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Sample records for enhances synaptic communication

  1. Network response synchronization enhanced by synaptic plasticity

    NASA Astrophysics Data System (ADS)

    Lobov, S.; Simonov, A.; Kastalskiy, I.; Kazantsev, V.

    2016-02-01

    Synchronization of neural network response on spatially localized periodic stimulation was studied. The network consisted of synaptically coupled spiking neurons with spike-timing-dependent synaptic plasticity (STDP). Network connectivity was defined by time evolving matrix of synaptic weights. We found that the steady-state spatial pattern of the weights could be rearranged due to locally applied external periodic stimulation. A method for visualization of synaptic weights as vector field was introduced to monitor the evolving connectivity matrix. We demonstrated that changes in the vector field and associated weight rearrangements underlay an enhancement of synchronization range.

  2. Attention Enhances Synaptic Efficacy and Signal-to-Noise in Neural Circuits

    PubMed Central

    Briggs, Farran; Mangun, George R.; Usrey, W. Martin

    2013-01-01

    Summary Attention is a critical component of perception. However, the mechanisms by which attention modulates neuronal communication to guide behavior are poorly understood. To elucidate the synaptic mechanisms of attention, we developed a sensitive assay of attentional modulation of neuronal communication. In alert monkeys performing a visual spatial attention task, we probed thalamocortical communication by electrically stimulating neurons in the lateral geniculate nucleus of the thalamus while simultaneously recording shock-evoked responses from monosynaptically connected neurons in primary visual cortex. We found that attention enhances neuronal communication by (1) increasing the efficacy of presynaptic input in driving postsynaptic responses, (2) increasing synchronous responses among ensembles of postsynaptic neurons receiving independent input, and (3) decreasing redundant signals between postsynaptic neurons receiving common input. These results demonstrate that attention finely tunes neuronal communication at the synaptic level by selectively altering synaptic weights, enabling enhanced detection of salient events in the noisy sensory milieu. PMID:23803766

  3. Synaptic plasticity can produce and enhance direction selectivity.

    PubMed

    Carver, Sean; Roth, Eatai; Cowan, Noah J; Fortune, Eric S

    2008-02-01

    The discrimination of the direction of movement of sensory images is critical to the control of many animal behaviors. We propose a parsimonious model of motion processing that generates direction selective responses using short-term synaptic depression and can reproduce salient features of direction selectivity found in a population of neurons in the midbrain of the weakly electric fish Eigenmannia virescens. The model achieves direction selectivity with an elementary Reichardt motion detector: information from spatially separated receptive fields converges onto a neuron via dynamically different pathways. In the model, these differences arise from convergence of information through distinct synapses that either exhibit or do not exhibit short-term synaptic depression--short-term depression produces phase-advances relative to nondepressing synapses. Short-term depression is modeled using two state-variables, a fast process with a time constant on the order of tens to hundreds of milliseconds, and a slow process with a time constant on the order of seconds to tens of seconds. These processes correspond to naturally occurring time constants observed at synapses that exhibit short-term depression. Inclusion of the fast process is sufficient for the generation of temporal disparities that are necessary for direction selectivity in the elementary Reichardt circuit. The addition of the slow process can enhance direction selectivity over time for stimuli that are sustained for periods of seconds or more. Transient (i.e., short-duration) stimuli do not evoke the slow process and therefore do not elicit enhanced direction selectivity. The addition of a sustained global, synchronous oscillation in the gamma frequency range can, however, drive the slow process and enhance direction selectivity to transient stimuli. This enhancement effect does not, however, occur for all combinations of model parameters. The ratio of depressing and nondepressing synapses determines the

  4. Mutual and intermittent enhancements of synchronization transitions by autaptic and synaptic delay in scale-free neuron networks

    NASA Astrophysics Data System (ADS)

    Wang, Qi; Gong, Yubing; Xie, Huijuan

    2016-05-01

    In neural networks, there exist both synaptic delays among different neurons and autaptic self-feedback delays in a neuron itself. In this paper, we study synchronization transitions induced by synaptic and autaptic delays in scale-free neuron networks, mainly exploring how these two time delays affect synchronization transitions induced by each other. It is found that the synchronization transitions induced by synaptic (autaptic) delay are intermittently enhanced when autaptic (synaptic) delay is varied. There are optimal autaptic strength and synaptic coupling strength by which the synchronization transitions induced by autaptic and synaptic delays become strongest. The underlying mechanisms are briefly discussed in terms of the relationships of autaptic delay, synaptic delay, and inter-burst interval. These results show that synaptic and autaptic delays could contribute to each other and enhance synchronization transitions in the neuronal networks. This implies that autaptic and synaptic delays could play a vital role for the information transmission in neural systems.

  5. Excitability and synaptic communication within the oligodendrocyte lineage.

    PubMed

    De Biase, Lindsay M; Nishiyama, Akiko; Bergles, Dwight E

    2010-03-10

    The mammalian CNS contains an abundant, widely distributed population of glial cells that serve as oligodendrocyte progenitors. It has been reported that these NG2-immunoreactive cells (NG2(+) cells) form synapses and generate action potentials, suggesting that neural-evoked excitation of these progenitors may regulate oligodendrogenesis. However, recent studies also suggest that NG2(+) cells are comprised of functionally distinct groups that differ in their ability to respond to neuronal activity, undergo differentiation, and experience injury following ischemia. To better define the physiological properties of NG2(+) cells, we used transgenic mice that allowed an unbiased sampling of this population and unambiguous identification of cells in discrete states of differentiation. Using acute brain slices prepared from developing and mature mice, we found that NG2(+) cells in diverse brain regions share a core set of physiological properties, including expression of voltage-gated Na(+) (NaV) channels and ionotropic glutamate receptors, and formation of synapses with glutamatergic neurons. Although small amplitude Na(+) spikes could be elicited in some NG2(+) cells during the first postnatal week, they were not capable of generating action potentials. Transition of these progenitors to the premyelinating stage was accompanied by the rapid removal of synaptic input, as well as downregulation of AMPA and NMDA receptors and NaV channels. Thus, prior reports of physiological heterogeneity among NG2(+) cells may reflect analysis of cells in later stages of maturation. These results suggest that NG2(+) cells are uniquely positioned within the oligodendrocyte lineage to monitor the firing patterns of surrounding neurons. PMID:20219994

  6. Facilitation of AMPA Receptor Synaptic Delivery as a Molecular Mechanism for Cognitive Enhancement

    PubMed Central

    Sánchez-Puelles, Cristina; Pereda-Peréz, Inmaculada; Franco, Ana; Sandi, Carmen; Suárez, Luz M.; Solís, José M.; Alonso-Nanclares, Lidia; Martín, Eduardo D.; Merino-Serrais, Paula; Borcel, Erika; Li, Shizhong; Chen, Yongshuo; Gonzalez-Soriano, Juncal; Berezin, Vladimir; Bock, Elisabeth; DeFelipe, Javier; Esteban, José A.

    2012-01-01

    Cell adhesion molecules and downstream growth factor-dependent signaling are critical for brain development and synaptic plasticity, and they have been linked to cognitive function in adult animals. We have previously developed a mimetic peptide (FGL) from the neural cell adhesion molecule (NCAM) that enhances spatial learning and memory in rats. We have now investigated the cellular and molecular basis of this cognitive enhancement, using biochemical, morphological, electrophysiological, and behavioral analyses. We have found that FGL triggers a long-lasting enhancement of synaptic transmission in hippocampal CA1 neurons. This effect is mediated by a facilitated synaptic delivery of AMPA receptors, which is accompanied by enhanced NMDA receptor-dependent long-term potentiation (LTP). Both LTP and cognitive enhancement are mediated by an initial PKC activation, which is followed by persistent CaMKII activation. These results provide a mechanistic link between facilitation of AMPA receptor synaptic delivery and improved hippocampal-dependent learning, induced by a pharmacological cognitive enhancer. PMID:22363206

  7. Communication Enhancement: Principles and Practices.

    ERIC Educational Resources Information Center

    Shane, Howard

    1988-01-01

    A physician discusses the work of the Communications Enhancement Clinic at Children's Hospital-Boston in providing assistance to children with severe speech problems. He describes the process of evaluating and matching a child's strengths and weaknesses to available technology, including educational software, speech or print output devices, and…

  8. Peripherally restricted viral challenge elevates extracellular glutamate and enhances synaptic transmission in the hippocampus.

    PubMed

    Hunsberger, Holly C; Wang, Desheng; Petrisko, Tiffany J; Alhowail, Ahmad; Setti, Sharay E; Suppiramaniam, Vishnu; Konat, Gregory W; Reed, Miranda N

    2016-07-01

    Peripheral infections increase the propensity and severity of seizures in susceptible populations. We have previously shown that intraperitoneal injection of a viral mimic, polyinosinic-polycytidylic acid (PIC), elicits hypersusceptibility of mice to kainic acid (KA)-induced seizures. This study was undertaken to determine whether this seizure hypersusceptibility entails alterations in glutamate signaling. Female C57BL/6 mice were intraperitoneally injected with PIC, and after 24 h, glutamate homeostasis in the hippocampus was monitored using the enzyme-based microelectrode arrays. PIC challenge robustly increased the level of resting extracellular glutamate. While pre-synaptic potassium-evoked glutamate release was not affected, glutamate uptake was profoundly impaired and non-vesicular glutamate release was augmented, indicating functional alterations of astrocytes. Electrophysiological examination of hippocampal slices from PIC-challenged mice revealed a several fold increase in the basal synaptic transmission as compared to control slices. PIC challenge also increased the probability of pre-synaptic glutamate release as seen from a reduction of paired-pulse facilitation and synaptic plasticity as seen from an enhancement of long-term potentiation. Altogether, our results implicate a dysregulation of astrocytic glutamate metabolism and an alteration of excitatory synaptic transmission as the underlying mechanism for the development of hippocampal hyperexcitability, and consequently seizure hypersusceptibility following peripheral PIC challenge. Peripheral infections/inflammations enhance seizure susceptibility. Here, we explored the effect of peritoneal inflammation induced by a viral mimic on glutamate homeostasis and glutamatergic neurotransmission in the mouse hippocampus. We found that peritoneal inflammation elevated extracellular glutamate concentration and enhanced the probability of pre-synaptic glutamate release resulting in hyperexcitability of

  9. Enhanced synaptic transmission at the squid giant synapse by artificial seawater based on physically modified saline

    PubMed Central

    Choi, Soonwook; Yu, Eunah; Rabello, Guilherme; Merlo, Suelen; Zemmar, Ajmal; Walton, Kerry D.; Moreno, Herman; Moreira, Jorge E.; Sugimori, Mutsuyuki; Llinás, Rodolfo R.

    2014-01-01

    Superfusion of the squid giant synapse with artificial seawater (ASW) based on isotonic saline containing oxygen nanobubbles (RNS60 ASW) generates an enhancement of synaptic transmission. This was determined by examining the postsynaptic response to single and repetitive presynaptic spike activation, spontaneous transmitter release, and presynaptic voltage clamp studies. In the presence of RNS60 ASW single presynaptic stimulation elicited larger postsynaptic potentials (PSP) and more robust recovery from high frequency stimulation than in control ASW. Analysis of postsynaptic noise revealed an increase in spontaneous transmitter release with modified noise kinetics in RNS60 ASW. Presynaptic voltage clamp demonstrated an increased EPSP, without an increase in presynaptic ICa++ amplitude during RNS60 ASW superfusion. Synaptic release enhancement reached stable maxima within 5–10 min of RNS60 ASW superfusion and was maintained for the entire recording time, up to 1 h. Electronmicroscopic morphometry indicated a decrease in synaptic vesicle density and the number at active zones with an increase in the number of clathrin-coated vesicles (CCV) and large endosome-like vesicles near junctional sites. Block of mitochondrial ATP synthesis by presynaptic injection of oligomycin reduced spontaneous release and prevented the synaptic noise increase seen in RNS60 ASW. After ATP block the number of vesicles at the active zone and CCV was reduced, with an increase in large vesicles. The possibility that RNS60 ASW acts by increasing mitochondrial ATP synthesis was tested by direct determination of ATP levels in both presynaptic and postsynaptic structures. This was implemented using luciferin/luciferase photon emission, which demonstrated a marked increase in ATP synthesis following RNS60 administration. It is concluded that RNS60 positively modulates synaptic transmission by up-regulating ATP synthesis, thus leading to synaptic transmission enhancement. PMID:24575037

  10. Enhanced synaptic transmission at the squid giant synapse by artificial seawater based on physically modified saline.

    PubMed

    Choi, Soonwook; Yu, Eunah; Rabello, Guilherme; Merlo, Suelen; Zemmar, Ajmal; Walton, Kerry D; Moreno, Herman; Moreira, Jorge E; Sugimori, Mutsuyuki; Llinás, Rodolfo R

    2014-01-01

    Superfusion of the squid giant synapse with artificial seawater (ASW) based on isotonic saline containing oxygen nanobubbles (RNS60 ASW) generates an enhancement of synaptic transmission. This was determined by examining the postsynaptic response to single and repetitive presynaptic spike activation, spontaneous transmitter release, and presynaptic voltage clamp studies. In the presence of RNS60 ASW single presynaptic stimulation elicited larger postsynaptic potentials (PSP) and more robust recovery from high frequency stimulation than in control ASW. Analysis of postsynaptic noise revealed an increase in spontaneous transmitter release with modified noise kinetics in RNS60 ASW. Presynaptic voltage clamp demonstrated an increased EPSP, without an increase in presynaptic ICa(++) amplitude during RNS60 ASW superfusion. Synaptic release enhancement reached stable maxima within 5-10 min of RNS60 ASW superfusion and was maintained for the entire recording time, up to 1 h. Electronmicroscopic morphometry indicated a decrease in synaptic vesicle density and the number at active zones with an increase in the number of clathrin-coated vesicles (CCV) and large endosome-like vesicles near junctional sites. Block of mitochondrial ATP synthesis by presynaptic injection of oligomycin reduced spontaneous release and prevented the synaptic noise increase seen in RNS60 ASW. After ATP block the number of vesicles at the active zone and CCV was reduced, with an increase in large vesicles. The possibility that RNS60 ASW acts by increasing mitochondrial ATP synthesis was tested by direct determination of ATP levels in both presynaptic and postsynaptic structures. This was implemented using luciferin/luciferase photon emission, which demonstrated a marked increase in ATP synthesis following RNS60 administration. It is concluded that RNS60 positively modulates synaptic transmission by up-regulating ATP synthesis, thus leading to synaptic transmission enhancement. PMID:24575037

  11. A robust and scalable neuromorphic communication system by combining synaptic time multiplexing and MIMO-OFDM.

    PubMed

    Srinivasa, Narayan; Zhang, Deying; Grigorian, Beayna

    2014-03-01

    This paper describes a novel architecture for enabling robust and efficient neuromorphic communication. The architecture combines two concepts: 1) synaptic time multiplexing (STM) that trades space for speed of processing to create an intragroup communication approach that is firing rate independent and offers more flexibility in connectivity than cross-bar architectures and 2) a wired multiple input multiple output (MIMO) communication with orthogonal frequency division multiplexing (OFDM) techniques to enable a robust and efficient intergroup communication for neuromorphic systems. The MIMO-OFDM concept for the proposed architecture was analyzed by simulating large-scale spiking neural network architecture. Analysis shows that the neuromorphic system with MIMO-OFDM exhibits robust and efficient communication while operating in real time with a high bit rate. Through combining STM with MIMO-OFDM techniques, the resulting system offers a flexible and scalable connectivity as well as a power and area efficient solution for the implementation of very large-scale spiking neural architectures in hardware. PMID:24807453

  12. Epsin 1 Promotes Synaptic Growth by Enhancing BMP Signal Levels in Motoneuron Nuclei

    PubMed Central

    Chastain, Lerin R.; Royer, Suzanne M.; Bao, Hong; Reist, Noreen E.; Zhang, Bing

    2013-01-01

    Bone morphogenetic protein (BMP) retrograde signaling is crucial for neuronal development and synaptic plasticity. However, how the BMP effector phospho-Mother against decapentaplegic (pMad) is processed following receptor activation remains poorly understood. Here we show that Drosophila Epsin1/Liquid facets (Lqf) positively regulates synaptic growth through post-endocytotic processing of pMad signaling complex. Lqf and the BMP receptor Wishful thinking (Wit) interact genetically and biochemically. lqf loss of function (LOF) reduces bouton number whereas overexpression of lqf stimulates bouton growth. Lqf-stimulated synaptic overgrowth is suppressed by genetic reduction of wit. Further, synaptic pMad fails to accumulate inside the motoneuron nuclei in lqf mutants and lqf suppresses synaptic overgrowth in spinster (spin) mutants with enhanced BMP signaling by reducing accumulation of nuclear pMad. Interestingly, lqf mutations reduce nuclear pMad levels without causing an apparent blockage of axonal transport itself. Finally, overexpression of Lqf significantly increases the number of multivesicular bodies (MVBs) in the synapse whereas lqf LOF reduces MVB formation, indicating that Lqf may function in signaling endosome recycling or maturation. Based on these observations, we propose that Lqf plays a novel endosomal role to ensure efficient retrograde transport of BMP signaling endosomes into motoneuron nuclei. PMID:23840387

  13. Dopamine and norepinephrine receptors participate in methylphenidate enhancement of in vivo hippocampal synaptic plasticity.

    PubMed

    Jenson, Daniel; Yang, Kechun; Acevedo-Rodriguez, Alexandra; Levine, Amber; Broussard, John I; Tang, Jianrong; Dani, John A

    2015-03-01

    Attention-deficit hyperactive disorder (ADHD) is the most commonly studied and diagnosed psychiatric disorder in children. Methylphenidate (MPH, e.g., Ritalin) has been used to treat ADHD for over 50 years. It is the most commonly prescribed treatment for ADHD, and in the past decade it was the drug most commonly prescribed to teenagers. In addition, MPH has become one of the most widely abused drugs on college campuses. In this study, we examined the effects of MPH on hippocampal synaptic plasticity, which serves as a measurable quantification of memory mechanisms. Field potentials were recorded with permanently implanted electrodes in freely-moving mice to quantify MPH modulation of perforant path synaptic transmission onto granule cells of the dentate gyrus. Our hypothesis was that MPH affects hippocampal synaptic plasticity underlying learning because MPH boosts catecholamine signaling by blocking the dopamine and norepinephrine transporters (DAT and NET respectively). In vitro hippocampal slice experiments indicated MPH enhances perforant path plasticity, and this MPH enhancement arose from action via D1-type dopamine receptors and β-type adrenergic receptors. Similarly, MPH boosted in vivo initiation of long-term potentiation (LTP). While there was an effect via both dopamine and adrenergic receptors in vivo, LTP induction was more dependent on the MPH-induced action via D1-type dopamine receptors. Under biologically reasonable experimental conditions, MPH enhances hippocampal synaptic plasticity via catecholamine receptors. PMID:25445492

  14. Autonomous CaMKII requires further stimulation by Ca2+/calmodulin for enhancing synaptic strength

    PubMed Central

    Barcomb, Kelsey; Buard, Isabelle; Coultrap, Steven J.; Kulbe, Jacqueline R.; O'Leary, Heather; Benke, Timothy A.; Bayer, K. Ulrich

    2014-01-01

    A hallmark feature of Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is generation of autonomous (Ca2+-independent) activity by T286 autophosphorylation. Biochemical studies have shown that “autonomous” CaMKII is ∼5-fold further stimulated by Ca2+/CaM, but demonstration of a physiological function for such regulation within cells has remained elusive. In this study, CaMKII-induced enhancement of synaptic strength in rat hippocampal neurons required both autonomous activity and further stimulation. Synaptic strength was decreased by CaMKIIα knockdown and rescued by reexpression, but not by mutants impaired for autonomy (T286A) or binding to NMDA-type glutamate receptor subunit 2B (GluN2B; formerly NR2B; I205K). Full rescue was seen with constitutively autonomous mutants (T286D), but only if they could be further stimulated (additional T305/306A mutation), and not with two other mutations that additionally impair Ca2+/CaM binding. Compared to rescue with wild-type CaMKII, the CaM-binding-impaired mutants even had reduced synaptic strength. One of these mutants (T305/306D) mimicked an inhibitory autophosphorylation of CaMKII, whereas the other one (Δstim) abolished CaM binding without introducing charged residues. Inhibitory T305/306 autophosphorylation also reduced GluN2B binding, but this effect was independent of reduced Ca2+/CaM binding and was not mimicked by T305/306D mutation. Thus, even autonomous CaMKII activity must be further stimulated by Ca2+/CaM for enhancement of synaptic strength.—Barcomb, K., Buard, I., Coultrap, S. J., Kulbe, J. R., O'Leary, H., Benke, T. A., Bayer, K. U. Autonomous CaMKII requires further stimulation by Ca2+/calmodulin for enhancing synaptic strength. PMID:24843070

  15. Nootropic dipeptide noopept enhances inhibitory synaptic transmission in the hippocampus.

    PubMed

    Povarov, I S; Kondratenko, R V; Derevyagin, V I; Ostrovskaya, R U; Skrebitskii, V G

    2015-01-01

    Application of nootropic agent Noopept on hippocampal slices from Wistar rats enhanced the inhibitory component of total current induced by stimulation of Shaffer collaterals in CA1 pyramidal neurons, but did not affect the excitatory component. A direct correlation between the increase in the amplitude of inhibitory current and agent concentration was found. The substance did not affect the release of inhibitory transmitters from terminals in the pyramidal neurons, which indicated changes in GABAergic interneurons. PMID:25573367

  16. GluN3A promotes NMDA spiking by enhancing synaptic transmission in Huntington's disease models.

    PubMed

    Mahfooz, Kashif; Marco, Sonia; Martínez-Turrillas, Rebeca; Raja, Mathan K; Pérez-Otaño, Isabel; Wesseling, John F

    2016-09-01

    Age-inappropriate expression of juvenile NMDA receptors (NMDARs) containing GluN3A subunits has been linked to synapse loss and death of spiny projection neurons of the striatum (SPNs) in Huntington's disease (HD). Here we show that suppressing GluN3A expression prevents a multivariate synaptic transmission phenotype that precedes morphological signs at early prodromal stages. We start by confirming that afferent fiber stimulation elicits larger synaptic responses mediated by both AMPA receptors and NMDARs in SPNs in the YAC128 mouse model of HD. We then show that the enhancement mediated by both is fully prevented by suppressing GluN3A expression. Strong fiber-stimulation unexpectedly elicited robust NMDAR-mediated electrogenic events (termed "upstates" or "NMDA spikes"), and the effective threshold for induction was more than 2-fold lower in YAC128 SPNs because of the enhanced synaptic transmission. The threshold could be restored to control levels by suppressing GluN3A expression or by applying the weak NMDAR blocker memantine. However, the threshold was not affected by preventing glutamate spillover from synaptic clefts. Instead, long-lasting NMDAR responses interpreted previously as activation of extrasynaptic receptors by spilled-over glutamate were caused by NMDA spikes occurring in voltage clamp mode as escape potentials. Together, the results implicate GluN3A reactivation in a broad spectrum of early-stage synaptic transmission deficits in YAC128 mice; question the current concept that NMDAR mislocalization is the pathological trigger in HD; and introduce NMDA spikes as a new candidate mechanism for coupling NMDARs to neurodegeneration. PMID:27072890

  17. Short-term environmental enrichment enhances synaptic plasticity in hippocampal slices from aged rats.

    PubMed

    Stein, Liana R; O'Dell, Kazuko A; Funatsu, Michiyo; Zorumski, Charles F; Izumi, Yukitoshi

    2016-08-01

    Age-associated changes in cognition are mirrored by impairments in cellular models of memory and learning, such as long-term potentiation (LTP) and long-term depression (LTD). In young rodents, environmental enrichment (EE) can enhance memory, alter LTP and LTD, as well as reverse cognitive deficits induced by aging. Whether short-term EE can benefit cognition and synaptic plasticity in aged rodents is unclear. Here, we tested if short-term EE could overcome age-associated impairments in induction of LTP and LTD. LTP and LTD could not be induced in the CA1 region of hippocampal slices in control, aged rats using standard stimuli that are highly effective in young rats. However, exposure of aged littermates to EE for three weeks enabled successful induction of LTP and LTD. EE-facilitated LTP was dependent upon N-methyl-d-aspartate receptors (NMDARs). These alterations in synaptic plasticity occurred with elevated levels of phosphorylated cAMP response element-binding protein and vascular endothelial growth factor, but in the absence of changes in several other synaptic and cellular markers. Importantly, our study suggests that even a relatively short period of EE is sufficient to alter synaptic plasticity and molecular markers linked to cognitive function in aged animals. PMID:27208617

  18. Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus

    PubMed Central

    Zhang, Hong; Leiser, Steven C; Xiao, Yixin; Lu, Dunguo; Yang, Charles R; Plath, Niels; Sanchez, Connie

    2014-01-01

    Vortioxetine, a novel antidepressant with multimodal action, is a serotonin (5-HT)3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (SERT) inhibitor. Vortioxetine has been shown to improve cognitive performance in several preclinical rat models and in patients with major depressive disorder. Here we investigated the mechanistic basis for these effects by studying the effect of vortioxetine on synaptic transmission, long-term potentiation (LTP), a cellular correlate of learning and memory, and theta oscillations in the rat hippocampus and frontal cortex. Vortioxetine was found to prevent the 5-HT-induced increase in inhibitory post-synaptic potentials recorded from CA1 pyramidal cells, most likely by 5-HT3 receptor antagonism. Vortioxetine also enhanced LTP in the CA1 region of the hippocampus. Finally, vortioxetine increased fronto-cortical theta power during active wake in whole animal electroencephalographic recordings. In comparison, the selective SERT inhibitor escitalopram showed no effect on any of these measures. Taken together, our results indicate that vortioxetine can increase pyramidal cell output, which leads to enhanced synaptic plasticity in the hippocampus. Given the central role of the hippocampus in cognition, these findings may provide a cellular correlate to the observed preclinical and clinical cognition-enhancing effects of vortioxetine. PMID:25122043

  19. Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus.

    PubMed

    Dale, Elena; Zhang, Hong; Leiser, Steven C; Xiao, Yixin; Lu, Dunguo; Yang, Charles R; Plath, Niels; Sanchez, Connie

    2014-10-01

    Vortioxetine, a novel antidepressant with multimodal action, is a serotonin (5-HT)3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (SERT) inhibitor. Vortioxetine has been shown to improve cognitive performance in several preclinical rat models and in patients with major depressive disorder. Here we investigated the mechanistic basis for these effects by studying the effect of vortioxetine on synaptic transmission, long-term potentiation (LTP), a cellular correlate of learning and memory, and theta oscillations in the rat hippocampus and frontal cortex. Vortioxetine was found to prevent the 5-HT-induced increase in inhibitory post-synaptic potentials recorded from CA1 pyramidal cells, most likely by 5-HT3 receptor antagonism. Vortioxetine also enhanced LTP in the CA1 region of the hippocampus. Finally, vortioxetine increased fronto-cortical theta power during active wake in whole animal electroencephalographic recordings. In comparison, the selective SERT inhibitor escitalopram showed no effect on any of these measures. Taken together, our results indicate that vortioxetine can increase pyramidal cell output, which leads to enhanced synaptic plasticity in the hippocampus. Given the central role of the hippocampus in cognition, these findings may provide a cellular correlate to the observed preclinical and clinical cognition-enhancing effects of vortioxetine. PMID:25122043

  20. Taurine-Induced Long-Lasting Enhancement of Synaptic Transmission in Mice: Role of Transporters

    PubMed Central

    Sergeeva, O A; Chepkova, A N; Doreulee, N; Eriksson, K S; Poelchen, W; Mönnighoff, I; Heller-Stilb, B; Warskulat, U; Häussinger, D; Haas, H L

    2003-01-01

    Taurine, a major osmolyte in the brain evokes a long-lasting enhancement (LLETAU) of synaptic transmission in hippocampal and cortico-striatal slices. Hippocampal LLETAU was abolished by the GABA uptake blocker nipecotic acid (NPA) but not by the taurine-uptake inhibitor guanidinoethyl sulphonate (GES). Striatal LLETAU was sensitive to GES but not to NPA. Semiquantitative PCR analysis and immunohistochemistry revealed that taurine transporter expression is significantly higher in the striatum than in the hippocampus. Taurine transporter-deficient mice displayed very low taurine levels in both structures and a low ability to develop LLETAU in the striatum, but not in the hippocampus. The different mechanisms of taurine-induced synaptic plasticity may reflect the different vulnerabilities of these brain regions under pathological conditions that are accompanied by osmotic changes such as hepatic encephalopathy. PMID:12824447

  1. Enhancement of synaptic transmission induced by BDNF in cultured cortical neurons

    NASA Astrophysics Data System (ADS)

    He, Jun; Gong, Hui; Zeng, Shaoqun; Li, Yanling; Luo, Qingming

    2005-03-01

    Brain-derived neurotrophic factor (BDNF), like other neurotrophins, has long-term effects on neuronal survival and differentiation; furthermore, BDNF has been reported to exert an acute potentiation of synaptic activity and are critically involved in long-term potentiation (LTP). We found that BDNF rapidly induced potentiation of synaptic activity and an increase in the intracellular Ca2+ concentration in cultured cortical neurons. Within minutes of BDNF application to cultured cortical neurons, spontaneous firing rate was dramatically increased as were the frequency and amplitude of excitatory spontaneous postsynaptic currents (EPSCs). Fura-2 recordings showed that BDNF acutely elicited an increase in intracellular calcium concentration ([Ca2+]c). This effect was partially dependent on [Ca2+]o; The BDNF-induced increase in [Ca2+]c can not be completely blocked by Ca2+-free solution. It was completely blocked by K252a and partially blocked by Cd2+ and TTX. The results demonstrate that BDNF can enhances synaptic transmission and that this effect is accompanied by a rise in [Ca2+]c that requires two route: the release of Ca2+ from intracellular calcium stores and influx of extracellular Ca2+ through voltage-dependent Ca2+ channels in cultured cortical neurons.

  2. Previous ethanol experience enhances synaptic plasticity of NMDA receptors in the ventral tegmental area.

    PubMed

    Bernier, Brian E; Whitaker, Leslie R; Morikawa, Hitoshi

    2011-04-01

    Alcohol addiction (alcoholism) is one of the most prevalent substance abuse disorders worldwide. Addiction is thought to arise, in part, from a maladaptive learning process in which enduring memories of drug experiences are formed. However, alcohol (ethanol) generally interferes with synaptic plasticity mechanisms in the CNS and thus impairs various types of learning and memory. Therefore, it is unclear how powerful memories associated with alcohol experience are formed during the development of alcoholism. Here, using brain slice electrophysiology in mice, we show that repeated in vivo ethanol exposure (2 g/kg, i.p., three times daily for 7 d) causes increased susceptibility to the induction of long-term potentiation (LTP) of NMDA receptor (NMDAR)-mediated transmission in mesolimbic dopamine neurons, a form of synaptic plasticity that may drive the learning of stimuli associated with rewards, including drugs of abuse. Enhancement of NMDAR plasticity results from an increase in the potency of inositol 1,4,5-trisphosphate (IP(3)) in producing facilitation of action potential-evoked Ca(2+) signals, which is critical for LTP induction. This increase in IP(3) effect, which lasts for a week but not a month after ethanol withdrawal, occurs through a protein kinase A (PKA)-dependent mechanism. Corticotropin-releasing factor, a stress-related neuropeptide implicated in alcoholism and other addictions, further amplifies the PKA-mediated increase in IP(3) effect in ethanol-treated mice. Finally, we found that ethanol-treated mice display enhanced place conditioning induced by the psychostimulant cocaine. These data suggest that repeated ethanol experience may promote the formation of drug-associated memories by enhancing synaptic plasticity of NMDARs in dopamine neurons. PMID:21471355

  3. Tenuigenin treatment improves behavioral Y-maze learning by enhancing synaptic plasticity in mice.

    PubMed

    Huang, Jun-ni; Wang, Chun-yang; Wang, Xiu-li; Wu, Bo-zhi; Gu, Xing-yang; Liu, Wen-xiao; Gong, Liang-wei; Xiao, Peng; Li, Chu-hua

    2013-06-01

    Polygala tenuifolia root has been used to improve memory and cognitive function in Traditional Chinese Medicine for more than 2000 years. Since tenuigenin (TEN) is one of the most utilized P. tenuifolia root extracts, it is surprising there is no evidence for the effects of TEN on learning and memory so far. In the present study, we investigated the effects of TEN on learning and memory with Y-maze test in mice. We found that oral administration of 4mg/kg TEN significantly improved learning and memory in Y-maze task. Treatment with 4mg/kg TEN markedly reduced the acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level, and increased superoxide dismutase (SOD) activity in hippocampus. In the electrophysiological test of hippocampal brain slice, 2μg/ml TEN perfusion substantially enhanced field excitatory postsynaptic potential (fEPSP) amplitude both in basic synaptic transmission and after high frequency stimulation (HFS) in Schaffer to CA1 pathway (Scha-CA1). These results indicate that TEN enhancing learning and memory may result from inhibiting AChE activity, improving antioxidation and enhancing synaptic plasticity in mice. Therefore, TEN shows promise as a potential nootropic product in improving learning and memory. PMID:23499702

  4. Can Communicative Principles Enhance Classical Language Acquisition?

    ERIC Educational Resources Information Center

    Overland, Paul; Fields, Lee; Noonan, Jennifer

    2011-01-01

    Is it feasible for nonfluent instructors to teach Biblical Hebrew by communicative principles? If it is feasible, will communicative instruction enhance postsecondary learning of a classical language? To begin answering these questions, two consultants representing second language acquisition (SLA) and technology-assisted language learning led 8…

  5. Smaller Dendritic Spines, Weaker Synaptic Transmission, but Enhanced Spatial Learning in Mice Lacking Shank1

    PubMed Central

    Hung, Albert Y.; Futai, Kensuke; Sala, Carlo; Valtschanoff, Juli G.; Ryu, Jubin; Woodworth, Mollie A.; Kidd, Fleur L.; Sung, Clifford C.; Miyakawa, Tsuyoshi; Bear, Mark F.; Weinberg, Richard J.; Sheng, Morgan

    2009-01-01

    Experience-dependent changes in the structure of dendritic spines may contribute to learning and memory. Encoded by three genes, the Shank family of postsynaptic scaffold proteins are abundant and enriched in the postsynaptic density (PSD) of central excitatory synapses. When expressed in cultured hippocampal neurons, Shank promotes the maturation and enlargement of dendritic spines. Recently, Shank3 has been genetically implicated in human autism, suggesting an important role for Shank proteins in normal cognitive development. Here, we report the phenotype of Shank1 knock-out mice. Shank1 mutants showed altered PSD protein composition; reduced size of dendritic spines; smaller, thinner PSDs; and weaker basal synaptic transmission. Standard measures of synaptic plasticity were normal. Behaviorally, they had increased anxiety-related behavior and impaired contextual fear memory. Remarkably, Shank1-deficient mice displayed enhanced performance in a spatial learning task; however, their long-term memory retention in this task was impaired. These results affirm the importance of Shank1 for synapse structure and function in vivo, and they highlight a differential role for Shank1 in specific cognitive processes, a feature that may be relevant to human autism spectrum disorders. PMID:18272690

  6. The Enhanced Rise and Delayed Fall of Memory in a Model of Synaptic Integration: Extension to Discrete State Synapses.

    PubMed

    Elliott, Terry

    2016-09-01

    Integrate-and-express models of synaptic plasticity propose that synapses may act as low-pass filters, integrating synaptic plasticity induction signals in order to discern trends before expressing synaptic plasticity. We have previously shown that synaptic filtering strongly controls destabilizing fluctuations in developmental models. When applied to palimpsest memory systems that learn new memories by forgetting old ones, we have also shown that with binary-strength synapses, integrative synapses lead to an initial memory signal rise before its fall back to equilibrium. Such an initial rise is in dramatic contrast to nonintegrative synapses, in which the memory signal falls monotonically. We now extend our earlier analysis of palimpsest memories with synaptic filters to consider the more general case of discrete state, multilevel synapses. We derive exact results for the memory signal dynamics and then consider various simplifying approximations. We show that multilevel synapses enhance the initial rise in the memory signal and then delay its subsequent fall by inducing a plateau-like region in the memory signal. Such dynamics significantly increase memory lifetimes, defined by a signal-to-noise ratio (SNR). We derive expressions for optimal choices of synaptic parameters (filter size, number of strength states, number of synapses) that maximize SNR memory lifetimes. However, we find that with memory lifetimes defined via mean-first-passage times, such optimality conditions do not exist, suggesting that optimality may be an artifact of SNRs. PMID:27391686

  7. Age-dependent enhancement of inhibitory synaptic transmission in CA1 pyramidal neurons via GluR5 kainate receptors.

    PubMed

    Xu, Changqing; Cui, Changhai; Alkon, Daniel L

    2009-08-01

    Changes in hippocampal synaptic networks during aging may contribute to age-dependent compromise of cognitive functions such as learning and memory. Previous studies have demonstrated that GABAergic synaptic transmission exhibits age-dependent changes. To better understand such age-dependent changes of GABAergic synaptic inhibition, we performed whole-cell recordings from pyramidal cells in the CA1 area of acute hippocampal slices on aged (24-26 months old) and young (2-4 months old) Brown-Norway rats. We found that the frequency and amplitude of spontaneous inhibitory postsynaptic current (IPSCs) were significantly increased in aged rats, but the frequency and amplitude of mIPSCs were decreased. Furthermore, the regulation of GABAergic synaptic transmission by GluR5 containing kainate receptors was enhanced in aged rats, which was revealed by using LY382884 (a GluR5 kainate receptor antagonist) and ATPA (a GluR5 kainate receptor agonist). Moreover, we demonstrated that vesicular glutamate transporters are involved in the kainate receptor dependent regulation of sIPSCs. Taken together, these results suggest that GABAergic synaptic transmission is potentiated in aged rats, and GluR5 containing kainate receptors regulate the inhibitory synaptic transmission through endogenous glutamate. These alterations of GABAergic input with aging could contribute to age-dependent cognitive decline. PMID:19123252

  8. Creative Methodologies to Enhance Communication

    ERIC Educational Resources Information Center

    Kennedy, Lucille; Brewer, Gayle

    2016-01-01

    The experiences and opinions of people with learning disabilities are often ignored or devalued. Oral and life history projects allow individuals to communicate their own opinions and experiences. This process can lead to more meaningful interactions between those with learning disabilities and support workers. Whilst the interview techniques…

  9. Acute lipopolysaccharide exposure facilitates epileptiform activity via enhanced excitatory synaptic transmission and neuronal excitability in vitro

    PubMed Central

    Gao, Fei; Liu, Zhiqiang; Ren, Wei; Jiang, Wen

    2014-01-01

    Growing evidence indicates brain inflammation has been involved in the genesis of seizures. However, the direct effect of acute inflammation on neuronal circuits is not well known. Lipopolysaccharide (LPS) has been used extensively to stimulate brain inflammatory responses both in vivo and in vitro. Here, we observed the contribution of inflammation induced by 10 μg/mL LPS to the excitability of neuronal circuits in acute hippocampal slices. When slices were incubated with LPS for 30 minutes, significant increased concentration of tumor necrosis factor α and interleukin 1β were detected by enzyme-linked immunosorbent assay. In electrophysiological recordings, we found that frequency of epileptiform discharges and spikes per burst increased 30 minutes after LPS application. LPS enhanced evoked excitatory postsynaptic currents but did not modify evoked inhibitory postsynaptic currents. In addition, exposure to LPS enhanced the excitability of CA1 pyramidal neurons, as demonstrated by a decrease in rheobase and an increase in action potential frequency elicited by depolarizing current injection. Our observations suggest that acute inflammation induced by LPS facilitates epileptiform activity in vitro and that enhancement of excitatory synaptic transmission and neuronal excitability may contribute to this facilitation. These results may provide new clues for treating seizures associated with brain inflammatory disease. PMID:25170268

  10. Enhanced susceptibility to spontaneous seizures of noda epileptic rats by loss of synaptic zn(2+).

    PubMed

    Takeda, Atsushi; Iida, Masashi; Ando, Masaki; Nakamura, Masatoshi; Tamano, Haruna; Oku, Naoto

    2013-01-01

    Zinc homeostasis in the brain is associated with the etiology and manifestation of epileptic seizures. Adult Noda epileptic rats (NER, >12-week-old) exhibit spontaneously generalized tonic-clonic convulsion about once a day. To pursue the involvement of synaptic Zn(2+) signal in susceptibility to spontaneous seizures, in the present study, the effect of zinc chelators on epileptogenesis was examined using adult NER. Clioquinol (CQ) and TPEN are lipophilic zinc chelotors, transported into the brain and reduce the levels of synaptic Zn(2+). The incidence of tonic-clonic convulsion was markedly increased after i.p. injection of CQ (30-100 mg/kg) and TPEN (1 mg/kg). The basal levels of extracellular Zn(2+) measured by ZnAF-2 were decreased before tonic-clonic convulsion was induced with zinc chelators. The hippocampal electroencephalograms during CQ (30 mg/kg)-induced convulsions were similar to those during sound-induced convulsions in NER reported previously. Exocytosis of hippocampal mossy fibers, which was measured with FM4-64, was significantly increased in hippocampal slices from CQ-injected NER that did not show tonic-clonic convulsion yet. These results indicate that the abnormal excitability of mossy fibers is induced prior to epileptic seizures by injection of zinc chelators into NER. The incidence of tonic-clonic convulsion induced with CQ (30 mg/kg) was significantly reduced by co-injection with aminooxyacetic acid (5-10 mg/kg), an anticonvulsant drug enhancing GABAergic activity, which did not affect locomotor activity. The present paper demonstrates that the abnormal excitability in the brain, especially in mossy fibers, which is potentially associated with the insufficient GABAergic neuron activity, may be a factor to reduce the threshold for epileptogenesis in NER. PMID:23951148

  11. Enhanced Susceptibility to Spontaneous Seizures of Noda Epileptic Rats by Loss of Synaptic Zn2+

    PubMed Central

    Takeda, Atsushi; Iida, Masashi; Ando, Masaki; Nakamura, Masatoshi; Tamano, Haruna; Oku, Naoto

    2013-01-01

    Zinc homeostasis in the brain is associated with the etiology and manifestation of epileptic seizures. Adult Noda epileptic rats (NER, >12-week-old) exhibit spontaneously generalized tonic-clonic convulsion about once a day. To pursue the involvement of synaptic Zn2+ signal in susceptibility to spontaneous seizures, in the present study, the effect of zinc chelators on epileptogenesis was examined using adult NER. Clioquinol (CQ) and TPEN are lipophilic zinc chelotors, transported into the brain and reduce the levels of synaptic Zn2+. The incidence of tonic-clonic convulsion was markedly increased after i.p. injection of CQ (30–100 mg/kg) and TPEN (1 mg/kg). The basal levels of extracellular Zn2+ measured by ZnAF-2 were decreased before tonic-clonic convulsion was induced with zinc chelators. The hippocampal electroencephalograms during CQ (30 mg/kg)-induced convulsions were similar to those during sound-induced convulsions in NER reported previously. Exocytosis of hippocampal mossy fibers, which was measured with FM4-64, was significantly increased in hippocampal slices from CQ-injected NER that did not show tonic-clonic convulsion yet. These results indicate that the abnormal excitability of mossy fibers is induced prior to epileptic seizures by injection of zinc chelators into NER. The incidence of tonic-clonic convulsion induced with CQ (30 mg/kg) was significantly reduced by co-injection with aminooxyacetic acid (5–10 mg/kg), an anticonvulsant drug enhancing GABAergic activity, which did not affect locomotor activity. The present paper demonstrates that the abnormal excitability in the brain, especially in mossy fibers, which is potentially associated with the insufficient GABAergic neuron activity, may be a factor to reduce the threshold for epileptogenesis in NER. PMID:23951148

  12. Platelet Activating Factor Enhances Synaptic Vesicle Exocytosis Via PKC, Elevated Intracellular Calcium, and Modulation of Synapsin 1 Dynamics and Phosphorylation

    PubMed Central

    Hammond, Jennetta W.; Lu, Shao-Ming; Gelbard, Harris A.

    2016-01-01

    Platelet activating factor (PAF) is an inflammatory phospholipid signaling molecule implicated in synaptic plasticity, learning and memory and neurotoxicity during neuroinflammation. However, little is known about the intracellular mechanisms mediating PAF’s physiological or pathological effects on synaptic facilitation. We show here that PAF receptors are localized at the synapse. Using fluorescent reporters of presynaptic activity we show that a non-hydrolysable analog of PAF (cPAF) enhances synaptic vesicle release from individual presynaptic boutons by increasing the size or release of the readily releasable pool and the exocytosis rate of the total recycling pool. cPAF also activates previously silent boutons resulting in vesicle release from a larger number of terminals. The underlying mechanism involves elevated calcium within presynaptic boutons and protein kinase C activation. Furthermore, cPAF increases synapsin I phosphorylation at sites 1 and 3, and increases dispersion of synapsin I from the presynaptic compartment during stimulation, freeing synaptic vesicles for subsequent release. These findings provide a conceptual framework for how PAF, regardless of its cellular origin, can modulate synapses during normal and pathologic synaptic activity. PMID:26778968

  13. Abnormal Synaptic Vesicle Biogenesis in Drosophila Synaptogyrin Mutants

    PubMed Central

    Stevens, Robin J.; Akbergenova, Yulia; Jorquera, Ramon A.; Littleton, J. Troy

    2012-01-01

    Sustained neuronal communication relies on the coordinated activity of multiple proteins that regulate synaptic vesicle biogenesis and cycling within the presynaptic terminal. Synaptogyrin and synaptophysin are conserved MARVEL domain-containing transmembrane proteins that are among the most abundant synaptic vesicle constituents, although their role in the synaptic vesicle cycle has remained elusive. To further investigate the function of these proteins, we generated and characterized a synaptogyrin (gyr) null mutant in Drosophila, whose genome encodes a single synaptogyrin isoform and lacks a synaptophysin homolog. We demonstrate that Drosophila synaptogyrin plays a modulatory role in synaptic vesicle biogenesis at larval neuromuscular junctions. Drosophila lacking synaptogyrin are viable and fertile and have no overt deficits in motor function. However, ultrastructural analysis of gyr larvae revealed increased synaptic vesicle diameter and enhanced variability in the size of synaptic vesicles. In addition, the resolution of endocytic cisternae into synaptic vesicles in response to strong stimulation is defective in gyr mutants. Electrophysiological analysis demonstrated an increase in quantal size and a concomitant decrease in quantal content, suggesting functional consequences for transmission caused by the loss of synaptogyrin. Furthermore, high-frequency stimulation resulted in increased facilitation and a delay in recovery from synaptic depression, indicating that synaptic vesicle exo-endocytosis is abnormally regulated during intense stimulation conditions. These results suggest that synaptogyrin modulates the synaptic vesicle exo-endocytic cycle and is required for the proper biogenesis of synaptic vesicles at nerve terminals. PMID:23238721

  14. Reelin Supplementation Enhances Cognitive Ability, Synaptic Plasticity, and Dendritic Spine Density

    ERIC Educational Resources Information Center

    Rogers, Justin T.; Rusiana, Ian; Trotter, Justin; Zhao, Lisa; Donaldson, Erika; Pak, Daniel T.S.; Babus, Lenard W.; Peters, Melinda; Banko, Jessica L.; Chavis, Pascale; Rebeck, G. William; Hoe, Hyang-Sook; Weeber, Edwin J.

    2011-01-01

    Apolipoprotein receptors belong to an evolutionarily conserved surface receptor family that has intimate roles in the modulation of synaptic plasticity and is necessary for proper hippocampal-dependent memory formation. The known lipoprotein receptor ligand Reelin is important for normal synaptic plasticity, dendritic morphology, and cognitive…

  15. Enhancing Disease Surveillance Event Communication Among Jurisdictions

    PubMed Central

    Tabernero, Nathaniel R.; Loschen, Wayne A.; Jorgensen, Joel; Suereth, Joshua; Coberly, Jacqueline S.; Holtry, Rekha S.; Sikes, Marvin L.; Babin, Steven M.; Lewis, Sheryl L. Happel

    2009-01-01

    Automated disease surveillance systems are becoming widely used by the public health community. However, communication among non-collocated and widely dispersed users still needs improvement. A web-based software tool for enhancing user communications was completely integrated into an existing automated disease surveillance system and was tested during two simulated exercises and operational use involving multiple jurisdictions. Evaluation of this tool was conducted by user meetings, anonymous surveys, and web logs. Public health officials found this tool to be useful, and the tool has been modified further to incorporate features suggested by user responses. Features of the automated disease surveillance system, such as alerts and time series plots, can be specifically referenced by user comments. The user may also indicate the alert response being considered by adding a color indicator to their comment. The web-based event communication tool described in this article provides a common ground for collaboration and communication among public health officials at different locations. PMID:27325909

  16. Monitoring Synaptic Vesicle Protein Sorting with Enhanced Horseradish Peroxidase in the Electron Microscope.

    PubMed

    Schikorski, Thomas

    2016-01-01

    Protein sorting is the fundamental cellular process that creates and maintains cell organelles and subcellular structures. The synaptic vesicle (SV) is a unique cell organelle that contains a plethora of specific SV proteins and its protein composition is crucial for its function. Thus understanding the mechanisms that sort proteins to SVs and other cell organelles is central to neuroscience and cell biology.While in the past protein sorting was studied in the fluorescence and confocal microscope, we here present a protocol that reveals SV protein trafficking and sorting in the electron microscope (EM). The protocol exploits tagging SV proteins with a new genetically encoded label for EM: enhanced horseradish peroxidase (eHRP). eHRP gained its high sensitivity through direct evolution of its catalytic activity and is detectable in the EM and LM after expression in neurons and other mammalian cells. The protocol describes the use of eHRP, labeling of SVs in cultured hippocampal neurons, and analysis via serial section reconstruction. PMID:27515091

  17. Enhanced quantum communication via optical refocusing

    NASA Astrophysics Data System (ADS)

    Lupo, Cosmo; Giovannetti, Vittorio; Pirandola, Stefano; Mancini, Stefano; Lloyd, Seth

    2011-07-01

    We consider the problem of quantum communication mediated by a passive optical refocusing system. The model captures the basic features of all those situations in which a signal is either refocused by a repeater for long-distance communication, or it is focused on a detector prior to the information decoding process. Introducing a general method for linear passive optical systems, we determine the conditions under which optical refocusing implies information transmission gain. Although the finite aperture of the repeater may cause loss of information, we show that the presence of the refocusing system can substantially enhance the rate of reliable communication with respect to the free-space propagation. We explicitly address the transferring of classical messages over the quantum channel, but the results can be easily extended to include the case of transferring quantum messages as well.

  18. Neurotrophin-3 Enhances the Synaptic Organizing Function of TrkC-Protein Tyrosine Phosphatase σ in Rat Hippocampal Neurons.

    PubMed

    Ammendrup-Johnsen, Ina; Naito, Yusuke; Craig, Ann Marie; Takahashi, Hideto

    2015-09-01

    Neurotrophin-3 (NT-3) and its high-affinity receptor TrkC play crucial trophic roles in neuronal differentiation, axon outgrowth, and synapse development and plasticity in the nervous system. We demonstrated previously that postsynaptic TrkC functions as a glutamatergic synapse-inducing (synaptogenic) cell adhesion molecule trans-interacting with presynaptic protein tyrosine phosphatase σ (PTPσ). Given that NT-3 and PTPσ bind distinct domains of the TrkC extracellular region, here we tested the hypothesis that NT-3 modulates TrkC/PTPσ binding and synaptogenic activity. NT-3 enhanced PTPσ binding to cell surface-expressed TrkC and facilitated the presynapse-inducing activity of TrkC in rat hippocampal neurons. Imaging of recycling presynaptic vesicles combined with TrkC knockdown and rescue approaches demonstrated that NT-3 rapidly potentiates presynaptic function via binding endogenous postsynaptic TrkC in a tyrosine kinase-independent manner. Thus, NT-3 positively modulates the TrkC-PTPσ complex for glutamatergic presynaptic assembly and function independently from TrkC kinase activation. Our findings provide new insight into synaptic roles of neurotrophin signaling and mechanisms controlling synaptic organizing complexes. Significance statement: Although many synaptogenic adhesion complexes have been identified in recent years, little is known about modulatory mechanisms. Here, we demonstrate a novel role of neurotrophin-3 in synaptic assembly and function as a positive modulator of the TrkC-protein tyrosine phosphatase σ complex. This study provides new insight into the involvement of neurotrophin signaling in synapse development and plasticity, presenting a molecular mechanism that may underlie previous observations of short- and long-term enhancement of presynaptic function by neurotrophin. Given the links of synaptogenic adhesion molecules to autism and schizophrenia, this study might also contribute to a better understanding of the pathogenesis of

  19. Lycopene oxidation product enhances gap junctional communication.

    PubMed

    Aust, O; Ale-Agha, N; Zhang, L; Wollersen, H; Sies, H; Stahl, W

    2003-10-01

    Carotenoids as well as their metabolites and oxidation products stimulate gap junctional communication (GJC) between cells, which is thought to be one of the protective mechanisms related to cancer-preventive activities of these compounds. Increased intake of lycopene by consumption of tomatoes or tomato products has been epidemiologically associated with a diminished risk of prostate cancer. Here, we report a stimulatory effect of a lycopene oxidation product on GJC in rat liver epithelial WB-F344 cells. The active compound was obtained by complete in vitro oxidation of lycopene with hydrogen peroxide/osmium tetroxide. For structural analysis high performance liquid chromatography, gas chromatography coupled with mass spectrometry, ultraviolet/visible-, and infrared spectrophotometry were applied. The biologically active oxidation product was identified as 2,7,11-trimethyl-tetradecahexaene-1,14-dial. The present data indicate a potential role of lycopene degradation products in cell signaling enhancing cell-to-cell communication via gap junctions. PMID:12909274

  20. Long-Term Exercise Is Needed to Enhance Synaptic Plasticity in the Hippocampus

    ERIC Educational Resources Information Center

    Patten, Anna R.; Sickmann, Helle; Hryciw, Brett N.; Kucharsky, Tessa; Parton, Roberta; Kernick, Aimee; Christie, Brian R.

    2013-01-01

    Exercise can have many benefits for the body, but it also benefits the brain by increasing neurogenesis, synaptic plasticity, and performance on learning and memory tasks. The period of exercise needed to realize the structural and functional benefits for the brain have not been well delineated, and previous studies have used periods of exercise…

  1. Spinal cord explants use carbon nanotube interfaces to enhance neurite outgrowth and to fortify synaptic inputs.

    PubMed

    Fabbro, Alessandra; Villari, Ambra; Laishram, Jummi; Scaini, Denis; Toma, Francesca M; Turco, Antonio; Prato, Maurizio; Ballerini, Laura

    2012-03-27

    New developments in nanotechnology are increasingly designed to modulate relevant interactions between nanomaterials and neurons, with the aim of exploiting the physical properties of synthetic materials to tune desired and specific biological processes. Carbon nanotubes have been applied in several areas of nerve tissue engineering to study cell behavior or to instruct the growth and organization of neural networks. Recent reports show that nanotubes can sustain and promote electrical activity in networks of cultured neurons. However, such results are usually limited to carbon nanotube/neuron hybrids formed on a monolayer of dissociated brain cells. In the present work, we used organotypic spinal slices to model multilayer tissue complexity, and we interfaced such spinal segments to carbon nanotube scaffolds for weeks. By immunofluorescence, scanning and transmission electronic microscopy, and atomic force microscopy, we investigated nerve fiber growth when neuronal processes exit the spinal explant and develop in direct contact to the substrate. By single-cell electrophysiology, we investigated the synaptic activity of visually identified ventral interneurons, within the ventral area of the explant, thus synaptically connected, but located remotely, to the substrate/network interface. Here we show that spinal cord explants interfaced for weeks to purified carbon nanotube scaffolds expand more neuronal fibers, characterized by different mechanical properties and displaying higher growth cones activity. On the other hand, exploring spontaneous and evoked synaptic activity unmasks an increase in synaptic efficacy in neurons located at as far as 5 cell layers from the cell-substrate interactions. PMID:22339712

  2. Enhancing the Communication of Climate Change Science

    NASA Astrophysics Data System (ADS)

    Somerville, R. C.; Hassol, S. J.

    2011-12-01

    Climate scientists have an important role to play in the critical task of informing the public, media and policymakers. Scientists can help in publicizing and illuminating climate science. However, this task requires combining climate science expertise with advanced communication skills. For example, it is entirely possible to convey scientific information accurately without using jargon or technical concepts unfamiliar to non-scientists. However, making this translation into everyday language is a job that few scientists have been trained to do. In this talk, we give examples from our recent experience working with scientists to enhance their ability to communicate well. Our work includes providing training, technical assistance, and communications tools to climate scientists and universities, government agencies, and research centers. Our experience ranges from preparing Congressional testimony to writing major climate science reports to appearing on television. We have also aided journalists in gathering reliable scientific information and identifying trustworthy experts. Additionally, we are involved in developing resources freely available online at climatecommunication.org. These include a feature on the links between climate change and extreme weather, a climate science primer, and graphics and video explaining key developments in climate change science.

  3. Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington's Disease Mouse Model

    PubMed Central

    Wu, Jun; Ryskamp, Daniel A.; Liang, Xia; Egorova, Polina; Zakharova, Olga; Hung, Gene

    2016-01-01

    prepared from YAC128 HD mice feature age-dependent MSN spine loss, mirroring YAC128 MSN spine loss in vivo. This finding establishes a system for mechanistic studies of synaptic instability in HD. We use it to demonstrate that sensitization of type 1 inositol (1,4,5)-trisphosphate receptors by mHtt, which depletes endoplasmic reticulum calcium, contributes to synaptotoxic enhancement of STIM2-dependent store-operated calcium (SOC) entry. Treatment with EVP4593, a neuroprotective inhibitor of neuronal SOC channels, rescues YAC128 MSN spine loss both in vitro and in vivo. These results suggest that enhanced neuronal SOC causes synaptic loss in HD-afflicted MSNs. PMID:26740655

  4. Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain

    PubMed Central

    Zhang, Zhan-chi; Luan, Feng; Xie, Chun-yan; Geng, Dan-dan; Wang, Yan-yong; Ma, Jun

    2015-01-01

    In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function. PMID:26199608

  5. Enhanced Faraday effect and its application to optical communication.

    PubMed

    Bomke, H A; Harmatz, M

    1977-03-01

    This paper shows that the enhanced Faraday effect of optical resonance lines can be applied to optical communication. A secure optical communication system was designed and successfully tested. It used the integrated enhanced Faraday effect at low fields to produce polarization modulation and the high dispersion of the enhanced effect at high fields to scramble and unscramble the transmitted messages. PMID:20168574

  6. Enhancing GRASS data communication with videographic technology

    SciTech Connect

    Sullivan, R.G. ); Gerdes, D.; Youngs, D. )

    1992-01-01

    Research at Argonne National Laboratory and the US Army Construction Engineering Research Laboratory has shown that computer videographic technology can be used to assist visualization and communication of GIS-generated geographic information. Videographic tools can be used to make results of GRASS analyses clear to decision-makers and to public interest groups, as well as to help GRASS users visualize geographic data more easily. Useful videographic visualization tools include graphic overlay of GRASS layers onto panchromatic images, allowing landscape features to be associated with GIS classifications; draping of GIS layers onto terrain models to create shaded relief maps; and incorporation of photographic imagery into GIS graphics. Useful videographic communications capabilities include convenient, direct interface to video formats, allowing incorporation of live video into GRASS graphics and output of GRASS graphics to video; convenient output of high-quality slides and prints; and enhanced labeling and editing of GRASS images. Conversion of GRASS imagery to standard videographic file formats also facilitates incorporation of GRASS images into other software programs, such as database and work-processing packages.

  7. Enhancing GRASS data communication with videographic technology

    SciTech Connect

    Sullivan, R.G.; Gerdes, D.; Youngs, D.

    1992-07-01

    Research at Argonne National Laboratory and the US Army Construction Engineering Research Laboratory has shown that computer videographic technology can be used to assist visualization and communication of GIS-generated geographic information. Videographic tools can be used to make results of GRASS analyses clear to decision-makers and to public interest groups, as well as to help GRASS users visualize geographic data more easily. Useful videographic visualization tools include graphic overlay of GRASS layers onto panchromatic images, allowing landscape features to be associated with GIS classifications; draping of GIS layers onto terrain models to create shaded relief maps; and incorporation of photographic imagery into GIS graphics. Useful videographic communications capabilities include convenient, direct interface to video formats, allowing incorporation of live video into GRASS graphics and output of GRASS graphics to video; convenient output of high-quality slides and prints; and enhanced labeling and editing of GRASS images. Conversion of GRASS imagery to standard videographic file formats also facilitates incorporation of GRASS images into other software programs, such as database and work-processing packages.

  8. Enhanced GABAergic synaptic transmission at VLPAG neurons and potent modulation by oxycodone in a bone cancer pain model

    PubMed Central

    Takasu, Keiko; Ogawa, Koichi; Nakamura, Atsushi; Kanbara, Tomoe; Ono, Hiroko; Tomii, Takako; Morioka, Yasuhide; Hasegawa, Minoru; Shibasaki, Masahiro; Mori, Tomohisa; Suzuki, Tsutomu; Sakaguchi, Gaku

    2015-01-01

    Background and Purpose We demonstrated previously that oxycodone has potent antinociceptive effects at supraspinal sites. In this study, we investigated changes in neuronal function and antinociceptive mechanisms of oxycodone at ventrolateral periaqueductal gray (VLPAG) neurons, which are a major site of opioid action, in a femur bone cancer (FBC) model with bone cancer-related pain. Experimental Approach We characterized the supraspinal antinociceptive profiles of oxycodone and morphine on mechanical hypersensitivity in the FBC model. Based on the disinhibition mechanism underlying supraspinal opioid antinociception, the effects of oxycodone and morphine on GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in VLPAG neurons were evaluated in slices from the FBC model. Key Results The supraspinal antinociceptive effects of oxycodone, but not morphine, were abolished by blocking G protein-gated inwardly rectifying potassium1 (Kir3.1) channels. In slices from the FBC model, GABAergic synaptic transmission at VLPAG neurons was enhanced, as indicated by a leftward shift of the input–output relationship curve of evoked IPSCs, the increased paired-pulse facilitation and the enhancement of miniature IPSC frequency. Following treatment with oxycodone and morphine, IPSCs were reduced in the FBC model, and the inhibition of presynaptic GABA release by oxycodone, but not morphine was enhanced and dependent on Kir3.1 channels. Conclusion and Implications Our results demonstrate that Kir3.1 channels are important for supraspinal antinociception and presynaptic GABA release inhibition by oxycodone in the FBC model. Enhanced GABAergic synaptic transmission at VLPAG neurons in the FBC model is an important site of supraspinal antinociception by oxycodone via Kir3.1 channel activation. PMID:25521524

  9. Intracellular Zn2+ accumulation enhances suppression of synaptic activity following spreading depolarization.

    PubMed

    Carter, Russell E; Seidel, Jessica L; Lindquist, Britta E; Sheline, Christian T; Shuttleworth, C William

    2013-06-01

    Spreading depolarization (SD) is a feed-forward wave that propagates slowly throughout brain tissue and recovery from SD involves substantial metabolic demand. Presynaptic Zn(2+) release and intracellular accumulation occurs with SD, and elevated intracellular Zn(2+) ([Zn(2+) ]i ) can impair cellular metabolism through multiple pathways. We tested here whether increased [Zn(2+) ]i could exacerbate the metabolic challenge of SD, induced by KCl, and delay recovery in acute murine hippocampal slices. [Zn(2+) ]i loading prior to SD, by transient ZnCl2 application with the Zn(2+) ionophore pyrithione (Zn/Pyr), delayed recovery of field excitatory post-synaptic potentials (fEPSPs) in a concentration-dependent manner, prolonged DC shifts, and significantly increased extracellular adenosine accumulation. These effects could be due to metabolic inhibition, occurring downstream of pyruvate utilization. Prolonged [Zn(2+) ]i accumulation prior to SD was required for effects on fEPSP recovery and consistent with this, endogenous synaptic Zn(2+) release during SD propagation did not delay recovery from SD. The effects of exogenous [Zn(2+) ]i loading were also lost in slices preconditioned with repetitive SDs, implying a rapid adaptation. Together, these results suggest that [Zn(2+) ]i loading prior to SD can provide significant additional challenge to brain tissue, and could contribute to deleterious effects of [Zn(2+) ]i accumulation in a range of brain injury models. PMID:23495967

  10. Mutation of the Dyslexia-Associated Gene Dcdc2 Enhances Glutamatergic Synaptic Transmission Between Layer 4 Neurons in Mouse Neocortex.

    PubMed

    Che, Alicia; Truong, Dongnhu T; Fitch, R Holly; LoTurco, Joseph J

    2016-09-01

    Variants in DCDC2 have been associated with reading disability in humans, and targeted mutation of Dcdc2 in mice causes impairments in both learning and sensory processing. In this study, we sought to determine whether Dcdc2 mutation affects functional synaptic circuitry in neocortex. We found mutation in Dcdc2 resulted in elevated spontaneous and evoked glutamate release from neurons in somatosensory cortex. The probability of release was decreased to wild-type level by acute application of N-methyl-d-aspartate receptor (NMDAR) antagonists when postsynaptic NMDARs were blocked by intracellular MK-801, and could not be explained by elevated ambient glutamate, suggesting altered, nonpostsynaptic NMDAR activation in the mutants. In addition, we determined that the increased excitatory transmission was present at layer 4-layer 4 but not thalamocortical connections in Dcdc2 mutants, and larger evoked synaptic release appeared to enhance the NMDAR-mediated effect. These results demonstrate an NMDAR activation-gated, increased functional excitatory connectivity between layer 4 lateral connections in somatosensory neocortex of the mutants, providing support for potential changes in cortical connectivity and activation resulting from mutation of dyslexia candidate gene Dcdc2. PMID:26250775

  11. Mice Overexpressing Type 1 Adenylyl Cyclase Show Enhanced Spatial Memory Flexibility in the Absence of Intact Synaptic Long-Term Depression

    ERIC Educational Resources Information Center

    Zhang, Ming; Wang, Hongbing

    2013-01-01

    There is significant interest in understanding the contribution of intracellular signaling and synaptic substrates to memory flexibility, which involves new learning and suppression of obsolete memory. Here, we report that enhancement of Ca[superscript 2+]-stimulated cAMP signaling by overexpressing type 1 adenylyl cyclase (AC1) facilitated…

  12. Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity

    PubMed Central

    Thibault, Karine; Rivière, Sébastien; Lenkei, Zsolt

    2016-01-01

    Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components. Our results show that chronic neuropathic orofacial pain is associated with decreased haemodynamic responsiveness to whisker stimulation in the barrel field cortex. This reduced functional activation is likely due to the increased basal neuronal activity (measured indirectly using cFos and phospho-ERK immunoreactivity) observed in several cortical areas, including the contralateral barrel field, motor and cingulate cortices. In the same animals, immunohistochemical analysis of markers for active pre- or postsynaptic elements (Piccolo and phospho-Cofilin, respectively) revealed an increased immunofluorescence in deep cortical layers of the contralateral barrel field, motor and cingulate cortices. These results suggest that long-lasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level. PMID:27548330

  13. Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity.

    PubMed

    Thibault, Karine; Rivière, Sébastien; Lenkei, Zsolt; Férézou, Isabelle; Pezet, Sophie

    2016-01-01

    Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components. Our results show that chronic neuropathic orofacial pain is associated with decreased haemodynamic responsiveness to whisker stimulation in the barrel field cortex. This reduced functional activation is likely due to the increased basal neuronal activity (measured indirectly using cFos and phospho-ERK immunoreactivity) observed in several cortical areas, including the contralateral barrel field, motor and cingulate cortices. In the same animals, immunohistochemical analysis of markers for active pre- or postsynaptic elements (Piccolo and phospho-Cofilin, respectively) revealed an increased immunofluorescence in deep cortical layers of the contralateral barrel field, motor and cingulate cortices. These results suggest that long-lasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level. PMID:27548330

  14. Human enhancement and communication: on meaning and shared understanding.

    PubMed

    Cabrera, Laura; Weckert, John

    2013-09-01

    Our technologies have enabled us to change both the world and our perceptions of the world, as well as to change ourselves and to find new ways to fulfil the human desire for improvement and for having new capacities. The debate around using technology for human enhancement has already raised many ethical concerns, however little research has been done in how human enhancement can affect human communication. The purpose of this paper is to explore whether some human enhancements could change our shared lifeworld so radically that human communication as we know it would not be possible any longer. After exploring the kinds of communication problems we are concerned with as well as mentioning some possible enhancement interventions that could bring about such problems, we will address some of the ethical implications that follow from these potential communication problems. We argue that because of the role that communication plays in human society, this issue deserves attention. PMID:23054673

  15. Enhanced corticosteroid signaling alters synaptic plasticity in the dentate gyrus in mice lacking the fragile X mental retardation protein.

