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Sample records for central synapse formation

  1. Synapse formation and remodeling

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Synapses are specialized structures that mediate information flow between neurons and target cells,and thus are the basis for neuronal system to execute various functions,including learning and memory.There are around 1011 neurons in the human brain,with each neuron receiving thousands of synaptic inputs,either excitatory or inhibitory.A synapse is an asymmetric structure that is composed of pre-synaptic axon terminals,synaptic cleft,and postsynaptic compartments.Synapse formation involves a number of cell adhesion molecules,extracellular factors,and intracellular signaling or structural proteins.After the establishment of synaptic connections,synapses undergo structural or functional changes,known as synaptic plasticity which is believed to be regulated by neuronal activity and a variety of secreted factors.This review summarizes recent progress in the field of synapse development,with particular emphasis on the work carried out in China during the past 10 years(1999-2009).

  2. Synapse formation on neurons born in the adult hippocampus.

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    Toni, Nicolas; Teng, E Matthew; Bushong, Eric A; Aimone, James B; Zhao, Chunmei; Consiglio, Antonella; van Praag, Henriette; Martone, Maryann E; Ellisman, Mark H; Gage, Fred H

    2007-06-01

    Although new and functional neurons are produced in the adult brain, little is known about how they integrate into mature networks. Here we explored the mechanisms of synaptogenesis on neurons born in the adult mouse hippocampus using confocal microscopy, electron microscopy and live imaging. We report that new neurons, similar to mature granule neurons, were contacted by axosomatic, axodendritic and axospinous synapses. Consistent with their putative role in synaptogenesis, dendritic filopodia were more abundant during the early stages of maturation and, when analyzed in three dimensions, the tips of all filopodia were found within 200 nm of preexisting boutons that already synapsed on other neurons. Furthermore, dendritic spines primarily synapsed on multiple-synapse boutons, suggesting that initial contacts were preferentially made with preexisting boutons already involved in a synapse. The connectivity of new neurons continued to change until at least 2 months, long after the formation of the first dendritic protrusions.

  3. Neuron-glia signaling: Implications for astrocyte differentiation and synapse formation.

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    Stipursky, Joice; Romão, Luciana; Tortelli, Vanessa; Neto, Vivaldo Moura; Gomes, Flávia Carvalho Alcantara

    2011-10-10

    Glial cells are currently viewed as active partners of neurons in synapse formation. The close proximity of astrocytes to the synaptic cleft implicates that they strongly influence synapse function as well as suggests that these cells might be potential targets for neuronal-released molecules. In this review, we discuss the signaling pathways of astrocyte generation and the role of astrocyte-derived molecules in synapse formation in the central nervous system. Further, we discuss the role of the excitatory neurotransmitter, glutamate and transforming growth factor beta 1 (TGF-β1) pathway in astrocyte generation and differentiation. We provide evidence that astrocytes surrounding synapses are target of neuronal activity and shed light into the role of astroglial cells into neurological disorders associated with glutamate neurotoxicity.

  4. Molecular mechanism of parallel fiber-Purkinje cell synapse formation.

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    Mishina, Masayoshi; Uemura, Takeshi; Yasumura, Misato; Yoshida, Tomoyuki

    2012-01-01

    The cerebellum receives two excitatory afferents, the climbing fiber (CF) and the mossy fiber-parallel fiber (PF) pathway, both converging onto Purkinje cells (PCs) that are the sole neurons sending outputs from the cerebellar cortex. Glutamate receptor δ2 (GluRδ2) is expressed selectively in cerebellar PCs and localized exclusively at the PF-PC synapses. We found that a significant number of PC spines lack synaptic contacts with PF terminals and some of residual PF-PC synapses show mismatching between pre- and postsynaptic specializations in conventional and conditional GluRδ2 knockout mice. Studies with mutant mice revealed that in addition to PF-PC synapse formation, GluRδ2 is essential for synaptic plasticity, motor learning, and the restriction of CF territory. GluRδ2 regulates synapse formation through the amino-terminal domain, while the control of synaptic plasticity, motor learning, and CF territory is mediated through the carboxyl-terminal domain. Thus, GluRδ2 is the molecule that bridges synapse formation and motor learning. We found that the trans-synaptic interaction of postsynaptic GluRδ2 and presynaptic neurexins (NRXNs) through cerebellin 1 (Cbln1) mediates PF-PC synapse formation. The synaptogenic triad is composed of one molecule of tetrameric GluRδ2, two molecules of hexameric Cbln1 and four molecules of monomeric NRXN. Thus, GluRδ2 triggers synapse formation by clustering four NRXNs. These findings provide a molecular insight into the mechanism of synapse formation in the brain.

  5. Molecular mechanism of parallel fiber-Purkinje cell synapse formation

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    Masayoshi eMishina

    2012-11-01

    Full Text Available The cerebellum receives two excitatory afferents, the climbing fiber (CF and the mossy fiber-parallel fiber (PF pathway, both converging onto Purkinje cells (PCs that are the sole neurons sending outputs from the cerebellar cortex. Glutamate receptor δ2 (GluRδ2 is expressed selectively in cerebellar PCs and localized exclusively at the PF-PC synapses. We found that a significant number of PC spines lack synaptic contacts with PF terminals and some of residual PF-PC synapses show mismatching between pre- and postsynaptic specializations in conventional and conditional GluRδ2 knockout mice. Studies with mutant mice revealed that in addition to PF-PC synapse formation, GluRδ2 is essential for synaptic plasticity, motor learning and the restriction of CF territory. GluRδ2 regulates synapse formation through the amino-terminal domain, while the control of synaptic plasticity, motor learning and CF territory is mediated through the carboxyl-terminal domain. Thus, GluRδ2 is the molecule that bridges synapse formation and motor learning. We found that the trans-synaptic interaction of postsynaptic GluRδ2 and presynaptic neurexins (NRXNs through Cbln1 mediates PF-PC synapse formation. The synaptogenic triad is composed of one molecule of tetrameric GluRδ2, two molecules of hexameric Cbln1 and four molecules of monomeric NRXN. Thus, GluRδ2 triggers synapse formation by clustering four NRXNs. These findings provide a molecular insight into the mechanism of synapse formation in the brain.

  6. The role of Cbln1 on Purkinje cell synapse formation.

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    Ito-Ishida, Aya; Okabe, Shigeo; Yuzaki, Michisuke

    2014-06-01

    Cbln1 is a glycoprotein which belongs to the C1q family. In the cerebellum, Cbln1 is produced and secreted from granule cells and works as a strong synapse organizer between Purkinje cells and parallel fibers, the axons of the granule cells. In this update article, we will describe the molecular mechanisms by which Cbln1 induces synapse formation and will review our findings on the axonal structural changes which occur specifically during this process. We will also describe our recent finding that Cbln1 has a suppressive role in inhibitory synapse formation between Purkinje cells and molecular layer interneurons. Our results have revealed that Cbln1 plays an essential role to establish parallel fiber-Purkinje cell synapses and to regulate balance between excitatory and inhibitory input on Purkinje cells.

  7. The formation of synapses in amphibian striated muscle during development.

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    Bennett, M R; Pettigrew, A G

    1975-10-01

    1. A study has been made of the formation of synapses in developing reinnervated and cross-reinnervated amphibian twitch muscles which receive either a focal (iliofibularis) or a distributed (sartorius) innervation from 'en plaque' nerve terminals using histological, ultrastructural and electrophysiological techniques. 2. During the development of the tadpole through metamorphosis to the adult frog, the sartorius myofibres increased in length at about twice the rate of the iliofibularis myofibres, due to a fast rate of growth at their insertions on to the pelvic tendon. 3. The short iliofibularis and sartorius myofibres of young tadpoles (800 mum long) possessed only a single synapse and the iliofibularis myofibres did not receive any further innervation during development. However the sartorius myofibres received further transient innervation on the new muscle laid down during development at the fast growing pelvic insertion, until the distance between the original synapse formed on the myofibres and the synapse at the pelvic end of the muscle was about 12 mm. 4. During development synapses possessed either skewed, multimodal, or unimodal m.e.p.p. amplitude-frequency distributions; the intervals between m.e.p.p.s. were not distributed randomly according to a Poisson process, as m.e.p.p.s. of similar amplitudes tended to be separated by very short intervals; the unit-size e.p.p. had a similar amplitude-frequency distribution as the m.e.p.p.s. if these had a unimodal distribution. 5. Reinnervation or cross-reinnervation of the sartorius and the iliofibularis muscles in adults or at a late stage of development simply reconstituted the normal focal and distributed innervation patterns of the muscles, as found in the control muscles of the contralateral and unoperated legs. 6. These observations on synapse formation in amphibia are consistent with the hypothesis that during development the axon making the initial synaptic contact on the muscle cells induces a property

  8. Loss of transforming growth factor-beta 2 leads to impairment of central synapse function

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    Rickmann Michael

    2008-10-01

    Full Text Available Abstract Background The formation of functional synapses is a crucial event in neuronal network formation, and with regard to regulation of breathing it is essential for life. Members of the transforming growth factor-beta (TGF-β superfamily act as intercellular signaling molecules during synaptogenesis of the neuromuscular junction of Drosophila and are involved in synaptic function of sensory neurons of Aplysia. Results Here we show that while TGF-β2 is not crucial for the morphology and function of the neuromuscular junction of the diaphragm muscle of mice, it is essential for proper synaptic function in the pre-Bötzinger complex, a central rhythm organizer located in the brainstem. Genetic deletion of TGF-β2 in mice strongly impaired both GABA/glycinergic and glutamatergic synaptic transmission in the pre-Bötzinger complex area, while numbers and morphology of central synapses of knock-out animals were indistinguishable from their wild-type littermates at embryonic day 18.5. Conclusion The results demonstrate that TGF-β2 influences synaptic function, rather than synaptogenesis, specifically at central synapses. The functional alterations in the respiratory center of the brain are probably the underlying cause of the perinatal death of the TGF-β2 knock-out mice.

  9. Quantification of synapse formation and maintenance in vivo in the absence of synaptic release

    NARCIS (Netherlands)

    Bouwman, J.J.; Maia, A.S.; Camoletto, P.G.; Posthuma, G.; Roubos, E.W.; Oorschot, V.M.J.; Klumperman, J.; Verhage, M.

    2004-01-01

    Outgrowing axons in the developing nervous system secrete neurotransmitters and neuromodulatory substances, which is considered to stimulate synaptogenesis. However, some synapses develop independent of presynaptic secretion. To investigate the role of secretion in synapse formation and maintenance

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

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    Yuzaki, Michisuke

    2010-07-01

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

  11. Inhibitory synapse dynamics: coordinated presynaptic and postsynaptic mobility and the major contribution of recycled vesicles to new synapse formation.

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    Dobie, Frederick A; Craig, Ann Marie

    2011-07-20

    Dynamics of GABAergic synaptic components have been studied previously over milliseconds to minutes, revealing mobility of postsynaptic scaffolds and receptors. Here we image inhibitory synapses containing fluorescently tagged postsynaptic scaffold Gephyrin, together with presynaptic vesicular GABA transporter (VGAT) or postsynaptic GABA(A) receptor γ2 subunit (GABA(A)Rγ2), over seconds to days in cultured rat hippocampal neurons, revealing modes of inhibitory synapse formation and remodeling. Entire synapses were mobile, translocating rapidly within a confined region and exhibiting greater nonstochastic motion over multihour periods. Presynaptic and postsynaptic components moved in unison, maintaining close apposition while translocating distances of several micrometers. An observed flux in the density of synaptic puncta partially resulted from the apparent merging and splitting of preexisting clusters. De novo formation of inhibitory synapses was observed, marked by the appearance of stably apposed Gephyrin and VGAT clusters at sites previously lacking either component. Coclustering of GABA(A)Rγ2 supports the identification of such new clusters as synapses. Nascent synapse formation occurred by gradual accumulation of components over several hours, with VGAT clustering preceding that of Gephyrin and GABA(A)Rγ2. Comparing VGAT labeling by active uptake of a luminal domain antibody with post hoc immunocytochemistry indicated that recycling vesicles from preexisting boutons significantly contribute to vesicle pools at the majority of new inhibitory synapses. Although new synapses formed primarily on dendrite shafts, some also formed on dendritic protrusions, without apparent interconversion. Altogether, the long-term imaging of GABAergic presynaptic and postsynaptic components reveals complex dynamics and perpetual remodeling with implications for mechanisms of assembly and synaptic integration.

  12. A peptide antagonist disrupts NK cell inhibitory synapse formation.

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    Borhis, Gwenoline; Ahmed, Parvin S; Mbiribindi, Bérénice; Naiyer, Mohammed M; Davis, Daniel M; Purbhoo, Marco A; Khakoo, Salim I

    2013-03-15

    Productive engagement of MHC class I by inhibitory NK cell receptors depends on the peptide bound by the MHC class I molecule. Peptide:MHC complexes that bind weakly to killer cell Ig-like receptors (KIRs) can antagonize the inhibition mediated by high-affinity peptide:MHC complexes and cause NK cell activation. We show that low-affinity peptide:MHC complexes stall inhibitory signaling at the step of Src homology protein tyrosine phosphatase 1 recruitment and do not go on to form the KIR microclusters induced by high-affinity peptide:MHC, which are associated with Vav dephosphorylation and downstream signaling. Furthermore, the low-affinity peptide:MHC complexes prevented the formation of KIR microclusters by high-affinity peptide:MHC. Thus, peptide antagonism of NK cells is an active phenomenon of inhibitory synapse disruption.

  13. LIME mediates immunological synapse formation through activation of VAV.

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    Son, Myoungsun; Park, Inyoung; Lee, Ok-Hee; Rhee, Inmoo; Park, Changwon; Yun, Yungdae

    2012-04-01

    Lck Interacting Membrane protein (LIME) was previously characterized as a transmembrane adaptor protein mediating TCR-dependent T cell activation. Here, we show that LIME associates with Vav in response to TCR stimulation and is required for Vav guanine nucleotide exchange factor (GEF) activity for Rac1. Consistent with this finding, actin polymerization at the immunological synapse (IS) was markedly enhanced by overexpression of LIME, but was reduced by expression of a LIME shRNA. Moreover, TCR-mediated cell adhesion to ICAM-1, laminin, or fibronectin was downregulated by expression of LIME shRNA. In addition, in the IS, LIME but not LAT was found to localize at the peripheral-supramolecular activation cluster (p-SMAC) where the integrins were previously shown to be localized. Together, these results establish LIME as a transmembrane adaptor protein linking TCR stimulation to IS formation and integrin activation through activation of Vav.

  14. Synapse formation between isolated axons requires presynaptic soma and redistribution of postsynaptic AChRs.

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    Meems, Ryanne; Munno, David; van Minnen, Jan; Syed, Naweed I

    2003-05-01

    The involvement of neuronal protein synthetic machinery and extrinsic trophic factors during synapse formation is poorly understood. Here we determine the roles of these processes by reconstructing synapses between the axons severed from identified Lymnaea neurons in cell culture, either in the presence or absence of trophic factors. We demonstrate that, although synapses are maintained between isolated pre- and postsynaptic axons for several days, the presynaptic, but not the postsynaptic, cell body, however, is required for new synapse formation between soma-axon pairs. The formation of cholinergic synapses between presynaptic soma and postsynaptic axon requires gene transcription and protein synthesis solely in the presynaptic neuron. We show that this synaptogenesis is contingent on extrinsic trophic factors present in brain conditioned medium (CM). The CM-induced excitatory synapse formation is mediated through receptor tyrosine kinases. We further demonstrate that, although the postsynaptic axon does not require new protein synthesis for synapse formation, its contact with the presynaptic cell in CM, but not in defined medium (no trophic factors), differentially alters its responsiveness to exogenously applied acetylcholine at synaptic compared with extrasynaptic sites. Together, these data suggest a synergetic action of cell-cell signaling and trophic factors to bring about specific changes in both pre- and postsynaptic neurons during synapse formation.

  15. Complexins facilitate neurotransmitter release at excitatory and inhibitory synapses in mammalian central nervous system.

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    Xue, Mingshan; Stradomska, Alicja; Chen, Hongmei; Brose, Nils; Zhang, Weiqi; Rosenmund, Christian; Reim, Kerstin

    2008-06-03

    Complexins (Cplxs) are key regulators of synaptic exocytosis, but whether they act as facilitators or inhibitors is currently being disputed controversially. We show that genetic deletion of all Cplxs expressed in the mouse brain causes a reduction in Ca(2+)-triggered and spontaneous neurotransmitter release at both excitatory and inhibitory synapses. Our results demonstrate that at mammalian central nervous system synapses, Cplxs facilitate neurotransmitter release and do not simply act as inhibitory clamps of the synaptic vesicle fusion machinery.

  16. Synapse organization and modulation via C1q family proteins and their receptors in the central nervous system.

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    Matsuda, Keiko

    2016-11-12

    Several C1q family members, related to the C1q complement component are extensively expressed in the central nervous system. Cbln1, which belongs to the Cbln subfamily of C1q proteins and released from cerebellar granule cells, plays an indispensable role in the synapse formation and function at parallel fiber-Purkinje cell synapses. This is achieved by formation of a trans-synaptic tripartite complex which is composed of one unit of the Cbln1 hexamer, monomeric neurexin (NRX) containing a splice site 4 insertion at presynaptic terminals and the postsynaptic GluD2 dimers. Recently an increasing number of soluble or transmembrane proteins have been identified to bind directly to the amino-terminal domains of iGluR and regulate the recruitment and function of iGluRs at synapses. Especially at mossy fiber (MF)-CA3 synapses in the hippocampus, postsynaptic kainate-type glutamate receptors (KARs) are involved in synaptic network activity through their characteristic channel kinetics. C1ql2 and C1ql3, which belong to the C1q-like subfamily of C1q proteins, are produced by MFs and serve as extracellular organizers to recruit functional postsynaptic KAR complexes at MF-CA3 synapses via binding to the amino-terminal domains of GluK2 and GluK4 KAR subunits. In addition, C1ql2 and C1ql3 directly bind to NRX3 containing sequences encoded by exon 25b insertion at splice site 5. In the present review, we highlighted the generality of the strategy by tripartite complex formation of the specific type of NRX and iGluR via C1q family members.

  17. Agrin and the molecular choreography of synapse formation.

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    Nastuk, M A; Fallon, J R

    1993-02-01

    High concentrations of neurotransmitter receptors characterize neuromuscular junctions as well as neuron-neuron synapses in the brain and periphery. Synaptic function is critically dependent upon this marshalling of neurotransmitter receptors to the post-synaptic membrane. This review discusses agrin's role in orchestrating the molecular topography of the post-synaptic apparatus at nerve-muscle synapses and the emerging evidence suggesting a role for agrin in synaptogenesis in the brain.

  18. The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain.

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    Okerlund, Nathan D; Stanley, Robert E; Cheyette, Benjamin N R

    2016-07-01

    The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity (PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine formation and glutamatergic synapse formation in mammalian central nervous system neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic synapse inputs on their dendrites than control neurons. Neurons from mice heterozygous for a semidominant Vangl2 mutation have similar but not identical phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue from adult mutant mice. Given increasing evidence linking psychiatric pathophysiology to these subneuronal sites and structures, our findings underscore the relevance of core PCP proteins including Vangl2 to the underlying biology of major mental illnesses and their treatment.

  19. Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons

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    Alvarez, Francisco J.; Titus-Mitchell, Haley E.; Bullinger, Katie L.; Kraszpulski, Michal; Nardelli, Paul; Cope, Timothy C.

    2011-01-01

    Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped fro...

  20. ApoE receptor 2 regulates synapse and dendritic spine formation.

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    Sonya B Dumanis

    Full Text Available BACKGROUND: Apolipoprotein E receptor 2 (ApoEr2 is a postsynaptic protein involved in long-term potentiation (LTP, learning, and memory through unknown mechanisms. We examined the biological effects of ApoEr2 on synapse and dendritic spine formation-processes critical for learning and memory. METHODOLOGY/PRINCIPAL FINDINGS: In a heterologous co-culture synapse assay, overexpression of ApoEr2 in COS7 cells significantly increased colocalization with synaptophysin in primary hippocampal neurons, suggesting that ApoEr2 promotes interaction with presynaptic structures. In primary neuronal cultures, overexpression of ApoEr2 increased dendritic spine density. Consistent with our in vitro findings, ApoEr2 knockout mice had decreased dendritic spine density in cortical layers II/III at 1 month of age. We also tested whether the interaction between ApoEr2 and its cytoplasmic adaptor proteins, specifically X11α and PSD-95, affected synapse and dendritic spine formation. X11α decreased cell surface levels of ApoEr2 along with synapse and dendritic spine density. In contrast, PSD-95 increased cell surface levels of ApoEr2 as well as synapse and dendritic spine density. CONCLUSIONS/SIGNIFICANCE: These results suggest that ApoEr2 plays important roles in structure and function of CNS synapses and dendritic spines, and that these roles are modulated by cytoplasmic adaptor proteins X11α and PSD-95.

  1. The Wnt/Planar Cell Polarity Pathway Component Vangl2 Induces Synapse Formation through Direct Control of N-Cadherin

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    Tadahiro Nagaoka

    2014-03-01

    Full Text Available Although regulators of the Wnt/planar cell polarity (PCP pathway are widely expressed in vertebrate nervous systems, their roles at synapses are unknown. Here, we show that Vangl2 is a postsynaptic factor crucial for synaptogenesis and that it coprecipitates with N-cadherin and PSD-95 from synapse-rich brain extracts. Vangl2 directly binds N-cadherin and enhances its internalization in a Rab5-dependent manner. This physical and functional interaction is suppressed by β-catenin, which binds the same intracellular region of N-cadherin as Vangl2. In hippocampal neurons expressing reduced Vangl2 levels, dendritic spine formation as well as synaptic marker clustering is significantly impaired. Furthermore, Prickle2, another postsynaptic PCP component, inhibits the N-cadherin-Vangl2 interaction and is required for normal spine formation. These results demonstrate direct control of classic cadherin by PCP factors; this control may play a central role in the precise formation and maturation of cell-cell adhesions at the synapse.

  2. Cbln1 downregulates the formation and function of inhibitory synapses in mouse cerebellar Purkinje cells.

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    Ito-Ishida, Aya; Kakegawa, Wataru; Kohda, Kazuhisa; Miura, Eriko; Okabe, Shigeo; Yuzaki, Michisuke

    2014-04-01

    The formation of excitatory and inhibitory synapses must be tightly coordinated to establish functional neuronal circuitry during development. In the cerebellum, the formation of excitatory synapses between parallel fibers and Purkinje cells is strongly induced by Cbln1, which is released from parallel fibers and binds to the postsynaptic δ2 glutamate receptor (GluD2). However, Cbln1's role, if any, in inhibitory synapse formation has been unknown. Here, we show that Cbln1 downregulates the formation and function of inhibitory synapses between Purkinje cells and interneurons. Immunohistochemical analyses with an anti-vesicular GABA transporter antibody revealed an increased density of interneuron-Purkinje cell synapses in the cbln1-null cerebellum. Whole-cell patch-clamp recordings from Purkinje cells showed that both the amplitude and frequency of miniature inhibitory postsynaptic currents were increased in cbln1-null cerebellar slices. A 3-h incubation with recombinant Cbln1 reversed the increased amplitude of inhibitory currents in Purkinje cells in acutely prepared cbln1-null slices. Furthermore, an 8-day incubation with recombinant Cbln1 reversed the increased interneuron-Purkinje cell synapse density in cultured cbln1-null slices. In contrast, recombinant Cbln1 did not affect cerebellar slices from mice lacking both Cbln1 and GluD2. Finally, we found that tyrosine phosphorylation was upregulated in the cbln1-null cerebellum, and acute inhibition of Src-family kinases suppressed the increased inhibitory postsynaptic currents in cbln1-null Purkinje cells. These findings indicate that Cbln1-GluD2 signaling inhibits the number and function of inhibitory synapses, and shifts the excitatory-inhibitory balance towards excitation in Purkinje cells. Cbln1's effect on inhibitory synaptic transmission is probably mediated by a tyrosine kinase pathway.

  3. Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum

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    Uemura, T; Lee, S. J.; Yasumura, M.; Takeuchi, T.; Yoshida, T.; Ra, M.; Taguchi, R.; Sakimura, K; Mishina, M.

    2010-01-01

    Elucidation of molecular mechanisms that regulate synapse formation is required for the understanding of neural wiring, higher brain functions, and mental disorders. Despite the wealth of in vitro information, fundamental questions about how glutamatergic synapses are formed in the mammalian brain remain unanswered. Glutamate receptor (GluR) δ2 is essential for cerebellar synapse formation in vivo. Here, we show that the N-terminal domain (NTD) of GluRδ2 interacts with presynaptic neurexins (...

  4. Neuroligins and neurexins: linking cell adhesion, synapse formation and cognitive function.

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    Dean, Camin; Dresbach, Thomas

    2006-01-01

    Cell adhesion represents the most direct way of coordinating synaptic connectivity in the brain. Recent evidence highlights the importance of a trans-synaptic interaction between postsynaptic neuroligins and presynaptic neurexins. These transmembrane molecules bind each other extracellularly to promote adhesion between dendrites and axons. This signals the recruitment of presynaptic and postsynaptic molecules to form a functional synapse. Remarkably, neuroligins alone can induce the formation of fully functional presynaptic terminals in contacting axons. Conversely, neurexins alone can induce postsynaptic differentiation and clustering of receptors in dendrites. Therefore, the neuroligin-neurexin interaction has the unique ability to act as a bi-directional trigger of synapse formation. Here, we review several recent studies that offer clues as to how these proteins form synapses and how they might function in the brain to establish and modify neuronal network properties and cognition.

  5. Endocytic structures and synaptic vesicle recycling at a central synapse in awake rats.

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    Körber, Christoph; Horstmann, Heinz; Sätzler, Kurt; Kuner, Thomas

    2012-12-01

    The synaptic vesicle (SV) cycle has been studied extensively in cultured cells and slice preparations, but not much is known about the roles and relative contributions of endocytic pathways and mechanisms of SV recycling in vivo, under physiological patterns of activity. We employed horseradish peroxidase (HRP) as an in vivo marker of endocytosis at the calyx of Held synapse in the awake rat. Ex vivo serial section scanning electron microscopy and 3D reconstructions revealed two categories of labelled structures: HRP-filled SVs and large cisternal endosomes. Inhibition of adaptor protein complexes 1 and 3 (AP-1, AP-3) by in vivo application of Brefeldin A (BFA) disrupted endosomal SV budding while SV recycling via clathrin-mediated endocytosis (CME) remained unaffected. In conclusion, our study establishes cisternal endosomes as an intermediate of the SV cycle and reveals CME and endosomal budding as the predominant mechanisms of SV recycling in a tonically active central synapse in vivo.

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

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

    2014-01-15

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

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

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

    2012-06-01

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

  8. Cbln1 regulates rapid formation and maintenance of excitatory synapses in mature cerebellar Purkinje cells in vitro and in vivo.

    Science.gov (United States)

    Ito-Ishida, Aya; Miura, Eriko; Emi, Kyoichi; Matsuda, Keiko; Iijima, Takatoshi; Kondo, Tetsuro; Kohda, Kazuhisa; Watanabe, Masahiko; Yuzaki, Michisuke

    2008-06-04

    Although many synapse-organizing molecules have been identified in vitro, their functions in mature neurons in vivo have been mostly unexplored. Cbln1, which belongs to the C1q/tumor necrosis factor superfamily, is the most recently identified protein involved in synapse formation in the mammalian CNS. In the cerebellum, Cbln1 is predominantly produced and secreted from granule cells; cbln1-null mice show ataxia and a severe reduction in the number of synapses between Purkinje cells and parallel fibers (PFs), the axon bundle of granule cells. Here, we show that application of recombinant Cbln1 specifically and reversibly induced PF synapse formation in dissociated cbln1-null Purkinje cells in culture. Cbln1 also rapidly induced electrophysiologically functional and ultrastructurally normal PF synapses in acutely prepared cbln1-null cerebellar slices. Furthermore, a single injection of recombinant Cbln1 rescued severe ataxia in adult cbln1-null mice in vivo by completely, but transiently, restoring PF synapses. Therefore, Cbln1 is a unique synapse organizer that is required not only for the normal development of PF-Purkinje cell synapses but also for their maintenance in the mature cerebellum both in vitro and in vivo. Furthermore, our results indicate that Cbln1 can also rapidly organize new synapses in adult cerebellum, implying its therapeutic potential for cerebellar ataxic disorders.

  9. GluRδ2 assembles four neurexins into trans-synaptic triad to trigger synapse formation.

    Science.gov (United States)

    Lee, Sung-Jin; Uemura, Takeshi; Yoshida, Tomoyuki; Mishina, Masayoshi

    2012-03-28

    Elucidation of molecular mechanisms of synapse formation is a prerequisite for the understanding of neural wiring, higher brain functions, and mental disorders. The trans-synaptic interaction of postsynaptic glutamate receptor δ2 (GluRδ2) and presynaptic neurexins (NRXNs) through cerebellin precursor protein 1 (Cbln1) mediates synapse formation in vivo in the cerebellum. Here, we asked how the trans-synaptic triad induces synapse formation. Native GluRδ2 existed as a tetramer in the membrane, whereas the N-terminal domain (NTD) of GluRδ2 formed a stable homodimer. When incubated with cultured mouse cerebellar granule cells (GCs), dimeric GluRδ2-NTD and Cbln1 exerted little effect on the accumulation of punctate immunostaining signals for Bassoon and vesicular glutamate transporter 1 in GC axons. However, tetramerized GluRδ2-NTD stimulated the accumulation of these presynaptic proteins in the axons. Analysis of Cbln1 mutants suggested that the binding sites of GluRδ2 and NRXN1β on Cbln1 are differential. Furthermore, there was no competition in the binding to Cbln1 between GluRδ2-NTD and the extracellular domain (ECD) of NRXN1β. Thus, GluRδ2 and Cbln1 interacted with each other rather independently of Cbln1-NRXN1β interaction and vice versa. Gel filtration and isothermal titration calorimetry analyses consistently showed that dimeric GluRδ2-NTD and hexameric Cbln1 assembled in the 1:1 ratio, whereas hexameric Cbln1 and the laminin-neurexin-sex hormone-binding globulin domain of NRXN1β-ECD assembled in the 1:2 ratio. Thus, the synaptogenic triad is assembled from tetrameric GluRδ2, hexameric Cbln1, and monomeric NRXN in the ratio of 1:2:4. These results suggest that GluRδ2 triggers synapse formation by clustering four NRXNs through triad formation.

  10. The role of neuronal activity and transmitter release on synapse formation.

    Science.gov (United States)

    Andreae, Laura C; Burrone, Juan

    2014-08-01

    The long history of probing the role of neuronal activity in the development of nervous system circuitry has recently taken an interesting turn. Although undoubtedly activity plays a critical part in the maintenance and refinement of synaptic connections, often via competitive mechanisms, evidence is building that it also drives the process of synapse formation itself. Perhaps predictably, this turns out not to be a uniform process. It seems that different circuits, indeed specific synaptic connections, are differentially sensitive to the effects of activity. We examine possible ways in which neurotransmitter may drive synapse formation, and speculate on how the environment of the developing brain may allow a different spatiotemporal range for neuronal activity to operate in the generation of connectivity.

  11. Inhibitory synapse formation in a co-culture model incorporating GABAergic medium spiny neurons and HEK293 cells stably expressing GABAA receptors.

    Science.gov (United States)

    Brown, Laura E; Fuchs, Celine; Nicholson, Martin W; Stephenson, F Anne; Thomson, Alex M; Jovanovic, Jasmina N

    2014-11-14

    Inhibitory neurons act in the central nervous system to regulate the dynamics and spatio-temporal co-ordination of neuronal networks. GABA (γ-aminobutyric acid) is the predominant inhibitory neurotransmitter in the brain. It is released from the presynaptic terminals of inhibitory neurons within highly specialized intercellular junctions known as synapses, where it binds to GABAA receptors (GABAARs) present at the plasma membrane of the synapse-receiving, postsynaptic neurons. Activation of these GABA-gated ion channels leads to influx of chloride resulting in postsynaptic potential changes that decrease the probability that these neurons will generate action potentials. During development, diverse types of inhibitory neurons with distinct morphological, electrophysiological and neurochemical characteristics have the ability to recognize their target neurons and form synapses which incorporate specific GABAARs subtypes. This principle of selective innervation of neuronal targets raises the question as to how the appropriate synaptic partners identify each other. To elucidate the underlying molecular mechanisms, a novel in vitro co-culture model system was established, in which medium spiny GABAergic neurons, a highly homogenous population of neurons isolated from the embryonic striatum, were cultured with stably transfected HEK293 cell lines that express different GABAAR subtypes. Synapses form rapidly, efficiently and selectively in this system, and are easily accessible for quantification. Our results indicate that various GABAAR subtypes differ in their ability to promote synapse formation, suggesting that this reduced in vitro model system can be used to reproduce, at least in part, the in vivo conditions required for the recognition of the appropriate synaptic partners and formation of specific synapses. Here the protocols for culturing the medium spiny neurons and generating HEK293 cells lines expressing GABAARs are first described, followed by detailed

  12. Rapid formation and selective stabilization of synapses for enduring motor memories.

    Science.gov (United States)

    Xu, Tonghui; Yu, Xinzhu; Perlik, Andrew J; Tobin, Willie F; Zweig, Jonathan A; Tennant, Kelly; Jones, Theresa; Zuo, Yi

    2009-12-17

    Novel motor skills are learned through repetitive practice and, once acquired, persist long after training stops. Earlier studies have shown that such learning induces an increase in the efficacy of synapses in the primary motor cortex, the persistence of which is associated with retention of the task. However, how motor learning affects neuronal circuitry at the level of individual synapses and how long-lasting memory is structurally encoded in the intact brain remain unknown. Here we show that synaptic connections in the living mouse brain rapidly respond to motor-skill learning and permanently rewire. Training in a forelimb reaching task leads to rapid (within an hour) formation of postsynaptic dendritic spines on the output pyramidal neurons in the contralateral motor cortex. Although selective elimination of spines that existed before training gradually returns the overall spine density back to the original level, the new spines induced during learning are preferentially stabilized during subsequent training and endure long after training stops. Furthermore, we show that different motor skills are encoded by different sets of synapses. Practice of novel, but not previously learned, tasks further promotes dendritic spine formation in adulthood. Our findings reveal that rapid, but long-lasting, synaptic reorganization is closely associated with motor learning. The data also suggest that stabilized neuronal connections are the foundation of durable motor memory.

  13. Early sequential formation of functional GABA(A) and glutamatergic synapses on CA1 interneurons of the rat foetal hippocampus.

    Science.gov (United States)

    Hennou, Sonia; Khalilov, Ilgam; Diabira, Diabé; Ben-Ari, Yehezkel; Gozlan, Henri

    2002-07-01

    During postnatal development of CA1 pyramidal neurons, GABAergic synapses are excitatory and established prior to glutamatergic synapses. As interneurons are generated before pyramidal cells, we have tested the hypothesis that the GABAergic interneuronal network is operative before glutamate pyramidal neurons and provides the initial patterns of activity. We patch-clamp recorded interneurons in foetal (69 neurons) and neonatal P0 (162 neurons) hippocampal slices and performed a morphofunctional analysis of biocytin-filled neurons. At P0, three types of interneurons were found: (i) non-innervated "silent" interneurons (5%) with no spontaneous or evoked synaptic currents; (ii) G interneurons (17%) with GABA(A) synapses only; and (iii) GG interneurons with GABA and glutamatergic synapses (78%). Relying on the neuronal capacitance, cell body size and arborization of dendrites and axons, the three types of interneurons correspond to three stages of development with non-innervated neurons and interneurons with GABA(A) and glutamatergic synapses being, respectively, the least and the most developed. Recordings from both pyramidal neurons and interneurons in foetuses (E18-20) revealed that the majority of interneurons (65%) had functional synapses whereas nearly 90% of pyramidal neurons were quiescent. Therefore, interneurons follow the same GABA-glutamate sequence of synapse formation but earlier than the principal cells. Interneurons are the source and the target of the first synapses formed in the hippocampus and are thus in a position to modulate the development of the hippocampus in the foetal stage.

  14. Cholesterol regulates multiple forms of vesicle endocytosis at a mammalian central synapse.

    Science.gov (United States)

    Yue, Hai-Yuan; Xu, Jianhua

    2015-07-01

    Endocytosis in synapses sustains neurotransmission by recycling vesicle membrane and maintaining the homeostasis of synaptic membrane. A role of membrane cholesterol in synaptic endocytosis remains controversial because of conflicting observations, technical limitations in previous studies, and potential interference from non-specific effects after cholesterol manipulation. Furthermore, it remains unclear whether cholesterol participates in distinct forms of endocytosis that function under different activity levels. In this study, applying the whole-cell membrane capacitance measurement to monitor endocytosis in real time at the rat calyx of Held terminals, we found that disrupting cholesterol with dialysis of cholesterol oxidase or methyl-β-cyclodextrin impaired three different forms of endocytosis, including slow endocytosis, rapid endocytosis, and endocytosis of the retrievable membrane that exists at the surface before stimulation. The effects were observed when disruption of cholesterol was mild enough not to change Ca(2+) channel current or vesicle exocytosis, indicative of stringent cholesterol requirement in synaptic endocytosis. Extracting cholesterol with high concentrations of methyl-β-cyclodextrin reduced exocytosis, mainly by decreasing the readily releasable pool and the vesicle replenishment after readily releasable pool depletion. Our study suggests that cholesterol is an important, universal regulator in multiple forms of vesicle endocytosis at mammalian central synapses.

  15. Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions.

    Science.gov (United States)

    Matsuda, Keiko; Yuzaki, Michisuke

    2011-04-01

    Cbln1 (a.k.a. precerebellin) is a unique bidirectional synaptic organizer that plays an essential role in the formation and maintenance of excitatory synapses between granule cells and Purkinje cells in the mouse cerebellum. Cbln1 secreted from cerebellar granule cells directly induces presynaptic differentiation and indirectly serves as a postsynaptic organizer by binding to its receptor, the δ2 glutamate receptor. However, it remains unclear how Cbln1 binds to the presynaptic sites and interacts with other synaptic organizers. Furthermore, although Cbln1 and its family members Cbln2 and Cbln4 are expressed in brain regions other than the cerebellum, it is unknown whether they regulate synapse formation in these brain regions. In this study, we showed that Cbln1 and Cbln2, but not Cbln4, specifically bound to its presynaptic receptor -α and β isoforms of neurexin carrying the splice site 4 insert [NRXs(S4+)] - and induced synaptogenesis in cerebellar, hippocampal and cortical neurons in vitro. Cbln1 competed with synaptogenesis mediated by neuroligin 1, which lacks the splice sites A and B, but not leucine-rich repeat transmembrane protein 2, possibly by sharing the presynaptic receptor NRXs(S4+). However, unlike neurexins/neuroligins or neurexins/leucine-rich repeat transmembrane proteins, the interaction between NRX1β(S4+) and Cbln1 was insensitive to extracellular Ca(2+) concentrations. These findings revealed the unique and general roles of Cbln family proteins in mediating the formation and maintenance of synapses not only in the cerebellum but also in various other brain regions.

  16. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells

    Directory of Open Access Journals (Sweden)

    Migneault Martine

    2010-01-01

    Full Text Available Abstract Background Cancer cells utilize a variety of mechanisms to evade immune detection and attack. Effective immune detection largely relies on the formation of an immune synapse which requires close contact between immune cells and their targets. Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets. Our results indicate that MUC16-mediated inhibition of immune synapse formation is an effective mechanism employed by ovarian tumors to evade immune recognition. Results Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells. MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls. This increased lysis was not due to differences in the expression levels of the ligands for the activating receptors DNAM-1 and NKG2D. The NK cell leukemia cell line (NKL, which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls. Tumor cells that survived the NKL challenge expressed higher levels of MUC16 indicating selective lysis of MUC16low targets. The higher csMUC16 levels on the NKL resistant tumor cells correlated with more protection from lysis as compared to target cells that were never exposed to the effectors. Conclusion MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets. Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells. The immune protection provided by MUC16 may lead to selective survival of ovarian cancer cells that are more efficient in

  17. Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons.

    Science.gov (United States)

    Alvarez, Francisco J; Titus-Mitchell, Haley E; Bullinger, Katie L; Kraszpulski, Michal; Nardelli, Paul; Cope, Timothy C

    2011-11-01

    Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped from motoneurons, but while other excitatory and inhibitory inputs eventually recover, VGLUT1 synapses are permanently lost on the cell body (75-95% synaptic losses) and on the proximal 100 μm of dendrite (50% loss). Lost VGLUT1 synapses did not recover, even many months after muscle reinnervation. Interestingly, VGLUT1 density in more distal dendrites did not change. To investigate whether losses are due to VGLUT1 downregulation in injured IA afferents or to complete synaptic disassembly and regression of IA ventral projections, we studied the central trajectories and synaptic varicosities of axon collaterals from control and regenerated afferents with IA-like responses to stretch that were intracellularly filled with neurobiotin. VGLUT1 was present in all synaptic varicosities, identified with the synaptic marker SV2, of control and regenerated afferents. However, regenerated afferents lacked axon collaterals and synapses in lamina IX. In conjunction with the companion electrophysiological study [Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01097.2010], we conclude that peripheral nerve injuries cause a permanent retraction of IA afferent synaptic varicosities from lamina IX and disconnection with motoneurons that is not recovered after peripheral regeneration and reinnervation of muscle by sensory and motor axons.

  18. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor.

    Science.gov (United States)

    Parkhurst, Christopher N; Yang, Guang; Ninan, Ipe; Savas, Jeffrey N; Yates, John R; Lafaille, Juan J; Hempstead, Barbara L; Littman, Dan R; Gan, Wen-Biao

    2013-12-19

    Microglia are the resident macrophages of the CNS, and their functions have been extensively studied in various brain pathologies. The physiological roles of microglia in brain plasticity and function, however, remain unclear. To address this question, we generated CX3CR1(CreER) mice expressing tamoxifen-inducible Cre recombinase that allow for specific manipulation of gene function in microglia. Using CX3CR1(CreER) to drive diphtheria toxin receptor expression in microglia, we found that microglia could be specifically depleted from the brain upon diphtheria toxin administration. Mice depleted of microglia showed deficits in multiple learning tasks and a significant reduction in motor-learning-dependent synapse formation. Furthermore, Cre-dependent removal of brain-derived neurotrophic factor (BDNF) from microglia largely recapitulated the effects of microglia depletion. Microglial BDNF increases neuronal tropomyosin-related kinase receptor B phosphorylation, a key mediator of synaptic plasticity. Together, our findings reveal that microglia serve important physiological functions in learning and memory by promoting learning-related synapse formation through BDNF signaling.

  19. Neuronal differentiation and synapse formation occur in space and time with fractal dimension.

    Science.gov (United States)

    Waliszewski, Przemyslaw; Konarski, Jerzy

    2002-03-15

    The analysis of a set of experimental data obtained by an independent team of researchers confirms that neuronal differentiation or synapse formation do occur in time and space with fractal dimension. The interacting cells create first a dynamic system with its own attractor, (i.e., a fragment of time and space where the dynamic processes occur and where no further evolution of the system is possible at all owing to the action of the intrasystemic forces unless some extrasystemic forces act upon it). This attractor is then modified in the active manner by the differentiating cells until the system attains a degenerated stationary state and differentiation ends. The fractal structure of the system is also lost in the course of tumor progression. Our data indicate that the cellular system can attain the degenerated stationary state, leaving the attractor with a fractal dimension directly or undergoing diversification into many attractors and going through the areas of deterministic chaos. Since evolution of the cellular system is driven by the cooperative dynamic processes, as reflected by the changes of the mean fractal dimension between the intervals of the Gompertzian curve, it is likely that cells differentiate into neurons and create synapses with a conjugated probability and non-Gaussian distribution rather than with the classical probability and the Gaussian distribution. These findings can help to optimize features of artificial neural networks. They also define a simple in vitro biological model for biophysical and biochemical studies on natural neural networks.

  20. The Effects of Neuregulin on Synapse Formation in Primary Muscle/Nerve Co-Cultures

    Directory of Open Access Journals (Sweden)

    Jessica Walsh

    2007-06-01

    Full Text Available In development, motor neurons innervate maturing myotubes to form the neuromuscular junction (NMJ. During this process, the nerve terminal secretes a protein called neuregulin (NRG1. NRG1 acts as a signal which increases the number of acetylcholine receptors (AChRs on the postsynaptic membrane. NRG1 binds to receptors on the surface of the muscle, known as erbB receptors. The binding of NRG1 causes the erbB receptor to auto-phosphorylate (Fu, 1999. As a result, there is an increase in transcription of the gene for AchRs, integral membrane proteins that respond to the binding of the neurotransmitter acetylcholine. In order to study the effects of NRG1 on early stages of synapse formation, we prepared co-cultures of dissociated muscle cells from postnatal day 1 (P1 mice and neural tube explants from embryonic day 11 (E11 mice. Silicone chambers were created as a system for growing dissociated muscle cells and neuronal explants in co-culture (Loeb, 1999. ErbB inhibitor (PD 158780 was added to chambers prior to the formation of the NMJ. After one week the tissue was fixed and stained to visualize the synapses. Based on the results of two experiments, the chambers that were not treated with the inhibitor had an average of 10 times more AchR (+ contacts. Therefore, at the time point studied, it appears that NRG1 signaling through the erbB receptor tyrosine kinases is necessary for the formation of AchR (+ receptor contacts at the motor terminal in the post-synaptic membrane.

  1. Nanodomain coupling explains Ca2+ independence of transmitter release time course at a fast central synapse

    OpenAIRE

    2014-01-01

    eLife digest The nervous system sends information around the body in the form of electrical signals that travel through cells called neurons. However, these electrical signals cannot cross the synapses between neurons. Instead, the information is carried across the synapse by molecules called neurotransmitters. Calcium ions control the release of neurotransmitters. There is a high concentration of calcium ions outside the neuron but they are not able to pass through the cell membrane under no...

  2. Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum.

    Science.gov (United States)

    Uemura, Takeshi; Lee, Sung-Jin; Yasumura, Misato; Takeuchi, Tomonori; Yoshida, Tomoyuki; Ra, Moonjin; Taguchi, Ryo; Sakimura, Kenji; Mishina, Masayoshi

    2010-06-11

    Elucidation of molecular mechanisms that regulate synapse formation is required for the understanding of neural wiring, higher brain functions, and mental disorders. Despite the wealth of in vitro information, fundamental questions about how glutamatergic synapses are formed in the mammalian brain remain unanswered. Glutamate receptor (GluR) delta2 is essential for cerebellar synapse formation in vivo. Here, we show that the N-terminal domain (NTD) of GluRdelta2 interacts with presynaptic neurexins (NRXNs) through cerebellin 1 precursor protein (Cbln1). The synaptogenic activity of GluRdelta2 is abolished in cerebellar primary cultures from Cbln1 knockout mice and is restored by recombinant Cbln1. Knockdown of NRXNs in cerebellar granule cells also hinders the synaptogenic activity of GluRdelta2. Both the NTD of GluRdelta2 and the extracellular domain of NRXN1beta suppressed the synaptogenic activity of Cbln1 in cerebellar primary cultures and in vivo. These results suggest that GluRdelta2 mediates cerebellar synapse formation by interacting with presynaptic NRXNs through Cbln1.

  3. Quantifying Signaling-Induced Reorientation of TCR's During Immunological Synapse Formation

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    Moss, W C; Irvine, D J; Davis, M M; Krummel, M F

    2002-10-17

    Productive T cell recognition of antigen-presenting cells (APCs) is normally accompanied by the formation of a cell-cell contact called the 'immunological synapse.' Our understanding of the steps leading up to this formation has been limited by the absence of tools for analyzing 3D surfaces and surface distributions as they change over time. Here we use a 3D fluorescence quantitation method to show that T cell receptors are recruited in bulk within the first minute after the onset of activation and with velocities ranging from 0.04 to 0.1 {micro}m/s; a speed significantly greater than unrestricted diffusion. Our method reveals a second feature of this reorientation: a conformational change as the T cell pushes more total membrane into the interface creating a larger contact area for additional receptors. Analysis of individual T cell receptor velocities using a single-particle tracking method confirms our velocity measurement. This method should permit the quantitation of other dynamic membrane events and the associated movement of cell-surface molecules.

  4. The adaptor molecule SAP plays essential roles during invariant NKT cell cytotoxicity and lytic synapse formation.

    Science.gov (United States)

    Das, Rupali; Bassiri, Hamid; Guan, Peng; Wiener, Susan; Banerjee, Pinaki P; Zhong, Ming-Chao; Veillette, André; Orange, Jordan S; Nichols, Kim E

    2013-04-25

    The adaptor molecule signaling lymphocytic activation molecule-associated protein (SAP) plays critical roles during invariant natural killer T (iNKT) cell ontogeny. As a result, SAP-deficient humans and mice lack iNKT cells. The strict developmental requirement for SAP has made it difficult to discern its possible involvement in mature iNKT cell functions. By using temporal Cre recombinase-mediated gene deletion to ablate SAP expression after completion of iNKT cell development, we demonstrate that SAP is essential for T-cell receptor (TCR)-induced iNKT cell cytotoxicity against T-cell and B-cell leukemia targets in vitro and iNKT-cell-mediated control of T-cell leukemia growth in vivo. These findings are not restricted to the murine system: silencing RNA-mediated suppression of SAP expression in human iNKT cells also significantly impairs TCR-induced cytolysis. Mechanistic studies reveal that iNKT cell killing requires the tyrosine kinase Fyn, a known SAP-binding protein. Furthermore, SAP expression is required within iNKT cells to facilitate their interaction with T-cell targets and induce reorientation of the microtubule-organizing center to the immunologic synapse (IS). Collectively, these studies highlight a novel and essential role for SAP during iNKT cell cytotoxicity and formation of a functional IS.

  5. Function and Dynamics of Tetraspanins during Antigen Recognition and Immunological Synapse Formation

    Directory of Open Access Journals (Sweden)

    Vera eRocha-Perugini

    2016-01-01

    Full Text Available Tetraspanin-enriched microdomains (TEMs are specialized membrane platforms driven by protein-protein interactions that integrate membrane receptors and adhesion molecules. Tetraspanins participate in antigen recognition and presentation by antigen presenting cells (APCs through the organization of pattern recognition receptors (PRRs and their downstream induced-signaling, as well as the regulation of MHC-II-peptide trafficking. T lymphocyte activation is triggered upon specific recognition of antigens present on the APC surface during immunological synapse (IS formation. This dynamic process is characterized by a defined spatial organization involving the compartmentalization of receptors and adhesion molecules in specialized membrane domains that are connected to the underlying cytoskeleton and signaling molecules. Tetraspanins contribute to the spatial organization and maturation of the IS by controlling receptor clustering and local accumulation of adhesion receptors and integrins, their downstream signaling and linkage to the actin cytoskeleton. This review offers a perspective on the important role of TEMs in the regulation of antigen recognition and presentation, and in the dynamics of IS architectural organization.

  6. Spontaneous synaptic activity is required for the formation of functional GABAergic synapses in the developing rat hippocampus.

    Science.gov (United States)

    Colin-Le Brun, Isabelle; Ferrand, Nadine; Caillard, Olivier; Tosetti, Patrizia; Ben-Ari, Yehezkel; Gaïarsa, Jean-Luc

    2004-08-15

    Here we examine the role of the spontaneous synaptic activity generated by the developing rat hippocampus in the formation of functional gamma-aminobutyric acid (GABA) synapses. Intact hippocampal formations (IHFs) were dissected at birth and incubated for 1 day in control or tetrodotoxin (TTX)-supplemented medium at 25 degrees C. After the incubation, miniature GABA(A)-mediated postsynaptic currents (mGABA(A)-PSCs) were recorded in whole-cell voltage-clamped CA3 pyramidal neurones from IHF-derived slices. After 1 day in vitro in control medium, the frequency of mGABA(A)-PSCs was similar to that recorded in acute slices obtained 1 day after birth, but significantly higher than the frequency recorded from acute slices just after birth. These results suggest that the factors required in vivo for the formation of functional GABAergic synapses are preserved in the IHFs in vitro. The frequency increase was prevented when IHFs were incubated for 1 day with TTX. TTX treatment affected neither the morphology of CA3 pyramidal neurones nor cell viability. The TTX effects were reproduced when IHFs were incubated in the presence of glutamatergic or GABAergic ionotropic receptor antagonists or in high divalent cationic medium. The present results indicate that the spontaneous synaptic activity generated by the developing hippocampus is a key player in the formation of functional GABAergic synapses, possibly via network events requiring both glutamatergic and GABAergic receptors.

  7. Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation.

    Science.gov (United States)

    Ito-Ishida, Aya; Miyazaki, Taisuke; Miura, Eriko; Matsuda, Keiko; Watanabe, Masahiko; Yuzaki, Michisuke; Okabe, Shigeo

    2012-11-08

    Differentiation of pre- and postsynaptic sites is coordinated by reciprocal interaction across synaptic clefts. At parallel fiber (PF)-Purkinje cell (PC) synapses, dendritic spines are autonomously formed without PF influence. However, little is known about how presynaptic structural changes are induced and how they lead to differentiation of mature synapses. Here, we show that Cbln1 released from PFs induces dynamic structural changes in PFs by a mechanism that depends on postsynaptic glutamate receptor delta2 (GluD2) and presynaptic neurexin (Nrx). Time-lapse imaging in organotypic culture and ultrastructural analyses in vivo revealed that Nrx-Cbln1-GluD2 signaling induces PF protrusions that often formed circular structures and encapsulated PC spines. Such structural changes in PFs were associated with the accumulation of synaptic vesicles and GluD2, leading to formation of mature synapses. Thus, PF protrusions triggered by Nrx-Cbln1-GluD2 signaling may promote bidirectional maturation of PF-PC synapses by a positive feedback mechanism.

  8. The Strip-Hippo Pathway Regulates Synaptic Terminal Formation by Modulating Actin Organization at the Drosophila Neuromuscular Synapses

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    Chisako Sakuma

    2016-08-01

    Full Text Available Synapse formation requires the precise coordination of axon elongation, cytoskeletal stability, and diverse modes of cell signaling. The underlying mechanisms of this interplay, however, remain unclear. Here, we demonstrate that Strip, a component of the striatin-interacting phosphatase and kinase (STRIPAK complex that regulates these processes, is required to ensure the proper development of synaptic boutons at the Drosophila neuromuscular junction. In doing so, Strip negatively regulates the activity of the Hippo (Hpo pathway, an evolutionarily conserved regulator of organ size whose role in synapse formation is currently unappreciated. Strip functions genetically with Enabled, an actin assembly/elongation factor and the presumptive downstream target of Hpo signaling, to modulate local actin organization at synaptic termini. This regulation occurs independently of the transcriptional co-activator Yorkie, the canonical downstream target of the Hpo pathway. Our study identifies a previously unanticipated role of the Strip-Hippo pathway in synaptic development, linking cell signaling to actin organization.

  9. Paracrine intercellular communication by a Ca2+- and SNARE-independent release of GABA and glutamate prior to synapse formation.

    Science.gov (United States)

    Demarque, Michael; Represa, Alfonso; Becq, Hélène; Khalilov, Ilgam; Ben-Ari, Yehezkel; Aniksztejn, Laurent

    2002-12-19

    GABA and glutamate receptors are expressed in immature "silent" CA1 pyramidal neurons prior to synapse formation, but their function is unknown. We now report the presence of tonic, spontaneous, and evoked currents in embryonic and neonatal CA1 neurons mediated primarily by the activation of GABA(A) receptors. These currents are mediated by a nonconventional release of transmitters, as they persist in the presence of calcium channel blockers or botulinium toxin and are observed in Munc18-1-deficient mice in which vesicular release is abolished. This paracrine communication is modulated by glutamate but not GABA transporters, which do not operate during this period of life. Thus, a Ca(2+)- and SNARE-independent release of transmitters underlies a paracrine mode of communication before synapse formation.

  10. Early cytoskeletal rearrangement during dendritic cell maturation enhances synapse formation and Ca(2+) signaling in CD8(+) T cells.

    Science.gov (United States)

    Averbeck, Marco; Braun, Thorsten; Pfeifer, Gunther; Sleeman, Jonathan; Dudda, Jan; Martin, Stefan F; Kremer, Bernhard; Aktories, Klaus; Simon, Jan C; Termeer, Christian

    2004-10-01

    The interplay between dendritic cells (DC) and T cells is a dynamic process critically depending on DC maturation. Ca(2+) influx is one of the initial events occurring during DC/T cell contacts. To determine how DC maturation influences DC/T cell contacts, time-lapse video microscopy was established using TCR-transgenic CD8(+) T cells from P14 mice. DC maturation shifted DC/T cell contacts from short-lived interactions with transient Ca(2+) influx in T cells to long-lasting interactions and sustained Ca(2+) influx of 30 min and more. Follow-up of DC/T cell interactions after 2 h using confocal microscopy revealed that long-lasting Ca(2+) responses in T cells were preferentially associated with the formation of an immunological synapse involving CD54 and H2-K(b) at the DC/T cell interface. Such synapse formation preceded MHC or B7 up-regulation, since DC developed into potent Ca(2+) stimulators 7 h after initiation of maturation. Instead, the enhanced capacity of 7 h-matured DC to induce sustained Ca(2+) responses in CD8(+) T cells is critically dependent on the polarization and rearrangement of the cytoskeleton, as shown by Clostridium difficile toxin B inhibitor experiments. These data indicate that already very early after receiving a maturation stimulus, DC display enhanced cytoskeletal activity resulting in the rapid formation of immunological synapses and effective CD8(+) T cell stimulation.

  11. Calcium Signalling Triggered by NAADP in T Cells Determines Cell Shape and Motility During Immune Synapse Formation

    Science.gov (United States)

    Nebel, Merle; Zhang, Bo; Odoardi, Francesca; Flügel, Alexander; Potter, Barry V. L.; Guse, Andreas H.

    2016-01-01

    Nicotinic acid adenine dinucleotide phosphate (NAADP) has been implicated as an initial Ca2+ trigger in T cell Ca2+ signalling, but its role in formation of the immune synapse in CD4+ effector T cells has not been analysed. CD4+ T cells are activated by the interaction with peptide-MHCII complexes on the surface of antigen-presenting cells. Establishing a two-cell system including primary rat CD4+ T cells specific for myelin basic protein and rat astrocytes enabled us to mirror this activation process in vitro and to analyse Ca2+ signalling, cell shape changes and motility in T cells during formation and maintenance of the immune synapse. After immune synapse formation, T cells showed strong, antigen-dependent increases in free cytosolic calcium concentration ([Ca2+]i). Analysis of cell shape and motility revealed rounding and immobilization of T cells depending on the amplitude of the Ca2+ signal. NAADP-antagonist BZ194 effectively blocked Ca2+ signals in T cells evoked by the interaction with antigen-presenting astrocytes. BZ194 reduced the percentage of T cells showing high Ca2+ signals thereby supporting the proposed trigger function of NAADP for global Ca2+ signalling. Taken together, the NAADP signalling pathway is further confirmed as a promising target for specific pharmacological intervention to modulate T cell activation. PMID:27747143

  12. Loss of SynDIG1 Reduces Excitatory Synapse Maturation But Not Formation In Vivo

    Science.gov (United States)

    Kaur, Inderpreet; Liu, Xiao-Bo; Kirk, Lyndsey M.; Speca, David J.; McMahon, Samuel A.; Zito, Karen

    2016-01-01

    Abstract Modification of the strength of excitatory synaptic connections is a fundamental mechanism by which neural circuits are refined during development and learning. Synapse Differentiation Induced Gene 1 (SynDIG1) has been shown to play a key role in regulating synaptic strength in vitro. Here, we investigated the role of SynDIG1 in vivo in mice with a disruption of the SynDIG1 gene rather than use an alternate loxP-flanked conditional mutant that we find retains a partial protein product. The gene-trap insertion with a reporter cassette mutant mice shows that the SynDIG1 promoter is active during embryogenesis in the retina with some activity in the brain, and postnatally in the mouse hippocampus, cortex, hindbrain, and spinal cord. Ultrastructural analysis of the hippocampal CA1 region shows a decrease in the average PSD length of synapses and a decrease in the number of synapses with a mature phenotype. Intriguingly, the total synapse number appears to be increased in SynDIG1 mutant mice. Electrophysiological analyses show a decrease in AMPA and NMDA receptor function in SynDIG1-deficient hippocampal neurons. Glutamate stimulation of individual dendritic spines in hippocampal slices from SynDIG1-deficient mice reveals increased short-term structural plasticity. Notably, the overall levels of PSD-95 or glutamate receptors enriched in postsynaptic biochemical fractions remain unaltered; however, activity-dependent synapse development is strongly compromised upon the loss of SynDIG1, supporting its importance for excitatory synapse maturation. Together, these data are consistent with a model in which SynDIG1 regulates the maturation of excitatory synapse structure and function in the mouse hippocampus in vivo.

  13. DC-SIGN-mediated infectious synapse formation enhances X4 HIV-1 transmission from dendritic cells to T cells.

    Science.gov (United States)

    Arrighi, Jean-François; Pion, Marjorie; Garcia, Eduardo; Escola, Jean-Michel; van Kooyk, Yvette; Geijtenbeek, Teunis B; Piguet, Vincent

    2004-11-15

    Dendritic cells (DCs) are essential for the early events of human immunodeficiency virus (HIV) infection. Model systems of HIV sexual transmission have shown that DCs expressing the DC-specific C-type lectin DC-SIGN capture and internalize HIV at mucosal surfaces and efficiently transfer HIV to CD4+ T cells in lymph nodes, where viral replication occurs. Upon DC-T cell clustering, internalized HIV accumulates on the DC side at the contact zone (infectious synapse), between DCs and T cells, whereas HIV receptors and coreceptors are enriched on the T cell side. Viral concentration at the infectious synapse may explain, at least in part, why DC transmission of HIV to T cells is so efficient.Here, we have investigated the role of DC-SIGN on primary DCs in X4 HIV-1 capture and transmission using small interfering RNA-expressing lentiviral vectors to specifically knockdown DC-SIGN. We demonstrate that DC-SIGN- DCs internalize X4 HIV-1 as well as DC-SIGN+ DCs, although binding of virions is reduced. Strikingly, DC-SIGN knockdown in DCs selectively impairs infectious synapse formation between DCs and resting CD4+ T cells, but does not prevent the formation of DC-T cells conjugates. Our results demonstrate that DC-SIGN is required downstream from viral capture for the formation of the infectious synapse between DCs and T cells. These findings provide a novel explanation for the role of DC-SIGN in the transfer and enhancement of HIV infection from DCs to T cells, a crucial step for HIV transmission and pathogenesis.

  14. The Effect of Desflurane on Neuronal Communication at a Central Synapse

    Science.gov (United States)

    Mapelli, Jonathan; Gandolfi, Daniela; Giuliani, Enrico; Prencipe, Francesco P.; Pellati, Federica; Barbieri, Alberto; D’Angelo, Egidio; Bigiani, Albertino

    2015-01-01

    Although general anesthetics are thought to modify critical neuronal functions, their impact on neuronal communication has been poorly examined. We have investigated the effect induced by desflurane, a clinically used general anesthetic, on information transfer at the synapse between mossy fibers and granule cells of cerebellum, where this analysis can be carried out extensively. Mutual information values were assessed by measuring the variability of postsynaptic output in relationship to the variability of a given set of presynaptic inputs. Desflurane synchronized granule cell firing and reduced mutual information in response to physiologically relevant mossy fibers patterns. The decrease in spike variability was due to an increased postsynaptic membrane excitability, which made granule cells more prone to elicit action potentials, and to a strengthened synaptic inhibition, which markedly hampered membrane depolarization. These concomitant actions on granule cells firing indicate that desflurane re-shapes the transfer of information between neurons by providing a less informative neurotransmission rather than completely silencing neuronal activity. PMID:25849222

  15. The contribution of electrical synapses to field potential oscillations in the hippocampal formation.

    Science.gov (United States)

    Posłuszny, Anna

    2014-01-01

    Electrical synapses are a type of cellular membrane junction referred to as gap junctions (GJs). They provide a direct way to exchange ions between coupled cells and have been proposed as a structural basis for fast transmission of electrical potentials between neurons in the brain. For this reason GJs have been regarded as an important component within the neuronal networks that underlie synchronous neuronal activity and field potential oscillations. Initially, GJs appeared to play a particularly key role in the generation of high frequency oscillatory patterns in field potentials. In order to assess the scale of neuronal GJs contribution to field potential oscillations in the hippocampal formation, in vivo and in vitro studies are reviewed here. These investigations have shown that blocking the main neuronal GJs, those containing connexin 36 (Cx36-GJs), or knocking out the Cx36 gene affect field potential oscillatory patterns related to awake active behavior (gamma and theta rhythm) but have no effect on high frequency oscillations occurring during silent wake and sleep. Precisely how Cx36-GJs influence population activity of neurons is more complex than previously thought. Analysis of studies on the properties of transmission through GJ channels as well as Cx36-GJs functioning in pairs of coupled neurons provides some explanations of the specific influence of Cx36-GJs on field potential oscillations. It is proposed here that GJ transmission is strongly modulated by the level of neuronal network activity and changing behavioral states. Therefore, contribution of GJs to field potential oscillatory patterns depends on the behavioral state. I propose here a model, based on large body of experimental data gathered in this field by several authors, in which Cx36-GJ transmission especially contributes to oscillations related to active behavior, where it plays a role in filtering and enhancing coherent signals in the network under high-noise conditions. In contrast

  16. Cbln1 and its family proteins in synapse formation and maintenance.

    Science.gov (United States)

    Yuzaki, Michisuke

    2011-04-01

    Cbln1 is a newly identified synaptic organizer belonging to the C1q family. Unlike other synaptic organizers, a deficiency in Cbln1 is sufficient to cause a severe reduction in the number of synapses between cerebellar Purkinje cells and parallel fibers (PFs). Furthermore, Cbln1 can rapidly induce synaptogenesis and is necessary for maintaining normal synapses in the mature cerebellum in vivo. Cbln1 was recently identified as the missing ligand for the orphan glutamate receptor δ2 (GluD2), which is expressed in Purkinje cells. Furthermore, Cbln1 released from PFs binds to neurexin (NRX) expressed on the presynaptic PFs and GluD2 at the postsynaptic site. The NRX/Cbln1/GluD2 tripartite complex is resistant to low extracellular Ca2+ levels and serves as a unique bidirectional synaptic organizer.

  17. Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses.

    Science.gov (United States)

    Sylantyev, Sergiy; Jensen, Thomas P; Ross, Ruth A; Rusakov, Dmitri A

    2013-03-26

    G protein-coupled receptor (GPR) 55 is sensitive to certain cannabinoids, it is expressed in the brain and, in cell cultures, it triggers mobilization of intracellular Ca(2+). However, the adaptive neurobiological significance of GPR55 remains unknown. Here, we use acute hippocampal slices and combine two-photon excitation Ca(2+) imaging in presynaptic axonal boutons with optical quantal analysis in postsynaptic dendritic spines to find that GPR55 activation transiently increases release probability at individual CA3-CA1 synapses. The underlying mechanism involves Ca(2+) release from presynaptic Ca(2+) stores, whereas postsynaptic stores (activated by spot-uncaging of inositol 1,4,5-trisphosphate) remain unaffected by GPR55 agonists. These effects are abolished by genetic deletion of GPR55 or by the GPR55 antagonist cannabidiol, a constituent of Cannabis sativa. GPR55 shows colocalization with synaptic vesicle protein vesicular glutamate transporter 1 in stratum radiatum. Short-term potentiation of CA3-CA1 transmission after a short train of stimuli reveals a presynaptic, Ca(2+) store-dependent component sensitive to cannabidiol. The underlying cascade involves synthesis of phospholipids, likely in the presynaptic cell, but not the endocannabinoids 2-arachidonoylglycerol or anandamide. Our results thus unveil a signaling role for GPR55 in synaptic circuits of the brain.

  18. Serotonin modulates transmitter release at central Lymnaea synapses through a G-protein-coupled and cAMP-mediated pathway.

    Science.gov (United States)

    McCamphill, P K; Dunn, T W; Syed, N I

    2008-04-01

    Neuromodulation is central to all nervous system function, although the precise mechanisms by which neurotransmitters affect synaptic efficacy between central neurons remain to be fully elucidated. In this study, we examined the neuromodulatory action of serotonin [5-hydroxytryptamine (5-HT)] at central synapses between identified neurons from the pond snail Lymnaea stagnalis. Using whole-cell voltage-clamp and sharp electrode recording, we show that 5-HT strongly depresses synaptic strength between cultured, cholinergic neuron visceral dorsal 4 (VD4 - presynaptic) and its serotonergic target left pedal dorsal 1 (LPeD1 - postsynaptic). This inhibition was accompanied by a reduction in synaptic depression, but had no effect on postsynaptic input resistance, indicating a presynaptic origin. In addition, serotonin inhibited the presynaptic calcium current (I(Ca)) on a similar time course as the change in synaptic transmission. Introduction of a non-condensable GDP analog, GDP-beta-S, through the presynaptic pipette inhibited the serotonin-mediated effect on I(Ca.) Similar results were obtained with a membrane-impermeable inactive cAMP analog, 8OH-cAMP. Furthermore, stimulation of the serotonergic postsynaptic cell also inhibited presynaptic currents, indicating the presence of a negative feedback loop between LPeD1 and VD4. Taken together, this study provides direct evidence for a negative feedback mechanism, whereby the activity of a presynaptic respiratory central pattern-generating neuron is regulated by its postsynaptic target cell. We demonstrate that either serotonin or LPeD1 activity-induced depression of presynaptic transmitter release from VD4 involves voltage-gated calcium channels and is mediated through a G-protein-coupled and cAMP-mediated system.

  19. Cross-dressing by donor dendritic cells after allogeneic bone marrow transplantation contributes to formation of the immunological synapse and maximizes responses to indirectly presented antigen.

