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Sample records for affects synapse function

  1. Understanding the Structure and Function of the Immunological Synapse

    OpenAIRE

    Dustin, Michael L.; Chakraborty, Arup K.; Shaw, Andrey S

    2010-01-01

    The immunological synapse has been an area of very active scientific interest over the last decade. Surprisingly, much about the synapse remains unknown or is controversial.  Here we review some of these current issues in the field:  how the synapse is defined, its potential role in T-cell function, and our current understanding about how the synapse is formed.

  2. Functions of axon guidance molecules in synapse formation

    OpenAIRE

    Chen, Shih-Yu; Cheng, Hwai-Jong

    2009-01-01

    Axon guidance and synapse formation are important developmental events for establishing a functional neuronal circuitry. These two related cellular processes occur in a coordinated fashion but previous studies from multiple model organisms seemed to suggest that axon guidance and synapse formation are mediated by distinct molecular cues. Thus, axon guidance molecules are responsible for guiding the navigating axon toward its target area, while other adhesion or ligand-receptor molecules speci...

  3. A Nutrient Combination that Can Affect Synapse Formation

    OpenAIRE

    Wurtman, Richard J.

    2014-01-01

    Brain neurons form synapses throughout the life span. This process is initiated by neuronal depolarization, however the numbers of synapses thus formed depend on brain levels of three key nutrients—uridine, the omega-3 fatty acid DHA, and choline. Given together, these nutrients accelerate formation of synaptic membrane, the major component of synapses. In infants, when synaptogenesis is maximal, relatively large amounts of all three nutrients are provided in bioavailable forms (e.g., uridine...

  4. [Synapse elimination and functional neural circuit formation in the cerebellum].

    Science.gov (United States)

    Kano, Masanobu

    2013-06-01

    Neuronal connections are initially redundant, but unnecessary connections are eliminated subsequently during postnatal development. This process, known as 'synapse elimination', is thought to be crucial for establishing functionally mature neural circuits. The climbing fiber (CF) to the Purkinje cell (PC) synapse in the cerebellum is a representative model of synapse elimination. We disclose that one-to-one connection from CF to PC is established through four distinct phases: (1) strengthening of a single CF among multiple CFs in each PC at P3-P7, (2) translocation of a single strengthened CF to PC dendrites from around P9, and (3) early phase (P7 to around P11) and (4) late phase (around P12 to P17) of elimination of weak CF synapses from PC somata. Mice with PC-selective deletion of P/Q-type voltage-dependent Ca2+ channel (VDCC) exhibit severe defects in strengthening of single CFs, dendritic translocation of single CFs and CF elimination from P7. In contrast, mice with a mutation of a single allele for the GABA-synthesizing enzyme GAD67 have a selective impairment of CF elimination from P10 due to reduced inhibition and elevated Ca2+ influx to PC somata. Thus, regulation of Ca2+ influx to PCs is crucial for the four phases of CF synapse elimination. PMID:25069248

  5. Liprin-alpha Proteins Regulate Neuronal Development and Synapse Function

    NARCIS (Netherlands)

    S.A. Spangler (Samantha)

    2009-01-01

    textabstractSynapses are specialized communication junctions between neurons whose plasticity provides the structural and functional basis for information processing and storage in the brain. Recent biochemical, genetic and imaging studies in diverse model systems are beginning to reveal the molecul

  6. A Nutrient Combination that Can Affect Synapse Formation

    Directory of Open Access Journals (Sweden)

    Richard J. Wurtman

    2014-04-01

    Full Text Available Brain neurons form synapses throughout the life span. This process is initiated by neuronal depolarization, however the numbers of synapses thus formed depend on brain levels of three key nutrients—uridine, the omega-3 fatty acid DHA, and choline. Given together, these nutrients accelerate formation of synaptic membrane, the major component of synapses. In infants, when synaptogenesis is maximal, relatively large amounts of all three nutrients are provided in bioavailable forms (e.g., uridine in the UMP of mothers’ milk and infant formulas. However, in adults the uridine in foods, mostly present at RNA, is not bioavailable, and no food has ever been compelling demonstrated to elevate plasma uridine levels. Moreover, the quantities of DHA and choline in regular foods can be insufficient for raising their blood levels enough to promote optimal synaptogenesis. In Alzheimer’s disease (AD the need for extra quantities of the three nutrients is enhanced, both because their basal plasma levels may be subnormal (reflecting impaired hepatic synthesis, and because especially high brain levels are needed for correcting the disease-related deficiencies in synaptic membrane and synapses.

