladding...... in 1996, and are today on their way to become the dominating technology within the specialty fiber field. Whether they will replace the standard fiber in the more traditional areas like telecommunication transmission, is not yet clear, but the nonlinear photonic crystal fibers are here to stay....

  1. Optical Fiber Fusion Splicing

    CERN Document Server

    Yablon, Andrew D

    2005-01-01

    This book is an up-to-date treatment of optical fiber fusion splicing incorporating all the recent innovations in the field. It provides a toolbox of general strategies and specific techniques that the reader can apply when optimizing fusion splices between novel fibers. It specifically addresses considerations important for fusion splicing of contemporary specialty fibers including dispersion compensating fiber, erbium-doped gain fiber, polarization maintaining fiber, and microstructured fiber. Finally, it discusses the future of optical fiber fusion splicing including silica and non-silica based optical fibers as well as the trend toward increasing automation. Whilst serving as a self-contained reference work, abundant citations from the technical literature will enable readers to readily locate primary sources.

  2. Neural networks within multi-core optic fibers.

    Science.gov (United States)

    Cohen, Eyal; Malka, Dror; Shemer, Amir; Shahmoon, Asaf; Zalevsky, Zeev; London, Michael

    2016-07-07

    Hardware implementation of artificial neural networks facilitates real-time parallel processing of massive data sets. Optical neural networks offer low-volume 3D connectivity together with large bandwidth and minimal heat production in contrast to electronic implementation. Here, we present a conceptual design for in-fiber optical neural networks. Neurons and synapses are realized as individual silica cores in a multi-core fiber. Optical signals are transferred transversely between cores by means of optical coupling. Pump driven amplification in erbium-doped cores mimics synaptic interactions. We simulated three-layered feed-forward neural networks and explored their capabilities. Simulations suggest that networks can differentiate between given inputs depending on specific configurations of amplification; this implies classification and learning capabilities. Finally, we tested experimentally our basic neuronal elements using fibers, couplers, and amplifiers, and demonstrated that this configuration implements a neuron-like function. Therefore, devices similar to our proposed multi-core fiber could potentially serve as building blocks for future large-scale small-volume optical artificial neural networks.

  3. Bidirectional Signaling of Neuregulin-2 Mediates Formation of GABAergic Synapses and Maturation of Glutamatergic Synapses in Newborn Granule Cells of Postnatal Hippocampus.

    Science.gov (United States)

    Lee, Kyu-Hee; Lee, Hyunsu; Yang, Che Ho; Ko, Jeong-Soon; Park, Chang-Hwan; Woo, Ran-Sook; Kim, Joo Yeon; Sun, Woong; Kim, Joung-Hun; Ho, Won-Kyung; Lee, Suk-Ho

    2015-12-16

    Expression of neuregulin-2 (NRG2) is intense in a few regions of the adult brain where neurogenesis persists; however, little is understood about its role in developments of newborn neurons. To study the role of NRG2 in synaptogenesis at different developmental stages, newborn granule cells in rat hippocampal slice cultures were labeled with retrovirus encoding tetracycline-inducible microRNA targeting NRG2 and treated with doxycycline (Dox) at the fourth or seventh postinfection day (dpi). The developmental increase of GABAergic postsynaptic currents (GPSCs) was suppressed by the early Dox treatment (4 dpi), but not by late treatment (7 dpi). The late Dox treatment was used to study the effect of NRG2 depletion specific to excitatory synaptogenesis. The Dox effect on EPSCs emerged 4 d after the impairment in dendritic outgrowth became evident (10 dpi). Notably, Dox treatment abolished the developmental increases of AMPA-receptor mediated EPSCs and the AMPA/NMDA ratio, indicating impaired maturation of glutamatergic synapses. In contrast to GPSCs, Dox effects on EPSCs and dendritic growth were independent of ErbB4 and rescued by concurrent overexpression of NRG2 intracellular domain. These results suggest that forward signaling of NRG2 mediates GABAergic synaptogenesis and its reverse signaling contributes to dendritic outgrowth and maturation of glutamatergic synapses. The hippocampal dentate gyrus is one of special brain regions where neurogenesis persists throughout adulthood. Synaptogenesis is a critical step for newborn neurons to be integrated into preexisting neural network. Because neuregulin-2 (NRG2), a growth factor, is intensely expressed in these regions, we investigated whether it plays a role in synaptogenesis and dendritic growth. We found that NRG2 has dual roles in the development of newborn neurons. For GABAergic synaptogenesis, the extracellular domain of NRG2 acts as a ligand for a receptor on GABAergic neurons. In contrast, its intracellular

  4. Amplitude-modulated fiber-ring laser

    DEFF Research Database (Denmark)

    Caputo, J. G.; Clausen, Carl A. Balslev; Sørensen, Mads Peter

    2000-01-01

    Soliton pulses generated by a fiber-ring laser are investigated by numerical simulation and perturbation methods. The mathematical modeling is based on the nonlinear Schrödinger equation with perturbative terms. We show that active mode locking with an amplitude modulator leads to a self......-starting of stable solitonic pulses from small random noise, provided the modulation depth is small. The perturbative analysis leads to a nonlinear coupled return map for the amplitude, phase, and position of the soliton pulses circulating in the fiber-ring laser. We established the validity of this approach...

  5. Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems

    Directory of Open Access Journals (Sweden)

    Arico Maurizo

    2011-06-01

    Full Text Available Abstract Background Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocytes (CTLs, this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. Secretory lysosomes are directed towards the centrosome along microtubules and delivered precisely to the point of target cell recognition within the immunological synapse, identified by the centrosome. We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK and invariant NKT (iNKT cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release. Results NK cells were conjugated with B-cell targets lacking major histocompatibility complex class I 721.221 cells, and iNKT cells were conjugated with glycolipid-pulsed CD1-bearing targets, then prepared for thin-section electron microscopy. High-resolution electron micrographs of the immunological synapse formed between NK and iNKT cytolytic cells with their targets revealed that in both NK and iNKT cells, the centrioles could be found associated (or 'docked' with the plasma membrane within the immunological synapse. Secretory clefts were visible within the synapses formed by both NK and iNKT cells, and secretory lysosomes were polarised along microtubules leading towards the docked centrosome. The Golgi apparatus and recycling endosomes were also polarised towards the centrosome at the plasma membrane within the synapse. Conclusions These results reveal that, like CTLs of the adaptive immune system, the centrosomes of NK and iNKT cells (cytolytic cells of the innate immune system direct secretory lysosomes to

  6. Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems.

    Science.gov (United States)

    Stinchcombe, Jane C; Salio, Mariolina; Cerundolo, Vincenzo; Pende, Daniela; Arico, Maurizo; Griffiths, Gillian M

    2011-06-28

    Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocytes (CTLs), this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. Secretory lysosomes are directed towards the centrosome along microtubules and delivered precisely to the point of target cell recognition within the immunological synapse, identified by the centrosome. We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK) and invariant NKT (iNKT) cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release. NK cells were conjugated with B-cell targets lacking major histocompatibility complex class I 721.221 cells, and iNKT cells were conjugated with glycolipid-pulsed CD1-bearing targets, then prepared for thin-section electron microscopy. High-resolution electron micrographs of the immunological synapse formed between NK and iNKT cytolytic cells with their targets revealed that in both NK and iNKT cells, the centrioles could be found associated (or 'docked') with the plasma membrane within the immunological synapse. Secretory clefts were visible within the synapses formed by both NK and iNKT cells, and secretory lysosomes were polarised along microtubules leading towards the docked centrosome. The Golgi apparatus and recycling endosomes were also polarised towards the centrosome at the plasma membrane within the synapse. These results reveal that, like CTLs of the adaptive immune system, the centrosomes of NK and iNKT cells (cytolytic cells of the innate immune system) direct secretory lysosomes to the immunological synapse. Morphologically, the

  7. Ceramic fiber reinforced filter

    Science.gov (United States)

    Stinton, David P.; McLaughlin, Jerry C.; Lowden, Richard A.

    1991-01-01

    A filter for removing particulate matter from high temperature flowing fluids, and in particular gases, that is reinforced with ceramic fibers. The filter has a ceramic base fiber material in the form of a fabric, felt, paper of the like, with the refractory fibers thereof coated with a thin layer of a protective and bonding refractory applied by chemical vapor deposition techniques. This coating causes each fiber to be physically joined to adjoining fibers so as to prevent movement of the fibers during use and to increase the strength and toughness of the composite filter. Further, the coating can be selected to minimize any reactions between the constituents of the fluids and the fibers. A description is given of the formation of a composite filter using a felt preform of commercial silicon carbide fibers together with the coating of these fibers with pure silicon carbide. Filter efficiency approaching 100% has been demonstrated with these filters. The fiber base material is alternately made from aluminosilicate fibers, zirconia fibers and alumina fibers. Coating with Al.sub.2 O.sub.3 is also described. Advanced configurations for the composite filter are suggested.

  8. Steel fiber reinforced concrete

    International Nuclear Information System (INIS)

    Baloch, S.U.

    2005-01-01

    Steel-Fiber Reinforced Concrete is constructed by adding short fibers of small cross-sectional size .to the fresh concrete. These fibers reinforce the concrete in all directions, as they are randomly oriented. The improved mechanical properties of concrete include ductility, impact-resistance, compressive, tensile and flexural strength and abrasion-resistance. These uniqlte properties of the fiber- reinforcement can be exploited to great advantage in concrete structural members containing both conventional bar-reinforcement and steel fibers. The improvements in mechanical properties of cementitious materials resulting from steel-fiber reinforcement depend on the type, geometry, volume fraction and material-properties of fibers, the matrix mix proportions and the fiber-matrix interfacial bond characteristics. Effects of steel fibers on the mechanical properties of concrete have been investigated in this paper through a comprehensive testing-programme, by varying the fiber volume fraction and the aspect-ratio (Lid) of fibers. Significant improvements are observed in compressive, tensile, flexural strength and impact-resistance of concrete, accompanied by marked improvement in ductility. optimum fiber-volume fraction and aspect-ratio of steel fibers is identified. Test results are analyzed in details and relevant conclusions drawn. The research is finally concluded with future research needs. (author)

  9. Synapses between parallel fibres and stellate cells express long-term changes in synaptic efficacy in rat cerebellum.

    Science.gov (United States)

    Rancillac, Armelle; Crépel, Francis

    2004-02-01

    Various forms of synaptic plasticity underlying motor learning have already been well characterized at cerebellar parallel fibre (PF)-Purkinje cell (PC) synapses. Inhibitory interneurones play an important role in controlling the excitability and synchronization of PCs. We have therefore tested the possibility that excitatory synapses between PFs and stellate cells (SCs) are also able to exhibit long-term changes in synaptic efficacy. In the present study, we show that long-term potentiation (LTP) and long-term depression (LTD) were induced at these synapses by a low frequency stimulation protocol (2 Hz for 60 s) and that pairing this low frequency stimulation protocol with postsynaptic depolarization induced a marked shift of synaptic plasticity in favour of LTP. This LTP was cAMP independent, but required nitric oxide (NO) production from pre- and/or postsynaptic elements, depending on the stimulation or pairing protocol used, respectively. In contrast, LTD was not dependent on NO production but it required activation of postsynaptic group II and possibly of group I metabotropic glutamate receptors. Finally, stimulation of PFs at 8 Hz for 15 s also induced LTP at PF-SC synapses. But in this case, LTP was cAMP dependent, as was also observed at PF-PC synapses for presynaptic LTP induced in the same conditions. Thus, long-term changes in synaptic efficacy can be accomplished by PF-SCs synapses as well as by PF-PC synapses, suggesting that both types of plasticity might co-operate during cerebellar motor learning.

  10. Fiber optics in adverse environments

    International Nuclear Information System (INIS)

    Lyous, P.B.

    1982-01-01

    Radiation effects in optical fibers are considered, taking into account recent progress in the investigation of radiation resistant optical fibers, radiation damage in optical fibers, radiation-induced transient absorption in optical fibers, X-ray-induced transient attenuation at low temperatures in polymer clad silica (PCS) fibers, optical fiber composition and radiation hardness, the response of irradiated optical waveguides at low temperatures, and the effect of ionizing radiation on fiber-optic waveguides. Other topics explored are related to environmental effects on components of fiber optic systems, and radiation detection systems using optical fibers. Fiber optic systems in adverse environments are also discussed, giving attention to the survivability of Army fiber optics systems, space application of fiber optics systems, fiber optic wavelength multiplexing for civil aviation applications, a new fiber optic data bus topology, fiber optics for aircraft engine/inlet control, and application of fiber optics in high voltage substations

  11. Fiber Optics Technology.

    Science.gov (United States)

    Burns, William E.

    1986-01-01

    Discusses various applications of fiber optics technology: information systems, industrial robots, medicine, television, transportation, and training. Types of jobs that will be available with fiber optics training (such as electricians and telephone cable installers and splicers) are examined. (CT)

  12. Fiber Optics Instrumentation Development

    Science.gov (United States)

    Chan, Patrick Hon Man; Parker, Allen R., Jr.; Richards, W. Lance

    2010-01-01

    This is a general presentation of fiber optics instrumentation development work being conducted at NASA Dryden for the past 10 years and recent achievements in the field of fiber optics strain sensors.

  13. Shaped fiber composites

    Science.gov (United States)

    Kinnan, Mark K.; Roach, Dennis P.

    2017-12-05

    A composite article is disclosed that has non-circular fibers embedded in a polymer matrix. The composite article has improved damage tolerance, toughness, bending, and impact resistance compared to composites having traditional round fibers.

  14. Advances in Fiber Lasers

    National Research Council Canada - National Science Library

    Morse, T

    1999-01-01

    Most of the time of this contract has been devoted toward improvements in optical fiber lasers and toward gathering experience to improve our program in high power, cladding pumped optical fiber lasers...

  15. Hierarchically Structured Electrospun Fibers

    Science.gov (United States)

    2013-01-07

    in the natural lotus and silver ragwort leaves. Figure 4. Examples of electrospun bio-mimics of natural hierarchical structures. (A) Lotus leaf...B) pillared poly(methyl methacrylate) (PMMA) electrospun fiber mimic; (C) silver ragwort leaf; (D) electrospun fiber mimic made from nylon 6 and...domains containing the protein in the surrounding EVA fibers [115]. A wide variety of core-shell fibers have been generated, including PCL/ gelatin

  16. Superlattice Microstructured Optical Fiber

    Science.gov (United States)

    Tse, Ming-Leung Vincent; Liu, Zhengyong; Cho, Lok-Hin; Lu, Chao; Wai, Ping-Kong Alex; Tam, Hwa-Yaw

    2014-01-01

    A generic three-stage stack-and-draw method is demonstrated for the fabrication of complex-microstructured optical fibers. We report the fabrication and characterization of a silica superlattice microstructured fiber with more than 800 rhomboidally arranged air-holes. A polarization-maintaining fiber with a birefringence of 8.5 × 10−4 is demonstrated. The birefringent property of the fiber is found to be highly insensitive to external environmental effects, such as pressure. PMID:28788693

  17. How informative are spatial CA3 representations established by the dentate gyrus?

    Directory of Open Access Journals (Sweden)

    Erika Cerasti

    2010-04-01

    Full Text Available In the mammalian hippocampus, the dentate gyrus (DG is characterized by sparse and powerful unidirectional projections to CA3 pyramidal cells, the so-called mossy fibers. Mossy fiber synapses appear to duplicate, in terms of the information they convey, what CA3 cells already receive from entorhinal cortex layer II cells, which project both to the dentate gyrus and to CA3. Computational models of episodic memory have hypothesized that the function of the mossy fibers is to enforce a new, well-separated pattern of activity onto CA3 cells, to represent a new memory, prevailing over the interference produced by the traces of older memories already stored on CA3 recurrent collateral connections. Can this hypothesis apply also to spatial representations, as described by recent neurophysiological recordings in rats? To address this issue quantitatively, we estimate the amount of information DG can impart on a new CA3 pattern of spatial activity, using both mathematical analysis and computer simulations of a simplified model. We confirm that, also in the spatial case, the observed sparse connectivity and level of activity are most appropriate for driving memory storage-and not to initiate retrieval. Surprisingly, the model also indicates that even when DG codes just for space, much of the information it passes on to CA3 acquires a non-spatial and episodic character, akin to that of a random number generator. It is suggested that further hippocampal processing is required to make full spatial use of DG inputs.

  18. Human tau increases amyloid β plaque size but not amyloid β-mediated synapse loss in a novel mouse model of Alzheimer's disease.

    Science.gov (United States)

    Jackson, Rosemary J; Rudinskiy, Nikita; Herrmann, Abigail G; Croft, Shaun; Kim, JeeSoo Monica; Petrova, Veselina; Ramos-Rodriguez, Juan Jose; Pitstick, Rose; Wegmann, Susanne; Garcia-Alloza, Monica; Carlson, George A; Hyman, Bradley T; Spires-Jones, Tara L

    2016-12-01

    Alzheimer's disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined. In this study, we generated a novel transgenic mouse line, the APP/PS1/rTg21221 line, by crossing APP/PS1 mice, which develop Aβ-plaques and synapse loss, with rTg21221 mice, which overexpress wild-type human tau. When compared to the APP/PS1 mice without human tau, the cross-sectional area of ThioS+ dense core plaques was increased by ~50%. Along with increased plaque size, we observed an increase in plaque-associated dystrophic neurites containing misfolded tau, but there was no exacerbation of neurite curvature or local neuron loss around plaques. Array tomography analysis similarly revealed no worsening of synapse loss around plaques, and no change in the accumulation of Aβ at synapses. Together, these results indicate that adding human wild-type tau exacerbates plaque pathology and neurite deformation but does not exacerbate plaque-associated synapse loss. © 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. High-fiber foods

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000193.htm High-fiber foods To use the sharing features on this page, ... Read food labels carefully to see how much fiber they have. Choose foods that have higher amounts of fiber, such as ...

  20. Resonant filtered fiber amplifiers

    DEFF Research Database (Denmark)

    Alkeskjold, Thomas Tanggaard; Laurila, Marko; Olausson, Christina Bjarnal Thulin

    2013-01-01

    In this paper we present our recent result on utilizing resonant/bandgap fiber designs to achieve high performance ytterbium doped fiber amplifers for achieving diffraction limited beam quality in large mode area fibers, robust bending performance and gain shaping for long wavelength operation...

  1. Fiber Singular Optics

    OpenAIRE

    A. V. Volyar

    2002-01-01

    The present review is devoted to the optical vortex behavior both in free space and optical fibers. The processes of the vortex transformations in perturbed optical fibers are analyzed on the base of the operator of the spin – orbit interaction in order to forecast the possible ways of manufacturing the vortex preserving fibers and their applications in supersensitive optical devices.

  2. The repetition timing of high frequency afferent stimulation drives the bidirectional plasticity at central synapses in the rat medial vestibular nuclei.

    Science.gov (United States)

    Scarduzio, M; Panichi, R; Pettorossi, V E; Grassi, S

    2012-10-25

    In this study we show that high frequency stimulation (HFS, 100Hz) of afferent fibers to the medial vestibular nucleus (MVN) can induce opposite long-term modifications of synaptic responses in the type B neurons depending upon the stimulation pattern. Long burst stimulation (LBS: 2s) and short burst stimulation (SBS: 0.55s) were applied with different burst number (BN) and inter-burst intervals (IBI). It results that both LBS and SBS can induce either N-methyl-d aspartate receptors (NMDARs)-mediated long-term potentiation (LTP) or long-term depression (LTD), depending on temporal organization of repetitive bursts. In particular, the IBI plays a relevant role in guiding the shift from LTP to LTD since by using both LBS and SBS LTP is induced by shorter IBI than LTD. By contrast, the sign of long-term effect does not depend on the mean impulse frequency evaluated within the entire stimulation period. Therefore, the patterns of repetitive vestibular activation with different ratios between periods of increased activity and periods of basal activity may lead to LTP or LTD probably causing different levels of postsynaptic Ca(2+). On the whole, this study demonstrates that glutamatergic vestibular synapse in the MVN can undergo NMDAR-dependent bidirectional plasticity and puts forward a new aspect for understanding the adaptive and compensatory plasticity of the oculomotor responses. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. ON Cone Bipolar Cell Axonal Synapses in the OFF Inner Plexiform Layer of the Rabbit Retina

    Science.gov (United States)

    Lauritzen, J. Scott; Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Mohammed, Shoeb; Hoang, John V.; Marc, Robert E.