    Science.gov (United States)

    Markey, Kate A; Koyama, Motoko; Gartlan, Kate H; Leveque, Lucie; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; MacDonald, Kelli P A; Hill, Geoffrey R

    2014-06-01

    The stimulation of naive donor T cells by recipient alloantigen is central to the pathogenesis of graft-versus-host disease after bone marrow transplantation (BMT). Using mouse models of transplantation, we have observed that donor cells become "cross-dressed" in very high levels of recipient hematopoietic cell-derived MHC class I and II molecules following BMT. Recipient-type MHC is transiently present on donor dendritic cells (DCs) after BMT in the setting of myeloablative conditioning but is persistent after nonmyeloablative conditioning, in which recipient hematopoietic cells remain in high numbers. Despite the high level of recipient-derived alloantigen present on the surface of donor DCs, donor T cell proliferative responses are generated only in response to processed recipient alloantigen presented via the indirect pathway and not in response to cross-dressed MHC. Assays in which exogenous peptide is added to cross-dressed MHC in the presence of naive TCR transgenic T cells specific to the MHC class II-peptide combination confirm that cross-dressed APC cannot induce T cell proliferation in isolation. Despite failure to induce T cell proliferation, cross-dressing by donor DCs contributes to generation of the immunological synapse between DCs and CD4 T cells, and this is required for maximal responses induced by classical indirectly presented alloantigen. We conclude that the process of cross-dressing by donor DCs serves as an efficient alternative pathway for the acquisition of recipient alloantigen and that once acquired, this cross-dressed MHC can assist in immune synapse formation prior to the induction of full T cell proliferative responses by concurrent indirect Ag presentation.

  20. Associations of Unilateral Whisker and Olfactory Signals Induce Synapse Formation and Memory Cell Recruitment in Bilateral Barrel Cortices: Cellular Mechanism for Unilateral Training Toward Bilateral Memory

    Science.gov (United States)

    Gao, Zilong; Chen, Lei; Fan, Ruicheng; Lu, Wei; Wang, Dangui; Cui, Shan; Huang, Li; Zhao, Shidi; Guan, Sudong; Zhu, Yan; Wang, Jin-Hui

    2016-01-01

    Somatosensory signals and operative skills learned by unilateral limbs can be retrieved bilaterally. In terms of cellular mechanism underlying this unilateral learning toward bilateral memory, we hypothesized that associative memory cells in bilateral cortices and synapse innervations between them were produced. In the examination of this hypothesis, we have observed that paired unilateral whisker and odor stimulations led to odorant-induced whisker motions in bilateral sides, which were attenuated by inhibiting the activity of barrel cortices. In the mice that showed bilateral cross-modal responses, the neurons in both sides of barrel cortices became to encode this new odor signal alongside the innate whisker signal. Axon projections and synapse formations from the barrel cortex, which was co-activated with the piriform cortex, toward its contralateral barrel cortex (CBC) were upregulated. Glutamatergic synaptic transmission in bilateral barrel cortices was upregulated and GABAergic synaptic transmission was downregulated. The associative activations of the sensory cortices facilitate new axon projection, glutamatergic synapse formation and GABAergic synapse downregulation, which drive the neurons to be recruited as associative memory cells in the bilateral cortices. Our data reveal the productions of associative memory cells and synapse innervations in bilateral sensory cortices for unilateral training toward bilateral memory. PMID:28018178

  1. Associations of unilateral whisker and olfactory signals induce synapse formation and memory cell recruitment in bilateral barrel cortices: cellular mechanism for unilateral training toward bilateral memory

    Directory of Open Access Journals (Sweden)

    Zilong Gao

    2016-12-01

    Full Text Available Somatosensory signals and operative skills learned by unilateral limbs can be retrieved bilaterally. In terms of cellular mechanism underlying this unilateral learning toward bilateral memory, we hypothesized that associative memory cells in bilateral cortices and synapse innervations between them were produced. In the examination of this hypothesis, we have observed that paired unilateral whisker and odor stimulations led to odorant-induced whisker motions in bilateral sides, which were attenuated by inhibiting the activity of barrel cortices. In the mice that showed bilateral cross-modal responses, the neurons in both sides of barrel cortices became to encode this new odor signal alongside the innate whisker signal. Axon projections and synapse formations from the barrel cortex, which was co-activated with the piriform cortex, toward its contralateral barrel cortex were upregulated. Glutamatergic synaptic transmission in bilateral barrel cortices was upregulated and GABAergic synaptic transmission was downregulated. The associative activations of the sensory cortices facilitate new axon projection, glutamatergic synapse formation and GABAergic synapse downregulation, which drive the neurons to be recruited as associative memory cells in the bilateral cortices. Our data reveals the productions of associative memory cells and synapse innervations in bilateral sensory cortices for unilateral training toward bilateral memory.

  2. Differential interactions of cerebellin precursor protein (Cbln) subtypes and neurexin variants for synapse formation of cortical neurons.

    Science.gov (United States)

    Joo, Jae-Yeol; Lee, Sung-Jin; Uemura, Takeshi; Yoshida, Tomoyuki; Yasumura, Misato; Watanabe, Masahiko; Mishina, Masayoshi

    2011-03-25

    Trans-synaptic interaction of postsynaptic glutamate receptor δ2 and presynaptic neurexins (NRXNs) through cerebellin precursor protein (Cbln) 1 mediates synapse formation in the cerebellum [T. Uemura, S.J. Lee, M. Yasumura, T. Takeuchi, T. Yoshida, M. Ra, R. Taguchi, K. Sakimura, M. Mishina, Cell 141 (2010) 1068-1079]. This finding raises a question whether other Cbln family members interact with NRXNs to regulate synapse formation in the forebrain. Here, we showed that Cbln1 and Cbln2 induced presynaptic differentiation of cultured cortical neurons, while Cbln4 exhibited little activity. When compared with neuroligin 1, Cbln1 and Cbln2 induced preferentially inhibitory presynaptic differentiation rather than excitatory one in cortical cultures. The synaptogenic activities of Cbln1 and Cbln2 were suppressed by the addition of the extracellular domain of NRXN1β to the cortical neuron cultures. Consistently, Cbln1 and Cbln2 showed robust binding activities to NRXN1α and three β-NRXNs, while only weak interactions were observed between Cbln4 and NRXNs. The interactions of Cbln1, Cbln2 and Cbln4 were selective for NRXN variants containing splice segment (S) 4. Affinities for NRXNs estimated by surface plasmon resonance analysis were variable among Cbln subtypes. Cbln1 showed higher affinities to NRXNs than Cbln2, while the binding ability of Cbln4 was much lower than those of Cbln1 and Cbln2. The affinities of Cbln1 and Cbln2 were comparable between NRXN1α and NRXN1β, but those for NRXN2β and NRXN3β were lower. These results suggest that Cbln subtypes exert synaptogenic activities in cortical neurons by differentially interacting with NRXN variants containing S4.

  3. IL1RAPL1 associated with mental retardation and autism regulates the formation and stabilization of glutamatergic synapses of cortical neurons through RhoA signaling pathway.

    Directory of Open Access Journals (Sweden)

    Takashi Hayashi

    Full Text Available Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1 is associated with X-linked mental retardation and autism spectrum disorder. We found that IL1RAPL1 regulates synapse formation of cortical neurons. To investigate how IL1RAPL1 controls synapse formation, we here screened IL1RAPL1-interacting proteins by affinity chromatography and mass spectroscopy. IL1RAPL1 interacted with Mcf2-like (Mcf2l, a Rho guanine nucleotide exchange factor, through the cytoplasmic Toll/IL-1 receptor domain. Knockdown of endogenous Mcf2l and treatment with an inhibitor of Rho-associated protein kinase (ROCK, the downstream kinase of RhoA, suppressed IL1RAPL1-induced excitatory synapse formation of cortical neurons. Furthermore, we found that the expression of IL1RAPL1 affected the turnover of AMPA receptor subunits. Insertion of GluA1-containing AMPA receptors to the cell surface was decreased, whereas that of AMPA receptors composed of GluA2/3 was enhanced. Mcf2l knockdown and ROCK inhibitor treatment diminished the IL1RAPL1-induced changes of AMPA receptor subunit insertions. Our results suggest that Mcf2l-RhoA-ROCK signaling pathway mediates IL1RAPL1-dependent formation and stabilization of glutamatergic synapses of cortical neurons.

  4. Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala.

    Science.gov (United States)

    Varodayan, Florence P; Soni, Neeraj; Bajo, Michal; Luu, George; Madamba, Samuel G; Schweitzer, Paul; Parsons, Loren H; Roberto, Marisa

    2016-07-01

    The endogenous cannabinoids (eCBs) influence the acute response to ethanol and the development of tolerance, dependence and relapse. Chronic alcohol exposure alters eCB levels and Type 1 cannabinoid receptor (CB1 ) expression and function in brain regions associated with addiction. CB1 inhibits GABA release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naive rats, CB1 agonist WIN 55,212-2 (WIN) decreased the frequency of spontaneous and miniature GABAA receptor-mediated inhibitory postsynaptic currents (s/mIPSCs). This effect was prevented by CB1 antagonism, but not Type 2 cannabinoid receptor (CB2 ) antagonism. After 2-3 weeks of intermittent ethanol exposure, these WIN inhibitory effects were attenuated, suggesting ethanol-induced impairments in CB1 function. The CB1 antagonist AM251 revealed a tonic eCB/CB1 control of GABAergic transmission in the alcohol-naive CeA that was occluded by calcium chelation in the postsynaptic cell. Chronic ethanol exposure abolished this tonic CB1 influence on mIPSC, but not sIPSC, frequency. Finally, acute ethanol increased CeA GABA release in both naive and ethanol-exposed rats. Although CB1 activation prevented this effect, the AM251- and ethanol-induced GABA release were additive, ruling out a direct participation of CB1 signaling in the ethanol effect. Collectively, these observations demonstrate an important CB1 influence on CeA GABAergic transmission and indicate that the CeA is particularly sensitive to alcohol-induced disruptions of CB1 signaling.

  5. Reciprocal regulation of microRNA and mRNA profiles in neuronal development and synapse formation

    Directory of Open Access Journals (Sweden)

    Grant Seth GN

    2009-09-01

    Full Text Available Abstract Background Synapse formation and the development of neural networks are known to be controlled by a coordinated program of mRNA synthesis. microRNAs are now recognized to be important regulators of mRNA translation and stability in a wide variety of organisms. While specific microRNAs are known to be involved in neural development, the extent to which global microRNA and mRNA profiles are coordinately regulated in neural development is unknown. Results We examined mouse primary neuronal cultures, analyzing microRNA and mRNA expression. Three main developmental patterns of microRNA expression were observed: steady-state levels, up-regulated and down-regulated. Co-expressed microRNAs were found to have related target recognition sites and to be encoded in distinct genomic locations. A number of 43 differentially expressed miRNAs were located in five genomic clusters. Their predicted mRNA targets show reciprocal levels of expression. We identified a set of reciprocally expressed microRNAs that target mRNAs encoding postsynaptic density proteins and high-level steady-state microRNAs that target non-neuronal low-level expressed mRNAs. Conclusion We characterized hundreds of miRNAs in neuronal culture development and identified three major modes of miRNA expression. We predict these miRNAs to regulate reciprocally expressed protein coding genes, including many genes involved in synaptogenesis. The identification of miRNAs that target mRNAs during synaptogenesis indicates a new level of regulation of the synapse.

  6. A multi nutrient concept to enhance synapse formation and function: science behind a medical food for Alzheimer’s disease

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    Sijben John W.C.

    2011-09-01

    Full Text Available Alzheimer’s Disease (AD is the leading cause of dementia. Epidemiological studies suggest that AD is linked with poor status of nutrients including DHA, B-vitamins and the vitamins E and C. Ongoing neurodegeneration, particularly synaptic loss, leads to the classical clinical features of AD namely, memory impairment, language deterioration, and executive and visuospatial dysfunction. The main constituents of neural and synaptic membranes are phospholipids. Supplemenation of animals with three dietary precursors of phospholipids namely, DHA, uridine monophosphate and choline, results in increased levels of brain phospholipids, synaptic proteins, neurite outgrowth, dendritic spines formation (i.e. the anatomical precursors of new synapses and an improvement in learning and memory. Other nutrients act as co-factors in the synthesis pathway of neuronal membranes. For example B-vitamins are involved in methylation processes, thereby enhancing the availability of choline as a synaptic membrane precursor. A multi-nutrient concept that includes these nutrients may improve membrane integrity, thereby influencing membrane-dependent processes such as receptor function and amyloid precursor protein (APP processing, as shown by reduced amyloid production and amyloid β plaque burden, as well as toxicity. Together, these insights provided the basis for the development of a medical food for patients with AD, Souvenaid®, containing a specific combination of nutrients (Fortasyn™ Connect and designed to enhance synapse formation in AD. The effect of Souvenaid on memory and cognitive performance was recently assessed in a proof-of-concept study, SOUVENIR I, with 212 drug-naïve mild AD patients (MMSE 20-26. This proof-of-concept study demonstrated that oral nutritional supplementation with Souvenaid® for 12 weeks improves memory in patients with mild AD. To confirm and extend these findings, we have designed and initiated three additional studies. Two of

  7. Top3β is an RNA topoisomerase that works with Fragile X syndrome protein to promote synapse formation

    Science.gov (United States)

    Xu, Dongyi; Shen, Weiping; Guo, Rong; Xue, Yutong; Peng, Wei; Sima, Jian; Yang, Jay; Sharov, Alexei; Srikantan, Subramanya; Yang, Jiandong; Fox, David; Qian, Yong; Martindale, Jennifer L.; Piao, Yulan; Machamer, James; Joshi, Samit R.; Mohanty, Subhasis; Shaw, Albert C.; Lloyd, Thomas E.; Brown, Grant W.; Ko, Minoru S.H.; Gorospe, Myriam; Zou, Sige; Wang, Weidong

    2013-01-01

    Topoisomerases are crucial to solve DNA topological problems, but they have not been linked to RNA metabolism. Here we show that human topoisomerase 3β (Top3β) is an RNA topoisomerase that biochemically and genetically interacts with FMRP, a protein deficient in Fragile X syndrome and known to regulate translation of mRNAs important for neuronal function and autism. Notably, the FMRP-Top3β interaction is abolished by a disease-associated FMRP mutation, suggesting that Top3β may contribute to pathogenesis of mental disorders. Top3β binds multiple mRNAs encoded by genes with neuronal functions related to schizophrenia and autism. Expression of one such gene, ptk2/FAK, is reduced in neuromuscular junctions of Top3β mutant flies. Synapse formation is defective in Top3β mutant flies and mice, as observed in FMRP mutant animals. Our findings suggest that Top3β acts as an RNA topoisomerase and works with FMRP to promote expression of mRNAs critical for neurodevelopment and mental health. PMID:23912945

  8. A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation

    Directory of Open Access Journals (Sweden)

    Shokat Kevan M

    2008-09-01

    Full Text Available Abstract Background Neurons assemble into a functional network through a sequence of developmental processes including neuronal polarization and synapse formation. In Caenorhabditis elegans, the serine/threonine SAD-1 kinase is essential for proper neuronal polarity and synaptic organization. To determine if SAD-1 activity regulates the establishment or maintenance of these neuronal structures, we examined its temporal requirements using a chemical-genetic method that allows for selective and reversible inactivation of its kinase activity in vivo. Results We generated a PP1 analog-sensitive variant of SAD-1. Through temporal inhibition of SAD-1 kinase activity we show that its activity is required for the establishment of both neuronal polarity and synaptic organization. However, while SAD-1 activity is needed strictly when neurons are polarizing, the temporal requirement for SAD-1 is less stringent in synaptic organization, which can also be re-established during maintenance. Conclusion This study reports the first temporal analysis of a neural kinase activity using the chemical-genetic system. It reveals that neuronal polarity and synaptic organization have distinct temporal requirements for SAD-1.

  9. The Role of TSC1 in the Formation and Maintenance of Excitatory Synapses

    Science.gov (United States)

    2006-03-01

    that link extracellular stimuli to synaptic refinement in neurons. For example, activation of the TrkB receptor tyrosine kinase by brain- derived...neurotrophic factor ( BDNF ) stimulates PI3K and Akt to promote dendritic growth14. BDNF also triggers long-term potentia- tion of synaptic strength in an mTOR...protein function in the brain. Biochem. Soc. Trans. 31, 579–583 (2003). 14. Dijkhuizen, P.A. & Ghosh, A. BDNF regulates primary dendrite formation in

  10. Enhanced mossy fiber sprouting and synapse formation in organotypic hippocampal cultures following transient domoic acid excitotoxicity.

    Science.gov (United States)

    Pérez-Gómez, Anabel; Tasker, R Andrew

    2014-05-01

    We have previously reported evidence of BDNF upregulation and increased neurogenesis in rat organotypic hippocampal slice cultures (OHSC) after a transient excitotoxic injury to the hippocampal CA1 area induced by low concentrations of the AMPA/kainate receptor agonist domoic acid (DOM). The changes observed in OHSC were consistent with observations in vivo, where low concentrations of DOM administered to rats during perinatal development caused increased BDNF and TrkB expression in the resulting adult animals. The in vivo low dose-DOM treatment also results in permanent alterations in hippocampal structure and function, including abnormal formation of dentate granule cell axons projecting to area CA3 (mossy fiber sprouting). Our objective in the current study is to determine if low concentrations of DOM induce mossy fiber sprouting and/or synaptogenesis in OHSC in order to facilitate future studies on the mechanisms of structural hippocampal plasticity induced by DOM. We report herein that application of a low concentration of DOM (2 μM) for 24 h followed by recovery induced a significant increase in the expression of the mossy fiber marker ZnT3 that progressed over time in culture. The DOM insult (2 μM, 24 h) also resulted in a significant upregulation of both the presynaptic marker synaptophysin and the postsynaptic marker PSD-95. All of the observed effects were fully antagonized by co-administration of the AMPA/kainate antagonists CNQX or NBQX but only partly by the NMDA antagonist CPP and not by the calcium channel blocker nifedipine. We conclude that exposure of OHSC to concentrations of DOM below those required to induce permanent neurotoxicity can induce a progressive change in hippocampal structure that can effectively model DOM effects in vivo.

  11. Localization of cerebellin-2 in late embryonic chicken brain: implications for a role in synapse formation and for brain evolution.

    Science.gov (United States)

    Reiner, Anton; Yang, Mao; Cagle, Michael C; Honig, Marcia G

    2011-08-01

    Cerebellin-1 (Cbln1), the most studied member of the cerebellin family of secreted proteins, is necessary for the formation and maintenance of parallel fiber-Purkinje cell synapses. However, the roles of the other Cblns have received little attention. We previously identified the chicken homolog of Cbln2 and examined its expression in dorsal root ganglia and spinal cord (Yang et al. [2010] J Comp Neurol 518:2818-2840). Interestingly, Cbln2 is expressed by mechanoreceptive and proprioceptive neurons and in regions of the spinal cord where those afferents terminate, as well as by preganglionic sympathetic neurons and their sympathetic ganglia targets. These findings suggest that Cbln2 may demonstrate a tendency to be expressed by synaptically connected neuronal populations. To further assess this possibility, we examined Cbln2 expression in chick brain. We indeed found that Cbln2 is frequently expressed by synaptically connected neurons, although there are exceptions, and we discuss the implications of these findings for Cbln2 function. Cbln2 expression tends to be more common in primary sensory neurons and in second-order sensory regions than it is in motor areas of the brain. Moreover, we found that the level of Cbln2 expression for many regions of the chicken brain is very similar to that of the mammalian homologs, consistent with the view that the expression patterns of molecules playing fundamental roles in processes such as neuronal communication are evolutionarily conserved. There are, however, large differences in the pattern of Cbln2 expression in avian as compared to mammalian telencephalon and in other regions that show the most divergence between the two lineages.

  12. Distinct target cell-dependent forms of short-term plasticity of the central visceral afferent synapses of the rat

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    Watabe Ayako M

    2010-10-01

    Full Text Available Abstract Background The visceral afferents from various cervico-abdominal sensory receptors project to the dorsal vagal complex (DVC, which is composed of the nucleus of the solitary tract (NTS, the area postrema and the dorsal motor nucleus of the vagus nerve (DMX, via the vagus and glossopharyngeal nerves and then the solitary tract (TS in the brainstem. While the excitatory transmission at the TS-NTS synapses shows strong frequency-dependent suppression in response to repeated stimulation of the afferents, the frequency dependence and short-term plasticity at the TS-DMX synapses, which also transmit monosynaptic information from the visceral afferents to the DVC neurons, remain largely unknown. Results Recording of the EPSCs activated by paired or repeated TS stimulation in the brainstem slices of rats revealed that, unlike NTS neurons whose paired-pulse ratio (PPR is consistently below 0.6, the distribution of the PPR of DMX neurons shows bimodal peaks that are composed of type I (PPR, 0.6-1.5; 53% of 120 neurons recorded and type II (PPR, Conclusions These two general types of short-term plasticity might contribute to the differential activation of distinct vago-vagal reflex circuits, depending on the firing frequency and type of visceral afferents.

  13. The Reorientation of T-Cell Polarity and Inhibition of Immunological Synapse Formation by CD46 Involves Its Recruitment to Lipid Rafts

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    Mandy J. Ludford-Menting

    2011-01-01

    Full Text Available Many infectious agents utilize CD46 for infection of human cells, and therapeutic applications of CD46-binding viruses are now being explored. Besides mediating internalization to enable infection, binding to CD46 can directly alter immune function. In particular, ligation of CD46 by antibodies or by measles virus can prevent activation of T cells by altering T-cell polarity and consequently preventing the formation of an immunological synapse. Here, we define a mechanism by which CD46 reorients T-cell polarity to prevent T-cell receptor signaling in response to antigen presentation. We show that CD46 associates with lipid rafts upon ligation, and that this reduces recruitment of both lipid rafts and the microtubule organizing centre to the site of receptor cross-linking. These data combined indicate that polarization of T cells towards the site of CD46 ligation prevents formation of an immunological synapse, and this is associated with the ability of CD46 to recruit lipid rafts away from the site of TCR ligation.

  14. Dendritic Target Region-Specific Formation of Synapses Between Excitatory Layer 4 Neurons and Layer 6 Pyramidal Cells.

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    Qi, Guanxiao; Feldmeyer, Dirk

    2016-04-01

    Excitatory connections between neocortical layer 4 (L4) and L6 are part of the corticothalamic feedback microcircuitry. Here we studied the intracortical element of this feedback loop, the L4 spiny neuron-to-L6 pyramidal cell connection. We found that the distribution of synapses onto both putative corticothalamic (CT) and corticocortical (CC) L6 pyramidal cells (PCs) depends on the presynaptic L4 neuron type but is independent of the postsynaptic L6 PC type. L4 spiny stellate cells establish synapses on distal apical tuft dendrites of L6 PCs and elicit slow unitary excitatory postsynaptic potentials (uEPSPs) in L6 somata. In contrast, the majority of L4 star pyramidal neurons target basal and proximal apical oblique dendrites of L6 PCs and show fast uEPSPs. Compartmental modeling suggests that the slow uEPSP time course is primarily the result of dendritic filtering. This suggests that the dendritic target specificity of the 2 L4 spiny neuron types is due to their different axonal projection patterns across cortical layers. The preferential dendritic targeting by different L4 neuron types may facilitate the generation of dendritic Ca(2+) or Na(+) action potentials in L6 PCs; this could play a role in synaptic gain modulation in the corticothalamic pathway.

  15. Up-regulation of Ras/Raf/ERK1/2 signaling in the spinal cord impairs neural cell migration, neurogenesis, synapse formation, and dendritic spine development

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    CAO Fu-jiang; ZHANG Xu; LIU Tao; LI Xia-wen; Mazar Malik; FENG Shi-qing

    2013-01-01

    Background The Ras/Raf/ERK1/2 signaling pathway controls many cellular responses such as cell proliferation,migration,differentiation,and death.In the nervous system,emerging evidence also points to a death-promoting role for ERK1/2 in both in vitro and in vivo models of neuronal death.To further investigate how Ras/Raf/ERK1/2 up-regulation may lead to the development of spinal cord injury,we developed a cellular model of Raf/ERK up-regulation by overexpressing c-Raf in cultured spinal cord neurons (SCNs) and dorsal root ganglions (DRGs).Methods DRGs and SCNs were prepared from C57BL/6J mouse pups.DRGs or SCNs were infected with Ad-Raf-1 or Ad-Null adenovirus alone.Cell adhesion assay and cell migration assay were investigated,Dil labeling was employed to examine the effect of the up-regulation of Ras/Raf/ERK1/2 signaling on the dendritic formation of spinal neurons.We used the TO-PRO-3 staining to examine the apoptotic effect of c-Raf on DRGs or SCNs.The effect on the synapse formation of neurons was measured by using immunofluorescence.Results We found that Raf/ERK up-regulation stimulates the migration of both SCNs and DRGs,and impairs the formation of excitatory synapses in SCNs.In addition,we found that Raf/ERK up-regulation inhibits the development of mature dendritic spines in SCNs.Investigating the possible mechanisms through which Raf/ERK up-regulation affects the excitatory synapse formation and dendritic spine development,we discovered that Raf/ERK up-regulation suppresses the development and maturation of SCNs.Conclusion The up-regulation of the Raf/ERK signaling pathway may contribute to the pathogenesis of spinal cord injury through both its impairment of the SCN development and causing neural circuit imbalances.

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

    Science.gov (United States)

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

    2008-01-01

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

  17. The Central Asian Armies Facing the Challenge of Formation

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    Sébastien Peyrouse

    2011-03-01

    Full Text Available This article focuses on one of the main challenges that Central Asian armies face, that is, the problem of training and formation. Having rapidly increased since 2007, Central Asian military budgets have been able to multiply the purchases of equipment and weapons from foreign partners (Russia, western countries, Israel, China, South Korea, etc.. Money is not enough, however, to get the military institution back on its feet in its most human aspect, that of formation. In fact, the teaching institutions and the training possibilities provided to conscripts and professional soldiers on contract are generally of inadequate quality and impede the overall military capacities of the Central Asian states. This article will examine the main problems of the Central Asian military institutions and will discuss the means that have been implemented by Central Asian governments to reduce the negative impact of difficulties in promoting human capital.

  18. Type I bHLH Proteins Daughterless and Tcf4 Restrict Neurite Branching and Synapse Formation by Repressing Neurexin in Postmitotic Neurons

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    Mitchell D’Rozario

    2016-04-01

    Full Text Available Proneural proteins of the class I/II basic-helix-loop-helix (bHLH family are highly conserved transcription factors. Class I bHLH proteins are expressed in a broad number of tissues during development, whereas class II bHLH protein expression is more tissue restricted. Our understanding of the function of class I/II bHLH transcription factors in both invertebrate and vertebrate neurobiology is largely focused on their function as regulators of neurogenesis. Here, we show that the class I bHLH proteins Daughterless and Tcf4 are expressed in postmitotic neurons in Drosophila melanogaster and mice, respectively, where they function to restrict neurite branching and synapse formation. Our data indicate that Daughterless performs this function in part by restricting the expression of the cell adhesion molecule Neurexin. This suggests a role for these proteins outside of their established roles in neurogenesis.

  19. Downregulation of genes with a function in axon outgrowth and synapse formation in motor neurones of the VEGFδ/δ mouse model of amyotrophic lateral sclerosis

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    Lambrechts Diether

    2010-03-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF is an endothelial cell mitogen that stimulates vasculogenesis. It has also been shown to act as a neurotrophic factor in vitro and in vivo. Deletion of the hypoxia response element of the promoter region of the gene encoding VEGF in mice causes a reduction in neural VEGF expression, and results in adult-onset motor neurone degeneration that resembles amyotrophic lateral sclerosis (ALS. Investigating the molecular pathways to neurodegeneration in the VEGFδ/δ mouse model of ALS may improve understanding of the mechanisms of motor neurone death in the human disease. Results Microarray analysis was used to determine the transcriptional profile of laser captured spinal motor neurones of transgenic and wild-type littermates at 3 time points of disease. 324 genes were significantly differentially expressed in motor neurones of presymptomatic VEGFδ/δ mice, 382 at disease onset, and 689 at late stage disease. Massive transcriptional downregulation occurred with disease progression, associated with downregulation of genes involved in RNA processing at late stage disease. VEGFδ/δ mice showed reduction in expression, from symptom onset, of the cholesterol synthesis pathway, and genes involved in nervous system development, including axonogenesis, synapse formation, growth factor signalling pathways, cell adhesion and microtubule-based processes. These changes may reflect a reduced capacity of VEGFδ/δ mice for maintenance and remodelling of neuronal processes in the face of demands of neural plasticity. The findings are supported by the demonstration that in primary motor neurone cultures from VEGFδ/δ mice, axon outgrowth is significantly reduced compared to wild-type littermates. Conclusions Downregulation of these genes involved in axon outgrowth and synapse formation in adult mice suggests a hitherto unrecognized role of VEGF in the maintenance of neuronal circuitry. Dysregulation of

  20. Emerging Roles of BAI Adhesion-GPCRs in Synapse Development and Plasticity

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    Joseph G. Duman

    2016-01-01

    Full Text Available Synapses mediate communication between neurons and enable the brain to change in response to experience, which is essential for learning and memory. The sites of most excitatory synapses in the brain, dendritic spines, undergo rapid remodeling that is important for neural circuit formation and synaptic plasticity. Abnormalities in synapse and spine formation and plasticity are associated with a broad range of brain disorders, including intellectual disabilities, autism spectrum disorders (ASD, and schizophrenia. Thus, elucidating the mechanisms that regulate these neuronal processes is critical for understanding brain function and disease. The brain-specific angiogenesis inhibitor (BAI subfamily of adhesion G-protein-coupled receptors (adhesion-GPCRs has recently emerged as central regulators of synapse development and plasticity. In this review, we will summarize the current knowledge regarding the roles of BAIs at synapses, highlighting their regulation, downstream signaling, and physiological functions, while noting the roles of other adhesion-GPCRs at synapses. We will also discuss the relevance of BAIs in various neurological and psychiatric disorders and consider their potential importance as pharmacological targets in the treatment of these diseases.

  1. Intranasal exposure to manganese disrupts neurotransmitter release from glutamatergic synapses in the central nervous system in vivo.

    Science.gov (United States)

    Moberly, Andrew H; Czarnecki, Lindsey A; Pottackal, Joseph; Rubinstein, Tom; Turkel, Daniel J; Kass, Marley D; McGann, John P

    2012-10-01

    Chronic exposure to aerosolized manganese induces a neurological disorder that includes extrapyramidal motor symptoms and cognitive impairment. Inhaled manganese can bypass the blood-brain barrier and reach the central nervous system by transport down the olfactory nerve to the brain's olfactory bulb. However, the mechanism by which Mn disrupts neural function remains unclear. Here we used optical imaging techniques to visualize exocytosis in olfactory nerve terminals in vivo in the mouse olfactory bulb. Acute Mn exposure via intranasal instillation of 2-200 μg MnCl(2) solution caused a dose-dependent reduction in odorant-evoked neurotransmitter release, with significant effects at as little as 2 μg MnCl(2) and a 90% reduction compared to vehicle controls with a 200 μg exposure. This reduction was also observed in response to direct electrical stimulation of the olfactory nerve layer in the olfactory bulb, demonstrating that Mn's action is occurring centrally, not peripherally. This is the first direct evidence that Mn intoxication can disrupt neurotransmitter release, and is consistent with previous work suggesting that chronic Mn exposure limits amphetamine-induced dopamine increases in the basal ganglia despite normal levels of dopamine synthesis (Guilarte et al., J Neurochem 2008). The commonality of Mn's action between glutamatergic neurons in the olfactory bulb and dopaminergic neurons in the basal ganglia suggests that a disruption of neurotransmitter release may be a general consequence wherever Mn accumulates in the brain and could underlie its pleiotropic effects.

  2. Axonal Type III Nrg1 Controls Glutamate Synapse Formation and GluA2 Trafficking in Hippocampal-Accumbens Connections

    Science.gov (United States)

    Akmentin, Wendy

    2017-01-01

    Abstract Altered neuregulin 1 (Nrg1)/ErbB signaling and glutamatergic hypofunction have been implicated in the pathophysiology of schizophrenia. Here, we employed gene chimeric ventral hippocampus (vHipp)-nucleus accumbens (nAcc) coculture from mouse, electrophysiology, immunocytochemistry, FM1-43 vesicle fusion, and electron microscopy techniques to examine the pre- and postsynaptic mechanisms of genetic deficits in Nrg1/ErbB signaling-induced glutamatergic dysfunctions. Reduced presynaptic type III Nrg1 expression along vHipp axons decreases the number of glutamate synapses and impairs GluA2 trafficking in the postsynaptic nAcc neurons, resulting in decreased frequency and amplitude of miniature EPSCs (mEPSCs). Reduced expression of axonal type III Nrg1 along vHipp projections also decreases functional synaptic vesicle (SV) clustering and vesicular trafficking to presynaptic vHipp axonal terminals. These findings suggest that Nrg1/ErbB signaling modulate glutamatergic transmission via both pre- and postsynaptic mechanisms. PMID:28275713

  3. Peculiar early-type galaxies with central star formation

    Institute of Scientific and Technical Information of China (English)

    Chong Ge; Qiu-Sheng Gu

    2012-01-01

    Early-type galaxies (ETGs) are very important for understanding the formation and evolution of galaxies.Recent observations suggest that ETGs are not simply old stellar spheroids as we previously thought.Widespread recent star formation,cool gas and dust have been detected in a substantial fraction of ETGs.We make use of the radial profiles of g - r color and the concentration index from the Sloan Digital Sky Survey database to pick out 31 peculiar ETGs with central blue cores.By analyzing the photometric and spectroscopic data,we suggest that the blue cores are caused by star formation activities rather than the central weak active galactic nucleus.From the results of stellar population synthesis,we find that the stellar population of the blue cores is relatively young,spreading from several Myr to less than one Gyr.In 14 galaxies with H I observations,we find that the average gas fraction of these galaxies is about 0.55.The bluer galaxies show a higher gas fraction,and the total star formation rate (SFR) correlates very well with the H l gas mass.The star formation history of these ETGs is affected by the environment,e.g.in the denser environment the H 1 gas is less and the total SFR is lower.We also discuss the origin of the central star formation of these early-type galaxies.

  4. Syntaxin 1B, but not syntaxin 1A, is necessary for the regulation of synaptic vesicle exocytosis and of the readily releasable pool at central synapses.

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    Tatsuya Mishima

    Full Text Available Two syntaxin 1 (STX1 isoforms, HPC-1/STX1A and STX1B, are coexpressed in neurons and function as neuronal target membrane (t-SNAREs. However, little is known about their functional differences in synaptic transmission. STX1A null mutant mice develop normally and do not show abnormalities in fast synaptic transmission, but monoaminergic transmissions are impaired. In the present study, we found that STX1B null mutant mice died within 2 weeks of birth. To examine functional differences between STX1A and 1B, we analyzed the presynaptic properties of glutamatergic and GABAergic synapses in STX1B null mutant and STX1A/1B double null mutant mice. We found that the frequency of spontaneous quantal release was lower and the paired-pulse ratio of evoked postsynaptic currents was significantly greater in glutamatergic and GABAergic synapses of STX1B null neurons. Deletion of STX1B also accelerated synaptic vesicle turnover in glutamatergic synapses and decreased the size of the readily releasable pool in glutamatergic and GABAergic synapses. Moreover, STX1A/1B double null neurons showed reduced and asynchronous evoked synaptic vesicle release in glutamatergic and GABAergic synapses. Our results suggest that although STX1A and 1B share a basic function as neuronal t-SNAREs, STX1B but not STX1A is necessary for the regulation of spontaneous and evoked synaptic vesicle exocytosis in fast transmission.

  5. Central star formation and metallicity in CALIFA interacting galaxies

    CERN Document Server

    Barrera-Ballesteros, J K; García-Lorenzo, B; Falcón-Barroso, J; Mast, D; García-Benito, R; Husemann, B; van de Ven, G; Iglesias-Páramo, J; Rosales-Ortega, F F; Pérez-Torres, M A; Márquez, I; Kehrig, C; Vilchez, J M; Galbany, L; López-Sánchez, Á R; Walcher, C J

    2015-01-01

    We use optical integral-field spectroscopic (IFS) data from 103 nearby galaxies at different stages of the merging event, from close pairs to merger remnants provided by the CALIFA survey, to study the impact of the interaction in the specific star formation and oxygen abundance on different galactic scales. To disentangle the effect of the interaction and merger from internal processes, we compared our results with a control sample of 80 non-interacting galaxies. We confirm the moderate enhancement (2-3 times) of specific star formation for interacting galaxies in central regions as reported by previous studies; however, the specific star formation is comparable when observed in extended regions. We find that control and interacting star-forming galaxies have similar oxygen abundances in their central regions, when normalized to their stellar masses. Oxygen abundances of these interacting galaxies seem to decrease compared to the control objects at the large aperture sizes measured in effective radius. Altho...

  6. Developmental expression profiles of axon guidance signaling and the immune system in the marmoset cortex: potential molecular mechanisms of pruning of dendritic spines during primate synapse formation in late infancy and prepuberty (I).

    Science.gov (United States)

    Sasaki, Tetsuya; Oga, Tomofumi; Nakagaki, Keiko; Sakai, Kazuhisa; Sumida, Kayo; Hoshino, Kohei; Miyawaki, Izuru; Saito, Koichi; Suto, Fumikazu; Ichinohe, Noritaka

    2014-02-14

    The synapse number and the related dendritic spine number in the cerebral cortex of primates shows a rapid increase after birth. Depending on the brain region and species, the number of synapses reaches a peak before adulthood, and pruning takes place after this peak (overshoot-type synaptic formation). Human mental disorders, such as autism and schizophrenia, are hypothesized to be a result of either too weak or excessive pruning after the peak is reached. Thus, it is important to study the molecular mechanisms underlying overshoot-type synaptic formation, particularly the pruning phase. To examine the molecular mechanisms, we used common marmosets (Callithrix jacchus). Microarray analysis of the marmoset cortex was performed in the ventrolateral prefrontal, inferior temporal, and primary visual cortices, where changes in the number of dendritic spines have been observed. The spine number of all the brain regions above showed a peak at 3 months (3 M) after birth and gradually decreased (e.g., at 6 M and in adults). In this study, we focused on genes that showed differential expression between ages of 3 M and 6 M and on the differences whose fold change (FC) was greater than 1.2. The selected genes were subjected to canonical pathway analysis, and in this study, we describe axon guidance signaling, which had high plausibility. The results showed a large number of genes belonging to subsystems within the axon guidance signaling pathway, macrophages/immune system, glutamate system, and others. We divided the data and discussion of these results into 2 papers, and this is the first paper, which deals with the axon guidance signaling and macrophage/immune system. Other systems will be described in the next paper. Many components of subsystems within the axon guidance signaling underwent changes in gene expression from 3 M to 6 M so that the synapse/dendritic spine number would decrease at 6 M. Thus, axon guidance signaling probably contributes to the decrease in

  7. Increased synapse formation obtained by T cell epitopes containing a CxxC motif in flanking residues convert CD4+ T cells into cytolytic effectors.

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    Vincent A Carlier

    Full Text Available The nature of MHC class II-binding epitopes not only determines the specificity of T cell responses, but may also alter effector cell functions. Cytolytic CD4+ T cells have been observed primarily in anti-viral responses, but very little is known about the conditions under which they can be elicited. Their potential as regulators of immune responses, however, deserves investigations. We describe here that inclusion of a thiol-disulfide oxidoreductase motif within flanking residues of class II-restricted epitopes results, both in vitro and in vivo, in elicitation of antigen-specific cytolytic CD4+ T cells through increased synapse formation. We show that both naïve and polarized CD4+ T cells, including Th17 cells, can be converted by cognate recognition of such modified epitopes. Cytolytic CD4+ T cells induce apoptosis on APCs by Fas-FasL interaction. These findings potentially open the way towards a novel form of antigen-specific immunosuppression.

  8. Ganymede crater dimensions - Implications for central peak and central pit formation and development

    Science.gov (United States)

    Bray, Veronica J.; Schenk, Paul M.; Jay Melosh, H.; Morgan, Joanna V.; Collins, Gareth S.

    2012-01-01

    The morphology of impact craters on the icy Galilean satellites differs from craters on rocky bodies. The differences are thought due to the relative weakness of ice and the possible presence of sub-surface water layers. Digital elevation models constructed from Galileo images were used to measure a range of dimensions of craters on the dark and bright terrains of Ganymede. Measurements were made from multiple profiles across each crater, so that natural variation in crater dimensions could be assessed and averaged scaling trends constructed. The additional depth, slope and volume information reported in this work has enabled study of central peak formation and development, and allowed a quantitative assessment of the various theories for central pit formation. We note a possible difference in the size-morphology progression between small craters on icy and silicate bodies, where central peaks occur in small craters before there is any slumping of the crater rim, which is the opposite to the observed sequence on the Moon. Conversely, our crater dimension analyses suggest that the size-morphology progression of large lunar craters from central peak to peak-ring is mirrored on Ganymede, but that the peak-ring is subsequently modified to a central pit morphology. Pit formation may occur via the collapse of surface material into a void left by the gradual release of impact-induced volatiles or the drainage of impact melt into sub-crater fractures.

  9. Resolving the Formation of Protogalaxies. II.Central Gravitational Collapse

    Energy Technology Data Exchange (ETDEWEB)

    Wise, John H.; Turk, Matthew J.; Abel, Tom

    2007-10-15

    Numerous cosmological hydrodynamic studies have addressed the formation of galaxies. Here we choose to study the first stages of galaxy formation, including non-equilibrium atomic primordial gas cooling, gravity and hydrodynamics. Using initial conditions appropriate for the concordance cosmological model of structure formation, we perform two adaptive mesh refinement simulations of {approx} 10{sup 8} M{sub {circle_dot}} galaxies at high redshift. The calculations resolve the Jeans length at all times with more than 16 cells and capture over 14 orders of magnitude in length scales. In both cases, the dense, 10{sup 5} solar mass, one parsec central regions are found to contract rapidly and have turbulent Mach numbers up to 4. Despite the ever decreasing Jeans length of the isothermal gas, we only find one site of fragmentation during the collapse. However, rotational secular bar instabilities transport angular momentum outwards in the central parsec as the gas continues to collapse and lead to multiple nested unstable fragments with decreasing masses down to sub-Jupiter mass scales. Although these numerical experiments neglect star formation and feedback, they clearly highlight the physics of turbulence in gravitationally collapsing gas. The angular momentum segregation seen in our calculations plays an important role in theories that form supermassive black holes from gaseous collapse.

  10. Interneurons are the source and the targets of the first synapses formed in the rat developing hippocampal circuit.

    Science.gov (United States)

    Gozlan, Henri; Ben-Ari, Yehezkel

    2003-06-01

    In hippocampal CA1 pyramidal neurons, GABAergic synapses are established before glutamatergic synapses. GABAergic interneurons should therefore develop and acquire synapses at an earlier stage to provide the source for GABAergic synapses. We now report that this is indeed the case. At birth and in utero, when nearly all pyramidal neurons are not yet functional, most interneurons have already either GABAergic only or GABAergic and glutamatergic postsynaptic currents. At birth, the morphological maturation of interneurons parallels their individual functional responses. In addition, the formation of functional interneurons types appears to be a sequential process. Interneurons that innervate other interneurons acquire GABA(A) synapses before peridendritic interneurons, but also before perisomatic interneurons that are not yet functional at birth. Therefore, interneurons are the source and the targets of the first synapses formed in the developing circuit. Since GABA was shown to be excitatory in utero, interneurons provide all the excitatory drive at a time when the principal cells are silent. They could therefore play a central role in the formation of the cortical circuit at early developmental stages.

  11. Transition of spatiotemporal patterns in neuronal networks with chemical synapses

    Science.gov (United States)

    Wang, Rong; Li, Jiajia; Du, Mengmeng; Lei, Jinzhi; Wu, Ying

    2016-11-01

    In mammalian neocortex plane waves, spiral and irregular waves appear alternately. In this paper, we study the transition of spatiotemporal patterns in neuronal networks in which neurons are coupled via two types of chemical synapses: fast excitatory synapse and fast inhibitory synapse. Our results indicate that the fast excitatory synapse connection is easier to induce regular spatiotemporal patterns than fast inhibitory synapse connection, and the mechanism is discussed through bifurcation analysis of a single neuron. We introduce the permutation entropy as a measure of network firing complexity to study the mechanisms of formation and transition of spatiotemporal patterns. Our calculations show that the spatiotemporal pattern transitions are closely connected to a sudden decrease in the firing complexity of neuronal networks, and the neuronal networks with fast excitatory synapses have higher firing complexity than those with fast inhibitory synapses.

  12. Enhanced cholinergic suppression of previously strengthened synapses enables the formation of self-organized representations in olfactory cortex.

    Science.gov (United States)

    Linster, Christiane; Maloney, Michaella; Patil, Madhvi; Hasselmo, Michael E

    2003-11-01

    Computational modeling assists in analyzing the specific functional role of the cellular effects of acetylcholine within cortical structures. In particular, acetylcholine may regulate the dynamics of encoding and retrieval of information by regulating the magnitude of synaptic transmission at excitatory recurrent connections. Many abstract models of associative memory function ignore the influence of changes in synaptic strength during the storage process and apply the effect of these changes only during a so-called recall-phase. Efforts to ensure stable activity with more realistic, continuous updating of the synaptic strength during the storage process have shown that the memory capacity of a realistic cortical network can be greatly enhanced if cholinergic modulation blocks transmission at synaptic connections of the association fibers during the learning process. We here present experimental data from an olfactory cortex brain slice preparation showing that previously potentiated fibers show significantly greater suppression (presynaptic inhibition) by the cholinergic agonist carbachol than unpotentiated fibers. We conclude that low suppression of non-potentiated fibers during the learning process ensures the formation of self-organized representations in the neural network while the higher suppression of previously potentiated fibers minimizes interference between overlapping patterns. We show in a computational model of olfactory cortex, that, together, these two phenomena reduce the overlap between patterns that are stored within the same neural network structure. These results further demonstrate the contribution of acetylcholine to mechanisms of cortical plasticity. The results are consistent with the extensive evidence supporting a role for acetylcholine in encoding of new memories and enhancement of response to salient sensory stimuli.

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

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    Adel Zeidan

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

  14. Central Star Formation in Pseudobulges and Classical Bulges

    CERN Document Server

    Fisher, D B

    2006-01-01

    I use Spitzer 3.6-8.0 \\mu m color profiles to compare the radial structure of star formation in pseudobulges and classical bulges. Pseudobulges are ``bulges'' which form through secular evolution, rather than mergers. In this study, pseudobulges are identified using the presence of disk-like structure in the center of the galaxy (nuclear spiral, nuclear bar, and/or high ellipticity in bulge); classical bulges are those galaxy bulges with smooth isophotes which are round compared to the outer disk, and show no disky structure in their bulge. I show that galaxies structurally identified as having pseudobulges have higher central star formation rates than those of classical bulges. Further, I also show that galaxies identified as having classical bulges have remarkably regular star formation profiles. The color profiles of galaxies with classical bulges show a star forming outer disk with a sharp change, consistent with a decline in star formation rates, toward the center of the galaxy. Classical bulges have a n...

  15. Signaling by postsynaptic AMPA receptors in glutamatergic synapse maturation

    OpenAIRE

    2010-01-01

    Excitatory transmission in the brain is largely mediated by synapses containing the neurotransmitter glutamate. Neuronal circuitry is first established early in brain development requiring the formation of vast numbers of glutamatergic synapses at individual sites of contact made between presynaptic axons and postsynaptic dendrites. Despite mounting efforts in the last decade to identify the complex molecular mechanisms underlying initial synaptogenesis and the subsequent steps of synapse m...

  16. Formation of Galactic Prominence in the Galactic Central Region

    Science.gov (United States)

    Peng, Chih-Han; Matsumoto, Ryoji

    2017-02-01

    We carried out 2.5-dimensional resistive MHD simulations to study the formation mechanism of molecular loops observed by Fukui et al. in the Galactic central region. Since it is hard to form molecular loops by lifting up dense molecular gas, we study the formation mechanism of molecular gas in rising magnetic arcades. This model is based on the in situ formation model of solar prominences, in which prominences are formed by cooling instability in helical magnetic flux ropes formed by imposing converging and shearing motion at footpoints of the magnetic arch anchored to the solar surface. We extended this model to Galactic center scale (a few hundreds of parsecs). Numerical results indicate that magnetic reconnection taking place in the current sheet that formed inside the rising magnetic arcade creates dense blobs confined by the rising helical magnetic flux ropes. Thermal instability taking place in the flux ropes forms dense molecular filaments floating at high Galactic latitude. The mass of the filament increases with time and can exceed {10}5 {M}ȯ .

  17. LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation.

    Science.gov (United States)

    Neuillé, Marion; Morgans, Catherine W; Cao, Yan; Orhan, Elise; Michiels, Christelle; Sahel, José-Alain; Audo, Isabelle; Duvoisin, Robert M; Martemyanov, Kirill A; Zeitz, Christina

    2015-08-01

    Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). The exact role of LRIT3 in ON-bipolar cell signaling cascade remains to be elucidated. Recently, we have characterized a novel mouse model lacking Lrit3 [no b-wave 6, (Lrit3(nob6/nob6) )], which displays similar abnormalities to patients with cCSNB with LRIT3 mutations. Here we compare the localization of components of the ON-bipolar cell signaling cascade in wild-type and Lrit3(nob6/nob6) retinal sections by immunofluorescence confocal microscopy. An anti-LRIT3 antibody was generated. Immunofluorescent staining of LRIT3 in wild-type mice revealed a specific punctate labeling in the outer plexiform layer (OPL), which was absent in Lrit3(nob6/nob6) mice. LRIT3 did not co-localize with ribeye or calbindin but co-localized with mGluR6. TRPM1 staining was severely decreased at the dendritic tips of all depolarizing bipolar cells in Lrit3(nob6/nob6) mice. mGluR6, GPR179, RGS7, RGS11 and Gβ5 immunofluorescence was absent at the dendritic tips of cone ON-bipolar cells in Lrit3(nob6/nob6) mice, while it was present at the dendritic tips of rod bipolar cells. Furthermore, peanut agglutinin (PNA) labeling was severely reduced in the OPL in Lrit3(nob6/nob6) mice. This study confirmed the localization of LRIT3 at the dendritic tips of depolarizing bipolar cells in mouse retina and demonstrated the dependence of TRPM1 localization on the presence of LRIT3. As tested components of the ON-bipolar cell signaling cascade and PNA revealed disrupted localization, an additional function of LRIT3 in cone synapse formation is suggested. These results point to a possibly different regulation of the mGluR6 signaling cascade between rod and cone ON-bipolar cells.

  18. Bar effects on central star formation and AGN activity

    CERN Document Server

    Oh, Seulhee; Yi, Sukyoung K

    2011-01-01

    Galactic bars are often suspected to be a channel of gas inflow to the galactic center and trigger central star formation and active galactic nuclei (AGN) activity. However, the current status on this issue based on empirical studies is unsettling, especially on AGN. We investigate this question based on the Sloan Digital Sky Survey (SDSS) Data Release 7. From the nearby (0.01 < z < 0.05) bright (Mr < -19) database, we have constructed a sample of 6,658 relatively face-on late-type galaxies through visual inspection. We found 36% of them to have a bar. Bars are found to be more common in galaxies with earlier morphology. This makes sample selection critical. Parameter-based selections would miss a large fraction of barred galaxies of early morphology. Bar effects on star formation or AGN are difficult to understand properly because multiple factors (bar frequency, stellar mass, black-hole mass, gas contents, etc.) seem to contribute to them in intricate manners. In the hope of breaking these degenera...

  19. Chondrichthyans from the Pennsylvanian (Desmoinesian) Naco Formation of central Arizona

    Science.gov (United States)

    Elliott, D.K.; Irmis, R.B.; Hansen, M.C.; Olson, T.J.

    2004-01-01

    Teeth, spines, and dermal denticles of chondrichthyans are reported from the Middle Pennsylvanian (Desmoinesian) Naco Formation of central Arizona. The most common elements are crushing teeth of the cochliodont Deltodus angularis, less common are teeth of D. sublaevis, Venustodus leidyi, Lagarodus angustus, "Cladodus" occidentalis, Petalodus ohioensis, Orodus sp., and Hybodontoidea. Fin spines of Acondylacanthus sp., Amelacanthus sp., and Physonemus sp., and the dermal denticle Petrodus patelliformis are also present. The material of Venustodus leidyi shows for the first time that this animal was heterodont, having arched anterior teeth with a v-shaped profile grading posteriorly into lower crescentic, and finally flattened teeth. Lagarodus angustus is shown to have at least three tooth morphotypes, and a new tooth arrangement is proposed in which small anterior teeth are replaced posteriorly by large crushing teeth arranged in whorls. This fauna is similar to others in New Mexico, Colorado, and Ohio and constitutes a western extension of such faunas in North America. In addition, the presence of Deltodus sublaevis and Lagarodus angustus documents a range extension from a known European distribution, reinforcing the cosmopolitan nature of chondrichthyan faunas at this time. ?? 2004 by the Society of Vertebrate Paleontology.

  20. A bionics chemical synapse.

    Science.gov (United States)

    Thanapitak, Surachoke; Toumazou, Christofer

    2013-06-01

    Implementation of the current mode CMOS circuit for chemical synapses (AMPA and NMDA receptors) with dynamic change of glutamate as the neurotransmitter input is presented in this paper. Additionally, circuit realisation for receptor GABA(A) and GABA(B) with an electrical signal which symbolises γ-Aminobutyric Acid (GABA) perturbation is introduced. The chemical sensor for glutamate sensing is the modified ISFET with enzyme (glutamate oxidase) immobilisation. The measured results from these biomimetics chemical synapse circuits closely match with the simulation result from the mathematical model. The total power consumption of the whole chip (four chemical synapse circuits and all auxiliary circuits) is 168.3 μW. The total chip area is 3 mm(2) in 0.35-μm AMS CMOS technology.

  1. Adenosine gates synaptic plasticity at hippocampal mossy fiber synapses

    Science.gov (United States)

    Moore, Kimberly A.; Nicoll, Roger A.; Schmitz, Dietmar

    2003-11-01

    The release properties of synapses in the central nervous system vary greatly, not only across anatomically distinct types of synapses but also among the same class of synapse. This variation manifests itself in large part by differences in the probability of transmitter release, which affects such activity-dependent presynaptic forms of plasticity as paired-pulse facilitation and frequency facilitation. This heterogeneity in presynaptic function reflects differences in the intrinsic properties of the synaptic terminal and the activation of presynaptic neurotransmitter receptors. Here we show that the unique presynaptic properties of the hippocampal mossy fiber synapse are largely imparted onto the synapse by the continuous local action of extracellular adenosine at presynaptic A1 adenosine receptors, which maintains a low basal probability of transmitter release.

  2. 小脑肽1对浦肯野细胞突触形成作用的最新研究进展%The Advance on Studies of Cerebellin 1 Effects on Synapses Formation of Purkinje Cells

    Institute of Scientific and Technical Information of China (English)

    遇春霖; 张忠玲

    2015-01-01

    Cerebellin 1 is a glycoprotein in the cerebellum, which is produced and secreted from granule cells and works as a strong synapse organizer between Purkinje cells and parallel ifbers, the axons of the granule cells. The molecular mechanisms by which Cbln1 induces synapse formation were described and the related literature was reviewed.%小脑肽1是一种小脑中的特异性糖蛋白,由颗粒细胞生成并分泌,在颗粒细胞的平行纤维和浦肯野细胞之间的兴奋性突触形成过程中发挥重要作用。文中将详细描述小脑肽1诱导新生突触形成的分子机制。复习相关方面的文献,就小脑肽1对于浦肯野细胞上突触的形成以及兴奋与抑制传入的调节作用的研究现状作详细介绍。

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

    Science.gov (United States)

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

    2016-04-12

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

  4. Rhythmic Changes in Synapse Numbers in Drosophila melanogaster Motor Terminals

    Science.gov (United States)

    Ruiz, Santiago; Ferreiro, Maria Jose; Menhert, Kerstin I.; Casanova, Gabriela; Olivera, Alvaro; Cantera, Rafael

    2013-01-01

    Previous studies have shown that the morphology of the neuromuscular junction of the flight motor neuron MN5 in Drosophila melanogaster undergoes daily rhythmical changes, with smaller synaptic boutons during the night, when the fly is resting, than during the day, when the fly is active. With electron microscopy and laser confocal microscopy, we searched for a rhythmic change in synapse numbers in this neuron, both under light:darkness (LD) cycles and constant darkness (DD). We expected the number of synapses to increase during the morning, when the fly has an intense phase of locomotion activity under LD and DD. Surprisingly, only our DD data were consistent with this hypothesis. In LD, we found more synapses at midnight than at midday. We propose that under LD conditions, there is a daily rhythm of formation of new synapses in the dark phase, when the fly is resting, and disassembly over the light phase, when the fly is active. Several parameters appeared to be light dependent, since they were affected differently under LD or DD. The great majority of boutons containing synapses had only one and very few had either two or more, with a 70∶25∶5 ratio (one, two and three or more synapses) in LD and 75∶20∶5 in DD. Given the maintenance of this proportion even when both bouton and synapse numbers changed with time, we suggest that there is a homeostatic mechanism regulating synapse distribution among MN5 boutons. PMID:23840613

  5. Astroglial cradle in the life of the synapse.

    Science.gov (United States)

    Verkhratsky, Alexei; Nedergaard, Maiken

    2014-10-19

    Astroglial perisynaptic sheath covers the majority of synapses in the central nervous system. This glial coverage evolved as a part of the synaptic structure in which elements directly responsible for neurotransmission (exocytotic machinery and appropriate receptors) concentrate in neuronal membranes, whereas multiple molecules imperative for homeostatic maintenance of the synapse (transporters for neurotransmitters, ions, amino acids, etc.) are shifted to glial membranes that have substantially larger surface area. The astrocytic perisynaptic processes act as an 'astroglial cradle' essential for synaptogenesis, maturation, isolation and maintenance of synapses, representing the fundamental mechanism contributing to synaptic connectivity, synaptic plasticity and information processing in the nervous system.

  6. Astroglial cradle in the life of the synapse

    OpenAIRE

    2014-01-01

    Astroglial perisynaptic sheath covers the majority of synapses in the central nervous system. This glial coverage evolved as a part of the synaptic structure in which elements directly responsible for neurotransmission (exocytotic machinery and appropriate receptors) concentrate in neuronal membranes, whereas multiple molecules imperative for homeostatic maintenance of the synapse (transporters for neurotransmitters, ions, amino acids, etc.) are shifted to glial membranes that have substantia...

  7. Transfer characteristics of a thermosensory synapse in Caenorhabditis elegans

    OpenAIRE

    Narayan, Anusha; Laurent, Gilles; Sternberg, Paul W.

    2011-01-01

    Caenorhabditis elegans is a compact, attractive system for neural circuit analysis. An understanding of the functional dynamics of neural computation requires physiological analyses. We undertook the characterization of transfer at a central synapse in C. elegans by combining optical stimulation of targeted neurons with electrophysiological recordings. We show that the synapse between AFD and AIY, the first stage in the thermotactic circuit, exhibits excitatory, tonic, and graded release. We...

  8. [A new role of GABA on synapses].

    Science.gov (United States)

    Hayama, Tatsuya; Kasai, Haruo

    2014-08-01

    Neurons connect and transmit information via synapses. The major excitatory and inhibitory (E-I) neurotransmitters are glutamate and γ-amino butyric acid (GABA), respectively. The E-I balance plays an important role in various brain functions. In this review, we summarize the role of GABA on synaptic integration and synaptic plasticity by introducing our own recent findings. In synaptic integration, GABA is considered to inhibit depolarization induced by glutamate and suppress action potentials. We found that GABA also has a more direct role on the synaptic plasticity of excitatory inputs. GABA effectively promotes the shrinkage and elimination of synapses by suppressing local dendritic Ca(2+) signaling, while keeping the Ca(2+) domain of the NMDA receptors intact. In this manner, GABA promoted the activation of calcineurin, which in turn activated cofilin. Interestingly, shrinkage tended to spread, likely due to the spread of cofilin, and induced competitive selection of synapses via its phosphorylation and dephosphorylation. The selection of synapses is key to the reorganization of the central nervous system during development and in adulthood, and GABA plays key roles in various mental disorders, such as autism and schizophrenia. Our results account well for the in vivo GABA functions on synaptic selection, and may help to develop new therapeutic compounds.

  9. The immunological synapse

    DEFF Research Database (Denmark)

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

    2003-01-01

    The induction of a proper adaptive immune response is dependent on the correct transfer of information between antigen-presenting cells (APCs) and antigen-specific T cells. Defects in information transfer may result in the development of diseases, e.g. immunodeficiencies and autoimmunity. A disti......The induction of a proper adaptive immune response is dependent on the correct transfer of information between antigen-presenting cells (APCs) and antigen-specific T cells. Defects in information transfer may result in the development of diseases, e.g. immunodeficiencies and autoimmunity....... A distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure has been termed the "immunological synapse" (IS). Here, we review molecular aspects concerning...

  10. Mast cell synapses and exosomes: membrane contacts for information exchange

    Directory of Open Access Journals (Sweden)

    Amanda eCarroll-Portillo

    2012-03-01

    Full Text Available In addition to their central role in allergy, mast cells are involved in a wide variety of cellular interactions during homeostasis and disease. In this review, we discuss the ability of mast cells to extend their mechanisms for intercellular communication beyond the release of soluble mediators. These include formation of mast cell synapses on antigen presenting surfaces, as well as cell-cell contacts with dendritic cells and T cells. Release of membrane-bound exosomes also provide for the transfer of antigen, mast cell proteins and RNA to other leukocytes. With the recognition of the extended role mast cells have during immune modulation, further investigation of the processes in which mast cells are involved is necessary. This reopens mast cell research to exciting possibilities, demonstrating it to be an immunological frontier.

  11. Chanco formation, a potential Cretaceous reservoir, central Chile

    Energy Technology Data Exchange (ETDEWEB)

    Cecione, G.

    1983-07-01

    The Chanco embayment lies 300 km SSW of Santiago, Chile. The sequence within this basin above the metamorphic basement is: Chanco Formation (very clean sandstone), Quiriquina Formation (glauconitic sandstone, rich in organic matter), and Navidad Group (a very good caprock). This section thus contains reservoir, source and caprocks, and is therefore very promising for petroleum investigations. The offshore C-1 well yielded salt-water with gas shows, and two wells drilled onshore yielded shows of gas. The C-1 well lies on a gently-dipping EW-striking anticlinal structure, the presence of which makes the area very prospective.

  12. Paleomagnetism of the Puente Piedra Formation, Central Peru

    Science.gov (United States)

    May, Steven R.; Butler, Robert F.

    1985-02-01

    Paleomagnetic samples were collected from 15 sites in the early Cretaceous Puente Piedra Formation near Lima, Peru. This formation consists of interbedded volcanic flows and marine sediments and represents the oldest known rocks of the Andean coastal province in this region. The Puente Piedra Formation is interpreted as a submarine volcanic arc assemblage which along with an overlying sequence of early Cretaceous clastic and carbonate rocks represents a terrane whose paleogeographic relationship with respect to the Peruvian miogeocline in pre-Albian time is unknown. Moderate to high coercivities, blocking temperatures below 320°C, and diagnostic strong-field thermomagnetic behavior indicate that pyrrhotite is the dominant magnetic phase in the Puente Piedra Formation. This pyrrhotite carries a stable CRM acquired during an event of copper mineralization associated with the intrusion of the Santa Rosa super-unit of the Coastal Batholith at about 90 ± 5 m.y. B.P. The tectonically uncorrected formation mean direction of: D = 343.2°, I = -28.6°, α 95 = 3.4° is statistically concordant in inclination but discordant in declination with respect to the expected direction calculated from the 90-m.y. reference pole for cratonic South America. The observed declination indicates approximately 20° of counterclockwise rotation of the Puente Piedra rocks since about 90 m.y. This is consistent with other paleomagnetic data from a larger crustal block which may indicate modest counterclockwise rotation during the Cenozoic associated with crustal shortening and thickening in the region of the Peru-Chile deflection.

  13. Transfer characteristics of a thermosensory synapse in Caenorhabditis elegans.

    Science.gov (United States)

    Narayan, Anusha; Laurent, Gilles; Sternberg, Paul W

    2011-06-07

    Caenorhabditis elegans is a compact, attractive system for neural circuit analysis. An understanding of the functional dynamics of neural computation requires physiological analyses. We undertook the characterization of transfer at a central synapse in C. elegans by combining optical stimulation of targeted neurons with electrophysiological recordings. We show that the synapse between AFD and AIY, the first stage in the thermotactic circuit, exhibits excitatory, tonic, and graded release. We measured the linear range of the input-output curve and estimate the static synaptic gain as 0.056 (<0.1). Release showed no obvious facilitation or depression. Transmission at this synapse is peptidergic. The AFD/AIY synapse thus seems to have evolved for reliable transmission of a scaled-down temperature signal from AFD, enabling AIY to monitor and integrate temperature with other sensory input. Combining optogenetics with electrophysiology is a powerful way to analyze C. elegans' neural function.

  14. Differential mechanisms of transmission and plasticity at mossy fiber synapses.

    Science.gov (United States)

    McBain, Chris J

    2008-01-01

    The last few decades have seen the hippocampal formation at front and center in the field of synaptic transmission. However, much of what we know about hippocampal short- and long-term plasticity has been obtained from research at one particular synapse; the Schaffer collateral input onto principal cells of the CA1 subfield. A number of recent studies, however, have demonstrated that there is much to be learned about target-specific mechanisms of synaptic transmission by study of the lesser known synapse made between the granule cells of the dentate gyrus; the so-called mossy fiber synapse, and its targets both within the hilar region and the CA3 hippocampus proper. Indeed investigation of this synapse has provided an embarrassment of riches concerning mechanisms of transmission associated with feedforward excitatory and inhibitory control of the CA3 hippocampus. Importantly, work from a number of labs has revealed that mossy fiber synapses possess unique properties at both the level of their anatomy and physiology, and serve as an outstanding example of a synapse designed for target-specific compartmentalization of synaptic transmission. The purpose of the present review is to highlight several aspects of this synapse as they pertain to a novel mechanism of bidirectional control of synaptic plasticity at mossy fiber synapses made onto hippocampal stratum lucidum interneurons. It is not my intention to pour over all that is known regarding the mossy fiber synapse since many have explored this topic exhaustively in the past and interested readers are directed to other fine reviews (Henze et al., 2000; Urban et al., 2001; Lawrence and McBain, 2003; Bischofberger et al., 2006; Nicoll and Schmitz, 2005).

  15. Central role of pyrophosphate in acellular cementum formation.

    Directory of Open Access Journals (Sweden)

    Brian L Foster

    Full Text Available BACKGROUND: Inorganic pyrophosphate (PP(i is a physiologic inhibitor of hydroxyapatite mineral precipitation involved in regulating mineralized tissue development and pathologic calcification. Local levels of PP(i are controlled by antagonistic functions of factors that decrease PP(i and promote mineralization (tissue-nonspecific alkaline phosphatase, Alpl/TNAP, and those that increase local PP(i and restrict mineralization (progressive ankylosis protein, ANK; ectonucleotide pyrophosphatase phosphodiesterase-1, NPP1. The cementum enveloping the tooth root is essential for tooth function by providing attachment to the surrounding bone via the nonmineralized periodontal ligament. At present, the developmental regulation of cementum remains poorly understood, hampering efforts for regeneration. To elucidate the role of PP(i in cementum formation, we analyzed root development in knock-out ((-/- mice featuring PP(i dysregulation. RESULTS: Excess PP(i in the Alpl(-/- mouse inhibited cementum formation, causing root detachment consistent with premature tooth loss in the human condition hypophosphatasia, though cementoblast phenotype was unperturbed. Deficient PP(i in both Ank and Enpp1(-/- mice significantly increased cementum apposition and overall thickness more than 12-fold vs. controls, while dentin and cellular cementum were unaltered. Though PP(i regulators are widely expressed, cementoblasts selectively expressed greater ANK and NPP1 along the root surface, and dramatically increased ANK or NPP1 in models of reduced PP(i output, in compensatory fashion. In vitro mechanistic studies confirmed that under low PP(i mineralizing conditions, cementoblasts increased Ank (5-fold and Enpp1 (20-fold, while increasing PP(i inhibited mineralization and associated increases in Ank and Enpp1 mRNA. CONCLUSIONS: Results from these studies demonstrate a novel developmental regulation of acellular cementum, wherein cementoblasts tune cementogenesis by modulating

  16. Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood

    Directory of Open Access Journals (Sweden)

    Aaron D Levy

    2014-10-01

    Full Text Available Dendritic spines are the receptive contacts at most excitatory synapses in the central nervous system. Spines are dynamic in the developing brain, changing shape as they mature as well as appearing and disappearing as they make and break connections. Spines become much more stable in adulthood, and spine structure must be actively maintained to support established circuit function. At the same time, adult spines must retain some plasticity so their structure can be modified by activity and experience. As such, the regulation of spine stability and remodeling in the adult animal is critical for normal function, and disruption of these processes is associated with a variety of late onset diseases including schizophrenia and Alzheimer’s disease. The extracellular matrix (ECM, composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity. While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands. Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults.

  17. Numerical Modeling of Flat Slab Formation in Central Chile

    Science.gov (United States)

    Manea, M.; Perez-Gussinye, M.; Manea, V.; Fernandez, M.

    2009-12-01

    Subduction of oceanic plates beneath large continental masses is a rare process and at present it occurs only along western South America and Central Mexico. Likewise, flat subduction, understood here as where the slab enters at a normal angle and reverses its curvature to flatten at ~70-120 km depth, only occurs at present beneath South America. In general, the angle at which subduction occurs in the depth range of ~100 to ~200 km reflects the balance between negative buoyancy of the slab, elastic resistance of the slab to change the angle of subduction, and non-hydrostatic pressure forces induced by subduction-driven flow within the asthenosphere. The latter force, known as suction force, acts to prevent the slab from sinking into the mantle, and its magnitude increases with increasing subduction velocity, narrowness and viscosity decrease of the mantle wedge [Manea and Gurnis, 2007]. Recent observations show that the upper plate structure varies along the Andean margin, indicating that it is thicker and stronger above flat subduction zones and suggesting a correlation between upper plate structure and subduction angle [Pérez-Gussinyé et al., 2008; Booker et al., 2004]. In this study we use numerical models to explore the extent to which upper plate structure, through its influence on asthenospheric wedge shape and viscosity, can affect the angle of subduction. We test for which upper plate thickness and asthenospheric viscosity repeated cycles of steep and flat subduction are reproduced and compare our results to estimations of lithospheric thickness and the duration of flat and steep subduction cycles hypothesized along the Andean margin. Our models are constrained by realistic plate velocities in hot spot reference frame for both Nazca and South American plates [Muller et al., 2008], the Miocene-Present shortening for the Andes [Schelart et al., 2007] and realistic Nazca plate age distribution [Sdrolias and Muller, 2006]. Using the finite element package

  18. Star Formation Quenching Timescale of Central Galaxies in a Hierarchical Universe

    CERN Document Server

    Hahn, ChangHoon; Wetzel, Andrew R

    2016-01-01

    Central galaxies make up the majority of the galaxy population, including the majority of the quiescent population at $\\mathcal{M}_* > 10^{10}\\mathrm{M}_\\odot$. Thus, the mechanism(s) responsible for quenching central galaxies plays a crucial role in galaxy evolution as whole. We combine a high resolution cosmological $N$-body simulation with observed evolutionary trends of the "star formation main sequence," quiescent fraction, and stellar mass function at $z < 1$ to construct a model that statistically tracks the star formation histories and quenching of central galaxies. Comparing this model to the distribution of central galaxy star formation rates in a group catalog of the SDSS Data Release 7, we constrain the timescales over which physical processes cease star formation in central galaxies. Over the stellar mass range $10^{9.5}$ to $10^{11} \\mathrm{M}_\\odot$ we infer quenching e-folding times that span $1.5$ to $0.5\\; \\mathrm{Gyr}$ with more massive central galaxies quenching faster. For $\\mathcal{M}...