    PubMed

    Ghilan, M; Hryciw, B N; Brocardo, P S; Bostrom, C A; Gil-Mohapel, J; Christie, B R

    2015-05-01

    The fragile X mental retardation protein (FMRP) is an important regulator of protein translation, and a lack of FMRP expression leads to a cognitive disorder known as fragile X syndrome (FXS). Clinical symptoms characterizing FXS include learning impairments and heightened anxiety in response to stressful situations. Here, we report that, in response to acute stress, mice lacking FMRP show a faster elevation of corticosterone and a more immediate impairment in N-methyl-d-aspartate receptor (NMDAR) dependent long-term potentiation (LTP) in the dentate gyrus (DG). These stress-induced LTP impairments were rescued by administering the glucocorticoid receptor (GR) antagonist RU38486. Administration of RU38486 also enhanced LTP in Fmr1(-/y) mice in the absence of acute stress to wild-type levels, and this enhancement was blocked by application of the NMDAR antagonist 2-amino-5-phosphonopentanoic acid. These results suggest that a loss of FMPR results in enhanced GR signaling that may adversely affect NMDAR dependent synaptic plasticity in the DG. PMID:25731748

  16. Effective Perioperative Communication to Enhance Patient Care.

    PubMed

    Garrett, J Hudson

    2016-08-01

    Breakdowns in health care communication are a significant cause of sentinel events and associated patient morbidity and mortality. Effective communication is a necessary component of a patient safety program, which enables all members of the interdisciplinary health care team to effectively manage their individual roles and responsibilities in the perioperative setting; set expectations for safe, high-reliability care; and measure and assess outcomes. To sustain a culture of safety, effective communication should be standardized, complete, clear, brief, and timely. Executive leadership and support helps remove institutional barriers and address challenges to support the engagement of patients in health care communication, which has been shown to improve outcomes, reduce costs, and improve the patient experience. PMID:27472971

  17. Enhancing Mathematical Communication: "Bag of Tricks" Game

    ERIC Educational Resources Information Center

    Patahuddin, Sitti Maesuri; Ramful, Ajay; Greenlees, Jane

    2015-01-01

    An engaging activity which prompts students to listen, talk, reason and write about geometrical properties. The "Bag of Tricks" encourages students to clarify their thoughts and communicate precisely using accurate mathematical language.

  18. Rabies Virus CVS-N2c(ΔG) Strain Enhances Retrograde Synaptic Transfer and Neuronal Viability.

    PubMed

    Reardon, Thomas R; Murray, Andrew J; Turi, Gergely F; Wirblich, Christoph; Croce, Katherine R; Schnell, Matthias J; Jessell, Thomas M; Losonczy, Attila

    2016-02-17

    Virally based transsynaptic tracing technologies are powerful experimental tools for neuronal circuit mapping. The glycoprotein-deletion variant of the SAD-B19 vaccine strain rabies virus (RABV) has been the reagent of choice in monosynaptic tracing, since it permits the mapping of synaptic inputs to genetically marked neurons. Since its introduction, new helper viruses and reagents that facilitate complementation have enhanced the efficiency of SAD-B19(ΔG) transsynaptic transfer, but there has been little focus on improvements to the core RABV strain. Here we generate a new deletion mutant strain, CVS-N2c(ΔG), and examine its neuronal toxicity and efficiency in directing retrograde transsynaptic transfer. We find that by comparison with SAD-B19(ΔG), the CVS-N2c(ΔG) strain exhibits a reduction in neuronal toxicity and a marked enhancement in transsynaptic neuronal transfer. We conclude that the CVS-N2c(ΔG) strain provides a more effective means of mapping neuronal circuitry and of monitoring and manipulating neuronal activity in vivo in the mammalian CNS. PMID:26804990

  19. Enhancing flood resilience through improved risk communications

    NASA Astrophysics Data System (ADS)

    O'Sullivan, J. J.; Bradford, R. A.; Bonaiuto, M.; De Dominicis, S.; Rotko, P.; Aaltonen, J.; Waylen, K.; Langan, S. J.

    2012-07-01

    A framework of guiding recommendations for effective pre-flood and flood warning communications derived from the URFlood project (2nd ERA-Net CRUE Research Funding Initiative) from extensive quantitative and qualitative research in Finland, Ireland, Italy and Scotland is presented. Eleven case studies in fluvial, pluvial, coastal, residual and "new" flood risk locations were undertaken. The recommendations were developed from questionnaire surveys by exploring statistical correlations of actions and understandings of individuals in flood risk situations to low, moderate and high resilience groupings. Groupings were based on a conceptual relationship of self-assessed levels of awareness, preparedness and worry. Focus groups and structured interviews were used to discuss barriers in flood communications, explore implementation of the recommendations and to rank the recommendations in order of perceived importance. Results indicate that the information deficit model for flood communications that relies on the provision of more and better information to mitigate risk in flood-prone areas is insufficient, and that the communications process is very much multi-dimensional. The recommendations are aimed at addressing this complexity and their careful implementation is likely to improve the penetration of flood communications. The recommendations are applicable to other risks and are transferrable to jurisdictions beyond the project countries.

  20. Relationship-Enhancing Communication Skills in "The Cosby Show."

    ERIC Educational Resources Information Center

    Aust, Charles F.

    A study examined the parenting behaviors portrayed on "The Cosby Show" to determine the use of specific parenting skills and family relationship-enhancing communication techniques. Videotapes of nine randomly chosen broadcast episodes were content analyzed according to family communication models of Thomas P. Gordon (1970), Bernard J. Guerney…

  1. Carbamazepine and oxcarbazepine, but not eslicarbazepine, enhance excitatory synaptic transmission onto hippocampal CA1 pyramidal cells through an antagonist action at adenosine A1 receptors.

    PubMed

    Booker, Sam A; Pires, Nuno; Cobb, Stuart; Soares-da-Silva, Patrício; Vida, Imre

    2015-06-01

    This study assessed the anticonvulsant and seizure generation effects of carbamazepine (CBZ), oxcarbazepine (OXC) and eslicarbazepine (S-Lic) in wild-type mice. Electrophysiological recordings were made to discriminate potential cellular and synaptic mechanisms underlying anti- and pro-epileptic actions. The anticonvulsant and pro-convulsant effects were evaluated in the MES, the 6-Hz and the Irwin tests. Whole-cell patch-clamp recordings were used to investigate the effects on fast excitatory and inhibitory synaptic transmission in hippocampal area CA1. The safety window for CBZ, OXC and eslicarbazepine (ED50 value against the MES test and the dose that produces grade 5 convulsions in all mice), was 6.3, 6.0 and 12.5, respectively. At high concentrations the three drugs reduced synaptic transmission. CBZ and OXC enhanced excitatory postsynaptic currents (EPSCs) at low, therapeutically-relevant concentrations. These effects were associated with no change in inhibitory postsynaptic currents (IPSCs) resulting in altered balance between excitation and inhibition. S-Lic had no effect on EPSC or IPSC amplitudes over the same concentration range. The CBZ mediated enhancement of EPSCs was blocked by DPCPX, a selective antagonist, and occluded by CCPA, a selective agonist of the adenosine A1 receptor. Furthermore, reduction of endogenous adenosine by application of the enzyme adenosine deaminase also abolished the CBZ- and OXC-induced increase of EPSCs, indicating that the two drugs act as antagonists at native adenosine receptors. In conclusion, CBZ and OXC possess pro-epileptic actions at clinically-relevant concentrations through the enhancement of excitatory synaptic transmission. S-Lic by comparison has no such effect on synaptic transmission, explaining its lack of seizure exacerbation. PMID:25656478

  2. Iowa Communications Network Enhancing Education in Iowa.

    ERIC Educational Resources Information Center

    Ivanovic, Greta

    1995-01-01

    Describes the Iowa Communications Network, a statewide fiber optic network capable of transporting interactive, two-way audio, video, voice, and data signals. Topics include statewide cooperation among educational and state organizations; classroom design, including interactive classrooms; access to the Internet; and use by noneducational…

  3. Enhancing Communication through Gesture and Naming Therapy

    ERIC Educational Resources Information Center

    Caute, Anna; Pring, Tim; Cocks, Naomi; Cruice, Madeline; Best, Wendy; Marshall, Jane

    2013-01-01

    Purpose: In this study, the authors investigated whether gesture, naming, and strategic treatment improved the communication skills of 14 people with severe aphasia. Method: All participants received 15 hr of gesture and naming treatment (reported in a companion article [Marshall et al., 2012]). Half the group received a further 15 hr of strategic…

  4. Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning.

    PubMed

    Stelly, Claire E; Pomrenze, Matthew B; Cook, Jason B; Morikawa, Hitoshi

    2016-01-01

    Enduring memories of sensory cues associated with drug intake drive addiction. It is well known that stressful experiences increase addiction vulnerability. However, it is not clear how repeated stress promotes learning of cue-drug associations, as repeated stress generally impairs learning and memory processes unrelated to stressful experiences. Here, we show that repeated social defeat stress in rats causes persistent enhancement of long-term potentiation (LTP) of NMDA receptor-mediated glutamatergic transmission in the ventral tegmental area (VTA). Protein kinase A-dependent increase in the potency of inositol 1,4,5-triphosphate-induced Ca(2+) signaling underlies LTP facilitation. Notably, defeated rats display enhanced learning of contextual cues paired with cocaine experience assessed using a conditioned place preference (CPP) paradigm. Enhancement of LTP in the VTA and cocaine CPP in behaving rats both require glucocorticoid receptor activation during defeat episodes. These findings suggest that enhanced glutamatergic plasticity in the VTA may contribute, at least partially, to increased addiction vulnerability following repeated stressful experiences. PMID:27374604

  5. Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning

    PubMed Central

    Stelly, Claire E; Pomrenze, Matthew B; Cook, Jason B; Morikawa, Hitoshi

    2016-01-01

    Enduring memories of sensory cues associated with drug intake drive addiction. It is well known that stressful experiences increase addiction vulnerability. However, it is not clear how repeated stress promotes learning of cue-drug associations, as repeated stress generally impairs learning and memory processes unrelated to stressful experiences. Here, we show that repeated social defeat stress in rats causes persistent enhancement of long-term potentiation (LTP) of NMDA receptor-mediated glutamatergic transmission in the ventral tegmental area (VTA). Protein kinase A-dependent increase in the potency of inositol 1,4,5-triphosphate-induced Ca2+ signaling underlies LTP facilitation. Notably, defeated rats display enhanced learning of contextual cues paired with cocaine experience assessed using a conditioned place preference (CPP) paradigm. Enhancement of LTP in the VTA and cocaine CPP in behaving rats both require glucocorticoid receptor activation during defeat episodes. These findings suggest that enhanced glutamatergic plasticity in the VTA may contribute, at least partially, to increased addiction vulnerability following repeated stressful experiences. DOI: http://dx.doi.org/10.7554/eLife.15448.001 PMID:27374604

  6. Isoflurane enhances both fast and slow synaptic inhibition in the hippocampus at amnestic concentrations

    PubMed Central

    Dai, Shuiping; Perouansky, Misha; Pearce, Robert A.

    2012-01-01

    Background Inhibition mediated by γ-aminobutyric acid type A (GABAA) receptors has long been considered an important target for a variety of general anesthetics. In the hippocampus, two types of phasic GABAA receptor-mediated inhibition coexist: GABAA,fast, which is expressed primarily at peri-somatic sites, and GABAA,slow, which is expressed primarily in the dendrites. Their spatial segregation suggests distinct functions: GABAA,slow may control plasticity of dendritic synapses, while GABAA,fast controls action potential initiation at the soma. We examined modulation of GABAA,fast and GABAA,slow inhibition by isoflurane at amnesic concentrations, and compared it to modulation by behaviorally equivalent doses of the GABAA receptor-selective drug etomidate. Methods Whole-cell recordings were conducted at near-physiological temperature from pyramidal cells in organotypic hippocampal cultures obtained from C57BL/6 x 129/SvJ F1 hybrid mice. GABAA receptor-mediated currents were isolated using glutamate receptor antagonists. GABAA,slow currents were evoked by electrical stimulation in the stratum lacunosum-moleculare. Miniature GABAA,fast currents were recorded in the presence of tetrodotoxin. Results 100 µM isoflurane (approximately EC50,amnesia) slowed fast and slow inhibitory postsynaptic current decay by approximately 25%. Higher concentrations, up to 400 µM, produced proportionally greater effects without altering current amplitudes. The effects on GABAA,slow were approximately one-half those produced by equi-amnesic concentrations of etomidate. Conclusions Isoflurane enhances both types of phasic GABAA receptor-mediated inhibition to similar degrees at amnesic concentrations. This pattern differs from etomidate, which at low concentrations selectively enhances slow inhibition. These effects of isoflurane are sufficiently large that they may contribute substantially to its suppression of hippocampal learning and memory. PMID:22343472

  7. Mobile Seamless Technology Enhanced CSL Oral Communication

    ERIC Educational Resources Information Center

    Lan, Yu-Ju; Lin, Yen-Ting

    2016-01-01

    The current study aimed at investigating how mobile seamless technology can be used to enhance the pragmatic competence of learners of Chinese as a second language (CSL). 34 overseas CSL learners participated in this study. They were randomly assigned into two groups: the classroom group, executing language tasks in fake contexts in a traditional…

  8. Efficacy Enhancing Communication within the Online Courseroom

    ERIC Educational Resources Information Center

    Kasitz, Christine M.

    2013-01-01

    Online learning is becoming more prevalent in high schools especially with at-risk students who may need to recover credits to meet graduation requirements. The purpose of this study was to examine the effects of an online courseroom design that delivers performance-based efficacy enhancing feedback at regular intervals, rather than relying on the…

  9. Entanglement enhances security in quantum communication

    SciTech Connect

    Demkowicz-Dobrzanski, Rafal; Sen, Aditi; Sen, Ujjwal; Lewenstein, Maciej

    2009-07-15

    Secret sharing is a protocol in which a 'boss' wants to send a classical message secretly to two 'subordinates', such that none of the subordinates is able to know the message alone, while they can find it if they cooperate. Quantum mechanics is known to allow for such a possibility. We analyze tolerable quantum bit error rates in such secret sharing protocols in the physically relevant case when the eavesdropping is local with respect to the two channels of information transfer from the boss to the two subordinates. We find that using entangled encoding states is advantageous to legitimate users of the protocol. We therefore find that entanglement is useful for secure quantum communication. We also find that bound entangled states with positive partial transpose are not useful as a local eavesdropping resource. Moreover, we provide a criterion for security in secret sharing--a parallel of the Csiszar-Koerner criterion in single-receiver classical cryptography.

  10. Enhancing Mediated Interpersonal Communication through Affective Haptics

    NASA Astrophysics Data System (ADS)

    Tsetserukou, Dzmitry; Neviarouskaya, Alena; Prendinger, Helmut; Kawakami, Naoki; Ishizuka, Mitsuru; Tachi, Susumu

    Driven by the motivation to enhance emotionally immersive experience of real-time messaging in 3D virtual world Second Life, we are proposing a conceptually novel approach to reinforcing (intensifying) own feelings and reproducing (simulating) the emotions felt by the partner through specially designed system, iFeel_IM!. In the paper we are describing the development of novel haptic devices (HaptiHeart, HaptiHug, HaptiTickler, HaptiCooler, and HaptiWarmer) integrated into iFeel_IM! system, which architecture is presented in detail.

  11. Willed-movement training reduces brain damage and enhances synaptic plasticity related proteins synthesis after focal ischemia.

    PubMed

    Nie, Jingjing; Yang, Xiaosu; Tang, Qingping; Shen, Qin; Li, Simin

    2016-01-01

    It has been wildly accepted that willed movement(WM) training promotes neurological rehabilitation in patients with stroke. However, it was not clear whether the effect of WM is better than other forms of exercise. The purpose of this study is to assess different effects of WM and other forms of exercise on rats with focal ischemia. The subjects are all had right middle cerebral artery occlusion (MCAO) surgery and randomly allocated to three groups of training and one control group with no training. Infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) dye, expression of PICK1 and synaptophysin in cerebral cortex and striatum of injured side by western blotting and immunofluorescence performed are analyzed. Exercise has done respectively on rats in each group for 15 days and 30 days. Compared with the control group, the brain damage is reduced in other groups after 15 days exercise. The protein expressions levels of synaptophysin and PICK1 are upregulated after exercise. Concentration of PICK1 protein in WM is greater than other exercise groups, and the expression of synaptophysin in WM and SM groups are higher than EM groups. The number of PICK1 positive cells, synaptophysin and PICK1 co-positive cells are increased by exercise. Synaptophysin is widely distributed in cortex surrounding the injury area in WM and EM. It is indicated in our result that willed-movement training is the most effective intervention in enhancing the PICK1-mediated synaptic plasticity in the area adjacent to the damage region of ischemic rats. PMID:26556240

  12. Alert signals enhance animal communication in “noisy” environments

    PubMed Central

    Ord, Terry J.; Stamps, Judy A.

    2008-01-01

    Environmental noise that reduces the probability that animals will detect communicative signals poses a special challenge for long-range communication. The application of signal-detection theory to animal communication lead to the prediction that signals directed at distant receivers in noisy environments will begin with conspicuous “alerting” components to attract the attention of receivers, before delivery of the information-rich portion of the signal. Whether animals actually adopt this strategy is not clear, despite suggestions that alerts might exist in a variety of taxa. By using a combination of behavioral observations and experimental manipulations with robotic lizard “playbacks,” we show that free-living territorial Anolis lizards add an “alert” to visual displays when communicating to distant receivers in situations of poor visibility, and that these introductory alerts in turn enhance signal detection in adverse signaling conditions. Our results show that Anolis lizards are able to evaluate environmental conditions that affect the degradation of long-distance signals and adjust their behavior accordingly. This study demonstrates that free-living animals enhance the efficiency of long-range communication through the modulation of signal design and the facultative addition of an alert. Our findings confirm that alert signals are an important strategy for communicating in “noisy” conditions and suggest a reexamination of the existence of alerts in other animals relying on long-range communication. PMID:19033197

  13. Privacy enhanced group communication in clinical environment

    NASA Astrophysics Data System (ADS)

    Li, Mingyan; Narayanan, Sreeram; Poovendran, Radha

    2005-04-01

    Privacy protection of medical records has always been an important issue and is mandated by the recent Health Insurance Portability and Accountability Act (HIPAA) standards. In this paper, we propose security architectures for a tele-referring system that allows electronic group communication among professionals for better quality treatments, while protecting patient privacy against unauthorized access. Although DICOM defines the much-needed guidelines for confidentiality of medical data during transmission, there is no provision in the existing medical security systems to guarantee patient privacy once the data has been received. In our design, we address this issue by enabling tracing back to the recipient whose received data is disclosed to outsiders, using watermarking technique. We present security architecture design of a tele-referring system using a distributed approach and a centralized web-based approach. The resulting tele-referring system (i) provides confidentiality during the transmission and ensures integrity and authenticity of the received data, (ii) allows tracing of the recipient who has either distributed the data to outsiders or whose system has been compromised, (iii) provides proof of receipt or origin, and (iv) can be easy to use and low-cost to employ in clinical environment.

  14. Zipper mast for enhanced communications and surveillance

    NASA Astrophysics Data System (ADS)

    Woodruff, George; Muench, Paul; Witus, Gary

    2011-05-01

    In this project, we further developed and tested a "ZipperMast" for small robots and legacy manned vehicles. The ZipperMast knits three coiled bands of spring steel together to form a rigid mast. As the mast is extended, it draws up a cable connecting the host platform to the payload, typically antennas and sensors. Elevating the payload improves line of sight, and thus improves radio communication and surveillance situation awareness. When the mast is retracted, the interior cable slides into a horizontal tray. The ZipperMast is a scaleable design. We have made systems that elevate to 8 and 20 feet. The 8 foot ZipperMast collapses to less that 8 inches high and 8 inches wide. The 20 foot ZipperMast collapses to less that 12 inches high and 18 inches wide. In this paper we report on tests of the mechanical properties of the mast, specifically the strength and stiffness under quasi-static and impulsive loading. These properties are important for specifying constraints on height as a function of speed and payload and on speed as a function of height and payload in order to ensure that the mast will not fail in the event of sudden stop, as in the event of a collision.

  15. Entanglement enhances security in quantum communication

    NASA Astrophysics Data System (ADS)

    Demkowicz-Dobrzański, Rafał; Sen(de), Aditi; Sen, Ujjwal; Lewenstein, Maciej

    2009-07-01

    Secret sharing is a protocol in which a “boss” wants to send a classical message secretly to two “subordinates,” such that none of the subordinates is able to know the message alone, while they can find it if they cooperate. Quantum mechanics is known to allow for such a possibility. We analyze tolerable quantum bit error rates in such secret sharing protocols in the physically relevant case when the eavesdropping is local with respect to the two channels of information transfer from the boss to the two subordinates. We find that using entangled encoding states is advantageous to legitimate users of the protocol. We therefore find that entanglement is useful for secure quantum communication. We also find that bound entangled states with positive partial transpose are not useful as a local eavesdropping resource. Moreover, we provide a criterion for security in secret sharing—a parallel of the Csiszár-Körner criterion in single-receiver classical cryptography.

  16. Novel technology for enhanced security and trust in communication networks

    NASA Astrophysics Data System (ADS)

    Milovanov, Alexander; Bukshpun, Leonid; Pradhan, Ranjit; Jannson, Tomasz

    2011-06-01

    A novel technology that significantly enhances security and trust in wireless and wired communication networks has been developed. It is based on integration of a novel encryption mechanism and novel data packet structure with enhanced security tools. This novel data packet structure results in an unprecedented level of security and trust, while at the same time reducing power consumption and computing/communication overhead in networks. As a result, networks are provided with protection against intrusion, exploitation, and cyber attacks and posses self-building, self-awareness, self-configuring, self-healing, and self-protecting intelligence.

  17. Enhancing Students' Communication Skills through Treffinger Teaching Model

    ERIC Educational Resources Information Center

    Alhaddad, Idrus; Kusumah, Yaya S.; Sabandar, Jozua; Dahlan, Jarnawi A.

    2015-01-01

    This research aims to investigate, compare, and describe the achievement and enhancement of students' mathematical communication skills (MCS). It based on the prior mathematical knowledge (PMK) category (high, medium and low) by using Treffinger models (TM) and conventional learning (CL). This research is an experimental study with the population…

  18. The Team Boat Exercise: Enhancing Team Communication Midsemester

    ERIC Educational Resources Information Center

    Cox, Pamela L.; Friedman, Barry A.

    2009-01-01

    This paper discusses the Team Boat Exercise, which was developed to provide students with a mechanism for addressing team problems and enhancing team communication midsemester. The inspiration for the exercise came from a video by Prentice Hall, Inc. (2001). Part III of the video, entitled "Corporate Coaching," shows senior staff members from the…

  19. Activation of Exchange Protein Activated by Cyclic-AMP Enhances Long-Lasting Synaptic Potentiation in the Hippocampus

    ERIC Educational Resources Information Center

    Gelinas, Jennifer N.; Banko, Jessica L.; Peters, Melinda M.; Klann, Eric; Weeber, Edwin J.; Nguyen, Peter V.

    2008-01-01

    cAMP is a critical second messenger implicated in synaptic plasticity and memory in the mammalian brain. Substantial evidence links increases in intracellular cAMP to activation of cAMP-dependent protein kinase (PKA) and subsequent phosphorylation of downstream effectors (transcription factors, receptors, protein kinases) necessary for long-term…

  20. Neutralization of Nogo-A Enhances Synaptic Plasticity in the Rodent Motor Cortex and Improves Motor Learning in Vivo

    PubMed Central

    Weinmann, Oliver; Kellner, Yves; Yu, Xinzhu; Vicente, Raul; Gullo, Miriam; Kasper, Hansjörg; Lussi, Karin; Ristic, Zorica; Luft, Andreas R.; Rioult-Pedotti, Mengia; Zuo, Yi; Zagrebelsky, Marta; Schwab, Martin E.

    2014-01-01

    The membrane protein Nogo-A is known as an inhibitor of axonal outgrowth and regeneration in the CNS. However, its physiological functions in the normal adult CNS remain incompletely understood. Here, we investigated the role of Nogo-A in cortical synaptic plasticity and motor learning in the uninjured adult rodent motor cortex. Nogo-A and its receptor NgR1 are present at cortical synapses. Acute treatment of slices with function-blocking antibodies (Abs) against Nogo-A or against NgR1 increased long-term potentiation (LTP) induced by stimulation of layer 2/3 horizontal fibers. Furthermore, anti-Nogo-A Ab treatment increased LTP saturation levels, whereas long-term depression remained unchanged, thus leading to an enlarged synaptic modification range. In vivo, intrathecal application of Nogo-A-blocking Abs resulted in a higher dendritic spine density at cortical pyramidal neurons due to an increase in spine formation as revealed by in vivo two-photon microscopy. To investigate whether these changes in synaptic plasticity correlate with motor learning, we trained rats to learn a skilled forelimb-reaching task while receiving anti-Nogo-A Abs. Learning of this cortically controlled precision movement was improved upon anti-Nogo-A Ab treatment. Our results identify Nogo-A as an influential molecular modulator of synaptic plasticity and as a regulator for learning of skilled movements in the motor cortex. PMID:24966370

  1. Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen-glucose deprivation.

    PubMed

    Kocsis, Kitti; Frank, Rita; Szabó, József; Knapp, Levente; Kis, Zsolt; Farkas, Tamás; Vécsei, László; Toldi, József

    2016-09-22

    Hypoxic circumstances result in functional and structural impairments of the brain. Oxygen-glucose deprivation (OGD) on hippocampal slices is a technique widely used to investigate the consequences of ischemic stroke and the potential neuroprotective effects of different drugs. Acetyl-l-carnitine (ALC) is a naturally occurring substance in the body, and it can therefore be administered safely even in relatively high doses. In previous experiments, ALC pretreatment proved to be effective against global hypoperfusion. In the present study, we investigated whether ALC can be protective in an OGD model. We are not aware of any earlier study in which the long-term potentiation (LTP) function on hippocampal slices was measured after OGD. Therefore, we set out to determine whether an effective ALC concentration has an effect on synaptic plasticity after OGD in the hippocampal CA1 subfield of rats. A further aim was to investigate the mechanism underlying the protective effect of this compound. The experiments revealed that ALC is neuroprotective against OGD in a dose-dependent manner, which is manifested not only in the regeneration of the impaired synaptic transmission after the OGD, but also in the inducibility and stability of the LTP. In the case of the most effective concentration of ALC (500μM), use of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) revealed that the PI3K/Akt signaling pathway has a key role in the restoration of the synaptic transmission and plasticity reached by ALC treatment. PMID:27378558

  2. TARP phosphorylation regulates synaptic AMPA receptors through lipid bilayers

    PubMed Central

    Sumioka, Akio; Yan, Dan; Tomita, Susumu

    2010-01-01

    Summary Neurons use neurotransmitters to communicate across synapses, constructing neural circuits in the brain. AMPA-type glutamate receptors are the predominant excitatory neurotransmitter receptors mediating fast synaptic transmission. AMPA receptors localize at synapses by forming protein complexes with transmembrane AMPA receptor regulatory proteins (TARPs) and PSD-95-like MAGUKs. Among the three classes of ionotropic glutamate receptors (AMPA-, NMDA, kainate-type), AMPA receptor activity is most regulatable by neuronal activity to adjust synaptic strength. Here, we mutated the prototypical TARP, stargazin, and found that TARP phosphorylation regulates synaptic AMPA receptor activity in vivo. We also found that stargazin interacts with negatively-charged lipid bilayers in its phosphorylation dependent manner, and that the lipid interaction inhibited stargazin binding to PSD-95. Cationic lipids dissociated stargazin from lipid bilayers and enhanced synaptic AMPA receptor activity in a stargazin phosphorylation-dependent manner. Thus, TARP phosphorylation plays a critical role in regulating AMPA receptor-mediated synaptic transmission via a lipid bilayer interaction. PMID:20547132

  3. Chronic Intermittent Ethanol Exposure Enhances the Excitability and Synaptic Plasticity of Lateral Orbitofrontal Cortex Neurons and Induces a Tolerance to the Acute Inhibitory Actions of Ethanol.

    PubMed

    Nimitvilai, Sudarat; Lopez, Marcelo F; Mulholland, Patrick J; Woodward, John J

    2016-03-01

    Alcoholism is associated with changes in brain reward and control systems, including the prefrontal cortex. In prefrontal areas, the orbitofrontal cortex (OFC) has been suggested to have an important role in the development of alcohol-abuse disorders and studies from this laboratory demonstrate that OFC-mediated behaviors are impaired in alcohol-dependent animals. However, it is not known whether chronic alcohol (ethanol) exposure alters the fundamental properties of OFC neurons. In this study, mice were exposed to repeated cycles of chronic intermittent ethanol (CIE) exposure to induce dependence and whole-cell patch-clamp electrophysiology was used to examine the effects of CIE treatment on lateral OFC (lOFC) neuron excitability, synaptic transmission, and plasticity. Repeated cycles of CIE exposure and withdrawal enhanced current-evoked action potential (AP) spiking and this was accompanied by a reduction in the after-hyperpolarization and a decrease in the functional activity of SK channels. CIE mice also showed an increase in the AMPA/NMDA ratio, and this was associated with an increase in GluA1/GluA2 AMPA receptor expression and a decrease in GluN2B NMDA receptor subunits. Following CIE treatment, lOFC neurons displayed a persistent long-term potentiation of glutamatergic synaptic transmission following a spike-timing-dependent protocol. Lastly, CIE treatment diminished the inhibitory effect of acute ethanol on AP spiking of lOFC neurons and reduced expression of the GlyT1 transporter. Taken together, these results suggest that chronic exposure to ethanol leads to enhanced intrinsic excitability and glutamatergic synaptic signaling of lOFC neurons. These alterations may contribute to the impairment of OFC-dependent behaviors in alcohol-dependent individuals. PMID:26286839

  4. Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels.

    PubMed

    Nishio, N; Taniguchi, W; Sugimura, Y K; Takiguchi, N; Yamanaka, M; Kiyoyuki, Yasukuni; Yamada, H; Miyazaki, N; Yoshida, M; Nakatsuka, T

    2013-09-01

    Central neuropathic pain (CNP) in the spinal cord, such as chronic pain after spinal cord injury (SCI), is an incurable ailment. However, little is known about the spinal cord mechanisms underlying CNP. Recently, reactive oxygen species (ROS) have been recognized to play an important role in CNP of the spinal cord. However, it is unclear how ROS affect synaptic transmission in the dorsal horn of the spinal cord. To clarify how ROS impact on synaptic transmission, we investigated the effects of ROS on synaptic transmission in rat spinal cord substantia gelatinosa (SG) neurons using whole-cell patch-clamp recordings. Administration of tert-butyl hydroperoxide (t-BOOH), an ROS donor, into the spinal cord markedly increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in SG neurons. This t-BOOH-induced enhancement was not suppressed by the Na(+) channel blocker tetrodotoxin. However, in the presence of a non-N-methyl-D-aspartate glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, t-BOOH did not generate any sEPSCs. Furthermore, in the presence of a transient receptor potential ankyrin 1 (TRPA1) channel antagonist (HC-030031) or a transient receptor potential vanilloid 1 (TRPV1) channel antagonist (capsazepine or AMG9810), the t-BOOH-induced increase in the frequency of sEPSCs was inhibited. These results indicate that ROS enhance the spontaneous release of glutamate from presynaptic terminals onto SG neurons through TRPA1 and TRPV1 channel activation. Excessive activation of these ion channels by ROS may induce central sensitization in the spinal cord and result in chronic pain such as that following SCI. PMID:23707800

  5. Coupled Electromagnetic Resonators for Enhanced Communications and Telemetry

    NASA Technical Reports Server (NTRS)

    Dimmock, John O.

    2005-01-01

    Future NASA missions will require the collection of an increasing quantity and quality of data which, in turn, will place increasing demands on advanced sensors and advanced high bandwidth telemetry and communications systems. The capabilities of communication and telemetry systems depend, among other factors, on the stability, controllability and spectral purity of the carrier wave. These, in turn, depend on the quality of the oscillator, or resonator, or the Q of the system. Recent work on high Q optical resonators has indicated that the Q, or quality factor, of optical microsphere resonators can be substantially enhanced by coupling several such resonators together.1-3 In addition to the possibility of enhanced Q and increased energy storage capacity, the coupled optical resonators indicate that a wide variety of interesting and potentially useful phenomena such as induced transparency and interactive mode splitting can be observed depending critically on the morphology and configuration of the microresonators. The purpose of this SFFP has been to examine several different coupled electromagnetic oscillator configurations in order to evaluate their potential for enhanced electromagnetic communications.

  6. Communication Labs Enhance Student Learning and Promote Awareness of the Discipline.

    ERIC Educational Resources Information Center

    Morreale, Sherwyn P.

    The use of a communication laboratory to support instruction in higher education is increasing in popularity. While enhancing communication education for majors and non-majors, a "comm lab" also promotes campus awareness and enhances the reputation of the communication department. The communication discipline lends itself to this form of pedagogy,…

  7. Reciprocity-enhanced optical communication through atmospheric turbulence - part II: communication architectures and performance

    NASA Astrophysics Data System (ADS)

    Puryear, Andrew L.; Shapiro, Jeffrey H.; Parenti, Ronald R.

    2012-10-01

    Free-space optical communication provides rapidly deployable, dynamic communication links that are capable of very high data rates compared with those of radio-frequency systems. As such, free-space optical communication is ideal for mobile platforms, for platforms that require the additional security afforded by the narrow divergence of a laser beam, and for systems that must be deployed in a relatively short time frame. In clear-weather conditions the data rate and utility of free-space optical communication links are primarily limited by fading caused by micro-scale atmospheric temperature variations that create parts-per-million refractive-index fluctuations known as atmospheric turbulence. Typical communication techniques to overcome turbulence-induced fading, such as interleavers with sophisticated codes, lose viability as the data rate is driven higher or the delay requirement is driven lower. This paper, along with its companion [J. H. Shapiro and A. Puryear, "Reciprocity-Enhanced Optical Communication through Atmospheric Turbulence-Part I: Reciprocity Proofs and Far-Field Power Transfer"], present communication systems and techniques that exploit atmospheric reciprocity to overcome turbulence which are viable for high data rate and low delay requirement systems. Part I proves that reciprocity is exhibited under rather general conditions, and derives the optimal power-transfer phase compensation for far-field operation. The Part II paper presents capacity-achieving architectures that exploit reciprocity to overcome the complexity and delay issues that limit state-of-the art free-space optical communications. Further, this paper uses theoretical turbulence models to determine the performance—delay, throughput, and complexity—of the proposed architectures.

  8. EDITORIAL: Synaptic electronics Synaptic electronics

    NASA Astrophysics Data System (ADS)

    Demming, Anna; Gimzewski, James K.; Vuillaume, Dominique

    2013-09-01

    Conventional computers excel in logic and accurate scientific calculations but make hard work of open ended problems that human brains handle easily. Even von Neumann—the mathematician and polymath who first developed the programming architecture that forms the basis of today's computers—was already looking to the brain for future developments before his death in 1957 [1]. Neuromorphic computing uses approaches that better mimic the working of the human brain. Recent developments in nanotechnology are now providing structures with very accommodating properties for neuromorphic approaches. This special issue, with guest editors James K Gimzewski and Dominique Vuillaume, is devoted to research at the serendipitous interface between the two disciplines. 'Synaptic electronics', looks at artificial devices with connections that demonstrate behaviour similar to synapses in the nervous system allowing a new and more powerful approach to computing. Synapses and connecting neurons respond differently to incident signals depending on the history of signals previously experienced, ultimately leading to short term and long term memory behaviour. The basic characteristics of a synapse can be replicated with around ten simple transistors. However with the human brain having around 1011 neurons and 1015 synapses, artificial neurons and synapses from basic transistors are unlikely to accommodate the scalability required. The discovery of nanoscale elements that function as 'memristors' has provided a key tool for the implementation of synaptic connections [2]. Leon Chua first developed the concept of the 'The memristor—the missing circuit element' in 1971 [3]. In this special issue he presents a tutorial describing how memristor research has fed into our understanding of synaptic behaviour and how they can be applied in information processing [4]. He also describes, 'The new principle of local activity, which uncovers a minuscule life-enabling "Goldilocks zone", dubbed the

  9. EDITORIAL: Synaptic electronics Synaptic electronics

    NASA Astrophysics Data System (ADS)

    Demming, Anna; Gimzewski, James K.; Vuillaume, Dominique

    2013-09-01

    Conventional computers excel in logic and accurate scientific calculations but make hard work of open ended problems that human brains handle easily. Even von Neumann—the mathematician and polymath who first developed the programming architecture that forms the basis of today's computers—was already looking to the brain for future developments before his death in 1957 [1]. Neuromorphic computing uses approaches that better mimic the working of the human brain. Recent developments in nanotechnology are now providing structures with very accommodating properties for neuromorphic approaches. This special issue, with guest editors James K Gimzewski and Dominique Vuillaume, is devoted to research at the serendipitous interface between the two disciplines. 'Synaptic electronics', looks at artificial devices with connections that demonstrate behaviour similar to synapses in the nervous system allowing a new and more powerful approach to computing. Synapses and connecting neurons respond differently to incident signals depending on the history of signals previously experienced, ultimately leading to short term and long term memory behaviour. The basic characteristics of a synapse can be replicated with around ten simple transistors. However with the human brain having around 1011 neurons and 1015 synapses, artificial neurons and synapses from basic transistors are unlikely to accommodate the scalability required. The discovery of nanoscale elements that function as 'memristors' has provided a key tool for the implementation of synaptic connections [2]. Leon Chua first developed the concept of the 'The memristor—the missing circuit element' in 1971 [3]. In this special issue he presents a tutorial describing how memristor research has fed into our understanding of synaptic behaviour and how they can be applied in information processing [4]. He also describes, 'The new principle of local activity, which uncovers a minuscule life-enabling "Goldilocks zone", dubbed the

  10. Fingolimod (FTY720) enhances hippocampal synaptic plasticity and memory in Huntington's disease by preventing p75NTR up-regulation and astrocyte-mediated inflammation.

    PubMed

    Miguez, Andrés; García-Díaz Barriga, Gerardo; Brito, Verónica; Straccia, Marco; Giralt, Albert; Ginés, Silvia; Canals, Josep M; Alberch, Jordi

    2015-09-01

    Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by motor and cognitive impairments, involving striatum, cortex and hippocampus. Synaptic and memory dysfunction in HD mouse models have been related to low levels of brain-derived neurotrophic factor (BDNF) and imbalance between TrkB and p75(NTR) receptors. In addition, astrocyte over-activation has also been suggested to contribute to HD cognitive deficits. Fingolimod (FTY720), a modulator of sphingosine-1 phosphate (S1P) receptors, has been shown to increase BDNF levels and to reduce astrogliosis, proving its potential to regulate trophic support and inflammatory response. In this view, we have investigated whether FTY720 improves synaptic plasticity and memory in the R6/1 mouse model of HD, through regulation of BDNF signaling and astroglial reactivity. Chronic administration of FTY720 from pre-symptomatic stages ameliorated long-term memory deficits and dendritic spine loss in CA1 hippocampal neurons from R6/1 mice. Furthermore, FTY720 delivery prevented astrogliosis and over-activation of nuclear factor kappa beta (NF-κB) signaling in the R6/1 hippocampus, reducing tumor necrosis factor alpha (TNFα) and induced nitric oxide synthase (iNOS) levels. TNFα decrease correlated with the normalization of p75(NTR) expression in the hippocampus of FTY720-treated R6/1 mice, thus preventing p75(NTR)/TrkB imbalance. In addition, FTY720 increased cAMP levels and promoted phosphorylation of CREB and RhoA in the hippocampus of R6/1 mice, further supporting its role in the enhancement of synaptic plasticity. Our findings provide new insights into the mechanism of action of FTY720 and reveal a novel therapeutic strategy to treat memory deficits in HD. PMID:26063761

  11. Molecular underpinnings of synaptic vesicle pool heterogeneity.

    PubMed

    Crawford, Devon C; Kavalali, Ege T

    2015-04-01

    Neuronal communication relies on chemical synaptic transmission for information transfer and processing. Chemical neurotransmission is initiated by synaptic vesicle fusion with the presynaptic active zone resulting in release of neurotransmitters. Classical models have assumed that all synaptic vesicles within a synapse have the same potential to fuse under different functional contexts. In this model, functional differences among synaptic vesicle populations are ascribed to their spatial distribution in the synapse with respect to the active zone. Emerging evidence suggests, however, that synaptic vesicles are not a homogenous population of organelles, and they possess intrinsic molecular differences and differential interaction partners. Recent studies have reported a diverse array of synaptic molecules that selectively regulate synaptic vesicles' ability to fuse synchronously and asynchronously in response to action potentials or spontaneously irrespective of action potentials. Here we discuss these molecular mediators of vesicle pool heterogeneity that are found on the synaptic vesicle membrane, on the presynaptic plasma membrane, or within the cytosol and consider some of the functional consequences of this diversity. This emerging molecular framework presents novel avenues to probe synaptic function and uncover how synaptic vesicle pools impact neuronal signaling. PMID:25620674

  12. Molecular Underpinnings of Synaptic Vesicle Pool Heterogeneity

    PubMed Central

    Crawford, Devon C.; Kavalali, Ege T.

    2015-01-01

    Neuronal communication relies on chemical synaptic transmission for information transfer and processing. Chemical neurotransmission is initiated by synaptic vesicle fusion with the presynaptic active zone resulting in release of neurotransmitters. Classical models have assumed that all synaptic vesicles within a synapse have the same potential to fuse under different functional contexts. In this model, functional differences among synaptic vesicle populations are ascribed to their spatial distribution in the synapse with respect to the active zone. Emerging evidence suggests, however, that synaptic vesicles are not a homogenous population of organelles, and they possess intrinsic molecular differences and differential interaction partners. Recent studies have reported a diverse array of synaptic molecules that selectively regulate synaptic vesicles' ability to fuse synchronously and asynchronously in response to action potentials or spontaneously irrespective of action potentials. Here we discuss these molecular mediators of vesicle pool heterogeneity that are found on the synaptic vesicle membrane, on the presynaptic plasma membrane, or within the cytosol and consider some of the functional consequences of this diversity. This emerging molecular framework presents novel avenues to probe synaptic function and uncover how synaptic vesicle pools impact neuronal signaling. PMID:25620674

  13. Enhancement of Global Communication Skill at the School of Engineering

    NASA Astrophysics Data System (ADS)

    Morimura, Kumiko

    Globalization is one of the most important challenges for universities. Especially for the School of Engineering, it is crucial to foster researchers or engineers with broader perspective. International communication competency is essential for them in order to deal with other professionals from overseas. Center for Innovation in Engineering Education established in the School of Engineering at the University of Tokyo in 2005 started two programs for graduate and undergraduate students to enhance their international communication competency and to increase international competitiveness. ‘English for Scientists and Engineers A, B’ are for the graduate students to learn how to write papers in English and how to make good presentations. Special English Lessons are for the undergraduate students to have a chance to practice English conversation or prepare for TOEFL test. In this paper, the authors discuss the details of the programs, their purpose and the future tasks.

  14. Multiple personalities: synaptic target cells as introverts and extroverts.

    PubMed

    Ritzenthaler, S; Chiba, A

    2001-10-01

    The intricate process of wiring a neuronetwork requires a high degree of accuracy in the communication between pre- and post-synaptic cells. While presynaptic cells have been widely recognized for their dynamic role in synaptic matchmaking, post-synaptic cells have historically been overlooked as passive targets. Recent studies in the Drosophila embryonic neuromuscular system provide compelling evidence that post-synaptic cells participate actively in the synaptogenic process. Endocytosis allows them to quickly modify the array of molecular cues they provide on their surfaces and the extension of dynamic filopodia allows post-synaptic cells to engage in direct long-distance communication. By making use of familiar cellular mechanisms such as endocytosis and filopodia formation, post-synaptic cells may be able to communicate more effectively with potential synaptic partners. PMID:11576167

  15. Synaptic plasticity and phosphorylation

    PubMed Central

    Lee, Hey-Kyoung

    2009-01-01

    A number of neuronal functions, including synaptic plasticity, depend on proper regulation of synaptic proteins, many of which can be rapidly regulated by phosphorylation. Neuronal activity controls the function of these synaptic proteins by exquisitely regulating the balance of various protein kinase and protein phosphatase activity. Recent understanding of synaptic plasticity mechanisms underscores important roles that these synaptic phosphoproteins play in regulating both pre- and post-synaptic functions. This review will focus on key postsynaptic phosphoproteins that have been implicated to play a role in synaptic plasticity. PMID:16904750

  16. Synaptic view of eukaryotic cell

    NASA Astrophysics Data System (ADS)

    Baluška, František; Mancuso, Stefano

    2014-10-01

    Synapses are stable adhesive domains between two neighbouring cells of the multicellular organisms which serve for cell-cell communication as well as for information processing and storing. The synaptic concept was developed over more than 100 years specifically for neuronal cell-cell communication. In the last ten years, this concept was adapted to embrace other cell-cell communication phenomena. Here, we focus on the recently emerged phagocytic synapse and propose new endosymbiotic synapses and "intracellular organellar synapses". All these synapses of eukaryotic cells are in a good position to explain the high capacity of eukaryotic cells for integration of diverse signalling inputs into coherent cellular behaviour.

  17. Prenatal Stress Enhances Excitatory Synaptic Transmission and Impairs Long-Term Potentiation in the Frontal Cortex of Adult Offspring Rats

    PubMed Central

    Sowa, Joanna; Bobula, Bartosz; Glombik, Katarzyna; Slusarczyk, Joanna; Basta-Kaim, Agnieszka; Hess, Grzegorz

    2015-01-01

    The effects of prenatal stress procedure were investigated in 3 months old male rats. Prenatally stressed rats showed depressive-like behavior in the forced swim test, including increased immobility, decreased mobility and decreased climbing. In ex vivo frontal cortex slices originating from prenatally stressed animals, the amplitude of extracellular field potentials (FPs) recorded in cortical layer II/III was larger, and the mean amplitude ratio of pharmacologically-isolated NMDA to the AMPA/kainate component of the field potential—smaller than in control preparations. Prenatal stress also resulted in a reduced magnitude of long-term potentiation (LTP). These effects were accompanied by an increase in the mean frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in layer II/III pyramidal neurons. These data demonstrate that stress during pregnancy may lead not only to behavioral disturbances, but also impairs the glutamatergic transmission and long-term synaptic plasticity in the frontal cortex of the adult offspring. PMID:25749097

  18. Enhancing Environmental Communication and Products Through Qualitative Research

    NASA Astrophysics Data System (ADS)

    DeLorme, D.; Hagen, S. C.

    2014-12-01

    This presentation discusses two ongoing interdisciplinary case studies that are using qualitative research to design and enhance environmental communication and science products for outreach and decision making purposes. Both cases demonstrate the viability and practical value of qualitative social science methodology, specifically focus group interviews, to better understand the viewpoints of target audiences, improve deliverables, and support project goals. The first case is a NOAA-funded project to conduct process-based modeling to project impact from climate change in general and sea level rise in particular to the natural and built environment. The project spans the Mississippi, Alabama, and Florida Panhandle coasts with concentration on the three National Estuarine Research Reserves. As part of the broader project, four annual focus groups were conducted with a purposive sample of coastal resource managers to capture their perspectives and suggestions to better meet their informational and operational needs. The second case is a Florida Sea Grant-funded project that is developing, implementing, and testing a cohesive outreach campaign to promote voluntary careful and responsible recreational boating to help protect sensitive marine life and habitats (especially seagrasses and oyster reefs) in the Mosquito Lagoon. Six focus groups were conducted with a purposive sample of the target audience of boaters to gain insights, feedback, and ideas on the direction of the campaign and design of the messages and products. The campaign materials created include a branded website, Facebook page, mobile app, information packets, brochures, pledge forms, and promotional items. A comparison of these two case studies will be provided and will explain how the qualitative findings were/are being implemented to tailor and refine the respective communication strategies and techniques including the emerging outreach products. The resulting outcomes are messages and tools that are

  19. Enhanced TCP for maritime communications over satellite network

    NASA Astrophysics Data System (ADS)

    Zong, Liang; Du, Wencai; Bai, Yong

    2014-10-01

    For maritime communications over satellite network, TCP performance is essential for data transmissions. TCP ADaLR is congestion control algorithm that the sender judgments the relevant window change and measures roundtrip time to control congestion window. It can adapt to the characteristics of the satellite link and improve the performance of TCP than conventional TCP. However, it does not take into account distinction of random packet loss and congestion loss like TCP Veno. In this paper, we propose further enhancement of TCP ADaLR, called TCP ADaLR+, that can distinguish between random packet loss and congestion loss. The improved performance of proposed TCP ADaLR+ is demonstrated by simulations.

  20. Synaptic Vesicle Proteins and Active Zone Plasticity

    PubMed Central

    Kittel, Robert J.; Heckmann, Manfred

    2016-01-01

    Neurotransmitter is released from synaptic vesicles at the highly specialized presynaptic active zone (AZ). The complex molecular architecture of AZs mediates the speed, precision and plasticity of synaptic transmission. Importantly, structural and functional properties of AZs vary significantly, even for a given connection. Thus, there appear to be distinct AZ states, which fundamentally influence neuronal communication by controlling the positioning and release of synaptic vesicles. Vice versa, recent evidence has revealed that synaptic vesicle components also modulate organizational states of the AZ. The protein-rich cytomatrix at the active zone (CAZ) provides a structural platform for molecular interactions guiding vesicle exocytosis. Studies in Drosophila have now demonstrated that the vesicle proteins Synaptotagmin-1 (Syt1) and Rab3 also regulate glutamate release by shaping differentiation of the CAZ ultrastructure. We review these unexpected findings and discuss mechanistic interpretations of the reciprocal relationship between synaptic vesicles and AZ states, which has heretofore received little attention. PMID:27148040

  1. YAC128 Huntington's disease transgenic mice show enhanced short-term hippocampal synaptic plasticity early in the course of the disease.

    PubMed

    Ghilan, Mohamed; Bostrom, Crystal A; Hryciw, Brett N; Simpson, Jessica M; Christie, Brian R; Gil-Mohapel, Joana

    2014-09-18

    Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by a polyglutamine expansion in the gene encoding the protein huntingtin. The disease progresses over decades, but often patients develop cognitive impairments that precede the onset of the classical motor symptoms. Similar to the disease progression in humans, the yeast artificial chromosome (YAC) 128 HD mouse model also exhibits cognitive dysfunction that precedes the onset of the neuropathological and motor impairments characteristic of HD. Thus, the purpose of this study was to evaluate whether short- and long-term synaptic plasticity in the hippocampus, two related biological models of learning and memory processes, were altered in YAC128 mice in early stages of disease progression. We show that the YAC128 hippocampal dentate gyrus (DG) displays marked reductions in paired-pulse depression both at 3 and 6 months of age. In addition, significantly enhanced post-tetanic and short-term potentiation are apparent in YAC128 mice after high-frequency stimulation at this time. Early and late forms of long-term plasticity were not altered at this stage. Together these findings indicate that there may be elevated neurotransmitter release in response to synaptic stimulation in YAC128 mice during the initial phase of disease progression. These abnormalities in short-term plasticity detected at this stage in YAC128 HD transgenic mice indicate that aberrant information processing at the level of the synapses may contribute, at least in part, to the early onset of cognitive deficits that are characteristic of this devastating neurodegenerative disorder. PMID:24949563

  2. Learning and reconsolidation implicate different synaptic mechanisms.

    PubMed

    Li, Yan; Meloni, Edward G; Carlezon, William A; Milad, Mohammed R; Pitman, Roger K; Nader, Karim; Bolshakov, Vadim Y

    2013-03-19

    Synaptic mechanisms underlying memory reconsolidation after retrieval are largely unknown. Here we report that synapses in projections to the lateral nucleus of the amygdala implicated in auditory fear conditioning, which are potentiated by learning, enter a labile state after memory reactivation, and must be restabilized through a postsynaptic mechanism implicating the mammalian target of rapamycin kinase-dependent signaling. Fear-conditioning-induced synaptic enhancements were primarily presynaptic in origin. Reconsolidation blockade with rapamycin, inhibiting mammalian target of rapamycin kinase activity, suppressed synaptic potentiation in slices from fear-conditioned rats. Surprisingly, this reduction of synaptic efficacy was mediated by post- but not presynaptic mechanisms. These findings suggest that different plasticity rules may apply to the processes underlying the acquisition of original fear memory and postreactivational stabilization of fear-conditioning-induced synaptic enhancements mediating fear memory reconsolidation. PMID:23487762

  3. Learning and reconsolidation implicate different synaptic mechanisms

    PubMed Central

    Li, Yan; Meloni, Edward G.; Carlezon, William A.; Milad, Mohammed R.; Pitman, Roger K.; Nader, Karim; Bolshakov, Vadim Y.

    2013-01-01

    Synaptic mechanisms underlying memory reconsolidation after retrieval are largely unknown. Here we report that synapses in projections to the lateral nucleus of the amygdala implicated in auditory fear conditioning, which are potentiated by learning, enter a labile state after memory reactivation, and must be restabilized through a postsynaptic mechanism implicating the mammalian target of rapamycin kinase-dependent signaling. Fear-conditioning–induced synaptic enhancements were primarily presynaptic in origin. Reconsolidation blockade with rapamycin, inhibiting mammalian target of rapamycin kinase activity, suppressed synaptic potentiation in slices from fear-conditioned rats. Surprisingly, this reduction of synaptic efficacy was mediated by post- but not presynaptic mechanisms. These findings suggest that different plasticity rules may apply to the processes underlying the acquisition of original fear memory and postreactivational stabilization of fear-conditioning–induced synaptic enhancements mediating fear memory reconsolidation. PMID:23487762

  4. Selective Activation of Microglia Facilitates Synaptic Strength

    PubMed Central

    Clark, Anna K.; Gruber-Schoffnegger, Doris; Drdla-Schutting, Ruth; Gerhold, Katharina J.; Malcangio, Marzia

    2015-01-01

    Synaptic plasticity is thought to be initiated by neurons only, with the prevailing view assigning glial cells mere specify supportive functions for synaptic transmission and plasticity. We now demonstrate that glial cells can control synaptic strength independent of neuronal activity. Here we show that selective activation of microglia in the rat is sufficient to rapidly facilitate synaptic strength between primary afferent C-fibers and lamina I neurons, the first synaptic relay in the nociceptive pathway. Specifically, the activation of the CX3CR1 receptor by fractalkine induces the release of interleukin-1β from microglia, which modulates NMDA signaling in postsynaptic neurons, leading to the release of an eicosanoid messenger, which ultimately enhances presynaptic neurotransmitter release. In contrast to the conventional view, this form of plasticity does not require enhanced neuronal activity to trigger the events leading to synaptic facilitation. Augmentation of synaptic strength in nociceptive pathways represents a cellular model of pain amplification. The present data thus suggest that, under chronic pain states, CX3CR1-mediated activation of microglia drives the facilitation of excitatory synaptic transmission in the dorsal horn, which contributes to pain hypersensitivity in chronic pain states. PMID:25788673

  5. In vivo trans-synaptic tract tracing from the murine striatum and amygdala utilizing manganese enhanced MRI (MEMRI).

    PubMed

    Pautler, Robia G; Mongeau, Raymond; Jacobs, Russell E

    2003-07-01

    Small focal injections of manganese ion (Mn(2+)) deep within the mouse central nervous system combined with in vivo high-resolution MRI delineate neuronal tracts originating from the site of injection. Previous work has shown that Mn(2+) can be taken up through voltage-gated Ca(2+) channels, transported along axons, and across synapses. Moreover, Mn(2+) is a paramagnetic MRI contrast agent, causing positive contrast enhancement in tissues where it has accumulated. These combined properties allow for its use as an effective MRI detectable neuronal tract tracer. Injections of low concentrations of MnCl(2) into either the striatum or amygdala produced significant contrast enhancement along the known neuronal circuitry. The observed enhancement pattern is different at each injection site and enhancement of the homotopic areas was observed in both cases. Ten days postinjection, the Mn(2+) had washed out, as evidenced by the absence of positive contrast enhancement within the brain. This methodology allows imaging of neuronal tracts long after the injection of the ion because Mn(2+) concentrates in active neurons and resides for extended periods of time. With appropriate controls, differentiation of subsets of neuronal pathways associated with behavioral and pharmacological paradigms should be feasible. PMID:12815676

  6. Digital photography: enhancing communication between burn therapists and nurses.

    PubMed

    Van, Lan B; Sicotte, K M; Lassiter, R R; Jablonski, K A; Crean, D A; Jeng, J C; Jordan, M H

    2004-01-01

    Burn rehabilitation therapists rely on nursing staff to follow through with the positioning and splinting programs. To communicate more effectively, a communication tool that consisted of digital photos and written instructions was created. Microsoft Word and Nikon View software were used to design the communication tool. The purpose of the study was to assess the perceived effectiveness of a communication tool between burn therapists and burn nurses for splinting and positioning. Thirty-two surveys were distributed to burn nursing staff to assess their perception of the communication tool (digital photographs with written instructions) compared with previous methods of instructions (without digital photographs). Seventy-three percent of nurses felt the communication tool with verbal instructions were the best methods of communicating splinting and positioning needs. All respondents felt that the rehabilitation staff should continue to use the communication tool. PMID:14726739

  7. Enhancing Distant Learning through Email Communication: A Case of BOU

    ERIC Educational Resources Information Center

    Rahman, K. M. Rezanur; Anwar, Sadat; Numan, Sharker Md.

    2008-01-01

    Today computer has replaced all means of traditional communication significantly. Many distant learning tools claim to be interactive, but few can offer two-way communication. Email is the most popular means of communication medium now-a-days. Therefore, it may be used as an educational tool for learning. In present socioeconomic condition of…

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

    PubMed

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

    2010-01-01

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

  9. Dendritic Spikes Amplify the Synaptic Signal to Enhance Detection of Motion in a Simulation of the Direction-Selective Ganglion Cell

    PubMed Central

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

    2010-01-01

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

  10. Do Enhanced Communication Technologies Inhibit or Facilitate Self-Regulated Learning?

    ERIC Educational Resources Information Center

    Banyard, Philip; Underwood, Jean; Twiner, Alison

    2006-01-01

    The assumption tested here is whether the introduction of enhanced communication technologies in the form of high-speed broadband connectivity has removed or ameliorated any of the barriers to efficient and effective teaching and learning. Evidence is presented of how enhanced communication technologies have facilitated self-regulated learning.…

  11. Synaptic Vesicle Endocytosis

    PubMed Central

    Saheki, Yasunori; De Camilli, Pietro

    2012-01-01

    Neurons can sustain high rates of synaptic transmission without exhausting their supply of synaptic vesicles. This property relies on a highly efficient local endocytic recycling of synaptic vesicle membranes, which can be reused for hundreds, possibly thousands, of exo-endocytic cycles. Morphological, physiological, molecular, and genetic studies over the last four decades have provided insight into the membrane traffic reactions that govern this recycling and its regulation. These studies have shown that synaptic vesicle endocytosis capitalizes on fundamental and general endocytic mechanisms but also involves neuron-specific adaptations of such mechanisms. Thus, investigations of these processes have advanced not only the field of synaptic transmission but also, more generally, the field of endocytosis. This article summarizes current information on synaptic vesicle endocytosis with an emphasis on the underlying molecular mechanisms and with a special focus on clathrin-mediated endocytosis, the predominant pathway of synaptic vesicle protein internalization. PMID:22763746

  12. Mechanism underlying unaltered cortical inhibitory synaptic transmission in contrast with enhanced excitatory transmission in CaV2.1 knockin migraine mice.

    PubMed

    Vecchia, Dania; Tottene, Angelita; van den Maagdenberg, Arn M J M; Pietrobon, Daniela

    2014-09-01

    Familial hemiplegic migraine type 1 (FHM1), a monogenic subtype of migraine with aura, is caused by gain-of-function mutations in CaV2.1 (P/Q-type) calcium channels. In FHM1 knockin mice, excitatory neurotransmission at cortical pyramidal cell synapses is enhanced, but inhibitory neurotransmission at connected pairs of fast-spiking (FS) interneurons and pyramidal cells is unaltered, despite being initiated by CaV2.1 channels. The mechanism underlying the unaltered GABA release at cortical FS interneuron synapses remains unknown. Here, we show that the FHM1 R192Q mutation does not affect inhibitory transmission at autapses of cortical FS and other types of multipolar interneurons in microculture from R192Q knockin mice, and investigate the underlying mechanism. Lowering the extracellular [Ca(2+)] did not reveal gain-of-function of evoked transmission neither in control nor after prolongation of the action potential (AP) with tetraethylammonium, indicating unaltered AP-evoked presynaptic calcium influx at inhibitory autapses in FHM1 KI mice. Neither saturation of the presynaptic calcium sensor nor short duration of the AP can explain the unaltered inhibitory transmission in the mutant mice. Recordings of the P/Q-type calcium current in multipolar interneurons in microculture revealed that the current density and the gating properties of the CaV2.1 channels expressed in these interneurons are barely affected by the FHM1 mutation, in contrast with the enhanced current density and left-shifted activation gating of mutant CaV2.1 channels in cortical pyramidal cells. Our findings suggest that expression of specific CaV2.1 channels differentially sensitive to modulation by FHM1 mutations in inhibitory and excitatory cortical neurons underlies the gain-of-function of excitatory but unaltered inhibitory synaptic transmission and the likely consequent dysregulation of the cortical excitatory-inhibitory balance in FHM1. PMID:24907493

  13. Does communication enhance pedestrians transport in the dark?

    NASA Astrophysics Data System (ADS)

    Cirillo, Emilio N. M.; Colangeli, Matteo; Muntean, Adrian

    2016-01-01

    We study the motion of pedestrians through an obscure tunnel where the lack of visibility hides the exits. Using a lattice model, we explore the effects of communication on the effective transport properties of the crowd of pedestrians. More precisely, we study the effect of two thresholds on the structure of the effective nonlinear diffusion coefficient. One threshold models pedestrian communication efficiency in the dark, while the other one describes the tunnel capacity. Essentially, we note that if the evacuees show a maximum trust (leading to a fast communication), they tend to quickly find the exit and hence the collective action tends to prevent the occurrence of disasters.

  14. Functional diversity on synaptic plasticity mediated by endocannabinoids

    PubMed Central

    Cachope, Roger

    2012-01-01

    Endocannabinoids (eCBs) act as modulators of synaptic transmission through activation of a number of receptors, including, but not limited to, cannabinoid receptor 1 (CB1). eCBs share CB1 receptors as a common target with Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana. Although THC has been used for recreational and medicinal purposes for thousands of years, little was known about its effects at the cellular level or on neuronal circuits. Identification of CB1 receptors and the subsequent development of its specific ligands has therefore enhanced our ability to study and bring together a substantial amount of knowledge regarding how marijuana and eCBs modify interneuronal communication. To date, the eCB system, composed of cannabinoid receptors, ligands and the relevant enzymes, is recognized as the best-described retrograde signalling system in the brain. Its impact on synaptic transmission is widespread and more diverse than initially thought. The aim of this review is to succinctly present the most common forms of eCB-mediated modulation of synaptic transmission, while also illustrating the multiplicity of effects resulting from specializations of this signalling system at the circuital level. PMID:23108543

  15. Using Communication Technology to Enhance Interprofessional Education Simulations

    PubMed Central

    Shrader, Sarah; Shin, Tiffany; Heble, Annie; Kempin, Brian; Miller, Astyn; Patykiewicz, Nick

    2016-01-01

    Objective. To determine the impact of simulations using an alternative method of communication on students’ satisfaction, attitudes, confidence, and performance related to interprofessional communication. Design. One hundred sixty-three pharmacy students participated in a required applications-based capstone course. Students were randomly assigned to one of three interprofessional education (IPE) simulations with other health professions students using communication methods such as telephone, e-mail, and video conferencing. Assessment. Pharmacy students completed a validated survey instrument, Attitude Toward Healthcare Teams Scale (ATHCTS) prior to and after course participation. Significant positive changes occurred for 5 out of 20 items. Written reflection papers and student satisfaction surveys completed after participation showed positive themes and satisfaction. Course instructors evaluated student performance using rubrics for formative feedback. Conclusion. Implementation of IPE simulations using various methods of communication technology is an effective way for pharmacy schools to incorporate IPE into their curriculum. PMID:26941439

  16. Conditioned taste aversion prevents the long-lasting BDNF-induced enhancement of synaptic transmission in the insular cortex: A metaplastic effect.

    PubMed

    Rivera-Olvera, Alejandro; Rodríguez-Durán, Luis F; Escobar, Martha L

    2016-04-01

    Homeostatic plasticity mechanisms dynamically adjust synaptic strengths to promote stability that is crucial for memory storage. Metaplasticity is an example of these forms of plasticity that modify the capacity of synapses to experience subsequent Hebbian modifications. In particular, training in several behavioral tasks modifies the ability to induce long-term potentiation (LTP). Recently, we have reported that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP generated by high frequency stimulation in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC). One of the key molecular players that underlie long-term synaptic plasticity is brain-derived neurotrophic factor (BDNF). Previous studies from our group reported that acute microinfusion of BDNF in the IC induces a lasting potentiation of synaptic efficacy at the Bla-IC projection. Thus, the aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent BDNF-induced potentiation of synaptic transmission in the Bla-IC projection in vivo. Accordingly, CTA trained rats received intracortical microinfusion of BDNF in order to induce lasting potentiation 48h after the aversion test. Our results show that CTA training prevents the induction of in vivo BDNF-LTP in the Bla-IC projection. The present results provide evidence that CTA modulates BDNF-dependent changes in IC synaptic strength. PMID:26854904

  17. MAGUKs, Synaptic Development, and Synaptic Plasticity

    PubMed Central

    Zheng, Chan-Ying; Seabold, Gail K.; Horak, Martin; Petralia, Ronald S.

    2011-01-01

    MAGUKs are proteins that act as key scaffolds in surface complexes containing receptors, adhesion proteins, and various signaling molecules. These complexes evolved prior to the appearance of multicellular animals and play key roles in cell-cell intercommunication. A major example of this is the neuronal synapse, which contains several presynaptic and postsynaptic MAGUKs including PSD-95, SAP102, SAP97, PSD-93, CASK, and MAGIs. Here, they play roles in both synaptic development and in later synaptic plasticity events. During development, MAGUKs help to organize the postsynaptic density via associations with other scaffolding proteins, such as Shank, and the actin cytoskeleton. They affect the clustering of glutamate receptors and other receptors, and these associations change with development. MAGUKs are involved in long-term potentiation and depression (e.g., via their phosphorylation by kinases and phosphorylation of other proteins associated with MAGUKs). Importantly, synapse development and function are dependent on the kind of MAGUK present. For example, SAP102 shows high mobility and is present in early synaptic development. Later, much of SAP102 is replaced by PSD-95, a more stable synaptic MAGUK; this is associated with changes in glutamate receptor types that are characteristic of synaptic maturation. PMID:21498811

  18. Synaptic Ribbons Require Ribeye for Electron Density, Proper Synaptic Localization, and Recruitment of Calcium Channels.

    PubMed

    Lv, Caixia; Stewart, William J; Akanyeti, Otar; Frederick, Courtney; Zhu, Jie; Santos-Sacchi, Joseph; Sheets, Lavinia; Liao, James C; Zenisek, David

    2016-06-21

    Synaptic ribbons are structures made largely of the protein Ribeye that hold synaptic vesicles near release sites in non-spiking cells in some sensory systems. Here, we introduce frameshift mutations in the two zebrafish genes encoding for Ribeye and thus remove Ribeye protein from neuromast hair cells. Despite Ribeye depletion, vesicles collect around ribbon-like structures that lack electron density, which we term "ghost ribbons." Ghost ribbons are smaller in size but possess a similar number of smaller vesicles and are poorly localized to synapses and calcium channels. These hair cells exhibit enhanced exocytosis, as measured by capacitance, and recordings from afferent neurons post-synaptic to hair cells show no significant difference in spike rates. Our results suggest that Ribeye makes up most of the synaptic ribbon density in neuromast hair cells and is necessary for proper localization of calcium channels and synaptic ribbons. PMID:27292637

  19. Coaching and feedback: enhancing communication teaching and learning in veterinary practice settings.

    PubMed

    Adams, Cindy L; Kurtz, Suzanne

    2012-01-01

    Communication is a critical clinical skill closely linked to clinical reasoning, medical problem solving, and significant outcomes of care such as accuracy, efficiency, supportiveness, adherence to treatment plans, and client and veterinarian satisfaction. More than 40 years of research on communication and communication education in human medicine and, more recently, in veterinary medicine provide a substantive rationale for formal communication teaching in veterinary education. As a result, veterinary schools are beginning to invest in communication training. However, if communication training is to result in development of veterinary communication skills to a professional level of competence, there must be follow-through with effective communication modeling and coaching in practice settings. The purpose of this article is to move the communication modeling and coaching done in the "real world" of clinical practice to the next level. The development of skills for communication coaching and feedback is demanding. We begin by comparing communication coaching with what is required for teaching other clinical skills in practice settings. Examining both, what it takes to teach others (whether DVM students or veterinarians in practice for several years) and what it takes to enhance one's own communication skills and capacities, we consider the why, what, and how of communication coaching. We describe the use of teaching instruments to structure this work and give particular attention to how to engage in feedback sessions, since these elements are so critical in communication teaching and learning. We consider the preconditions necessary to initiate and sustain communication skills training in practice, including the need for a safe and supportive environment within which to implement communication coaching and feedback. Finally we discuss the challenges and opportunities unique to coaching and to building and delivering communication skills training in practice

  20. Cooperative Learning and Enhanced Communication: Effects on Student Performance, Retention, and Attitudes in General Chemistry.

    ERIC Educational Resources Information Center

    Dougherty, R. C.; And Others

    1995-01-01

    Examines the effects of cooperative learning and enhanced communication on student performance, retention, and attitudes in general chemistry. Results indicate that cooperative homework, cooperative quizzes, electronic-mail communication, and open office hours were associated with significantly higher student retention and higher performance on…

  1. Using Virtual Interactions to Enhance the Teaching of Communication Skills to Information Technology Students

    ERIC Educational Resources Information Center

    Pineteh, Ernest A.