    2012-01-01

    Analysis of the rabbit retinal connectome RC1 reveals that the division between the ON and OFF inner plexiform layer (IPL) is not structurally absolute. ON cone bipolar cells make non-canonical axonal synapses onto specific targets and receive amacrine cell synapses in the nominal OFF layer, creating novel motifs, including inhibitory crossover networks. Automated transmission electron microscope (ATEM) imaging, molecular tagging, tracing, and rendering of ≈ 400 bipolar cells reveals axonal ribbons in 36% of ON cone bipolar cells, throughout the OFF IPL. The targets include GABA-positive amacrine cells (γACs), glycine-positive amacrine cells (GACs) and ganglion cells. Most ON cone bipolar cell axonal contacts target GACs driven by OFF cone bipolar cells, forming new architectures for generating ON-OFF amacrine cells. Many of these ON-OFF GACs target ON cone bipolar cell axons, ON γACs and/or ON-OFF ganglion cells, representing widespread mechanisms for OFF to ON crossover inhibition. Other targets include OFF γACs presynaptic to OFF bipolar cells, forming γAC-mediated crossover motifs. ON cone bipolar cell axonal ribbons drive bistratified ON-OFF ganglion cells in the OFF layer and provide ON drive to polarity-appropriate targets such as bistratified diving ganglion cells (bsdGCs). The targeting precision of ON cone bipolar cell axonal synapses shows that this drive incidence is necessarily a joint distribution of cone bipolar cell axonal frequency and target cell trajectories through a given volume of the OFF layer. Such joint distribution sampling is likely common when targets are sparser than sources and when sources are coupled, as are ON cone bipolar cells. PMID:23042441

  4. Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.

    Science.gov (United States)

    Thibault, Dominic; Giguère, Nicolas; Loustalot, Fabien; Bourque, Marie-Josée; Ducrot, Charles; El Mestikawy, Salah; Trudeau, Louis-Éric

    2016-05-01

    Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit.

  5. Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse.

    Science.gov (United States)

    Tomàs, Josep; Santafé, Manel M; Garcia, Neus; Lanuza, Maria A; Tomàs, Marta; Besalduch, Núria; Obis, Teresa; Priego, Mercedes; Hurtado, Erica

    2014-05-01

    Over the past few years, we have studied, in the mammalian neuromuscular junction (NMJ), the local involvement in transmitter release of the presynaptic muscarinic ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during development and in the adult. At any given moment, the way in which a synapse works is largely the logical outcome of the confluence of these (and other) metabotropic signalling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes. We propose an integrated interpretation of the complementary function of these receptors in the adult NMJ. The activity of a given receptor group can modulate a given combination of spontaneous, evoked, and activity-dependent release characteristics. For instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh (an A1 R action) and protect synapse function, because stimulation with adenosine reduces the magnitude of depression during repetitive activity. The overall outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output of ACh, save synapse function by decreasing the extent of evoked release (mainly an M2 action), and reduce depression. We have also identified several links among P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs and observed that the muscarinic group has to operate correctly if the tropomyosin-related kinase B receptor (trkB) is also to operate correctly, and vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs operating normally. Copyright © 2014 Wiley Periodicals, Inc.

  6. Merkel disc is a serotonergic synapse in the epidermis for transmitting tactile signals in mammals.

    Science.gov (United States)

    Chang, Weipang; Kanda, Hirosato; Ikeda, Ryo; Ling, Jennifer; DeBerry, Jennifer J; Gu, Jianguo G

    2016-09-13

    The evolution of sensory systems has let mammals develop complicated tactile end organs to enable sophisticated sensory tasks, including social interaction, environmental exploration, and tactile discrimination. The Merkel disc, a main type of tactile end organ consisting of Merkel cells (MCs) and Aβ-afferent endings, are highly abundant in fingertips, touch domes, and whisker hair follicles of mammals. The Merkel disc has high tactile acuity for an object's physical features, such as texture, shape, and edges. Mechanisms underlying the tactile function of Merkel discs are obscured as to how MCs transmit tactile signals to Aβ-afferent endings leading to tactile sensations. Using mouse whisker hair follicles, we show herein that tactile stimuli are transduced by MCs into excitatory signals that trigger vesicular serotonin release from MCs. We identify that both ionotropic and metabotropic 5-hydroxytryptamine (5-HT) receptors are expressed on whisker Aβ-afferent endings and that their activation by serotonin released from MCs initiates Aβ-afferent impulses. Moreover, we demonstrate that these ionotropic and metabotropic 5-HT receptors have a synergistic effect that is critical to both electrophysiological and behavioral tactile responses. These findings elucidate that the Merkel disc is a unique serotonergic synapse located in the epidermis and plays a key role in tactile transmission. The epidermal serotonergic synapse may have important clinical implications in sensory dysfunctions, such as the loss of tactile sensitivity and tactile allodynia seen in patients who have diabetes, inflammatory diseases, and undergo chemotherapy. It may also have implications in the exaggerated tactile sensations induced by recreational drugs that act on serotoninergic synapses.

  7. Role of the mouse retinal photoreceptor ribbon synapse in visual motion processing for optokinetic responses.

    Science.gov (United States)

    Sugita, Yuko; Araki, Fumiyuki; Chaya, Taro; Kawano, Kenji; Furukawa, Takahisa; Miura, Kenichiro

    2015-01-01

    The ribbon synapse is a specialized synaptic structure in the retinal outer plexiform layer where visual signals are transmitted from photoreceptors to the bipolar and horizontal cells. This structure is considered important in high-efficiency signal transmission; however, its role in visual signal processing is unclear. In order to understand its role in visual processing, the present study utilized Pikachurin-null mutant mice that show improper formation of the photoreceptor ribbon synapse. We examined the initial and late phases of the optokinetic responses (OKRs). The initial phase was examined by measuring the open-loop eye velocity of the OKRs to sinusoidal grating patterns of various spatial frequencies moving at various temporal frequencies for 0.5 s. The mutant mice showed significant initial OKRs with a spatiotemporal frequency tuning (spatial frequency, 0.09 ± 0.01 cycles/°; temporal frequency, 1.87 ± 0.12 Hz) that was slightly different from the wild-type mice (spatial frequency, 0.11 ± 0.01 cycles/°; temporal frequency, 1.66 ± 0.12 Hz). The late phase of the OKRs was examined by measuring the slow phase eye velocity of the optokinetic nystagmus induced by the sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that the optimal spatial and temporal frequencies of the mutant mice (spatial frequency, 0.11 ± 0.02 cycles/°; temporal frequency, 0.81 ± 0.24 Hz) were both lower than those in the wild-type mice (spatial frequency, 0.15 ± 0.02 cycles/°; temporal frequency, 1.93 ± 0.62 Hz). These results suggest that the ribbon synapse modulates the spatiotemporal frequency tuning of visual processing along the ON pathway by which the late phase of OKRs is mediated.

  8. Role of the mouse retinal photoreceptor ribbon synapse in visual motion processing for optokinetic responses.

    Directory of Open Access Journals (Sweden)

    Yuko Sugita

    Full Text Available The ribbon synapse is a specialized synaptic structure in the retinal outer plexiform layer where visual signals are transmitted from photoreceptors to the bipolar and horizontal cells. This structure is considered important in high-efficiency signal transmission; however, its role in visual signal processing is unclear. In order to understand its role in visual processing, the present study utilized Pikachurin-null mutant mice that show improper formation of the photoreceptor ribbon synapse. We examined the initial and late phases of the optokinetic responses (OKRs. The initial phase was examined by measuring the open-loop eye velocity of the OKRs to sinusoidal grating patterns of various spatial frequencies moving at various temporal frequencies for 0.5 s. The mutant mice showed significant initial OKRs with a spatiotemporal frequency tuning (spatial frequency, 0.09 ± 0.01 cycles/°; temporal frequency, 1.87 ± 0.12 Hz that was slightly different from the wild-type mice (spatial frequency, 0.11 ± 0.01 cycles/°; temporal frequency, 1.66 ± 0.12 Hz. The late phase of the OKRs was examined by measuring the slow phase eye velocity of the optokinetic nystagmus induced by the sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that the optimal spatial and temporal frequencies of the mutant mice (spatial frequency, 0.11 ± 0.02 cycles/°; temporal frequency, 0.81 ± 0.24 Hz were both lower than those in the wild-type mice (spatial frequency, 0.15 ± 0.02 cycles/°; temporal frequency, 1.93 ± 0.62 Hz. These results suggest that the ribbon synapse modulates the spatiotemporal frequency tuning of visual processing along the ON pathway by which the late phase of OKRs is mediated.

  9. Hypoxia-Induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons

    Science.gov (United States)

    Zhou, Chengwen; Bell, Jocelyn J. Lippman; Sun, Hongyu; Jensen, Frances E.

    2012-01-01

    Neonatal seizures can lead to epilepsy and long-term cognitive deficits in adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and “silent” N-methyl-D-aspartate receptor (NMDAR)-only synapses in hippocampal CA1. At 48-72 hours (hrs) post-HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, post-seizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early-life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits. PMID:22171027

  10. A cellular model of memory reconsolidation involves reactivation-induced destabilization and restabilization at the sensorimotor synapse in Aplysia.

    Science.gov (United States)

    Lee, Sue-Hyun; Kwak, Chuljung; Shim, Jaehoon; Kim, Jung-Eun; Choi, Sun-Lim; Kim, Hyoung F; Jang, Deok-Jin; Lee, Jin-A; Lee, Kyungmin; Lee, Chi-Hoon; Lee, Young-Don; Miniaci, Maria Concetta; Bailey, Craig H; Kandel, Eric R; Kaang, Bong-Kiun

    2012-08-28

    The memory reconsolidation hypothesis suggests that a memory trace becomes labile after retrieval and needs to be reconsolidated before it can be stabilized. However, it is unclear from earlier studies whether the same synapses involved in encoding the memory trace are those that are destabilized and restabilized after the synaptic reactivation that accompanies memory retrieval, or whether new and different synapses are recruited. To address this issue, we studied a simple nonassociative form of memory, long-term sensitization of the gill- and siphon-withdrawal reflex in Aplysia, and its cellular analog, long-term facilitation at the sensory-to-motor neuron synapse. We found that after memory retrieval, behavioral long-term sensitization in Aplysia becomes labile via ubiquitin/proteasome-dependent protein degradation and is reconsolidated by means of de novo protein synthesis. In parallel, we found that on the cellular level, long-term facilitation at the sensory-to-motor neuron synapse that mediates long-term sensitization is also destabilized by protein degradation and is restabilized by protein synthesis after synaptic reactivation, a procedure that parallels memory retrieval or retraining evident on the behavioral level. These results provide direct evidence that the same synapses that store the long-term memory trace encoded by changes in the strength of synaptic connections critical for sensitization are disrupted and reconstructed after signal retrieval.

  11. SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function

    Directory of Open Access Journals (Sweden)

    Lucas Matt

    2018-02-01

    Full Text Available Altering AMPA receptor (AMPAR content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1 encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1 modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP, while mEPSC amplitude is reduced by only 25%. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity.

  12. Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors

    Science.gov (United States)

    Pankratov, Yuriy

    2017-01-01

    Communication between neuronal and glial cells is important for neural plasticity. P2X receptors are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons and/or glia. Recent data show that postsynaptic P2X receptors underlie slow neuromodulatory actions rather than fast synaptic transmission at brain synapses. Here, we review these findings with a particular focus on the release of ATP by astrocytes and the diversity of postsynaptic P2X-mediated modulation of synaptic strength and plasticity in the CNS. PMID:28845311

  13. The networks scale and coupling parameter in synchronization of neural networks with diluted synapses

    International Nuclear Information System (INIS)

    Li Yanlong; Ma Jun; Chen Yuhong; Xu Wenke; Wang Yinghai

    2008-01-01

    In this paper the influence of the networks scale on the coupling parameter in the synchronization of neural networks with diluted synapses is investigated. Using numerical simulations, an exponential decay form is observed in the extreme case of global coupling among networks and full connection in each network; the larger linked degree becomes, the larger critical coupling intensity becomes; and the oscillation phenomena in the relationship of critical coupling intensity and the number of neural networks layers in the case of small-scale networks are found

  14. Sailing to and Docking at the Immune Synapse: Role of Tubulin Dynamics and Molecular Motors

    Directory of Open Access Journals (Sweden)

    Noa Beatriz Martín-Cófreces

    2018-05-01

    Full Text Available The different cytoskeleton systems and their connecting molecular motors move vesicles and intracellular organelles to shape cells. Polarized cells with specialized functions display an exquisite spatio-temporal regulation of both cytoskeletal and organelle arrangements that support their specific tasks. In particular, T cells rapidly change their shape and cellular function through the establishment of cell surface and intracellular polarity in response to a variety of cues. This review focuses on the contribution of the microtubule-based dynein/dynactin motor complex, the tubulin and actin cytoskeletons, and different organelles to the formation of the antigen-driven immune synapse.

  15. Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors

    Directory of Open Access Journals (Sweden)

    Eric Boué-Grabot

    2017-01-01

    Full Text Available Communication between neuronal and glial cells is important for neural plasticity. P2X receptors are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons and/or glia. Recent data show that postsynaptic P2X receptors underlie slow neuromodulatory actions rather than fast synaptic transmission at brain synapses. Here, we review these findings with a particular focus on the release of ATP by astrocytes and the diversity of postsynaptic P2X-mediated modulation of synaptic strength and plasticity in the CNS.

  16. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells

    Directory of Open Access Journals (Sweden)

    Migneault Martine

    2010-01-01

    Full Text Available Abstract Background Cancer cells utilize a variety of mechanisms to evade immune detection and attack. Effective immune detection largely relies on the formation of an immune synapse which requires close contact between immune cells and their targets. Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets. Our results indicate that MUC16-mediated inhibition of immune synapse formation is an effective mechanism employed by ovarian tumors to evade immune recognition. Results Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells. MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls. This increased lysis was not due to differences in the expression levels of the ligands for the activating receptors DNAM-1 and NKG2D. The NK cell leukemia cell line (NKL, which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls. Tumor cells that survived the NKL challenge expressed higher levels of MUC16 indicating selective lysis of MUC16low targets. The higher csMUC16 levels on the NKL resistant tumor cells correlated with more protection from lysis as compared to target cells that were never exposed to the effectors. Conclusion MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets. Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells. The immune protection provided by MUC16 may lead to selective survival of ovarian cancer cells that are more efficient in

  17. Excitatory Synaptic Drive and Feedforward Inhibition in the Hippocampal CA3 Circuit Are Regulated by SynCAM 1.

    Science.gov (United States)

    Park, Kellie A; Ribic, Adema; Laage Gaupp, Fabian M; Coman, Daniel; Huang, Yuegao; Dulla, Chris G; Hyder, Fahmeed; Biederer, Thomas

    2016-07-13

    Select adhesion proteins control the development of synapses and modulate their structural and functional properties. Despite these important roles, the extent to which different synapse-organizing mechanisms act across brain regions to establish connectivity and regulate network properties is incompletely understood. Further, their functional roles in different neuronal populations remain to be defined. Here, we applied diffusion tensor imaging (DTI), a modality of magnetic resonance imaging (MRI), to map connectivity changes in knock-out (KO) mice lacking the synaptogenic cell adhesion protein SynCAM 1. This identified reduced fractional anisotropy in the hippocampal CA3 area in absence of SynCAM 1. In agreement, mossy fiber refinement in CA3 was impaired in SynCAM 1 KO mice. Mossy fibers make excitatory inputs onto postsynaptic specializations of CA3 pyramidal neurons termed thorny excrescences and these structures were smaller in the absence of SynCAM 1. However, the most prevalent targets of mossy fibers are GABAergic interneurons and SynCAM 1 loss unexpectedly reduced the number of excitatory terminals onto parvalbumin (PV)-positive interneurons in CA3. SynCAM 1 KO mice additionally exhibited lower postsynaptic GluA1 expression in these PV-positive interneurons. These synaptic imbalances in SynCAM 1 KO mice resulted in CA3 disinhibition, in agreement with reduced feedforward inhibition in this network in the absence of SynCAM 1-dependent excitatory drive onto interneurons. In turn, mice lacking SynCAM 1 were impaired in memory tasks involving CA3. Our results support that SynCAM 1 modulates excitatory mossy fiber inputs onto both interneurons and principal neurons in the hippocampal CA3 area to balance network excitability. This study advances our understanding of synapse-organizing mechanisms on two levels. First, the data support that synaptogenic proteins guide connectivity and can function in distinct brain regions even if they are expressed broadly

  18. Excitatory and inhibitory pathways modulate kainate excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Casaccia-Bonnefil, P; Benedikz, Eirikur; Rai, R

    1993-01-01

    In organotypic hippocampal slice cultures, kainate (KA) specifically induces cell loss in the CA3 region while N-methyl-D-aspartate induces cell loss in the CA1 region. The sensitivity of slice cultures to KA toxicity appears only after 2 weeks in vitro which parallels the appearance of mossy...... fibers. KA toxicity is potentiated by co-application with the GABA-A antagonist, picrotoxin. These data suggest that the excitotoxicity of KA in slice cultures is modulated by both excitatory and inhibitory synapses....

  19. Superconducting tin core fiber

    International Nuclear Information System (INIS)

    Homa, Daniel; Liang, Yongxuan; Hill, Cary; Kaur, Gurbinder; Pickrell, Gary

    2015-01-01

    In this study, we demonstrated superconductivity in a fiber with a tin core and fused silica cladding. The fibers were fabricated via a modified melt-draw technique and maintained core diameters ranging from 50-300 microns and overall diameters of 125-800 microns. Superconductivity of this fiber design was validated via the traditional four-probe test method in a bath of liquid helium at temperatures on the order of 3.8 K. The synthesis route and fiber design are perquisites to ongoing research dedicated all-fiber optoelectronics and the relationships between superconductivity and the material structures, as well as corresponding fabrication techniques. (orig.)

  20. Airclad fiber laser technology

    DEFF Research Database (Denmark)

    Hansen, Kim P.; Olausson, Christina Bjarnal Thulin; Broeng, Jes

    2011-01-01

    High-power fiber lasers and amplifiers have gained tremendous momentum in the last 5 years. Many of the traditional manufacturers of gas and solid-state lasers are now pursuing the fiber-based systems, which are displacing the conventional technology in many areas. High-power fiber laser systems...... require reliable fibers with large cores, stable mode quality, and good power handling capabilities-requirements that are all met by the airclad fiber technology. In the present paper we go through many of the building blocks needed to build high-power systems and we show an example of a complete airclad...... laser system. We present the latest advancements within airclad fiber technology including a new 100 m single-mode polarization-maintaining rod-type fiber capable of amplifying to megawatt power levels. Furthermore, we describe the novel airclad-based pump combiners and their use in a completely...

  1. Airclad fiber laser technology

    DEFF Research Database (Denmark)

    Hansen, Kim P.; Olausson, Christina Bjarnal Thulin; Broeng, Jes

    2008-01-01

    High-power fiber lasers and amplifiers have gained tremendous momentum in the last five years, and many of the traditional manufactures of gas and solid-state lasers are pursuing the attractive fiber-based systems, which are now displacing the old technology in many areas. High-power fiber laser...... systems require specially designed fibers with large cores and good power handling capabilities - requirements that are all met by the airclad fiber technology. In the present paper we go through many of the building blocks needed to build high-power systems and we show an example of a complete airclad...... laser system. We present the latest advancements within airclad fiber technology including a new 70 μm single-mode polarization-maintaining rod-type fiber capable of amplifying to MW power levels. Furthermore we describe the novel airclad based pump combiners and their use in a completely monolithic 350...

  2. Deficits in synaptic function occur at medial perforant path-dentate granule cell synapses prior to Schaffer collateral-CA1 pyramidal cell synapses in the novel TgF344-Alzheimer's Disease Rat Model.