  19. Menin: a tumor suppressor that mediates postsynaptic receptor expression and synaptogenesis between central neurons of Lymnaea stagnalis.

    Directory of Open Access Journals (Sweden)

    Nichole Flynn

    Full Text Available Neurotrophic factors (NTFs support neuronal survival, differentiation, and even synaptic plasticity both during development and throughout the life of an organism. However, their precise roles in central synapse formation remain unknown. Previously, we demonstrated that excitatory synapse formation in Lymnaea stagnalis requires a source of extrinsic NTFs and receptor tyrosine kinase (RTK activation. Here we show that NTFs such as Lymnaea epidermal growth factor (L-EGF act through RTKs to trigger a specific subset of intracellular signalling events in the postsynaptic neuron, which lead to the activation of the tumor suppressor menin, encoded by Lymnaea MEN1 (L-MEN1 and the expression of excitatory nicotinic acetylcholine receptors (nAChRs. We provide direct evidence that the activation of the MAPK/ERK cascade is required for the expression of nAChRs, and subsequent synapse formation between pairs of neurons in vitro. Furthermore, we show that L-menin activation is sufficient for the expression of postsynaptic excitatory nAChRs and subsequent synapse formation in media devoid of NTFs. By extending our findings in situ, we reveal the necessity of EGFRs in mediating synapse formation between a single transplanted neuron and its intact presynaptic partner. Moreover, deficits in excitatory synapse formation following EGFR knock-down can be rescued by injecting synthetic L-MEN1 mRNA in the intact central nervous system. Taken together, this study provides the first direct evidence that NTFs functioning via RTKs activate the MEN1 gene, which appears sufficient to regulate synapse formation between central neurons. Our study also offers a novel developmental role for menin beyond tumour suppression in adult humans.

  20. Menin: A Tumor Suppressor That Mediates Postsynaptic Receptor Expression and Synaptogenesis between Central Neurons of Lymnaea stagnalis

    Science.gov (United States)

    Flynn, Nichole; Getz, Angela; Visser, Frank; Janes, Tara A.; Syed, Naweed I.

    2014-01-01

    Neurotrophic factors (NTFs) support neuronal survival, differentiation, and even synaptic plasticity both during development and throughout the life of an organism. However, their precise roles in central synapse formation remain unknown. Previously, we demonstrated that excitatory synapse formation in Lymnaea stagnalis requires a source of extrinsic NTFs and receptor tyrosine kinase (RTK) activation. Here we show that NTFs such as Lymnaea epidermal growth factor (L-EGF) act through RTKs to trigger a specific subset of intracellular signalling events in the postsynaptic neuron, which lead to the activation of the tumor suppressor menin, encoded by Lymnaea MEN1 (L-MEN1) and the expression of excitatory nicotinic acetylcholine receptors (nAChRs). We provide direct evidence that the activation of the MAPK/ERK cascade is required for the expression of nAChRs, and subsequent synapse formation between pairs of neurons in vitro. Furthermore, we show that L-menin activation is sufficient for the expression of postsynaptic excitatory nAChRs and subsequent synapse formation in media devoid of NTFs. By extending our findings in situ, we reveal the necessity of EGFRs in mediating synapse formation between a single transplanted neuron and its intact presynaptic partner. Moreover, deficits in excitatory synapse formation following EGFR knock-down can be rescued by injecting synthetic L-MEN1 mRNA in the intact central nervous system. Taken together, this study provides the first direct evidence that NTFs functioning via RTKs activate the MEN1 gene, which appears sufficient to regulate synapse formation between central neurons. Our study also offers a novel developmental role for menin beyond tumour suppression in adult humans. PMID:25347295

  1. ALPINE MAGMATIC-METALLOGENIC FORMATIONS OF THE NORTHWESTERN AND CENTRAL DINARIDES

    Directory of Open Access Journals (Sweden)

    Jakob Pamić

    1997-12-01

    Full Text Available In the paper are presented basic geological, petrologieca1, geochemi-cal and mineral deposit data for five main magmatic-metallogenic formations of the northwestern and central Dinarides: (lThe Permo Triassic rifting related andesite-diorite formations; (2 The Jurassic-Lower Cretaceous accretionary (ophiolite formations; (3 The Upper Cretaceous-Paleogene subduction related basalt-rhyohite formations; (4 The Paleogene collisional granite formations, and (5 The Oligo-cene-Neogene postsubduction andesite formations. All these magmatic-metallogenic formations originated in different geotectonic settings during the Alpine evolution of the Dinaridic parts of thc Tethys and the postorogenic evolution of the Paratethys and the Pannonian Basin, respectively.

  2. MODULATING EXCITATION THROUGH PLASTICITY AT INHIBITORY SYNAPSES

    Directory of Open Access Journals (Sweden)

    Vivien eChevaleyre

    2014-03-01

    Full Text Available Learning is believed to depend on lasting changes in synaptic efficacy such as long-term potentiation and long-term depression. As a result, a profusion of studies has tried to elucidate the mechanisms underlying these forms of plasticity. Traditionally, experience-dependent changes at excitatory synapses were assumed to underlie learning and memory formation. However, with the relatively more recent investigation of inhibitory transmission, it had become evident that inhibitory synapses are not only plastic, but also provide an additional way to modulate excitatory transmission and the induction of plasticity at excitatory synapses.Thanks to recent technological advances, progress has been made in understanding synaptic transmission and plasticity from particular interneuron subtypes. In this review article, we will describe various forms of synaptic plasticity that have been ascribed to two fairly well characterized populations of interneurons in the hippocampus, those expressing cholecystokinin (CCK and parvalbumin (PV. We will discuss the resulting changes in the strength and plasticity of excitatory transmission that occur in the local circuit as a result of the modulation of inhibitory transmission. We will focus on the hippocampus because this region has a relatively well-understood circuitry, numerous forms of activity-dependent plasticity and a multitude of identified interneuron subclasses.

  3. Gastropods from the Campanian-Maastrichtian Aruma Formation, Central Saudi Arabia

    Science.gov (United States)

    Gameil, Mohamed; El-Sorogy, Abdelbaset S.

    2015-03-01

    The gastropod fauna of the Upper Cretaceous Aruma Formation in central Saudi Arabia comprises fifteen species belonging to fifteen genera, fourteen families, and five clades. The species are not abundant at any individual stratigraphic level but are equally and irregularly scattered in the formation. The studied species come mainly from the Hajajah Member of Upper Cretaceous Aruma Formation in central Saudi Arabia. Calliomphalus orientalis (Douvillé, 1916); Coelobolma corbarica Cossmann, 1918; Turritella (Torquesia) figarii Quaas, 1902; Neoptyxis olisiponensis (Sharpe, 1850) and Otostoma (Otostoma) divaricatum (d'Orbigny, 1847) are recorded from the Upper Cretaceous of central Arabia for the first time. The identified species have a close affinity to the Tethyan fauna known from other parts in Asia, Africa and Europe. Herbivores and predators are the dominant trophic groups which may indicate shallow marine lagoonal and relatively open marine environment.

  4. Synapse rearrangements upon learning: from divergent-sparse connectivity to dedicated sub-circuits.

    Science.gov (United States)

    Caroni, Pico; Chowdhury, Ananya; Lahr, Maria

    2014-10-01

    Learning can involve formation of new synapses and loss of synapses, providing memory traces of learned skills. Recent findings suggest that these synapse rearrangements reflect assembly of task-related sub-circuits from initially broadly distributed and sparse connectivity in the brain. These local circuit remodeling processes involve rapid emergence of synapses upon learning, followed by protracted validation involving strengthening of some new synapses, and selective elimination of others. The timing of these consolidation processes can vary. Here, we review these findings, focusing on how molecular/cellular mechanisms of synapse assembly, strengthening, and elimination might interface with circuit/system mechanisms of learning and memory consolidation. An integrated understanding of these learning-related processes should provide a better basis to elucidate how experience, genetic background, and disease influence brain function.

  5. Distributed randomized algorithms for opinion formation, centrality computation and power systems estimation: A tutorial overview

    NARCIS (Netherlands)

    Frasca, Paolo; Ishii, Hideaki; Ravazzi, Chiara; Tempo, Roberto

    2015-01-01

    In this tutorial paper, we study three specific applications: opinion formation in social networks, centrality measures in complex networks and estimation problems in large-scale power systems. These applications fall under a general framework which aims at the construction of algorithms for distrib

  6. FORMATION 2005 Pour L'Afrique SURLA TECHNIQUE DES PETITES CENTRALES HYDRO-ELECTRIQUES

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    “Le stage de formation 2005 por l'Afrique sur la technique de petites centrales hydro-electrique”est subventionnte par le Gouvernement Chinois specialement pour les pays en voie de developpement,dans le cadre de l'aide aux pays en voie de developpement.Charge par le Ministere chinois du Commerce,

  7. Country-specific strategy and new venture formation in Central and East Europe

    NARCIS (Netherlands)

    Gil, A.; Brouthers, K.D.; Nakos, G.; Brouthers, L.E.

    2006-01-01

    In this study, we examine the influence of three country-specific strategies (market-seeking, client-following and resource-seeking) on new venture formation decisions for firms entering Central and East Europe. We found that market-seeking and resource-seeking strategies tend to influence venture c

  8. Intraflagellar transport: a new player at the immune synapse.

    Science.gov (United States)

    Finetti, Francesca; Paccani, Silvia Rossi; Rosenbaum, Joel; Baldari, Cosima T

    2011-04-01

    The assembly and maintenance of primary cilia, which orchestrate signaling pathways centrally implicated in cell proliferation, differentiation and migration, are ensured by multimeric protein particles in a process known as intraflagellar transport (IFT). It has recently been demonstrated that a number of IFT components are expressed in hematopoietic cells, which have no cilia. Here, we summarize data for an unexpected role of IFT proteins in immune synapse assembly and intracellular membrane trafficking in T lymphocytes, and discuss the hypothesis that the immune synapse could represent the functional homolog of the primary cilium in these cells.

  9. Centralized Dynamics and Control of Novel Orbiting Formations of Tethered Spacecraft

    Science.gov (United States)

    Quadrelli, Marco B.; Hadaegh, Fred Y.

    acting as leader of the tethered formation. An application of this problem arises when a distributed sensor array formed by a chain of tethered data-gathering vehicles is being commanded to reconfigure from a remote location by the formation leader. Another application is in radar mapping where multiple free-flying vehicles synthesize multiple apertures with the main tethered vehicle for increased coverage. In this way, a centralized control architecture distributes the information flow among the members of the sensor array. Defining an orbiting formation as an ensemble of orbiting spacecraft performing a cooperative task, we point out that, until now, only spacecraft modeled as rigid bodies have been analyzed in the literature of orbiting formations and constellations. After the formation is in place, one may identify what is known as the virtual truss, i.e. the connection between the elements of the formation, which provides structural rigidity on account of the information flow between them. Our problem is different than conventional formation dynamics problems in that the presence of a tethered spacecraft within the formation demands an investigation of the dynamics coupling between spacecraft caused by tether viscoelasticity. The dynamics model takes into account the orbital and spacecraft dynamics of each vehicle. The control architecture features a separated spacecraft, which has visibility to the entire group of tethered vehicles. This vehicle is the leader of the formation, and ensures that the spacecraft on the tether remain connected and move according to a pre-specified program. The control system design consists of a proportional-derivative feedback plus acceleration feedforward. This ensures that modeling errors are compensated appropriately, and that the commanded slew is tracked accurately. The leader is also where the centralized estimator is located. This estimator continuously updates the state of the formation and estimates inter

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

    Science.gov (United States)

    Luz, Liliana L; Currie, Stephen P; Daw, Michael I

    2017-01-01

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

  11. Distribution of input and output synapses on the central branches of bushcricket and cricket auditory afferent neurones: immunocytochemical evidence for GABA and glutamate in different populations of presynaptic boutons.

    Science.gov (United States)

    Hardt, M; Watson, A H

    1999-01-18

    In order to investigate the synapses on the terminals of primary auditory afferents in the bushcricket and cricket, these were impaled with microelectrodes and after physiological characterisation, injected intracellularly with horseradish peroxidase. The tissue was prepared for electron microscopy, and immunocytochemistry for gamma-aminobutyric acid (GABA) and glutamate was carried out on ultrathin sections by using a post-embedding immunogold technique. The afferent terminals received many input synapses. Between 60-65% of these were made by processes immunoreactive for GABA and approximately 25% from processes immunoreactive for glutamate. The relative distribution of the different classes of input were analysed from serial section reconstruction of terminal afferent branches. Inputs from GABA and glutamate-immunoreactive processes appeared to be scattered at random over the terminal arborisation of the afferents both with respect to each other and to the architecture of the terminals. They were, however, always found close to the output synapses. The possible roles of presynaptic inhibition in the auditory afferents is discussed in the context of the auditory responses of the animals.

  12. CHAMBERED HEXACTINELLID SPONGES FROM UPPER TRIASSIC(NORIAN-RHAETIAN? REEFS OF NAYBAND FORMATION IN CENTRAL IRAN

    Directory of Open Access Journals (Sweden)

    B. SENOWBARI-DARYAN

    2012-07-01

    Full Text Available This paper describes several chambered hexactinellid sponges, including Casearia iranica n.sp., C. vezvanensis n. sp., C. delijanensis n. sp., Esfahanella magna gen. n. n. sp., and E. parva gen. n. n. sp. from reefs of the Upper Triassic (Norian-Rhaetian Nayband Formation exposed south of the town of Delijan in central Iran. The relative abundance of chambered and non-chambered hexactinellid sponges at this locality - as compared to hypercalcified representatives - highlight the importance of this group of sponges in reef and reefal limestones in central and east Tethys (China, Caucasia, Iran. 

  13. Purinergic signaling at immunological synapses.

    Science.gov (United States)

    Dubyak, G R

    2000-07-01

    The early studies and hypotheses of Geoffrey Burnstock catalyzed intensive characterization of roles for nucleotides and P2 nucleotide receptors in neurotransmission and neuromodulation. These latter analyses have focused on the mechanisms of nucleotide release and action in the microenvironments of nerve endings and synapses. However, studies of various white blood cells, such as monocytes, neutrophils, and lymphocytes, suggest that locally released nucleotides also modulate intercellular signaling at so-called 'immunological synapses'. This communication describes recent findings and speculations regarding nucleotide release and signaling in several key phases of the immune and inflammatory responses.

  14. Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses.

    Directory of Open Access Journals (Sweden)

    Elena Frola

    Full Text Available The neurotransmitter GABA regulates many aspects of inhibitory synapse development. We tested the hypothesis that GABAA receptors (GABAARs work together with the synaptic adhesion molecule neuroligin 2 (NL2 to regulate synapse formation in different subcellular compartments. We investigated mice ("γ2 knockdown mice" with an engineered allele of the GABAAR γ2 subunit gene which produced a mosaic expression of synaptic GABAARs in neighboring neurons, causing a strong imbalance in synaptic inhibition. Deletion of the γ2 subunit did not abolish synapse formation or the targeting of NL2 to distinct types of perisomatic and axo-dendritic contacts. Thus synaptic localization of NL2 does not require synaptic GABAARs. However, loss of the γ2 subunit caused a selective decrease in the number of axo-dendritic synapses on cerebellar Purkinje cells and cortical pyramidal neurons, whereas perisomatic synapses were not significantly affected. Notably, γ2-positive cells had increased axo-dendritic innervation compared with both γ2-negative and wild-type counterparts. Moreover heterologous synapses on spines, that are found after total deletion of GABAARs from all Purkinje cells, were rare in cerebella of γ2 knockdown mice. These findings reveal a selective role of γ2 subunit-containing GABAARs in regulating synapse development in distinct subcellular compartments, and support the hypothesis that the refinement of axo-dendritic synapses is regulated by activity-dependent competition between neighboring neurons.

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

    Directory of Open Access Journals (Sweden)

    Uzi eHadad

    2015-09-01

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

  16. Laminins containing the beta2 chain modulate the precise organization of CNS synapses.

    Science.gov (United States)

    Egles, Christophe; Claudepierre, Thomas; Manglapus, Mary K; Champliaud, Marie-France; Brunken, William J; Hunter, Dale D

    2007-03-01

    Synapses are formed and stabilized by concerted interactions of pre-, intra-, and post-synaptic components; however, the precise nature of the intrasynaptic components in the CNS remains obscure. Potential intrasynaptic components include extracellular matrix molecules such as laminins; here, we isolate beta2-containing laminins, including perhaps laminins 13 (alpha3beta2gamma3) and 14 (alpha4beta2gamma3), from CNS synaptosomes suggesting a role for these molecules in synaptic organization. Indeed, hippocampal synapses that form in vivo in the absence of these laminins are malformed at the ultrastructural level and this malformation is replicated in synapses formed in vitro, where laminins are provided largely by the post-synaptic neuron. This recapitulation of the in vivo function of laminins in vitro suggests that the malformations are a direct consequence of the removal of laminins from the synapse. Together, these results support a role for neuronal laminins in the structural integrity of central synapses.

  17. Synapse Pathology in Psychiatric and Neurologic Disease

    NARCIS (Netherlands)

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

    2010-01-01

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

  18. FORMATION MECHANISM AND SPATIAL PATTERN OF URBAN AGGLOMERATION IN CENTRAL JILIN OF CHINA

    Institute of Scientific and Technical Information of China (English)

    QIN Gan; ZHANG Ping-yu; JIAO Bin

    2006-01-01

    Urban agglomeration is made up of cities with different sizes to be linked by traffic network in a given area, and it is an inevitable result when urbanization reaches a certain level. Taking urban agglomerationin central Jilin(UACJ) as an example, this article analyzes the formation mechanism and spatial pattern of urban agglomeration in the less-developed area. First, the dynamics of UACJ has been analyzed from the aspects of geographical condition, economic foundation, policy background, and traffic condition. Then the development process is divided into three stages-single city, city group and city cluster. Secondly, the central cities are identified from the aspects of city centrality, and the development axes are classified based on economic communication capacity. Finally, the urban agglomeration is divided into five urban economic regions in order to establish the reasonable distribution of industries.

  19. Deep structure of the central Lesser Antilles Island Arc : relevance for the formation of continental crust

    OpenAIRE

    H. Kopp; Weinzierl, W.; Becel, A.; Charvis, Philippe; Evain, M.; Flueh, E. R.; Gailler, A.; Galve, A.; Hirn, A.; Kandilarov, A.; D. Klaeschen; M. Laigle; Papenberg, C.; L. Planert; Roux, E.

    2011-01-01

    Oceanic island arcs are sites of high magma production and contribute to the formation of continental crust. Geophysical studies may provide information on the configuration and composition of island arc crust, however, to date only few seismic profiles exist across active island arcs, limiting our knowledge on the deep structure and processes related to the production of arc crust. We acquired active-source wide-angle seismic data crossing the central Lesser Antilles island arc north of Domi...

  20. QUENCHING OF STAR FORMATION IN SLOAN DIGITAL SKY SURVEY GROUPS: CENTRALS, SATELLITES, AND GALACTIC CONFORMITY

    Energy Technology Data Exchange (ETDEWEB)

    Knobel, Christian; Lilly, Simon J.; Woo, Joanna; Kovač, Katarina, E-mail: christian.knobel@phys.ethz.ch [Institute for Astronomy, ETH Zurich, CH-8093 Zurich (Switzerland)

    2015-02-10

    We re-examine the fraction of low-redshift Sloan Digital Sky Survey satellites and centrals in which star formation has been quenched, using the environment quenching efficiency formalism that separates out the dependence of stellar mass. We show that the centrals of the groups containing the satellites are responding to the environment in the same way as their satellites (at least for stellar masses above 10{sup 10.3} M {sub ☉}), and that the well-known differences between satellites and the general set of centrals arise because the latter are overwhelmingly dominated by isolated galaxies. The widespread concept of ''satellite quenching'' as the cause of environmental effects in the galaxy population can therefore be generalized to ''group quenching''. We then explore the dependence of the quenching efficiency of satellites on overdensity, group-centric distance, halo mass, the stellar mass of the satellite, and the stellar mass and specific star formation rate (sSFR) of its central, trying to isolate the effect of these often interdependent variables. We emphasize the importance of the central sSFR in the quenching efficiency of the associated satellites, and develop the meaning of this ''galactic conformity'' effect in a probabilistic description of the quenching of galaxies. We show that conformity is strong, and that it varies strongly across parameter space. Several arguments then suggest that environmental quenching and mass quenching may be different manifestations of the same underlying process. The marked difference in the apparent mass dependencies of environment quenching and mass quenching which produces distinctive signatures in the mass functions of centrals and satellites will arise naturally, since, for satellites at least, the distributions of the environmental variables that we investigate in this work are essentially independent of the stellar mass of the satellite.

  1. MOLECULAR GAS AND STAR-FORMATION PROPERTIES IN THE CENTRAL AND BAR REGIONS OF NGC 6946

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Hsi-An; Sorai, Kazuo [Department of Physics, Hokkaido University, Kita 10, Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810 (Japan); Kuno, Nario [Division of Physics, Faculty of Pure and Applied Sciences, University of Tsukuba, Tennodai, Tsukuba, Ibaraki 305-8571 (Japan); Koda, Jin [Department of Physics and Astronomy, Stony Brook University, Stony Brook, NY 11794-3800 (United States); Hirota, Akihiko [Joint ALMA Observatory, Alonso de Cordova 3107, Vitacura, Santiago (Chile); Kaneko, Hiroyuki, E-mail: hapan@astro1.sci.hokudai.ac.jp [Nobeyama Radio Observatory, NAOJ, Minamimaki, Minamisaku, Nagano 384-1305 (Japan)

    2015-12-10

    In this work, we investigate the molecular gas and star-formation properties in the barred spiral galaxy NGC 6946 using multiple molecular lines and star-formation tracers. A high-resolution image (100 pc) of {sup 13}CO (1–0) is created for the inner 2 kpc disk by the single-dish Nobeyama Radio Observatory 45 m telescope and interferometer Combined Array for Research in Millimeter-wave Astronomy, including the central region (nuclear ring and bar) and the offset ridges of the primary bar. Single-dish HCN (1–0) observations were also made to constrain the amount of dense gas. The physical properties of molecular gas are inferred from (1) the large velocity gradient calculations using our observations and archival {sup 12}CO (1–0), {sup 12}CO(2–1) data, (2) the dense gas fraction suggested by the luminosity ratio of HCN to {sup 12}CO (1–0), and (3) the infrared color. The results show that the molecular gas in the central region is warmer and denser than that of the offset ridges. The dense gas fraction of the central region is similar to that of luminous infrared galaxies/ultraluminous infrared galaxies, whereas the offset ridges are close to the global average of normal galaxies. The coolest and least-dense region is found in a spiral-like structure, which was misunderstood to be part of the southern primary bar in previous low-resolution observations. The star-formation efficiency (SFE) changes by about five times in the inner disk. The variation of SFE agrees with the prediction in terms of star formation regulated by the galactic bar. We find a consistency between the star-forming region and the temperature inferred by the infrared color, suggesting that the distribution of subkiloparsec-scale temperature is driven by star formation.

  2. What controls star formation in the central 500 pc of the Galaxy?

    CERN Document Server

    Kruijssen, J M Diederik; Elmegreen, Bruce G; Murray, Norman; Bally, John; Testi, Leonardo; Kennicutt, Robert C

    2013-01-01

    The star formation rate (SFR) in the Central Molecular Zone (CMZ, i.e. the central 500 pc) of the Milky Way is lower by a factor of >10 than expected for the substantial amount of dense gas it contains, which challenges current star formation theories. In this paper, we quantify which physical mechanisms could be causing this observation. On scales larger than the disc scale height, the low SFR is found to be consistent with episodic star formation due to secular instabilities or variations of the gas inflow along the Galactic bar. The CMZ is marginally Toomre-stable when including gas and stars, but highly Toomre-stable when only accounting for the gas, indicating that the condensation of self-gravitating clouds may be limited. On small scales, we find that the SFR in the CMZ is consistent with an elevated critical density for star formation due to the high turbulent pressure - potentially aided by weak magnetic effects and an underproduction of massive stars due to a bottom-heavy IMF. The existence of a uni...

  3. CABINETS OPERATING RULES AND COALITIONN FORMATION IN CENTRAL AND EASTERN EUROPE

    Directory of Open Access Journals (Sweden)

    DANA IRINA IONITA

    2011-04-01

    Full Text Available After the fall of communism in the late ’80 in Central and Eastern Europe, due to the appearance of several political parties in each state, there was the need to form coalitions in order to provide support for the governments. This paper aims to identify the institutional features that influence the coalition formation process using the rational choice institutionalism approach. In this case, the political parties, who seek to optimize their benefits in the government formation process, are constrained by the institutional environment. The institutional environment comprises the rules that determine how the governments are formed. Particularly, this paper aim is to identify how the cabinet operating rules affect the outcomes of the coalition formation process. In order to do so, I will develop a quantitative analysis of 110 cabinets in Estonia, Latvia, Lithuania, Poland, Czech Republic, Slovakia, Hungary, Slovenia, Romania and Bulgaria formed after the first free elections subsequent to the communist fall until the beginning of 2010. These countries represent the post-communist states that joined the European Union, finalizing the democratization process at least from a formal point a view. This cross-country comparison tries to explain how some institutional features influence the formation of coalitions in new democracies. This research is valuable due to the lack of this type of comparative studies on Central and Eastern European states.

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

    Directory of Open Access Journals (Sweden)

    Johannes eBill

    2014-12-01

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

  5. F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse.

    Science.gov (United States)

    Pérez-Martínez, Manuel; Gordón-Alonso, Mónica; Cabrero, José Román; Barrero-Villar, Marta; Rey, Mercedes; Mittelbrunn, María; Lamana, Amalia; Morlino, Giulia; Calabia, Carmen; Yamazaki, Hiroyuki; Shirao, Tomoaki; Vázquez, Jesús; González-Amaro, Roberto; Veiga, Esteban; Sánchez-Madrid, Francisco

    2010-04-01

    The adaptive immune response depends on the interaction of T cells and antigen-presenting cells at the immune synapse. Formation of the immune synapse and the subsequent T-cell activation are highly dependent on the actin cytoskeleton. In this work, we describe that T cells express drebrin, a neuronal actin-binding protein. Drebrin colocalizes with the chemokine receptor CXCR4 and F-actin at the peripheral supramolecular activation cluster in the immune synapse. Drebrin interacts with the cytoplasmic tail of CXCR4 and both proteins redistribute to the immune synapse with similar kinetics. Drebrin knockdown in T cells impairs the redistribution of CXCR4 and inhibits actin polymerization at the immune synapse as well as IL-2 production. Our data indicate that drebrin exerts an unexpected and relevant functional role in T cells during the generation of the immune response.

  6. Biofilm formation in long-term central venous catheters in children with cancer

    DEFF Research Database (Denmark)

    Handrup, Mette Møller; Fuursted, Kurt; Funch, Peter;

    2012-01-01

    Taurolidine has demonstrated inhibition of biofilm formation in vitro. The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters. Forty-eight children with cancer were randomized to catheter locking by heparin (n...... = 22) or taurolidine (n = 26), respectively. After removal, catheters were examined by standardized scanning electron microscopy to assess quantitative biofilm formation. Biofilm was present if morphologically typical structures and bacterial cells were identified. Quantitative and semi......-quantitative cultures were also performed. Biofilm was identified in 23 of 26 catheters from the taurolidine group and 21 of 22 catheters from the heparin group. A positive culture was made of six of the catheters locked with taurolidine and heparin, respectively (p = 0.78). The rate of catheter-related bloodstream...

  7. Cadherin-9 regulates synapse-specific differentiation in the developing hippocampus.

    Science.gov (United States)

    Williams, Megan E; Wilke, Scott A; Daggett, Anthony; Davis, Elizabeth; Otto, Stefanie; Ravi, Deepak; Ripley, Beth; Bushong, Eric A; Ellisman, Mark H; Klein, Gerd; Ghosh, Anirvan

    2011-08-25

    Our understanding of mechanisms that regulate the differentiation of specific classes of synapses is limited. Here, we investigate the formation of synapses between hippocampal dentate gyrus (DG) neurons and their target CA3 neurons and find that DG neurons preferentially form synapses with CA3 rather than DG or CA1 neurons in culture, suggesting that specific interactions between DG and CA3 neurons drive synapse formation. Cadherin-9 is expressed selectively in DG and CA3 neurons, and downregulation of cadherin-9 in CA3 neurons leads to a selective decrease in the number and size of DG synapses onto CA3 neurons. In addition, loss of cadherin-9 from DG or CA3 neurons in vivo leads to striking defects in the formation and differentiation of the DG-CA3 mossy fiber synapse. These observations indicate that cadherin-9 bidirectionally regulates DG-CA3 synapse development and highlight the critical role of differentially expressed molecular cues in establishing specific connections in the mammalian brain.

  8. 'Then give him to the crocodiles' : violence, State formation, and cultural discontinuity in west central Zambia, 1600-2000

    NARCIS (Netherlands)

    Binsbergen, van W.M.J.

    2003-01-01

    The purpose of this chapter is to explore the extent to which violence can be said to underlie any form of Stae formation in precolonial Africa. This is done by examining the role of violence in State formation in west central Zambia from the 17th century onwards. The chapter shows that State format

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

    Directory of Open Access Journals (Sweden)

    Carmen E Flores

    2014-10-01

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

  10. Climbing fiber synapse elimination in cerebellar Purkinje cells.

    Science.gov (United States)

    Watanabe, Masahiko; Kano, Masanobu

    2011-11-01

    Innervation of Purkinje cells (PCs) by multiple climbing fibers (CFs) is refined into mono-innervation during the first three postnatal weeks of rodents' lives. In this review article, we will integrate the current knowledge on developmental process and mechanisms of CF synapse elimination. In the 'creeper' stage of CF innervation (postnatal day 0 (P0)∼), CFs creep among PC somata to form transient synapses on immature dendrites. In the 'pericellular nest' stage (P5∼), CFs densely surround and innervate PC somata. CF innervation is then displaced to the apical portion of PC somata in the 'capuchon' stage (P9∼), and translocate to dendrites in the 'dendritic' (P12∼) stage. Along with the developmental changes in CF wiring, functional and morphological distinctions become larger among CF inputs. PCs are initially innervated by more than five CFs with similar strengths (∼P3). During P3-7 only a single CF is selectively strengthened (functional differentiation), and it undergoes dendritic translocation from P9 on (dendritic translocation). Following the functional differentiation, perisomatic CF synapses are eliminated nonselectively; this proceeds in two distinct phases. The early phase (P7-11) is conducted independently of parallel fiber (PF)-PC synapse formation, while the late phase (P12-17) critically depends on it. The P/Q-type voltage-dependent Ca(2+) channel in PCs triggers selective strengthening of single CF inputs, promotes dendritic translocation of the strengthened CFs, and drives the early phase of CF synapse elimination. In contrast, the late phase is mediated by the mGluR1-Gαq-PLCβ4-PKCγ signaling cascade in PCs driven at PF-PC synapses, whose structural connectivity is stabilized and maintained by the GluRδ2-Cbln1-neurexin system.

  11. Bar-induced central star formation as revealed by integral field spectroscopy from CALIFA

    CERN Document Server

    Lin, Lin; He, Yanqin; Xiao, Ting; Wang, Enci

    2016-01-01

    We investigate the recent star formation history (SFH) in the inner region of 57 nearly face-on spiral galaxies selected from the Calar Alto Legacy Integral Field Area (CALIFA) survey. For each galaxy we use the integral field spectroscopy from CALIFA to obtain two-dimensional maps and radial profiles of three parameters that are sensitive indicators of the recent SFH: the 4000\\AA\\ break (D$_n$(4000)), and the equivalent width of H$\\delta$ absorption (EW(H$\\delta_A$)) and H$\\alpha$ emission (EW(H$\\alpha$)). We have also performed photometric decomposition of bulge/bar/disk components based on SDSS optical image. We identify a class of 17 "turnover" galaxies whose central region present significant drop in D$_n$(4000), and most of them correspondingly show a central upturn in EW(H$\\delta_A$) and EW(H$\\alpha$). This indicates that the central region of the turnover galaxies has experienced star formation in the past 1-2 Gyr, which makes the bulge younger and more star-forming than surrounding regions. We find a...

  12. SMALLER FORAMINIFERS FROM THE LOWER PERMIAN EMARAT FORMATION, EAST OF FIRUZKUH (CENTRAL ALBORZ, IRAN

    Directory of Open Access Journals (Sweden)

    HAMED YARAHMADZAHI

    2016-10-01

    Full Text Available The uppermost Carboniferous-Lower Permian Dorud Group of the Gaduk section in Central Alborz (Iran is more than 44 m-thick; it includes thick succession of conglomerates, quartzarenites, calcareous sandstones, oncolitic fusulinid limestones, sandy limestones, sandstones and shales. The Toyeh, Emarat and Shah Zeid formations of this Group were dated from the Gzhelian to the Sakmarian. A review of the uppermost Gzhelian, Asselian and lower Sakmarian smaller foraminifers of the Emarat Formation of the Gaduk section is here presented. Three foraminiferal biozones are defined: the Nodosinelloides shikhanica-Geinitzina primitiva Zone is latest Gzhelian in age; the Nodosinelloides spp.-Geinitzina spp.-Pseudoacutella partoazari Zone is Asselian; the Rectogordius iranicus gadukensis-Endothyra cf. bamberi Zone is early Sakmarian in age. A new subspecies Rectogordius iranicus gadukensis n. subsp. is described, and the genera Pseudovidalina and Grovesella are discussed. The studied assemblages are correlated with those from the Carnic Alps (Austria-Italy, East European Platform of Russia, the Urals (Russia, Darvaz (Uzbekistan, the northern and central Pamirs (Tajikistan, Central Iran, northern Afghanistan and other classical regions of the Tethyan realm.

  13. Fear learning increases the number of polyribosomes associated with excitatory and inhibitory synapses in the barrel cortex.

    Directory of Open Access Journals (Sweden)

    Malgorzata Jasinska

    Full Text Available Associative fear learning, resulting from whisker stimulation paired with application of a mild electric shock to the tail in a classical conditioning paradigm, changes the motor behavior of mice and modifies the cortical functional representation of sensory receptors involved in the conditioning. It also induces the formation of new inhibitory synapses on double-synapse spines of the cognate barrel hollows. We studied density and distribution of polyribosomes, the putative structural markers of enhanced synaptic activation, following conditioning. By analyzing serial sections of the barrel cortex by electron microscopy and stereology, we found that the density of polyribosomes was significantly increased in dendrites of the barrel activated during conditioning. The results revealed fear learning-induced increase in the density of polyribosomes associated with both excitatory and inhibitory synapses located on dendritic spines (in both single- and double-synapse spines and only with the inhibitory synapses located on dendritic shafts. This effect was accompanied by a significant increase in the postsynaptic density area of the excitatory synapses on single-synapse spines and of the inhibitory synapses on double-synapse spines containing polyribosomes. The present results show that associative fear learning not only induces inhibitory synaptogenesis, as demonstrated in the previous studies, but also stimulates local protein synthesis and produces modifications of the synapses that indicate their potentiation.

  14. Bar Effects on Central Star Formation and Active Galactic Nucleus Activity

    Science.gov (United States)

    Oh, Seulhee; Oh, Kyuseok; Yi, Sukyoung K.

    2012-01-01

    Galactic bars are often suspected to be channels of gas inflow to the galactic center and to trigger central star formation and active galactic nucleus (AGN) activity. However, the current status on this issue based on empirical studies is unsettling, especially regarding AGNs. We investigate this question based on the Sloan Digital Sky Survey Data Release 7. From the nearby (0.01 inspection. We found 36% of them to have a bar. Bars are found to be more common in galaxies with earlier morphology. This makes sample selection critical. Parameter-based selections would miss a large fraction of barred galaxies of early morphology. Bar effects on star formation or AGNs are difficult to understand properly because multiple factors (bar frequency, stellar mass, black hole mass, gas contents, etc.) seem to contribute to them in intricate manners. In the hope of breaking these degeneracies, we inspect bar effects for fixed galaxy properties. Bar effects on central star formation seem higher in redder galaxies. Bar effects on AGNs on the other hand are higher in bluer and less massive galaxies. These effects seem more pronounced with increasing bar length. We discuss possible implications in terms of gas contents, bar strength, bar evolution, fueling timescale, and the dynamical role of supermassive black hole.

  15. Stellar Ages and Metallicities of Central and Satellite Galaxies: Implications for Galaxy Formation and Evolution

    CERN Document Server

    Pasquali, Anna; Fontanot, Fabio; Bosch, Frank C van den; De Lucia, Gabriella; Mo, H J; Yang, Xiaohu

    2009-01-01

    Using a large SDSS galaxy group catalogue, we study how the stellar ages and metallicities of central and satellite galaxies depend on stellar mass and halo mass. We find that satellites are older and metal-richer than centrals of the same stellar mass. In addition, the slopes of the age-stellar mass and metallicity-stellar mass relations are found to become shallower in denser environments. This is due to the fact that the average age and metallicity of low mass satellite galaxies increase with the mass of the halo in which they reside. A comparison with the semi-analytical model of Wang et al. (2008) shows that it succesfully reproduces the fact that satellites are older than centrals of the same stellar mass and that the age difference increases with the halo mass of the satellite. This is a consequence of strangulation, which leaves the stellar populations of satellites to evolve passively, while the prolonged star formation activity of centrals keeps their average ages younger. The resulting age offset i...

  16. Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala/piriform cortex.

    Science.gov (United States)

    Alexander, Georgia M; Huang, Yang Zhong; Soderblom, Erik J; He, Xiao-Ping; Moseley, M Arthur; McNamara, James O

    2017-02-01

    Vagal Nerve Stimulation (VNS) Therapy(®) is a United States Food and Drug Administration approved neurotherapeutic for medically refractory partial epilepsy and treatment-resistant depression. The molecular mechanisms underlying its beneficial effects are unclear. We hypothesized that one mechanism involves neuronal activity-dependent modifications of central nervous system excitatory synapses. To begin to test this hypothesis, we asked whether VNS modifies the activity of neurons in amygdala and hippocampus. Neuronal recordings from adult, freely moving rats revealed that activity in both amygdala and hippocampus was modified by VNS immediately after its application, and changes were detected following 1 week of stimulation. To investigate whether VNS modifies the proteome of excitatory synapses, we established a label-free, quantitative liquid chromatography-tandem mass spectrometry workflow that enables global analysis of the constituents of the postsynaptic density (PSD) proteome. PSD proteins were biochemically purified from amygdala/piriform cortex of VNS- or dummy-treated rats following 1-week stimulation, and individual PSD protein levels were quantified by liquid chromatography-tandem mass spectrometry analysis. We identified 1899 unique peptides corresponding to 425 proteins in PSD fractions, of which expression levels of 22 proteins were differentially regulated by VNS with changes greater than 150%. Changes in a subset of these proteins, including significantly increased expression of neurexin-1α, cadherin 13 and voltage-dependent calcium channel α2δ1, the primary target of the antiepileptic drug gabapentin, and decreased expression of voltage-dependent calcium channel γ3, were confirmed by western blot analysis of PSD samples. These results demonstrate that VNS modulates excitatory synapses through regulating a subset of the PSD proteome. Our study reveals molecular targets of VNS and point to possible mechanisms underlying its beneficial effects

  17. TwoB or not twoB: differential transmission at glutamatergic mossy fiber-interneuron synapses in the hippocampus.

    Science.gov (United States)

    Bischofberger, Josef; Jonas, Peter

    2002-12-01

    Mossy fiber (MF) synapses are key stations for flow of information through the hippocampal formation. A major component of the output of the MF system is directed towards inhibitory interneurons. Recent studies have revealed that the functional properties of MF-interneuron synapses differ substantially from those of MF-CA3 pyramidal neuron synapses. Mossy-fiber-interneuron synapses in the stratum lucidum represent a continuum of functional subtypes, in which the subunit composition of postsynaptic AMPA receptors and NMDA receptors appears to be regulated in a coordinated manner.

  18. Central Pit and Dome Formation as Seen in Occator Crater, Ceres

    Science.gov (United States)

    Schenk, Paul M.; Buczkowski, Debra; Scully, Jennifer E. C.; De Sanctis, Maria Cristina; Schmidt, Britney E.; O'Brien, David P.; Hiesinger, Harald; Sizemore, Hanna G.; Ammannito, Eleonora; Raymond, Carol; Russell, Christopher T.; Dawn Science Team

    2016-10-01

    Dawn mapping of Ceres revealed that central depressions (or pits) are common in craters >75 km. The best preserved of these is Occator (D~92 km), where the pit is associated with a major bright deposit dominated by carbonates. The pit is ~9 km wide, 600-800 m deep and flanked by asymmetric massifs 0.7 to 1.3 km high. The pit is partially filled by a fractured central dome ~3 km wide and 700 m high. Fracturing could have been due to dome inflation by "magma" or by subsurface freezing of ice. Within the bright material, two color units are mapped, including a paler surface unit and a more yellowish to reddish unit exposed within the most fractured parts of the dome surface and at small bright spots, at least some of which could be post-Occator small craters. Some bright materials form as discrete small spots midslope along the pit wall and others avoid small hills, suggesting partial topographic control. Stratigraphic relations are ambiguous but suggest formation of a smooth carapace some meters thick that was subsequently disrupted by fractures crossing the floor of Occator, and by uplift of the dome surface. Pit and dome morphologies, including dome fracturing are potentially analogous to central pits and domes in many craters on Ganymede and Callisto, suggesting some commonality in formation processes. The absence of center pits or domes on Saturnian satellites could be related to much lower temperatures on those bodies. The prominence of central pits and domes on Ceres confirms the importance of volatile materials, mostly likely water ice, in the outer layers of Ceres, especially as compared to Vesta.

  19. Formation of a galaxy with a central black hole in the Lemaitre-Tolman model

    CERN Document Server

    Krasinski, A; Krasinski, Andrzej; Hellaby, Charles

    2004-01-01

    We construct two models of the formation a galaxy with a central black hole, starting from a small initial fluctuation at recombination. This is an application of previously developed methods to find a Lemaitre-Tolman model that evolves from a given initial density or velocity profile to a given final density profile. We show that the black hole itself could be either a collapsed object, or a non-vacuum generalisation of a full Schwarzschild-Kruskal-Szekeres wormhole. Particular attention is paid to the black hole's apparent and event horizons.

  20. Rheomorphic ignimbrites of the Rogerson Formation, central Snake River plain, USA

    DEFF Research Database (Denmark)

    Knott, Thomas R.; Reichow, Marc K.; Branney, Michael J.

    2016-01-01

    Rogerson Graben, USA, is critically placed at the intersection between the Yellowstone hotspot track and the southern projection of the west Snake River rift. Eleven rhyolitic members of the re-defined, ≥420-m-thick, Rogerson Formation record voluminous high-temperature explosive eruptions...... by a trend towards less-evolved rhyolites that may record melting and hybridisation of a mid-crustal source region. Contemporaneous magmatism-induced crustal subsidence of the central Snake River Basin is recorded by successive ignimbrites offlapping and thinning up the N-facing limb of a regional basin...

  1. Astrocyte-Synapse Structural Plasticity

    OpenAIRE

    2014-01-01

    The function and efficacy of synaptic transmission are determined not only by the composition and activity of pre- and postsynaptic components but also by the environment in which a synapse is embedded. Glial cells constitute an important part of this environment and participate in several aspects of synaptic functions. Among the glial cell family, the roles played by astrocytes at the synaptic level are particularly important, ranging from the trophic support to the fine-tuning of transmissi...

  2. Astrocyte-Synapse Structural Plasticity

    Directory of Open Access Journals (Sweden)

    Yann Bernardinelli

    2014-01-01

    Full Text Available The function and efficacy of synaptic transmission are determined not only by the composition and activity of pre- and postsynaptic components but also by the environment in which a synapse is embedded. Glial cells constitute an important part of this environment and participate in several aspects of synaptic functions. Among the glial cell family, the roles played by astrocytes at the synaptic level are particularly important, ranging from the trophic support to the fine-tuning of transmission. Astrocytic structures are frequently observed in close association with glutamatergic synapses, providing a morphological entity for bidirectional interactions with synapses. Experimental evidence indicates that astrocytes sense neuronal activity by elevating their intracellular calcium in response to neurotransmitters and may communicate with neurons. The precise role of astrocytes in regulating synaptic properties, function, and plasticity remains however a subject of intense debate and many aspects of their interactions with neurons remain to be investigated. A particularly intriguing aspect is their ability to rapidly restructure their processes and modify their coverage of the synaptic elements. The present review summarizes some of these findings with a particular focus on the mechanisms driving this form of structural plasticity and its possible impact on synaptic structure and function.

  3. Microfacies and diagenesis of the reefal limestone, Callovian Tuwaiq Mountain Limestone Formation, central Saudi Arabia

    Science.gov (United States)

    EL-Sorogy, Abdelbaset S.; Almadani, Sattam A.; Al-Dabbagh, Mohammad E.

    2016-03-01

    In order to document the microfacies and diagenesis of the reefal limestone in the uppermost part of the Callovian Tuwaiq Mountain Limestone Formation at Khashm Al-Qaddiyah area, central Saudi Arabia, scleractinian corals and rock samples were collected and thin sections were prepared. Coral framestone, coral floatstone, pelloidal packstone, bioclastic packstone, bioclastic wacke/packstone, algal wackestone and bioclastic foraminiferal wacke/packstone were the recorded microfacies types. Cementation, recrystallization, silicification and dolomitization are the main diagenetic alterations affected the aragonitic skeletons of scleractinian corals. All coral skeletons were recrystallized, while some ones were dolomitized and silicified. Microfacies types, as well as the fossil content of sclearctinian corals, bivalves, gastropods, brachiopods and foraminifera indicated a deposition in environments ranging from shelf lagoon with open circulation in quiet water below wave base to shallow reef flank and organic build up for the uppermost reefal part of the Tuwaiq Formation in the study area.

  4. Shale gas reservoir characteristics of Ordovician-Silurian formations in the central Yangtze area, China

    Science.gov (United States)

    Shan, Chang'an; Zhang, Tingshan; Wei, Yong; Zhang, Zhao

    2017-03-01

    The characteristics of a shale gas reservoir and the potential of a shale gas resource of Ordovician-Silurian age in the north of the central Yangtze area were determined. Core samples from three wells in the study area were subjected to thin-section examination, scanning electron microscopy, nuclear magnetic resonance testing, X-ray diffraction mineral analysis, total organic carbon (TOC) testing, maturity testing, gas-bearing analysis, and gas component and isothermal adsorption experiments. A favorable segment of the gas shale reservoir was found in both the Wufeng Formation and the lower part of the Longmaxi Formation; these formations were formed from the late Katian to early Rhuddanian. The high-quality shale layers in wells J1, J2, and J3 featured thicknesses of 54.88 m, 48.49 m, and 52.00 m, respectively, and mainly comprised carbonaceous and siliceous shales. Clay and brittle minerals showed average contents of 37.5% and 62.5% (48.9% quartz), respectively. The shale exhibited type II1 kerogens with a vitrinite reflectance ranging from 1.94% to 3.51%. TOC contents of 0.22%-6.05% (average, 2.39%) were also observed. The reservoir spaces mainly included micropores and microfractures and were characterized by low porosity and permeability. Well J3 showed generally high gas contents, i.e., 1.12-3.16 m3/t (average 2.15 m3/t), and its gas was primarily methane. The relatively thick black shale reservoir featured high TOC content, high organic material maturity, high brittle mineral content, high gas content, low porosity, and low permeability. Shale gas adsorption was positively correlated with TOC content and organic maturity, weakly positive correlated with quartz content, and weakly negatively correlated with clay content. Therefore, the Wufeng and Longmaxi formations in the north of the central Yangtze area have a good potential for shale gas exploration.

  5. Shale gas reservoir characteristics of Ordovician-Silurian formations in the central Yangtze area, China

    Science.gov (United States)

    Shan, Chang'an; Zhang, Tingshan; Wei, Yong; Zhang, Zhao

    2016-07-01

    The characteristics of a shale gas reservoir and the potential of a shale gas resource of Ordovician-Silurian age in the north of the central Yangtze area were determined. Core samples from three wells in the study area were subjected to thin-section examination, scanning electron microscopy, nuclear magnetic resonance testing, X-ray diffraction mineral analysis, total organic carbon (TOC) testing, maturity testing, gas-bearing analysis, and gas component and isothermal adsorption experiments. A favorable segment of the gas shale reservoir was found in both the Wufeng Formation and the lower part of the Longmaxi Formation; these formations were formed from the late Katian to early Rhuddanian. The high-quality shale layers in wells J1, J2, and J3 featured thicknesses of 54.88 m, 48.49 m, and 52.00 m, respectively, and mainly comprised carbonaceous and siliceous shales. Clay and brittle minerals showed average contents of 37.5% and 62.5% (48.9% quartz), respectively. The shale exhibited type II1 kerogens with a vitrinite reflectance ranging from 1.94% to 3.51%. TOC contents of 0.22%-6.05% (average, 2.39%) were also observed. The reservoir spaces mainly included micropores and microfractures and were characterized by low porosity and permeability. Well J3 showed generally high gas contents, i.e., 1.12-3.16 m3/t (average 2.15 m3/t), and its gas was primarily methane. The relatively thick black shale reservoir featured high TOC content, high organic material maturity, high brittle mineral content, high gas content, low porosity, and low permeability. Shale gas adsorption was positively correlated with TOC content and organic maturity, weakly positive correlated with quartz content, and weakly negatively correlated with clay content. Therefore, the Wufeng and Longmaxi formations in the north of the central Yangtze area have a good potential for shale gas exploration.

  6. Towards a multi-scale understanding of the gas-star formation cycle in the Central Molecular Zone

    CERN Document Server

    Kruijssen, J M Diederik

    2016-01-01

    The Central Molecular Zone (CMZ, the central 500 pc of the Milky Way) contains the largest reservoir of high-density molecular gas in the Galaxy, but forms stars at a rate 10-100 times below commonly-used star formation relations. We discuss recent efforts in understanding how the nearest galactic nucleus forms its stars. The latest models of the gas inflow, star formation, and feedback duty cycle reproduce the main observable features of the CMZ, showing that star formation is episodic and that the CMZ currently resides at a star formation minimum. Using orbital modelling, we derive the three-dimensional geometry of the CMZ and show how the orbital dynamics and the star formation potential of the gas are closely coupled. We discuss how this coupling reveals the physics of star formation and feedback under the conditions seen in high-redshift galaxies, and promotes the formation of the densest stellar clusters in the Galaxy.

  7. Remodeling and Tenacity of Inhibitory Synapses: Relationships with Network Activity and Neighboring Excitatory Synapses.

    Science.gov (United States)

    Rubinski, Anna; Ziv, Noam E

    2015-11-01

    Glutamatergic synapse size remodeling is governed not only by specific activity forms but also by apparently stochastic processes with well-defined statistics. These spontaneous remodeling processes can give rise to skewed and stable synaptic size distributions, underlie scaling of these distributions and drive changes in glutamatergic synapse size "configurations". Where inhibitory synapses are concerned, however, little is known on spontaneous remodeling dynamics, their statistics, their activity dependence or their long-term consequences. Here we followed individual inhibitory synapses for days, and analyzed their size remodeling dynamics within the statistical framework previously developed for glutamatergic synapses. Similar to glutamatergic synapses, size distributions of inhibitory synapses were skewed and stable; at the same time, however, sizes of individual synapses changed considerably, leading to gradual changes in synaptic size configurations. The suppression of network activity only transiently affected spontaneous remodeling dynamics, did not affect synaptic size configuration change rates and was not followed by the scaling of inhibitory synapse size distributions. Comparisons with glutamatergic synapses within the same dendrites revealed a degree of coupling between nearby inhibitory and excitatory synapse remodeling, but also revealed that inhibitory synapse size configurations changed at considerably slower rates than those of their glutamatergic neighbors. These findings point to quantitative differences in spontaneous remodeling dynamics of inhibitory and excitatory synapses but also reveal deep qualitative similarities in the processes that control their sizes and govern their remodeling dynamics.

  8. Stratigraphy, sedimentology and paleontology of lower Eocene San Jose formation, central San Juan basin, New Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Lucas, S.G.; Smith, L.N. (New Mexico Museum of Natural History, Albuquerque (USA))

    1989-09-01

    The lower Eocene San Jose Formation in the central portion of the San Juan basin (Gobernador-Vigas Canyon area) consists of the Cuba Mesa, Regina, Llaves, and Tapicitos Members. Well log data indicate that, from its 100-m thickness, the Cuba Mesa Member thins toward the basin center and pinches out to the northeast by lat. 36{degree}40'N, long. 107{degree}19'W. The Regina Member has the most extensive outcrops in the central basin, and it decreases in sandstone/mud rock ratio to the north. The Llaves and Tapicitos Members occur only at the highest elevations, are thin due to erosion, and are not mappable as separate units. Well log data and 1,275 m of measured stratigraphic section in the Regina, Llaves, and Tapicitos Members indicate these strata are composed of approximately 35% medium to coarse-grained sandstone and 65% fine-grained sandstone and mud rock. Sedimentology and sediment-dispersal patterns indicate deposition by generally south-flowing streams that had sources to the northwest, northeast, and east. Low-sinuosity, sand-bedded, braided( ) streams shifted laterally across about 1 km-wide channel belts to produce sheet sandstones that are prominent throughout the San Jose Formation. Subtle levees separated channel environments from floodplain and local lacustrine areas. Avulsion relocated channels periodically to areas on the floodplain, resulting in the typically disconnected sheet sandstones within muddy overbank deposits of the Regina Member.

  9. Studying the Dynamics of TCR Internalization at the Immune Synapse.

    Science.gov (United States)

    Calleja, Enrique; Alarcón, Balbino; Oeste, Clara L

    2017-01-01

    Establishing a stable interaction between a T cell and an antigen presenting cell (APC) involves the formation of an immune synapse (IS). It is through this structure that the T cell can integrate all the signals provided by the APC. The IS also serves as a mechanism for TCR downregulation through internalization. Here, we describe methods for visualizing MHC-engaged T cell receptor (TCR) internalization from the IS in human cell lines and mouse primary T cells by confocal fluorescence microscopy techniques.

  10. Differential mechanisms of transmission and plasticity at mossy fiber synapses

    OpenAIRE

    McBain, Chris J.

    2008-01-01

    The last few decades have seen the hippocampal formation at front and center in the field of synaptic transmission. However, much of what we know about hippocampal short- and long-term plasticity has been obtained from research at one particular synapse; the Schaffer collateral input onto principal cells of the CA1 subfield. A number of recent studies, however, have demonstrated that there is much to be learned about target-specific mechanisms of synaptic transmission by study of the lesser k...

  11. Sedimentary characteristics of tide-dominated estuary in Donghetang Formation(Upper Devonian), central Tarim Basin

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The Donghetang Formation (Upper Devonian) in central Tarim Basin has been thought an important oil and gas reservoir since the abundant oil and gas resources were found in the wells W16, W20, W34, and other fields. However, the sedimentary environment of the Donghetang Formation has been disputed because it suffered from both tidal and fluvial actions and there were not rich fossils in the sandstone. After the authors analyzed sedimentary features by means of drill cores, well logging data, paleosols, and with SEM obseruations, three kinds of sedimentary environments were distinguished: alluvial fan, tide-dominated estuary, and shelf. Particularly, the sedimentary features of tide-dominated estuary were studied in detail. Besides, the authors discussed sedimentary characteristics of the Donghetang Formation which was divided into two fourth-order sequences and five system tracts. At the same time, according to the forming process of five system tracts, the whole vertical evolution and lateral transition of tide-dominated estuary were illustrated clearly. Finally, the reservoir quality was evaluated based on porosity and permeability.

  12. New Particle Formation Above a Loblolly Pine Forest at a New Tower Site in Central Virginia

    Science.gov (United States)

    Joerger, V.; O'Halloran, T. L.; Barr, J. G.

    2014-12-01

    We present initial results investigating the environmental controls on new particle formation events at a new research site in central Virginia. The Sweet Briar College Land-Atmosphere Research Station (SBC-LARS) became operational in July, 2014 and features a 37-meter tower within a ~30 year-old loblolly pine plantation that is surrounded by mixed deciduous forest at the eastern edge of the Blue Ridge Mountains. The tower supports meteorological instruments at three different heights (2, 26, and 37 meters) and two air sampling inlets located above the canopy. The inlets draw air samples into a climate-controlled shed where precursor gas concentrations (ozone, sulfur dioxide, and nitrogen oxides) are determined by gas analyzers. Aerosol size distributions between 10 and 470 nm are measured every 3 minutes by a Scanning Mobility Particle Sizer (SMPS). For this study, aerosol size distributions from July through November 2014 were analyzed along with HYSPLIT backwards trajectories, meteorological measurements, gas concentrations, and the condensational sink, to investigate controls on new particle formation. This station and corresponding dataset will contribute to a better understanding of the contribution of biogenic and anthropogenic emissions to aerosol formation in the southeastern United States.

  13. Regulation of vesicular traffic at the T cell immune synapse: lessons from the primary cilium.

    Science.gov (United States)

    Finetti, Francesca; Onnis, Anna; Baldari, Cosima T

    2015-03-01

    The signals that orchestrate the process of T cell activation are coordinated at the specialized interface that forms upon contact with an antigen presenting cell displaying a specific MHC-associated peptide ligand, known as the immune synapse. The central role of vesicular traffic in the assembly of the immune synapse has emerged only in recent years with the finding that sustained T-cell receptor (TCR) signaling involves delivery of TCR/CD3 complexes from an intracellular pool associated with recycling endosomes. A number of receptors as well as membrane-associated signaling mediators have since been demonstrated to exploit this process to localize to the immune synapse. Here, we will review our current understanding of the mechanisms responsible for TCR recycling, with a focus on the intraflagellar transport system, a multimolecular complex that is responsible for the assembly and function of the primary cilium which we have recently implicated in polarized endosome recycling to the immune synapse.

  14. β-Catenin-dependent transcription is central to Bmp-mediated formation of venous vessels.

    Science.gov (United States)

    Kashiwada, Takeru; Fukuhara, Shigetomo; Terai, Kenta; Tanaka, Toru; Wakayama, Yuki; Ando, Koji; Nakajima, Hiroyuki; Fukui, Hajime; Yuge, Shinya; Saito, Yoshinobu; Gemma, Akihiko; Mochizuki, Naoki

    2015-02-01

    β-catenin regulates the transcription of genes involved in diverse biological processes, including embryogenesis, tissue homeostasis and regeneration. Endothelial cell (EC)-specific gene-targeting analyses in mice have revealed that β-catenin is required for vascular development. However, the precise function of β-catenin-mediated gene regulation in vascular development is not well understood, since β-catenin regulates not only gene expression but also the formation of cell-cell junctions. To address this question, we have developed a novel transgenic zebrafish line that allows the visualization of β-catenin transcriptional activity specifically in ECs and discovered that β-catenin-dependent transcription is central to the bone morphogenetic protein (Bmp)-mediated formation of venous vessels. During caudal vein (CV) formation, Bmp induces the expression of aggf1, a putative causative gene for Klippel-Trenaunay syndrome, which is characterized by venous malformation and hypertrophy of bones and soft tissues. Subsequently, Aggf1 potentiates β-catenin transcriptional activity by acting as a transcriptional co-factor, suggesting that Bmp evokes β-catenin-mediated gene expression through Aggf1 expression. Bmp-mediated activation of β-catenin induces the expression of Nr2f2 (also known as Coup-TFII), a member of the nuclear receptor superfamily, to promote the differentiation of venous ECs, thereby contributing to CV formation. Furthermore, β-catenin stimulated by Bmp promotes the survival of venous ECs, but not that of arterial ECs. Collectively, these results indicate that Bmp-induced activation of β-catenin through Aggf1 regulates CV development by promoting the Nr2f2-dependent differentiation of venous ECs and their survival. This study demonstrates, for the first time, a crucial role of β-catenin-mediated gene expression in the development of venous vessels.

  15. Oceanic crust formation in the Egeria Fracture Zone Complex (Central Indian Ocean)

    Science.gov (United States)

    Le Minor, Marine; Gaina, Carmen; Sigloch, Karin; Minakov, Alexander

    2016-04-01

    This study aims to analyse in detail the oceanic crust fabric and volcanic features (seamounts) formed for the last 10 million years at the Central Indian Ridge between 19 and 21 latitude south. Multibeam bathymetry and magnetic data has been collected in 2013 as part of the French-German expedition RHUM-RUM (Reunion hotspot and upper mantle - Reunion's unterer mantel). Three long profiles perpendicular on the Central Indian Ridge (CIR), south of the Egeria fracture zone, document the formation of oceanic crust since 10 million years, along with changes in plate kinematics and variations in the magmatic input. We have inspected the abyssal hill geometry and orientation along conjugate oceanic flanks and within one fracture zone segment where we could identify J-shaped features that are indicators of changes in plate kinematics. The magnetic anomaly data shows a slight asymmetry in seafloor spreading rates on conjugate flanks: while a steady increase in spreading rate from 10 Ma to the present is shown by the western flank, the eastern part displays a slowing down from 5 Ma onwards. The deflection of the anti J-shaped abyssal hill lineations suggest that the left-stepping Egeria fracture zone complex (including the Egeria, Flinders and an un-named fracture zone to the southeast) was under transpression from 9 to 6 Ma and under transtension since 3 Ma. The transpressional event was triggered by a clockwise mid-ocean ridge reorientation and a decrease of its offset, whereas the transtensional regime was probably due to a counter-clockwise change in the spreading direction and an increase of the ridge offset. The new multibeam data along the three profiles reveal that crust on the eastern side is smoother (as shown by the abyssal hill number and structure) and hosts several seamounts (with age estimations of 7.67, 6.10 and 0.79 Ma), in contrast to the rougher conjugate western flank. Considering that the western flank was closer to the Reunion plume, and therefore

  16. Glycinergic Pathways of the Central Auditory System and Adjacent Reticular Formation of the Rat.

    Science.gov (United States)

    Hunter, Chyren

    The development of techniques to visualize and identify specific transmitters of neuronal circuits has stimulated work on the characterization of pathways in the rat central nervous system that utilize the inhibitory amino acid glycine as its neurotransmitter. Glycine is a major inhibitory transmitter in the spinal cord and brainstem of vertebrates where it satisfies the major criteria for neurotransmitter action. Some of these characteristics are: uneven distribution in brain, high affinity reuptake mechanisms, inhibitory neurophysiological actions on certain neuronal populations, uneven receptor distribution and the specific antagonism of its actions by the convulsant alkaloid strychnine. Behaviorally, antagonism of glycinergic neurotransmission in the medullary reticular formation is linked to the development of myoclonus and seizures which may be initiated by auditory as well as other stimuli. In the present study, decreases in the concentration of glycine as well as the density of glycine receptors in the medulla with aging were found and may be responsible for the lowered threshold for strychnine seizures observed in older rats. Neuroanatomical pathways in the central auditory system and medullary and pontine reticular formation (RF) were investigated using retrograde transport of tritiated glycine to identify glycinergic pathways; immunohistochemical techniques were used to corroborate the location of glycine neurons. Within the central auditory system, retrograde transport studies using tritiated glycine demonstrated an ipsilateral glycinergic pathway linking nuclei of the ascending auditory system. This pathway has its cell bodies in the medial nucleus of the trapezoid body (MNTB) and projects to the ventrocaudal division of the ventral nucleus of the lateral lemniscus (VLL). Collaterals of this glycinergic projection terminate in the ipsilateral lateral superior olive (LSO). Other glycinergic pathways found were afferent to the VLL and have their origin

  17. An X-ray View of Star Formation in the Central 3 kpc of NGC 2403

    CERN Document Server

    Yukita, Mihoko; Tennant, Allyn F; Soria, Roberto

    2009-01-01

    Archival Chandra observations are used to study the X-ray emission associated with star formation in the central region of the nearby SAB(s)cd galaxy NGC 2403. The distribution of X-ray emission is compared to the morphology visible at other wavelengths using complementary Spitzer, GALEX, and ground-based Halpha imagery. In general, the brightest extended X-ray emission is associated with HII regions and to other star-forming structures but is more pervasive; existing also in regions devoid of strong Halpha and UV emission. This X-ray emission has the spectral properties of diffuse hot gas (kT ~ 0.2keV) whose likely origin is in gas shock-heated by stellar winds and supernovae with < 20% coming from faint unresolved X-ray point sources. This hot gas may be slowly-cooling extra-planar remnants of past outflow events, or a disk component that either lingers after local star formation activity has ended or that has vented from active star-forming regions into a porous interstellar medium.

  18. STRATIGRAPHY AND PALYNOLOGY OF THE UPPER TRIASSIC NAYBAND FORMATION OF EAST-CENTRAL IRAN

    Directory of Open Access Journals (Sweden)

    SIMONETTA CIRILLI

    2005-07-01

    Full Text Available A palynological study of the Nayband Formation (central eastern Iran has been carried out in order to review and update its stratigraphic framework. In its type locality the formation crops out on the southern flank of Nayband Mountain, about 200 km south of Tabas. It consists of a thick, mixed siliciclastic-carbonate sequence subdivided into four members; in ascending order: the Gelkan Member (mainly shales and silstones, the Bidestan Member (marls, siltstones with minor sandstones and fossiliferous limestones, the Howz-e-Sheikh Member (sandstones and siltstones, and the Howz-e-Khan Member (sponge and coral dominated reefs alternating with marls and sandstones. Three palynological assemblages have been recognised; in ascending order: a an assemblage characterised by the presence of Annulispora folliculosa and A. microannulata which allows the Gelkan Member and most of the Bidestan Member to be assigned an early Norian age; (b an assemblage marked by the first occurrence of Polycingulatisporites mooniensis, which indicates the upper part of the Bidestan Member is mid-late Norian; c an assemblage containing Classopollis chateaunovi in association with Retitriletes austroclavatidites, Gliscopollis meyeriana, Limbosporites lundbladii, Rugaletes awakinoensis and Callialasporites dampieri that allows the Howz-e-Sheikh Member to be assigned a Rhaetian age. The presence of some Eurasian and/or cosmopolitan forms in the Rhaetian microflora reflects the position of the Iranian plate on the southern margin of Eurasia.   

  19. Central role of maladapted astrocytic plasticity in ischemic brain edema formation

    Directory of Open Access Journals (Sweden)

    Yu-Feng eWang

    2016-05-01

    Full Text Available Brain edema formation and the ensuing brain damages are the major cause of high mortality and long term disability following the occurrence of ischemic stroke. In this process, oxygen and glucose deprivation and the ensuing reperfusion injury play primary roles. In response to the ischemic insult, the neurovascular unit experiences both intracellular and extracellular edemas; the two processes are interactive closely under the driving of maladapted astrocytic plasticity. The astrocytic plasticity includes both morphologic and functional plasticity. The former involves a reactive gliosis and the ensuing glial retraction. It relates to the capacity of astrocytes to buffer changes in extracellular chemical levels, particularly K+ and glutamate, as well as the integrity of the blood-brain barrier. The latter involves the expression and activity of a series of ion and water transport proteins. These molecules are grouped together around glial fibrillary acidic protein and water channel protein aquaporin 4 to form functional networks, regulate hydromineral balance across cell membranes and maintain the integrity of the blood-brain barrier. Intense ischemic challenges can disrupt these capacities of astrocytes and result in their maladaptation. The maladapted astrocytic plasticity in ischemic stroke cannot only disrupt the hydromineral homeostasis across astrocyte membrane and the blood-brain barrier, but also lead to disorders of the whole neurovascular unit. This review focuses on how the maladapted astrocytic plasticity in ischemic stroke plays the central role in the brain edema formation.

  20. Emerging themes in GABAergic synapse development.

    Science.gov (United States)

    Kuzirian, Marissa S; Paradis, Suzanne

    2011-09-15

    Glutamatergic synapse development has been rigorously investigated for the past two decades at both the molecular and cell biological level yet a comparable intensity of investigation into the cellular and molecular mechanisms of GABAergic synapse development has been lacking until relatively recently. This review will provide a detailed overview of the current understanding of GABAergic synapse development with a particular emphasis on assembly of synaptic components, molecular mechanisms of synaptic development, and a subset of human disorders which manifest when GABAergic synapse development is disrupted. An unexpected and emerging theme from these studies is that glutamatergic and GABAergic synapse development share a number of overlapping molecular and cell biological mechanisms that will be emphasized in this review.

  1. The adhesion protein IgSF9b is coupled to neuroligin 2 via S-SCAM to promote inhibitory synapse development

    OpenAIRE

    Woo, Jooyeon; Kwon, Seok-Kyu; Nam, Jungyong; Choi, Seungwon; Takahashi, Hideto; Krueger, Dilja; Park, Joohyun; Lee, Yeunkum; Bae, Jin Young; Lee, Dongmin; Ko, Jaewon; Kim, Hyun; Kim, Myoung-Hwan; Bae, Yong Chul; Chang, Sunghoe

    2013-01-01

    Synaptic adhesion molecules regulate diverse aspects of synapse formation and maintenance. Many known synaptic adhesion molecules localize at excitatory synapses, whereas relatively little is known about inhibitory synaptic adhesion molecules. Here we report that IgSF9b is a novel, brain-specific, homophilic adhesion molecule that is strongly expressed in GABAergic interneurons. IgSF9b was preferentially localized at inhibitory synapses in cultured rat hippocampal and cortical interneurons an...

