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Sample records for synaptic transmission control

  1. Caffeine Controls Glutamatergic Synaptic Transmission and Pyramidal Neuron Excitability in Human Neocortex

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    Kerkhofs, Amber; Xavier, Ana C.; da Silva, Beatriz S.; Canas, Paula M.; Idema, Sander; Baayen, Johannes C.; Ferreira, Samira G.; Cunha, Rodrigo A.; Mansvelder, Huibert D.

    2018-01-01

    Caffeine is the most widely used psychoactive drug, bolstering attention and normalizing mood and cognition, all functions involving cerebral cortical circuits. Whereas studies in rodents showed that caffeine acts through the antagonism of inhibitory A1 adenosine receptors (A1R), neither the role of A1R nor the impact of caffeine on human cortical neurons is known. We here provide the first characterization of the impact of realistic concentrations of caffeine experienced by moderate coffee drinkers (50 μM) on excitability of pyramidal neurons and excitatory synaptic transmission in the human temporal cortex. Moderate concentrations of caffeine disinhibited several of the inhibitory A1R-mediated effects of adenosine, similar to previous observations in the rodent brain. Thus, caffeine restored the adenosine-induced decrease of both intrinsic membrane excitability and excitatory synaptic transmission in the human pyramidal neurons through antagonism of post-synaptic A1R. Indeed, the A1R-mediated effects of endogenous adenosine were more efficient to inhibit synaptic transmission than neuronal excitability. This was associated with a distinct affinity of caffeine for synaptic versus extra-synaptic human cortical A1R, probably resulting from a different molecular organization of A1R in human cortical synapses. These findings constitute the first neurophysiological description of the impact of caffeine on pyramidal neuron excitability and excitatory synaptic transmission in the human temporal cortex, providing adequate ground for the effects of caffeine on cognition in humans. PMID:29354052

  2. Caffeine Controls Glutamatergic Synaptic Transmission and Pyramidal Neuron Excitability in Human Neocortex

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    Amber Kerkhofs

    2018-01-01

    Full Text Available Caffeine is the most widely used psychoactive drug, bolstering attention and normalizing mood and cognition, all functions involving cerebral cortical circuits. Whereas studies in rodents showed that caffeine acts through the antagonism of inhibitory A1 adenosine receptors (A1R, neither the role of A1R nor the impact of caffeine on human cortical neurons is known. We here provide the first characterization of the impact of realistic concentrations of caffeine experienced by moderate coffee drinkers (50 μM on excitability of pyramidal neurons and excitatory synaptic transmission in the human temporal cortex. Moderate concentrations of caffeine disinhibited several of the inhibitory A1R-mediated effects of adenosine, similar to previous observations in the rodent brain. Thus, caffeine restored the adenosine-induced decrease of both intrinsic membrane excitability and excitatory synaptic transmission in the human pyramidal neurons through antagonism of post-synaptic A1R. Indeed, the A1R-mediated effects of endogenous adenosine were more efficient to inhibit synaptic transmission than neuronal excitability. This was associated with a distinct affinity of caffeine for synaptic versus extra-synaptic human cortical A1R, probably resulting from a different molecular organization of A1R in human cortical synapses. These findings constitute the first neurophysiological description of the impact of caffeine on pyramidal neuron excitability and excitatory synaptic transmission in the human temporal cortex, providing adequate ground for the effects of caffeine on cognition in humans.

  3. ANKS1B Gene Product AIDA-1 Controls Hippocampal Synaptic Transmission by Regulating GluN2B Subunit Localization.

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    Tindi, Jaafar O; Chávez, Andrés E; Cvejic, Svetlana; Calvo-Ochoa, Erika; Castillo, Pablo E; Jordan, Bryen A

    2015-06-17

    NMDA receptors (NMDARs) are key mediators of glutamatergic transmission and synaptic plasticity, and their dysregulation has been linked to diverse neuropsychiatric and neurodegenerative disorders. While normal NMDAR function requires regulated expression and trafficking of its different subunits, the molecular mechanisms underlying these processes are not fully understood. Here we report that the amyloid precursor protein intracellular domain associated-1 protein (AIDA-1), which associates with NMDARs and is encoded by ANKS1B, a gene recently linked to schizophrenia, regulates synaptic NMDAR subunit composition. Forebrain-specific AIDA-1 conditional knock-out (cKO) mice exhibit reduced GluN2B-mediated and increased GluN2A-mediated synaptic transmission, and biochemical analyses show AIDA-1 cKO mice have low GluN2B and high GluN2A protein levels at isolated hippocampal synaptic junctions compared with controls. These results are corroborated by immunocytochemical and electrophysiological analyses in primary neuronal cultures following acute lentiviral shRNA-mediated knockdown of AIDA-1. Moreover, hippocampal NMDAR-dependent but not metabotropic glutamate receptor-dependent plasticity is impaired in AIDA-1 cKO mice, further supporting a role for AIDA-1 in synaptic NMDAR function. We also demonstrate that AIDA-1 preferentially associates with GluN2B and with the adaptor protein Ca(2+)/calmodulin-dependent serine protein kinase and kinesin KIF17, which regulate the transport of GluN2B-containing NMDARs from the endoplasmic reticulum (ER) to synapses. Consistent with this function, GluN2B accumulates in ER-enriched fractions in AIDA-1 cKO mice. These findings suggest that AIDA-1 regulates NMDAR subunit composition at synapses by facilitating transport of GluN2B from the ER to synapses, which is critical for NMDAR plasticity. Our work provides an explanation for how AIDA-1 dysfunction might contribute to neuropsychiatric conditions, such as schizophrenia. Copyright

  4. Astrocytes optimize the synaptic transmission of information.

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    Suhita Nadkarni

    2008-05-01

    Full Text Available Chemical synapses transmit information via the release of neurotransmitter-filled vesicles from the presynaptic terminal. Using computational modeling, we predict that the limited availability of neurotransmitter resources in combination with the spontaneous release of vesicles limits the maximum degree of enhancement of synaptic transmission. This gives rise to an optimal tuning that depends on the number of active zones. There is strong experimental evidence that astrocytes that enwrap synapses can modulate the probabilities of vesicle release through bidirectional signaling and hence regulate synaptic transmission. For low-fidelity hippocampal synapses, which typically have only one or two active zones, the predicted optimal values lie close to those determined by experimentally measured astrocytic feedback, suggesting that astrocytes optimize synaptic transmission of information.

  5. Lateral regulation of synaptic transmission by astrocytes.

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    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. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Selective optical control of synaptic transmission in the subcortical visual pathway by activation of viral vector-expressed halorhodopsin.

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    Katsuyuki Kaneda

    Full Text Available The superficial layer of the superior colliculus (sSC receives visual inputs via two different pathways: from the retina and the primary visual cortex. However, the functional significance of each input for the operation of the sSC circuit remains to be identified. As a first step toward understanding the functional role of each of these inputs, we developed an optogenetic method to specifically suppress the synaptic transmission in the retino-tectal pathway. We introduced enhanced halorhodopsin (eNpHR, a yellow light-sensitive, membrane-targeting chloride pump, into mouse retinal ganglion cells (RGCs by intravitreously injecting an adeno-associated virus serotype-2 vector carrying the CMV-eNpHR-EYFP construct. Several weeks after the injection, whole-cell recordings made from sSC neurons in slice preparations revealed that yellow laser illumination of the eNpHR-expressing retino-tectal axons, putatively synapsing onto the recorded cells, effectively inhibited EPSCs evoked by electrical stimulation of the optic nerve layer. We also showed that sSC spike activities elicited by visual stimulation were significantly reduced by laser illumination of the sSC in anesthetized mice. These results indicate that photo-activation of eNpHR expressed in RGC axons enables selective blockade of retino-tectal synaptic transmission. The method established here can most likely be applied to a variety of brain regions for studying the function of individual inputs to these regions.

  7. Potentiation of electrical and chemical synaptic transmission mediated by endocannabinoids

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    Cachope, Roger; Mackie, Ken; Triller, Antoine; O’Brien, John; Pereda, Alberto E.

    2009-01-01

    SUMMARY Endocannabinoids are well established as inhibitors of chemical synaptic transmission via presynaptic activation of the cannabinoid type 1 receptor (CB1R). Contrasting this notion, we show that dendritic release of endocannabinoids mediates potentiation of synaptic transmission at mixed (electrical and chemical) synaptic contacts on the goldfish Mauthner cell. Remarkably, the observed enhancement was not restricted to the glutamatergic component of the synaptic response but also included a parallel increase in electrical transmission. This novel effect involved the activation of CB1 receptors and was indirectly mediated via the release of dopamine from nearby varicosities, which in turn led to potentiation of the synaptic response via a cAMP-dependent protein kinase-mediated postsynaptic mechanism. Thus, endocannabinoid release can potentiate synaptic transmission and its functional roles include the regulation of gap junction-mediated electrical synapses. Similar interactions between endocannabinoid and dopaminergic systems may be widespread and potentially relevant for the motor and rewarding effects of cannabis derivatives. PMID:18093525

  8. Defective Glycinergic Synaptic Transmission in Zebrafish Motility Mutants

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    Hirata, Hiromi; Carta, Eloisa; Yamanaka, Iori; Harvey, Robert J.; Kuwada, John Y.

    2010-01-01

    Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo) mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR) β subunit genes. These mutants exhibit a loss of glycinergic synaptic ...

  9. Tripartite synapses: astrocytes process and control synaptic information.

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    Perea, Gertrudis; Navarrete, Marta; Araque, Alfonso

    2009-08-01

    The term 'tripartite synapse' refers to a concept in synaptic physiology based on the demonstration of the existence of bidirectional communication between astrocytes and neurons. Consistent with this concept, in addition to the classic 'bipartite' information flow between the pre- and postsynaptic neurons, astrocytes exchange information with the synaptic neuronal elements, responding to synaptic activity and, in turn, regulating synaptic transmission. Because recent evidence has demonstrated that astrocytes integrate and process synaptic information and control synaptic transmission and plasticity, astrocytes, being active partners in synaptic function, are cellular elements involved in the processing, transfer and storage of information by the nervous system. Consequently, in contrast to the classically accepted paradigm that brain function results exclusively from neuronal activity, there is an emerging view, which we review herein, in which brain function actually arises from the coordinated activity of a network comprising both neurons and glia.

  10. How do astrocytes shape synaptic transmission? Insights from electrophysiology

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    Glenn eDallérac

    2013-10-01

    Full Text Available A major breakthrough in neuroscience has been the realization in the last decades that the dogmatic view of astroglial cells as being merely fostering and buffering elements of the nervous system is simplistic. A wealth of investigations now shows that astrocytes actually participate in the control of synaptic transmission in an active manner. This was first hinted by the intimate contacts glial processes make with neurons, particularly at the synaptic level, and evidenced using electrophysiological and calcium imaging techniques. Calcium imaging has provided critical evidence demonstrating that astrocytic regulation of synaptic efficacy is not a passive phenomenon. However, given that cellular activation is not only represented by calcium signaling, it is also crucial to assess concomitant mechanisms. We and others have used electrophysiological techniques to simultaneously record neuronal and astrocytic activity, thus enabling the study of multiple ionic currents and in depth investigation of neuro-glial dialogues. In the current review, we focus on the input such approach has provided in the understanding of astrocyte-neuron interactions underlying control of synaptic efficacy.

  11. Synaptic transmission and plasticity in an active cortical network.

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    Ramon Reig

    Full Text Available BACKGROUND: The cerebral cortex is permanently active during both awake and sleep states. This ongoing cortical activity has an impact on synaptic transmission and short-term plasticity. An activity pattern generated by the cortical network is a slow rhythmic activity that alternates up (active and down (silent states, a pattern occurring during slow wave sleep, anesthesia and even in vitro. Here we have studied 1 how network activity affects short term synaptic plasticity and, 2 how synaptic transmission varies in up versus down states. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular recordings obtained from cortex in vitro and in vivo were used to record synaptic potentials, while presynaptic activation was achieved either with electrical or natural stimulation. Repetitive activation of layer 4 to layer 2/3 synaptic connections from ferret visual cortex slices displayed synaptic augmentation that was larger and longer lasting in active than in silent slices. Paired-pulse facilitation was also significantly larger in an active network and it persisted for longer intervals (up to 200 ms than in silent slices. Intracortical synaptic potentials occurring during up states in vitro increased their amplitude while paired-pulse facilitation disappeared. Both intracortical and thalamocortical synaptic potentials were also significantly larger in up than in down states in the cat visual cortex in vivo. These enhanced synaptic potentials did not further facilitate when pairs of stimuli were given, thus paired-pulse facilitation during up states in vivo was virtually absent. Visually induced synaptic responses displayed larger amplitudes when occurring during up versus down states. This was further tested in rat barrel cortex, where a sensory activated synaptic potential was also larger in up states. CONCLUSIONS/SIGNIFICANCE: These results imply that synaptic transmission in an active cortical network is more secure and efficient due to larger amplitude of

  12. Synaptic adhesion molecule IgSF11 regulates synaptic transmission and plasticity

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    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

  13. Defective glycinergic synaptic transmission in zebrafish motility mutants

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    Hiromi Hirata

    2010-01-01

    Full Text Available Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR β subunit genes. These mutants exhibit a loss of glycinergic synaptic transmission due to a lack of synaptic aggregation of GlyRs. Due to the consequent loss of reciprocal inhibition of motor circuits between the two sides of the spinal cord, motor neurons activate simultaneously on both sides resulting in bilateral contraction of axial muscles of beo mutants, eliciting the so-called ‘accordion’ phenotype. Similar defects in GlyR subunit genes have been observed in several mammals and are the basis for human hyperekplexia/startle disease. By contrast, zebrafish shocked (sho mutants have a defect in slc6a9, encoding GlyT1, a glycine transporter that is expressed by astroglial cells surrounding the glycinergic synapse in the hindbrain and spinal cord. GlyT1 mediates rapid uptake of glycine from the synaptic cleft, terminating synaptic transmission. In zebrafish sho mutants, there appears to be elevated extracellular glycine resulting in persistent inhibition of postsynaptic neurons and subsequent reduced motility, causing the ‘twitch once’ phenotype. We review current knowledge regarding zebrafish ‘accordion’ and ‘twitch once’ mutants, including beo and sho, and report the identification of a new α2 subunit that revises the phylogeny of zebrafish GlyRs.

  14. Defective Glycinergic Synaptic Transmission in Zebrafish Motility Mutants

    Science.gov (United States)

    Hirata, Hiromi; Carta, Eloisa; Yamanaka, Iori; Harvey, Robert J.; Kuwada, John Y.

    2009-01-01

    Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo) mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR) β subunit genes. These mutants exhibit a loss of glycinergic synaptic transmission due to a lack of synaptic aggregation of GlyRs. Due to the consequent loss of reciprocal inhibition of motor circuits between the two sides of the spinal cord, motor neurons activate simultaneously on both sides resulting in bilateral contraction of axial muscles of beo mutants, eliciting the so-called ‘accordion’ phenotype. Similar defects in GlyR subunit genes have been observed in several mammals and are the basis for human hyperekplexia/startle disease. By contrast, zebrafish shocked (sho) mutants have a defect in slc6a9, encoding GlyT1, a glycine transporter that is expressed by astroglial cells surrounding the glycinergic synapse in the hindbrain and spinal cord. GlyT1 mediates rapid uptake of glycine from the synaptic cleft, terminating synaptic transmission. In zebrafish sho mutants, there appears to be elevated extracellular glycine resulting in persistent inhibition of postsynaptic neurons and subsequent reduced motility, causing the ‘twitch-once’ phenotype. We review current knowledge regarding zebrafish ‘accordion’ and ‘twitch-once’ mutants, including beo and sho, and report the identification of a new α2 subunit that revises the phylogeny of zebrafish GlyRs. PMID:20161699

  15. Inhibition of hippocampal synaptic transmission by impairment of Ral function

    DEFF Research Database (Denmark)

    Owe-Larsson, Björn; Chaves-Olarte, Esteban; Chauhan, Ashok

    2005-01-01

    Large clostridial cytotoxins and protein overexpression were used to probe for involvement of Ras-related GTPases (guanosine triphosphate) in synaptic transmission in cultured rat hippocampal neurons. The toxins TcdA-10463 (inactivates Rho, Rac, Cdc42, Rap) and TcsL-1522 (inactivates Ral, Rac, Ra...

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

    International Nuclear Information System (INIS)

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

    2011-01-01

    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

  17. Leptin potentiates GABAergic synaptic transmission in the developing rodent hippocampus.

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    Damien eGuimond

    2014-08-01

    Full Text Available It is becoming increasingly clear that leptin is not only a hormone regulating energy homeostasis but also a neurotrophic factor impacting a number of brain regions, including the hippocampus. Although leptin promotes the development of GABAergic transmission in the hypothalamus, little is known about its action on the GABAergic system in the hippocampus. Here we show that leptin modulates GABAergic transmission onto developing CA3 pyramidal cells of newborn rats. Specifically, leptin induces a long-lasting potentiation (LLP-GABAA of miniature GABAA receptor-mediated postsynaptic current (GABAA-PSC frequency. Leptin also increases the amplitude of evoked GABAA-PSCs in a subset of neurons along with a decrease in the coefficient of variation and no change in the paired-pulse ratio, pointing to an increased recruitment of functional synapses. Adding pharmacological blockers to the recording pipette showed that the leptin-induced LLP-GABAA requires postsynaptic calcium released from internal stores, as well as postsynaptic MAPK/ERK kinases 1 and/or 2 (MEK1/2, phosphoinositide 3 kinase (PI3K and calcium-calmodulin kinase kinase (CaMKK. Finally, study of CA3 pyramidal cells in leptin-deficient ob/ob mice revealed a reduction in the basal frequency of miniature GABAA-PSCs compared to wild type littermates. In addition, presynaptic GAD65 immunostaining was reduced in the CA3 stratum pyramidale of mutant animals, both results converging to suggest a decreased number of functional GABAergic synapses in ob/ob mice. Overall, these results show that leptin potentiates and promotes the development of GABAergic synaptic transmission in the developing hippocampus likely via an increase in the number of functional synapses, and provide insights into the intracellular pathways mediating this effect. This study further extends the scope of leptin’s neurotrophic action to a key regulator of hippocampal development and function, namely GABAergic transmission.

  18. Use-Dependent Inhibition of Synaptic Transmission by the Secretion of Intravesicularly Accumulated Antipsychotic Drugs

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    Tischbirek, Carsten H.; Wenzel, Eva M.; Zheng, Fang

    2012-01-01

    Tischbirek et al. find that weak-base antipsychotic drugs are accumulated in synaptic vesicles and are secreted upon exocytosis, leading to increased extracellular drug concentrations following neuronal activity. The secretion of the drugs in turn inhibits synaptic transmission in a use-dependent...

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

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    Rozan Vroman

    2014-05-01

    Full Text Available 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

  20. Very low concentrations of ethanol suppress excitatory synaptic transmission in rat visual cortex.

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    Luong, Lucas; Bannon, Nicholas M; Redenti, Andrew; Chistiakova, Marina; Volgushev, Maxim

    2017-05-01

    Ethanol is one of the most commonly used substances in the world. Behavioral effects of alcohol are well described, however, cellular mechanisms of its action are poorly understood. There is an apparent contradiction between measurable behavioral changes produced by low concentrations of ethanol, and lack of evidence of synaptic changes at these concentrations. Furthermore, effects of ethanol on synaptic transmission in the neocortex are poorly understood. Here, we set to determine effects of ethanol on excitatory synaptic transmission in the neocortex. We show that 1-50 mm ethanol suppresses excitatory synaptic transmission to layer 2/3 pyramidal neurons in rat visual cortex in a concentration-dependent manner. To the best of our knowledge, this is the first demonstration of the effects of very low concentrations of ethanol (from 1 mm) on synaptic transmission in the neocortex. We further show that a selective antagonist of A 1 adenosine receptors, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), blocks effects of 1-10 mm ethanol on synaptic transmission. However, the reduction in excitatory postsynaptic potential amplitude by 50 mm ethanol was not affected by DPCPX. We propose that ethanol depresses excitatory synaptic transmission in the neocortex by at least two mechanisms, engaged at different concentrations: low concentrations of ethanol reduce synaptic transmission via A 1 R-dependent mechanism and involve presynaptic changes, while higher concentrations activate additional, adenosine-independent mechanisms with predominantly postsynaptic action. Involvement of adenosine signaling in mediating effects of low concentrations of ethanol may have important implications for understanding alcohol's effects on brain function, and provide a mechanistic explanation to the interaction between alcohol and caffeine. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  1. Differential regulation of spontaneous and evoked inhibitory synaptic transmission in somatosensory cortex by retinoic acid.

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    Yee, Ada X; Chen, Lu

    2016-11-01

    Retinoic acid (RA), a developmental morphogen, has emerged in recent studies as a novel synaptic signaling molecule that acts in mature hippocampal neurons to modulate excitatory and inhibitory synaptic transmission in the context of homeostatic synaptic plasticity. However, it is unclear whether RA is capable of modulating neural circuits outside of the hippocampus, and if so, whether the mode of RA's action at synapses is similar to that within the hippocampal network. Here we explore for the first time RA's synaptic function outside the hippocampus and uncover a novel function of all-trans retinoic acid at inhibitory synapses. Acute RA treatment increases spontaneous inhibitory synaptic transmission in L2/3 pyramidal neurons of the somatosensory cortex, and this effect requires expression of RA's receptor RARα both pre- and post-synaptically. Intriguingly, RA does not seem to affect evoked inhibitory transmission assayed with either extracellular stimulation or direct activation of action potentials in presynaptic interneurons at connected pairs of interneurons and pyramidal neurons. Taken together, these results suggest that RA's action at synapses is not monotonous, but is diverse depending on the type of synaptic connection (excitatory versus inhibitory) and circuit (hippocampal versus cortical). Thus, synaptic signaling of RA may mediate multi-faceted regulation of synaptic plasticity. In addition to its classic roles in brain development, retinoic acid (RA) has recently been shown to regulate excitatory and inhibitory transmission in the adult brain. Here, the authors show that in layer 2/3 (L2/3) of the somatosensory cortex (S1), acute RA induces increases in spontaneous but not action-potential evoked transmission, and that this requires retinoic acid receptor (RARα) both in presynaptic PV-positive interneurons and postsynaptic pyramidal (PN) neurons. © 2016 Wiley Periodicals, Inc.

  2. Purines released from astrocytes inhibit excitatory synaptic transmission in the ventral horn of the spinal cord

    DEFF Research Database (Denmark)

    Carlsen, Eva Maria Meier; Perrier, Jean-Francois Marie

    2014-01-01

    . 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...... 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...

  3. Cannabidiol inhibits synaptic transmission in rat hippocampal cultures and slices via multiple receptor pathways

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    Ledgerwood, CJ; Greenwood, SM; Brett, RR; Pratt, JA; Bushell, TJ

    2011-01-01

    BACKGROUND AND PURPOSE Cannabidiol (CBD) has emerged as an interesting compound with therapeutic potential in several CNS disorders. However, whether it can modulate synaptic activity in the CNS remains unclear. Here, we have investigated whether CBD modulates synaptic transmission in rat hippocampal cultures and acute slices. EXPERIMENTAL APPROACH The effect of CBD on synaptic transmission was examined in rat hippocampal cultures and acute slices using whole cell patch clamp and standard extracellular recordings respectively. KEY RESULTS Cannabidiol decreased synaptic activity in hippocampal cultures in a concentration-dependent and Pertussis toxin-sensitive manner. The effects of CBD in culture were significantly reduced in the presence of the cannabinoid receptor (CB1) inverse agonist, LY320135 but were unaffected by the 5-HT1A receptor antagonist, WAY100135. In hippocampal slices, CBD inhibited basal synaptic transmission, an effect that was abolished by the proposed CB1 receptor antagonist, AM251, in addition to LY320135 and WAY100135. CONCLUSIONS AND IMPLICATIONS Cannabidiol reduces synaptic transmission in hippocampal in vitro preparations and we propose a role for both 5-HT1A and CB1 receptors in these CBD-mediated effects. These data offer some mechanistic insights into the effects of CBD and emphasize that further investigations into the actions of CBD in the CNS are required in order to elucidate the full therapeutic potential of CBD. PMID:20825410

  4. Cortical spreading depression modulates synaptic transmission of the rat lateral amygdala.

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    Dehbandi, Shahab; Speckmann, Erwin-Josef; Pape, Hans Christian; Gorji, Ali

    2008-04-01

    Clinical and pathophysiological evidence connects migraine and the amygdala. Cortical spreading depression (CSD) plays a causative role in the generation of aura symptoms. However, the role of CSD in the pathophysiology of other symptoms of migraine needs to be investigated. An in vitro brain slice technique was used to investigate CSD effects on tetanus-induced long-term potentiation (LTP) in the lateral amygdala (LA) of the combined rat amygdala-hippocampus-cortex slices. More than 75% of CSD induced in temporal cortex propagated to LA. Induction of CSD in combined amygdala-hippocampus-cortex slices in which CSD propagated from neocortex to LA significantly augmented LTP in LA. LTP was inhibited when CSD travelled only in the neocortical tissues. Separation of the amygdala from the remaining neocortical part of the slice, in which CSD propagation was limited to the neocortex, increased LTP close to the control levels. Pharmacological manipulations of the slices, in which CSD reached LA, revealed the involvement of NMDA and AMPA glutamate subreceptors as well as dopamine D2 receptors in the enhancement of LTP in LA. However, neither blocking of GABA receptors nor activation of dopamine D1 receptors affected LTP in these slices. The results indicate the disturbances of LA synaptic transmission triggered by propagation of CSD. This perturbation of LA synaptic transmission induced by CSD may relate to some symptoms occurring during migraine attacks.

  5. Localization of Presynaptic Plasticity Mechanisms Enables Functional Independence of Synaptic and Ectopic Transmission in the Cerebellum

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    Katharine L. Dobson

    2015-01-01

    Full Text Available In the cerebellar molecular layer parallel fibre terminals release glutamate from both the active zone and from extrasynaptic “ectopic” sites. Ectopic release mediates transmission to the Bergmann glia that ensheathe the synapse, activating Ca2+-permeable AMPA receptors and glutamate transporters. Parallel fibre terminals exhibit several forms of presynaptic plasticity, including cAMP-dependent long-term potentiation and endocannabinoid-dependent long-term depression, but it is not known whether these presynaptic forms of long-term plasticity also influence ectopic transmission to Bergmann glia. Stimulation of parallel fibre inputs at 16 Hz evoked LTP of synaptic transmission, but LTD of ectopic transmission. Pharmacological activation of adenylyl cyclase by forskolin caused LTP at Purkinje neurons, but only transient potentiation at Bergmann glia, reinforcing the concept that ectopic sites lack the capacity to express sustained cAMP-dependent potentiation. Activation of mGluR1 caused depression of synaptic transmission via retrograde endocannabinoid signalling but had no significant effect at ectopic sites. In contrast, activation of NMDA receptors suppressed both synaptic and ectopic transmission. The results suggest that the signalling mechanisms for presynaptic LTP and retrograde depression by endocannabinoids are restricted to the active zone at parallel fibre synapses, allowing independent modulation of synaptic transmission to Purkinje neurons and ectopic transmission to Bergmann glia.

  6. Experience-Dependent Equilibration of AMPAR-Mediated Synaptic Transmission during the Critical Period

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    Kyung-Seok Han

    2017-01-01

    Full Text Available Experience-dependent synapse refinement is essential for functional optimization of neural circuits. However, how sensory experience sculpts excitatory synaptic transmission is poorly understood. Here, we show that despite substantial remodeling of synaptic connectivity, AMPAR-mediated synaptic transmission remains at equilibrium during the critical period in the mouse primary visual cortex. The maintenance of this equilibrium requires neurogranin (Ng, a postsynaptic calmodulin-binding protein important for synaptic plasticity. With normal visual experience, loss of Ng decreased AMPAR-positive synapse numbers, prevented AMPAR-silent synapse maturation, and increased spine elimination. Importantly, visual deprivation halted synapse loss caused by loss of Ng, revealing that Ng coordinates experience-dependent AMPAR-silent synapse conversion to AMPAR-active synapses and synapse elimination. Loss of Ng also led to sensitized long-term synaptic depression (LTD and impaired visually guided behavior. Our synaptic interrogation reveals that experience-dependent coordination of AMPAR-silent synapse conversion and synapse elimination hinges upon Ng-dependent mechanisms for constructive synaptic refinement during the critical period.

  7. Exposure to cocaine regulates inhibitory synaptic transmission from the ventral tegmental area to the nucleus accumbens.

    Science.gov (United States)

    Ishikawa, Masago; Otaka, Mami; Neumann, Peter A; Wang, Zhijian; Cook, James M; Schlüter, Oliver M; Dong, Yan; Huang, Yanhua H

    2013-10-01

    Synaptic projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) make up the backbone of the brain reward pathway, a neural circuit that mediates behavioural responses elicited by natural rewards as well as by cocaine and other drugs of abuse. In addition to the well-known modulatory dopaminergic projection, the VTA also provides fast excitatory and inhibitory synaptic input to the NAc, directly regulating NAc medium spiny neurons (MSNs). However, the cellular nature of VTA-to-NAc fast synaptic transmission and its roles in drug-induced adaptations are not well understood. Using viral-mediated in vivo expression of channelrhodopsin 2, the present study dissected fast excitatory and inhibitory synaptic transmission from the VTA to NAc MSNs in rats. Our results suggest that, following repeated exposure to cocaine (15 mg kg(-1) day(-1) × 5 days, i.p., 1 or 21 day withdrawal), a presynaptic enhancement of excitatory transmission and suppression of inhibitory transmission occurred at different withdrawal time points at VTA-to-NAc core synapses. In contrast, no postsynaptic alterations were detected at either type of synapse. These results suggest that changes in VTA-to-NAc fast excitatory and inhibitory synaptic transmissions may contribute to cocaine-induced alteration of the brain reward circuitry.

  8. Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons.

    Science.gov (United States)

    Xia, J X; Xiong, J X; Wang, H K; Duan, S M; Ye, J N; Hu, Z A

    2012-01-10

    Hypocretin neurons in the lateral hypothalamus, a new wakefulness-promoting center, have been recently regarded as an important target involved in endogenous adenosine-regulating sleep homeostasis. The GABAergic synaptic transmissions are the main inhibitory afferents to hypocretin neurons, which play an important role in the regulation of excitability of these neurons. The inhibitory effect of adenosine, a homeostatic sleep-promoting factor, on the excitatory glutamatergic synaptic transmissions in hypocretin neurons has been well documented, whether adenosine also modulates these inhibitory GABAergic synaptic transmissions in these neurons has not been investigated. In this study, the effect of adenosine on inhibitory postsynaptic currents (IPSCs) in hypocretin neurons was examined by using perforated patch-clamp recordings in the acute hypothalamic slices. The findings demonstrated that adenosine suppressed the amplitude of evoked IPSCs in a dose-dependent manner, which was completely abolished by 8-cyclopentyltheophylline (CPT), a selective antagonist of adenosine A1 receptor but not adenosine A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl) xanthine. A presynaptic origin was suggested as following: adenosine increased paired-pulse ratio as well as reduced GABAergic miniature IPSC frequency without affecting the miniature IPSC amplitude. Further findings demonstrated that when the frequency of electrical stimulation was raised to 10 Hz, but not 1 Hz, a time-dependent depression of evoked IPSC amplitude was detected in hypocretin neurons, which could be partially blocked by CPT. However, under a higher frequency at 100 Hz stimulation, CPT had no action on the depressed GABAergic synaptic transmission induced by such tetanic stimulation in these hypocretin neurons. These results suggest that endogenous adenosine generated under certain stronger activities of synaptic transmissions exerts an inhibitory effect on GABAergic synaptic transmission in hypocretin

  9. Synaptic Control of Secretory Trafficking in Dendrites

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    Cyril Hanus

    2014-06-01

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

  10. Computational quest for understanding the role of astrocyte signaling in synaptic transmission and plasticity

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    Maurizio eDe Pitta'

    2012-12-01

    Full Text Available The complexity of the signaling network that underlies astrocyte-synapse interactions may seem discouraging when tackled from a theoretical perspective. Computational modeling is challenged by the fact that many details remain hitherto unknown and conventional approaches to describe synaptic function are unsuitable to explain experimental observations when astrocytic signaling is taken into account. Supported by experimental evidence is the possibility that astrocytes perform genuine information processing by means of their calcium signaling and are players in the physiological setting of the basal tone of synaptic transmission. Here we consider the plausibility of this scenario from a theoretical perspective, focusing on the modulation of synaptic release probability by the astrocyte and its implications on synaptic plasticity. The analysis of the signaling pathways underlying such modulation refines our notion of the tripartite synapse and has profound implications on our understanding of brain function.

  11. Automated manual transmission controller

    Science.gov (United States)

    Lawrie, Robert E.; Reed, Jr., Richard G.; Bernier, David R.

    1999-12-28

    A powertrain system for a hybrid vehicle. The hybrid vehicle includes a heat engine, such as a diesel engine, and an electric machine, which operates as both an electric motor and an alternator, to power the vehicle. The hybrid vehicle also includes a manual-style transmission configured to operate as an automatic transmission from the perspective of the driver. The engine and the electric machine drive an input shaft which in turn drives an output shaft of the transmission. In addition to driving the transmission, the electric machine regulates the speed of the input shaft in order to synchronize the input shaft during either an upshift or downshift of the transmission by either decreasing or increasing the speed of the input shaft. When decreasing the speed of the input shaft, the electric motor functions as an alternator to produce electrical energy which may be stored by a storage device. Operation of the transmission is controlled by a transmission controller which receives input signals and generates output signals to control shift and clutch motors to effect smooth launch, upshift shifts, and downshifts of the transmission, so that the transmission functions substantially as an automatic transmission from the perspective of the driver, while internally substantially functioning as a manual transmission.

  12. Postnatal aniracetam treatment improves prenatal ethanol induced attenuation of AMPA receptor-mediated synaptic transmission.

    Science.gov (United States)

    Wijayawardhane, Nayana; Shonesy, Brian C; Vaglenova, Julia; Vaithianathan, Thirumalini; Carpenter, Mark; Breese, Charles R; Dityatev, Alexander; Suppiramaniam, Vishnu

    2007-06-01

    Aniracetam is a nootropic compound and an allosteric modulator of AMPA receptors (AMPARs) which mediate synaptic mechanisms of learning and memory. Here we analyzed impairments in AMPAR-mediated synaptic transmission caused by moderate prenatal ethanol exposure and investigated the effects of postnatal aniracetam treatment on these abnormalities. Pregnant Sprague-Dawley rats were gavaged with ethanol or isocaloric sucrose throughout pregnancy, and subsequently the offspring were treated with aniracetam on postnatal days (PND) 18 to 27. Hippocampal slices prepared from these pups on PND 28 to 34 were used for the whole-cell patch-clamp recordings of AMPAR-mediated spontaneous and miniature excitatory postsynaptic currents in CA1 pyramidal cells. Our results indicate that moderate ethanol exposure during pregnancy results in impaired hippocampal AMPAR-mediated neurotransmission, and critically timed aniracetam treatment can abrogate this deficiency. These results highlight the possibility that aniracetam treatment can restore synaptic transmission and ameliorate cognitive deficits associated with the fetal alcohol syndrome.

  13. Slow GABAA mediated synaptic transmission in rat visual cortex

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    Sceniak Michael P

    2008-01-01

    Full Text Available Abstract Background Previous reports of inhibition in the neocortex suggest that inhibition is mediated predominantly through GABAA receptors exhibiting fast kinetics. Within the hippocampus, it has been shown that GABAA responses can take the form of either fast or slow response kinetics. Our findings indicate, for the first time, that the neocortex displays synaptic responses with slow GABAA receptor mediated inhibitory postsynaptic currents (IPSCs. These IPSCs are kinetically and pharmacologically similar to responses found in the hippocampus, although the anatomical specificity of evoked responses is unique from hippocampus. Spontaneous slow GABAA IPSCs were recorded from both pyramidal and inhibitory neurons in rat visual cortex. Results GABAA slow IPSCs were significantly different from fast responses with respect to rise times and decay time constants, but not amplitudes. Spontaneously occurring GABAA slow IPSCs were nearly 100 times less frequent than fast sIPSCs and both were completely abolished by the chloride channel blocker, picrotoxin. The GABAA subunit-specific antagonist, furosemide, depressed spontaneous and evoked GABAA fast IPSCs, but not slow GABAA-mediated IPSCs. Anatomical specificity was evident using minimal stimulation: IPSCs with slow kinetics were evoked predominantly through stimulation of layer 1/2 apical dendritic zones of layer 4 pyramidal neurons and across their basal dendrites, while GABAA fast IPSCs were evoked through stimulation throughout the dendritic arborization. Many evoked IPSCs were also composed of a combination of fast and slow IPSC components. Conclusion GABAA slow IPSCs displayed durations that were approximately 4 fold longer than typical GABAA fast IPSCs, but shorter than GABAB-mediated inhibition. The anatomical and pharmacological specificity of evoked slow IPSCs suggests a unique origin of synaptic input. Incorporating GABAA slow IPSCs into computational models of cortical function will help

  14. Dual Influence of Endocannabinoids on Long-Term Potentiation of Synaptic Transmission

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    Armando Silva-Cruz

    2017-12-01

    Full Text Available Cannabinoid receptor 1 (CB1R is widely distributed in the central nervous system, in excitatory and inhibitory neurons, and in astrocytes. CB1R agonists impair cognition and prevent long-term potentiation (LTP of synaptic transmission, but the influence of endogenously formed cannabinoids (eCBs on hippocampal LTP remains ambiguous. Based on the knowledge that eCBs are released upon high frequency neuronal firing, we hypothesized that the influence of eCBs upon LTP could change according to the paradigm of LTP induction. We thus tested the influence of eCBs on hippocampal LTP using two θ-burst protocols that induce either a weak or a strong LTP. LTP induced by a weak-θ-burst protocol is facilitated while preventing the endogenous activation of CB1Rs. In contrast, the same procedures lead to inhibition of LTP induced by the strong-θ-burst protocol, suggestive of a facilitatory action of eCBs upon strong LTP. Accordingly, an inhibitor of the metabolism of the predominant eCB in the hippocampus, 2-arachidonoyl-glycerol (2-AG, facilitates strong LTP. The facilitatory action of endogenous CB1R activation does not require the activity of inhibitory A1 adenosine receptors, is not affected by inhibition of astrocytic metabolism, but involves inhibitory GABAergic transmission. The continuous activation of CB1Rs via exogenous cannabinoids, or by drugs known to prevent metabolism of the non-prevalent hippocampal eCB, anandamide, inhibited LTP. We conclude that endogenous activation of CB1Rs by physiologically formed eCBs exerts a fine-tune homeostatic control of LTP in the hippocampus, acting as a high-pass filter, therefore likely reducing the signal-to-noise ratio of synaptic strengthening.

  15. 3D estimation of synaptic vesicle distributions in serial section transmission electron microscopy

    DEFF Research Database (Denmark)

    Khanmohammadi, Mahdieh; Darkner, Sune; Nava, Nicoletta

    directly. It is hypothesized that in a rat model of behavioral stress the vesicles distribution varies. We propose methods for estimating the 3-dimensional distribution of synaptic vesicles from the active zone through serial section transmission electron microscope images (ssTEM) from Sprague-Dawley rat...

  16. Nicotine uses neuron-glia communication to enhance hippocampal synaptic transmission and long-term memory.

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    Mónica López-Hidalgo

    Full Text Available Nicotine enhances synaptic transmission and facilitates long-term memory. Now it is known that bi-directional glia-neuron interactions play important roles in the physiology of the brain. However, the involvement of glial cells in the effects of nicotine has not been considered until now. In particular, the gliotransmitter D-serine, an endogenous co-agonist of NMDA receptors, enables different types of synaptic plasticity and memory in the hippocampus. Here, we report that hippocampal long-term synaptic plasticity induced by nicotine was annulled by an enzyme that degrades endogenous D-serine, or by an NMDA receptor antagonist that acts at the D-serine binding site. Accordingly, both effects of nicotine: the enhancement of synaptic transmission and facilitation of long-term memory were eliminated by impairing glial cells with fluoroacetate, and were restored with exogenous D-serine. Together, these results show that glial D-serine is essential for the long-term effects of nicotine on synaptic plasticity and memory, and they highlight the roles of glial cells as key participants in brain functions.

  17. A high-throughput model for investigating neuronal function and synaptic transmission in cultured neuronal networks.

    Science.gov (United States)

    Virdee, Jasmeet K; Saro, Gabriella; Fouillet, Antoine; Findlay, Jeremy; Ferreira, Filipa; Eversden, Sarah; O'Neill, Michael J; Wolak, Joanna; Ursu, Daniel

    2017-11-03

    Loss of synapses or alteration of synaptic activity is associated with cognitive impairment observed in a number of psychiatric and neurological disorders, such as schizophrenia and Alzheimer's disease. Therefore successful development of in vitro methods that can investigate synaptic function in a high-throughput format could be highly impactful for neuroscience drug discovery. We present here the development, characterisation and validation of a novel high-throughput in vitro model for assessing neuronal function and synaptic transmission in primary rodent neurons. The novelty of our approach resides in the combination of the electrical field stimulation (EFS) with data acquisition in spatially separated areas of an interconnected neuronal network. We integrated our methodology with state of the art drug discovery instrumentation (FLIPR Tetra) and used selective tool compounds to perform a systematic pharmacological validation of the model. We investigated pharmacological modulators targeting pre- and post-synaptic receptors (AMPA, NMDA, GABA-A, mGluR2/3 receptors and Nav, Cav voltage-gated ion channels) and demonstrated the ability of our model to discriminate and measure synaptic transmission in cultured neuronal networks. Application of the model described here as an unbiased phenotypic screening approach will help with our long term goals of discovering novel therapeutic strategies for treating neurological disorders.

  18. Depressed Synaptic Transmission and Reduced Vesicle Release Sites in Huntington's Disease Neuromuscular Junctions.

    Science.gov (United States)

    Khedraki, Ahmad; Reed, Eric J; Romer, Shannon H; Wang, Qingbo; Romine, William; Rich, Mark M; Talmadge, Robert J; Voss, Andrew A

    2017-08-23

    Huntington's disease (HD) is a progressive and fatal degenerative disorder that results in debilitating cognitive and motor dysfunction. Most HD studies have focused on degeneration of the CNS. We previously discovered that skeletal muscle from transgenic R6/2 HD mice is hyperexcitable due to decreased chloride and potassium conductances. The progressive and early onset of these defects suggest a primary myopathy in HD. In this study, we examined the relationship between neuromuscular transmission and skeletal muscle hyperexcitability. We used an ex vivo preparation of the levator auris longus muscle from male and female late-stage R6/2 mice and age-matched wild-type controls. Immunostaining of the synapses and molecular analyses revealed no evidence of denervation. Physiologically, we recorded spontaneous miniature endplate currents (mEPCs) and nerve-evoked EPCs (eEPCs) under voltage-clamp, which, unlike current-clamp records, were independent of the changes in muscle membrane properties. We found a reduction in the number of vesicles released per action potential (quantal content) in R6/2 muscle, which analysis of eEPC variance and morphology indicate is caused by a reduction in the number of vesicle release sites ( n ) rather than a change in the probability of release ( p rel ). Furthermore, analysis of high-frequency stimulation trains suggests an impairment in vesicle mobilization. The depressed neuromuscular transmission in R6/2 muscle may help compensate for the muscle hyperexcitability and contribute to motor impersistence. SIGNIFICANCE STATEMENT Recent evidence indicates that Huntington's disease (HD) is a multisystem disorder. Our examination of neuromuscular transmission in this study reveals defects in the motor nerve terminal that may compensate for the muscle hyperexcitability in HD. The technique we used eliminates the effects of the altered muscle membrane properties on synaptic currents and thus provides hitherto the most detailed analysis of

  19. Dynamic effects of TNF-α on synaptic transmission in mice over time following sciatic nerve chronic constriction injury.

    Science.gov (United States)

    Zhang, Hongmei; Zhang, Haijun; Dougherty, Patrick M

    2013-10-01

    Nerve injury-induced central sensitization can manifest as an increase in excitatory synaptic transmission and/or as a decrease in inhibitory synaptic transmission in spinal dorsal horn neurons. Cytokines such as tumor necrosis factor-α (TNF-α) are induced in the spinal cord under various injury conditions and contribute to neuropathic pain. In this study we examined the effect of TNF-α in modulating excitatory and inhibitory synaptic input to spinal substantia gelatinosa (SG) neurons over time in mice following chronic constriction injury (CCI) of the sciatic nerve. Whole cell patch-clamp studies from SG neurons showed that TNF-α enhanced overall excitability of the spinal cord early in time following nerve injury 3 days after CCI compared with that in sham control mice. In contrast, the effects of TNF were blunted 14 days after CCI in nerve-injured mice compared with sham surgery mice. Immunohistochemical staining showed that the expression of TNF-α receptor 1 (TNFR1) was increased at 3 days but decreased at 14 days following CCI in the ipsilateral vs. the contralateral spinal cord dorsal horn. These results suggest that TNF-α acting at TNFR1 is important in the development of neuropathic pain by facilitating excitatory synaptic signaling in the acute phases after nerve injury but has a reduced effect on spinal neuron signaling in the later phases of nerve injury-induced pain. Failure of the facilatory effects of TNF-α on excitatory synaptic signaling in the dorsal horn to resolve following nerve injury may be an important component in the transition between acute and chronic pain conditions.

  20. Effects of prostaglandin E2 on synaptic transmission in the rat spinal trigeminal subnucleus caudalis.

    Science.gov (United States)

    Mizutani, Yuka; Ohi, Yoshiaki; Kimura, Satoko; Miyazawa, Ken; Goto, Shigemi; Haji, Akira

    2015-11-02

    The spinal trigeminal subnucleus caudalis (Vc) receives preferentially nociceptive afferent signals from the orofacial area. Nociceptive stimuli to the orofacial area induce cyclooxygenase both peripherally and centrally, which can synthesize a major prostanoid prostaglandin E2 (PGE2) that implicates in diverse physiological functions. To clarify the roles of centrally-synthesized PGE2 in nociception, effects of exogenous PGE2 on synaptic transmission in the Vc neurons were investigated in the rat brainstem slice. Spontaneously occurring excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) were recorded, respectively, under pharmacological blockade of inhibitory and excitatory transmission by whole-cell patch-clamp mode. Perfusion of PGE2 (1-5 μM) increased the frequency of sIPSCs in a concentration-dependent manner but had no significant effect on the amplitude. Similarly to the effects on sIPSCs, PGE2 increased the sEPSC frequency without any effect on the amplitude. These facilitatory effects of PGE2 on spontaneous synaptic transmissions were blocked by an EP1 antagonist SC19220 but not by an EP4 antagonist AH23848. Electrical stimulation of the trigeminal tract evoked short latency EPSCs (eEPSCs) in the Vc neurons. PGE2 (5 μM) was ineffective on the eEPSCs. The present study demonstrated that PGE2 facilitated spontaneous synaptic transmissions in the Vc neurons through activating the presynaptic EP1 receptors but had no effect on the trigeminal tract-mediated excitatory transmission. These results suggest that centrally-synthesized PGE2 modifies the synaptic transmission in the Vc region, thereby contributing to the processing of nociceptive signals originated from the orofacial area. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Neuron-astrocyte interaction enhance GABAergic synaptic transmission in a manner dependent on key metabolic enzymes.

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    Przemysław eKaczor

    2015-04-01

    Full Text Available GABA is the major inhibitory neurotransmitter in the adult brain and mechanisms of GABAergic inhibition have been intensely investigated in the past decades. Recent studies provided evidence for an important role of astrocytes in shaping GABAergic currents. One of the most obvious, but yet poorly understood, mechanisms of the cross-talk between GABAergic currents and astrocytes is metabolism including neurotransmitter homeostasis. In particular, how modulation of GABAergic currents by astrocytes depends on key enzymes involved in cellular metabolism remains largely unknown. To address this issue, we have considered two simple models of neuronal cultures: nominally astrocyte-free neuronal culture (NC and neuronal-astrocytic co-cultures (ANCC and miniature Inhibitory Postsynaptic Currents (mIPSCs were recorded in control conditions and in the presence of respective enzyme blockers. We report that enrichment of neuronal culture with astrocytes results in a marked increase in mIPSC frequency. This enhancement of GABAergic activity was accompanied by increased number of GAD65 and vGAT puncta, indicating that at least a part of the frequency enhancement was due to increased number of synaptic contacts. Inhibition of glutamine synthetase (with MSO strongly reduced mIPSC frequency in ANCC but had no effect in NC. Moreover, treatment of ANCC with inhibitor of glycogen phosphorylase (BAYU6751 or with selective inhibitor of astrocytic Krebs cycle,fluoroacetate, resulted in a marked reduction of mIPSC frequency in ANCC having no effect in NC. We conclude that GABAergic synaptic transmission strongly depends on neuron-astrocyte interaction in a manner dependent on key metabolic enzymes as well as on the Krebs cycle.

  2. Dynamic inhibition of excitatory synaptic transmission by astrocyte-derived ATP in hippocampal cultures

    Science.gov (United States)

    Koizumi, Schuichi; Fujishita, Kayoko; Tsuda, Makoto; Shigemoto-Mogami, Yukari; Inoue, Kazuhide

    2003-09-01

    Originally ascribed passive roles in the CNS, astrocytes are now known to have an active role in the regulation of synaptic transmission. Neuronal activity can evoke Ca2+ transients in astrocytes, and Ca2+ transients in astrocytes can evoke changes in neuronal activity. The excitatory neurotransmitter glutamate has been shown to mediate such bidirectional communication between astrocytes and neurons. We demonstrate here that ATP, a primary mediator of intercellular Ca2+ signaling among astrocytes, also mediates intercellular signaling between astrocytes and neurons in hippocampal cultures. Mechanical stimulation of astrocytes evoked Ca2+ waves mediated by the release of ATP and the activation of P2 receptors. Mechanically evoked Ca2+ waves led to decreased excitatory glutamatergic synaptic transmission in an ATP-dependent manner. Exogenous application of ATP does not affect postsynaptic glutamatergic responses but decreased presynaptic exocytotic events. Finally, we show that astrocytes exhibit spontaneous Ca2+ waves mediated by extracellular ATP and that inhibition of these Ca2+ responses enhanced excitatory glutamatergic transmission. We therefore conclude that ATP released from astrocytes exerts tonic and activity-dependent down-regulation of synaptic transmission via presynaptic mechanisms.

  3. The Krebs Cycle Enzyme Isocitrate Dehydrogenase 3A Couples Mitochondrial Metabolism to Synaptic Transmission.

    Science.gov (United States)

    Ugur, Berrak; Bao, Huan; Stawarski, Michal; Duraine, Lita R; Zuo, Zhongyuan; Lin, Yong Qi; Neely, G Gregory; Macleod, Gregory T; Chapman, Edwin R; Bellen, Hugo J

    2017-12-26

    Neurotransmission is a tightly regulated Ca 2+ -dependent process. Upon Ca 2+ influx, Synaptotagmin1 (Syt1) promotes fusion of synaptic vesicles (SVs) with the plasma membrane. This requires regulation at multiple levels, but the role of metabolites in SV release is unclear. Here, we uncover a role for isocitrate dehydrogenase 3a (idh3a), a Krebs cycle enzyme, in neurotransmission. Loss of idh3a leads to a reduction of the metabolite, alpha-ketoglutarate (αKG), causing defects in synaptic transmission similar to the loss of syt1. Supplementing idh3a flies with αKG suppresses these defects through an ATP or neurotransmitter-independent mechanism. Indeed, αKG, but not glutamate, enhances Syt1-dependent fusion in a reconstitution assay. αKG promotes interaction between the C2-domains of Syt1 and phospholipids. The data reveal conserved metabolic regulation of synaptic transmission via αKG. Our studies provide a synaptic role for αKG, a metabolite that has been proposed as a treatment for aging and neurodegenerative disorders. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Astrocytes contribute to the effects of etomidate on synaptic transmission in rat primary somatosensory cortex.

    Science.gov (United States)

    Yang, Hao; Wang, Yuan; Zhang, Yu; Zhang, You; Xu, Mao-Sheng; Yuan, Jie; Yu, Tian

    2016-07-01

    Little is known about the mechanisms of unconsciousness induced by general anesthetics. Previous studies have shown that the primary somatosensory cortex (S1) is a sensitive region to a variety of intravenous general anesthetics. Etomidate is a widely used intravenous anesthetic that can influence synaptic transmission. Recently, there are some evidences suggesting that astrocytes, a type of glia cell, also contribute to information transmission in the brain, and modulate synaptic function by releasing neuroactive substances. However, it is unknown whether astrocytes influence the effects of etomidate on information transmission in S1 pyramidal neurons. In the present study, the role of astrocytes in etomidate-induced unconsciousness was investigated by using the whole-cell patch clamp technique. We observed etomidate at clinically relevant concentrations inhibited the spontaneous postsynaptic currents (sPSCs) of rat S1 pyramidal neurons in a concentration-dependent manner, and the EC50 value of etomidate for inhibiting sPSCs from the concentration-effect curve was 6.9μM. Furthermore, in the presence of fluorocitrate, a glia-selective metabolism inhibitor that blocks the aconitase enzyme, both the amplitude and frequency of sPSCs in rat S1 pyramidal neurons were reduced, and the inhibitory effects of etomidate on sPSCs amplitude was strengthened without affecting the effects of etomidate on frequency. From these data, we deduce that etomidate suppresses synaptic activity via presynaptic and postsynaptic components. Furthermore, astrocytes participate in synaptic transmission and influence the effects of etomidate on postsynaptic receptors. This study provides new insight into the role of astrocytes in etomidate-induced unconsciousness. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain

    Directory of Open Access Journals (Sweden)

    Christian Bonansco

    2016-01-01

    Full Text Available Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks.

  6. Effects of Modafinil on Behavioral Learning and Hippocampal Synaptic Transmission in Rats.

    Science.gov (United States)

    Yan, Wen-Wen; Yao, Li-Hua; Chen, Chong; Wang, Hai-Xia; Li, Chu-Hua; Huang, Jun-Ni; Xiao, Peng; Liu, Cheng-Yi

    2015-12-01

    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. 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. 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. 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.

  7. Attenuation of inhibitory synaptic transmission by glial dysfunction in rat thalamus.

    Science.gov (United States)

    Yang, Sunggu; Cox, Charles L

    2011-12-01

    The thalamus serves as the obligatory gateway to the neocortex for sensory processing, and also serves as a pathway for corticocortical communication. In addition, the reciprocal synaptic connectivity between the thalamic reticular nucleus (TRN) and adjacent thalamic relay nuclei generates rhythmic activities similar to that observed during different arousal states and certain neurological conditions such as absence epilepsy. Epileptiform activity can arise from a variety of neural mechanisms, but in addition glia are thought to have an important role in such activities as well. Glia serve a central role in glutamine synthesis, a precursor for glutamate or GABA in nerve terminals. While alterations in glutamine shuttling from glia to neurons can influence GABA and glutamate neurotransmission; the consequences of such action on synaptic transmission and subsequent network activities within thalamic circuits is less understood. We investigated the consequences of altering glutamine transport on inhibitory transmission and intrathalamic activities using the in vitro thalamic slice preparation. Disruption of the glutamine shuttling by the neuronal glutamine transporter (system A transporter) antagonist, α-(methylamino)isobutyric acid (MeAIB), or the selective gliotoxic drug, fluorocitric acid (Fc) dramatically decreased intrathalamic rhythmic activities. At the single cell level, MeAIB and Fc significantly attenuated electrically evoked inhibitory postsynaptic currents (eIPSCs) in thalamic relay neurons; however, miniature IPSCs were unaffected. These data indicate that glutamate-glutamine shuttle is critical for sustaining thalamic synaptic transmission, and thereby alterations in this shuttle can influence intrathalamic rhythmic activities associated with absence epilepsy. Copyright © 2011 Wiley-Liss, Inc.

  8. Adult Onset-hypothyroidism has Minimal Effects on Synaptic Transmission in the Hippocampus of Rats Independent of Hypothermia

    Science.gov (United States)

    Introduction: Thyroid hormones (TH) influence central nervous system (CNS) function during development and in adulthood. The hippocampus, a brain area critical for learning and memory is sensitive to TH insufficiency. Synaptic transmission in the hippocampus is impaired following...

  9. Effects of chronic stress in adolescence on learned fear, anxiety, and synaptic transmission in the rat prelimbic cortex.

    Science.gov (United States)

    Negrón-Oyarzo, Ignacio; Pérez, Miguel Ángel; Terreros, Gonzalo; Muñoz, Pablo; Dagnino-Subiabre, Alexies

    2014-02-01

    The prelimbic cortex and amygdala regulate the extinction of conditioned fear and anxiety, respectively. In adult rats, chronic stress affects the dendritic morphology of these brain areas, slowing extinction of learned fear and enhancing anxiety. The aim of this study was to determine whether rats subjected to chronic stress in adolescence show changes in learned fear, anxiety, and synaptic transmission in the prelimbic cortex during adulthood. Male Sprague Dawley rats were subjected to seven days of restraint stress on postnatal day forty-two (PND 42, adolescence). Afterward, the fear-conditioning paradigm was used to study conditioned fear extinction. Anxiety-like behavior was measured one day (PND 50) and twenty-one days (PND 70, adulthood) after stress using the elevated-plus maze and dark-light box tests, respectively. With another set of rats, excitatory synaptic transmission was analyzed with slices of the prelimbic cortex. Rats that had been stressed during adolescence and adulthood had higher anxiety-like behavior levels than did controls, while stress-induced slowing of learned fear extinction in adolescence was reversed during adulthood. As well, the field excitatory postsynaptic potentials of stressed adolescent rats had significantly lower amplitudes than those of controls, although the amplitudes were higher in adulthood. Our results demonstrate that short-term stress in adolescence induces strong effects on excitatory synaptic transmission in the prelimbic cortex and extinction of learned fear, where the effect of stress on anxiety is more persistent than on the extinction of learned fear. These data contribute to the understanding of stress neurobiology. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. 3D estimation of synaptic vesicle distributions in serial section transmission electron microscopy

    DEFF Research Database (Denmark)

    Khanmohammadi, Mahdieh; Darkner, Sune; Nava, Nicoletta

    directly. It is hypothesized that in a rat model of behavioral stress the vesicles distribution varies. We propose methods for estimating the 3-dimensional distribution of synaptic vesicles from the active zone through serial section transmission electron microscope images (ssTEM) from Sprague-Dawley rat...... brains. We demonstrate that ssTEM images have an additive bias field, which is well modelled by a quadratic polynomial. ssTEM images make a 3D study on very high-resolution images possible. However, due to the physical cutting of a section from a 3D embedded tissue, the relations between sections...... difference in the results with p-values less than 10^(-10) in both cases. We conclude that the two proposed modeling significantly improves the measures on the estimated synaptic vesicle distribution in relation to the active zone....

  11. Novel nootropic dipeptide Noopept increases inhibitory synaptic transmission in CA1 pyramidal cells.

    Science.gov (United States)

    Kondratenko, Rodion V; Derevyagin, Vladimir I; Skrebitsky, Vladimir G

    2010-05-31

    Effects of newly synthesized nootropic and anxiolytic dipeptide Noopept 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) significantly increased the frequency of spike-dependant spontaneous IPSCs whereas spike-independent mIPSCs remained unchanged. It was suggested that Noopept mediates its effect due to the activation of inhibitory interneurons terminating on CA1 pyramidal cells. Results of current clamp recording of inhibitory interneurons residing in stratum radiatum confirmed this suggestion. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  12. Plasticity of GABA transporters: an unconventional route to shape inhibitory synaptic transmission

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    Annalisa eScimemi

    2014-05-01

    Full Text Available The brain relies on GABAergic neurons to control the ongoing activity of neuronal networks. GABAergic neurons control the firing pattern of excitatory cells, the temporal structure of membrane potential oscillations and the time window for integration of synaptic inputs. These actions require a fine control of the timing of GABA receptor activation which, in turn, depends on the precise timing of GABA release from pre-synaptic terminals and GABA clearance from the extracellular space. Extracellular GABA is not subject to enzymatic breakdown, and its clearance relies entirely on diffusion and uptake by specific transporters. In contrast to glutamate transporters, GABA transporters are abundantly expressed in neuronal pre-synaptic terminals. GABA transporters move laterally within the plasma membrane and are continuously trafficked to/from intracellular compartments. It is hypothesized that due to their proximity to GABA release sites, changes in the concentration and lateral mobility of GABA transporters may have a significant effect on the time course of the GABA concentration profile in and out of the synaptic cleft. To date, this hypothesis remains to be tested. Here we use 3D Monte Carlo reaction-diffusion simulations to analyze how changes in the density of expression and lateral mobility of GABA transporters in the cell membrane affect the extracellular GABA concentration profile and the activation of GABA receptors. Our results indicate that these manipulations mainly alter the GABA concentration profile away from the synaptic cleft. These findings provide novel insights into how the ability of GABA transporters to undergo plastic changes may alter the strength of GABAergic signals and the activity of neuronal networks in the brain.

  13. Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission.

    Science.gov (United States)

    Wang, Haibin; Kohno, Tatsuro; Amaya, Fumimasa; Brenner, Gary J; Ito, Nobuko; Allchorne, Andrew; Ji, Ru-Rong; Woolf, Clifford J

    2005-08-31

    Bradykinin, an inflammatory mediator, sensitizes nociceptor peripheral terminals reducing pain threshold. We now show that the B2 kinin receptor is expressed in rat dorsal horn neurons and that bradykinin, a B2-specific agonist, augments AMPA- and NMDA-induced, and primary afferent-evoked EPSCs, and increases the frequency and amplitude of miniature EPSCs in superficial dorsal horn neurons in vitro. Administration of bradykinin to the spinal cord in vivo produces, moreover, an NMDA-dependent hyperalgesia. We also demonstrate that nociceptive inputs result in the production of bradykinin in the spinal cord and that an intrathecal B2-selective antagonist suppresses behavioral manifestations of central sensitization, an activity-dependent increase in glutamatergic synaptic efficacy. Primary afferent-evoked central sensitization is, in addition, reduced in B2 receptor knock-out mice. We conclude that bradykinin is released in the spinal cord in response to nociceptor inputs and acts as a synaptic neuromodulator, potentiating glutamatergic synaptic transmission to produce pain hypersensitivity.

  14. Tuning synaptic transmission in the hippocampus by stress: The CRH system

    Directory of Open Access Journals (Sweden)

    Yuncai eChen

    2012-04-01

    Full Text Available To enhance survival, an organism needs to remember--and learn from--threatening or stressful events. This fact necessitates the presence of mechanisms by which stress can influence synaptic transmission in brain regions, such as hippocampus, that subserve learning and memory. A major focus of this series of monographs is on the role and actions of adrenal-derived hormones, corticosteroids, and of brain-derived neurotransmitters, on synaptic function in the stressed hippocampus. Here we focus on the contribution of hippocampus-intrinsic, stress-activated CRH-CRH receptor signaling to the function and structure of hippocampal synapses. CRH is expressed in interneurons of adult hippocampus, and is released from axon terminals during stress. The peptide exerts time- and dose-dependent effects on learning and memory via modulation of synaptic function and plasticity. Whereas physiological levels of CRH, acting over seconds to minutes, augment memory processes, exposure to presumed severe-stress levels of the peptide results in spine retraction and loss of synapses over more protracted time-frames. Loss of dendritic spines (and hence of synapses takes place through actin cytoskeleton collapse downstream of CRHR1 receptors that reside within excitatory synapses on spine heads. Chronic exposure to stress levels of CRH may promote dying-back (atrophy of spine-carrying dendrites. Thus, the acute effects of CRH may contribute to stress-induced adaptive mechanisms, whereas chronic or excessive exposure to the peptide may promote learning problems and premature cognitive decline.

  15. SAD-B Phosphorylation of CAST Controls Active Zone Vesicle Recycling for Synaptic Depression

    Directory of Open Access Journals (Sweden)

    Sumiko Mochida

    2016-09-01

    Full Text Available 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.

  16. A novel component of cannabis extract potentiates excitatory synaptic transmission in rat olfactory cortex in vitro.

    Science.gov (United States)

    Whalley, Benjamin J; Wilkinson, Jonathan D; Williamson, Elizabeth M; Constanti, Andrew

    2004-07-15

    Cannabis is a potential treatment for epilepsy, although the few human studies supporting this use have proved inconclusive. Previously, we showed that a standardized cannabis extract (SCE), isolated Delta9-tetrahydrocannabinol (Delta9-THC), and even Delta9-THC-free SCE inhibited muscarinic agonist-induced epileptiform bursting in rat olfactory cortical brain slices, acting via CB1 receptors. The present work demonstrates that although Delta9-THC (1 microM) significantly depressed evoked depolarizing postsynaptic potentials (PSPs) in rat olfactory cortex neurones, both SCE and Delta9-THC-free SCE significantly potentiated evoked PSPs (all results were fully reversed by the CB1 receptor antagonist SR141716A, 1 microM); interestingly, the potentiation by Delta9-THC-free SCE was greater than that produced by SCE. On comparing the effects of Delta9-THC-free SCE upon evoked PSPs and artificial PSPs (aPSPs; evoked electrotonically following brief intracellular current injection), PSPs were enhanced, whereas aPSPs were unaffected, suggesting that the effect was not due to changes in background input resistance. Similar recordings made using CB1 receptor-deficient knockout mice (CB1-/-) and wild-type littermate controls revealed cannabinoid or extract-induced changes in membrane resistance, cell excitability and synaptic transmission in wild-type mice that were similar to those seen in rat neurones, but no effect on these properties were seen in CB1-/- cells. It appears that the unknown extract constituent(s) effects over-rode the suppressive effects of Delta9-THC on excitatory neurotransmitter release, which may explain some patients' preference for herbal cannabis rather than isolated Delta9-THC (due to attenuation of some of the central Delta9-THC side effects) and possibly account for the rare incidence of seizures in some individuals taking cannabis recreationally.

  17. Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons

    Science.gov (United States)

    Cristino, Luigia; Busetto, Giuseppe; Imperatore, Roberta; Ferrandino, Ida; Palomba, Letizia; Silvestri, Cristoforo; Petrosino, Stefania; Orlando, Pierangelo; Bentivoglio, Marina; Mackie, Kenneth; Di Marzo, Vincenzo

    2013-01-01

    Acute or chronic alterations in energy status alter the balance between excitatory and inhibitory synaptic transmission and associated synaptic plasticity to allow for the adaptation of energy metabolism to new homeostatic requirements. The impact of such changes on endocannabinoid and cannabinoid receptor type 1 (CB1)-mediated modulation of synaptic transmission and strength is not known, despite the fact that this signaling system is an important target for the development of new drugs against obesity. We investigated whether CB1-expressing excitatory vs. inhibitory inputs to orexin-A–containing neurons in the lateral hypothalamus are altered in obesity and how this modifies endocannabinoid control of these neurons. In lean mice, these inputs are mostly excitatory. By confocal and ultrastructural microscopic analyses, we observed that in leptin-knockout (ob/ob) obese mice, and in mice with diet-induced obesity, orexinergic neurons receive predominantly inhibitory CB1-expressing inputs and overexpress the biosynthetic enzyme for the endocannabinoid 2-arachidonoylglycerol, which retrogradely inhibits synaptic transmission at CB1-expressing axon terminals. Patch-clamp recordings also showed increased CB1-sensitive inhibitory innervation of orexinergic neurons in ob/ob mice. These alterations are reversed by leptin administration, partly through activation of the mammalian target of rapamycin pathway in neuropeptide-Y-ergic neurons of the arcuate nucleus, and are accompanied by CB1-mediated enhancement of orexinergic innervation of target brain areas. We propose that enhanced inhibitory control of orexin-A neurons, and their CB1-mediated disinhibition, are a consequence of leptin signaling impairment in the arcuate nucleus. We also provide initial evidence of the participation of this phenomenon in hyperphagia and hormonal dysregulation in obesity. PMID:23630288

  18. STDP with adaptive synaptic delay for robot navigation control

    Science.gov (United States)

    Arena, Paolo; Patané, Luca; Distefano, Francesco; Bucolo, Sebastiano; Aiello, Orazio

    2007-05-01

    In this work a biologically inspired network of spiking neurons is used for robot navigation control. The two tasks taken into account are obstacle avoidance and landmark-based navigation. The system learns the correlation among unconditioned stimuli (pre-wired sensors) and conditioned stimuli (high level sensors) through Spike Timing Dependent Plasticity (STDP). In order to improve the robot behaviours not only the synaptic weight but also the synaptic delay is subject to learning. Modulating the synaptic delay the robot is able to store the landmark position, like in a short time memory, and to use this information to smooth the turning actions prolonging the landmark effects also when it is no more visible. Simulations are carried out in a dynamic simulation environment and the robotic system considered is a cockroach-inspired hexapod robot. The locomotion signals are generated by a Central Pattern Generator and the spiking network is devoted to control the heading of the robot acting on the amplitude of the leg steps. Several scenarios have been proposed, for instance a T-shaped labyrinth, used in laboratory experiments with mice to demonstrate classical and operant conditioning, has been considered. Finally the proposed adaptive navigation control structure can be extended in a modular way to include other features detected by new sensors included in the correlation-based learning process.