  7. Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD

    OpenAIRE

    He, Qionger; Titley, Heather; Grasselli, Giorgio; Piochon, Claire; Hansel, Christian

    2012-01-01

    Ethanol profoundly influences cerebellar circuit function and motor control. It has recently been demonstrated that functional N-methyl-d-aspartate (NMDA) receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in the adult cerebellum. Using whole cell patch-clamp recordings from mouse cerebellar slices, we examined whether ethanol can affect NMDA receptor signaling in mature Purkinje cells. NMDA receptor-mediated currents were isolated by bath application of...

  8. 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.

  9. Pitx3 deficiency in mice affects cholinergic modulation of GABAergic synapses in the nucleus accumbens

    NARCIS (Netherlands)

    de Rover, Mischa; Lodder, Johannes C.; Smidt, Marten P.; Brussaard, Arjen B.

    2006-01-01

    Pitx3 deficiency in mice affects cholinergic modulation of GABAergic synapses in the nucleus accumbens. J Neurophysiol 96: 2034-2041, 2006. First published July 12, 2006; doi:10.1152/jn.00333.2006. We investigated to what extent Pitx3 deficiency, causing hyperdopaminergic transmission in the nucleus

  10. Structure and function of the hair cell ribbon synapse.

    OpenAIRE

    Nouvian, R.; Beutner, D.; Parsons, T D; Moser, T.

    2006-01-01

    Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1 ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. While the electron microscopy hallmark of the hair cel...

  11. Disrupted-in-Schizophrenia (DISC1) Functions Presynaptically at Glutamatergic Synapses

    OpenAIRE

    Brady J Maher; Joseph J LoTurco

    2012-01-01

    The pathophysiology of schizophrenia is believed to involve defects in synaptic transmission, and the function of many schizophrenia-associated genes, including DISC1, have been linked to synaptic function at glutamatergic synapses. Here we develop a rodent model via in utero electroporation to assay the presynaptic function of DISC1 at glutamatergic synapses. We used a combination of mosaic transgene expression, RNAi knockdown and optogenetics to restrict both genetic manipulation and synapt...

  12. Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD.

    Science.gov (United States)

    He, Qionger; Titley, Heather; Grasselli, Giorgio; Piochon, Claire; Hansel, Christian

    2013-03-01

    Ethanol profoundly influences cerebellar circuit function and motor control. It has recently been demonstrated that functional N-methyl-(D)-aspartate (NMDA) receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in the adult cerebellum. Using whole cell patch-clamp recordings from mouse cerebellar slices, we examined whether ethanol can affect NMDA receptor signaling in mature Purkinje cells. NMDA receptor-mediated currents were isolated by bath application of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzol[f]quinoxaline (NBQX). The remaining (D)-2-amino-5-phosphonovaleric acid ((D)-APV)-sensitive current was reduced by ethanol at concentrations as low as 10 mM. At a concentration of 50 mM ethanol, the blockade of (D)-APV-sensitive CF-excitatory postsynaptic currents was significantly stronger. Ethanol also altered the waveform of CF-evoked complex spikes by reducing the afterdepolarization. This effect was not seen when NMDA receptors were blocked by (D)-APV before ethanol wash-in. In contrast to CF synaptic transmission, parallel fiber (PF) synaptic inputs were not affected by ethanol. Finally, ethanol (10 mM) impaired long-term depression (LTD) at PF to Purkinje cell synapses as induced under control conditions by paired PF and CF activity. However, LTD induced by pairing PF stimulation with depolarizing voltage steps (substituting for CF activation) was not blocked by ethanol. These observations suggest that the sensitivity of cerebellar circuit function and plasticity to low concentrations of ethanol may be caused by an ethanol-mediated impairment of NMDA receptor signaling at CF synapses onto cerebellar Purkinje cells. PMID:23221414

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Qian-Kun Yang

    2013-01-01

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

  15. The function of RNA-binding proteins at the synapse: implications for neurodegeneration.

    Science.gov (United States)