  2. Graben formation during the Bárðarbunga rifting event in central Iceland

    KAUST Repository

    Ruch, Joel

    2015-04-01

    On the 16th of August 2014, an intense seismic swarm was detected at the Bárðarbunga caldera (central Iceland), which migrated to the east and then to the northeast during the following days. The swarm, highlighting magma propagation pathway from the caldera, migrated laterally during the following two weeks over 40 km. By the end of August, a volcanic eruption had started along a north-south oriented fissure located ~45 km from the caldera. Here we focus on the near-field deformation related to the dike emplacement in the shallow crust, which generated in few days an 8 km long by 0.8 km wide graben (depression) structure. The new graben extends from the northern edge of the Vatnajökull glacier and to the north to the eruptive fissure. We analyze the temporal evolution of the graben by integrating structural mapping using multiple acquisitions of TerraSAR-X amplitude radar images, InSAR and ground-truth data with GPS and structural measurements. Pixel-offset tracking of radar amplitude images shows clearly the graben subsidence, directly above the intrusion pathway, of up to 6 meters in the satellite line-of-sight direction. We installed a GPS profile of 15 points across the graben in October 2014 and measured its depth up to 8 meters, relative to the flanks of the graben. Field structural observations show graben collapse structures that typically accompany dike intrusions, with two tilted blocks dipping toward the graben axis, bordered by two normal faults. Extensive fractures at the center of the graben and at the graben edges show a cumulative extension of ~8 meters. The formation of the graben was also accompanied by strong seismic activity locally, constraining the time frame period of the main graben formation subsidence. Our results show a rare case of a graben formation captured from space and from ground observations. Such structures are the dominant features along rift zones, however, their formation remain poorly understood. The results also provide

  3. Opioids potentiate electrical transmission at mixed synapses on the Mauthner cell.

    Science.gov (United States)

    Cachope, Roger; Pereda, Alberto E

    2015-07-01

    Opioid receptors were shown to modulate a variety of cellular processes in the vertebrate central nervous system, including synaptic transmission. While the effects of opioid receptors on chemically mediated transmission have been extensively investigated, little is known of their actions on gap junction-mediated electrical synapses. Here we report that pharmacological activation of mu-opioid receptors led to a long-term enhancement of electrical (and glutamatergic) transmission at identifiable mixed synapses on the goldfish Mauthner cells. The effect also required activation of both dopamine D1/5 receptors and postsynaptic cAMP-dependent protein kinase A, suggesting that opioid-evoked actions are mediated indirectly via the release of dopamine from varicosities known to be located in the vicinity of the synaptic contacts. Moreover, inhibitory inputs situated in the immediate vicinity of these excitatory synapses on the lateral dendrite of the Mauthner cell were not affected by activation of mu-opioid receptors, indicating that their actions are restricted to electrical and glutamatergic transmissions co-existing at mixed contacts. Thus, as their chemical counterparts, electrical synapses can be a target for the modulatory actions of the opioid system. Because gap junctions at these mixed synapses are formed by fish homologs of the neuronal connexin 36, which is widespread in mammalian brain, it is likely that this regulatory property applies to electrical synapses elsewhere as well.

  4. Synapse clusters are preferentially formed by synapses with large recycling pool sizes.

    Directory of Open Access Journals (Sweden)

    Oliver Welzel

    Full Text Available Synapses are distributed heterogeneously in neural networks. The relationship between the spatial arrangement of synapses and an individual synapse's structural and functional features remains to be elucidated. Here, we examined the influence of the number of adjacent synapses on individual synaptic recycling pool sizes. When measuring the discharge of the styryl dye FM1-43 from electrically stimulated synapses in rat hippocampal tissue cultures, a strong positive correlation between the number of neighbouring synapses and recycling vesicle pool sizes was observed. Accordingly, vesicle-rich synapses were found to preferentially reside next to neighbours with large recycling pool sizes. Although these synapses with large recycling pool sizes were rare, they were densely arranged and thus exhibited a high amount of release per volume. To consolidate these findings, functional terminals were marked by live-cell antibody staining with anti-synaptotagmin-1-cypHer or overexpression of synaptopHluorin. Analysis of synapse distributions in these systems confirmed the results obtained with FM 1-43. Our findings support the idea that clustering of synapses with large recycling pool sizes is a distinct developmental feature of newly formed neural networks and may contribute to functional plasticity.

  5. Evolution of silicic volcanism following the transition to the modern High Cascades, Deschutes Formation, central Oregon

    Science.gov (United States)

    Eungard, D.; Kent, A. J.; Grunder, A.

    2012-12-01

    An understanding of the controls on silicic volcanism within convergent margin environments has important implications for crustal growth and modification during subduction. In the central Oregon Cascade range silicic volcanism has generally decreased in both size and frequency of eruptions over the last ~40 million years. Despite the general decrease, an increased abundance of silicic volcanism is observed from 5-8 Ma, corresponding to the transition from the Western Cascades to High Cascades volcanic regime. In order to constrain the processes that lead to formation of silicic magmas at this time we have studied the petrogenesis of two extensive and well-preserved ash-flow tuffs from this time period hosted within the Deschutes Formation of central Oregon. The Lower Bridge (LBT) and McKenzie Canyon Tuffs (MCT) produced ~5 km3 each of magma of predominantly rhyolitic and basaltic andesite composition. Both include large volumes of rhyolite, although the MCT also contains a significant mafic component. Both tuffs are normally zoned with mafic ejecta concentrated upsection. Geothermometry also shows that the rhyolitic component in both magmas was relatively hot (~830 degrees C). Distribution, thickness, welding facies, and paleoflow indications from imbricated pumice suggest that both eruptions derive from the same source region, probably near the present day Three Sisters complex, and were likely produced from the same magmatic system. Variations in major and trace element geochemistry also indicate that the magmas involved in both eruptions were produced through fractionation and mixing of mantle melts with a silicic partial melt derived from melting of mafic crust. Production of these voluminous silicic magmas required both crystal fractionation of incoming melts from the mantle, together with mixing with silicic partial melts derived from relatively hot mafic crust. This observation provides a potential explanation for the decrease in silicic melt production

  6. Staphylococcus aureus sarA regulates inflammation and colonization during central nervous system biofilm formation.

    Directory of Open Access Journals (Sweden)

    Jessica N Snowden

    Full Text Available Infection is a frequent and serious complication following the treatment of hydrocephalus with CSF shunts, with limited therapeutic options because of biofilm formation along the catheter surface. Here we evaluated the possibility that the sarA regulatory locus engenders S. aureus more resistant to immune recognition in the central nervous system (CNS based on its reported ability to regulate biofilm formation. We utilized our established model of CNS catheter-associated infection, similar to CSF shunt infections seen in humans, to compare the kinetics of bacterial titers, cytokine production and inflammatory cell influx elicited by wild type S. aureus versus an isogenic sarA mutant. The sarA mutant was more rapidly cleared from infected catheters compared to its isogenic wild type strain. Consistent with this finding, several pro-inflammatory cytokines and chemokines, including IL-17, CXCL1, and IL-1β were significantly increased in the brain following infection with the sarA mutant versus wild type S. aureus, in agreement with the fact that the sarA mutant displayed impaired biofilm growth and favored a planktonic state. Neutrophil influx into the infected hemisphere was also increased in the animals infected with the sarA mutant compared to wild type bacteria. These changes were not attributable to extracellular protease activity, which is increased in the context of SarA mutation, since similar responses were observed between sarA and a sarA/protease mutant. Overall, these results demonstrate that sarA plays an important role in attenuating the inflammatory response during staphylococcal biofilm infection in the CNS via a mechanism that remains to be determined.

  7. Efficient Associative Computation with Discrete Synapses.

    Science.gov (United States)

    Knoblauch, Andreas

    2016-01-01

    Neural associative networks are a promising computational paradigm for both modeling neural circuits of the brain and implementing associative memory and Hebbian cell assemblies in parallel VLSI or nanoscale hardware. Previous work has extensively investigated synaptic learning in linear models of the Hopfield type and simple nonlinear models of the Steinbuch/Willshaw type. Optimized Hopfield networks of size n can store a large number of about n(2)/k memories of size k (or associations between them) but require real-valued synapses, which are expensive to implement and can store at most C = 0.72 bits per synapse. Willshaw networks can store a much smaller number of about n(2)/k(2) memories but get along with much cheaper binary synapses. Here I present a learning model employing synapses with discrete synaptic weights. For optimal discretization parameters, this model can store, up to a factor ζ close to one, the same number of memories as for optimized Hopfield-type learning--for example, ζ = 0.64 for binary synapses, ζ = 0.88 for 2 bit (four-state) synapses, ζ = 0.96 for 3 bit (8-state) synapses, and ζ > 0.99 for 4 bit (16-state) synapses. The model also provides the theoretical framework to determine optimal discretization parameters for computer implementations or brainlike parallel hardware including structural plasticity. In particular, as recently shown for the Willshaw network, it is possible to store C(I) = 1 bit per computer bit and up to C(S) = log n bits per nonsilent synapse, whereas the absolute number of stored memories can be much larger than for the Willshaw model.

  8. Zeolites in the Miocene Briones Sandstone and related formations of the central Coast Ranges, California

    Science.gov (United States)

    Murata, K.J.; Whiteley, Karen R.

    1973-01-01

    Authigenic zeolites present in the generally tuffaceous Miocene Briones Sandstone and related formations of the central Coast Ranges of California indicate three stages of diagenetic history: (1) Initial alteration of pyroclastic materials to clinoptilolite (and montmorillonite) that is widely distributed in small amounts throughout the region. (2) Subsequent crystallization of heulandite followed by stilbite in fractures at a few places. (3) Widespread development of laumontite in only the southern part of the region, where the sandstone appears to have been downfolded and faulted to greater depths than elsewhere. Laumontite occurs both as pervasive cement of sandstone and as filling of fractures, and was produced through the reaction of interstitial solutions with other zeolites and with such major constituents of the sandstone as plagioclase, montmorillonite, and calcite at temperatures of 100° C or higher. Mordenite was found at only one locality, closely associated with clinoptilolite and opal. Analcite occurs in diverse settings, and its relation to the other zeolites is obscure.  Sparry calcite and coexisting stilbite, laumontite, or analcite in veins seem to make up nonequilibrium assemblages.

  9. Numerical and experimental investigation of central cavity formation in aluminum during forward extrusion process

    Energy Technology Data Exchange (ETDEWEB)

    Hosseini, S. H.; Sedighi, M.; Mosayebnezhad, J. [Iran Univ., Tehran (Iran, Islamic Republic of)

    2016-05-15

    In the presented paper central cavity formation during the forward extrusion of commercially pure aluminum was investigated. For this purpose finite element analysis was utilized for simulation of this defect. The experimental tests were carried out on commercially pure aluminum. A good agreement between finite element simulations and experimental tests verified the adaptability of finite element simulations with the real process conditions. Taguchi method was performed for classifying the simulations regarding to consider synergistic parameters. The parameters include reduction of area, friction coefficient and die angle. Critical thickness, the representative waste material, was presented as a new criterion for optimizing the parametric study. By utilizing the Analyze Taguchi design, critical thickness was optimized and the effect of each parameter was recognized for different levels. In addition, the best levels with the minimum waste material were gained in which friction coefficient, die angle and reduction of area were 0.2, 5 .deg. and 20%, respectively. Also the amount of waste material was forecasted by just about 2% errors without FEA by Taguchi method.

  10. Palynostratigraphy of the Nayband Formation, Tabas, Central Iran Basin: Paleogeographical and paleoecological implications

    Science.gov (United States)

    Sajjadi, F.; Hashemi, H.; Borzuee, E.

    2015-11-01

    Reasonably diverse and moderately preserved palynofloras of exclusively terrestrial derivation occur in surface samples of the Nayband Formation, Kamar Macheh Kuh, southeastern Tabas, east-central Iran. No marine palynomorphs encountered in the samples examined. The palynofloras comprise 62 species including radially symmetrical and monolete spores (37 species allocated to 27 genera) and pollen (25 species designated to 19 genera). Of the latter, such bisaccate taxa as Ovalipollis ovalis, Alisporites spp., Falcisporites nuthallensis, the inaperturate Araucariacites australis, and the monosulcate Chasmatosporites major dominate the assemblages. Representatives of such trilete spores as Dictyophyllidites mortonii, Kyrtomisporis laevigatus, and Gleicheiniidites senonicus are essentially abundant in the palynofloras examined. Vertical distribution of miospores allows erection within the Nayband Formation of three informal distinctive stratigraphically successive interval biozones, viz., A. australis-Annulispora folliculosa biozone, Conbaculatisporites sp.-Ricciisporites tuberculatus biozone, and R. tuberculatus-Polypodiisporites polymicroforatus biozone based on the First Observed Occurrence (FOO) and Last Observed Occurrence (LOO) of selected taxa. These are compared with palynozones from ±coeval strata in Iran and elsewhere. Additionally, two non-palyniferous intervals, one at the base (188 m thick) and another (18 m in thickness) at uppermost part of the section studied are identified. Based on the association of such key misopore species as Lunatisporites rhaeticus, O. ovalis (alias pseudoalatus), A. folliculosa, Polycingulatisporites mooniensis, Limbosporites lundbladii, Quadraeculina anellaeformis, R. tuberculatus, Conbaculatisporites sp., P. polymicroforatus, and Striatisaccus novimundi within the Nayband palynofloras, the host strata are assigned to Late Triassic (Norian-Rhaetian). This dating while corroborating previous attempts made with reference to mostly

  11. [Physiology of synapse: from molecular modules to retrograde modulation].

    Science.gov (United States)

    Brezhestovskiĭ, P D

    2010-09-01

    Synapses are highly organized, specific structures assuring rapid and highly selective interactions between cells. Synaptic transmission involves the release of neurotransmitter from presynaptic neurons and its detection by specific ligand-gated ion channels at the surface membrane of postsynaptic neurons. The protenomic analysis shows that for self-formation and functioning of synapses nearly 2000 proteins are involved in mammalian brain. The core complex in excitatory synapses includes glutamate receptors, potassium channels, CaMKII, scaffolding protein and actin. These proteins exist as part of a highly organized protein complex known as the postsynaptic density (PSD). The coordinated functioning of the different PSD components determines the strength of signalling between the pre- and postsynaptic neurons. Synaptic plasticity is regulated by changes in the amount of receptors on the postsynaptic membrane, changes in the shape and size of dendritic spines, posttranslational modification of PSD components, modulation kinetics of synthesis and degradation of proteins. Integration of these processes leads to long-lasting changes in synaptic function and neuronal networks underlying learning-related plasticity, memory and information treatment in nervous system of multicellular organisms.

  12. A Gata3-Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing.

    Science.gov (United States)

    Yu, Wei-Ming; Appler, Jessica M; Kim, Ye-Hyun; Nishitani, Allison M; Holt, Jeffrey R; Goodrich, Lisa V

    2013-12-10

    Information flow through neural circuits is determined by the nature of the synapses linking the subtypes of neurons. How neurons acquire features distinct to each synapse remains unknown. We show that the transcription factor Mafb drives the formation of auditory ribbon synapses, which are specialized for rapid transmission from hair cells to spiral ganglion neurons (SGNs). Mafb acts in SGNs to drive differentiation of the large postsynaptic density (PSD) characteristic of the ribbon synapse. In Mafb mutant mice, SGNs fail to develop normal PSDs, leading to reduced synapse number and impaired auditory responses. Conversely, increased Mafb accelerates synaptogenesis. Moreover, Mafb is responsible for executing one branch of the SGN differentiation program orchestrated by the Gata3 transcriptional network. Remarkably, restoration of Mafb rescues the synapse defect in Gata3 mutants. Hence, Mafb is a powerful regulator of cell-type specific features of auditory synaptogenesis that offers a new entry point for treating hearing loss. DOI: http://dx.doi.org/10.7554/eLife.01341.001.

  13. Early expression of KCC2 in rat hippocampal cultures augments expression of functional GABA synapses.

    Science.gov (United States)

    Chudotvorova, Ilona; Ivanov, Anton; Rama, Sylvain; Hübner, Christian A; Pellegrino, Christophe; Ben-Ari, Yehezkel; Medina, Igor

    2005-08-01

    The development of GABAergic synapses is associated with an excitatory to inhibitory shift of the actions of GABA because of a reduction of [Cl-]i. This is due to a delayed postnatal expression of the K+ -Cl- cotransporter KCC2, which has low levels at birth and peaks during the first few postnatal weeks. Whether the expression of the cotransporter and the excitatory to inhibitory shift have other consequences on the operation of GABA(A) receptors and synapses is not yet known. We have now expressed KCC2 in immature neurones at an early developmental stage and determined the consequences on the formation of GABA and glutamate synapses. We report that early expression of the cotransporter selectively enhances GABAergic synapses: there is a significant increase of the density of GABA(A) receptors and synapses and an increase of the frequency of GABAergic miniature postsynaptic currents. The density of glutamate synapses and frequency of AMPA miniature postsynaptic currents are not affected. We conclude that the expression of KCC2 and the reduction of [Cl-]i play a critical role in the construction of GABAergic networks that extends beyond the excitatory to inhibitory shift of the actions of GABA.

  14. Activation of α7-containing nicotinic receptors on astrocytes triggers AMPA receptor recruitment to glutamatergic synapses.

    Science.gov (United States)

    Wang, Xulong; Lippi, Giordano; Carlson, David M; Berg, Darwin K

    2013-12-01

    Astrocytes, an abundant form of glia, are known to promote and modulate synaptic signaling between neurons. They also express α7-containing nicotinic acetylcholine receptors (α7-nAChRs), but the functional relevance of these receptors is unknown. We show here that stimulation of α7-nAChRs on astrocytes releases components that induce hippocampal neurons to acquire more α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors post-synaptically at glutamatergic synapses. The increase is specific in that no change is seen in synaptic NMDA receptor clusters or other markers for glutamatergic synapses, or in markers for GABAergic synapses. Moreover, the increases in AMPA receptors on the neuron surface are accompanied by increases in the frequency of spontaneous miniature synaptic currents mediated by the receptors and increases in the ratio of evoked synaptic currents mediated by AMPA versus NMDA receptors. This suggests that stimulating α7-nAChRs on astrocytes can convert 'silent' glutamatergic synapses to functional status. Astrocyte-derived thrombospondin is necessary but not sufficient for the effect, while tumor necrosis factor-α is sufficient but not necessary. The results identify astrocyte α7-nAChRs as a novel pathway through which nicotinic cholinergic signaling can promote the development of glutamatergic networks, recruiting AMPA receptors to post-synaptic sites and rendering the synapses more functional. We find that activation of nicotinic receptors on astrocytes releases a component that specifically recruits AMPA receptors to glutamatergic synapses. The recruitment appears to occur preferentially at what may be 'silent synapses', that is, synapses that have all the components required for glutamatergic transmission (including NMDA receptors) but lack sufficient AMPA receptors to generate a response. The results are unexpected and open up new possibilities for mechanisms underlying network formation and synaptic plasticity.

  15. Sedimentology and sequence stratigraphy of the Cretaceous Nanushuk, Seabee, and Tuluvak formations exposed on Umiat Mountain, north-central Alaska

    Science.gov (United States)

    Houseknecht, David W.; Schenk, Christopher J.

    2005-01-01

    Upper Cretaceous strata of the upper part of the Nanushuk Formation, the Seabee Formation, and the lower part of the Tuluvak Formation are exposed along the Colville River on the east flank of Umiat Mountain in north-central Alaska. The Ninuluk sandstone, which is the uppermost unit of the Nanushuk Formation, displays a vertical succession of facies indicative of deposition in an upward-deepening estuarine through shoreface setting. A marine-flooding surface lies between the Ninuluk sandstone and organic-rich shale of the basal part of the Seabee Formation. The Ninuluk sandstone and the lower part of the Seabee Formation are interpreted as components of a transgressive-systems tract. The lowest, well-exposed strata in the Seabee Formation are a succession of shoreface sandstone beds in the middle of the formation. Integration of outcrop information and the Umiat No. 11 well log suggests that this sandstone succession rests on a sequence boundary and is capped by a marine-flooding surface. The sandstone succession is interpreted as a lowstand-systems tract. The upper part of the Seabee Formation includes a thick interval of organic-rich shale deposited in a dysaerobic offshore environment, and the gradational Seabee-Tuluvak contact is a coarsening-upward shale-to-sandstone succession deposited in a prodelta/delta-front environment. The observation that the upper part of the Seabee Formation correlates with seismic clinoforms suggests that dysaerobic conditions extended well up onto the prodelta slope during intervals of transgression and highstand. Correlation of the Umiat Mountain outcrop section with well logs and seismic data suggests that sequence boundaries and lowstand shoreface deposits may be common in the Seabee Formation and that wave action may have been important in transporting sand to the paleoshelf margin. These conclusions may contribute to an enhanced understanding of sand distribution in prospective lowstand turbidite deposits in the subsurface of

  16. A new measure for the strength of electrical synapses

    Directory of Open Access Journals (Sweden)

    Julie S Haas

    2015-09-01

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

  17. Stimulation of neural cell adhesion molecule L1 to the formation of neurite and functional synapse%神经细胞黏附分子L1促进神经细胞突起和功能性突触的形成

    Institute of Scientific and Technical Information of China (English)

    钟振国

    2004-01-01

    BACKGROUND: Neural cell adhesion molecule L1 plays an important role on the origin, development of neural cells as well as the adhesion between nerves. However, the effect of L1 to the formation of neuritis and functional synapse is still uncertain.OBJECTIVE:To explore the effects of neural cell adhesion molecule L1 on forming neurites and functional synapses.DESIGN:Completely randomized controlled trial.SETTING and MATERIALS: Experiment was conducted in Neuroscience Research Institute of Guangxi College of Traditional Chinese Medicine.Materials include NG108-15 nerve cell strain, L1 cDNA, anti-L1 antibody:provided by Kanazawa University.METHODS: L1 cDNA was transfected into NG108-15 cells by lipid transfecting agent in vitro culture. Optical microscope was used to observe the cellular morphology. Electrophysiological technique was used to test the postsynaptic membrane potential of cell-muscular process.MAIN OUTCOME MEASURES: Cell process index; rate of synapse formation, frequency of miniatureplate potential.RESULTS: Four days after being processed by differentiation agent cAMP,the cells with protuberance and bifurcation in L1-transfection group accounted for(31 ±8)% of the total cells. This figure was much higher than that of non-transfection group ( 13 ± 2) % or Mock transfection group ( 15 ± 5 ) % ( P < 0.01). The average length of cell process was(142.5 ± 12.3) μm, it was higher than that of non-transfection group(94.2 ± 12. 3) μ m or Mock transfection group(86. 8 ± 6.7) μm( P < 0.05). The rate of synapse formation in L1 transfection group was(58.0±11.5)% , it was higher than that of non-transfection group ( 36.7 ± 0. 83 ) % or Mock-transfection group ( 39.2± 0. 84) % ( P < 0.01 ) . However, there was no significant difference between the postsynaptic membrane potential of three groups ( P > 0.05).CONCLUSION: The high expression of L1 in NG108 - 15 cells can enhance the formation of neural cell process and functional synapse induced by c

  18. Comparative anatomy of phagocytic and immunological synapses

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    Florence eNiedergang

    2016-01-01

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

  19. The Diversity of Cortical Inhibitory Synapses

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    Yoshiyuki eKubota

    2016-04-01

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

  20. Gliotransmission and the tripartite synapse.

    Science.gov (United States)

    Santello, Mirko; Calì, Corrado; Bezzi, Paola

    2012-01-01

    In the last years, the classical view of glial cells (in particular of astrocytes) as a simple supportive cell for neurons has been replaced by a new vision in which glial cells are active elements of the brain. Such a new vision is based on the existence of a bidirectional communication between astrocytes and neurons at synaptic level. Indeed, perisynaptic processes of astrocytes express active G-protein-coupled receptors that are able (1) to sense neurotransmitters released from the synapse during synaptic activity, (2) to increase cytosolic levels of calcium, and (3) to stimulate the release of gliotransmitters that in turn can interact with the synaptic elements. The mechanism(s) by which astrocytes can release gliotransmitter has been extensively studied during the last years. Many evidences have suggested that a fraction of astrocytes in situ release neuroactive substances both with calcium-dependent and calcium-independent mechanism(s); whether these mechanisms coexist and under what physiological or pathological conditions they occur, it remains unclear. However, the calcium-dependent exocytotic vesicular release has received considerable attention due to its potential to occur under physiological conditions via a finely regulated way. By releasing gliotransmitters in millisecond time scale with a specific vesicular apparatus, astrocytes can integrate and process synaptic information and control or modulate synaptic transmission and plasticity.

  1. AGN Feedback, Host Halo Mass and Central Cooling Time: Implications for Galaxy Formation Efficiency and $M_{BH} - \\sigma$

    CERN Document Server

    Main, Robert; Nulsen, Paul; Russell, Helen; Vantyghem, Adrian

    2015-01-01

    We derive X-ray mass, luminosity, and temperature profiles for 45 galaxy clusters to explore relationships between halo mass, AGN feedback, and central cooling time. We find that radio--mechanical feedback power (referred to here as "AGN power") in central cluster galaxies correlates with halo mass, but only in halos with central atmospheric cooling times shorter than 1 Gyr. This timescale corresponds approximately to the cooling time (entropy) threshold for the onset of cooling instabilities and star formation in central galaxies (Rafferty et al. 2008). No correlation is found in systems with central cooling times greater than 1 Gyr. The trend with halo mass is consistent with self-similar scaling relations assuming cooling is regulated by feedback. The trend is also consistent with galaxy and central black hole co-evolution along the $M_{BH} - \\sigma $ relation. AGN power further correlates with X-ray gas mass and the host galaxy's K-band luminosity. AGN power in clusters with central atmospheric cooling ti...

  2. Palynostratigraphy of the Sanganeh Formation at the East and Central Kopeh-Dagh Basin based on dinoflagellate cysts

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    Narges Shokri

    2015-05-01

    Full Text Available The Sanganeh Formation (Lower Cretaceous has cropped out across the Kopeh-Dagh Basin. The formation conformably overly the Aptian Sarcheshmeh Formation and is in turn overlain conformably by glauconitic sandstone of the Aitamir Formation. The considered formation in eastern and central parts of the basin comprises predominantly dark shale with some interbeds of limestone and siltstone. In order to analyse dinoflagellate content of this rock unit , four stratigraphic sections from east to the center of the basin including Karizak (320m, Mozduran (355m, Sanganeh (550m, and Qarah-Su (580m were measured and sampled palynologically. A total of 370 rock samples taken from the four sections were processed palynologically and scanned under a light microscope. Of these, two sections including Karizak and Mozduran were barren of any preserved dinocysts while, the samples from other two sections (Sanganeh and Qarah-Su yielded a relatively diverse and well preserved assemblage. According to the recognized dinocysts, two zones DZ1 and DZ2 were established in Sanganeh and Qarah-Su sections. The differentiated dinozones were coincident to Odontochitina operculata and Pseudoceratium turneri which are index for late Aptian-early Albian for the Sanganeh Formation at the mentioned stratigraphic sections. In addition, distribution and dispersion of dinoflagellate cyst contents indicate an increasing trend of the depth from east to the central parts of the Kopeh-Dagh Basin.

  3. Effects of Trace Metal Profiles Characteristic for Autism on Synapses in Cultured Neurons

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    Simone Hagmeyer

    2015-01-01

    Full Text Available Various recent studies revealed that biometal dyshomeostasis plays a crucial role in the pathogenesis of neurological disorders such as autism spectrum disorders (ASD. Substantial evidence indicates that disrupted neuronal homeostasis of different metal ions such as Fe, Cu, Pb, Hg, Se, and Zn may mediate synaptic dysfunction and impair synapse formation and maturation. Here, we performed in vitro studies investigating the consequences of an imbalance of transition metals on glutamatergic synapses of hippocampal neurons. We analyzed whether an imbalance of any one metal ion alters cell health and synapse numbers. Moreover, we evaluated whether a biometal profile characteristic for ASD patients influences synapse formation, maturation, and composition regarding NMDA receptor subunits and Shank proteins. Our results show that an ASD like biometal profile leads to a reduction of NMDAR (NR/Grin/GluN subunit 1 and 2a, as well as Shank gene expression along with a reduction of synapse density. Additionally, synaptic protein levels of GluN2a and Shanks are reduced. Although Zn supplementation is able to rescue the aforementioned alterations, Zn deficiency is not solely responsible as causative factor. Thus, we conclude that balancing Zn levels in ASD might be a prime target to normalize synaptic alterations caused by biometal dyshomeostasis.

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

    Science.gov (United States)

    Wiera, Grzegorz; Mozrzymas, Jerzy W

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Grzegorz eWiera

    2015-11-01

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

  6. Presynaptic [Ca2+] and GCAPs: aspects on the structure and function of photoreceptor ribbon synapses

    Directory of Open Access Journals (Sweden)

    Frank eSchmitz

    2014-02-01

    Full Text Available Changes in intracellular calcium ions [Ca2+] play important roles in photoreceptor signalling. Consequently, intracellular [Ca2+] levels need to be tightly controlled. In the light-sensitive outer segments (OS of photoreceptors, Ca2+ regulates the activity of retinal guanylate cyclases (ret-GCs thus playing a central role in phototransduction and light-adaptation by restoring light-induced decreases in cGMP. In the synaptic terminals, changes of intracellular Ca2+ trigger various aspects of neurotransmission. Photoreceptors employ tonically active ribbon synapses that encode light-induced, graded changes of membrane potential into different rates of synaptic vesicle exocytosis. The active zones of ribbon synapses contain large electron-dense structures, synaptic ribbons, that are associated with large numbers of synaptic vesicles. Synaptic coding at ribbon synapses differs from synaptic coding at conventional (phasic synapses. Recent studies revealed new insights how synaptic ribbons are involved in this process. This review focuses on the regulation of [Ca2+] in presynaptic photoreceptor terminals and on the function of a particular Ca2+-regulated protein, the neuronal calcium sensor protein GCAP2 (guanylate cyclase-activating protein-2 in the photoreceptor ribbon synapse. GCAP2, an EF hand-containing protein plays multiple roles in the OS and in the photoreceptor synapse. In the OS, GCAP2 works as a Ca2+-sensor within a Ca2+-regulated feedback loop that adjusts cGMP levels. In the photoreceptor synapse, GCAP2 binds to RIBEYE, a component of synaptic ribbons, and mediates Ca2+-dependent plasticity at that site. Possible mechanisms are discussed.

  7. The Formation of New Monetary Policies: Decisions of Central Banks on the Great Recession

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    Ana Esther Castro

    2014-05-01

    Full Text Available The effect that the Great Recession had on monetary policies has led to the profound reorientation of central banks’ actions from 2007 to 2013. The purpose of this work is to analyze the monetary policies applied by the main central banks, mainly the European Central Bank, the Federal Reserve System of USA and the Bank of Japan, in order to raise thoughts on the guidelines that central banks should follow in the future. In the first section the bases of monetary policy before the crisis are described; in the second we explain the change in the orientation of the role of central banks during the crisis; and finally, we synthesize the bases on which the economic debate is taking place on the orientation of future monetary policies. We conclude that, in so far as the inoperativeness of transmission mechanisms still persists, monetary policies will remain in a process of change.

  8. The theoretical plausibility of central pit crater formation via melt drainage

    Science.gov (United States)

    Elder, Catherine M.; Bray, Veronica J.; Melosh, H. Jay

    2012-11-01

    Central pit craters are seen in large craters on some icy satellites and on Mars. We investigate the hypothesis that central pits form when impact melt drains into fractures beneath the impact crater. For this process to occur, the volume of melt generated during the impact, the volume of void space in fractures beneath the impact crater, and the volume of melt able to drain before the fractures freeze shut all must exceed the volume of the observed central pits. We estimate the volume of melt generated using results from previous numerical modeling studies. The fracture volume is estimated using gravity anomalies over terrestrial craters. To estimate the amount of melt able to drain before freezing, we consider flow through plane parallel fractures. These calculations all suggest that enough liquid water could drain into fractured ice beneath a crater on Ganymede to form a central pit. On Earth and the Moon, silicate impact melt will freeze before a large volume is able to drain, so we do not expect to see central pits in impact craters in targets with no ice. In summary, we find our calculations are consistent with observed central pits in craters on Ganymede and the lack of central pits in craters on Earth and the Moon.

  9. Pan-neurexin perturbation results in compromised synapse stability and a reduction in readily releasable synaptic vesicle pool size

    Science.gov (United States)

    Quinn, Dylan P.; Kolar, Annette; Wigerius, Michael; Gomm-Kolisko, Rachel N.; Atwi, Hanine; Fawcett, James P.; Krueger, Stefan R.

    2017-01-01

    Neurexins are a diverse family of cell adhesion molecules that localize to presynaptic specializations of CNS neurons. Heterologous expression of neurexins in non-neuronal cells leads to the recruitment of postsynaptic proteins in contacting dendrites of co-cultured neurons, implicating neurexins in synapse formation. However, isoform-specific knockouts of either all α- or all β-neurexins show defects in synaptic transmission but an unaltered density of glutamatergic synapses, a finding that argues against an essential function of neurexins in synaptogenesis. To address the role of neurexin in synapse formation and function, we disrupted the function of all α- and β-neurexins in cultured hippocampal neurons by shRNA knockdown or by overexpressing a neurexin mutant that is unable to bind to postsynaptic neurexin ligands. We show that neurexin perturbation results in an attenuation of neurotransmitter release that is in large part due to a reduction in the number of readily releasable synaptic vesicles. We also find that neurexin perturbation fails to alter the ability of neurons to form synapses, but rather leads to more frequent synapse elimination. These experiments suggest that neurexins are dispensable for the formation of initial synaptic contacts, but play an essential role in the stabilization and functional maturation of synapses. PMID:28220838

  10. Depositional environments and sequence stratigraphy of the Bahram Formation (middleelate Devonian) in north of Kerman, south-central Iran

    Institute of Scientific and Technical Information of China (English)

    Afshin Hashmie; Ali Rostamnejad; Fariba Nikbakht; Mansour Ghorbanie; Peyman Rezaie; Hossien Gholamalian

    2016-01-01

    This study is focused on sedimentary environments, facies distribution, and sequence stratigraphy. The facies and sequence stratigraphic analyses of the Bahram Formation (middleelate Devonian) in south-central Iran are based on two measured stratigraphic sections in the southern Tabas block. The Bah-ram Formation overlies red sandstones Padeha Formation in sections Hutk and Sardar and is overlain by Carboniferous carbonate deposits of Hutk Formation paraconformably, with a thickness of 354 and 386 m respectively. Mixed siliciclastic and carbonate sediments are present in this succession. The field observations and laboratory studies were used to identify 14 micro/petrofacies, which can be grouped into 5 depositional environments: shore, tidal flat, lagoon, shoal and shallow open marine. A mixed carbonate-detrital shallow shelf is suggested for the depositional environment of the Bahram Formation which deepens to the east (Sardar section) and thins in southern locations (Hutk section). Three 3rd-order cyclic siliciclastic and carbonate sequences in the Bahram Formation and one sequence shared with the overlying joint with Hutk Formation are identified, on the basis of shallowing upward patterns in the micro/pertofacies.

  11. Automated quantification of synapses by fluorescence microscopy.

    Science.gov (United States)

    Schätzle, Philipp; Wuttke, René; Ziegler, Urs; Sonderegger, Peter

    2012-02-15

    The quantification of synapses in neuronal cultures is essential in studies of the molecular mechanisms underlying synaptogenesis and synaptic plasticity. Conventional counting of synapses based on morphological or immunocytochemical criteria is extremely work-intensive. We developed a fully automated method which quantifies synaptic elements and complete synapses based on immunocytochemistry. Pre- and postsynaptic elements are detected by their corresponding fluorescence signals and their proximity to dendrites. Synapses are defined as the combination of a pre- and postsynaptic element within a given distance. The analysis is performed in three dimensions and all parameters required for quantification can be easily adjusted by a graphical user interface. The integrated batch processing enables the analysis of large datasets without any further user interaction and is therefore efficient and timesaving. The potential of this method was demonstrated by an extensive quantification of synapses in neuronal cultures from DIV 7 to DIV 21. The method can be applied to all datasets containing a pre- and postsynaptic labeling plus a dendritic or cell surface marker.

  12. Determining the neurotransmitter concentration profile at active synapses.

    Science.gov (United States)

    Scimemi, Annalisa; Beato, Marco

    2009-12-01

    Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission.

  13. Magnetization of three Nubia Sandstone formations from Central Western Desert of Egypt

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    H. El-Shayeb

    2013-06-01

    The first magnetic component obtained from the two older formations is considered primary, as the corresponding pole reflects the age when compared with the previously obtained Cretaceous poles for North Africa. On other hand, the second pole obtained from the Maghrabi formation (the younger is inconsistent with the Cretaceous pole positions for North Africa, but falls closer to the Eocene pole indicating that the rocks of this formation could have suffered remagnetization during the late Eocene time.

  14. Selective localization of Shanks to VGLUT1-positive excitatory synapses in the mouse hippocampus

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    Christopher eHeise

    2016-04-01

    Full Text Available AbstractMembers of the Shank family of multidomain proteins (Shank1, Shank2, and Shank3 are core components of the postsynaptic density (PSD of excitatory synapses. At synaptic sites Shanks serve as scaffolding molecules that cluster neurotransmitter receptors as well as cell adhesion molecules attaching them to the actin cytoskeleton. In this study we investigated the synapse specific localization of Shank1-3 and focused on well-defined synaptic contacts within the hippocampal formation. We found that all three family members are present only at VGLUT1-positive synapses, which is particularly visible at mossy fiber contacts. No costaining was found at VGLUT2-positive contacts indicating that the molecular organization of VGLUT2-associated PSDs diverges from classical VGLUT1-positive excitatory contacts in the hippocampus. In light of SHANK mutations in neuropsychiatric disorders, this study indicates which glutamatergic networks within the hippocampus will be primarily affected by shankopathies.

  15. Correlation, sedimentology, structural setting, chemical composition, and provenance of selected formations in Mesoproterozoic Lemhi Group, central Idaho

    Science.gov (United States)

    Tysdal, Russell G.; Lindsey, David A.; Taggart, Joseph E.

    2003-01-01

    A unit of the Mesoproterozoic Apple Creek Formation of the Lemhi Range previously was correlated with part of the lower subunit of the Mesoproterozoic Yellowjacket Formation in the Salmon River Mountains. Strata currently assigned to the middle subunit of the Yellowjacket Formation lie conformably above the Apple Creek unit in the Salmon River Mountains, and are here renamed the banded siltite unit and reassigned to the Apple Creek Formation. Almost all of the banded siltite unit is preserved within the Salmon River Mountains, where it grades upward into clastic rocks that currently are assigned to the upper subunit of the Yellowjacket Formation and that here are reassigned to the Gunsight Formation. The banded siltite unit of the Apple Creek Formation is composed of a turbidite sequence, as recognized by previous workers. Uppermost strata of the unit were reworked by currents, possibly storm generated, and adjusted to a high water content by developing abundant soft-sediment deformation features. Basal strata of the overlying Gunsight Formation in the Salmon River Mountains display abundant hummocky crossbeds, storm-generated features deposited below fair-weather wave base, that are conformable above the storm-reworked deposits. The hummocky crossbedded strata grade upward into marine shoreface strata deposited above fair-weather wave base, which in turn are succeeded by fluvial strata. Hummocky and shoreface strata are absent from the Gunsight Formation in the Lemhi Range. The major thickness of the Gunsight Formation in both the Salmon River Mountains and the Lemhi Range is composed of fluvial rocks, transitional in the upper part into marine rocks of the Swauger Formation. The fluvial strata are mainly characterized by stacked sheets of metasandstone and coarse siltite; they are interpreted as deposits of braided rivers. The Poison Creek thrust fault of the Lemhi Range extends northwestward through the study area in the east-central part of the Salmon River

  16. Structural characterization of the fracture systems in the porcelanites: Comparing data from the Monterey Formation in California USA and the Sap Bon Formation in Central Thailand

    Science.gov (United States)

    Kanjanapayont, Pitsanupong; Aydin, Atilla; Wongseekaew, Kanitsorn; Maneelok, Wichanee

    2016-09-01

    The fractures in the porcelanites from the Monterey Formation in California USA and the Sap Bon Formation in Central Thailand were documented for a comparative study of their modes, distribution, and their relationship to other structures such as folds and bedding planes. Both formations consist in thinly bedded stiff units that are prone to folding, flexural slip, and cross-bedding brittle fracturing under compression. There are two assemblages in the porcelanites. The first assemblage includes commonly vertical high-angle opening mode fractures, left-lateral strike-slip faults, normal faults, and thrust faults. The second one is sub-horizontal fractures which are associated with folds, bedding slip, and thrusts faults in both Monterey and Sap Bon formations. The structural architectures of these rocks and the associated groups of structures are remarkably similar in terms of both opening and shearing modes and their relationships with the bedding due to their depositional architecture and the compressional tectonic regimes, in spite of the fact that the two locations are more than ten thousand kilometers apart and have very different ages of deformation.

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

    Science.gov (United States)

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

    2014-05-01

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

  18. Copper at synapse: Release, binding and modulation of neurotransmission.

    Science.gov (United States)

    D'Ambrosi, Nadia; Rossi, Luisa

    2015-11-01

    Over the last decade, a piece of the research studying copper role in biological systems was devoted to unravelling a still elusive, but extremely intriguing, aspect that is the involvement of copper in synaptic function. These studies were prompted to provide a rationale to the finding that copper is released in the synaptic cleft upon depolarization. The copper pump ATP7A, which mutations are responsible for diseases with a prominent neurodegenerative component, seems to play a pivotal role in the release of copper at synapses. Furthermore, it was found that, when in the synaptic cleft, copper can control, directly or indirectly, the activity of the neurotransmitter receptors (NMDA, AMPA, GABA, P2X receptors), thus affecting excitability. In turn, neurotransmission can affect copper trafficking and delivery in neuronal cells. Furthermore, it was reported that copper can also modulate synaptic vesicles trafficking and the interaction between proteins of the secretory pathways. Interestingly, proteins with a still unclear role in neuronal system though associated with the pathogenesis of neurodegenerative diseases (the amyloid precursor protein, APP, the prion protein, PrP, α-synuclein, α-syn) show copper-binding domains. They may act as copper buffer at synapses and participate in the interplay between copper and the neurotransmitters receptors. Given that copper dysmetabolism occurs in several diseases affecting central and peripheral nervous system, the findings on the contribution of copper in synaptic transmission, beside its more consolidate role as a neuronal enzymes cofactor, may open new insights for therapy interventions.

  19. Astrocytes, Synapses and Brain Function: A Computational Approach

    Science.gov (United States)

    Nadkarni, Suhita

    2006-03-01

    Modulation of synaptic reliability is one of the leading mechanisms involved in long- term potentiation (LTP) and long-term depression (LTD) and therefore has implications in information processing in the brain. A recently discovered mechanism for modulating synaptic reliability critically involves recruitments of astrocytes - star- shaped cells that outnumber the neurons in most parts of the central nervous system. Astrocytes until recently were thought to be subordinate cells merely participating in supporting neuronal functions. New evidence, however, made available by advances in imaging technology has changed the way we envision the role of these cells in synaptic transmission and as modulator of neuronal excitability. We put forward a novel mathematical framework based on the biophysics of the bidirectional neuron-astrocyte interactions that quantitatively accounts for two distinct experimental manifestation of recruitment of astrocytes in synaptic transmission: a) transformation of a low fidelity synapse transforms into a high fidelity synapse and b) enhanced postsynaptic spontaneous currents when astrocytes are activated. Such a framework is not only useful for modeling neuronal dynamics in a realistic environment but also provides a conceptual basis for interpreting experiments. Based on this modeling framework, we explore the role of astrocytes for neuronal network behavior such as synchrony and correlations and compare with experimental data from cultured networks.

  20. The central dark matter content of early-type galaxies: scaling relations and connections with star formation histories

    CERN Document Server

    Napolitano, Nicola R; Tortora, Crescenzo

    2010-01-01

    We examine correlations between the masses, sizes, and star formation histories for a large sample of low-redshift early-type galaxies, using a simple suite of dynamical and stellar populations models. We confirm an anti-correlation between size and stellar age, and survey for trends with the central content of dark matter (DM). An average relation between central DM density and galaxy size of ~ Reff^-2 provides the first clear indication of cuspy DM haloes in these galaxies -- akin to standard LCDM haloes that have undergone adiabatic contraction. The DM density scales with galaxy mass as expected, deviating from suggestions of a universal halo profile for dwarf and late-type galaxies. We introduce a new fundamental constraint on galaxy formation by finding that the central DM fraction decreases with stellar age. This result is only partially explained by the size-age dependencies, and the residual trend is in the opposite direction to basic DM halo expectations. Therefore we suggest that there may be a con...

  1. A Reinterpretation of the Baturetno Formation: Stratigraphic Study of the Baturetno Basin, Wonogiri, Central Java

    Directory of Open Access Journals (Sweden)

    Purna Sulastya Putra

    2015-09-01

    Full Text Available This paper focuses on the Quaternary Baturetno Formation. An earlier research concluded that the black clay of the Baturetno Formation formed as a ‘palaeolake’ deposit. The ‘palaeolake’ was interpreted to form due to the shifting course of the Bengawan Solo Purba River in relation to Pliocene tectonic tilting in the southern Java. The stratigraphy of the Baturetno Formation was observed in the western part of the Baturetno Basin, and based on marker beds, the Baturetno Formation was classified into three units: (1 Gravel unit (GR in the upper part, (2 clay unit (CU in the middle part, and (3 sand-gravel unit (SG in the lower part. There are floating gravel fragments of andesite, claystone, coral, and limestone with diameters of up to 10 cm in the clay unit. The particle size of sediment reflects the environment, but the lake deposition occurs under very quiet conditions. The occurrence of these fragments within the clay cannot be explained if the clay was deposited within a lake environment. The occurrence of floating fragments in the black clay of Baturetno Formation can best be explained through mudflow process. The cohesive strength of the mudflow is responsible for the ability of large fragments to float within the mud matrix. In general, the Baturetno Formation is inferred to be an alluvial fan deposit. The presence of sand, gravel, and mud are characteristics of alluvial fan deposits.

  2. Hanadirella: A new problematic arthropod(?) from the Lower Ordovician (Llanvirn) Tabuk Formation, central Saudi Arabia

    NARCIS (Netherlands)

    El-Khayal, A.A.

    1985-01-01

    The new genus Hanadirella - with the type species H. bramkampi - from the Lower Ordovician (Llanvirn) of central Saudi Arabia represents a segmented organism which appears to have an arthropod affinity. The problematic genus is oval hat-shaped, less than 1 mm in diameter. Its affinity and palaeoecol

  3. Elastohydrodynamics and kinetics of protein patterning in the immunological synapse

    CERN Document Server

    Carlson, Andreas

    2015-01-01

    The cellular basis for the adaptive immune response during antigen recognition relies on a specialized protein interface known as the immunological synapse (IS). Understanding the biophysical basis for protein patterning by deciphering the quantitative rules for their formation and motion is an important aspect of characterizing immune cell recognition and thence the rules for immune system activation. We propose a minimal mathematical model for the physical basis of membrane protein patterning in the IS, which encompass membrane mechanics, protein binding kinetics and motion, and fluid flow in the synaptic cleft. Our theory leads to simple predictions for the spatial and temporal scales of protein cluster formation, growth and arrest as a function of membrane stiffness, rigidity and kinetics of the adhesive proteins, and the fluid in the synaptic cleft. Numerical simulations complement these scaling laws by quantifying the nucleation, growth and stabilization of proteins domains on the size of the cell. Dire...

  4. Stretching morphogenesis of the roof plate and formation of the central canal.

    Directory of Open Access Journals (Sweden)

    Igor Kondrychyn

    Full Text Available BACKGROUND: Neurulation is driven by apical constriction of actomyosin cytoskeleton resulting in conversion of the primitive lumen into the central canal in a mechanism driven by F-actin constriction, cell overcrowding and buildup of axonal tracts. The roof plate of the neural tube acts as the dorsal morphogenetic center and boundary preventing midline crossing by neural cells and axons. METHODOLOGY/PRINCIPAL FINDINGS: The roof plate zebrafish transgenics expressing cytosolic GFP were used to study and describe development of this structure in vivo for a first time ever. The conversion of the primitive lumen into the central canal causes significant morphogenetic changes of neuroepithelial cells in the dorsal neural tube. We demonstrated that the roof plate cells stretch along the D-V axis in parallel with conversion of the primitive lumen into central canal and its ventral displacement. Importantly, the stretching of the roof plate is well-coordinated along the whole spinal cord and the roof plate cells extend 3× in length to cover 2/3 of the neural tube diameter. This process involves the visco-elastic extension of the roof place cytoskeleton and depends on activity of Zic6 and the Rho-associated kinase (Rock. In contrast, stretching of the floor plate is much less extensive. CONCLUSIONS/SIGNIFICANCE: The extension of the roof plate requires its attachment to the apical complex of proteins at the surface of the central canal, which depends on activity of Zic6 and Rock. The D-V extension of the roof plate may change a range and distribution of morphogens it produces. The resistance of the roof plate cytoskeleton attenuates ventral displacement of the central canal in illustration of the novel mechanical role of the roof plate during development of the body axis.

  5. Toward a molecular catalogue of synapses.

    Science.gov (United States)

    Grant, Seth G N

    2007-10-01

    1906 was a landmark year in the history of the study of the nervous system, most notably for the first 'neuroscience' Nobel prize given to the anatomists Ramon Y Cajal and Camillo Golgi. 1906 is less well known for another event, also of great significance for neuroscience, namely the publication of Charles Sherrington's book 'The Integrative Action of the Nervous system'. It was Cajal and Golgi who debated the anatomical evidence for the synapse and it was Sherrington who laid its foundation in electrophysiological function. In tribute to these pioneers in synaptic biology, this article will address the issue of synapse diversity from the molecular point of view. In particular I will reflect upon efforts to obtain a complete molecular characterisation of the synapse and the unexpectedly high degree of molecular complexity found within it. A case will be made for developing approaches that can be used to generate a general catalogue of synapse types based on molecular markers, which should have wide application.

  6. Food restriction modifies ultrastructure of hippocampal synapses.

    Science.gov (United States)

    Babits, Réka; Szőke, Balázs; Sótonyi, Péter; Rácz, Bence

    2016-04-01

    Consumption of high-energy diets may compromise health and may also impair cognition; these impairments have been linked to tasks that require hippocampal function. Conversely, food restriction has been shown to improve certain aspects of hippocampal function, including spatial memory and memory persistence. These diet-dependent functional changes raise the possibility that the synaptic structure underlying hippocampal function is also affected. To examine how short-term food restriction (FR) alters the synaptic structure of the hippocampus, we used quantitative electron microscopy to analyze the organization of neuropil in the CA1 stratum radiatum of the hippocampus in young rats, consequent to reduced food. While four weeks of FR did not modify the density, size, or shape of postsynaptic spines, the synapses established by these spines were altered, displaying increased mean length, and more frequent perforations of postsynaptic densities. That the number of perforated synapses (believed to be an indicator of synaptic enhancement) increased, and that the CA1 spine population had on average significantly longer PSDs suggests that synaptic efficacy of axospinous synapses also increased in the CA1. Taken together, our ultrastructural data reveal previously unrecognized structural changes at hippocampal synapses as a function of food restriction, supporting a link between metabolic balance and synaptic plasticity.

  7. Facies distribution, depositional environment, and petrophysical features of the Sharawra Formation, Old Qusaiba Village, Central Saudi Arabia

    Science.gov (United States)

    Abbas, Muhammad Asif; Kaminski, Michael; Umran Dogan, A.

    2016-04-01

    The Silurian Sharawra Formation has great importance as it rests over the richest source rock of the Qusaiba Formation in central Saudi Arabia. The Sharawra Formation has four members including Jarish, Khanafriyah, Nayyal, and Zubliyat. The formation mainly consists of sandstone and siltstone with subordinate shale sequences. The lack of published research on this formation requires fundamental studies that can lay the foundation for future research. Three outcrops were selected from the Old Qusaiba Village in Central Saudi Arabia for field observations, petrographical and petrophysical study. Thin section study has been aided by quantitative mineralogical characterization using scanning electron microscopy - energy dispersive spectroscopy and powder x-ray diffraction (XRD) for both minerals, cements, and clay minerals (detrital and authigenic). The outcrops were logged in detail and nine different lithofacies have been identified. The thin section study has revealed the Sharawra Formation to be mainly subarkosic, while the mica content increases near to its contact with the Qusaiba Formation. The XRD data has also revealed a prominent change in mineralogy with inclusion of minerals like phlogopite and microcline with depths. Field observations delineated a prominent thinning of strata as lithofacies correlation clearly shows the thinning of strata in the southwestern direction. The absence of outcrop exposures further supports the idea of southwestern thinning of strata. This is mainly attributed to local erosion and the presence of thicker shale interbeds in the southeastern section, which was probably subjected to more intense erosion than the northwestern one. The Sharawra Formation rests conformably over the thick transgressive shale sequence, deposited during the post glacial depositional cycle. The lowermost massive sandstone bed of the Sharawra Formation represents the beginning of the regressive period. The shale interbeds in the lower part are evidence of

  8. Ultrafast action potentials mediate kilohertz signaling at a central synapse.

    Science.gov (United States)

    Ritzau-Jost, Andreas; Delvendahl, Igor; Rings, Annika; Byczkowicz, Niklas; Harada, Harumi; Shigemoto, Ryuichi; Hirrlinger, Johannes; Eilers, Jens; Hallermann, Stefan

    2014-10-01

    Fast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported in vivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission up to ∼1 kHz. Presynaptic APs are ultrafast, with ∼100 μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca(2+) channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling.

  9. The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse.

    Science.gov (United States)

    Baixauli, Francesc; Martín-Cófreces, Noa B; Morlino, Giulia; Carrasco, Yolanda R; Calabia-Linares, Carmen; Veiga, Esteban; Serrador, Juan M; Sánchez-Madrid, Francisco

    2011-04-06

    During antigen-specific T-cell activation, mitochondria mobilize towards the vicinity of the immune synapse. We show here that the mitochondrial fission factor dynamin-related protein 1 (Drp1) docks at mitochondria, regulating their positioning and activity near the actin-rich ring of the peripheral supramolecular activation cluster (pSMAC) of the immune synapse. Mitochondrial redistribution in response to T-cell receptor engagement was abolished by Drp1 silencing, expression of the phosphomimetic mutant Drp1S637D and the Drp1-specific inhibitor mdivi-1. Moreover, Drp1 knockdown enhanced mitochondrial depolarization and T-cell receptor signal strength, but decreased myosin phosphorylation, ATP production and T-cell receptor assembly at the central supramolecular activation cluster (cSMAC). Our results indicate that Drp1-dependent mitochondrial positioning and activity controls T-cell activation by fuelling central supramolecular activation cluster assembly at the immune synapse.

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

    Directory of Open Access Journals (Sweden)

    El-Husseini Alaa

    2005-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Isabelle Ayumi Spühler

    2016-05-01

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

  12. Ultrastructural and functional fate of recycled vesicles in hippocampal synapses.

    Science.gov (United States)

    Rey, Stephanie A; Smith, Catherine A; Fowler, Milena W; Crawford, Freya; Burden, Jemima J; Staras, Kevin

    2015-01-01

    Efficient recycling of synaptic vesicles is thought to be critical for sustained information transfer at central terminals. However, the specific contribution that retrieved vesicles make to future transmission events remains unclear. Here we exploit fluorescence and time-stamped electron microscopy to track the functional and positional fate of vesicles endocytosed after readily releasable pool (RRP) stimulation in rat hippocampal synapses. We show that most vesicles are recovered near the active zone but subsequently take up random positions in the cluster, without preferential bias for future use. These vesicles non-selectively queue, advancing towards the release site with further stimulation in an actin-dependent manner. Nonetheless, the small subset of vesicles retrieved recently in the stimulus train persist nearer the active zone and exhibit more privileged use in the next RRP. Our findings reveal heterogeneity in vesicle fate based on nanoscale position and timing rules, providing new insights into the origins of future pool constitution.

  13. Revisions to the stratigraphic nomenclature of the Abiquiu Formation, Abiquiu and contiguous areas, north-central New Mexico

    Science.gov (United States)

    Maldonado, Florian; Kelley, Shari A.

    2009-01-01

    Stratigraphic studies and geologic mapping on the Abiquiu 7.5-min quadrangle have led to revision of the stratigraphic nomenclature for the Oligocene to Miocene Abiquiu Formation in north-central New Mexico. The Abiquiu Formation had previously been defined to include informal upper, middle (Pedernal chert member), and lower members. The basement-derived conglomeratic lower member in the northern Jemez Mountains and Abiquiu embayment is here redefined. We propose removing the "lower member" from the Abiquiu Formation because provenance of these coarse sediments is dramatically different than the volcaniclastic strata of the "upper member." Furthermore, we propose that the term "lower member of the Abiquiu Formation" be replaced with an existing unit name, the Ritito Conglomerate of Barker (1958), and that the name Abiquiu Formation be restricted to the volcaniclastic succession. The lower part of the Ritito Conglomerate in Arroyo del Cobre on the Abiquiu quadrangle is 47 m (155 ft) thick and is composed of arkosic conglomeratic beds interbedded with arkosic sands and siltstones. Clasts include, in descending order of abundance, Proterozoic quartzite, granite, metavolcanic rocks, quartz, schist, and gneiss and a trace of Mesozoic sandstone and Paleozoic chert. Clasts are predominantly of pebble and cobble size but range from granule to boulder size. Paleocurrent data collected in the Arroyo del Cobre area indicate that the Ritito Conglomerate was deposited by a south-flowing river system during the Oligocene, eroding Laramide highlands such as the Tusas Mountains to the northeast, which contain predominantly Proterozoic rocks. This depositional setting has also been suggested by previous workers. The middle member or Pedernal chert member is present both at the top of the Ritito Conglomerate and as lenses within the lower part of the Abiquiu Formation. This post-depositional diagenetic chert remains an informal unit called the Pedernal chert.

  14. Sedimentology, petrology, and gas potential of the Brallier Formation: upper Devonian turbidite facies of the Central and Southern Appalachians

    Energy Technology Data Exchange (ETDEWEB)

    Lundegard, P.D.; Samuels, N.D.; Pryor, W.A.

    1980-03-01

    The Upper Devonian Brallier Formation of the central and southern Appalachian basin is a regressive sequence of siltstone turbidites interbedded with mudstones, claystones, and shales. It reaches 1000 meters in thickness and overlies basinal mudrocks and underlies deltaic sandstones and mudrocks. Facies and paleocurrent analyses indicate differences between the depositional system of the Brallier Formation and those of modern submarine fans and ancient Alpine flysch-type sequences. The Brallier system is of finer grain size and lower flow intensity. In addition, the stratigraphic transition from turbidites to deltaic sediments is gradual and differs in its facies succession from the deposits of the proximal parts of modern submarine fans. Such features as massive and pebbly sandstones, conglomerates, debris flows, and massive slump structures are absent from this transition. Paleocurrents are uniformly to the west at right angles to basin isopach, which is atypical of ancient turbidite systems. This suggests that turbidity currents had multiple point sources. The petrography and paleocurrents of the Brallier Formation indicate an eastern source of sedimentary and low-grade metasedimentary rocks with modern relief and rainfall. The depositional system of the Brallier Formation is interpreted as a series of small ephemeral turbidite lobes of low flow intensity which coalesced in time to produce a laterally extensive wedge. The lobes were fed by deltas rather than submarine canyons or upper fan channel systems. This study shows that the present-day turbidite facies model, based mainly on modern submarine fans and ancient Alpine flysch-type sequences, does not adequately describe prodeltaic turbidite systems such as the Brallier Formation. Thickly bedded siltstone bundles are common features of the Brallier Formation and are probably its best gas reservoir facies, especially when fracture porosity is well developed.

  15. FORMATIVE MECHANISM OF AKAISHI MOUNTAINS AND ENREI BASIN IN CENTRAL JAPAN

    Institute of Scientific and Technical Information of China (English)

    Yasu'uchi KUBOTA; Takao YANO

    2001-01-01

    @@ 1 Introduction It is common in mobile belts that uplifting mountains are neighbored by synchronously subsiding basins.The coupling mechanism of such subsidence and uplift is an important target to clarify the dynamics of mobile belts.We investigate the coupled mountain uplift and basin subsidence in the Central Japan highland,the junction of three island arcs (the Northeast Japan,the Southwest Japan and the Izu-Ogasawara arcs).The highland over 3 000 m in height is composed of mountain ranges,plateaus and intramountain basins (Fig.1).

  16. FORMATIVE MECHANISM OF AKAISHI MOUNTAINS AND ENREI BASIN IN CENTRAL JAPAN

    Institute of Scientific and Technical Information of China (English)

    Yasu'uchi; KUBOTA; Takao; YANO

    2001-01-01

    1 Introduction  It is common in mobile belts that uplifting mountains are neighbored by synchronously subsiding basins.The coupling mechanism of such subsidence and uplift is an important target to clarify the dynamics of mobile belts.We investigate the coupled mountain uplift and basin subsidence in the Central Japan highland,the junction of three island arcs (the Northeast Japan,the Southwest Japan and the Izu-Ogasawara arcs).The highland over 3 000 m in height is composed of mountain ranges,plateaus and intramountain basins (Fig.1).……

  17. Geologic framework, age, and lithologic characteristics of the North Park Formation in North Park, north-central Colorado

    Science.gov (United States)

    Shroba, Ralph R.

    2016-10-18

    Deposits of the North Park Formation of late Oligocene and Miocene age are locally exposed at small, widely spaced outcrops along the margins of the roughly northwest-trending North Park syncline in the southern part of North Park, a large intermontane topographic basin in Jackson County in north-central Colorado. These outcrops suggest that rocks and sediments of the North Park Formation consist chiefly of poorly consolidated sand, weakly cemented sandstone, and pebbly sandstone; subordinate amounts of pebble conglomerate; minor amounts of cobbly pebble gravel, siltstone, and sandy limestone; and rare beds of cobble conglomerate and altered tuff. These deposits partly filled North Park as well as a few small nearby valleys and half grabens. In North Park, deposits of the North Park Formation probably once formed a broad and relatively thick sedimentary apron composed chiefly of alluvial slope deposits (mostly sheetwash and stream-channel alluvium) that extended, over a distance of at least 150 kilometers (km), northwestward from the Never Summer Mountains and northward from the Rabbit Ears Range across North Park and extended farther northwestward into the valley of the North Platte River slightly north of the Colorado-Wyoming border. The maximum preserved thickness of the formation in North Park is about 550 meters near the southeastern end of the North Park syncline.The deposition of the North Park Formation was coeval in part with local volcanism, extensional faulting, development of half grabens, and deposition of the Browns Park Formation and Troublesome Formation and was accompanied by post-Laramide regional epeirogenic uplift. Regional deposition of extensive eolian sand sheets and loess deposits, coeval with the deposition of the North Park Formation, suggests that semiarid climatic conditions prevailed during the deposition of the North Park Formation during the late Oligocene and Miocene.The North Park Formation locally contains a 28.1-mega-annum (Ma

  18. The central role of heat shock factor 1 in synaptic fidelity and memory consolidation.

    Science.gov (United States)

    Hooper, Philip L; Durham, Heather D; Török, Zsolt; Hooper, Paul L; Crul, Tim; Vígh, László

    2016-09-01

    Networks of neuronal synapses are the fundamental basis for making and retaining memory. Reduced synapse number and quality correlates with loss of memory in dementia. Heat shock factor 1 (HSF1), the major transcription factor regulating expression of heat shock genes, plays a central role in proteostasis, in establishing and sustaining synaptic fidelity and function, and in memory consolidation. Support for this thesis is based on these observations: (1) heat shock induces improvements in synapse integrity and memory consolidation; (2) synaptic depolarization activates HSF1; (3) activation of HSF1 alone (independent of the canonical heat shock response) augments formation of essential synaptic elements-neuroligands, vesicle transport, synaptic scaffolding proteins, lipid rafts, synaptic spines, and axodendritic synapses; (4) HSF1 coalesces and activates memory receptors in the post-synaptic dendritic spine; (5) huntingtin or α-synuclein accumulation lowers HSF1 while HSF1 lowers huntingtin and α-synuclein aggregation-a potential vicious cycle; and (6) HSF1 agonists (including physical activity) can improve cognitive function in dementia models. Thus, via direct gene expression of synaptic elements, production of HSPs that assure high protein fidelity, and activation of other neuroprotective signaling pathways, HSF1 agonists could provide breakthrough therapy for dementia-associated disease.

  19. High-redshift formation and evolution of central massive objects II: The census of BH seeds

    CERN Document Server

    Devecchi, B; Rossi, E M; Colpi, M; Zwart, S Portegies

    2012-01-01

    We present results of simulations aimed at tracing the formation of nuclear star clusters (NCs) and black hole (BH) seeds, in a cosmological context. We focus on two mechanisms for the formation of BHs at high redshifts: as end-products of (1) Population III stars in metal free halos, and of (2) runaway stellar collisions in metal poor NCs. Our model tracks the chemical, radiative and mechanical feedback of stars on the baryonic component of the evolving halos. This procedure allows us to evaluate when and where the conditions for BH formation are met, and to trace the emergence of BH seeds arising from the dynamical channel, in a cosmological context. BHs start to appear already at z~30 as remnants of Population III stars. The efficiency of this mechanism begins decreasing once feedbacks become increasingly important. Around redshift z~15, BHs mostly form in the centre of mildly metal enriched halos inside dense NCs. The seed BHs that form along the two pathways have at birth a mass around 100-1000M\\odot. Th...

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

    Directory of Open Access Journals (Sweden)

    Ewan West

    2015-06-01

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

  1. Segregation of Central Ventricular Conduction System Lineages in Early SMA+ Cardiomyocytes Occurs Prior to Heart Tube Formation

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    Caroline Choquet

    2016-01-01

    Full Text Available The cardiac conduction system (CCS transmits electrical activity from the atria to the ventricles to coordinate heartbeats. Atrioventricular conduction diseases are often associated with defects in the central ventricular conduction system comprising the atrioventricular bundle (AVB and right and left branches (BBs. Conducting and contractile working myocytes share common cardiomyogenic progenitors, however the time at which the CCS lineage becomes specified is unclear. In order to study the fate and the contribution to the CCS of cardiomyocytes during early heart tube formation, we performed a genetic lineage analysis using a Sma-CreERT2 mouse line. Lineage tracing experiments reveal a sequential contribution of early Sma expressing cardiomyocytes to different cardiac compartments, labeling at embryonic day (E 7.5 giving rise to the interventricular septum and apical left ventricular myocardium. Early Sma expressing cardiomyocytes contribute to the AVB, BBs and left ventricular Purkinje fibers. Clonal analysis using the R26-confetti reporter mouse crossed with Sma-CreERT2 demonstrates that early Sma expressing cardiomyocytes include cells exclusively fated to give rise to the AVB. In contrast, lineage segregation is still ongoing for the BBs at E7.5. Overall this study highlights the early segregation of the central ventricular conduction system lineage within cardiomyocytes at the onset of heart tube formation.

  2. Dew formation on the surface of biological soil crusts in central European sand ecosystems

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    T. Fischer

    2012-11-01

    Full Text Available Dew formation was investigated in three developmental stages of biological soil crusts (BSC, which were collected along a catena of an inland dune and in the initial substrate. The Penman equation, which was developed for saturated surfaces, was modified for unsaturated surfaces and used for prediction of dewfall rates. The levels of surface saturation required for this approach were predicted using the water retention functions and the thicknesses of the BSCs. During a first field campaign (2–3 August 2011, dewfall increased from 0.042 kg m−2 for the initial sandy substrate to 0.058, 0.143 and 0.178 kg m−2 for crusts 1 to 3, respectively. During a second field campaign (17–18 August 2011, where dew formation was recorded in 1.5 to 2.75-h intervals after installation at 21:30 CEST, dewfall increased from 0.011 kg m−2 for the initial sandy substrate to 0.013, 0.028 and 0.055 kg m−2 for crusts 1 to 3, respectively. Dewfall rates remained on low levels for the substrate and for crust 1, and decreased overnight for crusts 2 and 3 (with crust 3 > crust 2 > crust 1 throughout the campaign. Dew formation was well reflected by the model response. The suggested mechanism of dew formation involves a delay in water saturation in near-surface soil pores and extracellular polymeric substances (EPS where the crusts were thicker and where the water capacity was high, resulting in elevated vapor flux towards the surface. The results also indicate that the amount of dewfall was too low to saturate the BSCs and to observe water flow into deeper soil. Analysis of the soil water retention curves revealed that, despite the sandy mineral matrix, moist crusts clogged by swollen EPS pores exhibited a clay-like behavior. It is hypothesized that BSCs gain double benefit from suppressing their competitors by runoff generation and from improving their water supply by dew collection. Despite higher amounts of dew, the

  3. Observations of Lyα and O vi: Signatures of Cooling and Star Formation in a Massive Central Cluster Galaxy

    Science.gov (United States)

    Donahue, Megan; Connor, Thomas; Voit, G. Mark; Postman, Marc

    2017-02-01

    We report new Hubble Space Telescope COS and Space Telescope Imaging Spectrograph spectroscopy of a star-forming region (∼ 100 {M}ȯ yr‑1) in the center of the X-ray cluster RX J1532.9+3021 (z = 0.362), to follow-up the CLASH team discovery of luminous UV filaments and knots in the central massive galaxy. We detect broad (∼500 km s‑1) Lyα emission lines with extraordinarily high equivalent widths (EQW ∼ 200 Å) and somewhat less broadened Hα (∼220 km s‑1). Ultraviolet emission lines of N v and O vi are not detected, which constrains the rate at which gas cools through temperatures of 106 K to be ≲10 M⊙ yr‑1. The COS spectra also show a flat rest-frame UV continuum with weak stellar photospheric features, consistent with the presence of recently formed hot stars forming at a rate of ∼10 M⊙ yr‑1, uncorrected for dust extinction. The slope and absorption lines in these UV spectra are similar to those of Lyman Break Galaxies at z≈ 3, albeit those with the highest Lyα equivalent widths and star formation rates. This high-EQW Lyα source is a high-metallicity galaxy rapidly forming stars in structures that look nothing like disks. This mode of star formation could significantly contribute to the spheroidal population of galaxies. The constraint on the luminosity of any O vi line emission is stringent enough to rule out steady and simultaneous gas cooling and star formation, unlike similar systems in the Phoenix Cluster and Abell 1795. The fact that the current star formation rate differs from the local mass cooling rate is consistent with recent simulations of episodic active galactic nucleus feedback and star formation in a cluster atmosphere.