  19. A Computational Model to Investigate Astrocytic Glutamate Uptake Influence on Synaptic Transmission and Neuronal Spiking

    Directory of Open Access Journals (Sweden)

    Sushmita Lakshmi Allam

    2012-10-01

    Full Text Available Over the past decades, our view of astrocytes has switched from passive support cells to active processing elements in the brain. The current view is that astrocytes shape neuronal communication and also play an important role in many neurodegenerative diseases. Despite the growing awareness of the importance of astrocytes, the exact mechanisms underlying neuron-astrocyte communication and the physiological consequences of astrocytic-neuronal interactions remain largely unclear. In this work, we define a modeling framework that will permit to address unanswered questions regarding the role of astrocytes. Our computational model of a detailed glutamatergic synapse facilitates the analysis of neural system responses to various stimuli and conditions that are otherwise difficult to obtain experimentally, in particular the readouts at the sub-cellular level. In this paper, we extend a detailed glutamatergic synaptic model, to include astrocytic glutamate transporters. We demonstrate how these glial transporters, responsible for the majority of glutamate uptake, modulate synaptic transmission mediated by ionotropic AMPA and NMDA receptors at glutamatergic synapses. Furthermore, we investigate how these local signaling effects at the synaptic level are translated into varying spatio-temporal patterns of neuron firing. Paired pulse stimulation results reveal that the effect of astrocytic glutamate uptake is more apparent when the input inter-spike interval is sufficiently long to allow the receptors to recover from desensitization. These results suggest an important functional role of astrocytes in spike timing dependent processes and demand further investigation of the molecular basis of certain neurological diseases specifically related to alterations in astrocytic glutamate uptake, such as epilepsy.

  20. Synaptic Transmission Optimization Predicts Expression Loci of Long-Term Plasticity.

    Science.gov (United States)

    Costa, Rui Ponte; Padamsey, Zahid; D'Amour, James A; Emptage, Nigel J; Froemke, Robert C; Vogels, Tim P

    2017-09-27

    Long-term modifications of neuronal connections are critical for reliable memory storage in the brain. However, their locus of expression-pre- or postsynaptic-is highly variable. Here we introduce a theoretical framework in which long-term plasticity performs an optimization of the postsynaptic response statistics toward a given mean with minimal variance. Consequently, the state of the synapse at the time of plasticity induction determines the ratio of pre- and postsynaptic modifications. Our theory explains the experimentally observed expression loci of the hippocampal and neocortical synaptic potentiation studies we examined. Moreover, the theory predicts presynaptic expression of long-term depression, consistent with experimental observations. At inhibitory synapses, the theory suggests a statistically efficient excitatory-inhibitory balance in which changes in inhibitory postsynaptic response statistics specifically target the mean excitation. Our results provide a unifying theory for understanding the expression mechanisms and functions of long-term synaptic transmission plasticity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Synaptic Cell Adhesion

    OpenAIRE

    Missler, Markus; Südhof, Thomas C.; Biederer, Thomas

    2012-01-01

    Chemical synapses are asymmetric intercellular junctions that mediate synaptic transmission. Synaptic junctions are organized by trans-synaptic cell adhesion molecules bridging the synaptic cleft. Synaptic cell adhesion molecules not only connect pre- and postsynaptic compartments, but also mediate trans-synaptic recognition and signaling processes that are essential for the establishment, specification, and plasticity of synapses. A growing number of synaptic cell adhesion molecules that inc...

  2. Effects of M1 and M4 activation on excitatory synaptic transmission in CA1.

    Science.gov (United States)

    Thorn, Catherine A; Popiolek, Michael; Stark, Eda; Edgerton, Jeremy R

    2017-07-01

    Hippocampal networks are particularly susceptible to dysfunction in many neurodegenerative diseases and neuropsychiatric disorders including Alzheimer's disease, Lewy body dementia, and schizophrenia. CA1, a major output region of the hippocampus, receives glutamatergic input from both hippocampal CA3 and entorhinal cortex, via the Schaffer collateral (SC) and temporoammonic (TA) pathways, respectively. SC and TA inputs to CA1 are thought to be differentially involved in the retrieval of previously stored memories versus the encoding of novel information, and switching between these two crucial hippocampal functions is thought to critically depend on acetylcholine (ACh) acting at muscarinic receptors. In this study, we aimed to determine the roles of specific subtypes of muscarinic receptors in mediating the neuromodulatory effects of ACh on glutamatergic synaptic transmission in the SC and TA pathways of CA1. Using selective pharmacological activation of M1 or M4 receptors along with extracellular and intracellular electrophysiology recordings from adult rat hippocampal slices, we demonstrate that activation of M1 receptors increases spontaneous spike rates of neuronal ensembles in CA1 and increases the intrinsic excitability of pyramidal neurons and interneurons. Selective activation of M4 receptors inhibits glutamate release in the SC pathway, while leaving synaptic transmission in the TA pathway comparatively intact. These results suggest specific mechanisms by which M1 and M4 activation may normalize CA1 circuit activity following disruptions of signaling that accompany neurodegenerative dementias or neuropsychiatric disorders. These findings are of particular interest in light of clinical findings that xanomeline, an M1/M4 preferring agonist, was able to improve cognitive and behavioral symptoms in patients with Alzheimer's disease or schizophrenia. © 2017 The Authors Hippocampus Published by Wiley Periodicals, Inc.

  3. Histamine H3 Heteroreceptors Suppress Glutamatergic and GABAergic Synaptic Transmission in the Rat Insular Cortex

    Directory of Open Access Journals (Sweden)

    Hiroki Takei

    2017-11-01

    Full Text Available Histamine H3 receptors are autoreceptors that regulate histamine release from histaminergic neuronal terminals. The cerebral cortex, including the insular cortex (IC, expresses abundant H3 receptors; however, the functions and mechanisms of H3 receptors remain unknown. The aim of this study was to elucidate the functional roles of H3 in synaptic transmission in layer V of the rat IC. Unitary excitatory and inhibitory postsynaptic currents (uEPSCs and uIPSCs were obtained through paired whole-cell patch-clamp recording in cerebrocortical slice preparations. The H3 receptor agonist, R-α-methylhistamine (RAMH, reduced the uEPSC amplitude obtained from pyramidal cell to pyramidal cell or GABAergic interneuron connections. Similarly, RAMH reduced the uIPSC amplitude in GABAergic interneuron to pyramidal cell connections. RAMH-induced decreases in both the uEPSC and uIPSC amplitudes were accompanied by increases in the failure rate and paired-pulse ratio. JNJ 5207852 dihydrochloride or thioperamide, H3 receptor antagonists, inhibited RAMH-induced suppression of uEPSCs and uIPSCs. Unexpectedly, thioperamide alone increased the uIPSC amplitude, suggesting that thioperamide was likely to act as an inverse agonist. Miniature EPSC or IPSC recordings support the hypothesis that the activation of H3 receptors suppresses the release of glutamate and GABA from presynaptic terminals. The colocalization of H3 receptors and glutamate decarboxylase or vesicular glutamate transport protein 1 in presynaptic axon terminals was confirmed through double pre-embedding microscopy, using a combination of pre-embedding immunogold and immunoperoxidase techniques. The suppressive regulation of H3 heteroreceptors on synaptic transmission might mediate the regulation of sensory information processes, such as gustation and visceral sensation, in the IC.

  4. New tools for targeted disruption of cholinergic synaptic transmission in Drosophila melanogaster.

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    Monica Mejia

    Full Text Available Nicotinic acetylcholine receptors (nAChRs are pentameric ligand-gated ion channels. The α7 subtype of nAChRs is involved in neurological pathologies such as Parkinson's disease, Alzheimer's disease, addiction, epilepsy and autism spectrum disorders. The Drosophila melanogaster α7 (Dα7 has the closest sequence homology to the vertebrate α7 subunit and it can form homopentameric receptors just as the vertebrate counterpart. The Dα7 subunits are essential for the function of the Giant Fiber circuit, which mediates the escape response of the fly. To further characterize the receptor function, we generated different missense mutations in the Dα7 nAChR's ligand binding domain. We characterized the effects of targeted expression of two UAS-constructs carrying a single mutation, D197A and Y195T, as well as a UAS-construct carrying a triple D77T, L117Q, I196P mutation in a Dα7 null mutant and in a wild type background. Expression of the triple mutation was able to restore the function of the circuit in Dα7 null mutants and had no disruptive effects when expressed in wild type. In contrast, both single mutations severely disrupted the synaptic transmission of Dα7-dependent but not glutamatergic or gap junction dependent synapses in wild type background, and did not or only partially rescued the synaptic defects of the null mutant. These observations are consistent with the formation of hybrid receptors, consisting of D197A or Y195T subunits and wild type Dα7 subunits, in which the binding of acetylcholine or acetylcholine-induced conformational changes of the Dα7 receptor are altered and causes inhibition of cholinergic responses. Thus targeted expression of D197A or Y195T can be used to selectively disrupt synaptic transmission of Dα7-dependent synapses in neuronal circuits. Hence, these constructs can be used as tools to study learning and memory or addiction associated behaviors by allowing the manipulation of neuronal processing in the

  5. Inhibition of excitatory synaptic transmission in the trigeminal motor nucleus by the nitric oxide-cyclic GMP signaling pathway.

    Science.gov (United States)

    Pose, Inés; Silveira, Valentina; Morales, Francisco R

    2011-06-01

    Nitric oxide (NO) and cyclic GMP (cGMP) suppressed glutamatergic synaptic transmission to trigeminal motoneurons in brain stem slices of neonatal rats. Histological studies showed guanylate cyclase (GC) containing fibers in the trigeminal motor pool. Glutamatergic excitatory postsynaptic currents (EPSCs) were recorded from neonatal trigeminal motoneurons in response to stimulation of the supratrigeminal nucleus (SuV). The NO donors DETA/NONOate (DETA/NO), at a concentration which released 275.1 nM of NO, and Spermine/NONOate (Sper/NO) reduced the amplitude of the EPSC to 52.7±0.6% and 60.1±10.8% of control values, respectively. These actions were not blocked by the GC inhibitors, ODQ or NS-2028. However, in the presence of YC-1 or BAY41-2272, modulators of GC that act as NO sensitizers, lower and otherwise ineffective concentrations of DETA/NO induced a reduction of the EPSC to 60.6±5.2%. Moreover, NO effects were mimicked by 8BrcGMP and by Zaprinast, an inhibitor of Phosphodiesterase 5. Glutamatergic currents evoked by exogenous glutamate were not reduced by DETA/NO nor 8BrcGMP. Paired-pulse facilitation was increased by NO donors. Under "minimal stimulation" conditions NO donors and cGMP increased the failure rate of evoked EPSCs. Protein kinase inhibitors antagonized cGMP effects. The results suggest that NO, through the synthesis of cGMP, presynaptically inhibits glutamatergic synaptic transmission on trigeminal motoneurons. We propose that NO has complex actions on motor pools; specific studies are needed to elucidate their physiological significance in the behaving animal. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Syncrip/hnRNP Q influences synaptic transmission and regulates BMP signaling at the Drosophila neuromuscular synapse

    Directory of Open Access Journals (Sweden)

    James M. Halstead

    2014-08-01

    Full Text Available Synaptic plasticity involves the modulation of synaptic connections in response to neuronal activity via multiple pathways. One mechanism modulates synaptic transmission by retrograde signals from the post-synapse that influence the probability of vesicle release in the pre-synapse. Despite its importance, very few factors required for the expression of retrograde signals, and proper synaptic transmission, have been identified. Here, we identify the conserved RNA binding protein Syncrip as a new factor that modulates the efficiency of vesicle release from the motoneuron and is required for correct synapse structure. We show that syncrip is required genetically and its protein product is detected only in the muscle and not in the motoneuron itself. This unexpected non-autonomy is at least partly explained by the fact that Syncrip modulates retrograde BMP signals from the muscle back to the motoneuron. We show that Syncrip influences the levels of the Bone Morphogenic Protein ligand Glass Bottom Boat from the post-synapse and regulates the pre-synapse. Our results highlight the RNA-binding protein Syncrip as a novel regulator of synaptic output. Given its known role in regulating translation, we propose that Syncrip is important for maintaining a balance between the strength of presynaptic vesicle release and postsynaptic translation.

  7. Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells.

    Science.gov (United States)

    Miyazaki, Taisuke; Yamasaki, Miwako; Hashimoto, Kouichi; Kohda, Kazuhisa; Yuzaki, Michisuke; Shimamoto, Keiko; Tanaka, Kohichi; Kano, Masanobu; Watanabe, Masahiko

    2017-07-11

    Astrocytes regulate synaptic transmission through controlling neurotransmitter concentrations around synapses. Little is known, however, about their roles in neural circuit development. Here we report that Bergmann glia (BG), specialized cerebellar astrocytes that thoroughly enwrap Purkinje cells (PCs), are essential for synaptic organization in PCs through the action of the l-glutamate/l-aspartate transporter (GLAST). In GLAST-knockout mice, dendritic innervation by the main ascending climbing fiber (CF) branch was significantly weakened, whereas the transverse branch, which is thin and nonsynaptogenic in control mice, was transformed into thick and synaptogenic branches. Both types of CF branches frequently produced aberrant wiring to proximal and distal dendrites, causing multiple CF-PC innervation. Our electrophysiological analysis revealed that slow and small CF-evoked excitatory postsynaptic currents (EPSCs) were recorded from almost all PCs in GLAST-knockout mice. These atypical CF-EPSCs were far more numerous and had significantly faster 10-90% rise time than those elicited by glutamate spillover under pharmacological blockade of glial glutamate transporters. Innervation by parallel fibers (PFs) was also affected. PF synapses were robustly increased in the entire dendritic trees, leading to impaired segregation of CF and PF territories. Furthermore, lamellate BG processes were retracted from PC dendrites and synapses, leading to the exposure of these neuronal elements to the extracellular milieus. These synaptic and glial phenotypes were reproduced in wild-type mice after functional blockade of glial glutamate transporters. These findings highlight that glutamate transporter function by GLAST on BG plays important roles in development and maintenance of proper synaptic wiring and wrapping in PCs.

  8. Proteasomal degradation of the metabotropic glutamate receptor 1α is mediated by Homer-3 via the proteasomal S8 ATPase: Signal transduction and synaptic transmission.

    Science.gov (United States)

    Rezvani, Khosrow; Baalman, Kelli; Teng, Yanfen; Mee, Maureen P; Dawson, Simon P; Wang, Hongmin; De Biasi, Mariella; Mayer, R John

    2012-07-01

    The metabotropic glutamate receptors (mGluRs) fine-tune the efficacy of synaptic transmission. This unique feature makes mGluRs potential targets for the treatment of various CNS disorders. There is ample evidence to show that the ubiquitin proteasome system mediates changes in synaptic strength leading to multiple forms of synaptic plasticity. The present study describes a novel interaction between post-synaptic adaptors, long Homer-3 proteins, and one of the 26S proteasome regulatory subunits, the S8 ATPase, that influences the degradation of the metabotropic glutamate receptor 1α (mGluR1α). We have shown that the two human long Homer-3 proteins specifically interact with human proteasomal S8 ATPase. We identified that mGluR1α and long Homer-3s immunoprecipitate with the 26S proteasome both in vitro and in vivo. We further found that the mGluR1α receptor can be ubiquitinated and degraded by the 26S proteasome and that Homer-3A facilitates this process. Furthermore, the siRNA mediated silencing of Homer-3 led to increased levels of total and plasma membrane-associated mGluR1α receptors. These results suggest that long Homer-3 proteins control the degradation of mGluR1α receptors by shuttling ubiquitinated mGluR-1α receptors to the 26S proteasome via the S8 ATPase which may modulate synaptic transmission. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  9. Novel Mutations in Synaptic Transmission Genes Suppress Neuronal Hyperexcitation in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Katherine A. McCulloch

    2017-07-01

    Full Text Available Acetylcholine (ACh receptors (AChR regulate neural circuit activity in multiple contexts. In humans, mutations in ionotropic acetylcholine receptor (iAChR genes can cause neurological disorders, including myasthenia gravis and epilepsy. In Caenorhabditis elegans, iAChRs play multiple roles in the locomotor circuit. The cholinergic motor neurons express an ACR-2-containing pentameric AChR (ACR-2R comprised of ACR-2, ACR-3, ACR-12, UNC-38, and UNC-63 subunits. A gain-of-function mutation in the non-α subunit gene acr-2 [acr-2(gf] causes defective locomotion as well as spontaneous convulsions. Previous studies of genetic suppressors of acr-2(gf have provided insights into ACR-2R composition and assembly. Here, to further understand how the ACR-2R regulates neuronal activity, we expanded the suppressor screen for acr-2(gf-induced convulsions. The majority of these suppressor mutations affect genes that play critical roles in synaptic transmission, including two novel mutations in the vesicular ACh transporter unc-17. In addition, we identified a role for a conserved major facilitator superfamily domain (MFSD protein, mfsd-6, in regulating neural circuit activity. We further defined a role for the sphingosine (SPH kinase (Sphk sphk-1 in cholinergic neuron activity, independent of previously known signaling pathways. Overall, the genes identified in our study suggest that optimal modulation of synaptic activity is balanced by the differential activities of multiple pathways, and the novel alleles provide valuable reagents to further dissect neuronal mechanisms regulating the locomotor circuit.

  10. Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Rudenko, Gabby (Texas-MED)

    2017-01-01

    Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, formingtrans-complexes spanning the synaptic cleft orcis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics.

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

    Science.gov (United States)

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

    2014-01-01

    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 [Ca2+] 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

  12. Alteration of AMPA Receptor-Mediated Synaptic Transmission by Alexa Fluor 488 and 594 in Cerebellar Stellate Cells123

    Science.gov (United States)

    2016-01-01

    Abstract The fluorescent dyes, Alexa Fluor 488 and 594 are commonly used to visualize dendritic structures and the localization of synapses, both of which are critical for the spatial and temporal integration of synaptic inputs. However, the effect of the dyes on synaptic transmission is not known. Here we investigated whether Alexa Fluor dyes alter the properties of synaptic currents mediated by two subtypes of AMPA receptors (AMPARs) at cerebellar stellate cell synapses. In naive mice, GluA2-lacking AMPAR-mediated synaptic currents displayed an inwardly rectifying current–voltage (I–V) relationship due to blockade by cytoplasmic spermine at depolarized potentials. We found that the inclusion of 100 µm Alexa Fluor dye, but not 10 µm, in the pipette solution led to a gradual increase in the amplitude of EPSCs at +40 mV and a change in the I–V relationship from inwardly rectifying to more linear. In mice exposed to an acute stress, AMPARs switched to GluA2-containing receptors, and 100 µm Alexa Fluor 594 did not alter the I–V relationship of synaptic currents. Therefore, a high concentration of Alexa Fluor dye changed the I–V relationship of EPSCs at GluA2-lacking AMPAR synapses. PMID:27280156

  13. Alteration of AMPA Receptor-Mediated Synaptic Transmission by Alexa Fluor 488 and 594 in Cerebellar Stellate Cells.

    Science.gov (United States)

    Maroteaux, Matthieu; Liu, Siqiong June

    2016-01-01

    The fluorescent dyes, Alexa Fluor 488 and 594 are commonly used to visualize dendritic structures and the localization of synapses, both of which are critical for the spatial and temporal integration of synaptic inputs. However, the effect of the dyes on synaptic transmission is not known. Here we investigated whether Alexa Fluor dyes alter the properties of synaptic currents mediated by two subtypes of AMPA receptors (AMPARs) at cerebellar stellate cell synapses. In naive mice, GluA2-lacking AMPAR-mediated synaptic currents displayed an inwardly rectifying current-voltage (I-V) relationship due to blockade by cytoplasmic spermine at depolarized potentials. We found that the inclusion of 100 µm Alexa Fluor dye, but not 10 µm, in the pipette solution led to a gradual increase in the amplitude of EPSCs at +40 mV and a change in the I-V relationship from inwardly rectifying to more linear. In mice exposed to an acute stress, AMPARs switched to GluA2-containing receptors, and 100 µm Alexa Fluor 594 did not alter the I-V relationship of synaptic currents. Therefore, a high concentration of Alexa Fluor dye changed the I-V relationship of EPSCs at GluA2-lacking AMPAR synapses.

  14. Xyloside primed glycosaminoglycans alter hair bundle micromechanical coupling and synaptic transmission: Pharmacokinetics

    Energy Technology Data Exchange (ETDEWEB)

    Holman, Holly A.; Nguyen, Lynn Y. [Bioengineering, University of Utah, Salt Lake City, Utah (United States); Tran, Vy M.; Arungundram, Sailaja; Kalita, Mausam [Medicinal Chemistry, University of Utah, Salt Lake City, Utah (United States); Kuberan, Balagurunathan [Medicinal Chemistry, University of Utah, Salt Lake City, Utah (United States); Neuroscience Program, University of Utah, Salt Lake City, Utah (United States); Rabbitt, Richard D. [Bioengineering, University of Utah, Salt Lake City, Utah (United States); Neuroscience Program, University of Utah, Salt Lake City, Utah (United States); Otolaryngology, University of Utah, Salt Lake City, Utah (United States); Marine Biological Laboratory, Woods Hole, Massachusetts (United States)

    2015-12-31

    Glycosaminoglycans (GAGs) are ubiquitous in the inner ear, and disorders altering their structure or production often result in debilitating hearing and balance deficits. The specific mechanisms responsible for loss of hair-cell function are not well understood. We recently reported that introduction of a novel BODIPY conjugated xyloside (BX) into the endolymph primes fluorescent GAGs in vivo [6, 15]. Confocal and two-photon fluorescence imaging revealed rapid turnover and assembly of a glycocalyx enveloping the kinocilia and extending into the cupula, a structure that presumably serves as a mechanical link between the hair bundle and the cupula. Extracellular fluorescence was also observed around the basolateral surface of hair cells and surrounding afferent nerve projections into the crista. Single unit afferent recordings during mechanical hair bundle stimulation revealed temporary interruption of synaptic transmission following BX administration followed by recovery, demonstrating an essential role for GAGs in function of the hair cell synapse. In the present work we present a pharmacokinetic model to quantify the time course of BX primed GAG production and turnover in the ear.

  15. Raised Intracellular Calcium Contributes to Ischemia-Induced Depression of Evoked Synaptic Transmission.

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    Shirin Jalini

    Full Text Available Oxygen-glucose deprivation (OGD leads to depression of evoked synaptic transmission, for which the mechanisms remain unclear. We hypothesized that increased presynaptic [Ca2+]i during transient OGD contributes to the depression of evoked field excitatory postsynaptic potentials (fEPSPs. Additionally, we hypothesized that increased buffering of intracellular calcium would shorten electrophysiological recovery after transient ischemia. Mouse hippocampal slices were exposed to 2 to 8 min of OGD. fEPSPs evoked by Schaffer collateral stimulation were recorded in the stratum radiatum, and whole cell current or voltage clamp recordings were performed in CA1 neurons. Transient ischemia led to increased presynaptic [Ca2+]i, (shown by calcium imaging, increased spontaneous miniature EPSP/Cs, and depressed evoked fEPSPs, partially mediated by adenosine. Buffering of intracellular Ca2+ during OGD by membrane-permeant chelators (BAPTA-AM or EGTA-AM partially prevented fEPSP depression and promoted faster electrophysiological recovery when the OGD challenge was stopped. The blocker of BK channels, charybdotoxin (ChTX, also prevented fEPSP depression, but did not accelerate post-ischemic recovery. These results suggest that OGD leads to elevated presynaptic [Ca2+]i, which reduces evoked transmitter release; this effect can be reversed by increased intracellular Ca2+ buffering which also speeds recovery.

  16. Raised Intracellular Calcium Contributes to Ischemia-Induced Depression of Evoked Synaptic Transmission.

    Science.gov (United States)

    Jalini, Shirin; Ye, Hui; Tonkikh, Alexander A; Charlton, Milton P; Carlen, Peter L

    2016-01-01

    Oxygen-glucose deprivation (OGD) leads to depression of evoked synaptic transmission, for which the mechanisms remain unclear. We hypothesized that increased presynaptic [Ca2+]i during transient OGD contributes to the depression of evoked field excitatory postsynaptic potentials (fEPSPs). Additionally, we hypothesized that increased buffering of intracellular calcium would shorten electrophysiological recovery after transient ischemia. Mouse hippocampal slices were exposed to 2 to 8 min of OGD. fEPSPs evoked by Schaffer collateral stimulation were recorded in the stratum radiatum, and whole cell current or voltage clamp recordings were performed in CA1 neurons. Transient ischemia led to increased presynaptic [Ca2+]i, (shown by calcium imaging), increased spontaneous miniature EPSP/Cs, and depressed evoked fEPSPs, partially mediated by adenosine. Buffering of intracellular Ca2+ during OGD by membrane-permeant chelators (BAPTA-AM or EGTA-AM) partially prevented fEPSP depression and promoted faster electrophysiological recovery when the OGD challenge was stopped. The blocker of BK channels, charybdotoxin (ChTX), also prevented fEPSP depression, but did not accelerate post-ischemic recovery. These results suggest that OGD leads to elevated presynaptic [Ca2+]i, which reduces evoked transmitter release; this effect can be reversed by increased intracellular Ca2+ buffering which also speeds recovery.

  17. Orexin-A modulates excitatory synaptic transmission and neuronal excitability in the spinal cord substantia gelatinosa.

    Science.gov (United States)

    Jeon, Younghoon; Park, Ki Bum; Pervin, Rokeya; Kim, Tae Wan; Youn, Dong-ho

    2015-09-14

    Although intrathecal orexin-A has been known to be antinociceptive in various pain models, the role of orexin-A in antinociception is not well characterized. In the present study, we examined whether orexin-A modulates primary afferent fiber-mediated or spontaneous excitatory synaptic transmission using transverse spinal cord slices with attached dorsal root. Bath-application of orexin-A (100nM) reduced the amplitude of excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation of Aδ- or C-primary afferent fibers. The magnitude of reduction was much larger for EPSCs evoked by polysynaptic C-fibers than polysynaptic Aδ-fibers, whereas it was similar in EPSCs evoked by monosynaptic Aδ- or C-fibers. SB674042, an orexin-1 receptor antagonist, but not EMPA, an orexin-2 receptor antagonist, significantly inhibited the orexin-A-induced reduction in EPSC amplitude from mono- or polysynaptic Aδ-fibers, as well as from mono- or polysynaptic C-fibers. Furthermore, orexin-A significantly increased the frequency of spontaneous EPSCs but not the amplitude. This increase was almost completely blocked by both SB674042 and EMPA. On the other hand, orexin-A produced membrane oscillations and inward currents in the SG neurons that were partially or completely inhibited by SB674042 or EMPA, respectively. Thus, this study suggests that the spinal actions of orexin-A underlie orexin-A-induced antinociceptive effects via different subtypes of orexin receptors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Presynaptic inhibition of synaptic transmission in the rat hippocampus by activation of muscarinic receptors: involvement of presynaptic calcium influx

    OpenAIRE

    Qian, Jing; Saggau, Peter

    1997-01-01

    Modulation of presynaptic voltage-dependent calcium channels (VDCCs) by muscarinic receptors at the CA3–CA1 synapse of rat hippocampal slices was investigated by using the calcium indicator fura-2. Stimulation-evoked presynaptic calcium transients ([Capre]t) and field excitatory postsynaptic potentials (fe.p.s.ps) were simultaneously recorded. The relationship between presynaptic calcium influx and synaptic transmission was studied.Activation of muscarinic receptors inhibited [Capre]t, thereb...

  19. The neurotoxin 1-methyl-4-phenylpyridinium (MPP+ alters hippocampal excitatory synaptic transmission by modulation of the GABAergic system

    Directory of Open Access Journals (Sweden)

    YuYing eHuang

    2015-08-01

    Full Text Available The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP induces Parkinson’s disease (PD-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. Moreover, the hippocampus contains dopaminergic fibers, which are projecting from the ventral tegmental area, substantia nigra 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 (DAT did not prevent but increased the depression of excitatory postsynaptic 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 postsynaptic 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

  20. Learning to discriminate through long-term changes of dynamical synaptic transmission.

    Science.gov (United States)

    Leibold, Christian; Bendels, Michael H K

    2009-12-01

    Short-term synaptic plasticity is modulated by long-term synaptic changes. There is, however, no general agreement on the computational role of this interaction. Here, we derive a learning rule for the release probability and the maximal synaptic conductance in a circuit model with combined recurrent and feedforward connections that allows learning to discriminate among natural inputs. Short-term synaptic plasticity thereby provides a nonlinear expansion of the input space of a linear classifier, whereas the random recurrent network serves to decorrelate the expanded input space. Computer simulations reveal that the twofold increase in the number of input dimensions through short-term synaptic plasticity improves the performance of a standard perceptron up to 100%. The distributions of release probabilities and maximal synaptic conductances at the capacity limit strongly depend on the balance between excitation and inhibition. The model also suggests a new computational interpretation of spikes evoked by stimuli outside the classical receptive field. These neuronal activities may reflect decorrelation of the expanded stimulus space by intracortical synaptic connections.

  1. Reduction of the cholesterol sensor SCAP in the brains of mice causes impaired synaptic transmission and altered cognitive function.

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    Ryo Suzuki

    Full Text Available The sterol sensor SCAP is a key regulator of SREBP-2, the major transcription factor controlling cholesterol synthesis. Recently, we showed that there is a global down-regulation of cholesterol synthetic genes, as well as SREBP-2, in the brains of diabetic mice, leading to a reduction of cholesterol synthesis. We now show that in mouse models of type 1 and type 2 diabetes, this is, in part, the result of a decrease of SCAP. Homozygous disruption of the Scap gene in the brains of mice causes perinatal lethality associated with microcephaly and gliosis. Mice with haploinsufficiency of Scap in the brain show a 60% reduction of SCAP protein and ~30% reduction in brain cholesterol synthesis, similar to what is observed in diabetic mice. This results in impaired synaptic transmission, as measured by decreased paired pulse facilitation and long-term potentiation, and is associated with behavioral and cognitive changes. Thus, reduction of SCAP and the consequent suppression of cholesterol synthesis in the brain may play an important role in the increased rates of cognitive decline and Alzheimer disease observed in diabetic states.

  2. Dopamine D1-like receptors depress excitatory synaptic transmissions in striatal neurons after transient forebrain ischemia.

    Science.gov (United States)

    Zhang, Yuchun; Deng, Ping; Ruan, Yiwen; Xu, Zao C

    2008-08-01

    Spiny neurons in the neostriatum are highly vulnerable to ischemia. Despite an enormous body of research suggesting that dopamine is involved in ischemia-induced neuronal loss in the striatum, it remains unclear how dopamine interacts with the glutamatergic excitotoxicity that is widely accepted as a major cause of ischemic cell death. Our study was designed to investigate the effects of dopamine D1 receptor (D1R) activation on excitatory neurotransmission in postischemic striatal neurons. We used the 4-vessel occlusion ischemia model and brain slice preparations. Whole-cell voltage-clamp recording was performed on striatal neurons to measure excitatory postsynaptic currents (EPSCs). Systemic administration of a D1R agonist after ischemia and hematoxylin/eosin staining were performed to evaluate the effects of D1R activation on ischemia-induced neuronal degeneration in the striatum. D1R activation depressed EPSCs in postischemic striatal neurons. The depression was attributable to inhibition of presynaptic release. An activator of cAMP-dependent protein kinase A (PKA) mimicked the depressive effects of D1R activation. Bath application of a PKA inhibitor blocked the depression of EPSCs, whereas intracellular postsynaptic application of the PKA inhibitor had no effect. The D1R agonist failed to reduce EPSC amplitude in the presence of an adenosine A1 receptor antagonist. Systemic administration of a D1R agonist after ischemia significantly attenuated ischemia-induced cell death in the striatum. These results indicate that D1R activation presynaptically depresses excitatory synaptic transmission in striatal neurons after ischemia through activation of PKA and adenosine A1 receptors and thus demonstrate a novel mechanism of D1R-mediated protection against ischemia.

  3. Fragile X mental retardation protein controls synaptic vesicle exocytosis by modulating N-type calcium channel density

    Science.gov (United States)

    Ferron, Laurent; Nieto-Rostro, Manuela; Cassidy, John S.; Dolphin, Annette C.

    2014-04-01

    Fragile X syndrome (FXS), the most common heritable form of mental retardation, is characterized by synaptic dysfunction. Synaptic transmission depends critically on presynaptic calcium entry via voltage-gated calcium (CaV) channels. Here we show that the functional expression of neuronal N-type CaV channels (CaV2.2) is regulated by fragile X mental retardation protein (FMRP). We find that FMRP knockdown in dorsal root ganglion neurons increases CaV channel density in somata and in presynaptic terminals. We then show that FMRP controls CaV2.2 surface expression by targeting the channels to the proteasome for degradation. The interaction between FMRP and CaV2.2 occurs between the carboxy-terminal domain of FMRP and domains of CaV2.2 known to interact with the neurotransmitter release machinery. Finally, we show that FMRP controls synaptic exocytosis via CaV2.2 channels. Our data indicate that FMRP is a potent regulator of presynaptic activity, and its loss is likely to contribute to synaptic dysfunction in FXS.

  4. Inhibitory Control of Synaptic and Behavioral Plasticity by Octopaminergic Signaling

    Science.gov (United States)

    Koon, Alex C.; Budnik, Vivian

    2012-01-01

    Adrenergic receptors and their ligands are important regulators of synaptic plasticity and metaplasticity, but the exact mechanisms underlying their action are still poorly understood. Octopamine, the invertebrate homolog of mammalian adrenaline or noradrenaline, plays important roles in modulating behavior and synaptic functions. We previously uncovered an octopaminergic positive feedback mechanism to regulate structural synaptic plasticity during development and in response to starvation. Under this mechanism, activation of Octß2R autoreceptors by octopamine at octopaminergic neurons initiated a cAMP-dependent cascade that stimulated the development of new synaptic boutons at the Drosophila larval neuromuscular junction (NMJ). However, the regulatory mechanisms that served to brake such positive feedback were not known. Here, we report the presence of an alternative octopamine autoreceptor, Octß1R, with antagonistic functions on synaptic growth. Mutations in octß1r result in the overgrowth of both glutamatergic and octopaminergic NMJs suggesting that Octß1R is a negative regulator of synaptic expansion. As Octß2R, Octß1R functioned in a cell autonomous manner at presynaptic motorneurons. However, unlike Octß2R, which activated a cAMP pathway, Octß1R likely inhibited cAMP production through inhibitory Goα. Despite its inhibitory role, Octß1R was required for acute changes in synaptic structure in response to octopamine and for starvation-induced increase in locomotor speed. These results demonstrate the dual action of octopamine on synaptic growth and behavioral plasticity, and highlight the important role of inhibitory influences for normal responses to physiological stimuli. PMID:22553037

  5. Ethanol extract of the seed of Zizyphus jujuba var. spinosa potentiates hippocampal synaptic transmission through mitogen-activated protein kinase, adenylyl cyclase, and protein kinase A pathways.

    Science.gov (United States)

    Jo, So Yeon; Jung, In Ho; Yi, Jee Hyun; Choi, Tae Joon; Lee, Seungheon; Jung, Ji Wook; Yun, Jeanho; Lee, Young Choon; Ryu, Jong Hoon; Kim, Dong Hyun

    2017-03-22

    As the seed of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) has been used to sleep disturbances in traditional Chinese and Korean medicine, many previous studies have focused on its sedative effect. Recently, we reported the neuroprotective effect of the effect of Z. jujuba var. spinosa. However, its effects on synaptic function have not yet been studied. In this project, we examined the action of ethanol extract of the seed of Z. jujuba var. spinosa (DHP1401) on synaptic transmission in the hippocampus. To investigate the effects of DHP1401, field recordings were conducted using hippocampal slices (400µm). Object recognition test was introduced to examine whether DHP1401 affect normal recognition memory. DHP1401 (50μg/ml) induced a significant increase in synaptic activity in Shaffer collateral pathway in a concentration-dependent manner. This increase of synaptic responses was blocked by NBQX, a broad spectrum α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, but not IEM-1460, a Ca 2+ -permeable AMPAR blocker. Moreover, U0126, a mitogen-activated protein kinase inhibitor, SQ22536, an adenylyl cyclase inhibitor, and PKI, a protein kinase A inhibitor, blocked DHP1401-induced increase in synaptic transmission. Finally, DHP1401 facilitated object recognition memory. These results suggest that DHP1401 increase synaptic transmission through increase of synaptic AMPAR transmission via MAPK, AC and PAK. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  6. Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice.

    Science.gov (United States)

    Smith, Stephen E P; Zhou, Yu-Dong; Zhang, Guangping; Jin, Zhe; Stoppel, David C; Anderson, Matthew P

    2011-10-05

    People with autism spectrum disorder are characterized by impaired social interaction, reduced communication, and increased repetitive behaviors. The disorder has a substantial genetic component, and recent studies have revealed frequent genome copy number variations (CNVs) in some individuals. A common CNV that occurs in 1 to 3% of those with autism--maternal 15q11-13 duplication (dup15) and triplication (isodicentric extranumerary chromosome, idic15)--affects several genes that have been suggested to underlie autism behavioral traits. To test this, we tripled the dosage of one of these genes, the ubiquitin protein ligase Ube3a, which is expressed solely from the maternal allele in mature neurons, and reconstituted the three core autism traits in mice: defective social interaction, impaired communication, and increased repetitive stereotypic behavior. The penetrance of these autism traits depended on Ube3a gene copy number. In animals with increased Ube3a gene dosage, glutamatergic, but not GABAergic, synaptic transmission was suppressed as a result of reduced presynaptic release probability, synaptic glutamate concentration, and postsynaptic action potential coupling. These results suggest that Ube3a gene dosage may contribute to the autism traits of individuals with maternal 15q11-13 duplication and support the idea that increased E3A ubiquitin ligase gene dosage results in reduced excitatory synaptic transmission.

  7. The role of APP and APLP for synaptic transmission, plasticity, and network function: lessons from genetic mouse models.

    Science.gov (United States)

    Korte, Martin; Herrmann, Ulrike; Zhang, Xiaomin; Draguhn, Andreas

    2012-04-01

    APP, APLP1, and APLP2 form a family of mammalian membrane proteins with unknown function. APP, however, plays a key role in the molecular pathology of Alzheimer's disease (AD), indicating that it is somehow involved in synaptic transmission, synaptic plasticity, memory formation, and maintenance of neurons. At present, most of our knowledge about the function of APP comes from consequences of AD-related mutations. The native role of APP, and even more of APLP1/2, remains largely unknown. New genetic knockout and knockin models involving several members of the APP/APLP family may yield better insight into the synaptic and systemic functions of these proteins. Here, we summarize recent results from such transgenic animals with special emphasis on synaptic plasticity and coherent patterns of memory-related network activity in the hippocampus. Data from APP knockout mice suggest that this protein is needed for the expression of long-term potentiation (LTP) in aged, but not in juvenile mice. The missing function can be rescued by expressing part of the protein, as well as by blocking inhibition. Double knockout mice lacking APP and APLP2 die shortly after birth indicating that different members of the APP/APLP family can mutually compensate for genetic ablation of single proteins. Recent techniques allow for analysis of tissue with combined defects, e.g., by expressing only part of APP in APLP2 knockout mice or by growing stem cells with multiple deletions on normal slice cultures. Data from these experiments confirm that APP and APLP2 do indeed play an important role in synaptic plasticity. Much less is known about the role of APP/APLP at the network level. Coherent patterns of activity like hippocampal network oscillations are believed to support formation and consolidation of memory. Analysis of such activity patterns in tissue from mice with altered expression of APP/APLP has just started and may shed further light on the importance of these proteins for cognitive

  8. Cholinergic Synaptic Transmissions Were Altered after Single Sevoflurane Exposure in Drosophila Pupa

    Directory of Open Access Journals (Sweden)

    Rongfa Chen

    2015-01-01

    Full Text Available Purpose. Sevoflurane, one of the most used general anesthetics, is widely used in clinical practice all over the world. Previous studies indicated that sevoflurane could induce neuron apoptosis and neural deficit causing query in the safety of anesthesia using sevoflurane. The present study was designed to investigate the effects of sevoflurane on electrophysiology in Drosophila pupa whose excitatory neurotransmitter is acetylcholine early after sevoflurane exposure using whole brain recording technique. Methods. Wide types of Drosophila (canton-s flies were allocated to control and sevoflurane groups randomly. Sevoflurane groups (1% sevoflurane; 2% sevoflurane; 3% sevoflurane were exposed to sevoflurane and the exposure lasted 5 hours, respectively. All flies were subjected to electrophysiology experiment using patch clamp 24 hours after exposure. Results. The results showed that, 24 hours after sevoflurane exposure, frequency but not the amplitude of miniature excitatory postsynaptic currents (mEPSCs was significantly reduced P<0.05. Furthermore, we explored the underlying mechanism and found that calcium currents density, which partially regulated the frequency of mEPSCs, was significantly reduced after sevoflurane exposure P<0.05. Conclusions. All these suggested that sevoflurane could alter the mEPSCs that are related to synaptic plasticity partially through modulating calcium channel early after sevoflurane exposure.

  9. Cholinergic synaptic transmissions were altered after single sevoflurane exposure in Drosophila pupa.

    Science.gov (United States)

    Chen, Rongfa; Zhang, Tao; Kuang, Liting; Chen, Zhen; Ran, Dongzhi; Niu, Yang; Xu, Kangqing; Gu, Huaiyu

    2015-01-01

    . Sevoflurane, one of the most used general anesthetics, is widely used in clinical practice all over the world. Previous studies indicated that sevoflurane could induce neuron apoptosis and neural deficit causing query in the safety of anesthesia using sevoflurane. The present study was designed to investigate the effects of sevoflurane on electrophysiology in Drosophila pupa whose excitatory neurotransmitter is acetylcholine early after sevoflurane exposure using whole brain recording technique. Wide types of Drosophila (canton-s flies) were allocated to control and sevoflurane groups randomly. Sevoflurane groups (1% sevoflurane; 2% sevoflurane; 3% sevoflurane) were exposed to sevoflurane and the exposure lasted 5 hours, respectively. All flies were subjected to electrophysiology experiment using patch clamp 24 hours after exposure. The results showed that, 24 hours after sevoflurane exposure, frequency but not the amplitude of miniature excitatory postsynaptic currents (mEPSCs) was significantly reduced (P < 0.05). Furthermore, we explored the underlying mechanism and found that calcium currents density, which partially regulated the frequency of mEPSCs, was significantly reduced after sevoflurane exposure (P < 0.05). All these suggested that sevoflurane could alter the mEPSCs that are related to synaptic plasticity partially through modulating calcium channel early after sevoflurane exposure.

  10. Gastrin-releasing peptide facilitates glutamatergic transmission in the hippocampus and effectively prevents vascular dementia induced cognitive and synaptic plasticity deficits.

    Science.gov (United States)

    Yang, Jiajia; Yao, Yang; Wang, Ling; Yang, Chunxiao; Wang, Faqi; Guo, Jie; Wang, Zhiyun; Yang, Zhuo; Ming, Dong

    2017-01-01

    Neuronal gastrin-releasing peptide (GRP) has been proved to be an important neuromodulator in the brain and involved in a variety of neurological diseases. Whether GRP could attenuate cognition impairment induced by vascular dementia (VD) in rats, and the mechanism of synaptic plasticity and GRP's action on synaptic efficiency are still poorly understood. In this study, we first investigated the effects of GRP on glutamatergic transmission with patch-clamp recording. We found that acute application of GRP enhanced the excitatory synaptic transmission in hippocampal CA1 neurons via GRPR in a presynaptic mechanism. Secondly, we examined whether exogenous GRP or its analogue neuromedin B (NMB) could prevent VD-induced cognitive deficits and the mechanism of synaptic plasticity. By using Morris water maze, long-term potentiation (LTP) recording, western blot assay and immunofluorescent staining, we verified for the first time that GRP or NMB substantially improved the spatial learning and memory abilities in VD rats, restored the impaired synaptic plasticity and was able to elevate the expression of synaptic proteins, synaptophysin (SYP) and CaMKII, which play pivotal roles in synaptic plasticity. These results suggest that the facilitatory effects of GRP on glutamate release may contribute to its long-term action on synaptic efficacy which is essential in cognitive function. Our findings present a new entry point for a better understanding of physiological function of GRP and raise the possibility that GRPR agonists might ameliorate cognitive deficits associated with neurological diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Mechanisms of hydrogen sulfide (H2S) action on synaptic transmission at the mouse neuromuscular junction.

    Science.gov (United States)

    Gerasimova, E; Lebedeva, J; Yakovlev, A; Zefirov, A; Giniatullin, R; Sitdikova, G

    2015-09-10

    Hydrogen sulfide (H2S) is a widespread gasotransmitter also known as a powerful neuroprotective agent in the central nervous system. However, the action of H2S in peripheral synapses is much less studied. In the current project we studied the modulatory effects of the H2S donor sodium hydrosulfide (NaHS) on synaptic transmission in the mouse neuromuscular junction using microelectrode technique. Using focal recordings of presynaptic response and evoked transmitter release we have shown that NaHS (300 μM) increased evoked end-plate currents (EPCs) without changes of presynaptic waveforms which indicated the absence of NaHS effects on sodium and potassium currents of motor nerve endings. Using intracellular recordings it was shown that NaHS increased the frequency of miniature end-plate potentials (MEPPs) without changing their amplitudes indicating a pure presynaptic effect. Furthermore, NaHS increased the amplitude of end-plate potentials (EPPs) without influencing the resting membrane potential of muscle fibers. L-cysteine, a substrate of H2S synthesis induced, similar to NaHS, an increase of EPC amplitudes whereas inhibitors of H2S synthesis (β-cyano-L-alanine and aminooxyacetic acid) had the opposite effect. Inhibition of adenylate cyclase using MDL 12,330A hydrochloride (MDL 12,330A) or elevation of cAMP level with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (pCPT-cAMP) completely prevented the facilitatory action of NaHS indicating involvement of the cAMP signaling cascade. The facilitatory effect of NaHS was significantly diminished when intracellular calcium (Ca(2+)) was buffered by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) and ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester (EGTA-AM). Activation of ryanodine receptors by caffeine or ryanodine increased acetylcholine release and prevented further action of NaHS on transmitter release, likely due to

  12. A Novel HumanCAMK2AMutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors.

    Science.gov (United States)

    Stephenson, Jason R; Wang, Xiaohan; Perfitt, Tyler L; Parrish, Walker P; Shonesy, Brian C; Marks, Christian R; Mortlock, Douglas P; Nakagawa, Terunaga; Sutcliffe, James S; Colbran, Roger J

    2017-02-22

    Characterizing the functional impact of novel mutations linked to autism spectrum disorder (ASD) provides a deeper mechanistic understanding of the underlying pathophysiological mechanisms. Here we show that a de novo Glu183 to Val (E183V) mutation in the CaMKIIα catalytic domain, identified in a proband diagnosed with ASD, decreases both CaMKIIα substrate phosphorylation and regulatory autophosphorylation, and that the mutated kinase acts in a dominant-negative manner to reduce CaMKIIα-WT autophosphorylation. The E183V mutation also reduces CaMKIIα binding to established ASD-linked proteins, such as Shank3 and subunits of l-type calcium channels and NMDA receptors, and increases CaMKIIα turnover in intact cells. In cultured neurons, the E183V mutation reduces CaMKIIα targeting to dendritic spines. Moreover, neuronal expression of CaMKIIα-E183V increases dendritic arborization and decreases both dendritic spine density and excitatory synaptic transmission. Mice with a knock-in CaMKIIα-E183V mutation have lower total forebrain CaMKIIα levels, with reduced targeting to synaptic subcellular fractions. The CaMKIIα-E183V mice also display aberrant behavioral phenotypes, including hyperactivity, social interaction deficits, and increased repetitive behaviors. Together, these data suggest that CaMKIIα plays a previously unappreciated role in ASD-related synaptic and behavioral phenotypes. SIGNIFICANCE STATEMENT Many autism spectrum disorder (ASD)-linked mutations disrupt the function of synaptic proteins, but no single gene accounts for >1% of total ASD cases. The molecular networks and mechanisms that couple the primary deficits caused by these individual mutations to core behavioral symptoms of ASD remain poorly understood. Here, we provide the first characterization of a mutation in the gene encoding CaMKIIα linked to a specific neuropsychiatric disorder. Our findings demonstrate that this ASD-linked de novo CAMK2A mutation disrupts multiple Ca

  13. Control of synaptic plasticity in deep cortical networks

    NARCIS (Netherlands)

    Roelfsema, Pieter R; Holtmaat, Anthony

    2018-01-01

    Humans and many other animals have an enormous capacity to learn about sensory stimuli and to master new skills. However, many of the mechanisms that enable us to learn remain to be understood. One of the greatest challenges of systems neuroscience is to explain how synaptic connections change to

  14. Neonatal Nicotine Exposure Increases Excitatory Synaptic Transmission and Attenuates Nicotine-stimulated GABA release in the Adult Rat Hippocampus

    Science.gov (United States)

    Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

    2014-01-01

    Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1–7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking. PMID:24950455

  15. Integrated Transmission and Distribution Control

    Energy Technology Data Exchange (ETDEWEB)

    Kalsi, Karanjit [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Fuller, Jason C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Tuffner, Francis K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lian, Jianming [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zhang, Wei [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Marinovici, Laurentiu D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Fisher, Andrew R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Chassin, Forrest S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hauer, Matthew L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2013-01-01

    Distributed, generation, demand response, distributed storage, smart appliances, electric vehicles and renewable energy resources are expected to play a key part in the transformation of the American power system. Control, coordination and compensation of these smart grid assets are inherently interlinked. Advanced control strategies to warrant large-scale penetration of distributed smart grid assets do not currently exist. While many of the smart grid technologies proposed involve assets being deployed at the distribution level, most of the significant benefits accrue at the transmission level. The development of advanced smart grid simulation tools, such as GridLAB-D, has led to a dramatic improvement in the models of smart grid assets available for design and evaluation of smart grid technology. However, one of the main challenges to quantifying the benefits of smart grid assets at the transmission level is the lack of tools and framework for integrating transmission and distribution technologies into a single simulation environment. Furthermore, given the size and complexity of the distribution system, it is crucial to be able to represent the behavior of distributed smart grid assets using reduced-order controllable models and to analyze their impacts on the bulk power system in terms of stability and reliability.

  16. pH modulation of glial glutamate transporters regulates synaptic transmission in the nucleus of the solitary tract

    Science.gov (United States)

    McCrimmon, Donald R.; Martina, Marco

    2013-01-01

    The nucleus of the solitary tract (NTS) is the major site for termination of visceral sensory afferents contributing to homeostatic regulation of, for example, arterial pressure, gastric motility, and breathing. Whereas much is known about how different neuronal populations influence these functions, information about the role of glia remains scant. In this article, we propose that glia may contribute to NTS functions by modulating excitatory neurotransmission. We found that acidification (pH 7.0) depolarizes NTS glia by inhibiting K+-selective membrane currents. NTS glia also showed functional expression of voltage-sensitive glutamate transporters, suggesting that extracellular acidification regulates synaptic transmission by compromising glial glutamate uptake. To test this hypothesis, we evoked glutamatergic slow excitatory potentials (SEPs) in NTS neurons with repetitive stimulation (20 pulses at 10 Hz) of the solitary tract. This SEP depends on accumulation of glutamate following repetitive stimulation, since it was potentiated by blocking glutamate uptake with dl-threo-β-benzyloxyaspartic acid (TBOA) or a glia-specific glutamate transport blocker, dihydrokainate (DHK). Importantly, extracellular acidification (pH 7.0) also potentiated the SEP. This effect appeared to be mediated through a depolarization-induced inhibition of glial transporter activity, because it was occluded by TBOA and DHK. In agreement, pH 7.0 did not directly alter d-aspartate-induced responses in NTS glia or properties of presynaptic glutamate release. Thus acidification-dependent regulation of glial function affects synaptic transmission within the NTS. These results suggest that glia play a modulatory role in the NTS by integrating local tissue signals (such as pH) with synaptic inputs from peripheral afferents. PMID:23615553

  17. P2Y Receptors in Synaptic Transmission and Plasticity: Therapeutic Potential in Cognitive Dysfunction

    Directory of Open Access Journals (Sweden)

    Segundo J. Guzman

    2016-01-01

    Full Text Available ATP released from neurons and astrocytes during neuronal activity or under pathophysiological circumstances is able to influence information flow in neuronal circuits by activation of ionotropic P2X and metabotropic P2Y receptors and subsequent modulation of cellular excitability, synaptic strength, and plasticity. In the present paper we review cellular and network effects of P2Y receptors in the brain. We show that P2Y receptors inhibit the release of neurotransmitters, modulate voltage- and ligand-gated ion channels, and differentially influence the induction of synaptic plasticity in the prefrontal cortex, hippocampus, and cerebellum. The findings discussed here may explain how P2Y1 receptor activation during brain injury, hypoxia, inflammation, schizophrenia, or Alzheimer’s disease leads to an impairment of cognitive processes. Hence, it is suggested that the blockade of P2Y1 receptors may have therapeutic potential against cognitive disturbances in these states.

  18. Biochemical plasticity of synaptic transmission: a critical review of Dale's Principle.

    Science.gov (United States)

    Sabelli, H C; Mosnaim, A D; Vazquez, A J; Giardina, W J; Borison, R L; Pedemonte, W A

    1976-08-01

    "Dale's Principle" states that each neuron releases one and only one synaptic transmitter. Mental disorders and behavioral drug effects are attributed to activation or blockade of one or more of these specific transmitters. A series of biochemical, electrophysiological, and behavioral studies suggests the alternative view that at each monoaminergic synapse the action of the transmitter is modulated by several metabolically related substances: amine analogs (2-phenylethylamine [PEA], p-tyramine, etc.), deaminated products (aldehydes, acids, and alcohols), and possibly also amino acid precursors. In support of this view, the authors present evidence for the presence, synthesis, metabolism, and biological activity (at the cellular level, using microelectrode techniques) of amino acid, amines, and deaminated compounds metabolically related to catecholamines and sorotonin. That neuroamino acids exert direct effects (not mediated via their amine metabolites) is illustrated by the rapid effects of microiontophoretic dopa upon cortical unit activity, and by the observation that neither the lethargic effect of 5-hydroxytryptophan (considered to support Jouvet's serotonergic theory of sleep) nor the behavioral stimulant effects of dopa (considered to support the catecholamine theory of affective behavior) are significantly prevented by L-aromatic amino acid decarboxylase inhibitors. The biological activity of the deaminated metabolites of catecholamines and serotonin is illustrated by the effects of their microiontophoretic administration upon cortical units. Further, probenecid (an inhibitor of acid transport across the blood-brain barrier) is shown to qualitatively alter the effects of intraventricularly administered PEA and of its metabolite phenylacetic acid upon visual evoked potentials. Rabbit brain is shown to synthesize a series of pharmacologically active noncatecholic phenylethylamines as by-products of catecholamine metabolism. Amine modulators such as PEA differ

  19. Potentiation of Inhibitory Synaptic Transmission by Extracellular ATP in Rat Suprachiasmatic Nuclei

    Czech Academy of Sciences Publication Activity Database

    Bhattacharya, Anirban; Vávra, Vojtěch; Svobodová, Irena; Bendová, Z.; Vereb, G.; Zemková, Hana

    2013-01-01

    Roč. 33, č. 18 (2013), s. 8035-8044 ISSN 0270-6474 R&D Projects: GA AV ČR(CZ) IAA500110910; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : suprachiasmatic nucleus * P2X receptors * P2Y receptors * ATP * GABA * spontaneous inhibitory synaptic currents Subject RIV: ED - Physiology Impact factor: 6.747, year: 2013

  20. Attenuation of inhibitory synaptic transmission by glial dysfunction in rat thalamus

    OpenAIRE

    Yang, Sunggu; Cox, Charles L.

    2011-01-01

    The thalamus serves as the obligatory gateway to the neocortex for sensory processing, and also serves as a pathway for corticocortical communication. In addition, the reciprocal synaptic connectivity between the thalamic reticular nucleus (TRN) and adjacent thalamic relay nuclei generates rhythmic activities similar to that observed during different arousal states and certain neurological conditions such as absence epilepsy. Epileptiform activity can arise from a variety of neural mechanisms...

  1. Control of synaptic function by endocannabinoid-mediated retrograde signaling

    Science.gov (United States)

    KANO, Masanobu

    2014-01-01

    Since the first reports in 2001, great advances have been made towards the understanding of endocannabinoid-mediated synaptic modulation. Electrophysiological studies have revealed that one of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG), is produced from membrane lipids upon postsynaptic Ca2+ elevation and/or activation of Gq/11-coupled receptors, and released from postsynaptic neurons. The released 2-AG then acts retrogradely onto presynaptic cannabinoid CB1 receptors and induces suppression of neurotransmitter release either transiently or persistently. These forms of 2-AG-mediated retrograde synaptic modulation are functional throughout the brain. The other major endocannabinoid, anandamide, mediates a certain form of endocannabinoid-mediated long-term depression (LTD). Anandamide also functions as an agonist for transient receptor potential vanilloid receptor type 1 (TRPV1) and mediates endocannabinoid-independent and TRPV1-dependent forms of LTD. It has also been demonstrated that the endocannabinoid system itself is plastic, which can be either up- or down-regulated by experimental or environmental conditions. In this review, I will make an overview of the mechanisms underlying endocannabinoid-mediated synaptic modulation. PMID:25169670

  2. EPO induces changes in synaptic transmission and plasticity in the dentate gyrus of rats.

    Science.gov (United States)

    Almaguer-Melian, William; Mercerón-Martínez, Daymara; Delgado-Ocaña, Susana; Pavón-Fuentes, Nancy; Ledón, Nuris; Bergado, Jorge A

    2016-06-01

    Erythropoietin has shown wide physiological effects on the central nervous system in animal models of disease, and in healthy animals. We have recently shown that systemic EPO administration 15 min, but not 5 h, after daily training in a water maze is able to induce the recovery of spatial memory in fimbria-fornix chronic-lesioned animals, suggesting that acute EPO triggers mechanisms which can modulate the active neural plasticity mechanism involved in spatial memory acquisition in lesioned animals. Additionally, this EPO effect is accompanied by the up-regulation of plasticity-related early genes. More remarkably, this time-dependent effects on learning recovery could signify that EPO in nerve system modulate specific living-cellular processes. In the present article, we focus on the question if EPO could modulate the induction of long-term synaptic plasticity like LTP and LTD, which presumably could support our previous published data. Our results show that acute EPO peripheral administration 15 min before the induction of synaptic plasticity is able to increase the magnitude of the LTP (more prominent in PSA than fEPSP-Slope) to facilitate the induction of LTD, and to protect LTP from depotentiation. These findings showing that EPO modulates in vivo synaptic plasticity sustain the assumption that EPO can act not only as a neuroprotective substance, but is also able to modulate transient neural plasticity mechanisms and therefore to promote the recovery of nerve function after an established chronic brain lesion. According to these results, EPO could be use as a molecular tool for neurorestaurative treatments. © 2016 Wiley Periodicals, Inc.

  3. All for One But Not One for All: Excitatory Synaptic Scaling and Intrinsic Excitability Are Coregulated by CaMKIV, Whereas Inhibitory Synaptic Scaling Is Under Independent Control.

    Science.gov (United States)

    Joseph, Annelise; Turrigiano, Gina G

    2017-07-12

    Neocortical circuits use a family of homeostatic plasticity mechanisms to stabilize firing, including excitatory and inhibitory synaptic scaling and homeostatic intrinsic plasticity (Turrigiano and Nelson, 2004). All three mechanisms can be induced in tandem in cultured rat neocortical pyramidal neurons by chronic manipulations of firing, but it is unknown whether they are coinduced by the same activity-sensors and signaling pathways, or whether they are under independent control. Calcium/calmodulin-dependent protein kinase type IV (CaMKIV) is a key sensory/effector in excitatory synaptic scaling that senses perturbations in firing through changes in calcium influx, and translates this into compensatory changes in excitatory quantal amplitude (Ibata et al., 2008; Goold and Nicoll, 2010). Whether CaMKIV also controls inhibitory synaptic scaling and intrinsic homeostatic plasticity was unknown. To test this we manipulated CaMKIV signaling in individual neurons using dominant-negative (dn) or constitutively-active (ca) forms of nuclear-localized CaMKIV and measured the induction of all three forms of homeostatic plasticity. We found that excitatory synaptic scaling and intrinsic plasticity were bidirectionally coinduced by these manipulations. In contrast, these cell-autonomous manipulations had no impact on inhibitory quantal amplitude. Finally, we found that spontaneous firing rates were shifted up or down by dnCaMKIV or caCaMKIV, respectively, suggesting that uncoupling CaMKIV activation from activity generates an error signal in the negative feedback mechanism that controls firing rates. Together, our data show that excitatory synaptic scaling and intrinsic excitability are tightly coordinated through bidirectional changes in the same signaling pathway, whereas inhibitory synaptic scaling is sensed and regulated through an independent control mechanism. SIGNIFICANCE STATEMENT Maintaining stable function in highly interconnected neural circuits is essential for

  4. Endocannabinoids blunt the augmentation of synaptic transmission by serotonin 2A receptors in the nucleus tractus solitarii (nTS)

    Science.gov (United States)

    Austgen, James R.; Kline, David D.

    2013-01-01

    Serotonin (5-Hydroxytryptamine, 5-HT) and the 5-HT2 receptor modulate cardiovascular and autonomic function in part through actions in the nTS, the primary termination and integration point for cardiorespiratory afferents in the brainstem. In other brain regions, 5-HT2 receptors (5-HT2R) modify synaptic transmission directly, as well as through 5-HT2AR-induced endocannabinoid release. This study examined the role of 5-HT2AR as well as their interaction with endocannabinoids on neurotransmission in the nucleus tractus solitarii (nTS). Excitatory postsynaptic currents (EPSCs) in monosynaptic nTS neurons were recorded in the horizontal brainstem slice during activation and blockade of 5-HT2ARs. 5-HT2AR activation augmented solitary tract (TS) evoked EPSC amplitude whereas 5-HT2AR blockade depressed TS-EPSC amplitude at low and high TS stimulation rates. The 5-HT2AR-induced increase in neurotransmission was reduced by endocannabinoid receptor block and increased endogenous endocannabinoids in the synaptic cleft during high frequency, but not low, TS stimulation. Endocannabinoids did not tonically modify EPSCs. These data suggest 5-HT acting through the 5-HT2AR is an excitatory neuromodulator in the nTS and its effects are modulated by the endocannabinoid system. PMID:24041777

  5. The BDNF val-66-met Polymorphism Affects Neuronal Morphology and Synaptic Transmission in Cultured Hippocampal Neurons from Rett Syndrome Mice

    Directory of Open Access Journals (Sweden)

    Xin Xu

    2017-07-01

    Full Text Available Brain-derived neurotrophic factor (Bdnf has been implicated in several neurological disorders including Rett syndrome (RTT, an X-linked neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional modulator methyl-CpG-binding protein 2 (MECP2. The human BDNF gene has a single nucleotide polymorphism (SNP—a methionine (met substitution for valine (val at codon 66—that affects BDNF’s trafficking and activity-dependent release and results in cognitive dysfunction. Humans that are carriers of the met-BDNF allele have subclinical memory deficits and reduced hippocampal volume and activation. It is still unclear whether this BDNF SNP affects the clinical outcome of RTT individuals. To evaluate whether this BDNF SNP contributes to RTT pathophysiology, we examined the consequences of expression of either val-BDNF or met-BDNF on dendrite and dendritic spine morphology, and synaptic function in cultured hippocampal neurons from wildtype (WT and Mecp2 knockout (KO mice. Our findings revealed that met-BDNF does not increase dendritic growth and branching, dendritic spine density and individual spine volume, and the number of excitatory synapses in WT neurons, as val-BDNF does. Furthermore, met-BDNF reduces dendritic complexity, dendritic spine volume and quantal excitatory synaptic transmission in Mecp2 KO neurons. These results suggest that the val-BDNF variant contributes to RTT pathophysiology, and that BDNF-based therapies should take into consideration the BDNF genotype of the RTT individuals.

  6. Peptide and lipid modulation of glutamatergic afferent synaptic transmission in the solitary tract nucleus

    Directory of Open Access Journals (Sweden)

    Michael C. Andresen

    2013-01-01

    Full Text Available The brainstem nucleus of the solitary tract (NTS holds the first central neurons in major homeostatic reflex pathways. These homeostatic reflexes regulate and coordinate multiple organ systems from gastrointestinal to cardiopulmonary functions. The core of many of these pathways arise from cranial visceral afferent neurons that enter the brain as the solitary tract (ST with more than two-thirds arising from the gastrointestinal system. About one quarter of ST afferents have myelinated axons but the majority are classed as unmyelinated C-fibers. All ST afferents release the fast neurotransmitter glutamate with remarkably similar, high-probability release characteristics. Second order NTS neurons receive surprisingly limited primary afferent information with one or two individual inputs converging on single second order NTS neurons. A- and C-fiber afferents never mix at NTS second order neurons. Many transmitters modify the basic glutamatergic excitatory postsynaptic current (EPSC often by reducing glutamate release or interrupting terminal depolarization. Thus, a distinguishing feature of ST transmission is presynaptic expression of G-protein coupled receptors for peptides common to peripheral or forebrain (e.g. hypothalamus neuron sources. Presynaptic receptors for angiotensin (AT1, vasopressin (V1a, oxytocin (OT, opioid (MOR, ghrelin (GHSR1 and cholecystokinin (CCK differentially control glutamate release on particular subsets of neurons with most other ST afferents unaffected. Lastly, lipid-like signals are transduced by two key ST presynaptic receptors, the transient receptor potential vanilloid type 1 (TRPV1 and the cannabinoid receptor (CB1 that oppositely control glutamate release. Increasing evidence suggests that peripheral nervous signaling mechanisms are repurposed at central terminals to control excitation and are major sites of signal integration of peripheral and central inputs particularly from the hypothalamus.