    2012-01-01

    This paper examines the use of virtual interactions in a Communication class at Cape Peninsula University of Technology (CPUT)-South Africa. It demonstrates how synthesising virtual and other computer-assisted exercises as well as traditional classroom-based activities can enhance the teaching and learning of communication concepts. The paper is…

  2. Computer Mediated Communication (CMC): Technology for Enhancing Foreign Language/Culture Education.

    ERIC Educational Resources Information Center

    Singhal, Meena

    1998-01-01

    Describes various studies and projects on computer-mediated communication for enhancing second language learning and culture education, examining their impact on participating elementary, secondary, and college students. Results indicate that e-mail and teleconferencing provide authentic communication and foster awareness of languages and…

  3. Facilitation of health care delivery through enhanced communications.

    PubMed

    Buffone, G J; Beck, J R

    1994-01-01

    To realize the advantages of advanced computing technology in medicine we will have to blend computing and communications facilities into a seamless entity that can support ubiquitous computing for medical use. Work-group computing applications, high speed networks linking a multiplicity of servers, and mobile computing platforms can provide the next generation of devices and services for the physician. Ultimately, the biggest challenge for communications and computing in medicine will be found in the requirement for standards in semantics and syntax in the highest levels of the OSI model. We present here our view of the functional requirements for physician communications and computing to meet standard medical practice in Western societies. PMID:8125649

  4. Lateral regulation of synaptic transmission by astrocytes.

    PubMed

    Covelo, A; Araque, A

    2016-05-26

    Fifteen years ago the concept of the "tripartite synapse" was proposed to conceptualize the functional view that astrocytes are integral elements of synapses. The signaling exchange between astrocytes and neurons within the tripartite synapse results in the synaptic regulation of synaptic transmission and plasticity through an autocrine form of communication. However, recent evidence indicates that the astrocyte synaptic regulation is not restricted to the active tripartite synapse but can be manifested through astrocyte signaling at synapses relatively distant from active synapses, a process termed lateral astrocyte synaptic regulation. This phenomenon resembles the classical heterosynaptic modulation but is mechanistically different because it involves astrocytes and its properties critically depend on the morphological and functional features of astrocytes. Therefore, the functional concept of the tripartite synapse as a fundamental unit must be expanded to include the interaction between tripartite synapses. Through lateral synaptic regulation, astrocytes serve as an active processing bridge for synaptic interaction and crosstalk between synapses with no direct neuronal connectivity, supporting the idea that neural network function results from the coordinated activity of astrocytes and neurons. PMID:25732135

  5. Strategic Interaction: A Method That Enhances Communicative Competence.

    ERIC Educational Resources Information Center

    Al-Khanji, Rajai

    The Strategic Interaction method has been found to be effective in developing oral skills among students in an intensive English language program at the University of Jordan, and holds promise for language instruction in other contexts. The method, which is predominantly communicative in nature, stresses language use and interaction in discourse…

  6. Enhanced Communication Network Solution for Positive Train Control Implementation

    NASA Technical Reports Server (NTRS)

    Fatehi, M. T.; Simon, J.; Chang, W.; Chow, E. T.; Burleigh, S. C.

    2011-01-01

    The commuter and freight railroad industry is required to implement Positive Train Control (PTC) by 2015 (2012 for Metrolink), a challenging network communications problem. This paper will discuss present technologies developed by the National Aeronautics and Space Administration (NASA) to overcome comparable communication challenges encountered in deep space mission operations. PTC will be based on a new cellular wireless packet Internet Protocol (IP) network. However, ensuring reliability in such a network is difficult due to the "dead zones" and transient disruptions we commonly experience when we lose calls in commercial cellular networks. These disruptions make it difficult to meet PTC s stringent reliability (99.999%) and safety requirements, deployment deadlines, and budget. This paper proposes innovative solutions based on space-proven technologies that would help meet these challenges: (1) Delay Tolerant Networking (DTN) technology, designed for use in resource-constrained, embedded systems and currently in use on the International Space Station, enables reliable communication over networks in which timely data acknowledgments might not be possible due to transient link outages. (2) Policy-Based Management (PBM) provides dynamic management capabilities, allowing vital data to be exchanged selectively (with priority) by utilizing alternative communication resources. The resulting network may help railroads implement PTC faster, cheaper, and more reliably.

  7. Neuro-Linguistic Programming: Enhancing Teacher-Student Communications.

    ERIC Educational Resources Information Center

    Childers, John H., Jr.

    1985-01-01

    Defines Neurolinguistic Programming (NCP) and discusses specific dimensions of the model that have applications for classroom teaching. Describes five representational systems individuals use to process information and gives examples of effective and ineffective teacher-student communication for each system. (MCF)

  8. Language Training for Enhanced Horizontal Communication: A Challenge for MNCs.

    ERIC Educational Resources Information Center

    Charles, Mirjaliisa; Marschan-Piekkari, Rebecca

    2002-01-01

    Identifies and examines the problems that staff in multinational corporations (MNCs) experience in horizontal communication with other units and discusses the implications of these problems for in-company language training. Concludes that illustrative interview data suggests that corporate training schemes should focus on the broad spectrum of…

  9. Synaptic pathology: A shared mechanism in neurological disease.

    PubMed

    Henstridge, Christopher M; Pickett, Eleanor; Spires-Jones, Tara L

    2016-07-01

    Synaptic proteomes have evolved a rich and complex diversity to allow the exquisite control of neuronal communication and information transfer. It is therefore not surprising that many neurological disorders are associated with alterations in synaptic function. As technology has advanced, our ability to study the anatomical and physiological function of synapses in greater detail has revealed a critical role for both central and peripheral synapses in neurodegenerative disease. Synapse loss has a devastating effect on cellular communication, leading to wide ranging effects such as network disruption within central neural systems and muscle wastage in the periphery. These devastating effects link synaptic pathology to a diverse range of neurological disorders, spanning Alzheimer's disease to multiple sclerosis. This review will highlight some of the current literature on synaptic integrity in animal models of disease and human post-mortem studies. Synaptic changes in normal brain ageing will also be discussed and finally the current and prospective treatments for neurodegenerative disorders will be summarised. PMID:27108053

  10. Enhanced nitric oxide production during lead (Pb²⁺) exposure recovers protein expression but not presynaptic localization of synaptic proteins in developing hippocampal neurons.

    PubMed

    Neal, April P; Stansfield, Kirstie H; Guilarte, Tomás R

    2012-02-23

    We have previously reported that lead (Pb(2+)) exposure results in both presynaptic and postsynaptic changes in developing neurons as a result of inhibition of the N-methyl-d-aspartate receptor (NMDAR). NMDAR inhibition by Pb(2+) during synaptogenesis disrupts downstream trans-synaptic signaling of brain-derived neurotrophic factor (BDNF) and exogenous addition of BDNF can recover the effects of Pb(2+) on both presynaptic protein expression and presynaptic vesicular release. NMDAR activity can modulate other trans-synaptic signaling pathways, such as nitric oxide (NO) signaling. Thus, it is possible that other trans-synaptic pathways in addition to BDNF signaling may be disrupted by Pb(2+) exposure. The current study investigated whether exogenous addition of NO could recover the presynaptic vesicular proteins lost as a result of Pb(2+) exposure during synaptogenesis, namely Synaptophysin (Syn) and Synaptobrevin (Syb). We observed that exogenous addition of NO during Pb(2+) exposure results in complete recovery of whole-cell Syn levels and partial recovery of Syn and Syb synaptic targeting in Pb(2+)-exposed neurons. PMID:22265330

  11. SPECS: Secure and Privacy Enhancing Communications Schemes for VANETs

    NASA Astrophysics Data System (ADS)

    Chim, T. W.; Yiu, S. M.; Hui, L. C. K.; Jiang, Zoe L.; Li, Victor O. K.

    Vehicular ad hoc network (VANET) is an emerging type of networks which facilitates vehicles on roads to communicate for driving safety. The basic idea is to allow arbitrary vehicles to broadcast ad hoc messages (e.g. traffic accidents) to other vehicles. However, this raises the concern of security and privacy. Messages should be signed and verified before they are trusted while the real identity of vehicles should not be revealed, but traceable by authorized party. Existing solutions either rely heavily on a tamper-proof hardware device, or cannot satisfy the privacy requirement and do not have an effective message verification scheme. In this paper, we provide a software-based solution which makes use of only two shared secrets to satisfy the privacy requirement and gives lower message overhead and at least 45% higher successful rate than previous solutions in the message verification phase using the bloom filter and the binary search techniques. We also provide the first group communication protocol to allow vehicles to authenticate and securely communicate with others in a group of known vehicles.

  12. Communication.

    ERIC Educational Resources Information Center

    Strauss, Andre

    The following essays on communication are presented: communication as a condition of survival, communication for special purposes, the means of transmission of communication, communication within social and economic structures, the teaching of communication through the press, the teaching of modern languages, communication as a point of departure,…

  13. Astrocytes: Orchestrating synaptic plasticity?

    PubMed

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

    2016-05-26

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

  14. COMMUNICATION: Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    NASA Astrophysics Data System (ADS)

    Serra, Michael; Chan, Amy; Dubey, Maya; Gilman, Vladimir; Shea, Thomas B.

    2008-12-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE-/- mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or -/-, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE-/- cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE-/- cultures, which may be a reflection of the reduced SAM levels in ApoE-/- mice. The differential impact of SAM on ApoE+/+ and -/- neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis.

  15. Enhancing risk communication for more effective epidemic control in Taiwan.

    PubMed

    Ou, Shih-Ming; Liu, Li-Ling; Chin, Ko-Chien

    2014-01-01

    This article investigates how to more effectively conduct risk communication to increase the probability of successful control of an epidemic in Taiwan. The epidemic control of H1N1 in Taiwan in 2010 was studied. We used factor analysis and Decision-Making Trial and Evaluation Laboratory (DEMATEL) to obtain the total influence for each factor and to determine the critical factors among them. After being processed using proposed operational procedures, we obtained the critical factors and found that the government plays the key role in successful epidemic control. To reduce the resistance to efforts that seek to prevent pandemic crises, some necessary intervention activities, such as fairly and honorably exploring the complete relevant information and revealing the side effects of vaccines in a manner that is easily understood, were recommended. These could lead to an increase in immunizations among Taiwanese people by gaining their trust and commitment, thus achieving control of this epidemic. PMID:23239748

  16. Learning with two sites of synaptic integration.

    PubMed

    Körding, K P; König, P

    2000-02-01

    Since the classical work of D O Hebb 1949 The Organization of Behaviour (New York: Wiley) it is assumed that synaptic plasticity solely depends on the activity of the pre- and the postsynaptic cells. Synapses influence the plasticity of other synapses exclusively via the post-synaptic activity. This confounds effects on synaptic plasticity and neuronal activation and, thus, makes it difficult to implement networks which optimize global measures of performance. Exploring solutions to this problem, inspired by recent research on the properties of apical dendrites, we examine a network of neurons with two sites of synaptic integration. These communicate in such a way that one set of synapses mainly influences the neurons' activity; the other set gates synaptic plasticity. Analysing the system with a constant set of parameters reveals: (1) the afferents that gate plasticity act as supervisors, individual to every cell. (2) While the neurons acquire specific receptive fields the net activity remains constant for different stimuli. This ensures that all stimuli are represented and, thus, contributes to information maximization. (3) Mechanisms for maximization of coherent information can easily be implemented. Neurons with non-overlapping receptive fields learn to fire correlated and preferentially transmit information that is correlated over space. (4) We demonstrate how a new measure of performance can be implemented: cells learn to represent only the part of the input that is relevant to the processing at higher stages. This criterion is termed 'relevant infomax'. PMID:10735527

  17. Enhancing the Performance of Medical Implant Communication Systems through Cooperative Diversity

    PubMed Central

    Hegyi, Barnabás; Levendovszky, János

    2010-01-01

    Battery-operated medical implants—such as pacemakers or cardioverter-defibrillators—have already been widely used in practical telemedicine and telecare applications. However, no solution has yet been found to mitigate the effect of the fading that the in-body to off-body communication channel is subject to. In this paper, we reveal and assess the potential of cooperative diversity to combat fading—hence to improve system performance—in medical implant communication systems. In the particular cooperative communication scenario we consider, multiple cooperating receiver units are installed across the room accommodating the patient with a medical implant inside his/her body. Our investigations have shown that the application of cooperative diversity is a promising approach to enhance the performance of medical implant communication systems in various aspects such as implant lifetime and communication link reliability. PMID:20379346

  18. Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade

    PubMed Central

    Gainey, Melanie A.; Tatavarty, Vedakumar; Nahmani, Marc; Lin, Heather; Turrigiano, Gina G.

    2015-01-01

    Synaptic scaling is a form of homeostatic plasticity that stabilizes neuronal firing in response to changes in synapse number and strength. Scaling up in response to action-potential blockade is accomplished through increased synaptic accumulation of GluA2-containing AMPA receptors (AMPAR), but the receptor trafficking steps that drive this process remain largely obscure. Here, we show that the AMPAR-binding protein glutamate receptor-interacting protein-1 (GRIP1) is essential for regulated synaptic AMPAR accumulation during scaling up. Synaptic abundance of GRIP1 was enhanced by activity deprivation, directly increasing synaptic GRIP1 abundance through overexpression increased the amplitude of AMPA miniature excitatory postsynaptic currents (mEPSCs), and shRNA-mediated GRIP1 knockdown prevented scaling up of AMPA mEPSCs. Furthermore, knockdown and replace experiments targeting either GRIP1 or GluA2 revealed that scaling up requires the interaction between GRIP1 and GluA2. Finally, GRIP1 synaptic accumulation during scaling up did not require GluA2 binding. Taken together, our data support a model in which activity-dependent trafficking of GRIP1 to synaptic sites drives the forward trafficking and enhanced synaptic accumulation of GluA2-containing AMPAR during synaptic scaling up. PMID:26109571

  19. Extracellular ATP hydrolysis inhibits synaptic transmission by increasing ph buffering in the synaptic cleft.

    PubMed

    Vroman, Rozan; Klaassen, Lauw J; Howlett, Marcus H C; Cenedese, Valentina; Klooster, Jan; Sjoerdsma, Trijntje; Kamermans, Maarten

    2014-05-01

    Neuronal computations strongly depend on inhibitory interactions. One such example occurs at the first retinal synapse, where horizontal cells inhibit photoreceptors. This interaction generates the center/surround organization of bipolar cell receptive fields and is crucial for contrast enhancement. Despite its essential role in vision, the underlying synaptic mechanism has puzzled the neuroscience community for decades. Two competing hypotheses are currently considered: an ephaptic and a proton-mediated mechanism. Here we show that horizontal cells feed back to photoreceptors via an unexpected synthesis of the two. The first one is a very fast ephaptic mechanism that has no synaptic delay, making it one of the fastest inhibitory synapses known. The second one is a relatively slow (τ≈200 ms), highly intriguing mechanism. It depends on ATP release via Pannexin 1 channels located on horizontal cell dendrites invaginating the cone synaptic terminal. The ecto-ATPase NTPDase1 hydrolyses extracellular ATP to AMP, phosphate groups, and protons. The phosphate groups and protons form a pH buffer with a pKa of 7.2, which keeps the pH in the synaptic cleft relatively acidic. This inhibits the cone Ca²⁺ channels and consequently reduces the glutamate release by the cones. When horizontal cells hyperpolarize, the pannexin 1 channels decrease their conductance, the ATP release decreases, and the formation of the pH buffer reduces. The resulting alkalization in the synaptic cleft consequently increases cone glutamate release. Surprisingly, the hydrolysis of ATP instead of ATP itself mediates the synaptic modulation. Our results not only solve longstanding issues regarding horizontal cell to photoreceptor feedback, they also demonstrate a new form of synaptic modulation. Because pannexin 1 channels and ecto-ATPases are strongly expressed in the nervous system and pannexin 1 function is implicated in synaptic plasticity, we anticipate that this novel form of synaptic

  20. Extracellular ATP Hydrolysis Inhibits Synaptic Transmission by Increasing pH Buffering in the Synaptic Cleft

    PubMed Central

    Vroman, Rozan; Klaassen, Lauw J.; Howlett, Marcus H.C.; Cenedese, Valentina; Klooster, Jan; Sjoerdsma, Trijntje; Kamermans, Maarten

    2014-01-01

    Neuronal computations strongly depend on inhibitory interactions. One such example occurs at the first retinal synapse, where horizontal cells inhibit photoreceptors. This interaction generates the center/surround organization of bipolar cell receptive fields and is crucial for contrast enhancement. Despite its essential role in vision, the underlying synaptic mechanism has puzzled the neuroscience community for decades. Two competing hypotheses are currently considered: an ephaptic and a proton-mediated mechanism. Here we show that horizontal cells feed back to photoreceptors via an unexpected synthesis of the two. The first one is a very fast ephaptic mechanism that has no synaptic delay, making it one of the fastest inhibitory synapses known. The second one is a relatively slow (τ≈200 ms), highly intriguing mechanism. It depends on ATP release via Pannexin 1 channels located on horizontal cell dendrites invaginating the cone synaptic terminal. The ecto-ATPase NTPDase1 hydrolyses extracellular ATP to AMP, phosphate groups, and protons. The phosphate groups and protons form a pH buffer with a pKa of 7.2, which keeps the pH in the synaptic cleft relatively acidic. This inhibits the cone Ca2+ channels and consequently reduces the glutamate release by the cones. When horizontal cells hyperpolarize, the pannexin 1 channels decrease their conductance, the ATP release decreases, and the formation of the pH buffer reduces. The resulting alkalization in the synaptic cleft consequently increases cone glutamate release. Surprisingly, the hydrolysis of ATP instead of ATP itself mediates the synaptic modulation. Our results not only solve longstanding issues regarding horizontal cell to photoreceptor feedback, they also demonstrate a new form of synaptic modulation. Because pannexin 1 channels and ecto-ATPases are strongly expressed in the nervous system and pannexin 1 function is implicated in synaptic plasticity, we anticipate that this novel form of synaptic modulation

  1. Communication: Enhanced dissociative chemisorption of CO2 via vibrational excitation

    NASA Astrophysics Data System (ADS)

    Jiang, Bin; Guo, Hua

    2016-03-01

    A fully coupled global nine-dimensional potential energy surface for the dissociative chemisorption of CO2 on Ni(100) is constructed from ˜18 000 density functional points. It reveals a complex reaction pathway dominated by two near iso-energetic transition states. The dissociation probabilities obtained by quasi-classical trajectories on the potential energy surface reproduced experimental trends, and indicate that vibrational excitations of CO2 significantly promote the dissociation. Using the sudden vector projection model, the behavior of the reactivity is rationalized by couplings with the reaction coordinate at each transition state. These results offer plausible rationalization for the observed enhancement of CO2 dissociation in non-thermal plasmas by metal surfaces.

  2. Communication: Enhanced dissociative chemisorption of CO2 via vibrational excitation.

    PubMed

    Jiang, Bin; Guo, Hua

    2016-03-01

    A fully coupled global nine-dimensional potential energy surface for the dissociative chemisorption of CO2 on Ni(100) is constructed from ∼18,000 density functional points. It reveals a complex reaction pathway dominated by two near iso-energetic transition states. The dissociation probabilities obtained by quasi-classical trajectories on the potential energy surface reproduced experimental trends, and indicate that vibrational excitations of CO2 significantly promote the dissociation. Using the sudden vector projection model, the behavior of the reactivity is rationalized by couplings with the reaction coordinate at each transition state. These results offer plausible rationalization for the observed enhancement of CO2 dissociation in non-thermal plasmas by metal surfaces. PMID:26957149

  3. Transgenic Expression of Glud1 (Glutamate Dehydrogenase 1) in Neurons: In Vivo Model of Enhanced Glutamate Release, Altered Synaptic Plasticity, and Selective Neuronal Vulnerability

    PubMed Central

    Bao, Xiaodong; Pal, Ranu; Hascup, Kevin N.; Wang, Yongfu; Wang, Wen-Tung; Xu, Wenhao; Hui, Dongwei; Agbas, Abdulbaki; Wang, Xinkun; Michaelis, Mary L.; Choi, In-Young; Belousov, Andrei B.; Gerhardt, Greg A.; Michaelis, Elias K.

    2010-01-01

    The effects of lifelong, moderate excess release of glutamate (Glu) in the CNS have not been previously characterized. We created a transgenic (Tg) mouse model of lifelong excess synaptic Glu release in the CNS by introducing the gene for glutamate dehydrogenase 1 (Glud1) under the control of the neuron-specific enolase promoter. Glud1 is, potentially, an important enzyme in the pathway of Glu synthesis in nerve terminals. Increased levels of GLUD protein and activity in CNS neurons of hemizygous Tg mice were associated with increases in the in vivo release of Glu after neuronal depolarization in striatum and in the frequency and amplitude of miniature EPSCs in the CA1 region of the hippocampus. Despite overexpression of Glud1 in all neurons of the CNS, the Tg mice suffered neuronal losses in select brain regions (e.g., the CA1 but not the CA3 region). In vulnerable regions, Tg mice had decreases in MAP2A labeling of dendrites and in synaptophysin labeling of presynaptic terminals; the decreases in neuronal numbers and dendrite and presynaptic terminal labeling increased with advancing age. In addition, the Tg mice exhibited decreases in long-term potentiation of synaptic activity and in spine density in dendrites of CA1 neurons. Behaviorally, the Tg mice were significantly more resistant than wild-type mice to induction and duration of anesthesia produced by anesthetics that suppress Glu neurotransmission. The Glud1 mouse might be a useful model for the effects of lifelong excess synaptic Glu release on CNS neurons and for age-associated neurodegenerative processes. PMID:19890003

  4. AMPKα1 knockout enhances nociceptive behaviors and spinal glutamatergic synaptic activities via production of reactive oxygen species in the spinal dorsal horn.

    PubMed

    Maixner, Dylan W; Yan, Xisheng; Hooks, Shelley B; Weng, Han-Rong

    2016-06-21

    Emerging studies have shown that pharmacological activation of adenosine monophosphate-activated protein kinase (AMPK) produces potent analgesic effects in different animal pain models. Currently, the spinal molecular and synaptic mechanism by which AMPK regulates the pain signaling system remains unclear. To address this issue, we utilized the Cre-LoxP system to conditionally knockout the AMPKα1 gene in the nervous system of mice. We demonstrated that AMPKα1 is imperative for maintaining normal nociception, and mice deficient for AMPKα1 exhibit mechanical allodynia. This is concomitantly associated with increased glutamatergic synaptic activities in neurons located in the superficial spinal dorsal horn, which results from the increased glutamate release from presynaptic terminals and function of ligand-gated glutamate receptors at the postsynaptic neurons. Additionally, AMPKα1 knockout mice have increased activities of extracellular signal-regulated kinases (ERK) and p38 mitogen-activated protein kinases (p38), as well as elevated levels of interleukin-1β (IL-1β), reactive oxygen species (ROS), and heme oxygenase 1 (HO-1) in the spinal dorsal horn. Systemic administration of a non-specific ROS scavenger (phenyl-N-tert-butylnitrone, PBN) or a HO-1 activator (Cobalt protoporphyrin IX, CoPP) attenuated allodynia in AMPKα1 knockout mice. Bath-perfusion of the ROS scavenger or HO-1 activator effectively attenuated the increased ROS levels and glutamatergic synaptic activities in the spinal dorsal horn. Our findings suggest that ROS are the key down-stream signaling molecules mediating the behavioral hypersensitivity in AMPKα1 knockout mice. Thus, targeting AMPKα1 may represent an effective approach for the treatment of pathological pain conditions associated with neuroinflammation at the spinal dorsal horn. PMID:27058143

  5. 77 FR 40072 - Assessment of the Program for Enhanced Review Transparency and Communication for New Molecular...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

    ...The Food and Drug Administration (FDA) is announcing an opportunity for public comment on the statement of work for an assessment of the Program for Enhanced Review Transparency and Communication for New Molecular Entity (NME) New Drug Applications (NDAs) and Original Biologics License Applications (BLAs) (the Program). The Program is part of the FDA performance commitments under the proposed......

  6. Enhancing the Utilization of Information Communication Technology (ICT) among Home Economics Lecturers in South Eastern Nigeria

    ERIC Educational Resources Information Center

    Ejinkeonye, Uju Bridget; Usoroh, Comfort I.

    2016-01-01

    The study was on enhancing the utilization of information communication Technology (ICT) among Home Economics lecturers in south Eastern Nigeria. The study adopted a survey method. The area of the study is south eastern Nigeria. Three research questions guided the study. The population was made up of 63 Home Economics lecturers from the six…

  7. Enhancing Learning with Information and Communication Technologies in Pre-School

    ERIC Educational Resources Information Center

    Stephen, Christine; Plowman, Lydia

    2008-01-01

    Earlier observations suggested that young children's engagement with information and communication technologies (ICT) could be unproductive. Interplay: Play, Learning and ICT in Pre-school Settings set out to explore how practitioners can enhance three-year-olds' to four-year-olds' encounters with new technologies in the playroom. The study took…

  8. Use of Information and Communication Technology to Enhance the Information Literacy Skills of Distance Students

    ERIC Educational Resources Information Center

    Pastula, Matthew

    2010-01-01

    Information and Communication Technology (ICT) has become an integral tool in enhancing library services worldwide. This article looks at ways technology is utilized at Massey University to bridge the gap between distance students and traditional library services. There are a variety of software providers, formats and implementation practices…

  9. Music and Sign Language to Promote Infant and Toddler Communication and Enhance Parent-Child Interaction

    ERIC Educational Resources Information Center

    Colwell, Cynthia; Memmott, Jenny; Meeker-Miller, Anne

    2014-01-01

    The purpose of this study was to determine the efficacy of using music and/or sign language to promote early communication in infants and toddlers (6-20 months) and to enhance parent-child interactions. Three groups used for this study were pairs of participants (care-giver(s) and child) assigned to each group: 1) Music Alone 2) Sign Language…

  10. Coping and Communication-Enhancing Intervention versus Supportive Counseling for Women Diagnosed with Gynecological Cancers

    ERIC Educational Resources Information Center

    Manne, Sharon L.; Rubin, Stephen; Edelson, Mitchell; Rosenblum, Norman; Bergman, Cynthia; Hernandez, Enrique; Carlson, John; Rocereto, Thomas; Winkel, Gary

    2007-01-01

    This study compared the efficacy of 2 psychological interventions, a coping and communication-enhancing intervention (CCI) and supportive counseling (SC), in reducing depressive symptoms and cancer-specific distress of women diagnosed with gynecological cancer. Demographic, medical, and psychological moderators of intervention effects were…

  11. Communication Enhancement Project. Manitoba Pool Elevators and United Grain Growers. Phase One Final Report.

    ERIC Educational Resources Information Center

    Howell, Sandi

    In 1992, United Grain Growers (UGG) and Manitoba Pool (MP) formed a partnership to examine the literacy and numeracy needs of their rural grain elevator operators and the potential of delivering a communications enhancement program in the rural areas. During part 1, the committee held a series of initial planning meetings. Both companies held…

  12. NEW MEDIA TECHNOLOGY DEVELOPMENT TO ENHANCE AND IMPROVE COMMUNICATIONS AT USEPA'S NATIONAL RISK MANAGEMENT RESEARCH LABORATORY

    EPA Science Inventory

    New media technology (NT) interactive applications are currently being developed in house at ORD/NRMRL to enhance and improve communication of NRMRL's 1) research projects, 2) workshops/conferences and 3) specialized training. NT is an exciting mix of cutting-edge information tec...

  13. Enhancing Willingness to Communicate: Relative Effects of Visualization and Goal Setting

    ERIC Educational Resources Information Center

    Munezane, Yoko

    2015-01-01

    This article examines the relative effects of two treatments--goal setting and visualization--on enhancing Willingness to Communicate (WTC) among a group of 373 Japanese university EFL learners. Although longitudinal studies in both EFL and ESL settings have been conducted to examine the developmental aspect of WTC, no solid results of enhancing…

  14. Relationship-Enhancing Communication Skills in Prime-Time Family-Oriented Situation Comedies.

    ERIC Educational Resources Information Center

    Aust, Charles F.

    Television situation comedies have been criticized for their portrayal of dysfunctional family behavior. An exploratory content analysis study assessed the extent of relationship-enhancing communication skills in family-oriented, prime-time situation comedies, a genre frequently targeted for both scorn and praise. Three episodes each of five shows…

  15. Enhancing Intercultural Communication and Understanding: Team Translation Project as a Student Engagement Learning Approach

    ERIC Educational Resources Information Center

    Yang, Ping

    2015-01-01

    This paper reflects on a team translation project on Aboriginal culture designed to enhance university students' intercultural communication competence and understanding through engaging in an interactive team translation project funded by the Australia-China Council. A selected group of Chinese speaking translation students participated in the…

  16. Enhancing HIV Communication between Parents and Children: Efficacy of the Parents Matter! Program

    ERIC Educational Resources Information Center

    Miller, Kim S.; Lin, Carol Y.; Poulsen, Melissa N.; Fasula, Amy; Wyckoff, Sarah C.; Forehand, Rex; Long, Nicholas; Armistead, Lisa

    2011-01-01

    We examine efficacy of the Parents Matter! Program (PMP), a program to teach African-American parents of preadolescents sexual communication and HIV-prevention skills, through a multicenter, randomized control trial. A total of 1115 parent-child participants were randomized to one of three intervention arms (enhanced, brief, control). Percentages…

  17. Grade/Study-Performance Contracts, Enhanced Communication, Cooperative Learning, and Student Performance in Undergraduate Organic Chemistry.

    ERIC Educational Resources Information Center

    Dougherty, Ralph C.

    1997-01-01

    Describes and evaluates a teaching strategy, designed to increase student retention while maintaining academic performance levels in undergraduate organic chemistry, that uses grade/study-performance contracts, enhanced communication using electronic mail, and cooperative learning. Concludes that a series of interventions can substantially…

  18. A Review of Information and Communication Technology Enhanced Social Work Interventions

    ERIC Educational Resources Information Center

    Chan, Chitat; Holosko, Michael J.

    2016-01-01

    Objectives: Information and communications technology (ICT) has impacted almost all human service disciplines and currently is evolving in social work. This study provides a systematic review of ICT-enhanced social work interventions, with particular reference to their intervention fidelity (IF), validity, and the role of ICT in the helping…

  19. How Can Mobile SMS Communication Support and Enhance a First Year Undergraduate Learning Environment?

    ERIC Educational Resources Information Center

    Jones, Geraldine; Edwards, Gabriele; Reid, Alan

    2009-01-01

    In this paper we discuss a case study investigating how the academic and personal development of first year students on an undergraduate sports education degree can be supported and enhanced with mobile SMS (Short Message Service) communication. SMS-based technologies were introduced in response to students' particular needs (in transition to…

  20. Synaptic Basis for Cross-modal Plasticity: Enhanced Supragranular Dendritic Spine Density in Anterior Ectosylvian Auditory Cortex of the Early Deaf Cat.

    PubMed

    Clemo, H Ruth; Lomber, Stephen G; Meredith, M Alex

    2016-04-01

    In the cat, the auditory field of the anterior ectosylvian sulcus (FAES) is sensitive to auditory cues and its deactivation leads to orienting deficits toward acoustic, but not visual, stimuli. However, in early deaf cats, FAES activity shifts to the visual modality and its deactivation blocks orienting toward visual stimuli. Thus, as in other auditory cortices, hearing loss leads to cross-modal plasticity in the FAES. However, the synaptic basis for cross-modal plasticity is unknown. Therefore, the present study examined the effect of early deafness on the density, distribution, and size of dendritic spines in the FAES. Young cats were ototoxically deafened and raised until adulthood when they (and hearing controls) were euthanized, the cortex stained using Golgi-Cox, and FAES neurons examined using light microscopy. FAES dendritic spine density averaged 0.85 spines/μm in hearing animals, but was significantly higher (0.95 spines/μm) in the early deaf. Size distributions and increased spine density were evident specifically on apical dendrites of supragranular neurons. In separate tracer experiments, cross-modal cortical projections were shown to terminate predominantly within the supragranular layers of the FAES. This distributional correspondence between projection terminals and dendritic spine changes indicates that cross-modal plasticity is synaptically based within the supragranular layers of the early deaf FAES. PMID:25274986

  1. Method of Enhancing On-Board State Estimation Using Communication Signals

    NASA Technical Reports Server (NTRS)

    Anzalone, Evan J. (Inventor); Chuang, Jason C. H. (Inventor)

    2015-01-01

    A method of enhancing on-board state estimation for a spacecraft utilizes a network of assets to include planetary-based assets and space-based assets. Communication signals transmitted from each of the assets into space are defined by a common protocol. Data is embedded in each communication signal transmitted by the assets. The data includes a time-of-transmission for a corresponding one of the communication signals and a position of a corresponding one of the assets at the time-of-transmission. A spacecraft is equipped to receive the communication signals, has a clock synchronized to the space-wide time reference frame, and has a processor programmed to generate state estimates of the spacecraft. Using its processor, the spacecraft determines a one-dimensional range from itself to at least one of the assets and then updates its state estimates using each one-dimensional range.

  2. NMDA Receptors Mediate Synaptic Competition in Culture

    PubMed Central

    She, Kevin; Craig, Ann Marie

    2011-01-01

    Background Activity through NMDA type glutamate receptors sculpts connectivity in the developing nervous system. This topic is typically studied in the visual system in vivo, where activity of inputs can be differentially regulated, but in which individual synapses are difficult to visualize and mechanisms governing synaptic competition can be difficult to ascertain. Here, we develop a model of NMDA-receptor dependent synaptic competition in dissociated cultured hippocampal neurons. Methodology/Principal Findings GluN1 -/- (KO) mouse hippocampal neurons lacking the essential NMDA receptor subunit were cultured alone or cultured in defined ratios with wild type (WT) neurons. The absence of functional NMDA receptors did not alter neuron survival. Synapse development was assessed by immunofluorescence for postsynaptic PSD-95 family scaffold and apposed presynaptic vesicular glutamate transporter VGlut1. Synapse density was specifically enhanced onto minority wild type neurons co-cultured with a majority of GluN1 -/- neighbour neurons, both relative to the GluN1 -/- neighbours and relative to sister pure wild type cultures. This form of synaptic competition was dependent on NMDA receptor activity and not conferred by the mere physical presence of GluN1. In contrast to these results in 10% WT and 90% KO co-cultures, synapse density did not differ by genotype in 50% WT and 50% KO co-cultures or in 90% WT and 10% KO co-cultures. Conclusions/Significance The enhanced synaptic density onto NMDA receptor-competent neurons in minority coculture with GluN1 -/- neurons represents a cell culture paradigm for studying synaptic competition. Mechanisms involved may include a retrograde ‘reward’ signal generated by WT neurons, although in this paradigm there was no ‘punishment’ signal against GluN1 -/- neurons. Cell culture assays involving such defined circuits may help uncover the rules and mechanisms of activity-dependent synaptic competition in the developing nervous

  3. Synaptic Vesicle Pools: An Update

    PubMed Central

    Denker, Annette; Rizzoli, Silvio O.

    2010-01-01

    During the last few decades synaptic vesicles have been assigned to a variety of functional and morphological classes or “pools”. We have argued in the past (Rizzoli and Betz, 2005) that synaptic activity in several preparations is accounted for by the function of three vesicle pools: the readily releasable pool (docked at active zones and ready to go upon stimulation), the recycling pool (scattered throughout the nerve terminals and recycling upon moderate stimulation), and finally the reserve pool (occupying most of the vesicle clusters and only recycling upon strong stimulation). We discuss here the advancements in the vesicle pool field which took place in the ensuing years, focusing on the behavior of different pools under both strong stimulation and physiological activity. Several new findings have enhanced the three-pool model, with, for example, the disparity between recycling and reserve vesicles being underlined by the observation that the former are mobile, while the latter are “fixed”. Finally, a number of altogether new concepts have also evolved such as the current controversy on the identity of the spontaneously recycling vesicle pool. PMID:21423521

  4. Synaptic vesicle pools: an update.

    PubMed

    Denker, Annette; Rizzoli, Silvio O

    2010-01-01

    During the last few decades synaptic vesicles have been assigned to a variety of functional and morphological classes or "pools". We have argued in the past (Rizzoli and Betz, 2005) that synaptic activity in several preparations is accounted for by the function of three vesicle pools: the readily releasable pool (docked at active zones and ready to go upon stimulation), the recycling pool (scattered throughout the nerve terminals and recycling upon moderate stimulation), and finally the reserve pool (occupying most of the vesicle clusters and only recycling upon strong stimulation). We discuss here the advancements in the vesicle pool field which took place in the ensuing years, focusing on the behavior of different pools under both strong stimulation and physiological activity. Several new findings have enhanced the three-pool model, with, for example, the disparity between recycling and reserve vesicles being underlined by the observation that the former are mobile, while the latter are "fixed". Finally, a number of altogether new concepts have also evolved such as the current controversy on the identity of the spontaneously recycling vesicle pool. PMID:21423521

  5. A synaptic mechanism for network synchrony

    PubMed Central

    Alford, Simon T.; Alpert, Michael H.

    2014-01-01

    Within neural networks, synchronization of activity is dependent upon the synaptic connectivity of embedded microcircuits and the intrinsic membrane properties of their constituent neurons. Synaptic integration, dendritic Ca2+ signaling, and non-linear interactions are crucial cellular attributes that dictate single neuron computation, but their roles promoting synchrony and the generation of network oscillations are not well understood, especially within the context of a defined behavior. In this regard, the lamprey spinal central pattern generator (CPG) stands out as a well-characterized, conserved vertebrate model of a neural network (Smith et al., 2013a), which produces synchronized oscillations in which neural elements from the systems to cellular level that control rhythmic locomotion have been determined. We review the current evidence for the synaptic basis of oscillation generation with a particular emphasis on the linkage between synaptic communication and its cellular coupling to membrane processes that control oscillatory behavior of neurons within the locomotor network. We seek to relate dendritic function found in many vertebrate systems to the accessible lamprey central nervous system in which the relationship between neural network activity and behavior is well understood. This enables us to address how Ca2+ signaling in spinal neuron dendrites orchestrate oscillations that drive network behavior. PMID:25278839

  6. CPP-TRS(C): On using visual cognitive symbols to enhance communication effectiveness

    NASA Astrophysics Data System (ADS)

    Tonfoni, Graziella

    1994-11-01

    Communicative Positioning Program/Text Representation Systems (CPP-TRS) is a visual language based on a system of 12 canvasses, 10 signals and 14 symbols. CPP-TRS is based on the fact that every communication action is the result of a set of cognitive processes and the whole system is based on the concept that you can enhance communication by visually perceiving text. With a simple syntax, CPP-TRS is capable of representing meaning and intention as well as communication functions visually. Those are precisely invisible aspects of natural language that are most relevant to getting the global meaning of a text. CPP-TRS reinforces natural language in human machine interaction systems. It complements natural language by adding certain important elements that are not represented by natural language by itself. These include communication intention and function of the text expressed by the sender, as well as the role the reader is supposed to play. The communication intention and function of a text and the reader's role are invisible in natural language because neither specific words nor punctuation conveys them sufficiently and unambiguously; they are therefore non-transparent.

  7. CPP-TRS(C): On using visual cognitive symbols to enhance communication effectiveness

    NASA Technical Reports Server (NTRS)

    Tonfoni, Graziella

    1994-01-01

    Communicative Positioning Program/Text Representation Systems (CPP-TRS) is a visual language based on a system of 12 canvasses, 10 signals and 14 symbols. CPP-TRS is based on the fact that every communication action is the result of a set of cognitive processes and the whole system is based on the concept that you can enhance communication by visually perceiving text. With a simple syntax, CPP-TRS is capable of representing meaning and intention as well as communication functions visually. Those are precisely invisible aspects of natural language that are most relevant to getting the global meaning of a text. CPP-TRS reinforces natural language in human machine interaction systems. It complements natural language by adding certain important elements that are not represented by natural language by itself. These include communication intention and function of the text expressed by the sender, as well as the role the reader is supposed to play. The communication intention and function of a text and the reader's role are invisible in natural language because neither specific words nor punctuation conveys them sufficiently and unambiguously; they are therefore non-transparent.

  8. Communications

    NASA Technical Reports Server (NTRS)

    Stouffer, Donald D.

    1990-01-01

    Communication in its many forms is a critical component for an effective Space Grant Program. Good communication is needed within individual Space Grant College/Consortia, for example between consortium affiliates and the consortium program office. Effective communication between the several programs, NASA Headquarters, and NASA field centers also is required. Further, communication among the above program elements, industry, local and state government, and the public also are necessary for meeting program objectives.

  9. An Evaluation of Protocol Enhancing Proxies and File Transport Protocols for Satellite Communication

    NASA Technical Reports Server (NTRS)

    Finch, Patrick Eugene; Sullivan, Donald; Ivancic, William D.

    2012-01-01

    NASA is utilizing Global Hawk aircraft in high-altitude, long-duration Earth science missions. Communications with the onboard research equipment and sensors (the science payload) is via Ku-Band radio utilizing satellites in geostationary orbits. All payload communications use standard Internet Protocols and routing, and much of the data to be transferred is comprised of very large files. The science community is interested in fully utilizing these communication links to retrieve data as quickly and reliably as possible. A test bed was developed at NASA Ames to evaluate modern transport protocols as well as Protocol Enhancing Proxies (PEPs) to determine what tools best fit the needs of the science community. This paper describes the test bed used, the protocols, the PEPs that were evaluated, the particular tests performed and the results and conclusions.

  10. Roles for short-term synaptic plasticity in behavior.

    PubMed

    Fortune, Eric S; Rose, Gary J

    2002-01-01

    Short-term synaptic plasticity is phylogenetically widespread in ascending sensory systems of vertebrate brains. Such plasticity is found at all levels of sensory processing, including in sensory cortices. The functional roles of this apparently ubiquitous short-term synaptic plasticity, however, are not well understood. Data obtained in midbrain electrosensory neurons of Eigenmannia suggest that this plasticity has at least two roles in sensory processing; enhancing low-pass temporal filtering and generating phase shifts used in processing moving sensory images. Short-term synaptic plasticity may serve similar roles in other sensory modalities, including vision. PMID:14692501

  11. Retinal synaptic regeneration via microfluidic guiding channels.

    PubMed

    Su, Ping-Jung; Liu, Zongbin; Zhang, Kai; Han, Xin; Saito, Yuki; Xia, Xiaojun; Yokoi, Kenji; Shen, Haifa; Qin, Lidong

    2015-01-01

    In vitro culture of dissociated retinal neurons is an important model for investigating retinal synaptic regeneration (RSR) and exploring potentials in artificial retina. Here, retinal precursor cells were cultured in a microfluidic chip with multiple arrays of microchannels in order to reconstruct the retinal neuronal synapse. The cultured retinal cells were physically connected through microchannels. Activation of electric signal transduction by the cells through the microchannels was demonstrated by administration of glycinergic factors. In addition, an image-based analytical method was used to quantify the synaptic connections and to assess the kinetics of synaptic regeneration. The rate of RSR decreased significantly below 100 μM of inhibitor glycine and then approached to a relatively constant level at higher concentrations. Furthermore, RSR was enhanced by chemical stimulation with potassium chloride. Collectively, the microfluidic synaptic regeneration chip provides a novel tool for high-throughput investigation of RSR at the cellular level and may be useful in quality control of retinal precursor cell transplantation. PMID:26314276

  12. Cholesterol and synaptic vesicle exocytosis

    PubMed Central

    Fratangeli, Alessandra

    2010-01-01

    Lipids may affect synaptic function in at least two ways: by acting as ligands for effector proteins [e.g., phosphatidylinositol (4,5) bisphosphate, diacylglycerol-mediated signaling] or by modifying the physicochemical properties and molecular organization of synaptic membranes. One that acts in the latter manner is cholesterol, an essential structural component of plasma membranes that is largely enriched in the membranes of synapses and synaptic vesicles, in which it may be involved in lipid-lipid and protein-lipid interactions. Cholesterol is an important constituent of the “membrane rafts” that may play a role in recruiting and organizing the specific proteins of the exocytic pathways. Furthermore, many synaptic proteins bind directly to cholesterol. The regulation of cholesterol and lipid levels may therefore influence the specific interactions and activity of synaptic proteins, and have a strong impact on synaptic functions. PMID:20798824

  13. Communication.

    ERIC Educational Resources Information Center

    Online-Offline, 1998

    1998-01-01

    This theme issue on communication includes annotated listings of Web sites, CD-ROM and computer software, videos, books, and professional resources that deal with various methods of communication. Sidebars discuss mythology, photojournalism, sharing ideas on the Web, and songs of protest. Suggestions for class activities are also included. (LRW)

  14. Cell–cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis

    PubMed Central

    Ellison, David; Mugler, Andrew; Brennan, Matthew D.; Lee, Sung Hoon; Huebner, Robert J.; Shamir, Eliah R.; Woo, Laura A.; Kim, Joseph; Amar, Patrick; Nemenman, Ilya; Ewald, Andrew J.; Levchenko, Andre

    2016-01-01

    Collective cell responses to exogenous cues depend on cell–cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and little is known about how multicellular signal processing modulates single-cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored whether cell–cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow epidermal growth factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in gradient sensing. Functional experiments strongly implicated intercellular communication through gap junctions and calcium release from intracellular stores as mediators of collective gradient sensing. The resulting integrative analysis provides a framework for understanding the advantages and limitations of sensory information processing by relays of chemically coupled cells. PMID:26792522

  15. Communication

    NASA Technical Reports Server (NTRS)

    Griner, James

    2010-01-01

    NASA s communication work for the UAS Command and Control area will build upon work currently being conducted under NASA Recovery Act funds. Communication portions of UAS NextGen ConOps, Stateof- the-Art assessment, and Gap Analysis. Preliminary simulations for UAS CNPC link scalability assessment. Surrogate UAS aircraft upgrades. This work will also leverage FY10 in-guide funding for communication link model development. UAS are currently managed through exceptions and are operating using DoD frequencies for line-of-sight (LOS) and satellite-based communications links, low-power LOS links in amateur bands, or unlicensed Instrument/Scientific/Medical (ISM) frequencies. None of these frequency bands are designated for Safety and Regularity of Flight. No radio-frequency (RF) spectrum has been allocated by the International Telecommunications Union (ITU) specifically for UAS command and control links, for either LOS or Beyond LOS (BLOS) communication.

  16. Cost effective optical coupling for enhanced rate polymer optical fiber communication

    NASA Astrophysics Data System (ADS)

    Chandrappan, Jayakrishnan; Zhang, Jing; Ramana, Pamidighantam V.; Lau, John Hon Shing; Kwong, Dim Lee

    2008-02-01

    Recent developments in the short distance communication have made polymer optical fibers (POF) an attractive product in the high speed data communication market. The requirement of a large bandwidth, low cost, light weight and flexibility in installation have placed them over the copper cables especially in applications like home networking and automotives. Since POFs are large core multimoded fibers, their band width is limited by intermodal dispersion. This confines POFs application to low data rate short distance communications. Restrictive mode launchers (RML) and higher order mode strippers placed in the data link helps to reduce the intermodal dispersion. The techniques used to implement these signal conditioners should be simple and cost effective to keep POFs attractive in the short distance communication. In this paper we explore the possibility of integrating the RML and mode stripping elements in the transmitter and receiver package itself. The pre-designed optical signal conditioning elements are projected to get molded in the plastic packages and are fiber plug in modules. This connector less package design, universal to any light source proposes to enhance the data rate and is widely manufacturable at an ease of installation and low cost.

  17. Improving Outcomes for Children with Developmental Disabilities through Enhanced Communication and Collaboration between School Psychologists and Physicians

    ERIC Educational Resources Information Center

    Ritzema, Anne M.; Sladeczek, Ingrid E.; Ghosh, Shuvo; Karagiannakis, Anastasia; Manay-Quian, Natalia

    2014-01-01

    A renewed call for enhanced communication and collaboration between school psychology and medicine is envisioned, in light of a transdisciplinary model, where school psychologists, family physicians, and other health professionals transcend disciplinary boundaries. Recommendations for optimal communication and collaboration are described, as well…

  18. Synaptic plasticity with discrete state synapses

    NASA Astrophysics Data System (ADS)

    Abarbanel, Henry D. I.; Talathi, Sachin S.; Gibb, Leif; Rabinovich, M. I.

    2005-09-01

    Experimental observations on synaptic plasticity at individual glutamatergic synapses from the CA3 Shaffer collateral pathway onto CA1 pyramidal cells in the hippocampus suggest that the transitions in synaptic strength occur among discrete levels at individual synapses [C. C. H. Petersen , Proc. Natl. Acad. Sci. USA 85, 4732 (1998); O’Connor, Wittenberg, and Wang, D. H. O’Connor , Proc. Natl. Acad. Sci. USA (to be published); J. M. Montgomery and D. V. Madison, Trends Neurosci. 27, 744 (2004)]. This happens for both long term potentiation (LTP) and long term depression (LTD) induction protocols. O’Connor, Wittenberg, and Wang have argued that three states would account for their observations on individual synapses in the CA3-CA1 pathway. We develop a quantitative model of this three-state system with transitions among the states determined by a competition between kinases and phosphatases shown by D. H. O’Connor , to be determinant of LTP and LTD, respectively. Specific predictions for various plasticity protocols are given by coupling this description of discrete synaptic α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor ligand gated ion channel conductance changes to a model of postsynaptic membrane potential and associated intracellular calcium fluxes to yield the transition rates among the states. We then present various LTP and LTD induction protocols to the model system and report the resulting whole cell changes in AMPA conductance. We also examine the effect of our discrete state synaptic plasticity model on the synchronization of realistic oscillating neurons. We show that one-to-one synchronization is enhanced by the plasticity we discuss here and the presynaptic and postsynaptic oscillations are in phase. Synaptic strength saturates naturally in this model and does not require artificial upper or lower cutoffs, in contrast to earlier models of plasticity.

  19. Active music classes in infancy enhance musical, communicative and social development.

    PubMed

    Gerry, David; Unrau, Andrea; Trainor, Laurel J

    2012-05-01

    Previous studies suggest that musical training in children can positively affect various aspects of development. However, it remains unknown as to how early in development musical experience can have an effect, the nature of any such effects, and whether different types of music experience affect development differently. We found that random assignment to 6 months of active participatory musical experience beginning at 6 months of age accelerates acquisition of culture-specific knowledge of Western tonality in comparison to a similar amount of passive exposure to music. Furthermore, infants assigned to the active musical experience showed superior development of prelinguistic communicative gestures and social behaviour compared to infants assigned to the passive musical experience. These results indicate that (1) infants can engage in meaningful musical training when appropriate pedagogical approaches are used, (2) active musical participation in infancy enhances culture-specific musical acquisition, and (3) active musical participation in infancy impacts social and communication development. PMID:22490179

  20. Surface-plasmon enhanced photodetection at communication band based on hot electrons

    NASA Astrophysics Data System (ADS)

    Wu, Kai; Zhan, Yaohui; Wu, Shaolong; Deng, Jiajia; Li, Xiaofeng

    2015-08-01

    Surface plasmons can squeeze light into a deep-subwavelength space and generate abundant hot electrons in the nearby metallic regions, enabling a new paradigm of photoconversion by the way of hot electron collection. Unlike the visible spectral range concerned in previous literatures, we focus on the communication band and design the infrared hot-electron photodetectors with plasmonic metal-insulator-metal configuration by using full-wave finite-element method. Titanium dioxide-silver Schottky interface is employed to boost the low-energy infrared photodetection. The photodetection sensitivity is strongly improved by enhancing the plasmonic excitation from a rationally engineered metallic grating, which enables a strong unidirectional photocurrent. With a five-step electrical simulation, the optimized device exhibits an unbiased responsivity of ˜0.1 mA/W and an ultra-narrow response band (FWHM = 4.66 meV), which promises to be a candidate as the compact photodetector operating in communication band.

  1. Pannexin 1 regulates bidirectional hippocampal synaptic plasticity in adult mice

    PubMed Central

    Ardiles, Alvaro O.; Flores-Muñoz, Carolina; Toro-Ayala, Gabriela; Cárdenas, Ana M.; Palacios, Adrian G.; Muñoz, Pablo; Fuenzalida, Marco; Sáez, Juan C.; Martínez, Agustín D.

    2014-01-01

    The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca2+ concentration and NMDA receptor (NMDAR) composition of GluN2 subunits. Pannexin 1 (Panx1), a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP), it remains unknown whether these channels also modulate long-term depression (LTD) or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory. PMID:25360084

  2. Technology and Research Requirements for Combating Human Trafficking: Enhancing Communication, Analysis, Reporting, and Information Sharing

    SciTech Connect

    Kreyling, Sean J.; West, Curtis L.; Olson, Jarrod

    2011-03-17

    DHS’ Science & Technology Directorate directed PNNL to conduct an exploratory study on the domain of human trafficking in the Pacific Northwest in order to examine and identify technology and research requirements for enhancing communication, analysis, reporting, and information sharing – activities that directly support efforts to track, identify, deter, and prosecute human trafficking – including identification of potential national threats from smuggling and trafficking networks. This effort was conducted under the Knowledge Management Technologies Portfolio as part of the Integrated Federal, State, and Local/Regional Information Sharing (RISC) and Collaboration Program.

  3. Reflections on learning and enhancing communication skills through community engagement: a student perspective.

    PubMed

    Hanks, S; Marples, C; Wall, E

    2016-07-22

    Students in Peninsula School of Dentistry (PSD), Plymouth, undertake community engagement projects during the first two years of their undergraduate curriculum. These projects involve interaction with a variety of specific community groups and the planning and delivery of an appropriate and meaningful oral health intervention. Many of the project outcomes are based on enhancing communication skills and encouraging students to transfer these into their patient treatment sessions. This report draws on the experience of students who undertook two specific projects to demonstrate how they feel this is achieved. PMID:27444599

  4. Synaptic Activity Regulates the Abundance and Binding of Complexin

    PubMed Central

    Wragg, Rachel T.; Gouzer, Géraldine; Bai, Jihong; Arianna, Gianluca; Ryan, Timothy A.; Dittman, Jeremy S.

    2015-01-01

    Nervous system function relies on precise chemical communication between neurons at specialized junctions known as synapses. Complexin (CPX) is one of a small number of cytoplasmic proteins that are indispensable in controlling neurotransmitter release through SNARE and synaptic vesicle interactions. However, the mechanisms that recruit and stabilize CPX are poorly understood. The mobility of CPX tagged with photoactivatable green fluorescent protein (pGFP) was quantified in vivo using Caenorhabditis elegans. Although pGFP escaped the synapse within seconds, CPX-pGFP displayed both fast and slow decay components, requiring minutes for complete exchange of the synaptic pool. The longer synaptic residence time of CPX arose from both synaptic vesicle and SNARE interactions, and surprisingly, CPX mobility depended on synaptic activity. Moreover, mouse CPX-GFP reversibly dispersed out of hippocampal presynaptic terminals during stimulation, and blockade of vesicle fusion prevented CPX dispersion. Hence, synaptic CPX can rapidly redistribute and this exchange is influenced by neuronal activity, potentially contributing to use-dependent plasticity. PMID:25809246

  5. Synaptic Plasticity and Translation Initiation

    ERIC Educational Resources Information Center

    Klann, Eric; Antion, Marcia D.; Banko, Jessica L.; Hou, Lingfei

    2004-01-01

    It is widely accepted that protein synthesis, including local protein synthesis at synapses, is required for several forms of synaptic plasticity. Local protein synthesis enables synapses to control synaptic strength independent of the cell body via rapid protein production from pre-existing mRNA. Therefore, regulation of translation initiation is…

  6. Synaptic electronics: materials, devices and applications.

    PubMed

    Kuzum, Duygu; Yu, Shimeng; Wong, H-S Philip

    2013-09-27

    In this paper, the recent progress of synaptic electronics is reviewed. The basics of biological synaptic plasticity and learning are described. The material properties and electrical switching characteristics of a variety of synaptic devices are discussed, with a focus on the use of synaptic devices for neuromorphic or brain-inspired computing. Performance metrics desirable for large-scale implementations of synaptic devices are illustrated. A review of recent work on targeted computing applications with synaptic devices is presented. PMID:23999572

  7. Synaptic plasticity in the pathophysiology and treatment of bipolar disorder.

    PubMed

    Du, Jing; Machado-Vieira, Rodrigo; Khairova, Rushaniya

    2011-01-01

    Emerging evidence suggests that synaptic plasticity is intimately involved in the pathophysiology and treatment of bipolar disorder (BPD). Under certain conditions, over-strengthened and/or weakened synapses at different circuits in the brain could disturb brain functions in parallel, causing manic-like or depressive-like behaviors in animal models. In this chapter, we summarize the regulation of synaptic plasticity by medications, psychological conditions, hormones, and neurotrophic factors, and their correlation with mood-associated animal behaviors. We conclude that increased serotonin, norepinephrine, dopamine, brain-derived neurotrophic factor (BDNF), acute corticosterone, and antidepressant treatments lead to enhanced synaptic strength in the hippocampus and also correlate with antidepressant-like behaviors. In contrast, inhibiting monoaminergic signaling, long-term stress, and pathophysiological concentrations of cytokines weakens glutamatergic synaptic strength in the hippocampus and is associated with depressive-like symptoms. PMID:25236555

  8. Molecular Mechanisms of Synaptic Specificity

    PubMed Central

    Margeta, Milica A.; Shen, Kang

    2011-01-01

    Synapses are specialized junctions that mediate information flow between neurons and their targets. A striking feature of the nervous system is the specificity of its synaptic connections: an individual neuron will form synapses only with a small subset of available presynaptic and postsynaptic partners. Synaptic specificity has been classically thought to arise from homophilic or heterophilic interactions between adhesive molecules acting across the synaptic cleft. Over the past decade, many new mechanisms giving rise to synaptic specificity have been identified. Synapses can be specified by secreted molecules that promote or inhibit synaptogenesis, and their source can be a neighboring guidepost cell, not just presynaptic and postsynaptic neurons. Furthermore, lineage, fate, and timing of development can also play critical roles in shaping neural circuits. Future work utilizing large-scale screens will aim to elucidate the full scope of cellular mechanisms and molecular players that can give rise to synaptic specificity. PMID:19969086

  9. A Model of Synaptic Reconsolidation

    PubMed Central

    Kastner, David B.; Schwalger, Tilo; Ziegler, Lorric; Gerstner, Wulfram

    2016-01-01

    Reconsolidation of memories has mostly been studied at the behavioral and molecular level. Here, we put forward a simple extension of existing computational models of synaptic consolidation to capture hippocampal slice experiments that have been interpreted as reconsolidation at the synaptic level. The model implements reconsolidation through stabilization of consolidated synapses by stabilizing entities combined with an activity-dependent reservoir of stabilizing entities that are immune to protein synthesis inhibition (PSI). We derive a reduced version of our model to explore the conditions under which synaptic reconsolidation does or does not occur, often referred to as the boundary conditions of reconsolidation. We find that our computational model of synaptic reconsolidation displays complex boundary conditions. Our results suggest that a limited resource of hypothetical stabilizing molecules or complexes, which may be implemented by protein phosphorylation or different receptor subtypes, can underlie the phenomenon of synaptic reconsolidation. PMID:27242410

  10. Improving multidisciplinary communication at ward board rounds using video enhanced reflective practice

    PubMed Central

    Hellier, Cyril; Tully, Vicki; Forrest, Sandra; Jaggard, Pamela; MacRae, Morag; Habicht, Dirk; Greene, Alexandra; Collins, Karen

    2015-01-01

    The priority to ensure patient safety and use resources effectively, demands attention and innovation. Video enhanced reflective practice (VERP) provides training based upon analysis of film clips of one's professional practice to develop practical insight into the processes of communication, so that effective changes can be made to ongoing behaviour and practice. In this case the focus was on multi-disciplinary communication within daily board rounds on an acute medicine and care of the elderly ward. Baseline assessment and post intervention testing of perceptions of change by both full and core team were undertaken to establish the impact of VERP training. In addition pre and post focus group discussion and film analysis supplemented evaluation. The findings support the view that after VERP training of a core team, board rounds were seen as consistently easier to participate in, providing improved focus, were more efficient in goal setting and resulting in better care for patients as well as improved pathways to discharge. This suggests benefits to the communication “culture” of a multidisciplinary team resulting in increased benefits for the wider team. It is concluded that the use of tailored VERP training for personal, professional and team development is relevant, feasible, and worthy of further testing and investigation. PMID:26734342

  11. Modulation bandwidth enhancement of white-LED-based visible light communications using electrical equalizations

    NASA Astrophysics Data System (ADS)

    Kwon, D. H.; Yang, S. H.; Han, S. K.

    2015-01-01

    Utilizing the modulation capability of LEDs, there have been many studies about convergence technology to combine illumination and communication. The visible light communication (VLC) system has several advantages such as high security, immunity to RF interference and lower additional cost than comparing to LEDs just for illumination. However, modulation bandwidth of LEDs is not enough for various wireless communication systems. Since the commercial LEDs are designed only for lighting systems; we need an effort to enhance the modulation characteristics of LEDs. When the area of LED is increased, internal junction capacitance of LED is also increased depending on the area of LEDs and then the RC delay time of LED is increased. As a result, the modulation bandwidth of LEDs is limited by large RC delay time. In addition, frequency response of commercial white LED is degraded by the slow response time of the used yellow phosphor. Thus, modulation bandwidth of VLC system is limited to several MHz which is not enough to accommodate high data rate transmission. In this paper, we designed equalization circuit using RLC component for compensating the white LEDs frequency response. Also, we used blue filtering to improve frequency response of white LEDs, which is degraded by yellow phosphorescent component. Power loss by optical filtering and distance is compensated by convex lens. Consequently, we extend the modulation bandwidth of VLC system from 3 MHz to more than 180 MHz, and it allows NRZ-OOK data transmission up to 400 Mbps at 50 cm.

  12. Classification: Molecular & Synaptic Mechanisms

    PubMed Central

    Lussier, Marc P.; Gu, Xinglong; Lu, Wei; Roche, Katherine W.

    2014-01-01

    Controlling the density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at synapses is essential for regulating the strength of excitatory neurotransmission. In particular, the phosphorylation of AMPARs is important for defining both synaptic expression and intracellular routing of receptors. Phosphorylation is a posttranslational modification known to regulate many cellular events and the C-termini of glutamate receptors are important targets. Recently, the first intracellular loop1 region of the GluA1 subunit of AMPARs was reported to regulate synaptic targeting through phosphorylation of S567 by Ca2+/calmodulin-dependent protein kinase II (CaMKII). Intriguingly, the loop1 region of all four AMPAR subunits contains many putative phosphorylation sites (S/T/Y), leaving the possibility that other kinases may regulate AMPAR surface expression via phosphorylation of the loop regions. To explore this hypothesis, we used in vitro phosphorylation assays with a small panel of purified kinases and found that casein kinase 2 (CK2) phosphorylates the GluA1 and GluA2 loop1 regions, but not GluA3 or GluA4. Interestingly, when we reduced the endogenous expression of CK2 using a specific shRNA against the regulatory subunit CK2β, we detected a reduction of GluA1 surface expression, whereas GluA2 was unchanged. Furthermore, we identified S579 of GluA1 as a substrate of CK2, and the expression of GluA1 phospho-deficient mutants in hippocampal neurons displayed reduced surface expression. Therefore, our study identifies CK2 as a regulator of GluA1 surface expression by phosphorylating the intracellular loop1 region. PMID:24712994

  13. Communications

    ERIC Educational Resources Information Center

    Bailenson, Jeremy; Buzzanell, Patrice; Deetz, Stanley; Tewksbury, David; Thompson, Robert J.; Turow, Joseph; Bichelmeyer, Barbara; Bishop, M. J.; Gayeski, Diane

    2013-01-01

    Scholars representing the field of communications were asked to identify what they considered to be the most exciting and imaginative work currently being done in their field, as well as how that work might change our understanding. The scholars included Jeremy Bailenson, Patrice Buzzanell, Stanley Deetz, David Tewksbury, Robert J. Thompson, and…

  14. Communications

    NASA Technical Reports Server (NTRS)

    Hathorn, S.

    1985-01-01

    An overview of NASA's Thin Route satellite telecommunication project is presented. Thin Route employs applications technology satellites (ATS) in place of more costly commercial multi- transponder telecommunications satellites. This system allows remote and underdeveloped areas to communicate with the outside world for purposes of obtaining medical assistance among other things. The system represents a substantial cost saving over commercial systems.

  15. proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus.

    PubMed

    Yang, Jianmin; Harte-Hargrove, Lauren C; Siao, Chia-Jen; Marinic, Tina; Clarke, Roshelle; Ma, Qian; Jing, Deqiang; Lafrancois, John J; Bath, Kevin G; Mark, Willie; Ballon, Douglas; Lee, Francis S; Scharfman, Helen E; Hempstead, Barbara L

    2014-05-01

    Experience-dependent plasticity shapes postnatal development of neural circuits, but the mechanisms that refine dendritic arbors, remodel spines, and impair synaptic activity are poorly understood. Mature brain-derived neurotrophic factor (BDNF) modulates neuronal morphology and synaptic plasticity, including long-term potentiation (LTP) via TrkB activation. BDNF is initially translated as proBDNF, which binds p75(NTR). In vitro, recombinant proBDNF modulates neuronal structure and alters hippocampal long-term plasticity, but the actions of endogenously expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates hippocampal dendritic complexity and spine density through p75(NTR). Hippocampal slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, and enhanced long-term depression (LTD) in area CA1. These results suggest that proBDNF acts in vivo as a biologically active factor that regulates hippocampal structure, synaptic transmission, and plasticity, effects that are distinct from those of mature BDNF. PMID:24746813

  16. Synaptic Tagging During Memory Allocation

    PubMed Central

    Rogerson, Thomas; Cai, Denise; Frank, Adam; Sano, Yoshitake; Shobe, Justin; Aranda, Manuel L.; Silva, Alcino J.

    2014-01-01

    There is now compelling evidence that the allocation of memory to specific neurons (neuronal allocation) and synapses (synaptic allocation) in a neurocircuit is not random and that instead specific mechanisms, such as increases in neuronal excitability and synaptic tagging and capture, determine the exact sites where memories are stored. We propose an integrated view of these processes, such that neuronal allocation, synaptic tagging and capture, spine clustering and metaplasticity reflect related aspects of memory allocation mechanisms. Importantly, the properties of these mechanisms suggest a set of rules that profoundly affect how memories are stored and recalled. PMID:24496410

  17. Circadian Regulation of Synaptic Plasticity.

    PubMed

    Frank, Marcos G

    2016-01-01

    Circadian rhythms refer to oscillations in biological processes with a period of approximately 24 h. In addition to the sleep/wake cycle, there are circadian rhythms in metabolism, body temperature, hormone output, organ function and gene expression. There is also evidence of circadian rhythms in synaptic plasticity, in some cases driven by a master central clock and in other cases by peripheral clocks. In this article, I review the evidence for circadian influences on synaptic plasticity. I also discuss ways to disentangle the effects of brain state and rhythms on synaptic plasticity. PMID:27420105

  18. Visible light communications using predistortion signal to enhance the response of passive optical receiver

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Chen, Hung-Yu; Liang, Kevin; Wei, Liang-Yu; Chow, Chi-Wai; Yeh, Chien-Hung

    2016-01-01

    Traditional visible light communication (VLC) uses positive-intrinsic-negative photodiode (PD) or avalanche PD as the optical receivers (Rx). We demonstrate using a solar cell as the VLC Rx. The solar cell is flexible and low cost and converts the optical signal into an electrical signal directly without the need of external power supply. In addition to acting as the VLC passive Rx, the converted electrical signal from the solar cell can charge up the battery of the Rx nodes. Hence, the proposed scheme can be a promising candidate for the future Internet of Things network. However, a solar cell acting as a VLC Rx is very challenging, since the response of the solar cell is limited. Here, we propose and demonstrate using predistortion to significantly enhance the solar cell Rx response for the first time up to the authors' knowledge. Experimental results show that the response of the solar cell Rx is significantly enhanced; and the original 2-kHz detection bandwidth of the solar cell can be enhanced by 250 times for receiving 500-kbit/s VLC signal at a transmission distance of 1 m. The operation principle, the generated voltage by the solar cell, and the maximum data rates achieved at different transmission distances are also studied.

  19. Baicalein increases the cytotoxicity of cisplatin by enhancing gap junction intercellular communication.

    PubMed

    Wang, Yiwen; Wang, Qin; Zhang, Suzhi; Zhang, Yuan; Tao, Liang

    2014-07-01

    Drug resistance limits the clinical application of cisplatin, a widely used chemotherapeutic agent. Gap junction (GJ) is a channel that enhances cytotoxicity of certain chemotherapeutic agents. Baicalein is well known for its antitumor activity. This study investigated the effect of baicalein on cisplatin cytotoxicity and the relationship between this effect and the modulation of the GJ function in connexin 26 (Cx26)‑transfected HeLa cells. The sulforhodamine B (SRB) assay was used to examine the effect of baicalein on cell viability. A 'parachute' assay was used to investigate the effect of baicalein on GJ function. The effects of baicalein on cisplatin cytotoxicity and GJ function were assayed by standard colony‑forming assays. The expression of Cx26 was monitored by western blotting. It was observed that exposure of Cx26‑transfected cells to cisplatin reduced the number of colonies formed in low‑density cultures (no GJ formation) and in high‑density cultures (GJ formation), but the toxic effect was greater when cells were seeded at a high density. In the absence of connexin expression or with blockage of connexin channels however, cell density had no effect on cisplatin toxicity. Baicalein significantly enhanced cisplatin cytotoxicity, but this effect required the presence of functional GJs between the cells. In conclusion, the dependence of cisplatin toxicity on cell density is mediated by GJs. Baicalein increases cisplatin cytotoxicity through enhancing GJ intercellular communication. PMID:24736991

  20. Enhancement of the assessment of physician-patient communication skills in the United States Medical Licensing Examination.