  4. D-serine and serine racemase are associated with PSD-95 and glutamatergic synapse stability

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    Hong eLin

    2016-02-01

    Full Text Available D-serine is an endogenous coagonist at the glycine site of synaptic NMDA receptors (NMDARs, synthesized by serine racemase (SR through conversion of L-serine. It is crucial for synaptic plasticity and is implicated in schizophrenia. Our previous studies demonstrated specific loss of SR, D-serine-responsive synaptic NMDARs, and glutamatergic synapses in cortical neurons lacking alpha7 nicotinic acetylcholine receptors, which promotes glutamatergic synapse formation and maturation during development. We thus hypothesize that D-serine and SR (D-serine/SR are associated with glutamatergic synaptic development. Using morphological and molecular studies in cortical neuronal cultures, we demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development. Endogenous D-serine and SR colocalize with PSD-95, but not presynaptic vesicular glutamate transporter 1 (VGLUT1, in glutamatergic synapses of cultured cortical neurons. Low-density astrocytes in cortical neuronal cultures lack SR expression but contain enriched D-serine in large vesicle-like structures, suggesting possible synthesis of D-serine in postsynaptic neurons and storage in astrocytes. More interestingly, endogenous D-serine and SR colocalize with PSD-95 in the postsynaptic terminals of glutamatergic synapses during early and late synaptic development, implicating involvement of D-serine/SR in glutamatergic synaptic development. Exogenous application of D-serine enhances the interactions of SR with PSD-95 and NR1, and increases the number of VGLUT1- and PSD-95-positive glutamatergic synapses, suggesting that exogenous D-serine enhances postsynaptic SR/PSD-95 signaling and stabilizes glutamatergic synapses during cortical synaptic development. This is blocked by NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5 and 7-chlorokynurenic acid (7-CK, a specific antagonist at the glycine site of NMDARs

  5. Whole organic electronic synapses for dopamine detection

    Science.gov (United States)

    Giordani, Martina; Di Lauro, Michele; Berto, Marcello; Bortolotti, Carlo A.; Vuillaume, Dominique; Gomes, Henrique L.; Zoli, Michele; Biscarini, Fabio

    2016-09-01

    A whole organic artificial synapse has been fabricated by patterning PEDOT:PSS electrodes on PDMS that are biased in frequency to yield a STP response. The timescale of the STP response is shown to be sensitive to the concentration of dopamine, DA, a neurotransmitter relevant for monitoring the development of Parkinson's disease and potential locoregional therapies. The sensitivity of the sensor towards DA has been validated comparing signal variation in the presence of DA and its principal interfering agent, ascorbic acid, AA. The whole organic synapse is biocompatible, soft and flexible, and is attractive for implantable devices aimed to real-time monitoring of DA concentration in bodily fluids. This may open applications in chronic neurodegenerative diseases such as Parkinson's disease.

  6. Double inverse stochastic resonance with dynamic synapses

    Science.gov (United States)

    Uzuntarla, Muhammet; Torres, Joaquin J.; So, Paul; Ozer, Mahmut; Barreto, Ernest

    2017-01-01

    We investigate the behavior of a model neuron that receives a biophysically realistic noisy postsynaptic current based on uncorrelated spiking activity from a large number of afferents. We show that, with static synapses, such noise can give rise to inverse stochastic resonance (ISR) as a function of the presynaptic firing rate. We compare this to the case with dynamic synapses that feature short-term synaptic plasticity and show that the interval of presynaptic firing rate over which ISR exists can be extended or diminished. We consider both short-term depression and facilitation. Interestingly, we find that a double inverse stochastic resonance (DISR), with two distinct wells centered at different presynaptic firing rates, can appear.

  7. Pumice in the interglacial Whidbey Formation at Blowers Bluff, central Whidbey Island, WA, USA

    Science.gov (United States)

    Dethier, D.P.; Dragovich, J.D.; Sarna-Wojcicki, A. M.; Fleck, R.J.

    2008-01-01

    A new 40Ar/39Ar age of 128??9 ka and chemical analyses of pumice layers from interglacial alluvium at Blowers Bluff, Whidbey Island, WA, show that the deposits are part of the Whidbey Formation, a widespread, mainly subsurface unit. Glass chemistry of the dated dacitic pumice does not match any analyzed northern Cascade source, but upper Pleistocene dacites from Glacier Peak and early Pleistocene silicic rocks from the Kulshan caldera are chemically similar. The chemistry of pumiceous dacite in younger units, including the latest Pleistocene Partridge Gravel, is similar to that of the dated material. The deep troughs of the modern northern Puget lowland must have been filled during deposition of the Whidbey Formation, allowing volcanic-rich sediment to reach what is now Whidbey Island. Topographic analysis of LIDAR images demonstrates that extensive erosion occurred during latest Pleistocene ice retreat. The Partridge Gravel likely records subglacial fluvial erosion along an ice tunnel and ice-marginal deposition into adjacent marine waters. Pumice in the Partridge Gravel probably was reworked from stratigraphically and topographically lower deposits, including those at Blowers Bluff. ?? 2007 Elsevier Ltd and INQUA.

  8. Prevention of Noise Damage to Cochlear Synapses

    Science.gov (United States)

    2015-10-01

    antibody blocking buffer 5% horse serum / 0.1% bovine serum albumin / 0.1% Triton / 0.02% NaN3 for 60 min at room temperature. Immunostaining: The hair...the possibility that osmotic stress is responsible in part for excitotoxic damage to synapses. Alternatively, it may be that the in vitro excitotoxic... stress is exceptionally strong and is not an accurate model of noise exposure in vivo. Methodology Using neonatal (postnatal day 5, P5) rat

  9. Optical Mapping of Release Properties in Synapses

    OpenAIRE

    Pablo Ariel; Ryan, Timothy A.

    2010-01-01

    Synapses are important functional units that determine how information flows through the brain. Understanding their biophysical properties and the molecules that underpin them is an important goal of cellular neuroscience. Thus, it is of interest to develop protocols that allow easy measurement of synaptic parameters in model systems that permit molecular manipulations. Here, we used a sensitive and high-time resolution optical approach that allowed us to characterize two functional parameter...

  10. Neurotrophic regulation of synapse development and plasticity

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Neurotrophic factors are traditionally thought to be secretory proteins that regulate long-tern survival and differe, ntiation of neurons. Recent studies have revealed a previously unexpected role for these factors in synaptie de velopment ami plasticity in diverse neuronal populations. Here we review experimeuts carried oul in our own laboratory in the last few years.. We have made two important discoveries.First,we were among the first to report that brain-derived. neurotrophie faclor (BDNF) facilitates hippocampal hmg-term potentiation (LTP), a form of synaptic plaslicity believed to be involved in learning and memory. BDNF modulates LTP al CAI synapses by enhaneing synaptic responses to high frequency, tetanic slimulalion. This is achieved primafily by facilitating synaptie vesicle doeking, possibly due to an in crease in the levels of the vesicle prolein synaptobrevin and synaptoplysin in the nerve terminals. Gene knockout study demonstrates thai the effects of BDNF are primarily mediated through presynaptic mechanisms. Second, we demonstrated a form of long-term, neurotrophin-mediated synaptic regulation. We showed that long-term treatment of the neuromuscu lar synapses with neurotrophin-3 (NT3) resulted in an enhancement of both spontaneous and evoked synaptic currcuts, as well as profound changes in thc number of synaptic varicosities and syuaptic vesicle proteins in motoneurons, all of which are indicative of more mature synapses. Our current work addresses the following issues:(i) activity-dependent trafficking of neurotrophin receptors, and its role in synapse-specific modulation; (ii) signal transduction mechanisms medialing the acute enhancement of synaplic transmission by neurotrophins; (iii) acute and long-tenn synaptie actions of the GDNF family; (iv) role of BDNF in late-phase LTP and in the development of hippocampal circuit.

  11. TPM analyses reveal that FtsK contributes both to the assembly and the activation of the XerCD-dif recombination synapse.

    Science.gov (United States)

    Diagne, Cheikh Tidiane; Salhi, Maya; Crozat, Estelle; Salomé, Laurence; Cornet, Francois; Rousseau, Philippe; Tardin, Catherine

    2014-02-01

    Circular chromosomes can form dimers during replication and failure to resolve those into monomers prevents chromosome segregation, which leads to cell death. Dimer resolution is catalysed by a highly conserved site-specific recombination system, called XerCD-dif in Escherichia coli. Recombination is activated by the DNA translocase FtsK, which is associated with the division septum, and is thought to contribute to the assembly of the XerCD-dif synapse. In our study, direct observation of the assembly of the XerCD-dif synapse, which had previously eluded other methods, was made possible by the use of Tethered Particle Motion, a single molecule approach. We show that XerC, XerD and two dif sites suffice for the assembly of XerCD-dif synapses in absence of FtsK, but lead to inactive XerCD-dif synapses. We also show that the presence of the γ domain of FtsK increases the rate of synapse formation and convert them into active synapses where recombination occurs. Our results represent the first direct observation of the formation of the XerCD-dif recombination synapse and its activation by FtsK.

  12. Formation mechanism of carbonate cemented zones adjacent to the top overpressured surface in the central Junggar Basin,NW China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Carbonate cemented zones are normally adjacent to the top overpressured surface in the central Junggar Basin,NW China.Stable carbon and oxygen isotopic compositions and petrological investigations of carbonate cements in the carbonate cemented zones indicate that:(1) carbonate cements are composed dominantly of ferrocalcite,ferroan dolomite,and ankerite;(2) carbonate cements are formed under a high temperature circumstance in the subsurface,and organic fluid migration has an important effect on the formation of them;and(3) carbon and oxygen ions in the carbonate cements migrate from the underlying overpressured system.This suggests that the occurrence of carbonate cemented zones in this region results from multiple phases of organic fluid expulsion out of the overpressure compartment through geological time.This study provides a plausible mechanism of the formation of carbonate cemented zones adjacent to the top overpressured surface in the clastic sedimentary basins,and has an important implication for understanding the internal correlation between the formation of carbonate cemented zones adjacent to top overpressured surface and geofluids expulsion out of overpressured system.

  13. Presynaptic nanodomains: a tale of two synapses

    Directory of Open Access Journals (Sweden)

    Lu-Yang eWANG

    2015-01-01

    Full Text Available Here we summarize the evidence from two giant presynaptic terminals - the squid giant synapse and the mammalian calyx of Held - supporting the involvement of nanodomain calcium signals in triggering of neurotransmitter release. At the squid synapse, there are three main lines of experimental evidence for nanodomain signaling. First, changing the size of the unitary calcium channel current by altering external calcium concentration causes a non-linear change in transmitter release, while changing the number of open channels by broadening the presynaptic action potential causes a linear change in release. Second, low-affinity calcium indicators, calcium chelators, and uncaging of calcium all suggest that presynaptic calcium concentrations are as high as hundreds of micromolar, which is more compatible with a nanodomain type of calcium signal. Finally, neurotransmitter release is much less affected by the slow calcium chelator, EGTA, in comparison to the rapid chelator BAPTA. Similarly, as the calyx of Held synapse matures, EGTA becomes less effective in attenuating transmitter release while the number of calcium channels required to trigger a single fusion event declines. This suggests a developmental transformation of microdomain to nanodomain coupling between calcium channels and transmitter release. Calcium imaging and uncaging experiments, in combination with simulations of calcium diffusion, indicate the peak calcium concentration seen by presynaptic calcium sensors reaches at least tens of micromolar. Taken together, data from these provide a compelling argument that nanodomain calcium signaling gates very rapid transmitter release.

  14. Star formation in the central 0.5 pc of the Milky Way

    CERN Document Server

    Paumard, Thibaut

    2008-01-01

    The supermassive black hole candidate at the Galactic Center is surrounded by a parsec-scale star cluster, which contains a number of early type stars. The presence of such stars has been called a "paradox of youth" as star formation in the immediate vicinity of a supermassive black hole seemed difficult, as well as the transport of stars from far out in a massive-star lifetime. I will recall 30 years of technological developments which led to the current understanding of the nuclear cluster stellar population. The number of early type stars known at present is sufficient to access the 3D structure of this population and its dynamics, which in turn allows discriminating between the various possible origins proposed along the years.

  15. Volcanic succession of the Borovnik Member (Mohorje Formation, Bloke Plateau area, Central Slovenia

    Directory of Open Access Journals (Sweden)

    Stevo Dozet

    2009-06-01

    Full Text Available A 75 m thick volcanic succession of the Borovnik Member, Mohorje Formation in the Bloke Plateau area consistsof dacitic and rhyolitic rocks deposited in a shallow-marine environment. Volcanic activity begun with lavaflows that underwent extensive disintegration, autobrecciation and mixing with the underlying unconsolidated fine-grained clastic sediments producing dacite/rhyolite-siltstone peperites. Peperites are very rich in fractured plagioclase phenocrysts, and owing to the incorporation of clastic material, they are commonly depleted in silica.The overlying fining-upward pyroclastic sequence is monotonous. Basal parts mainly consist of coarse-grained vitric tuffs that may contain some smaller pumice lapilli. The overlying volcaniclastics are fine-grained vitric tuffs,and in the uppermost parts of the sequence, they are interbedded with cherts.The study confirms the existence of primary volcaniclastic succession in the Bloke Plateau area and excludes its epiclastic or reworked origin.

  16. Eluvial gold placer formation on actively rising mountain ranges, Central Otago, New Zealand

    Science.gov (United States)

    Craw, D.; Youngson, J. H.

    1993-05-01

    Eluvial gold deposits in Central Otago, New Zealand, have formed and are still forming on the flanks of actively rising antiformal mountain ranges. These gold deposits are derived mainly by erosion and concentration of fine-grained ( soil and sequences (up to 60 m thick) of poorly sorted immature schist gravels. The gravel sequences consist mainly of matrix-supported mass flow deposits and channellised proximal fan deposits, intercalated on a 1-10 m scale. Gold is concentrated in coarse lag gravels (up to 40 cm clasts) at channel bases. Topographic slopes on the rising ranges show an evolutionary trend in space and time, from gentle weakly dissected surfaces, through slightly degraded but convex slopes, to deeply incised convex streams. Eluvial gold occurs sporadically on the gentle slopes, but the most efficient concentration processes occurred where steeper convex slopes yielded an apron of fan sediments. Gold concentration at these sites resulted from selective and localized removal ("winnowing") of most schist debris, leaving coarse lag gravels and gold. The combination of authigenic grain size increase and residual concentration ensures that the eluvial deposits retain coarse-grained gold, and that only fine-grained gold is released to the alluvial systems downstream.

  17. Carbonate platform facies development of the Turonian Wata Formation in central and eastern Sinai, Egypt

    Science.gov (United States)

    Khalifa, M. A.; Farouk, S.; Hassan, A. M.

    2016-12-01

    The Wata carbonate platform in central and eastern Sinai show a clear pattern of evolutionary development during sedimentation. Three facies are recognized in the carbonate platform. Inner-platform in the south, inter-platform basin in the middle, and outer-platform in the northwest. Such classification was probably performed by the effect of Syrian Arc System that culminated during Turonian in Sinai. Inner-platform includes fining-upward cycles, each begins with packstone, followed by wackestone and capped by lime-mudstone or claystone or molluscan bioclastic wackestone at the base capped by sandy oolitic packstone or dolostone. The dominant faunal associations are molluscs, and echinoids. Inter-platform basin occurs north of inner-platform and extends northwest-southeast direction and comprises fining-upward cycles, each of which begins with bioclastic ostracodal packstone, calcisphere packstone, bioclastic packstone, capped by wackestone and lime-mudstone The faunal association includes, sponge spines, ostracodes, molluscan debris and calcispheres. They were deposited in shoal marine and barrier. The outer-platform occurs at Gebel Giddi and extended northwestwards. The lithofacies are entirely represented by calcisphere wackestone/packstone, with a reduced thickness of 20 m.

  18. Micro bubble formation and bubble dissolution in domestic wet central heating systems

    Directory of Open Access Journals (Sweden)

    Ge Yunting

    2012-04-01

    Full Text Available 16 % of the carbon dioxide emissions in the UK are known to originate from wet domestic central heating systems. Contemporary systems make use of very efficient boilers known as condensing boilers that could result in efficiencies in the 90-100% range. However, research and development into the phenomenon of micro bubbles in such systems has been practically non-existent. In fact, such systems normally incorporate a passive deaerator that is installed as a ‘default’ feature with no real knowledge as to the micro bubble characteristics and their effect on such systems. High saturation ratios are known to occur due to the widespread use of untreated tap water in such systems and due to the inevitable leakage of air into the closed loop circulation system during the daily thermal cycling. The high temperatures at the boiler wall result in super saturation conditions which consequently lead to micro bubble nucleation and detachment, leading to bubbly two phase flow. Experiments have been done on a test rig incorporating a typical 19 kW domestic gas fired boiler to determine the expected saturation ratios and bubble production and dissolution rates in such systems.

  19. Micro bubble formation and bubble dissolution in domestic wet central heating systems

    Science.gov (United States)

    Fsadni, Andrew M.; Ge, Yunting

    2012-04-01

    16 % of the carbon dioxide emissions in the UK are known to originate from wet domestic central heating systems. Contemporary systems make use of very efficient boilers known as condensing boilers that could result in efficiencies in the 90-100% range. However, research and development into the phenomenon of micro bubbles in such systems has been practically non-existent. In fact, such systems normally incorporate a passive deaerator that is installed as a `default' feature with no real knowledge as to the micro bubble characteristics and their effect on such systems. High saturation ratios are known to occur due to the widespread use of untreated tap water in such systems and due to the inevitable leakage of air into the closed loop circulation system during the daily thermal cycling. The high temperatures at the boiler wall result in super saturation conditions which consequently lead to micro bubble nucleation and detachment, leading to bubbly two phase flow. Experiments have been done on a test rig incorporating a typical 19 kW domestic gas fired boiler to determine the expected saturation ratios and bubble production and dissolution rates in such systems.

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

    Directory of Open Access Journals (Sweden)

    Christine Laura Dixon

    2015-12-01

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

  1. NeuroD2 regulates the development of hippocampal mossy fiber synapses

    Directory of Open Access Journals (Sweden)

    Wilke Scott A

    2012-02-01

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

  2. Stratigraphic and geochemical evolution of an oceanic arc upper crustal section: The Jurassic Talkeetna Volcanic Formation, south-central Alaska

    Science.gov (United States)

    Clift, P.D.; Draut, A.E.; Kelemen, P.B.; Blusztajn, J.; Greene, A.

    2005-01-01

    The Early Jurassic Talkeetna Volcanic Formation forms the upper stratigraphic level of an oceanic volcanic arc complex within the Peninsular Terrane of south-central Alaska. The section comprises a series of lavas, tuffs, and volcaniclastic debris-How and flow turbidite deposits, showing significant lateral facies variability. There is a general trend toward more volcaniclastic sediment at the top of the section and more lavas and tuff breccias toward the base. Evidence for dominant submarine, mostly mid-bathyal or deeper (>500 m) emplacement is seen throughout the section, which totals ???7 km in thickness, similar to modern western Pacific arcs, and far more than any other known exposed section. Subaerial sedimentation was rare but occurred over short intervals in the middle of the section. The Talkeetna Volcanic Formation is dominantly calc-alkatine and shows no clear trend to increasing SiO2 up-section. An oceanic subduction petrogenesis is shown by trace element and Nd isotope data. Rocks at the base of the section show no relative enrichment of light rare earth elements (LREEs) versus heavy rare earth elements (REES) or in melt-incompatible versus compatible high field strength elements (HFSEs). Relative enrichment of LREEs and HFSEs increases slightly up-section. The Talkeetna Volcanic Formation is typically more REE depleted than average continental crust, although small volumes of light REE-enriched and heavy REE-depleted mafic lavas are recognized low in the stratigraphy. The Talkeetna Volcanic Formation was formed in an intraoceanic arc above a north-dipping subduction zone and contains no preserved record of its subsequent collisions with Wrangellia or North America. ?? 2005 Geological Society of America.

  3. Detection of central circuits implicated in the formation of novel pain memories

    Directory of Open Access Journals (Sweden)

    Upadhyay J

    2016-09-01

    Full Text Available Jaymin Upadhyay,1 Julia Granitzka,1 Thomas Bauermann,2 Ulf Baumgärtner,3 Markus Breimhorst,1 Rolf-Detlef Treede,3 Frank Birklein1 1Department of Neurology, 2Department of Neuroradiology, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, 3Department of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim (CBTM, Heidelberg University, Mannheim, Germany Abstract: Being able to remember physically and emotionally painful events in one’s own past may shape behavior, and can create an aversion to a variety of situations. Pain imagination is a related process that may include recall of past experiences, in addition to production of sensory and emotional percepts without external stimuli. This study aimed to understand 1 the central nervous system processes that underlie pain imagination, 2 the retrieval of pain memories, and 3 to compare the latter with visual object memory. These goals were achieved by longitudinally investigating brain function with functional magnetic resonance imaging in a unique group of healthy volunteers who had never experienced tooth pain. In these subjects, we compared brain responses elicited during three experimental conditions in the following order: imagination of tooth pain (pain imagination, remembering one’s own house (object memory, and remembrance of tooth pain following an episode of induced acute tooth pain (pain memory. Key observations stemming from group-level conjunction analyses revealed common activation in the posterior parietal cortex for both pain imagination and pain memory, while object and pain memory each had strong activation predominantly within the middle frontal gyrus. When contrasting pain imagination and memory, significant activation differences were observed in subcortical structures (ie, parahippocampus – pain imagination > pain memory; midbrain – pain memory > pain imagination. Importantly, these findings were observed in the presence of

  4. Detection of central circuits implicated in the formation of novel pain memories

    Science.gov (United States)

    Upadhyay, Jaymin; Granitzka, Julia; Bauermann, Thomas; Baumgärtner, Ulf; Breimhorst, Markus; Treede, Rolf-Detlef; Birklein, Frank

    2016-01-01

    Being able to remember physically and emotionally painful events in one’s own past may shape behavior, and can create an aversion to a variety of situations. Pain imagination is a related process that may include recall of past experiences, in addition to production of sensory and emotional percepts without external stimuli. This study aimed to understand 1) the central nervous system processes that underlie pain imagination, 2) the retrieval of pain memories, and 3) to compare the latter with visual object memory. These goals were achieved by longitudinally investigating brain function with functional magnetic resonance imaging in a unique group of healthy volunteers who had never experienced tooth pain. In these subjects, we compared brain responses elicited during three experimental conditions in the following order: imagination of tooth pain (pain imagination), remembering one’s own house (object memory), and remembrance of tooth pain following an episode of induced acute tooth pain (pain memory). Key observations stemming from group-level conjunction analyses revealed common activation in the posterior parietal cortex for both pain imagination and pain memory, while object and pain memory each had strong activation predominantly within the middle frontal gyrus. When contrasting pain imagination and memory, significant activation differences were observed in subcortical structures (ie, parahippocampus − pain imagination > pain memory; midbrain − pain memory > pain imagination). Importantly, these findings were observed in the presence of consistent and reproducible psychophysical and behavioral measures that informed on the subjects’ ability to imagine novel and familiar thoughts, as well as the subjects’ pain perception.

  5. The main principles of formation of structure of cultural-historical landscapes of Central Russia.

    Science.gov (United States)

    Nizovtsev, Vyacheslav; Natalia, Erman

    2014-05-01

    The forming and development of cultural-historical landscapes (CH) are obligate result of evolution of society and nature, as well as, man and landscapes during their coherent growth. CH landscapes are holistic historic-cultural and nature creations. They reflect the history of land use and spiritual development of ethnic community of concrete territory with determine homogeneous landscape characteristics. The majority of them appertain to the category of relict landscapes, which completed their evolution growth. That means that these are anthropogenic (AL) and cultural (CL) landscapes. They lost anthropogenic management and continue their growth obeying natural logic. These landscapes include elements of morphological structure and natural components, which have been transformed by men, and also artefacts, sociofacts and mental facts. These facts can be considered as peculiar "biographical chronicle" of activity of population in determinate landscape conditions in determinate historical period. These facts are evidences of material and spiritual cultural of society. The first AL begin to arise simultaneously with conversation of appropriating economy into generating economy. There was such conversation in Central Russia (Neolithic revolution) only in Bronze Age. Anthropogenic transformed landscape complexes and even man-made landscape complexes have been formed in Bronze Age. Some of these complexes exist now. Actual anthropogenic and cultural landscapes began to form only in Iron Age while permanent, long existed settlement and agriculture structure has organized. First, These are small settlement anthropogenic landscape complexes (selischa and gorodischa) with applied permanent miniature arable areas. These complexes located on the capes and on the areas between river banks and banks of streams. Second, these are pasture anthropogenic landscape complexes (on the level of podurochische and urochische), located in flood plain and valley-cavin position (pasture

  6. Facies development and paleoenvironment of the Hajajah Limestone Member, Aruma Formation, central Saudi Arabia

    Science.gov (United States)

    El-Sorogy, Abdelbaset S.; Ismail, Abdelmoneim; Youssef, Mohamed; Nour, Hamdy

    2016-12-01

    The Campanian Hajajah Limestone Member of the Aruma Formation was formed during two regressive episodes. Each of them formed of three depositional facies, from base to top: 1) intra-shelf basin facies, made up of fossiliferous green shale and mudstone with ostracods and badly preserved foraminifers. 2) fore-reef facies, consists of hard, massive, marly coralline limestone. The upper part is rich with low divers, badly to moderate preserved, solitary and colonial corals, and, 3) back reef and near-shore facies, consists of fossiliferous sandy dolomitized, bioturbated limestone with abundant reworked corals, bivalves, gastropods, and aggregate grains. On the basis of field observations, micro-and macrofossils and microfacies analysis, the Hajajah Limestone Member was deposited in distal marine settings below storm wave base in a low-energy environment changed upward to fore-reef framework in an open marine environment with moderate to high energy conditions and terminated with shallow marine facies with accumulation of skeletal grains by storms during regression.

  7. High Resolution Surveys of the Water and Methanol Star Formation Masers in the Central Molecular Zone

    Science.gov (United States)

    Rickert, Matthew; Yusef-Zadeh, Farhad; Ott, Juergen; Meier, David S.; Krieger, Nico; SWAG

    2017-01-01

    We present some of the first high resolution fully interferometric surveys of 6.7 GHz methanol and 22 GHz water masers towards the Central Molecular Zone (CMZ). These masers are good signposts for early (methanol masers with resolutions of 0.9” (0.04 pc) and 0.4 km/s (8 kHz) and an average channel sensitivity of ~0.01 Jy/beam. With this high resolution and sensitivity, we have detected ~100 methanol masers, which is over a factor of two more than has previously been detected. We have also conducted two surveys of water masers in this region. As part of the Survey of Water and Ammonia in the Galactic Center (SWAG), the Australia Telescope Compact Array (ATCA) was used to survey a variety of molecular lines, including the 22 GHz water line. With the ATCA, we have detected over 200 water masers using resolutions of 26” (1 pc) and 2 km/s (60 kHz) and an average channel sensitivity of ~0.01 Jy/beam. Afterward, we conducted the first on-the-fly (OTF) VLA survey of water masers with improved resolutions of 0.7” (0.03 pc) and 0.4 km/s (26 kHz) and an average channel sensitivity of ~0.05 Jy/beam. Although the analysis of this OTF survey is not yet complete, we have already identified water masers that were not visible in the SWAG data.The improvement in the number of detected masers allows us to better analyze the distribution of these masers. We show that the SWAG water masers appear uniformly distributed along the Galactic plane, despite the asymmetry of the molecular gas distribution, where ~2/3 of the gas mass is located at positive Galactic longitudes. The methanol masers follow the molecular gas distribution, with a majority of the masers being found at positive longitudes. This could indicate a difference in the star forming history of these two parts of the CMZ and/or that the 22 GHz water masers are contaminated by water masers produced from evolved stars as well as star forming regions, indicating that a larger percentage of 22 GHz water masers are produced

  8. Field Demonstration of Carbon Dioxide Miscible Flooding in the Lansing-Kansas City Formation, Central Kansas

    Energy Technology Data Exchange (ETDEWEB)

    Alan Byrnes; G. Paul Willhite; Don Green; Richard Pancake; JyunSyung Tsau; W. Lynn Watney; John Doveton; Willard Guy; Rodney Reynolds; Dave Murfin; James Daniels; Russell Martin; William Flanders; Dave Vander Griend; Eric Mork; Paul Cantrell

    2010-03-07

    A pilot carbon dioxide miscible flood was initiated in the Lansing Kansas City C formation in the Hall Gurney Field, Russell County, Kansas. The reservoir zone is an oomoldic carbonate located at a depth of about 2900 feet. The pilot consists of one carbon dioxide injection well and three production wells. Continuous carbon dioxide injection began on December 2, 2003. By the end of June 2005, 16.19 MM lb of carbon dioxide was injected into the pilot area. Injection was converted to water on June 21, 2005 to reduce operating costs to a breakeven level with the expectation that sufficient carbon dioxide was injected to displace the oil bank to the production wells by water injection. By March 7,2010, 8,736 bbl of oil were produced from the pilot. Production from wells to the northwest of the pilot region indicates that oil displaced from carbon dioxide injection was produced from Colliver A7, Colliver A3, Colliver A14 and Graham A4 located on adjacent leases. About 19,166 bbl of incremental oil were estimated to have been produced from these wells as of March 7, 2010. There is evidence of a directional permeability trend toward the NW through the pilot region. The majority of the injected carbon dioxide remains in the pilot region, which has been maintained at a pressure at or above the minimum miscibility pressure. Estimated oil recovery attributed to the CO2 flood is 27,902 bbl which is equivalent to a gross CO2 utilization of 4.8 MCF/bbl. The pilot project is not economic.

  9. The central region of M83: Massive star formation, kinematics, and the location and origin of the nucleus

    CERN Document Server

    Knapen, J H; Ryder, S D; Falcon-Barroso, J; Fathi, K; Gutierrez, L

    2010-01-01

    We report new near-IR integral field spectroscopy of the central starburst region of the barred spiral galaxy M83 obtained with CIRPASS on Gemini-S, which we analyse in conjunction with GHaFaS Fabry-Perot data, an AAT IRIS2 Ks-band image, and near- and mid-IR imaging from the Hubble and Spitzer space telescopes. The bulk of the current star formation activity is hidden from optical view by dust extinction, but is seen in the near- and mid-IR to the north of the nucleus. This region is being fed by inflow of gas through the bar of M83, traced by the prominent dust lane entering into the circumnuclear region from the north. An analysis of stellar ages confirms that the youngest stars are indeed in the northwest. A gradual age gradient, with older stars further to the south, characterises the well-known star-forming arc in the central region of M83. Detailed analyses of the Pa beta ionised gas kinematics and near-IR imaging confirm that the kinematic centre coincides with the photometric centre of M83, and that ...

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

    Science.gov (United States)

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

    2016-08-01

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

  11. Bidirectional Hebbian Plasticity at Hippocampal Mossy Fiber Synapses on CA3 Interneurons

    OpenAIRE

    Galván, Emilio J; Calixto, Eduardo; Barrionuevo, Germán

    2008-01-01

    Hippocampal area CA3 is critically involved in the formation of non-overlapping neuronal subpopulations (“pattern separation”) to store memory representations as distinct events. Efficient pattern separation relies on the strong and sparse excitatory input from the mossy fibers (MF) to pyramidal cells and feed-forward inhibitory interneurons. However, MF synapses on CA3 pyramidal cells undergo LTP, which, if unopposed, will degrade pattern separation as MF activation will now recruit addition...

  12. A Chandra X-ray Analysis of Abell 1664: Cooling, Feedback and Star Formation in the Central Cluster Galaxy

    CERN Document Server

    Kirkpatrick, C C; Rafferty, D A; Nulsen, P E J; Birzan, L; Kazemzadeh, F; Wise, M W; Gitti, M; Cavagnolo, K W

    2009-01-01

    The brightest cluster galaxy (BCG) in the Abell 1664 cluster is unusually blue and is forming stars at a rate of ~ 23 M_{\\sun} yr^{-1}. The BCG is located within 5 kpc of the X-ray peak, where the cooling time of 3.5x10^8 yr and entropy of 10.4 keV cm^2 are consistent with other star-forming BCGs in cooling flow clusters. The center of A1664 has an elongated, "bar-like" X-ray structure whose mass is comparable to the mass of molecular hydrogen, ~ 10^{10} M_{\\sun} in the BCG. We show that this gas is unlikely to have been stripped from interloping galaxies. The cooling rate in this region is roughly consistent with the star formation rate, suggesting that the hot gas is condensing onto the BCG. We use the scaling relations of Birzan et al. 2008 to show that the AGN is underpowered compared to the central X-ray cooling luminosity by roughly a factor of three. We suggest that A1664 is experiencing rapid cooling and star formation during a low-state of an AGN feedback cycle that regulates the rates of cooling and...

  13. Extrinsic sound stimulations and development of periphery auditory synapses

    Institute of Scientific and Technical Information of China (English)

    Kun Hou; Shiming Yang; Ke Liu

    2015-01-01

    The development of auditory synapses is a key process for the maturation of hearing function. However, it is still on debate regarding whether the development of auditory synapses is dominated by acquired sound stimulations. In this review, we summarize relevant publications in recent decades to address this issue. Most reported data suggest that extrinsic sound stimulations do affect, but not govern the development of periphery auditory synapses. Overall, periphery auditory synapses develop and mature according to its intrinsic mechanism to build up the synaptic connections between sensory neurons and/or interneurons.

  14. Analog VLSI Circuits for Short-Term Dynamic Synapses

    Directory of Open Access Journals (Sweden)

    Shih-Chii Liu

    2003-06-01

    Full Text Available Short-term dynamical synapses increase the computational power of neuronal networks. These synapses act as additional filters to the inputs of a neuron before the subsequent integration of these signals at its cell body. In this work, we describe a model of depressing and facilitating synapses derived from a hardware circuit implementation. This model is equivalent to theoretical models of short-term synaptic dynamics in network simulations. These circuits have been added to a network of leaky integrate-and-fire neurons. A cortical model of direction-selectivity that uses short-term dynamic synapses has been implemented with this network.

  15. The Drosophila larval neuromuscular junction as a model for scaffold complexes at glutamatergic synapses: benefits and limitations.

    Science.gov (United States)

    Thomas, Ulrich; Kobler, Oliver; Gundelfinger, Eckart D

    2010-09-01

    Based on unbeatable genetic accessibility and relative simplicity, the Drosophila larval neuromuscular junction has become a widely used model system for studying functional and structural aspects of excitatory glutamatergic synapses. Membrane-associated guanylate kinase-like proteins (MAGUKs) are first-order scaffolding molecules enriched at many cellular junctions, including synapses, where they coordinate multiple binding partners, including cell adhesion molecules and ion channels. The enrichment of the prototypic MAGUK Discs-Large at larval NMJs apparently parallels the high abundance of its homologs at excitatory synapses in the mammalian central nervous system. Here, the authors review selected aspects of the long-standing work on Dlg at fly neuromuscular junctions, thereby scrutinizing its subcellular localization, function, and regulation with regard to corresponding aspects of MAGUKs in vertebrate neurons.

  16. Timing of cut-and-fill sequences in the John Day Formation (Eocene-Oligocene), Painted Hills area, central Oregon

    Energy Technology Data Exchange (ETDEWEB)

    Bestland, E.A.; Retallack, G.J. (Univ. of Oregon, Eugene, OR (United States). Dept. of Geological Sciences); Swisher, C.C. III (Inst. of Human Origins, Berkeley, CA (United States)); Fremd, T.J. (John Day Fossil Beds National Monument, John Day, OR (United States))

    1993-04-01

    Large-scale cut-and-fill features in the Eocene-Oligocene part of the John Day Formation in the Pained Hills area of central Oregon can be interpreted as terrestrial depositional sequences, mapped as lithostratigraphic units, and correlated to North American Land Mammal Ages (NALMA). New laser-fusion 40Ar/39Ar single-crystal ages from the John Day Formation provide evidence for the timing of these sequences and a revised placement of the Eocene-Oligocene boundary. The sequences are bound by erosional surfaces that have relief of up to 60 m, are marked in places by claystone breccias full of reworked soil clasts, and separate otherwise conformable strata. The lowermost depositional sequence in the John Day Formation contains very well developed, Fe- and Al-rich paleosols, laterite horizons, and the welded tuff of member A (39.7 my), and probably correlates to the Duchesean and Chadronian NALMA. These brick-rid claystones are sharply truncated by prominent detrital laterite horizon. Overlying this basal sequence is a second sequence of much less well developed paleosols, abundant tuffs and lacustrine tuffaceous claystones. This sequence contains a distinctive biotite tuff (33 my) and the type locality of the Bridge Creek fossil flora and probably correlates to the Orellan NALMA. Above this biotite tuff are alternating red, dark gray, and tan paleosols and a prominent crystal vitric tuff (32.7 my). The Eocene-Oligocene boundary lies between these two sequences, associated with the laterite horizon that truncates the basal red beds. A major truncation surface cuts this sequence and is overlain by a third sequence of thin red paleosols which probably correlates with the Whitneyan NALMA. Above this is a fourth sequence (Arikareean NALMA) consisting of greenish-tan paleosols, a crystal vitric tuff near its base (29.8 my) and the Picture Gorge Ignimbrite (28.7 my).

  17. The redox-sensing regulator Rex modulates central carbon metabolism, stress tolerance response and biofilm formation by Streptococcus mutans.

    Directory of Open Access Journals (Sweden)

    Jacob P Bitoun

    Full Text Available The Rex repressor has been implicated in regulation of central carbon and energy metabolism in gram-positive bacteria. We have previously shown that Streptococcus mutans, the primary causative agent of dental caries, alters its transcriptome upon Rex-deficiency and renders S. mutans to have increased susceptibility to oxidative stress, aberrations in glucan production, and poor biofilm formation. In this study, we showed that rex in S. mutans is co-transcribed as an operon with downstream guaA, encoding a putative glutamine amidotransferase. Electrophoretic mobility shift assays showed that recombinant Rex bound promoters of target genes avidly and specifically, including those down-regulated in response to Rex-deficiency, and that the ability of recombinant Rex to bind to selected promoters was modulated by NADH and NAD(+. Results suggest that Rex in S. mutans can function as an activator in response to intracellular NADH/NAD(+ level, although the exact binding site for activator Rex remains unclear. Consistent with a role in oxidative stress tolerance, hydrogen peroxide challenge assays showed that the Rex-deficient mutant, TW239, and the Rex/GuaA double mutant, JB314, were more susceptible to hydrogen peroxide killing than the wildtype, UA159. Relative to UA159, JB314 displayed major defects in biofilm formation, with a decrease of more than 50-fold in biomass after 48-hours. Collectively, these results further suggest that Rex in S. mutans regulates fermentation pathways, oxidative stress tolerance, and biofilm formation in response to intracellular NADH/NAD(+ level. Current effort is being directed to further investigation of the role of GuaA in S. mutans cellular physiology.

  18. Presynaptic nanodomains: a tale of two synapses.

    Science.gov (United States)

    Wang, Lu-Yang; Augustine, George J

    2014-01-01

    Here we summarize the evidence from two "giant" presynaptic terminals-the squid giant synapse and the mammalian calyx of Held-supporting the involvement of nanodomain calcium signals in triggering of neurotransmitter release. At the squid synapse, there are three main lines of experimental evidence for nanodomain signaling. First, changing the size of the unitary calcium channel current by altering external calcium concentration causes a non-linear change in transmitter release, while changing the number of open channels by broadening the presynaptic action potential causes a linear change in release. Second, low-affinity calcium indicators, calcium chelators, and uncaging of calcium all suggest that presynaptic calcium concentrations are as high as hundreds of micromolar, which is more compatible with a nanodomain type of calcium signal. Finally, neurotransmitter release is much less affected by the slow calcium chelator, ethylene glycol tetraacetic acid (EGTA), in comparison to the rapid chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Similarly, as the calyx of Held synapse matures, EGTA becomes less effective in attenuating transmitter release while the number of calcium channels required to trigger a single fusion event declines. This suggests a developmental transformation of microdomain to nanodomain coupling between calcium channels and transmitter release. Calcium imaging and uncaging experiments, in combination with simulations of calcium diffusion, indicate the peak calcium concentration seen by presynaptic calcium sensors reaches at least tens of micromolar at the calyx of Held. Taken together, data from these provide a compelling argument that nanodomain calcium signaling gates very rapid transmitter release.

  19. Synapsin II desynchronizes neurotransmitter release at inhibitory synapses by interacting with presynaptic calcium channels.

    Science.gov (United States)

    Medrihan, Lucian; Cesca, Fabrizia; Raimondi, Andrea; Lignani, Gabriele; Baldelli, Pietro; Benfenati, Fabio

    2013-01-01

    In the central nervous system, most synapses show a fast mode of neurotransmitter release known as synchronous release followed by a phase of asynchronous release, which extends over tens of milliseconds to seconds. Synapsin II (SYN2) is a member of the multigene synapsin family (SYN1/2/3) of synaptic vesicle phosphoproteins that modulate synaptic transmission and plasticity, and are mutated in epileptic patients. Here we report that inhibitory synapses of the dentate gyrus of Syn II knockout mice display an upregulation of synchronous neurotransmitter release and a concomitant loss of delayed asynchronous release. Syn II promotes γ-aminobutyric acid asynchronous release in a Ca(2+)-dependent manner by a functional interaction with presynaptic Ca(2+) channels, revealing a new role in synaptic transmission for synapsins.

  20. Stratigraphy, age, and depositional setting of the Miocene Barstow Formation at Harvard Hill, central Mojave Desert, California

    Science.gov (United States)

    Leslie, Shannon R.; Miller, David M.; Wooden, Joseph L.; Vazquez, Jorge A.

    2010-01-01

    New detailed geologic mapping and geochronology of the Barstow Formation at Harvard Hill, 30 km east of Barstow, CA, help to constrain Miocene paleogeography and tectonics of the central Mojave Desert. A northern strand of the Quaternary ENE-striking, sinistral Manix fault divides the Barstow Formation at Harvard Hill into two distinct lithologic assemblages. Strata north of the fault consist of: a green rhyolitic tuff, informally named the Shamrock tuff; lacustrine sandstone; partially silicified thin-bedded to massive limestone; and alluvial sandstone to pebble conglomerate. Strata south of the fault consist of: lacustrine siltstone and sandstone; a rhyolitic tuff dated at 19.1 Ma (U-Pb); rock-avalanche breccia deposits; partially silicified well-bedded to massive limestone; and alluvial sandstone and conglomerate. Our U-Pb zircon dating of the Shamrock tuff by SHRIMP-RG yields a peak probability age of 18.7 ± 0.1 Ma. Distinctive outcrop characteristics, mineralogy, remanent magnetization, and zircon geochemistry (Th/U) suggest that the Shamrock tuff represents a lacustrine facies of the regionally extensive Peach Spring Tuff (PST). Here we compare zircon age and geochemical analyses from the Shamrock tuff with those of the PST at Stoddard Wash and provide new insight into the age of zircon crystallization in the PST rhyolite. Results of our field studies show that Miocene strata at Harvard Hill mostly accumulated in a lacustrine environment, although depositional environments varied from a relatively deep lake to a very shallow lake or even onshore setting. Rock-avalanche breccias and alluvial deposits near the base of the exposed section indicate proximity to a steep basin margin and detrital studies suggest a southern source for coarse-grained deposits; therefore, we may infer a southern basin-margin setting at Harvard Hill during the early Miocene. Our geochronology demonstrates that deposition of the Barstow Formation at Harvard Hill extended from before

  1. IL-4 induces the formation of multinucleated giant cells and expression of β5 integrin in central giant cell lesion

    Science.gov (United States)

    Aghbali, Amirala; Rafieyan, Sona; Mohamed-Khosroshahi, Leila; Baradaran, Behzad; Shanehbandi, Dariush

    2017-01-01

    Background It is now well established that IL-4 has a central role in the development of monocytes to multinucleated giant cells (MGCs) by inducing the expression of integrins on the surface of monocytes. The aim of this study was to investigate the potential role of IL-4 in induction of β5 integrin expression in the peripheral blood samples of patients with giant cell granuloma. Material and Methods Monocytes were isolated from peripheral blood samples of patients with central giant cell granuloma (CGCG) and healthy controls using human Monocyte Isolation Kit II. Isolated monocytes were then cultured in the absence or presence of IL-4 (10 and 20 ng/mL), and following RNA extraction and cDNA synthesis, Real-time PCR was performed to determine the level of β5 integrin expression. The formation of CGCGs and morphological analyses were done under light microscopy. For confirmation of CGCGs, immunocytochemistry technique was also carried out by anti-RANK (receptor-activator of NF-κB ligand) antibody. Results In both patient and control groups, β5 levels were significantly enhanced by increasing the IL-4 dose from 10 to 20 ng/mL. In addition, these differences were significant between patient and control groups without IL-4 treatment. On the other hand, the number of cells which expressed RANK and therefore the number of giant cells were significantly higher in the patient group in comparison to controls, as assessed by immunohistochemistry evaluations. Conclusions In this study, we showed an elevation in the expression levels of β5 integrin when stimulated by IL-4. It is strongly indicated that this integrin acts as an important mediator during macrophage to macrophage fusion and development of giant cells. Key words:β5 integrin, giant cell, Il-4, monocyte, rank. PMID:27918730

  2. New (but old) molecules regulating synapse integrity and plasticity: Cbln1 and the delta2 glutamate receptor.

    Science.gov (United States)

    Yuzaki, M

    2009-09-01

    The delta2 glutamate receptor (GluRdelta2) is predominantly expressed in cerebellar Purkinje cells and plays crucial roles in cerebellar functions: GluRdelta2-null mice display ataxia and impaired motor learning. Interestingly, the contact state of synapses between parallel fibers (PFs) and Purkinje cells is specifically and severely affected, and the number of normal PF synapses is markedly reduced in GluRdelta2-null Purkinje cells. Furthermore, long-term depression at PF-Purkinje cell synapses is abrogated. Cbln1, a member of the C1q/tumor necrosis factor (TNF) superfamily, is predominantly expressed and released from cerebellar granule cells. Unexpectedly, the behavioral, physiological and anatomical phenotypes of cbln1-null mice precisely mimic those of GluRdelta2-null mice. Thus, we propose that Cbln1, which is released from granule cells, and GluRdelta2, which is predominantly expressed in Purkinje cells, are involved in a common signaling pathway crucial for synapse formation/maintenance and plasticity in the cerebellum. Since molecules related to Cbln1 are expressed in various brain regions other than the cerebellum, other C1q/TNF superfamily proteins may also regulate various aspects of synapses in the CNS. Therefore, an understanding of the signaling mechanisms underlying Cbln1 and GluRdelta2 in the cerebellum will provide new insights into the roles of C1q/TNF superfamily proteins as new cytokines that regulate normal and abnormal brain functions.

  3. Modulation and metamodulation of synapses by adenosine.

    Science.gov (United States)

    Ribeiro, J A; Sebastião, A M

    2010-06-01

    The presence of adenosine in all nervous system cells (neurones and glia) together with its intensive release following insults makes adenosine as a sort of 'regulator' of synaptic communication, leading to the homeostatic coordination of brain function. Besides the direct actions of adenosine on the neurosecretory mechanisms, to tune neurotransmitter release, adenosine receptors interact with other receptors as well as with transporters as part of its attempt to fine-tune synaptic transmission. This review will focus on examples of the different ways adenosine can use to modulate or metamodulate synapses, in other words, to trigger or brake the action of some neurotransmitters and neuromodulators, to cross-talk with other G protein-coupled receptors, with ionotropic receptors and with receptor kinases as well as with transporters. Most of these interactions occur through A2A receptors, which in spite of their low density in some brain areas, such as the hippocampus, may function as amplifiers of the signalling of other mediators at synapses.

  4. MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function.

    Science.gov (United States)

    Barbosa, Ana C; Kim, Mi-Sung; Ertunc, Mert; Adachi, Megumi; Nelson, Erika D; McAnally, John; Richardson, James A; Kavalali, Ege T; Monteggia, Lisa M; Bassel-Duby, Rhonda; Olson, Eric N

    2008-07-08

    Learning and memory depend on the activity-dependent structural plasticity of synapses and changes in neuronal gene expression. We show that deletion of the MEF2C transcription factor in the CNS of mice impairs hippocampal-dependent learning and memory. Unexpectedly, these behavioral changes were accompanied by a marked increase in the number of excitatory synapses and potentiation of basal and evoked synaptic transmission. Conversely, neuronal expression of a superactivating form of MEF2C results in a reduction of excitatory postsynaptic sites without affecting learning and memory performance. We conclude that MEF2C limits excessive synapse formation during activity-dependent refinement of synaptic connectivity and thus facilitates hippocampal-dependent learning and memory.

  5. Not committing barbarisms: Sherrington and the synapse, 1897.

    Science.gov (United States)

    Tansey, E M

    1997-01-01

    The word synapse first appeared in 1897, in the seventh edition of Michael Foster's Textbook of Physiology. Foster was assisted in writing the volume on the nervous system by Charles Sherrington, who can be credited with developing and advocating the physiological concept of a synapse. The word itself however, was derived by a Cambridge classicist, Arthur Verrall.

  6. Glutamatergic Signaling at the Vestibular Hair Cell Calyx Synapse

    NARCIS (Netherlands)

    Sadeghi, Soroush G.; Pyott, Sonja J.; Yu, Zhou; Glowatzki, Elisabeth

    2014-01-01

    In the vestibular periphery a unique postsynaptic terminal, the calyx, completely covers the basolateral walls of type I hair cells and receives input from multiple ribbon synapses. To date, the functional role of this specialized synapse remains elusive. There is limited data supporting glutamaterg

  7. The geometry and lithology of the Cima Sandstone Lentil: a paleoseep-bearing interbed in the Moreno Formation, central California

    Science.gov (United States)

    Wheatley, P. V.; Schwartz, H.

    2007-12-01

    The Cima Sandstone Lentil outcrops over a relatively small area on the western side of the San Joaquin Valley in central California. Here this unit can be found in the Panoche Hills in the northern portion of the field area and the Tumey Hills in the southern portion of the field area. The Cima Sandstone resides within the 800m Moreno Formation that spans the Maastrichtian to the Danian. The Moreno Formation comprises four members, which are the Dosados Member, the Tierra Loma Member, the Marca Shale Member, and the Dos Palos Shale Member (of which the Cima Sandstone is an interbed). The Cima Sandstone contains numerous large carbonate mounds, concretions, and pavements, indicating paleoseep activity. The Cima Sandstone has never been studied in detail, but recent interest in sandstone injectites as well as interest in paleoseeps has prompted us to examine this interbed more carefully. The Cima is an immature sandstone composed primarily of quartz along with small amounts of micas and feldspars as well as varying amounts of glauconite. These minerals are generally cemented by carbonate but, occasionally, iron oxide cement is present locally. Much variation exists within the Cima Sandstone Lentil and we seek to characterize and understand this variation. One of the most obvious sources of variability is the thickness of the unit itself. The thickness ranges from near 60m in the northern Panoche Hills to only 9m in the Tumey Hills. Induration also varies noticeably, from well cemented in the north, to unconsolidated in the south. Similarly, the sandstone is grain-supported and houses some depositional structures in the northern outcrops but becomes largely matrix-supported and lacking bedding in the southern outcrops. Preliminary data suggests that proximity to carbonate concretions, fluid conduits, and underlying injectites may have some influence over grain size and sorting.

  8. Volcanostratigraphic Sequences of Kebo-Butak Formation at Bayat Geological Field Complex, Central Java Province and Yogyakarta Special Province, Indonesia

    Directory of Open Access Journals (Sweden)

    Sri Mulyaningsih

    2016-08-01

    Full Text Available Bayat Complex is usually used as a work field for students of geology and other geosciences. The study area is located in the southern part of the Bayat Complex. Administratively, it belongs to Central Java Province and Yogyakarta Special Province. The lithology of Bayat is very complex, composed of various kinds of igneous, sedimentary, metamorphic, and volcanic rocks. Most of previous researchers interpreted Bayat as a melange complex constructed within a subduction zone. Kebo-Butak is one of formations that forms the Bayat field complex. The formation is composed of basalt, layers of pumice, tuff, shale, and carbonaceous tuff. Most of them are known as volcanic rocks. These imply that volcanic activities are more probable to construct the geology of Bayat rather than the subducted melange complex. The geological mapping, supported by geomorphology, petrology, stratigraphy, and geological structures, had been conducted in a comprehensive manner using the deduction-induction method. The research encounters basalt, black pumice, tuff with basaltic glasses fragments, zeolite, argilic clay, as well as feldspathic- and pumice tuff. Petrographically, the basalt is composed of labradorite, olivine, clinopyroxene, and volcanic glass. Black pumice and tuff contain prismatic clinopyroxene, granular olivine, and volcanic glasses. Feldspathic tuff and pumice tuff are crystal vitric tuff due to more abundant feldspar, quartz, and amphibole than volcanic glass. Zeolite comprises chlorite and altered glasses as deep sea altered volcanic rocks. The geologic structure is very complex, the major structures are normal faults with pyrite in it. There were two deep submarine paleovolcanoes namely Tegalrejo and Baturagung. The first paleovolcano erupted effusively producing basaltic sequence, while the second one erupted explosively ejecting feldspathic-rich pyroclastic material. The two paleovolcanoes erupted simultaneously and repeatedly.

  9. Formats

    Directory of Open Access Journals (Sweden)

    Gehmann, Ulrich

    2012-03-01

    Full Text Available In the following, a new conceptual framework for investigating nowadays’ “technical” phenomena shall be introduced, that of formats. The thesis is that processes of formatting account for our recent conditions of life, and will do so in the very next future. It are processes whose foundations have been laid in modernity and which will further unfold for the time being. These processes are embedded in the format of the value chain, a circumstance making them resilient to change. In addition, they are resilient in themselves since forming interconnected systems of reciprocal causal circuits.Which leads to an overall situation that our entire “Lebenswelt” became formatted to an extent we don’t fully realize, even influencing our very percep-tion of it.

  10. Facilitation at single synapses probed with optical quantal analysis.

    Science.gov (United States)

    Oertner, Thomas G; Sabatini, Bernardo L; Nimchinsky, Esther A; Svoboda, Karel

    2002-07-01

    Many synapses can change their strength rapidly in a use-dependent manner, but the mechanisms of such short-term plasticity remain unknown. To understand these mechanisms, measurements of neurotransmitter release at single synapses are required. We probed transmitter release by imaging transient increases in [Ca(2+)] mediated by synaptic N-methyl-D-aspartate receptors (NMDARs) in individual dendritic spines of CA1 pyramidal neurons in rat brain slices, enabling quantal analysis at single synapses. We found that changes in release probability, produced by paired-pulse facilitation (PPF) or by manipulation of presynaptic adenosine receptors, were associated with changes in glutamate concentration in the synaptic cleft, indicating that single synapses can release a variable amount of glutamate per action potential. The relationship between release probability and response size is consistent with a binomial model of vesicle release with several (>5) independent release sites per active zone, suggesting that multivesicular release contributes to facilitation at these synapses.

  11. The secretory synapse: the secrets of a serial killer.

    Science.gov (United States)

    Bossi, Giovanna; Trambas, Christina; Booth, Sarah; Clark, Richard; Stinchcombe, Jane; Griffiths, Gillian M

    2002-11-01

    Cytotoxic T lymphocytes (CTLs) destroy their targets by a process involving secretion of specialized granules. The interactions between CTLs and target can be very brief; nevertheless, adhesion and signaling proteins segregate into an immunological synapse. Secretion occurs in a specialized secretory domain. Use of live and fixed cell microscopy allows this secretory synapse to be visualized both temporally and spatially. The combined use of confocal and electron microscopy has produced some surprising findings, which suggest that the secretory synapse may be important both in delivering the lethal hit and in facilitating membrane transfer from target to CTL. Studies on the secretory synapse in wild-type and mutant CTLs have been used to identify proteins involved in secretion. Further clues as to the signals required for secretion are emerging from comparisons of inhibitory and activating synapses formed by natural killer cells.

  12. ALMA Observations of Warm Dense Gas in NGC 1614 --- Breaking of Star Formation Law in the Central kpc

    CERN Document Server

    Xu, C K; Lu, N; Gao, Y; Diaz-Santos, T; Herrero-Illana, R; Meijerink, R; Privon, G; Zhao, Y -H; Evans, A S; König, S; Mazzarella, J M; Aalto, S; Appleton, P; Armus, L; Charmandaris, V; Chu, J; Haan, S; Inami, H; Murphy, E J; Sanders, D B; Schulz, B; van der Werf, P

    2014-01-01

    We present ALMA Cycle-0 observations of the CO (6-5) line emission and of the 435um dust continuum emission in the central kpc of NGC 1614, a local luminous infrared galaxy (LIRG) at a distance of 67.8 Mpc (1 arcsec = 329 pc). The CO emission is well resolved by the ALMA beam (0".26 x 0".20) into a circum-nuclear ring, with an integrated flux of f_{CO(6-5)} = 898 (+-153) Jy km/s, which is 63(+-12)% of the total CO(6-5) flux measured by Herschel. The molecular ring, located between 100pc < r < 350pc from the nucleus, looks clumpy and includes seven unresolved (or marginally resolved) knots with median velocity dispersion of 40 km/s. These knots are associated with strong star formation regions with \\Sigma_{SFR} 100 M_\\sun/yr/kpc^{2} and \\Sigma_{Gas} 1.0E4 M_\\sun/pc^{2}. The non-detections of the nucleus in both the CO (6-5) line emission and the 435um continuum rule out, with relatively high confidence, a Compton-thick AGN in NGC 1614. Comparisons with radio continuum emission show a strong deviation fro...

  13. Overview Chapter 5: Determinants of family formation and childbearing during the societal transition in Central and Eastern Europe

    Directory of Open Access Journals (Sweden)

    Tomas Frejka

    2008-07-01

    Full Text Available Societal conditions for early and high rates of childbearing were replaced by conditions generating late and low levels of fertility common in Western countries. Central among factors shaping the latter behaviour (job insecurity, unstable partnership relationships, expensive housing, and profound changes in norms, values and attitudes were the following: increasing proportions of young people were acquiring advanced education, a majority of women were gainfully employed, yet women were performing most household maintenance and childrearing duties. Two theories prevailed to explain what caused changes in family formation and fertility trends. One argues that the economic and social crises were the principal causes. The other considered the diffusion of western norms, values and attitudes as the prime factors of change. Neither reveals the root cause: the replacement of state socialist regimes with economic and political institutions of contemporary capitalism. The extraordinarily low period TFRs around 2000 were the result of low fertility of older women born around 1960 overlapping with low fertility of young women born during the 1970s.

  14. Milankovitch insulation forcing and cyclic formation of large-scale glacial, fluvial, and eolian landforms in central Alaska

    Science.gov (United States)

    Beget, J. E.

    1993-01-01

    Continuous marine and ice-core proxy climate records indicate that the Earth's orbital geometry modulates long-term changes. Until recently, little direct evidence has been available to demonstrate correlations between Milankovitch cycles and large-scale terrestrial landforms produced during worldwide glaciations. In central Alaska large areas of loess and sand fill valleys and basins near major outwash streams. The streams themselves are bordered by sets of outwash terraces, and the terraces grade up valley into sets of moraines. The discovery of the Stampede tephra (approximately 175,000 yr ago) reworked within push moraines of the Lignite Creek glaciation suggests that this event correlates with the glaciation of marine isotope stage 6. A new occurrence of the Old Crow tephra (approximately 140,000 yr ago) on the surface of the oldest outwash terrace of the Tanana River, correlated with Delta glaciation, suggests this event also occurred at this time. The penultimate Healy glaciation apparently correlates with marine isotope stage 4, while radiocarbon dates indicate the latest Pleistocene moraines correlate with marine isotope stage 2. Recognition of the importance of orbital forcing to the cyclical formation of glacial landforms and landscapes can help in interpretations of remotely sensed glacial and proglacial land forms.

  15. Depositional conditions of the coal-bearing Hirka Formation beneath late Miocene explosive volcanic products in NW central Anatolia, Turkey

    Energy Technology Data Exchange (ETDEWEB)

    Sener, M. [Nigde University, Nigde (Turkey). Dept. of Geology

    2007-04-15

    This work focuses on the relationship between the coal deposition and explosive volcanism of the Miocene basin, NW central Anatolia, Turkey. The coal-bearing Hirka Formation was deposited over the Galatian Andesitic Complex and/or massive lagoonal environments during the Miocene. The investigated lignite is a high ash (from 32 to 58%) and sulphur (from 1.43 to 3.03%) lignite which is petrographically characterised by a high humunite content. The mineral matter of the studied lignite samples is made up of mainly clay minerals (illite-smectite and kaolinite), plagioclase and quartz in Bolu coal field, clay minerals (illite-smectite, smectite and illite), quartz, calcite, plagioclase and gypsum in Seben coal field, quartz, K-feldspar, plagioclase and clay minerals (kaolinite and illite) in Kibriscik, and dolomite, quartz, clinoptilolite, opal CT and gypsum in Camhdere coal field. The differences in these four types of lignite with specific mineralogical patterns may be due to the explosive volcanic events and depositional conditions which changed from one coal field to the others. There is a zonation from SW to SE in the studied area for zeolites. Carbonate minerals are commonly calcite in Seben and Kibriscik coal fields. In Bolu, coal samples are devoid of calcite and dolomite. These analyses show that there is an increase in the amount of Mg and a decrease in the amount of Na from the northwestern part to the southern part in the study area.

  16. Analytical modelling of temperature effects on synapses

    CERN Document Server

    Kufel, Dominik S

    2016-01-01

    It was previously reported, that temperature may significantly influence neural dynamics on different levels of brain modelling. Due to this fact, while creating the model in computational neuroscience we would like to make it scalable for wide-range of various brain temperatures. However currently, because of a lack of experimental data and an absence of analytical model describing temperature influence on synapses, it is not possible to include temperature effects on multi-neuron modelling level. In this paper, we propose first step to deal with this problem: new analytical model of AMPA-type synaptic conductance, which is able to include temperature effects in low-frequency stimulations. It was constructed on basis of Markov model description of AMPA receptor kinetics and few simplifications motivated both experimentally and from Monte Carlo simulation of synaptic transmission. The model may be used for efficient and accurate implementation of temperature effects on AMPA receptor conductance in large scale...

  17. Organizing polarized delivery of exosomes at synapses.

    Science.gov (United States)

    Mittelbrunn, Maria; Vicente-Manzanares, Miguel; Sánchez-Madrid, Francisco

    2015-04-01

    Exosomes are extracellular vesicles that transport different molecules between cells. They are formed and stored inside multivesicular bodies (MVB) until they are released to the extracellular environment. MVB fuse along the plasma membrane, driving non-polarized secretion of exosomes. However, polarized signaling potentially directs MVBs to a specific point in the plasma membrane to mediate a focal delivery of exosomes. MVB polarization occurs across a broad set of cellular situations, e.g. in immune and neuronal synapses, cell migration and in epithelial sheets. In this review, we summarize the current state of the art of polarized MVB docking and the specification of secretory sites at the plasma membrane. The current view is that MVB positioning and subsequent exosome delivery requires a polarizing, cytoskeletal dependent-trafficking mechanism. In this context, we propose scenarios in which biochemical and mechanical signals could drive the polarized delivery of exosomes in highly polarized cells, such as lymphocytes, neurons and epithelia.

  18. Spine neck plasticity regulates compartmentalization of synapses.

    Science.gov (United States)

    Tønnesen, Jan; Katona, Gergely; Rózsa, Balázs; Nägerl, U Valentin

    2014-05-01

    Dendritic spines have been proposed to transform synaptic signals through chemical and electrical compartmentalization. However, the quantitative contribution of spine morphology to synapse compartmentalization and its dynamic regulation are still poorly understood. We used time-lapse super-resolution stimulated emission depletion (STED) imaging in combination with fluorescence recovery after photobleaching (FRAP) measurements, two-photon glutamate uncaging, electrophysiology and simulations to investigate the dynamic link between nanoscale anatomy and compartmentalization in live spines of CA1 neurons in mouse brain slices. We report a diversity of spine morphologies that argues against common categorization schemes and establish a close link between compartmentalization and spine morphology, wherein spine neck width is the most critical morphological parameter. We demonstrate that spine necks are plastic structures that become wider and shorter after long-term potentiation. These morphological changes are predicted to lead to a substantial drop in spine head excitatory postsynaptic potential (EPSP) while preserving overall biochemical compartmentalization.

  19. Production of adenosine from extracellular ATP at the striatal cholinergic synapse.

    Science.gov (United States)

    James, S; Richardson, P J

    1993-01-01

    The components of the ectonucleotidase pathway at the immunoaffinity-purified striatal cholinergic synapse have been studied. The ecto-ATPase (EC 3.6.1.15) had a Km of 131 microM, whereas the ecto-ADPase (EC 3.6.1.6) had a Km of 58 microM, was Ca(2+)-dependent, and was inhibited by the ATP analogue 5'-adenylylimidodiphosphate (AMPPNP). The ecto-5'-nucleotidase (EC 3.1.3.5) had a Km of 21 microM, was inhibited by AMPPNP and alpha,beta-methylene ADP, and by a specific antiserum. The Vmax values of the ATPase, ADPase, and 5'-nucleotidase enzymes present at this synapse were in a ratio of 30:14:1. Very little ecto-adenylate kinase activity was detected on these purified synapses. The intraterminal 5'-nucleotidase enzyme, which amounted to 40% of the total 5'-nucleotidase activity, was inhibited by AMPPNP, alpha,beta-methylene ADP, and the antiserum, and also had the same kinetic properties as the ectoenzyme. The time course of ATP degradation to adenosine outside the nerve terminals showed a delay, followed by a period of sustained adenosine production. The delay in adenosine production was proportional to the initial ATP concentration, was a consequence of feedforward inhibition of the ADPase and 5'-nucleotidase, and was inversely proportional to the ecto-5'-nucleotidase activity. The function and characteristics of this pathway and the central role of 5'-nucleotidase in the regulation of extraterminal adenosine concentrations are discussed.

  20. Neurotransmitter transporters expressed in glial cells as regulators of synapse function.

    Science.gov (United States)

    Eulenburg, Volker; Gomeza, Jesús

    2010-05-01

    Synaptic neurotransmission at high temporal and spatial resolutions requires efficient removal and/or inactivation of presynaptically released transmitter to prevent spatial spreading of transmitter by diffusion and allow for fast termination of the postsynaptic response. This action must be carefully regulated to result in the fine tuning of inhibitory and excitatory neurotransmission, necessary for the proper processing of information in the central nervous system. At many synapses, high-affinity neurotransmitter transporters are responsible for transmitter deactivation by removing it from the synaptic cleft. The most prevailing neurotransmitters, glutamate, which mediates excitatory neurotransmission, as well as GABA and glycine, which act as inhibitory neurotransmitters, use these uptake systems. Neurotransmitter transporters have been found in both neuronal and glial cells, thus suggesting high cooperativity between these cell types in the control of extracellular transmitter concentrations. The generation and analysis of animals carrying targeted disruptions of transporter genes together with the use of selective inhibitors have allowed examining the contribution of individual transporter subtypes to synaptic transmission. This revealed the predominant role of glial expressed transporters in maintaining low extrasynaptic neurotransmitter levels. Additionally, transport activity has been shown to be actively regulated on both transcriptional and post-translational levels, which has important implications for synapse function under physiological and pathophysiological conditions. The analysis of these mechanisms will enhance not only our understanding of synapse function but will reveal new therapeutic strategies for the treatment of human neurological diseases.

  1. Ultrastructural and Functional Properties of a Giant Synapse Driving the Piriform Cortex to Mediodorsal Thalamus Projection.

    Science.gov (United States)

    Pelzer, Patric; Horstmann, Heinz; Kuner, Thomas

    2017-01-01

    Neocortico-thalamo-cortical loops represent a common, yet poorly understood, circuit employing giant synapses also referred to as "class I", giant, or driver synapses. Here, we characterize a giant synapse formed by projection neurons of the paleocortical piriform cortex (PIR) onto neurons of the mediodorsal thalamus (MD). Three-dimensional (3D) ultrastructure of labeled PIR-MD terminals, obtained by using serial-section scanning electron microscopy (EM) combined with photooxidation-based detection of labeled terminals, revealed a large terminal engulfing multiple postsynaptic dendritic excrescences. The terminal contained multiple synaptic contacts, a high density of synaptic vesicles and several central mitochondria. Using targeted stimulations of single identified PIR-MD terminals in combination with patch-clamp recordings from the connected MD neuron, we found large postsynaptic currents with fast kinetics and strong short-term depression, yet fast recovery upon repetitive stimulation. We conclude that the phylogenetically old paleocortex already developed giant synaptic connections exhibiting similar functional properties as connections formed by giant neocortico-thalamic projections.