  7. Electrical coupling and excitatory synaptic transmission between rhythmogenic respiratory neurons in the preBötzinger complex

    DEFF Research Database (Denmark)

    Rekling, J C; Shao, X M; Feldman, J L

    2000-01-01

    Breathing pattern is postulated to be generated by brainstem neurons. However, determination of the underlying cellular mechanisms, and in particular the synaptic interactions between respiratory neurons, has been difficult. Here we used dual recordings from two distinct populations of brainstem...... respiratory neurons, hypoglossal (XII) motoneurons, and rhythmogenic (type-1) neurons in the preBötzinger complex (preBötC), the hypothesized site for respiratory rhythm generation, to determine whether electrical and chemical transmission is present. Using an in vitro brainstem slice preparation from newborn...... mice, we found that intracellularly recorded pairs of XII motoneurons and pairs of preBötC inspiratory type-1 neurons showed bidirectional electrical coupling. Coupling strength was low (neurons was heavily filtered (corner frequency,

  8. Structure and function of the amygdaloid NPY system: NPY Y2 receptors regulate excitatory and inhibitory synaptic transmission in the centromedial amygdala.

    Science.gov (United States)

    Wood, J; Verma, D; Lach, G; Bonaventure, P; Herzog, H; Sperk, G; Tasan, R O

    2016-09-01

    The amygdala is essential for generating emotional-affective behaviors. It consists of several nuclei with highly selective, elaborate functions. In particular, the central extended amygdala, consisting of the central amygdala (CEA) and the bed nucleus of the stria terminalis (BNST) is an essential component actively controlling efferent connections to downstream effectors like hypothalamus and brain stem. Both, CEA and BNST contain high amounts of different neuropeptides that significantly contribute to synaptic transmission. Among these, neuropeptide Y (NPY) has emerged as an important anxiolytic and fear-reducing neuromodulator. Here, we characterized the expression, connectivity and electrophysiological function of NPY and Y2 receptors within the CEA. We identified several NPY-expressing neuronal populations, including somatostatin- and calretinin-expressing neurons. Furthermore, in the main intercalated nucleus, NPY is expressed primarily in dopamine D1 receptor-expressing neurons but also in interspersed somatostatin-expressing neurons. Interestingly, NPY neurons did not co-localize with the Y2 receptor. Retrograde tract tracing experiments revealed that NPY neurons reciprocally connect the CEA and BNST. Functionally, the Y2 receptor agonist PYY3-36, reduced both, inhibitory as well as excitatory synaptic transmission in the centromedial amygdala (CEm). However, we also provide evidence that lack of NPY or Y2 receptors results in increased GABA release specifically at inhibitory synapses in the CEm. Taken together, our findings suggest that NPY expressed by distinct populations of neurons can modulate afferent and efferent projections of the CEA via presynaptic Y2 receptors located at inhibitory and excitatory synapses.

  9. Propagating dendritic action potential mediates synaptic transmission in CA1 pyramidal cells in situ.

    Science.gov (United States)

    Herreras, O

    1990-11-01

    1. The events leading to the Schaffer collateral-induced discharge of CA1 pyramidal neurons were investigated in the hippocampus of anesthetized rats by current source-density (CSD) analysis. 2. The earliest evoked currents detected shortly after a stimulus were a sink in the zone where synapses are known to be located (300-350 microns ventral to the somatic layer) flanked by two smaller sources in the distal portion of the apical dendrites and in the somatic layer. This synaptic sink (SyS) extended over 75-100 microns; it lasted for 15-20 ms, and it reached its maximum amplitude some milliseconds after the population spike (PS) and remained in the same location. Stimuli submaximal and supramaximal for evoking a PS yielded the same pattern of current distribution for the SyS. Presynaptic fiber volleys were not detected in these recordings. 3. During the rising phase of the SyS a second sink appeared in a more proximal portion of the apical dendrites. This late dendritic sink (LS) extended over 50-75 microns and was centered 100-150 microns ventral to the somatic layer. This proximal dendritic sink was of amplitude comparable with the SyS; it outlasted the latter and was not necessarily followed by a somatic PS. The LS was extinguished with the appearance of a PS, whereas the SyS persisted regardless of the presence of a PS. 4. After maximal stimuli the LS grew until it exceeded a threshold amplitude, and then, it started to move somatopetally as a continuously propagating sink (PrS). The average speed of propagation was approximately 0.2 m/s. In 0.5-0.7 ms the PrS reached the cell-body layer displacing the passive source that moved into the basal dendrites. The PrS then became the intensive sink corresponding to the main (negative) phase of the somatic PS. This was followed by the development of an active source in the soma layer, probably corresponding to the repolarization phase of the PS. 5. From these observations it appears that the LS and PrS are active

  10. [Nonuniform distribution and contribution of the P- and P/Q-type calcium channels to short-term inhibitory synaptic transmission in cultured hippocampal neurons].

    Science.gov (United States)

    Mizerna, O P; Fedulova, S A; Veselovs'kyĭ, M S

    2010-01-01

    In the present study, we investigated the sensitivity of GABAergic short-term plasticity to the selective P- and P/Q-type calcium channels blocker omega-agatoxin-IVA. To block the P-type channels we used 30 nM of this toxin and 200 nM of the toxin was used to block the P/Q channel types. The evoked inhibitory postsynaptic currents (eIPSC) were studied using patch-clamp technique in whole-cell configuration in postsynaptic neuron and local extracellular stimulation of single presynaptic axon by rectangular pulse. The present data show that the contribution of P- and P/Q-types channels to GABAergic synaptic transmission in cultured hippocampal neurons are 30% and 45%, respectively. It was shown that the mediate contribution of the P- and P/Q-types channels to the amplitudes of eIPSC is different to every discovered neuron. It means that distribution of these channels is non-uniform. To study the short-term plasticity of inhibitory synaptic transmission, axons of presynaptic neurons were paired-pulse stimulated with the interpulse interval of 150 ms. Neurons demonstrated both the depression and facilitation. The application of 30 nM and 200 nM of the blocker decreased the depression and increased facilitation to 8% and 11%, respectively. In addition, we found that the mediate contribution of the P- and P/Q-types channels to realization of synaptic transmission after the second stimuli is 4% less compared to that after the first one. Therefore, blocking of both P- and P/Q-types calcium channels can change the efficiency of synaptic transmission. In this instance it facilitates realization of the transmission via decreased depression or increased facilitation. These results confirm that the P- and P/Q-types calcium channels are involved in regulation of the short-term inhibitory synaptic plasticity in cultured hippocampal neurons.

  11. Neuropeptide S-mediated facilitation of synaptic transmission enforces subthreshold theta oscillations within the lateral amygdala.

    Directory of Open Access Journals (Sweden)

    Susanne Meis

    Full Text Available The neuropeptide S (NPS receptor system modulates neuronal circuit activity in the amygdala in conjunction with fear, anxiety and the expression and extinction of previously acquired fear memories. Using in vitro brain slice preparations of transgenic GAD67-GFP (Δneo mice, we investigated the effects of NPS on neural activity in the lateral amygdala as a key region for the formation and extinction of fear memories. We are able to demonstrate that NPS augments excitatory glutamatergic synaptic input onto both projection neurons and interneurons of the lateral amygdala, resulting in enhanced spike activity of both types of cells. These effects were at least in part mediated by presynaptic mechanisms. In turn, inhibition of projection neurons by local interneurons was augmented by NPS, and subthreshold oscillations were strengthened, leading to their shift into the theta frequency range. These data suggest that the multifaceted effects of NPS on amygdaloid circuitry may shape behavior-related network activity patterns in the amygdala and reflect the peptide's potent activity in various forms of affective behavior and emotional memory.

  12. D-cycloserine improves synaptic transmission in an animal model of Rett syndrome.

    Science.gov (United States)

    Na, Elisa S; De Jesús-Cortés, Héctor; Martinez-Rivera, Arlene; Kabir, Zeeba D; Wang, Jieqi; Ramesh, Vijayashree; Onder, Yasemin; Rajadhyaksha, Anjali M; Monteggia, Lisa M; Pieper, Andrew A

    2017-01-01

    Rett syndrome (RTT), a leading cause of intellectual disability in girls, is predominantly caused by mutations in the X-linked gene MECP2. Disruption of Mecp2 in mice recapitulates major features of RTT, including neurobehavioral abnormalities, which can be reversed by re-expression of normal Mecp2. Thus, there is reason to believe that RTT could be amenable to therapeutic intervention throughout the lifespan of patients after the onset of symptoms. A common feature underlying neuropsychiatric disorders, including RTT, is altered synaptic function in the brain. Here, we show that Mecp2tm1.1Jae/y mice display lower presynaptic function as assessed by paired pulse ratio, as well as decreased long term potentiation (LTP) at hippocampal Schaffer-collateral-CA1 synapses. Treatment of Mecp2tm1.1Jae/y mice with D-cycloserine (DCS), an FDA-approved analog of the amino acid D-alanine with antibiotic and glycinergic activity, corrected the presynaptic but not LTP deficit without affecting deficient hippocampal BDNF levels. DCS treatment did, however, partially restore lower BDNF levels in the brain stem and striatum. Thus, treatment with DCS may mitigate the severity of some of the neurobehavioral symptoms experienced by patients with Rett syndrome.

  13. Controllable SET process in O-Ti-Sb-Te based phase change memory for synaptic application

    Science.gov (United States)

    Ren, Kun; Li, Ruiheng; Chen, Xin; Wang, Yong; Shen, Jiabin; Xia, Mengjiao; Lv, Shilong; Ji, Zhenguo; Song, Zhitang

    2018-02-01

    The nonlinear resistance change and small bit resolution of phase change memory (PCM) under identical operation pulses will limit its performance as a synaptic device. The octahedral Ti-Te units in Ti-Sb-Te, regarded as nucleation seeds, are degenerated when Ti is bonded with O, causing a slower crystallization and a controllable SET process in PCM cells. A linear resistance change under identical pulses, a resolution of ˜8 bits, and an ON/OFF ratio of ˜102 has been achieved in O-Ti-Sb-Te based PCM, showing its potential application as a synaptic device to improve recognition performance of the neural network.

  14. Adolescent Social Stress Increases Anxiety-like Behavior and Alters Synaptic Transmission, Without Influencing Nicotine Responses, in a Sex-Dependent Manner.

    Science.gov (United States)

    Caruso, Michael J; Crowley, Nicole A; Reiss, Dana E; Caulfield, Jasmine I; Luscher, Bernhard; Cavigelli, Sonia A; Kamens, Helen M

    2018-03-01

    Early-life stress is a risk factor for comorbid anxiety and nicotine use. Because little is known about the factors underlying this comorbidity, we investigated the effects of adolescent stress on anxiety-like behavior and nicotine responses within individual animals. Adolescent male and female C57BL/6J mice were exposed to chronic variable social stress (CVSS; repeated cycles of social isolation + social reorganization) or control conditions from postnatal days (PND) 25-59. Anxiety-like behavior and social avoidance were measured in the elevated plus-maze (PND 61-65) and social approach-avoidance test (Experiment 1: PND 140-144; Experiment 2: 95-97), respectively. Acute nicotine-induced locomotor, hypothermic, corticosterone responses, (Experiment 1: PND 56-59; Experiment 2: PND 65-70) and voluntary oral nicotine consumption (Experiment 1: PND 116-135; Experiment 2: 73-92) were also examined. Finally, we assessed prefrontal cortex (PFC) and nucleus accumbens (NAC) synaptic transmission (PND 64-80); brain regions that are implicated in anxiety and addiction. Mice exposed to adolescent CVSS displayed increased anxiety-like behavior relative to controls. Further, CVSS altered synaptic excitability in PFC and NAC neurons in a sex-specific manner. For males, CVSS decreased the amplitude and frequency of spontaneous excitatory postsynaptic currents in the PFC and NAC, respectively. In females, CVSS decreased the amplitude of spontaneous inhibitory postsynaptic currents in the NAC. Adolescent CVSS did not affect social avoidance or nicotine responses and anxiety-like behavior was not reliably associated with nicotine responses within individual animals. Taken together, complex interactions between PFC and NAC function may contribute to adolescent stress-induced anxiety-like behavior without influencing nicotine responses. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Alterations in Striatal Synaptic Transmission are Consistent across Genetic Mouse Models of Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Damian M Cummings

    2010-05-01

    Full Text Available Since the identification of the gene responsible for HD (Huntington's disease, many genetic mouse models have been generated. Each employs a unique approach for delivery of the mutated gene and has a different CAG repeat length and background strain. The resultant diversity in the genetic context and phenotypes of these models has led to extensive debate regarding the relevance of each model to the human disorder. Here, we compare and contrast the striatal synaptic phenotypes of two models of HD, namely the YAC128 mouse, which carries the full-length huntingtin gene on a yeast artificial chromosome, and the CAG140 KI*** (knock-in mouse, which carries a human/mouse chimaeric gene that is expressed in the context of the mouse genome, with our previously published data obtained from the R6/2 mouse, which is transgenic for exon 1 mutant huntingtin. We show that striatal MSNs (medium-sized spiny neurons in YAC128 and CAG140 KI mice have similar electrophysiological phenotypes to that of the R6/2 mouse. These include a progressive increase in membrane input resistance, a reduction in membrane capacitance, a lower frequency of spontaneous excitatory postsynaptic currents and a greater frequency of spontaneous inhibitory postsynaptic currents in a subpopulation of striatal neurons. Thus, despite differences in the context of the inserted gene between these three models of HD, the primary electrophysiological changes observed in striatal MSNs are consistent. The outcomes suggest that the changes are due to the expression of mutant huntingtin and such alterations can be extended to the human condition.

  16. Facilitation of synaptic transmission and pain responses by CGRP in the amygdala of normal rats

    Directory of Open Access Journals (Sweden)

    Ji Guangchen

    2010-02-01

    Full Text Available Abstract Calcitonin gene-related peptide (CGRP plays an important role in peripheral and central sensitization. CGRP also is a key molecule in the spino-parabrachial-amygdaloid pain pathway. Blockade of CGRP1 receptors in the spinal cord or in the amygdala has antinociceptive effects in different pain models. Here we studied the electrophysiological mechanisms of behavioral effects of CGRP in the amygdala in normal animals without tissue injury. Whole-cell patch-clamp recordings of neurons in the latero-capsular division of the central nucleus of the amygdala (CeLC in rat brain slices showed that CGRP (100 nM increased excitatory postsynaptic currents (EPSCs at the parabrachio-amygdaloid (PB-CeLC synapse, the exclusive source of CGRP in the amygdala. Consistent with a postsynaptic mechanism of action, CGRP increased amplitude, but not frequency, of miniature EPSCs and did not affect paired-pulse facilitation. CGRP also increased neuronal excitability. CGRP-induced synaptic facilitation was reversed by an NMDA receptor antagonist (AP5, 50 μM or a PKA inhibitor (KT5720, 1 μM, but not by a PKC inhibitor (GF109203X, 1 μM. Stereotaxic administration of CGRP (10 μM, concentration in microdialysis probe into the CeLC by microdialysis in awake rats increased audible and ultrasonic vocalizations and decreased hindlimb withdrawal thresholds. Behavioral effects of CGRP were largely blocked by KT5720 (100 μM but not by GF109203X (100 μM. The results show that CGRP in the amygdala exacerbates nocifensive and affective behavioral responses in normal animals through PKA- and NMDA receptor-dependent postsynaptic facilitation. Thus, increased CGRP levels in the amygdala might trigger pain in the absence of tissue injury.

  17. Molecular Basis of Ion Channels and Receptors Involved in Nerve Excitation, Synaptic Transmission and Muscle Contraction

    Science.gov (United States)

    1993-12-20

    01923. For articles of more than 3 pages. tbe copying fee is $1.75. &~ The paper used in this publication meets the minimum requirements of American ...the chemical transmission concept. Prior to Takamine’s work, J. J. Abel, a distinguished American chemical physiologist, had isolated a substance he...an Increase in cellular cAMP levecls,ý Intracellular nuclco- tides, such as ATP, also regulate the (ITIR CI channel once phosphorylated b PIKA

  18. Adenosine (ADO) released during orthodromic stimulation of the frog sympathetic ganglion inhibits phosphatidylinositol turnover (PI) associated with synaptic transmission

    International Nuclear Information System (INIS)

    Curnish, R.; Bencherif, M.; Rubio, R.; Berne, R.M.

    1986-01-01

    The authors have previously demonstrated that 3 H-purine release was enhanced during synaptic activation of the prelabelled frog sympathetic ganglion. In addition, during orthodromic stimulation, there is an increased 3 H-inositol release (an index of PI) that occurs during the poststimulation period and not during the period of stimulation. They hypothesized that endogenous ADO inhibits PI turnover during orthodromic stimulation. To test this hypothesis (1) they performed experiments to directly measure ADO release in the extracellular fluid by placing the ganglion in a 5 μl drop of Ringer's and let it come to equilibrium with the interstitial fluid, (2) they destroyed endogenous ADO by suffusing adenosine deaminase (ADA) during the stimulation period. Their results show (1) orthodromic stimulation increases release of ADO into the bathing medium, (2) ADA induced an increase of PI during the stimulation period in contrast to an increase seen only during the poststimulation period when ADA was omitted. They conclude that there is dual control of PI during synaptic activity, a stimulatory effect (cause unknown) and a short lived inhibitory effect that is probably caused by adenosine

  19. NMDA Receptors Contribute to Retrograde Synaptic Transmission from Ganglion Cell Photoreceptors to Dopaminergic Amacrine Cells

    Directory of Open Access Journals (Sweden)

    Lei-Lei Liu

    2017-09-01

    Full Text Available Recently, a line of evidence has demonstrated that the vertebrate retina possesses a novel retrograde signaling pathway. In this pathway, phototransduction is initiated by the photopigment melanopsin, which is expressed in a small population of retinal ganglion cells. These ganglion cell photoreceptors then signal to dopaminergic amacrine cells (DACs through glutamatergic synapses, influencing visual light adaptation. We have previously demonstrated that in Mg2+-containing solution, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA receptors mediate this glutamatergic transmission. Here, we demonstrate that removing extracellular Mg2+ enhances melanopsin-based DAC light responses at membrane potentials more negative than −40 mV. Melanopsin-based responses in Mg2+-free solution were profoundly suppressed by the selective N-methyl-D-aspartate (NMDA receptor antagonist D-AP5. In addition, application of NMDA to the retina produced excitatory inward currents in DACs. These data strongly suggest that DACs express functional NMDA receptors. We further found that in the presence of Mg2+, D-AP5 reduced the peak amplitude of melanopsin-based DAC responses by ~70% when the cells were held at their resting membrane potential (−50 mV, indicating that NMDA receptors are likely to contribute to retrograde signal transmission to DACs under physiological conditions. Moreover, our data show that melanopsin-based NMDA-receptor-mediated responses in DACs are suppressed by antagonists specific to either the NR2A or NR2B receptor subtype. Immunohistochemical results show that NR2A and NR2B subunits are expressed on DAC somata and processes. These results suggest that DACs express functional NMDA receptors containing both NR2A and NR2B subunits. Collectively, our data reveal that, along with AMPA receptors, NR2A- and NR2B-containing NMDA receptors mediate retrograde signal transmission from ganglion cell photoreceptors to DACs.

  20. Inhibitory synaptic transmission in isolated patches of membrane from cultured rat spinal cord and medullary neurons.

    Science.gov (United States)

    Lewis, C A; Faber, D S

    1996-07-01

    1. To quantify the variability in the characteristics of inhibitory glycinergic and GABAergic currents at single synaptic connections between cultured rat embryonic spinal cord or medullary neurons, we have used patch-clamp techniques to record miniature inhibitory postsynaptic currents (mIPSCs) in cell-attached patches. Experiments were performed with the patch pipette containing either a low-calcium internal saline to allow comparison with subsequent whole cell recordings or external saline with tetrodotoxin, DL-2-amino-5-phosphonovaleric acid, and 6-cyano-7-nitroquinoxaline-2,3-dione, a solution that is more appropriate for bathing a nerve terminal. 2. The mIPSCs recorded from the synapses restricted to the cell-attached patches were characterized by their times to peak, amplitudes, and time constants of decay. The degree of variability in these characteristics was quantified with the use of the following model-independent parameters: the coefficient of variation, skewness, and kurtosis. The distribution of time to peak values has a mean value of 5.6 +/- 0.5 (SE) ms, has the lowest coefficient of variation (0.33 +/- 0.01), is fairly symmetrical, and has a Gaussian shape with respect to peakedness. On the other hand, both the amplitude and decay time constant distributions are highly skewed and more peaked than Gaussian distributions. The mean amplitude is -6.6 +/- 0.6 pA with a coefficient of variation of 0.60 +/- 0.05, whereas the mean decay time constant is 22.8 +/- 1.0 ms with a coefficient of variation of 0.81 +/- 0.03. 3. The amplitude distributions for spontaneous inhibitory currents recorded from cell-attached patches are best fitted by the sum of multiple Gaussians. The coefficient of variation for the first Gaussian peak fitted to the amplitude distributions is 0.290 +/- 0.028. 4. Decay time distributions were consistently best fitted by the sum of four Gaussians with decay constants as follows: D1 = 5.7 +/- 0.2 ms (n = 12), D2 = 11.2 +/- 0.7 ms (n = 11

  1. The Auxiliary Calcium Channel Subunit α2δ4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors.

    Science.gov (United States)

    Wang, Yuchen; Fehlhaber, Katherine E; Sarria, Ignacio; Cao, Yan; Ingram, Norianne T; Guerrero-Given, Debbie; Throesch, Ben; Baldwin, Kristin; Kamasawa, Naomi; Ohtsuka, Toshihisa; Sampath, Alapakkam P; Martemyanov, Kirill A

    2017-03-22

    Neural circuit wiring relies on selective synapse formation whereby a presynaptic release apparatus is matched with its cognate postsynaptic machinery. At metabotropic synapses, the molecular mechanisms underlying this process are poorly understood. In the mammalian retina, rod photoreceptors form selective contacts with rod ON-bipolar cells by aligning the presynaptic voltage-gated Ca 2+ channel directing glutamate release (Ca V 1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, α2δ4, which complexes with Ca V 1.4 and the rod synaptogenic mediator, ELFN1, for trans-synaptic alignment with mGluR6. Eliminating α2δ4 in mice abolishes rod synaptogenesis and synaptic transmission to rod ON-bipolar cells, and disrupts postsynaptic mGluR6 clustering. We further find that in rods, α2δ4 is crucial for organizing synaptic ribbons and setting Ca V 1.4 voltage sensitivity. In cones, α2δ4 is essential for Ca V 1.4 function, but is not required for ribbon organization, synaptogenesis, or synaptic transmission. These findings offer insights into retinal pathologies associated with α2δ4 dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Role for astroglial α1-adrenoreceptors in gliotransmission and control of synaptic plasticity in the neocortex

    Directory of Open Access Journals (Sweden)

    Yuriy ePankratov

    2015-06-01

    Full Text Available Communication between neuronal and glial cells is thought to be very important for many brain functions. Acting via release of gliotransmitters, astrocytes can modulate synaptic strength. The mechanisms underlying gliotransmission remain uncertain with exocytosis being the most intriguing and debated pathway.We demonstrate that astroglial α1-adrenoreceptors are very sensitive to noradrenaline and make a significant contribution to intracellular Ca2+-signalling in layer 2/3 neocortical astrocytes. We also show that astroglial α1-adrenoreceptors are prone to desensitization upon prolonged exposure to noradrenaline.We show that within neocortical slices, α-1adrenoreceptors can activate vesicular release of ATP and D-serine from cortical astrocytes which initiate a burst of ATP receptor-mediated currents in adjacent pyramidal neurons. These purinergic currents can be inhibited by intracellular perfusion of astrocytes with Tetanus Toxin light chain, verifying their origin via astroglial exocytosis.We show that α1 adrenoreceptor-activated release of gliotransmitters is important for the induction of synaptic plasticity in the neocortex:long-term potentiation (LTP of neocortical excitatory synaptic potentials can be abolished by the selective α1-adrenoreceptor antagonist terazosin. We show that weak sub-threshold theta-burst stimulation can induce LTP when astrocytes are additionally activated by 1 μM noradrenaline. This facilitation is dependent on the activation of neuronal ATP receptors and is abolished in neocortical slices from dn-SNARE mice which have impaired glial exocytosis. Importantly, facilitation of LTP by noradrenaline can be significantly reduced by perfusion of individual astrocytes with Tetanus Toxin. Our results strongly support the physiological importance of astroglial adrenergic signalling and exocytosis of gliotransmitters for modulation of synaptic transmission and plasticity .

  3. Real-time controller for hydrostatic transmission

    OpenAIRE

    2014-01-01

    M. Ing. (Electrical and Electronic Engineering) This dissertation describes the development of a modular real-time controller implemented on a personal computer for a hydrostatically driven vehicle. In such a vehicle the conventional mechanical transmission is replaced with a hydrostatic pump and two hydrostatic motors, making use of the secondary control principle. The infinitely variable transmission and wheel pair controller gives the vehicle superior traction and mobility over conventi...

  4. Different forms of glycine- and GABAA-receptor mediated inhibitory synaptic transmission in mouse superficial and deep dorsal horn neurons

    Directory of Open Access Journals (Sweden)

    Brichta Alan M

    2009-11-01

    Full Text Available Abstract Background Neurons in superficial (SDH and deep (DDH laminae of the spinal cord dorsal horn receive sensory information from skin, muscle, joints and viscera. In both regions, glycine- (GlyR and GABAA-receptors (GABAARs contribute to fast synaptic inhibition. For rat, several types of GABAAR coexist in the two regions and each receptor type provides different contributions to inhibitory tone. Recent work in mouse has discovered an additional type of GlyR, (containing alpha 3 subunits in the SDH. The contribution of differing forms of the GlyR to sensory processing in SDH and DDH is not understood. Methods and Results Here we compare fast inhibitory synaptic transmission in mouse (P17-37 SDH and DDH using patch-clamp electrophysiology in transverse spinal cord slices (L3-L5 segments, 23°C. GlyR-mediated mIPSCs were detected in 74% (25/34 and 94% (25/27 of SDH and DDH neurons, respectively. In contrast, GABAAR-mediated mIPSCs were detected in virtually all neurons in both regions (93%, 14/15 and 100%, 18/18. Several Gly- and GABAAR properties also differed in SDH vs. DDH. GlyR-mediated mIPSC amplitude was smaller (37.1 ± 3.9 vs. 64.7 ± 5.0 pA; n = 25 each, decay time was slower (8.5 ± 0.8 vs. 5.5 ± 0.3 ms, and frequency was lower (0.15 ± 0.03 vs. 0.72 ± 0.13 Hz in SDH vs. DDH neurons. In contrast, GABAAR-mediated mIPSCs had similar amplitudes (25.6 ± 2.4, n = 14 vs. 25. ± 2.0 pA, n = 18 and frequencies (0.21 ± 0.08 vs. 0.18 ± 0.04 Hz in both regions; however, decay times were slower (23.0 ± 3.2 vs. 18.9 ± 1.8 ms in SDH neurons. Mean single channel conductance underlying mIPSCs was identical for GlyRs (54.3 ± 1.6 pS, n = 11 vs. 55.7 ± 1.8, n = 8 and GABAARs (22.7 ± 1.7 pS, n = 10 vs. 22.4 ± 2.0 pS, n = 11 in both regions. We also tested whether the synthetic endocanabinoid, methandamide (methAEA, had direct effects on Gly- and GABAARs in each spinal cord region. MethAEA (5 μM reduced GlyR-mediated mIPSC frequency in SDH

  5. Klotho regulates CA1 hippocampal synaptic plasticity.

    Science.gov (United States)

    Li, Qin; Vo, Hai T; Wang, Jing; Fox-Quick, Stephanie; Dobrunz, Lynn E; King, Gwendalyn D

    2017-04-07

    Global klotho overexpression extends lifespan while global klotho-deficiency shortens it. As well, klotho protein manipulations inversely regulate cognitive function. Mice without klotho develop rapid onset cognitive impairment before they are 2months old. Meanwhile, adult mice overexpressing klotho show enhanced cognitive function, particularly in hippocampal-dependent tasks. The cognitive enhancing effects of klotho extend to humans with a klotho polymorphism that increases circulating klotho and executive function. To affect cognitive function, klotho could act in or on the synapse to modulate synaptic transmission or plasticity. However, it is not yet known if klotho is located at synapses, and little is known about its effects on synaptic function. To test this, we fractionated hippocampi and detected klotho expression in both pre and post-synaptic compartments. We find that loss of klotho enhances both pre and post-synaptic measures of CA1 hippocampal synaptic plasticity at 5weeks of age. However, a rapid loss of synaptic enhancement occurs such that by 7weeks, when mice are cognitively impaired, there is no difference from wild-type controls. Klotho overexpressing mice show no early life effects on synaptic plasticity, but decreased CA1 hippocampal long-term potentiation was measured at 6months of age. Together these data suggest that klotho affects cognition, at least in part, by regulating hippocampal synaptic plasticity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Modelling onchocerciasis transmission and control

    NARCIS (Netherlands)

    A.P. Plaisier (Anton)

    1996-01-01

    textabstractIn 1990 the World Health Organization (WHO) coordinated Onchocerciasis Control Programme in West Africa (OCP) used this slogan for evaluating fifteen years of control of the parasitic disease onchocerciasis and for expressing its optimism about the future. Based on the obvious success of

  7. Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats.

    Directory of Open Access Journals (Sweden)

    Tomoko Inagaki

    Full Text Available Transient global forebrain ischemia causes selective, delayed death of hippocampal CA1 pyramidal neurons, and the ovarian hormone 17β-estradiol (E2 reduces neuronal loss in young and middle-aged females. The neuroprotective efficacy of E2 after a prolonged period of hormone deprivation is controversial, and few studies examine this issue in aged animals given E2 treatment after induction of ischemia.The present study investigated the neuroprotective effects of E2 administered immediately after global ischemia in aged female rats (15-18 months after 6 months of hormone deprivation. We also used electrophysiological methods to assess whether CA1 synapses in the aging hippocampus remain responsive to E2 after prolonged hormone withdrawal. Animals were ovariohysterectomized and underwent 10 min global ischemia 6 months later. A single dose of E2 (2.25 µg infused intraventricularly after reperfusion significantly increased cell survival, with 45% of CA1 neurons surviving vs 15% in controls. Ischemia also induced moderate loss of CA3/CA4 pyramidal cells. Bath application of 1 nM E2 onto brain slices derived from non-ischemic aged females after 6 months of hormone withdrawal significantly enhanced excitatory transmission at CA1 synapses evoked by Schaffer collateral stimulation, and normal long-term potentiation (LTP was induced. The magnitude of LTP and of E2 enhancement of field excitatory postsynaptic potentials was indistinguishable from that recorded in slices from young rats.The data demonstrate that 1 acute post-ischemic infusion of E2 into the brain ventricles is neuroprotective in aged rats after 6 months of hormone deprivation; and 2 E2 enhances synaptic transmission in CA1 pyramidal neurons of aged long-term hormone deprived females. These findings provide evidence that the aging hippocampus remains responsive to E2 administered either in vivo or in vitro even after prolonged periods of hormone withdrawal.

  8. Control of Homeostatic Synaptic Plasticity by AKAP-Anchored Kinase and Phosphatase Regulation of Ca2+-Permeable AMPA Receptors.

    Science.gov (United States)

    Sanderson, Jennifer L; Scott, John D; Dell'Acqua, Mark L

    2018-02-13

    Neuronal information processing requires multiple forms of synaptic plasticity mediated by NMDA and AMPA-type glutamate receptors (NMDAR, AMPAR). These plasticity mechanisms include long-term potentiation (LTP) and depression (LTD), which are Hebbian, homosynaptic mechanisms locally regulating synaptic strength of specific inputs, and homeostatic synaptic scaling, which is a heterosynaptic mechanism globally regulating synaptic strength across all inputs. In many cases, LTP and homeostatic scaling regulate AMPAR subunit composition to increase synaptic strength via incorporation of Ca 2+ -permeable receptors (CP-AMPAR) containing GluA1, but lacking GluA2, subunits. Previous work by our group and others demonstrated that anchoring of the kinase PKA and the phosphatase calcineurin (CaN) to A-kinase anchoring protein (AKAP) 150 play opposing roles in regulation of GluA1 Ser845 phosphorylation and CP-AMPAR synaptic incorporation during hippocampal LTP and LTD. Here, using both male and female knock-in mice that are deficient in PKA or CaN anchoring, we show that AKAP150-anchored PKA and CaN also play novel roles in controlling CP-AMPAR synaptic incorporation during homeostatic plasticity in hippocampal neurons. We found that genetic disruption of AKAP-PKA anchoring prevented increases in Ser845 phosphorylation and CP-AMPAR synaptic recruitment during rapid homeostatic synaptic scaling-up induced by combined blockade of action potential firing and NMDAR activity. In contrast, genetic disruption of AKAP-CaN anchoring resulted in basal increases in Ser845 phosphorylation and CP-AMPAR synaptic activity that blocked subsequent scaling-up by preventing additional CP-AMPAR recruitment. Thus, the balanced, opposing phospho-regulation provided by AKAP-anchored PKA and CaN is essential for control of both Hebbian and homeostatic plasticity mechanisms that require CP-AMPARs. Significance statement: Neuronal circuit function is shaped by multiple forms of activity

  9. Flexible AC transmission systems modelling and control

    CERN Document Server

    Zhang, Xiao-Ping; Pal, Bikash

    2012-01-01

    The extended and revised second edition of this successful monograph presents advanced modeling, analysis and control techniques of Flexible AC Transmission Systems (FACTS). The book covers comprehensively a range of power-system control problems: from steady-state voltage and power flow control, to voltage and reactive power control, to voltage stability control, to small signal stability control using FACTS controllers. In the six years since the first edition of the book has been published research on the FACTS has continued to flourish while renewable energy has developed into a mature and

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

    Science.gov (United States)

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

    2013-09-05

    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. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission.

    Science.gov (United States)

    Kittler, Josef T; Chen, Guojun; Honing, Stephan; Bogdanov, Yury; McAinsh, Kristina; Arancibia-Carcamo, I Lorena; Jovanovic, Jasmina N; Pangalos, Menelas N; Haucke, Volker; Yan, Zhen; Moss, Stephen J

    2005-10-11

    The efficacy of synaptic inhibition depends on the number of gamma-aminobutyric acid type A receptors (GABA(A)Rs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABA(A)R endocytosis and, hence, surface receptor number. Here, we identify a previously uncharacterized atypical AP2 binding motif conserved within the intracellular domains of all GABA(A)R beta subunit isoforms. This AP2 binding motif (KTHLRRRSSQLK in the beta3 subunit) incorporates the major sites of serine phosphorylation within receptor beta subunits, and phosphorylation within this site inhibits AP2 binding. Furthermore, by using surface plasmon resonance, we establish that a peptide (pepbeta3) corresponding to the AP2 binding motif in the GABA(A)R beta3 subunit binds to AP2 with high affinity only when dephosphorylated. Moreover, the pepbeta3 peptide, but not its phosphorylated equivalent (pepbeta3-phos), enhanced the amplitude of miniature inhibitory synaptic current and whole cell GABA(A)R current. These effects of pepbeta3 on GABA(A)R current were occluded by inhibitors of dynamin-dependent endocytosis supporting an action of pepbeta3 on GABA(A)R endocytosis. Therefore phospho-dependent regulation of AP2 binding to GABA(A)Rs provides a mechanism to specify receptor cell surface number and the efficacy of inhibitory synaptic transmission.

  12. Facts controllers in power transmission and distribution

    CERN Document Server

    Padiyar, KR

    2007-01-01

    About the Book: The emerging technology of Flexible AC Transmission System (FACTS) enables planning and operation of power systems at minimum costs, without compromising security. This is based on modern high power electronic systems that provide fast controllability to ensure ''flexible'' operation under changing system conditions. This book presents a comprehensive treatment of the subject by discussing the operating principles, mathematical models, control design and issues that affect the applications. The concepts are explained often with illustrative examples and case studies. In partic

  13. Vectors control importance on leishmaniasis transmission

    Directory of Open Access Journals (Sweden)

    Alfredo M. Oliveira Filho

    1994-09-01

    Full Text Available We reviewed the control of transmission of leishmaniasis regarding chemotherapy, reservoirs elimination, vaccination and insect control through the use of chemical insecticides. We also discussed complementary measures like monitoring traps, impregnated bednets and curtains, repelents, pheromones, biological control, etc. A cost comparison of insecticide interventions through the use of products belonging to the four main chemical groups was also alone, comparing together conventional formulations versus a slow-release insecticide developed by the Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro. We finally did recommendations on the situation that would justify an insecticide intervention to control sandflies.

  14. Disruption of hippocampal synaptic transmission and long-term potentiation by psychoactive synthetic cannabinoid 'Spice' compounds: comparison with Δ9-tetrahydrocannabinol.

    Science.gov (United States)

    Hoffman, Alexander F; Lycas, Matthew D; Kaczmarzyk, Jakub R; Spivak, Charles E; Baumann, Michael H; Lupica, Carl R

    2017-03-01

    There has been a marked increase in the availability of synthetic drugs designed to mimic the effects of marijuana. These cannabimimetic drugs, sold illicitly as 'Spice' and related products, are associated with serious medical complications in some users. In vitro studies suggest that synthetic cannabinoids in these preparations are potent agonists at central cannabinoid CB1 receptors (CB1Rs), but few investigations have delineated their cellular effects, particularly in comparison with the psychoactive component of marijuana, Δ 9 -tetrahydrocannabinol (Δ 9 -THC). We compared the ability of three widely abused synthetic cannabinoids and Δ 9 -THC to alter glutamate release and long-term potentiation in the mouse hippocampus. JWH-018 was the most potent inhibitor of hippocampal synaptic transmission (EC 50 ~15 nM), whereas its fluoropentyl derivative, AM2201, inhibited synaptic transmission with slightly lower potency (EC 50 ~60 nM). The newer synthetic cannabinoid, XLR-11, displayed much lower potency (EC 50 ~900 nM) that was similar to Δ 9 -THC (EC 50 ~700 nM). The effects of all compounds occurred via activation of CB1Rs, as demonstrated by reversal with the selective antagonist/inverse agonist AM251 or the neutral CB1R antagonist PIMSR1. Moreover, AM2201 was without effect in the hippocampus of transgenic mice lacking the CB1R. Hippocampal slices exposed to either synthetic cannabinoids or Δ 9 -THC exhibited significantly impaired long-term potentiation (LTP). We find that, compared with Δ 9 -THC, the first-generation cannabinoids found in Spice preparations display higher potency, whereas a recent synthetic cannabinoid is roughly equipotent with Δ 9 -THC. The disruption of synaptic function by these synthetic cannabinoids is likely to lead to profound impairments in cognitive and behavioral function. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  15. Spike-timing control by dendritic plateau potentials in the presence of synaptic barrages

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    Adam Sol Shai

    2014-08-01

    Full Text Available Apical and tuft dendrites of pyramidal neurons support regenerative electrical potentials, giving rise to long-lasting (~ hundreds of milliseconds and strong (~50 mV from rest depolarizations. Such plateau events rely on clustered glutamatergic input, can be mediated by calcium and NMDA currents, and often generate somatic depolarizations that last for the time course of the dendritic plateau event. We address the computational significance of such single-neuron processing via reduced but biophysically realistic modeling. We introduce a model based on two discrete integration zones, a somatic and a dendritic one, that communicate via a long plateau-conductance. We show principled differences in the way dendritic versus somatic inhibition controls spike timing, and demonstrate how this could implement a mechanism of spike time control in the face of barrages of synaptic inputs.

  16. Microbial Rhodopsin Optogenetic Tools: Application for Analyses of Synaptic Transmission and of Neuronal Network Activity in Behavior.

    Science.gov (United States)

    Glock, Caspar; Nagpal, Jatin; Gottschalk, Alexander

    2015-01-01

    Optogenetics was introduced as a new technology in the neurosciences about a decade ago (Zemelman et al., Neuron 33:15-22, 2002; Boyden et al., Nat Neurosci 8:1263-1268, 2005; Nagel et al., Curr Biol 15:2279-2284, 2005; Zemelman et al., Proc Natl Acad Sci USA 100:1352-1357, 2003). It combines optics, genetics, and bioengineering to render neurons sensitive to light, in order to achieve a precise, exogenous, and noninvasive control of membrane potential, intracellular signaling, network activity, or behavior (Rein and Deussing, Mol Genet Genomics 287:95-109, 2012; Yizhar et al., Neuron 71:9-34, 2011). As C. elegans is transparent, genetically amenable, has a small nervous system mapped with synapse resolution, and exhibits a rich behavioral repertoire, it is especially open to optogenetic methods (White et al., Philos Trans R Soc Lond B Biol Sci 314:1-340, 1986; De Bono et al., Optogenetic actuation, inhibition, modulation and readout for neuronal networks generating behavior in the nematode Caenorhabditis elegans, In: Hegemann P, Sigrist SJ (eds) Optogenetics, De Gruyter, Berlin, 2013; Husson et al., Biol Cell 105:235-250, 2013; Xu and Kim, Nat Rev Genet 12:793-801, 2011). Optogenetics, by now an "exploding" field, comprises a repertoire of different tools ranging from transgenically expressed photo-sensor proteins (Boyden et al., Nat Neurosci 8:1263-1268, 2005; Nagel et al., Curr Biol 15:2279-2284, 2005) or cascades (Zemelman et al., Neuron 33:15-22, 2002) to chemical biology approaches, using photochromic ligands of endogenous channels (Szobota et al., Neuron 54:535-545, 2007). Here, we will focus only on optogenetics utilizing microbial rhodopsins, as these are most easily and most widely applied in C. elegans. For other optogenetic tools, for example the photoactivated adenylyl cyclases (PACs, that drive neuronal activity by increasing synaptic vesicle priming, thus exaggerating rather than overriding the intrinsic activity of a neuron, as occurs with

  17. 5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

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    Lucia eCiranna

    2014-08-01

    Full Text Available Serotonin type 7 receptors (5-HT7 are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD, including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD.

  18. Mathematical modeling for control zika transmission

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    Nugraha, Edwin Setiawan; Naiborhu, Janson; Nuraini, Nuning; Ahmadin

    2017-11-01

    After 70 years since the zika was identified in Uganda, zika is now documented in 62 countries. In general, people infected with this disease do not experience severe conditions, but for pregnant women can cause serious problems because the zika can spread to the fetus. One result, zika can cause abnormalities in the fetal brain called microcephaly. Control and prevention are very important to reduce the spread of this disease. Here, we discussed the problem of optimal control in the model of zika transmission associated with the use of insecticide-treated nets (ITN) and indoor residual spraying (IRS). Using the approach of optimal control theory, we completed the objective function so that the infected population and its control cost are minimum. Numerically using the Forward-Backward Sweep Method, we obtained the control design of ITN and IRS as a function of time. The results show that the use of both simultaneously is more effective in reducing the population of infection than the use of ITN alone or the IRS alone.

  19. Long-lasting nicotinic modulation of GABAergic synaptic transmission in the rat nucleus accumbens associated with behavioural sensitization to amphetamine

    NARCIS (Netherlands)

    de Rover, M.; Mansvelder, H.D.; Lodder, J.C.; Wardeh, G.; Schoffelmeer, A.N.M.; Brussaard, A.B.

    2004-01-01

    A robust increase in dopaminergic transmission in the nucleus accumbens (NAc) shell has been reported to be consistently associated with the long-term expression of behavioural sensitization to drugs of abuse. However, little is known about how this affects the neuronal network of the NAc. We made

  20. Turing mechanism for homeostatic control of synaptic density during C. elegans growth

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    Brooks, Heather A.; Bressloff, Paul C.

    2017-07-01

    We propose a mechanism for the homeostatic control of synapses along the ventral cord of Caenorhabditis elegans during development, based on a form of Turing pattern formation on a growing domain. C. elegans is an important animal model for understanding cellular mechanisms underlying learning and memory. Our mathematical model consists of two interacting chemical species, where one is passively diffusing and the other is actively trafficked by molecular motors, which switch between forward and backward moving states (bidirectional transport). This differs significantly from the standard mechanism for Turing pattern formation based on the interaction between fast and slow diffusing species. We derive evolution equations for the chemical concentrations on a slowly growing one-dimensional domain, and use numerical simulations to demonstrate the insertion of new concentration peaks as the length increases. Taking the passive component to be the protein kinase CaMKII and the active component to be the glutamate receptor GLR-1, we interpret the concentration peaks as sites of new synapses along the length of C. elegans, and thus show how the density of synaptic sites can be maintained.

  1. Mechanisms of glycine release, which build up synaptic and extrasynaptic glycine levels: the role of synaptic and non-synaptic glycine transporters.

    Science.gov (United States)

    Harsing, Laszlo G; Matyus, Peter

    2013-04-01

    Glycine is an amino acid neurotransmitter that is involved in both inhibitory and excitatory neurochemical transmission in the central nervous system. The role of glycine in excitatory neurotransmission is related to its coagonist action at glutamatergic N-methyl-D-aspartate receptors. The glycine levels in the synaptic cleft rise many times higher during synaptic activation assuring that glycine spills over into the extrasynaptic space. Another possible origin of extrasynaptic glycine is the efflux of glycine occurring from astrocytes associated with glutamatergic synapses. The release of glycine from neuronal or glial origins exhibits several differences compared to that of biogenic amines or other amino acid neurotransmitters. These differences appear in an external Ca(2+)- and temperature-dependent manner, conferring unique characteristics on glycine as a neurotransmitter. Glycine transporter type-1 at synapses may exhibit neural and glial forms and plays a role in controlling synaptic glycine levels and the spill over rate of glycine from the synaptic cleft into the extrasynaptic biophase. Non-synaptic glycine transporter type-1 regulates extrasynaptic glycine concentrations, either increasing or decreasing them depending on the reverse or normal mode operation of the carrier molecule. While we can, at best, only estimate synaptic glycine levels at rest and during synaptic activation, glycine concentrations are readily measurable via brain microdialysis technique applied in the extrasynaptic space. The non-synaptic N-methyl-D-aspartate receptor may obtain glycine for activation following its spill over from highly active synapses or from its release mediated by the reverse operation of non-synaptic glycine transporter-1. The sensitivity of non-synaptic N-methyl-D-aspartate receptors to glutamate and glycine is many times higher than that of synaptic N-methyl-D-aspartate receptors making the former type of receptor the primary target for drug action. Synaptic

  2. HPV disease transmission protection and control

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    Neil D. Christensen

    2016-09-01

    Full Text Available Human papillomaviruses (HPVs represent a large collection of viral types associated with significant clinical disease of cutaneous and mucosal epithelium. HPV-associated cancers are found in anogenital and oral mucosa, and at various cutaneous sites. Papillomaviruses are highly species and tissue restricted, and these viruses display both mucosotropic, cutaneotropic or dual tropism for epithelial tissues. A subset of HPV types, predominantly mucosal, are also oncogenic and cancers with these HPV types account for more than 200,000 deaths world-wide. Host control of HPV infections requires both innate and adaptive immunity, but the viruses have developed strategies to escape immune detection. Viral proteins can disrupt both innate pathogen-sensing pathways and T-cell based recognition and subsequent destruction of infected tissues. Current treatments to manage HPV infections include mostly ablative strategies in which recurrences are common and only active disease is treated. Although much is known about the papillomavirus life cycle, viral protein functions, and immune responsiveness, we still lack knowledge in a number of key areas of PV biology including tissue tropism, site-specific cancer progression, codon usage profiles, and what are the best strategies to mount an effective immune response to the carcinogenic stages of PV disease. In this review, disease transmission, protection and control are discussed together with questions related to areas in PV biology that will continue to provide productive opportunities of discovery and to further our understanding of this diverse set of human viral pathogens.

  3. Galantamine Prevents Long-Lasting Suppression of Excitatory Synaptic Transmission in CA1 Pyramidal Neurons of Soman-Challenged Guinea Pigs

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    Alexandrova, E. A.; Alkondon, M.; Aracava, Y.; Pereira, E. F. R.; Albuquerque, E. X.

    2014-01-01

    Galantamine, a drug currently approved for treatment of Alzheimer's disease, has recently emerged as an effective pretreatment against the acute toxicity and delayed cognitive deficits induced by organophosphorus (OP) nerve agents, including soman. Since cognitive deficits can result from impaired glutamatergic transmission in the hippocampus, the present study was designed to test the hypothesis that hippocampal glutamatergic transmission declines following an acute exposure to soman and that this effect can be prevented by galantamine. To test this hypothesis, spontaneous excitatory postsynaptic currents (EPSCs) were recorded from CA1 pyramidal neurons in hippocampal slices obtained at 1 h, 24 h, or 6-9 days after guinea pigs were injected with: (i) 1xLD50 soman (26.3 μg/kg, s.c.); (ii) galantamine (8 mg/kg, i.m.) followed 30 min later by 1xLD50 soman, (iii) galantamine (8 mg/kg, i.m.), or (iv) saline (0.5 ml/kg, i.m.). In soman-injected guinea pigs that were not pretreated with galantamine, the frequency of EPSCs was significantly lower than that recorded from saline-injected animals. There was no correlation between the severity of soman-induced acute toxicity and the magnitude of soman-induced reduction of EPSC frequency. Pretreatment with galantamine prevented the reduction of EPSC frequency observed at 6-9 days after the soman challenge. Prevention of soman-induced long-lasting reduction of hippocampal glutamatergic synaptic transmission may be an important determinant of the ability of galantamine to counter cognitive deficits that develop long after an acute exposure to the nerve agent. PMID:25064080

  4. Cortactin Is a Regulator of Activity-Dependent Synaptic Plasticity Controlled by Wingless.

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    Alicea, Daniel; Perez, Marizabeth; Maldonado, Carolina; Dominicci-Cotto, Carihann; Marie, Bruno

    2017-02-22

    Major signaling molecules initially characterized as key early developmental regulators are also essential for the plasticity of the nervous system. Previously, the Wingless (Wg)/Wnt pathway was shown to underlie the structural and electrophysiological changes during activity-dependent synaptic plasticity at the Drosophila neuromuscular junction. A challenge remains to understand how this signal mediates the cellular changes underlying this plasticity. Here, we focus on the actin regulator Cortactin, a major organizer of protrusion, membrane mobility, and invasiveness, and define its new role in synaptic plasticity. We show that Cortactin is present presynaptically and postsynaptically at the Drosophila NMJ and that it is a presynaptic regulator of rapid activity-dependent modifications in synaptic structure. Furthermore, animals lacking presynaptic Cortactin show a decrease in spontaneous release frequency, and presynaptic Cortactin is necessary for the rapid potentiation of spontaneous release frequency that takes place during activity-dependent plasticity. Most interestingly, Cortactin levels increase at stimulated synaptic terminals and this increase requires neuronal activity, de novo transcription and depends on Wg/Wnt expression. Because it is not simply the presence of Cortactin in the presynaptic terminal but its increase that is necessary for the full range of activity-dependent plasticity, we conclude that it probably plays a direct and important role in the regulation of this process. SIGNIFICANCE STATEMENT In the nervous system, changes in activity that lead to modifications in synaptic structure and function are referred to as synaptic plasticity and are thought to be the basis of learning and memory. The secreted Wingless/Wnt molecule is a potent regulator of synaptic plasticity in both vertebrates and invertebrates. Understanding the molecular mechanisms that underlie these plastic changes is a major gap in our knowledge. Here, we identify a

  5. Target-dependent control of synaptic inhibition by endocannabinoids in the thalamus

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    Sun, Yan-Gang; Wu, Chia-Shan; Lu, Hui-Chen; Beierlein, Michael

    2011-01-01

    Inhibitory neurons in the thalamic reticular nucleus (TRN) play a critical role in controlling information transfer between thalamus and neocortex. GABAergic synapses formed by TRN neurons contact both thalamic relay cells as well as neurons within TRN. These two types of synapses are thought to have distinct roles for the generation of thalamic network activity but their selective regulation is poorly understood. In many areas throughout the brain, retrograde signaling mediated by endocannabinoids acts to dynamically regulate synaptic strength over both short and long time scales. However, retrograde signaling has never been demonstrated in the thalamus. Here, we show that depolarization-induced suppression of inhibition (DSI) is prominent at inhibitory synapses interconnecting TRN neurons. DSI is completely abolished in the presence of a cannabinoid receptor 1 (CB1R) antagonist and in mice lacking CB1Rs. DSI is prevented by DAG lipase inhibitors and prolonged by blocking the 2-arachidonoylglycerol (2-AG) degradation enzyme monoacylglycerol lipase (MGL), indicating that it is mediated by the release of 2-AG from TRN neurons. By contrast, DSI is not observed at TRN synapses targeting thalamic relay neurons. A combination of pharmacological and immunohistochemical data indicate that the differences in endocannabinoid signaling at the two synapses are mediated by a synapse-specific targeting of CB1Rs, as well as differences in endocannabinoid release between the two target neurons. Taken together, our results show that endocannabinoids control transmitter release at specific thalamic synapses, and could dynamically regulate sensory information processing and thalamus-mediated synchronous oscillations. PMID:21697372

  6. Translational control by eIF2α phosphorylation regulates vulnerability to the synaptic and behavioral effects of cocaine

    Science.gov (United States)

    Huang, Wei; Placzek, Andon N; Viana Di Prisco, Gonzalo; Khatiwada, Sanjeev; Sidrauski, Carmela; Krnjević, Krešimir; Walter, Peter; Dani, John A; Costa-Mattioli, Mauro

    2016-01-01

    Adolescents are especially prone to drug addiction, but the underlying biological basis of their increased vulnerability remains unknown. We reveal that translational control by phosphorylation of the translation initiation factor eIF2α (p-eIF2α) accounts for adolescent hypersensitivity to cocaine. In adolescent (but not adult) mice, a low dose of cocaine reduced p-eIF2α in the ventral tegmental area (VTA), potentiated synaptic inputs to VTA dopaminergic neurons, and induced drug-reinforced behavior. Like adolescents, adult mice with reduced p-eIF2α-mediated translational control were more susceptible to cocaine-induced synaptic potentiation and behavior. Conversely, like adults, adolescent mice with increased p-eIF2α became more resistant to cocaine's effects. Accordingly, metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD)—whose disruption is postulated to increase vulnerability to drug addiction—was impaired in both adolescent mice and adult mice with reduced p-eIF2α mediated translation. Thus, during addiction, cocaine hijacks translational control by p-eIF2α, initiating synaptic potentiation and addiction-related behaviors. These insights may hold promise for new treatments for addiction. DOI: http://dx.doi.org/10.7554/eLife.12052.001 PMID:26928234

  7. Adenosine A2A Receptors Control Glutamatergic Synaptic Plasticity in Fast Spiking Interneurons of the Prefrontal Cortex

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    Amber Kerkhofs

    2018-03-01

    Full Text Available Adenosine A2A receptors (A2AR are activated upon increased synaptic activity to assist in the implementation of long-term plastic changes at synapses. While it is reported that A2AR are involved in the control of prefrontal cortex (PFC-dependent behavior such as working memory, reversal learning and effort-based decision making, it is not known whether A2AR control glutamatergic synapse plasticity within the medial PFC (mPFC. To elucidate that, we tested whether A2AR blockade affects long-term plasticity (LTP of excitatory post-synaptic potentials in pyramidal neurons and fast spiking (FS interneurons in layer 5 of the mPFC and of population spikes. Our results show that A2AR are enriched at mPFC synapses, where their blockade reversed the direction of plasticity at excitatory synapses onto layer 5 FS interneurons from LTP to long-term depression, while their blockade had no effect on the induction of LTP at excitatory synapses onto layer 5 pyramidal neurons. At the network level, extracellularly induced LTP of population spikes was reduced by A2AR blockade. The interneuron-specificity of A2AR in controlling glutamatergic synapse LTP may ensure that during periods of high synaptic activity, a proper excitation/inhibition balance is maintained within the mPFC.

  8. Translational control by eIF2α phosphorylation regulates vulnerability to the synaptic and behavioral effects of cocaine.

    Science.gov (United States)

    Huang, Wei; Placzek, Andon N; Viana Di Prisco, Gonzalo; Khatiwada, Sanjeev; Sidrauski, Carmela; Krnjević, Krešimir; Walter, Peter; Dani, John A; Costa-Mattioli, Mauro

    2016-03-01

    Adolescents are especially prone to drug addiction, but the underlying biological basis of their increased vulnerability remains unknown. We reveal that translational control by phosphorylation of the translation initiation factor eIF2α (p-eIF2α) accounts for adolescent hypersensitivity to cocaine. In adolescent (but not adult) mice, a low dose of cocaine reduced p-eIF2α in the ventral tegmental area (VTA), potentiated synaptic inputs to VTA dopaminergic neurons, and induced drug-reinforced behavior. Like adolescents, adult mice with reduced p-eIF2α-mediated translational control were more susceptible to cocaine-induced synaptic potentiation and behavior. Conversely, like adults, adolescent mice with increased p-eIF2α became more resistant to cocaine's effects. Accordingly, metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD)-whose disruption is postulated to increase vulnerability to drug addiction-was impaired in both adolescent mice and adult mice with reduced p-eIF2α mediated translation. Thus, during addiction, cocaine hijacks translational control by p-eIF2α, initiating synaptic potentiation and addiction-related behaviors. These insights may hold promise for new treatments for addiction.

  9. Controlled studies of chimpanzee cultural transmission.

    Science.gov (United States)

    Horner, Victoria; de Waal, Frans B M

    2009-01-01

    Following the first long-term field studies of chimpanzees in the 1960s, researchers began to suspect that chimpanzees from different African populations varied in their behavior, and that some of these variations were transmitted through social learning, thus suggesting culture. Additional reports of chimpanzee culture have since accumulated, which involve an increasing amount of behavioral variation that has no obvious ecological or genetic explanation. To date, close to 50 cultural variants have been reported, including subsistence behavior, tool-use, communication signals, and grooming patterns. Nevertheless, field studies lack the experimental controls and manipulations necessary to conclusively demonstrate that the observed variation results from differential invention and social transmission of behavior. This would require that behavioral variants have been learned from others, a question best addressed in a controlled experimental setting. The following chapter details a series of experimental studies at Yerkes National Primate Research Center of Emory University. In each case, the behavior of two captive groups (each N=12 individuals) was compared before and after the introduction of a novel foraging behavior by a trained conspecific "inventor." The studies were designed to investigate (i) the conditions under which chimpanzees learn from one another, (ii) how behaviors are transmitted, (iii) how cultures are maintained over generations. The results emphasize the importance of integrating both fieldwork and experimental approaches. Previous studies have reported deficits in chimpanzees' cultural capacities, but did so after testing them with human models, which are largely irrelevant to the problem at hand. A representative understanding of culture can only be gained when efforts are made to create a naturalistic learning environment in which chimpanzees have opportunities to learn spontaneously from conspecifics in a familiar social setting.

  10. Research on Travel Control System of Hydrostatic Transmission Chassis

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    Zhao Liang

    2017-01-01

    Full Text Available Aiming at the control problem of driving system of hydrostatic transmission chassis, the composition of the control system of hydrostatic transmission chassis is introduced and the control method of dual engine is solved. According to the number of driving axles in driving process, The external characteristic curve of the engine controls the variable hydraulic pump by one parameter, controls the rotational speed of the variable hydraulic motor according to the change of the vehicle speed, and introduces the control flow of the brake system. It provides a reference for the design of driving control system of multi-axis hydrostatic transmission chassis.

  11. Monoallelic deletion of the microRNA biogenesis gene Dgcr8 produces deficits in the development of excitatory synaptic transmission in the prefrontal cortex

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    Barker Alison J

    2011-04-01

    Full Text Available Abstract Background Neuronal phenotypes associated with hemizygosity of individual genes within the 22q11.2 deletion syndrome locus hold potential towards understanding the pathogenesis of schizophrenia and autism. Included among these genes is Dgcr8, which encodes an RNA-binding protein required for microRNA biogenesis. Dgcr8 haploinsufficient mice (Dgcr8+/- have reduced expression of microRNAs in brain and display cognitive deficits, but how microRNA deficiency affects the development and function of neurons in the cerebral cortex is not fully understood. Results In this study, we show that Dgcr8+/- mice display reduced expression of a subset of microRNAs in the prefrontal cortex, a deficit that emerges over postnatal development. Layer V pyramidal neurons in the medial prefrontal cortex of Dgcr8+/- mice have altered electrical properties, decreased complexity of basal dendrites, and reduced excitatory synaptic transmission. Conclusions These findings demonstrate that precise microRNA expression is critical for the postnatal development of prefrontal cortical circuitry. Similar defects in neuronal maturation resulting from microRNA deficiency could represent endophenotypes of certain neuropsychiatric diseases of developmental onset.

  12. Analysis of mutations in 7 genes associated with neuronal excitability and synaptic transmission in a cohort of children with non-syndromic infantile epileptic encephalopathy.

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    Anna Ka-Yee Kwong

    Full Text Available Epileptic Encephalopathy (EE is a heterogeneous condition in which cognitive, sensory and/or motor functions deteriorate as a consequence of epileptic activity, which consists of frequent seizures and/or major interictal paroxysmal activity. There are various causes of EE and they may occur at any age in early childhood. Genetic mutations have been identified to contribute to an increasing number of children with early onset EE which had been previously considered as cryptogenic. We identified 26 patients with Infantile Epileptic Encephalopathy (IEE of unknown etiology despite extensive workup and without any specific epilepsy syndromic phenotypes. We performed genetic analysis on a panel of 7 genes (ARX, CDKL5, KCNQ2, PCDH19, SCN1A, SCN2A, STXBP1 and identified 10 point mutations [ARX (1, CDKL5 (3, KCNQ2 (2, PCDH19 (1, SCN1A (1, STXBP1 (2] as well as one microdeletion involving both SCN1A and SCN2A. The high rate (42% of mutations suggested that genetic testing of this IEE panel of genes is recommended for cryptogenic IEE with no etiology identified. These 7 genes are associated with channelopathies or synaptic transmission and we recommend early genetic testing if possible to guide the treatment strategy.

  13. LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis.

    Science.gov (United States)

    Matta, Samer; Van Kolen, Kristof; da Cunha, Raquel; van den Bogaart, Geert; Mandemakers, Wim; Miskiewicz, Katarzyna; De Bock, Pieter-Jan; Morais, Vanessa A; Vilain, Sven; Haddad, Dominik; Delbroek, Lore; Swerts, Jef; Chávez-Gutiérrez, Lucía; Esposito, Giovanni; Daneels, Guy; Karran, Eric; Holt, Matthew; Gevaert, Kris; Moechars, Diederik W; De Strooper, Bart; Verstreken, Patrik

    2012-09-20

    LRRK2 is a kinase mutated in Parkinson's disease, but how the protein affects synaptic function remains enigmatic. We identified LRRK2 as a critical regulator of EndophilinA. Using genetic and biochemical studies involving Lrrk loss-of-function mutants and Parkinson-related LRRK2(G2019S) gain-of-kinase function, we show that LRRK2 affects synaptic endocytosis by phosphorylating EndoA at S75, a residue in the BAR domain. We show that LRRK2-mediated EndoA phosphorylation has profound effects on EndoA-dependent membrane tubulation and membrane association in vitro and in vivo and on synaptic vesicle endocytosis at Drosophila neuromuscular junctions in vivo. Our work uncovers a regulatory mechanism that indicates that reduced LRRK2 kinase activity facilitates EndoA membrane association, while increased kinase activity inhibits membrane association. Consequently, both too much and too little LRRK2-dependent EndoA phosphorylation impedes synaptic endocytosis, and we propose a model in which LRRK2 kinase activity is part of an EndoA phosphorylation cycle that facilitates efficient vesicle formation at synapses. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Activated CaMKII Couples GluN2B and Casein Kinase 2 to Control Synaptic NMDA Receptors

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    Antonio Sanz-Clemente

    2013-03-01

    Full Text Available Synaptic activity triggers a profound reorganization of the molecular composition of excitatory synapses. For example, NMDA receptors are removed from synapses in an activity- and calcium-dependent manner, via casein kinase 2 (CK2 phosphorylation of the PDZ ligand of the GluN2B subunit (S1480. However, how synaptic activity drives this process remains unclear because CK2 is a constitutively active kinase, which is not directly regulated by calcium. We show here that activated CaMKII couples GluN2B and CK2 to form a trimolecular complex and increases CK2-mediated phosphorylation of GluN2B S1480. In addition, a GluN2B mutant, which contains an insert to mimic the GluN2A sequence and cannot bind to CaMKII, displays reduced S1480 phosphorylation and increased surface expression. We find that although disrupting GluN2B/CaMKII binding reduces synapse number, it increases synaptic-GluN2B content. Therefore, the GluN2B/CaMKII association controls synapse density and PSD composition in an activity-dependent manner, including recruitment of CK2 for the removal of GluN2B from synapses.

  15. Evaluating the Stream Control Transmission Protocol Using Uppaal

    NARCIS (Netherlands)

    Saini, Shruti; Fehnker, Ansgar; Hermanns, Holger; Höfner, Peter

    2017-01-01

    The Stream Control Transmission Protocol (SCTP) is a Transport Layer protocol that has been proposed as an alternative to the Transmission Control Protocol (TCP) for the Internet of Things (IoT). SCTP, with its four-way handshake mechanism, claims to protect the Server from a Denial-of-Service (DoS)

  16. Behavior control in the sensorimotor loop with short-term synaptic dynamics induced by self-regulating neurons

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    Hazem eToutounji

    2014-05-01

    Full Text Available The behavior and skills of living systems depend on the distributed control provided by specialized and highly recurrent neural networks. Learning and memory in these systems is mediated by a set of adaptation mechanisms, known collectively as neuronal plasticity. Translating principles of recurrent neural control and plasticity to artificial agents has seen major strides, but is usually hampered by the complex interactions between the agent's body and its environment. One of the important standing issues is for the agent to support multiple stable states of behavior, so that its behavioral repertoire matches the requirements imposed by these interactions. The agent also must have the capacity to switch between these states in time scales that are comparable to those by which sensory stimulation varies. Achieving this requires a mechanism of short-term memory that allows the neurocontroller to keep track of the recent history of its input, which finds its biological counterpart in short-term synaptic plasticity. This issue is approached here by deriving synaptic dynamics in recurrent neural networks. Neurons are introduced as self-regulating units with a rich repertoire of dynamics. They exhibit homeostatic properties for certain parameter domains, which result in a set of stable states and the required short-term memory. They can also operate as oscillators, which allow them to surpass the level of activity imposed by their homeostatic operation conditions. Neural systems endowed with the derived synaptic dynamics can be utilized for the neural behavior control of autonomous mobile agents. The resulting behavior depends also on the underlying network structure, which is either engineered, or developed by evolutionary techniques. The effectiveness of these self-regulating units is demonstrated by controlling locomotion of a hexapod with eighteen degrees of freedom, and obstacle-avoidance of a wheel-driven robot.

  17. Modulation of firing and synaptic transmission of serotonergic neurons by intrinsic G protein-coupled receptors and ion channels

    Directory of Open Access Journals (Sweden)

    Takashi eMaejima

    2013-05-01

    Full Text Available Serotonergic neurons project to virtually all regions of the CNS and are consequently involved in many critical physiological functions such as mood, sexual behavior, feeding, sleep/wake cycle, memory, cognition, blood pressure regulation, breathing and reproductive success. Therefore serotonin release and serotonergic neuronal activity have to be precisely controlled and modulated by interacting brain circuits to adapt to specific emotional and environmental states. We will review the current knowledge about G protein-coupled receptors and ion channels involved in the regulation of serotonergic system, how their regulation is modulating the intrinsic activity of serotonergic neurons and its transmitter release and will discuss the latest methods for controlling the modulation of serotonin release and intracellular signaling in serotonergic neurons in vitro and in vivo.

  18. UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis

    Directory of Open Access Journals (Sweden)

    Jiandong Sun

    2015-07-01

    Full Text Available Gated solely by activity-induced changes in intracellular calcium, small-conductance potassium channels (SKs are critical for a variety of functions in the CNS, from learning and memory to rhythmic activity and sleep. While there is a wealth of information on SK2 gating, kinetics, and Ca2+ sensitivity, little is known regarding the regulation of SK2 subcellular localization. We report here that synaptic SK2 levels are regulated by the E3 ubiquitin ligase UBE3A, whose deficiency results in Angelman syndrome and overexpression in increased risk of autistic spectrum disorder. UBE3A directly ubiquitinates SK2 in the C-terminal domain, which facilitates endocytosis. In UBE3A-deficient mice, increased postsynaptic SK2 levels result in decreased NMDA receptor activation, thereby impairing hippocampal long-term synaptic plasticity. Impairments in both synaptic plasticity and fear conditioning memory in UBE3A-deficient mice are significantly ameliorated by blocking SK2. These results elucidate a mechanism by which UBE3A directly influences cognitive function.