    Science.gov (United States)

    Smith, Lindsey A; McMahon, Lori L

    2018-02-01

    Alzheimer's disease (AD) pathology begins decades prior to onset of clinical symptoms, and the entorhinal cortex and hippocampus are among the first and most extensively impacted brain regions. The TgF344-AD rat model, which more fully recapitulates human AD pathology in an age-dependent manner, is a next generation preclinical rodent model for understanding pathophysiological processes underlying the earliest stages of AD (Cohen et al., 2013). Whether synaptic alterations occur in hippocampus prior to reported learning and memory deficit is not known. Furthermore, it is not known if specific hippocampal synapses are differentially affected by progressing AD pathology, or if synaptic deficits begin to appear at the same age in males and females in this preclinical model. Here, we investigated the time-course of synaptic changes in basal transmission, paired-pulse ratio, as an indirect measure of presynaptic release probability, long-term potentiation (LTP), and dendritic spine density at two hippocampal synapses in male and ovariectomized female TgF344-AD rats and wildtype littermates, prior to reported behavioral deficits. Decreased basal synaptic transmission begins at medial perforant path-dentate granule cell (MPP-DGC) synapses prior to Schaffer-collateral-CA1 (CA3-CA1) synapses, in the absence of a change in paired-pulse ratio (PPR) or dendritic spine density. N-methyl-d-aspartate receptor (NMDAR)-dependent LTP magnitude is unaffected at CA3-CA1 synapses at 6, 9, and 12months of age, but is significantly increased at MPP-DGC synapses in TgF344-AD rats at 6months only. Sex differences were only observed at CA3-CA1 synapses where the decrease in basal transmission occurs at a younger age in males versus females. These are the first studies to define presymptomatic alterations in hippocampal synaptic transmission in the TgF344-AD rat model. The time course of altered synaptic transmission mimics the spread of pathology through hippocampus in human AD and provides

  3. Live cell linear dichroism imaging reveals extensive membrane ruffling within the docking structure of natural killer cell immune synapses

    DEFF Research Database (Denmark)

    Benninger, Richard K P; Vanherberghen, Bruno; Young, Stephen

    2009-01-01

    We have applied fluorescence imaging of two-photon linear dichroism to measure the subresolution organization of the cell membrane during formation of the activating (cytolytic) natural killer (NK) cell immune synapse (IS). This approach revealed that the NK cell plasma membrane is convoluted...... into ruffles at the periphery, but not in the center of a mature cytolytic NK cell IS. Time-lapse imaging showed that the membrane ruffles formed at the initial point of contact between NK cells and target cells and then spread radialy across the intercellular contact as the size of the IS increased, becoming...... absent from the center of the mature synapse. Understanding the role of such extensive membrane ruffling in the assembly of cytolytic synapses is an intriguing new goal....

  4. Inference of topology and the nature of synapses, and the flow of information in neuronal networks

    Science.gov (United States)

    Borges, F. S.; Lameu, E. L.; Iarosz, K. C.; Protachevicz, P. R.; Caldas, I. L.; Viana, R. L.; Macau, E. E. N.; Batista, A. M.; Baptista, M. S.

    2018-02-01

    The characterization of neuronal connectivity is one of the most important matters in neuroscience. In this work, we show that a recently proposed informational quantity, the causal mutual information, employed with an appropriate methodology, can be used not only to correctly infer the direction of the underlying physical synapses, but also to identify their excitatory or inhibitory nature, considering easy to handle and measure bivariate time series. The success of our approach relies on a surprising property found in neuronal networks by which nonadjacent neurons do "understand" each other (positive mutual information), however, this exchange of information is not capable of causing effect (zero transfer entropy). Remarkably, inhibitory connections, responsible for enhancing synchronization, transfer more information than excitatory connections, known to enhance entropy in the network. We also demonstrate that our methodology can be used to correctly infer directionality of synapses even in the presence of dynamic and observational Gaussian noise, and is also successful in providing the effective directionality of intermodular connectivity, when only mean fields can be measured.

  5. Visualizing presynaptic calcium dynamics and vesicle fusion with a single genetically encoded reporter at individual synapses

    Directory of Open Access Journals (Sweden)

    Rachel E Jackson

    2016-07-01

    Full Text Available Synaptic transmission depends on the influx of calcium into the presynaptic compartment, which drives neurotransmitter release. Genetically encoded reporters are widely used tools to understand these processes, particularly pHluorin-based reporters that report vesicle exocytosis and endocytosis through pH dependent changes in fluorescence, and genetically encoded calcium indicators (GECIs that exhibit changes in fluorescence upon binding to calcium. The recent expansion of the color palette of available indicators has made it possible to image multiple probes simultaneously within a cell. We have constructed a single molecule reporter capable of concurrent imaging of both presynaptic calcium influx and exocytosis, by fusion of sypHy, the vesicle associated protein synaptophysin containing a GFP-based pHluorin sensor, with the red-shifted GECI R-GECO1. Due to the fixed stoichiometry of the two probes, the ratio of the two responses can also be measured, providing an all optical correlate of the calcium dependence of release. Here, we have characterized stimulus-evoked sypHy-RGECO responses of hippocampal synapses in vitro, exploring the effects of different stimulus strengths and frequencies as well as variations in external calcium concentrations. By combining live sypHy-RGECO imaging with post-hoc fixation and immunofluorescence, we have also investigated correlations between structural and functional properties of synapses.

  6. 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

  7. 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.

  8. Fasudil, a Clinically Used ROCK Inhibitor, Stabilizes Rod Photoreceptor Synapses after Retinal Detachment.

    Science.gov (United States)

    Townes-Anderson, Ellen; Wang, Jianfeng; Halász, Éva; Sugino, Ilene; Pitler, Amy; Whitehead, Ian; Zarbin, Marco

    2017-06-01

    Retinal detachment disrupts the rod-bipolar synapse in the outer plexiform layer by retraction of rod axons. We showed that breakage is due to RhoA activation whereas inhibition of Rho kinase (ROCK), using Y27632, reduces synaptic damage. We test whether the ROCK inhibitor fasudil, used for other clinical applications, can prevent synaptic injury after detachment. Detachments were made in pigs by subretinal injection of balanced salt solution (BSS) or fasudil (1, 10 mM). In some animals, fasudil was injected intravitreally after BSS-induced detachment. After 2 to 4 hours, retinae were fixed for immunocytochemistry and confocal microscopy. Axon retraction was quantified by imaging synaptic vesicle label in the outer nuclear layer. Apoptosis was analyzed using propidium iodide staining. For biochemical analysis by Western blotting, retinal explants, detached from retinal pigmented epithelium, were cultured for 2 hours. Subretinal injection of fasudil (10 mM) reduced retraction of rod spherules by 51.3% compared to control detachments ( n = 3 pigs, P = 0.002). Intravitreal injection of 10 mM fasudil, a more clinically feasible route of administration, also reduced retraction (28.7%, n = 5, P ROCK, was decreased with 30 μM fasudil ( n = 8-10 explants, P ROCK signaling with fasudil reduced photoreceptor degeneration and preserved the rod-bipolar synapse after retinal detachment. These results support the possibility, previously tested with Y27632, that ROCK inhibition may attenuate synaptic damage in iatrogenic detachments.

  9. 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.

  10. Improving Spiking Dynamical Networks: Accurate Delays, Higher-Order Synapses, and Time Cells.

    Science.gov (United States)

    Voelker, Aaron R; Eliasmith, Chris

    2018-03-01

    Researchers building spiking neural networks face the challenge of improving the biological plausibility of their model networks while maintaining the ability to quantitatively characterize network behavior. In this work, we extend the theory behind the neural engineering framework (NEF), a method of building spiking dynamical networks, to permit the use of a broad class of synapse models while maintaining prescribed dynamics up to a given order. This theory improves our understanding of how low-level synaptic properties alter the accuracy of high-level computations in spiking dynamical networks. For completeness, we provide characterizations for both continuous-time (i.e., analog) and discrete-time (i.e., digital) simulations. We demonstrate the utility of these extensions by mapping an optimal delay line onto various spiking dynamical networks using higher-order models of the synapse. We show that these networks nonlinearly encode rolling windows of input history, using a scale invariant representation, with accuracy depending on the frequency content of the input signal. Finally, we reveal that these methods provide a novel explanation of time cell responses during a delay task, which have been observed throughout hippocampus, striatum, and cortex.

  11. Linking Mitochondria to Synapses: New Insights for Stress-Related Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Freddy Jeanneteau

    2016-01-01

    Full Text Available The brain evolved cellular mechanisms for adapting synaptic function to energy supply. This is particularly evident when homeostasis is challenged by stress. Signaling loops between the mitochondria and synapses scale neuronal connectivity with bioenergetics capacity. A biphasic “inverted U shape” response to the stress hormone glucocorticoids is demonstrated in mitochondria and at synapses, modulating neural plasticity and physiological responses. Low dose enhances neurotransmission, synaptic growth, mitochondrial functions, learning, and memory whereas chronic, higher doses produce inhibition of these functions. The range of physiological effects by stress and glucocorticoid depends on the dose, duration, and context at exposure. These criteria are met by neuronal activity and the circadian, stress-sensitive and ultradian, stress-insensitive modes of glucocorticoid secretion. A major hallmark of stress-related neuropsychiatric disorders is the disrupted glucocorticoid rhythms and tissue resistance to signaling with the glucocorticoid receptor (GR. GR resistance could result from the loss of context-dependent glucocorticoid signaling mediated by the downregulation of the activity-dependent neurotrophin BDNF. The coincidence of BDNF and GR signaling changes glucocorticoid signaling output with consequences on mitochondrial respiration efficiency, synaptic plasticity, and adaptive trajectories.

  12. Synaptic Conversion of Chloride-Dependent Synapses in Spinal Nociceptive Circuits: Roles in Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Mark S. Cooper

    2011-01-01

    Full Text Available Electrophysiological conversion of chloride-dependent synapses from inhibitory to excitatory function, as a result of aberrant neuronal chloride homeostasis, is a known mechanism for the genesis of neuropathic pain. This paper examines theoretically how this type of synaptic conversion can disrupt circuit logic in spinal nociceptive circuits. First, a mathematical scaling factor is developed to represent local aberration in chloride electrochemical driving potential. Using this mathematical scaling factor, electrophysiological symbols are developed to represent the magnitude of synaptic conversion within nociceptive circuits. When inserted into a nociceptive circuit diagram, these symbols assist in understanding the generation of neuropathic pain associated with the collapse of transmembrane chloride gradients. A more generalized scaling factor is also derived to represent the interplay of chloride and bicarbonate driving potentials on the function of GABAergic and glycinergic synapses. These mathematical and symbolic representations of synaptic conversion help illustrate the critical role that anion driving potentials play in the transduction of pain. Using these representations, we discuss ramifications of glial-mediated synaptic conversion in the genesis, and treatment, of neuropathic pain.

  13. Astrocyte-secreted thrombospondin-1 modulates synapse and spine defects in the fragile X mouse model.

    Science.gov (United States)

    Cheng, Connie; Lau, Sally K M; Doering, Laurie C

    2016-08-02

    Astrocytes are key participants in various aspects of brain development and function, many of which are executed via secreted proteins. Defects in astrocyte signaling are implicated in neurodevelopmental disorders characterized by abnormal neural circuitry such as Fragile X syndrome (FXS). In animal models of FXS, the loss in expression of the Fragile X mental retardation 1 protein (FMRP) from astrocytes is associated with delayed dendrite maturation and improper synapse formation; however, the effect of astrocyte-derived factors on the development of neurons is not known. Thrombospondin-1 (TSP-1) is an important astrocyte-secreted protein that is involved in the regulation of spine development and synaptogenesis. In this study, we found that cultured astrocytes isolated from an Fmr1 knockout (Fmr1 KO) mouse model of FXS displayed a significant decrease in TSP-1 protein expression compared to the wildtype (WT) astrocytes. Correspondingly, Fmr1 KO hippocampal neurons exhibited morphological deficits in dendritic spines and alterations in excitatory synapse formation following long-term culture. All spine and synaptic abnormalities were prevented in the presence of either astrocyte-conditioned media or a feeder layer derived from FMRP-expressing astrocytes, or following the application of exogenous TSP-1. Importantly, this work demonstrates the integral role of astrocyte-secreted signals in the establishment of neuronal communication and identifies soluble TSP-1 as a potential therapeutic target for Fragile X syndrome.

  14. Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36

    Science.gov (United States)

    Palacios-Prado, Nicolás; Chapuis, Sandrine; Panjkovich, Alejandro; Fregeac, Julien; Nagy, James I.; Bukauskas, Feliksas F.

    2014-08-01

    Neuronal gap junction (GJ) channels composed of connexin36 (Cx36) play an important role in neuronal synchronization and network dynamics. Here we show that Cx36-containing electrical synapses between inhibitory neurons of the thalamic reticular nucleus are bidirectionally modulated by changes in intracellular free magnesium concentration ([Mg2+]i). Chimeragenesis demonstrates that the first extracellular loop of Cx36 contains a Mg2+-sensitive domain, and site-directed mutagenesis shows that the pore-lining residue D47 is critical in determining high Mg2+-sensitivity. Single-channel analysis of Mg2+-sensitive chimeras and mutants reveals that [Mg2+]i controls the strength of electrical coupling mostly via gating mechanisms. In addition, asymmetric transjunctional [Mg2+]i induces strong instantaneous rectification, providing a novel mechanism for electrical rectification in homotypic Cx36 GJs. We suggest that Mg2+-dependent synaptic plasticity of Cx36-containing electrical synapses could underlie neuronal circuit reconfiguration via changes in brain energy metabolism that affects neuronal levels of intracellular ATP and [Mg2+]i.

  15. Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

    Science.gov (United States)

    Meredith, Rhiannon M.; van Ooyen, Arjen

    2012-01-01

    CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

  16. Persistent long-term facilitation at an identified synapse becomes labile with activation of short-term heterosynaptic plasticity.

    Science.gov (United States)

    Hu, Jiang-Yuan; Schacher, Samuel

    2014-04-02

    Short-term and long-term synaptic plasticity are cellular correlates of learning and memory of different durations. Little is known, however, how these two forms of plasticity interact at the same synaptic connection. We examined the reciprocal impact of short-term heterosynaptic or homosynaptic plasticity at sensorimotor synapses of Aplysia in cell culture when expressing persistent long-term facilitation (P-LTF) evoked by serotonin [5-hydroxytryptamine (5-HT)]. Short-term heterosynaptic plasticity induced by 5-HT (facilitation) or the neuropeptide FMRFa (depression) and short-term homosynaptic plasticity induced by tetanus [post-tetanic potentiation (PTP)] or low-frequency stimulation [homosynaptic depression (HSD)] of the sensory neuron were expressed in both control synapses and synapses expressing P-LTF in the absence or presence of protein synthesis inhibitors. All forms of short-term plasticity failed to significantly affect ongoing P-LTF in the absence of protein synthesis inhibitors. However, P-LTF reversed to control levels when either 5-HT or FMRFa was applied in the presence of rapamycin. In contrast, P-LTF was unaffected when either PTP or HSD was evoked in the presence of either rapamycin or anisomycin. These results indicate that synapses expressing persistent plasticity acquire a "new" baseline and functionally express short-term changes as naive synapses, but the new baseline becomes labile following selective activations-heterosynaptic stimuli that evoke opposite forms of plasticity-such that when presented in the presence of protein synthesis inhibitors produce a rapid reversal of the persistent plasticity. Activity-selective induction of a labile state at synapses expressing persistent plasticity may facilitate the development of therapies for reversing inappropriate memories.

  17. Polyribosomes at the base of dendritic spines of central nervous system neurons - their possible role in synapse construction and modification

    International Nuclear Information System (INIS)

    Steward, O.

    1983-01-01

    The selective localization of polyribosomes at the base of dendritic spines in granule cells of the dentate gyrus was studied. These polyribosomes seem optimally situated to produce proteins for the postsynaptic membrane specialization or the spine and to have their synthetic activity regulated by functional activity over the synapse. The present work will summarize observations on the polyribosome clusters that were found to be ubiquitous in spines throughout the vertebrate CNS. Evidence will be presented that suggests a role for the polyribosomes in synapse construction and modification. 42 refs., 8 figs., 2 tabs

  18. Repetitive activation of the corticospinal pathway by means of rTMS may reduce the efficiency of corticomotoneuronal synapses

    DEFF Research Database (Denmark)

    Taube, Wolfgang; Leukel, Christian; Nielsen, Jens Bo

    2015-01-01

    Low-frequency rTMS applied to the primary motor cortex (M1) may produce depression of motor-evoked potentials (MEPs). This depression is commonly assumed to reflect changes in cortical circuits. However, little is known about rTMS-induced effects on subcortical circuits. Therefore, the present st......-either at M1 and/or the CM synapse. As the early facilitation reflects activation of direct CM projections, the most likely site of action is the synapse of the CM neurons onto spinal motoneurons....

  19. Hierarchically Structured Electrospun Fibers

    Directory of Open Access Journals (Sweden)

    Nicole E. Zander

    2013-01-01

    Full Text Available Traditional electrospun nanofibers have a myriad of applications ranging from scaffolds for tissue engineering to components of biosensors and energy harvesting devices. The generally smooth one-dimensional structure of the fibers has stood as a limitation to several interesting novel applications. Control of fiber diameter, porosity and collector geometry will be briefly discussed, as will more traditional methods for controlling fiber morphology and fiber mat architecture. The remainder of the review will focus on new techniques to prepare hierarchically structured fibers. Fibers with hierarchical primary structures—including helical, buckled, and beads-on-a-string fibers, as well as fibers with secondary structures, such as nanopores, nanopillars, nanorods, and internally structured fibers and their applications—will be discussed. These new materials with helical/buckled morphology are expected to possess unique optical and mechanical properties with possible applications for negative refractive index materials, highly stretchable/high-tensile-strength materials, and components in microelectromechanical devices. Core-shell type fibers enable a much wider variety of materials to be electrospun and are expected to be widely applied in the sensing, drug delivery/controlled release fields, and in the encapsulation of live cells for biological applications. Materials with a hierarchical secondary structure are expected to provide new superhydrophobic and self-cleaning materials.

  20. Neurotrophin-3 Regulates Synapse Development by Modulating TrkC-PTPσ Synaptic Adhesion and Intracellular Signaling Pathways.

    Science.gov (United States)

    Han, Kyung Ah; Woo, Doyeon; Kim, Seungjoon; Choii, Gayoung; Jeon, Sangmin; Won, Seoung Youn; Kim, Ho Min; Heo, Won Do; Um, Ji Won; Ko, Jaewon

    2016-04-27

    Neurotrophin-3 (NT-3) is a secreted neurotrophic factor that binds neurotrophin receptor tyrosine kinase C (TrkC), which in turn binds to presynaptic protein tyrosine phosphatase σ (PTPσ) to govern excitatory synapse development. However, whether and how NT-3 cooperates with the TrkC-PTPσ synaptic adhesion pathway and TrkC-mediated intracellular signaling pathways in rat cultured neurons has remained unclear. Here, we report that NT-3 enhances TrkC binding affinity for PTPσ. Strikingly, NT-3 treatment bidirectionally regulates the synaptogenic activity of TrkC: at concentrations of 10-25 ng/ml, NT-3 further enhanced the increase in synapse density induced by TrkC overexpression, whereas at higher concentrations, NT-3 abrogated TrkC-induced increases in synapse density. Semiquantitative immunoblotting and optogenetics-based imaging showed that 25 ng/ml NT-3 or light stimulation at a power that produced a comparable level of NT-3 (6.25 μW) activated only extracellular signal-regulated kinase (ERK) and Akt, whereas 100 ng/ml NT-3 (light intensity, 25 μW) further triggered the activation of phospholipase C-γ1 and CREB independently of PTPσ. Notably, disruption of TrkC intracellular signaling pathways, extracellular ligand binding, or kinase activity by point mutations compromised TrkC-induced increases in synapse density. Furthermore, only sparse, but not global, TrkC knock-down in cultured rat neurons significantly decreased synapse density, suggesting that intercellular differences in TrkC expression level are critical for its synapse-promoting action. Together, our data demonstrate that NT-3 is a key factor in excitatory synapse development that may direct higher-order assembly of the TrkC/PTPσ complex and activate distinct intracellular signaling cascades in a concentration-dependent manner to promote competition-based synapse development processes. In this study, we present several lines of experimental evidences to support the conclusion that

  1. Fiber optics in SHIVA

    International Nuclear Information System (INIS)

    Severyn, J.; Parker, J.

    1978-01-01

    SHIVA is a twenty arm laser which is controlled with a network of fifty computers, interconnected with digital fiber optic links. Three different fiber optic systems employed on the Shiva laser will be described. Two of the systems are for digital communications, one at 9600 baud and the other at 1 megabaud. The third system uses fiber optics to distribute diagnostic triggers with subnanosecond jitter

  2. Continuous Fiber Ceramic Composites

    Energy Technology Data Exchange (ETDEWEB)

    Fareed, Ali [Honeywell Advanced Composites Inc. (HACI), Newark, DE (United States); Craig, Phillip A. [Honeywell Advanced Composites Inc. (HACI), Newark, DE (United States)

    2002-09-01

    Fiber-reinforced ceramic composites demonstrate the high-temperature stability of ceramics--with an increased fracture toughness resulting from the fiber reinforcement of the composite. The material optimization performed under the continuous fiber ceramic composites (CFCC) included a series of systematic optimizations. The overall goals were to define the processing window, to increase the robustinous of the process, to increase process yield while reducing costs, and to define the complexity of parts that could be fabricated.