    Sephton, Chantelle F; Yu, Gang

    2015-10-01

    The loss of synapses is a central event in neurodegenerative diseases. Synaptic proteins are often associated with disease neuropathology, but their role in synaptic loss is not fully understood. Of the many processes involved in sustaining the integrity of synapses, local protein translation can directly impact synaptic formation, communication, and maintenance. RNA-binding proteins and their association with RNA granules serve to regulate mRNA transportation and translation at synapses and in turn regulate the synapse. Genetic mutations in RNA-binding proteins FUS and TDP-43 have been linked with causing neurodegenerative diseases: amyotrophic lateral sclerosis and frontotemporal dementia. The observation that mutations in FUS and TDP-43 coincide with changes in RNA granules provides evidence that dysfunction of RNA metabolism may underlie the mechanism of synaptic loss in these diseases. However, we do not know how mutations in RNA-binding proteins would affect RNA granule dynamics and local translation, or if these alterations would cause neurodegeneration. Further investigation into this area will lead to important insights into how disruption of RNA metabolism and local translation at synapses can cause neurodegenerative diseases. PMID:26047658

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

    Directory of Open Access Journals (Sweden)

    Rosemarie eGrantyn

    2011-07-01

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

  17. The Active and Periactive Zone Organization and the Functional Properties of Small and Large Synapses.

    Science.gov (United States)

    Cano, Raquel; Tabares, Lucia

    2016-01-01

    The arrival of an action potential (AP) at a synaptic terminal elicits highly synchronized quanta release. Repetitive APs produce successive synaptic vesicle (SV) fusions that require management of spent SV components in the presynaptic membrane with minimum disturbance of the secretory apparatus. To this end, the synaptic machinery is structured accordingly to the strength and the range of frequencies at which each particular synapse operates. This results in variations in the number and dimension of Active Zones (AZs), amount and distribution of SVs, and probably, in the primary endocytic mechanisms they use. Understanding better how these structural differences determine the functional response in each case has been a matter of long-term interest. Here we review the structural and functional properties of three distinct types of synapses: the neuromuscular junction (NMJ; a giant, highly reliable synapse that must exocytose a large number of quanta with each stimulus to guarantee excitation of the postsynaptic cell), the hippocampal excitatory small synapse (which most often has a single release site and a relatively small pool of vesicles), and the cerebellar mossy fiber-granule cell synapse (which possesses hundreds of release sites and is able to translocate, dock and prime vesicles at high speed). We will focus on how the release apparatus is organized in each case, the relative amount of vesicular membrane that needs to be accommodated within the periAZ upon stimulation, the different mechanisms for retrieving the excess of membrane and finally, how these factors may influence the functioning of the release sites. PMID:27252645

  18. 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.

  19. GABAA receptors can initiate the formation of functional inhibitory GABAergic synapses

    OpenAIRE

    Fuchs, C.; Abitbol, K.; Burden, J. J.; A. Mercer; Brown, L.; Iball, J.; Anne Stephenson, F.; Thomson, A. M.; Jovanovic, J N

    2013-01-01

    The mechanisms that underlie the selection of an inhibitory GABAergic axon's postsynaptic targets and the formation of the first contacts are currently unknown. To determine whether expression of GABAA receptors (GABAA Rs) themselves - the essential functional postsynaptic components of GABAergic synapses - can be sufficient to initiate formation of synaptic contacts, a novel co-culture system was devised. In this system, the presynaptic GABAergic axons originated from embryonic rat basal gan...

  20. Functional and structural remodeling of glutamate synapses in prefrontal and frontal cortex induced by behavioral stress

    Directory of Open Access Journals (Sweden)

    Laura eMusazzi

    2015-04-01

    Full Text Available Increasing evidence has shown that the pathophysiology of neuropsychiatric disorders, including mood disorders, is associated with abnormal function and regulation of the glutamatergic system. Consistently, preclinical studies on stress-based animal models of pathology showed that glucocorticoids and stress exert crucial effects on neuronal excitability and function, especially in cortical and limbic areas. In prefrontal and frontal cortex, acute stress was shown to induce enhancement of glutamate release/transmission dependent on activation of corticosterone receptors. Although the mechanisms whereby stress affects glutamate transmission have not yet been fully understood, it was shown that synaptic, non-genomic action of corticosterone is required to increase the readily releasable pool of glutamate vesicles but is not sufficient to enhance transmission in prefrontal and frontal cortex. Slower, partly genomic mechanisms are probably necessary for the enhancement of glutamate transmission induced by stress.Combined evidence has suggested that the changes in glutamate release and transmission are responsible for the dendritic remodeling and morphological changes induced by stress and it has been argued that sustained alterations of glutamate transmission may play a key role in the long-term structural/functional changes associated with mood disorders in patients. Intriguingly, modifications of the glutamatergic system induced by stress in the prefrontal cortex seem to be biphasic. Indeed, while the fast response to stress suggests an enhancement in the number of excitatory synapses, synaptic transmission and working memory, long-term adaptive changes -including those consequent to chronic stress- induce opposite effects. Better knowledge of the cellular effectors involved in this biphasic effect of stress may be useful to understand the pathophysiology of stress-related disorders, and open new paths for the development of therapeutic approaches.