  19. Modeling and Control of VSC-HVDC Transmissions

    OpenAIRE

    Latorre, Hector

    2011-01-01

    Presently power systems are being operated under high stress level conditions unforeseen at the moment they were designed. These operating conditions have negatively impacted reliability, controllability and security margins. FACTS devices and HVDC transmissions have emerged as solutions to help power systems to increase the stability margins. VSC-HVDC transmissions are of particular interest since the principal characteristic of this type of transmission is its ability to independently contr...

  20. Security of the data transmission in the industrial control system

    Directory of Open Access Journals (Sweden)

    Marcin Bednarek

    2015-12-01

    Full Text Available The theme of this paper is to present the data transmission security system between the stations of the industrial control system. The possible options for secure communications between process stations, as well as between process and operator station are described. Transmission security mechanism is based on algorithms for symmetric and asymmetric encryption. The authentication process uses a software token algorithm and a one-way hash function. The algorithm for establishing a secured connection between the stations, including the authentication process and encryption of data transmission is given. The process of securing the transmission consists of 4 sub-processes: (I authentication; (II asymmetric, public keys transmission; (III symmetric key transmission; (IV data transmission. The presented process of securing the transmission was realized in the industrial controller and emulator. For this purpose, programming languages in accordance with EN 61131 were used. The functions were implemented as user function blocks. This allows us to include a mixed code in the structure of the block (both: ST and FBD. Available function categories: support of the asymmetric encryption; asymmetric encryption utility functions; support of the symmetric encryption; symmetric encryption utility functions; support of the hash value calculations; utility functions of conversion.[b]Keywords[/b]: transmission security, encryption, authentication, industrial control system

  1. Malaria Prevalence and Local Beliefs in Transmission and Control ...

    African Journals Online (AJOL)

    Malaria prevalence and local beliefs in transmission and control was studied in Ndiowu, a rural community in Anambra State, Nigeria. Microscopy was used to determine the malaria parasite. Structured questionnaire was used to determine the local beliefs on malaria transmission, prevention, and treatment-seeking ...

  2. Reversible optical switching memristors with tunable STDP synaptic plasticity: a route to hierarchical control in artificial intelligent systems.

    Science.gov (United States)

    Jaafar, Ayoub H; Gray, Robert J; Verrelli, Emanuele; O'Neill, Mary; Kelly, Stephen M; Kemp, Neil T

    2017-11-09

    Optical control of memristors opens the route to new applications in optoelectronic switching and neuromorphic computing. Motivated by the need for reversible and latched optical switching we report on the development of a memristor with electronic properties tunable and switchable by wavelength and polarization specific light. The device consists of an optically active azobenzene polymer, poly(disperse red 1 acrylate), overlaying a forest of vertically aligned ZnO nanorods. Illumination induces trans-cis isomerization of the azobenzene molecules, which expands or contracts the polymer layer and alters the resistance of the off/on states, their ratio and retention time. The reversible optical effect enables dynamic control of a memristor's learning properties including control of synaptic potentiation and depression, optical switching between short-term and long-term memory and optical modulation of the synaptic efficacy via spike timing dependent plasticity. The work opens the route to the dynamic patterning of memristor networks both spatially and temporally by light, thus allowing the development of new optically reconfigurable neural networks and adaptive electronic circuits.

  3. The global transmission and control of influenza.

    Directory of Open Access Journals (Sweden)

    Eben Kenah

    2011-05-01

    Full Text Available New strains of influenza spread around the globe via the movement of infected individuals. The global dynamics of influenza are complicated by different patterns of influenza seasonality in different regions of the world. We have released an open-source stochastic mathematical model of the spread of influenza across 321 major, strategically located cities of the world. Influenza is transmitted between cities via infected airline passengers. Seasonality is simulated by increasing the transmissibility in each city at the times of the year when influenza has been observed to be most prevalent. The spatiotemporal spread of pandemic influenza can be understood through clusters of global transmission and links between them, which we identify using the epidemic percolation network (EPN of the model. We use the model to explain the observed global pattern of spread for pandemic influenza A(H1N1 2009-2010 (pandemic H1N1 2009 and to examine possible global patterns of spread for future pandemics depending on the origin of pandemic spread, time of year of emergence, and basic reproductive number (. We also use the model to investigate the effectiveness of a plausible global distribution of vaccine for various pandemic scenarios. For pandemic H1N1 2009, we show that the biggest impact of vaccination was in the temperate northern hemisphere. For pandemics starting in the temperate northern hemisphere in May or April, vaccination would have little effect in the temperate southern hemisphere and a small effect in the tropics. With the increasing interconnectedness of the world's population, we must take a global view of infectious disease transmission. Our open-source, computationally simple model can help public health officials plan for the next pandemic as well as deal with interpandemic influenza.

  4. Synaptic Plasticity and Translation Initiation

    Science.gov (United States)

    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…

  5. Pre-synaptic control of remote fear extinction in the neocortex

    Directory of Open Access Journals (Sweden)

    Gisella eVetere

    2012-06-01

    Full Text Available Consolidation of remote memory enhances immediate early genes induction (IEGs, augments the expression of the presynaptic growth associated protein 43 (GAP-43, and increases the density and size of dendritic spines in anterior cingulate (aCC and infra-limbic (ILC cortices. Remote memory extinction, however, does not uniformly alter consolidation-induced structural changes. In the aCC, the density, but not the size, of spines is reset to pseudo-conditioning levels while novel thin spines are formed in the ILC. Whether IEGs and GAP-43 also undergo region-specific changes upon remote memory extinction is undetermined. Here we confirm in the same batch of mice that c-Fos induction and GAP-43 expression are increased in both the aCC and the ILC 36 days after contextual fear conditioning. We then show that, in both regions, remote memory extinction is associated with decrease of c-Fos induction but no change in GAP-43 expression thus revealing similar, although protein-specific, pre-synaptic adaptations in aCC and ILC neurons. These observations, in addition to our previous report of region-specific post-synaptic structural changes, disclose a complex pattern of extinction-driven neocortical alterations suitable to support erasure or reinstatement of fear according to the environment demand.

  6. Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc

    Science.gov (United States)

    Kühnle, Simone; Mothes, Benedikt; Matentzoglu, Konstantin; Scheffner, Martin

    2013-01-01

    Inactivation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with development of the Angelman syndrome. Recently, it was reported that in mice, loss of E6AP expression results in increased levels of the synaptic protein Arc and a concomitant impaired synaptic function, providing an explanation for some phenotypic features of Angelman syndrome patients. Accordingly, E6AP has been shown to negatively regulate activity-regulated cytoskeleton-associated protein (Arc) and it has been suggested that E6AP targets Arc for ubiquitination and degradation. In our study, we provide evidence that Arc is not a direct substrate for E6AP and binds only weakly to E6AP, if at all. Furthermore, we show that down-regulation of E6AP expression stimulates estradiol-induced transcription of the Arc gene. Thus, we propose that Arc protein levels are controlled by E6AP at the transcriptional rather than at the posttranslational level. PMID:23671107

  7. Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Robert Nisticò

    Full Text Available Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS and its mouse model, experimental autoimmune encephalomyelitis (EAE. In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP induction was favored over long-term depression (LTD in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS.

  8. Implications of asymptomatic carriers for infectious disease transmission and control.

    Science.gov (United States)

    Chisholm, Rebecca H; Campbell, Patricia T; Wu, Yue; Tong, Steven Y C; McVernon, Jodie; Geard, Nicholas

    2018-02-01

    For infectious pathogens such as Staphylococcus aureus and Streptococcus pneumoniae , some hosts may carry the pathogen and transmit it to others, yet display no symptoms themselves. These asymptomatic carriers contribute to the spread of disease but go largely undetected and can therefore undermine efforts to control transmission. Understanding the natural history of carriage and its relationship to disease is important for the design of effective interventions to control transmission. Mathematical models of infectious diseases are frequently used to inform decisions about control and should therefore accurately capture the role played by asymptomatic carriers. In practice, incorporating asymptomatic carriers into models is challenging due to the sparsity of direct evidence. This absence of data leads to uncertainty in estimates of model parameters and, more fundamentally, in the selection of an appropriate model structure. To assess the implications of this uncertainty, we systematically reviewed published models of carriage and propose a new model of disease transmission with asymptomatic carriage. Analysis of our model shows how different assumptions about the role of asymptomatic carriers can lead to different conclusions about the transmission and control of disease. Critically, selecting an inappropriate model structure, even when parameters are correctly estimated, may lead to over- or under-estimates of intervention effectiveness. Our results provide a more complete understanding of the role of asymptomatic carriers in transmission and highlight the importance of accurately incorporating carriers into models used to make decisions about disease control.

  9. 47 CFR 73.1400 - Transmission system monitoring and control.

    Science.gov (United States)

    2010-10-01

    ... monitoring and control. The licensee of an AM, FM, TV or Class A TV station is responsible for assuring that... person at the transmitter site; or (ii) Remote control of the transmission system by a person at the main... operate the station's transmitter and maintain technical parameters within licensed values. (3) A hybrid...

  10. Insulin-Like Growth Factor I Produces an Antidepressant-Like Effect and Elicits N-Methyl-D-Aspartate Receptor Independent Long-Term Potentiation of Synaptic Transmission in Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Colechio, Elizabeth M; Ghoreishi-Haack, Nayereh; Gross, Amanda; Kroes, Roger A; Stanton, Patric K; Moskal, Joseph R

    2015-09-15

    Growth factors play an important role in regulating neurogenesis and synapse formation and may be involved in regulating the antidepressant response to conventional antidepressants. To date, Insulin-like growth factor I (IGFI) is the only growth factor that has shown antidepressant properties in human clinical trials. However, its mechanism of action remains unclear. The antidepressant-like effect of a single IV dose of IGFI was determined using a chronic unpredictable stress paradigm in the rat Porsolt, sucrose preference, novelty-induced hypophagia, and ultrasonic vocalization models. The dependence of the medial prefrontal cortex for these effects was determined by direct medial prefrontal cortex injection followed by Porsolt testing as well as IGFI receptor activation in the medial prefrontal cortex following an optimal IV antidepressant-like dose of IGFI. The effect of IGFI on synaptic transmission and long-term potentiation (LTP) of synaptic strength was assessed in the hippocampus and medial prefrontal cortex. The dependence of these effects on IGFI and AMPA receptor activation and protein synthesis were also determined. IGFI produced a rapid-acting and long-lasting antidepressant-like effect in each of the depression models. These effects were blocked by IGFI and AMPA receptor antagonists, and medial prefrontal cortex was localized. IGFI robustly increased synaptic strength in the hippocampus and medial prefrontal cortex and these effects were IGFI receptor and protein synthesis-dependent but N-methyl-d-aspartate receptor independent. IGFI also robustly facilitated hippocampal metaplasticity 24 hours postdosing. These data support the conclusion that the antidepressant-like effects of IGFI are mediated by a persistent, LTP-like enhancement of synaptic strength requiring both IGFIR activation and ongoing protein synthesis. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  11. Optimal control of diarrhea transmission in a flood evacuation zone

    Science.gov (United States)

    Erwina, N.; Aldila, D.; Soewono, E.

    2014-03-01

    Evacuation of residents and diarrhea disease outbreak in evacuation zone have become serious problem that frequently happened during flood periods. Limited clean water supply and infrastructure in evacuation zone contribute to a critical spread of diarrhea. Transmission of diarrhea disease can be reduced by controlling clean water supply and treating diarrhea patients properly. These treatments require significant amount of budget, which may not be fulfilled in the fields. In his paper, transmission of diarrhea disease in evacuation zone using SIRS model is presented as control optimum problem with clean water supply and rate of treated patients as input controls. Existence and stability of equilibrium points and sensitivity analysis are investigated analytically for constant input controls. Optimum clean water supply and rate of treatment are found using optimum control technique. Optimal results for transmission of diarrhea and the corresponding controls during the period of observation are simulated numerically. The optimum result shows that transmission of diarrhea disease can be controlled with proper combination of water supply and rate of treatment within allowable budget.

  12. Research of pneumatic control transmission system for small irradiation samples

    International Nuclear Information System (INIS)

    Bai Zhongxiong; Zhang Haibing; Rong Ru; Zhang Tao

    2008-01-01

    In order to reduce the absorbed dose damage for the operator, pneumatic control has been adopted to realize the rapid transmission of small irradiation samples. On/off of pneumatic circuit and directions for the rapid transmission system are controlled by the electrical control part. The main program initializes the system and detects the location of the manual/automatic change-over switch, and call for the corresponding subprogram to achieve the automatic or manual operation. Automatic subprogram achieves the automatic sample transmission; Manual subprogram completes the deflation, and back and forth movement of the radiation samples. This paper introduces in detail the implementation of the system, in terms of both hardware and software design. (authors)

  13. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy

    NARCIS (Netherlands)

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

    2007-01-01

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action

  14. Evaluating the Stream Control Transmission Protocol Using Uppaal

    OpenAIRE

    Saini, Shruti; Fehnker, Ansgar

    2017-01-01

    The Stream Control Transmission Protocol (SCTP) is a Transport Layer protocol that has been proposed as an alternative to the Transmission Control Protocol (TCP) for the Internet of Things (IoT). SCTP, with its four-way handshake mechanism, claims to protect the Server from a Denial-of-Service (DoS) attack by ensuring the legitimacy of the Client, which has been a known issue pertaining to the three-way handshake of TCP. This paper compares the handshakes of TCP and SCTP to discuss its shortc...

  15. EDITORIAL: Synaptic electronics Synaptic electronics

    Science.gov (United States)

    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

  16. Transmission and control of Plasmodium knowlesi: a mathematical modelling study.

    Directory of Open Access Journals (Sweden)

    Natsuko Imai

    2014-07-01

    Full Text Available Plasmodium knowlesi is now recognised as a leading cause of malaria in Malaysia. As humans come into increasing contact with the reservoir host (long-tailed macaques as a consequence of deforestation, assessing the potential for a shift from zoonotic to sustained P. knowlesi transmission between humans is critical.A multi-host, multi-site transmission model was developed, taking into account the three areas (forest, farm, and village where transmission is thought to occur. Latin hypercube sampling of model parameters was used to identify parameter sets consistent with possible prevalence in macaques and humans inferred from observed data. We then explore the consequences of increasing human-macaque contact in the farm, the likely impact of rapid treatment, and the use of long-lasting insecticide-treated nets (LLINs in preventing wider spread of this emerging infection.Identified model parameters were consistent with transmission being sustained by the macaques with spill over infections into the human population and with high overall basic reproduction numbers (up to 2267. The extent to which macaques forage in the farms had a non-linear relationship with human infection prevalence, the highest prevalence occurring when macaques forage in the farms but return frequently to the forest where they experience higher contact with vectors and hence sustain transmission. Only one of 1,046 parameter sets was consistent with sustained human-to-human transmission in the absence of macaques, although with a low human reproduction number (R(0H = 1.04. Simulations showed LLINs and rapid treatment provide personal protection to humans with maximal estimated reductions in human prevalence of 42% and 95%, respectively.This model simulates conditions where P. knowlesi transmission may occur and the potential impact of control measures. Predictions suggest that conventional control measures are sufficient at reducing the risk of infection in humans, but they must

  17. Synaptic plasticity, neural circuits, and the emerging role of altered short-term information processing in schizophrenia.

    Science.gov (United States)

    Crabtree, Gregg W; Gogos, Joseph A

    2014-01-01

    Synaptic plasticity alters the strength of information flow between presynaptic and postsynaptic neurons and thus modifies the likelihood that action potentials in a presynaptic neuron will lead to an action potential in a postsynaptic neuron. As such, synaptic plasticity and pathological changes in synaptic plasticity impact the synaptic computation which controls the information flow through the neural microcircuits responsible for the complex information processing necessary to drive adaptive behaviors. As current theories of neuropsychiatric disease suggest that distinct dysfunctions in neural circuit performance may critically underlie the unique symptoms of these diseases, pathological alterations in synaptic plasticity mechanisms may be fundamental to the disease process. Here we consider mechanisms of both short-term and long-term plasticity of synaptic transmission and their possible roles in information processing by neural microcircuits in both health and disease. As paradigms of neuropsychiatric diseases with strongly implicated risk genes, we discuss the findings in schizophrenia and autism and consider the alterations in synaptic plasticity and network function observed in both human studies and genetic mouse models of these diseases. Together these studies have begun to point toward a likely dominant role of short-term synaptic plasticity alterations in schizophrenia while dysfunction in autism spectrum disorders (ASDs) may be due to a combination of both short-term and long-term synaptic plasticity alterations.

  18. Walking Posture Control of Transmission Line Single Arm Inspection Robot

    Science.gov (United States)

    Yan, Yu; Liu, Xiaqing; Li, Jinliang; Ou, Yuexiong

    2017-07-01

    To control the walking posture according to transmission line single arm inspection robot, the robot is divided into normal walking and climbing walking two state, and gives the definition, then based on the state space method of state variable feedback and PD control method is used to control the two states, two kinds of control method of simulation by using Matlab, in the end, the two control methods proposed is validated in the actual circuit structures. The results show that, the proposed control method is rapid and effective, and can meet the needs of practical application.

  19. Diacylglycerol Kinases in the Coordination of Synaptic Plasticity.

    Science.gov (United States)

    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.

  20. Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission

    OpenAIRE

    Kittler, Josef T.; Chen, Guojun; Honing, Stephan; Bogdanov, Yury; McAinsh, Kristina; Arancibia-Carcamo, I. Lorena; Jovanovic, Jasmina N.; Pangalos, Menelas N.; Haucke, Volker; Yan, Zhen; Moss, Stephen J.

    2005-01-01

    The efficacy of synaptic inhibition depends on the number of γ-aminobutyric acid type A receptors (GABAARs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABAAR endocytosis and, hence, surface receptor number. Here, we identify a previously uncharacterized atypical AP2 binding motif conserved within the intracellular domains of all GABAAR β subunit isoforms. This AP2 binding motif (KTHLRRRSSQLK in the β3 subunit) incorporates...

  1. New Intelligent Transmission Concept for Hybrid Mobile Robot Speed Control

    Directory of Open Access Journals (Sweden)

    Nazim Mir-Nasiri

    2005-09-01

    Full Text Available This paper presents a new concept of a mobile robot speed control by using two degree of freedom gear transmission. The developed intelligent speed controller utilizes a gear box which comprises of epicyclic gear train with two inputs, one coupled with the engine shaft and another with the shaft of a variable speed dc motor. The net output speed is a combination of the two input speeds and is governed by the transmission ratio of the planetary gear train. This new approach eliminates the use of a torque converter which is otherwise an indispensable part of all available automatic transmissions, thereby reducing the power loss that occurs in the box during the fluid coupling. By gradually varying the speed of the dc motor a stepless transmission has been achieved. The other advantages of the developed controller are pulling over and reversing the vehicle, implemented by intelligent mixing of the dc motor and engine speeds. This approach eliminates traditional braking system in entire vehicle design. The use of two power sources, IC engine and battery driven DC motor, utilizes the modern idea of hybrid vehicles. The new mobile robot speed controller is capable of driving the vehicle even in extreme case of IC engine failure, for example, due to gas depletion.

  2. New Intelligent Transmission Concept for Hybrid Mobile Robot Speed Control

    Directory of Open Access Journals (Sweden)

    Nazim Mir-Nasiri

    2008-11-01

    Full Text Available This paper presents a new concept of a mobile robot speed control by using two degree of freedom gear transmission. The developed intelligent speed controller utilizes a gear box which comprises of epicyclic gear train with two inputs, one coupled with the engine shaft and another with the shaft of a variable speed dc motor. The net output speed is a combination of the two input speeds and is governed by the transmission ratio of the planetary gear train. This new approach eliminates the use of a torque converter which is otherwise an indispensable part of all available automatic transmissions, thereby reducing the power loss that occurs in the box during the fluid coupling. By gradually varying the speed of the dc motor a stepless transmission has been achieved. The other advantages of the developed controller are pulling over and reversing the vehicle, implemented by intelligent mixing of the dc motor and engine speeds. This approach eliminates traditional braking system in entire vehicle design. The use of two power sources, IC engine and battery driven DC motor, utilizes the modern idea of hybrid vehicles. The new mobile robot speed controller is capable of driving the vehicle even in extreme case of IC engine failure, for example, due to gas depletion..

  3. Control strategies for VSC-based HVDC transmission system

    DEFF Research Database (Denmark)

    Stan, Ana-Irina; Stroe, Daniel Ioan; Silva, Rodrigo Da

    2011-01-01

    Throughout this paper the modeling and control of the VSC-based HVDC systems are investigated and described. Two different control methods capable of controlling such systems are proposed. Both developed control strategies are implemented in the dq synchronous reference frame. In order to analyze...... the behavior of the developed VSC-based HVDC transmission system two study cases are carried out using MATLAB/Simulink. The results obtained from simulations show acceptable performances, of the proposed strategies, when changes in the reference parameters are considered. The active power flow between...... the converters is succesfully achieved while, the independent control of active and reactive power is also verified....

  4. Foxp1 in Forebrain Pyramidal Neurons Controls Gene Expression Required for Spatial Learning and Synaptic Plasticity.

    Science.gov (United States)

    Araujo, Daniel J; Toriumi, Kazuya; Escamilla, Christine O; Kulkarni, Ashwinikumar; Anderson, Ashley G; Harper, Matthew; Usui, Noriyoshi; Ellegood, Jacob; Lerch, Jason P; Birnbaum, Shari G; Tucker, Haley O; Powell, Craig M; Konopka, Genevieve

    2017-11-08

    Genetic perturbations of the transcription factor Forkhead Box P1 ( FOXP1 ) are causative for severe forms of autism spectrum disorder that are often comorbid with intellectual disability. Recent work has begun to reveal an important role for FoxP1 in brain development, but the brain-region-specific contributions of Foxp1 to autism and intellectual disability phenotypes have yet to be determined fully. Here, we describe Foxp1 conditional knock-out ( Foxp1 cKO ) male and female mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus. Foxp1 cKO mice exhibit behavioral phenotypes that are of potential relevance to autism spectrum disorder, including hyperactivity, increased anxiety, communication impairments, and decreased sociability. In addition, Foxp1 cKO mice have gross deficits in learning and memory tasks of relevance to intellectual disability. Using a genome-wide approach, we identified differentially expressed genes in the hippocampus of Foxp1 cKO mice associated with synaptic function and development. Furthermore, using magnetic resonance imaging, we uncovered a significant reduction in the volumes of both the entire hippocampus as well as individual hippocampal subfields of Foxp1 cKO mice. Finally, we observed reduced maintenance of LTP in area CA1 of the hippocampus in these mutant mice. Together, these data suggest that proper expression of Foxp1 in the pyramidal neurons of the forebrain is important for regulating gene expression pathways that contribute to specific behaviors reminiscent of those seen in autism and intellectual disability. In particular, Foxp1 regulation of gene expression appears to be crucial for normal hippocampal development, CA1 plasticity, and spatial learning. SIGNIFICANCE STATEMENT Loss-of-function mutations in the transcription factor Forkhead Box P1 ( FOXP1 ) lead to autism spectrum disorder and intellectual disability. Understanding the potential brain

  5. Statistical Modelling of Synaptic Vesicles Distribution and Analysing their Physical Characteristics

    DEFF Research Database (Denmark)

    Khanmohammadi, Mahdieh

    This Ph.D. thesis deals with mathematical and statistical modeling of synaptic vesicle distribution, shape, orientation and interactions. The first major part of this thesis treats the problem of determining the effect of stress on synaptic vesicle distribution and interactions. Serial section...... transmission electron microscopy is used to acquire images from two experimental groups of rats: 1) rats subjected to a behavioral model of stress and 2) rats subjected to sham stress as the control group. The synaptic vesicle distribution and interactions are modeled by employing a point process approach...... on differences of statistical measures in section and the same measures in between sections. Three-dimensional (3D) datasets are reconstructed by using image registration techniques and estimated thicknesses. We distinguish the effect of stress by estimating the synaptic vesicle densities and modeling...

  6. A Model of Bidirectional Synaptic Plasticity: From Signaling Network to Channel Conductance

    Science.gov (United States)

    Castellani, Gastone C.; Quinlan, Elizabeth M.; Bersani, Ferdinando; Cooper, Leon N.; Shouval, Harel Z.

    2005-01-01

    In many regions of the brain, including the mammalian cortex, the strength of synaptic transmission can be bidirectionally regulated by cortical activity (synaptic plasticity). One line of evidence indicates that long-term synaptic potentiation (LTP) and long-term synaptic depression (LTD), correlate with the phosphorylation/dephosphorylation of…

  7. Computer controllable synchronous shifting of an automatic transmission

    Science.gov (United States)

    Davis, R.I.; Patil, P.B.

    1989-08-08

    A multiple forward speed automatic transmission produces its lowest forward speed ratio when a hydraulic clutch and hydraulic brake are disengaged and a one-way clutch connects a ring gear to the transmission casing. Second forward speed ratio results when the hydraulic clutch is engaged to connect the ring gear to the planetary carrier of a second gear set. Reverse drive and regenerative operation result when an hydraulic brake fixes the planetary and the direction of power flow is reversed. Various sensors produce signals representing the torque at the output of the transmission or drive wheels, the speed of the power source, and the hydraulic pressure applied to a clutch and brake. A control algorithm produces input data representing a commanded upshift, a commanded downshift, a commanded transmission output torque, and commanded power source speed. A microprocessor processes the inputs and produces a response to them in accordance with the execution of a control algorithm. Output or response signals cause selective engagement and disengagement of the clutch and brake at a rate that satisfies the requirements for a short gear ratio change and smooth torque transfer between the friction elements. 6 figs.

  8. Synaptic Determinants of Rett Syndrome

    Science.gov (United States)

    Boggio, Elena M.; Lonetti, Giuseppina; Pizzorusso, Tommaso; Giustetto, Maurizio

    2010-01-01

    There is mounting evidence showing that the structural and molecular organization of synaptic connections is affected both in human patients and in animal models of neurological and psychiatric diseases. As a consequence of these experimental observations, it has been introduced the concept of synapsopathies, a notion describing brain disorders of synaptic function and plasticity. A close correlation between neurological diseases and synaptic abnormalities is especially relevant for those syndromes including also mental retardation in their symptomatology, such as Rett syndrome (RS). RS (MIM312750) is an X-linked dominant neurological disorder that is caused in the majority of cases by mutations in methyl-CpG-binding protein 2 (MeCP2). This review will focus on the current knowledge of the synaptic alterations produced by mutations of the gene MeCP2 in mouse models of RS and will highlight prospects experimental therapies currently in use. Different experimental approaches have revealed that RS could be the consequence of an impairment in the homeostasis of synaptic transmission in specific brain regions. Indeed, several forms of experience-induced neuronal plasticity are impaired in the absence of MeCP2. Based on the results presented in this review, it is reasonable to propose that understanding how the brain is affected by diseases such as RS is at reach. This effort will bring us closer to identify the neurobiological bases of human cognition. PMID:21423514

  9. Synaptic determinants of Rett syndrome

    Directory of Open Access Journals (Sweden)

    Elena M B Boggio

    2010-08-01

    Full Text Available There is mounting evidence showing that the structural and molecular organization of synaptic connections are affected both in human patients and in animal models of neurological and psychiatric diseases. As a consequence of these experimental observations, it has been introduced the concept of synapsopathies, a notion describing brain disorders of synaptic function and plasticity. A close correlation between neurological diseases and synaptic abnormalities is especially relevant for those syndromes including also mental retardation in their symptomatology, such as Rett Syndrome (RS. RS (MIM312750 is an X-linked dominant neurological disorder that is caused, in the majority of cases by mutations in methyl-CpG-binding protein 2 (MeCP2. This review will focus on the current knowledge of the synaptic alterations produced by mutations of the gene MeCP2 in mouse models of RS and will highlight prospects experimental therapies currently in use. Different experimental approaches have revealed that RS could be the consequence of an impairment in the homeostasis of synaptic transmission in specific brain regions. Indeed, several forms of experience-induced neuronal plasticity are impaired in the absence of MeCP2. Based on the results presented in this review, it is reasonable to propose that understanding how the brain is affected by diseases such as RS is at reach. This effort will bring us closer to identify the neurobiological bases of human cognition.

  10. Sylvatic triatominae: a new challenge in vector control transmission.

    Science.gov (United States)

    Guhl, Felipe; Pinto, Nestor; Aguilera, Germán

    2009-07-01

    Over the last 10 years, Uruguay, Chile and Brazil have been certified as being free from disease transmission by Triatoma infestans, the main domiciliated vector for Chagas disease in the Southern Cone countries. This demonstrates that programmes addressing the vector for the disease's transmission are effective. These programmes have resulted in a dramatic decrease in the incidence of Chagas disease in Latin America. Guatemala was certified a few months ago as being free from disease transmission by Rhodnius prolixus, the main domiciliated vector for Chagas disease in Central American countries. However, the main concern for different countries' current control programmes is the continuity and sustainability of future vector control actions. The prevalence and incidence figures for individuals infected by Trypanosoma cruzi in Mexico and Andean and Central American countries highlights the need for broadened strategies in the struggle against the disease and its vectors. A number of triatomine insects are parasite vectors, each with a different life history. Therefore, it is important that new vector control strategies be proposed, keeping in mind that some species are found in peridomiciliary areas and wild ecotopes. The only viable control strategy is to reduce human interactions with vector insects so that the re-infestation and re-colonisation of human habitats will not take place.

  11. Sylvatic triatominae: a new challenge in vector control transmission

    Directory of Open Access Journals (Sweden)

    Felipe Guhl

    2009-07-01

    Full Text Available Over the last 10 years, Uruguay, Chile and Brazil have been certified as being free from disease transmission by Triatoma infestans, the main domiciliated vector for Chagas disease in the Southern Cone countries. This demonstrates that programmes addressing the vector for the disease's transmission are effective. These programmes have resulted in a dramatic decrease in the incidence of Chagas disease in Latin America. Guatemala was certified a few months ago as being free from disease transmission by Rhodnius prolixus, the main domiciliated vector for Chagas disease in Central American countries. However, the main concern for different countries' current control programmes is the continuity and sustainability of future vector control actions. The prevalence and incidence figures for individuals infected by Trypanosoma cruzi in Mexico and Andean and Central American countries highlights the need for broadened strategies in the struggle against the disease and its vectors. A number of triatomine insects are parasite vectors, each with a different life history. Therefore, it is important that new vector control strategies be proposed, keeping in mind that some species are found in peridomiciliary areas and wild ecotopes. The only viable control strategy is to reduce human interactions with vector insects so that the re-infestation and re-colonisation of human habitats will not take place.

  12. Extracellular phosphorylation of a receptor tyrosine kinase controls synaptic localization of NMDA receptors and regulates pathological pain

    Science.gov (United States)

    Sheffler-Collins, Sean I.; Xia, Nan L.; Henderson, Nathan; Tillu, Dipti V.; Hassler, Shayne; Spellman, Daniel S.; Zhang, Guoan; Neubert, Thomas A.; Price, Theodore J.

    2017-01-01

    Extracellular phosphorylation of proteins was suggested in the late 1800s when it was demonstrated that casein contains phosphate. More recently, extracellular kinases that phosphorylate extracellular serine, threonine, and tyrosine residues of numerous proteins have been identified. However, the functional significance of extracellular phosphorylation of specific residues in the nervous system is poorly understood. Here we show that synaptic accumulation of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) and pathological pain are controlled by ephrin-B-induced extracellular phosphorylation of a single tyrosine (p*Y504) in a highly conserved region of the fibronectin type III (FN3) domain of the receptor tyrosine kinase EphB2. Ligand-dependent Y504 phosphorylation modulates the EphB-NMDAR interaction in cortical and spinal cord neurons. Furthermore, Y504 phosphorylation enhances NMDAR localization and injury-induced pain behavior. By mediating inducible extracellular interactions that are capable of modulating animal behavior, extracellular tyrosine phosphorylation of EphBs may represent a previously unknown class of mechanism mediating protein interaction and function. PMID:28719605

  13. Transmission control unit drive based on the AUTOSAR standard

    Science.gov (United States)

    Guo, Xiucai; Qin, Zhen

    2018-03-01

    It is a trend of automotive electronics industry in the future that automotive electronics embedded system development based on the AUTOSAR standard. AUTOSAR automotive architecture standard has proposed the transmission control unit (TCU) development architecture and designed its interfaces and configurations in detail. This essay has discussed that how to drive the TCU based on AUTOSAR standard architecture. The results show that driving the TCU with the AUTOSAR system improves reliability and shortens development cycles.

  14. Analysis of rabies in China: transmission dynamics and control.

    Directory of Open Access Journals (Sweden)

    Juan Zhang

    Full Text Available Human rabies is one of the major public-health problems in China. The number of human rabies cases has increased dramatically in the last 15 years, partially due to the poor understanding of the transmission dynamics of rabies and the lack of effective control measures of the disease. In this article, in order to explore effective control and prevention measures we propose a deterministic model to study the transmission dynamics of rabies in China. The model consists of susceptible, exposed, infectious, and recovered subpopulations of both dogs and humans and describes the spread of rabies among dogs and from infectious dogs to humans. The model simulations agree with the human rabies data reported by the Chinese Ministry of Health. We estimate that the basic reproduction number R₀ = 2 for the rabies transmission in China and predict that the number of the human rabies is decreasing but may reach another peak around 2030. We also perform some sensitivity analysis of R₀ in terms of the model parameters and compare the effects of culling and immunization of dogs. Our study demonstrates that (i reducing dog birth rate and increasing dog immunization coverage rate are the most effective methods for controlling rabies in China; and (ii large scale culling of susceptible dogs can be replaced by immunization of them.

  15. Synaptic Regulation of a Thalamocortical Circuit Controls Depression-Related Behavior

    Directory of Open Access Journals (Sweden)

    Oliver H. Miller

    2017-08-01

    Full Text Available The NMDA receptor (NMDAR antagonist ketamine elicits a long-lasting antidepressant response in patients with treatment-resistant depression. Understanding how antagonism of NMDARs alters synapse and circuit function is pivotal to developing circuit-based therapies for depression. Using virally induced gene deletion, ex vivo optogenetic-assisted circuit analysis, and in vivo chemogenetics and fMRI, we assessed the role of NMDARs in the medial prefrontal cortex (mPFC in controlling depression-related behavior in mice. We demonstrate that post-developmental genetic deletion of the NMDAR subunit GluN2B from pyramidal neurons in the mPFC enhances connectivity between the mPFC and limbic thalamus, but not the ventral hippocampus, and reduces depression-like behavior. Using intersectional chemogenetics, we show that activation of this thalamocortical circuit is sufficient to elicit a decrease in despair-like behavior. Our findings reveal that GluN2B exerts input-specific control of pyramidal neuron innervation and identify a medial dorsal thalamus (MDT→mPFC circuit that controls depression-like behavior.

  16. Terahertz transmission control using polarization-independent metamaterials.

    Science.gov (United States)

    Lee, Sang-Hun; Lee, Dong-Kyu; Kim, Chulki; Jhon, Young Min; Son, Joo-Hiuk; Seo, Minah

    2017-05-15

    We present terahertz (THz) transmission control by several uniquely designed patterns of nano-slot antenna array. Collinearly aligned slot antenna arrays have been usually applied to THz filters with frequency band tunability by their geometry. Normally the amplitude in transmission (reflection) in the collinear alignment case can be varied via rotating the azimuthal angle with a sinusoidal trend, which can limit their utilization and performance only at fixed angle between the alignment of the resonant antennas and incident beam polarization. To pursue a variety of metamaterial uses, here, we present polarization-independent THz filters using variously aligned antenna array (asterisk, chlorophyll, and honeycomb patterns) in such counter-intuitive aspects. Besides, unprecedented multi resonance behaviors were observed in chlorophyll and honeycomb patterns, which can be explained with interferences by adjacent structures. The measured spectra were analyzed by harmonic oscillator model with simplified coupling between slots and their adjacent.

  17. Disturbance of Metabotropic Glutamate Receptor-Mediated Long-Term Depression (mGlu-LTD) of Excitatory Synaptic Transmission in the Rat Hippocampus After Prenatal Immune Challenge.

    Science.gov (United States)

    Cavalier, Mélanie; Ben Sedrine, Azza; Thevenet, Lea; Crouzin, Nadine; Guiramand, Janique; de Jésus Ferreira, Marie-Céleste; Cohen-Solal, Catherine; Barbanel, Gérard; Vignes, Michel

    2018-01-20

    Maternal immune challenge has proved to induce moderate to severe behavioral disabilities in the offspring. Cognitive/behavioral deficits are supported by changes in synaptic plasticity in different brain areas. We have reported previously that prenatal exposure to bacterial LPS could induce inhibition of hippocampal long-term potentiation (LTP) in the CA1 area of the juvenile/adult male offspring associated with spatial learning inabilities. Nevertheless, deficits in plasticity could be observed at earlier stages as shown by the early loss of long-term depression (LTD) in immature animals. Moreover, aberrant forms of plasticity were also evidenced such as the transient occurrence of LTP instead of LTD in 15-25 day-old animals. This switch from LTD to LTP seemed to involve the activation of metabotropic glutamate receptor subtype 1 and 5 (mGlu1/5). We have thus investigated here whether the long-term depression elicited by the direct activation of these receptors (mGlu-LTD) with a selective agonist was also disturbed after prenatal stress. We find that in prenatally stressed rats, mGlu1/5 stimulation elicits long-term potentiation (mGlu-LTP) independently of N-methyl-D-aspartate receptors. Both mGlu5 and mGlu1 receptors are involved in this switch of plasticity. Moreover, this mGlu-LTP is still observed at later developmental stages than previously reported, i.e. after 25 day-old. In addition, increasing synaptic GABA with tiagabine tends to inhibit mGlu-LTP occurrence. By contrast, long-term depression induced with the activation of CB1 cannabinoid receptor is unaffected by prenatal stress. Therefore, prenatal stress drastically alters mGlu1/5-associated plasticity throughout development. MGlu-mediated plasticity is an interesting parameter to probe the long-lasting deficits reported in this model.

  18. Deep mRNA sequencing of the Tritonia diomedea brain transcriptome provides access to gene homologues for neuronal excitability, synaptic transmission and peptidergic signalling.

    Directory of Open Access Journals (Sweden)

    Adriano Senatore

    Full Text Available The sea slug Tritonia diomedea (Mollusca, Gastropoda, Nudibranchia, has a simple and highly accessible nervous system, making it useful for studying neuronal and synaptic mechanisms underlying behavior. Although many important contributions have been made using Tritonia, until now, a lack of genetic information has impeded exploration at the molecular level.We performed Illumina sequencing of central nervous system mRNAs from Tritonia, generating 133.1 million 100 base pair, paired-end reads. De novo reconstruction of the RNA-Seq data yielded a total of 185,546 contigs, which partitioned into 123,154 non-redundant gene clusters (unigenes. BLAST comparison with RefSeq and Swiss-Prot protein databases, as well as mRNA data from other invertebrates (gastropod molluscs: Aplysia californica, Lymnaea stagnalis and Biomphalaria glabrata; cnidarian: Nematostella vectensis revealed that up to 76,292 unigenes in the Tritonia transcriptome have putative homologues in other databases, 18,246 of which are below a more stringent E-value cut-off of 1x10-6. In silico prediction of secreted proteins from the Tritonia transcriptome shotgun assembly (TSA produced a database of 579 unique sequences of secreted proteins, which also exhibited markedly higher expression levels compared to other genes in the TSA.Our efforts greatly expand the availability of gene sequences available for Tritonia diomedea. We were able to extract full length protein sequences for most queried genes, including those involved in electrical excitability, synaptic vesicle release and neurotransmission, thus confirming that the transcriptome will serve as a useful tool for probing the molecular correlates of behavior in this species. We also generated a neurosecretome database that will serve as a useful tool for probing peptidergic signalling systems in the Tritonia brain.

  19. Transmission Dynamics and Optimal Control of Malaria in Kenya

    Directory of Open Access Journals (Sweden)

    Gabriel Otieno

    2016-01-01

    Full Text Available This paper proposes and analyses a mathematical model for the transmission dynamics of malaria with four-time dependent control measures in Kenya: insecticide treated bed nets (ITNs, treatment, indoor residual spray (IRS, and intermittent preventive treatment of malaria in pregnancy (IPTp. We first considered constant control parameters and calculate the basic reproduction number and investigate existence and stability of equilibria as well as stability analysis. We proved that if R0≤1, the disease-free equilibrium is globally asymptotically stable in D. If R0>1, the unique endemic equilibrium exists and is globally asymptotically stable. The model also exhibits backward bifurcation at R0=1. If R0>1, the model admits a unique endemic equilibrium which is globally asymptotically stable in the interior of feasible region D. The sensitivity results showed that the most sensitive parameters are mosquito death rate and mosquito biting rates. We then consider the time-dependent control case and use Pontryagin’s Maximum Principle to derive the necessary conditions for the optimal control of the disease using the proposed model. The existence of optimal control problem is proved. Numerical simulations of the optimal control problem using a set of reasonable parameter values suggest that the optimal control strategy for malaria control in endemic areas is the combined use of treatment and IRS; for epidemic prone areas is the use of treatment and IRS; for seasonal areas is the use of treatment; and for low risk areas is the use of ITNs and treatment. Control programs that follow these strategies can effectively reduce the spread of malaria disease in different malaria transmission settings in Kenya.

  20. Pressure control of a pneumatic control system with a long transmission line

    International Nuclear Information System (INIS)

    Jang, Ji Seong; Lee, Kwang Kuk; Choi, Myung Soo

    2003-01-01

    In this study, a robust controller to control pressure in a pneumatic pressure vessel with a long transmission line is proposed. Frequency response of transmission line using compressible fluid is changed by the flowing state of the fluid. So, if a fixed gain controller designed based on a model supposed the flowing state to a specific state, the performance of the control system could be degraded because of the modelling error. The controller designed in this study is composed of two parts. One is a feedback controller to improve a feedback characteristics and to compensate the influence of the variation of transfer characteristics of a transmission line owing to the change of flowing state and the other is a feed forward controller to regulate command following performance. The experimental results with the designed controller show that the robustness of the control system is achieved regardless of the change of the model of the transmission line. Therefore, the designed controller can be utilized for the performance improvement of a pressure control system with a long transmission line using compressible fluid

  1. Transmission Control of Transport and Technological Cars in Acceleration Mode

    Directory of Open Access Journals (Sweden)

    B. I. Plujnikov

    2015-01-01

    Full Text Available In most structures a transmission of the transport-technological machine (TTM is controlled by automatic systems. In their creating it is necessary to specify the appropriate parameters and algorithms. In the total balance of the machine run time the acceleration mode is the most important. Therefore, an algorithm of the transmission gear ratio change during acceleration largely provides desirable rating of machines.It is known that the process of acceleration is estimated by its dynamic quality and fuel economy. To reach the best rating of both simultaneously is impossible. Therefore, as the criteria of estimate, were chosen the time and fuel consumption during acceleration to a fixed speed value.From a mathematical point of view, these criteria represent the sum of integrals, each of which defines the time or the fuel consumption during acceleration with a certain transmission gear ratio. The problem is formulated as follows: to determine the speed values of the TTM at the moments when the transmission gear ratio is changed providing the minimum values during fixed fuel supply for the estimate criteria. The latter condition in a certain way limits the task, but in explicit form there is no this control action in the dependence data.Given the variety of possible design options for the TTM, the solution is given by a specific example that simplifies the mathematics and makes it easier to understand the results obtained. As a TTM, is considered a passenger car with petrol engine and automatic transmission, which includes a hydrodynamic transformer and three-speed gearbox.A chosen way of solving the problem involves using the theory of ordinary maxima and minima, which allows finding the unknown values of independent variables. The expressions of sub-integral functions are in explicit form obtained and studied for meeting the necessary and sufficient conditions for existence of the extreme point. The result was a proof that in the case of

  2. Modelling of Rabies Transmission Dynamics Using Optimal Control Analysis

    Directory of Open Access Journals (Sweden)

    Joshua Kiddy K. Asamoah

    2017-01-01

    Full Text Available We examine an optimal way of eradicating rabies transmission from dogs into the human population, using preexposure prophylaxis (vaccination and postexposure prophylaxis (treatment due to public education. We obtain the disease-free equilibrium, the endemic equilibrium, the stability, and the sensitivity analysis of the optimal control model. Using the Latin hypercube sampling (LHS, the forward-backward sweep scheme and the fourth-order Range-Kutta numerical method predict that the global alliance for rabies control’s aim of working to eliminate deaths from canine rabies by 2030 is attainable through mass vaccination of susceptible dogs and continuous use of pre- and postexposure prophylaxis in humans.

  3. Wide-Area Emergency Control in Power Transmission

    DEFF Research Database (Denmark)

    Pedersen, Andreas Søndergaard

    , thus making the behaviour less predictable, suggesting the need for new intelligent wide-area emergency control algorithms. The fluctuating nature of the future power system calls for new methods of calculating remedial actions that are able to adapt to changing conditions. As part of this thesis......This thesis concerns the development of new emergency control algorithms for electric power transmission systems. Diminishing global resources and climate concerns forces operators to change production away from fossil fuels and towards distributed renewable energy sources. Along with the change...... on production side measures must be taken on the demand side to maintain power balance. Due to these changes, the operating point of the power system will be less predictable. Traditionally, emergency controls are designed off-line by extensive simulations. The future power system is expected to fluctuate more...

  4. Quantitative Proteomics of Synaptic and Nonsynaptic Mitochondria: Insights for Synaptic Mitochondrial Vulnerability

    Science.gov (United States)

    2015-01-01

    Synaptic mitochondria are essential for maintaining calcium homeostasis and producing ATP, processes vital for neuronal integrity and synaptic transmission. Synaptic mitochondria exhibit increased oxidative damage during aging and are more vulnerable to calcium insult than nonsynaptic mitochondria. Why synaptic mitochondria are specifically more susceptible to cumulative damage remains to be determined. In this study, the generation of a super-SILAC mix that served as an appropriate internal standard for mouse brain mitochondria mass spectrometry based analysis allowed for the quantification of the proteomic differences between synaptic and nonsynaptic mitochondria isolated from 10-month-old mice. We identified a total of 2260 common proteins between synaptic and nonsynaptic mitochondria of which 1629 were annotated as mitochondrial. Quantitative proteomic analysis of the proteins common between synaptic and nonsynaptic mitochondria revealed significant differential expression of 522 proteins involved in several pathways including oxidative phosphorylation, mitochondrial fission/fusion, calcium transport, and mitochondrial DNA replication and maintenance. In comparison to nonsynaptic mitochondria, synaptic mitochondria exhibited increased age-associated mitochondrial DNA deletions and decreased bioenergetic function. These findings provide insights into synaptic mitochondrial susceptibility to damage. PMID:24708184

  5. Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats

    Science.gov (United States)

    Liu, Zhi-Hua; Ding, Jin-Jun; Yang, Qian-Qian; Song, Hua-Zeng; Chen, Xiang-Tao; Xu, Yi; Xiao, Gui-Ran; Wang, Hui-Li

    2016-08-01

    Bisphenol-A (BPA, 4, 4‧-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.

  6. Prevention and control strategies for ticks and pathogen transmission.

    Science.gov (United States)

    de La Fuente, J; Kocan, K M; Contreras, M

    2015-04-01

    Ticks and tick-borne pathogens have evolved together, resulting in a complex relationship in which the pathogen's life cycle is perfectly coordinated with the tick's feeding cycle, and the tick can harbour high pathogen levels without affecting its biology. Tick-borne diseases (TBDs) continue to emerge and/or spread, and pose an increasing threatto human and animal health. The disruptive impacts of global change have resulted in ecosystem instability and the future outcomes of management and control programmes for ticks and TBDs are difficult to predict. In particular, the selection of acaricide-resistant ticks has reduced the value of acaricides as a sole means of tick control. Vaccines provide an alternative control method, but the use of tick vaccines has not advanced since the first vaccines were registered in the early 1990s. An understanding of the complex molecular relationship between hosts, ticks and pathogens and the use of systems biology and vaccinomics approaches are needed to discover proteins with the relevant biological function in tick feeding, reproduction, development, immune response, the subversion of host immunity and pathogen transmission, all of which mediate tick and pathogen success. The same approaches will also be required to characterise candidate protective antigens and to validate vaccine formulations. Tick vaccines with a dual effect on tick infestations and pathogen transmission could reduce both tick infestations and their vector capacity for humans, animals and reservoir hosts. The development of integrated tick control strategies, including vaccines and synthetic and botanical acaricides, in combination with managing drug resistance and educating producers, should lead to the sustainable control of ticks and TBDs.

  7. 3D analysis of synaptic vesicle density and distribution after acute foot-shock stress by using serial section transmission electron microscopy

    DEFF Research Database (Denmark)

    Khanmohammadi, Mahdieh; Darkner, Sune; Nava, Nicoletta

    2017-01-01

    Behavioural stress has shown to strongly affect neurotransmission within the neocortex. In this study, we analysed the effect of an acute stress model on density and distribution of neurotransmitter-containing vesicles within medial prefrontal cortex. Serial section transmission electron microsco...

  8. Ring-screening to control endemic transmission of Taenia solium.

    Directory of Open Access Journals (Sweden)

    Seth E O'Neal

    2014-09-01

    Full Text Available Taenia solium is a major cause of preventable epilepsy in developing nations. Screening and treatment of human intestinal stage infection (taeniasis within high-risk foci may reduce transmission and prevent epilepsy by limiting human exposure to infective eggs. We piloted a ring-strategy that involves screening and treatment for taeniasis among households located nearby pigs heavily-infected with the larval stage (cysticercosis. These pigs mark areas of increased transmission and can be identified by tongue examination.We selected two villages in northern Peru for a controlled prospective interventional cohort pilot study. In the intervention village (1,058 residents we examined the tongues of all pigs every 4 months for nodules characteristic of cysticercosis. We then screened all residents living within 100-meters of any tongue-positive pig using enzyme-linked immunosorbent assay to detect Taenia antigens in stool. Residents with taeniasis were treated with niclosamide. In both the intervention and control (753 residents we measured incidence of exposure by sampling the pig population every 4 months for serum antibodies against cysticercosis using enzyme-linked immunoelectrotransfer blot.Baseline seroincidence among pigs born during the study was 22.6 cases per 100 pigs per-month (95% confidence interval [CI] 17.0-30.0 in the intervention and 18.1 (95% CI 12.7-25.9 in the control. After one year we observed a 41% reduction in seroincidence in the intervention village compared to baseline (incidence rate ratio 0.59, 95% CI 0.41-0.87 while the seroincidence in the control village remained unchanged. At study end, the prevalence of taeniasis was nearly 4 times lower in the intervention than in the control (prevalence ratio 0.28, 95% CI 0.08-0.91.Ring-screening reduced transmission of T. solium in this pilot study and may provide an effective and practical approach for regions where resources are limited. However, this strategy requires validation

  9. Mathematical models for therapeutic approaches to control HIV disease transmission

    CERN Document Server

    Roy, Priti Kumar

    2015-01-01

    The book discusses different therapeutic approaches based on different mathematical models to control the HIV/AIDS disease transmission. It uses clinical data, collected from different cited sources, to formulate the deterministic as well as stochastic mathematical models of HIV/AIDS. It provides complementary approaches, from deterministic and stochastic points of view, to optimal control strategy with perfect drug adherence and also tries to seek viewpoints of the same issue from different angles with various mathematical models to computer simulations. The book presents essential methods and techniques for students who are interested in designing epidemiological models on HIV/AIDS. It also guides research scientists, working in the periphery of mathematical modeling, and helps them to explore a hypothetical method by examining its consequences in the form of a mathematical modelling and making some scientific predictions. The model equations, mathematical analysis and several numerical simulations that are...

  10. Analysis of synaptic growth and function in Drosophila with an extended larval stage.

    Science.gov (United States)

    Miller, Daniel L; Ballard, Shannon L; Ganetzky, Barry

    2012-10-03

    The Drosophila larval neuromuscular junction (NMJ) is a powerful system for the genetic and molecular analysis of neuronal excitability, synaptic transmission, and synaptic development. However, its use for studying age-dependent processes, such as maintenance of neuronal viability and synaptic stability, are temporally limited by the onset of pupariation and metamorphosis. Here we characterize larval NMJ growth, growth regulation, structure, and function in a developmental variant with an extended third instar (ETI). RNAi-knockdown of the prothoracicotropic hormone receptor, torso, in the ring gland of developing larvae leaves the timing of first and second instar molts largely unchanged, but triples duration of the third instar from 3 to 9.5 d (McBrayer et al., 2007; Rewitz et al., 2009). During this ETI period, NMJs undergo additional growth (adding >50 boutons/NMJ), and this growth remains under the control of the canonical regulators Highwire and the TGFβ/BMP pathway. NMJ growth during the ETI period occurs via addition of new branches, satellite boutons, and interstitial boutons, and continues even after muscle growth levels off. Throughout the ETI, organization of synapses and active zones remains normal, and synaptic transmission is unchanged. These results establish the ETI larval system as a viable model for studying motor neuron diseases and for investigating time-dependent effects of perturbations that impair mechanisms of neuroprotection, synaptic maintenance, and response to neural injury.

  11. Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis.

    Science.gov (United States)

    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.

  12. Emergent spatial synaptic structure from diffusive plasticity.

    Science.gov (United States)

    Sweeney, Yann; Clopath, Claudia

    2017-04-01

    Some neurotransmitters can diffuse freely across cell membranes, influencing neighbouring neurons regardless of their synaptic coupling. This provides a means of neural communication, alternative to synaptic transmission, which can influence the way in which neural networks process information. Here, we ask whether diffusive neurotransmission can also influence the structure of synaptic connectivity in a network undergoing plasticity. We propose a form of Hebbian synaptic plasticity which is mediated by a diffusive neurotransmitter. Whenever a synapse is modified at an individual neuron through our proposed mechanism, similar but smaller modifications occur in synapses connecting to neighbouring neurons. The effects of this diffusive plasticity are explored in networks of rate-based neurons. This leads to the emergence of spatial structure in the synaptic connectivity of the network. We show that this spatial structure can coexist with other forms of structure in the synaptic connectivity, such as with groups of strongly interconnected neurons that form in response to correlated external drive. Finally, we explore diffusive plasticity in a simple feedforward network model of receptive field development. We show that, as widely observed across sensory cortex, the preferred stimulus identity of neurons in our network become spatially correlated due to diffusion. Our proposed mechanism of diffusive plasticity provides an efficient mechanism for generating these spatial correlations in stimulus preference which can flexibly interact with other forms of synaptic organisation. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Peripheral control of the gain of a central synaptic connection between antagonistic motor neurones in the locust

    Science.gov (United States)

    Jellema; Heitler

    1996-01-01

    The metathoracic fast extensor tibiae (FETi) motor neurone of locusts is unusual amongst insect motor neurones because it makes output connections within the central nervous system as well as in the periphery. It makes excitatory chemical synaptic connections to most if not all of the antagonist flexor tibiae motor neurones. The gain of the FETi-flexor connection is dependent on the peripheral conditions at the time of the FETi spike. This dependency has two aspects. First, sensory input resulting from the extensor muscle contraction can sum with the central excitatory postsynaptic potential (EPSP) to augment its falling phase if the tibia is restrained in the flexed position (initiating a tension-dependent reflex) or is free to extend (initiating a movement-dependent resistance reflex). This effect is thus due to simple postsynaptic summation of the central EPSP with peripheral sensory input. Second, the static tibial position at the time of the FETi spike can change the amplitude of the central EPSP, in the absence of any extensor muscle contraction. The EPSP can be up to 30 % greater in amplitude if FETi spikes with the tibia held flexed rather than extended. The primary sense organ mediating this effect is the femoral chordotonal organ. Evidence is presented suggesting that the mechanism underlying this change in gain may be specifically localised to the FETi-flexor connection, rather than being due to general position-dependent sensory feedback summing with the EPSP. The change in the amplitude of the central EPSP is probably not caused by general postsynaptic summation with tonic sensory input, since a diminution in the amplitude of the central EPSP caused by tibial extension is often accompanied by overall tonic excitation of the flexor motor neurone. Small but significant changes in the peak amplitude of the FETi spike have a positive correlation with changes in the EPSP amplitude, suggesting a likely presynaptic component to the mechanism of gain control

  14. Hepatitis C virus transmission in hemodialysis units: importance of infection control practices and aseptic technique.

    Science.gov (United States)

    Thompson, Nicola D; Novak, Ryan T; Datta, Deblina; Cotter, Susanne; Arduino, Matthew J; Patel, Priti R; Williams, Ian T; Bialek, Stephanie R

    2009-09-01

    We investigated 4 hepatitis C virus (HCV) infection outbreaks at hemodialysis units to identify practices associated with transmission. Apparent failures to follow recommended infection control precautions resulted in patient-to-patient HCV transmission, through cross-contamination of the environment or intravenous medication vials. Fastidious attention to aseptic technique and infection control precautions are essential to prevent HCV transmission.

  15. Cortical synaptic transmission in CaV2.1 knockin mice with the S218L missense mutation which causes a severe familial hemiplegic migraine syndrome in humans.

    Directory of Open Access Journals (Sweden)

    Dania eVecchia

    2015-02-01

    Full Text Available Familial hemiplegic migraine type 1 (FHM1 is caused by gain-of-function mutations in CaV2.1 (P/Q-type Ca2+ channels. Knockin (KI mice carrying the FHM1 R192Q missense mutation show enhanced cortical excitatory synaptic transmission at pyramidal cell synapses but unaltered cortical inhibitory neurotransmission at fast-spiking interneuron synapses. Enhanced cortical glutamate release was shown to cause the facilitation of cortical spreading depression (CSD in R192Q KI mice. It, however, remains unknown how other FHM1 mutations affect cortical synaptic transmission. Here, we studied neurotransmission in cortical neurons in microculture from KI mice carrying the S218L mutation, which causes a severe FHM syndrome in humans and an allele-dosage dependent facilitation of experimental CSD in KI mice, which is larger than that caused by the R192Q mutation. We show gain-of-function of excitatory neurotransmission, due to increased action-potential evoked Ca2+ influx and increased probability of glutamate release at pyramidal cell synapses, but unaltered inhibitory neurotransmission at multipolar interneuron synapses in S218L KI mice. In contrast with the larger gain-of-function of neuronal CaV2.1 current in homozygous than heterozygous S218L KI mice, the gain-of-function of evoked glutamate release, the paired-pulse ratio and the Ca2+ dependence of the EPSC were all similar in homozygous and heterozygous S218L KI mice, suggesting compensatory changes in the homozygous mice. Furthermore, we reveal a unique feature of S218L KI cortical synapses which is the presence of a fraction of mutant CaV2.1 channels being open at resting potential. Our data suggest that, while the gain-of-function of evoked glutamate release may explain the facilitation of CSD in heterozygous S218L KI mice, the further facilitation of CSD in homozygous S218L KI mice is due to other CaV2.1-dependent mechanisms, that likely include Ca2+ influx at voltages sub-threshold for action

  16. Abnormal cortical synaptic transmission in CaV2.1 knockin mice with the S218L missense mutation which causes a severe familial hemiplegic migraine syndrome in humans

    Science.gov (United States)

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

    2015-01-01

    Familial hemiplegic migraine type 1 (FHM1) is caused by gain-of-function mutations in CaV2.1 (P/Q-type) Ca2+ channels. Knockin (KI) mice carrying the FHM1 R192Q missense mutation show enhanced cortical excitatory synaptic transmission at pyramidal cell synapses but unaltered cortical inhibitory neurotransmission at fast-spiking interneuron synapses. Enhanced cortical glutamate release was shown to cause the facilitation of cortical spreading depression (CSD) in R192Q KI mice. It, however, remains unknown how other FHM1 mutations affect cortical synaptic transmission. Here, we studied neurotransmission in cortical neurons in microculture from KI mice carrying the S218L mutation, which causes a severe FHM syndrome in humans and an allele-dosage dependent facilitation of experimental CSD in KI mice, which is larger than that caused by the R192Q mutation. We show gain-of-function of excitatory neurotransmission, due to increased action-potential evoked Ca2+ influx and increased probability of glutamate release at pyramidal cell synapses, but unaltered inhibitory neurotransmission at multipolar interneuron synapses in S218L KI mice. In contrast with the larger gain-of-function of neuronal CaV2.1 current in homozygous than heterozygous S218L KI mice, the gain-of-function of evoked glutamate release, the paired-pulse ratio and the Ca2+ dependence of the excitatory postsynaptic current were similar in homozygous and heterozygous S218L KI mice, suggesting compensatory changes in the homozygous mice. Furthermore, we reveal a unique feature of S218L KI cortical synapses which is the presence of a fraction of mutant CaV2.1 channels being open at resting potential. Our data suggest that, while the gain-of-function of evoked glutamate release may explain the facilitation of CSD in heterozygous S218L KI mice, the further facilitation of CSD in homozygous S218L KI mice is due to other CaV2.1-dependent mechanisms, that likely include Ca2+ influx at voltages sub-threshold for action

  17. Literature Survey on Operational Voltage Control and Reactive Power Management on Transmission and Sub-Transmission Networks

    Energy Technology Data Exchange (ETDEWEB)

    Elizondo, Marcelo A.; Samaan, Nader A.; Makarov, Yuri V.; Holzer, Jesse T.; Vallem, Mallikarjuna R.; Huang, Renke; Vyakaranam, Bharat GNVSR; Ke, Xinda; Pan, Feng

    2017-10-02

    Voltage and reactive power system control is generally performed following usual patterns of loads, based on off-line studies for daily and seasonal operations. This practice is currently challenged by the inclusion of distributed renewable generation, such as solar. There has been focus on resolving this problem at the distribution level; however, the transmission and sub-transmission levels have received less attention. This paper provides a literature review of proposed methods and solution approaches to coordinate and optimize voltage control and reactive power management, with an emphasis on applications at transmission and sub-transmission level. The conclusion drawn from the survey is that additional research is needed in the areas of optimizing switch shunt actions and coordinating all available resources to deal with uncertain patterns from increasing distributed renewable generation in the operational time frame. These topics are not deeply explored in the literature.

  18. Frequency-dependent depression of excitatory synaptic transmission is independent of activation of MCPG-sensitive presynaptic metabotropic glutamate receptors in cultured hippocampal neurons.

    Science.gov (United States)

    Maki, R; Cummings, D D; Dichter, M A

    1995-10-01

    1. A paired-pulse paradigm, and a high-frequency train followed by a test pulse, were used to investigate the possible role of presynaptic metabotropic glutamate receptors (mGluRs) in frequency-dependent modulation of the amplitude of excitatory post-synaptic currents (EPSCs). Paired whole cell patch-clamp recordings from monosynaptically connected hippocampal neurons maintained in very low-density cultures were performed, using the mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) and the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD, 100 microM]. 2. Paired-pulse depression (PPD) was observed in all the excitatory pairs recorded. The average PPD ratio (amplitude of the 2nd EPSC divided by the amplitude of the 1st EPSC) was 0.80 +/- 0.1 (SD) (n = 8). Application of the mGluR antagonist MCPG had no effect on the amplitude of the EPSCs and did not affect the ratio of the two EPSCs (PPD ratio 0.79 +/- 0.2). 3. The amplitudes of 10 successive EPSCs stimulated at a high frequency (20 Hz) decremented on average in both 4 mM extracellular Ca2+ (n = 5) and in 1 mM extracellular Ca2+ (n = 6). In all pairs tested, posttetanic depression (PTD) was observed (PTD ratio 0.7 +/- 0.2). Bath application of MCPG (500 microM) did not affect the amplitudes of the EPSCs during the train; MCPG also did not affect PTD. 4. The mGluR agonist (1S,3R)-ACPD depressed the amplitudes of the EPSCs in both the paired-pulse (1st EPSC, 35 +/- 9%; 2nd EPSC, 36 +/- 10%) and posttetanic pulse (1 and 4 mM extracellular Ca2+) paradigms. The amount of depression observed, both PPD and PTD, remained unaffected by application of (1S,3R)-ACPD. Coapplication of the antagonist MCPG (500 microM) blocked the effects of (1S,3R)-ACPD (100 microM). 5. We conclude that frequency-dependent depression of EPSC amplitudes occurs independent of endogenous activation of MCPG-sensitive mGluRs in cultured hippocampal neurons. Moreover, we demonstrate that exogenous

  19. The discovery of GluA3-dependent synaptic plasticity

    NARCIS (Netherlands)

    Renner, M.C.

    2016-01-01

    AMPA receptors (AMPARs) are responsible for fast excitatory synaptic transmission. GluA1-containing AMPARs have been extensively studied and play a key role in several forms of synaptic plasticity and memory. In contrast, GluA3-containing AMPARs have historically been ignored because they have

  20. Mathematical Modelling of Bacterial Meningitis Transmission Dynamics with Control Measures

    Directory of Open Access Journals (Sweden)

    Joshua Kiddy K. Asamoah

    2018-01-01

    Full Text Available Vaccination and treatment are the most effective ways of controlling the transmission of most infectious diseases. While vaccination helps susceptible individuals to build either a long-term immunity or short-term immunity, treatment reduces the number of disease-induced deaths and the number of infectious individuals in a community/nation. In this paper, a nonlinear deterministic model with time-dependent controls has been proposed to describe the dynamics of bacterial meningitis in a population. The model is shown to exhibit a unique globally asymptotically stable disease-free equilibrium E0, when the effective reproduction number RVT≤1, and a globally asymptotically stable endemic equilibrium E1, when RVT>1; and it exhibits a transcritical bifurcation at RVT=1. Carriers have been shown (by Tornado plot to have a higher chance of spreading the infection than those with clinical symptoms who will sometimes be bound to bed during the acute phase of the infection. In order to find the best strategy for minimizing the number of carriers and ill individuals and the cost of control implementation, an optimal control problem is set up by defining a Lagrangian function L to be minimized subject to the proposed model. Numerical simulation of the optimal problem demonstrates that the best strategy to control bacterial meningitis is to combine vaccination with other interventions (such as treatment and public health education. Additionally, this research suggests that stakeholders should press hard for the production of existing/new vaccines and antibiotics and their disbursement to areas that are most affected by bacterial meningitis, especially Sub-Saharan Africa; furthermore, individuals who live in communities where the environment is relatively warm (hot/moisture are advised to go for vaccination against bacterial meningitis.

  1. A Comparative Analysis of Transmission Control Protocol Improvement Techniques over Space-Based Transmission Media

    National Research Council Canada - National Science Library

    Lawson, Joseph M

    2006-01-01

    ... justification for the implementation of a given enhancement technique. The research questions were answered through model and simulation of a satellite transmission system via a Linux-based network topology...

  2. Transcriptional coupling of synaptic transmission and energy metabolism: role of nuclear respiratory factor 1 in co-regulating neuronal nitric oxide synthase and cytochrome c oxidase genes in neurons.

    Science.gov (United States)

    Dhar, Shilpa S; Liang, Huan Ling; Wong-Riley, Margaret T T

    2009-10-01

    Neuronal activity is highly dependent on energy metabolism; yet, the two processes have traditionally been regarded as independently regulated at the transcriptional level. Recently, we found that the same transcription factor, nuclear respiratory factor 1 (NRF-1) co-regulates an important energy-generating enzyme, cytochrome c oxidase, as well as critical subunits of glutamatergic receptors. The present study tests our hypothesis that the co-regulation extends to the next level of glutamatergic synapses, namely, neuronal nitric oxide synthase, which generates nitric oxide as a downstream signaling molecule. Using in silico analysis, electrophoretic mobility shift assay, chromatin immunoprecipitation, promoter mutations, and NRF-1 silencing, we documented that NRF-1 functionally bound to Nos1, but not Nos2 (inducible) and Nos3 (endothelial) gene promoters. Both COX and Nos1 transcripts were up-regulated by depolarizing KCl treatment and down-regulated by TTX-mediated impulse blockade in neurons. However, NRF-1 silencing blocked the up-regulation of both Nos1 and COX induced by KCl depolarization, and over-expression of NRF-1 rescued both Nos1 and COX transcripts down-regulated by TTX. These findings are consistent with our hypothesis that synaptic neuronal transmission and energy metabolism are tightly coupled at the molecular level.