  3. Anergic CD4+ T cells form mature immunological synapses with enhanced accumulation of c-Cbl and Cbl-b1

    Science.gov (United States)

    Doherty, Melissa; Osborne, Douglas G.; Browning, Diana L.; Parker, David C.; Wetzel, Scott A.

    2010-01-01

    CD4+ T cell recognition of MHC:peptide complexes in the context of a costimulatory signal results in the large-scale redistribution of molecules at the T-APC interface to form the immunological synapse. The immunological synapse is the location of sustained TCR signaling and delivery of a subset of effector functions. T cells activated in the absence of costimulation are rendered anergic and are hyporesponsive when presented with antigen in the presence of optimal costimulation. Several previous studies have looked at aspects of immunological synapses formed by anergic T cells, but it remains unclear whether there are differences in the formation or composition of anergic immunological synapses. In this study we anergized primary murine CD4+ T cells by incubation of costimulation-deficient, transfected fibroblast APC. Using a combination of TCR, MHC:peptide, and ICAM-1 staining, we found that anergic T cells make mature immunological synapses with characteristic cSMAC and pSMAC domains that were indistinguishable from control synapses. There were small increases in total phosphotyrosine at the anergic synapse along with significant decreases in phosphorylated ERK 1/2 accumulation. Most striking, there was specific accumulation of c-Cbl and Cbl-b to the anergic synapses. Cbl-b, previously shown to be essential in anergy induction, was found in both the pSMAC and the cSMAC of the anergic synapse. This Cbl-b (and c-Cbl) accumulation at the anergic synapse may play an important role in anergy maintenance and/or induction. PMID:20207996

  4. Agave Americana Leaf Fibers

    Directory of Open Access Journals (Sweden)

    Ashish Hulle

    2015-02-01

    Full Text Available The growing environmental problems, the problem of waste disposal and the depletion of non-renewable resources have stimulated the use of green materials compatible with the environment to reduce environmental impacts. Therefore, there is a need to design products by using natural resources. Natural fibers seem to be a good alternative since they are abundantly available and there are a number of possibilities to use all the components of a fiber-yielding crop; one such fiber-yielding plant is Agave Americana. The leaves of this plant yield fibers and all the parts of this plant can be utilized in many applications. The “zero-waste” utilization of the plant would enable its production and processing to be translated into a viable and sustainable industry. Agave Americana fibers are characterized by low density, high tenacity and high moisture absorbency in comparison with other leaf fibers. These fibers are long and biodegradable. Therefore, we can look this fiber as a sustainable resource for manufacturing and technical applications. Detailed discussion is carried out on extraction, characterization and applications of Agave Americana fiber in this paper.

  5. Loss of Synapse Repressor MDGA1 Enhances Perisomatic Inhibition, Confers Resistance to Network Excitation, and Impairs Cognitive Function

    Directory of Open Access Journals (Sweden)

    Steven A. Connor

    2017-12-01

    Full Text Available Synaptopathies contributing to neurodevelopmental disorders are linked to mutations in synaptic organizing molecules, including postsynaptic neuroligins, presynaptic neurexins, and MDGAs, which regulate their interaction. The role of MDGA1 in suppressing inhibitory versus excitatory synapses is controversial based on in vitro studies. We show that genetic deletion of MDGA1 in vivo elevates hippocampal CA1 inhibitory, but not excitatory, synapse density and transmission. Furthermore, MDGA1 is selectively expressed by pyramidal neurons and regulates perisomatic, but not distal dendritic, inhibitory synapses. Mdga1−/− hippocampal networks demonstrate muted responses to neural excitation, and Mdga1−/− mice are resistant to induced seizures. Mdga1−/− mice further demonstrate compromised hippocampal long-term potentiation, consistent with observed deficits in spatial and context-dependent learning and memory. These results suggest that mutations in MDGA1 may contribute to cognitive deficits through altered synaptic transmission and plasticity by loss of suppression of inhibitory synapse development in a subcellular domain- and cell-type-selective manner.

  6. 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

  7. Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses.

    Science.gov (United States)

    Sundaresan, Srividya; Kong, Jee-Hyun; Fang, Qing; Salles, Felipe T; Wangsawihardja, Felix; Ricci, Anthony J; Mustapha, Mirna

    2016-01-01

    Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell dwarf mouse (Pit1(dw)) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1(dw) mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1(dw) IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1(dw) IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1(dw) IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  8. On optical detection of densely labeled synapses in neuropil and mapping connectivity with combinatorially multiplexed fluorescent synaptic markers.

    Directory of Open Access Journals (Sweden)

    Yuriy Mishchenko

    Full Text Available We propose a new method for mapping neural connectivity optically, by utilizing Cre/Lox system Brainbow to tag synapses of different neurons with random mixtures of different fluorophores, such as GFP, YFP, etc., and then detecting patterns of fluorophores at different synapses using light microscopy (LM. Such patterns will immediately report the pre- and post-synaptic cells at each synaptic connection, without tracing neural projections from individual synapses to corresponding cell bodies. We simulate fluorescence from a population of densely labeled synapses in a block of hippocampal neuropil, completely reconstructed from electron microscopy data, and show that high-end LM is able to detect such patterns with over 95% accuracy. We conclude, therefore, that with the described approach neural connectivity in macroscopically large neural circuits can be mapped with great accuracy, in scalable manner, using fast optical tools, and straightforward image processing. Relying on an electron microscopy dataset, we also derive and explicitly enumerate the conditions that should be met to allow synaptic connectivity studies with high-resolution optical tools.

  9. Learning Discloses Abnormal Structural and Functional Plasticity at Hippocampal Synapses in the APP23 Mouse Model of Alzheimer's Disease

    Science.gov (United States)

    Middei, Silvia; Roberto, Anna; Berretta, Nicola; Panico, Maria Beatrice; Lista, Simone; Bernardi, Giorgio; Mercuri, Nicola B.; Ammassari-Teule, Martine; Nistico, Robert

    2010-01-01

    B6-Tg/Thy1APP23Sdz (APP23) mutant mice exhibit neurohistological hallmarks of Alzheimer's disease but show intact basal hippocampal neurotransmission and synaptic plasticity. Here, we examine whether spatial learning differently modifies the structural and electrophysiological properties of hippocampal synapses in APP23 and wild-type mice. While…

  10. Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity

    Directory of Open Access Journals (Sweden)

    Akiko Ueno

    2018-03-01

    Full Text Available Summary: In the vertebrate retina, cone photoreceptors play crucial roles in photopic vision by transmitting light-evoked signals to ON- and/or OFF-bipolar cells. However, the mechanisms underlying selective synapse formation in the cone photoreceptor pathway remain poorly understood. Here, we found that Lrit1, a leucine-rich transmembrane protein, localizes to the photoreceptor synaptic terminal and regulates the synaptic connection between cone photoreceptors and cone ON-bipolar cells. Lrit1-deficient retinas exhibit an aberrant morphology of cone photoreceptor pedicles, as well as an impairment of signal transmission from cone photoreceptors to cone ON-bipolar cells. Furthermore, we demonstrated that Lrit1 interacts with Frmpd2, a photoreceptor scaffold protein, and with mGluR6, an ON-bipolar cell-specific glutamate receptor. Additionally, Lrit1-null mice showed visual acuity impairments in their optokinetic responses. These results suggest that the Frmpd2-Lrit1-mGluR6 axis regulates selective synapse formation in cone photoreceptors and is essential for normal visual function. : Ueno et al. finds that Lrit1 plays an important role in regulating the synaptic connection between cone photoreceptors and cone ON-bipolar cells. The Frmpd2-Lrit1-mGluR6 axis is crucial for selective synapse formation in cone photoreceptors and for development of normal visual function. Keywords: retina, circuit, synapse formation, cone photoreceptor cell, ON-bipolar cell, visual acuity

  11. Remodelling at the calyx of Held-MNTB synapse in mice developing with unilateral conductive hearing loss.

    Science.gov (United States)

    Grande, Giovanbattista; Negandhi, Jaina; Harrison, Robert V; Wang, Lu-Yang

    2014-04-01

    Structure and function of central synapses are profoundly influenced by experience during developmental sensitive periods. Sensory synapses, which are the indispensable interface for the developing brain to interact with its environment, are particularly plastic. In the auditory system, moderate forms of unilateral hearing loss during development are prevalent but the pre- and postsynaptic modifications that occur when hearing symmetry is perturbed are not well understood. We investigated this issue by performing experiments at the large calyx of Held synapse. Principal neurons of the medial nucleus of the trapezoid body (MNTB) are innervated by calyx of Held terminals that originate from the axons of globular bushy cells located in the contralateral ventral cochlear nucleus. We compared populations of synapses in the same animal that were either sound deprived (SD) or sound experienced (SE) after unilateral conductive hearing loss (CHL). Middle ear ossicles were removed 1 week prior to hearing onset (approx. postnatal day (P) 12) and morphological and electrophysiological approaches were applied to auditory brainstem slices taken from these mice at P17-19. Calyces in the SD and SE MNTB acquired their mature digitated morphology but these were structurally more complex than those in normal hearing mice. This was accompanied by bilateral decreases in initial EPSC amplitude and synaptic conductance despite the CHL being unilateral. During high-frequency stimulation, some SD synapses displayed short-term depression whereas others displayed short-term facilitation followed by slow depression similar to the heterogeneities observed in normal hearing mice. However SE synapses predominantly displayed short-term facilitation followed by slow depression which could be explained in part by the decrease in release probability. Furthermore, the excitability of principal cells in the SD MNTB had increased significantly. Despite these unilateral changes in short-term plasticity

  12. REM sleep selectively prunes and maintains new synapses in development and learning.

    Science.gov (United States)

    Li, Wei; Ma, Lei; Yang, Guang; Gan, Wen-Biao

    2017-03-01

    The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation during development and when a new motor task is learned, indicating a role for REM sleep in pruning to balance the number of new spines formed over time. Moreover, REM sleep also strengthens and maintains newly formed spines, which are critical for neuronal circuit development and behavioral improvement after learning. We further show that dendritic calcium spikes arising during REM sleep are important for pruning and strengthening new spines. Together, these findings indicate that REM sleep has multifaceted functions in brain development, learning and memory consolidation by selectively eliminating and maintaining newly formed synapses via dendritic calcium spike-dependent mechanisms.

  13. Control of bursting synchronization in networks of Hodgkin-Huxley-type neurons with chemical synapses.

    Science.gov (United States)

    Batista, C A S; Viana, R L; Ferrari, F A S; Lopes, S R; Batista, A M; Coninck, J C P

    2013-04-01

    Thermally sensitive neurons present bursting activity for certain temperature ranges, characterized by fast repetitive spiking of action potential followed by a short quiescent period. Synchronization of bursting activity is possible in networks of coupled neurons, and it is sometimes an undesirable feature. Control procedures can suppress totally or partially this collective behavior, with potential applications in deep-brain stimulation techniques. We investigate the control of bursting synchronization in small-world networks of Hodgkin-Huxley-type thermally sensitive neurons with chemical synapses through two different strategies. One is the application of an external time-periodic electrical signal and another consists of a time-delayed feedback signal. We consider the effectiveness of both strategies in terms of protocols of applications suitable to be applied by pacemakers.

  14. Role of the MAGUK protein family in synapse formation and function.

    Science.gov (United States)

    Oliva, Carlos; Escobedo, Pía; Astorga, César; Molina, Claudia; Sierralta, Jimena

    2012-01-01

    Synaptic function is crucially dependent on the spatial organization of the presynaptic and postsynaptic apparatuses and the juxtaposition of both membrane compartments. This precise arrangement is achieved by a protein network at the submembrane region of each cell that is built around scaffold proteins. The membrane-associated guanylate kinase (MAGUK) family of proteins is a widely expressed and well-conserved group of proteins that plays an essential role in the formation and regulation of this scaffolding. Here, we review general features of this protein family, focusing on the discs large and calcium/calmodulin-dependent serine protein kinase subfamilies of MAGUKs in the formation, function, and plasticity of synapses. Copyright © 2011 Wiley Periodicals, Inc.

  15. Resolving dynamics of cell signaling via real-time imaging of the immunological synapse.

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, Mark A.; Pfeiffer, Janet R. (University of New Mexico, Albuquerque, NM); Wilson, Bridget S. (University of New Mexico, Albuquerque, NM); Timlin, Jerilyn Ann; Thomas, James L. (University of New Mexico, Albuquerque, NM); Lidke, Keith A. (University of New Mexico, Albuquerque, NM); Spendier, Kathrin (University of New Mexico, Albuquerque, NM); Oliver, Janet M. (University of New Mexico, Albuquerque, NM); Carroll-Portillo, Amanda (University of New Mexico, Albuquerque, NM); Aaron, Jesse S.; Mirijanian, Dina T.; Carson, Bryan D.; Burns, Alan Richard; Rebeil, Roberto

    2009-10-01

    This highly interdisciplinary team has developed dual-color, total internal reflection microscopy (TIRF-M) methods that enable us to optically detect and track in real time protein migration and clustering at membrane interfaces. By coupling TIRF-M with advanced analysis techniques (image correlation spectroscopy, single particle tracking) we have captured subtle changes in membrane organization that characterize immune responses. We have used this approach to elucidate the initial stages of cell activation in the IgE signaling network of mast cells and the Toll-like receptor (TLR-4) response in macrophages stimulated by bacteria. To help interpret these measurements, we have undertaken a computational modeling effort to connect the protein motion and lipid interactions. This work provides a deeper understanding of the initial stages of cellular response to external agents, including dynamics of interaction of key components in the signaling network at the 'immunological synapse,' the contact region of the cell and its adversary.

  16. Spatiotemporal regulation of ATP and Ca2+ dynamics in vertebrate rod and cone ribbon synapses.

    Science.gov (United States)

    Johnson, Jerry E; Perkins, Guy A; Giddabasappa, Anand; Chaney, Shawntay; Xiao, Weimin; White, Andrew D; Brown, Joshua M; Waggoner, Jenna; Ellisman, Mark H; Fox, Donald A

    2007-06-15

    In conventional neurons, Ca2+ enters presynaptic terminals during an action potential and its increased local concentration triggers transient exocytosis. In contrast, vertebrate photoreceptors are nonspiking neurons that maintain sustained depolarization and neurotransmitter release from ribbon synapses in darkness and produce light-dependent graded hyperpolarizing responses. Rods transmit single photon responses with high fidelity, whereas cones are less sensitive and exhibit faster response kinetics. These differences are likely due to variations in presynaptic Ca2+ dynamics. Metabolic coupling and cross-talk between mitochondria, endoplasmic reticulum (ER), plasma membrane Ca2+ ATPase (PMCA), and Na+-Ca2+ exchanger (NCX) coordinately control presynaptic ATP production and Ca2+ dynamics. The goal of our structural and functional studies was to determine the spatiotemporal regulation of ATP and Ca2+ dynamics in rod spherules and cone pedicles. Central retina tissue from C57BL/6 mice was used. Laser scanning confocal microscopy (LSCM) experiments were conducted on fixed-frozen vertical sections. Primary antibodies were selected for their tissue/cellular specificity and ability to recognize single, multiple or all splice variants of selected isoforms. Electron microscopy (EM) and 3-D electron tomography (ET) studies used our standard procedures on thin- and thick-sectioned retinas, respectively. Calibrated fluo-3-Ca2+ imaging experiments of dark- and light-adapted rod and cone terminals in retinal slices were conducted. Confocal microscopy showed that mitochondria, ER, PMCA, and NCX1 exhibited distinct retinal lamination patterns and differential distribution in photoreceptor synapses. Antibodies for three distinct mitochondrial compartments differentially labeled retinal areas with high metabolic demand: rod and cone inner segments, previously undescribed cone juxtanuclear mitochondria and the two plexiform layers. Rod spherule membranes uniformly and intensely

  17. Neurotrophin-4 couples to locally modulated ACh release at the end of neuromuscular synapse maturation.

    Science.gov (United States)

    Garcia, N; Santafe, M M; Tomas, M; Lanuza, M A; Besalduch, N; Tomas, J

    2010-01-01

    We use immunocytochemistry to show that neurotrophin-4 (NT-4) and its receptor proteins (p75(NTR) and tropomyosin-related tyrosine kinase B) are present in neonatal neuromuscular junctions (NMJ) colocalized with several synaptic markers. NT-4 incubation (1h, in the range 2-12 nM) does not change the size of the endplate potential between P6 and P45. However, extended exposure (3h) to a relatively low dose of NT-4 (2 nM) potentiates ACh release (approx. 70%) in adult but not in neonatal muscles. The present results suggest that the developmental mechanism of axonal competition and neonatal elimination of redundant synapses cannot be modulated by added NT-4. However, this neurotrophin was able to modulate synaptic transmission locally in the adult NMJ.

  18. Star-coupled Hindmarsh-Rose neural network with chemical synapses

    Science.gov (United States)

    Usha, K.; Subha, P. A.

    We analyze the patterns like synchrony, desynchrony, and Drum head mode in a network of Hindmarsh-Rose (HR) neurons interacting via chemical synapse in unidirectional and bidirectional star topology. A two-coupled system has been studied for synchronization by varying the coupling strength and the parameter describing the activation and inactivation of the fast ion channel. The transverse Lyapunov exponent spectrum is plotted to observe the point of transition from desynchrony to synchrony. The synchronized, desynchronized, and drum head mode regions are observed when the neurons are connected in unidirectional and bidirectional coupling configurations. A detailed analysis about the time evolution of membrane potential corresponding to each region is presented. The annihilation of synchronized region and the expansion of drum head mode region in bidirectional coupling is discussed using parameter space. Our work provides finer insight into the existence and stability of Drum head mode and is useful for designing communication networks.

  19. Building tolerance by dismantling synapses: inhibitory receptor signaling in natural killer cells.

    Science.gov (United States)

    Huse, Morgan; Catherine Milanoski, S; Abeyweera, Thushara P

    2013-01-01

    Cell surface receptors bearing immunotyrosine-based inhibitory motifs (ITIMs) maintain natural killer (NK) cell tolerance to normal host tissues. These receptors are difficult to analyze mechanistically because they block activating responses in a rapid and comprehensive manner. The advent of high-resolution single cell imaging techniques has enabled investigators to explore the cell biological basis of the inhibitory response. Recent studies using these approaches indicate that ITIM-containing receptors function at least in part by structurally undermining the immunological synapse between the NK cell and its target. In this review, we discuss these new advances and how they might relate to what is known about the biochemistry of inhibitory signaling in NK cells and other cell types. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  20. The Pathophysiology of Fragile X (and What It Teaches Us about Synapses)

    Science.gov (United States)

    Bhakar, Asha L.; Dölen, Gül; Bear, Mark F.

    2014-01-01

    Fragile X is the most common known inherited cause of intellectual disability and autism, and it typically results from transcriptional silencing of FMR1 and loss of the encoded protein, FMRP (fragile X mental retardation protein). FMRP is an mRNA-binding protein that functions at many synapses to inhibit local translation stimulated by metabotropic glutamate receptors (mGluRs) 1 and 5. Recent studies on the biology of FMRP and the signaling pathways downstream of mGluR1/5 have yielded deeper insight into how synaptic protein synthesis and plasticity are regulated by experience. This new knowledge has also suggested ways that altered signaling and synaptic function can be corrected in fragile X, and human clinical trials based on this information are under way. PMID:22483044

  1. USDA Flax fiber utilization research

    Science.gov (United States)

    The United States is pursuing natural fibers as sustainable, environmentally friendly sources for a variety of industrial applications. Flax (Linum usitatissimum L.) fiber offers many possibilities towards this goal. Research on flax fiber production, processing, and standards development is urgen...

  2. Ultrafine PBI fibers and yarns

    Science.gov (United States)

    Leal, J. R.; Tan, M.

    1979-01-01

    Gentle precisely controlled process is used to draw polybenzimidazole (PBI) fibers to denier as low as 0.17 per fiber. Yarns of lightweight fibers could be useful in applications where lightweight textiles must withstand high temperatures, corrosion, or radiation.