    PubMed

    Hoppe, Ruth B; King, Ann M; Mazor, Kathleen M; Furman, Gail E; Wick-Garcia, Penelope; Corcoran-Ponisciak, Heather; Katsufrakis, Peter J

    2013-11-01

    The National Board of Medical Examiners (NBME) reviewed all components of the United States Medical Licensing Examination as part of a strategic planning activity. One recommendation generated from the review called for enhancements of the communication skills component of the Step 2 Clinical Skills (Step 2 CS) examination. To address this recommendation, the NBME created a multidisciplinary team that comprised experts in communication content, communication measurement, and implementation of standardized patient (SP)-based examinations. From 2007 through 2012, the team reviewed literature in physician-patient communication, examined performance characteristics of the Step 2 CS exam, observed case development and quality assurance processes, interviewed SPs and their trainers, and reviewed video recordings of examinee-SP interactions. The authors describe perspectives gained by their team from the review process and outline the resulting enhancements to the Step 2 CS exam, some of which were rolled out in June 2012. PMID:24072122

  1. Synaptic dynamics in analog VLSI.

    PubMed

    Bartolozzi, Chiara; Indiveri, Giacomo

    2007-10-01

    Synapses are crucial elements for computation and information transfer in both real and artificial neural systems. Recent experimental findings and theoretical models of pulse-based neural networks suggest that synaptic dynamics can play a crucial role for learning neural codes and encoding spatiotemporal spike patterns. Within the context of hardware implementations of pulse-based neural networks, several analog VLSI circuits modeling synaptic functionality have been proposed. We present an overview of previously proposed circuits and describe a novel analog VLSI synaptic circuit suitable for integration in large VLSI spike-based neural systems. The circuit proposed is based on a computational model that fits the real postsynaptic currents with exponentials. We present experimental data showing how the circuit exhibits realistic dynamics and show how it can be connected to additional modules for implementing a wide range of synaptic properties. PMID:17716003

  2. Security-enhanced chaos communication with time-delay signature suppression and phase encryption.

    PubMed

    Xue, Chenpeng; Jiang, Ning; Lv, Yunxin; Wang, Chao; Li, Guilan; Lin, Shuqing; Qiu, Kun

    2016-08-15

    A security-enhanced chaos communication scheme with time delay signature (TDS) suppression and phase-encrypted feedback light is proposed, in virtue of dual-loop feedback with independent high-speed phase modulation. We numerically investigate the property of TDS suppression in the intensity and phase space and quantitatively discuss security of the proposed system by calculating the bit error rate of eavesdroppers who try to crack the system by directly filtering the detected signal or by using a similar semiconductor laser to synchronize the link signal and extract the data. The results show that TDS embedded in the chaotic carrier can be well suppressed by properly setting the modulation frequency, which can keep the time delay a secret from the eavesdropper. Moreover, because the feedback light is encrypted, without the accurate time delay and key, the eavesdropper cannot reconstruct the symmetric operation conditions and decode the correct data. PMID:27519064

  3. Diversity climate enhances work outcomes through trust and openness in workgroup communication.

    PubMed

    Hofhuis, Joep; van der Rijt, Pernill G A; Vlug, Martijn

    2016-01-01

    Diversity climate, defined as an organizational climate characterized by openness towards and appreciation of individual differences, has been shown to enhance outcomes in culturally diverse teams. To date, it remains unclear which processes are responsible for these findings. This paper presents two quantitative studies (n = 91; 246) that identify trust and openness in workgroup communication as possible mediators. We replicate earlier findings that perceived diversity climate positively relates to job satisfaction, sense of inclusion, work group identification and knowledge sharing in teams. In study 1, trust is shown to mediate the effects of perceived diversity climate on team members' sense of inclusion. In study 2, trust mediates the relationship between perceived diversity climate and workgroup identification and openness mediates its relationship with knowledge sharing. PMID:27375983

  4. Surface-plasmon enhanced photodetection at communication band based on hot electrons

    SciTech Connect

    Wu, Kai; Zhan, Yaohui E-mail: xfli@suda.edu.cn; Wu, Shaolong; Deng, Jiajia; Li, Xiaofeng E-mail: xfli@suda.edu.cn

    2015-08-14

    Surface plasmons can squeeze light into a deep-subwavelength space and generate abundant hot electrons in the nearby metallic regions, enabling a new paradigm of photoconversion by the way of hot electron collection. Unlike the visible spectral range concerned in previous literatures, we focus on the communication band and design the infrared hot-electron photodetectors with plasmonic metal-insulator-metal configuration by using full-wave finite-element method. Titanium dioxide-silver Schottky interface is employed to boost the low-energy infrared photodetection. The photodetection sensitivity is strongly improved by enhancing the plasmonic excitation from a rationally engineered metallic grating, which enables a strong unidirectional photocurrent. With a five-step electrical simulation, the optimized device exhibits an unbiased responsivity of ∼0.1 mA/W and an ultra-narrow response band (FWHM = 4.66 meV), which promises to be a candidate as the compact photodetector operating in communication band.

  5. Time reversal multiple-input/multiple-output acoustic communication enhanced by parallel interference cancellation.

    PubMed

    Song, Aijun; Badiey, Mohsen

    2012-01-01

    Multiple-input/multiple-output (MIMO) techniques can lead to significant improvements of underwater acoustic communication capabilities. In this paper, receivers based on time reversal processing are developed for high frequency underwater MIMO channels. Time reversal followed by a single channel decision feedback equalizer, aided by frequent channel updates, is used to compensate for the time-varying inter-symbol interference. A parallel interference cancellation method is incorporated to suppress the co-channel interference in the MIMO system. The receiver performance is demonstrated by a 2008 shallow water experiment in Kauai, Hawaii. In the experiment, high frequency MIMO signals centered at 16 kHz were transmitted every hour during a 35 h period from an 8-element source array to a wide aperture 16-element vertical receiving array at 4 km range. The interference cancellation method is shown to generate significant performance enhancement, on average 2-4 dB in the output signal-to-noise ratio per data stream, throughout the 35 h MIMO transmissions. Further, communication performance and achieved data rates exhibit significant changes over the 35 h period as a result of stratification of the water column. PMID:22280591

  6. Fbxo45, a Novel Ubiquitin Ligase, Regulates Synaptic Activity*

    PubMed Central

    Tada, Hirobumi; Okano, Hirotaka James; Takagi, Hiroshi; Shibata, Shinsuke; Yao, Ikuko; Matsumoto, Masaki; Saiga, Toru; Nakayama, Keiichi I.; Kashima, Haruo; Takahashi, Takuya; Setou, Mitsutoshi; Okano, Hideyuki

    2010-01-01

    Neurons communicate with each other through synapses. To establish the precise yet flexible connections that make up neural networks in the brain, continuous synaptic modulation is required. The ubiquitin-proteasome system of protein degradation is one of the critical mechanisms that underlie this process, playing crucial roles in the regulation of synaptic structure and function. We identified a novel ubiquitin ligase, Fbxo45, that functions at synapses. Fbxo45 is evolutionarily conserved and selectively expressed in the nervous system. We demonstrated that the knockdown of Fbxo45 in primary cultured hippocampal neurons resulted in a greater frequency of miniature excitatory postsynaptic currents. We also found that Fbxo45 induces the degradation of a synaptic vesicle-priming factor, Munc13-1. We propose that Fbxo45 plays an important role in the regulation of neurotransmission by modulating Munc13-1 at the synapse. PMID:19996097

  7. Communications and Control for Enhanced Autonomy in Underwater Vehicles for Deep Oceanographic Research

    NASA Astrophysics Data System (ADS)

    Jakuba, M.; Kinsey, J. C.; Yoerger, D. R.; Whitcomb, L. L.; Camilli, R.; Murphy, C.; Bowen, A.; German, C. R.

    2010-12-01

    NASA’s Astrobiology Science and Technology for Exploring Planets (ASTEP) program is a science-driven program to produce advances in scientific and technological capabilities for planetary exploration. Oceanographic robotic vehicles and planetary exploration robots have proven to be highly effective scientific tools for performing scientific research in remote, extreme, and hostile environments that preclude direct human presence. In both domains, the planets and the world’s oceans, human oversight of remote robotic exploration can dramatically enhance scientific return in comparison to purely pre-planned missions by combining the perception, intelligence, and domain knowledge of the human operators with the super-human physical and sensory capabilities of robots. The degree of human oversight, however, is restricted in sea and space by physical limits on the bandwidth and time delay of communications between human operators and remote robotic platforms. Enhanced robotic autonomy can alleviate this obstacle. We present a communications and control architecture for underwater oceanographic robot vehicles that has permitted us to introduce elements of enhanced autonomy into operations with the Woods Hole Oceanographic Institution's Autonomous Underwater Vehicles (AUVs) Nereus and Sentry. Our architecture is designed to facilitate: (1) autonomous distillation of scientific data and transmission of salient synopses from the remote vehicle to its human operators; (2) high-level near real-time human supervision and control of mission programming; (3) semi-supervised learning of environmental models for enhanced survey and search mission effectiveness. Specific capabilities our group has demonstrated include selective data delivery via acoustic link; near real-time reprogramming of vehicle mission programs during otherwise preplanned dives; and validation of autonomous decision-making processes with human-supervision. These elements have been recently demonstrated

  8. Communicative social capital and collective efficacy as determinants of access to health-enhancing resources in residential communities.

    PubMed

    Matsaganis, Matthew D; Wilkin, Holley A

    2015-04-01

    This article contributes to the burgeoning literature on the social determinants of health disparities. The authors investigate how communication resources and collective efficacy, independently and in combination, shape residents' access to health enhancing resources (including healthcare services, sources of healthier food options, and public recreation spaces) in their communities. Using random digit dial telephone survey data from 833 residents of South Los Angeles communities the authors show that communicative social capital-that is, an information and problem-solving resource that accrues to residents as they become more integrated into their local communication network of neighbors, community organizations, and local media-plays a significant role in access to health resources. This relationship is complicated by individuals' health insurance and health status, as communicative social capital magnifies the sense of absence of resources for those who are in worse health and lack insurance. Communicative social capital builds collective efficacy, which is positively related to access to health-enhancing resources, but it also mediates the negative relationship between communicative social capital and access to health resources. Residents with richer stores of communicative social capital and collective efficacy report better access to health resources. The authors conclude with a discussion of implications of these findings and suggestions for future research. PMID:25529115

  9. Persistent ERK Activation Maintains Learning-Induced Long-Lasting Modulation of Synaptic Connectivity

    ERIC Educational Resources Information Center

    Cohen-Matsliah, Sivan Ida; Seroussi, Yaron; Rosenblum, Kobi; Barkai, Edi

    2008-01-01

    Pyramidal neurons in the piriform cortex from olfactory-discrimination (OD) trained rats undergo synaptic modifications that last for days after learning. A particularly intriguing modification is reduced paired-pulse facilitation (PPF) in the synapses interconnecting these cells; a phenomenon thought to reflect enhanced synaptic release. The…

  10. Molecular Motors and Synaptic Assembly

    PubMed Central

    Cai, Qian; Sheng, Zu-Hang

    2016-01-01

    Proper synaptic function requires the seamless integration of the transport, assembly, and regulation of synaptic components and structures. Inasmuch as the synapse is often distant from the neuronal cell body, newly synthesized synaptic proteins, the precursors of synaptic vesicles, active zone compartments, channels and receptors, and mitochondria, must be transported along lengthy neuronal processes to participate in synaptogenesis. Neuronal transport is mediated by motor proteins that associate with their cargoes via adaptors (or receptors) and that travel along the cytoskeleton network within the neuronal processes. Thus, the identity of membranous protein cargoes and the specificity of motor-cargo interactions are critical for correctly targeting cargoes and properly assembling synapses in developing neurons and in remodeling synapses of mature neurons in response to neuronal activity. In this article, the authors review recent progress in characterizing microtubule- and actin-based motor proteins that are involved in delivering synaptic components and discuss potential mechanisms underlying the formation of motor- receptor-cargo complexes that contribute to synaptogenesis and activity-induced synaptic plasticity. PMID:19218232

  11. Theoretical models of synaptic short term plasticity

    PubMed Central

    Hennig, Matthias H.

    2013-01-01

    Short term plasticity is a highly abundant form of rapid, activity-dependent modulation of synaptic efficacy. A shared set of mechanisms can cause both depression and enhancement of the postsynaptic response at different synapses, with important consequences for information processing. Mathematical models have been extensively used to study the mechanisms and roles of short term plasticity. This review provides an overview of existing models and their biological basis, and of their main properties. Special attention will be given to slow processes such as calcium channel inactivation and the effect of activation of presynaptic autoreceptors. PMID:23626536

  12. Depression as a Glial-Based Synaptic Dysfunction.

    PubMed

    Rial, Daniel; Lemos, Cristina; Pinheiro, Helena; Duarte, Joana M; Gonçalves, Francisco Q; Real, Joana I; Prediger, Rui D; Gonçalves, Nélio; Gomes, Catarina A; Canas, Paula M; Agostinho, Paula; Cunha, Rodrigo A

    2015-01-01

    Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processes occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia) tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the "quad-partite" synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increased microglia "activation" in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, brain-derived neurotrophic factor, BDNF) affect glia functioning, whereas antidepressant treatments (serotonin-selective reuptake inhibitors, SSRIs, electroshocks, deep brain stimulation) recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication-such as the purinergic neuromodulation system operated by adenosine 5'-triphosphate (ATP) and adenosine-emerge as promising candidates to "re-normalize" synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to

  13. Synaptic Mechanisms of Blast-Induced Brain Injury.

    PubMed

    Przekwas, Andrzej; Somayaji, Mahadevabharath R; Gupta, Raj K

    2016-01-01

    Blast wave-induced traumatic brain injury (TBI) is one of the most common injuries to military personnel. Brain tissue compression/tension due to blast-induced cranial deformations and shear waves due to head rotation may generate diffuse micro-damage to neuro-axonal structures and trigger a cascade of neurobiological events culminating in cognitive and neurodegenerative disorders. Although diffuse axonal injury is regarded as a signature wound of mild TBI (mTBI), blast loads may also cause synaptic injury wherein neuronal synapses are stretched and sheared. This synaptic injury may result in temporary disconnect of the neural circuitry and transient loss in neuronal communication. We hypothesize that mTBI symptoms such as loss of consciousness or dizziness, which start immediately after the insult, could be attributed to synaptic injury. Although empirical evidence is beginning to emerge; the detailed mechanisms underlying synaptic injury are still elusive. Coordinated in vitro-in vivo experiments and mathematical modeling studies can shed light into the synaptic injury mechanisms and their role in the potentiation of mTBI symptoms. PMID:26834697

  14. Synaptic Mechanisms of Blast-Induced Brain Injury

    PubMed Central

    Przekwas, Andrzej; Somayaji, Mahadevabharath R.; Gupta, Raj K.

    2016-01-01

    Blast wave-induced traumatic brain injury (TBI) is one of the most common injuries to military personnel. Brain tissue compression/tension due to blast-induced cranial deformations and shear waves due to head rotation may generate diffuse micro-damage to neuro-axonal structures and trigger a cascade of neurobiological events culminating in cognitive and neurodegenerative disorders. Although diffuse axonal injury is regarded as a signature wound of mild TBI (mTBI), blast loads may also cause synaptic injury wherein neuronal synapses are stretched and sheared. This synaptic injury may result in temporary disconnect of the neural circuitry and transient loss in neuronal communication. We hypothesize that mTBI symptoms such as loss of consciousness or dizziness, which start immediately after the insult, could be attributed to synaptic injury. Although empirical evidence is beginning to emerge; the detailed mechanisms underlying synaptic injury are still elusive. Coordinated in vitro–in vivo experiments and mathematical modeling studies can shed light into the synaptic injury mechanisms and their role in the potentiation of mTBI symptoms. PMID:26834697

  15. Synaptic Cell Adhesion Molecules in Alzheimer's Disease

    PubMed Central

    Leshchyns'ka, Iryna

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative brain disorder associated with the loss of synapses between neurons in the brain. Synaptic cell adhesion molecules are cell surface glycoproteins which are expressed at the synaptic plasma membranes of neurons. These proteins play key roles in formation and maintenance of synapses and regulation of synaptic plasticity. Genetic studies and biochemical analysis of the human brain tissue, cerebrospinal fluid, and sera from AD patients indicate that levels and function of synaptic cell adhesion molecules are affected in AD. Synaptic cell adhesion molecules interact with Aβ, a peptide accumulating in AD brains, which affects their expression and synaptic localization. Synaptic cell adhesion molecules also regulate the production of Aβ via interaction with the key enzymes involved in Aβ formation. Aβ-dependent changes in synaptic adhesion affect the function and integrity of synapses suggesting that alterations in synaptic adhesion play key roles in the disruption of neuronal networks in AD. PMID:27242933

  16. Balance and stability of synaptic structures during synaptic plasticity.

    PubMed

    Meyer, Daniel; Bonhoeffer, Tobias; Scheuss, Volker

    2014-04-16

    Subsynaptic structures such as bouton, active zone, postsynaptic density (PSD) and dendritic spine, are highly correlated in their dimensions and also correlate with synapse strength. Why this is so and how such correlations are maintained during synaptic plasticity remains poorly understood. We induced spine enlargement by two-photon glutamate uncaging and examined the relationship between spine, PSD, and bouton size by two-photon time-lapse imaging and electron microscopy. In enlarged spines the PSD-associated protein Homer1c increased rapidly, whereas the PSD protein PSD-95 increased with a delay and only in cases of persistent spine enlargement. In the case of nonpersistent spine enlargement, the PSD proteins remained unchanged or returned to their original level. The ultrastructure at persistently enlarged spines displayed matching dimensions of spine, PSD, and bouton, indicating their correlated enlargement. This supports a model in which balancing of synaptic structures is a hallmark for the stabilization of structural modifications during synaptic plasticity. PMID:24742464

  17. Mediators of a Coping and Communication-Enhancing Intervention and a Supportive Counseling Intervention among Women Diagnosed with Gynecological Cancers

    ERIC Educational Resources Information Center

    Manne, Sharon L.; Winkel, Gary; Rubin, Stephen; Edelson, Mitchell; Rosenblum, Norman; Bergman, Cynthia; Hernandez, Enrique; Carlson, John; Rocereto, Thomas

    2008-01-01

    The authors evaluated mechanisms of change for a coping and communication-enhancing intervention (CCI) and supportive counseling (SC). They proposed that the effects of CCI on depressive symptoms would be mediated by psychological processes targeted by CCI, namely increases in the following: positive reappraisal, acceptance, planful problem…

  18. Efficacy of Information and Communication Technology in Enhancing Learning Outcomes of Students with Hearing Impairment in Ibadan

    ERIC Educational Resources Information Center

    Egaga, Patrick I.; Aderibigbe, S. Akinwumi

    2015-01-01

    The study aimed at examining the efficacy of Information and Communication Technology (ICT) in enhancing learning outcomes of students with hearing impairment in Ibadan. The study adopted a pretest, post-test, control group quasi-experimental research design. Purposive sampling techniques was used for the selection of thirty participants…

  19. Dephosphorylated synapsin I anchors synaptic vesicles to actin cytoskeleton: an analysis by videomicroscopy.

    PubMed

    Ceccaldi, P E; Grohovaz, F; Benfenati, F; Chieregatti, E; Greengard, P; Valtorta, F

    1995-03-01

    Synapsin I is a synaptic vesicle-associated protein which inhibits neurotransmitter release, an effect which is abolished upon its phosphorylation by Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). Based on indirect evidence, it was suggested that this effect on neurotransmitter release may be achieved by the reversible anchoring of synaptic vesicles to the actin cytoskeleton of the nerve terminal. Using video-enhanced microscopy, we have now obtained experimental evidence in support of this model: the presence of dephosphorylated synapsin I is necessary for synaptic vesicles to bind actin; synapsin I is able to promote actin polymerization and bundling of actin filaments in the presence of synaptic vesicles; the ability to cross-link synaptic vesicles and actin is specific for synapsin I and is not shared by other basic proteins; the cross-linking between synaptic vesicles and actin is specific for the membrane of synaptic vesicles and does not reflect either a non-specific binding of membranes to the highly surface active synapsin I molecule or trapping of vesicles within the thick bundles of actin filaments; the formation of the ternary complex is virtually abolished when synapsin I is phosphorylated by CaM kinase II. The data indicate that synapsin I markedly affects synaptic vesicle traffic and cytoskeleton assembly in the nerve terminal and provide a molecular basis for the ability of synapsin I to regulate the availability of synaptic vesicles for exocytosis and thereby the efficiency of neurotransmitter release. PMID:7876313

  20. Communication and Intimacy-Enhancing Interventions for Men Diagnosed with Prostate Cancer and Their Partners

    PubMed Central

    Nelson, Christian J.; Kenowitz, Joslyn

    2015-01-01

    Introduction The sexual dysfunction following prostate cancer treatments often leads to a reduction in intimate contact for couples. A number of psychosocial interventions have been developed to enhance intimacy in these couples. This paper reviews three of these interventions and is a summary of a presentation given as part of a symposium at the 2011 Cancer Survivorship and Sexual Health Meeting. Aim The goal of this presentation was to: (i) review three types of psychosocial interventions; and (ii) describe the methodological issues highlighted by these interventions. Main Outcome Measures Validated measures of relationship intimacy and communication. Methods To be selected, the interventions had to be: a randomized control trial, focus on a couples approach to therapy, and report at least one relationship outcome. Results The results were not consistent within or across studies, and suggest that some specific aspects of the interventions may be helpful for the patient, while other aspects of the studies may be helpful for the partner. The Northouse et al. study suggests that partners may benefit from a focus on couple work, as compared to the patient. The Canada et al. study indicates that when focusing on sexual functioning, working with a couple did not show significant benefit compared to working with a man alone. The study did show, however, that a sexual-based intervention can improve the use of erectile dysfunction treatments and suggests patients may benefit from specific focus on side effects of treatment. The Manne et al. study highlights the importance of targeting these interventions to couples who report distress, and for distressed couples, an intervention can show positive results. Conclusions Intimacy enhancing interventions can be effective for couples, while the partners may benefit more from couples work; the patients may benefit more from focus on specific side effects. PMID:23387918

  1. MPTP-meditated hippocampal dopamine deprivation modulates synaptic transmission and activity-dependent synaptic plasticity

    SciTech Connect

    Zhu Guoqi; Chen Ying; Huang Yuying; Li Qinglin; Behnisch, Thomas

    2011-08-01

    Parkinson's disease (PD)-like symptoms including learning deficits are inducible by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Therefore, it is possible that MPTP may disturb hippocampal memory processing by modulation of dopamine (DA)- and activity-dependent synaptic plasticity. We demonstrate here that intraperitoneal (i.p.) MPTP injection reduces the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) within 7 days. Subsequently, the TH expression level in SN and hippocampus and the amount of DA and its metabolite DOPAC in striatum and hippocampus decrease. DA depletion does not alter basal synaptic transmission and changes pair-pulse facilitation (PPF) of field excitatory postsynaptic potentials (fEPSPs) only at the 30 ms inter-pulse interval. In addition, the induction of long-term potentiation (LTP) is impaired whereas the duration of long-term depression (LTD) becomes prolonged. Since both LTP and LTD depend critically on activation of NMDA and DA receptors, we also tested the effect of DA depletion on NMDA receptor-mediated synaptic transmission. Seven days after MPTP injection, the NMDA receptor-mediated fEPSPs are decreased by about 23%. Blocking the NMDA receptor-mediated fEPSP does not mimic the MPTP-LTP. Only co-application of D1/D5 and NMDA receptor antagonists during tetanization resembled the time course of fEPSP potentiation as observed 7 days after i.p. MPTP injection. Together, our data demonstrate that MPTP-induced degeneration of DA neurons and the subsequent hippocampal DA depletion alter NMDA receptor-mediated synaptic transmission and activity-dependent synaptic plasticity. - Highlights: > I.p. MPTP-injection mediates death of dopaminergic neurons. > I.p. MPTP-injection depletes DA and DOPAC in striatum and hippocampus. > I.p. MPTP-injection does not alter basal synaptic transmission. > Reduction of LTP and enhancement of LTD after i.p. MPTP-injection. > Attenuation of NMDA-receptors mediated f

  2. Synaptic representation of locomotion in single cerebellar granule cells

    PubMed Central

    Powell, Kate; Mathy, Alexandre; Duguid, Ian; Häusser, Michael

    2015-01-01

    The cerebellum plays a crucial role in the regulation of locomotion, but how movement is represented at the synaptic level is not known. Here, we use in vivo patch-clamp recordings to show that locomotion can be directly read out from mossy fiber synaptic input and spike output in single granule cells. The increase in granule cell spiking during locomotion is enhanced by glutamate spillover currents recruited during movement. Surprisingly, the entire step sequence can be predicted from input EPSCs and output spikes of a single granule cell, suggesting that a robust gait code is present already at the cerebellar input layer and transmitted via the granule cell pathway to downstream Purkinje cells. Thus, synaptic input delivers remarkably rich information to single neurons during locomotion. DOI: http://dx.doi.org/10.7554/eLife.07290.001 PMID:26083712

  3. Long-term Synaptic Plasticity: Circuit Perturbation and Stabilization

    PubMed Central

    Jung, Sung-Cherl; Eun, Su-Yong

    2014-01-01

    At central synapses, activity-dependent synaptic plasticity has a crucial role in information processing, storage, learning, and memory under both physiological and pathological conditions. One widely accepted model of learning mechanism and information processing in the brain is Hebbian Plasticity: long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD are respectively activity-dependent enhancement and reduction in the efficacy of the synapses, which are rapid and synapse-specific processes. A number of recent studies have a strong focal point on the critical importance of another distinct form of synaptic plasticity, non-Hebbian plasticity. Non-Hebbian plasticity dynamically adjusts synaptic strength to maintain stability. This process may be very slow and occur cell-widely. By putting them all together, this mini review defines an important conceptual difference between Hebbian and non-Hebbian plasticity. PMID:25598658

  4. Cell-specific synaptic plasticity induced by network oscillations

    PubMed Central

    Zarnadze, Shota; Bäuerle, Peter; Santos-Torres, Julio; Böhm, Claudia; Schmitz, Dietmar; Geiger, Jörg RP

    2016-01-01

    Gamma rhythms are known to contribute to the process of memory encoding. However, little is known about the underlying mechanisms at the molecular, cellular and network levels. Using local field potential recording in awake behaving mice and concomitant field potential and whole-cell recordings in slice preparations we found that gamma rhythms lead to activity-dependent modification of hippocampal networks, including alterations in sharp wave-ripple complexes. Network plasticity, expressed as long-lasting increases in sharp wave-associated synaptic currents, exhibits enhanced excitatory synaptic strength in pyramidal cells that is induced postsynaptically and depends on metabotropic glutamate receptor-5 activation. In sharp contrast, alteration of inhibitory synaptic strength is independent of postsynaptic activation and less pronounced. Further, we found a cell type-specific, directionally biased synaptic plasticity of two major types of GABAergic cells, parvalbumin- and cholecystokinin-expressing interneurons. Thus, we propose that gamma frequency oscillations represent a network state that introduces long-lasting synaptic plasticity in a cell-specific manner. DOI: http://dx.doi.org/10.7554/eLife.14912.001 PMID:27218453

  5. Cell-specific synaptic plasticity induced by network oscillations.

    PubMed

    Zarnadze, Shota; Bäuerle, Peter; Santos-Torres, Julio; Böhm, Claudia; Schmitz, Dietmar; Geiger, Jörg Rp; Dugladze, Tamar; Gloveli, Tengis

    2016-01-01

    Gamma rhythms are known to contribute to the process of memory encoding. However, little is known about the underlying mechanisms at the molecular, cellular and network levels. Using local field potential recording in awake behaving mice and concomitant field potential and whole-cell recordings in slice preparations we found that gamma rhythms lead to activity-dependent modification of hippocampal networks, including alterations in sharp wave-ripple complexes. Network plasticity, expressed as long-lasting increases in sharp wave-associated synaptic currents, exhibits enhanced excitatory synaptic strength in pyramidal cells that is induced postsynaptically and depends on metabotropic glutamate receptor-5 activation. In sharp contrast, alteration of inhibitory synaptic strength is independent of postsynaptic activation and less pronounced. Further, we found a cell type-specific, directionally biased synaptic plasticity of two major types of GABAergic cells, parvalbumin- and cholecystokinin-expressing interneurons. Thus, we propose that gamma frequency oscillations represent a network state that introduces long-lasting synaptic plasticity in a cell-specific manner. PMID:27218453

  6. Sumoylation in Synaptic Function and Dysfunction

    PubMed Central

    Schorova, Lenka; Martin, Stéphane

    2016-01-01

    Sumoylation has recently emerged as a key post-translational modification involved in many, if not all, biological processes. Small Ubiquitin-like Modifier (SUMO) polypeptides are covalently attached to specific lysine residues of target proteins through a dedicated enzymatic pathway. Disruption of the SUMO enzymatic pathway in the developing brain leads to lethality indicating that this process exerts a central role during embryonic and post-natal development. However, little is still known regarding how this highly dynamic protein modification is regulated in the mammalian brain despite an increasing number of data implicating sumoylated substrates in synapse formation, synaptic communication and plasticity. The aim of this review is therefore to briefly describe the enzymatic SUMO pathway and to give an overview of our current knowledge on the function and dysfunction of protein sumoylation at the mammalian synapse. PMID:27199730

  7. Clinical Decision Support System to Enhance Quality Control of Spirometry Using Information and Communication Technologies

    PubMed Central

    2014-01-01

    Background We recently demonstrated that quality of spirometry in primary care could markedly improve with remote offline support from specialized professionals. It is hypothesized that implementation of automatic online assessment of quality of spirometry using information and communication technologies may significantly enhance the potential for extensive deployment of a high quality spirometry program in integrated care settings. Objective The objective of the study was to elaborate and validate a Clinical Decision Support System (CDSS) for automatic online quality assessment of spirometry. Methods The CDSS was done through a three step process including: (1) identification of optimal sampling frequency; (2) iterations to build-up an initial version using the 24 standard spirometry curves recommended by the American Thoracic Society; and (3) iterations to refine the CDSS using 270 curves from 90 patients. In each of these steps the results were checked against one expert. Finally, 778 spirometry curves from 291 patients were analyzed for validation purposes. Results The CDSS generated appropriate online classification and certification in 685/778 (88.1%) of spirometry testing, with 96% sensitivity and 95% specificity. Conclusions Consequently, only 93/778 (11.9%) of spirometry testing required offline remote classification by an expert, indicating a potential positive role of the CDSS in the deployment of a high quality spirometry program in an integrated care setting. PMID:25600957

  8. Grade/Performance Contracts, Enhanced Communication, Cooperative Learning and Student Performance in Undergraduate Organic Chemistry

    NASA Astrophysics Data System (ADS)

    Dougherty, Ralph C.

    1997-06-01

    This paper describes a grade/study-performance contract that was designed to increase student retention while maintaining academic performance levels in undergraduate organic chemistry. The experimental course included enhanced communication using electronic mail, and cooperative learning in addition to grade/study-performance contracts. The objective of the grade/study-performance contract was the development of learning skills with creation of a basis for unobtrusive auditing of performance. The retention rate in the experimental course was 0.82 for the first term and 0.93 for the second term. The overall retention was 0.76. This value was 3.8 times the average retention for the same sequence in the previous five years at the same institution. It was seven standard deviations away from the previous mean. The ACS Organic Chemistry Examination percentile score for the control section was 46+25 (n=117). The corresponding data for the experimental section was 53+23 (n=143). When the course was offered with the same instructor, cooperative learning, e-mail, but no grade/study-performance contract the ACS Exam percentile average 37+29. This represents a drop of 9.9 standard deviations for comparison of the means. We conclude that grade/study-performance contracts can be effective in increasing both student performance and retention in undergraduate organic chemistry.

  9. SynProt: A Database for Proteins of Detergent-Resistant Synaptic Protein Preparations

    PubMed Central

    Pielot, Rainer; Smalla, Karl-Heinz; Müller, Anke; Landgraf, Peter; Lehmann, Anne-Christin; Eisenschmidt, Elke; Haus, Utz-Uwe; Weismantel, Robert; Gundelfinger, Eckart D.; Dieterich, Daniela C.

    2012-01-01

    Chemical synapses are highly specialized cell–cell contacts for communication between neurons in the CNS characterized by complex and dynamic protein networks at both synaptic membranes. The cytomatrix at the active zone (CAZ) organizes the apparatus for the regulated release of transmitters from the presynapse. At the postsynaptic side, the postsynaptic density constitutes the machinery for detection, integration, and transduction of the transmitter signal. Both pre- and postsynaptic protein networks represent the molecular substrates for synaptic plasticity. Their function can be altered both by regulating their composition and by post-translational modification of their components. For a comprehensive understanding of synaptic networks the entire ensemble of synaptic proteins has to be considered. To support this, we established a comprehensive database for synaptic junction proteins (SynProt database) primarily based on proteomics data obtained from biochemical preparations of detergent-resistant synaptic junctions. The database currently contains 2,788 non-redundant entries of rat, mouse, and some human proteins, which mainly have been manually extracted from 12 proteomic studies and annotated for synaptic subcellular localization. Each dataset is completed with manually added information including protein classifiers as well as automatically retrieved and updated information from public databases (UniProt and PubMed). We intend that the database will be used to support modeling of synaptic protein networks and rational experimental design. PMID:22737123

  10. Botulinum neurotoxin type-A enters a non-recycling pool of synaptic vesicles

    PubMed Central

    Harper, Callista B.; Papadopulos, Andreas; Martin, Sally; Matthews, Daniel R.; Morgan, Garry P.; Nguyen, Tam H.; Wang, Tong; Nair, Deepak; Choquet, Daniel; Meunier, Frederic A.

    2016-01-01

    Neuronal communication relies on synaptic vesicles undergoing regulated exocytosis and recycling for multiple rounds of fusion. Whether all synaptic vesicles have identical protein content has been challenged, suggesting that their recycling ability may differ greatly. Botulinum neurotoxin type-A (BoNT/A) is a highly potent neurotoxin that is internalized in synaptic vesicles at motor nerve terminals and induces flaccid paralysis. Recently, BoNT/A was also shown to undergo retrograde transport, suggesting it might enter a specific pool of synaptic vesicles with a retrograde trafficking fate. Using high-resolution microscopy techniques including electron microscopy and single molecule imaging, we found that the BoNT/A binding domain is internalized within a subset of vesicles that only partially co-localize with cholera toxin B-subunit and have markedly reduced VAMP2 immunoreactivity. Synaptic vesicles loaded with pHrodo-BoNT/A-Hc exhibited a significantly reduced ability to fuse with the plasma membrane in mouse hippocampal nerve terminals when compared with pHrodo-dextran-containing synaptic vesicles and pHrodo-labeled anti-GFP nanobodies bound to VAMP2-pHluorin or vGlut-pHluorin. Similar results were also obtained at the amphibian neuromuscular junction. These results reveal that BoNT/A is internalized in a subpopulation of synaptic vesicles that are not destined to recycle, highlighting the existence of significant molecular and functional heterogeneity between synaptic vesicles. PMID:26805017

  11. Botulinum neurotoxin type-A enters a non-recycling pool of synaptic vesicles.

    PubMed

    Harper, Callista B; Papadopulos, Andreas; Martin, Sally; Matthews, Daniel R; Morgan, Garry P; Nguyen, Tam H; Wang, Tong; Nair, Deepak; Choquet, Daniel; Meunier, Frederic A

    2016-01-01

    Neuronal communication relies on synaptic vesicles undergoing regulated exocytosis and recycling for multiple rounds of fusion. Whether all synaptic vesicles have identical protein content has been challenged, suggesting that their recycling ability may differ greatly. Botulinum neurotoxin type-A (BoNT/A) is a highly potent neurotoxin that is internalized in synaptic vesicles at motor nerve terminals and induces flaccid paralysis. Recently, BoNT/A was also shown to undergo retrograde transport, suggesting it might enter a specific pool of synaptic vesicles with a retrograde trafficking fate. Using high-resolution microscopy techniques including electron microscopy and single molecule imaging, we found that the BoNT/A binding domain is internalized within a subset of vesicles that only partially co-localize with cholera toxin B-subunit and have markedly reduced VAMP2 immunoreactivity. Synaptic vesicles loaded with pHrodo-BoNT/A-Hc exhibited a significantly reduced ability to fuse with the plasma membrane in mouse hippocampal nerve terminals when compared with pHrodo-dextran-containing synaptic vesicles and pHrodo-labeled anti-GFP nanobodies bound to VAMP2-pHluorin or vGlut-pHluorin. Similar results were also obtained at the amphibian neuromuscular junction. These results reveal that BoNT/A is internalized in a subpopulation of synaptic vesicles that are not destined to recycle, highlighting the existence of significant molecular and functional heterogeneity between synaptic vesicles. PMID:26805017

  12. Effectively using communication to enhance the provision of pediatric palliative care in an acute care setting

    PubMed Central

    Hubble, Rosemary; Trowbridge, Kelly; Hubbard, Claudia; Ahsens, Leslie; Ward-Smith, Peggy

    2008-01-01

    The capability of effectively communicating is crucial when providing palliative care, especially when the patient is a child. Communication among healthcare professionals with the child and family members must be clear, concise, and consistent. Use of a communication tool provides documentation for conversations, treatment plans, and specific desires related to care. This paper describes communication theory, portrays the use of this theory to develop a communication tool, and illustrates the use of this tool by multidisciplinary members of a healthcare team to provide pediatric palliative care. PMID:21197332

  13. Spiritual Coping: A Gateway to Enhancing Family Communication During Cancer Treatment.

    PubMed

    Prouty, Anne M; Fischer, Judith; Purdom, Ann; Cobos, Everardo; Helmeke, Karen B

    2016-02-01

    The researchers examined the spiritual coping, family communication, and family functioning of 95 participants in 34 families by an online survey. Multilevel linear regression was used to test whether individuals' and families' higher endorsement of more use of spiritual coping strategies to deal with a member's cancer would be associated with higher scores on family communication and family functioning, and whether better communication would also be associated with higher family functioning scores. Results revealed that spiritual coping was positively associated with family communication, and family communication was positively associated with healthier family functioning. The researchers provide suggestions for further research. PMID:26311053

  14. Depression as a Glial-Based Synaptic Dysfunction

    PubMed Central

    Rial, Daniel; Lemos, Cristina; Pinheiro, Helena; Duarte, Joana M.; Gonçalves, Francisco Q.; Real, Joana I.; Prediger, Rui D.; Gonçalves, Nélio; Gomes, Catarina A.; Canas, Paula M.; Agostinho, Paula; Cunha, Rodrigo A.

    2016-01-01

    Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processes occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia) tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the “quad-partite” synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increased microglia “activation” in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, brain-derived neurotrophic factor, BDNF) affect glia functioning, whereas antidepressant treatments (serotonin-selective reuptake inhibitors, SSRIs, electroshocks, deep brain stimulation) recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication—such as the purinergic neuromodulation system operated by adenosine 5′-triphosphate (ATP) and adenosine—emerge as promising candidates to “re-normalize” synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future

  15. Membrane-derived phospholipids control synaptic neurotransmission and plasticity.

    PubMed

    García-Morales, Victoria; Montero, Fernando; González-Forero, David; Rodríguez-Bey, Guillermo; Gómez-Pérez, Laura; Medialdea-Wandossell, María Jesús; Domínguez-Vías, Germán; García-Verdugo, José Manuel; Moreno-López, Bernardo

    2015-05-01

    Synaptic communication is a dynamic process that is key to the regulation of neuronal excitability and information processing in the brain. To date, however, the molecular signals controlling synaptic dynamics have been poorly understood. Membrane-derived bioactive phospholipids are potential candidates to control short-term tuning of synaptic signaling, a plastic event essential for information processing at both the cellular and neuronal network levels in the brain. Here, we showed that phospholipids affect excitatory and inhibitory neurotransmission by different degrees, loci, and mechanisms of action. Signaling triggered by lysophosphatidic acid (LPA) evoked rapid and reversible depression of excitatory and inhibitory postsynaptic currents. At excitatory synapses, LPA-induced depression depended on LPA1/Gαi/o-protein/phospholipase C/myosin light chain kinase cascade at the presynaptic site. LPA increased myosin light chain phosphorylation, which is known to trigger actomyosin contraction, and reduced the number of synaptic vesicles docked to active zones in excitatory boutons. At inhibitory synapses, postsynaptic LPA signaling led to dephosphorylation, and internalization of the GABAAγ2 subunit through the LPA1/Gα12/13-protein/RhoA/Rho kinase/calcineurin pathway. However, LPA-induced depression of GABAergic transmission was correlated with an endocytosis-independent reduction of GABAA receptors, possibly by GABAAγ2 dephosphorylation and subsequent increased lateral diffusion. Furthermore, endogenous LPA signaling, mainly via LPA1, mediated activity-dependent inhibitory depression in a model of experimental synaptic plasticity. Finally, LPA signaling, most likely restraining the excitatory drive incoming to motoneurons, regulated performance of motor output commands, a basic brain processing task. We propose that lysophospholipids serve as potential local messengers that tune synaptic strength to precedent activity of the neuron. PMID:25996636

  16. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression.

    PubMed

    Li, Bo; Piriz, Joaquin; Mirrione, Martine; Chung, ChiHye; Proulx, Christophe D; Schulz, Daniela; Henn, Fritz; Malinow, Roberto

    2011-02-24

    The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression. PMID:21350486

  17. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression

    SciTech Connect

    Li, B.; Schulz, D.; Li, B; Piriz, J.; Mirrione, M.; Chung, C.H.; Proulx, C.D.; Schulz, D.; Henn, F.; Malinow, R.

    2011-02-24

    The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.

  18. Enhanced interprocessor communication strategies for parallel TMS320C40 digital signal processor systems

    NASA Astrophysics Data System (ADS)

    Hartley, David A.; Harvey, David M.

    1993-11-01

    The Texas Instruments' TMS320C40 digital signal processor contains communication hardware which enables processors to be connected together to form multiprocessing systems. Analysis of the devices communication channels suggests that it would be beneficial to use additional communication hardware to maximize system performance. The use of mesh routing chips in conjunction with the processors has been investigated. The two devices are interfaced using two TMS320C40 communication channels. Lower message latencies can be achieved by using TMS320C40 communication channels to perform nearest neighbor communications while using the routing chips to perform all other message routing. However, the use of additional TMS320C40 channels can degrade the rate at which packets are injected and consumed from the network, resulting in under utilization of the network bandwidth.

  19. Synaptic dysfunction in Parkinson's disease.

    PubMed

    Picconi, Barbara; Piccoli, Giovanni; Calabresi, Paolo

    2012-01-01

    Activity-dependent modifications in synaptic efficacy, such as long-term depression (LTD) and long-term potentiation (LTP), represent key cellular substrates for adaptive motor control and procedural memory. The impairment of these two forms of synaptic plasticity in the nucleus striatum could account for the onset and the progression of motor and cognitive symptoms of Parkinson's disease (PD), characterized by the massive degeneration of dopaminergic neurons. In fact, both LTD and LTP are peculiarly controlled and modulated by dopaminergic transmission coming from nigrostriatal terminals. Changes in corticostriatal and nigrostriatal neuronal excitability may influence profoundly the threshold for the induction of synaptic plasticity, and changes in striatal synaptic transmission efficacy are supposed to play a role in the occurrence of PD symptoms. Understanding of these maladaptive forms of synaptic plasticity has mostly come from the analysis of experimental animal models of PD. A series of cellular and synaptic alterations occur in the striatum of experimental parkinsonism in response to the massive dopaminergic loss. In particular, dysfunctions in trafficking and subunit composition of glutamatergic NMDA receptors on striatal efferent neurons contribute to the clinical features of the experimental parkinsonism. Interestingly, it has become increasingly evident that in striatal spiny neurons, the correct assembly of NMDA receptor complex at the postsynaptic site is a major player in early phases of PD, and it is sensitive to distinct degrees of DA denervation. The molecular defects at the basis of PD progression may be not confined just at the postsynaptic neuron: accumulating evidences have recently shown that the genes linked to PD play a critical role at the presynaptic site. DA release into the synaptic cleft relies on a proper presynaptic vesicular transport; impairment of SV trafficking, modification of DA flow, and altered presynaptic plasticity have

  20. Cortical Synaptic Inhibition Declines during Auditory Learning

    PubMed Central

    von Trapp, Gardiner; Mowery, Todd M.; Kotak, Vibhakar C.; Sanes, Dan H.

    2015-01-01

    Auditory learning is associated with an enhanced representation of acoustic cues in primary auditory cortex, and modulation of inhibitory strength is causally involved in learning. If this inhibitory plasticity is associated with task learning and improvement, its expression should emerge and persist until task proficiency is achieved. We tested this idea by measuring changes to cortical inhibitory synaptic transmission as adult gerbils progressed through the process of associative learning and perceptual improvement. Using either of two procedures, aversive or appetitive conditioning, animals were trained to detect amplitude-modulated noise and then tested daily. Following each training session, a thalamocortical brain slice was generated, and inhibitory synaptic properties were recorded from layer 2/3 pyramidal neurons. Initial associative learning was accompanied by a profound reduction in the amplitude of spontaneous IPSCs (sIPSCs). However, sIPSC amplitude returned to control levels when animals reached asymptotic behavioral performance. In contrast, paired-pulse ratios decreased in trained animals as well as in control animals that experienced unpaired conditioned and unconditioned stimuli. This latter observation suggests that inhibitory release properties are modified during behavioral conditioning, even when an association between the sound and reinforcement cannot occur. These results suggest that associative learning is accompanied by a reduction of postsynaptic inhibitory strength that persists for several days during learning and perceptual improvement. PMID:25904785

  1. Investigating interactional competence using video recordings in ESL classrooms to enhance communication

    NASA Astrophysics Data System (ADS)

    Krishnasamy, Hariharan N.

    2016-08-01

    Interactional competence, or knowing and using the appropriate skills for interaction in various communication situations within a given speech community and culture is important in the field of business and professional communication [1], [2]. Similar to many developing countries in the world, Malaysia is a growing economy and undergraduates will have to acquire appropriate communication skills. In this study, two aspects of the interactional communicative competence were investigated, that is the linguistic and paralinguistic behaviors in small group communication as well as conflict management in small group communication. Two groups of student participants were given a problem-solving task based on a letter of complaint. The two groups of students were video recorded during class hours for 40 minutes. The videos and transcription of the group discussions were analyzed to examine the use of language and interaction in small groups. The analysis, findings and interpretations were verified with three lecturers in the field of communication. The results showed that students were able to accomplish the given task using verbal and nonverbal communication. However, participation was unevenly distributed with two students talking for less than a minute. Negotiation was based more on alternative views and consensus was easily achieved. In concluding, suggestions are given on ways to improve English language communication.

  2. Enhancing medical students' communication skills: development and evaluation of an undergraduate training program

    PubMed Central

    2012-01-01

    Background There is a relative lack of current research on the effects of specific communication training offered at the beginning of the medical degree program. The newly developed communication training "Basics and Practice in Communication Skills" was pilot tested in 2008 and expanded in the following year at the University Medical Centre Hamburg-Eppendorf in Germany. The goal was to promote and improve the communicative skills of participants and show the usefulness of an early offered intervention on patient-physician communication within the medical curriculum. Methods The students participating in the project and a comparison group of students from the standard degree program were surveyed at the beginning and end of the courses. The survey consisted of a self-assessment of their skills as well as a standardised expert rating and an evaluation of the modules by means of a questionnaire. Results Students who attended the communication skills course exhibited a considerable increase of communication skills in this newly developed training. It was also observed that students in the intervention group had a greater degree of self-assessed competence following training than the medical students in the comparison group. This finding is also reflected in the results from a standardised objective measure. Conclusions The empirical results of the study showed that the training enabled students to acquire specialised competence in communication through the course of a newly developed training program. These findings will be used to establish new communication training at the University Medical Centre Hamburg-Eppendorf. PMID:22443807

  3. Synaptic dysfunction in Parkinson's disease.

    PubMed

    Bagetta, Vincenza; Ghiglieri, Veronica; Sgobio, Carmelo; Calabresi, Paolo; Picconi, Barbara

    2010-04-01

    In neuronal circuits, memory storage depends on activity-dependent modifications in synaptic efficacy, such as LTD (long-term depression) and LTP (long-term potentiation), the two main forms of synaptic plasticity in the brain. In the nucleus striatum, LTD and LTP represent key cellular substrates for adaptive motor control and procedural memory. It has been suggested that their impairment could account for the onset and progression of motor symptoms of PD (Parkinson's disease), a neurodegenerative disorder characterized by the massive degeneration of dopaminergic neurons projecting to the striatum. In fact, a peculiar aspect of striatal plasticity is the modulation exerted by DA (dopamine) on LTP and LTD. Our understanding of these maladaptive forms of plasticity has mostly come from the electrophysiological, molecular and behavioural analyses of experimental animal models of PD. In PD, a host of cellular and synaptic changes occur in the striatum in response to the massive loss of DA innervation. Chronic L-dopa therapy restores physiological synaptic plasticity and behaviour in treated PD animals, but most of them, similarly to patients, exhibit a reduction in the efficacy of the drug and disabling AIMs (abnormal involuntary movements) defined, as a whole, as L-dopa-induced dyskinesia. In those animals experiencing AIMs, synaptic plasticity is altered and is paralleled by modifications in the postsynaptic compartment. In particular, dysfunctions in trafficking and subunit composition of NMDARs [NMDA (N-methyl-D-aspartate) receptors] on striatal efferent neurons result from chronic non-physiological dopaminergic stimulation and contribute to the pathogenesis of dyskinesias. According to these pathophysiological concepts, therapeutic strategies targeting signalling proteins coupled to NMDARs within striatal spiny neurons could represent new pharmaceutical interventions for PD and L-dopa-induced dyskinesia. PMID:20298209

  4. Non-communicable diseases and global health governance: enhancing global processes to improve health development.

    PubMed

    Magnusson, Roger S

    2007-01-01

    This paper assesses progress in the development of a global framework for responding to non-communicable diseases, as reflected in the policies and initiatives of the World Health Organization (WHO), World Bank and the UN: the institutions most capable of shaping a coherent global policy. Responding to the global burden of chronic disease requires a strategic assessment of the global processes that are likely to be most effective in generating commitment to policy change at country level, and in influencing industry behaviour. WHO has adopted a legal process with tobacco (the WHO Framework Convention on Tobacco Control), but a non-legal, advocacy-based approach with diet and physical activity (the Global Strategy on Diet, Physical Activity and Health). The paper assesses the merits of the Millennium Development Goals (MDGs) and the FCTC as distinct global processes for advancing health development, before considering what lessons might be learned for enhancing the implementation of the Global Strategy on Diet. While global partnerships, economic incentives, and international legal instruments could each contribute to a more effective global response to chronic diseases, the paper makes a special case for the development of international legal standards in select areas of diet and nutrition, as a strategy for ensuring that the health of future generations does not become dependent on corporate charity and voluntary commitments. A broader frame of reference for lifestyle-related chronic diseases is needed: one that draws together WHO's work in tobacco, nutrition and physical activity, and that envisages selective use of international legal obligations, non-binding recommendations, advocacy and policy advice as tools of choice for promoting different elements of the strategy. PMID:17519005

  5. Non-communicable diseases and global health governance: enhancing global processes to improve health development

    PubMed Central

    Magnusson, Roger S

    2007-01-01

    This paper assesses progress in the development of a global framework for responding to non-communicable diseases, as reflected in the policies and initiatives of the World Health Organization (WHO), World Bank and the UN: the institutions most capable of shaping a coherent global policy. Responding to the global burden of chronic disease requires a strategic assessment of the global processes that are likely to be most effective in generating commitment to policy change at country level, and in influencing industry behaviour. WHO has adopted a legal process with tobacco (the WHO Framework Convention on Tobacco Control), but a non-legal, advocacy-based approach with diet and physical activity (the Global Strategy on Diet, Physical Activity and Health). The paper assesses the merits of the Millennium Development Goals (MDGs) and the FCTC as distinct global processes for advancing health development, before considering what lessons might be learned for enhancing the implementation of the Global Strategy on Diet. While global partnerships, economic incentives, and international legal instruments could each contribute to a more effective global response to chronic diseases, the paper makes a special case for the development of international legal standards in select areas of diet and nutrition, as a strategy for ensuring that the health of future generations does not become dependent on corporate charity and voluntary commitments. A broader frame of reference for lifestyle-related chronic diseases is needed: one that draws together WHO's work in tobacco, nutrition and physical activity, and that envisages selective use of international legal obligations, non-binding recommendations, advocacy and policy advice as tools of choice for promoting different elements of the strategy. PMID:17519005

  6. Presynaptic clathrin levels are a limiting factor for synaptic transmission.

    PubMed

    López-Murcia, Francisco J; Royle, Stephen J; Llobet, Artur

    2014-06-18

    To maintain communication, neurons must recycle their synaptic vesicles with high efficiency. This process places a huge burden on the clathrin-mediated endocytic machinery, but the consequences of this are poorly understood. We found that the amount of clathrin in a presynaptic terminal is not fixed. During stimulation, clathrin moves out of synapses as a function of stimulus strength and neurotransmitter release probability, which, together with membrane coat formation, transiently reduces the available pool of free clathrin triskelia. Correlative functional and morphological experiments in cholinergic autapses established by superior cervical ganglion neurons in culture show that presynaptic terminal function is compromised if clathrin levels fall by 20% after clathrin heavy chain knock down using RNAi. Synaptic transmission is depressed due to a reduction of cytoplasmic and readily releasable pools of vesicles. However, synaptic depression reverts after dialysis of exogenous clathrin, thus compensating RNAi-induced depletion. Lowering clathrin levels also reduces quantal size, which occurs concomitantly with a decrease in the size of synaptic vesicles. Large dense-core vesicles are unaffected by clathrin knock down. Together, our results show that clathrin levels are a dynamic property of presynaptic terminals that can influence short-term plasticity in a stimulus-dependent manner. PMID:24948816

  7. Finite Post Synaptic Potentials Cause a Fast Neuronal Response

    PubMed Central

    Helias, Moritz; Deger, Moritz; Rotter, Stefan; Diesmann, Markus

    2011-01-01

    A generic property of the communication between neurons is the exchange of pulses at discrete time points, the action potentials. However, the prevalent theory of spiking neuronal networks of integrate-and-fire model neurons relies on two assumptions: the superposition of many afferent synaptic impulses is approximated by Gaussian white noise, equivalent to a vanishing magnitude of the synaptic impulses, and the transfer of time varying signals by neurons is assessable by linearization. Going beyond both approximations, we find that in the presence of synaptic impulses the response to transient inputs differs qualitatively from previous predictions. It is instantaneous rather than exhibiting low-pass characteristics, depends non-linearly on the amplitude of the impulse, is asymmetric for excitation and inhibition and is promoted by a characteristic level of synaptic background noise. These findings resolve contradictions between the earlier theory and experimental observations. Here we review the recent theoretical progress that enabled these insights. We explain why the membrane potential near threshold is sensitive to properties of the afferent noise and show how this shapes the neural response. A further extension of the theory to time evolution in discrete steps quantifies simulation artifacts and yields improved methods to cross check results. PMID:21427776

  8. Reelin supplementation recovers synaptic plasticity and cognitive deficits in a mouse model for Angelman syndrome

    PubMed Central

    Hethorn, Whitney R; Ciarlone, Stephanie L; Filonova, Irina; Rogers, Justin T; Aguirre, Daniela; Ramirez, Raquel A; Grieco, Joseph C; Peters, Melinda M; Gulick, Danielle; Anderson, Anne E; L Banko, Jessica; Lussier, April L; Weeber, Edwin J

    2015-01-01

    The Reelin signaling pathway is implicated in processes controlling synaptic plasticity and hippocampus-dependent learning and memory. A single direct in vivo application of Reelin enhances long-term potentiation, increases dendritic spine density and improves associative and spatial learning and memory. Angelman syndrome (AS) is a neurological disorder that presents with an overall defect in synaptic function, including decreased long-term potentiation, reduced dendritic spine density, and deficits in learning and memory, making it an attractive model in which to examine the ability of Reelin to recover synaptic function and cognitive deficits. In this study, we investigated the effects of Reelin administration on synaptic plasticity and cognitive function in a mouse model of AS and demonstrated that bilateral, intraventricular injections of Reelin recover synaptic function and corresponding hippocampus-dependent associative and spatial learning and memory. Additionally, we describe alteration of the Reelin profile in tissue from both the AS mouse and post-mortem human brain. PMID:25864922

  9. LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction

    PubMed Central

    Penney, Jay; Tsurudome, Kazuya; Liao, Edward H.; Kauwe, Grant; Gray, Lindsay; Yanagiya, Akiko; R. Calderon, Mario; Sonenberg, Nahum; Haghighi, A. Pejmun

    2016-01-01

    Parkinson's disease gene leucine-rich repeat kinase 2 (LRRK2) has been implicated in a number of processes including the regulation of mitochondrial function, autophagy and endocytic dynamics; nevertheless, we know little about its potential role in the regulation of synaptic plasticity. Here we demonstrate that postsynaptic knockdown of the fly homologue of LRRK2 thwarts retrograde, homeostatic synaptic compensation at the larval neuromuscular junction. Conversely, postsynaptic overexpression of either the fly or human LRRK2 transgene induces a retrograde enhancement of presynaptic neurotransmitter release by increasing the size of the release ready pool of vesicles. We show that LRRK2 promotes cap-dependent translation and identify Furin 1 as its translational target, which is required for the synaptic function of LRRK2. As the regulation of synaptic homeostasis plays a fundamental role in ensuring normal and stable synaptic function, our findings suggest that aberrant function of LRRK2 may lead to destabilization of neural circuits. PMID:27432119

  10. Enhancing Parent-Teacher Communication Using Technology: A Reading Improvement Clinic Example

    ERIC Educational Resources Information Center

    Merkley, Donna; Schmidt, Denise; Dirksen, Carrie; Fuhler, Carol

    2006-01-01

    Effective communication between homes and schools can be essential in helping students experience success in the classroom. Unfortunately, the topic of establishing mechanisms for meaningful parent-teacher communication is often slighted during the preparation of teachers. New teachers entering classrooms need the opportunity to interact and…

  11. Does Increasing Communication through Visual Learning Environments Enhance Student Perceptions of Lecturers?

    ERIC Educational Resources Information Center

    Frumkin, Lara

    2006-01-01

    The current study was conducted in an effort to examine whether increased levels of communication using visual learning environments (VLEs) alters student perceptions of lecturers. Eighty-six MSc students in Computing Science participated by using She and Fisher's (2002) Teacher Communication Behavior Questionnaire (TCBQ). In addition to using the…

  12. Enhancing Graduate Student Communication to General Audiences through Blogging about Nanotechnology and Sustainability

    ERIC Educational Resources Information Center

    Bishop, Lee M.; Tillman, Ayesha S.; Geiger, Franz M.; Haynes, Christy L.; Klaper, Rebecca D.; Murphy, Catherine J.; Orr, Galya; Pedersen, Joel A.; DeStefano, Lizanne; Hamers, Robert J.

    2014-01-01

    We have developed and assessed a multiauthor science blog on the topic of nanotechnology and sustainability as a tool to improve the written communication and public engagement skills of graduate students. Focus group studies revealed that after participation in the blog, student authors felt more confident and capable of communicating technical…

  13. Designing for Communication at Work: A Case for Technology-Enhanced Boundary Objects

    ERIC Educational Resources Information Center

    Bakker, Arthur; Kent, Phillip; Hoyles, Celia; Noss, Richard

    2011-01-01

    In this article we conceptualise the challenges of communication between a mortgage company and its customers in terms of crossing boundaries between communities. Through an ethnographic study we first address the question: what are the challenges of communication between sales agents and customers of a mortgage company around mathematical…

  14. Enhancing Students' Communication Skills in the Science Classroom through Socioscientific Issues

    ERIC Educational Resources Information Center

    Chung, Yoonsook; Yoo, Jungsook; Kim, Sung-Won; Lee, Hyunju; Zeidler, Dana L.

    2016-01-01

    Communication skills are one of the most important competencies for 21st century global citizens. Our guiding presupposition was that socioscientific issues (SSIs) could be used as an effective pedagogical tool for promoting students' communication skills by increasing peer interactions, stimulating students' reasoning, and in constructing shared…

  15. Enhancing Parent-Child Communication about Drug Use: Strategies for Professionals Working with Parents and Guardians

    ERIC Educational Resources Information Center

    King, Keith A.; Vidourek, Rebecca A.

    2011-01-01

    Research indicates that family connectedness is the leading protective factor against youth involvement in alcohol and other drug use. A vital component to building positive family connections is effective parent-child communication. This article discusses the importance of building positive parent-child communication skills and provides practical…

  16. From a Medicinal to Educational Context: Implementing a Signature Pedagogy for Enhanced Parent-Teacher Communication

    ERIC Educational Resources Information Center

    Dotger, Benjamin H.

    2009-01-01

    Many teachers are not well prepared for, nor are they being trained to communicate effectively with, parents/caregivers from the different backgrounds and cultures with whom they will interact. Yet, one knows that teachers' professional communication skills are important as they work with parents to promote the success of all children in the…

  17. Teaching Communication Ethics and Diversity: Using Technology and Community Engagement to Enhance Learning

    ERIC Educational Resources Information Center

    Swenson-Lepper, Tammy

    2012-01-01

    The workforce in the United States is becoming more diverse. To help students prepare to work and live in a diverse society, the author developed a lower-division course called "Communication Ethics and Diversity." After this course, students should be able to: (1) define diversity and communication ethics; (2) understand a variety of approaches…

  18. Enhancing Communicative Competence and Cultural Adaptation of ESL Students: Using Dialogue Journals and Interactive Errands.

    ERIC Educational Resources Information Center

    Venditti, Phillip; Bahruth, Robert E.

    This report describes two out-of-class techniques used to promote communicative competence among community college students of English as a second language (ESL). Dialogue journals provide regular written communication between language students and their instructors. The journals can be used for validating, encouraging, and reinforcing students'…

  19. BCL-xL regulates synaptic plasticity.

    PubMed

    Jonas, Elizabeth

    2006-08-01

    Mitochondria are the predominant organelle within many presynaptic terminals. During times of high synaptic activity, they affect intracellular calcium homeostasis and provide the energy needed for synaptic vesicle recycling and for the continued operation of membrane ion pumps. Recent discoveries have altered our ideas about the role of mitochondria in the synapse. Mitochondrial localization, morphology, and docking at synaptic sites may indeed alter the kinetics of transmitter release and calcium homeostasis in the presynaptic terminal. In addition, the mitochondrial ion channel BCL-xL, known as a protector against programmed cell death, regulates mitochondrial membrane conductance and bioenergetics in the synapse and can thereby alter synaptic transmitter release and the recycling of pools of synaptic vesicles. BCL-xL, therefore, not only affects the life and death of the cell soma, but its actions in the synapse may underlie the regulation of basic synaptic processes that subtend learning, memory and synaptic development. PMID:16960143

  20. Glycosylated Synaptomatrix Regulation of Trans-Synaptic Signaling

    PubMed Central

    Dani, Neil; Broadie, Kendal

    2011-01-01

    Synapse formation is driven by precisely orchestrated intercellular communication between the presynaptic and the postsynaptic cell, involving a cascade of anterograde and retrograde signals. At the neuromuscular junction (NMJ), both neuron and muscle secrete signals into the heavily glycosylated synaptic cleft matrix sandwiched between the two synapsing cells. These signals must necessarily traverse and interact with the extracellular environment, for the ligand-receptor interactions mediating communication to occur. This complex synaptomatrix, rich in glycoproteins and proteoglycans, comprises heterogeneous, compartmentalized domains where specialized glycans modulate trans-synaptic signaling during synaptogenesis and subsequent synapse modulation. The general importance of glycans during development, homeostasis and disease is well established, but this important molecular class has received less study in the nervous system. Glycan modifications are now understood to play functional and modulatory roles as ligands and co-receptors in numerous model systems; however roles in synapse formation and modulation are less well understood. We highlight here properties of synaptomatrix glycans and glycan-interacting proteins with key roles in synaptogenesis, with a particular focus on recent advances made in the Drosophila NMJ genetic system. We discuss open questions and interesting new findings driving the current investigations of the complex, diverse and largely understudied glycan mechanisms. Keywords: Extracellular Matrix, Glycan, Synaptic Cleft, Neuromuscular Junction, Drosophila PMID:21509945

  1. Scrambled coherent superposition for enhanced optical fiber communication in the nonlinear transmission regime.

    PubMed

    Liu, Xiang; Chandrasekhar, S; Winzer, P J; Chraplyvy, A R; Tkach, R W; Zhu, B; Taunay, T F; Fishteyn, M; DiGiovanni, D J

    2012-08-13

    Coherent superposition of light waves has long been used in various fields of science, and recent advances in digital coherent detection and space-division multiplexing have enabled the coherent superposition of information-carrying optical signals to achieve better communication fidelity on amplified-spontaneous-noise limited communication links. However, fiber nonlinearity introduces highly correlated distortions on identical signals and diminishes the benefit of coherent superposition in nonlinear transmission regime. Here we experimentally demonstrate that through coordinated scrambling of signal constellations at the transmitter, together with appropriate unscrambling at the receiver, the full benefit of coherent superposition is retained in the nonlinear transmission regime of a space-diversity fiber link based on an innovatively engineered multi-core fiber. This scrambled coherent superposition may provide the flexibility of trading communication capacity for performance in future optical fiber networks, and may open new possibilities in high-performance and secure optical communications. PMID:23038549

  2. A correlated nickelate synaptic transistor

    NASA Astrophysics Data System (ADS)

    Shi, Jian; Ha, Sieu D.; Zhou, You; Schoofs, Frank; Ramanathan, Shriram

    2013-10-01

    Inspired by biological neural systems, neuromorphic devices may open up new computing paradigms to explore cognition, learning and limits of parallel computation. Here we report the demonstration of a synaptic transistor with SmNiO3, a correlated electron system with insulator-metal transition temperature at 130°C in bulk form. Non-volatile resistance and synaptic multilevel analogue states are demonstrated by control over composition in ionic liquid-gated devices on silicon platforms. The extent of the resistance modulation can be dramatically controlled by the film microstructure. By simulating the time difference between postneuron and preneuron spikes as the input parameter of a gate bias voltage pulse, synaptic spike-timing-dependent plasticity learning behaviour is realized. The extreme sensitivity of electrical properties to defects in correlated oxides may make them a particularly suitable class of materials to realize artificial biological circuits that can be operated at and above room temperature and seamlessly integrated into conventional electronic circuits.