  3. Development of a coordinated control system for BWR nuclear power plant and HVDC transmission system

    International Nuclear Information System (INIS)

    Ishikawa, M.; Hara, T.; Hirayama, K.; Sekiya, K.

    1986-01-01

    The combined use of dc and ac transmissions or so-called hybrid transmission was under study, employing both dc and ac systems to enable stable transmission of 10,000 MW of electric power generated by the BWR nuclear plant, scheduled to be built about 800 km away from the center of the load. It was thus necessary to develop a hybrid power transmission control system, the hybrid power transmission system consisting of a high voltage dc transmission system (HVDC) and an ultrahigh ac transmission system (UHVAC). It was also necessary to develop a control system for HVDC transmission which protects the BWR nuclear power plant from being influenced by any change in transmission mode that occurs as a result of faults on the UHVAC side when the entire power of the BWR plant is being sent by the HVDC transmission. This paper clarifies the requirements for the HVDC system control during hybrid transmission and also during dc transmission. The control method that satisfies these requirements was studied to develop a control algorithm

  4. Dopamine Receptors Differentially Control Binge Alcohol Drinking-Mediated Synaptic Plasticity of the Core Nucleus Accumbens Direct and Indirect Pathways.

    Science.gov (United States)

    Ji, Xincai; Saha, Sucharita; Kolpakova, Jenya; Guildford, Melissa; Tapper, Andrew R; Martin, Gilles E

    2017-05-31

    Binge alcohol drinking, a behavior characterized by rapid repeated alcohol intake, is most prevalent in young adults and is a risk factor for excessive alcohol consumption and alcohol dependence. Although the alteration of synaptic plasticity is thought to contribute to this behavior, there is currently little evidence that this is the case. We used drinking in the dark (DID) as a model of binge alcohol drinking to assess its effects on spike timing-dependent plasticity (STDP) in medium spiny neurons (MSNs) of the core nucleus accumbens (NAc) by combining patch-clamp recordings with calcium imaging and optogenetics. After 2 weeks of daily alcohol binges, synaptic plasticity was profoundly altered. STDP in MSNs expressing dopamine D1 receptors shifted from spike-timing-dependent long-term depression (tLTD), the predominant form of plasticity in naive male mice, to spike-timing-dependent long-term potentiation (tLTP) in DID mice, an effect that was totally reversed in the presence of 4 μm SCH23390, a dopamine D1 receptor antagonist. In MSNs presumably expressing dopamine D2 receptors, tLTP, the main form of plasticity in naive mice, was inhibited in DID mice. Interestingly, 1 μm sulpiride, a D2 receptor antagonist, restored tLTP. Although we observed no alterations of AMPA and NMDA receptor properties, we found that the AMPA/NMDA ratio increased at cortical and amygdaloid inputs but not at hippocampal inputs. Also, DID effects on STDP were accompanied by lower dendritic calcium transients. These data suggest that the role of dopamine in mediating the effects of binge alcohol drinking on synaptic plasticity of NAc MSNs differs markedly whether these neurons belong to the direct or indirect pathways. SIGNIFICANCE STATEMENT We examined the relationship between binge alcohol drinking and spike timing-dependent plasticity in nucleus accumbens (NAc) neurons. We found that repeated drinking bouts modulate differently synaptic plasticity in medium spiny neurons of the

  5. Presynaptic Active Zone Density during Development and Synaptic Plasticity.

    Science.gov (United States)

    Clarke, Gwenaëlle L; Chen, Jie; Nishimune, Hiroshi

    2012-01-01

    Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density) during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs), the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS), active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and β-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated.

  6. Presynaptic active zone density during development and synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Gwenaëlle L Clarke

    2012-02-01

    Full Text Available Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs, the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS, active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and β-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated.

  7. Oscillations control of a transmission belt by Excitation Clipping using Clutch Clamping Control (E4C)

    Science.gov (United States)

    Temporelli, Robin; Micheau, Philippe

    2017-04-01

    A transmission belt deals with non-linear phenomena such as parametric excitations that can bring the belt in an instability region resulting in large transverse oscillations. These oscillations can cause belt life deflection, noise and unexpected vibration on its environment. The present study proposes a new strategy to control oscillations of a transmission belt subject to periodic tension fluctuations. Indeed, for a transmission belt, periodic torque fluctuations cause periodic belt tension fluctuations which can be a source of excitation for the belt and resulting in belt oscillations under certain conditions. The presence of a clutch between the belt end-point and the source of torque fluctuations offers a means to clip torque fluctuations and thus to clip belt excitation. In keeping with this notion, belt oscillations can be controlled by an Excitation Clipping using Clutch Clamping Control (E4C) strategy. Through an example of a transmission belt subject to periodic tension fluctuations, the E4C strategy is presented and a new analytical model of belt behavior with its E4C strategy is constructed. Free belt oscillations (E4C is not activated) and controlled belt oscillations (E4C is activated) are observed through an experimental setup and predicted owing to the new analytical model. Finally, the E4C strategy leads to frequency unlocking that successfully removes belt oscillations. This new analytical model furthermore provides an accurate prediction of belt behavior with its E4C strategy.

  8. Research on cost control and management in high voltage transmission line construction

    Science.gov (United States)

    Xu, Xiaobin

    2017-05-01

    Enterprises. The cost control is of vital importance to the construction enterprises. It is the key to the profitability of the transmission line project, which is related to the survival and development of the electric power construction enterprises. Due to the long construction line, complex and changeable construction terrain as well as large construction costs of transmission line, it is difficult for us to take accurate and effective cost control on the project implementation of entire transmission line. Therefore, the cost control of transmission line project is a complicated and arduous task. It is of great theoretical and practical significance to study the cost control scheme of transmission line project by a more scientific and efficient way. Based on the characteristics of the construction project of the transmission line project, this paper analyzes the construction cost structure of the transmission line project and the current cost control problem of the transmission line project, and demonstrates the necessity and feasibility of studying the cost control scheme of the transmission line project more accurately. In this way, the dynamic cycle cost control process including plan, implementation, feedback, correction, modification and re-implement is achieved to realize the accurate and effective cost control of entire electric power transmission line project.

  9. Astrocytes and synaptic plasticity in health and disease.

    Science.gov (United States)

    Singh, A; Abraham, Wickliffe C

    2017-06-01

    Activity-dependent synaptic plasticity phenomena such as long-term potentiation and long-term depression are candidate mechanisms for storing information in the brain. Regulation of synaptic plasticity is critical for healthy cognition and learning and this is provided in part by metaplasticity, which can act to maintain synaptic transmission within a dynamic range and potentially prevent excitotoxicity. Metaplasticity mechanisms also allow neurons to integrate plasticity-associated signals over time. Interestingly, astrocytes appear to be critical for certain forms of synaptic plasticity and metaplasticity mechanisms. Synaptic dysfunction is increasingly viewed as an early feature of AD that is correlated with the severity of cognitive decline, and the development of these pathologies is correlated with a rise in reactive astrocytes. This review focuses on the contributions of astrocytes to synaptic plasticity and metaplasticity in normal tissue, and addresses whether astroglial pathology may lead to aberrant engagement of these mechanisms in neurological diseases such as Alzheimer's disease.

  10. Prenatal ethanol exposure alters synaptic plasticity in the dorsolateral striatum of rat offspring via changing the reactivity of dopamine receptor.

    Directory of Open Access Journals (Sweden)

    Rong Zhou

    Full Text Available Prenatal exposure to high-level ethanol (EtOH has been reported to produce hyperlocomotion in offspring. Previous studies have demonstrated synaptic plasticity in cortical afferent to the dorsolateral (DL striatum is involved in the pathogensis of hyperlocomotion. Here, prenatal EtOH-exposed rat offspring were used to investigate whether maternal EtOH exposure affected synaptic plasticity in the DL striatum. We found high-frequency stimulation (HFS induced a weaker long-term potentiation (LTP in EtOH rats than that in control rats at postnatal day (PD 15. The same protocol of HFS induced long-term depression (LTD in control group but still LTP in EtOH group at PD 30 or PD 40. Furthermore, enhancement of basal synaptic transmission accompanied by the decrease of pair-pulse facilitation (PPF was observed in PD 30 EtOH offspring. The perfusion with D1-type receptors (D1R antagonist SCH23390 recovered synaptic transmission and blocked the induction of abnormal LTP in PD 30 EtOH offspring. The perfusion with D2-type receptors (D2R agonist quinpirole reversed EtOH-induced LTP into D1R- and metabotropic glutamate receptor-dependent LTD. The data provide the functional evidence that prenatal ethanol exposure led to the persistent abnormal synaptic plasticity in the DL striatum via disturbing the balance between D1R and D2R.

  11. Synaptic Homeostasis and Its Immunological Disturbance in Neuromuscular Junction Disorders

    Directory of Open Access Journals (Sweden)

    Masaharu Takamori

    2017-04-01

    Full Text Available In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca2+ channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal. Focusing on neural agrin, Wnts, muscle-specific tyrosine kinase (a mediator of agrin and Wnts signalings and regulator of trans-synaptic communication, low-density lipoprotein receptor-related protein 4 (the receptor of agrin and Wnts and participant in retrograde signaling, laminin-network (including muscle-derived agrin, extracellular matrix proteins (participating in the synaptic stabilization and presynaptic receptors (including muscarinic and adenosine receptors, we review the functional structures of the synapse by making reference to immunological pathogenecities in postsynaptic disease, myasthenia gravis. The synapse-related proteins including cortactin, coronin-6, caveolin-3, doublecortin, R-spondin 2, amyloid precursor family proteins, glia cell-derived neurotrophic factor and neurexins are also discussed in terms of their possible contribution to efficient synaptic transmission at the neuromuscular junction.

  12. Co-Application of Corticosterone and Growth Hormone Upregulates NR2B Protein and Increases the NR2B:NR2A Ratio and Synaptic Transmission in the Hippocampus

    Directory of Open Access Journals (Sweden)

    Ghada S. Mahmoud

    2014-10-01

    Full Text Available Objectives: This in vitro study aimed to investigate the possible mechanism underlying the protective effect of growth hormone (GH on hippocampal function during periods of heightened glucocorticoid exposure. Methods: This study was conducted between January and June 2005 at the Joan C. Edwards School of Medicine, Marshall University, in Huntington, West Virginia, USA. The effects of the co-application of GH and corticosterone (CORT were tested at different concentrations on the field excitatory postsynaptic potentials (fEPSPs of the hippocampal slices of rats in two different age groups. Changes in the protein expression of N-methyl-D-aspartate receptor (NMDAR subunits NR1, NR2B and NR2A were measured in hippocampal brain slices treated with either artificial cerebrospinal fluid (ACSF, low doses of CORT alone or both CORT and GH for three hours. Results: The co-application of CORT and GH was found to have an additive effect on hippocampal synaptic transmission compared to either drug alone. Furthermore, the combined use of low concentrations of GH and CORT was found to have significantly higher effects on the enhancement of fEPSPs in older rats compared to young ones. Both GH and CORT enhanced the protein expression of the NR2A subunit. Simultaneous exposure to low concentrations of GH and CORT significantly enhanced NR2B expression and increased the NR2B:NR2A ratio. In contrast, perfusion with CORT alone caused significant suppression in the NR1 and NR2B protein expression and a decrease in the NR2B:NR2A ratio. Conclusion: These results suggest that NMDARs provide a potential target for mediating the GH potential protective effect against stress and age-related memory and cognitive impairment.

  13. Influence of Synaptic Depression on Memory Storage Capacity

    Science.gov (United States)

    Otsubo, Yosuke; Nagata, Kenji; Oizumi, Masafumi; Okada, Masato

    2011-08-01

    Synaptic efficacy between neurons is known to change within a short time scale dynamically. Neurophysiological experiments show that high-frequency presynaptic inputs decrease synaptic efficacy between neurons. This phenomenon is called synaptic depression, a short term synaptic plasticity. Many researchers have investigated how the synaptic depression affects the memory storage capacity. However, the noise has not been taken into consideration in their analysis. By introducing ``temperature'', which controls the level of the noise, into an update rule of neurons, we investigate the effects of synaptic depression on the memory storage capacity in the presence of the noise. We analytically compute the storage capacity by using a statistical mechanics technique called Self Consistent Signal to Noise Analysis (SCSNA). We find that the synaptic depression decreases the storage capacity in the case of finite temperature in contrast to the case of the low temperature limit, where the storage capacity does not change.

  14. Transmission dynamics of cholera: Mathematical modeling and control strategies

    Science.gov (United States)

    Sun, Gui-Quan; Xie, Jun-Hui; Huang, Sheng-He; Jin, Zhen; Li, Ming-Tao; Liu, Liqun

    2017-04-01

    Cholera, as an endemic disease around the world, has generated great threat to human society and caused enormous morbidity and mortality with weak surveillance system. In this paper, we propose a mathematical model to describe the transmission of Cholera. Moreover, basic reproduction number and the global dynamics of the dynamical model are obtained. Then we apply our model to characterize the transmission process of Cholera in China. It was found that, in order to avoid its outbreak in China, it may be better to increase immunization coverage rate and make effort to improve environmental management especially for drinking water. Our results may provide some new insights for elimination of Cholera.

  15. Transmission Magnitude and Phase Control for Polarization-Preserving Reflectionless Metasurfaces

    Science.gov (United States)

    Kwon, Do-Hoon; Ptitcyn, Grigorii; Díaz-Rubio, Ana; Tretyakov, Sergei A.

    2018-03-01

    For transmissive applications of electromagnetic metasurfaces, an array of subwavelength Huygens' meta-atoms are typically used to eliminate reflection and achieve a high-transmission power efficiency together with a wide transmission phase coverage. We show that the underlying principle of low reflection and full control over transmission is asymmetric scattering into the specular reflection and transmission directions that results from a superposition of symmetric and antisymmetric scattering components, with Huygens' meta-atoms being one example configuration. Available for oblique illumination in TM polarization, a meta-atom configuration comprising normal and tangential electric polarizations is presented, which is capable of reflectionless, full-power transmission and a 2 π transmission phase coverage as well as full absorption. For lossy metasurfaces, we show that a complete phase coverage is still available for reflectionless designs for any value of absorptance. Numerical examples in the microwave and optical regimes are provided.

  16. Controlled transmission of African cassava mosaic virus (ACMV) by ...

    African Journals Online (AJOL)

    Jatropha curcas, a plant with great biodiesel potential is also used to reduce the population of whiteflies, Bemisia tabaci on cassava fields when planted as a hedge. We therefore, investigated the transmission of African cassava mosaic virus (ACMV) by the whitefly vector from cassava to seedlings of 10 accessions of J.

  17. Controlled transmission of African cassava mosaic virus (ACMV) by ...

    African Journals Online (AJOL)

    Sarkodie

    2013-07-10

    Jul 10, 2013 ... Jatropha curcas, a plant with great biodiesel potential is also used to reduce the population of whiteflies, Bemisia tabaci on cassava fields when planted as a hedge. We therefore, investigated the transmission of African cassava mosaic virus (ACMV) by the whitefly vector from cassava to seedlings.

  18. Synapse geometry and receptor dynamics modulate synaptic strength.

    Directory of Open Access Journals (Sweden)

    Dominik Freche

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

  19. Mild hypoxia affects synaptic connectivity in cultured neuronal networks.

    Science.gov (United States)

    Hofmeijer, Jeannette; Mulder, Alex T B; Farinha, Ana C; van Putten, Michel J A M; le Feber, Joost

    2014-04-04

    Eighty percent of patients with chronic mild cerebral ischemia/hypoxia resulting from chronic heart failure or pulmonary disease have cognitive impairment. Overt structural neuronal damage is lacking and the precise cause of neuronal damage is unclear. As almost half of the cerebral energy consumption is used for synaptic transmission, and synaptic failure is the first abrupt consequence of acute complete anoxia, synaptic dysfunction is a candidate mechanism for the cognitive deterioration in chronic mild ischemia/hypoxia. Because measurement of synaptic functioning in patients is problematic, we use cultured networks of cortical neurons from new born rats, grown over a multi-electrode array, as a model system. These were exposed to partial hypoxia (partial oxygen pressure of 150Torr lowered to 40-50Torr) during 3 (n=14) or 6 (n=8) hours. Synaptic functioning was assessed before, during, and after hypoxia by assessment of spontaneous network activity, functional connectivity, and synaptically driven network responses to electrical stimulation. Action potential heights and shapes and non-synaptic stimulus responses were used as measures of individual neuronal integrity. During hypoxia of 3 and 6h, there was a statistically significant decrease of spontaneous network activity, functional connectivity, and synaptically driven network responses, whereas direct responses and action potentials remained unchanged. These changes were largely reversible. Our results indicate that in cultured neuronal networks, partial hypoxia during 3 or 6h causes isolated disturbances of synaptic connectivity. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Broad patterns in domestic vector-borne Trypanosoma cruzi transmission dynamics: synanthropic animals and vector control.

    Science.gov (United States)

    Peterson, Jennifer K; Bartsch, Sarah M; Lee, Bruce Y; Dobson, Andrew P

    2015-10-22

    Chagas disease (caused by Trypanosoma cruzi) is the most important neglected tropical disease (NTD) in Latin America, infecting an estimated 5.7 million people in the 21 countries where it is endemic. It is one of the NTDs targeted for control and elimination by the 2020 London Declaration goals, with the first goal being to interrupt intra-domiciliary vector-borne T. cruzi transmission. A key question in domestic T. cruzi transmission is the role that synanthropic animals play in T. cruzi transmission to humans. Here, we ask, (1) do synanthropic animals need to be targeted in Chagas disease prevention policies?, and (2) how does the presence of animals affect the efficacy of vector control? We developed a simple mathematical model to simulate domestic vector-borne T. cruzi transmission and to specifically examine the interaction between the presence of synanthropic animals and effects of vector control. We used the model to explore how the interactions between triatomine bugs, humans and animals impact the number and proportion of T. cruzi-infected bugs and humans. We then examined how T. cruzi dynamics change when control measures targeting vector abundance are introduced into the system. We found that the presence of synanthropic animals slows the speed of T. cruzi transmission to humans, and increases the sensitivity of T. cruzi transmission dynamics to vector control measures at comparable triatomine carrying capacities. However, T. cruzi transmission is amplified when triatomine carrying capacity increases with the abundance of syntathoropic hosts. Our results suggest that in domestic T. cruzi transmission scenarios where no vector control measures are in place, a reduction in synanthropic animals may slow T. cruzi transmission to humans, but it would not completely eliminate transmission. To reach the 2020 goal of interrupting intra-domiciliary T. cruzi transmission, it is critical to target vector populations. Additionally, where vector control measures

  1. Different CaV1.3 Channel Isoforms Control Distinct Components of the Synaptic Vesicle Cycle in Auditory Inner Hair Cells.

    Science.gov (United States)

    Vincent, Philippe F Y; Bouleau, Yohan; Charpentier, Gilles; Emptoz, Alice; Safieddine, Saaid; Petit, Christine; Dulon, Didier

    2017-03-15

    The mechanisms orchestrating transient and sustained exocytosis in auditory inner hair cells (IHCs) remain largely unknown. These exocytotic responses are believed to mobilize sequentially a readily releasable pool of vesicles (RRP) underneath the synaptic ribbons and a slowly releasable pool of vesicles (SRP) at farther distance from them. They are both governed by Ca v 1.3 channels and require otoferlin as Ca 2+ sensor, but whether they use the same Ca v 1.3 isoforms is still unknown. Using whole-cell patch-clamp recordings in posthearing mice, we show that only a proportion (∼25%) of the total Ca 2+ current in IHCs displaying fast inactivation and resistance to 20 μm nifedipine, a l-type Ca 2+ channel blocker, is sufficient to trigger RRP but not SRP exocytosis. This Ca 2+ current is likely conducted by short C-terminal isoforms of Ca v 1.3 channels, notably Ca v 1.3 42A and Ca v 1.3 43S , because their mRNA is highly expressed in wild-type IHCs but poorly expressed in Otof -/- IHCs, the latter having Ca 2+ currents with considerably reduced inactivation. Nifedipine-resistant RRP exocytosis was poorly affected by 5 mm intracellular EGTA, suggesting that the Ca v 1.3 short isoforms are closely associated with the release site at the synaptic ribbons. Conversely, our results suggest that Ca v 1.3 long isoforms, which carry ∼75% of the total IHC Ca 2+ current with slow inactivation and confer high sensitivity to nifedipine and to internal EGTA, are essentially involved in recruiting SRP vesicles. Intracellular Ca 2+ imaging showed that Ca v 1.3 long isoforms support a deep intracellular diffusion of Ca 2+ SIGNIFICANCE STATEMENT Auditory inner hair cells (IHCs) encode sounds into nerve impulses through fast and indefatigable Ca 2+ -dependent exocytosis at their ribbon synapses. We show that this synaptic process involves long and short C-terminal isoforms of the Ca v 1.3 Ca 2+ channel that differ in the kinetics of their Ca 2+ -dependent inactivation and their

  2. Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila

    Directory of Open Access Journals (Sweden)

    Samuel H. Friedman

    2013-11-01

    Fragile X syndrome (FXS, the most common inherited determinant of intellectual disability and autism spectrum disorders, is caused by loss of the fragile X mental retardation 1 (FMR1 gene product (FMRP, an mRNA-binding translational repressor. A number of conserved FMRP targets have been identified in the well-characterized Drosophila FXS disease model, but FMRP is highly pleiotropic in function and the full spectrum of FMRP targets has yet to be revealed. In this study, screens for upregulated neural proteins in Drosophila fmr1 (dfmr1 null mutants reveal strong elevation of two synaptic heparan sulfate proteoglycans (HSPGs: GPI-anchored glypican Dally-like protein (Dlp and transmembrane Syndecan (Sdc. Our recent work has shown that Dlp and Sdc act as co-receptors regulating extracellular ligands upstream of intracellular signal transduction in multiple trans-synaptic pathways that drive synaptogenesis. Consistently, dfmr1 null synapses exhibit altered WNT signaling, with changes in both Wingless (Wg ligand abundance and downstream Frizzled-2 (Fz2 receptor C-terminal nuclear import. Similarly, a parallel anterograde signaling ligand, Jelly belly (Jeb, and downstream ERK phosphorylation (dpERK are depressed at dfmr1 null synapses. In contrast, the retrograde BMP ligand Glass bottom boat (Gbb and downstream signaling via phosphorylation of the transcription factor MAD (pMAD seem not to be affected. To determine whether HSPG upregulation is causative for synaptogenic defects, HSPGs were genetically reduced to control levels in the dfmr1 null background. HSPG correction restored both (1 Wg and Jeb trans-synaptic signaling, and (2 synaptic architecture and transmission strength back to wild-type levels. Taken together, these data suggest that FMRP negatively regulates HSPG co-receptors controlling trans-synaptic signaling during synaptogenesis, and that loss of this regulation causes synaptic structure and function defects characterizing the FXS disease state.

  3. Electronic control of a 4-speed automatic transmission with lock-up clutch

    Energy Technology Data Exchange (ETDEWEB)

    Schwab, M.

    1984-01-01

    The paper describes the electronic control of an automatic 4-speed transmission with lock-up clutch. As compared to purely hydraulically controlled transmissions, this control offers a clearly improved quality of shifting and the possibility of achieving improvements in fuel consumption thanks to a special economy program. The electronic control unit is a Bosch MOTRONIC which has been expanded to include the functions of transmission control. A special feature is the engine torque control which is implemented by way of retarding the ignition when shifting. This opens up an additional degree of freedom for optimizing a transmission in terms of shift comfort, life of the friction elements and the power which can be transmitted.

  4. Oxide-based synaptic transistors gated by solution-processed gelatin electrolytes

    Science.gov (United States)

    He, Yinke; Sun, Jia; Qian, Chuan; Kong, Ling-An; Gou, Guangyang; Li, Hongjian

    2017-04-01

    In human brain, a large number of neurons are connected via synapses. Simulation of the synaptic behaviors using electronic devices is the most important step for neuromorphic systems. In this paper, proton conducting gelatin electrolyte-gated oxide field-effect transistors (FETs) were used for emulating synaptic functions, in which the gate electrode is regarded as pre-synaptic neuron and the channel layer as the post-synaptic neuron. In analogy to the biological synapse, a potential spike can be applied at the gate electrode and trigger ionic motion in the gelatin electrolyte, which in turn generates excitatory post-synaptic current (EPSC) in the channel layer. Basic synaptic behaviors including spike time-dependent EPSC, paired-pulse facilitation (PPF), self-adaptation, and frequency-dependent synaptic transmission were successfully mimicked. Such ionic/electronic hybrid devices are beneficial for synaptic electronics and brain-inspired neuromorphic systems.

  5. Design, Control and Application of Modular Multilevel Converters for HVDC Transmission Systems

    DEFF Research Database (Denmark)

    Sharifabadi, Kamran; Harnefors, Lennart; Nee, Hans-Peter

    Design, Control and Application of Modular Multilevel Converters for HVDC Transmission Systems is a comprehensive guide to semiconductor technologies applicable for MMC design, component sizing control, modulation, and application of the MMC technology for HVDC transmission. Separated into three...... distinct parts, the first offers an overview of MMC technology, including information on converter component sizing, Control and Communication, Protection and Fault Management, and Generic Modelling and Simulation. The second covers the applications of MMC in offshore WPP, including planning, technical...

  6. Effective Mechanism for Synthesis of Neurotransmitter Glutamate and its Loading into Synaptic Vesicles.

    Science.gov (United States)

    Takeda, Kouji; Ueda, Tetsufumi

    2017-01-01

    Glutamate accumulation into synaptic vesicles is a pivotal step in glutamate transmission. This process is achieved by a vesicular glutamate transporter (VGLUT) coupled to v-type proton ATPase. Normal synaptic transmission, in particular during intensive neuronal firing, would demand rapid transmitter re-filling of emptied synaptic vesicles. We have previously shown that isolated synaptic vesicles are capable of synthesizing glutamate from α-ketoglutarate (not from glutamine) by vesicle-bound aspartate aminotransferase for immediate uptake, in addition to ATP required for uptake by vesicle-bound glycolytic enzymes. This suggests that local synthesis of these substances, essential for glutamate transmission, could occur at the synaptic vesicle. Here we provide evidence that synaptosomes (pinched-off nerve terminals) also accumulate α-ketoglutarate-derived glutamate into synaptic vesicles within, at the expense of ATP generated through glycolysis. Glutamine-derived glutamate is also accumulated into synaptic vesicles in synaptosomes. The underlying mechanism is discussed. It is suggested that local synthesis of both glutamate and ATP at the presynaptic synaptic vesicle would represent an efficient mechanism for swift glutamate loading into synaptic vesicles, supporting maintenance of normal synaptic transmission.

  7. Design, control and application of modular multilevel converters for HVDC transmission systems

    CERN Document Server

    Sharifabadi, Kamran; Nee, Hans-Peter; Norrga, Staffan; Teodorescu, Remus

    2016-01-01

    Design, Control and Application of Modular Multilevel Converters for HVDC Transmission Systems is a comprehensive guide to semiconductor technologies applicable for MMC design, component sizing control, modulation, and application of the MMC technology for HVDC transmission. Separated into three distinct parts, the first offers an overview of MMC technology, including information on converter component sizing, Control and Communication, Protection and Fault Management, and Generic Modelling and Simulation. The second covers the applications of MMC in offshore WPP, including planning, technical and economic requirements and optimization options, fault management, dynamic and transient stability. Finally, the third chapter explores the applications of MMC in HVDC transmission and Multi Terminal configurations, including Supergrids.

  8. AMPA receptor trafficking and the mechanisms underlying synaptic plasticity and cognitive aging

    Science.gov (United States)

    Henley, Jeremy M.; Wilkinson, Kevin A.

    2013-01-01

    Even in healthy individuals there is an inexorable agerelated decline in cognitive function. This is due, in large part, to reduced synaptic plasticity caused by changes in the molecular composition of the postsynaptic membrane. AMPA receptors (AMPARs) are glutamate-gated cation channels that mediate the overwhelming majority of fast excitatory transmission in the brain. Changes in AMPAR number and/or function are a core feature of synaptic plasticity and age-related cognitive decline, AMPARs are highly dynamic proteins that are subject to highly controlled trafficking, recycling, and/or degradation and replacement. This active regulation of AMPAR synthesis, targeting, synaptic dwell time, and degradation is fundamentally important for memory formation and storage. Further, aberrant AMPAR trafficking and consequent detrimental changes in synapses are strongly implicated in many brain diseases, which represent a vast social and economic burden. The purpose of this article is to provide an overview of the molecular and cellular AMPA receptor trafficking events that control synaptic responsiveness and plasticity, and highlight what is known currently known about how these processes change with age and disease. PMID:23576886

  9. Medium Access Control for Opportunistic Concurrent Transmissions under Shadowing Channels

    Directory of Open Access Journals (Sweden)

    Seung Min Hur

    2009-06-01

    Full Text Available We study the problem of how to alleviate the exposed terminal effect in multihop wireless networks in the presence of log-normal shadowing channels. Assuming node location information, we propose an extension of the IEEE 802.11 MAC protocol that schedules concurrent transmissions in the presence of log-normal shadowing, thus mitigating the exposed terminal problem and improving network throughput and delay performance. We observe considerable improvements in throughput and delay achieved over the IEEE 802.11 MAC under various network topologies and channel conditions in ns-2 simulations, which justify the importance of considering channel randomness in MAC protocol design for multihop wireless networks.

  10. The roles of STP and LTP in synaptic encoding

    Directory of Open Access Journals (Sweden)

    Arturas Volianskis

    2013-02-01

    Full Text Available Long-term potentiation (LTP, a cellular model of learning and memory, is generally regarded as a unitary phenomenon that alters the strength of synaptic transmission by increasing the postsynaptic response to the release of a quantum of neurotransmitter. LTP, at CA3-CA1 synapses in the hippocampus, contains a stimulation-labile phase of short-term potentiation (STP, or transient LTP, t-LTP that decays into stable LTP. By studying the responses of populations of neurons to brief bursts of high-frequency afferent stimulation before and after the induction of LTP, we found that synaptic responses during bursts are potentiated equally during LTP but not during STP. We show that STP modulates the frequency response of synaptic transmission whereas LTP preserves the fidelity. Thus, STP and LTP have different functional consequences for the transfer of synaptic information.

  11. A Secondary Voltage Control Method for an AC/DC Coupled Transmission System Based on Model Predictive Control

    DEFF Research Database (Denmark)

    Xu, Fengda; Guo, Qinglai; Sun, Hongbin

    2015-01-01

    For an AC/DC coupled transmission system, the change of transmission power on the DC lines will significantly influence the AC systems’ voltage. This paper describes a method to coordinated control the reactive power of power plants and shunt capacitors at DC converter stations nearby, in order...

  12. Optimal treatment interruptions control of TB transmission model

    Science.gov (United States)

    Nainggolan, Jonner; Suparwati, Titik; Kawuwung, Westy B.

    2018-03-01

    A tuberculosis model which incorporates treatment interruptions of infectives is established. Optimal control of individuals infected with active TB is given in the model. It is obtained that the control reproduction numbers is smaller than the reproduction number, this means treatment controls could optimize the decrease in the spread of active TB. For this model, controls on treatment of infection individuals to reduce the actively infected individual populations, by application the Pontryagins Maximum Principle for optimal control. The result further emphasized the importance of controlling disease relapse in reducing the number of actively infected and treatment interruptions individuals with tuberculosis.

  13. Decentralized control of transmission rates in energy-critical wireless networks

    KAUST Repository

    Xia, Li

    2013-06-01

    In this paper, we discuss the decentralized optimization of delay and energy consumption in a multi-hop wireless network. The goal is to minimize the energy consumption of energy-critical nodes and the overall packet transmission delay of the network. The transmission rates of energy-critical nodes are adjustable according to the local information of nodes, i.e., the length of packets queued. The multi-hop network is modeled as a queueing network.We prove that the system performance is monotone w.r.t. (with respect to) the transmission rate, thus the “bang-bang” control is an optimal control. We also prove that there exists a threshold type control policy which is optimal. We propose a decentralized algorithm to control transmission rates of these energy-critical nodes. Some simulation experiments are conducted to demonstrate the effectiveness of our approach.

  14. Implementation of anomaly detection algorithms for detecting transmission control protocol synchronized flooding attacks

    CSIR Research Space (South Africa)

    Mkuzangwe, NNP

    2015-08-01

    Full Text Available This work implements two anomaly detection algorithms for detecting Transmission Control Protocol Synchronized (TCP SYN) flooding attack. The two algorithms are an adaptive threshold algorithm and a cumulative sum (CUSUM) based algorithm...

  15. Modeling the transmission dynamics and control of rabies in China.

    Science.gov (United States)

    Ruan, Shigui

    2017-04-01

    Human rabies was first recorded in ancient China in about 556 BC and is still one of the major public-health problems in China. From 1950 to 2015, 130,494 human rabies cases were reported in Mainland China with an average of 1977 cases per year. It is estimated that 95% of these human rabies cases are due to dog bites. The purpose of this article is to provide a review about the models, results, and simulations that we have obtained recently on studying the transmission of rabies in China. We first construct a basic susceptible, exposed, infectious, and recovered (SEIR) type model for the spread of rabies virus among dogs and from dogs to humans and use the model to simulate the human rabies data in China from 1996 to 2010. Then we modify the basic model by including both domestic and stray dogs and apply the model to simulate the human rabies data from Guangdong Province, China. To study the seasonality of rabies, in Section 4 we further propose a SEIR model with periodic transmission rates and employ the model to simulate the monthly data of human rabies cases reported by the Chinese Ministry of Health from January 2004 to December 2010. To understand the spatial spread of rabies, in Section 5 we add diffusion to the dog population in the basic SEIR model to obtain a reaction-diffusion equation model and determine the minimum wave speed connecting the disease-free equilibrium to the endemic equilibrium. Finally, in order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in Mainland China, in Section 6 we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans and use the two-patch submodel to investigate the rabies virus clades lineages and to simulate the human rabies data from Guizhou and Guangxi, Hebei and Fujian, and Sichuan and Shaanxi, respectively. Some discussions are provided in Section 7. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Medium Access Control for Opportunistic Concurrent Transmissions under Shadowing Channels.

    Science.gov (United States)

    Son, In Keun; Mao, Shiwen; Hur, Seung Min

    2009-01-01

    We study the problem of how to alleviate the exposed terminal effect in multi-hop wireless networks in the presence of log-normal shadowing channels. Assuming node location information, we propose an extension of the IEEE 802.11 MAC protocol that sched-ules concurrent transmissions in the presence of log-normal shadowing, thus mitigating the exposed terminal problem and improving network throughput and delay performance. We observe considerable improvements in throughput and delay achieved over the IEEE 802.11 MAC under various network topologies and channel conditions in ns-2 simulations, which justify the importance of considering channel randomness in MAC protocol design for multi-hop wireless networks.

  17. Reactive Power Role and Its Controllability in AC Power Transmission Systems

    DEFF Research Database (Denmark)

    Ebrahimzadeh, Esmaeil; Blaabjerg, Frede

    2017-01-01

    affect the power system operation. Different reactive power generation technologies based on capacitors and power electronic converters are reviewed as possible sources for the reactive power compensation. Also, voltage and reactive power control methods of the mentioned technologies are briefly......This chapter is a general introduction to the reactive power role in the voltage control and the stability in power transmission systems. It starts with a brief overview of the potential limitations related to the transmission system loading and also different ways that the reactive power can...... explained for use in AC power transmission systems....

  18. Information transmission via fiber optics in the shiva laser control system

    International Nuclear Information System (INIS)

    Parker, J.

    1978-01-01

    The Fiber Optic Serial Link package performs the functions of transmission and reception of signals over a pair of fiber optic cables and the I/O of serial data to a local device in EIA format. Present sysems requirements include fiber cable transmission length of up to 150 m and baud rates up to 9600, although the design criterium of transmission at 19.2 KB has been met. Fiber optic links are used between the central control area and each of the alignment control subsystems, in addition to sending timing signals over long distances between subsystems

  19. Intrinsic plasticity complements long-term potentiation in parallel fiber input gain control in cerebellar Purkinje cells

    NARCIS (Netherlands)

    A. Belmeguenai (Amor); E. Hosy; F. Bengtsson (Fredrik); C.M. Pedroarena (Christine); C. Piochon (Claire); E. Teuling (Eva); Q. He (Qionger); G. Ohtsuki (Gen); M.T.G. Jeu (Marcel); Y. Elgersma (Ype); C.I. de Zeeuw (Chris); H. Jörntell (Henrik); C.R.W. Hansel (Christian)

    2010-01-01

    textabstractSynaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here,weshowusingboth in vitroandin vivo recordingsfromthe rat cerebellum that tetanization protocols for the induction of LTP at

  20. Intrinsic plasticity complements long-term potentiation in parallel fiber input gain control in cerebellar Purkinje cells

    NARCIS (Netherlands)

    Belmeguenai, Amor; Hosy, Eric; Bengtsson, Fredrik; Pedroarena, Christine M.; Piochon, Claire; Teuling, Eva; He, Qionger; Ohtsuki, Gen; De Jeu, Marcel T. G.; Elgersma, Ype; De Zeeuw, Chris I.; Jorntell, Henrik; Hansel, Christian

    2010-01-01

    Synaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here, we show using both in vitro and in vivo recordings from the rat cerebellum that tetanization protocols for the induction of LTP at

  1. [Astrocytes and microglia: active players in synaptic plasticity].

    Science.gov (United States)

    Ronzano, Rémi

    2017-12-01

    Synaptic plasticity consists in a change in structure and composition of presynaptic and postsynaptic compartments. For a long time, synaptic plasticity had been thought as a neuronal mechanism only under the control of neural network activity. However, recently, with the growing knowledge about glial physiology, plasticity has been reviewed as a mechanism influenced by the synaptic environment. Thus, it appears that astrocytes and microglia modulate these mechanisms modifying neural environment by clearance of neurotransmitters, releasing essential factors and modulating inflammation. Moreover, glia can change its own activity and the expression pattern of many factors that modulate synaptic plasticity according to the environment. Hence, these populations of "non-neuronal" cells in the central nervous system seem to be active players in synaptic plasticity. This review discusses how glia modulates synaptic plasticity focusing on long-term potentiation and depression, and questions the role of the signaling processes between astrocytes and microglia in these mechanisms. © 2017 médecine/sciences – Inserm.

  2. Effect of prenatal auditory stimulation on numerical synaptic density and mean synaptic height in the posthatch Day 1 chick hippocampus.

    Science.gov (United States)

    Chaudhury, Sraboni; Nag, Tapas Chandra; Wadhwa, Shashi

    2009-02-01

    Previous studies on prenatal auditory stimulation by species-specific sound or sitar music showed enhanced morphological and biochemical changes in chick hippocampus, which plays an important role in learning and memory. Changes in the efficiency of synapses, synaptic morphology and de novo synapse formation affects learning and memory. Therefore, in the present study, we set out to investigate the mean synaptic density and mean synaptic height at posthatch Day 1 in dorsal and ventral part of chick hippocampus following prenatal auditory stimulation. Fertilized 0 day eggs of domestic chick incubated under normal conditions were exposed to patterned sounds of species-specific and sitar music at 65 dB levels for 15 min/h round the clock (frequency range: 100-6300 Hz) from embryonic Day 10 till hatching. The synapses identified under transmission electron microscope were estimated for their numerical density by physical disector method and also the mean synaptic height calculated. Our results demonstrate a significant increase in mean synaptic density with no alterations in the mean synaptic height following both types of auditory stimulation in the dorsal as well as ventral part of the hippocampus. The observed increase in mean synaptic density suggests enhanced synaptic substrate to strengthen hippocampal function. 2008 Wiley-Liss, Inc.

  3. Statistical mechanics of attractor neural network models with synaptic depression

    International Nuclear Information System (INIS)

    Igarashi, Yasuhiko; Oizumi, Masafumi; Otsubo, Yosuke; Nagata, Kenji; Okada, Masato

    2009-01-01

    Synaptic depression is known to control gain for presynaptic inputs. Since cortical neurons receive thousands of presynaptic inputs, and their outputs are fed into thousands of other neurons, the synaptic depression should influence macroscopic properties of neural networks. We employ simple neural network models to explore the macroscopic effects of synaptic depression. Systems with the synaptic depression cannot be analyzed due to asymmetry of connections with the conventional equilibrium statistical-mechanical approach. Thus, we first propose a microscopic dynamical mean field theory. Next, we derive macroscopic steady state equations and discuss the stabilities of steady states for various types of neural network models.

  4. INVOLVEMENT OF SYNAPTIC GENES IN THE PATHOGENESIS OF AUTISM SPECTRUM DISORDERS: THE CASE OF SYNAPSINS

    Directory of Open Access Journals (Sweden)

    Silvia eGiovedi

    2014-09-01

    Full Text Available 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 have been recently associated with ASD and epilepsy, diseases that display a frequent comorbidity. Synapsins are presynaptic 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.

  5. Application of a case–control study design to investigate genotypic signatures of HIV-1 transmission

    Directory of Open Access Journals (Sweden)

    Mota Talia M

    2012-06-01

    Full Text Available Abstract Background The characterization of HIV-1 transmission strains may inform the design of an effective vaccine. Shorter variable loops with fewer predicted glycosites have been suggested as signatures enriched in envelope sequences derived during acute HIV-1 infection. Specifically, a transmission-linked lack of glycosites within the V1 and V2 loops of gp120 provides greater access to an α4β7 binding motif, which promotes the establishment of infection. Also, a histidine at position 12 in the leader sequence of Env has been described as a transmission signature that is selected against during chronic infection. The purpose of this study is to measure the association of the presence of an α4β7 binding motif, the number of N-linked glycosites, the length of the variable loops, and the prevalence of histidine at position 12 with HIV-1 transmission. A case–control study design was used to measure the prevalence of these variables between subtype B and C transmission sequences and frequency-matched randomly-selected sequences derived from chronically infected controls. Results Subtype B transmission strains had shorter V3 regions than chronic strains (p = 0.031; subtype C transmission strains had shorter V1 loops than chronic strains (p = 0.047; subtype B transmission strains had more V3 loop glycosites (p = 0.024 than chronic strains. Further investigation showed that these statistically significant results were unlikely to be biologically meaningful. Also, there was no difference observed in the prevalence of a histidine at position 12 among transmission strains and controls of either subtype. Conclusions Although a genetic bottleneck is observed after HIV-1 transmission, our results indicate that summary characteristics of Env hypothesised to be important in transmission are not divergent between transmission and chronic strains of either subtype. The success of a transmission strain to initiate infection may be a random

  6. Feedforward control of sound transmission using an active acoustic metamaterial

    Science.gov (United States)

    Cheer, Jordan; Daley, Stephen; McCormick, Cameron

    2017-02-01

    Metamaterials have received significant interest in recent years due to their potential ability to exhibit behaviour not found in naturally occurring materials. This includes the generation of band gaps, which are frequency regions with high levels of wave attenuation. In the context of acoustics, these band gaps can be tuned to occur at low frequencies where the acoustic wavelength is large compared to the material, and where the performance of traditional passive noise control treatments is limited. Therefore, such acoustic metamaterials have been shown to offer a significant performance advantage compared to traditional passive control treatments, however, due to their resonant behaviour, the band gaps tend to occur over a relatively narrow frequency range. A similar long wavelength performance advantage can be achieved using active noise control, but the systems in this case do not rely on resonant behaviour. This paper demonstrates how the performance of an acoustic metamaterial, consisting of an array of Helmholtz resonators, can be significantly enhanced by the integration of an active control mechanism that is facilitated by embedding loudspeakers into the resonators. Crucially, it is then also shown how the active acoustic metamaterial significantly outperforms an equivalent traditional active noise control system. In both cases a broadband feedforward control strategy is employed to minimise the transmitted pressure in a one-dimensional acoustic control problem and a new method of weighting the control effort over a targeted frequency range is described.

  7. LQR Feedback Control Development for Wind Turbines Featuring a Digital Fluid Power Transmission System

    DEFF Research Database (Denmark)

    Pedersen, Niels Henrik; Johansen, Per; Andersen, Torben O.

    2016-01-01

    Research within digital fluid power (DFP) transmissions is receiving an increased attention as an alternative to conventional transmission technologies. The use of DFP displacement machines entail a need for applicable control algorithms. However, the design and analysis of controllers for such d......Research within digital fluid power (DFP) transmissions is receiving an increased attention as an alternative to conventional transmission technologies. The use of DFP displacement machines entail a need for applicable control algorithms. However, the design and analysis of controllers...... motor control strategy consists of a full stroke operation strategy, where a Delta-Sigma pulse density modulator is used to determine the chamber activation sequence. In the LQR-control design approach, the discrete behavior of the motor and Delta-Sigma modulator is described by a discrete linear time...... invariant model. Using full-field flow wind profiles as input, the design approach and control performance is verified by simulation in the dynamic model of the wind turbine featuring the DFP transmission. Additionally, the performance is compared to that of the conventional NREL reference turbine...

  8. From morbidity control to transmission control: time to change tactics against helminths on Unguja Island, Zanzibar.

    Science.gov (United States)

    Knopp, Stefanie; Stothard, J Russell; Rollinson, David; Mohammed, Khalfan A; Khamis, I Simba; Marti, Hanspeter; Utzinger, Jürg

    2013-11-01

    In Zanzibar, the prevalence and intensity of helminth infections have markedly declined over the past 25 years, which is generally attributed to morbidity control programmes emphasising 'preventive chemotherapy'. Here we provide an update of the current situation of soil-transmitted helminthiasis and urinary schistosomiasis on Unguja Island, and highlight socioeconomic development, improvement in sanitation and health education as additional drivers against helminthiases. Our data were obtained from cross-sectional surveys carried out between 2006 and 2009 with stool and urine samples from 2858 and 879 individuals, respectively, examined for helminth eggs and larvae. Additionally, several hundred people were interviewed on sanitation and hygienic behaviour. Data on Unguja's economic growth and improvements in access to clean water and household latrines in the recent past were derived from the extant literature. Pooled prevalences of Trichuris trichiura, Schistosoma haematobium, Ascaris lumbricoides, hookworm and Strongyloides stercoralis were 35%, 29%, 12%, 10% and 6%, respectively. However, there were considerable differences in prevalences between different age-groups and at village and district level. Moreover, some hotspots for A. lumbricoides, T. trichiura and S. haematobium were identified with prevalences above 60% among school-aged children. Availability of a latrine and washing hands before eating did not significantly lower the risk of helminth infections in our study population. Nevertheless, a considerable increase in access to household latrines (from 49% to 72%) and piped water (from 45% to 71%) between 1991 and 2005 is likely to have contributed to reducing the force of transmission of helminthiases in Zanzibar. The next logical step in Unguja is to change the tactics from morbidity control to interruption of helminth transmission and ultimately local elimination. Hence, 'preventive chemotherapy' needs to be further consolidated, placing particular

  9. Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons.

    Science.gov (United States)

    Eastwood, S L; Harrison, P J

    2005-03-01

    Synaptic protein gene expression is altered in schizophrenia. In the hippocampal formation there may be particular involvement of glutamatergic neurons and their synapses, but overall the profile remains unclear. In this in situ hybridization histochemistry (ISHH) study, we examined four informative synaptic protein transcripts: vesicular glutamate transporter (VGLUT) 1, VGLUT2, complexin I, and complexin II, in dorsolateral prefrontal cortex (DPFC), superior temporal cortex (STC), and hippocampal formation, in 13 subjects with schizophrenia and 18 controls. In these areas, VGLUT1 and complexin II are expressed primarily by excitatory neurons, whereas complexin I is mainly expressed by inhibitory neurons. In schizophrenia, VGLUT1 mRNA was decreased in hippocampal formation and DPFC, complexin II mRNA was reduced in DPFC and STC, and complexin I mRNA decreased in STC. Hippocampal VGLUT1 mRNA declined with age selectively in the schizophrenia group. VGLUT2 mRNA was not quantifiable due to its low level. The data provide additional evidence for a synaptic pathology in schizophrenia, in terms of a reduced expression of three synaptic protein genes. In the hippocampus, the loss of VGLUT1 mRNA supports data indicating that glutamatergic presynaptic deficits are prominent, whereas the pattern of results in temporal and frontal cortex suggests broadly similar changes may affect inhibitory and excitatory neurons. The impairment of synaptic transmission implied by the synaptic protein reductions may contribute to the dysfunction of cortical neural circuits that characterises the disorder.

  10. Stochastic lattice model of synaptic membrane protein domains

    Science.gov (United States)

    Li, Yiwei; Kahraman, Osman; Haselwandter, Christoph A.

    2017-05-01

    Neurotransmitter receptor molecules, concentrated in synaptic membrane domains along with scaffolds and other kinds of proteins, are crucial for signal transmission across chemical synapses. In common with other membrane protein domains, synaptic domains are characterized by low protein copy numbers and protein crowding, with rapid stochastic turnover of individual molecules. We study here in detail a stochastic lattice model of the receptor-scaffold reaction-diffusion dynamics at synaptic domains that was found previously to capture, at the mean-field level, the self-assembly, stability, and characteristic size of synaptic domains observed in experiments. We show that our stochastic lattice model yields quantitative agreement with mean-field models of nonlinear diffusion in crowded membranes. Through a combination of analytic and numerical solutions of the master equation governing the reaction dynamics at synaptic domains, together with kinetic Monte Carlo simulations, we find substantial discrepancies between mean-field and stochastic models for the reaction dynamics at synaptic domains. Based on the reaction and diffusion properties of synaptic receptors and scaffolds suggested by previous experiments and mean-field calculations, we show that the stochastic reaction-diffusion dynamics of synaptic receptors and scaffolds provide a simple physical mechanism for collective fluctuations in synaptic domains, the molecular turnover observed at synaptic domains, key features of the observed single-molecule trajectories, and spatial heterogeneity in the effective rates at which receptors and scaffolds are recycled at the cell membrane. Our work sheds light on the physical mechanisms and principles linking the collective properties of membrane protein domains to the stochastic dynamics that rule their molecular components.

  11. Stochastic lattice model of synaptic membrane protein domains.

    Science.gov (United States)

    Li, Yiwei; Kahraman, Osman; Haselwandter, Christoph A

    2017-05-01

    Neurotransmitter receptor molecules, concentrated in synaptic membrane domains along with scaffolds and other kinds of proteins, are crucial for signal transmission across chemical synapses. In common with other membrane protein domains, synaptic domains are characterized by low protein copy numbers and protein crowding, with rapid stochastic turnover of individual molecules. We study here in detail a stochastic lattice model of the receptor-scaffold reaction-diffusion dynamics at synaptic domains that was found previously to capture, at the mean-field level, the self-assembly, stability, and characteristic size of synaptic domains observed in experiments. We show that our stochastic lattice model yields quantitative agreement with mean-field models of nonlinear diffusion in crowded membranes. Through a combination of analytic and numerical solutions of the master equation governing the reaction dynamics at synaptic domains, together with kinetic Monte Carlo simulations, we find substantial discrepancies between mean-field and stochastic models for the reaction dynamics at synaptic domains. Based on the reaction and diffusion properties of synaptic receptors and scaffolds suggested by previous experiments and mean-field calculations, we show that the stochastic reaction-diffusion dynamics of synaptic receptors and scaffolds provide a simple physical mechanism for collective fluctuations in synaptic domains, the molecular turnover observed at synaptic domains, key features of the observed single-molecule trajectories, and spatial heterogeneity in the effective rates at which receptors and scaffolds are recycled at the cell membrane. Our work sheds light on the physical mechanisms and principles linking the collective properties of membrane protein domains to the stochastic dynamics that rule their molecular components.

  12. Automatic Voltage Control (AVC) of Danish Transmission System - Concept design

    DEFF Research Database (Denmark)

    Qin, Nan; Abildgaard, Hans; Lund, P.

    2014-01-01

    the buses are monitored where the voltage magnitudes are maintained continually. The loss minimization including switching cost is the objectives of the AVC system. The reactive power reserves as constraints are taken into account to limit the regulation capabilities of generators. The Day ahead and short......, objectives, constraints, algorithms for optimal power flow and some special functions in particular systems, which inspires the concept design of a Danish AVC system to address the future challenges of voltage control. In the concept, the Danish AVC design is based on a centralized control scheme. All...

  13. Voltage control in the future power transmission systems

    DEFF Research Database (Denmark)

    Qin, Nan

    is strongly tractable for improving the robustness. In case the centralized AVC system is malfunctioning, e.g. telecommunications fails, the distributed fallback controllers will take the control responsibility to maintain the voltage in the acceptable band. The fallback scheme installed at substations...... monitoring local voltage, switch in/out shunts following inverse time characteristics, maintaining the voltage without telecommunications. The entire AVC system robustness is therefore improved. In addition to the AVC system study, there is a chapter introducing the implementation of the advanced load flow...... to the existing AVC systems in term of the cost minimization and the robustness, which shed light to the industrial applications....

  14. Synaptic excitation mediated by AMPA receptors in rat cerebellar slices is selectively enhanced by aniracetam and cyclothiazide.

    Science.gov (United States)

    Boxall, A R; Garthwaite, J

    1995-05-01

    AMPA receptors mediate fast, glutamatergic synaptic transmission in the central nervous system. The time-course of the associated postsynaptic current has been suggested to be determined principally by the kinetics of glutamate binding and receptor desensitization. Aniracetam and cyclothiazide are drugs capable of selectively preventing desensitization of the AMPA receptor. To investigate the relevance of desensitization to fast synaptic transmission in the cerebellum we have tested these compounds against AMPA-induced depolarizations and postsynaptic potentials using the grease-gap recording technique. Aniracetam (1 microM-5 mM) and cyclothiazide (1 microM-500 microM) both enhanced the depolarising action of AMPA (1 microM) on Purkinje cells in a concentration-dependent manner. At the highest concentrations tested, the increases over controls were approximately 600% and 800% respectively. Aniracetam also increased, in a concentration-dependent manner, the amplitude of the evoked synaptic potentials of both parallel fibre-Purkinje cell and mossy fibre-granule cell pathways, with the highest concentrations tested enhancing the potentials by approximately 60% and 75% respectively. These data suggest that, at two different synapses in the cerebellum, AMPA receptor desensitization occurs physiologically and is likely to contribute to the shape of fast synaptic currents.

  15. The Ubiquitin-Proteasome Pathway and Synaptic Plasticity

    Science.gov (United States)

    Hegde, Ashok N.

    2010-01-01

    Proteolysis by the ubiquitin-proteasome pathway (UPP) has emerged as a new molecular mechanism that controls wide-ranging functions in the nervous system, including fine-tuning of synaptic connections during development and synaptic plasticity in the adult organism. In the UPP, attachment of a small protein, ubiquitin, tags the substrates for…

  16. Analysis of Basic Transmission Networks for Integrated Ship Control Systems

    DEFF Research Database (Denmark)

    Hansen, T.N.; Granum-Jensen, M.

    1993-01-01

    Description of a computer network for Integrated Ship Control Systems which is going to be developed as part of an EC-project. Today equipment of different make are not able to communicate with each other because most often each supplier of ISC systems has got their own proprietary network.....

  17. Effect of laparoscopic grasper force transmission ratio on grasp control

    NARCIS (Netherlands)

    Westebring-Van der Putten, E.P.; Van den Dobbelsteen, J.J.; Goossens, R.H.M.; Jakimowicz, J.J.; Dankelman, J.

    2008-01-01

    Background- Surgeons may cause tissue damage by incorrect laparoscopic pinch force control. Unpredictable tissue and grasper properties may cause slips or ruptures. This study investigated how different forms of haptic feedback influence the surgeon’s ability to generate a safe laparoscopic grasp

  18. Environment, arbovirus transmission and control of epidemics Ambiente, transmissão de arbovírus e controle de epidemias

    Directory of Open Access Journals (Sweden)

    Roger Cordellier

    1992-09-01

    Full Text Available In order to illustrate the relationships between the biotopes (or phytogeographical zones, arbovirus vectors and vertebrate hosts (including man, and epidemiology, current knowledge on the transmission of Yellow Fever virus in West Africa is reported. A dynamic scheme has been devised to integrate the observed geographical distribution of cases and the timing of their occurrence. Two principal areas, endemicity and epidetnicity, were defined according to the presence or absence of sylvatic monkey-mosquito transmission. The intensity and potential of contacts between humans and vectors depends on the degree of man-made changes in the environment, often increasing the extension of ecotone areas where the mosquitoes are easily biting at the ground level. Prevention and/or control of arbovirus diseases require detailed eco-epidemiological studies to determine: (1 the effective role of each potential vector in each phytogeographical region; (2 the risk factors for the people living in or near areas with a sylvatic transmission cycle; (3 the priorities - vaccination and/or control - for preventing the expansion of natural foci.Para ilustrar as relações existentes entre os biótopos (ou zonas fitogeográficas, os vetores e hospedeiros vertebrados (incluindo o homem de arbovírus e a epidemiologia, o conhecimento atual sobre a transmissão do vírus de febre amarela na África Ocidental é apresentado e discutido. Um modelo dinâmico foi desenvolvido para integrar a distribuição geográfica dos casos observados e o momento de sua ocorrência. Duas áreas principais, endemicidade e epidemicidade, foram definidas de acordo com a presença ou ausência de transmissão silvática macaco-mosquito. A intensidade e o potencial dos contatos entre homem e vetores depende do grau das alterações ambientais produzidas pelas atividades humanas, geralmente aumentando a extensão das áreas de ecótono onde os mosquitos estão ativos ao nível do solo. A preven

  19. Cadherin-8 expression, synaptic localization and molecular control of neuronal form in prefrontal cortico-striatal circuits

    OpenAIRE

    Friedman, Lauren G.; Riemslagh, Fréderike W.; Sullivan, Josefa M.; Mesias, Roxana; Williams, Frances M.; Huntley, George W.; Benson, Deanna L.

    2014-01-01

    Neocortical interactions with dorsal striatum support many motor and executive functions, and such underlying functional networks are particularly vulnerable to a variety of developmental, neurological, and psychiatric brain disorders, including autism spectrum disorders, Parkinson’s disease, and Huntington’s disease. Relatively little is known about the development of functional corticostriatal interactions, and in particular, virtually nothing is known of molecular mechanisms that control g...

  20. Ubiquitination-dependent mechanisms regulate synaptic growth and function.

    Science.gov (United States)

    DiAntonio, A; Haghighi, A P; Portman, S L; Lee, J D; Amaranto, A M; Goodman, C S

    2001-07-26

    The covalent attachment of ubiquitin to cellular proteins is a powerful mechanism for controlling protein activity and localization. Ubiquitination is a reversible modification promoted by ubiquitin ligases and antagonized by deubiquitinating proteases. Ubiquitin-dependent mechanisms regulate many important processes including cell-cycle progression, apoptosis and transcriptional regulation. Here we show that ubiquitin-dependent mechanisms regulate synaptic development at the Drosophila neuromuscular junction (NMJ). Neuronal overexpression of the deubiquitinating protease fat facets leads to a profound disruption of synaptic growth control; there is a large increase in the number of synaptic boutons, an elaboration of the synaptic branching pattern, and a disruption of synaptic function. Antagonizing the ubiquitination pathway in neurons by expression of the yeast deubiquitinating protease UBP2 (ref. 5) also produces synaptic overgrowth and dysfunction. Genetic interactions between fat facets and highwire, a negative regulator of synaptic growth that has structural homology to a family of ubiquitin ligases, suggest that synaptic development may be controlled by the balance between positive and negative regulators of ubiquitination.

  1. Multiagent System-Based Distributed Coordinated Control for Radial DC Microgrid Considering Transmission Time Delays

    DEFF Research Database (Denmark)

    Dou, Chun-Xia; Yue, Dong; Guerrero, Josep M.

    2017-01-01

    This paper focuses on a multi-agent based distributed coordinated control for radial DC microgrid considering trans-mission time delays. Firstly, a two-level multi-agent system is constructed, where local control is formulated based on local states and executed by means of the first-level agent...

  2. Domestic and peridomestic transmission of American cutaneous leishmaniasis: changing epidemiological patterns present new control opportunities

    Directory of Open Access Journals (Sweden)

    Diarmid Campbell-Lendrum

    2001-02-01

    Full Text Available Predictions that deforestation would reduce American cutaneous leishmaniasis incidence have proved incorrect. Presentations at a recent international workshop, instead, demonstrated frequent domestication of transmission throughout Latin America. While posing new threats, this process also increases the effectiveness of vector control in and around houses. New approaches for sand fly control and effective targeting of resources are reviewed.

  3. Arc protein: a flexible hub for synaptic plasticity and cognition.

    Science.gov (United States)

    Nikolaienko, Oleksii; Patil, Sudarshan; Eriksen, Maria Steene; Bramham, Clive R

    2017-09-07

    Mammalian excitatory synapses express diverse types of synaptic plasticity. A major challenge in neuroscience is to understand how a neuron utilizes different types of plasticity to sculpt brain development, function, and behavior. Neuronal activity-induced expression of the immediate early protein, Arc, is critical for long-term potentiation and depression of synaptic transmission, homeostatic synaptic scaling, and adaptive functions such as long-term memory formation. However, the molecular basis of Arc protein function as a regulator of synaptic plasticity and cognition remains a puzzle. Recent work on the biophysical and structural properties of Arc, its protein-protein interactions and post-translational modifications have shed light on the issue. Here, we present Arc protein as a flexible, multifunctional and interactive hub. Arc interacts with specific effector proteins in neuronal compartments (dendritic spines, nuclear domains) to bidirectionally regulate synaptic strength by distinct molecular mechanisms. Arc stability, subcellular localization, and interactions are dictated by synaptic activity and post-translational modification of Arc. This functional versatility and context-dependent signaling supports a view of Arc as a highly specialized master organizer of long-term synaptic plasticity, critical for information storage and cognition. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals.

    Science.gov (United States)

    Massari, V J; Dickerson, L W; Gray, A L; Lauenstein, J M; Blinder, K J; Newsome, J T; Rodak, D J; Fleming, T J; Gatti, P J; Gillis, R A

    1998-08-17

    Recent physiological evidence indicates that vagal postganglionic control of left ventricular contractility is mediated by neurons found in a ventricular epicardial fat pad ganglion. In the dog this region has been referred to as the cranial medial ventricular (CMV) ganglion [J.L. Ardell, Structure and function of mammalian intrinsic cardiac neurons, in: J.A. Armour, J.L. Ardell (Eds.). Neurocardiology, Oxford Univ. Press, New York, 1994, pp. 95-114; B.X. Yuan, J.L. Ardell, D.A. Hopkins, A.M. Losier, J.A. Armour, Gross and microscopic anatomy of the canine intrinsic cardiac nervous system, Anat. Rec., 239 (1994) 75-87]. Since activation of the vagal neuronal input to the CMV ganglion reduces left ventricular contractility without influencing cardiac rate or AV conduction, this ganglion contains a functionally selective pool of negative inotropic parasympathetic postganglionic neurons. In the present report we have defined the light microscopic distribution of preganglionic negative inotropic neurons in the CNS which are retrogradely labeled from the CMV ganglion. Some tissues were also processed for the simultaneous immunocytochemical visualization of tyrosine hydroxylase (TH: a marker for catecholaminergic neurons) and examined with both light microscopic and electron microscopic methods. Histochemically visualized neurons were observed in a long slender column in the ventrolateral nucleus ambiguus (NA-VL). The greatest number of retrogradely labeled neurons were observed just rostral to the level of the area postrema. TH perikarya and dendrites were commonly observed interspersed with vagal motoneurons in the NA-VL. TH nerve terminals formed axo-dendritic synapses upon negative inotropic vagal motoneurons, however the origin of these terminals remains to be determined. We conclude that synaptic interactions exist which would permit the parasympathetic preganglionic vagal control of left ventricular contractility to be modulated monosynaptically by

  5. Effects of rapamycin treatment after controlled cortical impact injury on neurogenesis and synaptic reorganization in the mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Corwin R Butler

    2015-11-01

    Full Text Available Post-traumatic epilepsy (PTE is one consequence of traumatic brain injury (TBI. A prominent cell signaling pathway activated in animal models of both TBI and epilepsy is the mammalian target of rapamycin (mTOR. Inhibition of mTOR with rapamycin has shown promise as a potential modulator of epileptogenesis in several animal models of epilepsy, but cellular mechanisms linking mTOR expression and epileptogenesis are unclear. In this study, the role of mTOR in modifying functional hippocampal circuit reorganization after focal TBI induced by controlled cortical impact was investigated. Rapamycin (3 or 10 mg/kg, an inhibitor of mTOR signaling, was administered by intraperitoneal injection beginning on the day of injury and continued daily until tissue collection. Relative to controls, rapamycin treatment reduced dentate granule cell area in the hemisphere ipsilateral to the injury two weeks post-injury. Brain injury resulted in a significant increase in doublecortin immunolabeling in the dentate gyrus ipsilateral to the injury, indicating increased neurogenesis shortly after TBI. Rapamycin treatment prevented the increase in doublecortin labeling, with no overall effect on Fluoro-Jade B staining in the ipsilateral hemisphere, suggesting that rapamycin treatment reduced posttraumatic neurogenesis but did not prevent cell loss after injury. At later times post-injury (8-13 weeks, evidence of mossy fiber sprouting and increased recurrent excitation of dentate granule cells was detected, which were attenuated by rapamycin treatment. Rapamycin treatment also diminished seizure prevalence relative to vehicle-treated controls after TBI. Collectively, these results support a role for adult neurogenesis in PTE development and suggest that suppression of epileptogenesis by mTOR inhibition includes effects on post-injury neurogenesis.

  6. Molecular Signatures Underlying Synaptic Vesicle Cargo Retrieval

    Science.gov (United States)

    Mori, Yasunori; Takamori, Shigeo

    2018-01-01

    Efficient retrieval of the synaptic vesicle (SV) membrane from the presynaptic plasma membrane, a process called endocytosis, is crucial for the fidelity of neurotransmission, particularly during sustained neural activity. Although multiple modes of endocytosis have been identified, it is clear that the efficient retrieval of the major SV cargos into newly formed SVs during any of these modes is fundamental for synaptic transmission. It is currently believed that SVs are eventually reformed via a clathrin-dependent pathway. Various adaptor proteins recognize SV cargos and link them to clathrin, ensuring the efficient retrieval of the cargos into newly formed SVs. Here, we summarize our current knowledge of the molecular signatures within individual SV cargos that underlie efficient retrieval into SV membranes, as well as discuss possible contributions of the mechanisms under physiological conditions. PMID:29379416

  7. Modeling Post-death Transmission of Ebola: Challenges for Inference and Opportunities for Control

    Science.gov (United States)

    Weitz, Joshua S.; Dushoff, Jonathan

    2015-03-01

    Multiple epidemiological models have been proposed to predict the spread of Ebola in West Africa. These models include consideration of counter-measures meant to slow and, eventually, stop the spread of the disease. Here, we examine one component of Ebola dynamics that is of ongoing concern - the transmission of Ebola from the dead to the living. We do so by applying the toolkit of mathematical epidemiology to analyze the consequences of post-death transmission. We show that underlying disease parameters cannot be inferred with confidence from early-stage incidence data (that is, they are not ``identifiable'') because different parameter combinations can produce virtually the same epidemic trajectory. Despite this identifiability problem, we find robustly that inferences that don't account for post-death transmission tend to underestimate the basic reproductive number - thus, given the observed rate of epidemic growth, larger amounts of post-death transmission imply larger reproductive numbers. From a control perspective, we explain how improvements in reducing post-death transmission of Ebola may reduce the overall epidemic spread and scope substantially. Increased attention to the proportion of post-death transmission has the potential to aid both in projecting the course of the epidemic and in evaluating a portfolio of control strategies.