  3. The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses

    Science.gov (United States)

    Garcia, Rolando A. G.; Vasudevan, Kuzhalini; Buonanno, Andres

    2000-01-01

    Neuregulins regulate the expression of ligand- and voltage-gated channels in neurons and skeletal muscle by the activation of their cognate tyrosine kinase receptors, ErbB 1–4. The subcellular distribution and mechanisms that regulate the localization of ErbB receptors are unknown. We have found that ErbB receptors are present in brain subcellular fractions enriched for postsynaptic densities (PSD). The ErbB-4 receptor is unique among the ErbB proteins because its C-terminal tail (T-V-V) conforms to a sequence that binds to a protein motif known as the PDZ domain. Using the yeast two-hybrid system, we found that the C-terminal region of ErbB-4 interacts with the three related membrane-associated guanylate kinases (MAGUKs) PSD-95/SAP90, PSD-93/chapsyn-110, and SAP 102, which harbor three PDZ domains, as well as with β2-syntrophin, which has a single PDZ domain. As with N-methyl-d-aspartate (NMDA) receptors, ErbB4 interacts with the first two PDZ domains of PSD-95. Using coimmunoprecipitation assays, we confirmed the direct interactions between ErbB-4 and PSD-95 in transfected heterologous cells, as well as in vivo, where both proteins are coimmunoprecipitated from brain lysates. Moreover, evidence for colocalization of these proteins was also observed by immunofluorescence in cultured hippocampal neurons. ErbB-4 colocalizes with PSD-95 and NMDA receptors at a subset of excitatory synapses apposed to synaptophysin-positive presynaptic terminals. The capacity of ErbB receptors to interact with PDZ-domain proteins at cell junctions is conserved from invertebrates to mammals. As discussed, the interactions found between receptor tyrosine kinases and MAGUKs at neuronal synapses may have important implications for activity-dependent plasticity. PMID:10725395

  4. Low voltage-activated calcium channels gate transmitter release at the dorsal root ganglion sandwich synapse.

    Science.gov (United States)

    Rozanski, Gabriela M; Nath, Arup R; Adams, Michael E; Stanley, Elise F

    2013-11-15

    A subpopulation of dorsal root ganglion (DRG) neurons are intimately attached in pairs and separated solely by thin satellite glial cell membrane septa. Stimulation of one neuron leads to transglial activation of its pair by a bi-, purinergic/glutamatergic synaptic pathway, a transmission mechanism that we term sandwich synapse (SS) transmission. Release of ATP from the stimulated neuron can be attributed to a classical mechanism involving Ca(2+) entry via voltage-gated calcium channels (CaV) but via an unknown channel type. Specific blockers and toxins ruled out CaV1, 2.1 and 2.2. Transmission was, however, blocked by a moderate depolarization (-50 mV) or low-concentration Ni(2+) (0.1 mM). Transmission persisted using a voltage pulse to -40 mV from a holding potential of -80 mV, confirming the involvement of a low voltage-activated channel type and limiting the candidate channel type to either CaV3.2 or a subpopulation of inactivation- and Ni(2+)-sensitive CaV2.3 channels. Resistance of the neuron calcium current and SS transmission to SNX482 argue against the latter. Hence, we conclude that inter-somatic transmission at the DRG SS is gated by CaV3.2 type calcium channels. The use of CaV3 family channels to gate transmission has important implications for the biological function of the DRG SS as information transfer would be predicted to occur not only in response to action potentials but also to sub-threshold membrane voltage oscillations. Thus, the SS synapse may serve as a homeostatic signalling mechanism between select neurons in the DRG and could play a role in abnormal sensation such as neuropathic pain.

  5. Applications of nonlinear fiber optics

    CERN Document Server

    Agrawal, Govind

    2008-01-01

    * The only book describing applications of nonlinear fiber optics * Two new chapters on the latest developments: highly nonlinear fibers and quantum applications* Coverage of biomedical applications* Problems provided at the end of each chapterThe development of new highly nonlinear fibers - referred to as microstructured fibers, holey fibers and photonic crystal fibers - is the next generation technology for all-optical signal processing and biomedical applications. This new edition has been thoroughly updated to incorporate these key technology developments.The bo

  6. Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus

    Science.gov (United States)

    Kitahara, Yosuke; Ohta, Keisuke; Hasuo, Hiroshi; Shuto, Takahide; Kuroiwa, Mahomi; Sotogaku, Naoki; Togo, Akinobu; Nakamura, Kei-ichiro; Nishi, Akinori

    2016-01-01

    A selective serotonin reuptake inhibitor is the most commonly prescribed antidepressant for the treatment of major depression. However, the mechanisms underlying the actions of selective serotonin reuptake inhibitors are not fully understood. In the dentate gyrus, chronic fluoxetine treatment induces increased excitability of mature granule cells (GCs) as well as neurogenesis. The major input to the dentate gyrus is the perforant path axons (boutons) from the entorhinal cortex (layer II). Through voltage-sensitive dye imaging, we found that the excitatory neurotransmission of the perforant path synapse onto the GCs in the middle molecular layer of the mouse dentate gyrus (perforant path-GC synapse) is enhanced after chronic fluoxetine treatment (15 mg/kg/day, 14 days). Therefore, we further examined whether chronic fluoxetine treatment affects the morphology of the perforant path-GC synapse, using FIB/SEM (focused ion beam/scanning electron microscopy). A three-dimensional reconstruction of dendritic spines revealed the appearance of extremely large-sized spines after chronic fluoxetine treatment. The large-sized spines had a postsynaptic density with a large volume. However, chronic fluoxetine treatment did not affect spine density. The presynaptic boutons that were in contact with the large-sized spines were large in volume, and the volumes of the mitochondria and synaptic vesicles inside the boutons were correlated with the size of the boutons. Thus, the large-sized perforant path-GC synapse induced by chronic fluoxetine treatment contains synaptic components that correlate with the synapse size and that may be involved in enhanced glutamatergic neurotransmission. PMID:26788851

  7. Multimode optical fiber

    Science.gov (United States)

    Bigot-Astruc, Marianne; Molin, Denis; Sillard, Pierre

    2014-11-04

    A depressed graded-index multimode optical fiber includes a central core, an inner depressed cladding, a depressed trench, an outer depressed cladding, and an outer cladding. The central core has an alpha-index profile. The depressed claddings limit the impact of leaky modes on optical-fiber performance characteristics (e.g., bandwidth, core size, and/or numerical aperture).

  8. Fiber Lasers V

    DEFF Research Database (Denmark)

    Hansen, Kim P.; Olausson, Christina Bjarnal Thulin; Broeng, Jes

    2008-01-01

    laser system. We present the latest advancements within airclad fiber technology including a new 70 μm single-mode polarization-maintaining rod-type fiber capable of amplifying to MW power levels. Furthermore we describe the novel airclad based pump combiners and their use in a completely monolithic 350...

  9. Fiber Sensor Technology Today

    Science.gov (United States)

    Hotate, Kazuo

    2006-08-01

    Fiber sensor technologies are overviewed. Since the early 1970s, this field has been developed, on the basis of the same devices and photonic principles as fiber communication technologies. Besides simple configurations, in which the fiber acts only as a data transmission line, sophisticated configurations have also been developed, in which the fiber is used as a device to realize unique sensing mechanisms. The fiber optic gyroscope (FOG) is a good example, and has been developed as an absolute rotation sensor used, for example, for navigation and/or attitude control applications. Compared with traditional spinning-mass gyroscopes, the FOG has advantages, such as a short warming-up time, a light weight, and easy handling. A Japanese satellite, which was launched in August 2005 with a mission to observe the aurora, is controlled with a FOG. The FOG has also been used in consumer applications, such as the camera stabilizer, radio-controlled (RC) helicopter navigation, and the control of humanoid robots. Recently, distributed and multiplexed sensing schemes, in particular, have been studied and developed, in which a long fiber acts like a “nerve” for feeling the strain and/or the temperature distribution along the fiber. Performances of artificial nerve systems have markedly improved within the last couple of years, in spatial resolution and measurement speed. By embedding the “fiber-optic nerve system” in aircraft wings, bridges and tall buildings, these materials and structures can sense damage to prevent disasters.

  10. Ways to Boost Fiber

    Science.gov (United States)

    ... can help to lower cholesterol. Third, it helps prevent constipation and diverticulosis. And fourth, adequate fiber from food ... is similar to a new sponge; it needs water to plump up pass smoothly. If you ... or constipation. Before you reach for the fiber supplements, consider ...

  11. Quartz fiber calorimeter

    International Nuclear Information System (INIS)

    Akchurin, N.; Doulas, S.; Ganel, O.; Gershtein, Y.; Gavrilov, V.; Kolosov, V.; Kuleshov, S.; Litvinsev, D.; Merlo, J.-P.; Onel, Y.; Osborne, D.; Rosowsky, A.; Stolin, V.; Sulak, L.; Sullivan, J.; Ulyanov, A.; Wigmans, R.; Winn, D.

    1996-01-01

    A calorimeter with optical quartz fibers embedded into an absorber matrix was proposed for the small angle region of the CMS detector at LHC (CERN). This type of calorimeter is expected to be radiation hard and to produce extremely fast signal. Some results from beam tests of the quartz fiber calorimeter prototype are presented. (orig.)

  12. High-density multicore fibers

    DEFF Research Database (Denmark)

    Takenaga, K.; Matsuo, S.; Saitoh, K.

    2016-01-01

    High-density single-mode multicore fibers were designed and fabricated. A heterogeneous 30-core fiber realized a low crosstalk of −55 dB. A quasi-single-mode homogeneous 31-core fiber attained the highest core count as a single-mode multicore fiber.......High-density single-mode multicore fibers were designed and fabricated. A heterogeneous 30-core fiber realized a low crosstalk of −55 dB. A quasi-single-mode homogeneous 31-core fiber attained the highest core count as a single-mode multicore fiber....

  13. A map of brain neuropils and fiber systems in the ant Cardiocondyla obscurior

    Directory of Open Access Journals (Sweden)

    Joris eBressan

    2015-02-01

    Full Text Available A wide spectrum of occupied ecological niches and spectacular morphological adaptations make social insects a prime object for comparative neuroanatomical studies. Eusocial insects have evolved complex societies based on caste polyphenism. A diverse behavioral repertoire of morphologically distinct castes of the same species requires a high degree of plasticity in the central nervous system. We have analyzed the central brain neuropils and fiber tract systems of the worker of the ant Cardiocondyla obscurior, a model for the study of social traits. Our analysis is based on whole mount preparations of adult brains labeled with an antibody against Drosophila-Synapsin, which cross-reacts strongly with synapses in Cardiocondyla. Neuropil compartments stand out as domains with a certain texture and intensity of the anti-Synapsin signal. By contrast, fiber tracts, which are composed of bundles of axons accompanied by glia and are devoid of synapses, appear as channels or sheaths with low anti-Synapsin signal. We have generated a digital 3D atlas of the Cardiocondyla brain neuropil. The atlas provides a reference for future studies of brain polymorphisms in distinct castes, brain development or localization of neurotransmitter systems.

  14. A map of brain neuropils and fiber systems in the ant Cardiocondyla obscurior.

    Science.gov (United States)

    Bressan, Joris M A; Benz, Martin; Oettler, Jan; Heinze, Jürgen; Hartenstein, Volker; Sprecher, Simon G

    2014-01-01

    A wide spectrum of occupied ecological niches and spectacular morphological adaptations make social insects a prime object for comparative neuroanatomical studies. Eusocial insects have evolved complex societies based on caste polyphenism. A diverse behavioral repertoire of morphologically distinct castes of the same species requires a high degree of plasticity in the central nervous system. We have analyzed the central brain neuropils and fiber tract systems of the worker of the ant Cardiocondyla obscurior, a model for the study of social traits. Our analysis is based on whole mount preparations of adult brains labeled with an antibody against Drosophila-Synapsin, which cross-reacts strongly with synapses in Cardiocondyla. Neuropil compartments stand out as domains with a certain texture and intensity of the anti-Synapsin signal. By contrast, fiber tracts, which are composed of bundles of axons accompanied by glia and are devoid of synapses, appear as channels or sheaths with low anti-Synapsin signal. We have generated a digital 3D atlas of the Cardiocondyla brain neuropil. The atlas provides a reference for future studies of brain polymorphisms in distinct castes, brain development or localization of neurotransmitter systems.

  15. Green insulation: hemp fibers

    Energy Technology Data Exchange (ETDEWEB)

    Anon,

    2011-09-15

    Indian hemp (Cannabis indica) is known for its psychotropic values and it is banned in most countries. However, industrial hemp (Cannabis sativa) is known for its tough fibers. Several manufactures in Europe including, small niche players, have been marketing hemp insulation products for several years. Hemp is a low environmental impact material. Neither herbicide nor pesticide is used during the growth of hemp. The fibers are extracted in a waste-free and chemical-free mechanical process. Hemp can consume CO2 during its growth. In addition, hemp fiber can be disposed of harmlessly by composting or incineration at the end of its life. Hemp fibers are processed and treated only minimally to resist rot and fungal activity. There is little health risk when producing and installing the insulation, thanks to the absence of toxic additive. Its thermal resistance is comparable to mineral wool. But the development and marketing of hemp fibers may be restricted in North America.

  16. Raman fiber lasers

    CERN Document Server

    2017-01-01

    This book serves as a comprehensive, up-to-date reference about this cutting-edge laser technology and its many new and interesting developments. Various aspects and trends of Raman fiber lasers are described in detail by experts in their fields. Raman fiber lasers have progressed quickly in the past decade, and have emerged as a versatile laser technology for generating high power light sources covering a spectral range from visible to mid-infrared. The technology is already being applied in the fields of telecommunication, astronomy, cold atom physics, laser spectroscopy, environmental sensing, and laser medicine. This book covers various topics relating to Raman fiber laser research, including power scaling, cladding and diode pumping, cascade Raman shifting, single frequency operation and power amplification, mid-infrared laser generation, specialty optical fibers, and random distributed feedback Raman fiber lasers. The book will appeal to scientists, students, and technicians seeking to understand the re...

  17. Birefringent hollow core fibers

    DEFF Research Database (Denmark)

    Roberts, John

    2007-01-01

    Hollow core photonic crystal fiber (HC-PCF), fabricated according to a nominally non-birefringent design, shows a degree of un-controlled birefringence or polarization mode dispersion far in excess of conventional non polarization maintaining fibers. This can degrade the output pulse in many...... applications, and places emphasis on the development of polarization maintaining (PM) HC-PCF. The polarization cross-coupling characteristics of PM HC-PCF are very different from those of conventional PM fibers. The former fibers have the advantage of suffering far less from stress-field fluctuations...... and an increased overlap between the polarization modes at the glass interfaces. The interplay between these effects leads to a wavelength for optimum polarization maintenance, lambda(PM), which is detuned from the wavelength of highest birefringence. By a suitable fiber design involving antiresonance of the core...

  18. Fiber optic hydrophone

    Science.gov (United States)

    Kuzmenko, Paul J.; Davis, Donald T.

    1994-01-01

    A miniature fiber optic hydrophone based on the principles of a Fabry-Perot interferometer. The hydrophone, in one embodiment, includes a body having a shaped flexible bladder at one end which defines a volume containing air or suitable gas, and including a membrane disposed adjacent a vent. An optic fiber extends into the body with one end terminating in spaced relation to the membrane. Acoustic waves in the water that impinge on the bladder cause the pressure of the volume therein to vary causing the membrane to deflect and modulate the reflectivity of the Fabry-Perot cavity formed by the membrane surface and the cleaved end of the optical fiber disposed adjacent to the membrane. When the light is transmitted down the optical fiber, the reflected signal is amplitude modulated by the incident acoustic wave. Another embodiment utilizes a fluid filled volume within which the fiber optic extends.

  19. Method for the preparation of carbon fiber from polyolefin fiber precursor, and carbon fibers made thereby

    Science.gov (United States)

    Naskar, Amit Kumar; Hunt, Marcus Andrew; Saito, Tomonori

    2015-08-04

    Methods for the preparation of carbon fiber from polyolefin fiber precursor, wherein the polyolefin fiber precursor is partially sulfonated and then carbonized to produce carbon fiber. Methods for producing hollow carbon fibers, wherein the hollow core is circular- or complex-shaped, are also described. Methods for producing carbon fibers possessing a circular- or complex-shaped outer surface, which may be solid or hollow, are also described.

  20. Fiber Pulling Apparatus

    Science.gov (United States)

    Workman, Gary L.; Smith, Guy A.; OBrien, Sue; Adcock, Leonard

    1998-01-01

    The fiber optics industry has grown into a multi-billion marketplace that will continue to grow into the 21st century. Optical fiber communications is currently dominated by silica glass technology. Successful efforts to improve upon the low loss transmission characteristics of silica fibers have propelled the technology into the forefront of the communications industry. However, reaching the theoretical transmission capability of silica fiber through improved processing has still left a few application areas in which other fiber systems can provide an influential role due to specific characteristics of high theoretical transmission in the 2 - 3 micron wavelength region. One of the other major materials used for optical fibers is the systems based upon Heavy Metal Fluoride Glass (HMFG). Commercial interest is driven primarily by the potential for low loss repeaterless infrared fibers. An example of the major communications marketplace which would benefit from the long distance repeaterless capability of infrared fibers is the submarine cables which link the continents. When considering commercial interests, optical fiber systems provide a healthy industrial position which continues to expand. Major investments in the systems used for optical fiber communications have continued to increase each year and are predicted to continue well into the next century. Estimates of 8.5% compounded annually are predicted through 1999 for the North American market and 1 1 % worldwide. The growth for the optical fiber cable itself is expected to continue between 44 and 50 per cent of the optical fiber communications budget through 1999. The total budget in 1999 world-wide is expected to be in the neighborhood of $9 billion. Another survey predicts that long haul telecommunications represents 15% of a world-wide fiber optics market in 1998. The actual amount allotted to cable was not specified. However, another market research had predicted that the cable costs alone represents more

  1. Fiber Optic Microphone

    Science.gov (United States)

    Cho, Y. C.; George, Thomas; Norvig, Peter (Technical Monitor)

    1999-01-01

    Research into advanced pressure sensors using fiber-optic technology is aimed at developing compact size microphones. Fiber optic sensors are inherently immune to electromagnetic noise, and are very sensitive, light weight, and highly flexible. In FY 98, NASA researchers successfully designed and assembled a prototype fiber-optic microphone. The sensing technique employed was fiber optic Fabry-Perot interferometry. The sensing head is composed of an optical fiber terminated in a miniature ferrule with a thin, silicon-microfabricated diaphragm mounted on it. The optical fiber is a single mode fiber with a core diameter of 8 micron, with the cleaved end positioned 50 micron from the diaphragm surface. The diaphragm is made up of a 0.2 micron thick silicon nitride membrane whose inner surface is metallized with layers of 30 nm titanium, 30 nm platinum, and 0.2 micron gold for efficient reflection. The active sensing area is approximately 1.5 mm in diameter. The measured differential pressure tolerance of this diaphragm is more than 1 bar, yielding a dynamic range of more than 100 dB.

  2. Persistent Associative Plasticity at an Identified Synapse Underlying Classical Conditioning Becomes Labile with Short-Term Homosynaptic Activation.