  3. A correlated nickelate synaptic transistor.

    PubMed

    Shi, Jian; Ha, Sieu D; Zhou, You; Schoofs, Frank; Ramanathan, Shriram

    2013-01-01

    Inspired by biological neural systems, neuromorphic devices may open up new computing paradigms to explore cognition, learning and limits of parallel computation. Here we report the demonstration of a synaptic transistor with SmNiO₃, a correlated electron system with insulator-metal transition temperature at 130°C in bulk form. Non-volatile resistance and synaptic multilevel analogue states are demonstrated by control over composition in ionic liquid-gated devices on silicon platforms. The extent of the resistance modulation can be dramatically controlled by the film microstructure. By simulating the time difference between postneuron and preneuron spikes as the input parameter of a gate bias voltage pulse, synaptic spike-timing-dependent plasticity learning behaviour is realized. The extreme sensitivity of electrical properties to defects in correlated oxides may make them a particularly suitable class of materials to realize artificial biological circuits that can be operated at and above room temperature and seamlessly integrated into conventional electronic circuits. PMID:24177330

  4. A Clinical Communication Strategy to Enhance Effectiveness and CAHPS Scores: The ALERT Model

    PubMed Central

    Hardee, James T; Kasper, Ilene K

    2008-01-01

    The Consumer Assessment of Healthcare Providers and Systems (CAHPS) program is a national annual report that surveys patients and rates health plans on a variety of metrics, including claims processing, customer service, office staff helpfulness, and ability to get needed care. Although physicians may feel they have no immediate control over many aspects of this questionnaire, there is an important area of the survey where they do have direct control: “how well the doctor communicates.” It is well established that effective physician–patient communication has beneficial effects not only on physician and patient satisfaction but also on adherence to medical advice, diagnostic accuracy, and malpractice risk. The creators of the CAHPS survey developed and incorporated four questions seeking to ascertain the patient's impression of the physician's communication skills. These questions assess how well the physician listened carefully to the patient, how often the physician explained things understandably, how often the physician showed respect for what the patient said, and how often the physician spent enough time with the patient. Many excellent clinical communication models exist that touch on aspects of the CAHPS topics, but it behooves physicians to be mindful of the exact survey questions. The ALERT model of communication was developed to facilitate physicians' recall of these measures. By incorporating key verbal and nonverbal communication skills, clinicians can address and improve their scores on this important area of the CAHPS survey. PMID:21331215

  5. Utilizing Trigger Films to Enhance Communication Skills of Home Care Clinicians.

    PubMed

    Brennan-Cook, Jill; Molloy, Margory A

    2016-01-01

    The purpose of this article is to describe an innovative method to help home care clinicians better communicate with older adults experiencing normal physiologic changes that impact their ability to communicate effectively. Developmental changes such as hearing, speech, vision, and cognition profoundly impede an older adult's ability to communicate with others, potentially undermining the quality of care delivered. The use of trigger films as an educational intervention can assist home care clinicians to improve communication with their patients. Trigger films are 2- to 4-minute video clips that end abruptly, encouraging learners to analyze clinical situations in a safe environment, such as a staff conference room. Trigger films are easy to make with the use of a smart phone and two staff members portraying the role of home care clinician and patient. Allowing discussion after viewing the trigger film places clinicians in an active learning role, thus fostering the sharing of ideas and best practice. Addressing age-related barriers to communication with this modality serves to improve patient interaction and healthcare outcomes. The use of trigger films is another tool that empowers the clinician to provide improved care for patients with communication deficits. PMID:27348031

  6. Sphingosine Facilitates SNARE Complex Assembly and Activates Synaptic Vesicle Exocytosis

    PubMed Central

    Darios, Frédéric; Wasser, Catherine; Shakirzyanova, Anastasia; Giniatullin, Artur; Goodman, Kerry; Munoz-Bravo, Jose L.; Raingo, Jesica; Jorgačevski, Jernej; Kreft, Marko; Zorec, Robert; Rosa, Juliana M.; Gandia, Luis; Gutiérrez, Luis M.; Binz, Thomas; Giniatullin, Rashid; Kavalali, Ege T.; Davletov, Bazbek

    2009-01-01

    Summary Synaptic vesicles loaded with neurotransmitters fuse with the plasma membrane to release their content into the extracellular space, thereby allowing neuronal communication. The membrane fusion process is mediated by a conserved set of SNARE proteins: vesicular synaptobrevin and plasma membrane syntaxin and SNAP-25. Recent data suggest that the fusion process may be subject to regulation by local lipid metabolism. Here, we have performed a screen of lipid compounds to identify positive regulators of vesicular synaptobrevin. We show that sphingosine, a releasable backbone of sphingolipids, activates synaptobrevin in synaptic vesicles to form the SNARE complex implicated in membrane fusion. Consistent with the role of synaptobrevin in vesicle fusion, sphingosine upregulated exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and hippocampal neurons, but not in neurons obtained from synaptobrevin-2 knockout mice. Further mechanistic insights suggest that sphingosine acts on the synaptobrevin/phospholipid interface, defining a novel function for this important lipid regulator. PMID:19524527

  7. Emerging Link between Alzheimer's Disease and Homeostatic Synaptic Plasticity

    PubMed Central

    Jang, Sung-Soo; Chung, Hee Jung

    2016-01-01

    Alzheimer's disease (AD) is an irreversible brain disorder characterized by progressive cognitive decline and neurodegeneration of brain regions that are crucial for learning and memory. Although intracellular neurofibrillary tangles and extracellular senile plaques, composed of insoluble amyloid-β (Aβ) peptides, have been the hallmarks of postmortem AD brains, memory impairment in early AD correlates better with pathological accumulation of soluble Aβ oligomers and persistent weakening of excitatory synaptic strength, which is demonstrated by inhibition of long-term potentiation, enhancement of long-term depression, and loss of synapses. However, current, approved interventions aiming to reduce Aβ levels have failed to retard disease progression; this has led to a pressing need to identify and target alternative pathogenic mechanisms of AD. Recently, it has been suggested that the disruption of Hebbian synaptic plasticity in AD is due to aberrant metaplasticity, which is a form of homeostatic plasticity that tunes the magnitude and direction of future synaptic plasticity based on previous neuronal or synaptic activity. This review examines emerging evidence for aberrant metaplasticity in AD. Putative mechanisms underlying aberrant metaplasticity in AD will also be discussed. We hope this review inspires future studies to test the extent to which these mechanisms contribute to the etiology of AD and offer therapeutic targets. PMID:27019755

  8. Reverse optical trawling for synaptic connections in situ.

    PubMed

    Sasaki, Takuya; Minamisawa, Genki; Takahashi, Naoya; Matsuki, Norio; Ikegaya, Yuji

    2009-07-01

    We introduce a new method to unveil the network connectivity among dozens of neurons in brain slice preparations. While synaptic inputs were whole cell recorded from given postsynaptic neurons, the spatiotemporal firing patterns of presynaptic neuron candidates were monitored en masse with functional multineuron calcium imaging, an optical technique that records action potential-evoked somatic calcium transients with single-cell resolution. By statistically screening the neurons that exhibited calcium transients immediately before the postsynaptic inputs, we identified the presynaptic cells that made synaptic connections onto the patch-clamped neurons. To enhance the detection power, we devised the following points: 1) [K+]e was lowered and [Ca2+]e and [Mg2+]e were elevated, to reduce background synaptic activity and minimize the failure rate of synaptic transmission; and 2) a small fraction of presynaptic neurons was specifically activated by glutamate applied iontophoretically through a glass pipette that was moved to survey the presynaptic network of interest ("trawling"). Then we could theoretically detect 96% of presynaptic neurons activated in the imaged regions with a 1% false-positive error rate. This on-line probing technique would be a promising tool in the study of the wiring topography of neuronal circuits. PMID:19386760

  9. Translational regulatory mechanisms in persistent forms of synaptic plasticity.

    PubMed

    Kelleher, Raymond J; Govindarajan, Arvind; Tonegawa, Susumu

    2004-09-30

    Memory and synaptic plasticity exhibit distinct temporal phases, with long-lasting forms distinguished by their dependence on macromolecular synthesis. Prevailing models for the molecular mechanisms underlying long-lasting synaptic plasticity have largely focused on transcriptional regulation. However, a growing body of evidence now supports a crucial role for neuronal activity-dependent mRNA translation, which may occur in dendrites for a subset of neuronal mRNAs. Recent work has begun to define the signaling mechanisms coupling synaptic activation to the protein synthesis machinery. The ERK and mTOR signaling pathways have been shown to regulate the activity of the general translational machinery, while the translation of particular classes of mRNAs is additionally controlled by gene-specific mechanisms. Rapid enhancement of the synthesis of a diverse array of neuronal proteins through such mechanisms provides the components necessary for persistent forms of LTP and LTD. These findings have important implications for the synapse specificity and associativity of protein synthesis-dependent changes in synaptic strength. PMID:15450160

  10. Open Access in the Natural and Social Sciences: The Correspondence of Innovative Moves to Enhance Access, Inclusion and Impact in Scholarly Communication

    ERIC Educational Resources Information Center

    Armbruster, Chris

    2008-01-01

    Online, open access is the superior model for scholarly communication. A variety of scientific communities in physics, the life sciences and economics have gone furthest in innovating their scholarly communication through open access, enhancing accessibility for scientists, students and the interested public. Open access enjoys a comparative…

  11. Clathrin regenerates synaptic vesicles from endosomes

    PubMed Central

    Watanabe, Shigeki; Trimbuch, Thorsten; Camacho-Pérez, Marcial; Rost, Benjamin R.; Brokowski, Bettina; Söhl-Kielczynski, Berit; Felies, Annegret; Davis, M. Wayne; Rosenmund, Christian; Jorgensen, Erik M.

    2014-01-01

    Summary Ultrafast endocytosis can retrieve a single large endocytic vesicle as fast as 50-100 ms after synaptic vesicle fusion. However, the fate of the large endocytic vesicles is not known. Here we demonstrate that these vesicles transition to a synaptic endosome about one second after stimulation. The endosome is resolved into coated vesicles after 3 seconds, which in turn become small-diameter synaptic vesicles 5-6 seconds after stimulation. We disrupted clathrin function using RNAi and found that clathrin is not required for ultrafast endocytosis but is required to generate synaptic vesicles from the endosome. Ultrafast endocytosis fails when actin polymerization is disrupted, or when neurons are stimulated at room temperature instead of physiological temperature. In the absence of ultrafast endocytosis, synaptic vesicles are retrieved directly from the plasma membrane by clathrin-mediated endocytosis. These results explain in large part discrepancies among published experiments concerning the role of clathrin in synaptic vesicle endocytosis. PMID:25296249

  12. Modulation of synaptic plasticity by the coactivation of spatially distinct synaptic inputs in rat hippocampal CA1 apical dendrites.

    PubMed

    Kondo, Masashi; Kitajima, Tatsuo; Fujii, Satoshi; Tsukada, Minoru; Aihara, Takeshi

    2013-08-14

    The phenomenon whereby the relative timing between presynaptic and postsynaptic spiking determines the direction and extent of synaptic changes in a critical temporal window is known as spike timing-dependent synaptic plasticity (STDP). We have previously reported that STDP profiles can be classified into two types depending on their layer-specific location along CA1 pyramidal neuron dendrites in the rat hippocampus, suggesting that there are differences in information processing between the proximal dendrite (PD) and distal dendrite (DD). However, how the different types of information processing interact at different dendritic locations remains unclear. To investigate how the temporal information of inputs to PD influences information processing at DD, PD stimulation was applied while the STDP protocol was simultaneously applied at DDs of CA1 pyramidal neurons. Synaptic plasticity induced by the STDP protocol at DDs was enhanced or depressed depending on the timing of the back-propagating action potentials (bAPs) and the excitatory and inhibitory postsynaptic potentials elicited by PD stimulation. These results suggested that bAPs function as carriers of temporal information of PD inputs to DD. Next, the influence of DD on PD was investigated using the same protocol. Synaptic plasticity at PD was modulated only if the pairing stimuli were applied to elicit coincidental timing of bAP and the excitatory postsynaptic potential. Such coding modulations could provide the basis for a novel learning rule and may be important factors in the integration of spatiotemporal input information in neural networks in the brain. PMID:23711890

  13. Nonvolatile programmable neural network synaptic array

    NASA Technical Reports Server (NTRS)

    Tawel, Raoul (Inventor)

    1994-01-01

    A floating-gate metal oxide semiconductor (MOS) transistor is implemented for use as a nonvolatile analog storage element of a synaptic cell used to implement an array of processing synaptic cells. These cells are based on a four-quadrant analog multiplier requiring both X and Y differential inputs, where one Y input is UV programmable. These nonvolatile synaptic cells are disclosed fully connected in a 32 x 32 synaptic cell array using standard very large scale integration (VLSI) complementary MOS (CMOS) technology.

  14. Enhancing the Speech and Language Development of Communicatively Disordered Children through Music and Movement.

    ERIC Educational Resources Information Center

    Leung, Katherine

    The paper examines the suprasegmental aspects of speech and focuses on the benefits of music and movement to facilitate language development in handicapped children. The paper discusses the current thinking of suprasegmental functions of intonation, stress, and rhythm as the foundation for the organization of speech communication. Strategies for…

  15. Evaluating iPad Technology for Enhancing Communication Skills of Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Boyd, Tara K.; Hart Barnett, Juliet E.; More, Cori M.

    2015-01-01

    Mobile technology has introduced a new communication opportunity for students with autism spectrum disorder. Tablets, like the iPad, allow users to customize applications for their needs. Users also have found iPads to be less stigmatizing because so many people own them and use them for various purposes. In the fast-paced world of technology,…

  16. Use of Information and Communication Technology in Enhancing Teaching and Learning

    ERIC Educational Resources Information Center

    Salleh, Siti Maliza Hj.; Jack, Suriani; Bohari, Zubaidah; Jusoff, Hj. Kamaruzaman

    2011-01-01

    The role of Information and Communication Technology (ICT) in education has been peripheral, with new technologies being added to the traditional teacher centred model of instruction. Students in the global economy of the 21st Century need to be creative thinkers and innovators. Thus, this paper provides an overview of the integration of…

  17. Can Email Communication Enhance Professor-Student Relationship and Student Evaluation of Professor?: Some Empirical Evidence

    ERIC Educational Resources Information Center

    Sheer, Vivian C.; Fung, Timothy K.

    2007-01-01

    Four hundred and eight undergraduate students participated in this study that examined professor-student email communication, interpersonal relationship and teaching evaluation. Several findings have been gleaned. First, academic task was the most frequent email topic and social-relationship less frequent between professors and students. Second,…

  18. An Integrated Science Course Designed with Information Communication Technologies to Enhance University Students' Learning Performance

    ERIC Educational Resources Information Center

    Su, King-Dow

    2008-01-01

    This study evaluated the performance of university students who learned science texts by using, information communication technologies (ICT) including animation, static figures, power point, and e-plus software. The characteristics of students and their achievements and attitudes toward 11 multimedia science courses were analyzed. The 11 samples…

  19. An Internet Web-Site To Enhance Communication with School Personnel and Parents.

    ERIC Educational Resources Information Center

    Flores, Jayne; Karr-Kidwell, PJ

    This document represents a Web site for Chisholm Trail Intermediate School (Keller Independent School District (KISD), Fort Worth, Texas). The first part of the document provides an introduction that discusses the importance of the communication environment and the sense of community that can be created within education. This section also…

  20. Enhancing Motivation in Online Courses with Mobile Communication Tool Support: A Comparative Study

    ERIC Educational Resources Information Center

    Chaiprasurt, Chantorn; Esichaikul, Vatcharaporn

    2013-01-01

    Mobile technologies have helped establish new channels of communication among learners and instructors, potentially providing greater access to course information, and promoting easier access to course activities and learner motivation in online learning environments. The paper compares motivation between groups of learners being taught through an…

  1. Enhancing University Teachers' Information and Communication Technology Usage by Using a Virtual Learning Environment Training Course

    ERIC Educational Resources Information Center

    Ageel, Mohammed; Woollard, John

    2012-01-01

    The research project is a case study focussing on the use of a virtual learning environment (VLE) implemented to increase the use of information and communication technology (ICT) by university teachers in Jazan University, Saudi Arabia. The study aims to investigate the effect of the VLE as the vehicle for a training course in ICT designed to…

  2. Social Media Use to Enhance Internal Communication: Course Design for Business Students

    ERIC Educational Resources Information Center

    Young, Amy M.; Hinesly, Mary D.

    2014-01-01

    Organizations are increasingly using social media to improve their internal communication. When successfully implemented, such initiatives can have a dramatic impact on internal efficiency, team collaboration, innovation, organizational alignment, and cultural transformation. This article describes a course offered by the Ross School of Business,…

  3. Untethering Education: Creating a Pilot Hybrid Class to Enhance Learning in Intercultural Communication

    ERIC Educational Resources Information Center

    Lawton, Bessie; Foeman, Anita; Thompsen, Philip

    2014-01-01

    Improvements in educational technology in the past couple of decades have led institutions of higher learning to encourage and implement various types of distance education courses. This article reports on the conversion process of a face-to-face Intercultural Communication class at a mid-Atlantic university in the USA. First, the impetus for its…

  4. Using Modern Communication Methods to Enhance Smallholder Training and Extension Programmes.

    ERIC Educational Resources Information Center

    Griffin, Robert S.

    There are three crucial communication links required for the successful transfer of technology in rubber smallholder programs: (1) from smallholder to program planners and managers, (2) within the administrative organization, and (3) from the planners and managers to the smallholders. All three links must be functioning adequately in order to…

  5. Native/Non-Native Speaker Interactions through Video-Web Communication: A Clue for Enhancing Motivation?

    ERIC Educational Resources Information Center

    Jauregi, Kristi; de Graaff, Rick; van den Bergh, Huub; Kriz, Milan

    2012-01-01

    One of the main objectives of the European Networked Interaction in Foreign Language Acquisition and Research (NIFLAR) project is to make foreign language learning and teaching processes more relevant and rewarding for reaching intercultural communicative competence. This is realized by offering foreign language learners and pre-service teachers…

  6. RPS23RG1 reduces Aβ oligomer-induced synaptic and cognitive deficits

    PubMed Central

    Yan, Li; Chen, Yaomin; Li, Wubo; Huang, Xiumei; Badie, Hedieh; Jian, Fan; Huang, Timothy; Zhao, Yingjun; Cohen, Stanley N.; Li, Limin; Zhang, Yun-wu; Luo, Huanmin; Tu, Shichun; Xu, Huaxi

    2016-01-01

    Alzheimer’s disease (AD) is the most common form of dementia in the elderly. It is generally believed that β-amyloidogenesis, tau-hyperphosphorylation, and synaptic loss underlie cognitive decline in AD. Rps23rg1, a functional retroposed mouse gene, has been shown to reduce Alzheimer’s β-amyloid (Aβ) production and tau phosphorylation. In this study, we have identified its human homolog, and demonstrated that RPS23RG1 regulates synaptic plasticity, thus counteracting Aβ oligomer (oAβ)-induced cognitive deficits in mice. The level of RPS23RG1 mRNA is significantly lower in the brains of AD compared to non-AD patients, suggesting its potential role in the pathogenesis of the disease. Similar to its mouse counterpart, human RPS23RG1 interacts with adenylate cyclase, activating PKA/CREB, and inhibiting GSK-3. Furthermore, we show that human RPS23RG1 promotes synaptic plasticity and offsets oAβ-induced synaptic loss in a PKA-dependent manner in cultured primary neurons. Overexpression of Rps23rg1 in transgenic mice consistently prevented oAβ-induced PKA inactivation, synaptic deficits, suppression of long-term potentiation, and cognitive impairment as compared to wild type littermates. Our study demonstrates that RPS23RG1 may reduce the occurrence of key elements of AD pathology and enhance synaptic functions to counteract oAβ-induced synaptic and cognitive deficits in AD. PMID:26733416

  7. Superpriming of synaptic vesicles as a common basis for intersynapse variability and modulation of synaptic strength

    PubMed Central

    Taschenberger, Holger; Woehler, Andrew; Neher, Erwin

    2016-01-01

    Glutamatergic synapses show large variations in strength and short-term plasticity (STP). We show here that synapses displaying an increased strength either after posttetanic potentiation (PTP) or through activation of the phospholipase-C–diacylglycerol pathway share characteristic properties with intrinsically strong synapses, such as (i) pronounced short-term depression (STD) during high-frequency stimulation; (ii) a conversion of that STD into a sequence of facilitation followed by STD after a few conditioning stimuli at low frequency; (iii) an equalizing effect of such conditioning stimulation, which reduces differences among synapses and abolishes potentiation; and (iv) a requirement of long periods of rest for reconstitution of the original STP pattern. These phenomena are quantitatively described by assuming that a small fraction of “superprimed” synaptic vesicles are in a state of elevated release probability (p ∼ 0.5). This fraction is variable in size among synapses (typically about 30%), but increases after application of phorbol ester or during PTP. The majority of vesicles, released during repetitive stimulation, have low release probability (p ∼ 0.1), are relatively uniform in number across synapses, and are rapidly recruited. In contrast, superprimed vesicles need several seconds to be regenerated. They mediate enhanced synaptic strength at the onset of burst-like activity, the impact of which is subject to modulation by slow modulatory transmitter systems. PMID:27432975

  8. Synaptic and extrasynaptic NMDA receptors differentially modulate neuronal COX-2 function, lipid peroxidation, and neuroprotection

    PubMed Central

    Stark, David T.; Bazan, Nicolas G.

    2011-01-01

    Stimulation of synaptic NMDA receptors (NMDARs) induces neuroprotection, while extrasynaptic NMDARs promote excitotoxic cell death. Neuronal expression of cyclooxygenase-2 (COX-2) is enhanced by synaptic NMDARs, and although this enzyme mediates neuronal functions, COX-2 is also regarded as a key modulator of neuroinflammation and is thought to exacerbate excitotoxicity via overproduction of prostaglandins. This raises an apparent paradox: synaptic NMDARs are pro-survival yet are essential for robust neuronal COX-2 expression. We hypothesized that stimulation of extrasynaptic NMDARs converts COX-2 signaling from a physiological to a potentially pathological process. We combined HPLC-ESI-MS/MS-based mediator lipidomics and unbiased image analysis in mouse dissociated and organotypic cortical cultures to uncover that synaptic and extrasynaptic NMDARs differentially modulate neuronal COX-2 expression and activity. We show that synaptic NMDARs enhance neuronal COX-2 expression, while sustained synaptic stimulation limits COX-2 activity by suppressing cellular levels of the primary COX-2 substrate, arachidonic acid (AA). In contrast, extrasynaptic NMDARs suppress COX-2 expression while activating phospholipase A2 (PLA2), which enhances AA levels by hydrolysis of membrane phospholipids. Thus, sequential activation of synaptic then extrasynaptic NMDARs maximizes COX-2-dependent prostaglandin synthesis. We also show that excitotoxic events only drive induction of COX-2 expression through abnormal synaptic network excitability. Finally, we show that non-enzymatic lipid peroxidation of arachidonic and other polyunsaturated fatty acids is a function of network activity history. A new paradigm emerges from our results suggesting that pathological COX-2 signaling associated with models of stroke, epilepsy, and neurodegeneration requires specific spatio-temporal NMDAR stimulation. PMID:21957234

  9. Enhancing Graduate Student Communication to General Audiences through Blogging about Nanotechnology and Sustainability

    SciTech Connect

    Bishop, Lee M.; Tillman, Ayesha S.; Geiger, Franz M.; Haynes, Christy L.; Klaper, Rebecca D.; Murphy, Catherine; Orr, Galya; Pedersen, Joel A.; DeStefano, Lizanne; Hamers, Robert J.

    2014-10-14

    We have developed and assessed a multiauthor science blog on the topic of nanotechnology and sustainability as a tool to improve the written communication and public engagement skills of graduate students. Focus group studies revealed that after participation in the blog, student authors felt more confident and capable of communicating technical topics to general audiences. Students' research mentors viewed this as an important component of their students' education, as indicated by survey data. Important design aspects of this effort include participation of an editor as well as having flexible content and target-audience guidelines. We have explicitly outlined aspects of the effort we see as critical in order to enable others to replicate this model in related settings.

  10. Synaptic Control of Motoneuronal Excitability

    PubMed Central

    Rekling, Jens C.; Funk, Gregory D.; Bayliss, Douglas A.; Dong, Xiao-Wei; Feldman, Jack L.

    2016-01-01

    Movement, the fundamental component of behavior and the principal extrinsic action of the brain, is produced when skeletal muscles contract and relax in response to patterns of action potentials generated by motoneurons. The processes that determine the firing behavior of motoneurons are therefore important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre- and postsynaptic actions, signal transduction, and functional role. Glutamate is the main excitatory, and GABA and glycine are the main inhibitory transmitters acting through ionotropic receptors. These amino acids signal the principal motor commands from peripheral, spinal, and supraspinal structures. Amines, such as serotonin and norepinephrine, and neuropeptides, as well as the glutamate and GABA acting at metabotropic receptors, modulate motoneuronal excitability through pre- and postsynaptic actions. Acting principally via second messenger systems, their actions converge on common effectors, e.g., leak K+ current, cationic inward current, hyperpolarization-activated inward current, Ca2+ channels, or presynaptic release processes. Together, these numerous inputs mediate and modify incoming motor commands, ultimately generating the coordinated firing patterns that underlie muscle contractions during motor behavior. PMID:10747207

  11. Subcellular Imbalances in Synaptic Activity.

    PubMed

    Takahashi, Naoya; Kobayashi, Chiaki; Ishikawa, Tomoe; Ikegaya, Yuji

    2016-02-16

    The dynamic interactions between synaptic excitation and inhibition (E/I) shape membrane potential fluctuations and determine patterns of neuronal outputs; however, the spatiotemporal organization of these interactions within a single cell is poorly understood. Here, we investigated the relationship between local synaptic excitation and global inhibition in hippocampal pyramidal neurons using functional dendrite imaging in combination with whole-cell recordings of inhibitory postsynaptic currents. We found that the sums of spine inputs over dendritic trees were counterbalanced by a proportional amount of somatic inhibitory inputs. This online E/I correlation was maintained in dendritic segments that were longer than 50 μm. However, at the single spine level, only 22% of the active spines were activated with inhibitory inputs. This inhibition-coupled activity occurred mainly in the spines with large heads. These results shed light on a microscopic E/I-balancing mechanism that operates at selected synapses and that may increase the accuracy of neural information. PMID:26854220

  12. Enhancing In-Flight Transoceanic Communications Using Swift-64 Packet Mode Service

    NASA Technical Reports Server (NTRS)

    Slywczak, Richard A.

    2004-01-01

    Current aeronautical communications can be divided into two segments. The first provides state of the art, packet switched technology to the cabin passengers so that they have access to e-mail and web services. The second provides basic circuit switch communication technology to the cockpit, which does not use bandwidth as efficiently as packet switching nor promotes resource sharing. This paper explores the research efforts currently being conducted by the NASA/Glenn Research Center (GRC) for transoceanic communications. The goal is to bring packet mode services to both the cabin and the cockpit of the aircraft and be able to attain benefits by sharing the data link with cabin services. First, this paper will outline the goals of the program and detail the benefits and issues related to this research. We will explain our current laboratory setup and show an architecture implemented in the testbed. Finally, we will present a work plan that will show the progression of research over the next year. This plan will describe a complete cycle from conceptual design and laboratory implementation to the final flight testing.

  13. Neuromodulator-evoked synaptic metaplasticity within a central pattern generator network.

    PubMed

    Kvarta, Mark D; Harris-Warrick, Ronald M; Johnson, Bruce R

    2012-11-01

    Synapses show short-term activity-dependent dynamics that alter the strength of neuronal interactions. This synaptic plasticity can be tuned by neuromodulation as a form of metaplasticity. We examined neuromodulator-induced metaplasticity at a graded chemical synapse in a model central pattern generator (CPG), the pyloric network of the spiny lobster stomatogastric ganglion. Dopamine, serotonin, and octopamine each produce a unique motor pattern from the pyloric network, partially through their modulation of synaptic strength in the network. We characterized synaptic depression and its amine modulation at the graded synapse from the pyloric dilator neuron to the lateral pyloric neuron (PD→LP synapse), driving the PD neuron with both long square pulses and trains of realistic waveforms over a range of presynaptic voltages. We found that the three amines can differentially affect the amplitude of graded synaptic transmission independently of the synaptic dynamics. Low concentrations of dopamine had weak and variable effects on the strength of the graded inhibitory postsynaptic potentials (gIPSPs) but reliably accelerated the onset of synaptic depression and recovery from depression independently of gIPSP amplitude. Octopamine enhanced gIPSP amplitude but decreased the amount of synaptic depression; it slowed the onset of depression and accelerated its recovery during square pulse stimulation. Serotonin reduced gIPSP amplitude but increased the amount of synaptic depression and accelerated the onset of depression. These results suggest that amine-induced metaplasticity at graded chemical synapses can alter the parameters of synaptic dynamics in multiple and independent ways. PMID:22933725

  14. Synaptic vesicle distribution by conveyor belt.

    PubMed

    Moughamian, Armen J; Holzbaur, Erika L F

    2012-03-01

    The equal distribution of synaptic vesicles among synapses along the axon is critical for robust neurotransmission. Wong et al. show that the continuous circulation of synaptic vesicles throughout the axon driven by molecular motors ultimately yields this even distribution. PMID:22385955

  15. Synaptic Transmission Correlates of General Mental Ability

    ERIC Educational Resources Information Center

    McRorie, Margaret; Cooper, Colin

    2004-01-01

    Nerve conduction velocity (NCV) and efficiency of synaptic transmission are two possible biological mechanisms that may underpin intelligence. Direct assessments of NCV, without synaptic transmission, show few substantial or reliable correlations with cognitive abilities ["Intelligence" 16 (1992) 273]. We therefore assessed the latencies of…

  16. Spontaneous vesicle recycling in the synaptic bouton

    PubMed Central

    Truckenbrodt, Sven; Rizzoli, Silvio O.

    2014-01-01

    The trigger for synaptic vesicle exocytosis is Ca2+, which enters the synaptic bouton following action potential stimulation. However, spontaneous release of neurotransmitter also occurs in the absence of stimulation in virtually all synaptic boutons. It has long been thought that this represents exocytosis driven by fluctuations in local Ca2+ levels. The vesicles responding to these fluctuations are thought to be the same ones that release upon stimulation, albeit potentially triggered by different Ca2+ sensors. This view has been challenged by several recent works, which have suggested that spontaneous release is driven by a separate pool of synaptic vesicles. Numerous articles appeared during the last few years in support of each of these hypotheses, and it has been challenging to bring them into accord. We speculate here on the origins of this controversy, and propose a solution that is related to developmental effects. Constitutive membrane traffic, needed for the biogenesis of vesicles and synapses, is responsible for high levels of spontaneous membrane fusion in young neurons, probably independent of Ca2+. The vesicles releasing spontaneously in such neurons are not related to other synaptic vesicle pools and may represent constitutively releasing vesicles (CRVs) rather than bona fide synaptic vesicles. In mature neurons, constitutive traffic is much dampened, and the few remaining spontaneous release events probably represent bona fide spontaneously releasing synaptic vesicles (SRSVs) responding to Ca2+ fluctuations, along with a handful of CRVs that participate in synaptic vesicle turnover. PMID:25538561

  17. Short-term synaptic plasticity and heterogeneity in neural systems

    NASA Astrophysics Data System (ADS)

    Mejias, J. F.; Kappen, H. J.; Longtin, A.; Torres, J. J.

    2013-01-01

    We review some recent results on neural dynamics and information processing which arise when considering several biophysical factors of interest, in particular, short-term synaptic plasticity and neural heterogeneity. The inclusion of short-term synaptic plasticity leads to enhanced long-term memory capacities, a higher robustness of memory to noise, and irregularity in the duration of the so-called up cortical states. On the other hand, considering some level of neural heterogeneity in neuron models allows neural systems to optimize information transmission in rate coding and temporal coding, two strategies commonly used by neurons to codify information in many brain areas. In all these studies, analytical approximations can be made to explain the underlying dynamics of these neural systems.

  18. Dopamine Regulates Aversive Contextual Learning and Associated In Vivo Synaptic Plasticity in the Hippocampus.

    PubMed

    Broussard, John I; Yang, Kechun; Levine, Amber T; Tsetsenis, Theodoros; Jenson, Daniel; Cao, Fei; Garcia, Isabella; Arenkiel, Benjamin R; Zhou, Fu-Ming; De Biasi, Mariella; Dani, John A

    2016-03-01

    Dopamine release during reward-driven behaviors influences synaptic plasticity. However, dopamine innervation and release in the hippocampus and its role during aversive behaviors are controversial. Here, we show that in vivo hippocampal synaptic plasticity in the CA3-CA1 circuit underlies contextual learning during inhibitory avoidance (IA) training. Immunohistochemistry and molecular techniques verified sparse dopaminergic innervation of the hippocampus from the midbrain. The long-term synaptic potentiation (LTP) underlying the learning of IA was assessed with a D1-like dopamine receptor agonist or antagonist in ex vivo hippocampal slices and in vivo in freely moving mice. Inhibition of D1-like dopamine receptors impaired memory of the IA task and prevented the training-induced enhancement of both ex vivo and in vivo LTP induction. The results indicate that dopamine-receptor signaling during an aversive contextual task regulates aversive memory retention and regulates associated synaptic mechanisms in the hippocampus that likely underlie learning. PMID:26904943

  19. Millisecond Coupling of Local Field Potentials to Synaptic Currents in the Awake Visual Cortex

    PubMed Central

    Haider, Bilal; Schulz, David P.A.; Häusser, Michael; Carandini, Matteo

    2016-01-01

    Summary The cortical local field potential (LFP) is a common measure of population activity, but its relationship to synaptic activity in individual neurons is not fully established. This relationship has been typically studied during anesthesia and is obscured by shared slow fluctuations. Here, we used patch-clamp recordings in visual cortex of anesthetized and awake mice to measure intracellular activity; we then applied a simple method to reveal its coupling to the simultaneously recorded LFP. LFP predicted membrane potential as accurately as synaptic currents, indicating a major role for synaptic currents in the relationship between cortical LFP and intracellular activity. During anesthesia, cortical LFP predicted excitation far better than inhibition; during wakefulness, it predicted them equally well, and visual stimulation further enhanced predictions of inhibition. These findings reveal a central role for synaptic currents, and especially inhibition, in the relationship between the subthreshold activity of individual neurons and the cortical LFP during wakefulness. PMID:27021173

  20. Analysis of Synaptic Gene Expression in the Neocortex of Primates Reveals Evolutionary Changes in Glutamatergic Neurotransmission

    PubMed Central

    Muntané, Gerard; Horvath, Julie E.; Hof, Patrick R.; Ely, John J.; Hopkins, William D.; Raghanti, Mary Ann; Lewandowski, Albert H.; Wray, Gregory A.; Sherwood, Chet C.

    2015-01-01

    Increased relative brain size characterizes the evolution of primates, suggesting that enhanced cognition plays an important part in the behavioral adaptations of this mammalian order. In addition to changes in brain anatomy, cognition can also be regulated by molecular changes that alter synaptic function, but little is known about modifications of synapses in primate brain evolution. The aim of the current study was to investigate the expression patterns and evolution of 20 synaptic genes from the prefrontal cortex of 12 primate species. The genes investigated included glutamate receptors, scaffolding proteins, synaptic vesicle components, as well as factors involved in synaptic vesicle release and structural components of the nervous system. Our analyses revealed that there have been significant changes during primate brain evolution in the components of the glutamatergic signaling pathway in terms of gene expression, protein expression, and promoter sequence changes. These results could entail functional modifications in the regulation of specific genes related to processes underlying learning and memory. PMID:24408959

  1. Topoisomerase 1 inhibition reversibly impairs synaptic function

    PubMed Central

    Mabb, Angela M.; Kullmann, Paul H. M.; Twomey, Margaret A.; Miriyala, Jayalakshmi; Philpot, Benjamin D.; Zylka, Mark J.

    2014-01-01

    Topotecan is a topoisomerase 1 (TOP1) inhibitor that is used to treat various forms of cancer. We recently found that topotecan reduces the expression of multiple long genes, including many neuronal genes linked to synapses and autism. However, whether topotecan alters synaptic protein levels and synapse function is currently unknown. Here we report that in primary cortical neurons, topotecan depleted synaptic proteins that are encoded by extremely long genes, including Neurexin-1, Neuroligin-1, Cntnap2, and GABAAβ3. Topotecan also suppressed spontaneous network activity without affecting resting membrane potential, action potential threshold, or neuron health. Topotecan strongly suppressed inhibitory neurotransmission via pre- and postsynaptic mechanisms and reduced excitatory neurotransmission. The effects on synaptic protein levels and inhibitory neurotransmission were fully reversible upon drug washout. Collectively, our findings suggest that TOP1 controls the levels of multiple synaptic proteins and is required for normal excitatory and inhibitory synaptic transmission. PMID:25404338

  2. Programmable synaptic chip for electronic neural networks

    NASA Technical Reports Server (NTRS)

    Moopenn, A.; Langenbacher, H.; Thakoor, A. P.; Khanna, S. K.

    1988-01-01

    A binary synaptic matrix chip has been developed for electronic neural networks. The matrix chip contains a programmable 32X32 array of 'long channel' NMOSFET binary connection elements implemented in a 3-micron bulk CMOS process. Since the neurons are kept off-chip, the synaptic chip serves as a 'cascadable' building block for a multi-chip synaptic network as large as 512X512 in size. As an alternative to the programmable NMOSFET (long channel) connection elements, tailored thin film resistors are deposited, in series with FET switches, on some CMOS test chips, to obtain the weak synaptic connections. Although deposition and patterning of the resistors require additional processing steps, they promise substantial savings in silicon area. The performance of synaptic chip in a 32-neuron breadboard system in an associative memory test application is discussed.

  3. A WIC-based curriculum to enhance parent communication with healthcare providers.

    PubMed

    Guerrero, Alma D; Inkelas, Moira; Whaley, Shannon E; Kuo, Alice A

    2013-10-01

    The objectives describe a curriculum to support parent-provider communication about child development, and to demonstrate its impact and effectiveness when delivered by staff from the Special Supplemental Nutrition Program for Women, Infants and Children (WIC). A curriculum was developed by a university-WIC partnership for a WIC center-based health education class to teach parents about child development and how to talk to their child's doctor about development. During a 90-min training session, university pediatricians used this curriculum and trained WIC paraprofessionals to conduct a 20-30 min center-based education session. WIC paraprofessionals completed an on-line survey to obtain their demographic characteristics, and their attitudes and perceptions about the training sessions and their experiences teaching the center-based health education session to parents. Approximately 500 WIC paraprofessionals received the 90-min training session across 60 centers in the Public Health Foundation Enterprises WIC Program in Southern California. About 250 WIC paraprofessionals completed the on-line survey and over 80 % of WIC staff reported that they had learned new information about child development as a result of the training, and 87 % of the WIC staff reported that the training was sufficient to feel comfortable teaching the class content to parents. We demonstrated the ability to build WIC paraprofessional capacity to promote parental participation in child developmental surveillance and communication with their child's doctor. With appropriate training, WIC staff are interested in supporting population-based efforts to improve parent-physician communication about child development that can complement WIC's existing maternal and child health topics. PMID:23760769

  4. Involvement of Synaptic Genes in the Pathogenesis of Autism Spectrum Disorders: The Case of Synapsins

    PubMed Central

    Giovedí, Silvia; Corradi, Anna; Fassio, Anna; Benfenati, Fabio

    2014-01-01

    Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders characterized by deficits in social interaction and social communication, restricted interests, and repetitive behaviors. Many synaptic protein genes are linked to the pathogenesis of ASDs, making them prototypical synaptopathies. An array of mutations in the synapsin (Syn) genes in humans has been recently associated with ASD and epilepsy, diseases that display a frequent comorbidity. Syns are pre-synaptic proteins regulating synaptic vesicle traffic, neurotransmitter release, and short-term synaptic plasticity. In doing so, Syn isoforms control the tone of activity of neural circuits and the balance between excitation and inhibition. As ASD pathogenesis is believed to result from dysfunctions in the balance between excitatory and inhibitory transmissions in neocortical areas, Syns are novel ASD candidate genes. Accordingly, deletion of single Syn genes in mice, in addition to epilepsy, causes core symptoms of ASD by affecting social behavior, social communication, and repetitive behaviors. Thus, Syn knockout mice represent a good experimental model to define synaptic alterations involved in the pathogenesis of ASD and epilepsy. PMID:25237665

  5. Communication: Enhanced oxygen reduction reaction and its underlying mechanism in Pd-Ir-Co trimetallic alloys

    SciTech Connect

    Ham, Hyung Chul; Hwang, Gyeong S.; Manogaran, Dhivya; Lee, Kang Hee; Jin, Seon-ah; You, Dae Jong; Pak, Chanho; Kwon, Kyungjung

    2013-11-28

    Based on a combined density functional theory and experimental study, we present that the electrochemical activity of Pd{sub 3}Co alloy catalysts toward oxygen reduction reaction (ORR) can be enhanced by adding a small amount of Ir. While Ir tends to favorably exist in the subsurface layers, the underlying Ir atoms are found to cause a substantial modification in the surface electronic structure. As a consequence, we find that the activation barriers of O/OH hydrogenation reactions are noticeably lowered, which would be mainly responsible for the enhanced ORR activity. Furthermore, our study suggests that the presence of Ir in the near-surface region can suppress Co out-diffusion from the Pd{sub 3}Co substrate, thereby improving the durability of Pd-Ir-Co catalysts. We also discuss the relative roles played by Ir and Co in enhancing the ORR activity relative to monometallic Pd catalysts.

  6. Synaptic dynamics: linear model and adaptation algorithm.

    PubMed

    Yousefi, Ali; Dibazar, Alireza A; Berger, Theodore W

    2014-08-01

    In this research, temporal processing in brain neural circuitries is addressed by a dynamic model of synaptic connections in which the synapse model accounts for both pre- and post-synaptic processes determining its temporal dynamics and strength. Neurons, which are excited by the post-synaptic potentials of hundred of the synapses, build the computational engine capable of processing dynamic neural stimuli. Temporal dynamics in neural models with dynamic synapses will be analyzed, and learning algorithms for synaptic adaptation of neural networks with hundreds of synaptic connections are proposed. The paper starts by introducing a linear approximate model for the temporal dynamics of synaptic transmission. The proposed linear model substantially simplifies the analysis and training of spiking neural networks. Furthermore, it is capable of replicating the synaptic response of the non-linear facilitation-depression model with an accuracy better than 92.5%. In the second part of the paper, a supervised spike-in-spike-out learning rule for synaptic adaptation in dynamic synapse neural networks (DSNN) is proposed. The proposed learning rule is a biologically plausible process, and it is capable of simultaneously adjusting both pre- and post-synaptic components of individual synapses. The last section of the paper starts with presenting the rigorous analysis of the learning algorithm in a system identification task with hundreds of synaptic connections which confirms the learning algorithm's accuracy, repeatability and scalability. The DSNN is utilized to predict the spiking activity of cortical neurons and pattern recognition tasks. The DSNN model is demonstrated to be a generative model capable of producing different cortical neuron spiking patterns and CA1 Pyramidal neurons recordings. A single-layer DSNN classifier on a benchmark pattern recognition task outperforms a 2-Layer Neural Network and GMM classifiers while having fewer numbers of free parameters and

  7. Effect of chronic stress on synaptic currents in rat hippocampal dentate gyrus neurons.

    PubMed

    Karst, Henk; Joëls, Marian

    2003-01-01

    We investigated the effect of chronic stress on synaptic responses of rat dentate granule cells to perforant path stimulation. Rats were subjected for 3 wk to unpredictable stressors twice daily or to control handling. One day after the last stressor, hippocampal slices were prepared and synaptic responses were determined with whole-cell recording. At that time, adrenal weight was found to be increased and thymus weight as well as gain in body weight were decreased in the stressed versus control animals, indicative of corticosterone hypersecretion during the stress period. In slices from rats with basal corticosteroid levels (at the circadian trough, under rest), no effect of prior stress exposure was observed on synaptic responses. However, synaptic responses of dentate granule cells from chronically stressed and control rats were differently affected by in vitro activation of glucocorticoid receptors, i.e., 1-4 h after administration of 100 nM corticosterone for 20 min. Thus the maximal response to synaptic activation of dentate cells at holding potential of -70 mV [when N-methyl-D-aspartate (NMDA) receptors are blocked by magnesium] was significantly enhanced after corticosterone administration in chronically stressed but not in control animals. In accordance, the amplitude of alpha-amino-3-hydroxy-5-methylisolazole-4-propionic acid (AMPA) but not of NMDA receptor-mediated currents was increased by corticosterone in stressed rats, over the entire voltage range. Corticosterone treatment also decreased the time to peak of AMPA currents, but this effect did not depend on prior stress exposure. The data indicate that following chronic stress exposure synaptic excitation of dentate granule cells may be enhanced when corticosterone levels rise. This enhanced synaptic flow could contribute to enhanced excitation of projection areas of the dentate gyrus, most notably the CA3 hippocampal region. PMID:12522207

  8. Enhancement of LED indoor communications using OPPM-PWM modulation and grouped bit-flipping decoding.

    PubMed

    Yang, Aiying; Li, Xiangming; Jiang, Tao

    2012-04-23

    Combination of overlapping pulse position modulation and pulse width modulation at the transmitter and grouped bit-flipping algorithm for low-density parity-check decoding at the receiver are proposed for visible Light Emitting Diode (LED) indoor communication system in this paper. The results demonstrate that, with the same Photodetector, the bit rate can be increased and the performance of the communication system can be improved by the scheme we proposed. Compared with the standard bit-flipping algorithm, the grouped bit-flipping algorithm can achieve more than 2.0 dB coding gain at bit error rate of 10-5. By optimizing the encoding of overlapping pulse position modulation and pulse width modulation symbol, the performance can be further improved. It is reasonably expected that the bit rate can be upgraded to 400 Mbit/s with a single available LED, thus transmission rate beyond 1 Gbit/s is foreseen by RGB LEDs. PMID:22535108

  9. Playback Theatre as a tool to enhance communication in medical education

    PubMed Central

    Salas, Ramiro; Steele, Kenya; Lin, Amy; Loe, Claire; Gauna, Leslie; Jafar-Nejad, Paymaan

    2013-01-01

    Playback Theatre (PT) is an improvisational form of theatre in which a group of actors “play back” real life stories told by audience members. In PT, a conductor elicits moments, feelings and stories from audience members, and conducts mini-interviews with those who volunteer a moment of their lives to be re-enacted or “played” for the audience. A musician plays music according to the theme of each story, and 4-5 actors listen to the interview and perform the story that has just been told. PT has been used in a large number of settings as a tool to share stories in an artistic manner. Despite its similarities to psychodrama, PT does not claim to be a form of therapy. We offered two PT performances to first year medical students at Baylor College of Medicine in Houston, Texas, to bring the students a safe and fun environment, conducive to sharing feelings and moments related to being a medical student. Through the moments and stories shared by students, we conclude that there is an enormous need in this population for opportunities to communicate the many emotions associated with medical school and with healthcare-related personal experiences, such as anxiety, pride, or anger. PT proved a powerful tool to help students communicate. PMID:24369762

  10. Playback Theatre as a tool to enhance communication in medical education.

    PubMed

    Salas, Ramiro; Steele, Kenya; Lin, Amy; Loe, Claire; Gauna, Leslie; Jafar-Nejad, Paymaan

    2013-01-01

    Playback Theatre (PT) is an improvisational form of theatre in which a group of actors "play back" real life stories told by audience members. In PT, a conductor elicits moments, feelings and stories from audience members, and conducts mini-interviews with those who volunteer a moment of their lives to be re-enacted or "played" for the audience. A musician plays music according to the theme of each story, and 4-5 actors listen to the interview and perform the story that has just been told. PT has been used in a large number of settings as a tool to share stories in an artistic manner. Despite its similarities to psychodrama, PT does not claim to be a form of therapy. We offered two PT performances to first year medical students at Baylor College of Medicine in Houston, Texas, to bring the students a safe and fun environment, conducive to sharing feelings and moments related to being a medical student. Through the moments and stories shared by students, we conclude that there is an enormous need in this population for opportunities to communicate the many emotions associated with medical school and with healthcare-related personal experiences, such as anxiety, pride, or anger. PT proved a powerful tool to help students communicate. PMID:24369762

  11. Enhancing self-protective behavior: efficacy beliefs and peer feedback in risk communication.

    PubMed

    Verroen, Stephan; Gutteling, Jan M; De Vries, Peter W

    2013-07-01

    In times of a high-impact safety incident citizens may have a variety of sources available to help them cope with the situation. This research focuses on the interplay of efficacy information in risk communication messages and peer feedback, such as responses on social network sites (SNSs) in the context of a high-impact risk on the intention to engage in self-protective behavior. The study pitted high and low efficacy information messages against supporting and opposing peer feedback (N = 242). Results show a significant interaction effect between efficacy information in a news article and peer feedback from SNS messages on both the intention to engage in self-protective behavior and levels of involvement. Participants who received the article with more efficacy information and also received supportive peer feedback via SNS messages were more likely to express higher levels of involvement and greater intentions to engage in protective behavior. When confronted with a low efficacious news article, the effect of peer feedback on these two variables was significantly stronger. Finally, implications for theory and government risk communication are discussed. PMID:23126483

  12. E-mentoring: Using Computer Mediated Communication To Enhance the Mentoring Process.

    ERIC Educational Resources Information Center

    Bierema, Laura L.; Merriam, Sharan B.

    2002-01-01

    Provides a definition of e-mentoring and an exploration of its potential for enhancing mentoring relationships from technical and social perspectives. Considers benefits of and barriers to e-mentoring and describes strategies for establishing an e-mentoring relationship. Includes Internet resources. (EV)

  13. Androgens enhance plasticity of an electric communication signal in female knifefish, Brachyhypopomus pinnicaudatus

    PubMed Central

    Allee, Susan J.; Markham, Michael R.; Stoddard, Philip K.

    2009-01-01

    Sex steroids were initially defined by their actions shaping sexually dimorphic behavioral patterns. More recently scientists have begun exploring the role of steroids in determining sex differences in behavioral plasticity. We investigated the role of androgens in potentiating circadian, pharmacological, and socially-induced plasticity in the amplitude and duration of electric organ discharges (EODs) of female gymnotiform fish. We first challenged female fish with injections of serotonin (5-HT) and adrenocorticotropic hormone (ACTH), and with social encounters with female and male conspecifics to characterize females’ pre-implant responses to each treatment. Each individual was then implanted with a pellet containing dihydrotestosterone (DHT) concentrations of 0.0, 0.03, 0.1, 0.3, or 1.0 mg 10g−1 body weight. We then repeated all challenges and compared each female’s pre- and post-implant responses. The highest implant dose enhanced EOD duration modulations in response to all challenge types, responses to male challenge were also greater at the second highest dose, and responses to ACTH challenge were enhanced in females receiving all but the smallest dose (and blank) implants. Alternatively, amplitude modulations were enhanced only during female challenges and only when females received the highest DHT dose. Our results highlight the differential regulation of EOD duration and amplitude, and suggest that DHT enhanced the intrinsic plasticity of the electrogenic cells that produce the EOD rather than modifying behavioral phenotypes. The relative failure of DHT to enhance EOD amplitude plasticity also implies that factors other than androgens are involved in regulating/promoting male-typical EOD circadian rhythms and waveform modulations displayed in social contexts. PMID:19450600

  14. Enhanced spectral efficiency using bandwidth switchable SAW filtering for mobile satellite communications systems

    NASA Technical Reports Server (NTRS)

    Peach, Robert; Malarky, Alastair

    1990-01-01

    Currently proposed mobile satellite communications systems require a high degree of flexibility in assignment of spectral capacity to different geographic locations. Conventionally this results in poor spectral efficiency which may be overcome by the use of bandwidth switchable filtering. Surface acoustic wave (SAW) technology makes it possible to provide banks of filters whose responses may be contiguously combined to form variable bandwidth filters with constant amplitude and phase responses across the entire band. The high selectivity possible with SAW filters, combined with the variable bandwidth capability, makes it possible to achieve spectral efficiencies over the allocated bandwidths of greater than 90 percent, while retaining full system flexibility. Bandwidth switchable SAW filtering (BSSF) achieves these gains with a negligible increase in hardware complexity.

  15. Experimental demonstration of security-enhanced WDM-PON based on chaotic optical communications

    NASA Astrophysics Data System (ADS)

    Yin, Hongxi; Chen, Xiaolei; Yue, Hehe; Zhao, Qingchun; Hao, Yang; Wu, Chenguang; Zhao, Nan

    2015-08-01

    The message-decryption process of subtracting chaotic synchronization carrier from receiving signal is explained by modeling and numerically solving the rate equations for semiconductor lasers. An experimental system of wavelength division multiplexing passive optical network (WDM-PON) based on chaotic-light secure communications is first built up. The bidirectional transmissions of downstream and upstream data are experimentally realized with only two lasers and a single wavelength channel in a WDM fiber-optic link. When the data rate is 1.25 Gb/s, the secure transmission distance can be up to 11 km with SSMF of G.652. After sampling and decision, the BER of the recovered messages is calculated to be approximately 1×10-4.

  16. Enhancing Space Science Communication with Cross-Cultural Venues in Latino Communities

    NASA Astrophysics Data System (ADS)

    Morris, P. A.; Reiff, P.; Sumners, C.; McKay, G. A.

    2006-12-01

    Brownsville, Texas in the Rio Grande Valley is the site of an annual space science outreach event that illustrates successful methods of communicating science across cultural and economical boundaries. The Lower Rio Grande valley is predominantly rural, Spanish speaking with large portions of the population at or below the poverty line. Many of the Latino students drop out of school before receiving a high school diploma. For the past four years the University of Texas at Brownsville (UTB) has brought a group of educators, high school and undergraduate students to Houston for training at Johnson Space Center and the Houston Museum of Natural Science. The group subsequently organizes a one day event for 5th-8th grade students, teachers and administrators that is focused on a space science theme. In 2006 over 500 participants learned about NASA's return to the Moon. The attendees listened to a talk by a NASA scientist, viewed exhibits of lunar materials and participated in 20 different hands-on activities. Examples of the activities were the effects of the Sun's solar winds on regolith formation, lunar craters, potential water resources and future exploration. The event is a success because it is locally supported and organized by UTB and its students. UTB has taken "ownership" of the yearly activity. Outside support is limited to scientific data and information, supplying a guest speaker and materials support. Materials support can include NASA displays, telescopes, a portable planetarium and selected planetarium shows. Communication barriers between English speaking and Spanish speaking are eliminated as over ninety percent of the local leaders are bilingual. Additionally the portable planetarium has Spanish language programs. This is an example of an activity that crosses across cultural boundaries and can be exported to other regions of the western hemisphere.

  17. Impact of Risk Perception on Risk Communication and Community Resilience Enhancement

    NASA Astrophysics Data System (ADS)

    Frazier, T. G.; Thompson, C. M.

    2014-12-01

    Past studies have demonstrated there is a relationship between risk perception, risk tolerance and mitigation planning. When people experience high-risk perception, their risk tolerance is typically lowered causing them to become more likely to support the implementation of mitigation policies including those that are either cost intensive or politically controversial. Understanding stakeholder risk perception could therefore provide information about the likelihood of implementation of various mitigation strategies. Varied risk communication methods are needed to accurately represent community risk so as to better inform decision-making. In response to this need, this research examines the effect of risk perception on community resilience through a case study of Fernan Lake, ID. Researchers conducted a survey of Fernan Lake residents to determine their risk perception of the impact of blue-green algae blooms on community resilience. Survey questions were developed based on traditional risk perception factors like vested interest, social trust, knowledge, possible benefits or losses, relevance to individual and potential for control. The results were used to determine residents' risk perception of the impact of blue green algae blooms on Socio-Ecological System resource availability and future development and growth potential. Focus groups were then conducted to validate the survey results. Research results demonstrate that residents are concerned about the impacts of blue-green algae blooms, but the level of interest in acting on those concerns and their willingness to consider more aggressive mitigation strategies varies across the study area. This research demonstrates the need for varied risk communication approaches, depending upon community mitigation goals.

  18. Calcineurin Mediates Synaptic Scaling Via Synaptic Trafficking of Ca2+-Permeable AMPA Receptors

    PubMed Central

    Kim, Seonil; Ziff, Edward B.

    2014-01-01

    Homeostatic synaptic plasticity is a negative-feedback mechanism for compensating excessive excitation or inhibition of neuronal activity. When neuronal activity is chronically suppressed, neurons increase synaptic strength across all affected synapses via synaptic scaling. One mechanism for this change is alteration of synaptic AMPA receptor (AMPAR) accumulation. Although decreased intracellular Ca2+ levels caused by chronic inhibition of neuronal activity are believed to be an important trigger of synaptic scaling, the mechanism of Ca2+-mediated AMPAR-dependent synaptic scaling is not yet understood. Here, we use dissociated mouse cortical neurons and employ Ca2+ imaging, electrophysiological, cell biological, and biochemical approaches to describe a novel mechanism in which homeostasis of Ca2+ signaling modulates activity deprivation-induced synaptic scaling by three steps: (1) suppression of neuronal activity decreases somatic Ca2+ signals; (2) reduced activity of calcineurin, a Ca2+-dependent serine/threonine phosphatase, increases synaptic expression of Ca2+-permeable AMPARs (CPARs) by stabilizing GluA1 phosphorylation; and (3) Ca2+ influx via CPARs restores CREB phosphorylation as a homeostatic response by Ca2+-induced Ca2+ release from the ER. Therefore, we suggest that synaptic scaling not only maintains neuronal stability by increasing postsynaptic strength but also maintains nuclear Ca2+ signaling by synaptic expression of CPARs and ER Ca2+ propagation. PMID:24983627

  19. Communication: Multiple atomistic force fields in a single enhanced sampling simulation

    NASA Astrophysics Data System (ADS)

    Hoang Viet, Man; Derreumaux, Philippe; Nguyen, Phuong H.

    2015-07-01

    The main concerns of biomolecular dynamics simulations are the convergence of the conformational sampling and the dependence of the results on the force fields. While the first issue can be addressed by employing enhanced sampling techniques such as simulated tempering or replica exchange molecular dynamics, repeating these simulations with different force fields is very time consuming. Here, we propose an automatic method that includes different force fields into a single advanced sampling simulation. Conformational sampling using three all-atom force fields is enhanced by simulated tempering and by formulating the weight parameters of the simulated tempering method in terms of the energy fluctuations, the system is able to perform random walk in both temperature and force field spaces. The method is first demonstrated on a 1D system and then validated by the folding of the 10-residue chignolin peptide in explicit water.

  20. Communication: Multiple atomistic force fields in a single enhanced sampling simulation

    SciTech Connect

    Hoang Viet, Man; Derreumaux, Philippe; Nguyen, Phuong H.

    2015-07-14

    The main concerns of biomolecular dynamics simulations are the convergence of the conformational sampling and the dependence of the results on the force fields. While the first issue can be addressed by employing enhanced sampling techniques such as simulated tempering or replica exchange molecular dynamics, repeating these simulations with different force fields is very time consuming. Here, we propose an automatic method that includes different force fields into a single advanced sampling simulation. Conformational sampling using three all-atom force fields is enhanced by simulated tempering and by formulating the weight parameters of the simulated tempering method in terms of the energy fluctuations, the system is able to perform random walk in both temperature and force field spaces. The method is first demonstrated on a 1D system and then validated by the folding of the 10-residue chignolin peptide in explicit water.

  1. Cellular and molecular mechanisms of chemical synaptic transmission.

    PubMed

    Millhorn, D E; Bayliss, D A; Erickson, J T; Gallman, E A; Szymeczek, C L; Czyzyk-Krzeska, M; Dean, J B

    1989-12-01

    During the last decade much progress has been made in understanding the cellular and molecular mechanisms by which nerve cells communicate with each other and nonneural (e.g., muscle) target tissue. This review is intended to provide the reader with an account of this work. We begin with an historical overview of research on cell-to-cell communication and then discuss recent developments that, in some instances, have led to dramatic changes in the concept of synaptic transmission. For instance, the finding that single neurons often contain multiple messengers (i.e., neurotransmitters) invalidated the long-held theory (i.e., Dale's Law) that individual neurons contain and release one and only one type of neurotransmitter. Moreover, the last decade witnessed the inclusion of an entire group of compounds, the neuropeptides, as messenger molecules. Enormous progress has also been made in elucidating postsynaptic receptor complexes and biochemical intermediaries involved in synaptic transmission. Here the development of recombinant DNA technology has made it possible to clone and determine the molecular structure for a number of receptors. This information has been used to gain insight into how these receptors function either as a ligand-gated channel or as a G protein-linked ligand recognition molecule. Perhaps the most progress made during this era was in understanding the molecular linkage of G protein-linked receptors to intramembranous and cytoplasmic macromolecules involved in signal amplification and transduction. We conclude with a brief discussion of how synaptic transmission leads to immediate alterations in the electrical activity and, in some cases, to a change in phenotype by altering gene expression. These alterations in cellular behavior are believed to be mediated by phosphoproteins, the final biochemical product of signal transduction. PMID:2575357

  2. Synaptic vesicle recycling: steps and principles

    PubMed Central

    Rizzoli, Silvio O

    2014-01-01

    Synaptic vesicle recycling is one of the best-studied cellular pathways. Many of the proteins involved are known, and their interactions are becoming increasingly clear. However, as for many other pathways, it is still difficult to understand synaptic vesicle recycling as a whole. While it is generally possible to point out how synaptic reactions take place, it is not always easy to understand what triggers or controls them. Also, it is often difficult to understand how the availability of the reaction partners is controlled: how the reaction partners manage to find each other in the right place, at the right time. I present here an overview of synaptic vesicle recycling, discussing the mechanisms that trigger different reactions, and those that ensure the availability of reaction partners. A central argument is that synaptic vesicles bind soluble cofactor proteins, with low affinity, and thus control their availability in the synapse, forming a buffer for cofactor proteins. The availability of cofactor proteins, in turn, regulates the different synaptic reactions. Similar mechanisms, in which one of the reaction partners buffers another, may apply to many other processes, from the biogenesis to the degradation of the synaptic vesicle. PMID:24596248

  3. SAD-B kinase regulates pre-synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory.

    PubMed

    Watabe, Ayako M; Nagase, Masashi; Hagiwara, Akari; Hida, Yamato; Tsuji, Megumi; Ochiai, Toshitaka; Kato, Fusao; Ohtsuka, Toshihisa

    2016-01-01

    Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD-B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre-synaptic kinase in the brain. We found that the paired-pulse ratio was significantly enhanced at Shaffer collateral synapses in the hippocampal CA1 region in SAD-B KO mice compared with wild-type littermates. We also found that the frequency of the miniature excitatory post-synaptic current was decreased in SAD-B KO mice. Moreover, synaptic depression following prolonged low-frequency synaptic stimulation was significantly enhanced in SAD-B KO mice. These results suggest that SAD-B kinase regulates vesicular release probability at pre-synaptic terminals and is involved in vesicular trafficking and/or regulation of the readily releasable pool size. Finally, we found that hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice. These observations suggest that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, but their roles in mature brains were only partially known. Here, we demonstrated, at mature pre-synaptic terminals, that SAD-B regulates vesicular release probability and synaptic plasticity. Moreover, hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice, suggesting that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. PMID:26444684

  4. Data communications

    SciTech Connect

    Preckshot, G.G.

    1993-08-01

    The purpose of this paper is to recommend regulatory guidance for reviewers examining computer communication systems used in nuclear power plants. The recommendations cover three areas important to these communications systems: system design, communication protocols, and communication media. The first area, system design, considers three aspects of system design--questions about architecture, specific risky design elements or omissions to look for in designs being reviewed, and recommendations for multiplexed data communication systems used in safety systems. The second area reviews pertinent aspects of communication protocol design and makes recommendations for newly designed protocols or the selection of existing protocols for safety system, information display, and non-safety control system use. The third area covers communication media selection, which differs significantly from traditional wire and cable. The recommendations for communication media extend or enhance the concerns of published IEEE standards about three subjects: data rate, imported hazards and maintainability.

  5. Synaptic strength modulation after cortical trauma: a role in epileptogenesis.

    PubMed

    Avramescu, Sinziana; Timofeev, Igor

    2008-07-01

    Traumatic brain injuries are often followed by abnormal hyperexcitability, leading to acute seizures and epilepsy. Previous studies documented the rewiring capacity of neocortical neurons in response to various cortical and subcortical lesions. However, little information is available on the functional consequences of these anatomical changes after cortical trauma and the adaptation of synaptic connectivity to a decreased input produced by chronic deafferentation. In this study, we recorded intracellular (IC) activities of cortical neurons simultaneously with extracellular (EC) unit activities and field potentials of neighboring cells in cat cortex, after a large transection of the white matter underneath the suprasylvian gyrus, in acute and chronic conditions (at 2, 4, and 6 weeks) in ketamine-xylazine-anesthetized cats. Using EC spikes to compute the spike-triggered averages of IC membrane potential, we found an increased connection probability and efficacy between cortical neurons weeks after cortical trauma. Inhibitory interactions showed no significant changes in the traumatized cortex compared with control. The increased synaptic efficacy was accompanied by enhanced input resistance and intrinsic excitability of cortical neurons, as well as by increased duration of silent network periods. Our electrophysiological data revealed functional consequences of previously reported anatomical changes in the injured cortex. We suggest that homeostatic synaptic plasticity compensating the decreased activity in the undercut cortex leads to an uncontrollable cortical hyperexcitability and seizure generation. PMID:18596152

  6. Enhanced channel estimation and symbol detection for high speed multi-input multi-output underwater acoustic communications.

    PubMed

    Ling, Jun; Yardibi, Tarik; Su, Xiang; He, Hao; Li, Jian

    2009-05-01

    The need for achieving higher data rates in underwater acoustic communications leverages the use of multi-input multi-output (MIMO) schemes. In this paper two key issues regarding the design of a MIMO communications system, namely, channel estimation and symbol detection, are addressed. To enhance channel estimation performance, a cyclic approach for designing training sequences and a channel estimation algorithm called the iterative adaptive approach (IAA) are presented. Sparse channel estimates can be obtained by combining IAA with the Bayesian information criterion (BIC). Moreover, the RELAX algorithm can be used to improve the IAA with BIC estimates further. Regarding symbol detection, a minimum mean-squared error based detection scheme, called RELAX-BLAST, which is a combination of vertical Bell Labs layered space-time (V-BLAST) algorithm and the cyclic principle of the RELAX algorithm, is presented and it is shown that RELAX-BLAST outperforms V-BLAST. Both simulated and experimental results are provided to validate the proposed MIMO scheme. RACE'08 experimental results employing a 4 x 24 MIMO system show that the proposed scheme enjoys an average uncoded bit error rate of 0.38% at a payload data rate of 31.25 kbps and an average coded bit error rate of 0% at a payload data rate of 15.63 kbps. PMID:19425650

  7. Surface plasmon-enhanced optical trapping of quantum-dot-conjugated surface molecules on neurons cultured on a plasmonic chip

    NASA Astrophysics Data System (ADS)

    Miyauchi, Kohei; Tawa, Keiko; Kudoh, Suguru N.; Taguchi, Takahisa; Hosokawa, Chie

    2016-06-01

    Living neurons in a complex neuronal network communicate with each other through synaptic connections. The molecular dynamics of cell surface molecules localized at synaptic terminals is essential for functional connections via synaptic plasticity in the neuronal network. Here, we demonstrate surface-plasmon-resonance-based optical trapping using a plasmonic chip toward realizing effective manipulation of molecules on the surface of neurons. Surface-plasmon-enhanced optical trapping was evaluated by the fluorescence analysis of nanoparticles suspended in water and neural cell adhesion molecules (NCAMs) labeled with quantum dots (Q-dots) on rat hippocampal neurons. The motion of nanoparticles in water and the molecular dynamics of NCAMs on neuronal cells cultured on a plasmonic chip were constrained at the laser focus more effectively than those on a glass substrate because of the surface plasmon resonance effect.

  8. Dysregulation of synaptic and extrasynaptic N-methyl-D-aspartate receptors induced by amyloid-β.

    PubMed

    Wang, Zhi-Cong; Zhao, Jie; Li, Shao

    2013-12-01

    The toxicity of amyloid-beta (Aβ) is strongly associated with Alzheimer's disease (AD), which has a high incidence in the elderly worldwide. Recent evidence showed that alteration in the activity of N-methyl-D-aspartate receptors (NMDARs) plays a key role in Aβ-induced neurotoxicity. However, the activation of synaptic and extrasynaptic NMDARs has distinct consequences for plasticity, gene regulation, neuronal death, and Aβ production. This review focuses on the dysregulation of synaptic and extrasynaptic NMDARs induced by Aβ. On one hand, Aβ downregulates the synaptic NMDAR response by promoting NMDAR endocytosis, leading to either neurotoxicity or neuroprotection. On the other hand, Aβ enhances the activation of extrasynaptic NMDARs by decreasing neuronal glutamate uptake and inducing glutamate spillover, subsequently causing neurotoxicity. In addition, selective enhancement of synaptic activity by low doses of NMDA, or reduction of extrasynaptic activity by memantine, a non-competitive NMDAR antagonist, halts Aβ-induced neurotoxicity. Therefore, future neuroprotective drugs for AD should aim at both the enhancement of synaptic activity and the disruption of extrasynaptic NMDAR-dependent death signaling. PMID:24136243

  9. Presynaptic Calcium Channel Localization and Calcium Dependent Synaptic Vesicle Exocytosis Regulated by the Fuseless Protein

    PubMed Central

    Long, A. Ashleigh; Kim, Eunju; Leung, Hung-Tat; Woodruff, Elvin; An, Lingling; Doerge, R. W.; Pak, William L.; Broadie, Kendal

    2009-01-01

    Summary A systematic forward genetic Drosophila screen for electroretinogram mutants lacking synaptic transients identified the fuseless (fusl) gene, which encodes a predicted 8-pass transmembrane protein in the presynaptic membrane. Null fusl mutants display >75% reduction in evoked synaptic transmission but, conversely, a ~3-fold increase in the frequency and amplitude of spontaneous synaptic vesicle fusion events. These neurotransmission defects are rescued by a wildtype fusl transgene targeted only to the presynaptic cell, demonstrating a strictly presynaptic requirement for Fusl function. Defects in FM dye turnover at the synapse show a severely impaired exo-endo synaptic vesicle cycling pool. Consistently, ultrastructural analyses reveal accumulated vesicles arrested in clustered and docked pools at presynaptic active zones. In the absence of Fusl, calcium-dependent neurotransmitter release is dramatically compromised and there is little enhancement of synaptic efficacy with elevated external Ca2+ concentrations. These defects are causally linked with severe loss of the Cacophony voltage-gated Ca2+ channels, which fail to localize normally at presynaptic active zone domains in the absence of Fusl. These data indicate that Fusl regulates assembly of the presynaptic active zone Ca2+ channel domains required for efficient coupling of the Ca2+ influx and synaptic vesicle exocytosis during neurotransmission. PMID:18385325

  10. β-Adrenergic Control of Hippocampal Function: Subserving the Choreography of Synaptic Information Storage and Memory

    PubMed Central

    Hagena, Hardy; Hansen, Niels; Manahan-Vaughan, Denise

    2016-01-01

    Noradrenaline (NA) is a key neuromodulator for the regulation of behavioral state and cognition. It supports learning by increasing arousal and vigilance, whereby new experiences are “earmarked” for encoding. Within the hippocampus, experience-dependent information storage occurs by means of synaptic plasticity. Furthermore, novel spatial, contextual, or associative learning drives changes in synaptic strength, reflected by the strengthening of long-term potentiation (LTP) or long-term depression (LTD). NA acting on β-adrenergic receptors (β-AR) is a key determinant as to whether new experiences result in persistent hippocampal synaptic plasticity. This can even dictate the direction of change of synaptic strength. The different hippocampal subfields play different roles in encoding components of a spatial representation through LTP and LTD. Strikingly, the sensitivity of synaptic plasticity in these subfields to β-adrenergic control is very distinct (dentate gyrus > CA3 > CA1). Moreover, NA released from the locus coeruleus that acts on β-AR leads to hippocampal LTD and an enhancement of LTD-related memory processing. We propose that NA acting on hippocampal β-AR, that is graded according to the novelty or saliency of the experience, determines the content and persistency of synaptic information storage in the hippocampal subfields and therefore of spatial memories. PMID:26804338

  11. Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic γ-actin levels

    PubMed Central

    Schreiber, Joerg; Végh, Marlene J.; Dawitz, Julia; Kroon, Tim; Loos, Maarten; Labonté, Dorthe; Li, Ka Wan; Van Nierop, Pim; Van Diepen, Michiel T.; De Zeeuw, Chris I.; Kneussel, Matthias; Meredith, Rhiannon M.; Smit, August B.