  2. Ultrastructural and Functional Properties of a Giant Synapse Driving the Piriform Cortex to Mediodorsal Thalamus Projection

    Science.gov (United States)

    Pelzer, Patric; Horstmann, Heinz; Kuner, Thomas

    2017-01-01

    Neocortico-thalamo-cortical loops represent a common, yet poorly understood, circuit employing giant synapses also referred to as “class I”, giant, or driver synapses. Here, we characterize a giant synapse formed by projection neurons of the paleocortical piriform cortex (PIR) onto neurons of the mediodorsal thalamus (MD). Three-dimensional (3D) ultrastructure of labeled PIR-MD terminals, obtained by using serial-section scanning electron microscopy (EM) combined with photooxidation-based detection of labeled terminals, revealed a large terminal engulfing multiple postsynaptic dendritic excrescences. The terminal contained multiple synaptic contacts, a high density of synaptic vesicles and several central mitochondria. Using targeted stimulations of single identified PIR-MD terminals in combination with patch-clamp recordings from the connected MD neuron, we found large postsynaptic currents with fast kinetics and strong short-term depression, yet fast recovery upon repetitive stimulation. We conclude that the phylogenetically old paleocortex already developed giant synaptic connections exhibiting similar functional properties as connections formed by giant neocortico-thalamic projections. PMID:28197093

  3. Two-stage formation model of the Junggar basin basement: Constraints to the growth style of Central Asian Orogenic Belt

    Science.gov (United States)

    He, Dengfa

    2016-04-01

    Junggar Basin is located in the central part of the Central Asian Orogenic Belt (CAOB). Its basement nature is a highly controversial scientific topic, involving the basic style and processes of crustal growth. Some researchers considered the basement of the Junggar Basin as a Precambrian continental crust, which is not consistent with the petrological compositions of the adjacent orogenic belts and the crust isotopic compositions revealed by the volcanic rocks in the basin. Others, on the contrary, proposed an oceanic crust basement model that does not match with the crustal thickness and geophysical characteristics of the Junggar area. Additionally, there are several viewponits, such as the duplex basement with the underlying Precambrian crystalline rocks and the overlying pre-Carboniferous folded basement, and the collaged basement by the Precambrian micro-continent block in the central part and the Hercynian accretionary folded belts circling it. Anyway, it is necessary to explain the property of basement rock, its strong inhomogeneous compositions as well as the geophysical features. In this paper, based on the borehole data from more than 300 industry wells drilled into the Carboniferous System, together with the high-resolution gravity and magnetic data (in a scale of 1:50,000), we made a detailed analysis of the basement structure, formation timing and processes and its later evolution on a basis of core geochemical and isotopic analysis. Firstly, we defined the Mahu Pre-Cambrian micro-continental block in the juvenile crust of Junggar Basin according to the Hf isotopic analysis of the Carboniferous volcanic rocks. Secondly, the results of the tectonic setting and basin analysis suggest that the Junggar area incorporates three approximately E-W trending island arc belts (from north to south: Yemaquan- Wulungu-Chingiz, Jiangjunmiao-Luliang-Darbut and Zhongguai-Mosuowan- Baijiahai-Qitai island arcs respectively) and intervened three approximately E-W trending

  4. Excitatory synapses are stronger in the hippocampus of Rett syndrome mice due to altered synaptic trafficking of AMPA-type glutamate receptors.

    Science.gov (United States)

    Li, Wei; Xu, Xin; Pozzo-Miller, Lucas

    2016-03-15

    Deficits in long-term potentiation (LTP) at central excitatory synapses are thought to contribute to cognitive impairments in neurodevelopmental disorders associated with intellectual disability and autism. Using the methyl-CpG-binding protein 2 (Mecp2) knockout (KO) mouse model of Rett syndrome, we show that naïve excitatory synapses onto hippocampal pyramidal neurons of symptomatic mice have all of the hallmarks of potentiated synapses. Stronger Mecp2 KO synapses failed to undergo LTP after either theta-burst afferent stimulation or pairing afferent stimulation with postsynaptic depolarization. On the other hand, basal synaptic strength and LTP were not affected in slices from younger presymptomatic Mecp2 KO mice. Furthermore, spine synapses in pyramidal neurons from symptomatic Mecp2 KO are larger and do not grow in size or incorporate GluA1 subunits after electrical or chemical LTP. Our data suggest that LTP is occluded in Mecp2 KO mice by already potentiated synapses. The higher surface levels of GluA1-containing receptors are consistent with altered expression levels of proteins involved in AMPA receptor trafficking, suggesting previously unidentified targets for therapeutic intervention for Rett syndrome and other MECP2-related disorders.

  5. Isotopic and geochemical characterization of groundwater of the Carnot-Berbérati sandstone formation (Western Central African Republic)

    Science.gov (United States)

    Djebebe-Ndjiguim, Chantal; Foto, Eric; Backo, Salé; Zoudamba, Narcisse; Basse-Keke, Eric; Nguerekossi, Bruno; Alladin, Oscar; Huneau, Frederic; Garel, Emilie; Celle-Jeanton, Helene; Mabingui, Joseph

    2016-04-01

    The hydrogeology of the Cretaceous sandstone formations of Carnot-Berbérati (covering an area of 46.000 km2) in the western part of the central African Republic is poorly known. In order to improve the access of local populations to a clean and safe drinking water resource, new investigations have been carried out in order to characterize groundwater in terms of quality, origin, residence time and sustainability. Two sampling campaigns were organized in August 2014 (rainy period) and April 2015 (dry period) on respectively 31 and 43 points including boreholes, wells and river waters. Conventional hydrogeochemical tools in conjunction with isotope hydrology tools were used to evaluate the water types and the anthropogenic fingerprint on groundwater, their recharge processes and the flow organization scheme. Investigations have shown the existence of interesting amounts of groundwater within what seems a single, well hydraulically connected unconfined aquifer of max. 400m thick. Groundwaters are characterized by two main water types: CaMg-HCO3 (for deep boreholes and river waters) and CaMg-ClNO3 (shallow wells). The latter clearly showing the very strong influence of anthropogenic activities (washing, dumps, latrines) in the near vicinity of wells and boreholes used for the drinking water supply. This is also highlighting the total lack of protection zone around the wells and boreholes. Stable isotopes of the water molecule (18O and 2H) are in agreement with a local recharge of groundwater and show a relatively homogeneous composition within the whole aquifer system. Tritium data indicate a modern recharge with a high renewability potential for shallow groundwater but very low tritium levels are observed in the deepest boreholes indicating the probable occurrence of complex flow conditions within the system in some sectors. From these results and because of its extension and storage potential, the Carnot-Berbérati sandstone aquifer appears as a groundwater resource

  6. Structural and functional characterization of synapse-associated protein-97

    Science.gov (United States)

    Wang, Lei

    Synapse-associated protein-97 (SAP97) as a scaffold protein plays an important role in regulating neural signal transmission in the central nervous system by coupling with activated membrane receptors, ion channels, and downstream signaling proteins. SAP97 consists of six functional domains: L27, PDZ1, PDZ2, PDZ3, SH3, and GK. Each of these domains mediates the interactions of SAP97 with other proteins. Understanding the molecular mechanism of these interactions in neural signal transmission is a goal of this study. Here high-resolution nuclear magnetic resonance spectroscopy and fluorescence anisotropy are employed towards the goal of the structural and functional characterization of SAP97; specifically, we (a) characterize the binding of the PDZ domains of SAP97 with the C-terminus of NR2B, and determine the structure of the PDZ1-NR2B; (b) characterize the binding of the PDZ domains with the C-terminus of stargazin and multiple mutants, and identify the perturbed amino acids in PDZ2 upon the binding of stargazin; (c) characterize the binding specificity carried by the beta2/beta3 loop of the PDZ3 domain. These results provide insight into the molecular mechanism for the binding specificities of the PDZ domains of SAP97, thereby furthering the development of drugs that target these domains to treat neurological diseases.

  7. Electrical synapses and synchrony: the role of intrinsic currents.

    Science.gov (United States)

    Pfeuty, Benjamin; Mato, Germán; Golomb, David; Hansel, David

    2003-07-16

    Electrical synapses are ubiquitous in the mammalian CNS. Particularly in the neocortex, electrical synapses have been shown to connect low-threshold spiking (LTS) as well as fast spiking (FS) interneurons. Experiments have highlighted the roles of electrical synapses in the dynamics of neuronal networks. Here we investigate theoretically how intrinsic cell properties affect the synchronization of neurons interacting by electrical synapses. Numerical simulations of a network of conductance-based neurons randomly connected with electrical synapses show that potassium currents promote synchrony, whereas the persistent sodium current impedes it. Furthermore, synchrony varies with the firing rate in qualitatively different ways depending on the intrinsic currents. We also study analytically a network of quadratic integrate-and-fire neurons. We relate the stability of the asynchronous state of this network to the phase-response function (PRF), which characterizes the effect of small perturbations on the firing timing of the neurons. In particular, we show that the greater the skew of the PRF toward the first half of the period, the more stable the asynchronous state. Combining our simulations with our analytical results, we establish general rules to predict the dynamic state of large networks of neurons coupled with electrical synapses. Our work provides a natural explanation for surprising experimental observations that blocking electrical synapses may increase the synchrony of neuronal activity. It also suggests different synchronization properties for LTS and FS cells. Finally, we propose to further test our predictions in experiments using dynamic clamp techniques.

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

    Directory of Open Access Journals (Sweden)

    Nicolas Schleinitz

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

  9. Functioning of an ancient sediment routing system; Mass balance and sediment budget of the Eocene Escanilla Formation, Spanish central Pyrenees

    Science.gov (United States)

    Michael, N. A.; Whittaker, A. C.; Allen, P. A.

    2013-12-01

    One of the key challenges that sedimentologists and stratigraphers face is trying to understand what controls grain-size and sedimentary facies in basins, with the ultimate goal of stratigraphic prediction. It has been shown that the crucial parameters that control grain-size trends are the sediment discharge into the basin, the characteristic grain size mix of the supply, and the spatial distribution of subsidence. In this paper we present an outcrop case study of the Escanilla Formation, where all these parameters have been constrained, and explore how knowledge of these parameters translates into stratigraphic architecture. The mid-upper Eocene Escanilla Formation is part of a 200 km-long sediment routing system that was sourced primarily from the Axial Zone of the South-Central Pyrenees and deposited in a series of wedge-top basins (La Pobla, Tremp-Graus, Ainsa and Jaca basins). The Escanilla system consists of a wide variety of depositional environments and is one of the rare examples where all components of the ancient routing system are readily available for study: from proximal alluvial fanglomerates in the Sis and Gurb paleovalleys, braided river deposits in the Tremp-Graus and eastern Ainsa basins, deltaic, shallow marine and continental slope deposits in the western Ainsa Basin, and deep marine turbidite deposits in the Jaca Basin. This makes it a world class siliciclastic analogue for hydrocarbon exploration. In this study we examine how the mass balance and sediment budget influenced sedimentary trends within this paleo-sediment routing system. The entire sediment routing system has been delimited using new provenance data and a correlation from source to sink is proposed, subdividing the 7.7 Myr duration of deposition into three time intervals of roughly equal duration. Within these time intervals, the sedimentary budgets of the Escanilla system have been calculated and a mass balance framework established, enabling the quantitative assessment of how

  10. Streamlined subglacial bedforms on the Närke plain, south-central Sweden - Areal distribution, morphometrics, internal architecture and formation

    Science.gov (United States)

    Möller, Per; Dowling, Thomas P. F.

    2016-08-01

    A flow set of close to 1000 drumlins has been mapped by means of LiDAR-derived digital elevation models and investigated by trenching. The area is situated on the SW part of the Närke plain and its surrounding uplands in south-central Sweden, which was deglaciated in the early Preboreal in a glacioaquatic setting. We find that there is considerable morphological difference in drumlin distribution patterns over crystalline basement areas compared to streamlined terrain over Palaeozoic sedimentary rock basement. The former area is characterized by thin Quaternary drift and the drumlins are all of the rock-cored type, built due to active deposition of sediment around obstacles to glacier flow. The latter area is characterized by deep Quaternary drift and the drumlins are more elongate and also larger in all dimensions, as compared to rock-cored drumlins. Irrespective of these geomorphological differences on local landscape scale we find that drumlin morphometric values remain part of a morphological continuum at the regional scale. Based on the internal sediment architecture as revealed in two cross-drumlin sections we find that the soft-cored drumlins were formed by compressional constructive deformation, along with excavational deformation along the flanks of the emerging drumlins, which shaped the separating troughs. Intermediate-type drumlins are those that demonstrate a coupling between underlying Palaeozoic sediment strata in areas of shallow drift sheet. These are the result of differing rheological response between incorporated sedimentary rock and a deforming bed below the ice-bed interface. An overall conclusion is that we find geomorphic and architectural compositional differences between the drumlins and the flowset they form. We can closely relate these differences to contextual geological variations with respect to basement type and drift depth. We argue that drumlin formation is better explained not by one single 'unifying' process but rather a set of

  11. Axonal synapses utilize multiple synaptic ribbons in the mammalian retina.

    Directory of Open Access Journals (Sweden)

    Hong-Lim Kim

    Full Text Available In the mammalian retina, bipolar cells and ganglion cells which stratify in sublamina a of the inner plexiform layer (IPL show OFF responses to light stimuli while those that stratify in sublamina b show ON responses. This functional relationship between anatomy and physiology is a key principle of retinal organization. However, there are at least three types of retinal neurons, including intrinsically photosensitive retinal ganglion cells (ipRGCs and dopaminergic amacrine cells, which violate this principle. These cell types have light-driven ON responses, but their dendrites mainly stratify in sublamina a of the IPL, the OFF sublayer. Recent anatomical studies suggested that certain ON cone bipolar cells make axonal or ectopic synapses as they descend through sublamina a, thus providing ON input to cells which stratify in the OFF sublayer. Using immunoelectron microscopy with 3-dimensional reconstruction, we have identified axonal synapses of ON cone bipolar cells in the rabbit retina. Ten calbindin ON cone bipolar axons made en passant ribbon synapses onto amacrine or ganglion dendrites in sublamina a of the IPL. Compared to the ribbon synapses made by bipolar terminals, these axonal ribbon synapses were characterized by a broad postsynaptic element that appeared as a monad and by the presence of multiple short synaptic ribbons. These findings confirm that certain ON cone bipolar cells can provide ON input to amacrine and ganglion cells whose dendrites stratify in the OFF sublayer via axonal synapses. The monadic synapse with multiple ribbons may be a diagnostic feature of the ON cone bipolar axonal synapse in sublamina a. The presence of multiple ribbons and a broad postsynaptic density suggest these structures may be very efficient synapses. We also identified axonal inputs to ipRGCs with the architecture described above.

  12. On the peritidal cycles and their diagenetic evolution in the Lower Jurassic carbonates of the Calcare Massiccio Formation (Central Apennines

    Directory of Open Access Journals (Sweden)

    Brandano Marco

    2015-10-01

    Full Text Available This paper shows the environmental changes and high-frequency cyclicity recorded by Lower Jurassic shallow-water carbonates known as the Calcare Massiccio Formation which crop out in the central Apennines of Italy. Three types of sedimentary cycle bounded by subaerial erosion have been recognized: Type I consists of a shallowing upward cycle with oncoidal floatstones to rudstones passing gradationally up into peloidal packstone alternating with cryptoalgal laminites and often bounded by desiccation cracks and pisolitic-peloidal wackestones indicating a period of subaerial exposure. Type II shows a symmetrical trend in terms of facies arrangement with peloidal packstones and cryptoalgal laminites present both at the base and in the upper portion of the cycle, separated by oncoidal floatstones to rudstones. Type III displays a shallowing upward trend with an initial erosion surface overlain by oncoidal floatstones to rudstones that, in turn, are capped by pisolitic-peloidal wackestones and desiccation sheet cracks. Sheet cracks at the top of cycles formed during the initial phase of subaerial exposure were successively enlarged by dissolution during prolonged subaerial exposure. The following sea-level fall produced dissolution cavities in subtidal facies, while the successive sea-level rise resulted in the precipitation of marine cements in dissolution cavities. Spectral analysis revealed six peaks, five of which are consistent with orbital cycles. While a tectonic control cannot be disregarded, the main signal recorded by the sedimentary succession points toward a main control related to orbital forcing. High frequency sea-level fluctuations also controlled diagenetic processes.

  13. Depositional conditions of the coal-bearing Hirka Formation beneath Late Miocene explosive volcanic products in NW central Anatolia, Turkey

    Indian Academy of Sciences (India)

    Mehmet Şener

    2007-04-01

    This work focuses on the relationship between the coal deposition and explosive volcanism of the Miocene basin, NW central Anatolia, Turkey. The coal-bearing Hirka Formation was deposited over the Galatian Andesitic Complex and/or massive lagoonal environments during the Miocene. The investigated lignite is a high ash (from 32 to 58%) and sulphur (from 1.43 to 3.03%) lignite which is petrographically characterised by a high humunite content. The mineral matter of the studied lignite samples is made up of mainly clay minerals (illite–smectite and kaolinite), plagioclase and quartz in Bolu coal field, clay minerals (illite–smectite, smectite and illite), quartz, calcite, plagioclase and gypsum in Seben coal field, quartz, K-feldspar, plagioclase and clay minerals (kaolinite and illite) in Kıbrıscık, and dolomite, quartz, clinoptilolite, opal CT and gypsum in C¸ amlıdere coal field. The differences in these four types of lignite with specific mineralogical patterns may be due to the explosive volcanic events and depositional conditions which changed from one coal field to the others. There is a zonation from SW to SE in the studied area for zeolites such as Opal CT+smectite-clinoptilolite-analcime-K-feldspar. Carbonate minerals are commonly calcite in Seben and Kıbrıscık coal fields. In Bolu, coal samples are devoid of calcite and dolomite. These analyses show that there is an increase in the amount of Mg and a decrease in the amount of Na from the northwestern part to the southern part in the study area.

  14. Characterization of physiological phenotypes of dentate gyrus synapses of PDZ1/2 domain-deficient PSD-95-knockin mice.

    Science.gov (United States)

    Nagura, Hitoshi; Doi, Tomoko; Fujiyoshi, Yoshinori

    2016-03-01

    The hippocampal formation is involved in several important brain functions of animals, such as memory formation and pattern separation, and the synapses in the dentate gyrus (DG) play critical roles as the first step in the hippocampal circuit. Previous studies have reported that mice with genetic modifications of the PDZ1/2 domains of postsynaptic density (PSD)-95 exhibit altered synaptic properties in the DG and impaired hippocampus-dependent behaviors. Based on the involvement of the DG in the regulation of behaviors, these data suggest that the abnormal behavior of these knockin (KI) mice is due partly to altered DG function. Precise understanding of the phenotypes of these mutant mice requires characterization of the synaptic properties of the DG, and here we provide detailed studies of DG synapses. We have demonstrated global changes in the PSD membrane-associated guanylate kinase expression pattern in the DG of mutant mice, and DG synapses in these mice exhibited increased long-term potentiation under a wide range of stimulus intensities, although the N-methyl-d-aspartic acid receptor dependence of the long-term potentiation was unchanged. Furthermore, our data also indicate increased silent synapses in the DG of the KI mice. These findings suggest that abnormal protein expression and physiological properties disrupt the function of DG neurons in these KI mice.

  15. MicroRNA-8 promotes robust motor axon targeting by coordinate regulation of cell adhesion molecules during synapse development.

    Science.gov (United States)

    Lu, Cecilia S; Zhai, Bo; Mauss, Alex; Landgraf, Matthias; Gygi, Stephen; Van Vactor, David

    2014-09-26

    Neuronal connectivity and specificity rely upon precise coordinated deployment of multiple cell-surface and secreted molecules. MicroRNAs have tremendous potential for shaping neural circuitry by fine-tuning the spatio-temporal expression of key synaptic effector molecules. The highly conserved microRNA miR-8 is required during late stages of neuromuscular synapse development in Drosophila. However, its role in initial synapse formation was previously unknown. Detailed analysis of synaptogenesis in this system now reveals that miR-8 is required at the earliest stages of muscle target contact by RP3 motor axons. We find that the localization of multiple synaptic cell adhesion molecules (CAMs) is dependent on the expression of miR-8, suggesting that miR-8 regulates the initial assembly of synaptic sites. Using stable isotope labelling in vivo and comparative mass spectrometry, we find that miR-8 is required for normal expression of multiple proteins, including the CAMs Fasciclin III (FasIII) and Neuroglian (Nrg). Genetic analysis suggests that Nrg and FasIII collaborate downstream of miR-8 to promote accurate target recognition. Unlike the function of miR-8 at mature larval neuromuscular junctions, at the embryonic stage we find that miR-8 controls key effectors on both sides of the synapse. MiR-8 controls multiple stages of synapse formation through the coordinate regulation of both pre- and postsynaptic cell adhesion proteins.

  16. Activity-dependent repression of Cbln1 expression: mechanism for developmental and homeostatic regulation of synapses in the cerebellum.

    Science.gov (United States)

    Iijima, Takatoshi; Emi, Kyoichi; Yuzaki, Michisuke

    2009-04-29

    Cbln1, which belongs to the C1q/tumor necrosis factor superfamily, is released from cerebellar granule cells and plays a crucial role in forming and maintaining excitatory synapses between parallel fibers (PFs; axons of granule cells) and Purkinje cells not only during development but also in the adult cerebellum. Although neuronal activity is known to cause morphological changes at synapses, how Cbln1 signaling is affected by neuronal activity remains unclear. Here, we show that chronic stimulation of neuronal activity by elevating extracellular K(+) levels or by adding kainate decreased the expression of cbln1 mRNA within several hours in mature granule cells in a manner dependent on L-type voltage-dependent Ca(2+) channels and calcineurin. Chronic activity also reduced Cbln1 protein levels within a few days, during which time the number of excitatory synapses on Purkinje cell dendrites was reduced; this activity-induced reduction of synapses was prevented by the addition of exogenous Cbln1 to the culture medium. Therefore, the activity-dependent downregulation of cbln1 may serve as a new presynaptic mechanism by which PF-Purkinje cell synapses adapt to chronically elevated activity, thereby maintaining homeostasis. In addition, the expression of cbln1 mRNA was prevented when immature granule cells were maintained in high-K(+) medium. Since immature granule cells are chronically depolarized before migrating to the internal granule layer, this depolarization-dependent regulation of cbln1 mRNA expression may also serve as a developmental switch to facilitate PF synapse formation in mature granule cells in the internal granule layer.

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

    Directory of Open Access Journals (Sweden)

    Tanaka Mika

    2013-01-01

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

  18. Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.

    Directory of Open Access Journals (Sweden)

    Alice C N Brown

    2011-09-01

    Full Text Available Natural Killer (NK cells are innate immune cells that secrete lytic granules to directly kill virus-infected or transformed cells across an immune synapse. However, a major gap in understanding this process is in establishing how lytic granules pass through the mesh of cortical actin known to underlie the NK cell membrane. Research has been hampered by the resolution of conventional light microscopy, which is too low to resolve cortical actin during lytic granule secretion. Here we use two high-resolution imaging techniques to probe the synaptic organisation of NK cell receptors and filamentous (F-actin. A combination of optical tweezers and live cell confocal microscopy reveals that microclusters of NKG2D assemble into a ring-shaped structure at the centre of intercellular synapses, where Vav1 and Grb2 also accumulate. Within this ring-shaped organisation of NK cell proteins, lytic granules accumulate for secretion. Using 3D-structured illumination microscopy (3D-SIM to gain super-resolution of ~100 nm, cortical actin was detected in a central region of the NK cell synapse irrespective of whether activating or inhibitory signals dominate. Strikingly, the periodicity of the cortical actin mesh increased in specific domains at the synapse when the NK cell was activated. Two-colour super-resolution imaging revealed that lytic granules docked precisely in these domains which were also proximal to where the microtubule-organising centre (MTOC polarised. Together, these data demonstrate that remodelling of the cortical actin mesh occurs at the central region of the cytolytic NK cell immune synapse. This is likely to occur for other types of cell secretion and also emphasises the importance of emerging super-resolution imaging technology for revealing new biology.

  19. Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.

    Science.gov (United States)

    Brown, Alice C N; Oddos, Stephane; Dobbie, Ian M; Alakoskela, Juha-Matti; Parton, Richard M; Eissmann, Philipp; Neil, Mark A A; Dunsby, Christopher; French, Paul M W; Davis, Ilan; Davis, Daniel M

    2011-09-01

    Natural Killer (NK) cells are innate immune cells that secrete lytic granules to directly kill virus-infected or transformed cells across an immune synapse. However, a major gap in understanding this process is in establishing how lytic granules pass through the mesh of cortical actin known to underlie the NK cell membrane. Research has been hampered by the resolution of conventional light microscopy, which is too low to resolve cortical actin during lytic granule secretion. Here we use two high-resolution imaging techniques to probe the synaptic organisation of NK cell receptors and filamentous (F)-actin. A combination of optical tweezers and live cell confocal microscopy reveals that microclusters of NKG2D assemble into a ring-shaped structure at the centre of intercellular synapses, where Vav1 and Grb2 also accumulate. Within this ring-shaped organisation of NK cell proteins, lytic granules accumulate for secretion. Using 3D-structured illumination microscopy (3D-SIM) to gain super-resolution of ~100 nm, cortical actin was detected in a central region of the NK cell synapse irrespective of whether activating or inhibitory signals dominate. Strikingly, the periodicity of the cortical actin mesh increased in specific domains at the synapse when the NK cell was activated. Two-colour super-resolution imaging revealed that lytic granules docked precisely in these domains which were also proximal to where the microtubule-organising centre (MTOC) polarised. Together, these data demonstrate that remodelling of the cortical actin mesh occurs at the central region of the cytolytic NK cell immune synapse. This is likely to occur for other types of cell secretion and also emphasises the importance of emerging super-resolution imaging technology for revealing new biology.

  20. Palynological dating of the Mandal formation (uppermost Jurassic - lowermost Cretaceous, Norwegian Central Graben) and correlation to organic-rich shales in the Danish sector

    Energy Technology Data Exchange (ETDEWEB)

    Dybkjaer, K.

    1998-10-01

    Palynological investigation of the organic-rich Mandal Formation in the type well, 7/12-3A indicates that the age of the formation is mainly Late Volgian to Early Ryazanian although the lower part may extend into the Middle Volgian. Dating is based on the last occurrence of Rotosphaeropsis thula at the upper boundary of the formation and of Glossodinium dimorphum immediately below the lower boundary. Identification of a number of stratigraphically important bioevents has permitted a detailed correlation of the Mandal Formation in its type well with equivalent organic-rich shale sin the Bo-1 well from the Danish Central Graben. The very close similarities in gamma-log patterns from the two wells, despite the considerable distance (about 180 km) between the wells suggests that the origin of these `hot shales` should be attributed to regional rather than local factors. (au) 6 fig., 29 refs.

  1. Electronic system with memristive synapses for pattern recognition

    Science.gov (United States)

    Park, Sangsu; Chu, Myonglae; Kim, Jongin; Noh, Jinwoo; Jeon, Moongu; Hun Lee, Byoung; Hwang, Hyunsang; Lee, Boreom; Lee, Byung-Geun

    2015-05-01

    Memristive synapses, the most promising passive devices for synaptic interconnections in artificial neural networks, are the driving force behind recent research on hardware neural networks. Despite significant efforts to utilize memristive synapses, progress to date has only shown the possibility of building a neural network system that can classify simple image patterns. In this article, we report a high-density cross-point memristive synapse array with improved synaptic characteristics. The proposed PCMO-based memristive synapse exhibits the necessary gradual and symmetrical conductance changes, and has been successfully adapted to a neural network system. The system learns, and later recognizes, the human thought pattern corresponding to three vowels, i.e. /a /, /i /, and /u/, using electroencephalography signals generated while a subject imagines speaking vowels. Our successful demonstration of a neural network system for EEG pattern recognition is likely to intrigue many researchers and stimulate a new research direction.

  2. The Jurassic of Denmark and Greenland: Sedimentology and sequence stratigraphy of the Bryne and Lulu Formations, Middle Jurassic, northern Danish Central Graben

    Directory of Open Access Journals (Sweden)

    Andsbjerg, Jan

    2003-10-01

    Full Text Available The Middle Jurassic Bryne and Lulu Formations of the Søgne Basin (northern part of the Danish Central Graben consist of fluvially-dominated coastal plain deposits, overlain by interfingering shoreface and back-barrier deposits. Laterally continuous, mainly fining-upwards fluvial channel sandstones that locally show evidence for tidal influence dominate the alluvial/coastal plain deposits of the lower Bryne Formation. The sandstones are separated by units of fine-grained floodplain sediments that show a fining-upwards - coarsening-upwards pattern and locally grade into lacustrine mudstones. A regional unconformity that separates the lower Bryne Formation from the mainly estuarine upper Bryne Formation is defined by the strongly erosional base of a succession of stacked channel sandstones, interpreted as the fill of a system of incised valleys. Most of the stacked channel sandstones show abundant mud laminae and flasers, and rare herringbone structures, suggesting that they were deposited in a tidal environment, probably an estuary. Several tens of metres of the lower Bryne Formation may have been removed by erosion at this unconformity. The estuarine channel sandstone succession is capped by coal beds that attain a thickness of several metres in the western part of the Søgne Basin, but are thin and poorly developed in the central part of the basin. Above the coal beds, the Lulu Formation is dominated by various types of tidally influenced paralic deposits in the western part of the basin and by coarsening-upwards shoreface and beach deposits in central parts. Westwards-thickening wedges of paralic deposits interfinger with eastwards-thickening wedges of shallow marine deposits. The Middle Jurassic succession is subdivided into nine sequences. In the lower Bryne Formation, sequence boundaries are situated at the base of laterally continuous fluvial channel sandstones whereas maximum flooding surfaces are placed in laterally extensive floodplain

  3. GLAUBERITE-HALITE ASSOCIATION IN BOZKIR FORMATION (PLİOCENE, ÇANKIRI-ÇORUM BASİN, CENTRAL ANATOLİA, TURKEY)

    OpenAIRE

    SÖNMEZ, İLHAN

    2014-01-01

    Tertiary Çankırı – Çorum Basin is one of the biggest basin covering evaporitic formationsin the Central Anatolia. During borehole drills carried out in Bozkır Formation whichcontain Pliocene aged evaporites in the basin, a thick rocksalt (halite, NaCl) deposit wasdetected that consisting of glauberite (Na2Ca(SO4)2) interlayers (sabhka) synchronouswith sedimentation. Rocksalt bearing layers in Bozkır formation which was deposited inplaya-lake – sabhka environment, where seasonal changes are ef...

  4. Predicting Quiescence: The Dependence of Specific Star Formation Rate on Galaxy Size and Central Density at 0.5

    CERN Document Server

    Whitaker, Katherine E; van Dokkum, Pieter G; Franx, Marijn; van der Wel, Arjen; Brammer, Gabriel; Forster-Schreiber, Natascha M; Giavalisco, Mauro; Labbe, Ivo; Momcheva, Ivelina G; Nelson, Erica J; Skelton, Rosalind

    2016-01-01

    In this paper, we investigate the relationship between star formation and structure, using a mass-complete sample of 27,893 galaxies at 0.50.5 dex from z~2 to z~0.7. Neither a compact galaxy size nor a high n are sufficient to assess the likelihood of quiescence for the average galaxy; rather, it is the combination of these two parameters together with stellar mass that results in a unique quenching threshold in central density or velocity.

  5. CRED 20 m Gridded bathymetry of Johnston Atoll, Pacific Remote Island Areas, Central Pacific (Arc ASCII Format)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Gridded bathymetry (20 m cell size) of the shelf and slope environments of Johnston Atoll, Pacific Remote Island Areas, Central Pacific. Almost complete bottom...

  6. CRED 5 m Gridded bathymetry of Baker Island, Pacific Remote Island Areas, Central Pacific (Arc ASCII Format)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Gridded (5 m cell size) bathymetry of the shelf and slope environments of Baker Island, Pacific Remote Isand Areas, Central Pacific. Almost complete bottom coverage...

  7. CRED 40 m Gridded bathymetry of Baker Island, Pacific Remote Island Areas, Central Pacific (Arc ASCII Format)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Gridded (40 m cell size) bathymetry of the shelf and slope environments of Baker Island, Pacific Remote Island Areas, Central Pacific. Almost complete bottom...

  8. CRED 40 m Gridded bathymetry of Howland Island, Pacific Remote Island Areas, Central Pacific (NetCDF Format)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Gridded (40 m cell size) bathymetry of the shelf and slope environments of Howland Island, Pacific Remote Island Areas, Central Pacific. Almost complete bottom...

  9. CRED Reson 8101 multibeam backscatter data of Johnston Island, Pacific Remote Island Areas, Central Pacific in netCDF format

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Multibeam backscatter imagery extracted from gridded bathymetry of the lagoon, shelf, and slope environments of Palmyra Atoll, Pacific Island Areas, Central Pacific....

  10. CRED 5 m Gridded bathymetry of Johnston Atoll, Pacific Remote Island Areas, Central Pacific (NetCDF Format)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Gridded bathymetry (5 m cell size) of the shelf and slope environments of Johnston Atoll, Pacific Remote Island Areas, Central Pacific. Almost complete bottom...

  11. CRED 5 m Gridded bathymetry of Kingman Reef, Pacific Remote Island Areas, Central Pacific (Arc ASCII Format)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Gridded (5 m cell size) bathymetry of the lagoon, shelf and slope environments of Kingman Reef, Pacific Remote Island Areas, Central Pacific. Almost complete bottom...

  12. Formation of diapiric structure in the deformation zone, central Indian Ocean: A model from gravity and seismic reflection data

    Digital Repository Service at National Institute of Oceanography (India)

    Krishna, K.S.; Rao, D.G.; Neprochnov, Y.P.

    Analyses of bathymetry, gravity and seismic reflection data of the diffusive plate boundary in the central Indian Ocean reveal a new kind of deformed structure besides the well-reported structures of long-wavelength anticlinal basement rises...

  13. CRED 5 m Gridded bathymetry of Baker Island, Pacific Remote Island Areas, Central Pacific (NetCDF Format)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Gridded (5 m cell size) bathymetry of the shelf and slope environments of Baker Island, Pacific Remote Island Areas, Central Pacific. Almost complete bottom coverage...

  14. CRED Reson 8101 multibeam backscatter data of Howland Island, Pacific Remote Island Areas, Central Pacific in GeoTIFF format

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Multibeam backscatter imagery extracted from gridded bathymetry of the shelf and slope environments of Howland Atoll, Pacific Island Areas, Central Pacific. These...

  15. CRED 40 m Gridded bathymetry of Baker Island, Pacific Remote Island Areas, Central Pacific (NetCDF Format)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Gridded (40 m cell size) bathymetry of the shelf and slope environments of Baker Island, Pacific Remote Island Areas, Central Pacific. Almost complete bottom...

  16. CRED Reson 8101 multibeam backscatter data of Johnston Island, Pacific Remote Island Areas, Central Pacific in GeoTIFF format

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Multibeam backscatter imagery extracted from gridded bathymetry of the lagoon, shelf, and slope environments of Palmyra Atoll, Pacific Island Areas, Central Pacific....

  17. Imaging and analysis of evoked excitatory-postsynaptic-calcium-transients by individual presynaptic-boutons of cultured Aplysia sensorimotor synapse.

    Science.gov (United States)

    Malkinson, Guy; Spira, Micha E

    2010-04-01

    The use of the sensory-motor (SN-MN) synapse of the Aplysia gill withdrawal reflex has contributed immensely to the understanding of synaptic transmission, learning and memory acquisition processes. Whereas the majority of the studies focused on analysis of the presynaptic mechanisms, recent studies indicated that as in mammalian synapses, long term potentiation (LTP) formed by Aplysia SN-MN synapse depends on elevation of the postsynaptic free intracellular calcium concentration ([Ca2+](i)). Consistently, injection of the fast calcium chelator BAPTA to the MN prevents the formation of serotonin-induced LTP. Nevertheless, currently there are no published reports that directly examine and document whether evoked synaptic transmission is associated with transient increase in the postsynaptic [Ca2+](i). In the present study we imaged, for the first time, alterations in the postsynaptic [Ca2+](i) in response to presynaptic stimulation and analyzed the underlying mechanisms. Using live imaging of the postsynaptic [Ca2+](i) while monitoring the EPSP, we found that evoked transmitter release generates excitatory postsynaptic calcium concentration transients (EPSCaTs) by two mechanisms: (a) activation of DNQX-sensitive postsynaptic receptors-gated calcium influx and (b) calcium influx through nitrendipine-sensitive voltage-gated calcium channels (VGCCs). Concomitant confocal imaging of presynaptic boutons and EPSCaTs revealed that approximately 86% of the presynaptic boutons are associated with functional synapses.

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

    Institute of Scientific and Technical Information of China (English)

    GUI-LIN LI; MOHAMMAD FAROOQUE; JONAS ISAKSSON; YNGVE OLSSON

    2004-01-01

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

  19. Magnetostratigraphy: the key to a global correlation of the classic Germanic Trias-case study Volpriehausen Formation (Middle Buntsandstein), Central Germany

    Science.gov (United States)

    Szurlies, Michael

    2004-11-01

    An integrated lithostratigraphic-magnetostratigraphic study was carried out in order to provide a magnetic record for the Volpriehausen Formation of the classic Germanic Trias. In its type area of Central Germany, the ˜150-m thick Volpriehausen Formation consists of nine small-scale fining-upward cycles, ranging from about 10 to 20 m in thickness. They can readily be correlated over large parts of the Central European Basin using a combination of cyclic stratigraphy and gamma ray logging. Based on this robust high-resolution lithostratigraphic framework, a precise positioning and verification of paleomagnetic data has been realized. To this end, the classic outcrop Kleines Bodetal and the continuously cored well Bockenem A100 were collected, yielding a total of 361 paleomagnetic samples. From about 87% of them, a characteristic remanence was obtained in both the magnetite-bearing gray lithologies as well as the hematite-bearing red-brown lithologies. The between-site correlation allows the creation of a well-defined composite magnetostratigraphy of the uppermost Bernburg Formation to lowermost Detfurth Formation, encompassing a total of five magnetic polarity intervals, which can be combined unambiguously with a recently established polarity scale for the uppermost Zechstein and Lower Buntsandstein. Moreover, the resulting composite magnetostratigraphy can be correlated with corresponding records from the Continental, Boreal, and Tethyan realms. Thus, the Buntsandstein magnetostratigraphy is important in that it provides valuable anchors to link the Germanic Trias high-resolution lithostratigraphy to the biostratigraphically calibrated Triassic substages.

  20. Early maternal deprivation immunologically primes hippocampal synapses by redistributing interleukin-1 receptor type I in a sex dependent manner.

    Science.gov (United States)

    Viviani, Barbara; Boraso, Mariaserena; Valero, Manuel; Gardoni, Fabrizio; Marco, Eva Maria; Llorente, Ricardo; Corsini, Emanuela; Galli, Corrado Lodovico; Di Luca, Monica; Marinovich, Marina; López-Gallardo, Meritxell; Viveros, Maria-Paz

    2014-01-01

    Challenges experienced in early life cause an enduring phenotypical shift of immune cells towards a sensitised state that may lead to an exacerbated reaction later in life and contribute to increased vulnerability to neurological diseases. Peripheral and central inflammation may affect neuronal function through cytokines such as IL-1. The extent to which an early life challenge induces long-term alteration of immune receptors organization in neurons has not been shown. We investigated whether a single episode of maternal deprivation (MD) on post-natal day (PND) 9 affects: (i) the synapse distribution of IL-1RI together with subunits of NMDA and AMPA receptors; and (ii) the interactions between IL-1RI and the GluN2B subunit of the NMDAR in the long-term, at PND 45. MD increased IL-1RI levels and IL-1RI interactions with GluN2B at the synapse of male hippocampal neurons, without affecting the total number of IL-1RI or NMDAR subunits. Although GluN2B and GluN2A were slightly but not significantly changed at the synapse, their ratio was significantly decreased in the hippocampus of the male rats who had experienced MD; the levels of the GluA1 and GluA2 subunits of the AMPAR were also decreased. These changes were not observed immediately after the MD episode. None of the observed alterations occurred in the hippocampus of the females or in the prefrontal cortex of either sex. These data reveal a long-term, sex-dependent modification in receptor organisation at the hippocampal post-synapses following MD. We suggest that this effect might contribute to priming hippocampal synapses to the action of IL-1β.

  1. Biofilm formation in long-term central venous catheters in children with cancer: a randomized controlled open-labelled trial of taurolidine versus heparin

    DEFF Research Database (Denmark)

    Handrup, Mette Møller; Fuursted, Kurt; Funch, Peter;

    2012-01-01

    Taurolidine has demonstrated inhibition of biofilm formation in vitro. The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters. Forty-eight children with cancer were randomized to catheter locking by heparin (n...... = 22) or taurolidine (n = 26), respectively. After removal, catheters were examined by standardized scanning electron microscopy to assess quantitative biofilm formation. Biofilm was present if morphologically typical structures and bacterial cells were identified. Quantitative and semi......-quantitative cultures were also performed. Biofilm was identified in 23 of 26 catheters from the taurolidine group and 21 of 22 catheters from the heparin group. A positive culture was made of six of the catheters locked with taurolidine and heparin, respectively (p = 0.78). The rate of catheter-related bloodstream...

  2. Palynology, palynofacies and petroleum potential of the Upper Cretaceous-Eocene Matulla, Brown Limestone and Thebes formations, Belayim oilfields, central Gulf of Suez, Egypt

    Science.gov (United States)

    El Diasty, W. Sh.; El Beialy, S. Y.; Abo Ghonaim, A. A.; Mostafa, A. R.; El Atfy, H.

    2014-07-01

    Palynological, palynofacies and organic geochemical results of 46 samples retrieved from the Upper Cretaceous - Eocene Matulla, Brown Limestone and Thebes formations, Belayim oilfields, central Gulf of Suez, Egypt are presented. The two latter formations are not dated palynologically as their lithology is not promising for palynological yield. However the Matulla Formation is dated as Turonian-Santonian age, based on the combined evidence of pollen and dinocysts. Palynofacies analysis carried out under both transmitted and fluorescent microscopy indicated that both the Thebes and Brown Limestone formations are deposited under a distal suboxic-anoxic environment. On the other hand, the Turonian-Santonian Matulla Formation supported the existence of a marginal marine deposition under dysoxic-anoxic basin to proximal suboxic-anoxic shelf environments. Rock-Eval pyrolysis and TOC results indicated that most of the studied formations are thermally immature to marginally mature and have a good petroleum potential. They are organically-rich in both oil- and gas-prone kerogen Type-II and II/III, deposited under marine reducing conditions favorable for hydrocarbon generation and expulsion.

  3. Dendrodendritic Synapses in the Mouse Olfactory Bulb External Plexiform Layer

    Science.gov (United States)

    Bartel, Dianna L.; Rela, Lorena; Hsieh, Lawrence; Greer, Charles A.

    2014-01-01

    Odor information relayed by olfactory bulb projection neurons, mitral and tufted cells (M/T), is modulated by pairs of reciprocal dendrodendritic synaptic circuits in the external plexiform layer (EPL). Interneurons, which are accounted for largely by granule cells, receive depolarizing input from M/T dendrites and in turn inhibit current spread in M/T dendrites via hyperpolarizing reciprocal dendrodendritic synapses. Because the location of dendrodendritic synapses may significantly affect the cascade of odor information, we assessed synaptic properties and density within sublaminae of the EPL and along the length of M/T secondary dendrites. In electron micrographs the M/T to granule cell synapse appeared to predominate and were equivalent in both the outer and inner EPL. However, the dendrodendritic synapses from granule cell spines onto M/T dendrites, were more prevalent in the outer EPL. In contrast, individual gephyrin-IR puncta, a postsynaptic scaffolding protein at inhibitory synapses used here as a proxy for the granule to M/T dendritic synapse was equally distributed throughout the EPL. Of significance to the organization of intrabulbar circuits, gephyrin-IR synapses are not uniformly distributed along M/T secondary dendrites. Synaptic density, expressed as a function of surface area, increases distal to the cell body. Furthermore, the distributions of gephyrin-IR puncta are heterogeneous and appear as clusters along the length of the M/T dendrites. Consistent with computational models, our data suggest that temporal coding in M/T cells is achieved by precisely located inhibitory input and that distance from the soma is compensated with an increase in synaptic density. PMID:25420934

  4. IgSF8: a developmentally and functionally regulated cell adhesion molecule in olfactory sensory neuron axons and synapses

    OpenAIRE

    Ray, Arundhati; Treloar, Helen B.

    2012-01-01

    Here, we investigated an Immunoglobulin (Ig) superfamily protein IgSF8 which is abundantly expressed in olfactory sensory neuron (OSN) axons and their developing synapses. We demonstrate that expression of IgSF8 within synaptic neuropil is transitory, limited to the period of glomerular formation. Glomerular expression decreases after synaptic maturation and compartmental glomerular organization is achieved, although expression is maintained at high levels within the olfactory nerve layer (ON...

  5. Essential Role for Vav GEFs in Brain-derived Neurotrophic Factor (BDNF)-induced Dendritic Spine Growth and Synapse Plasticity

    OpenAIRE

    Hale, Carly F.; Dietz, Karen C.; Varela, Juan A.; Wood, Cody B.; Zirlin, Benjamin C.; Leah S. Leverich; Greene, Robert W.; Cowan, Christopher W.

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB, regulate a wide range of cellular processes, including dendritic spine formation and functional synapse plasticity. However, the signaling mechanisms that link BDNF-activated TrkB to F-actin remodeling enzymes and dendritic spine morphological plasticity remain poorly understood. We report here that BDNF/TrkB signaling in neurons activates the Vav family of Rac/RhoA guanine nucleotide exchange factors (GEFs) through a no...

  6. Mother Centriole Distal Appendages Mediate Centrosome Docking at the Immunological Synapse and Reveal Mechanistic Parallels with Ciliogenesis.

    Science.gov (United States)

    Stinchcombe, Jane C; Randzavola, Lyra O; Angus, Karen L; Mantell, Judith M; Verkade, Paul; Griffiths, Gillian M

    2015-12-21

    Cytotoxic T lymphocytes (CTLs) are highly effective serial killers capable of destroying virally infected and cancerous targets by polarized release from secretory lysosomes. Upon target contact, the CTL centrosome rapidly moves to the immunological synapse, focusing microtubule-directed release at this point [1-3]. Striking similarities have been noted between centrosome polarization at the synapse and basal body docking during ciliogenesis [1, 4-8], suggesting that CTL centrosomes might dock with the plasma membrane during killing, in a manner analogous to primary cilia formation [1, 4]. However, questions remain regarding the extent and function of centrosome polarization at the synapse, and recent reports have challenged its role [9, 10]. Here, we use high-resolution transmission electron microscopy (TEM) tomography analysis to show that, as in ciliogenesis, the distal appendages of the CTL mother centriole contact the plasma membrane directly during synapse formation. This is functionally important as small interfering RNA (siRNA) targeting of the distal appendage protein, Cep83, required for membrane contact during ciliogenesis [11], impairs CTL secretion. Furthermore, the regulatory proteins CP110 and Cep97, which must dissociate from the mother centriole to allow cilia formation [12], remain associated with the mother centriole in CTLs, and neither axoneme nor transition zone ciliary structures form. Moreover, complete centrosome docking can occur in proliferating CTLs with multiple centriole pairs. Thus, in CTLs, centrosomes dock transiently with the membrane, within the cell cycle and without progression into ciliogenesis. We propose that this transient centrosome docking without cilia formation is important for CTLs to deliver rapid, repeated polarized secretion directed by the centrosome.

  7. Stabilization of memory States by stochastic facilitating synapses.

    Science.gov (United States)

    Miller, Paul

    2013-12-06

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

  8. Formation, production and viability of oospores of Phytophthora infestans from potato and Solanum demissum in the Toluca Valley, central Mexico

    NARCIS (Netherlands)

    Flier, W.G.; Grünwald, N.J.; Fry, W.E.; Turkensteen, L.J.

    2001-01-01

    Aspects of the ecology of oospores of Phytophthora infestans were studied in the highlands of central Mexico. From an investigation of a random sample of strains, it was found that isolates differed in their average capability to form oospores when engaged in compatible pairings. Most crosses produc

  9. Sedimentology and Sequence Stratigraphy of the Lower Cretaceous Fortress Mountain and Torok Formations Exposed Along the Siksikpuk River, North-Central Alaska

    Science.gov (United States)

    Houseknecht, David W.; Schenk, Christopher J.; Wartes, Marwan A.

    2007-01-01

    An exposure of the Lower Cretaceous Fortress Mountain and Torok Formations along the Siksikpuk River in north-central Alaska provides a rare opportunity to observe the stratigraphic contact between these two formations and to interpret the depositional facies and sequence stratigraphy of the exposed strata. The Fortress Mountain Formation at the base of the measured section includes braided-fluvial and coastal-plain facies deposited in a lowstand-systems tract, and an overlying succession of mostly shallow marine facies deposited in the basal part of a transgressive-systems tract. The overlying Torok Formation includes a thick, upward-deepening succession of marine-shelf to marine-slope facies deposited in the upper part of the transgressive-systems tract. The upper part of the section includes marine-slope and incised-slope-channel turbidite deposits of the Torok Formation, interpreted as a highstand-systems tract. Consideration of the balance between accommodation and sediment flux inferred from the sequence-stratigraphic analysis suggests that both tectonics and eustasy may have influenced deposition of the lowstand-systems and transgressive-systems tracts. In contrast, the highstand-systems tract may have been primarily influenced by progradation of a regional sediment-dispersal system and by subsidence induced by sediment loading.

  10. Amphibian, reptilian, and avian remains from the Fox Hills Formation (Maastrichtian): Shoreline and estuarine deposits of the Pierre Sea in south-central North Dakota

    Science.gov (United States)

    Hoganson, J.W.; Erickson, J.M.; Holland, F.D.

    2007-01-01

    Although vertebrate fossils, except for fish, are not common in the Maastrichtian Fox Hills Formation, amphibian, reptilian, and avian remains have been recovered at several localities in south-central North Dakota from shoreline facies of the retreating Pierre-Fox Hills seaway. This mixed fauna of aquatic, terrestrial, and marine taxa provides insight into the composition of coastal communities and habitats at the interface between the Hell Creek delta and the Western Interior Seaway. The delta-platform aquatic paleocommunity is represented by the efficient swimming salamanders Opistho- trition kayi and Lisserpeton bairdi, the carnivorous soft-shelled turtle "Aspideretes" sensu lato, the underwater piscivorous predator Champsosaurus laramiensis, and the large, predatory crocodile IBorealosuchus. Terrestrial areas were inhabited by the tortoise-like Basilemys and the predatory dinosaurs Tyrannosaurus and cf. Saurornit- holestes. Birds occupied niches in the warm-temperate to subtropical, forested delta platform and shoreline areas. These nonmarine taxa in the Fox Hills Formation indicate that the geographic range of these animals extended to shoreline areas of the Western Interior Seaway. The toxochelyid turtle Lophochelys and the ambush predators Mosasaurus dekayi and IPlioplatecarpus resided in the shallow marine and estuarine habitats. These taxa and marine fish taxa reported earlier indicate that normal marine conditions in south- central North Dakota persisted into the latest Late Cretaceous in comparison with coeval Hell Creek Formation sites more distal from the Western Interior Seaway. ?? 2007 The Geological Society of America. All rights reserved.

  11. Nuclear envelope lamin-A couples actin dynamics with immunological synapse architecture and T cell activation.

    Science.gov (United States)

    González-Granado, José M; Silvestre-Roig, Carlos; Rocha-Perugini, Vera; Trigueros-Motos, Laia; Cibrián, Danay; Morlino, Giulia; Blanco-Berrocal, Marta; Osorio, Fernando G; Freije, José M P; López-Otín, Carlos; Sánchez-Madrid, Francisco; Andrés, Vicente

    2014-04-22

    In many cell types, nuclear A-type lamins regulate multiple cellular functions, including higher-order genome organization, DNA replication and repair, gene transcription, and signal transduction; however, their role in specialized immune cells remains largely unexplored. We showed that the abundance of A-type lamins was almost negligible in resting naïve T lymphocytes, but was increased upon activation of the T cell receptor (TCR). The increase in lamin-A was an early event that accelerated formation of the immunological synapse between T cells and antigen-presenting cells. Polymerization of F-actin in T cells is a critical step for immunological synapse formation, and lamin-A interacted with the linker of nucleoskeleton and cytoskeleton (LINC) complex to promote F-actin polymerization. We also showed that lamin-A expression accelerated TCR clustering and led to enhanced downstream signaling, including extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, as well as increased target gene expression. Pharmacological inhibition of the ERK pathway reduced lamin-A-dependent T cell activation. Moreover, mice lacking lamin-A in immune cells exhibited impaired T cell responses in vivo. These findings underscore the importance of A-type lamins for TCR activation and identify lamin-A as a previously unappreciated regulator of the immune response.

  12. Functional imaging of single synapses in brain slices.

    Science.gov (United States)

    Oertner, Thomas G

    2002-11-01

    The strength of synaptic connections in the brain is not fixed, but can be modulated by numerous mechanisms. Traditionally, electrophysiology has been used to characterize connections between neurons. Electrophysiology typically reports the activity of populations of synapses, while most mechanisms of plasticity are thought to operate at the level of single synapses. Recently, two-photon laser scanning microscopy has enabled us to perform optical quantal analysis of individual synapses in intact brain tissue. Here we introduce the basic principle of the two-photon microscope and discuss its main differences compared to the confocal microscope. Using calcium imaging in dendritic spines as an example, we explain the advantages of simultaneous dual-dye imaging for quantitative calcium measurements and address two common problems, dye saturation and background fluorescence subtraction.

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

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

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

  14. Relating structure and function of inner hair cell ribbon synapses.

    Science.gov (United States)

    Wichmann, C; Moser, T

    2015-07-01

    In the mammalian cochlea, sound is encoded at synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Each SGN receives input from a single IHC ribbon-type active zone (AZ) and yet SGNs indefatigably spike up to hundreds of Hz to encode acoustic stimuli with submillisecond precision. Accumulating evidence indicates a highly specialized molecular composition and structure of the presynapse, adapted to suit these high functional demands. However, we are only beginning to understand key features such as stimulus-secretion coupling, exocytosis mechanisms, exo-endocytosis coupling, modes of endocytosis and vesicle reformation, as well as replenishment of the readily releasable pool. Relating structure and function has become an important avenue in addressing these points and has been applied to normal and genetically manipulated hair cell synapses. Here, we review some of the exciting new insights gained from recent studies of the molecular anatomy and physiology of IHC ribbon synapses.

  15. Microglial interactions with synapses are modulated by visual experience.

    Directory of Open Access Journals (Sweden)

    Marie-Ève Tremblay

    Full Text Available Microglia are the immune cells of the brain. In the absence of pathological insult, their highly motile processes continually survey the brain parenchyma and transiently contact synaptic elements. Aside from monitoring, their physiological roles at synapses are not known. To gain insight into possible roles of microglia in the modification of synaptic structures, we used immunocytochemical electron microscopy, serial section electron microscopy with three-dimensional reconstructions, and two-photon in vivo imaging to characterize microglial interactions with synapses during normal and altered sensory experience, in the visual cortex of juvenile mice. During normal visual experience, most microglial processes displayed direct apposition with multiple synapse-associated elements, including synaptic clefts. Microglial processes were also distinctively surrounded by pockets of extracellular space. In terms of dynamics, microglial processes localized to the vicinity of small and transiently growing dendritic spines, which were typically lost over 2 d. When experience was manipulated through light deprivation and reexposure, microglial processes changed their morphology, showed altered distributions of extracellular space, displayed phagocytic structures, apposed synaptic clefts more frequently, and enveloped synapse-associated elements more extensively. While light deprivation induced microglia to become less motile and changed their preference of localization to the vicinity of a subset of larger dendritic spines that persistently shrank, light reexposure reversed these behaviors. Taken together, these findings reveal different modalities of microglial interactions with synapses that are subtly altered by sensory experience. These findings suggest that microglia may actively contribute to the experience-dependent modification or elimination of a specific subset of synapses in the healthy brain.

  16. Isotopic and fluid-inclusion constraints on the formation of polymetallic vein deposits in the central Argentinian Patagonia

    Science.gov (United States)

    Dejonghe, Léon; Darras, Benoît; Hughes, Guillermo; Muchez, Philippe; Scoates, James S.; Weis, Dominique

    2002-03-01

    The lead isotope compositions of galena and the fluid-inclusion systematics of nine barite-bearing polymetallic (Au, Ag, Pb, Zn) deposits of the central Argentinian Patagonia (Chubut and Rio Negro provinces) have been investigated to constrain the compositions and sources of the mineralizing fluids. Most of the deposits occur as veins, with less common wall-rock disseminations and/or stockworks, and are low-sulfidation epithermal deposits hosted in Jurassic volcanic rocks. Fluid-inclusion homogenization temperatures (Th) from quartz and sphalerite from the deposits fall within the range of 100-300 °C, with the highest measured average temperatures for the most eastern deposits (Mina Angela - 298 °C; Cañadón Bagual - 343 °C). The salinities of the hydrothermal fluids at all deposits were low to moderate (≤10.4 equiv. wt% NaCl). Three groups of ore deposits can be defined on the basis of 206Pb/204Pb ratios for galena and these show a general decrease from west to east (from 18.506 to 18.000). The central Argentinian Patagonia deposits have distinctly less radiogenic lead isotope compositions than similar deposits from Peru and Chile, except for the porphyry copper deposits of central and southern Peru. Galena from the Mina Angela deposit is characterized by very low radiogenic lead isotope compositions (18.000Precambrian basement. The geographic trend in lead isotope compositions of both galena and whole rocks indicates a crustal contribution which increases eastwards, also reflected in the strontium-neodymium isotope systematics of the host lavas. Finally, due to the lack of precise age determinations for the central Patagonian polymetallic deposits, a potential link with Andean porphyry copper systems remains an open question.

  17. TRANSPORT DEVELOPMENT IN CHINA AND CENTRAL ASIA IN THE CONTEXT FORMATION OF TRANS-EURASIAN TRANSPORT CORRIDORS

    Directory of Open Access Journals (Sweden)

    E. V. Savkovic

    2011-01-01

    Full Text Available Abstract: In accordance with its economic interests, China advances coherent policy for development of transport infrastructure both on its own territory and in neighbouring countries. Throughout the last two decades it facilitated the widening trade activity and broader economic cooperation between Xinjiang Uygur Autonomous Region and Central Asian states. Its further development foresees a network of Trans-Eurasian links, which will connect China not only with all nearby countries, but with European region as well.

  18. Formation of relativistic non-viscous fluid in central collisions of protons with energy 0.8 TeV with photoemulsion nuclei

    CERN Document Server

    Abdurakhmanov, U U

    2013-01-01

    By the methods of mathematical statistics we test a qualitative prediction of the old theory of relativistic hydrodynamics non-viscous liquid which can be used as a part of the process of hadronization within the modern hydrodynamical approach for the description of the quark-gluon plasma. Experimental data on the interaction of protons with the energies of 0.8 TeV with emulsion nuclei are used. Results do not contradict the formation of relativistic ideal non-viscous liquid in rare central collisions.

  19. Electrolyte-gated organic synapse transistor interfaced with neurons

    CERN Document Server

    Desbief, Simon; Casalini, Stefano; Guerin, David; Tortorella, Silvia; Barbalinardo, Marianna; Kyndiah, Adrica; Murgia, Mauro; Cramer, Tobias; Biscarini, Fabio; Vuillaume, Dominique

    2016-01-01

    We demonstrate an electrolyte-gated hybrid nanoparticle/organic synapstor (synapse-transistor, termed EGOS) that exhibits short-term plasticity as biological synapses. The response of EGOS makes it suitable to be interfaced with neurons: short-term plasticity is observed at spike voltage as low as 50 mV (in a par with the amplitude of action potential in neurons) and with a typical response time in the range of tens milliseconds. Human neuroblastoma stem cells are adhered and differentiated into neurons on top of EGOS. We observe that the presence of the cells does not alter short-term plasticity of the device.

  20. Meet the players: local translation at the synapse

    Directory of Open Access Journals (Sweden)

    Sandra eFernandez Moya

    2014-11-01

    Full Text Available It is widely believed that activity-dependent synaptic plasticity is the basis for learning and memory. Both processes are dependent on new protein synthesis at the synapse. Here, we describe a mechanism how dendritic mRNAs are transported and subsequently translated at activated synapses. Furthermore, we present the players involved in the regulation of local dendritic translation upon neuronal stimulation and their molecular interplay that maintain local proteome homeostasis. Any dysregulation causes several types of neurological disorders including muscular atrophies, cancers, neuropathies, neurodegenerative and cognitive disorders.

  1. A New Efficient-Silicon Area MDAC Synapse

    Directory of Open Access Journals (Sweden)

    Zied Gafsi

    2007-01-01

    Full Text Available Using the binary representation in the Multiplier digital to analog converter (MDAC synapse designs have crucial drawbacks. Silicon area of transistors, constituting the MDAC circuit, increases exponentially according to the number of bits. This latter is generated by geometric progression of common ratio equal to 2. To reduce this exponential increase to a linear growth, a new synapse named Arithmetic MDAC (AMDAC is designed. It functions with a new representation based on arithmetic progressions. Using the AMS CMOS 0.35µm technology the silicon area is reduced by a factor of 40%.

  2. Paleoecology of Benthic Foraminifera in Coral Reefs Recorded in the Jurassic Tuwaiq Mountain Formation of the Khashm Al-Qaddiyah Area, Central Saudi Arabia

    Institute of Scientific and Technical Information of China (English)

    Mohamed Youssef; Abdelbaset S El-Sorogy

    2015-01-01

    Thirty three benthic foraminiferal species belong to 23 genera and 16 families have been recorded from the coral reefs of the Callovian Tuwaiq Formation, Khashm Al-Qaddiyah area, Central Saudi Arabia. Three species:Astacolus qaddiyahensis, Nodosaria riyadhensis, Siderolites jurassica are believed to be new. Nearly all identified foraminifera are of Atlantic-Miditeranean affinity. The fo-raminiferal assemblage recorded in the present work is mixed of open marine, moderately deep ma-rine conditions associations and shallow to deep lagoon. The reefal part of upper Twiaq Formation may have been deposited in shallow water of lower to middle shelf depth (20–50 m) as indicated by abundant corals and benthic foraminifera. The coral fauna and bearing benthic foraminifera indi-cated moderate water energy.

  3. Conodonts, stratigraphy, and relative sea-level changes of the tribes hill formation (lower ordovician, east-central New York)

    Science.gov (United States)

    Landing, E.D.; Westrop, S.R.; Knox, L.A.

    1996-01-01

    Tremadocian onlap is recorded by the Tribes Hill Formation. The formation is a lower Lower Ordovician (upper conodont Fauna B Interval(?)- Rossodus manitouensis Zone) depositional sequence that unconformably overlies the Upper Cambrian Little Falls Formation. Depositional environments and stratigraphy indicate that the Tribes Hill was deposited on a wave-, not tide-, dominated shelf and that a uniform, 'layer-cake' stratigraphy is present. The deepening-shoaling sequence of the Tribes Hill includes the: 1) Sprakers Member (new; peritidal carbonate and overlying tempestite limestone and shale); 2) Van Wie Member (new; subtidal shale and limestone); 3) Wolf Hollow Member (revised; massive carbonates with thrombolitic cap); and 4) Canyon Road Member (new; glauconitic limestone and overlying evaporitic dolostone). The shoaling half-cycle of the Tribes Hill is older than a shoaling event in western Newfoundland, and suggests epeirogenic factors in earliest Ordovician sea-level change in east Laurentia. Conodont and trilobite biofacies track lithofacies, and Rossodus manitouensis Zone conodonts and Bellefontia Biofacies trilobites appear in the distal, middle Tribes Hill Formation. Twenty-four conodont species are illustrated. Ansella? protoserrata new species, lapetognathus sprakersi new species, Leukorhinion ambonodes new genus and species, and Laurentoscandodus new genus are described.

  4. Ordovician and Silurian Phi Kappa and Trail Creek formations, Pioneer Mountains, central Idaho; stratigraphic and structural revisions, and new data on graptolite faunas

    Science.gov (United States)

    Dover, James H.; Berry, William B.N.; Ross, Reuben James

    1980-01-01

    clastic rocks reported in previously measured sections of the Phi Kappa, as well as the sequence along Phi Kappa Creek from which the name originates, are excluded from the Phi Kappa as revised and are reassigned to two structural plates of Mississippian Copper Basin Formation; other strata now excluded from the formation are reassigned to the Trail Creek Formation and to an unnamed Silurian and Devonian unit. As redefined, the Phi Kappa Formation is only about 240 m thick, compared with the 3,860 m originally estimated, and it occupies only about 25 percent of the outcrop area previously mapped in 1930 by H. G. Westgate and C. P. Ross. Despite this drastic reduction in thickness and the exclusion of the rocks along Phi Kappa Creek, the name Phi Kappa is retained because of widely accepted prior usage to denote the Ordovician graptolitic shale facies of central Idaho, and because the Phi Kappa Formation as revised is present in thrust slices on Phi Kappa Mountain, at the head of Phi Kappa Creek. The lithic and faunal consistency of this unit throughout the area precludes the necessity for major facies telescoping along individual faults within the outcrop belt. However, tens of kilometers of tectonic shortening seems required to juxtapose the imbricated Phi Kappa shale facies with the Middle Ordovician part of the carbonate and quartzite shale sequence of east central Idaho. The shelf rocks are exposed in the Wildhorse structural window of the northeastern Pioneer Mountains, and attain a thickness of at least 1,500 m throughout the region north and east of the Pioneer Mountains. The Phi Kappa is in direct thrust contact on intensely deformed medium- to high-grade metamorphic equivalents of the same shelf sequence in the Pioneer window at the south end of the Phi Kappa-Trail Creek outcrop belt. Along East Pass, Big Lake, and Pine Creeks, north of the Pioneer Mountains, some rocks previously mapped as Ramshorn Slate are lithologically and faunally equivalent to the P

  5. Biofilm formation in long-term central venous catheters in children with cancer: a randomized controlled open-labelled trial of taurolidine versus heparin.

    Science.gov (United States)

    Handrup, Mette Møller; Fuursted, Kurt; Funch, Peter; Møller, Jens Kjølseth; Schrøder, Henrik

    2012-10-01

    Taurolidine has demonstrated inhibition of biofilm formation in vitro. The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters. Forty-eight children with cancer were randomized to catheter locking by heparin (n = 22) or taurolidine (n = 26), respectively. After removal, catheters were examined by standardized scanning electron microscopy to assess quantitative biofilm formation. Biofilm was present if morphologically typical structures and bacterial cells were identified. Quantitative and semi-quantitative cultures were also performed. Biofilm was identified in 23 of 26 catheters from the taurolidine group and 21 of 22 catheters from the heparin group. A positive culture was made of six of the catheters locked with taurolidine and heparin, respectively (p = 0.78). The rate of catheter-related bloodstream infections (CRBSI) was 0.1 per 1000 catheter-days using taurolidine and 0.9 per 1000 catheter-days using heparin (p = 0.03). This randomized trial confirmed that the use of taurolidine as catheter-lock compared with heparin reduced the rate of CRBSIs; this reduction was not related to a reduction in the intraluminal biofilm formation and the rate of bacterial colonization detected by scanning electron microscopy in the two groups.

  6. Palaeoecological Analysis of Paleogene Shahejie Formation in North Central Raoyang Sag of Central Hebei Depression%冀中坳陷饶阳凹陷中北部古近纪沙河街组古生态分析

    Institute of Scientific and Technical Information of China (English)

    袭著纲; 国景星; 赵晓颖

    2011-01-01

    According to the identification of sporopollen fossils from the 42 wells in north central Raoyang Sag, Central Hebei Depression, the palaeoecological classification of palynoflora in Shahejie Formation was discussed; one palynological assemblage with high proportion of QuercoiditesUlmi pollenites was recognized, and five sub-assemblages were established, including Ephedripites-Ulmoideipites sub-assemblages, Pinacear-Ephedripites-Podocarpidites sub-assemblages, Ephedripites-Pinaceae-Labitricolpiles sub-assemblages, Pinaceae-Podocarpidites sub-assemblages and Piceaepollenites-Ephedripites-Cedripites sub-assemblages. Contrast to the palynological assemblage of offshore Shahejie Formation in Huanghua Depression, the palaeoecological change of Shahejie Formation in north central Raoyang Sag was discussed according to the different characteristics of palynological assemblage during various periods. The results showed that the proportion of mesic sporopollen was stable, with an average of 70% or higher, while there was a little change for the proportion of xerophilous and hygrophilous sporopollen; vegetation pattern during the late member 4 of Shahejie Formation was mainly evergreen and deciduous broad-leaved forest in semi-arid warm temperate climate; vegetation pattern during the member 3 of Shahejie Formation was mainly coniferous forest, and secondly broad-leaved forest in sub-humid sub-tropical climate; vegetation pattern during the member 2 of Shahejie Formation was mainly coniferous and broad-leaf forest in semi-arid sub-tropical climate; vegetation pattern during the member 1 of Shahejie Formation was mainly coniferous and broad-leaf forest with an increase of hygrophilous herbaceous vegetation in humid sub-tropical climate.%基于对冀中坳陷饶阳凹陷中北部42口井孢粉化石的鉴定,讨论了该区沙河街组孢粉植物群的古生态分类,建立了一个Quercoidites-Ulmipollenites高比例组合和5

  7. New views of the human NK cell immunological synapse: recent advances enabled by super- and high- resolution imaging techniques

    Directory of Open Access Journals (Sweden)

    Emily M. Mace

    2013-01-01

    Full Text Available Imaging technology has undergone rapid growth with the development of super resolution microscopy, which enables resolution below the diffraction barrier of light (~200 nm. In addition, new techniques for single molecule imaging are being added to the cell biologist’s arsenal. Immunologists have exploited these techniques to advance understanding of NK biology, particularly that of the immune synapse. The immune synapse’s relatively small size and complex architecture combined with its exquisitely controlled signaling milieu have made it a challenge to visualize. In this review we highlight and discuss new insights into NK cell immune synapse formation and regulation revealed by cutting edge imaging techniques, including super resolution microscopy and high resolution total internal reflection microscopy and Förster resonance energy transfer.

  8. Differential mechanisms of transmission at three types of mossy fiber synapse.

    Science.gov (United States)

    Toth, K; Suares, G; Lawrence, J J; Philips-Tansey, E; McBain, C J

    2000-11-15

    The axons of the dentate gyrus granule cells, the so-called mossy fibers, innervate their inhibitory interneuron and pyramidal neuron targets via both anatomically and functionally specialized synapses. Mossy fiber synapses onto inhibitory interneurons were comprised of either calcium-permeable (CP) or calcium-impermeable (CI) AMPA receptors, whereas only calcium-impermeable AMPA receptors existed at CA3 principal neuron synapses. In response to brief trains of high-frequency stimuli (20 Hz), pyramidal neuron synapses invariably demonstrated short-term facilitation, whereas interneuron EPSCs demonstrated either short-term facilitation or depression. Facilitation at all CI AMPA synapses was voltage independent, whereas EPSCs at CP AMPA synapses showed greater facilitation at -20 than at -80 mV, consistent with a role for the postsynaptic unblock of polyamines. At pyramidal cell synapses, mossy fiber EPSCs possessed marked frequency-dependent facilitation (commencing at stimulation frequencies >0.1 Hz), whereas EPSCs at either type of interneuron synapse showed only moderate frequency-dependent facilitation or underwent depression. Presynaptic metabotropic glutamate receptors (mGluRs) decreased transmission at all three synapse types in a frequency-dependent manner. However, after block of presynaptic mGluRs, transmission at interneuron synapses still did not match the dynamic range of EPSCs at pyramidal neuron synapses. High-frequency stimulation of mossy fibers induced long-term potentiation (LTP), long-term depression (LTD), or no change at pyramidal neuron synapses, interneuron CP AMPA synapses, and CI AMPA synapses, respectively. Induction of LTP or LTD altered the short-term plasticity of transmission onto both pyramidal cells and interneuron CP AMPA synapses by a mechanism consistent with changes in release probability. These data reveal differential mechanisms of transmission at three classes of mossy fiber synapse made onto distinct targets.