    Science.gov (United States)

    Hu, Jiangyuan; Schacher, Samuel

    2015-12-09

    Synapses express different forms of plasticity that contribute to different forms of memory, and both memory and plasticity can become labile after reactivation. We previously reported that a persistent form of nonassociative long-term facilitation (PNA-LTF) of the sensorimotor synapses in Aplysia californica, a cellular analog of long-term sensitization, became labile with short-term heterosynaptic reactivation and reversed when the reactivation was followed by incubation with the protein synthesis inhibitor rapamycin. Here we examined the reciprocal impact of different forms of short-term plasticity (reactivations) on a persistent form of associative long-term facilitation (PA-LTF), a cellular analog of classical conditioning, which was expressed at Aplysia sensorimotor synapses when a tetanic stimulation of the sensory neurons was paired with a brief application of serotonin on 2 consecutive days. The expression of short-term homosynaptic plasticity [post-tetanic potentiation or homosynaptic depression (HSD)], or short-term heterosynaptic plasticity [serotonin-induced facilitation or neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFa)-induced depression], at synapses expressing PA-LTF did not affect the maintenance of PA-LTF. The kinetics of HSD was attenuated at synapses expressing PA-LTF, which required activation of protein kinase C (PKC). Both PA-LTF and the attenuated kinetics of HSD were reversed by either a transient blockade of PKC activity or a homosynaptic, but not heterosynaptic, reactivation when paired with rapamycin. These results indicate that two different forms of persistent synaptic plasticity, PA-LTF and PNA-LTF, expressed at the same synapse become labile when reactivated by different stimuli. Activity-dependent changes in neural circuits mediate long-term memories. Some forms of long-term memories become labile and can be reversed with specific types of reactivations, but the mechanism is complex. At the cellular level, reactivations that induce a

  3. Optical fiber spectrophotometer

    International Nuclear Information System (INIS)

    Zhuang Weixin; Tian Guocheng; Ye Guoan; Zhou Zhihong; Cheng Weiwei; Huang Lifeng; Liu Suying; Tang Yanji; Hu Jingxin; Zhao Yonggang

    1998-12-01

    A method called 'Two Arm's Photo out and Electricity Send-back' is introduced. UV-365 UV/VIS/NIR spectrophotometer has been reequipped by this way with 5 meters long optical fiber. Another method called 'One Arm's Photo out and Photo Send-back' is also introduced. λ 19 UV/VIS/NIR spectrophotometer has been reequipped by this way with 10 meters long optical fiber. Optical fiber spectrophotometer can work as its main set. So it is particularly applicable to radio activity work

  4. Chemistry Research of Optical Fibers.

    Science.gov (United States)

    1982-09-27

    BROADENING IN OPTICAL FIBERS Herbert B. Rosenstock* Naval Research Laboratory Washington, DC 20375 ABSTRACT A light pulse transmitted through a fiber...Marcatili, Marcuse , and Personick, "Dispersion Properties of Fibers" (Ch. 4 in "Optical Fiber Telecommunications," S. E. Miller and A. C. Chynoweth, eds

  5. Robust fiber clustering of cerebral fiber bundles in white matter

    Science.gov (United States)

    Yao, Xufeng; Wang, Yongxiong; Zhuang, Songlin

    2014-11-01

    Diffusion tensor imaging fiber tracking (DTI-FT) has been widely accepted in the diagnosis and treatment of brain diseases. During the rendering pipeline of specific fiber tracts, the image noise and low resolution of DTI would lead to false propagations. In this paper, we propose a robust fiber clustering (FC) approach to diminish false fibers from one fiber tract. Our algorithm consists of three steps. Firstly, the optimized fiber assignment continuous tracking (FACT) is implemented to reconstruct one fiber tract; and then each curved fiber in the fiber tract is mapped to a point by kernel principal component analysis (KPCA); finally, the point clouds of fiber tract are clustered by hierarchical clustering which could distinguish false fibers from true fibers in one tract. In our experiment, the corticospinal tract (CST) in one case of human data in vivo was used to validate our method. Our method showed reliable capability in decreasing the false fibers in one tract. In conclusion, our method could effectively optimize the visualization of fiber bundles and would help a lot in the field of fiber evaluation.

  6. TACTILE STIMULATION EVOKES LONG-LASTING POTENTIATION OF PURKINJE CELL DISCHARGE IN VIVO

    Directory of Open Access Journals (Sweden)

    Ramakrishnan eKanchipuram

    2016-02-01

    Full Text Available In the cerebellar network, a precise relationship between plasticity and neuronal discharge has been predicted. However, the potential generation of persistent changes in PC spike discharge as a consequence of plasticity following natural stimulation patterns has not been clearly determined. Here we show that facial tactile stimuli organized in theta-patterns can induce stereotyped NMDA and GABA-A receptor-dependent changes in Purkinje cell (PCs and molecular layer interneuron (MLIs firing: invariably, all PCs showed a long-lasting increase (spike-related potentiation or SR-P and MLIs a long-lasting decrease (spike-related suppression or SR-S in baseline activity and spike response probability. These observations suggests that natural sensory stimulation engages multiple long-term plastic changes that are distributed along the mossy fiber – parallel fiber pathway and operate synergistically to potentiate spike generation in PCs. In contrast, theta-pattern electrical stimulation of PFs indistinctly induced SR-P and SR-S both in PCs and MLIs, suggesting that natural sensory stimulation preordinates plasticity upstream of the PF-PC synapse. All these effects occurred in the absence of complex spike changes, supporting the theoretical prediction that Purkinje cell activity is potentiated when the mossy fiber - parallel fiber system is activated in the absence of conjunctive climbing fiber activity.

  7. Actin Cytoskeleton-Based Plant Synapse as Gravitransducer in the Transition Zone of the Root Apex

    Science.gov (United States)

    Baluska, Frantisek; Barlow, Peter; Volkmann, Dieter; Mancuso, Stefano

    The actin cytoskeleton was originally proposed to act as the signal transducer in the plant gravity sensory-motoric circuit. Surprisingly, however, several studies have documented that roots perfom gravisensing and gravitropism more effectively if exposed to diverse anti-F-actin drugs. Our study, using decapped maize root apices, has revealed that depolymerization of F-actin stimulates gravity perception in cells of the transition zone where root gravitropism is initiated (Mancuso et al. 2006). It has been proposed (Balǔka et al. 2005, 2009a) that s the non-growing adhesive end-poles, enriched with F-actin and myosin VIII, and active in endocytic recycling of both PIN transporters and cell wall pectins cross-linked with calcium and boron, act as the gravisensing domains, and that these impinge directly upon the root motoric responses via control of polar auxin transport. This model suggests that mechanical asymmetry at these plant synapses determines vectorial gravity-controlled auxin transport. Due to the gravity-imposed mechanical load upon the protoplast, a tensional stress is also imposed upon the plasma membrane of the physically lower synaptic cell pole. This stress is then relieved by shifting the endocytosis-exocytosis balance towards exocytosis (Balǔka et al. s 2005, 2009a,b). This `Synaptic Auxin Secretion' hypothesis does not conflict with the `Starch Statolith' hypothesis, which is based on amyloplast sedimentation. In fact, the `Synaptic Auxin Secretion' hypothesis has many elements which allow its unification with the Starch-Statolith model (Balǔka et al. 2005, 2009a,b). s References Balǔka F, Volkmann D, Menzel D (2005) Plant synapses: actin-based adhesion s domains for cell-to-cell communication. Trends Plant Sci 10: 106-111 Balǔka F, Schlicht M, s Wan Y-L, Burbach C, Volkmann D (2009a) Intracellular domains and polarity in root apices: from synaptic domains to plant neurobiology. Nova Acta Leopoldina 96: 103-122 Balǔka s F, Mancuso S

  8. Fiber optics standard dictionary

    CERN Document Server

    Weik, Martin H

    1997-01-01

    Fiber Optics Vocabulary Development In 1979, the National Communications System published Technical InfonnationBulle­ tin TB 79-1, Vocabulary for Fiber Optics and Lightwave Communications, written by this author. Based on a draft prepared by this author, the National Communications System published Federal Standard FED-STD-1037, Glossary of Telecommunications Terms, in 1980 with no fiber optics tenns. In 1981, the first edition of this dictionary was published under the title Fiber Optics and Lightwave Communications Standard Dictionary. In 1982, the then National Bureau of Standards, now the National Institute of Standards and Technology, published NBS Handbook 140, Optical Waveguide Communications Glossary, which was also published by the General Services Admin­ istration as PB82-166257 under the same title. Also in 1982, Dynamic Systems, Inc. , Fiberoptic Sensor Technology Handbook, co-authored and edited by published the this author, with an extensive Fiberoptic Sensors Glossary. In 1989, the handbook w...

  9. Fiber Optics: No Illusion.

    Science.gov (United States)

    American School and University, 1983

    1983-01-01

    A campus computer center at Hofstra University (New York) that holds 70 terminals for student use was first a gymnasium, then a language laboratory. Strands of fiber optics are used for the necessary wiring. (MLF)

  10. Fiber optic gas sensor

    Science.gov (United States)

    Chen, Peng (Inventor); Buric, Michael P. (Inventor); Swinehart, Philip R. (Inventor); Maklad, Mokhtar S. (Inventor)

    2010-01-01

    A gas sensor includes an in-fiber resonant wavelength device provided in a fiber core at a first location. The fiber propagates a sensing light and a power light. A layer of a material is attached to the fiber at the first location. The material is able to absorb the gas at a temperature dependent gas absorption rate. The power light is used to heat the material and increases the gas absorption rate, thereby increasing sensor performance, especially at low temperatures. Further, a method is described of flash heating the gas sensor to absorb more of the gas, allowing the sensor to cool, thereby locking in the gas content of the sensor material, and taking the difference between the starting and ending resonant wavelengths as an indication of the concentration of the gas in the ambient atmosphere.

  11. Photonic Crystal Fibers

    National Research Council Canada - National Science Library

    Kristiansen, Rene E

    2005-01-01

    This report results from a contract tasking Crystal Fibre A/S as follows: Crystal Fibre will conduct research and development of large mode area, dual clad multi-core Yb-doped photonic crystal fiber...

  12. Fiber Laser Array

    National Research Council Canada - National Science Library

    Simpson, Thomas

    2002-01-01

    ...., field-dependent, loss within the coupled laser array. During this program, Jaycor focused on the construction and use of an experimental apparatus that can be used to investigate the coherent combination of an array of fiber lasers...

  13. Robust Fiber Coatings

    National Research Council Canada - National Science Library

    Goettler, Richard

    2002-01-01

    The highly desired ceramic matrix composite is the one in which the high strength and strain-to-failure is achieved through judicious selection of a fiber coating that can survive the high-temperature...

  14. Fiber Optic Bragg Gratings

    National Research Council Canada - National Science Library

    Battiato, James

    1998-01-01

    Coupled mode theory was used to model reflection fiber gratings. The effects of experimental parameters on grating characteristics were modeled for both uniform and non-uniform grating profiles using this approach...

  15. Cerenkov fiber sampling calorimeters

    International Nuclear Information System (INIS)

    Arrington, K.; Kefford, D.; Kennedy, J.; Pisani, R.; Sanzeni, C.; Segall, K.; Wall, D.; Winn, D.R.; Carey, R.; Dye, S.; Miller, J.; Sulak, L.; Worstell, W.; Efremenko, Y.; Kamyshkov, Y.; Savin, A.; Shmakov, K.; Tarkovsky, E.

    1994-01-01

    Clear optical fibers were used as a Cerenkov sampling media in Pb (electromagnetic) and Cu (hadron) absorbers in spaghetti calorimeters, for high rate and high radiation dose experiments, such as the forward region of high energy colliders. The fiber axes were aligned close to the direction of the incident particles (1 degree--7 degree). The 7 λ deep hadron tower contained 2.8% by volume 1.5 mm diameter core clear plastic fibers. The 27 radiation length deep electromagnetic towers had packing fractions of 6.8% and 7.2% of 1 mm diameter core quartz fibers as the active Cerenkov sampling medium. The energy resolution on electrons and pions, energy response, pulse shapes and angular studies are presented

  16. Fiber optics welder

    Science.gov (United States)

    Higgins, R.W.; Robichaud, R.E.

    A system is described for welding fiber optic waveguides together. The ends of the two fibers to be joined together are accurately, collinearly aligned in a vertical orientation and subjected to a controlled, diffuse arc to effect welding and thermal conditioning. A front-surfaced mirror mounted at a 45/sup 0/ angle to the optical axis of a stereomicroscope mounted for viewing the junction of the ends provides two orthogonal views of the interface during the alignment operation.

  17. A model of microsaccade-related neural responses induced by short-term depression in thalamocortical synapses

    Directory of Open Access Journals (Sweden)

    Wujie eYuan

    2013-04-01

    Full Text Available Microsaccades during fixation have been suggested to counteract visual fading. Recent experi- ments have also observed microsaccade-related neural responses from cellular record, scalp elec- troencephalogram (EEG and functional magnetic resonance imaging (fMRI. The underlying mechanism, however, is not yet understood and highly debated. It has been proposed that the neural activity of primary visual cortex (V1 is a crucial component for counteracting visual adaptation. In this paper, we use computational modeling to investigate how short-term depres- sion (STD in thalamocortical synapses might affect the neural responses of V1 in the presence of microsaccades. Our model not only gives a possible synaptic explanation for microsaccades in counteracting visual fading, but also reproduces several features in experimental findings. These modeling results suggest that STD in thalamocortical synapses plays an important role in microsaccade-related neural responses and the model may be useful for further investigation of behavioral properties and functional roles of microsaccades.

  18. A model of microsaccade-related neural responses induced by short-term depression in thalamocortical synapses

    Science.gov (United States)

    Yuan, Wu-Jie; Dimigen, Olaf; Sommer, Werner; Zhou, Changsong

    2013-01-01

    Microsaccades during fixation have been suggested to counteract visual fading. Recent experiments have also observed microsaccade-related neural responses from cellular record, scalp electroencephalogram (EEG), and functional magnetic resonance imaging (fMRI). The underlying mechanism, however, is not yet understood and highly debated. It has been proposed that the neural activity of primary visual cortex (V1) is a crucial component for counteracting visual adaptation. In this paper, we use computational modeling to investigate how short-term depression (STD) in thalamocortical synapses might affect the neural responses of V1 in the presence of microsaccades. Our model not only gives a possible synaptic explanation for microsaccades in counteracting visual fading, but also reproduces several features in experimental findings. These modeling results suggest that STD in thalamocortical synapses plays an important role in microsaccade-related neural responses and the model may be useful for further investigation of behavioral properties and functional roles of microsaccades. PMID:23630494

  19. Presynaptic learning and memory with a persistent firing neuron and a habituating synapse: a model of short term persistent habituation.

    Science.gov (United States)

    Ramanathan, Kiruthika; Ning, Ning; Dhanasekar, Dhiviya; Li, Guoqi; Shi, Luping; Vadakkepat, Prahlad

    2012-08-01

    Our paper explores the interaction of persistent firing axonal and presynaptic processes in the generation of short term memory for habituation. We first propose a model of a sensory neuron whose axon is able to switch between passive conduction and persistent firing states, thereby triggering short term retention to the stimulus. Then we propose a model of a habituating synapse and explore all nine of the behavioral characteristics of short term habituation in a two neuron circuit. We couple the persistent firing neuron to the habituation synapse and investigate the behavior of short term retention of habituating response. Simulations show that, depending on the amount of synaptic resources, persistent firing either results in continued habituation or maintains the response, both leading to longer recovery times. The effectiveness of the model as an element in a bio-inspired memory system is discussed.

  20. RAE-1, a novel PHR binding protein, is required for axon termination and synapse formation in Caenorhabditis elegans.

    Science.gov (United States)

    Grill, Brock; Chen, Lizhen; Tulgren, Erik D; Baker, Scott T; Bienvenut, Willy; Anderson, Matthew; Quadroni, Manfredo; Jin, Yishi; Garner, Craig C

    2012-02-22

    Previous studies in Caenorhabditis elegans showed that RPM-1 (Regulator of Presynaptic Morphology-1) regulates axon termination and synapse formation. To understand the mechanism of how rpm-1 functions, we have used mass spectrometry to identify RPM-1 binding proteins, and have identified RAE-1 (RNA Export protein-1) as an evolutionarily conserved binding partner. We define a RAE-1 binding region in RPM-1, and show that this binding interaction is conserved and also occurs between Rae1 and the human ortholog of RPM-1 called Pam (protein associated with Myc). rae-1 loss of function causes similar axon and synapse defects, and synergizes genetically with two other RPM-1 binding proteins, GLO-4 and FSN-1. Further, we show that RAE-1 colocalizes with RPM-1 in neurons, and that rae-1 functions downstream of rpm-1. These studies establish a novel postmitotic function for rae-1 in neuronal development.

  1. Size and receptor density of glutamatergic synapses: a viewpoint from left-right asymmetry of CA3-CA1 connections

    Directory of Open Access Journals (Sweden)

    Yoshiaki Shinohara

    2009-07-01

    Full Text Available Synaptic plasticity is considered to be the main mechanism for learning and memory. Excitatory synapses in the cerebral cortex and hippocampus undergo plastic changes during development and in response to electric stimulation. It is widely accepted that this process is mediated by insertion and elimination of various glutamate receptors. In a series of recent investigations on left-right asymmetry of hippocampal CA3-CA1 synapses, glutamate receptor subunits have been found to have distinctive expression patterns that depend on the postsynaptic density (PSD area. Particularly notable are the GluR1 AMPA receptor subunit and NR2B NMDA receptor subunit, where receptor density has either a supra-linear (GluR1 AMPA or inverse (NR2B NMDAR relationship to the PSD area. We review current understanding of structural and physiological synaptic plasticity and propose a scheme to classify receptor subtypes by their expression pattern with respect to PSD area.

  2. Regulation of the Postsynaptic Compartment of Excitatory Synapses by the Actin Cytoskeleton in Health and Its Disruption in Disease

    Directory of Open Access Journals (Sweden)

    Holly Stefen

    2016-01-01

    Full Text Available Disruption of synaptic function at excitatory synapses is one of the earliest pathological changes seen in wide range of neurological diseases. The proper control of the segregation of neurotransmitter receptors at these synapses is directly correlated with the intact regulation of the postsynaptic cytoskeleton. In this review, we are discussing key factors that regulate the structure and dynamics of the actin cytoskeleton, the major cytoskeletal building block that supports the postsynaptic compartment. Special attention is given to the complex interplay of actin-associated proteins that are found in the synaptic specialization. We then discuss our current understanding of how disruption of these cytoskeletal elements may contribute to the pathological events observed in the nervous system under disease conditions with a particular focus on Alzheimer’s disease pathology.

  3. FIBER OPTIC LIGHTING SYSTEMS

    Directory of Open Access Journals (Sweden)

    Munir BATUR

    2013-01-01

    Full Text Available Recently there have been many important and valuable developments in the communication industry. The huge increase in the sound, data and visual communications has caused a parallel increase in the demand for systems with wider capacity, higher speed and higher quality. Communication systems that use light to transfer data are immensely increased. There have recently many systems in which glass or plastic fiber cables were developed for light wave to be transmitted from a source to a target place. Fiber optic systems, are nowadays widely used in energy transmission control systems, medicine, industry and lighting. The basics of the system is, movement of light from one point to another point in fiber cable with reflections. Fiber optic lighting systems are quite secure than other lighting systems and have flexibility for realizing many different designs. This situation makes fiber optics an alternative for other lighting systems. Fiber optic lighting systems usage is increasing day-by-day in our life. In this article, these systems are discussed in detail.

  4. Electrospun amplified fiber optics.

    Science.gov (United States)

    Morello, Giovanni; Camposeo, Andrea; Moffa, Maria; Pisignano, Dario

    2015-03-11

    All-optical signal processing is the focus of much research aiming to obtain effective alternatives to existing data transmission platforms. Amplification of light in fiber optics, such as in Erbium-doped fiber amplifiers, is especially important for efficient signal transmission. However, the complex fabrication methods involving high-temperature processes performed in a highly pure environment slow the fabrication process and make amplified components expensive with respect to an ideal, high-throughput, room temperature production. Here, we report on near-infrared polymer fiber amplifiers working over a band of ∼20 nm. The fibers are cheap, spun with a process entirely carried out at room temperature, and shown to have amplified spontaneous emission with good gain coefficients and low levels of optical losses (a few cm(-1)). The amplification process is favored by high fiber quality and low self-absorption. The found performance metrics appear to be suitable for short-distance operations, and the large variety of commercially available doping dyes might allow for effective multiwavelength operations by electrospun amplified fiber optics.

  5. The effect of STDP temporal kernel structure on the learning dynamics of single excitatory and inhibitory synapses.

    Directory of Open Access Journals (Sweden)

    Yotam Luz

    Full Text Available Spike-Timing Dependent Plasticity (STDP is characterized by a wide range of temporal kernels. However, much of the theoretical work has focused on a specific kernel - the "temporally asymmetric Hebbian" learning rules. Previous studies linked excitatory STDP to positive feedback that can account for the emergence of response selectivity. Inhibitory plasticity was associated with negative feedback that can balance the excitatory and inhibitory inputs. Here we study the possible computational role of the temporal structure of the STDP. We represent the STDP as a superposition of two processes: potentiation and depression. This allows us to model a wide range of experimentally observed STDP kernels, from Hebbian to anti-Hebbian, by varying a single parameter. We investigate STDP dynamics of a single excitatory or inhibitory synapse in purely feed-forward architecture. We derive a mean-field-Fokker-Planck dynamics for the synaptic weight and analyze the effect of STDP structure on the fixed points of the mean field dynamics. We find a phase transition along the Hebbian to anti-Hebbian parameter from a phase that is characterized by a unimodal distribution of the synaptic weight, in which the STDP dynamics is governed by negative feedback, to a phase with positive feedback characterized by a bimodal distribution. The critical point of this transition depends on general properties of the STDP dynamics and not on the fine details. Namely, the dynamics is affected by the pre-post correlations only via a single number that quantifies its overlap with the STDP kernel. We find that by manipulating the STDP temporal kernel, negative feedback can be induced in excitatory synapses and positive feedback in inhibitory. Moreover, there is an exact symmetry between inhibitory and excitatory plasticity, i.e., for every STDP rule of inhibitory synapse there exists an STDP rule for excitatory synapse, such that their dynamics is identical.