  8. Possibilities for Automatic Control of Hydro-Mechanical Transmission and Birotating Electric Machine

    Directory of Open Access Journals (Sweden)

    V. V. Mikhailov

    2014-01-01

    Full Text Available The paper presents mathematical models and results of virtual investigations pertaining to the selected motion parameters of a mobile machine equipped with hydro mechanical and modernized transmissions. The machine has been tested in similar technological cycles and it has been equipped with a universal automatic control system. Changes in structure and type of power transmission have been obtained with the help of a control algorithm including an extra reversible electric machine which is switched in at some operational modes.Implementation of the proposed  concept makes it possible to obtain and check the improved C-code of the control system and enhance operational parameters of the transmission and machine efficiency, reduce slippage and tire wear while using braking energy for its later beneficial use which is usually considered as a consumable element.

  9. Distributed Recurrent Neural Forward Models with Synaptic Adaptation and CPG-based control for Complex Behaviors of Walking Robots

    Directory of Open Access Journals (Sweden)

    Sakyasingha eDasgupta

    2015-09-01

    Full Text Available Walking animals, like stick insects, cockroaches or ants, demonstrate a fascinating range of locomotive abilities and complex behaviors. The locomotive behaviors can consist of a variety of walking patterns along with adaptation that allow the animals to deal with changes in environmental conditions, like uneven terrains, gaps, obstacles etc. Biological study has revealed that such complex behaviors are a result of a combination of biomechanics and neural mechanism thus representing the true nature of embodied interactions. While the biomechanics helps maintain flexibility and sustain a variety of movements, the neural mechanisms generate movements while making appropriate predictions crucial for achieving adaptation. Such predictions or planning ahead can be achieved by way of internal models that are grounded in the overall behavior of the animal. Inspired by these findings, we present here, an artificial bio-inspired walking system which effectively combines biomechanics (in terms of the body and leg structures with the underlying neural mechanisms. The neural mechanisms consist of 1 central pattern generator based control for generating basic rhythmic patterns and coordinated movements, 2 distributed (at each leg recurrent neural network based adaptive forward models with efference copies as internal models for sensory predictions and instantaneous state estimations, and 3 searching and elevation control for adapting the movement of an individual leg to deal with different environmental conditions. Using simulations we show that this bio-inspired approach with adaptive internal models allows the walking robot to perform complex locomotive behaviors as observed in insects, including walking on undulated terrains, crossing large gaps as well as climbing over high obstacles. Furthermore we demonstrate that the newly developed recurrent network based approach to sensorimotor prediction outperforms the previous state of the art adaptive neuron

  10. A Study of Transmission Control Method for Distributed Parameters Measurement in Large Factories and Storehouses

    Directory of Open Access Journals (Sweden)

    Shujing Su

    2015-01-01

    Full Text Available For the characteristics of parameters dispersion in large factories, storehouses, and other applications, a distributed parameter measurement system is designed that is based on the ring network. The structure of the system and the circuit design of the master-slave node are described briefly. The basic protocol architecture about transmission communication is introduced, and then this paper comes up with two kinds of distributed transmission control methods. Finally, the reliability, extendibility, and control characteristic of these two methods are tested through a series of experiments. Moreover, the measurement results are compared and discussed.

  11. Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1

    Directory of Open Access Journals (Sweden)

    Neugebauer Volker

    2010-12-01

    Full Text Available Abstract Neuroplasticity in the central nucleus of the amygdala (CeA, particularly its latero-capsular division (CeLC, is an important contributor to the emotional-affective aspects of pain. Previous studies showed synaptic plasticity of excitatory transmission to the CeLC in different pain models, but pain-related changes of inhibitory transmission remain to be determined. The CeLC receives convergent excitatory inputs from the parabrachial nucleus in the brainstem and from the basolateral amygdala (BLA. In addition, feedforward inhibition of CeA neurons is driven by glutamatergic projections from the BLA area to a cluster of GABAergic neurons in the intercalated cell masses (ITC. Using patch-clamp in rat brain slices we measured monosynaptic excitatory postsynaptic currents (EPSCs and polysynaptic inhibitory currents (IPSCs that were evoked by electrical stimulation in the BLA. In brain slices from arthritic rats, input-output functions of excitatory synaptic transmission were enhanced whereas inhibitory synaptic transmission was decreased compared to control slices from normal untreated rats. A non-NMDA receptor antagonist (NBQX blocked the EPSCs and reduced the IPSCs, suggesting that non-NMDA receptors mediate excitatory transmission and also contribute to glutamate-driven feed-forward inhibition of CeLC neurons. IPSCs were blocked by a GABAA receptor antagonist (bicuculline. Bicuculline increased EPSCs under normal conditions but not in slices from arthritic rats, which indicates a loss of GABAergic control of excitatory transmission. A metabotropic glutamate receptor subtype 1 (mGluR1 antagonist (LY367385 reversed both the increase of excitatory transmission and the decrease of inhibitory transmission in the arthritis pain model but had no effect on basal synaptic transmission in control slices from normal rats. The inhibitory effect of LY367385 on excitatory transmission was blocked by bicuculline suggesting the involvement of a GABAergic

  12. A Beacon Transmission Power Control Algorithm Based on Wireless Channel Load Forecasting in VANETs.

    Science.gov (United States)

    Mo, Yuanfu; Yu, Dexin; Song, Jun; Zheng, Kun; Guo, Yajuan

    2015-01-01

    In a vehicular ad hoc network (VANET), the periodic exchange of single-hop status information broadcasts (beacon frames) produces channel loading, which causes channel congestion and induces information conflict problems. To guarantee fairness in beacon transmissions from each node and maximum network connectivity, adjustment of the beacon transmission power is an effective method for reducing and preventing channel congestion. In this study, the primary factors that influence wireless channel loading are selected to construct the KF-BCLF, which is a channel load forecasting algorithm based on a recursive Kalman filter and employs multiple regression equation. By pre-adjusting the transmission power based on the forecasted channel load, the channel load was kept within a predefined range; therefore, channel congestion was prevented. Based on this method, the CLF-BTPC, which is a transmission power control algorithm, is proposed. To verify KF-BCLF algorithm, a traffic survey method that involved the collection of floating car data along a major traffic road in Changchun City is employed. By comparing this forecast with the measured channel loads, the proposed KF-BCLF algorithm was proven to be effective. In addition, the CLF-BTPC algorithm is verified by simulating a section of eight-lane highway and a signal-controlled urban intersection. The results of the two verification process indicate that this distributed CLF-BTPC algorithm can effectively control channel load, prevent channel congestion, and enhance the stability and robustness of wireless beacon transmission in a vehicular network.

  13. A Beacon Transmission Power Control Algorithm Based on Wireless Channel Load Forecasting in VANETs.

    Directory of Open Access Journals (Sweden)

    Yuanfu Mo

    Full Text Available In a vehicular ad hoc network (VANET, the periodic exchange of single-hop status information broadcasts (beacon frames produces channel loading, which causes channel congestion and induces information conflict problems. To guarantee fairness in beacon transmissions from each node and maximum network connectivity, adjustment of the beacon transmission power is an effective method for reducing and preventing channel congestion. In this study, the primary factors that influence wireless channel loading are selected to construct the KF-BCLF, which is a channel load forecasting algorithm based on a recursive Kalman filter and employs multiple regression equation. By pre-adjusting the transmission power based on the forecasted channel load, the channel load was kept within a predefined range; therefore, channel congestion was prevented. Based on this method, the CLF-BTPC, which is a transmission power control algorithm, is proposed. To verify KF-BCLF algorithm, a traffic survey method that involved the collection of floating car data along a major traffic road in Changchun City is employed. By comparing this forecast with the measured channel loads, the proposed KF-BCLF algorithm was proven to be effective. In addition, the CLF-BTPC algorithm is verified by simulating a section of eight-lane highway and a signal-controlled urban intersection. The results of the two verification process indicate that this distributed CLF-BTPC algorithm can effectively control channel load, prevent channel congestion, and enhance the stability and robustness of wireless beacon transmission in a vehicular network.

  14. A controlled human malaria infection model enabling evaluation of transmission-blocking interventions.

    Science.gov (United States)

    Collins, Katharine A; Wang, Claire Yt; Adams, Matthew; Mitchell, Hayley; Rampton, Melanie; Elliott, Suzanne; Reuling, Isaie J; Bousema, Teun; Sauerwein, Robert; Chalon, Stephan; Möhrle, Jörg J; McCarthy, James S

    2018-03-12

    Drugs and vaccines that can interrupt the transmission of Plasmodium falciparum will be important for malaria control and elimination. However, models for early clinical evaluation of candidate transmission-blocking interventions are currently unavailable. Here, we describe a new model for evaluating malaria transmission from humans to Anopheles mosquitoes using controlled human malaria infection (CHMI). Seventeen healthy malaria-naive volunteers underwent CHMI by intravenous inoculation of P. falciparum-infected erythrocytes to initiate blood-stage infection. Seven to eight days after inoculation, participants received piperaquine (480 mg) to attenuate asexual parasite replication while allowing gametocytes to develop and mature. Primary end points were development of gametocytemia, the transmissibility of gametocytes from humans to mosquitoes, and the safety and tolerability of the CHMI transmission model. To investigate in vivo gametocytocidal drug activity in this model, participants were either given an experimental antimalarial, artefenomel (500 mg), or a known gametocytocidal drug, primaquine (15 mg), or remained untreated during the period of gametocyte carriage. Male and female gametocytes were detected in all participants, and transmission to mosquitoes was achieved from 8 of 11 (73%) participants evaluated. Compared with results in untreated controls (n = 7), primaquine (15 mg, n = 5) significantly reduced gametocyte burden (P = 0.01), while artefenomel (500 mg, n = 4) had no effect. Adverse events (AEs) were mostly mild or moderate. Three AEs were assessed as severe - fatigue, elevated alanine aminotransferase, and elevated aspartate aminotransferase - and were attributed to malaria infection. Transaminase elevations were transient, asymptomatic, and resolved without intervention. We report the safe and reproducible induction of P. falciparum gametocytes in healthy malaria-naive volunteers at densities infectious to mosquitoes, thereby demonstrating the

  15. A digital, decentralized power station control system with bus-transmission facilitates the problem of backfitting

    International Nuclear Information System (INIS)

    Kaiser, G.E.; Schemmel, R.R.

    1985-01-01

    Current NPP control equipment technology is essentially characterized by the transmission of information in parallel using individual cables, and utilizes hardwired techniques for the processing of information. Progress in the area of semiconductor development characterized by micro-processors and LSI-circuits, has opened up new possibilities for the solution of the control tasks. The new power station control system PROCONTROL P utilizes these possibilities

  16. Dynamic Analysis and Control of the Clutch Filling Process in Clutch-to-Clutch Transmissions

    OpenAIRE

    Wei Guo; Yanfang Liu; Jing Zhang; Xiangyang Xu

    2014-01-01

    Clutch fill control in clutch-to-clutch transmissions influences shift quality considerably. An oncoming clutch should be applied synchronously with the release of an offgoing clutch to shift gear smoothly; therefore, the gap between the piston and clutch plates should be eliminated when the torque capacity is near zero at the end of the clutch fill phase. Open-loop control is typically implemented for the clutch fill because of the cost of pressure sensor. Low control precision causes underf...

  17. Coordinated corrective control for transient stability enhancement in future Great Britain transmission system

    OpenAIRE

    Martinez Sanz, I; Chaudhuri, B; Strbac, G

    2016-01-01

    This paper demonstrates a corrective control strategy through fast actuators (TCSC FACTS and HVDC links, both LCC and VSC) in order to enhance the transient stability in the future Great Britain (GB) transmission network. A model predictive control (MPC) scheme that relies on system wide-area measurements is employed for coordinated control action through these power electronic devices with the aim of preserving the system stability without having to constrain pre-fault transfer levels. Case ...

  18. Multilevel Modular Converter for VSC-HVDC Transmission Applications: Control and Operational Aspects

    DEFF Research Database (Denmark)

    Gnanarathna, Udana N.; Gole, Aniruddha M.; Chaudhary, Sanjay Kumar

    2010-01-01

    Control methods for a new class of converter, the multilevel modular converter (MMC), recently introduced for HVDC transmission are discussed. The paper discusses converter-level controls including firing pulse generation and capacitor voltage balancing. It also covers higher level controls...... for incorporating the converter into a larger power network, with a weak ac receiving end. The performance behavior is studied using electromagnetic transients simulation....

  19. Cholinergic Interneurons Amplify Corticostriatal Synaptic Responses in the Q175 Model of Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Asami Tanimura

    2016-12-01

    Full Text Available Huntington’s disease (HD is a neurodegenerative disorder characterized by deficits in movement control that are widely viewed as stemming from pathophysiological changes in the striatum. Giant, aspiny cholinergic interneurons (ChIs are key elements in the striatal circuitry controlling movement, but whether their physiological properties are intact in the HD brain is unclear. To address this issue, the synaptic properties of ChIs were examined using optogenetic approaches in the Q175 mouse model of HD. In ex vivo brain slices, synaptic facilitation at thalamostriatal synapses onto ChIs was reduced in Q175 mice. The alteration in thalamostriatal transmission was paralleled by an increased response to optogenetic stimulation of cortical axons, enabling these inputs to more readily induce burst-pause patterns of activity in ChIs. This adaptation was dependent upon amplification of cortically evoked responses by a post-synaptic upregulation of voltage-dependent Na+ channels. This upregulation also led to an increased ability of somatic spikes to invade ChI dendrites. However, there was not an alteration in the basal pacemaking rate of ChIs, possibly due to increased availability of Kv4 channels. Thus, there is a functional ‘re-wiring’ of the striatal networks in Q175 mice, which results in greater cortical control of phasic ChI activity, which is widely thought to shape the impact of salient stimuli on striatal action selection.

  20. Synaptic Scaling in Combination with Many Generic Plasticity Mechanisms Stabilizes Circuit Connectivity

    Science.gov (United States)

    Tetzlaff, Christian; Kolodziejski, Christoph; Timme, Marc; Wörgötter, Florentin

    2011-01-01

    Synaptic scaling is a slow process that modifies synapses, keeping the firing rate of neural circuits in specific regimes. Together with other processes, such as conventional synaptic plasticity in the form of long term depression and potentiation, synaptic scaling changes the synaptic patterns in a network, ensuring diverse, functionally relevant, stable, and input-dependent connectivity. How synaptic patterns are generated and stabilized, however, is largely unknown. Here we formally describe and analyze synaptic scaling based on results from experimental studies and demonstrate that the combination of different conventional plasticity mechanisms and synaptic scaling provides a powerful general framework for regulating network connectivity. In addition, we design several simple models that reproduce experimentally observed synaptic distributions as well as the observed synaptic modifications during sustained activity changes. These models predict that the combination of plasticity with scaling generates globally stable, input-controlled synaptic patterns, also in recurrent networks. Thus, in combination with other forms of plasticity, synaptic scaling can robustly yield neuronal circuits with high synaptic diversity, which potentially enables robust dynamic storage of complex activation patterns. This mechanism is even more pronounced when considering networks with a realistic degree of inhibition. Synaptic scaling combined with plasticity could thus be the basis for learning structured behavior even in initially random networks. PMID:22203799

  1. GABAA Receptor-Mediated Bidirectional Control of Synaptic Activity, Intracellular Ca2+, Cerebral Blood Flow, and Oxygen Consumption in Mouse Somatosensory Cortex In Vivo

    DEFF Research Database (Denmark)

    Jessen, Sanne Barsballe; Brazhe, Alexey; Lind, Barbara Lykke

    2015-01-01

    concentrations of THIP suppressed ΔCBF and ΔCMRO2 at high stimulation frequencies. Zolpidem had similar but less-pronounced effects, with similar dependence on drug concentration and stimulation frequency. Our present findings suggest that slight increases in both synaptic and extrasynaptic GABAAR activity might...

  2. Design and control of electromagnetic clutch actuation system for automated manual transmission

    Science.gov (United States)

    Ranjan, Ashish; Prasanth, S.; Cherian, Fenin; Baskar, P.

    2017-11-01

    There is a growing interest towards Automatic Transmission in India as it provides better comfort and drivability. But the high cost of this system is limiting itself to be successful in the Indian markets. Due to this, Automated Manual Transmission (AMT) is considered which provides a better solution towards automation as it enhances the drivability and fuel consumption characteristics of a manual transmission at lower costs. However, torque lag and comfort are major issues with AMT which can be addressed by reducing the shift time. In this paper we describe an Electromagnetic Linear Clutch Actuator as a replacement to current electrohydraulic and electromechanical actuator. A control system for the actuator is presented and a clutch engagement strategy is also implemented which reduces the engagement time to 0.78 seconds while reducing jerk and torque lag. The actuator and control system is simulated on a MATLAB Simulink and agreeable results have been obtained.

  3. Remote Control System of the TJ-II Microwave Transmission Lines Mirrors

    International Nuclear Information System (INIS)

    Lopez Sanchez, A.; Fernandez, A.; Cappa, A.; Gama, J. de la; Olivares, J.; Garcia, R.; Chamorro, M.

    2007-01-01

    The ECRH system of the TJ-II stellarator has two gyrotrons, which deliver a maximum power of 300 kW each at a frequency of 53.2 GHz. Another 28 GHz gyrotron will be used to heat the plasma by electron Bernstein waves (EBWH). The microwave power is transmitted from the gyrotrons to the vacuum chamber by two quasi-optical transmission lines for ECRH and a corrugated waveguide for EBWH. All transmission lines have an internal movable mirror inside the vacuum chamber to focus the beam and to be able to change the launching angle. The control of the beam polarization is very important and the lines have two corrugated mirrors, which actuate as polarizers. In this report the control system of the position of these three internal mirrors and the polarizers of the EBWH transmission line is described. (Author) 20 refs

  4. Operation and control of a DC-grid offshore wind farm under DC transmission system faults

    DEFF Research Database (Denmark)

    Deng, Fujin; Chen, Zhe

    2013-01-01

    . Consequently, the protection and control strategies of dc systems need to be established. This paper studies a dc-grid offshore wind farm, where the wind power collection system and power transmission system adopt dc technology. In this paper, the redundancy of the HVDC transmission system under faults...... is studied, and a fault ridethrough strategy for the dc-grid offshore wind farm is proposed. The proposed strategy can effectively minimize the impacts of the power transmission system disturbance on the offshore wind farm, and on the ac grid. A dc-grid offshore wind farm example is simulated with PSCAD....../EMTDC, and the results validate the feasibility of the presented redundancy configuration and operation approach, and the fault ridethrough control strategy....

  5. Optimal control of a wind turbine with digital fluid power transmission

    DEFF Research Database (Denmark)

    Pedersen, Niels Henrik; Johansen, Per; Andersen, Torben O.

    2018-01-01

    Digital fluid power (DFP) technology may lead to a paradigm shift in large-scale transmission systems in, e.g., wind and wave energy. Therefore, the development of applicable control algorithms is of major importance, but is complicated by the non-smooth behavior of the DFP displacement machines....... The power throughput of a full stroke operated digital displacement machine is quantized by the number of pressure chambers. The dynamics of each pressure chamber may be described by highly nonlinear continuous differential equations, whereas the input is discretely updated and binary (active or inactive......) control theory. The control strategy is validated for control of a digital fluid power wind turbine transmission, where both a deterministic and a stochastic optimal controllers are synthesized. The study is based on the NREL 5-MW reference wind turbine, where its model is combined with a nonlinear model...

  6. A unified modeling and control design for precision transmission system with friction and backlash

    Directory of Open Access Journals (Sweden)

    Xiulan Bao

    2016-05-01

    Full Text Available The structural flexibility, nonlinear friction, and backlash are the major factors limiting the control performance of precision transmission systems. If uncompensated, these factors compromise the positioning and tracking accuracy of precision transmission systems and even cause limit cycles and oscillation. In this article, a framework for integrated design from dynamic modeling to controller design is proposed. A multi-state dynamic model is presented, which can unify the modeling for a multi-state, discontinuous system including the motor state, the motion state, the mechanical contact state, and the friction state. Then, a control design method related to the dynamic modeling using perturbation separation of the model parameters is presented. Using the proposed modeling method, a continuous dynamic model is established to include all different partition models. The model comprehensively describes the mechanical and electrical characteristics of the precision transmission system. A robust controller is designed using the proposed control method. Experimental results demonstrate that the proposed modeling method is accurate and the proposed control method significantly improves accuracy and robustness of the controller compared to traditional control methods.

  7. Controlling risks of pathogen transmission by flies on organic pig farms

    NARCIS (Netherlands)

    Meerburg, B.G.; Vermeer, H.M.; Kijlstra, A.

    2007-01-01

    Fly prevention and control on animal production units is necessary to prevent the transmission of pathogens that could affect animal and human health and the maintenance of good hygiene. Organic farmers are often hesitant to apply insecticides for this purpose because of their farming philosophy.

  8. Optimal control of a wind turbine with digital fluid power transmission

    DEFF Research Database (Denmark)

    Pedersen, Niels Henrik; Johansen, Per; Andersen, Torben O.

    2018-01-01

    Digital fluid power (DFP) technology may lead to a paradigm shift in large-scale transmission systems in, e.g., wind and wave energy. Therefore, the development of applicable control algorithms is of major importance, but is complicated by the non-smooth behavior of the DFP displacement machines....

  9. (facts) to improve the power flow control in the nigeria transmission n

    African Journals Online (AJOL)

    BARTH EKWUEME

    reliability of power supply to consumers. KEYWORDS: FACTS, Transmission, Power Flow, Compensation, Power Loss, Voltage drop, UPFC. INTRODUCTION. The developing of interest in tools for power flow control in a power system has increased significantly during the last 10 years. Demand for research in this.

  10. Intervention methods to control the transmission of noroviruses and other enteric and respiratory viruses

    NARCIS (Netherlands)

    Tuladhar, E.

    2014-01-01

    Intervention methods to control the transmission of noroviruses and other enteric and respiratory viruses

    Era Tuladhar

    Abstract

    Human noroviruses are the leading cause of acute and outbreak associated gastroenteritis worldwide. The outbreaks

  11. Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle.

    Directory of Open Access Journals (Sweden)

    Wilfredo Blanco

    2015-05-01

    Full Text Available Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS followed by a rebound during rapid-eye-movement sleep (REM. The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes

  12. Synaptic control of motoneuronal excitability

    DEFF Research Database (Denmark)

    Rekling, J C; Funk, G D; Bayliss, D A

    2000-01-01

    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 therefor...

  13. Effects of early life stress on rodent hippocampal synaptic plasticity : a systematic review

    NARCIS (Netherlands)

    Derks, Nienke AV; Krugers, Harm J; Hoogenraad, Casper C.; Joëls, Marian; Sarabdjitsingh, R.A.

    2017-01-01

    Early life stress shapes brain development and animal behavior. Neurophysiological properties such as signal transmission and synaptic plasticity are thought to underlie the animal's behavioral performance. We carried out a systematic review to determine how early life stress relates to

  14. Prediction and control of brucellosis transmission of dairy cattle in Zhejiang Province, China.

    Science.gov (United States)

    Zhang, Juan; Sun, Gui-Quan; Sun, Xiang-Dong; Hou, Qiang; Li, Mingtao; Huang, Baoxu; Wang, Haiyan; Jin, Zhen

    2014-01-01

    Brucellosis is a bacterial disease caused by brucella; mainly spread by direct contact transmission through the brucella carriers, or indirect contact transmission by the environment containing large quantities of bacteria discharged by the infected individuals. At the beginning of 21st century, the epidemic among dairy cows in Zhejiang province, began to come back and has become a localized prevalent epidemic. Combining the pathology of brucellosis, the reported positive data characteristics, and the feeding method in Zhejiang province, this paper establishes an SEIV dynamic model to excavate the internal transmission dynamics, fit the real disease situation, predict brucellosis tendency and assess control measures in dairy cows. By careful analysis, we give some quantitative results as follows. (1) The external input of dairy cows from northern areas may lead to high fluctuation of the number of the infectious cows in Zhejiang province that can reach several hundreds. In this case, the disease cannot be controlled and the infection situation cannot easily be predicted. Thus, this paper encourages cows farms to insist on self-supplying production of the dairy cows. (2) The effect of transmission rate of brucella in environment to dairy cattle on brucellosis spreading is greater than transmission rate of the infectious dairy cattle to susceptible cattle. The prevalence of the epidemic is mainly aroused by environment transmission. (3) Under certain circumstances, the epidemic will become a periodic phenomenon. (4) For Zhejiang province, besides measures that have already been adopted, sterilization times of the infected regions is suggested as twice a week, and should be combined with management of the birth rate of dairy cows to control brucellosis spread.

  15. Phase control of light transmission and reflection based biexciton coherence in a defect dielectric medium.

    Science.gov (United States)

    Asadpour, Seyyed Hossein; Soleimani, H Rahimpour

    2014-10-01

    Phase control of two weak probe lights' transmission and reflection based biexciton coherence in a defect dielectric medium doped by four-level GaAs/AlGaAs multiple quantum wells with 15 periods of 17.5 nm GaAs wells and 15 nm Al0.3Ga0.7As barriers is theoretically investigated. The biexciton coherence in this scheme is set up by two continuous wave control fields that couple to a resonance of biexcitons. It is shown that the transmission and reflection properties versus relative phase between applied fields can be controlled by the intensity of control fields and exciton spin relaxation between exciton states. Our studies show that many-particle interactions due to Coulomb correlations in semiconductors can be harnessed by quantum coherence in an interacting many-particle system.

  16. Clutch fill control of an automatic transmission for heavy-duty vehicle applications

    Science.gov (United States)

    Meng, Fei; Chen, Huiyan; Zhang, Tao; Zhu, Xiaoyuan

    2015-12-01

    In this paper an integrated clutch filling phase control for gearshifts on wet clutch transmissions is developed. In a clutch-to-clutch shift of an automatic transmission, in order to obtain smooth gearshift, it should synchronize the oncoming clutch and the off-going clutch timely as well as precise pressure control for the engagement of the oncoming clutch. However, before the oncoming clutch pressure starts to increase, the initial cavity of the clutch chamber has to be filled first. The filling time and stability of the fill phase are very important for the clutch control. In order to improve the shift quality of the automatic transmission which is equipped on heavy-duty vehicles, the electro-hydraulic clutch actuation system is analysed and modelled. A new fill phase control strategy is proposed based on the system analysis as well as the control parameters are optimized according to the variation of the oil temperature and engine speed. The designed strategy is validated by a simulation work. The results demonstrate that the proposed control strategy and parameters modified method can transit the shift process from the fill phase to the torque phase effectively.

  17. BDNF-induced local protein synthesis and synaptic plasticity.

    Science.gov (United States)

    Leal, Graciano; Comprido, Diogo; Duarte, Carlos B

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and long-term potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-γ (PLC-γ) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre- and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short- and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. The impact of illness on social networks: implications for transmission and control of influenza.

    Science.gov (United States)

    Van Kerckhove, Kim; Hens, Niel; Edmunds, W John; Eames, Ken T D

    2013-12-01

    We expect social networks to change as a result of illness, but social contact data are generally collected from healthy persons. Here we quantified the impact of influenza-like illness on social mixing patterns. We analyzed the contact patterns of persons from England measured when they were symptomatic with influenza-like illness during the 2009 A/H1N1pdm influenza epidemic (2009-2010) and again 2 weeks later when they had recovered. Illness was associated with a reduction in the number of social contacts, particularly in settings outside the home, reducing the reproduction number to about one-quarter of the value it would otherwise have taken. We also observed a change in the age distribution of contacts. By comparing the expected age distribution of cases resulting from transmission by (a)symptomatic persons with incidence data, we estimated the contribution of both groups to transmission. Using this, we calculated the fraction of transmission resulting from (a)symptomatic persons, assuming equal duration of infectiousness. We estimated that 66% of transmission was attributable to persons with symptomatic disease (95% confidence interval: 0.23, 1.00). This has important implications for control: Treating symptomatic persons with antiviral agents or encouraging home isolation would be expected to have a major impact on transmission, particularly since the reproduction number for this strain was low.

  19. The RNA-binding protein, ZC3H14, is required for proper poly(A) tail length control, expression of synaptic proteins, and brain function in mice.

    Science.gov (United States)

    Rha, Jennifer; Jones, Stephanie K; Fidler, Jonathan; Banerjee, Ayan; Leung, Sara W; Morris, Kevin J; Wong, Jennifer C; Inglis, George Andrew S; Shapiro, Lindsey; Deng, Qiudong; Cutler, Alicia A; Hanif, Adam M; Pardue, Machelle T; Schaffer, Ashleigh; Seyfried, Nicholas T; Moberg, Kenneth H; Bassell, Gary J; Escayg, Andrew; García, Paul S; Corbett, Anita H

    2017-10-01

    A number of mutations in genes that encode ubiquitously expressed RNA-binding proteins cause tissue specific disease. Many of these diseases are neurological in nature revealing critical roles for this class of proteins in the brain. We recently identified mutations in a gene that encodes a ubiquitously expressed polyadenosine RNA-binding protein, ZC3H14 (Zinc finger CysCysCysHis domain-containing protein 14), that cause a nonsyndromic, autosomal recessive form of intellectual disability. This finding reveals the molecular basis for disease and provides evidence that ZC3H14 is essential for proper brain function. To investigate the role of ZC3H14 in the mammalian brain, we generated a mouse in which the first common exon of the ZC3H14 gene, exon 13 is removed (Zc3h14Δex13/Δex13) leading to a truncated ZC3H14 protein. We report here that, as in the patients, Zc3h14 is not essential in mice. Utilizing these Zc3h14Δex13/Δex13mice, we provide the first in vivo functional characterization of ZC3H14 as a regulator of RNA poly(A) tail length. The Zc3h14Δex13/Δex13 mice show enlarged lateral ventricles in the brain as well as impaired working memory. Proteomic analysis comparing the hippocampi of Zc3h14+/+ and Zc3h14Δex13/Δex13 mice reveals dysregulation of several pathways that are important for proper brain function and thus sheds light onto which pathways are most affected by the loss of ZC3H14. Among the proteins increased in the hippocampi of Zc3h14Δex13/Δex13 mice compared to control are key synaptic proteins including CaMK2a. This newly generated mouse serves as a tool to study the function of ZC3H14 in vivo. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Drivability Improvement Control for Vehicle Start-Up Applied to an Automated Manual Transmission

    Directory of Open Access Journals (Sweden)

    Danna Jiang

    2017-01-01

    Full Text Available Drivability is the key factor for the automated manual transmission. It includes fast response to the driver’s demand and the driving comfort. This paper deals with a control methodology applied to an automated manual transmission vehicle for drivability enhancement during vehicle start-up phase. Based on a piecewise model of powertrain, a multiple-model predictive controller (mMPC is designed with the engine speed, clutch disc speed, and wheel speed as the measurable input variables and the engine torque reference and clutch friction torque reference as the controller’s output variables. The model not only includes the clutch dynamic, the flexible shaft dynamic, but also includes the actuators’ delay character. Considering the driver’s intention, a slipping speed trajectory is generated based on the acceleration pedal dynamically. The designed control strategy is verified on a complete powertrain and longitudinal vehicle dynamic model with different driver’s torque demands.

  1. The Role of Proteases in Hippocampal Synaptic Plasticity: Putting Together Small Pieces of a Complex Puzzle.

    Science.gov (United States)

    Salazar, Ivan L; Caldeira, Margarida V; Curcio, Michele; Duarte, Carlos B

    2016-02-01

    Long-term synaptic plasticity in the hippocampus is thought to underlie the formation of certain forms of memory, including spatial memory. The early phase of long-term synaptic potentiation and synaptic depression depends on post-translational modifications of synaptic proteins, while protein synthesis is also required for the late-phase of both forms of synaptic plasticity (L-LTP and L-LTD). Numerous pieces of evidence show a role for different types of proteases in synaptic plasticity, further increasing the diversity of mechanisms involved in the regulation of the intracellular and extracellular protein content. The cleavage of extracellular proteins is coupled to changes in postsynaptic intracellular mechanisms, and additional alterations in this compartment result from the protease-mediated targeting of intracellular proteins. Both mechanisms contribute to initiate signaling cascades that drive downstream pathways coupled to synaptic plasticity. In this review we summarize the evidence pointing to a role for extracellular and intracellular proteases, with distinct specificities, in synaptic plasticity. Where in the cells the proteases are located, and how they are regulated is also discussed. The combined actions of proteases and translation mechanisms contribute to a tight control of the synaptic proteome relevant for long-term synaptic potentiation and synaptic depression in the hippocampus. Additional studies are required to elucidate the mechanisms whereby these changes in the synaptic proteome are related with plasticity phenomena.

  2. Nuclear calcium signaling controls expression of a large gene pool: identification of a gene program for acquired neuroprotection induced by synaptic activity.

    Science.gov (United States)

    Zhang, Sheng-Jia; Zou, Ming; Lu, Li; Lau, David; Ditzel, Désirée A W; Delucinge-Vivier, Celine; Aso, Yoshinori; Descombes, Patrick; Bading, Hilmar

    2009-08-01

    Synaptic activity can boost neuroprotection through a mechanism that requires synapse-to-nucleus communication and calcium signals in the cell nucleus. Here we show that in hippocampal neurons nuclear calcium is one of the most potent signals in neuronal gene expression. The induction or repression of 185 neuronal activity-regulated genes is dependent upon nuclear calcium signaling. The nuclear calcium-regulated gene pool contains a genomic program that mediates synaptic activity-induced, acquired neuroprotection. The core set of neuroprotective genes consists of 9 principal components, termed Activity-regulated Inhibitor of Death (AID) genes, and includes Atf3, Btg2, GADD45beta, GADD45gamma, Inhibin beta-A, Interferon activated gene 202B, Npas4, Nr4a1, and Serpinb2, which strongly promote survival of cultured hippocampal neurons. Several AID genes provide neuroprotection through a common process that renders mitochondria more resistant to cellular stress and toxic insults. Stereotaxic delivery of AID gene-expressing recombinant adeno-associated viruses to the hippocampus confers protection in vivo against seizure-induced brain damage. Thus, treatments that enhance nuclear calcium signaling or supplement AID genes represent novel therapies to combat neurodegenerative conditions and neuronal cell loss caused by synaptic dysfunction, which may be accompanied by a deregulation of calcium signal initiation and/or propagation to the cell nucleus.

  3. Nuclear calcium signaling controls expression of a large gene pool: identification of a gene program for acquired neuroprotection induced by synaptic activity.

    Directory of Open Access Journals (Sweden)

    Sheng-Jia Zhang

    2009-08-01

    Full Text Available Synaptic activity can boost neuroprotection through a mechanism that requires synapse-to-nucleus communication and calcium signals in the cell nucleus. Here we show that in hippocampal neurons nuclear calcium is one of the most potent signals in neuronal gene expression. The induction or repression of 185 neuronal activity-regulated genes is dependent upon nuclear calcium signaling. The nuclear calcium-regulated gene pool contains a genomic program that mediates synaptic activity-induced, acquired neuroprotection. The core set of neuroprotective genes consists of 9 principal components, termed Activity-regulated Inhibitor of Death (AID genes, and includes Atf3, Btg2, GADD45beta, GADD45gamma, Inhibin beta-A, Interferon activated gene 202B, Npas4, Nr4a1, and Serpinb2, which strongly promote survival of cultured hippocampal neurons. Several AID genes provide neuroprotection through a common process that renders mitochondria more resistant to cellular stress and toxic insults. Stereotaxic delivery of AID gene-expressing recombinant adeno-associated viruses to the hippocampus confers protection in vivo against seizure-induced brain damage. Thus, treatments that enhance nuclear calcium signaling or supplement AID genes represent novel therapies to combat neurodegenerative conditions and neuronal cell loss caused by synaptic dysfunction, which may be accompanied by a deregulation of calcium signal initiation and/or propagation to the cell nucleus.

  4. Control apparatus for vehicle power transmitting system including continuously variable transmission

    Energy Technology Data Exchange (ETDEWEB)

    Nakawaki, Y.; Numazawa, A.; Hayashi, T.

    1989-06-06

    This patent describes a control apparatus for a power transmitting system for an automotive vehicle, including a continuously variable transmission whose speed ratio is continuously variable, wherein power is transmitted from an engine of the vehicle to drive wheels of the vehicle. The control apparatus consists of: first detector means for detecting a currently required output of the engine; second detector means for detecting a running speed of the vehicle; mode selector means responsive to the first detector means, for selecting one of a continuously variable speed mode in which the speed ratio of the continuously variable transmission is continuously variable transmission is continuously changed, and a stepping shift mode in which the speed ratio is changed in steps, the continuously variable transmission having speed-ratio positions which correspond to the steps, the mode selector means selecting the continuously variable speed mode while the currently required output of the engine detected by the first detector means is equal to or smaller than a predetermined reference value, and selecting the stepping shift mode when the currently required output of the engine exceeds the predetermined reference value during an increase in the detected required output of the engine.

  5. Short report: secondary transmission in porcine cysticercosis: description and their potential implications for control sustainability.

    Science.gov (United States)

    Gonzalez, Armando E; López-Urbina, Teresa; Tsang, Byron Y; Gavidia, César M; Garcia, Héctor H; Silva, María E; Ramos, Daphne D; Manzanedo, Rafael; Sánchez-Hidalgo, Lelia; Gilman, Robert H; Tsang, Victor C W

    2005-09-01

    Taenia solium taeniasis/cysticercosis is one of few potentially eradicable infectious diseases and is the target of control programs in several countries. The larval stage of this zoonotic cestode invades the human brain and is responsible for most cases of adult-onset epilepsy in the world. The pig is the natural intermediate host, harboring the larvae or cysticerci. Our current understanding of the life cycle implicates humans as the only definitive host and tapeworm carrier (developing taeniasis) and thus the sole source of infective eggs that are responsible for cysticercosis in both human and pigs through oral-fecal transmission. Here we show evidence of an alternative pig-to-pig route of transmission, previously not suspected to exist. In a series of four experiments, naive sentinel pigs were exposed to pigs that had been infected orally with tapeworm segments (containing infective eggs) and moved to a clean environment. Consistently in all four experiments, at least one of the sentinel pigs became seropositive or infected with parasite cysts with much lower cyst burdens than did primarily infected animals. Second-hand transmission of Taenia solium eggs could explain the overdispersed pattern of porcine cysticercosis, with few pigs harboring heavy parasite burdens and many more harboring small numbers of parasites. This route of transmission opens new avenues for consideration with respect to control strategies.

  6. Modelling lymphatic filariasis transmission and control: modelling frameworks, lessons learned and future directions.

    Science.gov (United States)

    Stolk, Wilma A; Stone, Chris; de Vlas, Sake J

    2015-03-01

    Mathematical modelling provides a useful tool for policy making and planning in lymphatic filariasis control programmes, by providing trend forecasts based on sound scientific knowledge and principles. This is now especially true, in view of the ambitious target to eliminate lymphatic filariasis as a public health problem globally by the year 2020 and the short remaining timeline to achieve this. To meet this target, elimination programmes need to be accelerated, requiring further optimization of strategies and tailoring to local circumstances. Insights from epidemiological transmission models provide a useful basis. Two general models of lymphatic filariasis transmission and control are nowadays in use to support decision-making, namely a population-based deterministic model (EPIFIL) and an individual-based stochastic model (LYMFASIM). Model predictions confirm that lymphatic filariasis transmission can be interrupted by annual mass drug administration (MDA), but this may need to be continued much longer than the initially suggested 4-6 years in areas with high transmission intensity or poor treatment coverage. However, the models have not been validated against longitudinal data describing the impact of MDA programmes. Some critical issues remain to be incorporated in one or both of the models to make predictions on elimination more realistic, including the possible occurrence of systematic noncompliance, the risk of emerging parasite resistance to anthelmintic drugs, and spatial heterogeneities. Rapid advances are needed to maximize the utility of models in decision-making for the ongoing ambitious lymphatic filariasis elimination programmes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Synaptic electronics: materials, devices and applications.

    Science.gov (United States)

    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.

  8. Alleviation SSR and Low Frequency Power Oscillations in Series Compensated Transmission Line using SVC Supplementary Controllers

    Science.gov (United States)

    Kumar, Sanjiv; Kumar, Narendra

    2017-06-01

    In this work, supplementary sub-synchronous damping controllers (SSDC) are proposed for damping sub-synchronous oscillations in power systems with series compensated transmission lines. Series compensation have extensively been used as effective means of increasing the power transfer capability of a transmission lines and improving transient stability limits of power systems. Series compensation with transmission lines may cause sub-synchronous resonance (SSR). The eigenvalue investigation tool is used to ascertain the existence of SSR. It is shown that the addition of supplementary controller is able to stabilize all unstable modes for T-network model. Eigenvalue investigation and time domain transient simulation of detailed nonlinear system are considered to investigate the performance of the controllers. The efficacies of the suggested supplementary controllers are compared on the IEEE first benchmark model for computer simulations of SSR by means of time domain simulation in Matlab/Simulink environment. Supplementary SSDC are considered in order to compare effectiveness of SSDC during higher loading in alleviating the small signal stability problem.

  9. Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex.

    Science.gov (United States)

    Xing, Bo; Li, Yan-Chun; Gao, Wen-Jun

    2016-06-15

    Among the neuromodulators that regulate prefrontal cortical circuit function, the catecholamine transmitters norepinephrine (NE) and dopamine (DA) stand out as powerful players in working memory and attention. Perturbation of either NE or DA signaling is implicated in the pathogenesis of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia, and drug addiction. Although the precise mechanisms employed by NE and DA to cooperatively control prefrontal functions are not fully understood, emerging research indicates that both transmitters regulate electrical and biochemical aspects of neuronal function by modulating convergent ionic and synaptic signaling in the prefrontal cortex (PFC). This review summarizes previous studies that investigated the effects of both NE and DA on excitatory and inhibitory transmissions in the prefrontal cortical circuitry. Specifically, we focus on the functional interaction between NE and DA in prefrontal cortical local circuitry, synaptic integration, signaling pathways, and receptor properties. Although it is clear that both NE and DA innervate the PFC extensively and modulate synaptic function by activating distinctly different receptor subtypes and signaling pathways, it remains unclear how these two systems coordinate their actions to optimize PFC function for appropriate behavior. Throughout this review, we provide perspectives and highlight several critical topics for future studies. This article is part of a Special Issue entitled SI: Noradrenergic System. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Synaptic Homeostasis and Allostasis in the Dentate Gyrus Caused by Inflammatory and Neuropathic Pain Conditions

    Directory of Open Access Journals (Sweden)

    Rui-Rui Wang

    2018-01-01

    Full Text Available It has been generally accepted that pain can cause imbalance between excitation and inhibition (homeostasis at the synaptic level. However, it remains poorly understood how this imbalance (allostasis develops in the CNS under different pain conditions. Here, we analyzed the changes in both excitatory and inhibitory synaptic transmission and modulation of the dentate gyrus (DG under two pain conditions with different etiology and duration. First, it was revealed that the functions of the input-output (I/O curves for evoked excitatory postsynaptic currents (eEPSCs following the perforant path (PP stimulation were gained under both acute inflammatory and chronic neuropathic pain conditions relative to the controls. However, the functions of I/O curves for the PP-evoked inhibitory postsynaptic currents (eIPSCs differed between the two conditions, namely it was greatly gained under inflammatory condition, but was reduced under neuropathic condition in reverse. Second, both the frequency and amplitude of miniature IPSCs (mIPSCs were increased under inflammatory condition, however a decrease in frequency of mIPSCs was observed under neuropathic condition. Finally, the spike discharge of the DG granule cells in response to current injection was significantly increased by neuropathic pain condition, however, no different change was found between inflammatory pain condition and the control. These results provide another line of evidence showing homeostatic and allostatic modulation of excitatory synaptic transmission by inhibitory controls under different pathological pain conditions, hence implicating use of different therapeutic approaches to maintain the homeostasis between excitation and inhibition while treating different conditions of pathological pain.

  11. Radix Puerariae modulates glutamatergic synaptic architecture and potentiates functional synaptic plasticity in primary hippocampal neurons.

    Science.gov (United States)

    Bhuiyan, Mohammad Maqueshudul Haque; Haque, Md Nazmul; Mohibbullah, Md; Kim, Yung Kyu; Moon, Il Soo

    2017-09-14

    Neurologic disorders are frequently characterized by synaptic pathology, including abnormal density and morphology of dendritic spines, synapse loss, and aberrant synaptic signaling and plasticity. Therefore, to promote and/or protect synapses by the use of natural molecules capable of modulating neurodevelopmental events, such as, spinogenesis and synaptic plasticity, could offer a preventive and curative strategy for nervous disorders associated with synaptic pathology. Radix Puerariae, the root of Pueraria monatana var. lobata (Willd.) Sanjappa&Pradeep, is a Chinese ethnomedicine, traditionally used for the treatment of memory-related nervous disorders including Alzheimer's disease. In the previous study, we showed that the ethanolic extracts of Radix Puerariae (RPE) and its prime constituent, puerarin induced neuritogenesis and synapse formation in cultured hippocampal neurons, and thus could improve memory functions. In the present study, we specifically investigated the abilities of RPE and puerarin to improve memory-related brain disorders through modulating synaptic maturation and functional potentiation. Rat embryonic (E19) brain neurons were cultured in the absence or presence of RPE or puerarin. At predetermined times, cells were live-stained with DiO or fixed and immunostained to visualize neuronal morphologies, or lysed for protein harvesting. Morphometric analyses of dendritic spines and synaptogenesis were performed using Image J software. Functional pre- and postsynaptic plasticity was measured by FM1-43 staining and whole-cell patch clamping, respectively. RPE or puerarin-mediated changes in actin-related protein 2 were assessed by Western blotting. Neuronal survivals were measured using propidium iodide exclusion assay. RPE and puerarin both: (1) promoted a significant increase in the numbers, and maturation, of dendritic spines; (2) modulated the formation of glutamatergic synapses; (3) potentiated synaptic transmission by increasing the sizes of

  12. Pannexin 1 Regulates Bidirectional Hippocampal Synaptic Plasticity in Adult Mice

    Directory of Open Access Journals (Sweden)

    Alvaro O. Ardiles

    2014-10-01

    Full Text Available 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.

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

    Science.gov (United States)

    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 Ca(2+) 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.

  14. Microwave power transmission system wherein level of transmitted power is controlled by reflections from receiver

    Science.gov (United States)

    Robinson, W. J., Jr. (Inventor)

    1974-01-01

    A microwave, wireless, power transmission system is described in which the transmitted power level is adjusted to correspond with power required at a remote receiving station. Deviations in power load produce an antenna impedance mismatch causing variations in energy reflected by the power receiving antenna employed by the receiving station. The variations in reflected energy are sensed by a receiving antenna at the transmitting station and used to control the output power of a power transmitter.

  15. Infection control intervention on meticillin resistant Staphylococcus aureus transmission in residential care homes for the elderly.

    Science.gov (United States)

    Chuang, Vivien Wm; Tsang, Iris Hl; Keung, Jessica Py; Leung, June Yy; Yuk, Janet Mt; Wong, Doris Kw; Au, Sui-Sum; Tam, Rebekah Ky; Lam, Wendy Wy; Kwan, Martin Ct; Wong, Andrew Ty

    2015-03-01

    The objectives were to evaluate the effectiveness of an infection control bundle in controlling the meticillin resistant Staphylococcus aureus (MRSA) transmission in residential care homes for the elderly (RCHEs) in Hong Kong. This was a two-arm cluster randomised controlled trial. Infection control bundles focused on hand hygiene (HH), environmental hygiene, and modified contact precautions were applied to the intervention arm. Nasal swabs from residents; staff HH compliance and effectiveness; and environmental hygiene were assessed by microbiological sampling or observation at the baseline and quarterly after the intervention. A total of 2776 residents from 36 RCHEs were recruited. The overall MRSA prevalence was 20.4% (95% confidence interval, 18.9%-21.9%). The intervention elicited an immediate effect of 2.4% absolute decrease in the prevalence and 3.7% in the intra-facility transmission, though the difference between the two arms was insignificant. Staff HH compliance increased substantially from 5.9% to 45.6% post-intervention ( p  < 0.001). We initiated the infection control culture into the RCHEs and gained their acceptance. However, this behavioural change takes time to emerge. Our study shows that relying on the bundle alone could not bring sustainable MRSA reduction. Administrative control for strengthening infection control infrastructure is important for continuous compliance and improvement.

  16. Optimal control of the gear shifting process for shift smoothness in dual-clutch transmissions

    Science.gov (United States)

    Li, Guoqiang; Görges, Daniel

    2018-03-01

    The control of the transmission system in vehicles is significant for the driving comfort. In order to design a controller for smooth shifting and comfortable driving, a dynamic model of a dual-clutch transmission is presented in this paper. A finite-time linear quadratic regulator is proposed for the optimal control of the two friction clutches in the torque phase for the upshift process. An integral linear quadratic regulator is introduced to regulate the relative speed difference between the engine and the slipping clutch under the optimization of the input torque during the inertia phase. The control objective focuses on smoothing the upshift process so as to improve the driving comfort. Considering the available sensors in vehicles for feedback control, an observer design is presented to track the immeasurable variables. Simulation results show that the jerk can be reduced both in the torque phase and inertia phase, indicating good shift performance. Furthermore, compared with conventional controllers for the upshift process, the proposed control method can reduce shift jerk and improve shift quality.

  17. DC Grid Control Concept for Expandable Multi-terminal HVDC Transmission Systems

    DEFF Research Database (Denmark)

    Irnawan, Roni; Silva, Filipe Miguel Faria da; Bak, Claus Leth

    2018-01-01

    In areas where there are already several HVDC links in operation or under construction, it is more likely that a DC grid emerges as a gradual process. Although the DC grid control concept has been widely discussed, the implementation in the expandable multi-terminal HVDC (MTDC) transmission systems...... still faces challenges. The existing converter control system needs to be adjusted when a point-to-point (PtP) link is operated into MTDC system, or when an additional converter is interconnected with an existing MTDC system, or even when a new DC grid control strategy is applied. In this paper, a new...... DC grid control concept is proposed that conserves and uses the existing converter control when an existing PtP link is extended into MTDC system or the existing MTDC system is expanded. An interface is proposed to decouple the DC grid secondary with converter control structures. By using...

  18. Nonlinear gearshifts control of dual-clutch transmissions during inertia phase.

    Science.gov (United States)

    Hu, Yunfeng; Tian, Lu; Gao, Bingzhao; Chen, Hong

    2014-07-01

    In this paper, a model-based nonlinear gearshift controller is designed by the backstepping method to improve the shift quality of vehicles with a dual-clutch transmission (DCT). Considering easy-implementation, the controller is rearranged into a concise structure which contains a feedforward control and a feedback control. Then, robustness of the closed-loop error system is discussed in the framework of the input to state stability (ISS) theory, where model uncertainties are considered as the additive disturbance inputs. Furthermore, due to the application of the backstepping method, the closed-loop error system is ordered as a linear system. Using the linear system theory, a guideline for selecting the controller parameters is deduced which could reduce the workload of parameters tuning. Finally, simulation results and Hardware in the Loop (HiL) simulation are presented to validate the effectiveness of the designed controller. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

  19. Controlling the optical bistability and transmission coefficient in a four-level atomic medium

    International Nuclear Information System (INIS)

    Asadpour, Seyyed Hossein; Eslami-Majd, Abdullah

    2012-01-01

    A novel four level atomic configuration is proposed for controlling the optical bistability and transmission coefficient with application on all-optical switching. Two circularly polarized components from a weak linearly-polarized probe beam are interacted separately by two transitions of this medium. A coherent coupling field has derived another atomic transition. It is demonstrated that the transmission coefficient of two orthogonally polarized beams at different frequencies can be achieved by adjusting the magnitude of the external magnetic field. It is found that the threshold of the optical bistability can be controlled by magnitude of the external magnetic field. Also, it is shown that optical bistability can be converted to optical multistability by switching the two orthogonally polarized beams. - Highlights: ► An inverted Y-type four level atomic system is proposed. ► Transmission coefficient can be controlled by a novel interesting parameter. ► Optical bistability and multistability can be achieved via external magnetic field. ► It is shown that our proposed model is suitable for all optical switching application.

  20. Development of BLDC Electric Motor Control System In Hydraulic Servo Drive Based on Variable Hydrostatic Transmission

    Directory of Open Access Journals (Sweden)

    O. I. Tarasov

    2014-01-01

    Full Text Available Modern robotic systems require the use of servo drives. Owing to encoder and negative feedback these drives ensure highly accurate motion parameters. In case of autonomous systems drives must also have high power characteristics. Moreover, in most cases, it was impossible to select the motor so that the speed and torque on its shaft were in compliance with those of required by the actuator. To match these parameters different types of reducers are used. The article justifies and considers a selection criterion of the gear ratios for such transmission. For clarity, there is an example of selecting a motor and a gear for above transmission, taking into account the proposed criterion. In addition, the article discusses the advantages of using hydrostatic transmission in the drive, which monitors the angular position of the output level, in comparison with a mechanical gearbox. Due to the fact that, at the moment, BLDC motors have the best power characteristics, such a servo drive requires a special control system that will take into account the features of variable hydrostatic transmission and electric BLDC motor. Therefore, the paper proposes a structure of such a system and set out the principles of its construction. Various embodiments of sensor types that may be used in this system and their installation scheme explained.

  1. A calcium-dependent plasticity rule for HCN channels maintains activity homeostasis and stable synaptic learning.

    Science.gov (United States)

    Honnuraiah, Suraj; Narayanan, Rishikesh

    2013-01-01

    for experimentally observed plasticity in HCN channels accompanying synaptic plasticity in hippocampal neurons, and uncover potential links between HCN-channel plasticity and calcium influx, dynamic gain control and stable synaptic learning.

  2. A calcium-dependent plasticity rule for HCN channels maintains activity homeostasis and stable synaptic learning.

    Directory of Open Access Journals (Sweden)

    Suraj Honnuraiah

    physiological roles for experimentally observed plasticity in HCN channels accompanying synaptic plasticity in hippocampal neurons, and uncover potential links between HCN-channel plasticity and calcium influx, dynamic gain control and stable synaptic learning.

  3. A Calcium-Dependent Plasticity Rule for HCN Channels Maintains Activity Homeostasis and Stable Synaptic Learning

    Science.gov (United States)

    Honnuraiah, Suraj; Narayanan, Rishikesh

    2013-01-01

    for experimentally observed plasticity in HCN channels accompanying synaptic plasticity in hippocampal neurons, and uncover potential links between HCN-channel plasticity and calcium influx, dynamic gain control and stable synaptic learning. PMID:23390543

  4. Conditional reduction of adult neurogenesis impairs bidirectional hippocampal synaptic plasticity

    Science.gov (United States)

    Massa, Federico; Koehl, Muriel; Wiesner, Theresa; Grosjean, Noelle; Revest, Jean-Michel; Piazza, Pier-Vincenzo; Abrous, Djoher Nora; Oliet, Stéphane H. R.

    2011-01-01

    Adult neurogenesis is a process by which the brain produces new neurons once development has ceased. Adult hippocampal neurogenesis has been linked to the relational processing of spatial information, a role attributed to the contribution of newborn neurons to long-term potentiation (LTP). However, whether newborn neurons also influence long-term depression (LTD), and how synaptic transmission and plasticity are affected as they incorporate their network, remain to be determined. To address these issues, we took advantage of a genetic model in which a majority of adult-born neurons can be selectively ablated in the dentate gyrus (DG) and, most importantly, in which neurogenesis can be restored on demand. Using electrophysiological recordings, we show that selective reduction of adult-born neurons impairs synaptic transmission at medial perforant pathway synapses onto DG granule cells. Furthermore, LTP and LTD are largely compromised at these synapses, probably as a result of an increased induction threshold. Whereas the deficits in synaptic transmission and plasticity are completely rescued by restoring neurogenesis, these synapses regain their ability to express LTP much faster than their ability to express LTD. These results demonstrate that both LTP and LTD are influenced by adult neurogenesis. They also indicate that as newborn neurons integrate their network, the ability to express bidirectional synaptic plasticity is largely improved at these synapses. These findings establish that adult neurogenesis is an important process for synaptic transmission and bidirectional plasticity in the DG, accounting for its role in efficiently integrating novel incoming information and in forming new memories. PMID:21464314

  5. Circadian Regulation of Synaptic Plasticity

    Directory of Open Access Journals (Sweden)

    Marcos G. Frank

    2016-07-01

    Full Text Available 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.

  6. GluR2 protein-protein interactions and the regulation of AMPA receptors during synaptic plasticity.

    OpenAIRE

    Duprat, Fabrice; Daw, Michael; Lim, Wonil; Collingridge, Graham; Isaac, John

    2003-01-01

    AMPA-type glutamate receptors mediate most fast excitatory synaptic transmissions in the mammalian brain. They are critically involved in the expression of long-term potentiation and long-term depression, forms of synaptic plasticity that are thought to underlie learning and memory. A number of synaptic proteins have been identified that interact with the intracellular C-termini of AMPA receptor subunits. Here, we review recent studies and present new experimental data on the roles of these i...

  7. PRRT2: from Paroxysmal Disorders to Regulation of Synaptic Function.

    Science.gov (United States)

    Valtorta, Flavia; Benfenati, Fabio; Zara, Federico; Meldolesi, Jacopo

    2016-10-01

    In the past few years, proline-rich transmembrane protein (PRRT)2 has been identified as the causative gene for several paroxysmal neurological disorders. Recently, an important role of PRRT2 in synapse development and function has emerged. Knock down of the protein strongly impairs the formation of synaptic contacts and neurotransmitter release. At the nerve terminal, PRRT2 endows synaptic vesicle exocytosis with Ca 2+ sensitivity by interacting with proteins of the fusion complex and with the Ca 2+ sensors synaptotagmins (Syts). In the postsynaptic compartment, PRRT2 interacts with glutamate receptors. The study of PRRT2 and of its mutations may help in refining our knowledge of the process of synaptic transmission and elucidating the pathogenetic mechanisms leading to derangement of network function in paroxysmal disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Carrier-envelope phase stabilization and control using a transmission grating compressor and an AOPDF.

    Science.gov (United States)

    Canova, Lorenzo; Chen, Xiaowei; Trisorio, Alexandre; Jullien, Aurélie; Assion, Andreas; Tempea, Gabriel; Forget, Nicolas; Oksenhendler, Thomas; Lopez-Martens, Rodrigo

    2009-05-01

    Carrier-envelope phase (CEP) stabilization of a femtosecond chirped-pulse amplification system featuring a compact transmission grating compressor is demonstrated. The system includes two amplification stages and routinely generates phase-stable (approximately 250 mrad rms) 2 mJ, 25 fs pulses at 1 kHz. Minimizing the optical pathway in the compressor enables phase stabilization without feedback control of the grating separation or beam pointing. We also demonstrate for the first time to the best of our knowledge, out-of-loop control of the CEP using an acousto-optic programmable dispersive filter inside the laser chain.

  9. Isolation of Synaptosomes, Synaptic Plasma Membranes, and Synaptic Junctional Complexes.

    Science.gov (United States)

    Michaelis, Mary L; Jiang, Lei; Michaelis, Elias K

    2017-01-01

    Isolation of synaptic nerve terminals or synaptosomes provides an opportunity to study the process of neurotransmission at many levels and with a variety of approaches. For example, structural features of the synaptic terminals and the organelles within them, such as synaptic vesicles and mitochondria, have been elucidated with electron microscopy. The postsynaptic membranes are joined to the presynaptic "active zone" of transmitter release through cell adhesion molecules and remain attached throughout the isolation of synaptosomes. These "post synaptic densities" or "PSDs" contain the receptors for the transmitters released from the nerve terminals and can easily be seen with electron microscopy. Biochemical and cell biological studies with synaptosomes have revealed which proteins and lipids are most actively involved in synaptic release of neurotransmitters. The functional properties of the nerve terminals, such as responses to depolarization and the uptake or release of signaling molecules, have also been characterized through the use of fluorescent dyes, tagged transmitters, and transporter substrates. In addition, isolated synaptosomes can serve as the starting material for the isolation of relatively pure synaptic plasma membranes (SPMs) that are devoid of organelles from the internal environment of the nerve terminal, such as mitochondria and synaptic vesicles. The isolated SPMs can reseal and form vesicular structures in which transport of ions such as sodium and calcium, as well as solutes such as neurotransmitters can be studied. The PSDs also remain associated with the presynaptic membranes during isolation of SPM fractions, making it possible to isolate the synaptic junctional complexes (SJCs) devoid of the rest of the plasma membranes of the nerve terminals and postsynaptic membrane components. Isolated SJCs can be used to identify the proteins that constitute this highly specialized region of neurons. In this chapter, we describe the steps involved

  10. Synaptic plasticity in the auditory system: a review.

    Science.gov (United States)

    Friauf, Eckhard; Fischer, Alexander U; Fuhr, Martin F

    2015-07-01

    Synaptic transmission via chemical synapses is dynamic, i.e., the strength of postsynaptic responses may change considerably in response to repeated synaptic activation. Synaptic strength is increased during facilitation, augmentation and potentiation, whereas a decrease in synaptic strength is characteristic for depression and attenuation. This review attempts to discuss the literature on short-term and long-term synaptic plasticity in the auditory brainstem of mammals and birds. One hallmark of the auditory system, particularly the inner ear and lower brainstem stations, is information transfer through neurons that fire action potentials at very high frequency, thereby activating synapses >500 times per second. Some auditory synapses display morphological specializations of the presynaptic terminals, e.g., calyceal extensions, whereas other auditory synapses do not. The review focuses on short-term depression and short-term facilitation, i.e., plastic changes with durations in the millisecond range. Other types of short-term synaptic plasticity, e.g., posttetanic potentiation and depolarization-induced suppression of excitation, will be discussed much more briefly. The same holds true for subtypes of long-term plasticity, like prolonged depolarizations and spike-time-dependent plasticity. We also address forms of plasticity in the auditory brainstem that do not comprise synaptic plasticity in a strict sense, namely short-term suppression, paired tone facilitation, short-term adaptation, synaptic adaptation and neural adaptation. Finally, we perform a meta-analysis of 61 studies in which short-term depression (STD) in the auditory system is opposed to short-term depression at non-auditory synapses in order to compare high-frequency neurons with those that fire action potentials at a lower rate. This meta-analysis reveals considerably less STD in most auditory synapses than in non-auditory ones, enabling reliable, failure-free synaptic transmission even at

  11. Cerebellar Synaptic Plasticity and the Credit Assignment Problem.

    Science.gov (United States)

    Jörntell, Henrik

    2016-04-01

    The mechanism by which a learnt synaptic weight change can contribute to learning or adaptation of brain function is a type of credit assignment problem, which is a key issue for many parts of the brain. In the cerebellum, detailed knowledge not only of the local circuitry connectivity but also of the topography of different sources of afferent/external information makes this problem particularly tractable. In addition, multiple forms of synaptic plasticity and their general rules of induction have been identified. In this review, we will discuss the possible roles of synaptic and cellular plasticity at specific locations in contributing to behavioral changes. Focus will be on the parts of the cerebellum that are devoted to limb control, which constitute a large proportion of the cortex and where the knowledge of the external connectivity is particularly well known. From this perspective, a number of sites of synaptic plasticity appear to primarily have the function of balancing the overall level of activity in the cerebellar circuitry, whereas the locations at which synaptic plasticity leads to functional changes in terms of limb control are more limited. Specifically, the postsynaptic forms of long-term potentiation (LTP) and long-term depression (LTD) at the parallel fiber synapses made on interneurons and Purkinje cells, respectively, are the types of plasticity that mediate the widest associative capacity and the tightest link between the synaptic change and the external functions that are to be controlled.

  12. Prospective malaria control using entomopathogenic fungi: comparative evaluation of impact on transmission and selection for resistance

    Directory of Open Access Journals (Sweden)

    Lynch Penelope A

    2012-11-01

    Full Text Available Abstract Background Chemical insecticides against adult mosquitoes are a key element in most malaria management programmes, but their efficacy is threatened by the evolution of insecticide-resistant mosquitoes. By killing only older mosquitoes, entomopathogenic fungi can in principle significantly impact parasite transmission while imposing much less selection for resistance. Here an assessment is made as to which of the wide range of possible virulence characteristics for fungal biopesticides best realise this potential. Methods With mathematical models that capture relevant timings and survival probabilities within successive feeding cycles, transmission and resistance-management metrics are used to compare susceptible and resistant mosquitoes exposed to no intervention, to conventional instant-kill interventions, and to delayed-action biopesticides with a wide range of virulence characteristics. Results Fungal biopesticides that generate high rates of mortality at around the time mosquitoes first become able to transmit the malaria parasite offer potential for large reductions in transmission while imposing low fitness costs. The best combinations of control and resistance management are generally accessed at high levels of coverage. Strains which have high virulence in malaria-infected mosquitoes but lower virulence in malaria-free mosquitoes offer the ultimate benefit in terms of minimizing selection pressure whilst maximizing impact on transmission. Exploiting this phenotype should be a target for product development. For indoor residual spray programmes, biopesticides may offer substantial advantages over the widely used pyrethroid-based insecticides. Not only do fungal biopesticides provide substantial resistance management gains in the long term, they may also provide greater reductions in transmission before resistance has evolved. This is because fungal spores do not have contact irritancy, reducing the chances that a blood

  13. Prospective malaria control using entomopathogenic fungi: comparative evaluation of impact on transmission and selection for resistance.

    Science.gov (United States)

    Lynch, Penelope A; Grimm, Uwe; Thomas, Matthew B; Read, Andrew F

    2012-11-22

    Chemical insecticides against adult mosquitoes are a key element in most malaria management programmes, but their efficacy is threatened by the evolution of insecticide-resistant mosquitoes. By killing only older mosquitoes, entomopathogenic fungi can in principle significantly impact parasite transmission while imposing much less selection for resistance. Here an assessment is made as to which of the wide range of possible virulence characteristics for fungal biopesticides best realise this potential. With mathematical models that capture relevant timings and survival probabilities within successive feeding cycles, transmission and resistance-management metrics are used to compare susceptible and resistant mosquitoes exposed to no intervention, to conventional instant-kill interventions, and to delayed-action biopesticides with a wide range of virulence characteristics. Fungal biopesticides that generate high rates of mortality at around the time mosquitoes first become able to transmit the malaria parasite offer potential for large reductions in transmission while imposing low fitness costs. The best combinations of control and resistance management are generally accessed at high levels of coverage. Strains which have high virulence in malaria-infected mosquitoes but lower virulence in malaria-free mosquitoes offer the ultimate benefit in terms of minimizing selection pressure whilst maximizing impact on transmission. Exploiting this phenotype should be a target for product development. For indoor residual spray programmes, biopesticides may offer substantial advantages over the widely used pyrethroid-based insecticides. Not only do fungal biopesticides provide substantial resistance management gains in the long term, they may also provide greater reductions in transmission before resistance has evolved. This is because fungal spores do not have contact irritancy, reducing the chances that a blood-fed mosquito can survive an encounter and thus live long enough to

  14. Solid-state nanopores of controlled geometry fabricated in a transmission electron microscope

    Science.gov (United States)

    Qian, Hui; Egerton, Ray F.

    2017-11-01

    Energy-filtered transmission electron microscopy and electron tomography were applied to in situ studies of the formation, shape, and diameter of nanopores formed in a silicon nitride membrane in a transmission electron microscope. The nanopore geometry was observed in three dimensions by electron tomography. Drilling conditions, such as probe current, beam convergence angle, and probe position, affect the formation rate and the geometry of the pores. With a beam convergence semi-angle of α = 22 mrad, a conical shaped nanopore is formed but at α = 45 mrad, double-cone (hourglass-shaped) nanopores were produced. Nanopores with an effective diameter between 10 nm and 1.8 nm were fabricated by controlling the drilling time.