    2015-01-01

    Synaptic plasticity requires remodeling of the actin cytoskeleton. Although two actin isoforms, β- and γ-actin, are expressed in dendritic spines, the specific contribution of γ-actin in the expression of synaptic plasticity is unknown. We show that synaptic γ-actin levels are regulated by the E3 ubiquitin ligase TRIM3. TRIM3 protein and Actg1 transcript are colocalized in messenger ribonucleoprotein granules responsible for the dendritic targeting of messenger RNAs. TRIM3 polyubiquitylates γ-actin, most likely cotranslationally at synaptic sites. Trim3−/− mice consequently have increased levels of γ-actin at hippocampal synapses, resulting in higher spine densities, increased long-term potentiation, and enhanced short-term contextual fear memory consolidation. Interestingly, hippocampal deletion of Actg1 caused an increase in long-term fear memory. Collectively, our findings suggest that temporal control of γ-actin levels by TRIM3 is required to regulate the timing of hippocampal plasticity. We propose a model in which TRIM3 regulates synaptic γ-actin turnover and actin filament stability and thus forms a transient inhibitory constraint on the expression of hippocampal synaptic plasticity. PMID:26527743

  12. Pycnogenol protects CA3-CA1 synaptic function in a rat model of traumatic brain injury.

    PubMed

    Norris, Christopher M; Sompol, Pradoldej; Roberts, Kelly N; Ansari, Mubeen; Scheff, Stephen W

    2016-02-01

    Pycnogenol (PYC) is a patented mix of bioflavonoids with potent anti-oxidant and anti-inflammatory properties. Previously, we showed that PYC administration to rats within hours after a controlled cortical impact (CCI) injury significantly protects against the loss of several synaptic proteins in the hippocampus. Here, we investigated the effects of PYC on CA3-CA1 synaptic function following CCI. Adult Sprague-Dawley rats received an ipsilateral CCI injury followed 15 min later by intravenous injection of saline vehicle or PYC (10 mg/kg). Hippocampal slices from the injured (ipsilateral) and uninjured (contralateral) hemispheres were prepared at seven and fourteen days post-CCI for electrophysiological analyses of CA3-CA1 synaptic function and induction of long-term depression (LTD). Basal synaptic strength was impaired in slices from the ipsilateral, relative to the contralateral, hemisphere at seven days post-CCI and susceptibility to LTD was enhanced in the ipsilateral hemisphere at both post-injury timepoints. No interhemispheric differences in basal synaptic strength or LTD induction were observed in rats treated with PYC. The results show that PYC preserves synaptic function after CCI and provides further rationale for investigating the use of PYC as a therapeutic in humans suffering from neurotrauma. PMID:26607913

  13. Depression of synaptic efficacy at intermolt in crayfish neuromuscular junctions by 20-hydroxyecdysone, a molting hormone.

    PubMed

    Cooper, R L; Ruffner, M E

    1998-04-01

    This report demonstrates that ecdysteroids can reduce synaptic transmission at an intermolt stage of a crustacean tonic neuromuscular junction by acting at a presynaptic site. The steroid molting hormone, 20-hydroxyecdysone (20-HE), appears to act through a rapid, nongenomic mechanism that decreases the probability of synaptic vesicle release and reduces the number of release sites. Quantal analysis revealed that fewer vesicles were released for a given stimulus when 20-HE was present, and this in turn accounted for the reduced synaptic efficacy. Reduced synaptic efficacy produced smaller evoked postsynaptic currents and smaller excitatory postsynaptic potentials (EPSPs) across the muscle fiber membrane. The reduction in EPSPs was observed among muscle fibers that were innervated by high- or low-output terminals. The behavior of crustaceans/crayfish during the molt cycle, when 20-HE is high, may be explained by the reduction in synaptic transmission. Crustaceans become quiescent during the premolt periods as do insects. The effects of 20-HE can be reversed with the application of the crustacean neuromodulator serotonin, which enhances synaptic transmission. PMID:9535959

  14. Dopamine attenuates evoked inhibitory synaptic currents in central amygdala neurons

    PubMed Central

    Naylor, Jennifer C.; Li, Qiang; Kang-Park, Maeng-hee; Wilson, Wilkie A.; Kuhn, Cynthia; Moore, Scott D.

    2010-01-01

    The central nucleus of the amygdala (CeA) plays a critical role in regulating the behavioral, autonomic and endocrine response to stress. Dopamine (DA) participates in mediating the stress response and DA release is enhanced in the CeA during stressful events. However, the electrophysiological effects of DA on CeA neurons have not yet been characterized. Therefore, the purpose of this study was to identify and characterize the effect of DA application on electrophysiological responses of CeA neurons in coronal brain sections of male Sprague Dawley rats. We used whole cell patch clamp electrophysiological techniques to record evoked synaptic responses and to determine basic membrane properties of CeA neurons both before and after DA superfusion. DA (20–250μM) did not significantly alter membrane conductance over the voltage range tested. However, DA significantly reduced peak amplitude of evoked inhibitory synaptic currents in CeA neurons. Pretreatment with the D2 receptor antagonist eticlopride failed to significantly block the inhibitory effects of DA. In contrast, pretreatment with the D1 receptor antagonist SCH-23390 significantly reduced DA effects on evoked inhibitory neurotransmission in these neurons. Moreover, bath superfusion of the specific D1 receptor agonist SKF-39393, but not the D2 receptor agonist quinpirole, significantly reduced peak amplitude of evoked inhibitory synaptic events. DA reduced the frequency of miniature IPSCs without altering the amplitude, while having no effect on the amplitude of IPSCs elicited by pressure application of GABA. These results suggest that DA may modulate inhibitory synaptic transmission in CeA through D1 receptor activation primarily by a presynaptic mechanism. PMID:20955472

  15. Examination of Synaptic Vesicle Recycling Using FM Dyes During Evoked, Spontaneous, and Miniature Synaptic Activities

    PubMed Central

    Iwabuchi, Sadahiro; Kakazu, Yasuhiro; Koh, Jin-Young; Goodman, Kirsty M.; Harata, N. Charles

    2014-01-01

    Synaptic vesicles in functional nerve terminals undergo exocytosis and endocytosis. This synaptic vesicle recycling can be effectively analyzed using styryl FM dyes, which reveal membrane turnover. Conventional protocols for the use of FM dyes were designed for analyzing neurons following stimulated (evoked) synaptic activity. Recently, protocols have become available for analyzing the FM signals that accompany weaker synaptic activities, such as spontaneous or miniature synaptic events. Analysis of these small changes in FM signals requires that the imaging system is sufficiently sensitive to detect small changes in intensity, yet that artifactual changes of large amplitude are suppressed. Here we describe a protocol that can be applied to evoked, spontaneous, and miniature synaptic activities, and use cultured hippocampal neurons as an example. This protocol also incorporates a means of assessing the rate of photobleaching of FM dyes, as this is a significant source of artifacts when imaging small changes in intensity. PMID:24747983

  16. Short-term Music Training Enhances Complex, Distributed Neural Communication during Music and Linguistic Tasks.

    PubMed

    Carpentier, Sarah M; Moreno, Sylvain; McIntosh, Anthony R

    2016-10-01

    Musical training is frequently associated with benefits to linguistic abilities, and recent focus has been placed on possible benefits of bilingualism to lifelong executive functions; however, the neural mechanisms for such effects are unclear. The aim of this study was to gain better understanding of the whole-brain functional effects of music and second-language training that could support such previously observed cognitive transfer effects. We conducted a 28-day longitudinal study of monolingual English-speaking 4- to 6-year-old children randomly selected to receive daily music or French language training, excluding weekends. Children completed passive EEG music note and French vowel auditory oddball detection tasks before and after training. Brain signal complexity was measured on source waveforms at multiple temporal scales as an index of neural information processing and network communication load. Comparing pretraining with posttraining, musical training was associated with increased EEG complexity at coarse temporal scales during the music and French vowel tasks in widely distributed cortical regions. Conversely, very minimal decreases in complexity at fine scales and trends toward coarse-scale increases were displayed after French training during the tasks. Spectral analysis failed to distinguish between training types and found overall theta (3.5-7.5 Hz) power increases after all training forms, with spatially fewer decreases in power at higher frequencies (>10 Hz). These findings demonstrate that musical training increased diversity of brain network states to support domain-specific music skill acquisition and music-to-language transfer effects. PMID:27243611

  17. Energy efficiency enhancements for semiconductors, communications, sensors and software achieved in cool silicon cluster project

    NASA Astrophysics Data System (ADS)

    Ellinger, Frank; Mikolajick, Thomas; Fettweis, Gerhard; Hentschel, Dieter; Kolodinski, Sabine; Warnecke, Helmut; Reppe, Thomas; Tzschoppe, Christoph; Dohl, Jan; Carta, Corrado; Fritsche, David; Tretter, Gregor; Wiatr, Maciej; Detlef Kronholz, Stefan; Mikalo, Ricardo Pablo; Heinrich, Harald; Paulo, Robert; Wolf, Robert; Hübner, Johannes; Waltsgott, Johannes; Meißner, Klaus; Richter, Robert; Michler, Oliver; Bausinger, Markus; Mehlich, Heiko; Hahmann, Martin; Möller, Henning; Wiemer, Maik; Holland, Hans-Jürgen; Gärtner, Roberto; Schubert, Stefan; Richter, Alexander; Strobel, Axel; Fehske, Albrecht; Cech, Sebastian; Aßmann, Uwe; Pawlak, Andreas; Schröter, Michael; Finger, Wolfgang; Schumann, Stefan; Höppner, Sebastian; Walter, Dennis; Eisenreich, Holger; Schüffny, René

    2013-07-01

    An overview about the German cluster project Cool Silicon aiming at increasing the energy efficiency for semiconductors, communications, sensors and software is presented. Examples for achievements are: 1000 times reduced gate leakage in transistors using high-fc (HKMG) materials compared to conventional poly-gate (SiON) devices at the same technology node; 700 V transistors integrated in standard 0.35 μm CMOS; solar cell efficiencies above 19% at < 200 W/m2 irradiation; 0.99 power factor, 87% efficiency and 0.088 distortion factor for dc supplies; 1 ns synchronization resolution via Ethernet; database accelerators allowing 85% energy savings for servers; adaptive software yielding energy reduction of 73% for e-Commerce applications; processors and corresponding data links with 40% and 70% energy savings, respectively, by adaption of clock frequency and supply voltage in less than 20 ns; clock generator chip with tunable frequency from 83-666 MHz and 0.62-1.6 mW dc power; 90 Gb/s on-chip link over 6 mm and efficiency of 174 fJ/mm; dynamic biasing system doubling efficiency in power amplifiers; 60 GHz BiCMOS frontends with dc power to bandwidth ratio of 0.17 mW/MHz; driver assistance systems reducing energy consumption by 10% in cars Contribution to the Topical Issue “International Semiconductor Conference Dresden-Grenoble - ISCDG 2012”, Edited by Gérard Ghibaudo, Francis Balestra and Simon Deleonibus.

  18. A Simple E-Mail Mechanism To Enhance Reflection, Independence, and Communication in Young Researchers

    PubMed Central

    Lom, Barbara

    2006-01-01

    Providing undergraduates with mentored research experiences is a critical component of contemporary undergraduate science education. Although the benefits of undergraduate research experiences are apparent, the methods for mentoring young scientists as they first begin navigating the research lab environment are reinvented in labs all over the world. Students come to research labs with varied skills, motivations, needs, and dispositions, placing each student and mentor in a unique relationship. How can we help students become aware of their own intellectual progress? How can we encourage our students to take initial steps toward independent investigation? When do we need to let setbacks happen? We have developed a simple mechanism to address these common problems. Each week, students in our labs answer a series of five questions by e-mail that improve lab communication and help students develop into mature scientists without taxing an instructor's already busy schedule. Our observations, experiences, and student feedback indicate that this approach is a useful mechanism to help faculty who mentor young scientists in the research lab. PMID:17146038

  19. Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture

    PubMed Central

    Pollmann, Mary-Ann; Shao, Qing; Laird, Dale W; Sandig, Martin

    2005-01-01

    Introduction Metastasis involves the emigration of tumor cells through the vascular endothelium, a process also known as diapedesis. The molecular mechanisms regulating tumor cell diapedesis are poorly understood, but may involve heterocellular gap junctional intercellular communication (GJIC) between tumor cells and endothelial cells. Method To test this hypothesis we expressed connexin 43 (Cx43) in GJIC-deficient mammary epithelial tumor cells (HBL100) and examined their ability to form gap junctions, establish heterocellular GJIC and migrate through monolayers of human microvascular endothelial cells (HMVEC) grown on matrigel-coated coverslips. Results HBL100 cells expressing Cx43 formed functional heterocellular gap junctions with HMVEC monolayers within 30 minutes. In addition, immunocytochemistry revealed Cx43 localized to contact sites between Cx43 expressing tumor cells and endothelial cells. Quantitative analysis of diapedesis revealed a two-fold increase in diapedesis of Cx43 expressing cells compared to empty vector control cells. The expression of a functionally inactive Cx43 chimeric protein in HBL100 cells failed to increase migration efficiency, suggesting that the observed up-regulation of diapedesis in Cx43 expressing cells required heterocellular GJIC. This finding is further supported by the observation that blocking homocellular and heterocellular GJIC with carbenoxolone in co-cultures also reduced diapedesis of Cx43 expressing HBL100 tumor cells. Conclusion Collectively, our results suggest that heterocellular GJIC between breast tumor cells and endothelial cells may be an important regulatory step during metastasis. PMID:15987459

  20. Potential Use of the Australian Satellite Communications System for School of the Air and Enhanced Educational Services. Report Prepared for the Commonwealth/State Advisory Committee on the Educational Use of Communications Technology.

    ERIC Educational Resources Information Center

    Davies, N. G.; Gillam, J. A.

    This report considers the potential for the use of the Australian Communications Satellite System (ACSS) for the Australian Schools of the Air (SOTAs) and the delivery of enhanced educational services, and develops the concept of all SOTAs operating through one transponder in a national beam. An evolutionary introduction of satellite transmission…

  1. A Study of Umbilical Communication Interface of Simulator Kernel to Enhance Visibility and Controllability

    NASA Astrophysics Data System (ADS)

    Koo, Cheol Hea; Lee, Hoon Hee; Moon, Sung Tae; Han, Sang Hyuck; Ju, Gwang Hyeok

    2013-08-01

    In aerospace research and practical development area, increasing the usage of simulation in software development, component design and system operation has been maintained and the increasing speed getting faster. This phenomenon can be found from the easiness of handling of simulation and the powerfulness of the output from the simulation. Simulation brings lots of benefit from the several characteristics of it as following, - easy to handle ; it is never broken or damaged by mistake - never wear out ; it is never getting old - cost effective ; once it is built, it can be distributed over 100 ~ 1000 people GenSim (Generic Simulator) which is developing by KARI and compatible with ESA SMP standard provides such a simulation platform to support flight software validation and mission operation verification. User interface of GenSim is shown in Figure 1 [1,2]. As shown in Figure 1, as most simulation platform typically has, GenSim has GRD (Graphical Display) and AND (Alpha Numeric Display). But frequently more complex and powerful handling of the simulated data is required at the actual system validation for example mission operation. In Figure 2, system simulation result of COMS (Communication, Ocean, and Meteorological Satellite, launched at June 28 2008) is being drawn by Celestia 3D program. In this case, the needed data from Celestia is given by one of the simulation model resident in system simulator through UDP network connection in this case. But the requirement of displaying format, data size, and communication rate is variable so developer has to manage the connection protocol manually at each time and each case. It brings a chaos in the simulation model design and development, also to the performance issue at last. Performance issue is happen when the required data magnitude is higher than the capacity of simulation kernel to process the required data safely. The problem is that the sending data to a visualization tool such as celestia is given by a

  2. Programmable synaptic devices for electronic neural nets

    NASA Technical Reports Server (NTRS)

    Moopenn, A.; Thakoor, A. P.

    1990-01-01

    The architecture, design, and operational characteristics of custom VLSI and thin film synaptic devices are described. The devices include CMOS-based synaptic chips containing 1024 reprogrammable synapses with a 6-bit dynamic range, and nonvolatile, write-once, binary synaptic arrays based on memory switching in hydrogenated amorphous silicon films. Their suitability for embodiment of fully parallel and analog neural hardware is discussed. Specifically, a neural network solution to an assignment problem of combinatorial global optimization, implemented in fully parallel hardware using the synaptic chips, is described. The network's ability to provide optimal and near optimal solutions over a time scale of few neuron time constants has been demonstrated and suggests a speedup improvement of several orders of magnitude over conventional search methods.

  3. Autophagy in synaptic development, function, and pathology.

    PubMed

    Shen, Dan-Na; Zhang, Li-Hui; Wei, Er-Qing; Yang, Yi

    2015-08-01

    In the nervous system, neurons contact each other to form neuronal circuits and drive behavior, relying heavily on synaptic connections. The proper development and growth of synapses allows functional transmission of electrical information between neurons or between neurons and muscle fibers. Defects in synapse-formation or development lead to many diseases. Autophagy, a major determinant of protein turnover, is an essential process that takes place in developing synapses. During the induction of autophagy, proteins and cytoplasmic components are encapsulated in autophagosomes, which fuse with lysosomes to form autolysosomes. The cargoes are subsequently degraded and recycled. However, aberrant autophagic activity may lead to synaptic dysfunction, which is a common pathological characteristic in several disorders. Here, we review the current understanding of autophagy in regulating synaptic development and function. In addition, autophagy-related synaptic dysfunction in human diseases is also summarized. PMID:26139541

  4. Communication: Enhanced chemical reactivity of graphene on a Ni(111) substrate.

    PubMed

    Ambrosetti, Alberto; Silvestrelli, Pier Luigi

    2016-03-21

    Due to the unique combination of structural, mechanical, and transport properties, graphene has emerged as an exceptional candidate for catalysis applications. The low chemical reactivity caused by sp(2) hybridization and strongly delocalized π electrons, however, represents a main challenge for straightforward use of graphene in its pristine, free-standing form. Following recent experimental indications, we show that due to charge hybridization, a Ni(111) substrate can enhance the chemical reactivity of graphene, as exemplified by the interaction with the CO molecule. While CO only physisorbs on free-standing graphene, chemisorption of CO involving formation of ethylene dione complexes is predicted in Ni(111)-graphene. Higher chemical reactivity is also suggested in the case of oxidized graphene, opening the way to a simple and efficient control of graphene chemical properties, devoid of complex defect patterning or active metallic structures deposition. PMID:27004853

  5. Enhanced hybrid asymmetrically clipped orthogonal frequency division multiplexing for optical wireless communications

    NASA Astrophysics Data System (ADS)

    Guan, Rui; Huang, Nuo; Wang, Jin-Yuan; Wang, Houyu; Chen, Ming

    2016-05-01

    This paper presents an enhanced hybrid asymmetrically clipped optical orthogonal frequency division multiplexing (EHACO-OFDM) scheme, which benefits from the simultaneous transmission of ACO-OFDM, pulse-amplitude-modulated discrete multitone modulation, and direct-current-biased optical orthogonal frequency division multiplexing (DCO-OFDM). Since the entire available bandwidth is utilized for data modulation, this scheme can achieve higher spectral efficiency than HACO-OFDM and ACO-OFDM. Moreover, as a smaller DC bias is introduced in our scheme, it is more power efficient than asymmetrically clipped DC-biased optical OFDM (ADO-OFDM) and DCO-OFDM. A modified receiver is also designed for this system, taking advantage of an iterative algorithm and a pairwise averaging. It has been shown by simulation that our three-path simultaneous transmission scheme can surpass the existing mixed OFDM-based schemes at high data rates. In addition, compared with the noniterative receiver, the modified receiver exhibits significant gains.

  6. Communication: Conductivity enhancement in plastic-crystalline solid-state electrolytes

    NASA Astrophysics Data System (ADS)

    Geirhos, K.; Lunkenheimer, P.; Michl, M.; Reuter, D.; Loidl, A.

    2015-08-01

    Finding new ionic conductors that enable significant advancements in the development of energy-storage devices is a challenging goal of current material science. Aside of material classes as ionic liquids or amorphous ion conductors, the so-called plastic crystals (PCs) have been shown to be good candidates combining high conductivity and favorable mechanical properties. PCs are formed by molecules whose orientational degrees of freedom still fluctuate despite the material exhibits a well-defined crystalline lattice. In the present work, we show that the conductivity of Li+ ions in succinonitrile, the most prominent molecular PC electrolyte, can be enhanced by several decades when replacing part of the molecules in the crystalline lattice by larger ones. Dielectric spectroscopy reveals that this is accompanied by a stronger coupling of ionic and reorientational motions. These findings, which can be understood in terms of an optimized "revolving door" mechanism, open a new path towards the development of better solid-state electrolytes.

  7. Rate-constrained source separation for speech enhancement in wireless-communicated binaural hearing aids

    NASA Astrophysics Data System (ADS)

    Ayllón, David; Gil-Pita, Roberto; Rosa-Zurera, Manuel

    2013-12-01

    A recent trend in hearing aids is the connection of the left and right devices to collaborate between them. Binaural systems can provide natural binaural hearing and support the improvement of speech intelligibility in noise, but they require data transmission between both devices, which increases the power consumption. This paper presents a novel sound source separation algorithm for binaural speech enhancement based on supervised machine learning and time-frequency masking. The system is designed considering the power restrictions in hearing aids, constraining both the computational cost of the algorithm and the transmission bit rate. The transmission schema is optimized using a tailored evolutionary algorithm that assigns a different number of bits to each frequency band. The proposed algorithm requires less than 10% of the available computational resources for signal processing and obtains good separation performance using bit rates lower than 64 kbps.

  8. Communication: Enhanced chemical reactivity of graphene on a Ni(111) substrate

    NASA Astrophysics Data System (ADS)

    Ambrosetti, Alberto; Silvestrelli, Pier Luigi

    2016-03-01

    Due to the unique combination of structural, mechanical, and transport properties, graphene has emerged as an exceptional candidate for catalysis applications. The low chemical reactivity caused by sp2 hybridization and strongly delocalized π electrons, however, represents a main challenge for straightforward use of graphene in its pristine, free-standing form. Following recent experimental indications, we show that due to charge hybridization, a Ni(111) substrate can enhance the chemical reactivity of graphene, as exemplified by the interaction with the CO molecule. While CO only physisorbs on free-standing graphene, chemisorption of CO involving formation of ethylene dione complexes is predicted in Ni(111)-graphene. Higher chemical reactivity is also suggested in the case of oxidized graphene, opening the way to a simple and efficient control of graphene chemical properties, devoid of complex defect patterning or active metallic structures deposition.

  9. Plant-Microbe Communication Enhances Auxin Biosynthesis by a Root-Associated Bacterium, Bacillus amyloliquefaciens SQR9.

    PubMed

    Liu, Yunpeng; Chen, Lin; Zhang, Nan; Li, Zunfeng; Zhang, Guishan; Xu, Yu; Shen, Qirong; Zhang, Ruifu

    2016-04-01

    Mechanisms by which beneficial rhizobacteria promote plant growth include tryptophan-dependent indole-3-acetic acid (IAA) synthesis. The abundance of tryptophan in the rhizosphere, however, may influence the level of benefit provided by IAA-producing rhizobacteria. This study examined the cucumber-Bacillus amyloliquefaciens SQR9 system and found that SQR9, a bacterium previously shown to enhance the growth of cucumber, increased root secretion of tryptophan by three- to fourfold. Using a split-root system, SQR9 colonization of roots in one chamber not only increased tryptophan secretion from the noninoculated roots but also increased the expression of the cucumber tryptophan transport gene but not the anthranilate synthesis gene in those roots. The increased tryptophan in isolated rhizosphere exudates was sufficient to support increased IAA production by SQR9. Moreover, SQR9 colonization of roots in one chamber in the split-root system resulted in sufficient tryptophan production by the other roots to upregulate SQR9 IAA biosynthesis genes, including a 27-fold increase in the indole-3-acetonitrilase gene yhcX during subsequent colonization of those roots. Deletion of yhcX eliminated SQR9-mediated increases in root surface area, likely by reducing IAA-stimulated lateral root growth. This study demonstrates a chemical dialogue between B. amyloliquefaciens and cucumber in which this communication contributes to bacteria-mediated plant-growth enhancement. PMID:26808445

  10. Fast Learning with Weak Synaptic Plasticity.

    PubMed

    Yger, Pierre; Stimberg, Marcel; Brette, Romain

    2015-09-30

    New sensory stimuli can be learned with a single or a few presentations. Similarly, the responses of cortical neurons to a stimulus have been shown to increase reliably after just a few repetitions. Long-term memory is thought to be mediated by synaptic plasticity, but in vitro experiments in cortical cells typically show very small changes in synaptic strength after a pair of presynaptic and postsynaptic spikes. Thus, it is traditionally thought that fast learning requires stronger synaptic changes, possibly because of neuromodulation. Here we show theoretically that weak synaptic plasticity can, in fact, support fast learning, because of the large number of synapses N onto a cortical neuron. In the fluctuation-driven regime characteristic of cortical neurons in vivo, the size of membrane potential fluctuations grows only as √N, whereas a single output spike leads to potentiation of a number of synapses proportional to N. Therefore, the relative effect of a single spike on synaptic potentiation grows as √N. This leverage effect requires precise spike timing. Thus, the large number of synapses onto cortical neurons allows fast learning with very small synaptic changes. Significance statement: Long-term memory is thought to rely on the strengthening of coactive synapses. This physiological mechanism is generally considered to be very gradual, and yet new sensory stimuli can be learned with just a few presentations. Here we show theoretically that this apparent paradox can be solved when there is a tight balance between excitatory and inhibitory input. In this case, small synaptic modifications applied to the many synapses onto a given neuron disrupt that balance and produce a large effect even for modifications induced by a single stimulus. This effect makes fast learning possible with small synaptic changes and reconciles physiological and behavioral observations. PMID:26424883

  11. Nonconserved Ca2+/Calmodulin Binding Sites in Munc13s Differentially Control Synaptic Short-Term Plasticity

    PubMed Central

    Lipstein, Noa; Schaks, Sabine; Dimova, Kalina; Kalkhof, Stefan; Ihling, Christian; Kölbel, Knut; Ashery, Uri; Rhee, JeongSeop; Brose, Nils

    2012-01-01

    Munc13s are presynaptic proteins that mediate synaptic vesicle priming and thereby control the size of the readily releasable pool of vesicles. During high synaptic activity, Munc13-1 and its closely related homolog, ubMunc13-2, bind Ca2+/calmodulin, resulting in enhanced priming activity and in changes of short-term synaptic plasticity characteristics. Here, we studied whether bMunc13-2 and Munc13-3, two remote isoforms of Munc13-1 with a neuronal subtype-specific expression pattern, mediate synaptic vesicle priming and regulate short-term synaptic plasticity in a Ca2+/calmodulin-dependent manner. We identified a single functional Ca2+/calmodulin binding site in these isoforms and provide structural evidence that all Munc13s employ a common mode of interaction with calmodulin despite the lack of sequence homology between their Ca2+/calmodulin binding sites. Electrophysiological analysis showed that, during high-frequency activity, Ca2+/calmodulin binding positively regulates the priming activity of bMunc13-2 and Munc13-3, resulting in an increase in the size of the readily releasable pool of vesicles and subsequently in strong short-term synaptic enhancement of neurotransmission. We conclude that Ca2+/calmodulin-dependent regulation of priming activity is structurally and functionally conserved in all Munc13 proteins, and that the composition of Munc13 isoforms in a neuron differentially controls its short-term synaptic plasticity characteristics. PMID:22966208

  12. Space-Data Routers: Enhancing Deep Space communications for scientific data transmission and exploitation from Mars through Space Internetworking

    NASA Astrophysics Data System (ADS)

    Sykioti, Olga; Daglis, Ioannis; Rontogiannis, Athanasios; Tsaoussidis, Vassilis; Diamantopoulos, Sotirios

    2014-05-01

    Dissemination and exploitation of data from Deep Space missions, such as planetary missions, face two major impediments: limited access capabilities due to narrow connectivity window via satellites (thus, resulting to confined scientific capacity) and lack of sufficient communication and dissemination mechanisms between deep space missions such the current missions to Mars, space data receiving centers, space-data collection centers and the end-user community. Although large quantities of data have to be transferred from deep space to the operation centers and then to the academic foundations and research centers, due to the aforementioned impediments more and more stored space data volumes remain unexploited, until they become obsolete or useless and are consequently removed. In the near future, these constraints on space and ground segment resources will rapidly increase due to the launch of new missions. The Space-Data Routers (SDR) project aims into boosting collaboration and competitiveness between the European Space Agency, the European Space Industry and the European Academic Institutions towards meeting these new challenges through Space Internetworking. Space internetworking gradually replaces or assists traditional telecommunication protocols. Future deep space operations, such as those to Mars, are scheduled to be more dynamic and flexible; many of the procedures, which are now human-operated, will become automated, interoperable and collaborative. As a consequence, space internetworking will bring a revolution in space communications. For this purpose, one of the main scientific objectives of the project is, through the examination of a specific scenario, the enhanced transmission and dissemination of Deep Space data from Mars, through unified communication channels. Specifically, the scenario involves enhanced data transmission acquired by the OMEGA sensor on-board ESA's Mars Express satellite. We consider two separate issues considering the

  13. Enhancing Communication of Climate Impacts Assessments: Examples of Local Stories, Animations and Video.

    NASA Astrophysics Data System (ADS)

    Fitzpatrick, M. F.; Grigholm, B. O.

    2014-12-01

    Comprehensive climate impacts assessments are important vehicles for conveying salient information to the public and policy makers. However, over the last few decades communication of this important information has been hampered for a number of reasons. Firstly, we have a rapidly changing social media landscape, where there are fewer opportunities for in-depth treatment of issues. To compete in this arena, climate information needs to be packaged in sound bites, and much of the nuance and complexity may be lost. Secondly, scientific literacy among the general U.S. population is not particularly high, which creates a barrier to understanding and limits the audiences that can be reached. Thirdly, climate science has been undermined by misinformation over many years often funded by fossil fuel interests. While this latter obstacle is clearly diminishing - largely in the face of evidence from the undeniable climate impacts that are already being seen by communities - there has been much confusion generated to date. Despite the fact that 97% of active climate scientists agree that the planet is warming as a result of human greenhouse gas emission, only 42% of the U.S. population agrees (Pew Research, 2013). In the face of these challenges, much of the work that the Union of Concerned Scientists does to translate climate impacts assessments has shifted to visuals, animations, and videos that people can relate to and connect with more readily. In this session we will share some of the general design features, discuss target audiences, and outline production limitations of several local stories involving videos and animations, as well as present some recent infographics. One example of this work are case studies that focus on sea level rise and involve a local personality who can speak to climate impacts at the community level. We understand the power of visual images and stories in creating messages that stick, and we use this in designing animations that explain the

  14. Wake-up-word speech recognition application for first responder communication enhancement

    NASA Astrophysics Data System (ADS)

    Këpuska, Veton; Breitfeller, Jason

    2006-05-01

    Speech Recognition systems, historically, have proven to be cumbersome and insufficiently accurate for a range of applications. The ultimate goal of our proposed technology is to fundamentally change the way current Speech Recognition (SR) systems interact with humans and develop an application that is extremely hardware efficient. Accurate SR and reasonable hardware requirements will afford the average first responder officer, e.g., police officer, a true break-through technology that will change the way an officer performs his duties. The presented technology provides a cutting-edge solution for human-machine interaction through the utilization of a properly solved Wake-Up-Word (WUW) SR problem. This paradigm-shift provides the basis for development of SR systems with truly "Voice Activated" capabilities, impacting all SR based technologies and the way in which humans interact with computers. This shift is a radical departure from the current "push-to-talk" paradigm currently applied to all speech-to-text or speech-recognition applications. To be able to achieve this goal, a significantly more accurate pattern classification and scoring technique is required, which in turn provides SR systems enhanced performance for correct recognition (i.e., minimization of false rejection) as well as correct rejection (i.e., minimization of false acceptance). A revolutionary and innovative classification and scoring technique is used that is a significant enhancement over an earlier method presented in reference [1]. The solution in reference [1] has been demonstrated to meet the stringent requirements of the WUW-SR task. Advanced solution of [1] is a novel technique that is model and algorithm independent. Therefore, it could be used to significantly improve performance of existing recognition algorithms and systems. Reduction of error rates of over 40% are commonly observed for both false rejections and false acceptance. In this paper the architecture of the WUW-SR based

  15. Augmenting the spectral efficiency of enhanced PAM-DMT-based optical wireless communications.

    PubMed

    Islim, Mohamed Sufyan; Haas, Harald

    2016-05-30

    The energy efficiency of pulse-amplitude-modulated discrete multitone modulation (PAM-DMT) decreases as the modulation order of M-PAM modulation increases. Enhanced PAM-DMT (ePAM-DMT) was proposed as a solution to the reduced energy efficiency of PAM-DMT. This was achieved by allowing multiple streams of PAM-DMT to be superimposed and successively demodulated at the receiver side. In order to maintain a distortion-free unipolar ePAM-DMT system, the multiple time-domain PAM-DMT streams are required to be aligned. However, aligning the antisymmetry in ePAM-DMT is complex and results in efficiency losses. In this paper, a novel simplified method to apply the superposition modulation on M-PAM modulated discrete multitone (DMT) is introduced. Contrary to ePAM-DMT, the signal generation of the proposed system, termed augmented spectral efficiency discrete multitone (ASE-DMT), occurs in the frequency domain. This results in an improved spectral and energy efficiency. The analytical bit error rate (BER) performance bound of the proposed system is derived and compared with Monte-Carlo simulations. The system performance is shown to offer significant electrical and optical energy savings compared with ePAM-DMT and DC-biased optical orthogonal frequency division multiplexing (DCO-OFDM). PMID:27410116

  16. Activity-dependent synaptic plasticity modulates the critical phase of brain development.

    PubMed

    Chaudhury, Sraboni; Sharma, Vikram; Kumar, Vivek; Nag, Tapas C; Wadhwa, Shashi

    2016-04-01

    Plasticity or neuronal plasticity is a unique and adaptive feature of nervous system which allows neurons to reorganize their interactions in response to an intrinsic or extrinsic stimulation and shapes the formation and maintenance of a functional neuronal circuit. Synaptic plasticity is the most important form of neural plasticity and plays critical role during the development allowing the formation of precise neural connectivity via the process of pruning. In the sensory systems-auditory and visual, this process is heavily dependent on the external cues perceived during the development. Environmental enrichment paradigms in an activity-dependent manner result in early maturation of the synapses and more efficient trans-synaptic signaling or communication flow. This has been extensively observed in the avian auditory system. On the other hand, stimuli results in negative effect can cause alterations in the synaptic connectivity and strength resulting in various developmental brain disorders including autism, fragile X syndrome and rett syndrome. In this review we discuss the role of different forms of activity (spontaneous or environmental) during the development of the nervous system in modifying synaptic plasticity necessary for shaping the adult brain. Also, we try to explore various factors (molecular, genetic and epigenetic) involved in altering the synaptic plasticity in positive and negative way. PMID:26515724

  17. An event-based neural network architecture with an asynchronous programmable synaptic memory.

    PubMed

    Moradi, Saber; Indiveri, Giacomo

    2014-02-01

    We present a hybrid analog/digital very large scale integration (VLSI) implementation of a spiking neural network with programmable synaptic weights. The synaptic weight values are stored in an asynchronous Static Random Access Memory (SRAM) module, which is interfaced to a fast current-mode event-driven DAC for producing synaptic currents with the appropriate amplitude values. These currents are further integrated by current-mode integrator synapses to produce biophysically realistic temporal dynamics. The synapse output currents are then integrated by compact and efficient integrate and fire silicon neuron circuits with spike-frequency adaptation and adjustable refractory period and spike-reset voltage settings. The fabricated chip comprises a total of 32 × 32 SRAM cells, 4 × 32 synapse circuits and 32 × 1 silicon neurons. It acts as a transceiver, receiving asynchronous events in input, performing neural computation with hybrid analog/digital circuits on the input spikes, and eventually producing digital asynchronous events in output. Input, output, and synaptic weight values are transmitted to/from the chip using a common communication protocol based on the Address Event Representation (AER). Using this representation it is possible to interface the device to a workstation or a micro-controller and explore the effect of different types of Spike-Timing Dependent Plasticity (STDP) learning algorithms for updating the synaptic weights values in the SRAM module. We present experimental results demonstrating the correct operation of all the circuits present on the chip. PMID:24681923

  18. Spike timing-dependent serotonergic neuromodulation of synaptic strength intrinsic to a central pattern generator circuit.

    PubMed

    Sakurai, Akira; Katz, Paul S

    2003-11-26

    Neuromodulation is often thought to have a static, gain-setting function in neural circuits. Here we report a counter example: the neuromodulatory effect of a serotonergic neuron is dependent on the interval between its spikes and those of the neuron being modulated. The serotonergic dorsal swim interneurons (DSIs) are members of the escape swim central pattern generator (CPG) in the mollusk Tritonia diomedea. DSI spike trains heterosynaptically enhanced synaptic potentials evoked by another CPG neuron, ventral swim interneuron B (VSI-B), when VSI-B action potentials occurred within 10 sec of a DSI spike train; however, if VSI-B was stimulated 20-120 sec after DSI, then the amplitude of VSI-B synaptic potentials decreased. Consistent with this, VSI-B-evoked synaptic currents exhibited a temporally biphasic and bidirectional change in amplitude after DSI stimulation. Both the DSI-evoked enhancement and decrement were occluded by serotonin and blocked by the serotonin receptor antagonist methysergide, suggesting that both phases are mediated by serotonin. In most preparations, however, bath-applied serotonin caused only a sustained enhancement of VSI-B synaptic strength. The heterosynaptic modulation interacted with short-term homosynaptic plasticity: DSI-evoked depression was offset by VSI-B homosynaptic facilitation. This caused a complicated temporal pattern of neuromodulation when DSI and VSI-B were stimulated to fire in alternating bursts to mimic the natural motor pattern: DSI strongly enhanced summated VSI-B synaptic potentials and suppressed single synaptic potentials after the cessation of the artificial motor pattern. Thus, spike timing-dependent serotonergic neuromodulatory actions can impart temporal information that may be relevant to the operation of the CPG. PMID:14645466

  19. A role for synaptic plasticity in the adolescent development of executive function

    PubMed Central

    Selemon, L D

    2013-01-01

    Adolescent brain maturation is characterized by the emergence of executive function mediated by the prefrontal cortex, e.g., goal planning, inhibition of impulsive behavior and set shifting. Synaptic pruning of excitatory contacts is the signature morphologic event of late brain maturation during adolescence. Mounting evidence suggests that glutamate receptor-mediated synaptic plasticity, in particular long term depression (LTD), is important for elimination of synaptic contacts in brain development. This review examines the possibility (1) that LTD mechanisms are enhanced in the prefrontal cortex during adolescence due to ongoing synaptic pruning in this late developing cortex and (2) that enhanced synaptic plasticity in the prefrontal cortex represents a key molecular substrate underlying the critical period for maturation of executive function. Molecular sites of interaction between environmental factors, such as alcohol and stress, and glutamate receptor mediated plasticity are considered. The accentuated negative impact of these factors during adolescence may be due in part to interference with LTD mechanisms that refine prefrontal cortical circuitry and when disrupted derail normal maturation of executive function. Diminished prefrontal cortical control over risk-taking behavior could further exacerbate negative outcomes associated with these behaviors, as for example addiction and depression. Greater insight into the neurobiology of the adolescent brain is needed to fully understand the molecular basis for heightened vulnerability during adolescence to the injurious effects of substance abuse and stress. PMID:23462989

  20. Nitric oxide signaling is recruited as a compensatory mechanism for sustaining synaptic plasticity in Alzheimer's disease mice.

    PubMed

    Chakroborty, Shreaya; Kim, Joyce; Schneider, Corinne; West, Anthony R; Stutzmann, Grace E

    2015-04-29

    Synaptic plasticity deficits are increasingly recognized as causing the memory impairments which define Alzheimer's disease (AD). In AD mouse models, evidence of abnormal synaptic function is present before the onset of cognitive deficits, and presents as increased synaptic depression revealed only when synaptic homeostasis is challenged, such as with suppression of ryanodine receptor (RyR)-evoked calcium signaling. Otherwise, at early disease stages, the synaptic physiology phenotype appears normal. This suggests compensatory mechanisms are recruited to maintain a functionally normal net output of the hippocampal circuit. A candidate calcium-regulated synaptic modulator is nitric oxide (NO), which acts presynaptically to boost vesicle release and glutamatergic transmission. Here we tested whether there is a feedforward cycle between the increased RyR calcium release seen in presymptomatic AD mice and aberrant NO signaling which augments synaptic plasticity. Using a combination of electrophysiological approaches, two-photon calcium imaging, and protein biochemistry in hippocampal tissue from presymptomatic 3xTg-AD and NonTg mice, we show that blocking NO synthesis results in markedly augmented synaptic depression mediated through presynaptic mechanisms in 3xTg-AD mice. Additionally, blocking NO reduces the augmented synaptically evoked dendritic calcium release mediated by enhanced RyR calcium release. This is accompanied by increased nNOS levels in the AD mice and is reversed upon normalization of RyR-evoked calcium release with chronic dantrolene treatment. Thus, recruitment of NO is serving a compensatory role to boost synaptic transmission and plasticity during early AD stages. However, NO's dual role in neuroprotection and neurodegeneration may convert to maladaptive functions as the disease progresses. PMID:25926464

  1. Long-Term Relationships between Synaptic Tenacity, Synaptic Remodeling, and Network Activity

    PubMed Central

    Minerbi, Amir; Kahana, Roni; Goldfeld, Larissa; Kaufman, Maya; Marom, Shimon; Ziv, Noam E.

    2009-01-01

    Synaptic plasticity is widely believed to constitute a key mechanism for modifying functional properties of neuronal networks. This belief implicitly implies, however, that synapses, when not driven to change their characteristics by physiologically relevant stimuli, will maintain these characteristics over time. How tenacious are synapses over behaviorally relevant time scales? To begin to address this question, we developed a system for continuously imaging the structural dynamics of individual synapses over many days, while recording network activity in the same preparations. We found that in spontaneously active networks, distributions of synaptic sizes were generally stable over days. Following individual synapses revealed, however, that the apparently static distributions were actually steady states of synapses exhibiting continual and extensive remodeling. In active networks, large synapses tended to grow smaller, whereas small synapses tended to grow larger, mainly during periods of particularly synchronous activity. Suppression of network activity only mildly affected the magnitude of synaptic remodeling, but dependence on synaptic size was lost, leading to the broadening of synaptic size distributions and increases in mean synaptic size. From the perspective of individual neurons, activity drove changes in the relative sizes of their excitatory inputs, but such changes continued, albeit at lower rates, even when network activity was blocked. Our findings show that activity strongly drives synaptic remodeling, but they also show that significant remodeling occurs spontaneously. Whereas such spontaneous remodeling provides an explanation for “synaptic homeostasis” like processes, it also raises significant questions concerning the reliability of individual synapses as sites for persistently modifying network function. PMID:19554080

  2. Synaptic adhesion molecule IgSF11 regulates synaptic transmission and plasticity

    PubMed Central

    Shin, Hyewon; van Riesen, Christoph; Whitcomb, Daniel; Warburton, Julia M.; Jo, Jihoon; Kim, Doyoun; Kim, Sun Gyun; Um, Seung Min; Kwon, Seok-kyu; Kim, Myoung-Hwan; Roh, Junyeop Daniel; Woo, Jooyeon; Jun, Heejung; Lee, Dongmin; Mah, Won; Kim, Hyun; Kaang, Bong-Kiun; Cho, Kwangwook; Rhee, Jeong-Seop; Choquet, Daniel; Kim, Eunjoon

    2016-01-01

    Summary Synaptic adhesion molecules regulate synapse development and plasticity through mechanisms including trans-synaptic adhesion and recruitment of diverse synaptic proteins. We report here that the immunoglobulin superfamily member 11 (IgSF11), a homophilic adhesion molecule preferentially expressed in the brain, is a novel and dual-binding partner of the postsynaptic scaffolding protein PSD-95 and AMPAR glutamate receptors (AMPARs). IgSF11 requires PSD-95 binding for its excitatory synaptic localization. In addition, IgSF11 stabilizes synaptic AMPARs, as shown by IgSF11 knockdown-induced suppression of AMPAR-mediated synaptic transmission and increased surface mobility of AMPARs, measured by high-throughput, single-molecule tracking. IgSF11 deletion in mice leads to suppression of AMPAR-mediated synaptic transmission in the dentate gyrus and long-term potentiation in the CA1 region of the hippocampus. IgSF11 does not regulate the functional characteristics of AMPARs, including desensitization, deactivation, or recovery. These results suggest that IgSF11 regulates excitatory synaptic transmission and plasticity through its tripartite interactions with PSD-95 and AMPARs. PMID:26595655

  3. Diacylglycerol Kinases in the Coordination of Synaptic Plasticity

    PubMed Central

    Lee, Dongwon; Kim, Eunjoon; Tanaka-Yamamoto, Keiko

    2016-01-01

    Synaptic plasticity is activity-dependent modification of the efficacy of synaptic transmission. Although, detailed mechanisms underlying synaptic plasticity are diverse and vary at different types of synapses, diacylglycerol (DAG)-associated signaling has been considered as an important regulator of many forms of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). Recent evidences indicate that DAG kinases (DGKs), which phosphorylate DAG to phosphatidic acid to terminate DAG signaling, are important regulators of LTP and LTD, as supported by the results from mice lacking specific DGK isoforms. This review will summarize these studies and discuss how specific DGK isoforms distinctly regulate different forms of synaptic plasticity at pre- and postsynaptic sites. In addition, we propose a general role of DGKs as coordinators of synaptic plasticity that make local synaptic environments more permissive for synaptic plasticity by regulating DAG concentration and interacting with other synaptic proteins.

  4. Burst Firing Enhances Neural Output Correlation

    PubMed Central

    Chan, Ho Ka; Yang, Dong-Ping; Zhou, Changsong; Nowotny, Thomas

    2016-01-01

    Neurons communicate and transmit information predominantly through spikes. Given that experimentally observed neural spike trains in a variety of brain areas can be highly correlated, it is important to investigate how neurons process correlated inputs. Most previous work in this area studied the problem of correlation transfer analytically by making significant simplifications on neural dynamics. Temporal correlation between inputs that arises from synaptic filtering, for instance, is often ignored when assuming that an input spike can at most generate one output spike. Through numerical simulations of a pair of leaky integrate-and-fire (LIF) neurons receiving correlated inputs, we demonstrate that neurons in the presence of synaptic filtering by slow synapses exhibit strong output correlations. We then show that burst firing plays a central role in enhancing output correlations, which can explain the above-mentioned observation because synaptic filtering induces bursting. The observed changes of correlations are mostly on a long time scale. Our results suggest that other features affecting the prevalence of neural burst firing in biological neurons, e.g., adaptive spiking mechanisms, may play an important role in modulating the overall level of correlations in neural networks. PMID:27242499

  5. Metabolic Turnover of Synaptic Proteins: Kinetics, Interdependencies and Implications for Synaptic Maintenance

    PubMed Central

    Cohen, Laurie D.; Zuchman, Rina; Sorokina, Oksana; Müller, Anke; Dieterich, Daniela C.; Armstrong, J. Douglas; Ziv, Tamar; Ziv, Noam E.

    2013-01-01

    Chemical synapses contain multitudes of proteins, which in common with all proteins, have finite lifetimes and therefore need to be continuously replaced. Given the huge numbers of synaptic connections typical neurons form, the demand to maintain the protein contents of these connections might be expected to place considerable metabolic demands on each neuron. Moreover, synaptic proteostasis might differ according to distance from global protein synthesis sites, the availability of distributed protein synthesis facilities, trafficking rates and synaptic protein dynamics. To date, the turnover kinetics of synaptic proteins have not been studied or analyzed systematically, and thus metabolic demands or the aforementioned relationships remain largely unknown. In the current study we used dynamic Stable Isotope Labeling with Amino acids in Cell culture (SILAC), mass spectrometry (MS), Fluorescent Non–Canonical Amino acid Tagging (FUNCAT), quantitative immunohistochemistry and bioinformatics to systematically measure the metabolic half-lives of hundreds of synaptic proteins, examine how these depend on their pre/postsynaptic affiliation or their association with particular molecular complexes, and assess the metabolic load of synaptic proteostasis. We found that nearly all synaptic proteins identified here exhibited half-lifetimes in the range of 2–5 days. Unexpectedly, metabolic turnover rates were not significantly different for presynaptic and postsynaptic proteins, or for proteins for which mRNAs are consistently found in dendrites. Some functionally or structurally related proteins exhibited very similar turnover rates, indicating that their biogenesis and degradation might be coupled, a possibility further supported by bioinformatics-based analyses. The relatively low turnover rates measured here (∼0.7% of synaptic protein content per hour) are in good agreement with imaging-based studies of synaptic protein trafficking, yet indicate that the metabolic load

  6. Metabolic turnover of synaptic proteins: kinetics, interdependencies and implications for synaptic maintenance.

    PubMed

    Cohen, Laurie D; Zuchman, Rina; Sorokina, Oksana; Müller, Anke; Dieterich, Daniela C; Armstrong, J Douglas; Ziv, Tamar; Ziv, Noam E

    2013-01-01

    Chemical synapses contain multitudes of proteins, which in common with all proteins, have finite lifetimes and therefore need to be continuously replaced. Given the huge numbers of synaptic connections typical neurons form, the demand to maintain the protein contents of these connections might be expected to place considerable metabolic demands on each neuron. Moreover, synaptic proteostasis might differ according to distance from global protein synthesis sites, the availability of distributed protein synthesis facilities, trafficking rates and synaptic protein dynamics. To date, the turnover kinetics of synaptic proteins have not been studied or analyzed systematically, and thus metabolic demands or the aforementioned relationships remain largely unknown. In the current study we used dynamic Stable Isotope Labeling with Amino acids in Cell culture (SILAC), mass spectrometry (MS), Fluorescent Non-Canonical Amino acid Tagging (FUNCAT), quantitative immunohistochemistry and bioinformatics to systematically measure the metabolic half-lives of hundreds of synaptic proteins, examine how these depend on their pre/postsynaptic affiliation or their association with particular molecular complexes, and assess the metabolic load of synaptic proteostasis. We found that nearly all synaptic proteins identified here exhibited half-lifetimes in the range of 2-5 days. Unexpectedly, metabolic turnover rates were not significantly different for presynaptic and postsynaptic proteins, or for proteins for which mRNAs are consistently found in dendrites. Some functionally or structurally related proteins exhibited very similar turnover rates, indicating that their biogenesis and degradation might be coupled, a possibility further supported by bioinformatics-based analyses. The relatively low turnover rates measured here (∼0.7% of synaptic protein content per hour) are in good agreement with imaging-based studies of synaptic protein trafficking, yet indicate that the metabolic load

  7. Emerging links between homeostatic synaptic plasticity and neurological disease

    PubMed Central

    Wondolowski, Joyce; Dickman, Dion

    2013-01-01

    Homeostatic signaling systems are ubiquitous forms of biological regulation, having been studied for hundreds of years in the context of diverse physiological processes including body temperature and osmotic balance. However, only recently has this concept been brought to the study of excitatory and inhibitory electrical activity that the nervous system uses to establish and maintain stable communication. Synapses are a primary target of neuronal regulation with a variety of studies over the past 15 years demonstrating that these cellular junctions are under bidirectional homeostatic control. Recent work from an array of diverse systems and approaches has revealed exciting new links between homeostatic synaptic plasticity and a variety of seemingly disparate neurological and psychiatric diseases. These include autism spectrum disorders, intellectual disabilities, schizophrenia, and Fragile X Syndrome. Although the molecular mechanisms through which defective homeostatic signaling may lead to disease pathogenesis remain unclear, rapid progress is likely to be made in the coming years using a powerful combination of genetic, imaging, electrophysiological, and next generation sequencing approaches. Importantly, understanding homeostatic synaptic plasticity at a cellular and molecular level may lead to developments in new therapeutic innovations to treat these diseases. In this review we will examine recent studies that demonstrate homeostatic control of postsynaptic protein translation, retrograde signaling, and presynaptic function that may contribute to the etiology of complex neurological and psychiatric diseases. PMID:24312013

  8. Information and Communication Technologies (ICT) as keys to the enhancement of public awareness about potential earth impacts

    NASA Astrophysics Data System (ADS)

    Usikov, Denis A.

    2013-09-01

    The 2007 Planetary Defense Conference recommends "to provide or enhance Internet sites to show how threats evolve and to illustrate possible action scenarios". Thereby, establishment of informational and communicational AsteroidAware web-site with the exact, authentic data about the past and the present of Earth's impact events will assist in achievement of positive results and progress in different directions on political, international, social and scientific levels. Expanded ICT's capabilities for popularization of planetary defense can help in resolving the problem of low public interest. The project's primary intent lies in popularizing the concept of planetary defenses and attracting attention to the potential dangers that threaten the Earth from outer space. The result of the efforts falling into the boundaries of this project would be an increased amount of social participation in the process of developing solutions for and increasing awareness of potential collisions between various astral bodies and the Earth. The project is also aimed at creating a foundation for the interaction between scientists and executives from around the world to facilitate international efforts of searching for fitting measures towards lowering threat levels and developing strategies revolving around united actions against potential threats.

  9. Mediators of a Coping and Communication-Enhancing Intervention and a Supportive Counseling Intervention among Women Diagnosed with Gynecological Cancers

    PubMed Central

    Manne, Sharon L.; Winkel, Gary; Rubin, Stephen; Edelson, Mitchell; Rosenblum, Norman; Bergman, Cynthia; Hernandez, Enrique; Carlson, John; Rocereto, Thomas

    2009-01-01

    We evaluated mechanisms of change for a Coping and Communication-enhancing Intervention (CCI) and Supportive Counseling (SC). We proposed that the effects of CCI on depressive symptoms would be mediated by psychological processes targeted by CCI: increased positive reappraisal, acceptance, planful problem solving, attempts to understand emotional reactions to cancer, increased emotional expression, increased seeking of emotional and instrumental support, and improved self-esteem. We hypothesized that the effects of SC on depressive symptoms would be mediated by the processes encouraged by SC: increasing the expression of emotions, attempts to understand emotional reactions to cancer, and self-esteem. Three hundred and fifty three women were randomized to CCI, SC, or a usual care control and completed measures at pre-intervention, 3, 6, and 9 months later. The effects of CCI were fully mediated by positive reappraisal, problem solving, and self-esteem, and partially mediated by emotional expression. The effects of SC were partially mediated by positive reappraisal. These findings provide support for hypothesized mediators for CCI. We were less able to identify of mediators for SC. Future research might benefit from identifying SC mediators. PMID:19045971

  10. Brain-Generated Estradiol Drives Long-Term Optimization of Auditory Coding to Enhance the Discrimination of Communication Signals

    PubMed Central

    Tremere, Liisa A.; Pinaud, Raphael

    2011-01-01

    Auditory processing and hearing-related pathologies are heavily influenced by steroid hormones in a variety of vertebrate species including humans. The hormone estradiol has been recently shown to directly modulate the gain of central auditory neurons, in real-time, by controlling the strength of inhibitory transmission via a non-genomic mechanism. The functional relevance of this modulation, however, remains unknown. Here we show that estradiol generated in the songbird homologue of the mammalian auditory association cortex, rapidly enhances the effectiveness of the neural coding of complex, learned acoustic signals in awake zebra finches. Specifically, estradiol increases mutual information rates, coding efficiency and the neural discrimination of songs. These effects are mediated by estradiol’s modulation of both rate and temporal coding of auditory signals. Interference with the local action or production of estradiol in the auditory forebrain of freely-behaving animals disrupts behavioral responses to songs, but not to other behaviorally-relevant communication signals. Our findings directly show that estradiol is a key regulator of auditory function in the adult vertebrate brain. PMID:21368039

  11. Bidirectional regulation of synaptic transmission by BRAG1/IQSEC2 and its requirement in long-term depression

    PubMed Central

    Brown, Joshua C.; Petersen, Amber; Zhong, Ling; Himelright, Miranda L.; Murphy, Jessica A.; Walikonis, Randall S.; Gerges, Nashaat Z.

    2016-01-01

    Dysfunction of the proteins regulating synaptic function can cause synaptic plasticity imbalance that underlies neurological disorders such as intellectual disability. A study found that four distinct mutations within BRAG1, an Arf-GEF synaptic protein, each led to X-chromosome-linked intellectual disability (XLID). Although the physiological functions of BRAG1 are poorly understood, each of these mutations reduces BRAG1's Arf-GEF activity. Here we show that BRAG1 is required for the activity-dependent removal of AMPA receptors in rat hippocampal pyramidal neurons. Moreover, we show that BRAG1 bidirectionally regulates synaptic transmission. On one hand, BRAG1 is required for the maintenance of synaptic transmission. On the other hand, BRAG1 expression enhances synaptic transmission, independently of BRAG1 Arf-GEF activity or neuronal activity, but dependently on its C-terminus interactions. This study demonstrates a dual role of BRAG1 in synaptic function and highlights the functional relevance of reduced BRAG1 Arf-GEF activity as seen in the XLID-associated human mutations. PMID:27009485

  12. PSD-95 regulates synaptic transmission and plasticity in rat cerebral cortex

    PubMed Central

    Béïque, Jean-Claude; Andrade, Rodrigo

    2003-01-01

    PSD-95 is one of the most abundant proteins found in the postsynaptic density of excitatory synapses. However, the precise functional role played by PSD-95 in regulating synaptic transmission and plasticity remains undefined. To address this issue, we have overexpressed PSD-95 in cortical pyramidal neurons in organotypic brain slices using particle-mediated gene transfer and assessed the consequences on synaptic transmission and plasticity. The AMPA receptor/NMDA receptor (AMPAR/NMDAR) ratio of evoked EPSCs recorded at +40 mV was greater in PSD-95-transfected pyramidal neurons than in controls. This difference could not be accounted for by a change in rectification of AMPAR-mediated synaptic currents since the current-voltage curves obtained in controls and in PSD-95-transfected neurons were indistinguishable. However, the amplitude of AMPAR-mediated evoked EPSCs was larger in PSD-95-transfected neurons compared to matched controls. Paired-pulse ratio analysis suggested that overexpression of PSD-95 did not alter presynaptic release probability. Transfection of PSD-95 was further accompanied by an increase in the frequency, but not amplitude, of AMPAR-mediated mEPSCs. Together, these results indicate that transfection of PSD-95 increased AMPAR-mediated synaptic transmission. Furthermore, they suggest that this phenomenon reflects an increased number of synapses expressing AMPARs rather than an increased number or function of these receptors at individual synapses. We tested the consequences of these changes on synaptic plasticity and found that PSD-95 transfection greatly enhanced the probability of observing long-term depression. These results thus identify a physiological role for PSD-95 and demonstrate that this protein can play a decisive role in controlling synaptic strength and activity-dependent synaptic plasticity. PMID:12563010

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

    PubMed Central

    Buschler, Arne; Manahan-Vaughan, Denise

    2012-01-01

    Long-term environmental enrichment (EE) elicits enduring effects on the adult brain, including altered synaptic plasticity. Synaptic plasticity may underlie memory formation and includes robust (>24 h) and weak (<2 h) forms of long-term potentiation (LTP) and long-term depression (LTD). Most studies of the effect of EE on synaptic efficacy have examined the consequences of very prolonged EE-exposure. It is unclear whether brief exposure to EE can alter synaptic plasticity. Clarifying this issue could help develop strategies to address cognitive deficits arising from neglect in children or adults. We assessed whether short-term EE elicits alterations in hippocampal synaptic plasticity and if social context may play a role. Adult mice were exposed to EE for 14 consecutive days. We found that robust late-LTP (>24 h) and short-term depression (<2 h) at Schaffer-collateral-CA1 synapses in freely behaving mice were unaltered, whereas early-LTP (E-LTP, <2 h) was significantly enhanced by EE. Effects were transient: E-LTP returned to control levels 1 week after cessation of EE. Six weeks later, animals were re-exposed to EE for 14 days. Under these conditions, E-LTP was facilitated into L-LTP (>24 h), suggesting that metaplasticity was induced during the first EE experience and that EE-mediated modifications are cumulative. Effects were absent in mice that underwent solitary enrichment or were group-housed without EE. These data suggest that EE in naïve animals strengthens E-LTP, and also promotes L-LTP in animals that underwent EE in the past. This indicates that brief exposure to EE, particularly under social conditions can elicit lasting positive effects on synaptic strength that may have beneficial consequences for cognition that depends on synaptic plasticity. PMID:23248592

  14. Synaptic Function of Rab11Fip5: Selective Requirement for Hippocampal Long-Term Depression.

    PubMed

    Bacaj, Taulant; Ahmad, Mohiuddin; Jurado, Sandra; Malenka, Robert C; Südhof, Thomas C

    2015-05-13

    Postsynaptic AMPA-type glutamate receptors (AMPARs) are among the major determinants of synaptic strength and can be trafficked into and out of synapses. Neuronal activity regulates AMPAR trafficking during synaptic plasticity to induce long-term changes in synaptic strength, including long-term potentiation (LTP) and long-term depression (LTD). Rab family GTPases regulate most membrane trafficking in eukaryotic cells; particularly, Rab11 and its effectors are implicated in mediating postsynaptic AMPAR insertion during LTP. To explore the synaptic function of Rab11Fip5, a neuronal Rab11 effector and a candidate autism-spectrum disorder gene, we performed shRNA-mediated knock-down and genetic knock-out (KO) studies. Surprisingly, we observed robust shRNA-induced synaptic phenotypes that were rescued by a Rab11Fip5 cDNA but that were nevertheless not observed in conditional KO neurons. Both in cultured neurons and acute slices, KO of Rab11Fip5 had no significant effect on basic parameters of synaptic transmission, indicating that Rab11Fip5 is not required for fundamental synaptic operations, such as neurotransmitter release or postsynaptic AMPAR insertion. KO of Rab11Fip5 did, however, abolish hippocampal LTD as measured both in acute slices or using a chemical LTD protocol in cultured neurons but did not affect hippocampal LTP. The Rab11Fip5 KO mice performed normally in several behavioral tasks, including fear conditioning, but showed enhanced contextual fear extinction. These are the first findings to suggest a requirement for Rab11Fip5, and presumably Rab11, during LTD. PMID:25972173

  15. The calcium sensor synaptotagmin 7 is required for synaptic facilitation

    PubMed Central

    Jackman, Skyler L.; Turecek, Josef; Belinsky, Justine E.

    2015-01-01

    It has been known for over 70 years that synaptic strength is dynamically regulated in a use-dependent manner1. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement where each subsequent action potential evokes greater neurotransmitter release2. Facilitation can enhance neurotransmitter release manyfold and profoundly influence information transfer across synapses3, but the underlying mechanism remains a mystery. Among the proposed mechanisms is that a specialized calcium sensor for facilitation transiently increases the probability of release2,4 and is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed5,6. Here we show that synaptotagmin 7 (syt7) is a calcium sensor that is required for facilitation at multiple central synapses. In syt7 knockout mice, facilitation is eliminated even though the initial probability of release and presynaptic residual calcium signals are unaltered. Expression of wild-type syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated syt7 with a calcium-insensitive C2A domain did not. By revealing the role of syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation. PMID:26738595

  16. The calcium sensor synaptotagmin 7 is required for synaptic facilitation.

    PubMed

    Jackman, Skyler L; Turecek, Josef; Belinsky, Justine E; Regehr, Wade G

    2016-01-01

    It has been known for more than 70 years that synaptic strength is dynamically regulated in a use-dependent manner. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement in which each subsequent action potential evokes greater neurotransmitter release. Facilitation can enhance neurotransmitter release considerably and can profoundly influence information transfer across synapses, but the underlying mechanism remains a mystery. One proposed mechanism is that a specialized calcium sensor for facilitation transiently increases the probability of release, and this sensor is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed. Here we show that synaptotagmin 7 (Syt7) is a calcium sensor that is required for facilitation at several central synapses. In Syt7-knockout mice, facilitation is eliminated even though the initial probability of release and the presynaptic residual calcium signals are unaltered. Expression of wild-type Syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated Syt7 with a calcium-insensitive C2A domain did not. By revealing the role of Syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation. PMID:26738595

  17. Low-voltage protonic/electronic hybrid indium zinc oxide synaptic transistors on paper substrates

    NASA Astrophysics Data System (ADS)

    Wu, Guodong; Wan, Changjin; Zhou, Jumei; Zhu, Liqiang; Wan, Qing

    2014-03-01

    Low-voltage (1.5 V) indium zinc oxide (IZO)-based electric-double-layer (EDL) thin-film transistors (TFTs) gated by nanogranular proton conducting SiO2 electrolyte films are fabricated on paper substrates. Both enhancement-mode and depletion-mode operation are obtained by tuning the thickness of the IZO channel layer. Furthermore, such flexible IZO protonic/electronic hybrid EDL TFTs can be used as artificial synapses, and synaptic stimulation response and short-term synaptic plasticity function are demonstrated. The protonic/electronic hybrid EDL TFTs on paper substrates proposed here are promising for low-power flexible paper electronics, artificial synapses and bioelectronics.

  18. Probing the interior of synaptic vesicles with internalized nanoparticles

    NASA Astrophysics Data System (ADS)

    Gadd, Jennifer C.; Budzinski, Kristi L.; Chan, Yang-Hsiang; Ye, Fangmao; Chiu, Daniel T.

    2012-03-01

    Synaptic vesicles are subcellular organelles that are found in the synaptic bouton and are responsible for the propagation of signals between neurons. Synaptic vesicles undergo endo- and exocytosis with the neuronal membrane to load and release neurotransmitters. Here we discuss how we utilize this property to load nanoparticles as a means of probing the interior of synaptic vesicles. To probe the intravesicular region of synaptic vesicles, we have developed a highly sensitive pH-sensing polymer dot. We feel the robust nature of the pH-sensing polymer dot will provide insight into the dynamics of proton loading into synaptic vesicles.

  19. Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission

    NASA Astrophysics Data System (ADS)

    Rouach, Nathalie; Koulakoff, Annette; Abudara, Veronica; Willecke, Klaus; Giaume, Christian

    2008-12-01

    Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.

  20. Synaptic consolidation: from synapses to behavioral modeling.

    PubMed

    Ziegler, Lorric; Zenke, Friedemann; Kastner, David B; Gerstner, Wulfram

    2015-01-21

    Synaptic plasticity, a key process for memory formation, manifests itself across different time scales ranging from a few seconds for plasticity induction up to hours or even years for consolidation and memory retention. We developed a three-layered model of synaptic consolidation that accounts for data across a large range of experimental conditions. Consolidation occurs in the model through the interaction of the synaptic efficacy with a scaffolding variable by a read-write process mediated by a tagging-related variable. Plasticity-inducing stimuli modify the efficacy, but the state of tag and scaffold can only change if a write protection mechanism is overcome. Our model makes a link from depotentiation protocols in vitro to behavioral results regarding the influence of novelty on inhibitory avoidance memory in rats. PMID:25609644

  1. Synaptic modulation of excitatory synaptic transmission by nicotinic acetylcholine receptors in spinal ventral horn neurons.

    PubMed

    Mine, N; Taniguchi, W; Nishio, N; Izumi, N; Miyazaki, N; Yamada, H; Nakatsuka, T; Yoshida, M

    2015-04-01

    Nicotinic acetylcholine receptors (nAChRs) are distributed widely in the central nervous system and play important roles in higher brain functions, including learning, memory, and recognition. However, functions of the cholinergic system in spinal motoneurons remain poorly understood. In this study, we investigated the actions of presynaptic and postsynaptic nAChRs in spinal ventral horn neurons by performing whole-cell patch-clamp recordings on lumbar slices from male rats. The application of nicotine or acetylcholine generated slow inward currents and increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). Slow inward currents by acetylcholine or nicotine were not inhibited by tetrodotoxin (TTX) or glutamate receptor antagonists. In the presence of TTX, the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) were also increased by acetylcholine or nicotine. A selective α4β2 nicotinic receptor antagonist, dihydro-β-erythroidine hydrobromide (DhβE), significantly decreased nicotine-induced inward currents without affecting the enhancement of sEPSCs and mEPSCs. In addition, a selective α7 nicotinic receptor antagonist, methyllycaconitine, did not affect either nicotine-induced inward currents or the enhancement of sEPSCs and mEPSCs. These results suggest that α4β2 AChRs are localized at postsynaptic sites in the spinal ventral horn, non-α4β2 and non-α7 nAChRs are located presynaptically, and nAChRs enhance excitatory synaptic transmission in the spinal ventral horn. PMID:25613686

  2. Stereotyped spatial patterns of functional synaptic connectivity in the cerebellar cortex.

    PubMed

    Valera, Antoine M; Binda, Francesca; Pawlowski, Sophie A; Dupont, Jean-Luc; Casella, Jean-François; Rothstein, Jeffrey D; Poulain, Bernard; Isope, Philippe

    2016-01-01

    Motor coordination is supported by an array of highly organized heterogeneous modules in the cerebellum. How incoming sensorimotor information is channeled and communicated between these anatomical modules is still poorly understood. In this study, we used transgenic mice expressing GFP in specific subsets of Purkinje cells that allowed us to target a given set of cerebellar modules. Combining in vitro recordings and photostimulation, we identified stereotyped patterns of functional synaptic organization between the granule cell layer and its main targets, the Purkinje cells, Golgi cells and molecular layer interneurons. Each type of connection displayed position-specific patterns of granule cell synaptic inputs that do not strictly match with anatomical boundaries but connect distant cortical modules. Although these patterns can be adjusted by activity-dependent processes, they were found to be consistent and predictable between animals. Our results highlight the operational rules underlying communication between modules in the cerebellar cortex. PMID:26982219

  3. Levetiracetam mitigates doxorubicin-induced DNA and synaptic damage in neurons.

    PubMed

    Manchon, Jose Felix Moruno; Dabaghian, Yuri; Uzor, Ndidi-Ese; Kesler, Shelli R; Wefel, Jeffrey S; Tsvetkov, Andrey S

    2016-01-01

    Neurotoxicity may occur in cancer patients and survivors during or after chemotherapy. Cognitive deficits associated with neurotoxicity can be subtle or disabling and frequently include disturbances in memory, attention, executive function and processing speed. Searching for pathways altered by anti-cancer treatments in cultured primary neurons, we discovered that doxorubicin, a commonly used anti-neoplastic drug, significantly decreased neuronal survival. The drug promoted the formation of DNA double-strand breaks in primary neurons and reduced synaptic and neurite density. Pretreatment of neurons with levetiracetam, an FDA-approved anti-epileptic drug, enhanced survival of chemotherapy drug-treated neurons, reduced doxorubicin-induced formation of DNA double-strand breaks, and mitigated synaptic and neurite loss. Thus, levetiracetam might be part of a valuable new approach for mitigating synaptic damage and, perhaps, for treating cognitive disturbances in cancer patients and survivors. PMID:27168474

  4. Fusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking.

    PubMed

    Wang, Shan Shan H; Held, Richard G; Wong, Man Yan; Liu, Changliang; Karakhanyan, Aziz; Kaeser, Pascal S

    2016-08-17

    In a nerve terminal, synaptic vesicle docking and release are restricted to an active zone. The active zone is a protein scaffold that is attached to the presynaptic plasma membrane and opposed to postsynaptic receptors. Here, we generated conditional knockout mice removing the active zone proteins RIM and ELKS, which additionally led to loss of Munc13, Bassoon, Piccolo, and RIM-BP, indicating disassembly of the active zone. We observed a near-complete lack of synaptic vesicle docking and a strong reduction in vesicular release probability and the speed of exocytosis, but total vesicle numbers, SNARE protein levels, and postsynaptic densities remained unaffected. Despite loss of the priming proteins Munc13 and RIM and of docked vesicles, a pool of releasable vesicles remained. Thus, the active zone is necessary for synaptic vesicle docking and to enhance release probability, but releasable vesicles can be localized distant from the presynaptic plasma membrane. PMID:27537483

  5. Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation.