  6. A VLSI recurrent network of integrate-and-fire neurons connected by plastic synapses with long-term memory.

    Science.gov (United States)

    Chicca, E; Badoni, D; Dante, V; D'Andreagiovanni, M; Salina, G; Carota, L; Fusi, S; Del Giudice, P

    2003-01-01

    Electronic neuromorphic devices with on-chip, on-line learning should be able to modify quickly the synaptic couplings to acquire information about new patterns to be stored (synaptic plasticity) and, at the same time, preserve this information on very long time scales (synaptic stability). Here, we illustrate the electronic implementation of a simple solution to this stability-plasticity problem, recently proposed and studied in various contexts. It is based on the observation that reducing the analog depth of the synapses to the extreme (bistable synapses) does not necessarily disrupt the performance of the device as an associative memory, provided that 1) the number of neurons is large enough; 2) the transitions between stable synaptic states are stochastic; and 3) learning is slow. The drastic reduction of the analog depth of the synaptic variable also makes this solution appealing from the point of view of electronic implementation and offers a simple methodological alternative to the technological solution based on floating gates. We describe the full custom analog very large-scale integration (VLSI) realization of a small network of integrate-and-fire neurons connected by bistable deterministic plastic synapses which can implement the idea of stochastic learning. In the absence of stimuli, the memory is preserved indefinitely. During the stimulation the synapse undergoes quick temporary changes through the activities of the pre- and postsynaptic neurons; those changes stochastically result in a long-term modification of the synaptic efficacy. The intentionally disordered pattern of connectivity allows the system to generate a randomness suited to drive the stochastic selection mechanism. We check by a suitable stimulation protocol that the stochastic synaptic plasticity produces the expected pattern of potentiation and depression in the electronic network.

  7. Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea.

    Science.gov (United States)

    Barclay, M; Constable, R; James, N R; Thorne, P R; Montgomery, J M

    2016-06-14

    Neural activity during early development is known to alter innervation pathways in the central and peripheral nervous systems. We sought to examine how reduced sound-induced sensory activity in the cochlea affected the consolidation of glutamatergic synapses between inner hair cells (IHC) and the primary auditory neurons as these synapses play a primary role in transmitting sound information to the brain. A unilateral conductive hearing loss was induced prior to the onset of sound-mediated stimulation of the sensory hair cells, by rupturing the tympanic membrane and dislocating the auditory ossicles in the left ear of P11 mice. Auditory brainstem responses at P15 and P21 showed a 40-50-dB increase in thresholds for frequencies 8-32kHz in the dislocated ear relative to the control ear. Immunohistochemistry and confocal microscopy were subsequently used to examine the effect of this attenuation of sound stimulation on the expression of RIBEYE, which comprises the presynaptic ribbons, Shank-1, a postsynaptic scaffolding protein, and the GluA2/3 and 4 subunits of postsynaptic AMPA receptors. Our results show that dislocation did not alter the number of pre- or postsynaptic protein puncta. However, dislocation did increase the size of RIBEYE, GluA4, GluA2/3 and Shank-1 puncta, with postsynaptic changes preceding presynaptic changes. Our data suggest that a reduction in sound stimulation during auditory development induces plasticity in the molecular make-up of IHC glutamatergic synapses, but does not affect the number of these synapses. Up-regulation of synaptic proteins with sound attenuation may facilitate a compensatory increase in synaptic transmission due to the reduced sensory stimulation of the IHC. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Genetic targeting of NRXN2 in mice unveils role in excitatory cortical synapse function and social behaviors

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    Gesche eBorn

    2015-02-01

    Full Text Available Human genetics has identified rare copy number variations and deleterious mutations for all neurexin genes (NRXN1-3 in patients with neurodevelopmental diseases, and electrophysiological recordings in animal brains have shown that Nrxns are important for synaptic transmission. While several mouse models for Nrxn1α inactivation have previously been studied for behavioral changes, very little information is available for other variants. Here, we validate that mice lacking Nrxn2α exhibit behavioral abnormalities, characterized by social interaction deficits and increased anxiety-like behavior, which partially overlap, partially differ from Nrxn1α mutant behaviors. Using patch-clamp recordings in Nrxn2α knockout brains, we observe reduced spontaneous transmitter release at excitatory synapses in the neocortex. We also analyse at this cellular level a novel NRXN2 mouse model that carries a combined deletion of Nrxn2α and Nrxn2β. Electrophysiological analysis of this Nrxn2-mutant mouse shows surprisingly similar defects of excitatory release to Nrxn2α, indicating that the β-variant of Nrxn2 has no strong function in basic transmission at these synapses. Inhibitory transmission as well as synapse densities and ultrastructure remain unchanged in the neocortex of both models. Furthermore, at Nrxn2α and Nrxn2-mutant excitatory synapses we find an altered facilitation and N-methyl-D-aspartate receptor (NMDAR function because NMDAR-dependent decay time and NMDAR-mediated responses are reduced. As Nrxn can indirectly be linked to NMDAR via neuroligin and PSD-95, the trans-synaptic nature of this complex may help to explain occurrence of presynaptic and postsynaptic effects. Since excitatory/inhibitory imbalances and impairment of NMDAR function are alledged to have a role in autism and schizophrenia, our results support the idea of a related pathomechanism in these disorders.

  9. Mother Centriole Distal Appendages Mediate Centrosome Docking at the Immunological Synapse and Reveal Mechanistic Parallels with Ciliogenesis.

    Science.gov (United States)

    Stinchcombe, Jane C; Randzavola, Lyra O; Angus, Karen L; Mantell, Judith M; Verkade, Paul; Griffiths, Gillian M

    2015-12-21

    Cytotoxic T lymphocytes (CTLs) are highly effective serial killers capable of destroying virally infected and cancerous targets by polarized release from secretory lysosomes. Upon target contact, the CTL centrosome rapidly moves to the immunological synapse, focusing microtubule-directed release at this point [1-3]. Striking similarities have been noted between centrosome polarization at the synapse and basal body docking during ciliogenesis [1, 4-8], suggesting that CTL centrosomes might dock with the plasma membrane during killing, in a manner analogous to primary cilia formation [1, 4]. However, questions remain regarding the extent and function of centrosome polarization at the synapse, and recent reports have challenged its role [9, 10]. Here, we use high-resolution transmission electron microscopy (TEM) tomography analysis to show that, as in ciliogenesis, the distal appendages of the CTL mother centriole contact the plasma membrane directly during synapse formation. This is functionally important as small interfering RNA (siRNA) targeting of the distal appendage protein, Cep83, required for membrane contact during ciliogenesis [11], impairs CTL secretion. Furthermore, the regulatory proteins CP110 and Cep97, which must dissociate from the mother centriole to allow cilia formation [12], remain associated with the mother centriole in CTLs, and neither axoneme nor transition zone ciliary structures form. Moreover, complete centrosome docking can occur in proliferating CTLs with multiple centriole pairs. Thus, in CTLs, centrosomes dock transiently with the membrane, within the cell cycle and without progression into ciliogenesis. We propose that this transient centrosome docking without cilia formation is important for CTLs to deliver rapid, repeated polarized secretion directed by the centrosome. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Continuous Natural Fiber Reinforced Thermoplastic Composites by Fiber Surface Modification

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    Patcharat Wongsriraksa

    2013-01-01

    Full Text Available Continuous natural fiber reinforced thermoplastic materials are expected to replace inorganic fiber reinforced thermosetting materials. However, in the process of fabricating the composite, it is difficult to impregnate the thermoplastic resin into reinforcement fiber because of the high melt viscosity. Therefore, intermediate material, which allows high impregnation during molding, has been investigated for fabricating continuous fiber reinforced thermoplastic composite by aligning resin fiber alongside reinforcing fiber with braiding technique. This intermediate material has been called “microbraid yarn (MBY.” Moreover, it is well known that the interfacial properties between natural fiber and resin are low; therefore, surface treatment on continuous natural fiber was performed by using polyurethane (PU and flexible epoxy (FLEX to improve the interfacial properties. The effect of surface treatment on the mechanical properties of continuous natural fiber reinforced thermoplastic composites was examined. From these results, it was suggested that surface treatment by PU with low content could produce composites with better mechanical properties.

  11. Phencyclidine-induced Loss of Asymmetric Spine Synapses in Rodent Prefrontal Cortex is Reversed by Acute and Chronic Treatment with Olanzapine

    Science.gov (United States)

    Elsworth, John D; Morrow, Bret A; Hajszan, Tibor; Leranth, Csaba; Roth, Robert H

    2011-01-01

    Enduring cognitive deficits exist in schizophrenic patients, long-term abusers of phencyclidine (PCP), as well as in animal PCP models of schizophrenia. It has been suggested that cognitive performance and memory processes are coupled with remodeling of pyramidal dendritic spine synapses in prefrontal cortex (PFC), and that reduced spine density and number of spine synapses in the medial PFC of PCP-treated rats may potentially underlie, at least partially, the cognitive dysfunction previously observed in this animal model. The present data show that the decrease in number of asymmetric (excitatory) spine synapses in layer II/III of PFC, previously noted at 1-week post PCP treatment also occurs, to a lesser degree, in layer V. The decrease in the number of spine synapses in layer II/III was sustained and persisted for at least 4 weeks, paralleling the observed cognitive deficits. Both acute and chronic treatment with the atypical antipsychotic drug, olanzapine, starting at 1 week after PCP treatment at doses that restore cognitive function, reversed the asymmetric spine synapse loss in PFC of PCP-treated rats. Olanzapine had no significant effect on spine synapse number in saline-treated controls. These studies demonstrate that the effect of PCP on asymmetric spine synapse number in PFC lasts at least 4 weeks in this model. This spine synapse loss in PFC is reversed by acute treatment with olanzapine, and this reversal is maintained by chronic oral treatment, paralleling the time course of the restoration of the dopamine deficit, and normalization of cognitive function produced by olanzapine. PMID:21677652

  12. DISC1, PDE4B, and NDE1 at the centrosome and synapse

    International Nuclear Information System (INIS)

    Bradshaw, Nicholas J.; Ogawa, Fumiaki; Antolin-Fontes, Beatriz; Chubb, Jennifer E.; Carlyle, Becky C.; Christie, Sheila; Claessens, Antoine; Porteous, David J.; Millar, J. Kirsty

    2008-01-01

    Disrupted-In-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and other major mental illnesses. Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D). We demonstrate that NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. LIS1 and NDEL1 have been previously suggested to be synaptic, and we now demonstrate localisation of DISC1, NDE1, and PDE4B at synapses in cultured neurons. NDE1 is phosphorylated by cAMP-dependant Protein Kinase A (PKA), whose activity is, in turn, regulated by the cAMP hydrolysis activity of phosphodiesterases, including PDE4. We propose that DISC1 acts as an assembly scaffold for all of these proteins and that the NDE1/NDEL1/LIS1/dynein complex is modulated by cAMP levels via PKA and PDE4.

  13. Imaging Polarized Secretory Traffic at the Immune Synapse in Living T Lymphocytes.

    Science.gov (United States)

    Calvo, Víctor; Izquierdo, Manuel

    2018-01-01

    Immune synapse (IS) formation by T lymphocytes constitutes a crucial event involved in antigen-specific, cellular and humoral immune responses. After IS formation by T lymphocytes and antigen-presenting cells, the convergence of secretory vesicles toward the microtubule-organizing center (MTOC) and MTOC polarization to the IS are involved in polarized secretion at the synaptic cleft. This specialized mechanism appears to specifically provide the immune system with a fine strategy to increase the efficiency of crucial secretory effector functions of T lymphocytes, while minimizing non-specific, cytokine-mediated stimulation of bystander cells, target cell killing and activation-induced cell death. The molecular bases involved in the polarized secretory traffic toward the IS in T lymphocytes have been the focus of interest, thus different models and several imaging strategies have been developed to gain insights into the mechanisms governing directional secretory traffic. In this review, we deal with the most widely used, state-of-the-art approaches to address the molecular mechanisms underlying this crucial, immune secretory response.

  14. Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic Synapses.

    Directory of Open Access Journals (Sweden)

    Gabriel Koch Ocker

    2015-08-01

    Full Text Available The synaptic connectivity of cortical networks features an overrepresentation of certain wiring motifs compared to simple random-network models. This structure is shaped, in part, by synaptic plasticity that promotes or suppresses connections between neurons depending on their joint spiking activity. Frequently, theoretical studies focus on how feedforward inputs drive plasticity to create this network structure. We study the complementary scenario of self-organized structure in a recurrent network, with spike timing-dependent plasticity driven by spontaneous dynamics. We develop a self-consistent theory for the evolution of network structure by combining fast spiking covariance with a slow evolution of synaptic weights. Through a finite-size expansion of network dynamics we obtain a low-dimensional set of nonlinear differential equations for the evolution of two-synapse connectivity motifs. With this theory in hand, we explore how the form of the plasticity rule drives the evolution of microcircuits in cortical networks. When potentiation and depression are in approximate balance, synaptic dynamics depend on weighted divergent, convergent, and chain motifs. For additive, Hebbian STDP these motif interactions create instabilities in synaptic dynamics that either promote or suppress the initial network structure. Our work provides a consistent theoretical framework for studying how spiking activity in recurrent networks interacts with synaptic plasticity to determine network structure.

  15. Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic Synapses.

    Science.gov (United States)

    Ocker, Gabriel Koch; Litwin-Kumar, Ashok; Doiron, Brent

    2015-08-01

    The synaptic connectivity of cortical networks features an overrepresentation of certain wiring motifs compared to simple random-network models. This structure is shaped, in part, by synaptic plasticity that promotes or suppresses connections between neurons depending on their joint spiking activity. Frequently, theoretical studies focus on how feedforward inputs drive plasticity to create this network structure. We study the complementary scenario of self-organized structure in a recurrent network, with spike timing-dependent plasticity driven by spontaneous dynamics. We develop a self-consistent theory for the evolution of network structure by combining fast spiking covariance with a slow evolution of synaptic weights. Through a finite-size expansion of network dynamics we obtain a low-dimensional set of nonlinear differential equations for the evolution of two-synapse connectivity motifs. With this theory in hand, we explore how the form of the plasticity rule drives the evolution of microcircuits in cortical networks. When potentiation and depression are in approximate balance, synaptic dynamics depend on weighted divergent, convergent, and chain motifs. For additive, Hebbian STDP these motif interactions create instabilities in synaptic dynamics that either promote or suppress the initial network structure. Our work provides a consistent theoretical framework for studying how spiking activity in recurrent networks interacts with synaptic plasticity to determine network structure.

  16. Cell Biological Mechanisms of Activity-Dependent Synapse to Nucleus Translocation of CRTC1 in Neurons

    Directory of Open Access Journals (Sweden)

    Toh Hean eCh'ng

    2015-09-01

    Full Text Available Previous studies have revealed a critical role for CREB-regulated transcriptional coactivator (CRTC1 in regulating neuronal gene expression during learning and memory. CRTC1 localizes to synapses but undergoes activity-dependent nuclear translocation to regulate the transcription of CREB target genes. Here we investigate the long-distance retrograde transport of CRTC1 in hippocampal neurons. We show that local elevations in calcium, triggered by activation of synaptic glutamate receptors and L-type voltage-gated calcium channels, initiate active, dynein-mediated retrograde transport of CRTC1 along microtubules. We identify a nuclear localization signal within CRTC1, and characterize three conserved serine residues whose dephosphorylation is required for nuclear import. Domain analysis reveals that the amino-terminal third of CRTC1 contains all of the signals required for regulated nucleocytoplasmic trafficking. We fuse this region to Dendra2 to generate a reporter construct and perform live-cell imaging coupled with local uncaging of glutamate and photoconversion to characterize the dynamics of stimulus-induced retrograde transport and nuclear accumulation.

  17. The adaptor molecule SAP plays essential roles during invariant NKT cell cytotoxicity and lytic synapse formation.

    Science.gov (United States)

    Das, Rupali; Bassiri, Hamid; Guan, Peng; Wiener, Susan; Banerjee, Pinaki P; Zhong, Ming-Chao; Veillette, André; Orange, Jordan S; Nichols, Kim E

    2013-04-25

    The adaptor molecule signaling lymphocytic activation molecule-associated protein (SAP) plays critical roles during invariant natural killer T (iNKT) cell ontogeny. As a result, SAP-deficient humans and mice lack iNKT cells. The strict developmental requirement for SAP has made it difficult to discern its possible involvement in mature iNKT cell functions. By using temporal Cre recombinase-mediated gene deletion to ablate SAP expression after completion of iNKT cell development, we demonstrate that SAP is essential for T-cell receptor (TCR)-induced iNKT cell cytotoxicity against T-cell and B-cell leukemia targets in vitro and iNKT-cell-mediated control of T-cell leukemia growth in vivo. These findings are not restricted to the murine system: silencing RNA-mediated suppression of SAP expression in human iNKT cells also significantly impairs TCR-induced cytolysis. Mechanistic studies reveal that iNKT cell killing requires the tyrosine kinase Fyn, a known SAP-binding protein. Furthermore, SAP expression is required within iNKT cells to facilitate their interaction with T-cell targets and induce reorientation of the microtubule-organizing center to the immunologic synapse (IS). Collectively, these studies highlight a novel and essential role for SAP during iNKT cell cytotoxicity and formation of a functional IS.

  18. Taurine Induces Proliferation of Neural Stem Cells and Synapse Development in the Developing Mouse Brain

    Science.gov (United States)

    Shivaraj, Mattu Chetana; Marcy, Guillaume; Low, Guoliang; Ryu, Jae Ryun; Zhao, Xianfeng; Rosales, Francisco J.; Goh, Eyleen L. K.

    2012-01-01

    Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC) proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5) hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems. PMID:22916184

  19. Multiple proviral integration events after virological synapse-mediated HIV-1 spread

    International Nuclear Information System (INIS)

    Russell, Rebecca A.; Martin, Nicola; Mitar, Ivonne; Jones, Emma; Sattentau, Quentin J.

    2013-01-01

    HIV-1 can move directly between T cells via virological synapses (VS). Although aspects of the molecular and cellular mechanisms underlying this mode of spread have been elucidated, the outcomes for infection of the target cell remain incompletely understood. We set out to determine whether HIV-1 transfer via VS results in productive, high-multiplicity HIV-1 infection. We found that HIV-1 cell-to-cell spread resulted in nuclear import of multiple proviruses into target cells as seen by fluorescence in-situ hybridization. Proviral integration into the target cell genome was significantly higher than that seen in a cell-free infection system, and consequent de novo viral DNA and RNA production in the target cell detected by quantitative PCR increased over time. Our data show efficient proviral integration across VS, implying the probability of multiple integration events in target cells that drive productive T cell infection. - Highlights: • Cell-to-cell HIV-1 infection delivers multiple vRNA copies to the target cell. • Cell-to-cell infection results in productive infection of the target cell. • Cell-to-cell transmission is more efficient than cell-free HIV-1 infection. • Suggests a mechanism for recombination in cells infected with multiple viral genomes

  20. Real-Time Million-Synapse Simulation of Rat Barrel Cortex

    Directory of Open Access Journals (Sweden)

    Thomas eSharp

    2014-05-01

    Full Text Available Simulations of neural circuits are bounded in scale and speed by available computing resources, and particularly by the differences in parallelism and communication patterns between the brain and high-performance computers. SpiNNaker is a computer architecture designed to address this problem by emulating the structure and function of neural tissue, using very many low-power processors and an interprocessor communication mechanism inspired by axonal arbors. Here we demonstrate that thousand-processor SpiNNaker prototypes can simulate models of the rodent barrel system comprising fifty thousand neurons and fifty million synapses. We use the PyNN library to specify models, and the intrinsic features of Python to control experimental procedures and analysis. The models reproduce known thalamocortical response transformations, exhibit known, balanced dynamics of excitation and inhibition, and show a spatiotemporal spread of activity though the superficial cortical layers. These demonstrations are a significant step towards tractable simulations of entire cortical areas on the million-processor SpiNNaker machines in development.

  1. Real-time million-synapse simulation of rat barrel cortex.

    Science.gov (United States)

    Sharp, Thomas; Petersen, Rasmus; Furber, Steve

    2014-01-01

    Simulations of neural circuits are bounded in scale and speed by available computing resources, and particularly by the differences in parallelism and communication patterns between the brain and high-performance computers. SpiNNaker is a computer architecture designed to address this problem by emulating the structure and function of neural tissue, using very many low-power processors and an interprocessor communication mechanism inspired by axonal arbors. Here we demonstrate that thousand-processor SpiNNaker prototypes can simulate models of the rodent barrel system comprising 50,000 neurons and 50 million synapses. We use the PyNN library to specify models, and the intrinsic features of Python to control experimental procedures and analysis. The models reproduce known thalamocortical response transformations, exhibit known, balanced dynamics of excitation and inhibition, and show a spatiotemporal spread of activity though the superficial cortical layers. These demonstrations are a significant step toward tractable simulations of entire cortical areas on the million-processor SpiNNaker machines in development.