  15. Adaptive control of the packet transmission period with solar energy harvesting prediction in wireless sensor networks.

    Science.gov (United States)

    Kwon, Kideok; Yang, Jihoon; Yoo, Younghwan

    2015-04-24

    A number of research works has studied packet scheduling policies in energy scavenging wireless sensor networks, based on the predicted amount of harvested energy. Most of them aim to achieve energy neutrality, which means that an embedded system can operate perpetually while meeting application requirements. Unlike other renewable energy sources, solar energy has the feature of distinct periodicity in the amount of harvested energy over a day. Using this feature, this paper proposes a packet transmission control policy that can enhance the network performance while keeping sensor nodes alive. Furthermore, this paper suggests a novel solar energy prediction method that exploits the relation between cloudiness and solar radiation. The experimental results and analyses show that the proposed packet transmission policy outperforms others in terms of the deadline miss rate and data throughput. Furthermore, the proposed solar energy prediction method can predict more accurately than others by 6.92%.

  16. Adaptive Control of the Packet Transmission Period with Solar Energy Harvesting Prediction in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Kideok Kwon

    2015-04-01

    Full Text Available A number of research works has studied packet scheduling policies in energy scavenging wireless sensor networks, based on the predicted amount of harvested energy. Most of them aim to achieve energy neutrality, which means that an embedded system can operate perpetually while meeting application requirements. Unlike other renewable energy sources, solar energy has the feature of distinct periodicity in the amount of harvested energy over a day. Using this feature, this paper proposes a packet transmission control policy that can enhance the network performance while keeping sensor nodes alive. Furthermore, this paper suggests a novel solar energy prediction method that exploits the relation between cloudiness and solar radiation. The experimental results and analyses show that the proposed packet transmission policy outperforms others in terms of the deadline miss rate and data throughput. Furthermore, the proposed solar energy prediction method can predict more accurately than others by 6.92%.

  17. Microcontroller Based Proportional Derivative Plus Conditional Integral Controller for Electro-Mechanical Dual Acting Pulley Continuously Variable Transmission Ratio Control

    Science.gov (United States)

    Budianto, A.; Tawi, K. B.; Hussein, M.; Supriyo, B.; Ariyono, S.; Che Kob, M. S.; Ezlamy Zulkifli, Mohd; K, Khairuldean A.; Daraoh, Aishah

    2012-09-01

    Electro-Mechanical Dual Acting Pulley (EMDAP) Continuously Variable Transmission (CVT) is a transmission utilized by electro-mechanical actuated system. It has a potential to reduce energy consumption because it only needs power during changing CVT ratio and no power is needed to maintain CVT ratio due to self lock mechanism design. This paper proposed simple proportional derivative plus conditional integral (PDCI) controller to control EMDAP CVT ratio which can be simply implemented on a microcontroller. This proposed controller used Astrom-Hagglund method and Ziegler-Nichols formula to tune PDCI gain. The Proportional Derivative controller is directly activated from the start but Integral controller is only activated when the error value reaches error value setting point. Simulation using Matlab/Simulink software was conducted to evaluate PDCI system performance. The simulation results showed PDCI controller has ability to perform maximum overshoot 0.1%, 0.001 steady state error and 0.5s settling time. For clamping condition, settling time is about 11.46s during changing ratio from 2.0 to 0.7, while for release condition, settling time is about 8.33s during changing ratio from 0.7 to 2.0.

  18. Bayesian inference of synaptic quantal parameters from correlated vesicle release

    Directory of Open Access Journals (Sweden)

    Alexander D Bird

    2016-11-01

    Full Text Available Synaptic transmission is both history-dependent and stochastic, resulting in varying responses to presentations of the same presynaptic stimulus. This complicates attempts to infer synaptic parameters and has led to the proposal of a number of different strategies for their quantification. Recently Bayesian approaches have been applied to make more efficient use of the data collected in paired intracellular recordings. Methods have been developed that either provide a complete model of the distribution of amplitudes for isolated responses or approximate the amplitude distributions of a train of post-synaptic potentials, with correct short-term synaptic dynamics but neglecting correlations. In both cases the methods provided significantly improved inference of model parameters as compared to existing mean-variance fitting approaches. However, for synapses with high release probability, low vesicle number or relatively low restock rate and for data in which only one or few repeats of the same pattern are available, correlations between serial events can allow for the extraction of significantly more information from experiment: a more complete Bayesian approach would take this into account also. This has not been possible previously because of the technical difficulty in calculating the likelihood of amplitudes seen in correlated post-synaptic potential trains; however, recent theoretical advances have now rendered the likelihood calculation tractable for a broad class of synaptic dynamics models. Here we present a compact mathematical form for the likelihood in terms of a matrix product and demonstrate how marginals of the posterior provide information on covariance of parameter distributions. The associated computer code for Bayesian parameter inference for a variety of models of synaptic dynamics is provided in the supplementary material allowing for quantal and dynamical parameters to be readily inferred from experimental data sets.

  19. Synaptic vesicle dynamic changes in a model of fragile X.

    Science.gov (United States)

    Broek, Jantine A C; Lin, Zhanmin; de Gruiter, H Martijn; van 't Spijker, Heleen; Haasdijk, Elize D; Cox, David; Ozcan, Sureyya; van Cappellen, Gert W A; Houtsmuller, Adriaan B; Willemsen, Rob; de Zeeuw, Chris I; Bahn, Sabine

    2016-01-01

    Fragile X syndrome (FXS) is a single-gene disorder that is the most common heritable cause of intellectual disability and the most frequent monogenic cause of autism spectrum disorders (ASD). FXS is caused by an expansion of trinucleotide repeats in the promoter region of the fragile X mental retardation gene (Fmr1). This leads to a lack of fragile X mental retardation protein (FMRP), which regulates translation of a wide range of messenger RNAs (mRNAs). The extent of expression level alterations of synaptic proteins affected by FMRP loss and their consequences on synaptic dynamics in FXS has not been fully investigated. Here, we used an Fmr1 knockout (KO) mouse model to investigate the molecular mechanisms underlying FXS by monitoring protein expression changes using shotgun label-free liquid-chromatography mass spectrometry (LC-MS(E)) in brain tissue and synaptosome fractions. FXS-associated candidate proteins were validated using selected reaction monitoring (SRM) in synaptosome fractions for targeted protein quantification. Furthermore, functional alterations in synaptic release and dynamics were evaluated using live-cell imaging, and interpretation of synaptic dynamics differences was investigated using electron microscopy. Key findings relate to altered levels of proteins involved in GABA-signalling, especially in the cerebellum. Further exploration using microscopy studies found reduced synaptic vesicle unloading of hippocampal neurons and increased vesicle unloading in cerebellar neurons, which suggests a general decrease of synaptic transmission. Our findings suggest that FMRP is a regulator of synaptic vesicle dynamics, which supports the role of FMRP in presynaptic functions. Taken together, these studies provide novel insights into the molecular changes associated with FXS.

  20. Deconvolution of Voltage Sensor Time Series and Electro-diffusion Modeling Reveal the Role of Spine Geometry in Controlling Synaptic Strength.

    Science.gov (United States)

    Cartailler, Jerome; Kwon, Taekyung; Yuste, Rafael; Holcman, David

    2018-03-07

    Most synaptic excitatory connections are made on dendritic spines. But how the voltage in spines is modulated by its geometry remains unclear. To investigate the electrical properties of spines, we combine voltage imaging data with electro-diffusion modeling. We first present a temporal deconvolution procedure for the genetically encoded voltage sensor expressed in hippocampal cultured neurons and then use electro-diffusion theory to compute the electric field and the current-voltage conversion. We extract a range for the neck resistances of 〈R〉=100±35MΩ. When a significant current is injected in a spine, the neck resistance can be inversely proportional to its radius, but not to the radius square, as predicted by Ohm's law. We conclude that the postsynaptic voltage cannot only be modulated by changing the number of receptors, but also by the spine geometry. Thus, spine morphology could be a key component in determining synaptic transduction and plasticity. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Synaptic devices based on purely electronic memristors

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Ruobing [Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China); Institute of Materials Science, School of Materials Science and Engineering, Shanghai University, Shanghai 200072 (China); Li, Jun; Zhuge, Fei, E-mail: zhugefei@nimte.ac.cn, E-mail: h-cao@nimte.ac.cn; Zhu, Liqiang; Liang, Lingyan; Zhang, Hongliang; Gao, Junhua; Cao, Hongtao, E-mail: zhugefei@nimte.ac.cn, E-mail: h-cao@nimte.ac.cn; Fu, Bing; Li, Kang [Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China)

    2016-01-04

    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.

  2. Endocannabinoid signaling and synaptic function

    Science.gov (United States)

    Castillo, Pablo E.; Younts, Thomas J.; Chávez, Andrés E.; Hashimotodani, Yuki

    2012-01-01

    Endocannabinoids are key modulators of synaptic function. By activating cannabinoid receptors expressed in the central nervous system, these lipid messengers can regulate several neural functions and behaviors. As experimental tools advance, the repertoire of known endocannabinoid-mediated effects at the synapse, and their underlying mechanism, continues to expand. Retrograde signaling is the principal mode by which endocannabinoids mediate short- and long-term forms of plasticity at both excitatory and inhibitory synapses. However, growing evidence suggests that endocannabinoids can also signal in a non-retrograde manner. In addition to mediating synaptic plasticity, the endocannabinoid system is itself subject to plastic changes. Multiple points of interaction with other neuromodulatory and signaling systems have now been identified. Synaptic endocannabinoid signaling is thus mechanistically more complex and diverse than originally thought. In this review, we focus on new advances in endocannabinoid signaling and highlight their role as potent regulators of synaptic function in the mammalian brain. PMID:23040807

  3. TrkB kinase activity maintains synaptic function and structural integrity at adult neuromuscular junctions

    Science.gov (United States)

    Stowe, Jessica M.; Sieck, Dylan C.; Ermilov, Leonid G.; Greising, Sarah M.; Zhang, Chao; Shokat, Kevan M.; Sieck, Gary C.

    2014-01-01

    Activation of the tropomyosin-related kinase receptor B (TrkB) by brain-derived neurotrophic factor acutely regulates synaptic transmission at adult neuromuscular junctions (NMJs). The role of TrkB kinase activity in the maintenance of NMJ function and structure at diaphragm muscle NMJs was explored using a chemical-genetic approach that permits reversible inactivation of TrkB kinase activity in TrkBF616A mice by 1NMPP1. Inhibiting TrkB kinase activity for 7 days resulted in significant, yet reversible, impairments in neuromuscular transmission at diaphragm NMJs. Neuromuscular transmission failure following 2 min of repetitive phrenic nerve stimulation increased from 42% in control to 59% in 1NMPP1-treated TrkBF616A mice (P = 0.010). Recovery of TrkB kinase activity following withdrawal of 1NMPP1 treatment improved neuromuscular transmission (P = 0.006). Electrophysiological measurements at individual diaphragm NMJs documented lack of differences in quantal content in control and 1NMPP1-treated mice (P = 0.845). Morphological changes at diaphragm NMJs were modest following inhibition and recovery of TrkB kinase activity. Three-dimensional reconstructions of diaphragm NMJs revealed no differences in volume at motor end plates (labeled by α-bungarotoxin; P = 0.982) or presynaptic terminals (labeled by synaptophysin; P = 0.515). Inhibition of TrkB kinase activity by 1NMPP1 resulted in more compact NMJs, with increased apposition of presynaptic terminals and motor end plates (P = 0.017) and reduced fragmentation of motor end plates (P = 0.005). Recovery of TrkB kinase activity following withdrawal of 1NMPP1 treatment resulted in postsynaptic remodeling likely reflecting increased gutter depth (P = 0.007), without significant presynaptic changes. These results support an essential role for TrkB kinase activity in maintaining synaptic function and structural integrity at NMJs in the adult mouse diaphragm muscle. PMID:25170066

  4. Recurrent-neural-network-based identification of a cascade hydraulic actuator for closed-loop automotive power transmission control

    International Nuclear Information System (INIS)

    You, Seung Han; Hahn, Jin Oh

    2012-01-01

    By virtue of its ease of operation compared with its conventional manual counterpart, automatic transmissions are commonly used as automotive power transmission control system in today's passenger cars. In accordance with this trend, research efforts on closed-loop automatic transmission controls have been extensively carried out to improve ride quality and fuel economy. State-of-the-art power transmission control algorithms may have limitations in performance because they rely on the steady-state characteristics of the hydraulic actuator rather than fully exploit its dynamic characteristics. Since the ultimate viability of closed-loop power transmission control is dominated by precise pressure control at the level of hydraulic actuator, closed-loop control can potentially attain superior efficacy in case the hydraulic actuator can be easily incorporated into model-based observer/controller design. In this paper, we propose to use a recurrent neural network (RNN) to establish a nonlinear empirical model of a cascade hydraulic actuator in a passenger car automatic transmission, which has potential to be easily incorporated in designing observers and controllers. Experimental analysis is performed to grasp key system characteristics, based on which a nonlinear system identification procedure is carried out. Extensive experimental validation of the established model suggests that it has superb one-step-ahead prediction capability over appropriate frequency range, making it an attractive approach for model-based observer/controller design applications in automotive systems

  5. An optimal control problem arising from a dengue disease transmission model.

    Science.gov (United States)

    Aldila, Dipo; Götz, Thomas; Soewono, Edy

    2013-03-01

    An optimal control problem for a host-vector Dengue transmission model is discussed here. In the model, treatments with mosquito repellent are given to adults and children and those who undergo treatment are classified in treated compartments. With this classification, the model consists of 11 dynamic equations. The basic reproductive ratio that represents the epidemic indicator is obtained from the largest eigenvalue of the next generation matrix. The optimal control problem is designed with four control parameters, namely the treatment rates for children and adult compartments, and the drop-out rates from both compartments. The cost functional accounts for the total number of the infected persons, the cost of the treatment, and the cost related to reducing the drop-out rates. Numerical results for the optimal controls and the related dynamics are shown for the case of epidemic prevention and outbreak reduction strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Coordinated Control of Downshift Powertrain of Combined Clutch Transmissions for Electric Vehicles

    Directory of Open Access Journals (Sweden)

    Junqiu Li

    2014-01-01

    Full Text Available To improve the shift quality of electric vehicles equipped with two-gear automatic transmissions, the coordinated control of the combined clutch and the motor is proposed. The dynamic model of shift process is built up, the dynamic characteristics of each phase of downshift process are analyzed, and linear quadratic optimal control is used to optimize the shift process. As a result, the optimal trajectories of the motor torque and oil pressure of the combined clutch are obtained. Compared to the clutch control only, the simulation results indicate that shift quality is improved remarkably by employing the proposed coordinated control. Specifically, the shift jerk and sliding friction work are decreased by 43% and 44%, respectively, with accelerator pedal angle 50%. In contrast, the reduced percentages are 57% and 89% when accelerator pedal is not depressed.

  7. Optogenetic Examination of Prefrontal-Amygdala Synaptic Development.

    Science.gov (United States)

    Arruda-Carvalho, Maithe; Wu, Wan-Chen; Cummings, Kirstie A; Clem, Roger L

    2017-03-15

    A brain network comprising the medial prefrontal cortex (mPFC) and amygdala plays important roles in developmentally regulated cognitive and emotional processes. However, very little is known about the maturation of mPFC-amygdala circuitry. We conducted anatomical tracing of mPFC projections and optogenetic interrogation of their synaptic connections with neurons in the basolateral amygdala (BLA) at neonatal to adult developmental stages in mice. Results indicate that mPFC-BLA projections exhibit delayed emergence relative to other mPFC pathways and establish synaptic transmission with BLA excitatory and inhibitory neurons in late infancy, events that coincide with a massive increase in overall synaptic drive. During subsequent adolescence, mPFC-BLA circuits are further modified by excitatory synaptic strengthening as well as a transient surge in feedforward inhibition. The latter was correlated with increased spontaneous inhibitory currents in excitatory neurons, suggesting that mPFC-BLA circuit maturation culminates in a period of exuberant GABAergic transmission. These findings establish a time course for the onset and refinement of mPFC-BLA transmission and point to potential sensitive periods in the development of this critical network. SIGNIFICANCE STATEMENT Human mPFC-amygdala functional connectivity is developmentally regulated and figures prominently in numerous psychiatric disorders with a high incidence of adolescent onset. However, it remains unclear when synaptic connections between these structures emerge or how their properties change with age. Our work establishes developmental windows and cellular substrates for synapse maturation in this pathway involving both excitatory and inhibitory circuits. The engagement of these substrates by early life experience may support the ontogeny of fundamental behaviors but could also lead to inappropriate circuit refinement and psychopathology in adverse situations. Copyright © 2017 the authors 0270-6474/17/372976-10$15.00/0.

  8. A new role for GABAergic transmission in the control of male rat sexual behavior expression.

    Science.gov (United States)

    Rodríguez-Manzo, Gabriela; Canseco-Alba, Ana

    2017-03-01

    GABAergic transmission in the ventral tegmental area (VTA) exerts a tonic inhibitory influence on mesolimbic dopaminergic neurons' activity. Blockade of VTA GABA A receptors increases dopamine release in the nucleus accumbens (NAcc). Increases in NAcc dopamine levels typically accompany sexual behavior display. Copulation to satiety is characterized by the instatement of a long lasting (72h) sexual behavior inhibition and the mesolimbic system appears to be involved in this phenomenon. GABAergic transmission in the VTA might play a role in the maintenance of this long lasting sexual inhibitory state. To test this hypothesis, in the present work we investigated the effect of GABA A receptor blockade in sexually exhausted males 24h after copulation to satiety, once the sexual inhibitory state is established, and compared it with its effect in sexually experienced rats. Results showed that low doses of systemically administered bicuculline induced sexual behavior expression in sexually exhausted rats, but lacked an effect on copulation of sexually experienced animals. Intra-VTA bilateral infusion of bicuculline did not modify sexual behavior of sexually experienced rats, but induced sexual behavior expression in all the sexually exhausted males. Hence, GABA plays a role in the control of sexual behavior expression at the VTA. The role played by GABAergic transmission in male sexual behavior expression of animals with distinct sexual behavior conditions is discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Modelling the transmission and control strategies of varicella among school children in Shenzhen, China.

    Directory of Open Access Journals (Sweden)

    Xiujuan Tang

    Full Text Available Varicella (chickenpox is a highly transmissible childhood disease. Between 2010 and 2015, it displayed two epidemic waves annually among school populations in Shenzhen, China. However, their transmission dynamics remain unclear and there is no school-based vaccination programme in Shenzhen to-date. In this study, we developed a mathematical model to compare a school-based vaccination intervention scenario with a baseline (i.e. no intervention scenario.Data on varicella reported cases were downloaded from the Infectious Disease Reporting Information Management System. We obtained the population size, age structure of children aged 15 or under, the class and school distribution from Shenzhen Education Bureau. We developed an Agent-Based Susceptible-Exposed-Infectious-Recovered (ABM-SEIR Model that considered within-class, class-to-class and out-of-school transmission modes. The intervention scenario was that school-wide vaccination intervention occurred when an outbreak threshold was reached within a school. We varied this threshold level from five to ten cases. We compared the reduction of disease outbreak size and estimated the key epidemiological parameters under the intervention strategy.Our ABM-SEIR model provided a good model fit to the two annual varicella epidemic waves from 2013 to 2015. The transmission dynamics displayed strong seasonality. Our results suggested that a school-based vaccination strategy could effectively prevent large outbreaks at different thresholds.There was a considerable increase in reported varicella cases from 2013 to 2015 in Shenzhen. Our modelling study provided important theoretical support for disease control decision making during school outbreaks and the development of a school-based vaccination programme.

  10. Hebbian Wiring Plasticity Generates Efficient Network Structures for Robust Inference with Synaptic Weight Plasticity

    Science.gov (United States)

    Hiratani, Naoki; Fukai, Tomoki

    2016-01-01

    In the adult mammalian cortex, a small fraction of spines are created and eliminated every day, and the resultant synaptic connection structure is highly nonrandom, even in local circuits. However, it remains unknown whether a particular synaptic connection structure is functionally advantageous in local circuits, and why creation and elimination of synaptic connections is necessary in addition to rich synaptic weight plasticity. To answer these questions, we studied an inference task model through theoretical and numerical analyses. We demonstrate that a robustly beneficial network structure naturally emerges by combining Hebbian-type synaptic weight plasticity and wiring plasticity. Especially in a sparsely connected network, wiring plasticity achieves reliable computation by enabling efficient information transmission. Furthermore, the proposed rule reproduces experimental observed correlation between spine dynamics and task performance. PMID:27303271

  11. Hebbian Wiring Plasticity Generates Efficient Network Structures for Robust Inference with Synaptic Weight Plasticity.

    Science.gov (United States)

    Hiratani, Naoki; Fukai, Tomoki

    2016-01-01

    In the adult mammalian cortex, a small fraction of spines are created and eliminated every day, and the resultant synaptic connection structure is highly nonrandom, even in local circuits. However, it remains unknown whether a particular synaptic connection structure is functionally advantageous in local circuits, and why creation and elimination of synaptic connections is necessary in addition to rich synaptic weight plasticity. To answer these questions, we studied an inference task model through theoretical and numerical analyses. We demonstrate that a robustly beneficial network structure naturally emerges by combining Hebbian-type synaptic weight plasticity and wiring plasticity. Especially in a sparsely connected network, wiring plasticity achieves reliable computation by enabling efficient information transmission. Furthermore, the proposed rule reproduces experimental observed correlation between spine dynamics and task performance.

  12. Understanding Cognitive and Collaborative Work: Observations in an Electric Transmission Operations Control Center

    Energy Technology Data Exchange (ETDEWEB)

    Obradovich, Jodi H.

    2011-09-30

    This paper describes research that is part of an ongoing project to design tools to assist in the integration of renewable energy into the electric grid. These tools will support control room dispatchers in real-time system operations of the electric power transmission system which serves much of the Western United States. Field observations comprise the first phase of this research in which 15 operators have been observed over various shifts and times of day for approximately 90 hours. Findings describing some of the cognitive and environmental challenges of managing the dynamically changing electric grid are presented.

  13. Mathematical models for lymphatic filariasis transmission and control: Challenges and prospects

    Directory of Open Access Journals (Sweden)

    Kaliannagounder Krishnamoorthy

    2008-02-01

    Full Text Available Abstract Background Mathematical models developed for describing the dynamics of transmission, infection, disease and control of lymphatic filariasis (LF gained momentum following the 1997 World Health Assembly resolution and the launching of the Global Programme to Eliminate Lymphatic Filariasis (GPELF in 2000. Model applications could provide valuable inputs for making decisions while implementing large scale programmes. However these models need to be evaluated at different epidemiological settings for optimization and fine-tuning with new knowledge and understanding on infection/disease dynamics. Discussion EPIFIL and LYMFASIM are the two mathematical simulation models currently available for lymphatic filariasis transmission and control. Both models have been used for prediction and evaluation of control programmes under research settings. Their widespread application in evaluating large-scale elimination programmes warrants validation of assumptions governing the dynamics of infection and disease in different epidemiological settings. Furthermore, the predictive power of the models for decision support can be enhanced by generating knowledge on some important issues that pose challenges and incorporating such knowledge into the models. We highlight factors related to the efficacy of the drugs of choice, their mode of action, and the possibility that drug resistance may develop; the role of vector-parasite combinations; the magnitude of transmission thresholds; host-parasite interactions and their effects on the dynamics of infection and immunity; parasite biology, and progression to LF-associated disease. Summary The two mathematical models developed offer potential decision making tools for transmission and control of LF. In view of the goals of the GPELF, the predictive power of these models needs to be enhanced for their wide-spread application in large scale programmes. Assimilation and translation of new information into the models is

  14. The effect of vector control strategy against Dengue transmission between mosquitoes and humans

    Directory of Open Access Journals (Sweden)

    Chen-Xia Yang

    2017-03-01

    Full Text Available With the consideration of mechanism of prevention and control for the spread of dengue fever, a mathematical model of dengue fever dynamical transmission between mosquitoes and humans, incorporating a vector control strategy of impulsive culling of mosquitoes, is proposed in this paper. By using the comparison principle, Floquet theorem and some of analytical methods, we obtain the basic reproductive number $\\mathcal{R}_0$ for this infectious disease, which illustrates the stability of the disease-free periodic solution and the uniform persistence of the disease. Further, the explicit conditions determining the backward or forward bifurcation are obtained and the culling rate $\\phi$ is a major effect on the occurrence of backward bifurcation. Finally, numerical simulations are given to verify the correctness of theoretical results and the most efficiency of vector control strategy.

  15. Source and Channel Adaptive Rate Control for Multicast Layered Video Transmission Based on a Clustering Algorithm

    Directory of Open Access Journals (Sweden)

    Jérôme Viéron

    2004-03-01

    Full Text Available This paper introduces source-channel adaptive rate control (SARC, a new congestion control algorithm for layered video transmission in large multicast groups. In order to solve the well-known feedback implosion problem in large multicast groups, we first present a mechanism for filtering RTCP receiver reports sent from receivers to the whole session. The proposed filtering mechanism provides a classification of receivers according to a predefined similarity measure. An end-to-end source and FEC rate control based on this distributed feedback aggregation mechanism coupled with a video layered coding system is then described. The number of layers, their rate, and their levels of protection are adapted dynamically to aggregated feedbacks. The algorithms have been validated with the NS2 network simulator.

  16. To the problem of topological optimization of data processing and transmission networks in development of the automatic control system ''Atom''

    International Nuclear Information System (INIS)

    Gal'berg, V.P.

    1981-01-01

    Some optimization problems occurring in developing the automatic control system (ASC) of a commercial amalgamation (ACS-ATOM), assessments of economically optimal structure of location of computation centres and means of data transmission in particular are considered [ru

  17. NPY gene transfer in the hippocampus attenuates synaptic plasticity and learning

    DEFF Research Database (Denmark)

    Sørensen, Andreas T; Kanter-Schlifke, Irene; Carli, Mirjana

    2008-01-01

    . Future clinical progress, however, requires more detailed evaluation of possible side effects of this treatment. Until now it has been unknown whether rAAV vector-based NPY overexpression in the hippocampus alters normal synaptic transmission and plasticity, which could disturb learning and memory...... processing. Here we show, by electrophysiological recordings in CA1 of the hippocampal formation of rats, that hippocampal NPY gene transfer into the intact brain does not affect basal synaptic transmission, but slightly alters short-term synaptic plasticity, most likely via NPY Y2 receptor...... is partially impaired and animals have a slower rate of hippocampal-based spatial discrimination learning. These data provide the first evidence that rAAV-based gene therapy using NPY exerts relative limited effect on synaptic plasticity and learning in the hippocampus, and therefore this approach could...

  18. An optimal control strategies using vaccination and fogging in dengue fever transmission model

    Science.gov (United States)

    Fitria, Irma; Winarni, Pancahayani, Sigit; Subchan

    2017-08-01

    This paper discussed regarding a model and an optimal control problem of dengue fever transmission. We classified the model as human and vector (mosquito) population classes. For the human population, there are three subclasses, such as susceptible, infected, and resistant classes. Then, for the vector population, we divided it into wiggler, susceptible, and infected vector classes. Thus, the model consists of six dynamic equations. To minimize the number of dengue fever cases, we designed two optimal control variables in the model, the giving of fogging and vaccination. The objective function of this optimal control problem is to minimize the number of infected human population, the number of vector, and the cost of the controlling efforts. By giving the fogging optimally, the number of vector can be minimized. In this case, we considered the giving of vaccination as a control variable because it is one of the efforts that are being developed to reduce the spreading of dengue fever. We used Pontryagin Minimum Principle to solve the optimal control problem. Furthermore, the numerical simulation results are given to show the effect of the optimal control strategies in order to minimize the epidemic of dengue fever.

  19. Host outdoor exposure variability affects the transmission and spread of Zika virus: Insights for epidemic control.

    Directory of Open Access Journals (Sweden)

    Marco Ajelli

    2017-09-01

    Full Text Available Zika virus transmission dynamics in urban environments follow a complex spatiotemporal pattern that appears unpredictable and barely related to high mosquito density areas. In this context, human activity patterns likely have a major role in Zika transmission dynamics. This paper examines the effect of host variability in the amount of time spent outdoors on Zika epidemiology in an urban environment.First, we performed a survey on time spent outdoors by residents of Miami-Dade County, Florida. Second, we analyzed both the survey and previously published national data on outdoors time in the U.S. to provide estimates of the distribution of the time spent outdoors. Third, we performed a computational modeling evaluation of Zika transmission dynamics, based on the time spent outdoors by each person. Our analysis reveals a strong heterogeneity of the host population in terms of time spent outdoors-data are well captured by skewed gamma distributions. Our model-based evaluation shows that in a heterogeneous population, Zika would cause a lower number of infections than in a more homogenous host population (up to 4-fold differences, but, at the same time, the epidemic would spread much faster. We estimated that in highly heterogeneous host populations the timing of the implementation of vector control measures is the major factor for limiting the number of Zika infections.Our findings highlight the need of considering host variability in exposure time for managing mosquito-borne infections and call for the revision of the triggers for vector control strategies, which should integrate mosquito density data and human outdoor activity patterns in specific areas.

  20. CystiSim - An Agent-Based Model for Taenia solium Transmission and Control.

    Directory of Open Access Journals (Sweden)

    Uffe Christian Braae

    2016-12-01

    Full Text Available Taenia solium taeniosis/cysticercosis was declared eradicable by the International Task Force for Disease Eradication in 1993, but remains a neglected zoonosis. To assist in the attempt to regionally eliminate this parasite, we developed cystiSim, an agent-based model for T. solium transmission and control. The model was developed in R and available as an R package (http://cran.r-project.org/package=cystiSim. cystiSim was adapted to an observed setting using field data from Tanzania, but adaptable to other settings if necessary. The model description adheres to the Overview, Design concepts, and Details (ODD protocol and consists of two entities-pigs and humans. Pigs acquire cysticercosis through the environment or by direct contact with a tapeworm carrier's faeces. Humans acquire taeniosis from slaughtered pigs proportional to their infection intensity. The model allows for evaluation of three interventions measures or combinations hereof: treatment of humans, treatment of pigs, and pig vaccination, and allows for customary coverage and efficacy settings. cystiSim is the first agent-based transmission model for T. solium and suggests that control using a strategy consisting of an intervention only targeting the porcine host is possible, but that coverage and efficacy must be high if elimination is the ultimate goal. Good coverage of the intervention is important, but can be compensated for by including an additional intervention targeting the human host. cystiSim shows that the scenarios combining interventions in both hosts, mass drug administration to humans, and vaccination and treatment of pigs, have a high probability of success if coverage of 75% can be maintained over at least a four year period. In comparison with an existing mathematical model for T. solium transmission, cystiSim also includes parasite maturation, host immunity, and environmental contamination. Adding these biological parameters to the model resulted in new insights in

  1. A Novel Egr-1-Agrin Pathway and Potential Implications for Regulation of Synaptic Physiology and Homeostasis at the Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Ryen MacDonald

    2017-08-01

    Full Text Available Synaptic transmission requires intricate coordination of the components involved in processing of incoming signals, formation and stabilization of synaptic machinery, neurotransmission and in all related signaling pathways. Changes to any of these components cause synaptic imbalance and disruption of neuronal circuitry. Extensive studies at the neuromuscular junction (NMJ have greatly aided in the current understanding of synapses and served to elucidate the underlying physiology as well as associated adaptive and homeostatic processes. The heparan sulfate proteoglycan agrin is a vital component of the NMJ, mediating synaptic formation and maintenance in both brain and muscle, but very little is known about direct control of its expression. Here, we investigated the relationship between agrin and transcription factor early growth response-1 (Egr-1, as Egr-1 regulates the expression of many genes involved in synaptic homeostasis and plasticity. Using chromatin immunoprecipitation (ChIP, cell culture with cell lines derived from brain and muscle, and animal models, we show that Egr-1 binds to the AGRN gene locus and suppresses its expression. When compared with wild type (WT, mice deficient in Egr-1 (Egr-1−/− display a marked increase in AGRN mRNA and agrin full-length and cleavage fragment protein levels, including the 22 kDa, C-terminal fragment in brain and muscle tissue homogenate. Because agrin is a crucial component of the NMJ, we explored possible physiological implications of the Egr-1-agrin relationship. In the diaphragm, Egr-1−/− mice display increased NMJ motor endplate density, individual area and area of innervation. In addition to increased density, soleus NMJs also display an increase in fragmented and faint endplates in Egr-1−/− vs. WT mice. Moreover, the soleus NMJ electrophysiology of Egr-1−/− mice revealed increased quantal content and motor testing showed decreased movement and limb muscle strength compared with

  2. Frequency of Synaptic Autoantibody Accompaniments and Neurological Manifestations of Thymoma.

    Science.gov (United States)

    Zekeridou, Anastasia; McKeon, Andrew; Lennon, Vanda A

    2016-07-01

    Thymoma is commonly recognized in association with paraneoplastic autoimmune myasthenia gravis (MG), an IgG-mediated impairment of synaptic transmission targeting the nicotinic acetylcholine receptor of muscle. Newly identified synaptic autoantibodies may expand the serological profile of thymoma. To investigate the frequency of potentially pathogenic neural synaptic autoantibodies in patients with thymoma. We retrospectively identified patients with histopathologically confirmed thymoma and serum available to test for synaptic autoantibodies (collected 1986-2014) at the Mayo Clinic Neuroimmunology Laboratory. We identified and classified 193 patients with thymoma into 4 groups: (1) lacking neurological autoimmunity (n = 43); (2) isolated MG (n = 98); (3) MG plus additional autoimmune neurological manifestations (n = 26); and (4) neurological autoimmunity other than MG (n = 26). Clinical presentation and serum profile of autoantibodies reactive with molecularly defined synaptic plasma membrane proteins of muscle, peripheral, and central nervous systems. Of the 193 patients with thymoma, mean patient age was 52 years and did not significantly differ by sex (106 women) or group. Myasthenia gravis was the most prevalent clinical manifestation (64%) followed by dysautonomia (16 patients [8%]) and encephalopathy (15 patients [8%]); 164 patients (85%) had at least 1 synaptic autoantibody, and 63 of these patients (38%) had at least 1 more. Muscle acetylcholine receptor was most frequent (78%), followed by ganglionic acetylcholine receptor (20%), voltage-gated Kv1 potassium channel-complex (13%), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (5%). Less frequent were aquaporin-4, voltage-gated Kv1 potassium channel-complex related proteins (leucine-rich glioma-inactivated 1 and contactin-associated protein-like 2), glycine receptor, and γ-aminobutyric acid-A receptor. Synaptic autoantibodies were significantly more frequent in patients

  3. MFTF-B quasi-control ECRH transmission system/waveguide transmission system for TMX-U

    International Nuclear Information System (INIS)

    Porter, G.

    1983-01-01

    The MFTF-B ECRH transmission system is designed to transmit the rf produced by each gyrotron quasi-optically from a launch point inside of the vacuum vessel wall in a linearly polarized guassian beam mode to an open cavity enclosing the plasma. The open cavity allows the microwave beam to be reflected numerous times through the plasma before it is lost. This increases the heating efficiency at low densities and temperatures when absorption on a single pass is small and also at high (relativistic) temperatures. In addition, the cavities allow unobstructed passage of neutral beams and simplify compensation for resonant zone shifts caused by beta depression, doppler shifting and relativistic effects. The microwave beam feeding the cavity has a guassian amplitude profile and a nominal diameter of 50 cm

  4. Ribbon Synaptic Plasticity in Gravity Sensors of Rats Flown on Neurolab

    Science.gov (United States)

    Ross, Muriel D.; Varelas, Joseph

    2003-01-01

    Previous spaceflight experiments (Space Life Sciences-1 and -2 (SLS-1 and SLS-2)) first demonstrated the extraordinary ability of gravity sensor hair cells to change the number, kind, and distribution of connections (synapses) they make to other cells while in weightlessness. The number of synapses in hair cells in one part of the inner ear (the utricle) was markedly elevated on flight day 13 (FD13) of SLS-2. Unanswered questions, however, were whether these increases in synapses occur rapidly and whether they remain stable in weightlessness. The answers have implications for long-duration human space travel. If gravity sensors can adapt quickly, crews may be able to move easily between different gravity levels, since the sensors will adapt rapidly to weightlessness on the spacecraft and then back to Earth's gravity when the mission ends. This ability to adapt is also important for recovery from balance disorders. To further our understanding of this adaptive potential (a property called neuronal synaptic plasticity), the present Neurolab research was undertaken. Our experiment examined whether: (a) increases in synapses would remain stable throughout the flight, (b) changes in the number of synapses were uniform across different portions of the gravity sensors (the utricle and saccule), and (c) synaptic changes were similar for the different types of hair cells (Type I and Type II). Utricular and saccular maculae (the gravity-sensing portions of the inner ear) were collected in flight from rats on FD2 and FD14. Samples were also collected from control rats on the ground. Tissues were prepared for ultrastructural study. Hair cells and their ribbon synapses were examined in a transmission electron microscope. Synapses were counted in all hair cells in 50 consecutive sections that crossed the striolar zone. Results indicate that utricular hair cell synapses initially increased significantly in number in both types of hair cells by FD2. Counts declined by FD14, but

  5. Role of DHA in aging-related changes in mouse brain synaptic plasma membrane proteome.

    Science.gov (United States)

    Sidhu, Vishaldeep K; Huang, Bill X; Desai, Abhishek; Kevala, Karl; Kim, Hee-Yong

    2016-05-01

    Aging has been related to diminished cognitive function, which could be a result of ineffective synaptic function. We have previously shown that synaptic plasma membrane proteins supporting synaptic integrity and neurotransmission were downregulated in docosahexaenoic acid (DHA)-deprived brains, suggesting an important role of DHA in synaptic function. In this study, we demonstrate aging-induced synaptic proteome changes and DHA-dependent mitigation of such changes using mass spectrometry-based protein quantitation combined with western blot or messenger RNA analysis. We found significant reduction of 15 synaptic plasma membrane proteins in aging brains including fodrin-α, synaptopodin, postsynaptic density protein 95, synaptic vesicle glycoprotein 2B, synaptosomal-associated protein 25, synaptosomal-associated protein-α, N-methyl-D-aspartate receptor subunit epsilon-2 precursor, AMPA2, AP2, VGluT1, munc18-1, dynamin-1, vesicle-associated membrane protein 2, rab3A, and EAAT1, most of which are involved in synaptic transmission. Notably, the first 9 proteins were further reduced when brain DHA was depleted by diet, indicating that DHA plays an important role in sustaining these synaptic proteins downregulated during aging. Reduction of 2 of these proteins was reversed by raising the brain DHA level by supplementing aged animals with an omega-3 fatty acid sufficient diet for 2 months. The recognition memory compromised in DHA-depleted animals was also improved. Our results suggest a potential role of DHA in alleviating aging-associated cognitive decline by offsetting the loss of neurotransmission-regulating synaptic proteins involved in synaptic function. Published by Elsevier Inc.

  6. Simulation of synaptic coupling of neuron-like generators via a memristive device

    Science.gov (United States)

    Gerasimova, S. A.; Mikhaylov, A. N.; Belov, A. I.; Korolev, D. S.; Gorshkov, O. N.; Kazantsev, V. B.

    2017-08-01

    A physical model of synaptically coupled neuron-like generators interacting via a memristive device has been presented. The model simulates the synaptic transmission of pulsed signals between brain neurons. The action on the receiving generator has been performed via a memristive device that demonstrates adaptive behavior. It has been established that the proposed coupling channel provides the forced synchronization with the parameters depending on the memristive device sensitivity. Synchronization modes 1: 1 and 2: 1 have been experimentally observed.

  7. Electrically controlled infrared optical transmission and reflection through metallic grating using NEMS technology

    Science.gov (United States)

    Yamaguchi, Kenzo; Fujii, Masamitsu

    2015-12-01

    The enhanced optical properties of metallic subwavelength gratings with very narrow slits have recently been extensively studied in the field of plasmonics. The optical transmission and reflection of such nanostructures, which act as nano-electro-mechanical systems (NEMS) actuators, can be electrically controlled by varying their geometrical parameters, giving them great flexibility for numerous applications in photonics, opto-electronics, and sensing. The previous challenges in controlling the optical properties were overcome by forming a metallic subwavelength grating with an NEMS actuator in mid-air, allowing the grating to be physically moved with the bias voltage. The device can shift the plasmon resonance wavelength with an electrical signal. The resonance wavelength for Wood's anomaly at the infrared region is predicted through simulations to shift by approximately 150 nm. We discuss the effect of polarization on the optical properties and grating mechanism. The reported effect may be used to achieve active spectral tuning and switching in a wide range of applications.

  8. Impact of Cyber Attacks on High Voltage DC Transmission Damping Control

    Directory of Open Access Journals (Sweden)

    Rui Fan

    2018-04-01

    Full Text Available Hybrid AC/HVDC (AC-HVDC grids have evolved to become huge cyber-physical systems that are vulnerable to cyber attacks because of the wide attack surface and increasing dependence on intelligent electronic devices, computing resources and communication networks. This paper, for the first time, studies the impact of cyber attacks on HVDC transmission oscillation damping control.Three kinds of cyber attack models are considered: timing attack, replay attack and false data injection attack. Followed by a brief introduction of the HVDC model and conventional oscillation damping control method, the design of three attack models is described in the paper. These attacks are tested on a modified IEEE New England 39-Bus AC-HVDC system. Simulation results have shown that all three kinds of attacks are capable of driving the AC-HVDC system into large oscillations or even unstable conditions.

  9. Optimal control of vaccination rate in an epidemiological model of Clostridium difficile transmission.

    Science.gov (United States)

    Stephenson, Brittany; Lanzas, Cristina; Lenhart, Suzanne; Day, Judy

    2017-12-01

    The spore-forming, gram-negative bacteria Clostridium difficile can cause severe intestinal illness. A striking increase in the number of cases of C. difficile infection (CDI) among hospitals has highlighted the need to better understand how to prevent the spread of CDI. In our paper, we modify and update a compartmental model of nosocomial C. difficile transmission to include vaccination. We then apply optimal control theory to determine the time-varying optimal vaccination rate that minimizes a combination of disease prevalence and spread in the hospital population as well as cost, in terms of time and money, associated with vaccination. Various hospital scenarios are considered, such as times of increased antibiotic prescription rate and times of outbreak, to see how such scenarios modify the optimal vaccination rate. By comparing the values of the objective functional with constant vaccination rates to those with time-varying optimal vaccination rates, we illustrate the benefits of time-varying controls.

  10. Control-Oriented Models for Real-Time Simulation of Automotive Transmission Systems

    Directory of Open Access Journals (Sweden)

    Cavina N.

    2015-01-01

    Full Text Available A control-oriented model of a Dual Clutch Transmission (DCT was developed for real-time Hardware In the Loop (HIL applications, to support model-based development of the DCT controller and to systematically test its performance. The model is an innovative attempt to reproduce the fast dynamics of the actuation system while maintaining a simulation step size large enough for real-time applications. The model comprehends a detailed physical description of hydraulic circuit, clutches, synchronizers and gears, and simplified vehicle and internal combustion engine sub-models. As the oil circulating in the system has a large bulk modulus, the pressure dynamics are very fast, possibly causing instability in a real-time simulation; the same challenge involves the servo valves dynamics, due to the very small masses of the moving elements. Therefore, the hydraulic circuit model has been modified and simplified without losing physical validity, in order to adapt it to the real-time simulation requirements. The results of offline simulations have been compared to on-board measurements to verify the validity of the developed model, which was then implemented in a HIL system and connected to the Transmission Control Unit (TCU. Several tests have been performed on the HIL simulator, to verify the TCU performance: electrical failure tests on sensors and actuators, hydraulic and mechanical failure tests on hydraulic valves, clutches and synchronizers, and application tests comprehending all the main features of the control actions performed by the TCU. Being based on physical laws, in every condition the model simulates a plausible reaction of the system. A test automation procedure has finally been developed to permit the execution of a pattern of tests without the interaction of the user; perfectly repeatable tests can be performed for non-regression verification, allowing the testing of new software releases in fully automatic mode.

  11. Propagation of Homeostatic Sleep Signals by Segregated Synaptic Microcircuits of the Drosophila Mushroom Body.

    Science.gov (United States)

    Sitaraman, Divya; Aso, Yoshinori; Jin, Xin; Chen, Nan; Felix, Mario; Rubin, Gerald M; Nitabach, Michael N

    2015-11-16

    The Drosophila mushroom body (MB) is a key associative memory center that has also been implicated in the control of sleep. However, the identity of MB neurons underlying homeostatic sleep regulation, as well as the types of sleep signals generated by specific classes of MB neurons, has remained poorly understood. We recently identified two MB output neuron (MBON) classes whose axons convey sleep control signals from the MB to converge in the same downstream target region: a cholinergic sleep-promoting MBON class and a glutamatergic wake-promoting MBON class. Here, we deploy a combination of neurogenetic, behavioral, and physiological approaches to identify and mechanistically dissect sleep-controlling circuits of the MB. Our studies reveal the existence of two segregated excitatory synaptic microcircuits that propagate homeostatic sleep information from different populations of intrinsic MB "Kenyon cells" (KCs) to specific sleep-regulating MBONs: sleep-promoting KCs increase sleep by preferentially activating the cholinergic MBONs, while wake-promoting KCs decrease sleep by preferentially activating the glutamatergic MBONs. Importantly, activity of the sleep-promoting MB microcircuit is increased by sleep deprivation and is necessary for homeostatic rebound sleep (i.e., the increased sleep that occurs after, and in compensation for, sleep lost during deprivation). These studies reveal for the first time specific functional connections between subsets of KCs and particular MBONs and establish the identity of synaptic microcircuits underlying transmission of homeostatic sleep signals in the MB. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Synaptic ultrastructure changes in trigeminocervical complex posttrigeminal nerve injury.

    Science.gov (United States)

    Park, John; Trinh, Van Nancy; Sears-Kraxberger, Ilse; Li, Kang-Wu; Steward, Oswald; Luo, Z David

    2016-02-01

    Trigeminal nerves collecting sensory information from the orofacial area synapse on second-order neurons in the dorsal horn of subnucleus caudalis and cervical C1/C2 spinal cord (Vc/C2, or trigeminocervical complex), which is critical for sensory information processing. Injury to the trigeminal nerves may cause maladaptive changes in synaptic connectivity that plays an important role in chronic pain development. Here we examined whether injury to the infraorbital nerve, a branch of the trigeminal nerves, led to synaptic ultrastructural changes when the injured animals have developed neuropathic pain states. Transmission electron microscopy was used to examine synaptic profiles in Vc/C2 at 3 weeks postinjury, corresponding to the time of peak behavioral hypersensitivity following chronic constriction injury to the infraorbital nerve (CCI-ION). Using established criteria, synaptic profiles were classified as associated with excitatory (R-), inhibitory (F-), and primary afferent (C-) terminals. Each type was counted within the superficial dorsal horn of the Vc/C2 and the means from each rat were compared between sham and injured animals; synaptic contact length was also measured. The overall analysis indicates that rats with orofacial pain states had increased numbers and decreased mean synaptic length of R-profiles within the Vc/C2 superficial dorsal horn (lamina I) 3 weeks post-CCI-ION. Increases in the number of excitatory synapses in the superficial dorsal horn of Vc/C2 could lead to enhanced activation of nociceptive pathways, contributing to the development of orofacial pain states. © 2015 Wiley Periodicals, Inc.

  13. Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

    Science.gov (United States)

    Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B.; Zhang, Hailin; Gamper, Nikita

    2014-01-01

    Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

  14. Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

    Directory of Open Access Journals (Sweden)

    Christoph Straub

    2016-07-01

    Full Text Available Synaptic communication between neurons requires the precise localization of neurotransmitter receptors to the correct synapse type. Kainate-type glutamate receptors restrict synaptic localization that is determined by the afferent presynaptic connection. The mechanisms that govern this input-specific synaptic localization remain unclear. Here, we examine how subunit composition and specific subunit domains contribute to synaptic localization of kainate receptors. The cytoplasmic domain of the GluK2 low-affinity subunit stabilizes kainate receptors at synapses. In contrast, the extracellular domain of the GluK4/5 high-affinity subunit synergistically controls the synaptic specificity of kainate receptors through interaction with C1q-like proteins. Thus, the input-specific synaptic localization of the native kainate receptor complex involves two mechanisms that underlie specificity and stabilization of the receptor at synapses.

  15. Would the control of invasive alien plants reduce malaria transmission? A review.

    Science.gov (United States)

    Stone, Christopher M; Witt, Arne B R; Walsh, Guillermo Cabrera; Foster, Woodbridge A; Murphy, Sean T

    2018-02-01

    Vector control has been the most effective preventive measure against malaria and other vector-borne diseases. However, due to concerns such as insecticide resistance and budget shortfalls, an integrated control approach will be required to ensure sustainable, long-term effectiveness. An integrated management strategy should entail some aspects of environmental management, relying on coordination between various scientific disciplines. Here, we review one such environmental control tactic: invasive alien plant management. This covers salient plant-mosquito interactions for both terrestrial and aquatic invasive plants and how these affect a vector's ability to transmit malaria. Invasive plants tend to have longer flowering durations, more vigorous growth, and their spread can result in an increase in biomass, particularly in areas where previously little vegetation existed. Some invasive alien plants provide shelter or resting sites for adult mosquitoes and are also attractive nectar-producing hosts, enhancing their vectorial capacity. We conclude that these plants may increase malaria transmission rates in certain environments, though many questions still need to be answered, to determine how often this conclusion holds. However, in the case of aquatic invasive plants, available evidence suggests that the management of these plants would contribute to malaria control. We also examine and review the opportunities for large-scale invasive alien plant management, including options for biological control. Finally, we highlight the research priorities that must be addressed in order to ensure that integrated vector and invasive alien plant management operate in a synergistic fashion.

  16. Sensor fault-tolerant control for gear-shifting engaging process of automated manual transmission

    Science.gov (United States)

    Li, Liang; He, Kai; Wang, Xiangyu; Liu, Yahui

    2018-01-01

    Angular displacement sensor on the actuator of automated manual transmission (AMT) is sensitive to fault, and the sensor fault will disturb its normal control, which affects the entire gear-shifting process of AMT and results in awful riding comfort. In order to solve this problem, this paper proposes a method of fault-tolerant control for AMT gear-shifting engaging process. By using the measured current of actuator motor and angular displacement of actuator, the gear-shifting engaging load torque table is built and updated before the occurrence of the sensor fault. Meanwhile, residual between estimated and measured angular displacements is used to detect the sensor fault. Once the residual exceeds a determined fault threshold, the sensor fault is detected. Then, switch control is triggered, and the current observer and load torque table estimates an actual gear-shifting position to replace the measured one to continue controlling the gear-shifting process. Numerical and experiment tests are carried out to evaluate the reliability and feasibility of proposed methods, and the results show that the performance of estimation and control is satisfactory.

  17. Optimal autaptic and synaptic delays enhanced synchronization transitions induced by each other in Newman–Watts neuronal networks

    International Nuclear Information System (INIS)

    Wang, Baoying; Gong, Yubing; Xie, Huijuan; Wang, Qi

    2016-01-01

    Highlights: • Optimal autaptic delay enhanced synchronization transitions induced by synaptic delay in neuronal networks. • Optimal synaptic delay enhanced synchronization transitions induced by autaptic delay. • Optimal coupling strength enhanced synchronization transitions induced by autaptic or synaptic delay. - Abstract: In this paper, we numerically study the effect of electrical autaptic and synaptic delays on synchronization transitions induced by each other in Newman–Watts Hodgkin–Huxley neuronal networks. It is found that the synchronization transitions induced by synaptic delay vary with varying autaptic delay and become strongest when autaptic delay is optimal. Similarly, the synchronization transitions induced by autaptic delay vary with varying synaptic delay and become strongest at optimal synaptic delay. Also, there is optimal coupling strength by which the synchronization transitions induced by either synaptic or autaptic delay become strongest. These results show that electrical autaptic and synaptic delays can enhance synchronization transitions induced by each other in the neuronal networks. This implies that electrical autaptic and synaptic delays can cooperate with each other and more efficiently regulate the synchrony state of the neuronal networks. These findings could find potential implications for the information transmission in neural systems.

  18. Middle East respiratory syndrome coronavirus transmission among health care workers: Implication for infection control.

    Science.gov (United States)

    Alfaraj, Sarah H; Al-Tawfiq, Jaffar A; Altuwaijri, Talal A; Alanazi, Marzouqa; Alzahrani, Nojoom; Memish, Ziad A

    2018-02-01

    Many outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in health care settings and involved health care workers (HCWs). We describe the occurrence of an outbreak among HCWs and attempt to characterize at-risk exposures to improve future infection control interventions. This study included an index case and all HCW contacts. All contacts were screened for MERS-CoV using polymerase chain reaction. During the study period in 2015, the index case was a 30-year-old Filipino nurse who had a history of unprotected exposure to a MERS-CoV-positive case on May 15, 2015, and had multiple negative tests for MERS-CoV. Weeks later, she was diagnosed with pulmonary tuberculosis and MERS-CoV infection. A total of 73 staff were quarantined for 14 days, and nasopharyngeal swabs were taken on days 2, 5, and 12 postexposure. Of those contacts, 3 (4%) were confirmed positive for MERS-CoV. An additional 18 staff were quarantined and had MERS-CoV swabs. A fourth case was confirmed positive on day 12. Subsequent contact investigations revealed a fourth-generation transmission. Only 7 (4.5%) of the total 153 contacts were positive for MERS-CoV. The role of HCWs in MERS-CoV transmission is complex. Although most MERS-CoV-infected HCWs are asymptomatic or have mild disease, fatal infections can occur and HCWs can play a major role in propagating health care facility outbreaks. This investigation highlights the need to continuously review infection control guidance relating to the role of HCWs in MERS-CoV transmission in health care outbreaks, especially as it relates to the complex questions on definition of risky exposures, who to test, and the frequency of MERS-CoV testing; criteria for who to quarantine and for how long; and clearance and return to active duty criteria. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  19. Learning, memory and synaptic plasticity in hippocampus in rats exposed to sevoflurane.

    Science.gov (United States)

    Xiao, Hongyan; Liu, Bing; Chen, Yali; Zhang, Jun

    2016-02-01

    Developmental exposure to volatile anesthetics has been associated with cognitive deficits at adulthood. Rodent studies have revealed impairments in performance in learning tasks involving the hippocampus. However, how the duration of anesthesia exposure impact on hippocampal synaptic plasticity, learning, and memory is as yet not fully elucidated. On postnatal day 7(P7), rat pups were divided into 3 groups: control group (n=30), 3% sevoflurane treatment for 1h (Sev 1h group, n=30) and 3% sevoflurane treatment for 6h (Sev 6h group, n=28). Following anesthesia, synaptic vesicle-associated proteins and dendrite spine density and synapse ultrastructure were measured using western blotting, Golgi staining, and transmission electron microscopy (TEM) on P21. In addition, the effects of sevoflurane treatment on long-term potentiation (LTP) and long-term depression (LTD), two molecular correlates of memory, were studied in CA1 subfields of the hippocampus, using electrophysiological recordings of field potentials in hippocampal slices on P35-42. Rats' neurocognitive performance was assessed at 2 months of age, using the Morris water maze and novel-object recognition tasks. Our results showed that neonatal exposure to 3% sevoflurane for 6h results in reduced spine density of apical dendrites along with elevated expression of synaptic vesicle-associated proteins (SNAP-25 and syntaxin), and synaptic ultrastructure damage in the hippocampus. The electrophysiological evidence indicated that hippocampal LTP, but not LTD, was inhibited and that learning and memory performance were impaired in two behavioral tasks in the Sev 6h group. In contrast, lesser structural and functional damage in the hippocampus was observed in the Sev 1h group. Our data showed that 6-h exposure of the developing brain to 3% sevoflurane could result in synaptic plasticity impairment in the hippocampus and spatial and nonspatial hippocampal-dependent learning and memory deficits. In contrast, shorter

  20. VAChT overexpression increases acetylcholine at the synaptic cleft and accelerates aging of neuromuscular junctions.

    Science.gov (United States)

    Sugita, Satoshi; Fleming, Leland L; Wood, Caleb; Vaughan, Sydney K; Gomes, Matheus P S M; Camargo, Wallace; Naves, Ligia A; Prado, Vania F; Prado, Marco A M; Guatimosim, Cristina; Valdez, Gregorio

    2016-01-01

    Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS). Chat-ChR2-EYFP (VAChT Hyp ) mice containing multiple copies of the vesicular acetylcholine transporter (VAChT), mutant superoxide dismutase 1 (SOD1 G93A ), and Chat-IRES-Cre and tdTomato transgenic mice were used in this study. NMJs, muscle fibers, and α-motor neurons' somata and their axons were examined using a light microscope. Transcripts for select genes in muscles and spinal cords were assessed using real-time quantitative PCR. Motor function tests were carried out using an inverted wire mesh and a rotarod. Electrophysiological recordings were collected to examine miniature endplate potentials (MEPP) in muscles. We show that VAChT is elevated in the spinal cord and at NMJs of VAChT Hyp mice. We also show that the amplitude of MEPPs is significantly higher in VAChT Hyp muscles, indicating that more ACh is loaded into synaptic vesicles and released into the synaptic cleft at NMJs of VAChT Hyp mice compared to control mice. While the development of NMJs was not affected in VAChT Hyp mice, NMJs prematurely acquired age-related structural alterations in adult VAChT Hyp mice. These structural changes at NMJs were accompanied by motor deficits in VAChT Hyp mice. However, cellular features of muscle fibers and levels of molecules with critical functions at the NMJ and in muscle fibers were largely unchanged in VAChT Hyp mice. In the SOD1 G93A mouse model for ALS, increasing synaptic ACh accelerated degeneration of NMJs caused motor deficits and

  1. Short-Circuit Calculations for a Transmission Line in the Algerian Power Network Compensated by Thyristor Controlled Voltage Regulator

    Directory of Open Access Journals (Sweden)

    ZELLAGUI Mohamed

    2014-10-01

    Full Text Available In this paper, the impact of using the Thyristor Controlled Voltage Regulator (TCVR on short-circuit calculations is studied for a high voltage transmission line in case of a phase to earth fault in the presence of a fault resistance (RF. A 400 kV single transmission line, in the Algerian power network, is used for this study where the line is compensated by TCVR FACTS device to control the voltage and active power of the line. The impact of the fault resistance is studied to reflect its effect on short-circuit calculations including symmetrical current components, transmission line currents, voltage symmetrical components, and transmission line voltages, without and with TCVR. The obtained simulation results match the presented theoretical analysis.

  2. The potential for sexual transmission to compromise control of Ebola virus outbreaks

    OpenAIRE

    Vinson, John E.; Drake, John M.; Rohani, Pejman; Park, Andrew W.

    2016-01-01

    Recent evidence suggests that sexual contact may give rise to transmission of Ebola virus long after infection has been cleared from blood. We develop a simple mathematical model that incorporates contact transmission and sexual transmission parametrized from data relating to the 2013���2015 West African Ebola epidemic. The model explores scenarios where contact transmission is reduced following infection events, capturing behaviour change, and quantifies how these actions reducing transmissi...

  3. Mode Shift Control for a Hybrid Heavy-Duty Vehicle with Power-Split Transmission

    Directory of Open Access Journals (Sweden)

    Kun Huang

    2017-02-01

    Full Text Available Given that power-split transmission (PST is considered to be a major powertrain technology for hybrid heavy-duty vehicles (HDVs, the development and application of PST in the HDVs make mode shift control an essential aspect of powertrain system design. This paper presents a shift schedule design and torque control strategy for a hybrid HDV with PST during mode shift, intended to reduce the output torque variation and improve the shift quality (SQ. Firstly, detailed dynamic models of the hybrid HDV are developed to analyze the mode shift characteristics. Then, a gear shift schedule calculation method including a dynamic shift schedule and an economic shift schedule is provided. Based on the dynamic models and the designed shift schedule, a mode shift performance simulator is built using MATLAB/Simulink, and simulations are carried out. Through analysis of the dynamic equations, it is seen that the inertia torques of the motor–generator lead to the occurrence of transition torque. To avoid the unwanted transition torque, we use a mode shift control strategy that coordinates the motor–generator torque to compensate for the transition torque. The simulation and experimental results demonstrate that the output torque variation during mode shift is effectively reduced by the proposed control strategy, thereby improving the SQ.

  4. The potential for sexual transmission to compromise control of Ebola virus outbreaks.

    Science.gov (United States)

    Vinson, John E; Drake, John M; Rohani, Pejman; Park, Andrew W

    2016-06-01

    Recent evidence suggests that sexual contact may give rise to transmission of Ebola virus long after infection has been cleared from blood. We develop a simple mathematical model that incorporates contact transmission and sexual transmission parametrized from data relating to the 2013-2015 West African Ebola epidemic. The model explores scenarios where contact transmission is reduced following infection events, capturing behaviour change, and quantifies how these actions reducing transmission may be compromised by sexual transmission in terms of increasing likelihood, size and duration of outbreaks. We characterize the extent to which sexual transmission operates in terms of the probability of initial infection resolving to sexual infectiousness and the sexual transmission rate, and relate these parameters to the overall case burden. We find that sexual transmission can have large effects on epidemic dynamics (increasing attack ratios from 25% in scenarios without sexual transmission but with contact-transmission-reducing behaviour, up to 80% in equivalent scenarios with sexual transmission). © 2016 The Author(s).

  5. Shingles Transmission

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Shingles (Herpes Zoster) Note: Javascript is disabled or is ... message, please visit this page: About CDC.gov . Shingles Home About Shingles Overview Signs & Symptoms Transmission Complications ...

  6. Polarization control of high transmission/reflection switching by all-dielectric metasurfaces

    Science.gov (United States)

    Shibanuma, Toshihiko; Maier, Stefan A.; Albella, Pablo

    2018-02-01

    Metasurfaces built of high refractive dielectric nanostructures could play a key role in controlling the electromagnetic wave propagation, due to their low energy losses and their ability to excite not only electric but also magnetic resonances. In this study, we theoretically and experimentally demonstrate that an array of high-index dielectric nanodimers can perform as tuneable metasurfaces that can be switched from a high transmitter to a high reflector, by just changing the linear polarization of excitation. The incident polarization alters the hybridization mode of the excited electric and magnetic dipoles in the dimer, and this leads to either spectral overlap or separation of the two dipoles. The hybridization of the electric and magnetic modes modifies the effective permittivity and permeability of the tuneable dielectric metasurface, exhibiting the high transmission and reflection that can be easily switched by simply changing the linear polarization.

  7. Preventing and controlling emerging and reemerging transmissible diseases in the homeless.

    Science.gov (United States)

    Badiaga, Sékéné; Raoult, Didier; Brouqui, Philippe

    2008-09-01

    Homelessness is an increasing public health problem. Because of poor living conditions and limited access to healthcare systems, homeless persons are exposed to many communicable infections. We summarize the intervention measures reported to be efficient for the control and the prevention of common transmissible infections among homeless populations. Evidence suggests that appropriate street- or shelter-based interventions for targeted populations are the most efficient methods. Depending on the populations targeted, these interventions may include education, free condom distribution, syringe and needle prescription programs, chest radiography screening for tuberculosis, directly observed therapy for tuberculosis treatment, improvement of personal clothing and bedding hygiene, and widespread use of ivermectin for scabies and body louse infestation. Systematic vaccination against hepatitis B virus, hepatitis A virus, influenza, Streptococcus pneumoniae, and diphtheria is strongly recommended. National public health programs specific to homeless populations are required.

  8. Performance Analysis of Diversity-Controlled Multi-User Superposition Transmission for 5G Wireless Networks.

    Science.gov (United States)

    Yeom, Jeong Seon; Chu, Eunmi; Jung, Bang Chul; Jin, Hu

    2018-02-10

    In this paper, we propose a novel low-complexity multi-user superposition transmission (MUST) technique for 5G downlink networks, which allows multiple cell-edge users to be multiplexed with a single cell-center user. We call the proposed technique diversity-controlled MUST technique since the cell-center user enjoys the frequency diversity effect via signal repetition over multiple orthogonal frequency division multiplexing (OFDM) sub-carriers. We assume that a base station is equipped with a single antenna but users are equipped with multiple antennas. In addition, we assume that the quadrature phase shift keying (QPSK) modulation is used for users. We mathematically analyze the bit error rate (BER) of both cell-edge users and cell-center users, which is the first theoretical result in the literature to the best of our knowledge. The mathematical analysis is validated through extensive link-level simulations.

  9. The Peak Control Function and its Applications to Transmission Line Effects in Class D Amplifiers

    Directory of Open Access Journals (Sweden)

    VUZA, D. T.

    2014-08-01

    Full Text Available Class D amplifiers find new applications in RFID systems, because of their high efficiency. Most textbooks describe the case of a load directly connected to the amplifier. However, in most RFID systems the usage of a transmission line is mandatory and this may introduce some novel effects, in the form of an infinite series of peaks in the system frequency response functions. If not appropriately taken care of, these effects may lead to electromagnetic compatibility problems. The purpose of the paper is to develop the theory of the peak control function, which is conceived as a tool that allows the designer to keep the magnitude of the peaks, and hence their influence on the system, into well defined limits.

  10. High temperature x-ray diffraction in transmission under controlled environment

    International Nuclear Information System (INIS)

    Margulies, L.; Kramer, M.J.; Williams, J.J.; Deters, E.M.; McCallum, R.W.; Goldman, A.I.; Haeffner, D.R.; Lang, J.C.; Kycia, S.

    1998-01-01

    A compact tube furnace has been developed for high temperature X-ray diffraction studies using high energy synchrotron radiation. The furnace design has a low absorption path in transmission yet allows for a high degree of control of the sample atmosphere and a minimal temperature gradient across the sample. The design allows for a maximum temperature of 1,500 C with a variety of atmospheres including inert, reducing, and oxidizing. Preliminary results obtained at the SRI-CAT 1-ID undulator line (60 keV) at the APS facility and the A2 24 pole wiggler line (45 keV) at CHESS on the Ti 5 Si 3 Z .5 (Z = C, N, O) system will be presented to demonstrate the feasibility of this approach

  11. Synaptically evoked glutamate transporter currents in Spinal Dorsal Horn Astrocytes

    Directory of Open Access Journals (Sweden)

    Dougherty Patrick M

    2009-07-01

    Full Text Available Abstract Background Removing and sequestering synaptically released glutamate from the extracellular space is carried out by specific plasma membrane transporters that are primarily located in astrocytes. Glial glutamate transporter function can be monitored by recording the currents that are produced by co-transportation of Na+ ions with the uptake of glutamate. The goal of this study was to characterize glutamate transporter function in astrocytes of the spinal cord dorsal horn in real time by recording synaptically evoked glutamate transporter currents. Results Whole-cell patch clamp recordings were obtained from astrocytes in the spinal substantia gelatinosa (SG area in spinal slices of young adult rats. Glutamate transporter currents were evoked in these cells by electrical stimulation at the spinal dorsal root entry zone in the presence of bicuculline, strychnine, DNQX and D-AP5. Transporter currents were abolished when synaptic transmission was blocked by TTX or Cd2+. Pharmacological studies identified two subtypes of glutamate transporters in spinal astrocytes, GLAST and GLT-1. Glutamate transporter currents were graded with stimulus intensity, reaching peak responses at 4 to 5 times activation threshold, but were reduced following low-frequency (0.1 – 1 Hz repetitive stimulation. Conclusion These results suggest that glutamate transporters of spinal astrocytes could be activated by synaptic activation, and recording glutamate transporter currents may provide a means of examining the real time physiological responses of glial cells in spinal sensory processing, sensitization, hyperalgesia and chronic pain.