    PubMed

    Lui, Hansen; Zhang, Jiasheng; Makinson, Stefanie R; Cahill, Michelle K; Kelley, Kevin W; Huang, Hsin-Yi; Shang, Yulei; Oldham, Michael C; Martens, Lauren Herl; Gao, Fuying; Coppola, Giovanni; Sloan, Steven A; Hsieh, Christine L; Kim, Charles C; Bigio, Eileen H; Weintraub, Sandra; Mesulam, Marek-Marsel; Rademakers, Rosa; Mackenzie, Ian R; Seeley, William W; Karydas, Anna; Miller, Bruce L; Borroni, Barbara; Ghidoni, Roberta; Farese, Robert V; Paz, Jeanne T; Barres, Ben A; Huang, Eric J

    2016-05-01

    Microglia maintain homeostasis in the brain, but whether aberrant microglial activation can cause neurodegeneration remains controversial. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive upregulation of lysosomal and innate immunity genes, increased complement production, and enhanced synaptic pruning in microglia. During aging, Grn(-/-) mice show profound microglia infiltration and preferential elimination of inhibitory synapses in the ventral thalamus, which lead to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors. Remarkably, deleting C1qa gene significantly reduces synaptic pruning by Grn(-/-) microglia and mitigates neurodegeneration, behavioral phenotypes, and premature mortality in Grn(-/-) mice. Together, our results uncover a previously unrecognized role of progranulin in suppressing aberrant microglia activation during aging. These results represent an important conceptual advance that complement activation and microglia-mediated synaptic pruning are major drivers, rather than consequences, of neurodegeneration caused by progranulin deficiency. PMID:27114033

  6. Levetiracetam mitigates doxorubicin-induced DNA and synaptic damage in neurons

    PubMed Central

    Manchon, Jose Felix Moruno; Dabaghian, Yuri; Uzor, Ndidi-Ese; Kesler, Shelli R.; Wefel, Jeffrey S.; Tsvetkov, Andrey S.

    2016-01-01

    Neurotoxicity may occur in cancer patients and survivors during or after chemotherapy. Cognitive deficits associated with neurotoxicity can be subtle or disabling and frequently include disturbances in memory, attention, executive function and processing speed. Searching for pathways altered by anti-cancer treatments in cultured primary neurons, we discovered that doxorubicin, a commonly used anti-neoplastic drug, significantly decreased neuronal survival. The drug promoted the formation of DNA double-strand breaks in primary neurons and reduced synaptic and neurite density. Pretreatment of neurons with levetiracetam, an FDA-approved anti-epileptic drug, enhanced survival of chemotherapy drug-treated neurons, reduced doxorubicin-induced formation of DNA double-strand breaks, and mitigated synaptic and neurite loss. Thus, levetiracetam might be part of a valuable new approach for mitigating synaptic damage and, perhaps, for treating cognitive disturbances in cancer patients and survivors. PMID:27168474

  7. Nitric Oxide–mediated Modulation of Synaptic Activity by Astrocytic P2Y Receptors

    PubMed Central

    Mehta, Bhupesh; Begum, Gulnaz; Joshi, Nanda B.; Joshi, Preeti G.

    2008-01-01

    We investigated the mechanism of synaptic suppression by P2Y receptors in mixed hippocampal cultures wherein networked neurons exhibit synchronized Ca2+ oscillations (SCO) due to spontaneous glutamatergic synaptic transmission. Pharmacological studies suggested that SCO suppression was mediated by P2Y2/P2Y4 receptors. Immunostaining studies and characterization of ATP/UTP-stimulated Ca2+ responses in solitary neurons and astrocytes revealed that the SCO attenuation was effectuated by astrocytes. We demonstrate that nitric oxide released from activated astrocytes causes synaptic suppression by inhibiting neurotransmitter release. Physiological concentrations of ATP and UTP evoked NO production in astrocytes. SCO suppression was considerably diminished by removal of extracellular NO by membrane-impermeable scavenger c-PTIO or by pretreatment of cells with nitric oxide synthase inhibitor L-NAME. The nitric oxide donor DETA/NO effectively suppressed the SCO. ATP/UTP inhibited KCl-induced exocytosis at presynaptic terminals in an NO-dependent manner. In the absence of exogenously added ATP/UTP, both the NO scavenger and NOS inhibitor enhanced the frequency of SCO, implying that astrocytes release NO during spontaneous synaptic activity and exert a suppressive effect. We report for the first time that under physiological conditions astrocytes use NO as a messenger molecule to modulate the synaptic strength in the networked neurons. PMID:18725529

  8. Synaptic transmission at retinal ribbon synapses

    PubMed Central

    Heidelberger, Ruth; Thoreson, Wallace B.; Witkovsky, Paul

    2006-01-01

    The molecular organization of ribbon synapses in photoreceptors and ON bipolar cells is reviewed in relation to the process of neurotransmitter release. The interactions between ribbon synapse-associated proteins, synaptic vesicle fusion machinery and the voltage-gated calcium channels that gate transmitter release at ribbon synapses are discussed in relation to the process of synaptic vesicle exocytosis. We describe structural and mechanistic specializations that permit the ON bipolar cell to release transmitter at a much higher rate than the photoreceptor does, under in vivo conditions. We also consider the modulation of exocytosis at photoreceptor synapses, with an emphasis on the regulation of calcium channels. PMID:16027025

  9. Time-dependent reversal of synaptic plasticity induced by physiological concentrations of oligomeric Aβ42: an early index of Alzheimer's disease.

    PubMed

    Koppensteiner, Peter; Trinchese, Fabrizio; Fà, Mauro; Puzzo, Daniela; Gulisano, Walter; Yan, Shijun; Poussin, Arthur; Liu, Shumin; Orozco, Ian; Dale, Elena; Teich, Andrew F; Palmeri, Agostino; Ninan, Ipe; Boehm, Stefan; Arancio, Ottavio

    2016-01-01

    The oligomeric amyloid-β (Aβ) peptide is thought to contribute to the subtle amnesic changes in Alzheimer's disease (AD) by causing synaptic dysfunction. Here, we examined the time course of synaptic changes in mouse hippocampal neurons following exposure to Aβ42 at picomolar concentrations, mimicking its physiological levels in the brain. We found opposite effects of the peptide with short exposures in the range of minutes enhancing synaptic plasticity, and longer exposures lasting several hours reducing it. The plasticity reduction was concomitant with an increase in the basal frequency of spontaneous neurotransmitter release, a higher basal number of functional presynaptic release sites, and a redistribution of synaptic proteins including the vesicle-associated proteins synapsin I, synaptophysin, and the post-synaptic glutamate receptor I. These synaptic alterations were mediated by cytoskeletal changes involving actin polymerization and p38 mitogen-activated protein kinase. These in vitro findings were confirmed in vivo with short hippocampal infusions of picomolar Aβ enhancing contextual memory and prolonged infusions impairing it. Our findings provide a model for initiation of synaptic dysfunction whereby exposure to physiologic levels of Aβ for a prolonged period of time causes microstructural changes at the synapse which result in increased transmitter release, failure of synaptic plasticity, and memory loss. PMID:27581852

  10. Time-dependent reversal of synaptic plasticity induced by physiological concentrations of oligomeric Aβ42: an early index of Alzheimer’s disease

    PubMed Central

    Koppensteiner, Peter; Trinchese, Fabrizio; Fà, Mauro; Puzzo, Daniela; Gulisano, Walter; Yan, Shijun; Poussin, Arthur; Liu, Shumin; Orozco, Ian; Dale, Elena; Teich, Andrew F.; Palmeri, Agostino; Ninan, Ipe; Boehm, Stefan; Arancio, Ottavio

    2016-01-01

    The oligomeric amyloid-β (Aβ) peptide is thought to contribute to the subtle amnesic changes in Alzheimer’s disease (AD) by causing synaptic dysfunction. Here, we examined the time course of synaptic changes in mouse hippocampal neurons following exposure to Aβ42 at picomolar concentrations, mimicking its physiological levels in the brain. We found opposite effects of the peptide with short exposures in the range of minutes enhancing synaptic plasticity, and longer exposures lasting several hours reducing it. The plasticity reduction was concomitant with an increase in the basal frequency of spontaneous neurotransmitter release, a higher basal number of functional presynaptic release sites, and a redistribution of synaptic proteins including the vesicle-associated proteins synapsin I, synaptophysin, and the post-synaptic glutamate receptor I. These synaptic alterations were mediated by cytoskeletal changes involving actin polymerization and p38 mitogen-activated protein kinase. These in vitro findings were confirmed in vivo with short hippocampal infusions of picomolar Aβ enhancing contextual memory and prolonged infusions impairing it. Our findings provide a model for initiation of synaptic dysfunction whereby exposure to physiologic levels of Aβ for a prolonged period of time causes microstructural changes at the synapse which result in increased transmitter release, failure of synaptic plasticity, and memory loss. PMID:27581852

  11. Ral-GTPase influences the regulation of the readily releasable pool of synaptic vesicles.

    PubMed

    Polzin, Atsuko; Shipitsin, Michail; Goi, Takanori; Feig, Larry A; Turner, Timothy J

    2002-03-01

    The Ral proteins are members of the Ras superfamily of GTPases. Because they reside in synaptic vesicles, we used transgenic mice expressing a dominant inhibitory form of Ral to investigate the role of Ral in neurosecretion. Using a synaptosomal secretion assay, we found that while K(+)-evoked secretion of glutamate was normal, protein kinase C-mediated enhancement of glutamate secretion was suppressed in the mutant mice. Since protein kinase C effects on secretion have been shown to be due to enhancement of the size of the readily releasable pool of synaptic vesicles docked at the plasma membrane, we directly measured the refilling of this readily releasable pool of synaptic vesicles after Ca(2+)-triggered exocytosis. Refilling of the readily releasable pool was suppressed in synaptosomes from mice expressing dominant inhibitory Ral. Moreover, we found that protein kinase C and calcium-induced phosphorylation of proteins thought to influence synaptic vesicle function, such as MARCKS, synapsin, and SNAP-25, were all reduced in synaptosomes from these transgenic mice. Concomitant with these studies, we searched for new functions of Ral by detecting proteins that specifically bind to it in cells. Consistent with the phenotype of the transgenic mice described above, we found that active but not inactive RalA binds to the Sec6/8 (exocyst) complex, whose yeast counterpart is essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. These findings demonstrate a role for Ral-GTPase signaling in the modulation of the readily releasable pool of synaptic vesicles and suggest the possible involvement of Ral-Sec6/8 (exocyst) binding in modulation of synaptic strength. PMID:11865051

  12. Flexible Proton-Gated Oxide Synaptic Transistors on Si Membrane.

    PubMed

    Zhu, Li Qiang; Wan, Chang Jin; Gao, Ping Qi; Liu, Yang Hui; Xiao, Hui; Ye, Ji Chun; Wan, Qing

    2016-08-24

    Ion-conducting materials have received considerable attention for their applications in fuel cells, electrochemical devices, and sensors. Here, flexible indium zinc oxide (InZnO) synaptic transistors with multiple presynaptic inputs gated by proton-conducting phosphorosilicate glass-based electrolyte films are fabricated on ultrathin Si membranes. Transient characteristics of the proton gated InZnO synaptic transistors are investigated, indicating stable proton-gating behaviors. Short-term synaptic plasticities are mimicked on the proposed proton-gated synaptic transistors. Furthermore, synaptic integration regulations are mimicked on the proposed synaptic transistor networks. Spiking logic modulations are realized based on the transition between superlinear and sublinear synaptic integration. The multigates coupled flexible proton-gated oxide synaptic transistors may be interesting for neuroinspired platforms with sophisticated spatiotemporal information processing. PMID:27471861

  13. Impact of Synaptic Neurotransmitter Concentration Time Course on the Kinetics and Pharmacological Modulation of Inhibitory Synaptic Currents

    PubMed Central

    Barberis, Andrea; Petrini, Enrica Maria; Mozrzymas, Jerzy W.

    2011-01-01

    The time course of synaptic currents is a crucial determinant of rapid signaling between neurons. Traditionally, the mechanisms underlying the shape of synaptic signals are classified as pre- and post-synaptic. Over the last two decades, an extensive body of evidence indicated that synaptic signals are critically shaped by the neurotransmitter time course which encompasses several phenomena including pre- and post-synaptic ones. The agonist transient depends on neurotransmitter release mechanisms, diffusion within the synaptic cleft, spill-over to the extra-synaptic space, uptake, and binding to post-synaptic receptors. Most estimates indicate that the neurotransmitter transient is very brief, lasting between one hundred up to several hundreds of microseconds, implying that post-synaptic activation is characterized by a high degree of non-equilibrium. Moreover, pharmacological studies provide evidence that the kinetics of agonist transient plays a crucial role in setting the susceptibility of synaptic currents to modulation by a variety of compounds of physiological or clinical relevance. More recently, the role of the neurotransmitter time course has been emphasized by studies carried out on brain slice models that revealed a striking, cell-dependent variability of synaptic agonist waveforms ranging from rapid pulses to slow volume transmission. In the present paper we review the advances on studies addressing the impact of synaptic neurotransmitter transient on kinetics and pharmacological modulation of synaptic currents at inhibitory synapses. PMID:21734864

  14. Inter-satellite ranging and inter-satellite communication links for enhancing GNSS satellite broadcast navigation data

    NASA Astrophysics Data System (ADS)

    Fernández, Francisco Amarillo

    2011-03-01

    Recently the European Space Agency (ESA) has initiated a number of exploratory Projects, within the General Studies Programme (GSP), to analyze what potential improvements on a GNSS system navigation determination and dissemination performance could be brought by introducing inter-satellite ranging & inter-satellite communication-links. The key improvements targeted by these Projects are the enhancement of the orbit and clock prediction accuracy and the reduction of the dependency from ground infrastructure. Both projects adopted the Galileo system architecture as the initial working point.The first exploratory Project, which was labelled as GNSS+ (Amarillo and Gerner, 2007; Amarillo et al., 2008), indicated the practical difficulty to implement these new on-board functionalities except at the price of a visible increase of the payload mass and power (e.g. relative to mass and power of the Galileo IOV navigation payload) (Sánchez and Pulido, 2008); it allowed to define a preliminary system architecture, and it also allowed to identify the technological problems that in practise would likely be encountered.A second exploratory Project, which was labelled as ADVISE, continued the research, targeting a visible simplification of the GNSS+ architecture and an overall consolidation of the design of the most demanding constituents from technology perspective.This article describes the results of the GNSS+ Project as well as the improvements proposed in the frame of the ADVISE Project. As result of the ADVISE Project it has been possible to low very visibly the payload maximum RF power, and to keep the orbit and clock estimation accuracy, which was already on the few cm level.

  15. Cholesterol reduction impairs exocytosis of synaptic vesicles.

    PubMed

    Linetti, Anna; Fratangeli, Alessandra; Taverna, Elena; Valnegri, Pamela; Francolini, Maura; Cappello, Valentina; Matteoli, Michela; Passafaro, Maria; Rosa, Patrizia

    2010-02-15

    Cholesterol and sphingolipids are abundant in neuronal membranes, where they help the organisation of the membrane microdomains involved in major roles such as axonal and dendritic growth, and synapse and spine stability. The aim of this study was to analyse their roles in presynaptic physiology. We first confirmed the presence of proteins of the exocytic machinery (SNARES and Ca(v)2.1 channels) in the lipid microdomains of cultured neurons, and then incubated the neurons with fumonisin B (an inhibitor of sphingolipid synthesis), or with mevastatin or zaragozic acid (two compounds that affect the synthesis of cholesterol by inhibiting HMG-CoA reductase or squalene synthase). The results demonstrate that fumonisin B and zaragozic acid efficiently decrease sphingolipid and cholesterol levels without greatly affecting the viability of neurons or the expression of synaptic proteins. Electron microscopy showed that the morphology and number of synaptic vesicles in the presynaptic boutons of cholesterol-depleted neurons were similar to those observed in control neurons. Zaragozic acid (but not fumonisin B) treatment impaired synaptic vesicle uptake of the lipophilic dye FM1-43 and an antibody directed against the luminal epitope of synaptotagmin-1, effects that depended on the reduction in cholesterol because they were reversed by cholesterol reloading. The time-lapse confocal imaging of neurons transfected with ecliptic SynaptopHluorin showed that cholesterol depletion affects the post-depolarisation increase in fluorescence intensity. Taken together, these findings show that reduced cholesterol levels impair synaptic vesicle exocytosis in cultured neurons. PMID:20103534

  16. Effects of rectification on synaptic efficacy.

    PubMed Central

    Joyner, R W; Westerfield, M

    1982-01-01

    We have investigated the effects of postsynaptic membrane properties on the shape of synaptic potentials generated by time-varying synaptic conductances. We used numerical simulation techniques to model cells of several different geometrical forms, from an isopotential sphere to a neuron with a soma and a dendritic tree. A variety of postsynaptic membrane properties were tested: (a) a passive resistance-capacitance membrane, (b) a membrane represented by the Hodgkin and Huxley (HH) equations, and (c) a membrane that was passive except for a delayed rectification represented by a voltage- and time-dependent increase in GK. In all cases we investigated the effects of these postsynaptic membrane properties on synaptic potentials produced by synaptic conductances that were fast or slow compared with the membrane time constant. In all cases the effects of postsynaptic rectification occurred on postsynaptic potentials of amplitudes as low as 1 mV. The HH model (compared with the passive model) produced an increased peak amplitude (from the increase in GNa) but a decreased half-width and a decreased time integral (from the increase in GK). These effects of the HH GK change were duplicated by a simple analytical rectifier model. PMID:7074198

  17. Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration.

    PubMed

    Häusser, M; Clark, B A

    1997-09-01

    Irregular firing patterns are observed in most central neurons in vivo, but their origin is controversial. Here, we show that two types of inhibitory neurons in the cerebellar cortex fire spontaneously and regularly in the absence of synaptic input but generate an irregular firing pattern in the presence of tonic synaptic inhibition. Paired recordings between synaptically connected neurons revealed that single action potentials in inhibitory interneurons cause highly variable delays in action potential firing in their postsynaptic cells. Activity in single and multiple inhibitory interneurons also significantly reduces postsynaptic membrane time constant and input resistance. These findings suggest that the time window for synaptic integration is a dynamic variable modulated by the level of tonic inhibition, and that rate coding and temporal coding strategies may be used in parallel in the same cell type. PMID:9331356

  18. Family-School Communication in Preschool and Kindergarten in the Context of a Relationship-Enhancing Intervention

    ERIC Educational Resources Information Center

    Rimm-Kaufman, Sara E.; Pianta, Robert C.

    2005-01-01

    The present study is a longitudinal examination of family-school communication in preschool and kindergarten. Preschool and kindergarten teachers and family workers of 75 children from families with low SES logged the frequency and characteristics of family-school communication, resulting in over 22,000 contacts. Data were collected during a…

  19. Enhancing the Educational Potential of Non-Oral Children through Matching Communication Device Capabilities to Children's Needs. Final Report.

    ERIC Educational Resources Information Center

    Coleman, Colette L.; And Others

    The report describes activities and results of a project to identify communication characteristics that would help match augmentative communication system (ACS) capabilities to the needs of nonoral children. Ss had a variety of handicapping conditions, including cerebral palsy and other developmental disabilities. Introductory sections cover the…

  20. A Model for Enhancing Social Communication and Interaction in Everyday Activities for Primary School Children with ASD

    ERIC Educational Resources Information Center

    Peters, Brenda

    2016-01-01

    Children with a diagnosis of Autism Spectrum Disorder may find the social aspects of learning particularly challenging because of the traits of diffculty with social communication and interaction. This paper evaluates the impact of an interactive model designed to support social communication and interaction for twelve students with ASD, who…

  1. Urocortin 2 But Not Urocortin 3 Promotes the Synaptic Formation in Hipppocampal Neurons via Induction of NGF Production by Astrocytes.

    PubMed

    Zheng, You; Zhang, Yan-Min; Ni, Xin

    2016-03-01

    CRH family peptides play differential role during various physiological and pathophysiological responses, such as stress. Urocortins (UCNs) have been implicated to play complementary or contrasting actions for the effects of CRH during stress. It has been shown that activation of CRH receptor type 1 (CRHR1) results in decreased synapse formation in hippocampus. We therefore explored the effect of UCN2 and UCN3, the exclusive CRHR2 agonists, on synaptic formation in hippocampus. In hippocampal slices cultures, UCN2 but not UCN3 treatment increased the levels of presynaptic protein synapsinI and postsynaptic protein postsynaptic density 95 (PSD95), which was reversed by CRHR2 antagonist astressin 2B. In isolated hippocampal neurons, however, UCN2 decreased the numbers of synapsinI- and PSD95-labeled terminals/clusters via CRHR2. Treatment of hippocampal neurons with the media of UCN2-treated astrocytes led to an increase in synapsinI- and PSD95-labeled terminals. In neuron-astrocyte cocultures, UCN2 also enhanced the numbers and level of synapsinI- and PSD95-labeled terminals. These effects did not occur if glial cells were transfected with CRHR2 small interfering RNA. UCN2 but not UCN3 treatment induced nerve growth factor (NGF) production in astrocytes via CRHR2. The effects of the media of UCN2-treated glial cells on synapse formation in hippocampal neurons were prevented by administration of NGF receptor antagonists. Our data indicate that UCN2 promotes synapse formation in hippocampus via induction of NGF secretion from astrocytes. CRHR2 in glial cells mediates the stimulatory effects of CRH. Glia-neuron communication is critical for neuronal circuits remodeling and synaptic plasticity in response to neurohormones or neuromodulators. PMID:26713785

  2. Synaptic islands defined by the territory of a single astrocyte.

    PubMed

    Halassa, Michael M; Fellin, Tommaso; Takano, Hajime; Dong, Jing-Hui; Haydon, Philip G

    2007-06-13

    In the mammalian brain, astrocytes modulate neuronal function, in part, by synchronizing neuronal firing and coordinating synaptic networks. Little, however, is known about how this is accomplished from a structural standpoint. To investigate the structural basis of astrocyte-mediated neuronal synchrony and synaptic coordination, the three-dimensional relationships between cortical astrocytes and neurons was investigated. Using a transgenic and viral approach to label astrocytes with enhanced green fluorescent protein, we performed a three-dimensional reconstruction of astrocytes from tissue sections or live animals in vivo. We found that cortical astrocytes occupy nonoverlapping territories similar to those described in the hippocampus. Using immunofluorescence labeling of neuronal somata, a single astrocyte enwraps on average four neuronal somata with an upper limit of eight. Single-neuron dye-fills allowed us to estimate that one astrocyte contacts 300-600 neuronal dendrites. Together with the recent findings showing that glial Ca2+ signaling is restricted to individual astrocytes in vivo, and that Ca2+ signaling leads to gliotransmission, we propose the concept of functional islands of synapses in which groups of synapses confined within the boundaries of an individual astrocyte are modulated by the gliotransmitter environment controlled by that astrocyte. Our description offers a new structurally based conceptual framework to evaluate functional data involving interactions between neurons and astrocytes in the mammalian brain. PMID:17567808

  3. Nuclear Calcium Signaling Induces Expression of the Synaptic Organizers Lrrtm1 and Lrrtm2*

    PubMed Central

    Hayer, Stefanie N.; Bading, Hilmar

    2015-01-01

    Calcium transients in the cell nucleus evoked by synaptic activity in hippocampal neurons function as a signaling end point in synapse-to-nucleus communication. As an important regulator of neuronal gene expression, nuclear calcium is involved in the conversion of synaptic stimuli into functional and structural changes of neurons. Here we identify two synaptic organizers, Lrrtm1 and Lrrtm2, as targets of nuclear calcium signaling. Expression of both Lrrtm1 and Lrrtm2 increased in a synaptic NMDA receptor- and nuclear calcium-dependent manner in hippocampal neurons within 2–4 h after the induction of action potential bursting. Induction of Lrrtm1 and Lrrtm2 occurred independently of the need for new protein synthesis and required calcium/calmodulin-dependent protein kinases and the nuclear calcium signaling target CREB-binding protein. Analysis of reporter gene constructs revealed a functional cAMP response element in the proximal promoter of Lrrtm2, indicating that at least Lrrtm2 is regulated by the classical nuclear Ca2+/calmodulin-dependent protein kinase IV-CREB/CREB-binding protein pathway. These results suggest that one mechanism by which nuclear calcium signaling controls neuronal network function is by regulating the expression of Lrrtm1 and Lrrtm2. PMID:25527504

  4. Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus?

    PubMed Central

    Matamales, Miriam

    2012-01-01

    Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucleus, the possible co-existence of these models and their relevance in physiological conditions remain elusive. One model suggests that synaptic activation triggers the translocation to the nucleus of certain transcription regulators localised at postsynaptic sites that function as synapto-nuclear messengers. Alternatively, it has been hypothesised that synaptic activity initiates propagating regenerative intracellular calcium waves that spread through dendrites into the nucleus where nuclear transcription machinery is thereby regulated. It has also been postulated that membrane depolarisation of voltage-gated calcium channels on the somatic membrane is sufficient to increase intracellular calcium concentration and activate transcription without the need for transported signals from distant synapses. Here I provide a critical overview of the suggested mechanisms for coupling synaptic stimulation to transcription, the underlying assumptions behind them and their plausible physiological significance. PMID:24327840

  5. Tau pathology induces loss of GABAergic interneurons leading to altered synaptic plasticity and behavioral impairments

    PubMed Central

    2013-01-01

    Background Tau is a microtubule stabilizing protein and is mainly expressed in neurons. Tau aggregation into oligomers and tangles is considered an important pathological event in tauopathies, such as frontotemporal dementia (FTD) and Alzheimer’s disease (AD). Tauopathies are also associated with deficits in synaptic plasticity such as long-term potentiation (LTP), but the specific role of tau in the manifestation of these deficiencies is not well-understood. We examined long lasting forms of synaptic plasticity in JNPL3 (BL6) mice expressing mutant tau that is identified in some inherited FTDs. Results We found that aged (>12 months) JNPL3 (BL6) mice exhibit enhanced hippocampal late-phase (L-LTP), while young JNPL3 (BL6) mice (age 6 months) displayed normal L-LTP. This enhanced L-LTP in aged JNPL3 (BL6) mice was rescued with the GABAAR agonist, zolpidem, suggesting a loss of GABAergic function. Indeed, we found that mutant mice displayed a reduction in hippocampal GABAergic interneurons. Finally, we also found that expression of mutant tau led to severe sensorimotor-gating and hippocampus-dependent memory deficits in the aged JNPL3 (BL6) mice. Conclusions We show for the first time that hippocampal GABAergic function is impaired by pathological tau protein, leading to altered synaptic plasticity and severe memory deficits. Increased understanding of the molecular mechanisms underlying the synaptic failure in AD and FTD is critical to identifying targets for therapies to restore cognitive deficiencies associated with tauopathies. PMID:24252661

  6. The synaptic glycoprotein neuroplastin is involved in long-term potentiation at hippocampal CA1 synapses

    PubMed Central

    Smalla, K. -H.; Matthies, H.; Langnäse, K.; Shabir, S.; Böckers, T. M.; Wyneken, U.; Staak, S.; Krug, M.; Beesley, P. W.; Gundelfinger, E. D.

    2000-01-01

    Neuroplastin-65 and -55 (previously known as gp65 and gp55) are glycoproteins of the Ig superfamily that are enriched in rat forebrain synaptic membrane preparations. Whereas the two-Ig domain isoform neuroplastin-55 is expressed in many tissues, the three-Ig domain isoform neuroplastin-65 is brain-specific and enriched in postsynaptic density (PSD) protein preparations. Here, we have assessed the function of neuroplastin in long-term synaptic plasticity. Immunocytochemical studies with neuroplastin-65-specific antibodies differentially stain distinct synaptic neuropil regions of the rat hippocampus with most prominent immunoreactivity in the CA1 region and the proximal molecular layer of the dentate gyrus. Kainate-induced seizures cause a significant enhancement of neuroplastin-65 association with PSDs. Similarly, long-term potentiation (LTP) of CA1 synapses in hippocampal slices enhanced the association of neuroplastin-65 with a detergent-insoluble PSD-enriched protein fraction. Several antibodies against the neuroplastins, including one specific for neuroplastin-65, inhibited the maintenance of LTP. A similar effect was observed when recombinant fusion protein containing the three extracellular Ig domains of neuroplastin-65 was applied to hippocampal slices before LTP induction. Microsphere binding experiments using neuroplastin-Fc chimeric proteins show that constructs containing Ig1–3 or Ig1 domains, but not Ig2–3 domains mediate homophilic adhesion. These data suggest that neuroplastin plays an essential role in implementing long-term changes in synaptic activity, possibly by means of a homophilic adhesion mechanism. PMID:10759566

  7. Gene expression parallels synaptic excitability and plasticity changes in Alzheimer’s disease

    PubMed Central

    Saura, Carlos A.; Parra-Damas, Arnaldo; Enriquez-Barreto, Lilian

    2015-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by abnormal accumulation of β-amyloid and tau and synapse dysfunction in memory-related neural circuits. Pathological and functional changes in the medial temporal lobe, a region essential for explicit memory encoding, contribute to cognitive decline in AD. Surprisingly, functional imaging studies show increased activity of the hippocampus and associated cortical regions during memory tasks in presymptomatic and early AD stages, whereas brain activity declines as the disease progresses. These findings suggest an emerging scenario where early pathogenic events might increase neuronal excitability leading to enhanced brain activity before clinical manifestations of the disease, a stage that is followed by decreased brain activity as neurodegeneration progresses. The mechanisms linking pathology with synaptic excitability and plasticity changes leading to memory loss in AD remain largely unclear. Recent studies suggest that increased brain activity parallels enhanced expression of genes involved in synaptic transmission and plasticity in preclinical stages, whereas expression of synaptic and activity-dependent genes are reduced by the onset of pathological and cognitive symptoms. Here, we review recent evidences indicating a relationship between transcriptional deregulation of synaptic genes and neuronal activity and memory loss in AD and mouse models. These findings provide the basis for potential clinical applications of memory-related transcriptional programs and their regulatory mechanisms as novel biomarkers and therapeutic targets to restore brain function in AD and other cognitive disorders. PMID:26379494

  8. Synaptic Synthesis, Dephosphorylation, and Degradation

    PubMed Central

    La Montanara, Paolo; Rusconi, Laura; Locarno, Albina; Forti, Lia; Barbiero, Isabella; Tramarin, Marco; Chandola, Chetan; Kilstrup-Nielsen, Charlotte; Landsberger, Nicoletta

    2015-01-01

    Mutations in the X-linked CDKL5 (cyclin-dependent kinase-like 5) gene have been associated with several forms of neurodevelopmental disorders, including atypical Rett syndrome, autism spectrum disorders, and early infantile epileptic encephalopathy. Accordingly, loss of CDKL5 in mice results in autistic-like features and impaired neuronal communication. Although the biological functions of CDKL5 remain largely unknown, recent pieces of evidence suggest that CDKL5 is involved in neuronal plasticity. Herein, we show that, at all stages of development, neuronal depolarization induces a rapid increase in CDKL5 levels, mostly mediated by extrasomatic synthesis. In young neurons, this induction is prolonged, whereas in more mature neurons, NMDA receptor stimulation induces a protein phosphatase 1-dependent dephosphorylation of CDKL5 that is mandatory for its proteasome-dependent degradation. As a corollary, neuronal activity leads to a prolonged induction of CDKL5 levels in immature neurons but to a short lasting increase of the kinase in mature neurons. Recent results demonstrate that many genes associated with autism spectrum disorders are crucial components of the activity-dependent signaling networks regulating the composition, shape, and strength of the synapse. Thus, we speculate that CDKL5 deficiency disrupts activity-dependent signaling and the consequent synapse development, maturation, and refinement. PMID:25555910

  9. Regulation of AMPA Receptor Trafficking and Synaptic Plasticity

    PubMed Central

    Anggono, Victor; Huganir, Richard L.

    2012-01-01

    AMPA receptors (AMPARs) mediate the majority of fast excitatory synaptic transmission in the brain. Dynamic changes in neuronal synaptic efficacy, termed synaptic plasticity, are thought to underlie information coding and storage in learning and memory. One major mechanism that regulates synaptic strength involves the tightly regulated trafficking of AMPARs into and out of synapses. The life cycle of AMPARs from their biosynthesis, membrane trafficking and synaptic targeting to their degradation are controlled by a series of orchestrated interactions with numerous intracellular regulatory proteins. Here we review recent progress made towards the understanding the regulation of AMPAR trafficking, focusing on the roles of several key intracellular AMPAR interacting proteins. PMID:22217700

  10. Working memory impairment in calcineurin knock-out mice is associated with alterations in synaptic vesicle cycling and disruption of high-frequency synaptic and network activity in prefrontal cortex.

    PubMed

    Cottrell, Jeffrey R; Levenson, Jonathan M; Kim, Sung Hyun; Gibson, Helen E; Richardson, Kristen A; Sivula, Michael; Li, Bing; Ashford, Crystle J; Heindl, Karen A; Babcock, Ryan J; Rose, David M; Hempel, Chris M; Wiig, Kjesten A; Laeng, Pascal; Levin, Margaret E; Ryan, Timothy A; Gerber, David J

    2013-07-01

    Working memory is an essential component of higher cognitive function, and its impairment is a core symptom of multiple CNS disorders, including schizophrenia. Neuronal mechanisms supporting working memory under normal conditions have been described and include persistent, high-frequency activity of prefrontal cortical neurons. However, little is known about the molecular and cellular basis of working memory dysfunction in the context of neuropsychiatric disorders. To elucidate synaptic and neuronal mechanisms of working memory dysfunction, we have performed a comprehensive analysis of a mouse model of schizophrenia, the forebrain-specific calcineurin knock-out mouse. Biochemical analyses of cortical tissue from these mice revealed a pronounced hyperphosphorylation of synaptic vesicle cycling proteins known to be necessary for high-frequency synaptic transmission. Examination of the synaptic vesicle cycle in calcineurin-deficient neurons demonstrated an impairment of vesicle release enhancement during periods of intense stimulation. Moreover, brain slice and in vivo electrophysiological analyses showed that loss of calcineurin leads to a gene dose-dependent disruption of high-frequency synaptic transmission and network activity in the PFC, correlating with selective working memory impairment. Finally, we showed that levels of dynamin I, a key presynaptic protein and calcineurin substrate, are significantly reduced in prefrontal cortical samples from schizophrenia patients, extending the disease relevance of our findings. Our data provide support for a model in which impaired synaptic vesicle cycling represents a critical node for disease pathologies underlying the cognitive deficits in schizophrenia. PMID:23825400

  11. Purines released from astrocytes inhibit excitatory synaptic transmission in the ventral horn of the spinal cord

    PubMed Central

    Carlsen, Eva Meier; Perrier, Jean-François

    2014-01-01

    Spinal neuronal networks are essential for motor function. They are involved in the integration of sensory inputs and the generation of rhythmic motor outputs. They continuously adapt their activity to the internal state of the organism and to the environment. This plasticity can be provided by different neuromodulators. These substances are usually thought of being released by dedicated neurons. However, in other networks from the central nervous system synaptic transmission is also modulated by transmitters released from astrocytes. The star-shaped glial cell responds to neurotransmitters by releasing gliotransmitters, which in turn modulate synaptic transmission. Here we investigated if astrocytes present in the ventral horn of the spinal cord modulate synaptic transmission. We evoked synaptic inputs in ventral horn neurons recorded in a slice preparation from the spinal cord of neonatal mice. Neurons responded to electrical stimulation by monosynaptic EPSCs (excitatory monosynaptic postsynaptic currents). We used mice expressing the enhanced green fluorescent protein under the promoter of the glial fibrillary acidic protein to identify astrocytes. Chelating calcium with BAPTA in a single neighboring astrocyte increased the amplitude of synaptic currents. In contrast, when we selectively stimulated astrocytes by activating PAR-1 receptors with the peptide TFLLR, the amplitude of EPSCs evoked by a paired stimulation protocol was reduced. The paired-pulse ratio was increased, suggesting an inhibition occurring at the presynaptic side of synapses. In the presence of blockers for extracellular ectonucleotidases, TFLLR did not induce presynaptic inhibition. Puffing adenosine reproduced the effect of TFLLR and blocking adenosine A1 receptors with 8-Cyclopentyl-1,3-dipropylxanthine prevented it. Altogether our results show that ventral horn astrocytes are responsible for a tonic and a phasic inhibition of excitatory synaptic transmission by releasing ATP, which gets

  12. Use of communications. [satellite communication

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Progress in the field of satellite communications is reviewed, and useful services which may be provided by future satellite communications systems are considered. Recommendations are made with regard to mobile communications for use on land and at sea, position determination, mineral and energy exploration, the possibility of using electronic means to assist in main delivery, education and health-care experiments, and the use of satellite telecommunications to enhance the quality of life in rural areas by making available a full range of educational and entertainment programs. The needs of the amateur radio community are also considered.

  13. The Virtual Environmental Microbiology Center - A Social Network for Enhanced Communication between Water Researchers and Policy Makers

    EPA Science Inventory

    Effective communication within and between organizations involved in research and policy making activities is essential. Sharing information across organizational and geographic boundaries can also facilitate coordination and collaboration, promote a better understanding of tech...

  14. Sulforhodamine 101 induces long-tem potentiation of intrinsic excitability and synaptic efficacy in hippocampal CA1 pyramidal neurons

    PubMed Central

    Kang, Jian; Kang, Ning; Yu, Yufei; Zhang, Jinsong; Petersen, Nicolas; Tian, Guo-Feng; Nedergaard, Maiken

    2010-01-01

    Sulforhodamine 101 (SR101) has been extensively used for investigation as a specific marker for astroglia in vivo and activity-dependent dye for monitoring regulated exocytosis. Here, we report that SR101 has bioactive effects on neuronal activity. Perfusion of slices with SR101 (1 μM) for 10 min induced long-term potentiation of intrinsic neuronal excitability (LTP-IE) and a long-lasting increase in evoked EPSCs (eEPSCs) in CA1 pyramidal neurons in hippocampal slices. The increase in intrinsic neuronal excitability was a result of negative shifts in the action potential (AP) threshold. The N-methyl D-aspartate receptor (NMDAR) antagonist, AP-5 (50 μM), blocked SR101-induced LTP-IE, but glutamate receptor blockers, AP-5 (50 μM), MCPG (200 μM), and MSOP (100 μM), only partially blocked SR101-induced potentiation of eEPSCs. SR101 induced an enhancement of evoked synaptic NMDAR currents, suggesting that SR101 enhances activation of synaptic NMDARs. SR101-induced LTP-IE and potentiation of synaptic transmission triggered spontaneous neuronal firing in slices and in vivo epileptic seizures. Our results suggest that SR101 is an epileptogenic agent that long-lastingly lowers the AP threshold to increase intrinsic neuronal excitability and enhances the synaptic efficacy to increase synaptic inputs. As such, SR101 can be used as an experimental tool to induce epileptic seizures. PMID:20600669

  15. Connexin 30 sets synaptic strength by controlling astroglial synapse invasion.

    PubMed

    Pannasch, Ulrike; Freche, Dominik; Dallérac, Glenn; Ghézali, Grégory; Escartin, Carole; Ezan, Pascal; Cohen-Salmon, Martine; Benchenane, Karim; Abudara, Veronica; Dufour, Amandine; Lübke, Joachim H R; Déglon, Nicole; Knott, Graham; Holcman, David; Rouach, Nathalie

    2014-04-01

    Astrocytes play active roles in brain physiology by dynamic interactions with neurons. Connexin 30, one of the two main astroglial gap-junction subunits, is thought to be involved in behavioral and basic cognitive processes. However, the underlying cellular and molecular mechanisms are unknown. We show here in mice that connexin 30 controls hippocampal excitatory synaptic transmission through modulation of astroglial glutamate transport, which directly alters synaptic glutamate levels. Unexpectedly, we found that connexin 30 regulated cell adhesion and migration and that connexin 30 modulation of glutamate transport, occurring independently of its channel function, was mediated by morphological changes controlling insertion of astroglial processes into synaptic clefts. By setting excitatory synaptic strength, connexin 30 plays an important role in long-term synaptic plasticity and in hippocampus-based contextual memory. Taken together, these results establish connexin 30 as a critical regulator of synaptic strength by controlling the synaptic location of astroglial processes. PMID:24584052

  16. Redistribution of synaptic efficacy between neocortical pyramidal neurons

    NASA Astrophysics Data System (ADS)

    Markram, Henry; Tsodyks, Misha

    1996-08-01

    EXPERiENCE-dependent potentiation and depression of synaptic strength has been proposed to subserve learning and memory by changing the gain of signals conveyed between neurons1,2. Here we examine synaptic plasticity between individual neocortical layer-5 pyramidal neurons. We show that an increase in the synaptic response, induced by pairing action-potential activity in pre- and postsynaptic neurons, was only observed when synaptic input occurred at low frequencies. This frequency-dependent increase in synaptic responses arises because of a redistribution of the available synaptic efficacy and not because of an increase in the efficacy. Redistribution of synaptic efficacy could represent a mechanism to change the content, rather than the gain, of signals conveyed between neurons.

  17. Carbon Nanotube Synaptic Transistor Network for Pattern Recognition.

    PubMed

    Kim, Sungho; Yoon, Jinsu; Kim, Hee-Dong; Choi, Sung-Jin

    2015-11-18

    Inspired by the human brain, a neuromorphic system combining complementary metal-oxide semiconductor (CMOS) and adjustable synaptic devices may offer new computing paradigms by enabling massive neural-network parallelism. In particular, synaptic devices, which are capable of emulating the functions of biological synapses, are used as the essential building blocks for an information storage and processing system. However, previous synaptic devices based on two-terminal resistive devices remain challenging because of their variability and specific physical mechanisms of resistance change, which lead to a bottleneck in the implementation of a high-density synaptic device network. Here we report that a three-terminal synaptic transistor based on carbon nanotubes can provide reliable synaptic functions that encode relative timing and regulate weight change. In addition, using system-level simulations, the developed synaptic transistor network associated with CMOS circuits can perform unsupervised learning for pattern recognition using a simplified spike-timing-dependent plasticity scheme. PMID:26512729

  18. Cdk5 is a New Rapid Synaptic Homeostasis Regulator Capable of Initiating the Early Alzheimer-Like Pathology.

    PubMed

    Sheng, Yanghui; Zhang, Lei; Su, Susan C; Tsai, Li-Huei; Julius Zhu, J

    2016-07-01

    Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase implicated in synaptic plasticity, behavior, and cognition, yet its synaptic function remains poorly understood. Here, we report that physiological Cdk5 signaling in rat hippocampal CA1 neurons regulates homeostatic synaptic transmission using an unexpectedly rapid mechanism that is different from all known slow homeostatic regulators, such as beta amyloid (Aβ) and activity-regulated cytoskeleton-associated protein (Arc, aka Arg3.1). Interestingly, overproduction of the potent Cdk5 activator p25 reduces synapse density, and dynamically regulates synaptic size by suppressing or enhancing Aβ/Arc production. Moreover, chronic overproduction of p25, seen in Alzheimer's patients, induces initially concurrent reduction in synapse density and increase in synaptic size characteristic of the early Alzheimer-like pathology, and later persistent synapse elimination in intact brains. These results identify Cdk5 as the regulator of a novel rapid form of homeostasis at central synapses and p25 as the first molecule capable of initiating the early Alzheimer's synaptic pathology. PMID:26088971

  19. Regulation of synaptic connectivity: levels of Fasciclin II influence synaptic growth in the Drosophila CNS.

    PubMed

    Baines, Richard A; Seugnet, Laurent; Thompson, Annemarie; Salvaterra, Paul M; Bate, Michael

    2002-08-01

    Much of our understanding of synaptogenesis comes from studies that deal with the development of the neuromuscular junction (NMJ). Although well studied, it is not clear how far the NMJ represents an adequate model for the formation of synapses within the CNS. Here we investigate the role of Fasciclin II (Fas II) in the development of synapses between identified motor neurons and cholinergic interneurons in the CNS of Drosophila. Fas II is a neural cell adhesion molecule homolog that is involved in both target selection and synaptic plasticity at the NMJ in Drosophila. In this study, we show that levels of Fas II are critical determinants of synapse formation and growth in the CNS. The initial establishment of synaptic contacts between these identified neurons is seemingly independent of Fas II. The subsequent proliferation of these synaptic connections that occurs postembryonically is, in contrast, significantly retarded by the absence of Fas II. Although the initial formation of synaptic connectivity between these neurons is seemingly independent of Fas II, we show that their formation is, nevertheless, significantly affected by manipulations that alter the relative balance of Fas II in the presynaptic and postsynaptic neurons. Increasing expression of Fas II in either the presynaptic or postsynaptic neurons, during embryogenesis, is sufficient to disrupt the normal level of synaptic connectivity that occurs between these neurons. This effect of Fas II is isoform specific and, moreover, phenocopies the disruption to synaptic connectivity observed previously after tetanus toxin light chain-dependent blockade of evoked synaptic vesicle release in these neurons. PMID:12151538

  20. A method for the three-dimensional reconstruction of Neurobiotin™-filled neurons and the location of their synaptic inputs.

    PubMed

    Fogarty, Matthew J; Hammond, Luke A; Kanjhan, Refik; Bellingham, Mark C; Noakes, Peter G

    2013-01-01

    Here, we describe a robust method for mapping the number and type of neuro-chemically distinct synaptic inputs that a single reconstructed neuron receives. We have used individual hypoglossal motor neurons filled with Neurobiotin by semi-loose seal electroporation in thick brainstem slices. These filled motor neurons were then processed for excitatory and inhibitory synaptic inputs, using immunohistochemical-labeling procedures. For excitatory synapses, we used anti-VGLUT2 to locate glutamatergic pre-synaptic terminals and anti-PSD-95 to locate post-synaptic specializations on and within the surface of these filled motor neurons. For inhibitory synapses, we used anti-VGAT to locate GABAergic pre-synaptic terminals and anti-GABA-A receptor subunit α1 to locate the post-synaptic domain. The Neurobiotin-filled and immuno-labeled motor neuron was then processed for optical sectioning using confocal microscopy. The morphology of the motor neuron including its dendritic tree and the distribution of excitatory and inhibitory synapses were then determined by three-dimensional reconstruction using IMARIS software (Bitplane). Using surface rendering, fluorescence thresholding, and masking of unwanted immuno-labeling, tools found in IMARIS, we were able to obtain an accurate 3D structure of an individual neuron including the number and location of its glutamatergic and GABAergic synaptic inputs. The power of this method allows for a rapid morphological confirmation of the post-synaptic responses recorded by patch-clamp prior to Neurobiotin filling. Finally, we show that this method can be adapted to super-resolution microscopy techniques, which will enhance its applicability to the study of neural circuits at the level of synapses. PMID:24101895

  1. NR2B-dependent cyclophilin D translocation suppresses the recovery of synaptic transmission after oxygen-glucose deprivation.

    PubMed

    Zhang, Zhihua; Wang, Yongfu; Yan, Shijun; Du, Fang; Yan, Shirley Shidu

    2015-10-01

    N-methyl d-aspartate receptor (NMDA) subunit 2B (NR2B)-containing NMDA receptors and mitochondrial protein cyclophilin D (CypD) are well characterized in mediating neuronal death after ischemia, respectively. However, whether and how NR2B and CypD work together in mediating synaptic injury after ischemia remains elusive. Using an ex vivo ischemia model of oxygen-glucose deprivation (OGD) in hippocampal slices, we identified a NR2B-dependent mechanism for CypD translocation onto the mitochondrial inner membrane. CypD depletion (CypD null mice) prevented OGD-induced impairment in synaptic transmission recovery. Overexpression of neuronal CypD mice (CypD+) exacerbated OGD-induced loss of synaptic transmission. Inhibition of CypD-dependent mitochondrial permeability transition pore (mPTP) opening by cyclosporine A (CSA) attenuated ischemia-induced synaptic perturbation in CypD+ and non-transgenic (non-Tg) mice. The treatment of antioxidant EUK134 to suppress mitochondrial oxidative stress rescued CypD-mediated synaptic dysfunction following OGD in CypD+ slices. Furthermore, OGD provoked the interaction of CypD with P53, which was enhanced in slices overexpressing CypD but was diminished in CypD-null slices. Inhibition of p53 using a specific inhibitor of p53 (pifithrin-μ) attenuated the CypD/p53 interaction following OGD, along with a restored synaptic transmission in both non-Tg and CypD+ hippocampal slices. Our results indicate that OGD-induced CypD translocation potentiates CypD/P53 interaction in a NR2B dependent manner, promoting oxidative stress and loss of synaptic transmission. We also evaluate a new ex vivo chronic OGD-induced ischemia model for studying the effect of oxidative stress on synaptic damage. PMID:26232180

  2. Spontaneous network activity and synaptic development

    PubMed Central

    Kerschensteiner, Daniel

    2014-01-01

    Throughout development, the nervous system produces patterned spontaneous activity. Research over the last two decades has revealed a core group of mechanisms that mediate spontaneous activity in diverse circuits. Many circuits engage several of these mechanisms sequentially to accommodate developmental changes in connectivity. In addition to shared mechanisms, activity propagates through developing circuits and neuronal pathways (i.e. linked circuits in different brain areas) in stereotypic patterns. Increasing evidence suggests that spontaneous network activity shapes synaptic development in vivo. Variations in activity-dependent plasticity may explain how similar mechanisms and patterns of activity can be employed to establish diverse circuits. Here, I will review common mechanisms and patterns of spontaneous activity in emerging neural networks and discuss recent insights into their contribution to synaptic development. PMID:24280071

  3. Morphological plasticity of astroglia: Understanding synaptic microenvironment

    PubMed Central

    2015-01-01

    Memory formation in the brain is thought to rely on the remodeling of synaptic connections which eventually results in neural network rewiring. This remodeling is likely to involve ultrathin astroglial protrusions which often occur in the immediate vicinity of excitatory synapses. The phenomenology, cellular mechanisms, and causal relationships of such astroglial restructuring remain, however, poorly understood. This is in large part because monitoring and probing of the underpinning molecular machinery on the scale of nanoscopic astroglial compartments remains a challenge. Here we briefly summarize the current knowledge regarding the cellular organisation of astroglia in the synaptic microenvironment and discuss molecular mechanisms potentially involved in use‐dependent astroglial morphogenesis. We also discuss recent observations concerning morphological astroglial plasticity, the respective monitoring methods, and some of the newly emerging techniques that might help with conceptual advances in the area. GLIA 2015;63:2133–2151 PMID:25782611

  4. Novel synaptic memory device for neuromorphic computing

    PubMed Central

    Mandal, Saptarshi; El-Amin, Ammaarah; Alexander, Kaitlyn; Rajendran, Bipin; Jha, Rashmi

    2014-01-01

    This report discusses the electrical characteristics of two-terminal synaptic memory devices capable of demonstrating an analog change in conductance in response to the varying amplitude and pulse-width of the applied signal. The devices are based on Mn doped HfO2 material. The mechanism behind reconfiguration was studied and a unified model is presented to explain the underlying device physics. The model was then utilized to show the application of these devices in speech recognition. A comparison between a 20 nm × 20 nm sized synaptic memory device with that of a state-of-the-art VLSI SRAM synapse showed ~10× reduction in area and >106 times reduction in the power consumption per learning cycle. PMID:24939247

  5. Control of neural chaos by synaptic noise.

    PubMed

    Cortes, J M; Torres, J J; Marro, J

    2007-02-01

    We study neural automata - or neurobiologically inspired cellular automata - which exhibits chaotic itinerancy among the different stored patterns or memories. This is a consequence of activity-dependent synaptic fluctuations, which continuously destabilize the attractor and induce irregular hopping to other possible attractors. The nature of these irregularities depends on the dynamic details, namely, on the intensity of the synaptic noise and the number of sites of the network, which are synchronously updated at each time step. Varying these factors, different regimes occur, ranging from regular to chaotic dynamics. As a result, and in absence of external agents, the chaotic behavior may turn regular after tuning the noise intensity. It is argued that a similar mechanism might be on the basis of self-controlling chaos in natural systems. PMID:17084962

  6. Corticostriatal synaptic adaptations in Huntington's disease.

    PubMed

    Plotkin, Joshua L; Surmeier, D James

    2015-08-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder that profoundly impairs corticostriatal information processing. While late stage pathology includes cell death, the appearance of motor symptoms parallels more subtle changes in neuronal function and synaptic integration. Because of the difficulty in modeling the disease and the complexity of the corticostriatal network, understanding the mechanisms driving pathology has been slow to develop. In recent years, advances in animal models and network analysis tools have begun to shed light on the circuit-specific deficits. These studies have revealed a progressive impairment of corticostriatal synaptic signaling in subpopulations of striatal neurons, turning classical excitotoxicity models of HD upside down. Disrupted brain derived neurotrophic factor signaling appears to be a key factor in this decline. PMID:25700146

  7. Synaptic devices based on purely electronic memristors

    NASA Astrophysics Data System (ADS)

    Pan, Ruobing; Li, Jun; Zhuge, Fei; Zhu, Liqiang; Liang, Lingyan; Zhang, Hongliang; Gao, Junhua; Cao, Hongtao; Fu, Bing; Li, Kang

    2016-01-01

    Memristive devices have been widely employed to emulate biological synaptic behavior. In these cases, the memristive switching generally originates from electrical field induced ion migration or Joule heating induced phase change. In this letter, the Ti/ZnO/Pt structure was found to show memristive switching ascribed to a carrier trapping/detrapping of the trap sites (e.g., oxygen vacancies or zinc interstitials) in ZnO. The carrier trapping/detrapping level can be controllably adjusted by regulating the current compliance level or voltage amplitude. Multi-level conductance states can, therefore, be realized in such memristive device. The spike-timing-dependent plasticity, an important Hebbian learning rule, has been implemented in this type of synaptic device. Compared with filamentary-type memristive devices, purely electronic memristors have potential to reduce their energy consumption and work more stably and reliably, since no structural distortion occurs.

  8. Pregnenolone sulfate as a modulator of synaptic plasticity

    PubMed Central

    Smith, Conor C.; Gibbs, Terrell T.

    2015-01-01

    Rationale The neurosteroid pregnenolone sulfate (PregS) acts as a cognitive enhancer and modulator of neurotransmission, yet aligning its pharmacological and physiological effects with reliable measurements of endogenous local concentrations and pharmacological and therapeutic targets has remained elusive for over 20 years. Objectives New basic and clinical research concerning neurosteroid modulation of the central nervous system (CNS) function has emerged over the past 5 years, including important data involving pregnenolone and various neurosteroid precursors of PregS that point to a need for a critical status update. Results Highly specific actions of PregS affecting excitatory N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic transmission and the pharmacological effects of PregS on various receptors and ion channels are discussed. The discovery of a high potency (nanomolar) signal transduction pathway for PregS-induced NMDAR trafficking to the cell surface via a Ca2+- and G protein-coupled receptor (GPCR)-dependent mechanism and a potent (EC50 ~2 pM) direct enhancement of intracellular Ca2+ levels is discussed in terms of its agonist effects on long-term potentiation (LTP) and memory. Lastly, preclinical and clinical studies assessing the promnestic effects of PregS and pregnenolone toward cognitive dysfunction in schizophrenia, and altered serum levels in epilepsy and alcohol dependence, are reviewed. Conclusions PregS is present in human and rodent brain at physiologically relevant concentrations and meets most of the criteria for an endogenous neurotransmitter/neuromodulator. PregS likely plays a significant role in modulation of glutamatergic excitatory synaptic transmission underlying learning and memory, yet the molecular target(s) for its action awaits identification. PMID:24997854

  9. Synapsin Isoforms and Synaptic Vesicle Trafficking

    PubMed Central

    Song, Sang-Ho; Augustine, George J.

    2015-01-01

    Synapsins were the first presynaptic proteins identified and have served as the flagship of the presynaptic protein field. Here we review recent studies demonstrating that different members of the synapsin family play different roles at presynaptic terminals employing different types of synaptic vesicles. The structural underpinnings for these functions are just beginning to be understood and should provide a focus for future efforts. PMID:26627875

  10. Depletion of the AMPAR reserve pool impairs synaptic plasticity in a model of hepatic encephalopathy.

    PubMed

    Schroeter, Annett; Wen, Shuping; Mölders, Andrea; Erlenhardt, Nadine; Stein, Valentin; Klöcker, Nikolaj

    2015-09-01

    Hepatic encephalopathy (HE) is the most common neuropsychiatric complication of acute or chronic liver failure. Clinical symptoms include cognitive and intellectual dysfunction as well as impaired motor activity and coordination. There is general consensus that increased levels of ammonia play a central role in the pathogenesis of HE. However, it is still elusive how cognitive performance including the ability to learn and memorize information is affected by ammonia at molecular levels. In the present study, we have employed a neuroglial co-culture model, which preserves neuroglial interplay but allows for cell-type specific molecular and functional analyses, to investigate glutamatergic neurotransmission under conditions of high ammonia. Chronic exposure to ammonia significantly reduced neuronal mRNA and protein expression of AMPA-subtype glutamate receptors (AMPARs), which mediate most fast excitatory neurotransmission in the brain. Surprisingly, neurons were able to fully maintain basal glutamatergic neurotransmission as recorded by AMPAR-mediated miniature excitatory postsynaptic currents (mEPSCs) even when >50% of total AMPARs were lost. However, long-lasting, activity-dependent changes in the efficacy of synaptic communication, which model the capability of the brain to learn and store information, were severely constrained. Whereas synaptic efficacy could still be depressed, an increase in synaptic strength was abolished. We conclude that neurons retain basal glutamatergic transmission at the expense of the extrasynaptic population of AMPARs, which is revealed when the extrasynaptic reserve pool is recruited in vain for synaptic potentiation. Our findings thus offer a molecular model, which might not only explain impaired synaptic plasticity in HE but also in other neurological diseases accompanied by a decrease in extrasynaptic AMPAR expression. PMID:26363416

  11. Modulation of swimming behavior in the medicinal leech. IV. Serotonin-induced alteration of synaptic interactions between neurons of the swim circuit.

    PubMed

    Mangan, P S; Cometa, A K; Friesen, W O

    1994-12-01

    Serotonin enhances the expression of swimming in the medicinal leech Hirudo medicinalis. These two reports examine the physiological causes underlying this modulation. The initial paper (Mangan et al. 1994) demonstrated that serotonin enhanced the participation of inhibitory swim motor neurons (MNs) in the generation of the swimming rhythm in the isolated nerve cord. In experiments reported here, we examined whether synaptic interactions between neurons of the swim circuit are altered by serotonin. Following exposure to 50 microM serotonin, pairwise intracellular recording revealed the presence of a time-dependent synaptic decrement. Synaptic decrement was characterized by: 1) a substantial decline in synaptic inhibition (half-decay time about 0.4 s) during constant presynaptic excitation; 2) a reduced half-time of recovery from synaptic inhibition; and 3) a strong dependence on the presynaptic neuron's membrane potential. We found little alteration in the physiology of synaptic transmission involving MNs following amine depletion in leech nerve cords. We propose that alterations in synaptic interactions resulting from exposure to elevated serotonin levels, coupled with the changes in MN cellular properties described earlier, are crucial to the increased efficacy of MNs in participating in generating and expressing the leech swimming rhythm. PMID:7807416

  12. Synaptic kainate currents reset interneuron firing phase

    PubMed Central

    Yang, Ellen J; Harris, Alexander Z; Pettit, Diana L

    2007-01-01

    Hippocampal interneuron activity has been linked to epileptogenesis, seizures and the oscillatory synaptic activity detected in behaving rats. Interneurons fire at specific times in the rhythmic cycles that comprise these oscillations; however, the mechanisms controlling these firing patterns remain unclear. We have examined the role of synaptic input in modulating the firing of spontaneously active rat hippocampal interneurons. We find that synaptic glutamate receptor currents of 20–30 pA increase instantaneous firing frequency and reset the phase of spontaneously firing CA1 stratum oriens interneurons. Kainate receptor (KAR)-mediated currents are particularly effective at producing this phase reset, while AMPA receptor currents are relatively ineffective. The efficacy of KAR-mediated currents is probably due to their 3-fold longer decay. Given the small amplitude of the currents needed for this phase reset, coincident activation of only a few KAR-containing synapses could synchronize firing in groups of interneurons. These data suggest that KARs are potent modulators of circuit behaviour and their activation alters hippocampal interneuron output. PMID:17068102

  13. Auditory neuropathy--neural and synaptic mechanisms.

    PubMed

    Moser, Tobias; Starr, Arnold

    2016-03-01

    Sensorineural hearing impairment is the most common form of hearing loss, and encompasses pathologies of the cochlea and the auditory nerve. Hearing impairment caused by abnormal neural encoding of sound stimuli despite preservation of sensory transduction and amplification by outer hair cells is known as 'auditory neuropathy'. This term was originally coined for a specific type of hearing impairment affecting speech comprehension beyond changes in audibility: patients with this condition report that they "can hear but cannot understand". This type of hearing impairment can be caused by damage to the sensory inner hair cells (IHCs), IHC ribbon synapses or spiral ganglion neurons. Human genetic and physiological studies, as well as research on animal models, have recently shown that disrupted IHC ribbon synapse function--resulting from genetic alterations that affect presynaptic glutamate loading of synaptic vesicles, Ca(2+) influx, or synaptic vesicle exocytosis--leads to hearing impairment termed 'auditory synaptopathy'. Moreover, animal studies have demonstrated that sound overexposure causes excitotoxic loss of IHC ribbon synapses. This mechanism probably contributes to hearing disorders caused by noise exposure or age-related hearing loss. This Review provides an update on recently elucidated sensory, synaptic and neural mechanisms of hearing impairment, their corresponding clinical findings, and discusses current rehabilitation strategies as well as future therapies. PMID:26891769

  14. The developmental stages of synaptic plasticity

    PubMed Central

    Lohmann, Christian; Kessels, Helmut W

    2014-01-01

    Abstract The brain is programmed to drive behaviour by precisely wiring the appropriate neuronal circuits. Wiring and rewiring of neuronal circuits largely depends on the orchestrated changes in the strengths of synaptic contacts. Here, we review how the rules of synaptic plasticity change during development of the brain, from birth to independence. We focus on the changes that occur at the postsynaptic side of excitatory glutamatergic synapses in the rodent hippocampus and neocortex. First we summarize the current data on the structure of synapses and the developmental expression patterns of the key molecular players of synaptic plasticity, N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as pivotal kinases (Ca2+/calmodulin-dependent protein kinase II, protein kinase A, protein kinase C) and phosphatases (PP1, PP2A, PP2B). In the second part we relate these findings to important characteristics of the emerging network. We argue that the concerted and gradual shifts in the usage of plasticity molecules comply with the changing need for (re)wiring neuronal circuits. PMID:24144877

  15. Characterization and extraction of the synaptic apposition surface for synaptic geometry analysis

    PubMed Central

    Morales, Juan; Rodríguez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Merchán-Pérez, Angel

    2013-01-01

    Geometrical features of chemical synapses are relevant to their function. Two critical components of the synaptic junction are the active zone (AZ) and the postsynaptic density (PSD), as they are related to the probability of synaptic release and the number of postsynaptic receptors, respectively. Morphological studies of these structures are greatly facilitated by the use of recent electron microscopy techniques, such as combined focused ion beam milling and scanning electron microscopy (FIB/SEM), and software tools that permit reconstruction of large numbers of synapses in three dimensions. Since the AZ and the PSD are in close apposition and have a similar surface area, they can be represented by a single surface—the synaptic apposition surface (SAS). We have developed an efficient computational technique to automatically extract this surface from synaptic junctions that have previously been three-dimensionally reconstructed from actual tissue samples imaged by automated FIB/SEM. Given its relationship with the release probability and the number of postsynaptic receptors, the surface area of the SAS is a functionally relevant measure of the size of a synapse that can complement other geometrical features like the volume of the reconstructed synaptic junction, the equivalent ellipsoid size and the Feret's diameter. PMID:23847474

  16. Characterization and extraction of the synaptic apposition surface for synaptic geometry analysis.

    PubMed

    Morales, Juan; Rodríguez, Angel; Rodríguez, José-Rodrigo; Defelipe, Javier; Merchán-Pérez, Angel

    2013-01-01

    Geometrical features of chemical synapses are relevant to their function. Two critical components of the synaptic junction are the active zone (AZ) and the postsynaptic density (PSD), as they are related to the probability of synaptic release and the number of postsynaptic receptors, respectively. Morphological studies of these structures are greatly facilitated by the use of recent electron microscopy techniques, such as combined focused ion beam milling and scanning electron microscopy (FIB/SEM), and software tools that permit reconstruction of large numbers of synapses in three dimensions. Since the AZ and the PSD are in close apposition and have a similar surface area, they can be represented by a single surface-the synaptic apposition surface (SAS). We have developed an efficient computational technique to automatically extract this surface from synaptic junctions that have previously been three-dimensionally reconstructed from actual tissue samples imaged by automated FIB/SEM. Given its relationship with the release probability and the number of postsynaptic receptors, the surface area of the SAS is a functionally relevant measure of the size of a synapse that can complement other geometrical features like the volume of the reconstructed synaptic junction, the equivalent ellipsoid size and the Feret's diameter. PMID:23847474

  17. Modulation of GABA-mediated synaptic transmission by endogenous zinc in the immature rat hippocampus in vitro.

    PubMed Central

    Xie, X; Hider, R C; Smart, T G

    1994-01-01

    1. Intracellular recordings from postnatal 2- to 12-day-old (P2-12) rat hippocampal CA3 pyramidal neurones exhibited spontaneous synaptic potentials mediated by GABAA receptors. These potentials can be separated on the basis of amplitude into two classes which are referred to as small and large. 2. The large depolarizing potentials were reversibly inhibited by the Zn2+ chelator 1,2-diethyl-3-hydroxypyridin-4-one (CP94). The small inhibitory postsynaptic potentials. (IPSPs) were apparently unaffected. 3. Stimulation of the mossy fibre pathway evoked composite excitatory postsynaptic potentials (EPSPs) and IPSPs. Threshold stimulus-evoked synaptic potentials were mediated by GABAA receptors and were reversibly blocked by CP94. The responses evoked by suprathreshold stimulation and persisting in the presence of bicuculline or CP94 were partially inhibited by 2-amino-5-phosphonopropionic acid (AP5) and were completely blocked with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 4. L-Histidine, which preferentially forms complexes with Cu2+ > Zn2+ > Fe2+ > Mn2+, inhibited both naturally occurring spontaneous and evoked GABAA-mediated large synaptic potentials without affecting the neuronal resting membrane properties. Exogenously applied Zn2+ induced large spontaneous synaptic potentials and prolonged the duration of the evoked potentials. These effects were reversibly blocked by histidine. 5. The metal chelating agent diethyldithiocarbamate had little effect on the large amplitude synaptic potentials. 6. The transition metal divalent cations Fe2+ and Mn2+ did not initiate large synaptic potentials in CA3 neurones; however, Cu2+ depolarized the membrane and enhanced both excitatory and inhibitory synaptic transmission, resulting in a transient increase in the frequency of the large amplitude events. In comparison, zinc increased the frequency of the large potentials and also induced such events in neurons (P4-21) where innate potentials were absent. The postsynaptic

  18. Methods to Enhance Verbal Communication between Individuals with Alzheimer's Disease and Their Formal and Informal Caregivers: A Systematic Review

    PubMed Central

    Egan, Mary; Bérubé, Daniel; Racine, Geneviève; Leonard, Carol; Rochon, Elizabeth

    2010-01-01

    Alzheimer's disease is the leading cause of dementia in older adults. Although memory problems are the most characteristic symptom of this disorder, many individuals also experience progressive problems with communication. This systematic review investigates the effectiveness of methods to improve the verbal communication of individuals with Alzheimer's disease with their caregivers. The following databases were reviewed: PsychINFO, CINAHL, EMBASE, MEDLINE, REHABDATA, and COMDIS. The inclusion criteria were: (i) experimentally based studies, (ii) quantitative results, (iii) intervention aimed at improving verbal communication of the affected individual with a caregiver, and (iv) at least 50% of the sample having a confirmed diagnosis of Alzheimer's disease. A total of 13 studies met all of the inclusion criteria. One technique emerged as potentially effective: the use of memory aids combined with specific caregiver training programs. The strength of this evidence was restricted by methodological limitations of the studies. Both adoption of and further research on these interventions are recommended. PMID:20798856

  19. Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis

    PubMed Central

    Arendt, Kristin L.; Zhang, Zhenjie; Ganesan, Subhashree; Hintze, Maik; Shin, Maggie M.; Tang, Yitai; Cho, Ahryon; Graef, Isabella A.; Chen, Lu

    2015-01-01

    Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that maintains stability of the network and fidelity for information processing in response to prolonged perturbation of network and synaptic activity. Prolonged blockade of synaptic activity decreases resting Ca2+ levels in neurons, thereby inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic plasticity; however, the signal transduction pathway that links reduced Ca2+-levels to RA synthesis remains unknown. Here we identify the Ca2+-dependent protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA synthesis in neurons, and leads to increased excitatory and decreased inhibitory synaptic transmission. These effects of CaN inhibitors on synaptic transmission are blocked by pharmacological inhibitors of RA synthesis or acute genetic deletion of the RA receptor RARα. Thus, CaN, acting upstream of RA, plays a critical role in gating RA signaling pathway in response to synaptic activity. Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831 and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic signaling, and defines CaN as the Ca2+-sensing signaling molecule that mediates RA-dependent homeostatic synaptic plasticity. PMID:26443861

  20. Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis.