  2. IGF-1 Receptor Differentially Regulates Spontaneous and Evoked Transmission via Mitochondria at Hippocampal Synapses

    Science.gov (United States)

    Gazit, Neta; Vertkin, Irena; Shapira, Ilana; Helm, Martin; Slomowitz, Edden; Sheiba, Maayan; Mor, Yael; Rizzoli, Silvio; Slutsky, Inna

    2016-01-01

    Summary The insulin-like growth factor-1 receptor (IGF-1R) signaling is a key regulator of lifespan, growth, and development. While reduced IGF-1R signaling delays aging and Alzheimer’s disease progression, whether and how it regulates information processing at central synapses remains elusive. Here, we show that presynaptic IGF-1Rs are basally active, regulating synaptic vesicle release and short-term plasticity in excitatory hippocampal neurons. Acute IGF-1R blockade or transient knockdown suppresses spike-evoked synaptic transmission and presynaptic cytosolic Ca2+ transients, while promoting spontaneous transmission and resting Ca2+ level. This dual effect on transmitter release is mediated by mitochondria that attenuate Ca2+ buffering in the absence of spikes and decrease ATP production during spiking activity. We conclude that the mitochondria, activated by IGF-1R signaling, constitute a critical regulator of information processing in hippocampal neurons by maintaining evoked-to-spontaneous transmission ratio, while constraining synaptic facilitation at high frequencies. Excessive IGF-1R tone may contribute to hippocampal hyperactivity associated with Alzheimer’s disease. Video Abstract PMID:26804996

  3. Recent advances in basic neurosciences and brain disease: from synapses to behavior

    Directory of Open Access Journals (Sweden)

    Salter Michael W

    2006-12-01

    Full Text Available Abstract Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21–23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1 to promote new and cutting edge research in neuroscience; (2 to encourage international information exchange and scientific collaborations; and (3 to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting was in part sponsored by Molecular Pain, together with University of Toronto (Faculty of Medicine, Department of Physiology as well as Center for the Study of Pain. Our goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches. The second international meeting on Neurons and Brain Disease will be held in Toronto (August 29–31, 2007.

  4. Function and Dynamics of Tetraspanins during Antigen Recognition and Immunological Synapse Formation

    Directory of Open Access Journals (Sweden)

    Vera eRocha-Perugini

    2016-01-01

    Full Text Available Tetraspanin-enriched microdomains (TEMs are specialized membrane platforms driven by protein-protein interactions that integrate membrane receptors and adhesion molecules. Tetraspanins participate in antigen recognition and presentation by antigen presenting cells (APCs through the organization of pattern recognition receptors (PRRs and their downstream induced-signaling, as well as the regulation of MHC-II-peptide trafficking. T lymphocyte activation is triggered upon specific recognition of antigens present on the APC surface during immunological synapse (IS formation. This dynamic process is characterized by a defined spatial organization involving the compartmentalization of receptors and adhesion molecules in specialized membrane domains that are connected to the underlying cytoskeleton and signaling molecules. Tetraspanins contribute to the spatial organization and maturation of the IS by controlling receptor clustering and local accumulation of adhesion receptors and integrins, their downstream signaling and linkage to the actin cytoskeleton. This review offers a perspective on the important role of TEMs in the regulation of antigen recognition and presentation, and in the dynamics of IS architectural organization.

  5. Effect of synapse dilution on the memory retrieval in structured attractor neural networks

    Science.gov (United States)

    Brunel, N.

    1993-08-01

    We investigate a simple model of structured attractor neural network (ANN). In this network a module codes for the category of the stored information, while another group of neurons codes for the remaining information. The probability distribution of stabilities of the patterns and the prototypes of the categories are calculated, for two different synaptic structures. The stability of the prototypes is shown to increase when the fraction of neurons coding for the category goes down. Then the effect of synapse destruction on the retrieval is studied in two opposite situations : first analytically in sparsely connected networks, then numerically in completely connected ones. In both cases the behaviour of the structured network and that of the usual homogeneous networks are compared. When lesions increase, two transitions are shown to appear in the behaviour of the structured network when one of the patterns is presented to the network. After the first transition the network recognizes the category of the pattern but not the individual pattern. After the second transition the network recognizes nothing. These effects are similar to syndromes caused by lesions in the central visual system, namely prosopagnosia and agnosia. In both types of networks (structured or homogeneous) the stability of the prototype is greater than the stability of individual patterns, however the first transition, for completely connected networks, occurs only when the network is structured.

  6. Function and Dynamics of Tetraspanins during Antigen Recognition and Immunological Synapse Formation

    Science.gov (United States)

    Rocha-Perugini, Vera; Sánchez-Madrid, Francisco; Martínez del Hoyo, Gloria

    2016-01-01

    Tetraspanin-enriched microdomains (TEMs) are specialized membrane platforms driven by protein–protein interactions that integrate membrane receptors and adhesion molecules. Tetraspanins participate in antigen recognition and presentation by antigen-­presenting cells (APCs) through the organization of pattern-recognition receptors (PRRs) and their downstream-induced signaling, as well as the regulation of MHC-II–peptide trafficking. T lymphocyte activation is triggered upon specific recognition of antigens present on the APC surface during immunological synapse (IS) formation. This dynamic process is characterized by a defined spatial organization involving the compartmentalization of receptors and adhesion molecules in specialized membrane domains that are connected to the underlying cytoskeleton and signaling molecules. Tetraspanins contribute to the spatial organization and maturation of the IS by controlling receptor clustering and local accumulation of adhesion receptors and integrins, their downstream signaling, and linkage to the actin cytoskeleton. This review offers a perspective on the important role of TEMs in the regulation of antigen recognition and presentation and in the dynamics of IS architectural organization. PMID:26793193

  7. Supervised Learning Using Spike-Timing-Dependent Plasticity of Memristive Synapses.

    Science.gov (United States)

    Nishitani, Yu; Kaneko, Yukihiro; Ueda, Michihito

    2015-12-01

    We propose a supervised learning model that enables error backpropagation for spiking neural network hardware. The method is modeled by modifying an existing model to suit the hardware implementation. An example of a network circuit for the model is also presented. In this circuit, a three-terminal ferroelectric memristor (3T-FeMEM), which is a field-effect transistor with a gate insulator composed of ferroelectric materials, is used as an electric synapse device to store the analog synaptic weight. Our model can be implemented by reflecting the network error to the write voltage of the 3T-FeMEMs and introducing a spike-timing-dependent learning function to the device. An XOR problem was successfully demonstrated as a benchmark learning by numerical simulations using the circuit properties to estimate the learning performance. In principle, the learning time per step of this supervised learning model and the circuit is independent of the number of neurons in each layer, promising a high-speed and low-power calculation in large-scale neural networks.

  8. A Re-configurable On-line Learning Spiking Neuromorphic Processor comprising 256 neurons and 128K synapses

    Directory of Open Access Journals (Sweden)

    Ning eQiao

    2015-04-01

    Full Text Available Implementing compact, low-power artificial neural processing systems with real-time on-line learning abilities is still an open challenge. In this paper we present a full-custom mixed-signal VLSI device with neuromorphic learning circuits that emulate the biophysics of real spiking neurons and dynamic synapses for exploring the properties of computational neuroscience models and for building brain-inspired computing systems. The proposed architecture allows the on-chip configuration of a wide range of network connectivities, including recurrent and deep networks with short-term and long-term plasticity. The device comprises 128 K analog synapse and 256 neuron circuits with biologically plausible dynamics and bi-stable spike-based plasticity mechanisms that endow it with on-line learning abilities. In addition to the analog circuits, the device comprises also asynchronous digital logic circuits for setting different synapse and neuron properties as well as different network configurations. This prototype device, fabricated using a 180 nm 1P6M CMOS process, occupies an area of 51.4 mm 2 , and consumes approximately 4 mW for typical experiments, for example involving attractor networks. Here we describe the details of the overall architecture and of the individual circuits and present experimental results that showcase its potential. By supporting a wide range of cortical-like computational modules comprising plasticity mechanisms, this device will enable the realization of intelligent autonomous systems with on-line learning capabilities.

  9. LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons.

    Science.gov (United States)

    Kwon, Seok-Kyu; Sando, Richard; Lewis, Tommy L; Hirabayashi, Yusuke; Maximov, Anton; Polleux, Franck

    2016-07-01

    Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca2+ homeostasis in the mammalian brain are still poorly understood. Using electrophysiology and genetically encoded Ca2+ sensors targeted to the mitochondrial matrix or to presynaptic boutons of cortical pyramidal neurons, we demonstrate that the presence or absence of mitochondria at presynaptic boutons dictates neurotransmitter release properties through Mitochondrial Calcium Uniporter (MCU)-dependent Ca2+ clearance. We demonstrate that the serine/threonine kinase LKB1 regulates MCU expression, mitochondria-dependent Ca2+ clearance, and thereby, presynaptic release properties. Re-establishment of MCU-dependent mitochondrial Ca2+ uptake at glutamatergic synapses rescues the altered neurotransmitter release properties characterizing LKB1-null cortical axons. Our results provide novel insights into the cellular and molecular mechanisms whereby mitochondria control neurotransmitter release properties in a bouton-specific way through presynaptic Ca2+ clearance.

  10. The short- and long-term proteomic effects of sleep deprivation on the cortical and thalamic synapses.

    Science.gov (United States)

    Simor, Attila; Györffy, Balázs András; Gulyássy, Péter; Völgyi, Katalin; Tóth, Vilmos; Todorov, Mihail Ivilinov; Kis, Viktor; Borhegyi, Zsolt; Szabó, Zoltán; Janáky, Tamás; Drahos, László; Juhász, Gábor; Kékesi, Katalin Adrienna

    2017-03-01

    Acute total sleep deprivation (SD) impairs memory consolidation, attention, working memory and perception. Structural, electrophysiological and molecular experimental approaches provided evidences for the involvement of sleep in synaptic functions. Despite the wide scientific interest on the effects of sleep on the synapse, there is a lack of systematic investigation of sleep-related changes in the synaptic proteome. We isolated parietal cortical and thalamic synaptosomes of rats after 8h of total SD by gentle handling and 16h after the end of deprivation to investigate the short- and longer-term effects of SD on the synaptic proteome, respectively. The SD efficiency was verified by electrophysiology. Protein abundance alterations of the synaptosomes were analyzed by fluorescent two-dimensional differential gel electrophoresis and by tandem mass spectrometry. As several altered proteins were found to be involved in synaptic strength regulation, our data can support the synaptic homeostasis hypothesis function of sleep and highlight the long-term influence of SD after the recovery sleep period, mostly on cortical synapses. Furthermore, the large-scale and brain area-specific protein network change in the synapses may support both ideas of sleep-related synaptogenesis and molecular maintenance and reorganization in normal rat brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection.

    Science.gov (United States)

    Real, Fernando; Sennepin, Alexis; Ganor, Yonatan; Schmitt, Alain; Bomsel, Morgane

    2018-05-08

    During sexual intercourse, HIV-1 crosses epithelial barriers composing the genital mucosa, a poorly understood feature that requires an HIV-1-infected cell vectoring efficient mucosal HIV-1 entry. Therefore, urethral mucosa comprising a polarized epithelium and a stroma composed of fibroblasts and macrophages were reconstructed in vitro. Using this system, we demonstrate by live imaging that efficient HIV-1 transmission to stromal macrophages depends on cell-mediated transfer of the virus through virological synapses formed between HIV-1-infected CD4 + T cells and the epithelial cell mucosal surface. We visualized HIV-1 translocation through mucosal epithelial cells via transcytosis in regions where virological synapses occurred. In turn, interleukin-13 is secreted and HIV-1 targets macrophages, which develop a latent state of infection reversed by lipopolysaccharide (LPS) activation. The live observation of virological synapse formation reported herein is key in the design of vaccines and antiretroviral therapies aimed at blocking HIV-1 access to cellular reservoirs in genital mucosa. Copyright © 2018. Published by Elsevier Inc.

  12. Reduced cortical distribution volume of iodine-123 iomazenil in Alzheimer's disease as a measure of loss of synapses

    International Nuclear Information System (INIS)

    Soricelli, A.; Postiglione, A.; Grivet-Fojaja, M.R.; Mainenti, P.P.; Discepolo, A.; Varrone, A.; Salvatore, M.; Lassen, N.A.

    1996-01-01

    Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABA A receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (V d ) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer's disease (AD), where synaptic loss tends indiscriminately to affect all cortical neurons, albeit more so in some areas than in others. In this pilot study we measured V d in six patients with probable AD and in five age-matched controls using a brain-dedicated single-photon emission tomography scanner allowing all cortical levels to be sampled simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex V d was significantly (P d averaged 69 ml/ml in normals and 51 ml/ml in AD, and parietal V d averaged 71 ml/ml in normals and 48 ml/ml in AD. These results accord well with emission tomographic studies of blood flow or labelled glucose. This supports the idea that while only measuring a subpopulation of synapses, the IMZ method reflects synaptic loss and hence functional loss in AD. The method constitutes an in vivo version of synaptic quantitation that in histopathological studies has been shown to correlated closely with the mental deterioration in AD. (orig.)

  13. Thulium fiber laser lithotripsy using a muzzle brake fiber tip

    Science.gov (United States)

    Hutchens, Thomas C.; Gonzalez, David A.; Irby, Pierce B.; Fried, Nathaniel M.

    2017-02-01

    The Thulium fiber laser (TFL) is being explored as an alternative to Holmium:YAG laser for lithotripsy. TFL beam profile allows coupling of higher power into smaller fibers than multimode Holmium laser beam, without proximal fiber tip degradation. A smaller fiber provides more space in ureteroscope working channel for increased saline irrigation and allows maximum ureteroscope flexion. However, distal fiber tip burnback increases as fiber diameter decreases. Previous studies utilizing hollow steel sheaths around recessed distal fiber tips reduced fiber burnback, but increased retropulsion. In this study, a "fiber muzzle brake" was tested for reducing fiber burnback and stone retropulsion. TFL lithotripsy studies were performed at 1908 nm, 35 mJ, 500 μs, and 300 Hz using a 100-μm-core fiber. The optimal stainless steel muzzle brake tip tested consisted of a 1-cm-long, 560-μm-OD, 360-μm-ID tube with 275-μm thru hole located 250-μm from the distal end. The fiber tip was recessed a distance of 500 μm. Stone phantom retropulsion, fiber tip burnback, and calcium oxalate stone ablation studies were performed, ex vivo. Small stones with a mass of 40 +/- 4 mg and 4-mm-diameter were ablated over a 1.5-mm sieve in 25 +/- 4 s (n=10), without distal fiber tip burnback. Reduction in stone phantom retropulsion distance by 50% and 85% was observed when using muzzle brake tips versus 100-μm-core bare fibers and hollow steel tip fibers. The muzzle brake fiber tip provided efficient stone ablation, reduced stone retropulsion, and minimal fiber degradation during TFL lithotripsy.

  14. Visualization by high resolution immunoelectron microscopy of the transient receptor potential vanilloid-1 at inhibitory synapses of the mouse dentate gyrus.

    Directory of Open Access Journals (Sweden)

    Miren-Josune Canduela

    Full Text Available We have recently shown that the transient receptor potential vanilloid type 1 (TRPV1, a non-selective cation channel in the peripheral and central nervous system, is localized at postsynaptic sites of the excitatory perforant path synapses in the hippocampal dentate molecular layer (ML. In the present work, we have studied the distribution of TRPV1 at inhibitory synapses in the ML. With this aim, a preembedding immunogold method for high resolution electron microscopy was applied to mouse hippocampus. About 30% of the inhibitory synapses in the ML are TRPV1 immunopositive, which is mostly localized perisynaptically (∼60% of total immunoparticles at postsynaptic dendritic membranes receiving symmetric synapses in the inner 1/3 of the layer. This TRPV1 pattern distribution is not observed in the ML of TRPV1 knock-out mice. These findings extend the knowledge of the subcellular localization of TRPV1 to inhibitory synapses of the dentate molecular layer where the channel, in addition to excitatory synapses, is present.

  15. Cellulosic Fibers: Effect of Processing on Fiber Bundle Strength

    DEFF Research Database (Denmark)

    Thygesen, Anders; Madsen, Bo; Thomsen, Anne Belinda

    2011-01-01

    A range of differently processed cellulosic fibers from flax and hemp plants were investigated to study the relation between processing of cellulosic fibers and fiber bundle strength. The studied processing methods are applied for yarn production and include retting, scutching, carding, and cotto......A range of differently processed cellulosic fibers from flax and hemp plants were investigated to study the relation between processing of cellulosic fibers and fiber bundle strength. The studied processing methods are applied for yarn production and include retting, scutching, carding...

  16. Study on basalt fiber parameters affecting fiber-reinforced mortar

    Science.gov (United States)

    Orlov, A. A.; Chernykh, T. N.; Sashina, A. V.; Bogusevich, D. V.

    2015-01-01

    This article considers the effect of different dosages and diameters of basalt fibers on tensile strength increase during bending of fiberboard-reinforced mortar samples. The optimal dosages of fiber, providing maximum strength in bending are revealed. The durability of basalt fiber in an environment of cement, by means of microscopic analysis of samples of fibers and fiberboard-reinforced mortar long-term tests is examined. The article also compares the behavior of basalt fiber in the cement stone environment to a glass one and reveals that the basalt fiber is not subject to destruction.

  17. Optical fiber stripper positioning apparatus

    Science.gov (United States)

    Fyfe, Richard W.; Sanchez, Jr., Amadeo

    1990-01-01

    An optical fiber positioning apparatus for an optical fiber stripping device is disclosed which is capable of providing precise axial alignment between an optical fiber to be stripped of its outer jacket and the cutting blades of a stripping device. The apparatus includes a first bore having a width approximately equal to the diameter of an unstripped optical fiber and a counter bore axially aligned with the first bore and dimensioned to precisely receive a portion of the stripping device in axial alignment with notched cutting blades within the stripping device to thereby axially align the notched cutting blades of the stripping device with the axis of the optical fiber to permit the notched cutting blades to sever the jacket on the optical fiber without damaging the cladding on the optical fiber. In a preferred embodiment, the apparatus further includes a fiber stop which permits determination of the length of jacket to be removed from the optical fiber.

  18. Questioning the cerebellar doctrine.

    Science.gov (United States)

    Galliano, Elisa; De Zeeuw, Chris I

    2014-01-01

    The basic principles of cerebellar function were originally described by Flourens, Cajal, and Marr/Albus/Ito, and they constitute the pillars of what can be considered to be the classic cerebellar doctrine. In their concepts, the main cerebellar function is to control motor behavior, Purkinje cells are the only cortical neuron receiving and integrating inputs from climbing fiber and mossy-parallel fiber pathways, and plastic modification at the parallel fiber synapses onto Purkinje cells constitutes the substrate of motor learning. Yet, because of recent technical advances and new angles of investigation, all pillars of the cerebellar doctrine now face regular re-examination. In this review, after summarizing the classic concepts and recent disputes, we attempt to synthesize an integrated view and propose a revisited version of the cerebellar doctrine. © 2014 Elsevier B.V. All rights reserved.

  19. Natural Fiber Composites: A Review

    Energy Technology Data Exchange (ETDEWEB)

    Westman, Matthew P.; Fifield, Leonard S.; Simmons, Kevin L.; Laddha, Sachin; Kafentzis, Tyler A.

    2010-03-07

    The need for renewable fiber reinforced composites has never been as prevalent as it currently is. Natural fibers offer both cost savings and a reduction in density when compared to glass fibers. Though the strength of natural fibers is not as great as glass, the specific properties are comparable. Currently natural fiber composites have two issues that need to be addressed: resin compatibility and water absorption. The following preliminary research has investigated the use of Kenaf, Hibiscus cannabinus, as a possible glass replacement in fiber reinforced composites.

  20. Enhanced radiation resistant fiber optics

    International Nuclear Information System (INIS)

    Lyons, P.B.; Looney, L.D.

    1993-01-01

    A process for producing an optical fiber having enhanced radiation resistance is provided, the process including maintaining an optical fiber within a hydrogen-containing atmosphere for sufficient time to yield a hydrogen-permeated optical fiber having an elevated internal hydrogen concentration, and irradiating the hydrogen-permeated optical fiber at a time while the optical fiber has an elevated internal hydrogen concentration with a source of ionizing radiation. The radiation source is typically a cobalt-60 source and the fiber is pre-irradiated with a dose level up to about 1000 kilorads of radiation. 4 figures