  12. Optogenetic analysis of synaptic function

    NARCIS (Netherlands)

    Liewald, Jana F.; Brauner, Martin; Stephens, Greg J.; Bouhours, Magali; Schultheis, Christian; Zhen, Mei; Gottschalk, Alexander

    2008-01-01

    We introduce optogenetic investigation of neurotransmission (OptIoN) for time-resolved and quantitative assessment of synaptic function via behavioral and electrophysiological analyses. We photo-triggered release of acetylcholine or γ-aminobutyric acid at Caenorhabditis elegans neuromuscular

  13. Synaptic AMPA receptor plasticity and behavior

    NARCIS (Netherlands)

    Kessels, Helmut W.; Malinow, Roberto

    2009-01-01

    The ability to change behavior likely depends on the selective strengthening and weakening of brain synapses. The cellular models of synaptic plasticity, long-term potentiation (LTP) and depression (LTD) of synaptic strength, can be expressed by the synaptic insertion or removal of AMPA receptors

  14. Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control.

    Science.gov (United States)

    Seuberlich, Torsten; Heim, Dagmar; Zurbriggen, Andreas

    2010-11-01

    Since 1987, when bovine spongiform encephalopathy (BSE) emerged as a novel disease in cattle, enormous efforts were undertaken to monitor and control the disease in ruminants worldwide. The driving force was its high economic impact, which resulted from trade restrictions and the loss of consumer confidence in beef products, the latter because BSE turned out to be a fatal zoonosis, causing variant Creutzfeldt-Jakob disease in human beings. The ban on meat and bone meal in livestock feed and the removal of specified risk materials from the food chain were the main measures to successfully prevent infection in cattle and to protect human beings from BSE exposure. However, although BSE is now under control, previously unknown, so-called atypical transmissible spongiform encephalopathies (TSEs) in cattle and small ruminants have been identified by enhanced disease surveillance. This report briefly reviews and summarizes the current level of knowledge on the spectrum of TSEs in cattle and small ruminants and addresses the question of the extent to which such atypical TSEs have an effect on disease surveillance and control strategies.

  15. Stream Control Transmission Protocol as a Transport for SIP: a case study

    Directory of Open Access Journals (Sweden)

    Giuseppe De Marco

    2004-06-01

    Full Text Available The dominant signalling protocol both in future wireless and wired networks will be the Session Initiation Protocol (SIP, as pointed out in the 3G IP-based mobile networks specifications, entailing a fully Internet integrated network. The use of SIP in the IP Multimedia Subsytem (IMS of Release 5 involves the development of servers capable to handle a large number of call requests. The signaling traffic associated to such requests could explode, if an intelligent congestion control were not introduced. Stream Control Transmission Protocol (SCTP was born to support transport of SS7 signaling messages. However, many of the SCTP features are also useful for transport of SIP messages, as: congestion control mechanism, good separation among independent messages, multihoming. Indeed, adoption of SCTP as transport of SIP signaling might prove useful in some situations where usual transport protocols, like TCP and UDP, suffer performance degradation. In this paper, we analyse the general framework wherein SIP operates and we discuss the benefits of using SCTP as a transport for SIP, toward fair sharing of network resources. This study is carried on in the context of the implementation of an high-performance SIP Proxy Server. We also present some preliminar results of an implementation of SIP over SCTP/UDP in a real LAN environment.

  16. Self-adaptive optimal control of dry dual clutch transmission (DCT) during starting process

    Science.gov (United States)

    Zhao, Zhiguo; He, Lu; Zheng, Zhengxing; Yang, Yunyun; Wu, Chaochun

    2016-02-01

    An optimal control based on the minimum principle is proposed to solve the problems with the starting process of the self-developed five-speed dry dual clutch transmission (DCT). For the slipping phase, the minimum principle and improved engine constant speed control are adopted to obtain the optimal clutch and engine torques and their rotating speeds, with the minimum jerk intensity and friction work as optimization indices. For the stable running phase, the engine torque is converted to the driver's level of demand. The Matlab/Simulink software platform was used to simulate the DCT vehicle in the starting stage. The simulation and related analysis were conducted for different engine speeds and intentions of the driver. The results showed that the proposed clutch starting control strategy not only reduces the level of jerk and the frictional energy loss but also follows the different starting intentions of the driver. The optimum clutch engagement principle was transformed into the clutch position principle, and a test was carried out on the test bench to validate the effectiveness of the optimum clutch position curve.

  17. A history of chagas disease transmission, control, and re-emergence in peri-rural La Joya, Peru.

    Science.gov (United States)

    Delgado, Stephen; Castillo Neyra, Ricardo; Quispe Machaca, Víctor R; Ancca Juárez, Jenny; Chou Chu, Lily; Verastegui, Manuela Renee; Moscoso Apaza, Giovanna M; Bocángel, César D; Tustin, Aaron W; Sterling, Charles R; Comrie, Andrew C; Náquira, César; Cornejo del Carpio, Juan G; Gilman, Robert H; Bern, Caryn; Levy, Michael Z

    2011-02-22

    The history of Chagas disease control in Peru and many other nations is marked by scattered and poorly documented vector control campaigns. The complexities of human migration and sporadic control campaigns complicate evaluation of the burden of Chagas disease and dynamics of Trypanosoma cruzi transmission. We conducted a cross-sectional serological and entomological study to evaluate temporal and spatial patterns of T. cruzi transmission in a peri-rural region of La Joya, Peru. We use a multivariate catalytic model and Bayesian methods to estimate incidence of infection over time and thereby elucidate the complex history of transmission in the area. Of 1,333 study participants, 101 (7.6%; 95% CI: 6.2-9.0%) were confirmed T. cruzi seropositive. Spatial clustering of parasitic infection was found in vector insects, but not in human cases. Expanded catalytic models suggest that transmission was interrupted in the study area in 1996 (95% credible interval: 1991-2000), with a resultant decline in the average annual incidence of infection from 0.9% (95% credible interval: 0.6-1.3%) to 0.1% (95% credible interval: 0.005-0.3%). Through a search of archival newspaper reports, we uncovered documentation of a 1995 vector control campaign, and thereby independently validated the model estimates. High levels of T. cruzi transmission had been ongoing in peri-rural La Joya prior to interruption of parasite transmission through a little-documented vector control campaign in 1995. Despite the efficacy of the 1995 control campaign, T. cruzi was rapidly reemerging in vector populations in La Joya, emphasizing the need for continuing surveillance and control at the rural-urban interface.

  18. A history of chagas disease transmission, control, and re-emergence in peri-rural La Joya, Peru.

    Directory of Open Access Journals (Sweden)

    Stephen Delgado

    2011-02-01

    Full Text Available The history of Chagas disease control in Peru and many other nations is marked by scattered and poorly documented vector control campaigns. The complexities of human migration and sporadic control campaigns complicate evaluation of the burden of Chagas disease and dynamics of Trypanosoma cruzi transmission.We conducted a cross-sectional serological and entomological study to evaluate temporal and spatial patterns of T. cruzi transmission in a peri-rural region of La Joya, Peru. We use a multivariate catalytic model and Bayesian methods to estimate incidence of infection over time and thereby elucidate the complex history of transmission in the area. Of 1,333 study participants, 101 (7.6%; 95% CI: 6.2-9.0% were confirmed T. cruzi seropositive. Spatial clustering of parasitic infection was found in vector insects, but not in human cases. Expanded catalytic models suggest that transmission was interrupted in the study area in 1996 (95% credible interval: 1991-2000, with a resultant decline in the average annual incidence of infection from 0.9% (95% credible interval: 0.6-1.3% to 0.1% (95% credible interval: 0.005-0.3%. Through a search of archival newspaper reports, we uncovered documentation of a 1995 vector control campaign, and thereby independently validated the model estimates.High levels of T. cruzi transmission had been ongoing in peri-rural La Joya prior to interruption of parasite transmission through a little-documented vector control campaign in 1995. Despite the efficacy of the 1995 control campaign, T. cruzi was rapidly reemerging in vector populations in La Joya, emphasizing the need for continuing surveillance and control at the rural-urban interface.

  19. Toltrazuril treatment to control diaplacental Neospora caninum transmission in experimentally infected pregnant mice.

    Science.gov (United States)

    Gottstein, B; Razmi, G R; Ammann, P; Sager, H; Müller, N

    2005-01-01

    We addressed the question whether diaplacental transmission of Neospora caninum can be controlled by metaphylactic chemotherapy using toltrazuril or enrofloxacin. Female C57/BL6 mice, infected on day 10 of pregnancy, were medicated for 6 consecutive days p.i. with 52.5 mg toltrazuril or - as an out-group control medication--16.7 mg enrofloxacin per kg body weight per day. Other control groups received either infection but no medication or vice versa. Toltrazuril treatment significantly reduced pre- and perinatal losses (10 deliveries of healthy newborns, versus 1 abortion and 4 failures) when compared to control-enrofloxacin (2 deliveries, versus 1 abortion, 7 failures and 2 pre-parturient deaths of dams) and non-treated animals (3 deliveries, versus 6 abortions, 8 failures and 4 pre-parturient deaths). Simultaneously, PCR-based parasite detection in the brain of mothers, histopathological findings as well as clinical fatality were significantly less frequent in toltrazuril-treated dams. The overall toltrazuril treatment efficacy was determined as 87 %, that of enrofloxacin-treatment as 17 %. The progenies of toltrazuril-treated dams also exhibited a very low rate of PCR-positivity in their brain (3 out of 39), whereas untreated dams delivered litters with mostly PCR-positive brains (12 out of 14) and a relatively high death rate post-partum (5 out of 19 newborns died). Mice subjected to a second mating delivered newborns all negative by N. caninum-PCR, indicating that diaplacental tachyzoite passage does not occur in a later, repeated pregnancy. Overall, our experiments showed that toltrazuril-treatment of an acute N. caninum-infection--induced during pregnancy--results in a clear reduction of fetal losses and a marked reduction of diaplacental passage of the parasite to the fetal brain, whereas enrofloxacin, as an out-group control substance, failed to show the same effect.

  20. Intelligent Multiobjective Slip and Speed Ratio Control of a Novel Dual-Belt Continuously Variable Transmission for Automobiles

    Directory of Open Access Journals (Sweden)

    Zhengchao Xie

    2014-01-01

    Full Text Available Van Doorne’s continuously variable transmission (CVT is the most popular CVT design for automotive transmission, but it is only applicable to low-power passenger cars because of its low torque capacity. To overcome this limitation of traditional single-belt CVT, a novel dual-belt Van Doorne’s CVT (DBVCVT system, which is applicable to heavy-duty vehicles, has been previously proposed by the authors. This paper, based on the published analytical model and test rig of DBVCVT, further proposes an intelligent multiobjective fuzzy controller for slip and speed ratio control of DBVCVT. The controller aims to safely control the clamping forces of both the primary and the secondary pulleys in order to improve the transmission efficiency, achieve the accurate speed ratio, and avoid the belt slip under different engine loads and vehicle speeds. The slip, speed ratio, and transmission efficiency dynamics of DBVCVT are firstly analyzed and modeled in this paper. With the aid of a flexible objective function, the analytical model, and fuzzy logic, a Pareto rule base for fuzzy controller is developed for multiobjective DBVCVT control. Experimental results show that the proposed controller for slip and speed ratio regulation of DBVCVT is effective and performs well under different user-defined weights.

  1. The Hypoxia Mimetic Protocatechuic Acid Ethyl Ester Inhibits Synaptic Signaling and Plasticity in the Rat Hippocampus.

    Science.gov (United States)

    Lanigan, Sinead M; O'Connor, John J

    2018-01-15

    During hypoxia a number of physiological changes occur within neurons including the stabilization of hypoxia-inducible factors (HIFs). The activity of these proteins is regulated by O 2 , Fe 2+ , 2-OG and ascorbate-dependant hydroxylases which contain prolyl-4-hydroxylase domains (PHDs). PHD inhibitors have been widely used and have been shown to have a preconditioning and protective effect against a later and more severe hypoxic insult. In this study we have investigated the neuroprotective effects of the PHD inhibitor, protocatechuic acid ethyl ester (ethyl 3,4, dihydroxybenzoate: EDHB), as well as its effects on synaptic transmission and plasticity in the rat hippocampus using electrophysiological techniques. We report for the first time, an acute concentration-dependent and reversible inhibitory effect of EDHB (10-100 μM) on synaptic transmission in the dentate gyrus but not Cornu Ammonis 1 (CA1) region which does not affect cell viability. This effect was attenuated through the application of the NMDA or GABA A receptor antagonists, AP-5 and picrotoxin in the dentate gyrus. There were no changes in the ratio of paired responses after EDHB application suggesting a post-synaptic mechanism of action. EDHB (100 μM), was found to inhibit synaptic plasticity in both the dentate gyrus and CA1 regions. Application of exogenous Fe 2+ (100 μM) or digoxin (100 nM) did not reverse EDHB's inhibitory effect on synaptic transmission or plasticity in both regions, suggesting that its effects may be HIF-independent. These results highlight a novel modulatory role for the PHD inhibitor EDHB in hippocampal synaptic transmission and plasticity. A novel post-synaptic mechanism of action may be involved, possibly involving NMDA and GABA A receptor activation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. New World feline APOBEC3 potently controls inter-genus lentiviral transmission.

    Science.gov (United States)

    Konno, Yoriyuki; Nagaoka, Shumpei; Kimura, Izumi; Yamamoto, Keisuke; Kagawa, Yumiko; Kumata, Ryuichi; Aso, Hirofumi; Ueda, Mahoko Takahashi; Nakagawa, So; Kobayashi, Tomoko; Koyanagi, Yoshio; Sato, Kei

    2018-04-10

    The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) gene family appears only in mammalian genomes. Some A3 proteins can be incorporated into progeny virions and inhibit lentiviral replication. In turn, the lentiviral viral infectivity factor (Vif) counteracts the A3-mediated antiviral effect by degrading A3 proteins. Recent investigations have suggested that lentiviral vif genes evolved to combat mammalian APOBEC3 proteins, and have further proposed that the Vif-A3 interaction may help determine the co-evolutionary history of cross-species lentiviral transmission in mammals. Here we address the co-evolutionary relationship between two New World felids, the puma (Puma concolor) and the bobcat (Lynx rufus), and their lentiviruses, which are designated puma lentiviruses (PLVs). We demonstrate that PLV-A Vif counteracts the antiviral action of APOBEC3Z3 (A3Z3) of both puma and bobcat, whereas PLV-B Vif counteracts only puma A3Z3. The species specificity of PLV-B Vif is irrespective of the phylogenic relationships of feline species in the genera Puma, Lynx and Acinonyx. We reveal that the amino acid at position 178 in the puma and bobcat A3Z3 is exposed on the protein surface and determines the sensitivity to PLV-B Vif-mediated degradation. Moreover, although both the puma and bobcat A3Z3 genes are polymorphic, their sensitivity/resistance to PLV Vif-mediated degradation is conserved. To the best of our knowledge, this is the first study suggesting that the host A3 protein potently controls inter-genus lentiviral transmission. Our findings provide the first evidence suggesting that the co-evolutionary arms race between lentiviruses and mammals has occurred in the New World.

  3. Exercise-Induced Fatigue Impairs Bidirectional Corticostriatal Synaptic Plasticity.

    Science.gov (United States)

    Ma, Jing; Chen, Huimin; Liu, Xiaoli; Zhang, Lingtao; Qiao, Decai

    2018-01-01

    Exercise-induced fatigue (EF) is a ubiquitous phenomenon in sports competition and training. It can impair athletes' motor skill execution and cognition. Corticostriatal synaptic plasticity is considered to be the cellular mechanism of movement control and motor learning. However, the effect of EF on corticostriatal synaptic plasticity remains elusive. In the present study, using field excitatory postsynaptic potential recording, we found that the corticostriatal long-term potentiation (LTP) and long-term depression (LTD) were both impaired in EF mice. To further investigate the cellular mechanisms underlying the impaired synaptic plasticity in corticostriatal pathway, whole-cell patch clamp recordings were carried out on striatal medium spiny neurons (MSNs). MSNs in EF mice exhibited increased spontaneous excitatory postsynaptic current (sEPSC) frequency and decreased paired-pulse ratio (PPR), while with normal basic electrophysiological properties and normal sEPSC amplitude. Furthermore, the N-methyl-D-aspartate (NMDA)/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) ratio of MSNs was reduced in EF mice. These results suggest that the enhanced presynaptic glutamate (Glu) release and downregulated postsynaptic NMDA receptor function lead to the impaired corticostriatal plasticity in EF mice. Taken together, our findings for the first time show that the bidirectional corticostriatal synaptic plasticity is impaired after EF, and suggest that the aberrant corticostriatal synaptic plasticity may be involved in the production and/or maintenance of EF.

  4. Contrasting Transmission Dynamics of Co-endemic Plasmodium vivax and P. falciparum: Implications for Malaria Control and Elimination.

    Science.gov (United States)

    Noviyanti, Rintis; Coutrier, Farah; Utami, Retno A S; Trimarsanto, Hidayat; Tirta, Yusrifar K; Trianty, Leily; Kusuma, Andreas; Sutanto, Inge; Kosasih, Ayleen; Kusriastuti, Rita; Hawley, William A; Laihad, Ferdinand; Lobo, Neil; Marfurt, Jutta; Clark, Taane G; Price, Ric N; Auburn, Sarah

    2015-05-01

    Outside of Africa, P. falciparum and P. vivax usually coexist. In such co-endemic regions, successful malaria control programs have a greater impact on reducing falciparum malaria, resulting in P. vivax becoming the predominant species of infection. Adding to the challenges of elimination, the dormant liver stage complicates efforts to monitor the impact of ongoing interventions against P. vivax. We investigated molecular approaches to inform the respective transmission dynamics of P. falciparum and P. vivax and how these could help to prioritize public health interventions. Genotype data generated at 8 and 9 microsatellite loci were analysed in 168 P. falciparum and 166 P. vivax isolates, respectively, from four co-endemic sites in Indonesia (Bangka, Kalimantan, Sumba and West Timor). Measures of diversity, linkage disequilibrium (LD) and population structure were used to gauge the transmission dynamics of each species in each setting. Marked differences were observed in the diversity and population structure of P. vivax versus P. falciparum. In Bangka, Kalimantan and Timor, P. falciparum diversity was low, and LD patterns were consistent with unstable, epidemic transmission, amenable to targeted intervention. In contrast, P. vivax diversity was higher and transmission appeared more stable. Population differentiation was lower in P. vivax versus P. falciparum, suggesting that the hypnozoite reservoir might play an important role in sustaining local transmission and facilitating the spread of P. vivax infections in different endemic settings. P. vivax polyclonality varied with local endemicity, demonstrating potential utility in informing on transmission intensity in this species. Molecular approaches can provide important information on malaria transmission that is not readily available from traditional epidemiological measures. Elucidation of the transmission dynamics circulating in a given setting will have a major role in prioritising malaria control strategies

  5. Contrasting Transmission Dynamics of Co-endemic Plasmodium vivax and P. falciparum: Implications for Malaria Control and Elimination.

    Directory of Open Access Journals (Sweden)

    Rintis Noviyanti

    2015-05-01

    Full Text Available Outside of Africa, P. falciparum and P. vivax usually coexist. In such co-endemic regions, successful malaria control programs have a greater impact on reducing falciparum malaria, resulting in P. vivax becoming the predominant species of infection. Adding to the challenges of elimination, the dormant liver stage complicates efforts to monitor the impact of ongoing interventions against P. vivax. We investigated molecular approaches to inform the respective transmission dynamics of P. falciparum and P. vivax and how these could help to prioritize public health interventions.Genotype data generated at 8 and 9 microsatellite loci were analysed in 168 P. falciparum and 166 P. vivax isolates, respectively, from four co-endemic sites in Indonesia (Bangka, Kalimantan, Sumba and West Timor. Measures of diversity, linkage disequilibrium (LD and population structure were used to gauge the transmission dynamics of each species in each setting. Marked differences were observed in the diversity and population structure of P. vivax versus P. falciparum. In Bangka, Kalimantan and Timor, P. falciparum diversity was low, and LD patterns were consistent with unstable, epidemic transmission, amenable to targeted intervention. In contrast, P. vivax diversity was higher and transmission appeared more stable. Population differentiation was lower in P. vivax versus P. falciparum, suggesting that the hypnozoite reservoir might play an important role in sustaining local transmission and facilitating the spread of P. vivax infections in different endemic settings. P. vivax polyclonality varied with local endemicity, demonstrating potential utility in informing on transmission intensity in this species.Molecular approaches can provide important information on malaria transmission that is not readily available from traditional epidemiological measures. Elucidation of the transmission dynamics circulating in a given setting will have a major role in prioritising malaria

  6. Depression as a Glial-Based Synaptic Dysfunction

    Science.gov (United States)

    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

  7. Depression as a Glial-Based Synaptic Dysfunction

    Directory of Open Access Journals (Sweden)

    Daniel eRial

    2016-01-01

    Full Text Available Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processing 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 increase 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, BDNF affect glia functioning, whereas antidepressant treatments (SSRIs, electroshock, 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 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 manage depression.

  8. A new algorithm for optimum voltage and reactive power control for minimizing transmission lines losses

    International Nuclear Information System (INIS)

    Ghoudjehbaklou, H.; Danai, B.

    2001-01-01

    Reactive power dispatch for voltage profile modification has been of interest to power utilities. Usually local bus voltages can be altered by changing generator voltages, reactive shunts, ULTC transformers and SVCs. Determination of optimum values for control parameters, however, is not simple for modern power system networks. Heuristic and rather intelligent algorithms have to be sought. In this paper a new algorithm is proposed that is based on a variant of a genetic algorithm combined with simulated annealing updates. In this algorithm a fuzzy multi-objective a approach is used for the fitness function of the genetic algorithm. This fuzzy multi-objective function can efficiently modify the voltage profile in order to minimize transmission lines losses, thus reducing the operating costs. The reason for such a combination is to utilize the best characteristics of each method and overcome their deficiencies. The proposed algorithm is much faster than the classical genetic algorithm and cna be easily integrated into existing power utilities software. The proposed algorithm is tested on an actual system model of 1284 buses, 799 lines, 1175 fixed and ULTC transformers, 86 generators, 181 controllable shunts and 425 loads

  9. Controlling the transmission of ultrahigh frequency bulk acoustic waves in silicon by 45° mirrors.

    Science.gov (United States)

    Wang, Shengxiang; Gao, Jiaming; Carlier, Julien; Campistron, Pierre; NDieguene, Assane; Guo, Shishang; Matar, Olivier Bou; Dorothee, Debavelaere-Callens; Nongaillard, Bertrand

    2011-07-01

    In this paper, we present a feasible microsystem in which the direction of localized ultrahigh frequency (∼1GHz) bulk acoustic wave can be controlled in a silicon wafer. Deep etching technology on the silicon wafer makes it possible to achieve high aspect ratio etching patterns which can be used to control bulk acoustic wave to transmit in the directions parallel to the surface of the silicon wafer. Passive 45° mirror planes obtained by wet chemical etching were employed to reflect the bulk acoustic wave. Zinc oxide (ZnO) thin film transducers were deposited by radio frequency sputtering with a thickness of about 1μm on the other side of the wafer, which act as emitter/receptor after aligned with the mirrors. Two opponent vertical mirrors were inserted between the 45° mirrors to guide the transmission of the acoustic waves. The propagation of the bulk acoustic wave was studied with simulations and the characterization of S(21) scattering parameters, indicating that the mirrors were efficient to guide bulk acoustic waves in the silicon wafer. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Optimization of a pressure control valve for high power automatic transmission considering stability

    Science.gov (United States)

    Jian, Hongchao; Wei, Wei; Li, Hongcai; Yan, Qingdong

    2018-02-01

    The pilot-operated electrohydraulic clutch-actuator system is widely utilized by high power automatic transmission because of the demand of large flowrate and the excellent pressure regulating capability. However, a self-excited vibration induced by the inherent non-linear characteristics of valve spool motion coupled with the fluid dynamics can be generated during the working state of hydraulic systems due to inappropriate system parameters, which causes sustaining instability in the system and leads to unexpected performance deterioration and hardware damage. To ensure a stable and fast response performance of the clutch actuator system, an optimal design method for the pressure control valve considering stability is proposed in this paper. A non-linear dynamic model of the clutch actuator system is established based on the motion of the valve spool and coupling fluid dynamics in the system. The stability boundary in the parameter space is obtained by numerical stability analysis. Sensitivity of the stability boundary and output pressure response time corresponding to the valve parameters are identified using design of experiment (DOE) approach. The pressure control valve is optimized using particle swarm optimization (PSO) algorithm with the stability boundary as constraint. The simulation and experimental results reveal that the optimization method proposed in this paper helps in improving the response characteristics while ensuring the stability of the clutch actuator system during the entire gear shift process.

  11. Lateral Preoptic Control of the Lateral Habenula through Convergent Glutamate and GABA Transmission

    Directory of Open Access Journals (Sweden)

    David J. Barker

    2017-11-01

    Full Text Available Summary: The lateral habenula (LHb is a brain structure that participates in cognitive and emotional processing and has been implicated in several mental disorders. Although one of the largest inputs to the LHb originates in the lateral preoptic area (LPO, little is known about how the LPO participates in the regulation of LHb function. Here, we provide evidence that the LPO exerts bivalent control over the LHb through the convergent transmission of LPO glutamate and γ-aminobutyric acid (GABA onto single LHb neurons. In vivo, both LPO-glutamatergic and LPO-GABAergic inputs to the LHb are activated by aversive stimuli, and their predictive cues yet produce opposing behaviors when stimulated independently. These results support a model wherein the balanced response of converging LPO-glutamate and LPO-GABA are necessary for a normal response to noxious stimuli, and an imbalance in LPO→LHb glutamate or GABA results in the type of aberrant processing that may underlie mental disorders. : Barker et al. show that distinct populations of lateral preoptic area glutamate and GABA neurons synapse together on single lateral habenula neurons and find that this “convergent neurotransmission” allows preoptic area neurons to exert bivalent control over single lateral habenula neurons and drive opposing motivational states. Keywords: preoptic, habenula, reward, aversion, synapse, glutamate, GABA, stress, calcium imaging, optogenetics, electron microscopy

  12. Development of data acquisition and control system for ICH & CD transmission line components test facility

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Manoj, E-mail: manoj.patel@iter-india.org [ITER-India, Institute for Plasma Research, Bhat, Gandhinagar 382428, Gujarat (India); Jha, Akhil [ITER-India, Institute for Plasma Research, Bhat, Gandhinagar 382428, Gujarat (India); Patel, Nidhi [Department of Instrumentation & Control Engineering, Dharmsinh Desai University, Nadiad 387001, Gujarat (India); Krishna, J.V.S. Hari; Rajnish, Kumar; Soni, Dipal; Verma, Sriprakash; Patel, Hriday; Trivedi, Rajesh; Mukherjee, Aparajita [ITER-India, Institute for Plasma Research, Bhat, Gandhinagar 382428, Gujarat (India)

    2016-11-15

    Highlights: • Traveling Wave Resonator (TWR) gain achieved is 13.58 dB using 10 dB coupler. • Software module for Automatic calibration for power detector is developed and integrated. • Application module is developed using LabVIEW™ for high power RF operation of TWR. - Abstarct: India is developing a very high power test bed (∼MW level) based on concept of Travelling Wave Resonator (TWR) for testing of passive transmission line components [3]. Data acquisition and control system is required for safe and reliable operation of TWR. It includes online monitoring of input power and circulating ring power. Acquired RF signal provides information about forward and reflected RF power. For MW power level testing, system is protected against arc and thermal effect during CW operation. National Instrument make hardware and software have been used to acquire signals from RF detector, Arc detectors, IR camera and thermocouples etc. LabVIEW™ based software has been developed for calculation of RF parameters. Graphical user interface is developed for better visualization. Initial testing of the TWR setup with 10 dB coupler provides a power gain of 13.58 dB (22X). For future 3 MW TWR test bed the required power gain is ∼20 dB (100X) since the available source is ∼40 kW. This paper describes the detail design and integrated test results for data acquisition and control system for TWR test bed.

  13. Transmission dynamics and economics of rabies control in dogs and humans in an African city

    OpenAIRE

    Zinsstag, J.; Dürr, S.; Penny, M. A.; Mindekem, R.; Roth, F.; Gonzalez, S. Menendez; Naissengar, S.; Hattendorf, J.

    2009-01-01

    Human rabies in developing countries can be prevented through interventions directed at dogs. Potential cost-savings for the public health sector of interventions aimed at animal-host reservoirs should be assessed. Available deterministic models of rabies transmission between dogs were extended to include dog-to-human rabies transmission. Model parameters were fitted to routine weekly rabid-dog and exposed-human cases reported in N′Djaména, the capital of Chad. The estimated transmission rate...

  14. Phosphorylation of AMPA receptors is required for sensory deprivation-induced homeostatic synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Anubhuti Goel

    Full Text Available Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca(2+-permeable AMPA receptors (CP-AMPARs. However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1 subunit at the serine 845 (S845 site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants, which is a substrate of cAMP-dependent kinase (PKA, show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity.

  15. Phosphorylation of AMPA receptors is required for sensory deprivation-induced homeostatic synaptic plasticity.

    Science.gov (United States)

    Goel, Anubhuti; Xu, Linda W; Snyder, Kevin P; Song, Lihua; Goenaga-Vazquez, Yamila; Megill, Andrea; Takamiya, Kogo; Huganir, Richard L; Lee, Hey-Kyoung

    2011-03-31

    Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca(2+)-permeable AMPA receptors (CP-AMPARs). However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1) subunit at the serine 845 (S845) site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants), which is a substrate of cAMP-dependent kinase (PKA), show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity.

  16. Vesicular GABA Uptake Can Be Rate Limiting for Recovery of IPSCs from Synaptic Depression

    Directory of Open Access Journals (Sweden)

    Manami Yamashita

    2018-03-01

    Full Text Available Summary: Synaptic efficacy plays crucial roles in neuronal circuit operation and synaptic plasticity. Presynaptic determinants of synaptic efficacy are neurotransmitter content in synaptic vesicles and the number of vesicles undergoing exocytosis at a time. Bursts of presynaptic firings depress synaptic efficacy, mainly due to depletion of releasable vesicles, whereas recovery from strong depression is initiated by endocytic vesicle retrieval followed by refilling of vesicles with neurotransmitter. We washed out presynaptic cytosolic GABA to induce a rundown of IPSCs at cerebellar inhibitory cell pairs in slices from rats and then allowed fast recovery by elevating GABA concentration using photo-uncaging. The time course of this recovery coincided with that of IPSCs from activity-dependent depression induced by a train of high-frequency stimulation. We conclude that vesicular GABA uptake can be a limiting step for the recovery of inhibitory neurotransmission from synaptic depression. : Recovery of inhibitory synaptic transmission from activity-dependent depression requires refilling of vesicles with GABA. Yamashita et al. find that vesicular uptake rate of GABA is a slow process, limiting the recovery rate of IPSCs from depression.

  17. Modulation of Synaptic Plasticity by Exercise Training as a Basis for Ischemic Stroke Rehabilitation.

    Science.gov (United States)

    Nie, Jingjing; Yang, Xiaosu

    2017-01-01

    In recent years, rehabilitation of ischemic stroke draws more and more attention in the world, and has been linked to changes of synaptic plasticity. Exercise training improves motor function of ischemia as well as cognition which is associated with formation of learning and memory. The molecular basis of learning and memory might be synaptic plasticity. Research has therefore been conducted in an attempt to relate effects of exercise training to neuroprotection and neurogenesis adjacent to the ischemic injury brain. The present paper reviews the current literature addressing this question and discusses the possible mechanisms involved in modulation of synaptic plasticity by exercise training. This review shows the pathological process of synaptic dysfunction in ischemic roughly and then discusses the effects of exercise training on scaffold proteins and regulatory protein expression. The expression of scaffold proteins generally increased after training, but the effects on regulatory proteins were mixed. Moreover, the compositions of postsynaptic receptors were changed and the strength of synaptic transmission was enhanced after training. Finally, the recovery of cognition is critically associated with synaptic remodeling in an injured brain, and the remodeling occurs through a number of local regulations including mRNA translation, remodeling of cytoskeleton, and receptor trafficking into and out of the synapse. We do provide a comprehensive knowledge of synaptic plasticity enhancement obtained by exercise training in this review.

  18. Mitochondria and Synaptic Plasticity in the Mature and Aging Nervous System.

    Science.gov (United States)

    Todorova, Vyara; Blokland, Arjan

    2017-01-01

    Synaptic plasticity in the adult brain is believed to represent the cellular mechanisms of learning and memory. Mitochondria are involved in the regulation of the complex processes of synaptic plasticity. This paper reviews the current knowledge on the regulatory roles of mitochondria in the function and plasticity of synapses and the implications of mitochondrial dysfunctions in synaptic transmission. First, the importance of mitochondrial distribution and motility for maintenance and strengthening of dendritic spines, but also for new spines/synapses formation is presented. Secondly, the major mitochondrial functions as energy supplier and calcium buffer organelles are considered as possible explanation for their essential and regulatory roles in neuronal plasticity processes. Thirdly, the effects of synaptic potentiation on mitochondrial gene expression are discussed. And finally, the relation between age-related alterations in synaptic plasticity and mitochondrial dysfunctions is considered. It appears that memory loss and neurodegeneration during aging are related to mitochondrial (dys)function. Although, it is clear that mitochondria are essential for synaptic plasticity, further studies are indicated to scrutinize the intracellular and molecular processes that regulate the functions of mitochondria in synaptic plasticity.

  19. Imaging dopamine transmission in schizophrenia

    International Nuclear Information System (INIS)

    Laruelle, M.

    1998-01-01

    Over the last ten years, several positron emission tomography (PET) and single photon computerized tomography (SPECT) studies of the dopamine (DA) system in patients with schizophrenia were performed to test the hypothesis that DA hyperactivity is associated with this illness. In this paper are reviewed the results of fifteen brain imaging studies comparing indices of DA function in drug naive or drug free patients with schizophrenia and healthy controls: thirteen studies included measurements of Da D 2 receptor density, two studies compared amphetamine-induced DA release, and two studies measured DOPA decarboxylase activity, an enzyme involved in DA synthesis. It was conducted a meta-analysis of the studies measuring D 2 receptor density parameters, under the assumption that all tracers labeled the same population of D 2 receptors. This analysis revealed that, compared to healthy controls, patients with schizophrenia present a significant but mild elevation of D 2 receptor density parameters and a significant larger variability of these indices. It was found no statistical evidence that studies performed with radiolabeled butyrophenones detected a larger increase in D 2 receptor density parameters than studies performed with other radioligands, such as benzamides. Studies of presynaptic activity revealed an increase in DA transmission response to amphetamine challenge, and an increase in DOPA decarboxylase activity. Together, these data are compatible with both pre- and post-synaptic alterations of DA transmission in schizophrenia. Future studies should aim at a better characterization of these alterations, and at defining their role in the pathophysiology of the illness

  20. Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity

    Science.gov (United States)

    Beckhauser, Thiago Fernando; Francis-Oliveira, José; De Pasquale, Roberto

    2016-01-01

    In the mammalian central nervous system, reactive oxygen species (ROS) generation is counterbalanced by antioxidant defenses. When large amounts of ROS accumulate, antioxidant mechanisms become overwhelmed and oxidative cellular stress may occur. Therefore, ROS are typically characterized as toxic molecules, oxidizing membrane lipids, changing the conformation of proteins, damaging nucleic acids, and causing deficits in synaptic plasticity. High ROS concentrations are associated with a decline in cognitive functions, as observed in some neurodegenerative disorders and age-dependent decay of neuroplasticity. Nevertheless, controlled ROS production provides the optimal redox state for the activation of transductional pathways involved in synaptic changes. Since ROS may regulate neuronal activity and elicit negative effects at the same time, the distinction between beneficial and deleterious consequences is unclear. In this regard, this review assesses current research and describes the main sources of ROS in neurons, specifying their involvement in synaptic plasticity and distinguishing between physiological and pathological processes implicated. PMID:27625575

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

    Science.gov (United States)

    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.

  2. AMPA Receptor Trafficking in Homeostatic Synaptic Plasticity: Functional Molecules and Signaling Cascades

    Directory of Open Access Journals (Sweden)

    Guan Wang

    2012-01-01

    Full Text Available Homeostatic synaptic plasticity is a negative-feedback response employed to compensate for functional disturbances in the nervous system. Typically, synaptic activity is strengthened when neuronal firing is chronically suppressed or weakened when neuronal activity is chronically elevated. At both the whole cell and entire network levels, activity manipulation leads to a global up- or downscaling of the transmission efficacy of all synapses. However, the homeostatic response can also be induced locally at subcellular regions or individual synapses. Homeostatic synaptic scaling is expressed mainly via the regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR trafficking and synaptic expression. Here we review the recently identified functional molecules and signaling pathways that are involved in homeostatic plasticity, especially the homeostatic regulation of AMPAR localization at excitatory synapses.

  3. Molecular Recognition within Synaptic Scaffolds

    DEFF Research Database (Denmark)

    Erlendsson, Simon

    -length structural model of the PICK1 dimer in-solution. We found the PICK1 BAR dimer to resemble an elongated crescent-shaped structure, spanning ~160 Å, with the PICK1 PDZ domains loosely attached to the BAR domain. This finding is in contrast to previous findings for other BAR domain proteins, where adjacent......Scaffolding proteins are abundant participants and regulators of the extensive intracellular framework required for maintaining cellular functions such as cellular adhesion and signal transduction cascades. In excitatory neuronal synapses these scaffolding proteins often contain one or more PDZ...... domains, responsible for tethering their respective synaptic protein ligands. Therefore, understanding the specificity and binding mechanisms of PDZ domain proteins is essential to understand regulation of synaptic plasticity. PICK1 is a PDZ domain-containing scaffolding protein predominantly expressed...

  4. Control of sleep-to-wake transitions via fast amino acid and slow neuropeptide transmission

    International Nuclear Information System (INIS)

    Mosqueiro, Thiago; Lecea, Luis de; Huerta, Ramon

    2014-01-01

    The locus coeruleus (LC) modulates cortical, subcortical, cerebellar, brainstem and spinal cord circuits and it expresses receptors for neuromodulators that operate on a time scale of several seconds. Evidence from anatomical, electrophysiological and optogenetic experiments has shown that LC neurons receive input from a group of neurons called hypocretin neurons that release a neuropeptide called hypocretin. It is less well known how these two groups of neurons can be coregulated using GABAergic (GABA standing for gamma aminobutyric acid) neurons. As the time scale for GABA A inhibition is several orders of magnitude faster than that for the hypocretin neuropeptide effect, we investigate the limits of circuit activity regulation using a realistic model of neurons. Our investigation shows that GABA A inhibition is insufficient to control the activity levels of the LCs. Although slower forms of GABA A can in principle work, there is not much plausibility due to the low probability of the presence of slow GABA A and lack of robust stability at the maximum firing frequencies. The best possible control mechanism predicted by our modeling analysis is the presence of inhibitory neuropeptides, which exert effects on a similar time scale to the hypocretin/orexin. Although the nature of these inhibitory neuropeptides has not been identified yet, it provides the most efficient mechanism in the modeling analysis. Finally, we present a reduced mean-field model that perfectly captures the dynamics and the phenomena generated by this circuit. This investigation shows that brain communication involving multiple time scales can be better controlled by employing orthogonal mechanisms of neural transmission to decrease interference between cognitive processes and hypothalamic functions. (paper)

  5. Integrated powertrain control for hybrid electric vehicles with electric variable transmission

    NARCIS (Netherlands)

    Kessels, J.T.B.A.; Foster, D.L.; Bosch, P.P.J. van den

    2009-01-01

    The electric variable transmission (EVT) offers a powersplit for hybrid electric vehicles by integrating two motor/ generator sets into one electric machine. This double rotor concept implements a continuously variable transmission between the engine and the driveline, including the possibility for

  6. BACE1 Is Necessary for Experience-Dependent Homeostatic Synaptic Plasticity in Visual Cortex

    Directory of Open Access Journals (Sweden)

    Emily Petrus

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is the most common form of age-related dementia, which is thought to result from overproduction and/or reduced clearance of amyloid-beta (Aβ peptides. Studies over the past few decades suggest that Aβ is produced in an activity-dependent manner and has physiological relevance to normal brain functions. Similarly, physiological functions for β- and γ-secretases, the two key enzymes that produce Aβ by sequentially processing the amyloid precursor protein (APP, have been discovered over recent years. In particular, activity-dependent production of Aβ has been suggested to play a role in homeostatic regulation of excitatory synaptic function. There is accumulating evidence that activity-dependent immediate early gene Arc is an activity “sensor,” which acts upstream of Aβ production and triggers AMPA receptor endocytosis to homeostatically downregulate the strength of excitatory synaptic transmission. We previously reported that Arc is critical for sensory experience-dependent homeostatic reduction of excitatory synaptic transmission in the superficial layers of visual cortex. Here we demonstrate that mice lacking the major neuronal β-secretase, BACE1, exhibit a similar phenotype: stronger basal excitatory synaptic transmission and failure to adapt to changes in visual experience. Our results indicate that BACE1 plays an essential role in sensory experience-dependent homeostatic synaptic plasticity in the neocortex.

  7. Specific cells in the primary salivary glands of the whitefly Bemisia tabaci control retention and transmission of begomoviruses.

    Science.gov (United States)

    Wei, Jing; Zhao, Juan-Juan; Zhang, Tong; Li, Fang-Fang; Ghanim, Murad; Zhou, Xue-Ping; Ye, Gong-Yin; Liu, Shu-Sheng; Wang, Xiao-Wei

    2014-11-01

    The majority of plant viruses are vectored by arthropods via persistent-circulative or noncirculative transmission. Previous studies have shown that specific binding sites for noncirculative viruses reside within the stylet or foregut of insect vectors, whereas the transmission mechanisms of circulative viruses remain ambiguous. Here we report the critical roles of whitefly primary salivary glands (PSGs) in the circulative transmission of two begomoviruses. The Middle East Asia Minor 1 (MEAM1) species of the whitefly Bemisia tabaci complex efficiently transmits both Tomato yellow leaf curl China virus (TYLCCNV) and Tomato yellow leaf curl virus (TYLCV), whereas the Mediterranean (MED) species transmits TYLCV but not TYLCCNV. PCR and fluorescence in situ hybridization experiments showed that TYLCCNV efficiently penetrates the PSGs of MEAM1 but not MED whiteflies. When a fragment of the coat protein of TYLCCNV was exchanged with that of TYLCV, mutated TYLCCNV accumulated in the PSGs of MED whiteflies, while mutant TYLCV was nearly undetectable. Confocal microscopy revealed that virion transport in PSGs follows specific paths to reach secretory cells in the central region, and the accumulation of virions in the secretory region of PSGs was correlated with successful virus transmission. Our findings demonstrate that whitefly PSGs, in particular the cells around the secretory region, control the specificity of begomovirus transmission. Over 75% of plant viruses are transmitted by insects. However, the mechanisms of virus transmission by insect vectors remain largely unknown. Begomoviruses and whiteflies are a complex of viruses and vectors which threaten many crops worldwide. We investigated the transmission of two begomoviruses by two whitefly species. We show that specific cells of the whitefly primary salivary glands control viral transmission specificity and that virion transport in the glands follows specific paths to reach secretory cells in the central region and

  8. AC Transmission Emulation Control Strategies for the BTB VSC HVDC System in the Metropolitan Area of Seoul

    Directory of Open Access Journals (Sweden)

    Sungyoon Song

    2017-08-01

    Full Text Available In the Korean power system, growing power loads have recently created the problems of voltage instability and fault current in the Seoul Capital Area (SCA. Accordingly, the back-to-back (BTB voltage source converter (VSC high-voltage direct-current (HVDC system is emerging to resolve such problems with grid segmentation. However, non-convergence problems occur in this metropolitan area, due to the large change of power flow in some contingencies. Therefore, this paper proposes two kinds of AC transmission emulation control (ATEC strategies to improve the metropolitan transient stability, and to resolve the non-convergence problem. The proposed ATEC strategies are able to mitigate possible overloading of adjacent AC transmission, and maintain power balance between metropolitan regions. The first ATEC strategy uses a monitoring system that permits the reverse power flow of AC transmission, and thus effectively improves the grid stability based on the power transfer equation. The second ATEC strategy emulates AC transmission with DC link capacitors in a permissible DC-link voltage range according to angle difference, and securely improves the gird stability, without requiring grid operator schedule decisions. This paper compares two kinds of ATEC schemes: it demonstrates the first ATEC strategy with specific fault scenario with PSS/E (Power Transmission System Planning Software, and evaluates the second ATEC strategy with internal controller performance with PSCAD/EMTDC (Power System Electromagnetic Transients Simulation Software.

  9. Regulation of hippocampal synaptic plasticity thresholds and changes in exploratory and learning behavior in dominant negative NPR-B mutant rats

    Directory of Open Access Journals (Sweden)

    Gleb eBarmashenko

    2014-12-01

    Full Text Available The second messenger cyclic GMP affects synaptic transmission and modulates synaptic plasticity and certain types of learning and memory processes. The impact of the natriuretic peptide receptor B (NPR-B and its ligand C-type natriuretic peptide (CNP, one of several cGMP producing signalling systems, on hippocampal synaptic plasticity and learning is, however, less well understood. We have previously shown that the NPR-B ligand CNP increases the magnitude of long-term depression (LTD in hippocampal area CA1, while reducing the induction of long-term potentiation (LTP. We have extended this line of research to show that bidirectional plasticity is affected in the opposite way in rats expressing a dominant-negative mutant of NPR-B (NSE-NPR-BdeltaKC lacking the intracellular guanylyl cyclase domain under control of a promoter for neuron-specific enolase. The brain cells of these transgenic rats express functional dimers of the NPR-B receptor containing the dominant-negative NPR-BdeltaKC mutant, and therefore show decreased CNP-stimulated cGMP-production in brain membranes. The NPR-B transgenic rats display enhanced LTP but reduced LTD in hippocampal slices. When the frequency-dependence of synaptic modification to afferent stimulation in the range of 1-100 Hz was assessed in transgenic rats the threshold for LTP induction was raised, but LTD induction was facilitated. In parallel, NPR-BdeltaKC rats exhibited an enhancement in exploratory and learning behavior. These results indicate that bidirectional plasticity and learning and memory mechanism are affected in transgenic rats expressing a dominant-negative mutant of NPR-B. Our data substantiate the hypothesis that NPR-B-dependent cGMP signalling has a modulatory role for synaptic information storage and learning.

  10. Ebola virus disease outbreak in Nigeria: Transmission dynamics and rapid control

    Directory of Open Access Journals (Sweden)

    C.L. Althaus

    2015-06-01

    Full Text Available International air travel has already spread Ebola virus disease (EVD to major cities as part of the unprecedented epidemic that started in Guinea in December 2013. An infected airline passenger arrived in Nigeria on July 20, 2014 and caused an outbreak in Lagos and then Port Harcourt. After a total of 20 reported cases, including 8 deaths, Nigeria was declared EVD free on October 20, 2014. We quantified the impact of early control measures in preventing further spread of EVD in Nigeria and calculated the risk that a single undetected case will cause a new outbreak. We fitted an EVD transmission model to data from the outbreak in Nigeria and estimated the reproduction number of the index case at 9.0 (95% confidence interval [CI]: 5.2–15.6. We also found that the net reproduction number fell below unity 15 days (95% CI: 11–21 days after the arrival of the index case. Hence, our study illustrates the time window for successful containment of EVD outbreaks caused by infected air travelers.

  11. Spectral Control of Transmission of Diffuse Irradiation using Piled AR Coated Quartz Glass Filters

    Science.gov (United States)

    Kumano, Tomoyuki; Hanamura, Katsunori

    2004-11-01

    Spectral transmission characteristics of piled quartz glass filters with anti-reflection (AR) coating and without coating were investigated for diffuse irradiation through ray tracing numerical simulation. The spectral transmittance for diffuse irradiation is lower than that for normal irradiation because surface reflection becomes large with increasing incident zenith angle. By using the AR coating, the transmittance for diffuse irradiation becomes much higher than that without coating around a wavelength of 1.1 μm that is specified for the coating thickness design. On the other hand, for the long wavelength region, the transmittance reduced largely due to multiple-surface and absorption. The most striking feature is that difference between transmittances for the specified and the long wavelength region is enhanced using the piled AR coated quartz glass filters. If the refractive index of the coating material were 1.19, which was an ideal value for the design of the coating, the effect is the most remarkable. As a result, it is revealed that this spectral control method is useful for the energy recirculation TPV system using super-adiabatic combustion in porous media.

  12. Extreme control of impulse transmission by cylinder-based nonlinear phononic crystals

    Science.gov (United States)

    Chaunsali, Rajesh; Toles, Matthew; Yang, Jinkyu; Kim, Eunho

    2017-10-01

    We present a novel device that can offer two extremes of elastic wave propagation - nearly complete transmission and strong attenuation under impulse excitation. The mechanism of this highly tunable device relies on intermixing effects of dispersion and nonlinearity. The device consists of identical cylinders arranged in a chain, which interact with each other as per nonlinear Hertz contact law. For a 'dimer' configuration, i.e., two different contact angles alternating in the chain, we analytically, numerically, and experimentally show that impulse excitation can either propagate as a localized wave, or it can travel as a highly dispersive wave. Remarkably, these extremes can be achieved in this periodic arrangement simply by in-situ control of contact angles between cylinders. We close the discussion by highlighting the key characteristics of the mechanisms that facilitate strong attenuation of incident impulse. These include low-to-high frequency scattering, and turbulence-like cascading in a periodic system. We thus envision that these adaptive, cylinder-based nonlinear phononic crystals, in conjunction with conventional impact mitigation mechanisms, could be used to design highly tunable and efficient impact manipulation devices.

  13. Modelling the Transmission Dynamics and Control of Mumps in Mainland China

    Directory of Open Access Journals (Sweden)

    Yong Li

    2017-12-01

    Full Text Available Mumps is a common childhood viral disease and children have been vaccinated throughout the world since 1967. The incidence of mumps has increased with more than 300,000 young people infected with mumps annually in mainland China since 2005. Therefore, we designed and analyzed long-term mumps surveillance data in an SVEILR (susceptible–vaccinated–exposed–severely infectious–mildly infectious–recovered dynamic transmission model with optimized parameter values to describe the dynamics of mumps infections in China. There were 18.02% of mumps infected young adults seeking medical advice. The vaccine coverage has been insufficient in China. Young adults with frequent contact and mild infection were identified as a major driver of mumps epidemics. The reproduction number of mumps was determined 4.28 in China. Sensitivity analysis of the basic reproduction number and the endemic equilibrium was conducted to evaluate the effectiveness of mumps control measures. We propose to increase the vaccine coverage and make two doses of MMR (Measles, mumps and rubella vaccines freely available in China.

  14. cystiSim - an agent-based model for Taenia solium transmission and control

    DEFF Research Database (Denmark)

    Braae, Uffe Christian; Devleesschauwer, Brecht; Gabriël, Sarah

    Sim, an agent-based model for T. solium transmission and control. The model was developed in R and is publicly available as an R package (https://github.com/brechtdv/cystiSim/). The model description adheres to the Overview, Design concepts, and Details (ODD) protocol. The model consists of two entities: pigs...

  15. Chains of transmission and control of Ebola virus disease in Conakry, Guinea, in 2014: an observational study.

    Science.gov (United States)

    Faye, Ousmane; Boëlle, Pierre-Yves; Heleze, Emmanuel; Faye, Oumar; Loucoubar, Cheikh; Magassouba, N'Faly; Soropogui, Barré; Keita, Sakoba; Gakou, Tata; Bah, El Hadji Ibrahima; Koivogui, Lamine; Sall, Amadou Alpha; Cauchemez, Simon

    2015-03-01

    An epidemic of Ebola virus disease of unprecedented size continues in parts of west Africa. For the first time, large urban centres such as Conakry, the capital of Guinea, are affected. We did an observational study of patients with Ebola virus disease in three regions of Guinea, including Conakry, aiming to map the routes of transmission and assess the effect of interventions. Between Feb 10, 2014, and Aug 25, 2014, we obtained data from the linelist of all confirmed and probable cases in Guinea (as of Sept 16, 2014), a laboratory database of information about patients, and interviews with patients and their families and neighbours. With this information, we mapped chains of transmission, identified which setting infections most probably originated from (community, hospitals, or funerals), and computed the context-specific and overall reproduction numbers. Of 193 confirmed and probable cases of Ebola virus disease reported in Conakry, Boffa, and Télimélé, 152 (79%) were positioned in chains of transmission. Health-care workers contributed little to transmission. In March, 2014, individuals with Ebola virus disease who were not health-care workers infected a mean of 2·3 people (95% CI 1·6-3·2): 1·4 (0·9-2·2) in the community, 0·4 (0·1-0·9) in hospitals, and 0·5 (0·2-1·0) at funerals. After the implementation of infection control in April, the reproduction number in hospitals and at funerals reduced to lower than 0·1. In the community, the reproduction number dropped by 50% for patients that were admitted to hospital, but remained unchanged for those that were not. In March, hospital transmissions constituted 35% (seven of 20) of all transmissions and funeral transmissions constituted 15% (three); but from April to the end of the study period, they constituted only 9% (11 of 128) and 4% (five), respectively. 82% (119 of 145) of transmission occurred in the community and 72% (105) between family members. Our simulations show that a 10% increase in

  16. Optical fiber sources and transmission controls for multi-Tb/s systems

    Science.gov (United States)

    Nowak, George Adelbert

    The accelerating demand for bandwidth capacity in backbone links of terrestrial communications systems is projected to exceed 1Tb/s by 2002. Lightwave carrier frequencies and fused-silica optical fibers provide the natural combination of high passband frequencies and low- loss medium to satisfy this evolving demand for bandwidth capacity. This thesis addresses three key technologies for enabling multi-Tb/s optical fiber communication systems. The first technology is a broadband source based on supercontinuum generation in optical fiber. Using a single modelocked laser with output pulsewidths of 0.5psec pulses, we generate in ~2m of dispersion-shifted fiber more that 200nm of spectral continuum in the vicinity of 1550nm that is flat to better than +/- 0.5 dB over more than 60nm. The short fiber length prevents degradation of timing jitter of the seed pulses and preserves coherence of the continuum by inhibiting environmental perturbations and mapping of random noise from the vicinity of the input pulse across the continuum. Through experiments and simulations, we find that the continuum characteristics result from 3rd order dispersion effects on higher-order soliton compression. We determine optimal fiber properties to provide desired continuum broadness and flatness for given input pulsewidth and energy conditions. The second technology is a novel delay-shifted nonlinear optical loop mirror (DS-NOLM) that performs a transmission control function by serving as an intensity filter and frequency compensator for 4ps soliton transmission over 75km of standard dispersion fiber, with 25km spacing between amplifiers, by filtering the dispersive waves and compensating for Raman-induced soliton self-frequency shift. The third technology is all-fiber wavelength conversion employing induced modulational instability. We obtain wavelength conversion over 40nm with a peak conversion efficiency of 28dB using 600mW pump pulses in 720m of high-nonlinearity optical fiber. We show

  17. Transmission dynamics of rabies virus in Thailand: Implications for disease control

    Directory of Open Access Journals (Sweden)

    Puanghat Apirom

    2005-06-01

    Full Text Available Abstract Background In Thailand, rabies remains a neglected disease with authorities continuing to rely on human death statistics while ignoring the financial burden resulting from an enormous increase in post-exposure prophylaxis. Past attempts to conduct a mass dog vaccination and sterilization program have been limited to Bangkok city and have not been successful. We have used molecular epidemiology to define geographic localization of rabies virus phylogroups and their pattern of spread in Thailand. Methods We analyzed 239 nucleoprotein gene sequences from animal and human brain samples collected from all over Thailand between 1998 and 2002. We then reconstructed a phylogenetic tree correlating these data with geographical information. Results All sequences formed a monophyletic tree of 2 distinct phylogroups, TH1 and TH2. Three subgroups were identified in the TH1 subgroup and were distributed in the middle region of the country. Eight subgroups of TH2 viruses were identified widely distributed throughout the country overlapping the TH1 territory. There was a correlation between human-dependent transportation routes and the distribution of virus. Conclusion Inter-regional migration paths of the viruses might be correlated with translocation of dogs associated with humans. Interconnecting factors between human socioeconomic and population density might determine the transmission dynamics of virus in a rural-to-urban polarity. The presence of 2 or more rabies virus groups in a location might be indicative of a gene flow, reflecting a translocation of dogs within such region and adjacent areas. Different approaches may be required for rabies control based on the homo- or heterogeneity of the virus. Areas containing homogeneous virus populations should be targeted first. Control of dog movement associated with humans is essential.

  18. Transmission dynamics and control of Rickettsia rickettsii in populations of Hydrochoerus hydrochaeris and Amblyomma sculptum.

    Directory of Open Access Journals (Sweden)

    Gina Polo

    2017-06-01

    Full Text Available Brazilian Spotted Fever (BSF, caused by the bacterium Rickettsia rickettsii, is the tick-borne disease that generates the largest number of human deaths in the world. In Brazil, the current increase of BSF human cases has been associated with the presence and expansion of capybaras Hydrochoerus hydrochaeris, which act as primary hosts for the tick Amblyomma sculptum, vector of the R. rickettsii in this area.We proposed a semi-discrete-time stochastic model to evaluate the role of capybaras in the transmission dynamics of R. rickettsii. Through a sensitivity analysis, we identified the parameters with significant influence on the R. rickettsii establishment. Afterward, we implemented the Gillespie's algorithm to simulate the impact of potential public health interventions to prevent BSF human cases.The introduction of a single infected capybara with at least one infected attached tick is enough to trigger the disease in a non-endemic area. We found that to avoid the formation of new BSF-endemic areas, it is crucial to impede the emigration of capybaras from endemic areas by reducing their birth rate by more than 58%. Model results were corroborated by ex-situ data generated from field studies, and this supports our proposal to prevent BSF human cases by implementing control strategies focused on capybaras.The proposed stochastic model illustrates how strategies for the control and prevention of vector-borne infectious diseases can be focused on amplifier hosts management practices. This work provides a basis for future prevention strategies for other neglected vector-borne diseases.

  19. Quantifying Transmission.

    Science.gov (United States)

    Woolhouse, Mark

    2017-07-01

    Transmissibility is the defining characteristic of infectious diseases. Quantifying transmission matters for understanding infectious disease epidemiology and designing evidence-based disease control programs. Tracing individual transmission events can be achieved by epidemiological investigation coupled with pathogen typing or genome sequencing. Individual infectiousness can be estimated by measuring pathogen loads, but few studies have directly estimated the ability of infected hosts to transmit to uninfected hosts. Individuals' opportunities to transmit infection are dependent on behavioral and other risk factors relevant given the transmission route of the pathogen concerned. Transmission at the population level can be quantified through knowledge of risk factors in the population or phylogeographic analysis of pathogen sequence data. Mathematical model-based approaches require estimation of the per capita transmission rate and basic reproduction number, obtained by fitting models to case data and/or analysis of pathogen sequence data. Heterogeneities in infectiousness, contact behavior, and susceptibility can have substantial effects on the epidemiology of an infectious disease, so estimates of only mean values may be insufficient. For some pathogens, super-shedders (infected individuals who are highly infectious) and super-spreaders (individuals with more opportunities to transmit infection) may be important. Future work on quantifying transmission should involve integrated analyses of multiple data sources.

  20. The improbable transmission of Trypanosoma cruzi to human: the missing link in the dynamics and control of Chagas disease.

    Directory of Open Access Journals (Sweden)

    Pierre Nouvellet

    2013-11-01

    Full Text Available Chagas disease has a major impact on human health in Latin America and is becoming of global concern due to international migrations. Trypanosoma cruzi, the etiological agent of the disease, is one of the rare human parasites transmitted by the feces of its vector, as it is unable to reach the salivary gland of the insect. This stercorarian transmission is notoriously poorly understood, despite its crucial role in the ecology and evolution of the pathogen and the disease. The objective of this study was to quantify the probability of T. cruzi vectorial transmission to humans, and to use such an estimate to predict human prevalence from entomological data. We developed several models of T. cruzi transmission to estimate the probability of transmission from vector to host. Using datasets from the literature, we estimated the probability of transmission per contact with an infected triatomine to be 5.8 × 10(-4 (95%CI: [2.6 ; 11.0] × 10(-4. This estimate was consistent across triatomine species, robust to variations in other parameters, and corresponded to 900-4,000 contacts per case. Our models subsequently allowed predicting human prevalence from vector abundance and infection rate in 7/10 independent datasets covering various triatomine species and epidemiological situations. This low probability of T. cruzi transmission reflected well the complex and unlikely mechanism of transmission via insect feces, and allowed predicting human prevalence from basic entomological data. Although a proof of principle study would now be valuable to validate our models' predictive ability in an even broader range of entomological and ecological settings, our quantitative estimate could allow switching the evaluation of disease risk and vector control program from purely entomological indexes to parasitological measures, as commonly done for other major vector borne diseases. This might lead to different quantitative perspectives as these indexes are well known

  1. The improbable transmission of Trypanosoma cruzi to human: the missing link in the dynamics and control of Chagas disease.

    Science.gov (United States)

    Nouvellet, Pierre; Dumonteil, Eric; Gourbière, Sébastien

    2013-11-01

    Chagas disease has a major impact on human health in Latin America and is becoming of global concern due to international migrations. Trypanosoma cruzi, the etiological agent of the disease, is one of the rare human parasites transmitted by the feces of its vector, as it is unable to reach the salivary gland of the insect. This stercorarian transmission is notoriously poorly understood, despite its crucial role in the ecology and evolution of the pathogen and the disease. The objective of this study was to quantify the probability of T. cruzi vectorial transmission to humans, and to use such an estimate to predict human prevalence from entomological data. We developed several models of T. cruzi transmission to estimate the probability of transmission from vector to host. Using datasets from the literature, we estimated the probability of transmission per contact with an infected triatomine to be 5.8 × 10(-4) (95%CI: [2.6 ; 11.0] × 10(-4)). This estimate was consistent across triatomine species, robust to variations in other parameters, and corresponded to 900-4,000 contacts per case. Our models subsequently allowed predicting human prevalence from vector abundance and infection rate in 7/10 independent datasets covering various triatomine species and epidemiological situations. This low probability of T. cruzi transmission reflected well the complex and unlikely mechanism of transmission via insect feces, and allowed predicting human prevalence from basic entomological data. Although a proof of principle study would now be valuable to validate our models' predictive ability in an even broader range of entomological and ecological settings, our quantitative estimate could allow switching the evaluation of disease risk and vector control program from purely entomological indexes to parasitological measures, as commonly done for other major vector borne diseases. This might lead to different quantitative perspectives as these indexes are well known not to be

  2. Interface Control Document for the EMPACT Module that Estimates Electric Power Transmission System Response to EMP-Caused Damage

    Energy Technology Data Exchange (ETDEWEB)

    Werley, Kenneth Alan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mccown, Andrew William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)ory

    2016-06-26

    The EPREP code is designed to evaluate the effects of an Electro-Magnetic Pulse (EMP) on the electric power transmission system. The EPREP code embodies an umbrella framework that allows a user to set up analysis conditions and to examine analysis results. The code links to three major physics/engineering modules. The first module describes the EM wave in space and time. The second module evaluates the damage caused by the wave on specific electric power (EP) transmission system components. The third module evaluates the consequence of the damaged network on its (reduced) ability to provide electric power to meet demand. This third module is the focus of the present paper. The EMPACT code serves as the third module. The EMPACT name denotes EMP effects on Alternating Current Transmission systems. The EMPACT algorithms compute electric power transmission network flow solutions under severely damaged network conditions. Initial solutions are often characterized by unacceptible network conditions including line overloads and bad voltages. The EMPACT code contains algorithms to adjust optimally network parameters to eliminate network problems while minimizing outages. System adjustments include automatically adjusting control equipment (generator V control, variable transformers, and variable shunts), as well as non-automatic control of generator power settings and minimal load shedding. The goal is to evaluate the minimal loss of customer load under equilibrium (steady-state) conditions during peak demand.

  3. [Role of socio-economy and management in sustainable transmission control of schistosomiasis in Taoyuan County, Hunan Province, China].

    Science.gov (United States)

    Luo, Zhi-Hong; Li, Sheng-Ming; Zhou, Xiao-Nong; Yi, Ping; Ren, Guang-Hui; Franziska, Bieri; Zhao, Zheng-Yuan; Hou, Xun-Ya; Ren, Mao-Yuan; Li, Yi-Yi; Dong, Ru-Lan; Zeng, Jin-Yuan; She, Shu-Ping

    2013-02-01

    To clarify the role of socio-economy and management in the sustainable schistosomiasis-control in Taoyuan County, an endemic area in hilly region, Hunan Province, China. From 1996 to 2011, the data of socio-economy, the management of schistosomiasis control organizations, environment, and the changes in schistosomiasis prevalence were collected in Taoyuan County where schistosomiasis transmission had been controlled since 2008. A sampling survey of schistosomiasis prevalence of human and bovine was performed in 2011 to verify the current status of schistosomiasis transmission. All the data were analyzed statistically to evaluate the role of socio-economy and management in the sustainable schistosomiasis control. During the period from 1998 to 2012, the socio-economy including the residents' productive mode and daily life in Taoyuan County improved dramatically, but the recurrence risk of schistosomiasis endemic still existed due to the retuning of out-going workers and the migrating population. Moreover, the introduction of exotic species of plants and animals may increase the risk. The low running cost of schistosomiasis control organization as well as the efficient and adequate resource allocation in the county was in line with the national requirement to strengthen the rural grass-roots public health system. The harmonious development of socio-economy and the scientific and efficient health system in Taoyuan County are the key factors for the sustainable transmission control of schistosomiasis.

  4. Novel application of continuously variable transmission system using composite recurrent Laguerre orthogonal polynomials modified PSO NN control system.

    Science.gov (United States)

    Lin, Chih-Hong

    2016-09-01

    Because the V-belt continuously variable transmission system spurred by permanent magnet (PM) synchronous motor has much unknown nonlinear and time-varying characteristics, the better control performance design for the linear control design is a time consuming procedure. In order to overcome difficulties for design of the linear controllers, the composite recurrent Laguerre orthogonal polynomials modified particle swarm optimization (PSO) neural network (NN) control system which has online learning capability to come back to the nonlinear and time-varying of system, is developed for controlling PM synchronous motor servo-driven V-belt continuously variable transmission system with the lumped nonlinear load disturbances. The composite recurrent Laguerre orthogonal polynomials NN control system consists of an inspector control, a recurrent Laguerre orthogonal polynomials NN control with adaptation law and a recouped control with estimation law. Moreover, the adaptation law of online parameters in the recurrent Laguerre orthogonal polynomials NN is originated from Lyapunov stability theorem. Additionally, two optimal learning rates of the parameters by means of modified PSO are posed in order to achieve better convergence. At last, comparative studies shown by experimental results are illustrated to demonstrate the control performance of the proposed control scheme. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  5. Regulation of Synaptic Transmission by Ambient Extracellular Glutamate

    OpenAIRE

    FEATHERSTONE, DAVID E.; SHIPPY, SCOTT A.

    2007-01-01

    Many neuroscientists assume that ambient extracellular glutamate concentrations in the nervous system are biologically negligible under nonpathological conditions. This assumption is false. Hundreds of studies over several decades suggest that ambient extracellular glutamate levels in the intact mammalian brain are ~0.5 to ~5 μM. This has important implications. Glutamate receptors are desensitized by glutamate concentrations significantly lower than needed for receptor activation; 0.5 to 5 μ...

  6. Astrocytes gate synaptic transmission from unmyelinated sensory afferents

    DEFF Research Database (Denmark)

    Perrier, Jean-Francois Marie; Christensen, Rasmus Kordt; Delgado-Lezama, R.

    2015-01-01

    Maternal immune activation (MIA) is known to affect neuronal precursor gene expression, proliferation and differentiation, and has been shown in mice to produce abnormal phenotypes resembling human neurodevelopmental disorders, particularly schizophrenia and autism. The relative contributions of ...

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