  9. Suppression of Star Formation in the central 200 kpc of a z = 1.4 Galaxy Cluster

    CERN Document Server

    Grutzbauch, Ruth; Jørgensen, Inger; Varela, Jesus

    2012-01-01

    We present the results of an extended narrow-band H{\\alpha} study of the massive galaxy cluster XMMU J2235.3-2557 at z = 1.39. This paper represents a follow up study to our previous investigation of star-formation in the cluster centre, extending our analysis out to a projected cluster radius of 1.5 Mpc. Using the Near InfraRed Imager and Spectrograph (NIRI) on Gemini North we obtained deep H narrow-band imaging corresponding to the rest-frame wavelength of H{\\alpha} at the cluster's redshift. We identify a total of 163 potential cluster members in both pointings, excluding stars based on their near-IR colours derived from VLT/HAWK-I imaging. Of these 163 objects 14 are spectroscopically confirmed cluster members, and 20% are excess line-emitters. We find no evidence of star formation activity within a radius of 200 kpc of the brightest cluster galaxy in the cluster core. Dust-corrected star formation rates (SFR) of excess emitters outside this cluster quenching radius, RQ \\sim 200 kpc, are on average = 2.7...

  10. The UK Infrared Telescope M33 monitoring project. II. The star formation history in the central square kiloparsec

    CERN Document Server

    Javadi, Atefeh; Mirtorabi, Mohammad Taghi

    2011-01-01

    We have conducted a near-infrared monitoring campaign at the UK InfraRed Telescope (UKIRT), of the Local Group spiral galaxy M33 (Triangulum). The main aim was to identify stars in the very final stage of their evolution, and for which the luminosity is more directly related to the birth mass than the more numerous less-evolved giant stars that continue to increase in luminosity. In this second paper of the series, we construct the birth mass function and hence derive the star formation history. The star formation rate has varied between ~0.002 and 0.007 M ̇ yr^-1 kpc^-2. We give evidence of two epochs of a star formation rate enhanced by a factor of a few -- one that happened \\geq 6 Gyr ago and produced \\geq 80% of the total mass in stars, and one around 250 Myr ago that lasted ~ 200 Myr and formed \\leq 6% of the mass in stars. We construct radial and azimuthal distributions in the image plane and in the galaxy plane for populations associated with old first-ascent red giant branch (RGB) stars, intermedia...

  11. Significant melting of ice-wedges and formation of thermocirques on hill-slopes of thermokarst lakes in Central Yakutia (Siberia)

    Science.gov (United States)

    Séjourné, Antoine; Costard, François; Gargani, Julien; Fedorov, Alexander; Skorve, Johnny

    2013-04-01

    On Earth, permafrost containing a high ice volume (referred as ice-rich) are sensible to climate change, they have been regionally degraded (thermokarst) during the early Holocene climatic optimum forming numerous thermokarst lakes in Central Yakutia (eastern Siberia). Recent temperature increases in the Arctic and Subarctic have been significantly greater than global averages. The frequency and magnitude of terrain disturbances associated with thawing permafrost are increasing in these regions and are thought to intensify in the future. Therefore, understand how is the current development of thermokarst is a critical question. Here, we describe the significant melting of ice-wedges on slopes of thermokarst lakes that leads to formation of amphitheatrical hollows referred as thermocirques. The evolution of thermocirques in Central Yakutia has been little studied and analyzing their formation could help to understand the recent thermokarst in relation to climate change in Central Yakutia. We studied the thermocirques at two scales: (i) field surveys of different thermocirques in July 2009-2010 and October 2012 to examine the processes and origin of melting of ice-wedges and; (ii) photo-interpretation of time series of satellite images (KH-9 Hexagon images of 6-9 m/pixel and GeoEye images of 50 cm/pixel) to study the temporal evolution of thermocirques. The melting of ground-ice on the scarp of thermocirque triggers falls and small mud-flows that induce the retreat of the scarp parallel to itself. Based on field studies and on GeoEye image comparison, we show that their rate of retrogressive growth is 1-2 m/year. On the hill-slopes of lakes, the thermokarst could be initiated by different processes that lead to the uncover and then melting of ice-wedges: thermal erosion by the waves of the ice-rich bluff; active-layer detachment (a form of slope failure linked to detachment of the seasonally thawed upper ground); flowing of water on the slope (precipitation) or

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

    DEFF Research Database (Denmark)

    Lansner, John; Lehmann, Torsten

    1992-01-01

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

  13. Efficient supervised learning in networks with binary synapses

    CERN Document Server

    Baldassi, Carlo; Brunel, Nicolas; Zecchina, Riccardo

    2007-01-01

    Recent experimental studies indicate that synaptic changes induced by neuronal activity are discrete jumps between a small number of stable states. Learning in systems with discrete synapses is known to be a computationally hard problem. Here, we study a neurobiologically plausible on-line learning algorithm that derives from Belief Propagation algorithms. We show that it performs remarkably well in a model neuron with binary synapses, and a finite number of `hidden' states per synapse, that has to learn a random classification task. Such system is able to learn a number of associations close to the theoretical limit, in time which is sublinear in system size. This is to our knowledge the first on-line algorithm that is able to achieve efficiently a finite number of patterns learned per binary synapse. Furthermore, we show that performance is optimal for a finite number of hidden states which becomes very small for sparse coding. The algorithm is similar to the standard `perceptron' learning algorithm, with a...

  14. A New Mechanism for Neuron-synapse Maturation Discovered

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ A group of CAS scientists recently made a research breakthrough in the development of synapse, the key structure of the nervous system that transmits signals from one nerve cell to another. This work was reported as a cover story in the May 4th issue of prestigious journal Neuron.

  15. Stratigraphical and sedimentary characters of Late Cretaceous formations outcropping in central and southern Tunisia, Tethyan southern margin

    Science.gov (United States)

    Jaballah, J.; Negra, M. H.

    2016-12-01

    The main goals of our approach are to identify some local to global events in relation with tectonic instabilities and/or sea-level changes, occurring during the deposition of Cenomanian-Coniacian carbonate series in Tunisia. Several sections surveyed in Central-Southern Tunisia, along a North-South transect extending from Sidi Bouzid to Gafsa area, show that the Cenomanian-Coniacian series include rudist-rich facies associated to other shallow marine to deeper deposits. Detailed sedimentological studies supported by new biostratigraphical data (provided by H. Bismuth, oral comm.), have allowed to add more precisions on the lithostratigraphical stacking and thus on the Central Tunisia Stratigraphic Chart. Some carbonate members such as the Middle Turonian Bireno and the Late Turonian-Coniacian Douleb have been identified in certain localities for the first time. Indeed, these members were never described before at Jebel el Kébar and Jebel Meloussi. In the Sidi Bouzid area, especially at Jebel el Kébar, the Cenomanian-Coniacian carbonate members are characterized by frequent and rapid changes, related to the existence of highs (horsts, probably) and depressed depositional domains (grabens, probably), which formed during the deposition of the two lower Units of the Middle Turonian Bireno Member. Above, the Late Turonian to Coniacian deposits, have tended to seal the irregular paleotopography affected, at least locally, by Middle Turonian extensional tectonic movements. They could be related, in contrast, to a drowning linked to a sea level rise. Similar events were described abroad during Late Turonian times; a partial drowning of carbonate platforms was already identified in other localities of the African Tethyan margin. However, the global drowning corresponding to the C/T event was not identified in the present study, although previous works have described this event North of the studied sector. As demonstrated in other localities, a global eustatic event could

  16. The contribution of sulphuric acid to atmospheric particle formation and growth: a comparison between boundary layers in Northern and Central Europe

    Directory of Open Access Journals (Sweden)

    V. Fiedler

    2005-01-01

    Full Text Available Atmospheric gaseous sulphuric acid was measured and its influence on particle formation and growth was investigated building on aerosol data. The measurements were part of the EU-project QUEST and took place at two different measurement sites in Northern and Central Europe (Hyytiälä, Finland, March-April 2003 and Heidelberg, Germany, March-April 2004. From a comprehensive data set including sulphuric acid, particle number size distributions and meteorological data, particle growth rates, particle formation rates and source rates of condensable vapors were inferred. Growth rates were determined in two different ways, from particle size distributions as well as from a so-called timeshift analysis. Moreover, correlations between sulphuric acid and particle number concentration between 3 and 6 nm were examined and the influence of air masses of different origin was investigated. Measured maximum concentrations of sulphuric acid were in the range from 1x106 to 16x106cm-3. The gaseous sulphuric acid lifetime with respect to condensation on aerosol particles ranged from 2 to 33min in Hyytiälä and from 0.5 to 8 min in Heidelberg. Most calculated values (growth rates, formation rates, vapor source rates were considerably higher in Central Europe (Heidelberg, due to the more polluted air and higher preexistent aerosol concentrations. Close correlations between H2SO4 and nucleation mode particles (size range: 3-6 nm were found on most days at both sites. The percentage contribution of sulphuric acid to particle growth was below 10% at both places and to initial growth below 20%. An air mass analysis indicated that at Heidelberg new particles were formed predominantly in air advected from southwesterly directions.

  17. Analog memristive synapse in spiking networks implementing unsupervised learning

    Directory of Open Access Journals (Sweden)

    Erika Covi

    2016-10-01

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

  18. Cardiac fibroblasts regulate sympathetic nerve sprouting and neurocardiac synapse stability.

    Directory of Open Access Journals (Sweden)

    Céline Mias

    Full Text Available Sympathetic nervous system (SNS plays a key role in cardiac homeostasis and its deregulations always associate with bad clinical outcomes. To date, little is known about molecular mechanisms regulating cardiac sympathetic innervation. The aim of the study was to determine the role of fibroblasts in heart sympathetic innervation. RT-qPCR and western-blots analysis performed in cardiomyocytes and fibroblasts isolated from healthy adult rat hearts revealed that Pro-Nerve growth factor (NGF and pro-differentiating mature NGF were the most abundant neurotrophins expressed in cardiac fibroblasts while barely detectable in cardiomyocytes. When cultured with cardiac fibroblasts or fibroblast-conditioned medium, PC12 cells differentiated into/sympathetic-like neurons expressing axonal marker Tau-1 at neurites in contact with cardiomyocytes. This was prevented by anti-NGF blocking antibodies suggesting a paracrine action of NGF secreted by fibroblasts. When co-cultured with cardiomyocytes to mimic neurocardiac synapse, differentiated PC12 cells exhibited enhanced norepinephrine secretion as quantified by HPLC compared to PC12 cultured alone while co-culture with fibroblasts had no effect. However, when supplemented to PC12-cardiomyocytes co-culture, fibroblasts allowed long-term survival of the neurocardiac synapse. Activated fibroblasts (myofibroblasts isolated from myocardial infarction rat hearts exhibited significantly higher mature NGF expression than normal fibroblasts and also promoted PC12 cells differentiation. Within the ischemic area lacking cardiomyocytes and neurocardiac synapses, tyrosine hydroxylase immunoreactivity was increased and associated with local anarchical and immature sympathetic hyperinnervation but tissue norepinephrine content was similar to that of normal cardiac tissue, suggesting depressed sympathetic function. Collectively, these findings demonstrate for the first time that fibroblasts are essential for the setting of

  19. Centenary of the synapse: from Sherrington to the molecular biology of the synapse and beyond.

    Science.gov (United States)

    Shepherd, G M; Erulkar, S D

    1997-09-01

    Few concepts have meant more to neuroscience than the synapse, commonly understood to mean the junction between two excitable cells. The term was introduced by Charles Sherrington in 1897. The centenary of this event is an appropriate time to review the term's origins and utility. There are some surprises. The term didn't actually come from him. His concept was more functional than structural. The pioneering physiological and structural studies in the 1950s in fact did not lead to a rigorous definition. There is still confusion on how to define neurotransmitters. As molecular biological approaches are increasingly refining the concept of a fundamental synaptic unit, many types of neuronal interactions are appearing that do not fit with the synaptic concept. Are the neural circuits underlying behaviour strictly synaptic? In dealing with these questions, a longer perspective is useful for understanding how the term arose, how it has evolved to the present, and what kinds of challenges may be coming in the future.

  20. Making synapses strong: metaplasticity prolongs associativity of long-term memory by switching synaptic tag mechanisms.

    Science.gov (United States)

    Li, Qin; Rothkegel, Martin; Xiao, Zhi Cheng; Abraham, Wickliffe C; Korte, Martin; Sajikumar, Sreedharan

    2014-02-01

    One conceptual mechanism for the induction of associative long-term memory is that a synaptic tag, set by a weak event, can capture plasticity-related proteins from a nearby strong input, thus enabling associativity between the 2 (synaptic tagging and capture, STC). So far, STC has been observed for only a limited time of 60 min. Nevertheless, association of weak memory forms can occur beyond this period and its mechanism is not well understood. Here we report that metaplasticity induced by ryanodine receptor activation or synaptic activation of metabotropic glutamate receptors prolongs the durability of the synaptic tag, thus extending the time window for associative interactions mediating storage of long-term memory. We provide evidence that such metaplasticity alters the mechanisms of STC from a CaMKII-mediated (in non-primed STC) to a protein kinase Mzeta (PKMζ)-mediated process (in primed STC). Thus the association of weak synapses with strong synapses in the "late" stage of associative memory formation occurs only through metaplasticity. The results also reveal that the short-lived, CaMKII-mediated tag may contribute to a mechanism for a fragile form of memory while metaplasticity enables a PKMζ-mediated synaptic tag capable of prolonged interactions that induce a more stable form of memory that is resistant to reversal.

  1. "Hybrid" synapses formed by foreign innervation of parasympathetic neurons: a model for selectivity during competitive reinnervation.

    Science.gov (United States)

    Proctor, W; Frenk, S; Taylor, B; Roper, S

    1979-01-01

    Selectivity of synapse formation after nerve regeneration was tested in the parasympathetic cardiac ganglion of frogs (Rana pipiens). First, we tested the ability of somatic motor axons to establish synaptic connections with denervated ganglion cells by implanting the hypoglossus nerve into the vagotomized heart. After several weeks, stimulation of the implanted hypoglossus mediated a parasympathetic-like inhibition of the heart rate, and synaptic responses produced by hypoglossal stimulation were recorded intracellularly in ganglion cells. Light and electron microscopy indicated that implanted hypoglossal nerve terminals contacted parasympathetic ganglion cells only on their axons and not on the cell body (where most vagal synapses are found in control animals). Second, we tested whether regenerating vagal preganglionic axons would complete with foreign (hypoglossal) terminals for innervation of cardiac ganglion cells. We allowed the vagus nerve to regenerate in animals in which the implanted hypoglossus had established functional contacts with the cardiac ganglion. Vagal axons were able to reinnervate the heart and reestablish synaptic connections on the cell bodies of ganglion cells. Furthermore, functional transmission at the foriegn (hypoglossal) terminals disappeared concomitant with vagal reinnervation. Images PMID:315564

  2. Mantle xenoliths from Central Vietnam: evidence for at least Meso-Proterozoic formation of the lithospheric mantle

    Science.gov (United States)

    Proßegger, Peter; Ntaflos, Theodoros; Ackerman, Lukáš; Hauzenberger, Christoph; Tran, Tuan Anh

    2016-04-01

    Intraplate Cenozoic basalts that are widely dispersed along the continental margin of East Asia belong to the Western Pacific "diffuse" igneous province. They consist mainly of alkali basalts, basanites,rarely nephelinites, which are mantle xenolith-bearing, potassic rocks and quartz tholeiites. The volcanism in this area has been attributed to the continental extension caused by the collision of India with Asia and by the subduction of the Pacific Ocean below Asia. We studied a suite of 24 mantle xenoliths from La Bang Lake, Dak Doa district and Bien Ho, Pleiku city in the Gia Province, Central Vietnam. They are predominantly spinel lherzolites (19) but spinel harburgites (3) and two garnet pyroxenites are present as well. The sizes of the xenoliths range from 5 to 40 cm in diameter with medium to coarse-grained protogranular textures. Whole rock major and trace element analyses display a wide range of compositions. The MgO concentration varies from 36.0 to 45.8 wt% whereas Al2O3 and CaO range from 0.63 to 4.36 wt% and from 0.52 to 4.21 wt% (with one sample having CaO of 6.63 wt%) respectively. Both CaO and Al2O3 positively correlate with MgO most likely indicating that the sampled rocks were derived from a common mantle source experienced variable degrees of partial melting. Mineral analyses show that the rock forming minerals are chemically homogeneous. The Fo contents of olivine vary between 89.2 and 91.2 and the Mg# of orthopyroxene and clinopyroxene range from 89 to 92 and 89 to 94 respectively. The range of Cr# for spinel is 0.06-0.26. Model calculations in both whole rock and clinopyroxenes show that lithospheric mantle underneath Central Vietnam experienced melt extractions that vary between 2-7, 12-15 and 20-30%. The majority of the primitive mantle-normalized whole rock and clinopyroxene REE patterns are parallel to each other indicating that clinopyroxene is the main repository of the trace elements. Clinopyroxenes are divided into two groups: group A

  3. FORMATION AND INFLUENCING FACTORS OF FREE SURFACE VORTEX IN A BARREL WITH A CENTRAL ORIFICE AT BOTTOM

    Institute of Scientific and Technical Information of China (English)

    LI Hai-feng; CHEN Hong-xun; MA Zheng; ZHOU Yi

    2009-01-01

    Based on the Navier-Stokes equations with considering the effect of the Coriolis force, the finite volume method was employed to discretize the governing equations, the SIMPLE method was adopted to solve the discretized equations, and the flow field in a barrel with an outlet at the center of the bottom was simulated. The numerical results agree well with the experimental data. From the Lagrangian, the relations among the acceleration, the Coriolis force and the viscosity force were analyzed. The results show that the Coriolis force is the major factor that causes the formation of the vortex. The flow fields in the flume under different incoming flow conditions were numerically simulated using the software Fluent. The numerical simulations show good agreement with the experiments for the shape and position of the vortex.

  4. Effect of Associative Learning on Memory Spine Formation in Mouse Barrel Cortex

    Directory of Open Access Journals (Sweden)

    Malgorzata Jasinska

    2016-01-01

    Full Text Available Associative fear learning, in which stimulation of whiskers is paired with mild electric shock to the tail, modifies the barrel cortex, the functional representation of sensory receptors involved in the conditioning, by inducing formation of new inhibitory synapses on single-synapse spines of the cognate barrel hollows and thus producing double-synapse spines. In the barrel cortex of conditioned, pseudoconditioned, and untreated mice, we analyzed the number and morphological features of dendritic spines at various maturation and stability levels: sER-free spines, spines containing smooth endoplasmic reticulum (sER, and spines containing spine apparatus. Using stereological analysis of serial sections examined by transmission electron microscopy, we found that the density of double-synapse spines containing spine apparatus was significantly increased in the conditioned mice. Learning also induced enhancement of the postsynaptic density area of inhibitory synapses as well as increase in the number of polyribosomes in such spines. In single-synapse spines, the effects of conditioning were less pronounced and included increase in the number of polyribosomes in sER-free spines. The results suggest that fear learning differentially affects single- and double-synapse spines in the barrel cortex: it promotes maturation and stabilization of double-synapse spines, which might possibly contribute to permanent memory formation, and upregulates protein synthesis in single-synapse spines.

  5. Volcanic settings and their reservoir potential: An outcrop analog study on the Miocene Tepoztlán Formation, Central Mexico

    Science.gov (United States)

    Lenhardt, Nils; Götz, Annette E.

    2011-07-01

    The reservoir potential of volcanic and associated sedimentary rocks is less documented in regard to groundwater resources, and oil and gas storage compared to siliciclastic and carbonate systems. Outcrop analog studies within a volcanic setting enable to identify spatio-temporal architectural elements and geometric features of different rock units and their petrophysical properties such as porosity and permeability, which are important information for reservoir characterization. Despite the wide distribution of volcanic rocks in Mexico, their reservoir potential has been little studied in the past. In the Valley of Mexico, situated 4000 m above the Neogene volcanic rocks, groundwater is a matter of major importance as more than 20 million people and 42% of the industrial capacity of the Mexican nation depend on it for most of their water supply. Here, we present porosity and permeability data of 108 rock samples representing five different lithofacies types of the Miocene Tepoztlán Formation. This 800 m thick formation mainly consists of pyroclastic rocks, mass flow and fluvial deposits and is part of the southern Transmexican Volcanic Belt, cropping out south of the Valley of Mexico and within the two states of Morelos and Mexico State. Porosities range from 1.4% to 56.7%; average porosity is 24.8%. Generally, permeabilities are low to median (0.2-933.3 mD) with an average permeability of 88.5 mD. The lavas are characterized by the highest porosity values followed by tuffs, conglomerates, sandstones and tuffaceous breccias. On the contrary, the highest permeabilities can be found in the conglomerates, followed by tuffs, tuffaceous breccias, sandstones and lavas. The knowledge of these petrophysical rock properties provides important information on the reservoir potential of volcanic settings to be integrated to 3D subsurface models.

  6. Formation of diapiric structure in the deformation zone, central Indian Ocean: A model from gravity and seismic reflection data

    Indian Academy of Sciences (India)

    K S Krishna; D Gopala Rao; Yu P Neprochnov

    2002-03-01

    Analyses of bathymetry, gravity and seismic reflection data of the diffusive plate boundary in the central Indian Ocean reveal a new kind of deformed structure besides the well-reported structures of long-wavelength anticlinal basement rises and high-angle reverse faults. The structure (basement trough) has a length of about 150 km and deepens by up to 1 km from its regional trend (northward dipping). The basement trough includes a rise at its center with a height of about 1.5 km. The rise is about 10 km wide with rounded upper surface and bounded by vertical faults. A broad free-air gravity low of about 20 mGal and a local high of 8 mGal in its center are associated with the identified basement trough and rise structure respectively. Seismic results reveal that the horizontal crustal compression prevailing in the diffusive plate boundary might have formed the basement trough possibly in early Pliocene time. Differential loading stresses have been generated from unequal crust/sediment thickness on lower crustal and upper mantle rocks. A thin semi-ductile serpentinite layer existing near the base of the crust that is interpreted to have been formed at mid-ocean ridge and become part of the lithosphere, may have responded to the downward loading stresses generated by the sediments and crustal rocks to inject the serpentinites into the overlying strata to form a classic diapiric structure.

  7. Process modeling studies of physical mechanisms of the formation of an anticyclonic eddy in the central Red Sea

    KAUST Repository

    Chen, Changsheng

    2014-02-01

    Surface drifters released in the central Red Sea during April 2010 detected a well-defined anticyclonic eddy around 23°N. This eddy was ∼45–60 km in radius, with a swirl speed up to ∼0.5 m/s. The eddy feature was also evident in monthly averaged sea surface height fields and in current profiles measured on a cross-isobath, shipboard CTD/ADCP survey around that region. The unstructured-grid, Finite-Volume Community Ocean Model (FVCOM) was configured for the Red Sea and process studies were conducted to establish the conditions necessary for the eddy to form and to establish its robustness. The model was capable of reproducing the observed anticyclonic eddy with the same location and size. Diagnosis of model results suggests that the eddy can be formed in a Red Sea that is subject to seasonally varying buoyancy forcing, with no wind, but that its location and structure are significantly altered by wind forcing, initial distribution of water stratification and southward coastal flow from the upstream area. Momentum analysis indicates that the flow field of the eddy was in geostrophic balance, with the baroclinic pressure gradient forcing about the same order of magnitude as the surface pressure gradient forcing.

  8. An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence.

    Science.gov (United States)

    Frahm, Silke; Antolin-Fontes, Beatriz; Görlich, Andreas; Zander, Johannes-Friedrich; Ahnert-Hilger, Gudrun; Ibañez-Tallon, Ines

    2015-12-01

    A great deal of interest has been focused recently on the habenula and its critical role in aversion, negative-reward and drug dependence. Using a conditional mouse model of the ACh-synthesizing enzyme choline acetyltransferase (Chat), we report that local elimination of acetylcholine (ACh) in medial habenula (MHb) neurons alters glutamate corelease and presynaptic facilitation. Electron microscopy and immuno-isolation analyses revealed colocalization of ACh and glutamate vesicular transporters in synaptic vesicles (SVs) in the central IPN. Glutamate reuptake in SVs prepared from the IPN was increased by ACh, indicating vesicular synergy. Mice lacking CHAT in habenular neurons were insensitive to nicotine-conditioned reward and withdrawal. These data demonstrate that ACh controls the quantal size and release frequency of glutamate at habenular synapses, and suggest that the synergistic functions of ACh and glutamate may be generally important for modulation of cholinergic circuit function and behavior.

  9. Astroglial type-1 cannabinoid receptor (CB1): A new player in the tripartite synapse.

    Science.gov (United States)

    Oliveira da Cruz, J F; Robin, L M; Drago, F; Marsicano, G; Metna-Laurent, M

    2016-05-26

    The endocannabinoid system is an important regulator of physiological functions. In the brain, this control is mainly exerted through the type-1-cannabinoid (CB1) receptors. CB1 receptors are abundant at neuron terminals where their stimulation inhibits neurotransmitter release. However, CB1 receptors are also expressed in astrocytes and recent studies showed that astroglial cannabinoid signaling is a key element of the tripartite synapse. In this review we discuss the different mechanisms by which astroglial CB1 receptors control synaptic transmission and plasticity. The recent involvement of astroglial CB1 receptors in the effects of cannabinoids on memory highlights their key roles in cognitive processes and further indicates that astrocytes are central active elements of high-order brain functions.

  10. Altered Connectivity and Synapse Maturation of the Hippocampal Mossy Fiber Pathway in a Mouse Model of the Fragile X Syndrome.

    Science.gov (United States)

    Scharkowski, F; Frotscher, Michael; Lutz, David; Korte, Martin; Michaelsen-Preusse, Kristin

    2017-01-10

    The Fragile X syndrome (FXS) as the most common monogenetic cause of cognitive impairment and autism indicates how tightly the dysregulation of synapse development is linked to cognitive deficits. Symptoms of FXS include excessive adherence to patterns that point to compromised hippocampal network formation. Surprisingly, one of the most complex hippocampal synapses connecting the dentate gyrus (DG) to CA3 pyramidal neurons has not been analyzed in FXS yet. Intriguingly, we found altered synaptic function between DG and CA3 in a mouse model of FXS (fmr1 knockout [KO]) demonstrated by increased mossy fiber-dependent miniature excitatory postsynaptic current (mEPSC) frequency at CA3 pyramidal neurons together with increased connectivity between granule cells and CA3 neurons. This phenotype is accompanied by increased activity of fmr1 KO animals in the marble burying task, detecting repetitive and obsessive compulsive behavior. Spine apparatus development and insertion of AMPA receptors is enhanced at postsynaptic thorny excrescences (TEs) in fmr1 KO mice. We report age-dependent alterations in TE morphology and in the underlying actin dynamics possibly linked to a dysregulation in profilin1 expression. TEs form detonator synapses guiding CA3 network activity. Thus, alterations described here are likely to contribute substantially to the impairment in hippocampal function and therefore to the pathogenesis of FXS.

  11. VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses

    Science.gov (United States)

    Mittelbrunn, María; Molina, Ana; Escribese, María M.; Yáñez-Mó, María; Escudero, Ester; Ursa, Ángeles; Tejedor, Reyes; Mampaso, Francisco; Sánchez-Madrid, Francisco

    2004-07-01

    The integrin 41 (VLA-4) not only mediates the adhesion and transendothelial migration of leukocytes, but also provides costimulatory signals that contribute to the activation of T lymphocytes. However, the behavior of 41 during the formation of the immune synapse is currently unknown. Here, we show that 41 is recruited to both human and murine antigen-dependent immune synapses, when the antigen-presenting cell is a B lymphocyte or a dendritic cell, colocalizing with LFA-1 at the peripheral supramolecular activation complex. However, when conjugates are formed in the presence of anti-4 antibodies, VLA-4 colocalizes with the CD3- chain at the center of the synapse. In addition, antibody engagement of 4 integrin promotes polarization toward a T helper 1 (Th1) response in human in vitro models of CD4+ T cell differentiation and naïve T cell priming by dendritic cells. The in vivo administration of anti-4 integrin antibodies also induces an immune deviation to Th1 response that dampens a Th2-driven autoimmune nephritis in Brown Norway rats. These data reveal a regulatory role of 4 integrins on T lymphocyte-antigen presenting cell cognate immune interactions.

  12. Shallow structure and its formation process of an active flexure in the forearc basin of the central Nankai subduction zone

    Science.gov (United States)

    Ashi, J.; Ikehara, K.; Omura, A.; Ojima, T.; Murayama, M.

    2013-12-01

    ENE-WSW trending active faults, named Enshu fault system, are developed in the forearc basins of the eastern and central Nankai subduction zone. Three parallel faults developed in the Enshu forearc basin of the eastern Nankai have right lateral slip on the basis of dextral displacement of the canyon axis. Moreover, bathymetry data and side-scan sonar imageries indicate relative uplift of the northern region and the multichannel seismic (MCS) reflection profiles show northward dipping fault planes. In the central Nankai subuduction zone, an ENE-WSW trending step is distributed at the northern part of the Kumano forearc basin and is regarded as the western extension of the Enshu fault system. Although MCS records show deformations including an anticlinal fold beneath the bathymetric step, they have less resolution to identify deformation of basin sequence just below the seafloor. In contrast, deformation seems to reach to the seafloor on a profile by SBP mounted on a mother ship. Investigation of shallow deformation structures is significant for understanding of recent tectonic activity. We carried out deep towed SBP survey by ROV NSS (Navigable Sampling System) during Hakuho-maru KH-11-9 cruise. High resolution mapping of shallow structures was successfully conducted by a chirp SBP system of EdgeTech DW-106. ROV NSS also has capability to take a long core with a pinpoint accuracy around complex topographic region. The Kumano forearc basin is topographically divided into the northern part at a water depth of 2038 m and the other major region at a depth of 2042 m by the ENE-WSW linear step. Three deep towed SBP lines intersected this topographical step and revealed the following structures. This step is composed of 100 m wide gentle slope with an inclination of about 8 degrees. An anticlinal axis is located beneath the upper edge of this slope. Sedimentary layers continue at this slope region without any abut/termination and rapidly increase their thickness toward the

  13. Analysis of Dose at the Site of Second Tumor Formation After Radiotherapy to the Central Nervous System

    Energy Technology Data Exchange (ETDEWEB)

    Galloway, Thomas J. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org [University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Amdur, Robert J.; Morris, Christopher G.; Swanson, Erika L. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Marcus, Robert B. [University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

    2012-01-01

    Purpose: Second tumors are an uncommon complication of multimodality treatment of childhood cancer. The present analysis attempted to correlate the dose received as a component of primary treatment and the site of the eventual development of a second tumor. Methods and Materials: We retrospectively identified 16 patients who had received radiotherapy to sites in the craniospinal axis and subsequently developed a second tumor. We compared the historical fields and port films of the primary treatment with the modern imaging of the second tumor locations. We classified the location of the second tumors as follows: in the boost field; marginal to the boost field, but in a whole-brain field; in a whole-brain field; marginal to the whole brain/primary treatment field; and distant to the field. We divided the dose received into 3 broad categories: high dose (>45 Gy), moderate dose (20-36 Gy), and low dose (<20 Gy). Results: The most common location of the second tumor was in the whole brain field (57%) and in the moderate-dose range (81%). Conclusions: Our data contradict previous publications that suggested that most second tumors develop in tissues that receive a low radiation dose. Almost all the second tumors in our series occurred in tissue within a target volume in the cranium that had received a moderate dose (20-36 Gy). These findings suggest that a major decrease in the brain volume that receives a moderate radiation dose is the only way to substantially decrease the second tumor rate after central nervous system radiotherapy.

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

    Science.gov (United States)

    2015-04-23

    controls (Figure 2A). To con- firm that the reduction of APs was caused by the loss of synap- tic drive rather than decreased intrinsic excitability, passive...indicates a P < 0.05; ** indicates a P < 0.01; *** indicates a P < 0.001. significantly increased IBI and APs per burst within 10min, con- firming network...A may undergo retrograde transport and be released from motor neurons to intoxicate central synapses (Restani et al., 2012a,b; Marchand-Pauvert et al

  15. The spatially resolved star formation relation in two HI-rich galaxies with central post-starburst signature

    CERN Document Server

    Klitsch, Anne; Kuntschner, Harald; Couch, Warrick J; Pracy, Michael B

    2016-01-01

    E+A galaxies are post-starburst systems that are identified from their optical spectra. These galaxies contain a substantial young A-type stellar component, but have only little ongoing star formation (SF). HI 21-cm line emission is found in approximately half of the nearby E+A galaxies, indicating that they contain a reservoir of gas that could fuel active SF. Here, we study two HI-rich galaxies, which show a typical E+A spectrum at the centre and SF at larger radii. We present new high spatial resolution radio interferometric observations of the HI 21-cm emission line using the VLA and of the CO(1-0) emission line using ALMA. We combine these data sets to predict the SFR and show that it does not correlate well with the SFR derived from H alpha on sub-kpc scales. We apply a recently developed statistical model for the small scale behaviour of the SF relation to predict and interpret the observed scatter. We find smoothly distributed, regularly rotating HI gas. The CO(1-0) emission line is not detected for b...

  16. Insights into the dolomitization process and porosity modification in sucrosic dolostones, Avon Park Formation (Middle Eocene), East-Central Florida, U.S.A.

    KAUST Repository

    Maliva,, Robert G.

    2011-03-01

    The Avon Park Formation (middle Eocene) in central Florida, U.S.A., contains shallow-water carbonates that have been replaced by dolomite to varying degrees, ranging from partially replaced limestones, to highly porous sucrosic dolostones, to, less commonly, low-porosity dense dolostones. The relationships between dolomitization and porosity and permeability were studied focusing on three 305-m-long cores taken in the City of Daytona Beach. Stable-isotope data from pure dolostones (mean δ 18O = +3.91% V-PDB) indicate dolomite precipitation in Eocene penesaline pore waters, which would be expected to have been at or above saturation with respect to calcite. Nuclear magnetic log-derived porosity and permeability data indicate that dolomitization did not materially change total porosity values at the bed and formation scale, but did result in a general increase in pore size and an associated substantial increase in permeability compared to limestone precursors. Dolomitization differentially affects the porosity and permeability of carbonate strata on the scale of individual crystals, beds, and formations. At the crystal scale, dolomitization occurs in a volume-for-volume manner in which the space occupied by the former porous calcium carbonate is replaced by a solid dolomite crystal with an associated reduction in porosity. Dolomite crystal precipitation was principally responsible for calcite dissolution both at the actual site of dolomite crystal growth and in the adjoining rock mass. Carbonate is passively scavenged from the formation, which results in no significant porosity change at the formation scale. Moldic pores after allochems formed mainly in beds that experienced high degrees of dolomitization, which demonstrates the intimate association of the dolomitization process with carbonate dissolution. The model of force of crystallization-controlled replacement provides a plausible explanation for key observations concerning the dolomitization process in the

  17. Reactive overprint of the Central Indian Ridge mantle and formation of hybrid troctolites: reassessing the significance of bulk oceanic crust

    Science.gov (United States)

    Sanfilippo, A.; Morishita, T.; Kumagai, H.; Nakamura, K.; Okino, K.; Tamura, A.; Arai, S.

    2014-12-01

    The idea that hybridized mantle rocks can contribute to the oceanic crust composition has recently emerged thanks to studies on primitive (olivine-rich) troctolites [e.g. 1]. These rocks are considered to be formed by melt-rock interaction, but the exact reaction process by which they originate is still debated and their role on the bulk oceanic crust composition has been never defined. Olivine-rich troctolites have been mostly found at slow spreading ridges [2] or at their fossil analogues [3]. Similar rocks have been recently collected in the 25ºS area of the intermediate spreading Central Indian Ridge (CIR), and rarely characterize the crust mantle boundary at fast spreading ridges [4]. We show that textural and chemical inheritances of the pre-existing mantle are preserved in the CIR troctolites. In particular, the local occurrence of granular, mantle-derived orthopyroxenes and the composition of the associated clinopyroxene indicate that these crustal rocks formed through a direct (one-stage) conversion of a mantle peridotite. We use chemical evidence to infer the same origin of the olivine-rich troctolites worldwide, concluding that the reactive overprint of the oceanic mantle is a process diffused over the entire spreading rate spectrum. Bulk oceanic crust estimates of the Hess Deep (Pacific) and Atlantis Massif (Atlantic) crustal sections are used to quantify and compare the effect of these rocks on the bulk crust composition at fast and slow spreading ridges. Our inferences suggest that the significance of the bulk oceanic crust should be reassessed. When hybrid troctolites are included at crustal levels, the oceanic crust cannot be considered equal to the composition of the melt extracted from the mantle, but it results more primitive and importantly thicker. References: [1] Suhr G., Hellebrand E., Johnson K., Brunelli D., 2008, Geochem. Geophys. Geosyst. 9, doi:10.1029/2008GC002012; [2] Drouin M., Godard M., Ildefonse B., Bruguier O., Garrido C

  18. Valey-Fill Sandstones in the Kootenai Formation on the Crow Indian Reservation, South-Central Montana

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, David A

    1998-04-07

    Subsurface data is being collected, organized, and a digital database is being prepared for the project. An ACCESS database and PC-Arcview is being used to manage and interpret the data. Well data and base map data have been successfully imported into Arcview and customized to meet the needs of this project. Log tops and other data from about ½ of the exploration wells in the area have been incorporated into the data base. All of the four 30" X 60" geologic quadrangles have been scanned to produce a digital surface geologic data base for the Crow Reservation and all are nearing completion. Formal technical review prior to publication has been completed for the Billings and Bridger Quadrangles; and are underway for the Hardin and Lodge Grass Quadrangles. Field investigations were completed during the last quarter. With the help of a student field assistant from the Crow Tribe, the entire project area was inventoried for the presence of valley-fill deposits in the Kootenai Formation. Field inventory has resulted in the identification of nine exposures of thick valley-fill deposits. These appear to represent at least four major westward-trending valley systems. All the channel localities have been measured and described in detail and paleocurrent data has been collected from all but one locality. In addition, two stratigraphic sections were measured in areas where channels are absent. One channel has bee traced over a distance of about 60 miles and exhibits definite paleostructural control. An abstract describing this channel has been submitted and accepted for presentation at the Williston Basin Symposium in October, 1998.

  19. Valley-Fill Sandstones in the Kootenai Formation on the Crow Indian Reservation, South-Central Montana

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, David A

    1998-07-03

    Subsurface data continues to be collected, organized, and a digital database is being prepared for the project. An ACCESS database and PC-Arcview is being used to manage and interpret the data. Well data and base map data have been successfully imported into Arcview and customized to meet the needs of this project. Log tops and other data from about ¾ of the exploration wells in the area have been incorporated into the data base. All of the four 30" X 60" geologic quadrangles have been scanned to produce a digital surface geologic data base for the Crow Reservation and all are nearing completion. Formal technical review prior to publication has been completed for all the quadrangles; Billings, Bridger; Hardin, and Lodge Grass. Final GIS edits are being made before being forwarded to the Bureau's Publications Department. Field investigations were completed during the third quarter, 1997. With the help of a student field assistant from the Crow Tribe, the entire project area was inventoried for the presence of valley-fill deposits in the Kootenai Formation. Field inventory has resulted in the identification of nine exposures of thick valley-fill deposits. These appear to represent at least four major westward-trending valley systems. All the channel localities have been measured and described in detail and paleocurrent data has been collected from all but one locality. In addition, two stratigraphic sections were measured in areas where channels are absent. One channel has bee traced over a distance of about 60 miles and exhibits definite paleostructural control. An abstract describing this channel has been submitted and accepted for presentation at the Williston Basin Symposium in October, 1998.

  20. Sedimentary environments and stratigraphy of the carbonate-silicilastic deposits of the Shirgesht Formation: implications for eustasy and local tectonism in the Kalmard Block, Central Iran

    Directory of Open Access Journals (Sweden)

    aram bayetgoll

    2015-10-01

    Full Text Available Introduction   Sedimentological and sequence stratigraphic analysis providing insight into the main relationships between sequence architecture and stacking pattern, syn/post-depositional tectonics, and eustatic sea-level fluctuations (Gawthorpe and Leeder 2000; Zecchin et al. 2003, 2004; Carpentier et al. 2007. Relative variations in sea level are due to tectonic activity and eustasy. The Shirgesht Formation in the Kalmard Block of Central Iran provides a useful case study for to determine the processes responsible on internal architecture and stacking pattern of depositional sequences in a half-graben basin. In the Shirgesht Formation, siliciclastic and carbonate successions of the Kalmard Basin, the cyclic stratigraphic record is the result of the complex interaction of regional uplift, eustasy, local tectonics, sediment supply, and sedimentary processes (Bayet-Goll 2009, 2014; Hosseini-Barzi and Bayet-Goll 2009.     Material & Methods   Lower Paleozoic successions in Tabas and Kalmard blocks from Central Iran share the faunal and floral characteristics with other Gondwana sectors such as south-western Europe and north Africa–Middle East (Ghaderi et al. 2009. The geology of these areas was outlined by Ruttner et al. (1968 and by Bruton et al. (2004. The Cambrian-Middle Triassic strata in the Kalmard Block were deposited in a shallow water platform that possesses lithologic dissimilarities with the Tabas area (Aghanabati 2004. The occurrence of two active faults indicates clearly that Kalmard basin formed a mobile zone throughout the Paleozoic so that lithostratigraphic units show considerably contrasting facies in comparison with Tabas basin (Hosseini-Barzi and Bayet-Goll 2009; Bayet-Goll 2014 . The Shirgesht Formation in the Block Kalmard is mainly composed of carbonate-siliciclastic successions that disconformability overlain Kalmard Formation (attributed to Pre-Cambrian and is underlain by Gachal (Carboniferous or Rahdar (Devonian

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

    Science.gov (United States)

    Kurup, Naina; Jin, Yishi

    2016-01-01

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

  2. Can dynamical synapses produce true self-organized criticality?

    Science.gov (United States)

    Costa, Ariadne de Andrade; Copelli, Mauro; Kinouchi, Osame

    2015-06-01

    Neuronal networks can present activity described by power-law distributed avalanches presumed to be a signature of a critical state. Here we study a random-neighbor network of excitable cellular automata coupled by dynamical synapses. The model exhibits a very similar to conservative self-organized criticality (SOC) models behavior even with dissipative bulk dynamics. This occurs because in the stationary regime the model is conservative on average, and, in the thermodynamic limit, the probability distribution for the global branching ratio converges to a delta-function centered at its critical value. So, this non-conservative model pertain to the same universality class of conservative SOC models and contrasts with other dynamical synapses models that present only self-organized quasi-criticality (SOqC). Analytical results show very good agreement with simulations of the model and enable us to study the emergence of SOC as a function of the parametric derivatives of the stationary branching ratio.

  3. Temporal coding at the immature depolarizing GABAergic synapse

    Directory of Open Access Journals (Sweden)

    Guzel Valeeva

    2010-07-01

    Full Text Available In the developing hippocampus, GABA exerts depolarizing and excitatory actions and contributes to the generation of neuronal network driven Giant Depolarizing Potentials (GDPs. Here, we studied spike time coding at immature GABAergic synapses and its impact on synchronization of the neuronal network during GDPs in the neonatal (postnatal days P2-6 rat hippocampal slices. Using extracellular recordings, we found that the delays of action potentials (APs evoked by synaptic activation of GABA(A receptors are long (mean, 65 ms and variable (within a time window of 10-200 ms. During patch-clamp recordings, depolarizing GABAergic responses were mainly subthreshold and their amplification by persistent sodium conductance was required to trigger APs. AP delays at GABAergic synapses shortened and their variability reduced with an increase in intracellular chloride concentration during whole-cell recordings. Negative shift of the GABA reversal potential (EGABA with low concentrations of bumetanide, or potentiation of GABA(A receptors with diazepam reduced GDPs amplitude, desynchronized neuronal firing during GDPs and slowed down GDPs propagation. Partial blockade of GABA(A receptors with bicuculline increased neuronal synchronization and accelerated GDPs propagation. We propose that spike-timing at depolarizing GABA synapses is determined by intracellular chloride concentration. At physiological levels of intracellular chloride GABAergic depolarization does not reach the action potential threshold and amplification of GABAergic responses by non-inactivating sodium conductance is required for postsynaptic AP initiation. Slow and variable excitation at GABAergic synapse determines the level of neuronal synchrony and the rate of GDPs propagation in the developing hippocampus.

  4. Temporal coding at the immature depolarizing GABAergic synapse.

    Science.gov (United States)

    Valeeva, Guzel; Abdullin, Azat; Tyzio, Roman; Skorinkin, Andrei; Nikolski, Evgeny; Ben-Ari, Yehezkiel; Khazipov, Rustem

    2010-01-01

    In the developing hippocampus, GABA exerts depolarizing and excitatory actions and contributes to the generation of neuronal network driven giant depolarizing potentials (GDPs). Here, we studied spike time coding at immature GABAergic synapses and its impact on synchronization of the neuronal network during GDPs in the neonatal (postnatal days P2-6) rat hippocampal slices. Using extracellular recordings, we found that the delays of action potentials (APs) evoked by synaptic activation of GABA(A) receptors are long (mean, 65 ms) and variable (within a time window of 10-200 ms). During patch-clamp recordings, depolarizing GABAergic responses were mainly subthreshold and their amplification by persistent sodium conductance was required to trigger APs. AP delays at GABAergic synapses shortened and their variability reduced with an increase in intracellular chloride concentration during whole-cell recordings. Negative shift of the GABA reversal potential (E(GABA)) with low concentrations of bumetanide, or potentiation of GABA(A) receptors with diazepam reduced GDPs amplitude, desynchronized neuronal firing during GDPs and slowed down GDPs propagation. Partial blockade of GABA(A) receptors with bicuculline increased neuronal synchronization and accelerated GDPs propagation. We propose that spike timing at depolarizing GABA synapses is determined by intracellular chloride concentration. At physiological levels of intracellular chloride GABAergic depolarization does not reach the action potential threshold and amplification of GABAergic responses by non-inactivating sodium conductance is required for postsynaptic AP initiation. Slow and variable excitation at GABAergic synapse determines the level of neuronal synchrony and the rate of GDPs propagation in the developing hippocampus.

  5. A composite foraminiferal biostratigraphic sequence for the Lower Miocene deposits in the type area of the Qom Formation, central Iran, developed by constrained optimization (CONOP)

    Science.gov (United States)

    Daneshian, Jahanbakhsh; Ramezani Dana, Leila; Sadler, Peter

    2017-01-01

    Benthic foraminifera species commonly outnumber planktic species in the type area of the Lower Miocene Qom Formation, in north central Iran, where it records the Tethyan link between the eastern Mediterranean and Indo- Pacific provinces. Because measured sections preserve very different sequences of first and last occurrences of these species, no single section provides a completely suitable baseline for correlation. To resolve this problem, we combined bioevents from three stratigraphic sections into a single composite sequence by constrained optimization (CONOP). The composite section arranges the first and last appearance events (FAD and LAD) of 242 foraminifera in an optimal order that minimizes the implied diachronism between sections. The composite stratigraphic ranges of the planktic foraminifera support a practical biozonation which reveals substantial local changes of accumulation rate during Aquitanian to Burdigalian times. Traditional biozone boundaries emerge little changed but an order of magnitude more correlations can be interpolated. The top of the section at Dobaradar is younger than previously thought and younger than sections at Dochah and Tigheh Reza-Abad. The latter two sections probably extend older into the Aquitanian than the Dobaradar section, but likely include a hiatus near the base of the Burdigalian. The bounding contacts with the Upper Red and Lower Red Formations are shown to be diachronous.

  6. Synapses lacking astrocyte appear in the amygdala during consolidation of Pavlovian threat conditioning.

    Science.gov (United States)

    Ostroff, Linnaea E; Manzur, Mustfa K; Cain, Christopher K; Ledoux, Joseph E

    2014-06-15

    There is growing evidence that astrocytes, long held to merely provide metabolic support in the adult brain, participate in both synaptic plasticity and learning and memory. Astrocytic processes are sometimes present at the synaptic cleft, suggesting that they might act directly at individual synapses. Associative learning induces synaptic plasticity and morphological changes at synapses in the lateral amygdala (LA). To determine whether astrocytic contacts are involved in these changes, we examined LA synapses after either threat conditioning (also called fear conditioning) or conditioned inhibition in adult rats by using serial section transmission electron microscopy (ssTEM) reconstructions. There was a transient increase in the density of synapses with no astrocytic contact after threat conditioning, especially on enlarged spines containing both polyribosomes and a spine apparatus. In contrast, synapses with astrocytic contacts were smaller after conditioned inhibition. This suggests that during memory consolidation astrocytic processes are absent if synapses are enlarging but present if they are shrinking. We measured the perimeter of each synapse and its degree of astrocyte coverage, and found that only about 20-30% of each synapse was ensheathed. The amount of synapse perimeter surrounded by astrocyte did not scale with synapse size, giving large synapses a disproportionately long astrocyte-free perimeter and resulting in a net increase in astrocyte-free perimeter after threat conditioning. Thus astrocytic processes do not mechanically isolate LA synapses, but may instead interact through local signaling, possibly via cell-surface receptors. Our results suggest that contact with astrocytic processes opposes synapse growth during memory consolidation.

  7. Extracerebellar role for Cerebellin1: modulation of dendritic spine density and synapses in striatal medium spiny neurons.

    Science.gov (United States)

    Kusnoor, S V; Parris, J; Muly, E C; Morgan, J I; Deutch, A Y

    2010-07-01

    Cerebellin1 (Cbln1) is a secreted glycoprotein that was originally isolated from the cerebellum and subsequently found to regulate synaptic development and stability. Cbln1 has a heterogeneous distribution in brain, but the only site in which it has been shown to have central effects is the cerebellar cortex, where loss of Cbln1 causes a reduction in granule cell-Purkinje cell synapses. Neurons of the thalamic parafascicular nucleus (PF), which provide glutamatergic projections to the striatum, also express high levels of Cbln1. We first examined Cbln1 in thalamostriatal neurons and then determined if cbln1 knockout mice exhibit structural deficits in striatal neurons. Virtually all PF neurons express Cbln1-immunoreactivity (-ir). In contrast, only rare Cbln1-ir neurons are present in the central medial complex, the other thalamic region that projects heavily to the dorsal striatum. In the striatum Cbln1-ir processes are apposed to medium spiny neuron (MSN) dendrites; ultrastructural studies revealed that Cbln1-ir axon terminals form axodendritic synapses with MSNs. Tract-tracing studies found that all PF cells retrogradely labeled from the striatum express Cbln1-ir. We then examined the dendritic structure of Golgi-impregnated MSNs in adult cbln1 knockout mice. MSN dendritic spine density was markedly increased in cbln1(-/-) mice relative to wildtype littermates, but total dendritic length was unchanged. Ultrastructural examination revealed an increase in the density of MSN axospinous synapses in cbln1(-/-) mice, with no change in postsynaptic density length. Thus, Cbln1 determines the dendritic structure of striatal MSNs, with effects distinct from those seen in the cerebellum.

  8. Spike timing and synaptic dynamics at the awake thalamocortical synapse.

    Science.gov (United States)

    Swadlow, Harvey A; Bezdudnaya, Tatiana; Gusev, Alexander G

    2005-01-01

    Thalamocortical (TC) neurons form only a small percentage of the synapses onto neurons of cortical layer 4, but the response properties of these cortical neurons are arguably dominated by thalamic input. This discrepancy is explained, in part, by studies showing that TC synapses are of high efficacy. However, TC synapses display activity-dependent depression. Because of this, in vitro measures of synaptic efficacy will not reflect the situation in vivo, where different neuronal populations have widely varying levels of "spontaneous" activity. Indeed, TC neurons of awake subjects generate high rates of spontaneous activity that would be expected, in a depressing synapse, to result in a chronic state of synaptic depression. Here, we review recent work in the somatosensory thalamocortical system of awake rabbits in which the relationship between TC spike timing and TC synaptic efficacy was examined during both thalamic "relay mode" (alert state) and "burst mode" (drowsy state). Two largely independent methodological approaches were used. First, we employed cross-correlation methods to examine the synaptic impact of single TC "barreloid" neurons on a single neuronal subtype in the topographically aligned layer 4 "barrel" - putative fast-spike inhibitory interneurons. We found that the initial spike of a TC burst, as well as isolated TC spikes with long preceding interspike intervals (ISIs) elicited postsynaptic action potentials far more effectively than did TC impulses with short ISIs. Our second approach took a broader view of the postsynaptic impact of TC impulses. In these experiments we examined spike-triggered extracellular field potentials and synaptic currents (using current source-density analysis) generated through the depths of a cortical barrel column by the impulses of single topographically aligned TC neurons. We found that (a) closely neighboring TC neurons may elicit very different patterns of monosynaptic activation within layers 4 and 6 of the aligned

  9. The establishment of GABAergic and glutamatergic synapses on CA1 pyramidal neurons is sequential and correlates with the development of the apical dendrite.

    Science.gov (United States)

    Tyzio, R; Represa, A; Jorquera, I; Ben-Ari, Y; Gozlan, H; Aniksztejn, L

    1999-12-01

    We have performed a morphofunctional analysis of CA1 pyramidal neurons at birth to examine the sequence of formation of GABAergic and glutamatergic postsynaptic currents (PSCs) and to determine their relation to the dendritic arborization of pyramidal neurons. We report that at birth pyramidal neurons are heterogeneous. Three stages of development can be identified: (1) the majority of the neurons (80%) have small somata, an anlage of apical dendrite, and neither spontaneous nor evoked PSCs; (2) 10% of the neurons have a small apical dendrite restricted to the stratum radiatum and PSCs mediated only by GABA(A) receptors; and (3) 10% of the neurons have an apical dendrite that reaches the stratum lacunosum moleculare and PSCs mediated both by GABA(A) and glutamate receptors. These three groups of pyramidal neurons can be differentiated by their capacitance (C(m) = 17.9 +/- 0.8; 30.2 +/- 1.6; 43.2 +/- 3.0 pF, respectively). At birth, the synaptic markers synapsin-1 and synaptophysin labeling are present in dendritic layers but not in the stratum pyramidale, suggesting that GABAergic peridendritic synapses are established before perisomatic ones. The present observations demonstrate that GABAergic and glutamatergic synapses are established sequentially with GABAergic synapses being established first most likely on the apical dendrites of the principal neurons. We propose that different sets of conditions are required for the establishment of functional GABA and glutamate synapses, the latter necessitating more developed neurons that have apical dendrites that reach the lacunosum moleculare region.

  10. Complement and microglia mediate early synapse loss in Alzheimer mouse models.

    Science.gov (United States)

    Hong, Soyon; Beja-Glasser, Victoria F; Nfonoyim, Bianca M; Frouin, Arnaud; Li, Shaomin; Ramakrishnan, Saranya; Merry, Katherine M; Shi, Qiaoqiao; Rosenthal, Arnon; Barres, Ben A; Lemere, Cynthia A; Selkoe, Dennis J; Stevens, Beth

    2016-05-06

    Synapse loss in Alzheimer's disease (AD) correlates with cognitive decline. Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease. Here we show in mouse models that complement and microglia mediate synaptic loss early in AD. C1q, the initiating protein of the classical complement cascade, is increased and associated with synapses before overt plaque deposition. Inhibition of C1q, C3, or the microglial complement receptor CR3 reduces the number of phagocytic microglia, as well as the extent of early synapse loss. C1q is necessary for the toxic effects of soluble β-amyloid (Aβ) oligomers on synapses and hippocampal long-term potentiation. Finally, microglia in adult brains engulf synaptic material in a CR3-dependent process when exposed to soluble Aβ oligomers. Together, these findings suggest that the complement-dependent pathway and microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in AD.

  11. The Calmodulin-Binding Transcription Activator CAMTA1 Is Required for Long-Term Memory Formation in Mice

    Science.gov (United States)

    Bas-Orth, Carlos; Tan, Yan-Wei; Oliveira, Ana M. M.; Bengtson, C. Peter; Bading, Hilmar

    2016-01-01

    The formation of long-term memory requires signaling from the synapse to the nucleus to mediate neuronal activity-dependent gene transcription. Synapse-to-nucleus communication is initiated by influx of calcium ions through synaptic NMDA receptors and/or L-type voltage-gated calcium channels and involves the activation of transcription factors by…

  12. Elfn1 regulates target-specific release probability at CA1-interneuron synapses

    OpenAIRE

    Sylwestrak, Emily L.; Ghosh, Anirvan

    2012-01-01

    Although synaptic transmission may be unidirectional, the establishment of synaptic connections with specific properties can involve bidirectional signaling. Pyramidal neurons in the hippocampus form functionally distinct synapses onto two types of interneurons. Excitatory synapses onto oriens-lacunosum moleculare (O-LM) interneurons are facilitating and have a low release probability, whereas synapses onto parvalbumin interneurons are depressing and have a high release probability. Here, we ...

  13. Targeting CD28, CTLA-4 and PD-L1 costimulation differentially controls immune synapses and function of human regulatory and conventional T-cells.

    Directory of Open Access Journals (Sweden)

    Nahzli Dilek

    Full Text Available CD28, CTLA-4 and PD-L1, the three identified ligands for CD80/86, are pivotal positive and negative costimulatory molecules that, among other functions, control T cell motility and formation of immune synapse between T cells and antigen-presenting cells (APCs. What remains incompletely understood is how CD28 leads to the activation of effector T cells (Teff but inhibition of suppression by regulatory T cells (Tregs, while CTLA-4 and PD-L1 inhibit Teff function but are crucial for the suppressive function of Tregs. Using alloreactive human T cells and blocking antibodies, we show here by live cell dynamic microscopy that CD28, CTLA-4, and PD-L1 differentially control velocity, motility and immune synapse formation in activated Teff versus Tregs. Selectively antagonizing CD28 costimulation increased Treg dwell time with APCs and induced calcium mobilization which translated in increased Treg suppressive activity, in contrast with the dampening effect on Teff responses. The increase in Treg suppressive activity after CD28 blockade was also confirmed with polyclonal Tregs. Whereas CTLA-4 played a critical role in Teff by reversing TCR-induced STOP signals, it failed to affect motility in Tregs but was essential for formation of the Treg immune synapse. Furthermore, we identified a novel role for PD-L1-CD80 interactions in suppressing motility specifically in Tregs. Thus, our findings reveal that the three identified ligands of CD80/86, CD28, CTLA-4 and PD-L1, differentially control immune synapse formation and function of the human Teff and Treg cells analyzed here. Individually targeting CD28, CTLA-4 and PD-L1 might therefore represent a valuable therapeutic strategy to treat immune disorders where effector and regulatory T cell functions need to be differentially targeted.

  14. Tricornered Kinase Regulates Synapse Development by Regulating the Levels of Wiskott-Aldrich Syndrome Protein.

    Directory of Open Access Journals (Sweden)

    Rajalaxmi Natarajan

    Full Text Available Precise regulation of synapses during development is essential to ensure accurate neural connectivity and function of nervous system. Many signaling pathways, including the mTOR (mechanical Target of Rapamycin pathway operate in neurons to maintain genetically determined number of synapses during development. mTOR, a kinase, is shared between two functionally distinct multi-protein complexes- mTORC1 and mTORC2, that act downstream of Tuberous Sclerosis Complex (TSC. We and others have suggested an important role for TSC in synapse development at the Drosophila neuromuscular junction (NMJ synapses. In addition, our data suggested that the regulation of the NMJ synapse numbers in Drosophila largely depends on signaling via mTORC2. In the present study, we further this observation by identifying Tricornered (Trc kinase, a serine/threonine kinase as a likely mediator of TSC signaling. trc genetically interacts with Tsc2 to regulate the number of synapses. In addition, Tsc2 and trc mutants exhibit a dramatic reduction in synaptic levels of WASP, an important regulator of actin polymerization. We show that Trc regulates the WASP levels largely, by regulating the transcription of WASP. Finally, we show that overexpression of WASP (Wiskott-Aldrich Syndrome Protein in trc mutants can suppress the increase in the number of synapses observed in trc mutants, suggesting that WASP regulates synapses downstream of Trc. Thus, our data provide a novel insight into how Trc may regulate the genetic program that controls the number of synapses during development.

  15. The link between turbulence, magnetic fields, filaments, and star formation in the Central Molecular Zone cloud G0.253+0.016

    CERN Document Server

    Federrath, C; Longmore, S N; Kruijssen, J M D; Bally, J; Contreras, Y; Crocker, R M; Garay, G; Jackson, J M; Testi, L; Walsh, A J

    2016-01-01

    Star formation is primarily controlled by the interplay between gravity, turbulence, and magnetic fields. However, the turbulence and magnetic fields in molecular clouds near the Galactic Center may differ substantially from spiral-arm clouds. Here we determine the physical parameters of the central molecular zone (CMZ) cloud G0.253+0.016, its turbulence, magnetic field and filamentary structure. Using column-density maps based on dust-continuum emission observations with ALMA+Herschel, we identify filaments and show that at least one dense core is located along them. We measure the filament width W_fil=0.17$\\pm$0.08pc and the sonic scale {\\lambda}_sonic=0.15$\\pm$0.11pc of the turbulence, and find W_fil~{\\lambda}_sonic. A strong velocity gradient is seen in the HNCO intensity-weighted velocity maps obtained with ALMA+Mopra, which is likely caused by large-scale shearing of G0.253+0.016, producing a wide double-peaked velocity PDF. After subtracting the gradient to isolate the turbulent motions, we find a near...

  16. The Starburst in the Abell 1835 Cluster Central Galaxy: A Case Study of Galaxy Formation Regulated by an Outburst from a Supermassive Black Hole

    CERN Document Server

    McNamara, B R; Carilli, C L; Nulsen, P E J; Rafferty, D A; Ryan, R; Sharma, M; Steiner, J; Wise, M W

    2006-01-01

    We present an optical, X-ray, and radio analysis of the starburst in the Abell 1835 cluster's central cD galaxy. The dense gas surrounding the galaxy is radiating X-rays with a luminosity of ~1E45 erg/s consistent with a cooling rate of ~1000-2000 solar masses per year. However, new Chandra and XMM-Newton observations find less than 200 solar masses per year of gas cooling below ~2 keV, a level that is consistent with the cD's current star formation rate of 100-180 solar masses per year. One or more heating agents (feedback) must then be replenishing the remaining radiative losses. The heat fluxes from supernova explosions and thermal conduction alone are unable to do so. However, a pair of X-ray cavities from an AGN outburst has deposited ~1.7E60 erg into the surrounding gas over the past 40 Myr. The corresponding jet power 1.4E45 erg/sec is enough to offset most of the radiative losses from the cooling gas. The jet power exceeds the radio synchrotron power by ~4000 times, making this one of the most radiati...

  17. Innovative design of composite structures: The use of curvilinear fiber format to improve buckling resistance of composite plates with central circular holes

    Science.gov (United States)

    Hyer, M. W.; Lee, H. H.

    1990-01-01

    The gains in buckling performance are explored that can be achieved by deviating from the conventional straightline fiber format and considering the situation whereby the fiber orientation in a layer, or a group of layers, can vary from point to point. The particular situation studied is a simply supported square plate with a centrally located hole loaded in compression. By using both a sensitivity analysis and a gradient-search technique, fiber orientation in a number of regions of the plate are selected so as to increase the buckling load relative to baseline straightline designs. The sensitivity analysis is used to determine which regions of the plate have the most influence on buckling load, and the gradient search is used to find the design that is believed to represent the absolute maximum buckling load for the conditions prescribed. Convergence studies and sensitivity of the final design are discussed. By examining the stress resultant contours, it is shown how the curvilinear fibers move the load away from the unsupported hole region of the plate to the supported edges, thus increasing the buckling capacity. The tensile capacity of the improved buckling design is investigated, and it is shown that both tensile capacity and buckling capacity can be improved with the curvilinear fiber concept.

  18. Carbonate Sequence Stratigraphy of a Back-Arc Basin: A Case Study of the Qom Formation in the Kashan Area, Central Iran

    Institute of Scientific and Technical Information of China (English)

    XU Guoqiang; ZHANG Shaonan; LI Zhongdong; SONG Lailiang; LIU Huimin

    2007-01-01

    The Qom Formation comprises Oligo-Miocene deposits from a marine succession distributed in the Central Basin of Iran. It is composed of five members designated as A-F. Little previous work exists on the sequence stratigraphy. Based on an integrated study of sequence stratigraphy with outcrop data, wells and regional seismic profiles, the Qom Formation is interpreted as a carbonate succession deposited in a mid-Tertiary back-arc basin. There are two second-order sequences (designated as SS1 and SS2) and five third-order sequences (designated as S1-S5). Five distinct systems tracts including transgressive, highstand, forced regressive, slope margin and lowstand have been recognized. The relationship between the sequences and lithologic sub-units has been collated and defined (S1 to S5 individually corresponding to A-C1, C2-C4, D-E, the lower and upper portions of F); a relative sea level change curve and the sequence stratigraphic framework have been established and described in detail. The coincidence of relative sea level change between that of the determined back-arc basin and the world indicates that the sedimentary cycles of the Qom Formation are mainly controlled by eustatic cycles. The variable combination of the systems tracts and special tectonic-depositional setting causally underpin multiple sequence stratigraphic framework styles seen in the carbonates of the back-arc basin revealing: (1) a continental margin basin that developed some form of barrier, characterized by the development of multiple cycles of carbonate-evaporites; (2) a flat carbonate ramp, which occurred on the southern shelf formed by the lack of clastic supply from nearby magmatic islands plus mixed siliciclastics and carbonates that occurred on the northern shelf due to a sufficient clastics supply from the land; and (3) a forced regressive stratigraphic stacking pattern that occured on the southern shelf and in basin lows due to the uplifting of the southern shelf. Thick and widespread

  19. Genetic deletion of NR3A accelerates glutamatergic synapse maturation.

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    Maile A Henson

    Full Text Available Glutamatergic synapse maturation is critically dependent upon activation of NMDA-type glutamate receptors (NMDARs; however, the contributions of NR3A subunit-containing NMDARs to this process have only begun to be considered. Here we characterized the expression of NR3A in the developing mouse forebrain and examined the consequences of NR3A deletion on excitatory synapse maturation. We found that NR3A is expressed in many subcellular compartments, and during early development, NR3A subunits are particularly concentrated in the postsynaptic density (PSD. NR3A levels dramatically decline with age and are no longer enriched at PSDs in juveniles and adults. Genetic deletion of NR3A accelerates glutamatergic synaptic transmission, as measured by AMPAR-mediated postsynaptic currents recorded in hippocampal CA1. Consistent with the functional observations, we observed that the deletion of NR3A accelerated the expression of the glutamate receptor subunits NR1, NR2A, and GluR1 in the PSD in postnatal day (P 8 mice. These data support the idea that glutamate receptors concentrate at synapses earlier in NR3A-knockout (NR3A-KO mice. The precocious maturation of both AMPAR function and glutamate receptor expression are transient in NR3A-KO mice, as AMPAR currents and glutamate receptor protein levels are similar in NR3A-KO and wildtype mice by P16, an age when endogenous NR3A levels are normally declining. Taken together, our data support a model whereby NR3A negatively regulates the developmental stabilization of glutamate receptors involved in excitatory neurotransmission, synaptogenesis, and spine growth.

  20. GABA and Endocannabinoids Mediate Depotentiation of Schaffer Collateral Synapses Induced by Stimulation of Temperoammonic Inputs.

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    Yukitoshi Izumi

    Full Text Available Long-term potentiation (LTP of Schaffer collateral (SC synapses in the hippocampus is thought to play a key role in episodic memory formation. Because the hippocampus is a shorter-term, limited capacity storage system, repeated bouts of learning and synaptic plasticity require that SC synapses reset to baseline at some point following LTP. We previously showed that repeated low frequency activation of temperoammonic (TA inputs to the CA1 region depotentiates SC LTP without persistently altering basal transmission. This heterosynaptic depotentiation involves adenosine A1 receptors but not N-methyl-D-aspartate receptors, metabotropic glutamate receptors or L-type calcium channels. In the present study, we used rat hippocampal slices to explore other messengers contributing to TA-induced SC depotentiation, and provide evidence for the involvement of cannabinoid-1 and γ-aminobutyric acid (GABA type-A receptors as more proximal signaling events leading to synaptic resetting, with A1 receptor activation serving as a downstream event. Surprisingly, we found that TA-induced SC depotentiation is independent of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA/kainate glutamate receptors. We also examined the involvement of mitogen-activated protein kinases (MAPKs, and found a role for extracellular-signal related kinase 1/2 and p38 MAPK, but not c-Jun-N-terminal kinase. These results indicate that low frequency stimulation of TA inputs to CA1 activates a complex signaling network that instructs SC synaptic resetting. The involvement of GABA and endocannabinoids suggest mechanisms that could contribute to cognitive dysfunction associated with substance abuse and neuropsychiatric disorders.

  1. Bidirectional Hebbian plasticity at hippocampal mossy fiber synapses on CA3 interneurons.

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    Galván, Emilio J; Calixto, Eduardo; Barrionuevo, Germán

    2008-12-24

    Hippocampal area CA3 is critically involved in the formation of nonoverlapping neuronal subpopulations ("pattern separation") to store memory representations as distinct events. Efficient pattern separation relies on the strong and sparse excitatory input from the mossy fibers (MFs) to pyramidal cells and feedforward inhibitory interneurons. However, MF synapses on CA3 pyramidal cells undergo long-term potentiation (LTP), which, if unopposed, will degrade pattern separation because MF activation will now recruit additional CA3 pyramidal cells. Here, we demonstrate MF LTP in stratum lacunosum-moleculare (L-M) interneurons induced by the same stimulation protocol that induces MF LTP in pyramidal cells. This LTP was NMDA receptor (NMDAR) independent and occurred at MF Ca(2+)-impermeable AMPA receptor synapses. LTP was prevented by with voltage clamping the postsynaptic cell soma during high-frequency stimulation (HFS), intracellular injections of the Ca(2+) chelator BAPTA (20 mm), or bath applications of the L-type Ca(2+) channel blocker nimodipine (10 microm). We propose that MF LTP in L-M interneurons preserves the sparsity of pyramidal cell activation, thus allowing CA3 to maintain its role in pattern separation. In the presence of the mGluR1alpha antagonist LY367385 [(S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic acid] (100 microm), the same HFS that induces MF LTP in naive slices triggered NMDAR-independent MF LTD. This LTD, like LTP, required activation of the L-type Ca(2+) channel and also was induced after blockade of IP(3) receptors with heparin (4 mg/ml) or the selective depletion of receptor-gated Ca(2+) stores with ryanodine (10 or 100 microm). We conclude that L-M interneurons are endowed with Ca(2+) signaling cascades suitable for controlling the polarity of MF long-term plasticity induced by joint presynaptic and postsynaptic activities.