    PubMed

    Arendt, Kristin L; Zhang, Zhenjie; Ganesan, Subhashree; Hintze, Maik; Shin, Maggie M; Tang, Yitai; Cho, Ahryon; Graef, Isabella A; Chen, Lu

    2015-10-20

    Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that maintains stability of the network and fidelity for information processing in response to prolonged perturbation of network and synaptic activity. Prolonged blockade of synaptic activity decreases resting Ca(2+) levels in neurons, thereby inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic plasticity; however, the signal transduction pathway that links reduced Ca(2+)-levels to RA synthesis remains unknown. Here we identify the Ca(2+)-dependent protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA synthesis in neurons, and leads to increased excitatory and decreased inhibitory synaptic transmission. These effects of CaN inhibitors on synaptic transmission are blocked by pharmacological inhibitors of RA synthesis or acute genetic deletion of the RA receptor RARα. Thus, CaN, acting upstream of RA, plays a critical role in gating RA signaling pathway in response to synaptic activity. Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831 and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic signaling, and defines CaN as the Ca(2+)-sensing signaling molecule that mediates RA-dependent homeostatic synaptic plasticity. PMID:26443861

  1. Reduced expression of the vesicular acetylcholine transporter and neurotransmitter content affects synaptic vesicle distribution and shape in mouse neuromuscular junction.

    PubMed

    Rodrigues, Hermann A; Fonseca, Matheus de C; Camargo, Wallace L; Lima, Patrícia M A; Martinelli, Patrícia M; Naves, Lígia A; Prado, Vânia F; Prado, Marco A M; Guatimosim, Cristina

    2013-01-01

    In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KD(HOM)) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KD(HOM) mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1-43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or no stimulation, VAChT KD(HOM) neuromuscular junctions did not differ from WT on total number of vesicles but showed altered distribution. Additionally, motor nerve terminals in VAChT KD(HOM) exhibited small and flattened synaptic vesicles similar to that observed in WT mice treated with vesamicol that blocks acetylcholine uptake. Based on these results, we propose that decreased VAChT levels affect synaptic vesicle biogenesis and distribution whereas a lower ACh content affects vesicles shape. PMID:24260111

  2. Differential balance of prefrontal synaptic activity in successful versus unsuccessful cognitive aging.

    PubMed

    Bories, Cyril; Husson, Zoé; Guitton, Matthieu J; De Koninck, Yves

    2013-01-23

    Normal aging is associated with a variable decline in cognitive functions. Among these, executive function, decision-making, and working memory are primarily associated with the prefrontal cortex. Although a number of studies have examined the structural substrates of cognitive decline associated with aging within this cortical area, their functional correlates remain poorly understood. To fill this gap, we aimed to identify functional synaptic substrates of age-associated frontal-dependent deficits in layer 2/3 pyramidal neurons of medial prefrontal cortex of 3-, 9-, and ≥ 23-month-old Fischer 344 rats. We combined, in the same animals, novelty recognition and exploratory behavioral tasks with assessment of structural and functional aspects of prefrontal synaptic properties. We found that subsets of aged animals displayed stereotyped exploratory behavior or memory deficits. Despite an age-dependent dendritic spine loss, patch-clamp recording of synaptic activity revealed an increase in miniature EPSC frequency restricted to aged animals with preserved exploratory behavior. In contrast, we found a strong positive relationship between miniature IPSC frequency and the occurrence of both stereotyped exploratory behavior and novelty-related memory deficits. The enhanced miniature inhibitory tone was accompanied by a deficit in activity-driven inhibition, also suggesting an impaired dynamic range for modulation of inhibition in the aged, cognitively impaired animals. Together, our data indicate that differential changes in the balance of inhibitory to excitatory synaptic tone may underlie distinct trajectories in the evolution of cognitive performance during aging. PMID:23345211

  3. Rab8, POSH, and TAK1 regulate synaptic growth in a Drosophila model of frontotemporal dementia

    PubMed Central

    West, Ryan J.H.; Lu, Yubing; Marie, Bruno; Gao, Fen-Biao

    2015-01-01

    Mutations in genes essential for protein homeostasis have been identified in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Why mature neurons should be particularly sensitive to such perturbations is unclear. We identified mutations in Rab8 in a genetic screen for enhancement of an FTD phenotype associated with ESCRT-III dysfunction. Examination of Rab8 mutants or motor neurons expressing a mutant ESCRT-III subunit, CHMP2BIntron5, at the Drosophila melanogaster neuromuscular junction synapse revealed synaptic overgrowth and endosomal dysfunction. Expression of Rab8 rescued overgrowth phenotypes generated by CHMP2BIntron5. In Rab8 mutant synapses, c-Jun N-terminal kinase (JNK)/activator protein-1 and TGF-β signaling were overactivated and acted synergistically to potentiate synaptic growth. We identify novel roles for endosomal JNK-scaffold POSH (Plenty-of-SH3s) and a JNK kinase kinase, TAK1, in regulating growth activation in Rab8 mutants. Our data uncover Rab8, POSH, and TAK1 as regulators of synaptic growth responses and point to recycling endosome as a key compartment for synaptic growth regulation during neurodegenerative processes. PMID:25800055

  4. MeCP2 Controls Excitatory Synaptic Strength by Regulating Glutamatergic Synapse Number

    PubMed Central

    Chao, Hsiao-Tuan; Zoghbi, Huda Y.; Rosenmund, Christian

    2007-01-01

    SUMMARY MeCP2 is a transcriptional repressor critical for normal neurological function. Prior studies demonstrated that either loss or doubling of MeCP2 results in postnatal neurodevelopmental disorders. To understand the impact of MeCP2 expression on neuronal function, we studied the synaptic properties of individual neurons from mice that either lack or express twice the normal levels of MeCP2. Hippocampal glutamatergic neurons that lack MeCP2 display a 46% reduction in synaptic response whereas neurons with doubling of MeCP2 exhibit a two-fold enhancement in synaptic response. Further analysis shows that these changes were primarily due to the number of synapses formed. These results reveal that MeCP2 is a key rate-limiting factor in regulating glutamatergic synapse formation in early postnatal development, and that changes in excitatory synaptic strength may underlie global network alterations in neurological disorders due to altered MeCP2 levels. PMID:17920015

  5. Consumption of palatable food primes food approach behavior by rapidly increasing synaptic density in the VTA

    PubMed Central

    Liu, Shuai; Globa, Andrea K.; Mills, Fergil; Naef, Lindsay; Qiao, Min; Bamji, Shernaz X.; Borgland, Stephanie L.

    2016-01-01

    In an environment with easy access to highly palatable and energy-dense food, food-related cues drive food-seeking regardless of satiety, an effect that can lead to obesity. The ventral tegmental area (VTA) and its mesolimbic projections are critical structures involved in the learning of environmental cues used to predict motivationally relevant outcomes. Priming effects of food-related advertising and consumption of palatable food can drive food intake. However, the mechanism by which this effect occurs, and whether these priming effects last days after consumption, is unknown. Here, we demonstrate that short-term consumption of palatable food can prime future food approach behaviors and food intake. This effect is mediated by the strengthening of excitatory synaptic transmission onto dopamine neurons that is initially offset by a transient increase in endocannabinoid tone, but lasts days after an initial 24-h exposure to sweetened high-fat food (SHF). This enhanced synaptic strength is mediated by a long-lasting increase in excitatory synaptic density onto VTA dopamine neurons. Administration of insulin into the VTA, which suppresses excitatory synaptic transmission onto dopamine neurons, can abolish food approach behaviors and food intake observed days after 24-h access to SHF. These results suggest that even a short-term exposure to palatable foods can drive future feeding behavior by “rewiring” mesolimbic dopamine neurons. PMID:26884159

  6. SAD-B Phosphorylation of CAST Controls Active Zone Vesicle Recycling for Synaptic Depression.

    PubMed

    Mochida, Sumiko; Hida, Yamato; Tanifuji, Shota; Hagiwara, Akari; Hamada, Shun; Abe, Manabu; Ma, Huan; Yasumura, Misato; Kitajima, Isao; Sakimura, Kenji; Ohtsuka, Toshihisa

    2016-09-13

    Short-term synaptic depression (STD) is a common form of activity-dependent plasticity observed widely in the nervous system. Few molecular pathways that control STD have been described, but the active zone (AZ) release apparatus provides a possible link between neuronal activity and plasticity. Here, we show that an AZ cytomatrix protein CAST and an AZ-associated protein kinase SAD-B coordinately regulate STD by controlling reloading of the AZ with release-ready synaptic vesicles. SAD-B phosphorylates the N-terminal serine (S45) of CAST, and S45 phosphorylation increases with higher firing rate. A phosphomimetic CAST (S45D) mimics CAST deletion, which enhances STD by delaying reloading of the readily releasable pool (RRP), resulting in a pool size decrease. A phosphonegative CAST (S45A) inhibits STD and accelerates RRP reloading. Our results suggest that the CAST/SAD-B reaction serves as a brake on synaptic transmission by temporal calibration of activity and synaptic depression via RRP size regulation. PMID:27626661

  7. Consumption of palatable food primes food approach behavior by rapidly increasing synaptic density in the VTA.

    PubMed

    Liu, Shuai; Globa, Andrea K; Mills, Fergil; Naef, Lindsay; Qiao, Min; Bamji, Shernaz X; Borgland, Stephanie L

    2016-03-01

    In an environment with easy access to highly palatable and energy-dense food, food-related cues drive food-seeking regardless of satiety, an effect that can lead to obesity. The ventral tegmental area (VTA) and its mesolimbic projections are critical structures involved in the learning of environmental cues used to predict motivationally relevant outcomes. Priming effects of food-related advertising and consumption of palatable food can drive food intake. However, the mechanism by which this effect occurs, and whether these priming effects last days after consumption, is unknown. Here, we demonstrate that short-term consumption of palatable food can prime future food approach behaviors and food intake. This effect is mediated by the strengthening of excitatory synaptic transmission onto dopamine neurons that is initially offset by a transient increase in endocannabinoid tone, but lasts days after an initial 24-h exposure to sweetened high-fat food (SHF). This enhanced synaptic strength is mediated by a long-lasting increase in excitatory synaptic density onto VTA dopamine neurons. Administration of insulin into the VTA, which suppresses excitatory synaptic transmission onto dopamine neurons, can abolish food approach behaviors and food intake observed days after 24-h access to SHF. These results suggest that even a short-term exposure to palatable foods can drive future feeding behavior by "rewiring" mesolimbic dopamine neurons. PMID:26884159

  8. Role of motor cortex NMDA receptors in learning-dependent synaptic plasticity of behaving mice

    PubMed Central

    Hasan, Mazahir T.; Hernández-González, Samuel; Dogbevia, Godwin; Treviño, Mario; Bertocchi, Ilaria; Gruart, Agnès; Delgado-García, José M.

    2013-01-01

    The primary motor cortex has an important role in the precise execution of learned motor responses. During motor learning, synaptic efficacy between sensory and primary motor cortical neurons is enhanced, possibly involving long-term potentiation and N-methyl-D-aspartate (NMDA)-specific glutamate receptor function. To investigate whether NMDA receptor in the primary motor cortex can act as a coincidence detector for activity-dependent changes in synaptic strength and associative learning, here we generate mice with deletion of the Grin1 gene, encoding the essential NMDA receptor subunit 1 (GluN1), specifically in the primary motor cortex. The loss of NMDA receptor function impairs primary motor cortex long-term potentiation in vivo. Importantly, it impairs the synaptic efficacy between the primary somatosensory and primary motor cortices and significantly reduces classically conditioned eyeblink responses. Furthermore, compared with wild-type littermates, mice lacking primary motor cortex show slower learning in Skinner-box tasks. Thus, primary motor cortex NMDA receptors are necessary for activity-dependent synaptic strengthening and associative learning. PMID:23978820

  9. Role of motor cortex NMDA receptors in learning-dependent synaptic plasticity of behaving mice.

    PubMed

    Hasan, Mazahir T; Hernández-González, Samuel; Dogbevia, Godwin; Treviño, Mario; Bertocchi, Ilaria; Gruart, Agnès; Delgado-García, José M

    2013-01-01

    The primary motor cortex has an important role in the precise execution of learned motor responses. During motor learning, synaptic efficacy between sensory and primary motor cortical neurons is enhanced, possibly involving long-term potentiation and N-methyl-D-aspartate (NMDA)-specific glutamate receptor function. To investigate whether NMDA receptor in the primary motor cortex can act as a coincidence detector for activity-dependent changes in synaptic strength and associative learning, here we generate mice with deletion of the Grin1 gene, encoding the essential NMDA receptor subunit 1 (GluN1), specifically in the primary motor cortex. The loss of NMDA receptor function impairs primary motor cortex long-term potentiation in vivo. Importantly, it impairs the synaptic efficacy between the primary somatosensory and primary motor cortices and significantly reduces classically conditioned eyeblink responses. Furthermore, compared with wild-type littermates, mice lacking NMDA receptors in the [corrected] primary motor cortex show slower learning in Skinner-box tasks. Thus, primary motor cortex NMDA receptors are necessary for activity-dependent synaptic strengthening and associative learning. PMID:23978820

  10. PLPP/CIN regulates bidirectional synaptic plasticity via GluN2A interaction with postsynaptic proteins

    PubMed Central

    Kim, Ji-Eun; Kim, Yeon-Joo; Lee, Duk-Shin; Kim, Ji Yang; Ko, Ah-Reum; Hyun, Hye-Won; Kim, Min Ju; Kang, Tae-Cheon

    2016-01-01

    Dendritic spines are dynamic structures whose efficacies and morphologies are modulated by activity-dependent synaptic plasticity. The actin cytoskeleton plays an important role in stabilization and structural modification of spines. However, the regulatory mechanism by which it alters the plasticity threshold remains elusive. Here, we demonstrate the role of pyridoxal-5′-phosphate phosphatase/chronophin (PLPP/CIN), one of the cofilin-mediated F-actin regulators, in modulating synaptic plasticity in vivo. PLPP/CIN transgenic (Tg) mice had immature spines with small heads, while PLPP/CIN knockout (KO) mice had gigantic spines. Furthermore, PLPP/CIN Tg mice exhibited enhanced synaptic plasticity, but KO mice showed abnormal synaptic plasticity. The PLPP/CIN-induced alterations in synaptic plasticity were consistent with the acquisition and the recall capacity of spatial learning. PLPP/CIN also enhanced N-methyl-D-aspartate receptor (GluN) functionality by regulating the coupling of GluN2A with interacting proteins, particularly postsynaptic density-95 (PSD95). Therefore, these results suggest that PLPP/CIN may be an important factor for regulating the plasticity threshold. PMID:27212638

  11. Exocytosis of gliotransmitters from cortical astrocytes: implications for synaptic plasticity and aging.

    PubMed

    Lalo, Ulyana; Rasooli-Nejad, Seyed; Pankratov, Yuriy

    2014-10-01

    Maintaining brain function during aging is very important for mental and physical health. Recent studies showed a crucial importance of communication between two major types of brain cells: neurons transmitting electrical signals, and glial cells, which maintain the well-being and function of neurons. Still, the study of age-related changes in neuron-glia signalling is far from complete. We have shown previously that cortical astrocytes are capable of releasing ATP by a quantal soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) complex-dependent mechanism. Release of ATP from cortical astrocytes can be activated via various pathways, including direct UV-uncaging of intracellular Ca²⁺ or G-protein-coupled receptors. Importantly, release of both ATP and glutamate from neocortical astrocytes was not observed in brain slices of dominant-negative SNARE (dnSNARE) mice, expressing dnSNARE domain selectively in astrocytes. We also discovered that astrocyte-driven ATP can cause significant attenuation of synaptic inhibition in the pyramidal neurons via Ca²⁺-interaction between the neuronal ATP and γ-aminobutyric acid (GABA) receptors. Furthermore, we showed that astrocyte-derived ATP can facilitate the induction of long-term potentiation of synaptic plasticity in the neocortex. Our recent data have shown that an age-related decrease in the astroglial Ca²⁺ signalling can cause a substantial decrease in the exocytosis of gliotransmitters, in particular ATP. Age-related impairment of ATP release from cortical astrocytes can cause a decrease in the extent of astroglial modulation of synaptic transmission in the neocortex and can therefore contribute to the age-related impairment of synaptic plasticity and cognitive decline. Combined, our results strongly support the physiological relevance of glial exocytosis for glia-neuron communications and brain function. PMID:25233403

  12. Enhancing the Communication Abilities of Preschoolers at Risk for Behavior Problems: Effectiveness of a Parent-Implemented Language Intervention

    ERIC Educational Resources Information Center

    Brassart, Elise; Schelstraete, Marie-Anne

    2015-01-01

    Communication deficits are frequently associated with externalizing behavior problems in preschoolers but, in most cases, unsuspected in clinical practice. This exploratory study evaluated the effectiveness of a relatively brief parent-implemented language intervention on preschoolers at risk for behavior problems. Participants were randomly…

  13. Peer Feedback Enhances a "Journal Club" for Undergraduate Science Students That Develops Oral Communication and Critical Evaluation Skills

    ERIC Educational Resources Information Center

    Colthorpe, Kay; Chen, Xuebin; Zimbardi, Kirsten

    2014-01-01

    Effective science communication is one of the key skills undergraduates must achieve and is one of the threshold learning outcomes for Science (TLO 4.1). In addition, presenting published research to their peers allows students to critically evaluate scientific research (TLO 3.1) and develop a deeper appreciation for the link between experimental…

  14. Effects of Infant-Parent Play with a Technology-Enhanced Toy: Affordance-Related Actions and Communicative Interactions

    ERIC Educational Resources Information Center

    Bergen, Doris; Hutchinson, Kathleen; Nolan, Joan T.; Weber, Deborah

    2010-01-01

    Infant-parent play with toys is an early form of social communication, and the toy features (i.e., affordances), as well as the child's language competence, contribute to the developmental level of the play and the types of play actions that occur. This research, conducted in cooperation with a toy manufacturer, investigated how the affordances of…

  15. "Physiology in the News": Using Press Releases to Enhance Lay Communication and Introduce Current Physiology Research to Undergraduates

    ERIC Educational Resources Information Center

    Kelly, Kevin L.; Poteracki, James M.; Steury, Michael D.; Wehrwein, Erica A.

    2015-01-01

    Michigan State University's senior-level undergraduate physiology capstone laboratory uses a simple exercise termed "Physiology in the News," to help students explore the current research within the field of physiology while also learning to communicate science in lay terms. "Physiology in the News" is an activity that charges…

  16. Technology Enhancing Learning: Analysing Uses of Information and Communication Technologies by Primary and Secondary School Pupils with Learning Frameworks

    ERIC Educational Resources Information Center

    Passey, Don

    2006-01-01

    Successive national policy in England has striven to develop uses of information and communication technologies (ICT) to support teaching and learning, and has promoted the adoption of ICT in schools over a period of some 25 years (since the "Microcomputer in schools initiative" of 1981). The current level of deployment of ICT in schools is high.…

  17. Diabetes and Low-Health Literacy: A Preliminary Outcome Report of a Mediated Intervention to Enhance Patient-Physician Communication

    ERIC Educational Resources Information Center

    Shue, Carolyn K.; O'Hara, Laura L. S.; Marini, David; McKenzie, Jim; Schreiner, Melanie

    2010-01-01

    Patients with diabetes who experience low-health literacy often struggle in their roles as health consumers. A multi-disciplinary group of educators and researchers collaborated to develop a video intervention to help these patients better understand their disease and communicate more effectively with their physician. We describe the assessment…

  18. Enhancement of Pedagogical Skills in Nigerian Schools through Information and Communication Technology (ICT): Issues for the Future

    ERIC Educational Resources Information Center

    Aluede, Oyaziwo

    2013-01-01

    The history of information and communication technology (ICT) in Nigerian schools is patchy. The first experience of Internet services started about 1990 with University of Ilorin through the assistance of McMaster University in Canada. Currently, though, many staff members of universities in Nigeria have email accounts, and over forty-four…

  19. Enhancing Student Learning in Knowledge-Based Courses: Integrating Team-Based Learning in Mass Communication Theory Classes

    ERIC Educational Resources Information Center

    Han, Gang; Newell, Jay

    2014-01-01

    This study explores the adoption of the team-based learning (TBL) method in knowledge-based and theory-oriented journalism and mass communication (J&MC) courses. It first reviews the origin and concept of TBL, the relevant theories, and then introduces the TBL method and implementation, including procedures and assessments, employed in an…

  20. Assessing the Success of a Discipline-Based Communication Skills Development and Enhancement Program in a Graduate Accounting Course

    ERIC Educational Resources Information Center

    Barratt, Catherine; Hanlon, Dean; Rankin, Michaela

    2011-01-01

    In this paper we present results of the impact diagnostic testing and associated context-specific workshops have on students' written communication skills in a graduate-level accounting course. We find that students who undertook diagnostic testing performed better in their first semester accounting subject. This improvement is positively…

  1. Happy Family Kitchen: A community-based research for enhancing family communication and well-being in Hong Kong.

    PubMed

    Ho, Henry C Y; Mui, Moses; Wan, Alice; Ng, Yin-Lam; Stewart, Sunita M; Yew, Carol; Lam, Tai Hing; Chan, Sophia S

    2016-09-01

    Urban families worldwide are often characterized by busy working lives which leave little time for family gatherings and communication. The Happy Family Kitchen project, which emphasized cooking and dining with family members, was conducted in a deprived district in Hong Kong. We hypothesized that the community-based family intervention, derived from a positive psychology framework, can improve family communication, family well-being, and subjective happiness. Twenty-three social service units organized and delivered the intervention programs for 1,419 individuals from 612 families. The core intervention was developed with emphasis on 1 of 5 positive psychology themes: gratitude, flow, happiness, health, and savoring. Intervention outcomes were assessed at preintervention, immediate postintervention, and 6 weeks and 12 weeks postintervention. Results showed that family communication, family well-being, and subjective happiness improved with small effect sizes which were sustained up to 12 weeks. The gratitude intervention improved all of the outcome measures. Qualitative data provided additional evidence for effectiveness with in-depth insights into family dynamics. We concluded that this brief intervention was a low-cost and simple approach to improve family communication and well-being. (PsycINFO Database Record PMID:27513284

  2. Enhancing Extemporaneous Speaking Skills in the Advanced Oral Communication Course and Team Testing Techniques in the Basic Course.

    ERIC Educational Resources Information Center

    Reppert, James E.

    In an advanced oral communication course, students make five major presentations. One of the foundations of extemporaneous speaking is the ability to outline relevant points and phrases in a coherent, orderly manner. Advanced students must be able to take any topic and dissect it quickly to determine the most succinct way to present it to an…

  3. Enhancing Learner-Learner Interaction Using Video Communications in Higher Education: Implications from Theorising about a New Model

    ERIC Educational Resources Information Center

    Smyth, Robyn

    2011-01-01

    As visual connectivity improves, an opportunity to enrich and rethink the place of learning design in online and distance education is presenting itself. The opportunity is derived from the increasing scope for personalised synchronous interaction which has been missing in computer mediated communications (CMC) and previous generations of distance…

  4. Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function

    PubMed Central

    Kim, Gukhan; Luján, Rafael; Schwenk, Jochen; Kelley, Melissa H; Aguado, Carolina; Watanabe, Masahiko; Fakler, Bernd; Maylie, James; Adelman, John P

    2016-01-01

    Mouse CA1 pyramidal neurons express apamin-sensitive SK2-containing channels in the post-synaptic membrane, positioned close to NMDA-type (N-methyl-D-aspartate) glutamate receptors. Activated by synaptically evoked NMDAR-dependent Ca2+ influx, the synaptic SK2-containing channels modulate excitatory post-synaptic responses and the induction of synaptic plasticity. In addition, their activity- and protein kinase A-dependent trafficking contributes to expression of long-term potentiation (LTP). We have identified a novel synaptic scaffold, MPP2 (membrane palmitoylated protein 2; p55), a member of the membrane-associated guanylate kinase (MAGUK) family that interacts with SK2-containing channels. MPP2 and SK2 co-immunopurified from mouse brain, and co-immunoprecipitated when they were co-expressed in HEK293 cells. MPP2 is highly expressed in the post-synaptic density of dendritic spines on CA1 pyramidal neurons. Knocking down MPP2 expression selectively abolished the SK2-containing channel contribution to synaptic responses and decreased LTP. Thus, MPP2 is a novel synaptic scaffold that is required for proper synaptic localization and function of SK2-containing channels. DOI: http://dx.doi.org/10.7554/eLife.12637.001 PMID:26880549

  5. E.M.P.A.T.H.Y.: a tool to enhance nonverbal communication between clinicians and their patients.

    PubMed

    Riess, Helen; Kraft-Todd, Gordon

    2014-08-01

    There is a gap in the medical education literature on teaching nonverbal detection and expression of empathy. Many articles do not address nonverbal interactions, instead focusing on "what to say" rather than "how to be." This focus on verbal communication overlooks the essential role nonverbal signals play in the communication of emotions, which has significant effects on patient satisfaction, health outcomes, and malpractice claims. This gap is addressed with a novel teaching tool for assessing nonverbal behavior using the acronym E.M.P.A.T.H.Y.-E: eye contact; M: muscles of facial expression; P: posture; A: affect; T: tone of voice; H: hearing the whole patient; Y: your response. This acronym was the cornerstone of a randomized controlled trial of empathy training at Massachusetts General Hospital, 2010-2012. Used as an easy-to-remember checklist, the acronym orients medical professionals to key aspects of perceiving and responding to nonverbal emotional cues. An urgent need exists to teach nonverbal aspects of communication as medical practices must be reoriented to the increasing cultural diversity represented by patients presenting for care. Where language proficiency may be limited, nonverbal communication becomes more crucial for understanding patients' communications. Furthermore, even in the absence of cultural differences, many patients are reluctant to disagree with their clinicians, and subtle nonverbal cues may be the critical entry point for discussions leading to shared medical decisions. A detailed description of the E.M.P.A.T.H.Y. acronym and a brief summary of the literature that supports each component of the teaching tool are provided. PMID:24826853

  6. On the Teneurin track: a new synaptic organization molecule emerges

    PubMed Central

    Mosca, Timothy J.

    2015-01-01

    To achieve proper synaptic development and function, coordinated signals must pass between the pre- and postsynaptic membranes. Such transsynaptic signals can be comprised of receptors and secreted ligands, membrane associated receptors, and also pairs of synaptic cell adhesion molecules. A critical open question bridging neuroscience, developmental biology, and cell biology involves identifying those signals and elucidating how they function. Recent work in Drosophila and vertebrate systems has implicated a family of proteins, the Teneurins, as a new transsynaptic signal in both the peripheral and central nervous systems. The Teneurins have established roles in neuronal wiring, but studies now show their involvement in regulating synaptic connections between neurons and bridging the synaptic membrane and the cytoskeleton. This review will examine the Teneurins as synaptic cell adhesion molecules, explore how they regulate synaptic organization, and consider how some consequences of human Teneurin mutations may have synaptopathic origins. PMID:26074772

  7. Effects of Modafinil on Behavioral Learning and Hippocampal Synaptic Transmission in Rats

    PubMed Central

    Chen, Chong; Wang, Hai-Xia; Li, Chu-Hua; Huang, Jun-Ni; Xiao, Peng

    2015-01-01

    Purpose: Modafinil is a wake-promoting agent that has been proposed to improve cognitive performance at the preclinical and clinical levels. Since there is insufficient evidence for modafinil to be regarded as a cognitive enhancer, the aim of this study was to investigate the effects of chronic modafinil administration on behavioral learning in healthy adult rats. Methods: Y-maze training was used to assess learning performance, and the whole-cell patch clamp technique was used to assess synaptic transmission in pyramidal neurons of the hippocampal CA1 region of rats. Results: Intraperitoneal administration of modafinil at 200 mg/kg or 300 mg/kg significantly improved learning performance. Furthermore, perfusion with 1mM modafinil enhanced the frequency and amplitude of spontaneous postsynaptic currents and spontaneous excitatory postsynaptic currents in CA1 pyramidal neurons in hippocampal slices. However, the frequency and amplitude of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons were inhibited by treatment with 1mM modafinil. Conclusions: These results indicate that modafinil improves learning and memory in rats possibly by enhancing glutamatergic excitatory synaptic transmission and inhibiting GABAergic (gamma-aminobutyric acid-ergic) inhibitory synaptic transmission. PMID:26739176

  8. SYNAPTIC VESICLE PROTEIN TRAFFICKING AT THE GLUTAMATE SYNAPSE

    PubMed Central

    Santos, Magda S.; Li, Haiyan; Voglmaier, Susan M.

    2009-01-01

    Expression of the integral and associated proteins of synaptic vesicles is subject to regulation over time, by region, and in response to activity. The process by which changes in protein levels and isoforms result in different properties of neurotransmitter release involves protein trafficking to the synaptic vesicle. How newly synthesized proteins are incorporated into synaptic vesicles at the presynaptic bouton is poorly understood. During synaptogenesis, synaptic vesicle proteins sort through the secretory pathway and are transported down the axon in precursor vesicles that undergo maturation to form synaptic vesicles. Changes in protein content of synaptic vesicles could involve the formation of new vesicles that either mix with the previous complement of vesicles or replace them, presumably by their degradation or inactivation. Alternatively, new proteins could individually incorporate into existing synaptic vesicles, changing their functional properties. Glutamatergic vesicles likely express many of the same integral membrane proteins and share certain common mechanisms of biogenesis, recycling, and degradation with other synaptic vesicles. However, glutamatergic vesicles are defined by their ability to package glutamate for release, a property conferred by the expression of a vesicular glutamate transporter (VGLUT). VGLUTs are subject to regional, developmental, and activity-dependent changes in expression. In addition, VGLUT isoforms differ in their trafficking, which may target them to different pathways during biogenesis or after recycling, which may in turn sort them to different vesicle pools. Emerging data indicate that differences in the association of VGLUTs and other synaptic vesicle proteins with endocytic adaptors may influence their trafficking. These observations indicate that independent regulation of synaptic vesicle protein trafficking has the potential to influence synaptic vesicle protein composition, the maintenance of synaptic vesicle

  9. Possible Contributions of a Novel Form of Synaptic Plasticity in "Aplysia" to Reward, Memory, and Their Dysfunctions in Mammalian Brain

    ERIC Educational Resources Information Center

    Hawkins, Robert D.

    2013-01-01

    Recent studies in "Aplysia" have identified a new variation of synaptic plasticity in which modulatory transmitters enhance spontaneous release of glutamate, which then acts on postsynaptic receptors to recruit mechanisms of intermediate- and long-term plasticity. In this review I suggest the hypothesis that similar plasticity occurs in…

  10. Mapping homeostatic synaptic plasticity using cable properties of dendrites.

    PubMed

    Queenan, B N; Lee, K J; Tan, H; Huganir, R L; Vicini, S; Pak, D T S

    2016-02-19

    When chronically silenced, cortical and hippocampal neurons homeostatically upregulate excitatory synaptic function. However, the subcellular position of such changes on the dendritic tree is not clear. We exploited the cable-filtering properties of dendrites to derive a parameter, the dendritic filtering index (DFI), to map the spatial distribution of synaptic currents. Our analysis indicates that young rat cortical neurons globally scale AMPA receptor-mediated currents, while mature hippocampal neurons do not, revealing distinct homeostatic strategies between brain regions and developmental stages. The DFI presents a useful tool for mapping the dendritic origin of synaptic currents and the location of synaptic plasticity changes. PMID:26701298

  11. Experimental implementation of a biometric laser synaptic sensor.

    PubMed

    Pisarchik, Alexander N; Sevilla-Escoboza, Ricardo; Jaimes-Reátegui, Rider; Huerta-Cuellar, Guillermo; García-Lopez, J Hugo; Kazantsev, Victor B

    2013-01-01

    We fabricate a biometric laser fiber synaptic sensor to transmit information from one neuron cell to the other by an optical way. The optical synapse is constructed on the base of an erbium-doped fiber laser, whose pumped diode current is driven by a pre-synaptic FitzHugh-Nagumo electronic neuron, and the laser output controls a post-synaptic FitzHugh-Nagumo electronic neuron. The implemented laser synapse displays very rich dynamics, including fixed points, periodic orbits with different frequency-locking ratios and chaos. These regimes can be beneficial for efficient biorobotics, where behavioral flexibility subserved by synaptic connectivity is a challenge. PMID:24351638

  12. Synaptic circuit remodelling by matrix metalloproteinases in health and disease

    PubMed Central

    Huntley, George W.

    2016-01-01

    Matrix metalloproteinases (MMPs) are extracellularly acting enzymes that have long been known to have deleterious roles in brain injury and disease. In particular, widespread and protracted MMP activity can contribute to neuronal loss and synaptic dysfunction. However, recent studies show that rapid and focal MMP-mediated proteolysis proactively drives synaptic structural and functional remodelling that is crucial for ongoing cognitive processes. Deficits in synaptic remodelling are associated with psychiatric and neurological disorders, and aberrant MMP expression or function may contribute to the molecular mechanisms underlying these deficits. This Review explores the paradigm shift in our understanding of the contribution of MMPs to normal and abnormal synaptic plasticity and function. PMID:23047773

  13. Computational Neuroscience: Modeling the Systems Biology of Synaptic Plasticity

    PubMed Central

    Kotaleski, Jeanette Hellgren; Blackwell, Kim T.

    2016-01-01

    Preface Synaptic plasticity is a mechanism proposed to underlie learning and memory. The complexity of the interactions between ion channels, enzymes, and genes involved in synaptic plasticity impedes a deep understanding of this phenomenon. Computer modeling is an approach to investigate the information processing that is performed by signaling pathways underlying synaptic plasticity. In the past few years, new software developments that blend computational neuroscience techniques with systems biology techniques have allowed large-scale, quantitative modeling of synaptic plasticity in neurons. We highlight significant advancements produced by these modeling efforts and introduce promising approaches that utilize advancements in live cell imaging. PMID:20300102

  14. Multi-gate synergic modulation in laterally coupled synaptic transistors

    NASA Astrophysics Data System (ADS)

    Zhu, Li Qiang; Xiao, Hui; Liu, Yang Hui; Wan, Chang Jin; Shi, Yi; Wan, Qing

    2015-10-01

    Laterally coupled oxide-based synaptic transistors with multiple gates are fabricated on phosphorosilicate glass electrolyte films. Electrical performance of the transistor can be evidently improved when the device is operated in a tri-gate synergic modulation mode. Excitatory post-synaptic current and paired pulse facilitation (PPF) behavior of biological synapses are mimicked, and PPF index can be effectively tuned by the voltage applied on the modulatory terminal. At last, superlinear to sublinear synaptic integration regulation is also mimicked by applying a modulatory pulse on the third modulatory terminal. The multi-gate oxide-based synaptic transistors may find potential applications in biochemical sensors and neuromorphic systems.

  15. Enhancing Parent–Child Communication and Parental Self-Esteem With a Video-Feedback Intervention: Outcomes With Prelingual Deaf and Hard-of-Hearing Children

    PubMed Central

    Wadnerkar-Kamble, Meghana B.; James, Deborah M.

    2015-01-01

    Evidence on best practice for optimizing communication with prelingual deaf and hard-of-hearing (DHH) children is lacking. This study examined the effect of a family-focused psychosocial video intervention program on parent–child communication in the context of childhood hearing loss. Fourteen hearing parents with a prelingual DHH child (Mage = 2 years 8 months) completed three sessions of video interaction guidance intervention. Families were assessed in spontaneous free play interactions at pre and postintervention using the Emotional Availability (EA) Scales. The Rosenberg Self-esteem Scale was also used to assess parental report of self-esteem. Compared with nontreatment baselines, increases were shown in the EA subscales: parental sensitivity, parental structuring, parental nonhostility, child responsiveness, and child involvement, and in reported self-esteem at postintervention. Video-feedback enhances communication in families with prelingual DHH children and encourages more connected parent–child interaction. The results raise implications regarding the focus of early intervention strategies for prelingual DHH children. PMID:25819293

  16. Enhancing Parent-Child Communication and Parental Self-Esteem With a Video-Feedback Intervention: Outcomes With Prelingual Deaf and Hard-of-Hearing Children.

    PubMed

    Lam-Cassettari, Christa; Wadnerkar-Kamble, Meghana B; James, Deborah M

    2015-07-01

    Evidence on best practice for optimizing communication with prelingual deaf and hard-of-hearing (DHH) children is lacking. This study examined the effect of a family-focused psychosocial video intervention program on parent-child communication in the context of childhood hearing loss. Fourteen hearing parents with a prelingual DHH child (Mage = 2 years 8 months) completed three sessions of video interaction guidance intervention. Families were assessed in spontaneous free play interactions at pre and postintervention using the Emotional Availability (EA) Scales. The Rosenberg Self-esteem Scale was also used to assess parental report of self-esteem. Compared with nontreatment baselines, increases were shown in the EA subscales: parental sensitivity, parental structuring, parental nonhostility, child responsiveness, and child involvement, and in reported self-esteem at postintervention. Video-feedback enhances communication in families with prelingual DHH children and encourages more connected parent-child interaction. The results raise implications regarding the focus of early intervention strategies for prelingual DHH children. PMID:25819293

  17. [Peptidergic modulation of the hippocampus synaptic activity].

    PubMed

    Skrebitskiĭ, V G; Kondratenko, R V; Povarov, I S; Dereviagin, V I

    2011-11-01

    Effects of two newly synthesized nootropic and anxiolytic dipeptides: Noopept and Selank on inhibitory synaptic transmission in hippocampal CA1 pyramidal cells were investigated using patch-clamp technique in whole-cell configuration. Bath application of Noopept (1 microM) or Selank (2 microM) significantly increased the frequency of spike-dependent spontaneous m1PSCs, whereas spike-independent mlPSCs remained unchanged. It was suggested that both peptides mediated their effect sue to activation of inhibitory interneurons terminating on CA1 pyramidal cells. Results of current clamp recording of inhibitory interneurons residing in stratum radiatum confirmed this suggestion, at least for Noonent. PMID:22390072

  18. Effect of acute fentanyl treatment on synaptic plasticity in the hippocampal CA1 region in rats

    PubMed Central

    Tian, Hai; Xu, Yueming; Liu, Fucun; Wang, Guowei; Hu, Sanjue

    2015-01-01

    Postoperative cognitive dysfunction (POCD), mainly characterized by short-term decline of learning and memory, occurs after operations under anesthesia. However, the underlying mechanisms are poorly understood. The μ-opioid receptors (MOR) are highly expressed in interneurons of hippocampus, and is believed to be critical for the dysfunction of synaptic plasticity between hippocampal neurons. Therefore, we investigated the effect of fentanyl, a strong agonist of MOR and often used for anesthesia and analgesia in clinical settings, on hippocampal synaptic plasticity in the Schaffer-collateral CA1 pathway during acute exposure and washout in vitro. Our results revealed that acute fentanyl exposure (0.01, 0.1, 1 μM) dose-dependently increased the field excitatory postsynaptic potentials (fEPSPs), which was prevented by pre-administration of picrotoxin (50 μM) or MOR antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH2 (CTOP, 10 μM). While fentanyl exposure-increased fEPSPs amplitude was prevented by picrotoxin [an inhibitor of γ-aminobutyric acid receptor (GABAR)] treatment or fentanyl washout, pretreatment of picrotoxin failed to prevent the fentanyl-impaired long-term potentiation (LTP) of synaptic strength as well as the fentanyl-enhanced long-term depression (LTD). These results demonstrated that fentanyl acute exposure and washout increases hippocampal excitability in the Schaffer-collateral CA1 pathway, depending on disinhibiting interneurons after MOR activation. In addition, fentanyl acute exposure and washout modulated synaptic plasticity, but the inhibitory activation was not critical. Elucidating the detailed mechanisms for synaptic dysfunction after fentanyl exposure and washout may provide insights into POCD generation after fentanyl anesthesia. PMID:26578961

  19. Synaptic actions of neuropeptide FF in the rat parabrachial nucleus: interactions with opioid receptors.

    PubMed

    Chen, X; Zidichouski, J A; Harris, K H; Jhamandas, J H

    2000-08-01

    The pontine parabrachial nucleus (PBN) receives both opioid and Neuropeptide FF (NPFF) projections from the lower brain stem and/or the spinal cord. Because of this anatomical convergence and previous evidence that NPFF displays both pro- and anti-opioid activities, this study examined the synaptic effects of NPFF in the PBN and the mechanisms underlying these effects using an in vitro brain slice preparation and the nystatin-perforated patch-clamp recording technique. Under voltage-clamp conditions, NPFF reversibly reduced the evoked excitatory postsynaptic currents (EPSCs) in a dose-dependent fashion. This effect was not accompanied by apparent changes in the holding current, the current-voltage relationship or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced inward currents in the PBN cells. When a paired-pulse protocol was used, NPFF increased the ratio of these synaptic currents. Analysis of miniature EPSCs showed that NPFF caused a rightward shift in the frequency-distribution curve, whereas the amplitude-distribution curve remained unchanged. Collectively, these experiments indicate that NPFF reduces the evoked EPSCs through a presynaptic mechanism of action. The synaptic effects induced by NPFF (5 microM) could not be blocked by the specific mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (1 microM), but application of delta-opioid receptor antagonist Tyr-Tic-Phe-Phe (5 microM) almost completely prevented effects of NPFF. Moreover, the delta-opioid receptor agonist, Deltorphin (1 microM), mimicked the effects as NPFF and also occluded NPFF's actions on synaptic currents. These results indicate that NPFF modulates excitatory synaptic transmission in the PBN through an interaction with presynaptic delta-opioid receptors. These observations provide a cellular basis for NPFF enhancement of the antinociceptive effects consequent to central activation of delta-opioid receptors. PMID:10938301

  20. Short-term synaptic plasticity contributes to the temporal filtering of electrosensory information.

    PubMed

    Fortune, E S; Rose, G J

    2000-09-15

    Short-term synaptic depression and facilitation often are elicited by different temporal patterns of activity. Short-term plasticity may contribute, therefore, to temporal filtering by impeding synaptic transmission for some temporal patterns of activity and facilitating transmission for other patterns. We examined this hypothesis by investigating whether short-term plasticity contributes to the temporal filtering properties of midbrain electrosensory neurons. Postsynaptic potentials were recorded in response to sensory stimuli and to direct stimulation of afferents, in vivo. Stimulating afferents with pairs of pulses at a rate of 20 pairs/sec ["tetanus (20 Hz)"] induced PSP depression. This PSP depression was similar to that observed for electrosensory stimuli of the same temporal frequency. Analysis of PSPs elicited by a pair of pulses that preceded versus followed the tetanus revealed that PSP depression was caused by synaptic depression, not by a loss of facilitation. Behavioral studies indicate that fish can detect slow changes in signal amplitude (slow AM) in backgrounds of fast fluctuations. Correspondingly, midbrain neurons respond well to slow AM even in the presence of fast AM. In many neurons, facilitation enhanced responses to trains (8-10 pulses; 100 Hz) that represented activity patterns elicited by slow AM, despite induction of synaptic depression by a tetanus (20 Hz). The interplay between synaptic depression and facilitation, therefore, can act as a filter of temporal information. Some neurons that showed little facilitation nonetheless responded to low temporal-frequency information after induction of depression by fast information; this likely results from the convergence of inputs with different temporal filtering properties. PMID:10995860

  1. The flavonoid baicalein rescues synaptic plasticity and memory deficits in a mouse model of Alzheimer's disease.

    PubMed

    Gu, Xun-Hu; Xu, Li-Jun; Liu, Zhi-Qiang; Wei, Bo; Yang, Yuan-Jian; Xu, Guo-Gang; Yin, Xiao-Ping; Wang, Wei

    2016-09-15

    Increasing evidence suggests that disruptions of synaptic functions correlate with the severity of cognitive deficit in Alzheimer's disease (AD). Our previous study demonstrated that baicalein enhances long-term potentiation (LTP) in acute rat hippocampal slices and improves hippocampus-dependent contextual fear conditioning in rats. Given that baicalein possess various biological activities, especially its effects on synaptic plasticity and cognitive function, we examined the effect of baicalein on synaptic function both in vitro and in vivo in AD model. The effect of baicalein on Aβ42 oligomer impaired LTP was investigated by electrophysiological methods. Baicalein was administered orally via drinking water to the APP/PS1 mice and sex- and age-matched wild-type mice. Treatment started at 5 months of age and mice were assessed for cognition and AD-like pathology at 7-month-old. Cognition was analyzed by Morris water maze test, fear conditioning test, and novel object recognition test. Changes in hippocampal 12/15 Lipoxygenase (12/15LO) and glycogen synthase kinase 3β (GSK3β) activity, Aβ production, tau phosphorylation, synaptic plasticity, and dendritic spine density were evaluated. Baicalein prevented Aβ-induced impairments in hippocampal LTP through activation of serine threonine Kinase (Akt) phosphorylation. Long-term oral administration of baicalein inhibited 12/15LO and GSK3β activity, reduced β-secretase enzyme (BACE1), decreased the concentration of total Aβ, and prevented phosphorylation of tau in APP/PS1 mice. Meanwhile, baicalein restored spine number, synaptic plasticity, and memory deficits. Our results strengthen the potential of the flavonoid baicalein as a novel and promising oral bioactive therapeutic agent that prevents memory deficits in AD. PMID:27233830

  2. Modulation of CaV2.1 channels by neuronal calcium sensor-1 induces short-term synaptic facilitation.

    PubMed

    Yan, Jin; Leal, Karina; Magupalli, Venkat G; Nanou, Evanthia; Martinez, Gilbert Q; Scheuer, Todd; Catterall, William A

    2014-11-01

    Facilitation and inactivation of P/Q-type Ca2+ currents mediated by Ca2+/calmodulin binding to Ca(V)2.1 channels contribute to facilitation and rapid depression of synaptic transmission, respectively. Other calcium sensor proteins displace calmodulin from its binding site and differentially modulate P/Q-type Ca2 + currents, resulting in diverse patterns of short-term synaptic plasticity. Neuronal calcium sensor-1 (NCS-1, frequenin) has been shown to enhance synaptic facilitation, but the underlying mechanism is unclear. We report here that NCS-1 directly interacts with IQ-like motif and calmodulin-binding domain in the C-terminal domain of Ca(V)2.1 channel. NCS-1 reduces Ca2 +-dependent inactivation of P/Q-type Ca2+ current through interaction with the IQ-like motif and calmodulin-binding domain without affecting peak current or activation kinetics. Expression of NCS-1 in presynaptic superior cervical ganglion neurons has no effect on synaptic transmission, eliminating effects of this calcium sensor protein on endogenous N-type Ca2+ currents and the endogenous neurotransmitter release machinery. However, in superior cervical ganglion neurons expressing wild-type Ca(V)2.1 channels, co-expression of NCS-1 induces facilitation of synaptic transmission in response to paired pulses and trains of depolarizing stimuli, and this effect is lost in Ca(V)2.1 channels with mutations in the IQ-like motif and calmodulin-binding domain. These results reveal that NCS-1 directly modulates Ca(V)2.1 channels to induce short-term synaptic facilitation and further demonstrate that CaS proteins are crucial in fine-tuning short-term synaptic plasticity. PMID:25447945

  3. Glutamate-induced long-term potentiation of the frequency of miniature synaptic currents in cultured hippocampal neurons

    NASA Astrophysics Data System (ADS)

    Malgaroli, Antonio; Tsien, Richard W.

    1992-05-01

    Glutamate application at synapses between hippocampal neurons in culture produces long-term potentiation of the frequency of spontaneous miniature synaptic currents, together with long-term potentiation of evoked synaptic currents. The mini frequency potentiation is initiated postsynaptically and requires activity of NMDA receptors. Although the frequency of unitary quanta! responses increases strongly, their amplitude remains little changed with potentiation. Tests of postsynaptic responsiveness rule out recruitment of latent glutamate receptor clusters. Thus, postsynaptic induction can lead to enhancement of presynaptic transmitter release. The sustained potentiation of mini frequency is expressed even in the absence of Ca2+ entry into presynaptic terminals.

  4. Antiproliferative Action of Conjugated Linoleic Acid on Human MCF-7 Breast Cancer Cells Mediated by Enhancement of Gap Junctional Intercellular Communication through Inactivation of NF-κB

    PubMed Central

    Rakib, Md. Abdur; Lee, Won Sup; Kim, Gon Sup; Han, Jae Hee; Kim, Jeong Ok

    2013-01-01

    The major conjugated linoleic acid (CLA) isomers, c9,t11-CLA and t10,c12-CLA, have anticancer effects; however, the exact mechanisms underlying these effects are unknown. Evidence suggests that reversal of reduced gap junctional intercellular communication (GJIC) in cancer cells inhibits cell growth and induces cell death. Hence, we determined that CLA isomers enhance GJIC in human MCF-7 breast cancer cells and investigated the underlying molecular mechanisms. The CLA isomers significantly enhanced GJIC of MCF-7 cells at 40 μM concentration, whereas CLA inhibited cell growth and induced caspase-dependent apoptosis. CLA increased connexin43 (Cx43) expression both at the transcriptional and translational levels. CLA inhibited nuclear factor-κB (NF-κB) activity and enhanced reactive oxygen species (ROS) generation. No significant difference was observed in the efficacy of c9,t11-CLA and t10,c12-CLA. These results suggest that the anticancer effect of CLA is associated with upregulation of GJIC mediated by enhanced Cx43 expression through inactivation of NF-κB and generation of ROS in MCF-7 cells. PMID:24371460

  5. Ultrafast Synaptic Events in a Chalcogenide Memristor

    PubMed Central

    Li, Yi; Zhong, Yingpeng; Xu, Lei; Zhang, Jinjian; Xu, Xiaohua; Sun, Huajun; Miao, Xiangshui

    2013-01-01

    Compact and power-efficient plastic electronic synapses are of fundamental importance to overcoming the bottlenecks of developing a neuromorphic chip. Memristor is a strong contender among the various electronic synapses in existence today. However, the speeds of synaptic events are relatively slow in most attempts at emulating synapses due to the material-related mechanism. Here we revealed the intrinsic memristance of stoichiometric crystalline Ge2Sb2Te5 that originates from the charge trapping and releasing by the defects. The device resistance states, representing synaptic weights, were precisely modulated by 30 ns potentiating/depressing electrical pulses. We demonstrated four spike-timing-dependent plasticity (STDP) forms by applying programmed pre- and postsynaptic spiking pulse pairs in different time windows ranging from 50 ms down to 500 ns, the latter of which is 105 times faster than the speed of STDP in human brain. This study provides new opportunities for building ultrafast neuromorphic computing systems and surpassing Von Neumann architecture. PMID:23563810

  6. Ultrafast synaptic events in a chalcogenide memristor.

    PubMed

    Li, Yi; Zhong, Yingpeng; Xu, Lei; Zhang, Jinjian; Xu, Xiaohua; Sun, Huajun; Miao, Xiangshui

    2013-01-01

    Compact and power-efficient plastic electronic synapses are of fundamental importance to overcoming the bottlenecks of developing a neuromorphic chip. Memristor is a strong contender among the various electronic synapses in existence today. However, the speeds of synaptic events are relatively slow in most attempts at emulating synapses due to the material-related mechanism. Here we revealed the intrinsic memristance of stoichiometric crystalline Ge2Sb2Te5 that originates from the charge trapping and releasing by the defects. The device resistance states, representing synaptic weights, were precisely modulated by 30 ns potentiating/depressing electrical pulses. We demonstrated four spike-timing-dependent plasticity (STDP) forms by applying programmed pre- and postsynaptic spiking pulse pairs in different time windows ranging from 50 ms down to 500 ns, the latter of which is 10(5) times faster than the speed of STDP in human brain. This study provides new opportunities for building ultrafast neuromorphic computing systems and surpassing Von Neumann architecture. PMID:23563810

  7. Synaptic Democracy and Vesicular Transport in Axons

    NASA Astrophysics Data System (ADS)

    Bressloff, Paul C.; Levien, Ethan

    2015-04-01

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

  8. The classic cadherins in synaptic specificity

    PubMed Central

    Basu, Raunak; Taylor, Matthew R; Williams, Megan E

    2015-01-01

    During brain development, billions of neurons organize into highly specific circuits. To form specific circuits, neurons must build the appropriate types of synapses with appropriate types of synaptic partners while avoiding incorrect partners in a dense cellular environment. Defining the cellular and molecular rules that govern specific circuit formation has significant scientific and clinical relevance because fine scale connectivity defects are thought to underlie many cognitive and psychiatric disorders. Organizing specific neural circuits is an enormously complicated developmental process that requires the concerted action of many molecules, neural activity, and temporal events. This review focuses on one class of molecules postulated to play an important role in target selection and specific synapse formation: the classic cadherins. Cadherins have a well-established role in epithelial cell adhesion, and although it has long been appreciated that most cadherins are expressed in the brain, their role in synaptic specificity is just beginning to be unraveled. Here, we review past and present studies implicating cadherins as active participants in the formation, function, and dysfunction of specific neural circuits and pose some of the major remaining questions. PMID:25837840

  9. Transient ECM protease activity promotes synaptic plasticity.

    PubMed

    Magnowska, Marta; Gorkiewicz, Tomasz; Suska, Anna; Wawrzyniak, Marcin; Rutkowska-Wlodarczyk, Izabela; Kaczmarek, Leszek; Wlodarczyk, Jakub

    2016-01-01

    Activity-dependent proteolysis at a synapse has been recognized as a pivotal factor in controlling dynamic changes in dendritic spine shape and function; however, excessive proteolytic activity is detrimental to the cells. The exact mechanism of control of these seemingly contradictory outcomes of protease activity remains unknown. Here, we reveal that dendritic spine maturation is strictly controlled by the proteolytic activity, and its inhibition by the endogenous inhibitor (Tissue inhibitor of matrix metalloproteinases-1 - TIMP-1). Excessive proteolytic activity impairs long-term potentiation of the synaptic efficacy (LTP), and this impairment could be rescued by inhibition of protease activity. Moreover LTP is altered persistently when the ability of TIMP-1 to inhibit protease activity is abrogated, further demonstrating the role of such inhibition in the promotion of synaptic plasticity under well-defined conditions. We also show that dendritic spine maturation involves an intermediate formation of elongated spines, followed by their conversion into mushroom shape. The formation of mushroom-shaped spines is accompanied by increase in AMPA/NMDA ratio of glutamate receptors. Altogether, our results identify inhibition of protease activity as a critical regulatory mechanism for dendritic spines maturation. PMID:27282248

  10. Synaptic dimorphism in Onychophoran cephalic ganglia.

    PubMed

    Peña-Contreras, Z; Mendoza-Briceño, R V; Miranda-Contreras, L; Palacios-Prü, E L

    2007-03-01

    The taxonomic location of the Onychophora has been controversial because of their phenotypic and genotypic characteristics, related to both annelids and arthropods. We analyzed the ultrastructure of the neurons and their synapses in the cephalic ganglion of a poorly known invertebrate, the velvet worm Peripatus sedgwicki, from the mountainous region of El Valle, Mérida, Venezuela. Cephalic ganglia were dissected, fixed and processed for transmission electron microscopy. The animal has a high degree of neurobiological development, as evidenced by the presence of asymmetric (excitatory) and symmetric (inhibitory) synapses, as well as the existence of glial cell processes in a wide neuropile zone. The postsynaptic terminals were seen to contain subsynaptic cisterns formed by membranes of smooth endoplasmic reticulum beneath the postsynaptic density, whereas the presynaptic terminal showed numerous electron transparent synaptic vesicles. From the neurophylogenetic perspectives, the ultrastructural characteristics of the central nervous tissue of the Onychophora show important evolutionary acquirements, such as the presence of both excitatory and inhibitory synapses, indicating functional synaptic transmission, and the appearance of mature glial cells. PMID:18457135

  11. Transient ECM protease activity promotes synaptic plasticity

    PubMed Central

    Magnowska, Marta; Gorkiewicz, Tomasz; Suska, Anna; Wawrzyniak, Marcin; Rutkowska-Wlodarczyk, Izabela; Kaczmarek, Leszek; Wlodarczyk, Jakub

    2016-01-01

    Activity-dependent proteolysis at a synapse has been recognized as a pivotal factor in controlling dynamic changes in dendritic spine shape and function; however, excessive proteolytic activity is detrimental to the cells. The exact mechanism of control of these seemingly contradictory outcomes of protease activity remains unknown. Here, we reveal that dendritic spine maturation is strictly controlled by the proteolytic activity, and its inhibition by the endogenous inhibitor (Tissue inhibitor of matrix metalloproteinases-1 – TIMP-1). Excessive proteolytic activity impairs long-term potentiation of the synaptic efficacy (LTP), and this impairment could be rescued by inhibition of protease activity. Moreover LTP is altered persistently when the ability of TIMP-1 to inhibit protease activity is abrogated, further demonstrating the role of such inhibition in the promotion of synaptic plasticity under well-defined conditions. We also show that dendritic spine maturation involves an intermediate formation of elongated spines, followed by their conversion into mushroom shape. The formation of mushroom-shaped spines is accompanied by increase in AMPA/NMDA ratio of glutamate receptors. Altogether, our results identify inhibition of protease activity as a critical regulatory mechanism for dendritic spines maturation. PMID:27282248

  12. Synaptic Structure Quantification in Cultured Neurons

    PubMed Central

    Guizzetti, Marina; Costa, Lucio G.

    2014-01-01

    Behavioral problems (e.g. learning and memory) following developmental exposure to toxicants suggests that dysregulation of the process of synapse formation and function may occur. The ability to assess these changes is thus of value. This protocol describes a method to investigate toxicant-induced changes to synaptic structure formation in primary hippocampal neurons using immunocytochemical labeling of the pre- and post-synaptic markers synaptophysin and PSD-95, confocal imaging, and three-dimensional object analysis. Protocols for the long-term culturing of primary hippocampal neurons and of primary cortical astrocytes, as well as their co-culture are included. While the described methods focus on how astrocytes influence synapse formation and how toxicants may interfere in this process, modifications to the experimental plan can easily be implemented. This would allow for the investigation of the effects of toxicants after treating neurons alone, or both astrocytes and neurons in co-culture. With the common endpoint of synapse structure formation, differences between varying treatment paradigms can expand our understanding of the influence of particular toxicants on these diverse cell types and provide insight into potential mechanisms of effect and the contributions of each to synapse formation. PMID:24865645

  13. Role of Hydrogen Sulfide in Brain Synaptic Remodeling

    PubMed Central

    Kamat, Pradip Kumar; Kalani, Anuradha; Tyagi, Neetu

    2015-01-01

    Synapses are the functional connection between neurons which are necessary for the transfer of electric activity or chemical activity from one cell to another. Synapses are formed by the pre- and postsynaptic membrane which communicates between pre- and postneurons while a neurochemical modulator is operated in this process. H2S has been known as a toxic gas with rotten eggs smell. However, increasing number of researches show that it regulate a variety of physiological and pathological processes in mammals. Hence, H2S is a physiologically important molecule and has been referred to as the third gaseous molecule alongside carbon monoxide and nitric oxide. The previous era has made an exponential development in the physiological and pathological significance of H2S. Specifically, in the central nervous system, H2S facilitates long-term potentiation and regulates intracellular calcium concentration in brain cells. We as well as others have also shown that H2S has antioxidant, antiapoptotic, and anti-inflammatory properties against various neurodegenerative disorders such as stroke, Alzheimer's disease, and vascular dementia. In this chapter, we highlight the current knowledge of H2S and its neuroprotective effects with a special emphasis on synaptic remodeling. PMID:25747482

  14. Role of hydrogen sulfide in brain synaptic remodeling.

    PubMed

    Kamat, Pradip Kumar; Kalani, Anuradha; Tyagi, Neetu

    2015-01-01

    Synapses are the functional connection between neurons which are necessary for the transfer of electric activity or chemical activity from one cell to another. Synapses are formed by the pre- and postsynaptic membrane which communicates between pre- and postneurons while a neurochemical modulator is operated in this process. H2S has been known as a toxic gas with rotten eggs smell. However, increasing number of researches show that it regulate a variety of physiological and pathological processes in mammals. Hence, H2S is a physiologically important molecule and has been referred to as the third gaseous molecule alongside carbon monoxide and nitric oxide. The previous era has made an exponential development in the physiological and pathological significance of H2S. Specifically, in the central nervous system, H2S facilitates long-term potentiation and regulates intracellular calcium concentration in brain cells. We as well as others have also shown that H2S has antioxidant, antiapoptotic, and anti-inflammatory properties against various neurodegenerative disorders such as stroke, Alzheimer's disease, and vascular dementia. In this chapter, we highlight the current knowledge of H2S and its neuroprotective effects with a special emphasis on synaptic remodeling. PMID:25747482

  15. Synaptic long-term potentiation realized in Pavlov's dog model based on a NiOx-based memristor

    NASA Astrophysics Data System (ADS)

    Hu, S. G.; Liu, Y.; Liu, Z.; Chen, T. P.; Yu, Q.; Deng, L. J.; Yin, Y.; Hosaka, Sumio

    2014-12-01

    Synaptic Long-Term Potentiation (LTP), which is a long-lasting enhancement in signal transmission between neurons, is widely considered as the major cellular mechanism during learning and memorization. In this work, a NiOx-based memristor is found to be able to emulate the synaptic LTP. Electrical conductance of the memristor is increased by electrical pulse stimulation and then spontaneously decays towards its initial state, which resembles the synaptic LTP. The lasting time of the LTP in the memristor can be estimated with the relaxation equation, which well describes the conductance decay behavior. The LTP effect of the memristor has a dependence on the stimulation parameters, including pulse height, width, interval, and number of pulses. An artificial network consisting of three neurons and two synapses is constructed to demonstrate the associative learning and LTP behavior in extinction of association in Pavlov's dog experiment.

  16. Roles of N-Type and Q-Type Ca2+ Channels in Supporting Hippocampal Synaptic Transmission

    NASA Astrophysics Data System (ADS)

    Wheeler, David B.; Randall, Andrew; Tsien, Richard W.

    1994-04-01

    Several types of calcium channels found in the central nervous system are possible participants in triggering neurotransmitter release. Synaptic transmission between hippocampal CA3 and CA1 neurons was mediated by N-type calcium channels, together with calcium channels whose pharmacology differs from that of L- and P-type channels but resembles that of the Q-type channel encoded by the α1A subunit gene. Blockade of either population of channels strongly increased enhancement of synaptic transmission with repetitive stimuli. Even after complete blockade of N-type channels, transmission was strongly modulated by stimulation of neurotransmitter receptors or protein kinase C. These findings suggest a role for α1A subunits in synaptic transmission and support the idea that neurotransmitter release may depend on multiple types of calcium channels under physiological conditions.

  17. Synaptic NF-kappa B pathway in neuronal plasticity and memory.

    PubMed

    Salles, Angeles; Romano, Arturo; Freudenthal, Ramiro

    2014-01-01

    Several transcription factors are present at the synapse, and among these are the Rel-NF-kappa B pathway components. NF-kappa B is a constitutive transcription factor, with a strong presence in the brain of which a considerable part is located in the neuropiles. This localization of the transcription factor, plus evidence pointing to different functions, is what gave place to two general hypotheses for synaptic NF-kappa B: (a) The transcription factor plays a role in the synapse to nucleus communication, and it is retrogradely transported from polarized localizations to regulate gene expression; (b) The transcription factor modulates the synaptic function locally. Evidence indicates that both mechanisms can operate simultaneously; here we will present different possibilities of these hypotheses that are supported by an increasing amount of data. We pay special attention to the local role of the transcription factor at the synapse, and based in the described evidence from different animal models, we propose several processes in which the transcription factor may change the synaptic strength. PMID:24854662

  18. Tracking the activity-dependent diffusion of synaptic proteins using restricted photoconversion of Dendra2

    PubMed Central

    Cassé, Frédéric; Martin, Stéphane

    2015-01-01

    Spines are small protrusions on dendritic membranes receiving inputs from axonal termini. They consist in a head connected to the dendritic shaft by a narrow neck and contain multiple synaptic proteins that interact in a coordinated manner to allow for synaptic communication. This process involves many proteins that are moving in and out spines. However, comparing this synaptodendritic movement in basal and stimulated conditions is very challenging. Here we describe an elegant method to measure the activity-dependent diffusion of synaptic proteins using Dendra2 photoconversion. We provide a successful method to obtain Dendra2-photoconverted images and a step-by-step procedure to analyze the data. This live-imaging approach may also apply to investigate the diffusion of proteins across other subcellular compartments or organelles including but not restricted to, nucleus, nucleolus, ER, or vesicular structures. Once the imaging system is set up, data can be acquired in 1–30 min and analyzed in approximately 1–4 h. PMID:26441538

  19. Neurosteroid interactions with synaptic and extrasynaptic GABAa receptors: regulation of subunit plasticity, phasic and tonic inhibition, and neuronal network excitability

    PubMed Central

    Chase Matthew, Carver; Doodipala Samba, Reddy

    2013-01-01

    Rationale Neurosteroids are steroids synthesized within the brain with rapid effects on neuronal excitability. Allopregnanolone, allotetrahydrodeoxycorticosterone, and androstanediol are three widely explored prototype endogenous neurosteroids. They have very different targets and functions compared to conventional steroid hormones. Neuronal GABAa receptors are one of the prime molecular targets of neurosteroids. Objective This review provides a critical appraisal of recent advances in the pharmacology of endogenous neurosteroids that interact with GABAa receptors in the brain. Neurosteroids possess distinct, characteristic effects on the membrane potential and current conductance of the neuron, mainly via potentiation of GABAa receptors at low concentrations and direct activation of receptor chloride channel at higher concentrations. The GABAa receptor mediates two types of inhibition, now characterized as synaptic (phasic) and extrasynaptic (tonic) inhibition. Synaptic release of GABA results in the activation of low-affinity γ2-containing synaptic receptors, while high-affinity δ-containing extrasynaptic receptors are persistently activated by the ambient GABA present in the extracellular fluid. Neurosteroids are potent positive allosteric modulators of synaptic and extrasynaptic GABAa receptors and therefore enhance both phasic and tonic inhibition. Tonic inhibition is specifically more sensitive to neurosteroids. The resulting tonic conductance generates a form of shunting inhibition that controls neuronal network excitability, seizure susceptibility, and behavior. Conclusion The growing understanding of the mechanisms of neurosteroid regulation of the structure and function of the synaptic and extrasynaptic GABAa receptors provide many opportunities to create improved therapies for sleep, anxiety, stress, epilepsy, and other neuropsychiatric conditions. PMID:24071826

  20. The neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) alters hippocampal excitatory synaptic transmission by modulation of the GABAergic system.

    PubMed

    Huang, YuYing; Chen, JunFang; Chen, Ying; Zhuang, YingHan; Sun, Mu; Behnisch, Thomas

    2015-01-01

    The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces Parkinson's disease-like symptoms following administration to mice, monkeys, and humans. A common view is that MPTP is metabolized to 1-methyl-4-phenylpyridinium ion (MPP(+)) to induce its neurodegenerative effects on dopaminergic neurons in the substantia nigra (SN). Moreover, the hippocampus contains dopaminergic fibers, which are projecting from the ventral tegmental area, SN and pars compacta and contain the whole machinery required for dopamine synthesis making them sensitive to MPTP and MPP(+). Here, we present data showing that acute bath-application of MPP(+) elicited a dose-dependent facilitation followed by a depression of synaptic transmission of hippocampal Schaffer collaterals-CA1 synapses in mice. The effects of MPP(+) were not mediated by D1/D5- and D2-like receptor activation. Inhibition of the dopamine transporters did not prevent but increased the depression of excitatory post-synaptic field potentials. In the search for a possible mechanism, we observed that MPP(+) reduced the appearance of polyspikes in population spikes recorded in str. pyramidale and increased the frequency of miniature inhibitory post-synaptic currents. The acute effect of MPP(+) on synaptic transmission was attenuated by co-application of a GABAA receptor antagonist. Taking these data together, we suggest that MPP(+) affects hippocampal synaptic transmission by enhancing some aspects of the hippocampal GABAergic system. PMID:26300734