  2. GABA and Endocannabinoids Mediate Depotentiation of Schaffer Collateral Synapses Induced by Stimulation of Temperoammonic Inputs.

    Science.gov (United States)

    Izumi, Yukitoshi; Zorumski, Charles F

    2016-01-01

    Long-term potentiation (LTP) of Schaffer collateral (SC) synapses in the hippocampus is thought to play a key role in episodic memory formation. Because the hippocampus is a shorter-term, limited capacity storage system, repeated bouts of learning and synaptic plasticity require that SC synapses reset to baseline at some point following LTP. We previously showed that repeated low frequency activation of temperoammonic (TA) inputs to the CA1 region depotentiates SC LTP without persistently altering basal transmission. This heterosynaptic depotentiation involves adenosine A1 receptors but not N-methyl-D-aspartate receptors, metabotropic glutamate receptors or L-type calcium channels. In the present study, we used rat hippocampal slices to explore other messengers contributing to TA-induced SC depotentiation, and provide evidence for the involvement of cannabinoid-1 and γ-aminobutyric acid (GABA) type-A receptors as more proximal signaling events leading to synaptic resetting, with A1 receptor activation serving as a downstream event. Surprisingly, we found that TA-induced SC depotentiation is independent of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptors. We also examined the involvement of mitogen-activated protein kinases (MAPKs), and found a role for extracellular-signal related kinase 1/2 and p38 MAPK, but not c-Jun-N-terminal kinase. These results indicate that low frequency stimulation of TA inputs to CA1 activates a complex signaling network that instructs SC synaptic resetting. The involvement of GABA and endocannabinoids suggest mechanisms that could contribute to cognitive dysfunction associated with substance abuse and neuropsychiatric disorders.

  3. Choline Uptake by Glomerular Synapses Isolated from Bovine Cerebellar Vermis.

    Science.gov (United States)

    1986-01-01

    28 034 UNCLASSIFIED -7t. holing uptake by glomerular aynapaea isolated from bovine cerebellar venni - . 1) N1 IrRRIAN.E L NfISINndwr EtIIOMAS86 .t...w. -%FAt~Jr~a~etn 0,oAAM TX78215-5301 IL’SAJ) A-xpid ( kaolin 22nd. 19W5) hh.lhoac-anln uplake -ainalnnn 177 DIOMIDICAL DmIVIIN,~ F-5’. . Brain...Research. 366 (1986) 401-404 401 Elsevier BRE 21387 Choline uptake by glomerular synapses isolated from bovine cerebellar vermis D.M. TERRIAN, E.L

  4. Chronic lead exposure reduces junctional resistance at an electrical synapse.

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    Audesirk, G; Audesirk, T

    1984-01-01

    Both acute and chronic lead exposure have been found to inhibit transmission at chemical synapses, possibly by interfering with inward calcium current. We have found that chronic lead exposure slightly reduces input resistance and greatly reduces the junctional resistance between two strongly electrically coupled neurons in the pond snail Lymnaea stagnalis. The net effect is to increase the strength of electrical coupling. A reduction in gap junctional resistance would also be expected to increase the flow of small molecules between cells. However, Lucifer Yellow injections did not reveal dye-coupling between the cells. Lead exposure also increases the capacitance of the neurons.

  5. Mammalian Cochlear Hair Cell Regeneration and Ribbon Synapse Reformation

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    Xiaoling Lu

    2016-01-01

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

  6. Depositional Characteristics of Lake-Floor Fan of Cretaceous Lower Yaojia Formation in Western Part of Central Depression Region,Songliao Basin

    Institute of Scientific and Technical Information of China (English)

    Xin Renchen; Li Guifan; Feng Zhiqiang; Liang Jiangping; Lin Changsong

    2009-01-01

    Based on the integrated subsurface data,including those of over 600 m drilled cores,more than 30 drilled wells and 600 km2 three-dimensional (3D) seismic-reflection data of the study area, the characteristics of the lake-floor fan of lower Yaojia(姚家) Formation have been clarified.An evident lacustrine slope break and a steep slope belt developed in the west of Songliao(松辽)basin during depositional period of Qingshankou(青山口)-Yaojia formations(K2).The slope gradient was about 15 m/km.During the depositional period of lower Yaojia Formation,the lake shrank and the shore line of the western Songliao basin shifted to the lacustrine slope-break.The wedge-shaped sediment body,which is interpreted as the lowstand system tract of SQy1 (LSTy1),developed in the area below the slope-break.The LSTyl is pinched out in the west of the study area.As to the thickness of LSTyl,ft is thicker in the east with SO m in its thickness than in the west The LSTyl,rich in sandstone,can be divided into lower part LSTylL and upper part LSTy1u based on two onlap seismic reflection phases,and core and logging data clearly.The various sediments' gravity flow deposits developed and the complex of lake-floor fan formed in the LSTyl under the slope-break in the western part of the central depression region.The lake-floor fan consists of various sediments' gravity flow deposits,including: (1) turbidity deposits with characteristics of Bouma sequences; (2) sand-bearing muddy debrite dominated by mud and mixed by sand; (3) mud-bearing sandy debrites characterized by dominated sand and mixed by mud; (4) sandy debris laminar flow deposits with massive or inclined bedding,and (5) sandy slump deposits developed as deforma tional sedimentary structure.During the lower lake-level period (LSTy1L),the western clinoform region was erosion or sediment pass-by area; the terrigenous clastic was directly transported to deep-water area,converted to channelized sandy debris flow,and combined with slump

  7. The Middle Jurassic basinal deposits of the Surmeh Formation in the Central Zagros Mountains, southwest Iran: Facies, sequence stratigraphy, and controls

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    Lasemi, Y.; Jalilian, A.H.

    2010-01-01

    The lower part of the Lower to Upper Jurassic Surmeh Formation consists of a succession of shallow marine carbonates (Toarcian-Aalenian) overlain by a deep marine basinal succession (Aalenian-Bajocian) that grades upward to Middle to Upper Jurassic platform carbonates. The termination of shallow marine carbonate deposition of the lower part of the Surmeh Formation and the establishment of deep marine sedimentation indicate a change in the style of sedimentation in the Neotethys passive margin of southwest Iran during the Middle Jurassic. To evaluate the reasons for this change and to assess the basin configuration during the Middle Jurassic, this study focuses on facies analysis and sequence stratigraphy of the basinal deposits (pelagic and calciturbidite facies) of the Surmeh Formation, referred here as 'lower shaley unit' in the Central Zagros region. The upper Aalenian-Bajocian 'lower shaley unit' overlies, with an abrupt contact, the Toarcian-lower Aalenian platform carbonates. It consists of pelagic (calcareous shale and limestone) and calciturbidite facies grading to upper Bajocian-Bathonian platform carbonates. Calciturbidite deposits in the 'lower shaley unit' consist of various graded grainstone to lime mudstone facies containing mixed deep marine fauna and platform-derived material. These facies include quartz-bearing lithoclast/intraclast grainstone to lime mudstone, bioclast/ooid/peloid intraclast grainstone, ooid grainstone to packstone, and lime wackestone to mudstone. The calciturbidite layers are erosive-based and commonly exhibit graded bedding, incomplete Bouma turbidite sequence, flute casts, and load casts. They consist chiefly of platform-derived materials including ooids, intraclasts/lithoclasts, peloids, echinoderms, brachiopods, bivalves, and open-ocean biota, such as planktonic bivalves, crinoids, coccoliths, foraminifers, and sponge spicules. The 'lower shaley unit' constitutes the late transgressive and the main part of the highstand

  8. Bibliometric analysis of the Korean Journal of Parasitology: measured from SCI, PubMed, Scopus, and Synapse databases.

    Science.gov (United States)

    Lee, Choon Shil

    2009-10-01

    The Korean Journal of Parasitology (KJP) is the official journal of the Korean Society for Parasitology which is celebrating its 50th anniversary in 2009. To assess the contributions and achievements of the KJP, bibliometric analysis was conducted based on the citation data retrieved from 4 major databases; SCI, PubMed, Synapse, and Scopus. It was found that the KJP articles were constantly cited by the articles published in major international journals represented in these databases. More than 60% of 1,370 articles published in the KJP from 1963 to June 2009 were cited at least once by SCI articles. The overall average times cited by SCI articles are 2.6. The rate is almost 3 times higher for the articles published in the last 10 years compared to 1.0 for the articles of the 1960s. The SCI journal impact factor for 2008 is calculated as 0.871. It is increasing and it is expected to increase further with the introduction of the KJP in the database in 2008. The more realistic h-indices were measured from the study data set covering all the citations to the KJP; 17 for SCI, 6 for PubMed, 19 for Synapse, and 17 for Scopus. Synapse extensively picked up the citations to the earlier papers not retrievable from the other 3 databases. It identified many papers published in the 1960s and in the 1980s which have been cited heavily, proving the central role of the KJP in the dissemination of the important research findings over the last 5 decades.

  9. Potentiation decay of synapses and length distributions of synfire chains self-organized in recurrent neural networks.

    Science.gov (United States)

    Miller, Aaron; Jin, Dezhe Z

    2013-12-01

    Synfire chains are thought to underlie precisely timed sequences of spikes observed in various brain regions and across species. How they are formed is not understood. Here we analyze self-organization of synfire chains through the spike-timing dependent plasticity (STDP) of the synapses, axon remodeling, and potentiation decay of synaptic weights in networks of neurons driven by noisy external inputs and subject to dominant feedback inhibition. Potentiation decay is the gradual, activity-independent reduction of synaptic weights over time. We show that potentiation decay enables a dynamic and statistically stable network connectivity when neurons spike spontaneously. Periodic stimulation of a subset of neurons leads to formation of synfire chains through a random recruitment process, which terminates when the chain connects to itself and forms a loop. We demonstrate that chain length distributions depend on the potentiation decay. Fast potentiation decay leads to long chains with wide distributions, while slow potentiation decay leads to short chains with narrow distributions. We suggest that the potentiation decay, which corresponds to the decay of early long-term potentiation of synapses, is an important synaptic plasticity rule in regulating formation of neural circuity through STDP.

  10. Water quality of the Ogallala Formation, central High Plains aquifer within the North Plains Groundwater Conservation District, Texas Panhandle, 2012-13

    Science.gov (United States)

    Baldys, Stanley; Haynie, Monti M.; Beussink, Amy M.

    2014-01-01

    In cooperation with the North Plains Groundwater Conservation District (NPGCD), the U.S. Geological Survey collected and analyzed water-quality samples at 30 groundwater monitor wells in the NPGCD in the Texas Panhandle. All of the wells were completed in the Ogallala Formation of the central High Plains aquifer. Samples from each well were collected during February–March 2012 and in March 2013. Depth to groundwater in feet below land surface was measured at each well before sampling to determine the water-quality sampling depths. Water-quality samples were analyzed for physical properties, major ions, nutrients, and trace metals, and 6 of the 30 samples were analyzed for pesticides. There was a strong relation between specific conductance and dissolved solids as evidenced by a coefficient of determination (R2) value of 0.98. The dissolved-solids concentration in water from five wells exceeded the secondary drinking-water standard of 500 milligrams per liter set by the U.S. Environmental Protection Agency. Water from 3 of these 5 wells was near the north central part of the NPGCD. Nitrate values exceeded the U.S. Environmental Protection Agency maximum contaminant level of 10 milligrams per liter in 2 of the 30 wells. A sodium-adsorption ratio of 23.4 was measured in the sample collected from well Da-3589 in Dallam County, with the next largest sodium-adsorption ratio measured in the sample collected from well Da-3588 (12.5), also in Dallum County. The sodium-adsorption ratios measured in all other samples were less than 10. The groundwater was generally a mixed cation-bicarbonate plus carbonate type. Twenty-three trace elements were analyzed, and no concentrations exceeded the secondary drinking-water standard or maximum contaminant level set by the U.S. Environmental Protection Agency for water supplies. In 2012, 6 of the 30 wells were sampled for commonly used pesticides. Atrazine and its degradate 2-Chloro-4-isopropylamino-6-amino-s-triazine were detected in

  11. Integration of nanoscale memristor synapses in neuromorphic computing architectures

    Science.gov (United States)

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Legenstein, Robert; Deligeorgis, George; Prodromakis, Themistoklis

    2013-09-01

    Conventional neuro-computing architectures and artificial neural networks have often been developed with no or loose connections to neuroscience. As a consequence, they have largely ignored key features of biological neural processing systems, such as their extremely low-power consumption features or their ability to carry out robust and efficient computation using massively parallel arrays of limited precision, highly variable, and unreliable components. Recent developments in nano-technologies are making available extremely compact and low power, but also variable and unreliable solid-state devices that can potentially extend the offerings of availing CMOS technologies. In particular, memristors are regarded as a promising solution for modeling key features of biological synapses due to their nanoscale dimensions, their capacity to store multiple bits of information per element and the low energy required to write distinct states. In this paper, we first review the neuro- and neuromorphic computing approaches that can best exploit the properties of memristor and scale devices, and then propose a novel hybrid memristor-CMOS neuromorphic circuit which represents a radical departure from conventional neuro-computing approaches, as it uses memristors to directly emulate the biophysics and temporal dynamics of real synapses. We point out the differences between the use of memristors in conventional neuro-computing architectures and the hybrid memristor-CMOS circuit proposed, and argue how this circuit represents an ideal building block for implementing brain-inspired probabilistic computing paradigms that are robust to variability and fault tolerant by design.

  12. Developmental patterning of glutamatergic synapses onto retinal ganglion cells

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    Schubert Timm

    2008-03-01

    Full Text Available Abstract Background Neurons receive excitatory synaptic inputs that are distributed across their dendritic arbors at densities and with spatial patterns that influence their output. How specific synaptic distributions are attained during development is not well understood. The distribution of glutamatergic inputs across the dendritic arbors of mammalian retinal ganglion cells (RGCs has long been correlated to the spatial receptive field profiles of these neurons. Thus, determining how glutamatergic inputs are patterned onto RGC dendritic arbors during development could provide insight into the cellular mechanisms that shape their functional receptive fields. Results We transfected developing and mature mouse RGCs with plasmids encoding fluorescent proteins that label their dendrites and glutamatergic postsynaptic sites. We found that as dendritic density (dendritic length per unit area of dendritic field decreases with maturation, the density of synapses along the dendrites increases. These changes appear coordinated such that RGCs attain the mature average density of postsynaptic sites per unit area (areal density by the time synaptic function emerges. Furthermore, stereotypic centro-peripheral gradients in the areal density of synapses across the arbor of RGCs are established at an early developmental stage. Conclusion The spatial pattern of glutamatergic inputs onto RGCs arises early in synaptogenesis despite ensuing reorganization of dendritic structure. We raise the possibility that these early patterns of synaptic distributions may arise from constraints placed on the number of contacts presynaptic neurons are able to make with the RGCs.

  13. NANC transmission at a varicosity: the individuality of single synapses.

    Science.gov (United States)

    Bennett, M R

    2000-07-01

    Nerve terminals consist of several hundred varicosities or synapses, each with a single active zone. The smooth muscle membrane apposing varicosities within about 50 nm is occupied by a 1-microm diameter cluster of P2X(1) receptors together with a mixture of other P2X subtypes; the rest of the membrane possesses small (0.4 microm diameter) clusters of P2X(1) to P2X(6) subunits. The small P2X clusters appear to form large clusters during development. This is supported by the observation that chimeras of P2X(1) subunits and green fluorescent protein (P2X(1)-GFP), when packaged into adenoviruses used to infect excitable cells, initially form a diffuse distribution of small clusters of P2X(1)-GFP in the membrane; these can be later observed in real time to form large clusters. Recording the electrical signs of ATP release from single adjacent varicosities, or using antibodies to label the extent of exocytosis from them, shows that they release with quite different probabilities. There are large quantitative differences in the extent of P2X autoreceptors on the membranes of individual varicosities. These will contribute to the differences in the probability of secretion from individual varicosities. The present analysis of NANC transmission at single varicosities indicates that individual synapses possess different probabilities for the secretion of transmitter as well as different complements of autoreceptors and mixtures of postjunctional receptor subunits.

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

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    Karim El-Laithy

    2011-01-01

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

  15. Endogenous APP accumulates in synapses after BACE1 inhibition.

    Science.gov (United States)

    Nigam, Saket Milind; Xu, Shaohua; Ackermann, Frauke; Gregory, Joshua A; Lundkvist, Johan; Lendahl, Urban; Brodin, Lennart

    2016-08-01

    BACE1-mediated cleavage of APP is a pivotal step in the production of the Alzheimer related Aβ peptide and inhibitors of BACE1 are currently in clinical development for the treatment of Alzheimer disease (AD). While processing and trafficking of APP has been extensively studied in non-neuronal cells, the fate of APP at neuronal synapses and in response to reduced BACE1 activity has not been fully elucidated. Here we examined the consequence of reduced BACE1 activity on endogenous synaptic APP by monitoring N- and C-terminal APP epitopes by immunocytochemistry. In control rodent primary hippocampal neuron cultures, labeling with antibodies directed to N-terminal APP epitopes showed a significant overlap with synaptic vesicle markers (SV2 or synaptotagmin). In contrast, labeling with antibodies directed to C-terminal epitopes of APP showed only a limited overlap with these proteins. In neurons derived from BACE1-deficient mice, and in control neurons treated with a BACE1 inhibitor, both the N-terminal and the C-terminal APP labeling overlapped significantly with synaptic vesicle markers. Moreover, BACE1 inhibition increased the proximity between the APP C-terminus and SV2 as shown by a proximity ligation assay. These results, together with biochemical observations, indicate that BACE1 can regulate the levels of full-length APP at neuronal synapses.

  16. An Endothelial Planar Cell Model for Imaging Immunological Synapse Dynamics.

    Science.gov (United States)

    Martinelli, Roberta; Carman, Christopher V

    2015-12-24

    Adaptive immunity is regulated by dynamic interactions between T cells and antigen presenting cells ('APCs') referred to as 'immunological synapses'. Within these intimate cell-cell interfaces discrete sub-cellular clusters of MHC/Ag-TCR, F-actin, adhesion and signaling molecules form and remodel rapidly. These dynamics are thought to be critical determinants of both the efficiency and quality of the immune responses that develop and therefore of protective versus pathologic immunity. Current understanding of immunological synapses with physiologic APCs is limited by the inadequacy of the obtainable imaging resolution. Though artificial substrate models (e.g., planar lipid bilayers) offer excellent resolution and have been extremely valuable tools, they are inherently non-physiologic and oversimplified. Vascular and lymphatic endothelial cells have emerged as an important peripheral tissue (or stromal) compartment of 'semi-professional APCs'. These APCs (which express most of the molecular machinery of professional APCs) have the unique feature of forming virtually planar cell surface and are readily transfectable (e.g., with fluorescent protein reporters). Herein a basic approach to implement endothelial cells as a novel and physiologic 'planar cellular APC model' for improved imaging and interrogation of fundamental antigenic signaling processes will be described.

  17. Rock magnetic and other geophysical signatures of relative sea level change in the Middle Cambrian Wheeler Formation, Drum Mountains, West-Central Utah

    Science.gov (United States)

    Halgedahl, S. L.; Jarrard, R. D.

    2011-12-01

    The Wheeler Formation of West-Central Utah is a succession of mixed carbonate-siliciclastic rocks deposited during the Middle Cambrian along a passive continental margin of Laurentia (western margin, in today's coordinates). The depositional setting was a gentle ramp, bounded by a normal fault on the south. The present study focuses on the Wheeler Formation in the Drum Mountains, Utah, which is thought to have recorded Middle Cambrian sea level changes and which is known to yield exceptionally-preserved fossils with soft parts, similar to the famed Burgess shale. An integrated approach has been used here to investigate the following: (1) high-resolution changes in water depth (sea level changes?) with stratigraphic position; (2) where exceptionally preserved fossils are most likely to occur; and (3) mineralogical indicators of sea level change, such as magnetic susceptibility and other rock magnetic properties. Rocks consist of limestones, argillaceous limestones, and finely-bedded mudstones (shales). Methods used here are: measurements of magnetic susceptibility, natural remanent magnetization, and viscous remanent magnetization; hysteresis loops; spectral gamma ray; coulometry to determine calcite content; X-ray diffraction; and field mapping. In these rocks, mineralogical analyses indicate primarily a 2-component system of calcite and terrigenous minerals, mainly illite. Magnetic susceptibility, gamma ray, and coulometry results strongly indicate that magnetic susceptibility stems primarily from the paramagnetic clay component, namely, illite. Thus, both magnetic susceptibility and gamma ray increase linearly with decreasing calcite content throughout the section studied. Deep-water shales yield very high values of gamma ray and magnetic susceptibility; by contrast, carbonates with low gamma ray and low magnetic susceptibilities were deposited in relatively shallow water. These results lead to the following conclusions: (1) changes in relative water depth have

  18. Rheomorphic ignimbrites of the Rogerson Formation, central Snake River plain, USA: record of mid-Miocene rhyolitic explosive eruptions and associated crustal subsidence along the Yellowstone hotspot track

    Science.gov (United States)

    Knott, Thomas R.; Reichow, Marc K.; Branney, Michael J.; Finn, David R.; Coe, Robert S.; Storey, Michael; Bonnichsen, Bill

    2016-04-01

    Rogerson Graben, USA, is critically placed at the intersection between the Yellowstone hotspot track and the southern projection of the west Snake River rift. Eleven rhyolitic members of the re-defined, ≥420-m-thick, Rogerson Formation record voluminous high-temperature explosive eruptions, emplacing extensive ashfall and rheomorphic ignimbrite sheets. Yet, each member has subtly distinct field, chemical and palaeomagnetic characteristics. New regional correlations reveal that the Brown's View ignimbrite covers ≥3300 km2, and the Wooden Shoe ignimbrite covers ≥4400 km2 and extends into Nevada. Between 11.9 and ˜8 Ma, the average frequency of large explosive eruptions in this region was 1 per 354 ky, about twice that at Yellowstone. The chemistry and mineralogy of the early rhyolites show increasing maturity with time possibly by progressive fractional crystallisation. This was followed by a trend towards less-evolved rhyolites that may record melting and hybridisation of a mid-crustal source region. Contemporaneous magmatism-induced crustal subsidence of the central Snake River Basin is recorded by successive ignimbrites offlapping and thinning up the N-facing limb of a regional basin-margin monocline, which developed between 10.59 and 8 Ma. The syn-volcanic basin topography contrasted significantly with the present-day elevated Yellowstone hotspot plateau. Concurrent basin-and-range extension produced the N-trending Rogerson Graben: early uplift of the Shoshone Hills (≥10.34 Ma) was followed by initiation of the Shoshone Fault and an E-sloping half-graben (˜10.3-10.1 Ma). The graben asymmetry then reversed with initiation of the Brown's Bench Fault (≥8 Ma), which remained intermittently active until the Pliocene.

  19. Concentration, ozone formation potential and source analysis of volatile organic compounds (VOCs) in a thermal power station centralized area: A study in Shuozhou, China.

    Science.gov (United States)

    Yan, Yulong; Peng, Lin; Li, Rumei; Li, Yinghui; Li, Lijuan; Bai, Huiling

    2017-04-01

    Volatile organic compounds (VOCs) from two sampling sites (HB and XB) in a power station centralized area, in Shuozhou city, China, were sampled by stainless steel canisters and measured by gas chromatography-mass selective detection/flame ionization detection (GC-MSD/FID) in the spring and autumn of 2014. The concentration of VOCs was higher in the autumn (HB, 96.87 μg/m(3); XB, 58.94 μg/m(3)) than in the spring (HB, 41.49 μg/m(3); XB, 43.46 μg/m(3)), as lower wind speed in the autumn could lead to pollutant accumulation, especially at HB, which is a new urban area surrounded by residential areas and a transportation hub. Alkanes were the dominant group at both HB and XB in both sampling periods, but the contribution of aromatic pollutants at HB in the autumn was much higher than that of the other alkanes (11.16-19.55%). Compared to other cities, BTEX pollution in Shuozhou was among the lowest levels in the world. Because of the high levels of aromatic pollutants, the ozone formation potential increased significantly at HB in the autumn. Using the ratio analyses to identify the age of the air masses and analyze the sources, the results showed that the atmospheric VOCs at XB were strongly influenced by the remote sources of coal combustion, while at HB in the spring and autumn were affected by the remote sources of coal combustion and local sources of vehicle emission, respectively. Source analysis conducted using the Positive Matrix Factorization (PMF) model at Shuozhou showed that coal combustion and vehicle emissions made the two largest contributions (29.98% and 21.25%, respectively) to atmospheric VOCs. With further economic restructuring, the influence of vehicle emissions on the air quality should become more significant, indicating that controlling vehicle emissions is key to reducing the air pollution.

  20. Differential localization of delta glutamate receptors in the rat cerebellum: coexpression with AMPA receptors in parallel fiber-spine synapses and absence from climbing fiber-spine synapses.

    Science.gov (United States)

    Landsend, A S; Amiry-Moghaddam, M; Matsubara, A; Bergersen, L; Usami, S; Wenthold, R J; Ottersen, O P

    1997-01-15

    The delta 2 glutamate receptors are prominently expressed in Purkinje cells and are thought to play a key role in the induction of cerebellar long-term depression. The synaptic and subsynaptic localization of delta receptors in rat cerebellar cortex was investigated with sensitive and high-resolution immunogold procedures. After postembedding incubation with an antibody raised to a C-terminal peptide of delta 2, high gold particle densities occurred in all parallel fiber synapses with Purkinje cell dendritic spines, whereas other synapses were consistently devoid of labeling. Among the types of immunonegative synapse were climbing fiber synapses with spines and parallel fiber synapses with dendritic stems of interneurons. At the parallel fiber-spine synapse, gold particles signaling delta receptors were restricted to the postsynaptic specialization. By the use of double labeling with two different gold particle sizes, it was shown that delta and AMPA GluR2/3 receptors were colocalized along the entire extent of the postsynaptic specialization without forming separate domains. The distribution of gold particles representing delta receptors was consistent with a cytoplasmic localization of the C terminus and an absence of a significant presynaptic pool of receptor molecules. The present data suggest that the delta 2 receptors are targeted selectively to a subset of Purkinje cell spines and that they are coexpressed with ionotropic receptors in the postsynaptic specialization. This arrangement could allow for a direct interaction between the two classes of receptor.

  1. Ultrastructural analysis of neuronal synapses using state-of-the-art nano-imaging techniques

    Institute of Scientific and Technical Information of China (English)

    Changlu Tao; Chenglong Xia; Xiaobing Chen; Z. Hong Zhou; Guoqiang Bi

    2012-01-01

    Neuronal synapses are functional nodes in neural circuits.Their organization and activity define an individual's level of intelligence,emotional state and mental health.Changes in the structure and efficacy of synapses are the biological basis of learning and memory.However,investigation of the molecular architecture of synapses has been impeded by the lack of efficient techniques with sufficient resolution.Recent developments in state-of-the-art nano-imaging techniques have opened up a new window for dissecting the molecular organization of neuronal synapses with unprecedented resolution.Here,we review recent technological advances in nano-imaging techniques as well as their applications to the study of synapses,emphasizing super-resolution light microscopy and 3-dimensional electron tomography.

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

    Science.gov (United States)

    Gainey, Melanie A; Wolfe, Renna; Pourzia, Olivia; Feldman, Daniel E

    2016-01-01

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

  3. Activity of nAChRs containing alpha9 subunits modulates synapse stabilization via bidirectional signaling programs.

    Science.gov (United States)

    Murthy, Vidya; Taranda, Julián; Elgoyhen, A Belén; Vetter, Douglas E

    2009-12-01

    Although the synaptogenic program for cholinergic synapses of the neuromuscular junction is well known, little is known of the identity or dynamic expression patterns of proteins involved in non-neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss of nicotinic acetylcholine receptor (nAChR) alpha9 subunit expression in adult cochleae. However, the molecular mechanisms underlying these changes have remained obscure. To better understand synapse formation and the role of cholinergic activity in the synaptogenesis of the inner ear, we exploit the nAChR alpha9 subunit null mouse. In this mouse, functional acetylcholine (ACh) neurotransmission to the hair cells is completely silenced. Results demonstrate a premature, effusive innervation to the synaptic pole of the outer hair cells in alpha9 null mice coinciding with delayed expression of cell adhesion proteins during the period of effusive contact. Collapse of the ectopic innervation coincides with an age-related hyperexpression pattern in the null mice. In addition, we document changes in expression of presynaptic vesicle recycling/trafficking machinery in the alpha9 null mice that suggests a bidirectional information flow between the target of the neural innervation (the hair cells) and the presynaptic terminal that is modified by hair cell nAChR activity. Loss of nAChR activity may alter transcriptional activity, as CREB binding protein expression is decreased coincident with the increased expression of N-Cadherin in the adult alpha9 null mice. Finally, by using mice expressing the nondesensitizing alpha9 L9'T point mutant nAChR subunit, we show that increased nAChR activity drives synaptic hyperinnervation.

  4. Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits

    Science.gov (United States)

    Bonasera, Stephen J.; Arikkath, Jyothi; Boska, Michael D.; Chaudoin, Tammy R.; DeKorver, Nicholas W.; Goulding, Evan H.; Hoke, Traci A.; Mojtahedzedah, Vahid; Reyelts, Crystal D.; Sajja, Balasrinivasa; Schenk, A. Katrin; Tecott, Laurence H.; Volden, Tiffany A.

    2016-01-01

    We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene expression accompany these phenotypes. Aging evokes upregulation of immune pattern recognition receptors and cell adhesion molecules. However, these changes do not localize to microglia, the major CNS immunocyte. Consistent with a neuronal role, there is a marked age-related increase in excitatory synapses over the cerebellum and hypothalamus. Functional imaging of these regions is consistent with age-related synaptic impairments. These studies suggest that aging reactivates a developmental program employed during embryogenesis where immune molecules guide synapse formation and pruning. Renewed activity in this program may disrupt excitatory neurotransmission, causing significant behavioral deficits. PMID:27689748

  5. Motor axon synapses on renshaw cells contain higher levels of aspartate than glutamate.

    Directory of Open Access Journals (Sweden)

    Dannette S Richards

    Full Text Available Motoneuron synapses on spinal cord interneurons known as Renshaw cells activate nicotinic, AMPA and NMDA receptors consistent with co-release of acetylcholine and excitatory amino acids (EAA. However, whether these synapses express vesicular glutamate transporters (VGLUTs capable of accumulating glutamate into synaptic vesicles is controversial. An alternative possibility is that these synapses release other EAAs, like aspartate, not dependent on VGLUTs. To clarify the exact EAA concentrated at motor axon synapses we performed a quantitative postembedding colloidal gold immunoelectron analysis for aspartate and glutamate on motor axon synapses (identified by immunoreactivity to the vesicular acetylcholine transporter; VAChT contacting calbindin-immunoreactive (-IR Renshaw cell dendrites. The results show that 71% to 80% of motor axon synaptic boutons on Renshaw cells contained aspartate immunolabeling two standard deviations above average neuropil labeling. Moreover, VAChT-IR synapses on Renshaw cells contained, on average, aspartate immunolabeling at 2.5 to 2.8 times above the average neuropil level. In contrast, glutamate enrichment was lower; 21% to 44% of VAChT-IR synapses showed glutamate-IR two standard deviations above average neuropil labeling and average glutamate immunogold density was 1.7 to 2.0 times the neuropil level. The results were not influenced by antibody affinities because glutamate antibodies detected glutamate-enriched brain homogenates more efficiently than aspartate antibodies detecting aspartate-enriched brain homogenates. Furthermore, synaptic boutons with ultrastructural features of Type I excitatory synapses were always labeled by glutamate antibodies at higher density than motor axon synapses. We conclude that motor axon synapses co-express aspartate and glutamate, but aspartate is concentrated at higher levels than glutamate.

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

    Science.gov (United States)

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

    2014-01-01

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

  7. Cyanobacteria/Foraminifera Association from Anoxic/Dysoxic Beds of the Agua Nueva Formation (Upper Cretaceous - Cenomanian/Turonian) at Xilitla, San Luis Potosi, Central Mexico

    Science.gov (United States)

    Blanco-Piñón, A.; Maurrasse, F. J.; Rojas-León, A.; Duque-Botero, F.

    2008-05-01

    The Agua Nueva Formation in the vicinity of Xilitla, State of San Luis Potosí, Central Mexico, consists of interbedded brown shale (Grayish orange 10YR 7/4 to Moderate yellowish brown 10YR 5/4) and dark-gray fossiliferous limestone (Bluish gray 5B 6/1 to Dark bluish gray 5B 4/1), varying between 10 and 20 cm in thickness. The sequence also includes 2 to 4 cm- thick intermittent bentonite layers (Moderate greenish yellow 10Y 7/4, to dark greenish yellow 10Y 6/6 and Light olive 10Y 5/4). At the field scale, shaly intervals show no apparent internal structures, whereas most limestone beds show primary lamination at the millimeter scale (1-2 mm), and intermittent layers of black chert of about 5 cm thick. Pyrite is present as disseminated crystals and as 2 cm-thick layers. Bioturbation or macrobenthic organisms other than inoceramids do not occur in the Agua Nueva Formation at Xilitla. Unusual macrofossils are present only in limestone strata, and consist of well- preserved diverse genera of fishes such as sharks, Ptychodus sp. and teleosteans, Rhynchodercetis sp., Tselfatia sp., Goulmimichthys sp., and scales of Ichtyodectiformes, as well as ammonites and inoceramids (Blanco et al., 2006). The presence of Inoceramus (Mytyloides) labiatus (Maldonado-Koederll, 1956) indicates an Early Turonian age for the sequence. Total carbonate content (CaCO3 = TIC) varies between 62 and 94% in the Limestone beds, which yield Total Organic Carbon (TOC) from 0.4% to 2.5%; the shale intervals contain TIC values consistently lower than 33% and TOC lower than 0.8% Microscopically the limestone beds vary from mudstone to packstone composed essentially of coccoid cyanobacteria similar to coeval deposits in northeastern Mexico, Coahuila State, at Parras de La Fuente (Duque- Botero 2006). Similarly, the microspheroids are spherical to sub-spherical, and occur as isolated elements or aggregates forming series of chains of parallel-packed light lamina 1-2 mm thick. Filamentous cyanobacteria

  8. Spin switches for compact implementation of neuron and synapse

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-02

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

  9. Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses

    OpenAIRE

    2013-01-01

    G protein-coupled receptor (GPR) 55 is sensitive to certain cannabinoids, it is expressed in the brain and, in cell cultures, it triggers mobilization of intracellular Ca(2+). However, the adaptive neurobiological significance of GPR55 remains unknown. Here, we use acute hippocampal slices and combine two-photon excitation Ca(2+) imaging in presynaptic axonal boutons with optical quantal analysis in postsynaptic dendritic spines to find that GPR55 activation transiently increases release prob...

  10. Glycine-mediated changes of onset reliability at a mammalian central synapse.

    Science.gov (United States)

    Kopp-Scheinpflug, C; Dehmel, S; Tolnai, S; Dietz, B; Milenkovic, I; Rübsamen, R

    2008-11-19

    Glycine is an inhibitory neurotransmitter activating a chloride conductance in the mammalian CNS. In vitro studies from brain slices revealed a novel presynaptic site of glycine action in the medial nucleus of the trapezoid body (MNTB) which increases the release of the excitatory transmitter glutamate from the calyx of Held. Here, we investigate the action of glycine on action potential firing of single MNTB neurons from the gerbil under acoustic stimulation in vivo. Iontophoretic application of the glycine receptor antagonist strychnine caused a significant decrease in spontaneous and sound-evoked firing rates throughout the neurons' excitatory response areas, with the largest changes at the respective characteristic frequency (CF). The decreased firing rate was accompanied by longer and more variable onset latencies of sound-evoked responses. Outside the neurons' excitatory response areas, firing rates increased during the application of strychnine due to a reduction of inhibitory sidebands, causing a broadening of frequency tuning. These results indicate that glycine enhances the efficacy for on-CF stimuli, while simultaneously suppressing synaptic transmission for off-CF stimuli. These in vivo results provide evidence of multiple excitatory and inhibitory glycine effects on the same neuronal population in the mature mammalian CNS.

  11. The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis

    Science.gov (United States)

    Onnis, A; Finetti, F; Patrussi, L; Gottardo, M; Cassioli, C; Spanò, S; Baldari, C T

    2015-01-01

    Accumulating evidence underscores the T-cell immune synapse (IS) as a site of intense vesicular trafficking, on which productive signaling and cell activation crucially depend. Although the T-cell antigen receptor (TCR) is known to exploit recycling to accumulate to the IS, the specific pathway that controls this process remains to be elucidated. Here we demonstrate that the small GTPase Rab29 is centrally implicated in TCR trafficking and IS assembly. Rab29 colocalized and interacted with Rab8, Rab11 and IFT20, a component of the intraflagellar transport system that regulates ciliogenesis and participates in TCR recycling in the non-ciliated T cell, as assessed by co-immunoprecipitation and immunofluorescence analysis. Rab29 depletion resulted in the inability of TCRs to undergo recycling to the IS, thereby compromizing IS assembly. Under these conditions, recycling TCRs accumulated in Rab11+ endosomes that failed to polarize to the IS due to defective Rab29-dependent recruitment of the dynein microtubule motor. Remarkably, Rab29 participates in a similar pathway in ciliated cells to promote primary cilium growth and ciliary localization of Smoothened. These results provide a function for Rab29 as a regulator of receptor recycling and identify this GTPase as a shared participant in IS and primary cilium assembly. PMID:26021297

  12. Patient-specific models of microglia-mediated engulfment of synapses and neural progenitors

    Science.gov (United States)

    Sellgren, C M; Sheridan, S D; Gracias, J; Xuan, D; Fu, T; Perlis, R H

    2017-01-01

    Engulfment of synapses and neural progenitor cells (NPCs) by microglia is critical for the development and maintenance of proper brain circuitry, and has been implicated in neurodevelopmental as well as neurodegenerative disease etiology. We have developed and validated models of these mechanisms by reprogramming microglia-like cells from peripheral blood mononuclear cells, and combining them with NPCs and neurons derived from induced pluripotent stem cells to create patient-specific cellular models of complement-dependent synaptic pruning and elimination of NPCs. The resulting microglia-like cells express appropriate markers and function as primary human microglia, while patient-matched macrophages differ markedly. As a demonstration of disease-relevant application, we studied the role of C4, recently implicated in schizophrenia, in engulfment of synaptic structures by human microglia. The ability to create complete patient-specific cellular models of critical microglial functions utilizing samples taken during a single clinical visit will extend the ability to model central nervous system disease while facilitating high-throughput screening. PMID:27956744

  13. Ammonoids from the Dalle des Iridet of the Mouydir and Ahnet (Central Sahara and the Formation d'Hassi Sguilma of the Saoura Valley (Late Tournaisian–Early Viséan; Algeria

    Directory of Open Access Journals (Sweden)

    D. Korn

    2010-02-01

    Full Text Available Four ammonoid species are described from the Early Carboniferous (Mississippian Iridet Formation of the Ahnet and Mouydir (Central Sahara, Algeria; three of which are new: Eurites temertassetensis n. sp., Trimorphoceras teguentourense n. sp., and Trimorphoceras azzelmattiense n. sp. The species can be attributed to the North African Ammonellipsites-Merocanites Assemblage (Fascipericyclus-Ammonellipsites Genus Zone; Late Tournaisian to Early Viséan. Additionally, the two new species Ammonellipsites sguilmensis n. sp. and Muensteroceras beniabbesense n. sp. are described from the time equivalent Hassi Sguilma Formation of the Saoura Valley (north-western Algeria. doi:10.1002/mmng.200900012

  14. Synaptic and molecular mechanisms of glutamatergic synapses in pain and memory%谷氨酸性突触在痛觉和记忆中的突触和分子机制

    Institute of Scientific and Technical Information of China (English)

    卓敏

    2003-01-01

    谷氨酸是哺乳动物脑中的兴奋性递质.中枢神经系统的谷氨酸性突触广泛参与痛觉传递, 突触可塑性和递质的调节.谷氨酸的NMDA受体参与前脑相关的学习及功能.在这篇综述中, 我们提出前脑的NMDA受体通过增强谷氨酸性突触传递导致长期性的炎痛.具有增强NMDA受体功能的小鼠会产生更多的慢性痛.NMDA NR2B受体抑制剂在未来可能被用来控制人类的慢性痛.%Glutamate is a fast excitatory transmitter in mammalian brains. Glutamatergic synapses are found in central regions related to pain transmission, plasticity and modulation. Glutamate NMDA receptors in forebrain structures are well known to contribute to the formation and storage of information. Here we propose the hypothesis that forebrain NMDA receptors play an important role in persistent inflammatory pain by re-enforcing glutamate sensory transmission in the brain. Mice with enhanced function of forebrain NMDA receptors demonstrate selective enhancement of persistent pain and allodynia. Drugs targeting forebrain NMDA NR2B receptors may serve as a new class of medicine to control persistent pain in humans.

  15. PETROGENESIS OF THE METACARBONATE AND RELATED ROCKS OF THE SILGARÁ FORMATION, CENTRAL SANTANDER MASSIF, COLOMBIAN ANDES: AN OVERVIEW OF A “REACTION CALCIC EXOSCARN”

    Directory of Open Access Journals (Sweden)

    Castellanos O.M

    2008-06-01

    Full Text Available Metacarbonate rocks (pure and impure marbles, carbonate-silicate rocks, calc-silicate rocks and carbonate-bearing silicate rocks form a very complex group within the metamorphic sequence of the Silgará Formation at the central Santander Massif (CSM. These rocks are interpreted as derived from a sedimentary sequence (including limestones and dolostones, carbonate-bearing mudstones,  sandstones, tuffaceous and evaporitic sediments and marlstones overprinted by near-isochemical regional metamorphism. They usually appear as scarce intercalations from millimeter up to meter scale, within the high-grade pelitic rocks, in the lower part of the metamorphic section, although the proportion of metacarbonate rocks can be higher and different marble layers are exploited. We report for the first time the occurrence of a "reaction calcic exoskarn", which corresponds to
    such metacarbonate rocks, taking into account that a skarn can be developed during regional metamorphism and by different metasomatic processes, adjacent to intrusive bodies, along faults and shear zones, and what defines these rocks as a skarn is its mineralogy, which includes a variety of calc-silicate and associated minerals, usually dominated by garnet and pyroxene. Therefore, this paper focus attention to the occurrence of metacarbonate and
    related rocks, which occurs as small scale reactions zones that show a gradational contact from garnet-bearing pelitic rocks to marbles or carbonate-silicate rocks, giving particular interest to the calc-silicate rocks, which are characterized by the presence of elongated grains of banded clinopyroxene (diopside and scapolite and massive
    or scattered garnet. Several reaction-zones occur in the contact between impure calcite marble and garnet-bearing metapelite and the sequence of mineral assemblages in these reaction zones is: biotite + plagioclase K-feldspar garnet (Zone I, biotite + plagioclase K-feldspar garnet staurolite epidote

  16. Two Loci of expression for long-term depression at hippocampal mossy fiber-interneuron synapses.

    Science.gov (United States)

    Lei, Saobo; McBain, Chris J

    2004-03-03

    Two distinct forms of long-term depression (LTD) exist at mossy fiber synapses between dentate gyrus granule cells and hippocampal CA3 stratum lucidum interneurons. Although induction of each form of LTD requires an elevation of postsynaptic intracellular Ca2+, at Ca2+-impermeable AMPA receptor (CI-AMPAR) synapses, induction is NMDA receptor (NMDAR) dependent, whereas LTD at Ca2+-permeable AMPA receptor (CP-AMPAR) synapses is NMDAR independent. However, the expression locus of either form of LTD is not known. Using a number of criteria, including the coefficient of variation, paired-pulse ratio, AMPA-NMDA receptor activity, and the low-affinity AMPAR antagonist gamma-D-glutamyl-glycine, we demonstrate that LTD expression at CP-AMPAR synapses is presynaptic and results from reduced transmitter release, whereas LTD expression at CI-AMPAR synapses is postsynaptic. The N-ethylmaleimide-sensitive fusion protein-AP2-clathrin adaptor protein 2 inhibitory peptide pep2m occluded LTD expression at CI-AMPAR synapses but not at CP-AMPAR synapses, confirming that CI-AMPAR LTD involves postsynaptic AMPAR trafficking. Thus, mossy fiber innervation of CA3 stratum lucidum interneurons occurs via two parallel systems targeted to either Ca2+-permeable or Ca2+-impermeable AMPA receptors, each with a distinct expression locus for long-term synaptic plasticity.

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

    Directory of Open Access Journals (Sweden)

    Renee Baran

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

  18. Normal distribution of VGLUT1 synapses on spinal motoneuron dendrites and their reorganization after nerve injury.

    Science.gov (United States)

    Rotterman, Travis M; Nardelli, Paul; Cope, Timothy C; Alvarez, Francisco J

    2014-03-05

    Peripheral nerve injury induces permanent alterations in spinal cord circuitries that are not reversed by regeneration. Nerve injury provokes the loss of many proprioceptive IA afferent synapses (VGLUT1-IR boutons) from motoneurons, the reduction of IA EPSPs in motoneurons, and the disappearance of stretch reflexes. After motor and sensory axons successfully reinnervate muscle, lost IA VGLUT1 synapses are not re-established and the stretch reflex does not recover; however, electrically evoked EPSPs do recover. The reasons why remaining IA synapses can evoke EPSPs on motoneurons, but fail to transmit useful stretch signals are unknown. To better understand changes in the organization of VGLUT1 IA synapses that might influence their input strength, we analyzed their distribution over the entire dendritic arbor of motoneurons before and after nerve injury. Adult rats underwent complete tibial nerve transection followed by microsurgical reattachment and 1 year later motoneurons were intracellularly recorded and filled with neurobiotin to map the distribution of VGLUT1 synapses along their dendrites. We found in control motoneurons an average of 911 VGLUT1 synapses; ~62% of them were lost after injury. In controls, VGLUT1 synapses were focused to proximal dendrites where they were grouped in tight clusters. After injury, most synaptic loses occurred in the proximal dendrites and remaining synapses were declustered, smaller, and uniformly distributed throughout the dendritic arbor. We conclude that this loss and reorganization renders IA afferent synapses incompetent for efficient motoneuron synaptic depolarization in response to natural stretch, while still capable of eliciting EPSPs when synchronously fired by electrical volleys.

  19. Vesicular Trafficking to the Immune Synapse: How to Assemble Receptor-Tailored Pathways from a Basic Building Set.

    Science.gov (United States)

    Onnis, Anna; Finetti, Francesca; Baldari, Cosima T

    2016-01-01

    The signals that orchestrate T-cell activation are coordinated within a highly organized interface with the antigen-presenting cell (APC), known as the immune synapse (IS). IS assembly depends on T-cell antigen receptor engagement by a specific peptide antigen-major histocompatibility complex ligand. This primary event leads to polarized trafficking of receptors and signaling mediators associated with recycling endosomes to the cellular interface, which contributes to IS assembly as well as signal termination and favors information transfer from T cells to APCs. Here, we will review recent advances on the vesicular pathways implicated in IS assembly and maintenance, focusing on the spatiotemporal regulation of the traffic of specific receptors by Rab GTPases. Based on accumulating evidence that the IS is a functional homolog of the primary cilium, which coordinates several central signaling pathways in ciliated cells, we will also discuss the similarities in the mechanisms regulating vesicular trafficking to these specialized membrane domains.

  20. CRED Simrad em300 multibeam backscatter data of Jarvis Island, Pacific Remote Island Areas, Central Pacific in GeoTIFF format

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Multibeam backscatter imagery extracted from gridded bathymetry of the shelf and slope environments of Jarvis Atoll, Pacific Island Areas, Central Pacific. These...

  1. CRED Simrad em300 multibeam backscatter data from shelf and slope environments at Howland Island, Pacific Remote Island Areas, Central Pacific in netCDF format

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Multibeam backscatter imagery extracted from gridded bathymetry of Howland Island, Pacific Remote Island Areas, Central Pacific. These data provide coverage between...

  2. CRED Reson 8101 multibeam backscatter data of Palmyra Atoll, Pacific Remote Island Areas, Central Pacific with 1 meter resolution in GeoTIFF format

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Multibeam backscatter imagery extracted from gridded bathymetry of the lagoon, shelf, and slope environments of Palmyra Atoll, Pacific Island Areas, Central Pacific....

  3. The Rab GTPase Rab8 as a shared regulator of ciliogenesis and immune synapse assembly: From a conserved pathway to diverse cellular structures

    Science.gov (United States)

    Patrussi, Laura; Baldari, Cosima T.

    2016-01-01

    ABSTRACT Rab GTPases, which form the largest branch of the Ras GTPase superfamily, regulate almost every step of vesicle-mediated trafficking. Among them, Rab8 is an essential participant in primary cilium formation. In a report recently published in the Journal of Cell Science, Finetti and colleagues identify Rab8 as a novel player in vesicular traffic in the non-ciliated T lymphocytes, which contributes to the assembly of the specialized signaling platform known as the immune synapse. By interacting with the v-SNARE VAMP-3, Rab8 is indeed responsible for the final docking/fusion step in T cell receptor (TCR) recycling to the immune synapse. A second important take-home message which comes to light from this work is that VAMP-3 also interacts with Rab8 at the base of the cilium in NIH-3T3 cells, where it regulates ciliary growth and targeting of Smoothened at the plasma membrane. Hence the data presented in this report, in addition to identifying Rab8 as a novel player in vesicular traffic to the immune synapse, reveal how both ciliated and non-ciliated cells take advantage of a conserved pathway to build highly specific cellular structures. PMID:26587735

  4. Essential role for vav Guanine nucleotide exchange factors in brain-derived neurotrophic factor-induced dendritic spine growth and synapse plasticity.

    Science.gov (United States)

    Hale, Carly F; Dietz, Karen C; Varela, Juan A; Wood, Cody B; Zirlin, Benjamin C; Leverich, Leah S; Greene, Robert W; Cowan, Christopher W

    2011-08-31

    Brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB, regulate a wide range of cellular processes, including dendritic spine formation and functional synapse plasticity. However, the signaling mechanisms that link BDNF-activated TrkB to F-actin remodeling enzymes and dendritic spine morphological plasticity remain poorly understood. We report here that BDNF/TrkB signaling in neurons activates the Vav family of Rac/RhoA guanine nucleotide exchange factors through a novel TrkB-dependent mechanism. We find that Vav is required for BDNF-stimulated Rac-GTP production in cortical and hippocampal neurons. Vav is partially enriched at excitatory synapses in the postnatal hippocampus but does not appear to be required for normal dendritic spine density. Rather, we observe significant reductions in both BDNF-induced, rapid, dendritic spine head growth and in CA3-CA1 theta burst-stimulated long-term potentiation in Vav-deficient mouse hippocampal slices, suggesting that Vav-dependent regulation of dendritic spine morphological plasticity facilitates normal functional synapse plasticity.

  5. FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons

    Directory of Open Access Journals (Sweden)

    Carles eBosch

    2015-05-01

    Full Text Available The fine analysis of synaptic contacts is usually performed using transmission electron microscopy (TEM and its combination with neuronal labeling techniques. However, the complex 3D architecture of neuronal samples calls for their reconstruction from serial sections. Here we show that focused ion beam/scanning electron microscopy (FIB/SEM allows efficient, complete, and automatic 3D reconstruction of identified dendrites, including their spines and synapses, from GFP/DAB-labeled neurons, with a resolution comparable to that of TEM. We applied this technology to analyze the synaptogenesis of labeled adult-generated granule cells (GCs in mice. 3D reconstruction of spines in GCs aged 3–4 and 8–9 weeks revealed two different stages of spine development and unexpected features of synapse formation, including vacant and branched spines and presynaptic terminals establishing synapses with up to 10 spines. Given the reliability, efficiency, and high resolution of FIB/SEM technology and the wide use of DAB in conventional EM, we consider FIB/SEM fundamental for the detailed characterization of identified synaptic contacts in neurons in a high-throughput manner.

  6. FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons.

    Science.gov (United States)

    Bosch, Carles; Martínez, Albert; Masachs, Nuria; Teixeira, Cátia M; Fernaud, Isabel; Ulloa, Fausto; Pérez-Martínez, Esther; Lois, Carlos; Comella, Joan X; DeFelipe, Javier; Merchán-Pérez, Angel; Soriano, Eduardo

    2015-01-01

    The fine analysis of synaptic contacts is usually performed using transmission electron microscopy (TEM) and its combination with neuronal labeling techniques. However, the complex 3D architecture of neuronal samples calls for their reconstruction from serial sections. Here we show that focused ion beam/scanning electron microscopy (FIB/SEM) allows efficient, complete, and automatic 3D reconstruction of identified dendrites, including their spines and synapses, from GFP/DAB-labeled neurons, with a resolution comparable to that of TEM. We applied this technology to analyze the synaptogenesis of labeled adult-generated granule cells (GCs) in mice. 3D reconstruction of dendritic spines in GCs aged 3-4 and 8-9 weeks revealed two different stages of dendritic spine development and unexpected features of synapse formation, including vacant and branched dendritic spines and presynaptic terminals establishing synapses with up to 10 dendritic spines. Given the reliability, efficiency, and high resolution of FIB/SEM technology and the wide use of DAB in conventional EM, we consider FIB/SEM fundamental for the detailed characterization of identified synaptic contacts in neurons in a high-throughput manner.

  7. FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons

    Science.gov (United States)

    Bosch, Carles; Martínez, Albert; Masachs, Nuria; Teixeira, Cátia M.; Fernaud, Isabel; Ulloa, Fausto; Pérez-Martínez, Esther; Lois, Carlos; Comella, Joan X.; DeFelipe, Javier; Merchán-Pérez, Angel; Soriano, Eduardo

    2015-01-01

    The fine analysis of synaptic contacts is usually performed using transmission electron microscopy (TEM) and its combination with neuronal labeling techniques. However, the complex 3D architecture of neuronal samples calls for their reconstruction from serial sections. Here we show that focused ion beam/scanning electron microscopy (FIB/SEM) allows efficient, complete, and automatic 3D reconstruction of identified dendrites, including their spines and synapses, from GFP/DAB-labeled neurons, with a resolution comparable to that of TEM. We applied this technology to analyze the synaptogenesis of labeled adult-generated granule cells (GCs) in mice. 3D reconstruction of dendritic spines in GCs aged 3–4 and 8–9 weeks revealed two different stages of dendritic spine development and unexpected features of synapse formation, including vacant and branched dendritic spines and presynaptic terminals establishing synapses with up to 10 dendritic spines. Given the reliability, efficiency, and high resolution of FIB/SEM technology and the wide use of DAB in conventional EM, we consider FIB/SEM fundamental for the detailed characterization of identified synaptic contacts in neurons in a high-throughput manner. PMID:26052271

  8. BK potassium channels control transmitter release at CA3-CA3 synapses in the rat hippocampus.

    Science.gov (United States)

    Raffaelli, Giacomo; Saviane, Chiara; Mohajerani, Majid H; Pedarzani, Paola; Cherubini, Enrico

    2004-05-15

    Large conductance calcium- and voltage-activated potassium channels (BK channels) activate in response to calcium influx during action potentials and contribute to the spike repolarization and fast afterhyperpolarization. BK channels targeted to active zones in presynaptic nerve terminals have been shown to limit calcium entry and transmitter release by reducing the duration of the presynaptic spike at neurosecretory nerve terminals and at the frog neuromuscular junction. However, their functional role in central synapses is still uncertain. In the hippocampus, BK channels have been proposed to act as an 'emergency brake' that would control transmitter release only under conditions of excessive depolarization and accumulation of intracellular calcium. Here we demonstrate that in the CA3 region of hippocampal slice cultures, under basal experimental conditions, the selective BK channel blockers paxilline (10 microM) and iberiotoxin (100 nM) increase the frequency, but not the amplitude, of spontaneously occurring action potential-dependent EPSCs. These drugs did not affect miniature currents recorded in the presence of tetrodotoxin, suggesting that their action was dependent on action potential firing. Moreover, in double patch-clamp recordings from monosynaptically interconnected CA3 pyramidal neurones, blockade of BK channels enhanced the probability of transmitter release, as revealed by the increase in success rate, EPSC amplitude and the concomitant decrease in paired-pulse ratio in response to pairs of presynaptic action potentials delivered at a frequency of 0.05 Hz. BK channel blockers also enhanced the appearance of delayed responses, particularly following the second action potential in the paired-pulse protocol. These results are consistent with the hypothesis that BK channels are powerful modulators of transmitter release and synaptic efficacy in central neurones.

  9. Afadin regulates puncta adherentia junction formation and presynaptic differentiation in hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Daisaku Toyoshima

    Full Text Available The formation and remodeling of mossy fiber-CA3 pyramidal cell synapses in the stratum lucidum of the hippocampus are implicated in the cellular basis of learning and memory. Afadin and its binding cell adhesion molecules, nectin-1 and nectin-3, together with N-cadherin, are concentrated at puncta adherentia junctions (PAJs in these synapses. Here, we investigated the roles of afadin in PAJ formation and presynaptic differentiation in mossy fiber-CA3 pyramidal cell synapses. At these synapses in the mice in which the afadin gene was conditionally inactivated before synaptogenesis by using nestin-Cre mice, the immunofluorescence signals for the PAJ components, nectin-1, nectin-3 and N-cadherin, disappeared almost completely, while those for the presynaptic components, VGLUT1 and bassoon, were markedly decreased. In addition, these signals were significantly decreased in cultured afadin-deficient hippocampal neurons. Furthermore, the interevent interval of miniature excitatory postsynaptic currents was prolonged in the cultured afadin-deficient hippocampal neurons compared with control neurons, indicating that presynaptic functions were suppressed or a number of synapse was reduced in the afadin-deficient neurons. Analyses of presynaptic vesicle recycling and paired recordings revealed that the cultured afadin-deficient neurons showed impaired presynaptic functions. These results indicate that afadin regulates both PAJ formation and presynaptic differentiation in most mossy fiber-CA3 pyramidal cell synapses, while in a considerable population of these neurons, afadin regulates only PAJ formation but not presynaptic differentiation.

  10. Afadin Regulates Puncta Adherentia Junction Formation and Presynaptic Differentiation in Hippocampal Neurons

    Science.gov (United States)

    Toyoshima, Daisaku; Mandai, Kenji; Maruo, Tomohiko; Supriyanto, Irwan; Togashi, Hideru; Inoue, Takahito; Mori, Masahiro; Takai, Yoshimi

    2014-01-01

    The formation and remodeling of mossy fiber-CA3 pyramidal cell synapses in the stratum lucidum of the hippocampus are implicated in the cellular basis of learning and memory. Afadin and its binding cell adhesion molecules, nectin-1 and nectin-3, together with N-cadherin, are concentrated at puncta adherentia junctions (PAJs) in these synapses. Here, we investigated the roles of afadin in PAJ formation and presynaptic differentiation in mossy fiber-CA3 pyramidal cell synapses. At these synapses in the mice in which the afadin gene was conditionally inactivated before synaptogenesis by using nestin-Cre mice, the immunofluorescence signals for the PAJ components, nectin-1, nectin-3 and N-cadherin, disappeared almost completely, while those for the presynaptic components, VGLUT1 and bassoon, were markedly decreased. In addition, these signals were significantly decreased in cultured afadin-deficient hippocampal neurons. Furthermore, the interevent interval of miniature excitatory postsynaptic currents was prolonged in the cultured afadin-deficient hippocampal neurons compared with control neurons, indicating that presynaptic functions were suppressed or a number of synapse was reduced in the afadin-deficient neurons. Analyses of presynaptic vesicle recycling and paired recordings revealed that the cultured afadin-deficient neurons showed impaired presynaptic functions. These results indicate that afadin regulates both PAJ formation and presynaptic differentiation in most mossy fiber-CA3 pyramidal cell synapses, while in a considerable population of these neurons, afadin regulates only PAJ formation but not presynaptic differentiation. PMID:24587018

  11. VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

    Directory of Open Access Journals (Sweden)

    Benagiano Vincenzo

    2011-11-01

    Full Text Available Abstract Background The aim of this study was to assess the distribution of key SNARE proteins in glutamatergic and GABAergic synapses of the adult rat cerebellar cortex using light microscopy immunohistochemical techniques. Analysis was made of co-localizations of vGluT-1 and vGluT-2, vesicular transporters of glutamate and markers of glutamatergic synapses, or GAD, the GABA synthetic enzyme and marker of GABAergic synapses, with VAMP-2, SNAP-25A/B and syntaxin-1. Results The examined SNARE proteins were found to be diffusely expressed in glutamatergic synapses, whereas they were rarely observed in GABAergic synapses. However, among glutamatergic synapses, subpopulations which did not contain VAMP-2, SNAP-25A/B and syntaxin-1 were detected. They included virtually all the synapses established by terminals of climbing fibres (immunoreactive for vGluT-2 and some synapses established by terminals of parallel and mossy fibres (immunoreactive for vGluT-1, and for vGluT-1 and 2, respectively. The only GABA synapses expressing the SNARE proteins studied were the synapses established by axon terminals of basket neurons. Conclusion The present study supplies a detailed morphological description of VAMP-2, SNAP-25A/B and syntaxin-1 in the different types of glutamatergic and GABAergic synapses of the rat cerebellar cortex. The examined SNARE proteins characterize most of glutamatergic synapses and only one type of GABAergic synapses. In the subpopulations of glutamatergic and GABAergic synapses lacking the SNARE protein isoforms examined, alternative mechanisms for regulating trafficking of synaptic vesicles may be hypothesized, possibly mediated by different isoforms or homologous proteins.

  12. Microtubule-organizing center polarity and the immunological synapse: protein kinase C and beyond

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    Morgan eHuse

    2012-07-01

    Full Text Available Cytoskeletal polarization is crucial for many aspects of immune function, ranging from neutrophil migration to the sampling of gut flora by intestinal dendritic cells. It also plays a key role during lymphocyte cell-cell interactions, the most conspicuous of which is perhaps the immunological synapse (IS formed between a T cell and an antigen-presenting cell (APC. IS formation is associated with the reorientation of the T cell’s microtubule-organizing center (MTOC to a position just beneath the cell-cell interface. This cytoskeletal remodeling event aligns secretory organelles inside the T cell with the IS, enabling the directional release of cytokines and cytolytic factors toward the APC. MTOC polarization is therefore crucial for maintaining the specificity of a T cell’s secretory and cytotoxic responses. It has been known for some time that T cell receptor (TCR stimulation activates the MTOC polarization response. It has been difficult, however, to identify the machinery that couples early TCR signaling to cytoskeletal remodeling. Over the past few years, considerable progress has been made in this area. This review will present an overview of recent advances, touching on both the mechanisms that drive MTOC polarization and the effector responses that require it. Particular attention will be paid to both novel and atypical members of the protein kinase C family, which are now known to play important roles in both the establishment and the maintenance of the polarized state.

  13. Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses.

    Science.gov (United States)

    Clement, James P; Aceti, Massimiliano; Creson, Thomas K; Ozkan, Emin D; Shi, Yulin; Reish, Nicholas J; Almonte, Antoine G; Miller, Brooke H; Wiltgen, Brian J; Miller, Courtney A; Xu, Xiangmin; Rumbaugh, Gavin

    2012-11-09

    Mutations that cause intellectual disability (ID) and autism spectrum disorder (ASD) are commonly found in genes that encode for synaptic proteins. However, it remains unclear how mutations that disrupt synapse function impact intellectual ability. In the SYNGAP1 mouse model of ID/ASD, we found that dendritic spine synapses develop prematurely during the early postnatal period. Premature spine maturation dramatically enhanced excitability in the developing hippocampus, which corresponded with the emergence of behavioral abnormalities. Inducing SYNGAP1 mutations after critical developmental windows closed had minimal impact on spine synapse function, whereas repairing these pathogenic mutations in adulthood did not improve behavior and cognition. These data demonstrate that SynGAP protein acts as a critical developmental repressor of neural excitability that promotes the development of life-long cognitive abilities. We propose that the pace of dendritic spine synapse maturation in early life is a critical determinant of normal intellectual development.

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

    Science.gov (United States)

    Soares, Helena; Lasserre, Rémi; Alcover, Andrés

    2013-11-01

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

  15. Munc18-1 expression levels control synapse recovery by regulating readily releasable pool size

    Science.gov (United States)

    Toonen, Ruud F. G.; Wierda, Keimpe; Sons, Michèle S.; de Wit, Heidi; Cornelisse, L. Niels; Brussaard, Arjen; Plomp, Jaap J.; Verhage, Matthijs

    2006-01-01

    Prompt recovery after intense activity is an essential feature of most mammalian synapses. Here we show that synapses with reduced expression of the presynaptic gene munc18-1 suffer from increased depression during intense stimulation at glutamatergic, GABAergic, and neuromuscular synapses. Conversely, munc18-1 overexpression makes these synapses recover faster. Concomitant changes in the readily releasable vesicle pool and its refill kinetics were found. The number of vesicles docked at the active zone and the total number of vesicles per terminal correlated with both munc18-1 expression levels and the size of the releasable vesicle pool. These data show that varying expression of a single gene controls synaptic recovery by modulating the number of docked, release-ready vesicles and thereby replenishment of the secretion capacity. PMID:17110441

  16. A positive feedback synapse from retinal horizontal cells to cone photoreceptors.

    Directory of Open Access Journals (Sweden)

    Skyler L Jackman

    2011-05-01

    Full Text Available Cone photoreceptors and horizontal cells (HCs have a reciprocal synapse that underlies lateral inhibition and establishes the antagonistic center-surround organization of the visual system. Cones transmit to HCs through an excitatory synapse and HCs feed back to cones through an inhibitory synapse. Here we report that HCs also transmit to cone terminals a positive feedback signal that elevates intracellular Ca(2+ and accelerates neurotransmitter release. Positive and negative feedback are both initiated by AMPA receptors on HCs, but positive feedback appears to be mediated by a change in HC Ca(2+, whereas negative feedback is mediated by a change in HC membrane potential. Local uncaging of AMPA receptor agonists suggests that positive feedback is spatially constrained to active HC-cone synapses, whereas the negative feedback signal spreads through HCs to affect release from surrounding cones. By locally offsetting the effects of negative feedback, positive feedback may amplify photoreceptor synaptic release without sacrificing HC-mediated contrast enhancement.

  17. The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons

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    Lingfeng Meng

    2015-06-01

    Full Text Available Synapse elimination occurs in development, plasticity, and disease. Although the importance of synapse elimination has been documented in many studies, the molecular mechanisms underlying this process are unclear. Here, using the development of C. elegans RME neurons as a model, we have uncovered a function for the apoptosis pathway in synapse elimination. We find that the conserved apoptotic cell death (CED pathway and axonal mitochondria are required for the elimination of transiently formed clusters of presynaptic components in RME neurons. This function of the CED pathway involves the activation of the actin-filament-severing protein, GSNL-1. Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. Our data suggest that activation of the CED pathway contributes to selective elimination of synapses through disassembly of the actin filament network.

  18. Investigation and Manipulation of Different Analog Behaviors of Memristor as Electronic Synapse for Neuromorphic Applications.

    Science.gov (United States)

    Wang, Changhong; He, Wei; Tong, Yi; Zhao, Rong

    2016-03-14

    Low-power and high-density electronic synapse is an important building block of brain-inspired systems. The recent advancement in memristor has provided an opportunity to advance electronic synapse design. However, a guideline on designing and manipulating the memristor's analog behaviors is still lacking. In this work, we reveal that compliance current (Icomp) of electroforming process played an important role in realizing a stable analog behavior, which is attributed to the generation of conical-type conductive filament. A proper Icomp could result in a large conductance window, good stability, and low voltage analog switching. We further reveal that different pulse conditions can lead to three analog behaviors, where the conductance changes in monotonic increase, plateau after initial jump, and impulse-like shape, respectively. These behaviors could benefit the design of electronic synapse with enriched learning capabilities. This work will provide a useful guideline for designing and manipulating memristor as electronic synapses for brain-inspired systems.

  19. Fundamental GABAergic amacrine cell circuitries in the retina: nested feedback, concatenated inhibition, and axosomatic synapses.

    Science.gov (United States)

    Marc, R E; Liu, W

    2000-10-01

    Presynaptic gamma-aminobutyrate-immunoreactive (GABA+) profiles were mapped in the cyprinid retina with overlay microscopy: a fusion of electron and optical imaging affording high-contrast ultrastructural and immunocytochemical visualization. GABA+ synapses, deriving primarily from amacrine cells (ACs), compose 92% of conventional synapses and 98% of the input to bipolar cells (BCs) in the inner plexiform layer. GABA+ AC synapses, the sign-inverting elements of signal processing, are deployed in micronetworks and distinctive synaptic source/target topologies. Nested feedback micronetworks are formed by three types of links (BC --> AC, reciprocal BC AC synapses) arranged as nested BC [AC --> AC] loops. Circuits using nested feedback can possess better temporal performance than those using simple reciprocal feedback loops. Concatenated GABA+ micronetworks of AC --> AC and AC --> AC --> AC chains are common and must be key elements for lateral spatial, temporal, and spectral signal processing. Concatenated inhibitions may represent exceptionally stable, low-gain, sign-conserving devices for receptive field construction. Some chain elements are GABA immunonegative (GABA-) and are, thus, likely glycinergic synapses. GABA+ synaptic baskets target the somas of certain GABA+ and GABA- cells, resembling cortical axosomatic synapses. Finally, all myelinated intraretinal profiles are GABA+, suggesting that some efferent systems are sources of GABAergic inhibition in the cyprinid retina and may comprise all axosomatic synapses. These micronetworks are likely the fundamental elements for receptive field shaping in the inner plexiform layer, although few receptive field models incorporate them as functional components. Conversely, simple feedback and feedforward synapses may often be chimeras: the result of an incomplete view of synaptic topology.

  20. Characterization of Axo-Axonic Synapses in the Piriform Cortex of Mus musculus

    OpenAIRE

    Wang, Xinjun; Sun, Qian-Quan

    2012-01-01