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

    International Nuclear Information System (INIS)

    Spike-timing-dependent synaptic plasticity (STDP) is demonstrated in a synapse device based on a ferroelectric-gate field-effect transistor (FeFET). STDP is a key of the learning functions observed in human brains, where the synaptic weight changes only depending on the spike timing of the pre- and post-neurons. The FeFET is composed of the stacked oxide materials with ZnO/Pr(Zr,Ti)O3 (PZT)/SrRuO3. In the FeFET, the channel conductance can be altered depending on the density of electrons induced by the polarization of PZT film, which can be controlled by applying the gate voltage in a non-volatile manner. Applying a pulse gate voltage enables the multi-valued modulation of the conductance, which is expected to be caused by a change in PZT polarization. This variation depends on the height and the duration of the pulse gate voltage. Utilizing these characteristics, symmetric and asymmetric STDP learning functions are successfully implemented in the FeFET-based synapse device by applying the non-linear pulse gate voltage generated from a set of two pulses in a sampling circuit, in which the two pulses correspond to the spikes from the pre- and post-neurons. The three-terminal structure of the synapse device enables the concurrent learning, in which the weight update can be performed without canceling signal transmission among neurons, while the neural networks using the previously reported two-terminal synapse devices need to stop signal transmission for learning.

  2. 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.

  3. Disrupted-in-schizophrenia (DISC1 functions presynaptically at glutamatergic synapses.

    Directory of Open Access Journals (Sweden)

    Brady J Maher

    Full Text Available The pathophysiology of schizophrenia is believed to involve defects in synaptic transmission, and the function of many schizophrenia-associated genes, including DISC1, have been linked to synaptic function at glutamatergic synapses. Here we develop a rodent model via in utero electroporation to assay the presynaptic function of DISC1 at glutamatergic synapses. We used a combination of mosaic transgene expression, RNAi knockdown and optogenetics to restrict both genetic manipulation and synaptic stimulation of glutamatergic neurons presynaptic to other layer 2/3 neocortical pyramidal neurons that were then targeted for whole-cell patch-clamp recording. We show that expression of the DISC1 c-terminal truncation variant that is associated with Schizophrenia alters the frequency of mEPSCs and the kinetics of evoked glutamate release. In addition, we show that expression level of DISC1 is correlated with the probability of glutamate release such that increased DISC1 expression results in paired-pulse depression and RNAi knockdown of DISC1 produces paired-pulse facilitation. Overall, our results support a direct presynaptic function for the schizophrenia-associated gene, DISC1.

  4. Contribution of plasma membrane Ca2+ ATPase to cerebellar synapse function

    Institute of Scientific and Technical Information of China (English)

    Helena; Huang; Raghavendra; Y; Nagaraja; Molly; L; Garside; Walther; Akemann; Thomas; Knpfel; Ruth; M; Empson

    2010-01-01

    The cerebellum expresses one of the highest levels of the plasma membrane Ca2+ATPase,isoform 2 in the mammalian brain.This highly efficient plasma membrane calcium transporter protein is enriched within the main output neurons of the cerebellar cortex;i.e. the Purkinje neurons(PNs) .Here we review recent evidence,including electrophysiological and calcium imaging approaches using the plasma membrane calcium ATPase 2(PMCA2) knockout mouse,to show that PMCA2 is critical for the physiological control of calcium at cerebellar synapses and cerebellar dependent behaviour.These studies have also revealed that deletionof PMCA2 throughout cerebellar development in the PMCA2 knockout mouse leads to permanent signalling and morphological alterations in the PN dendrites. Whilst these findings highlight the importance of PMCA2 during cerebellar synapse function and development,they also reveal some limitations in the use of the PMCA2 knockout mouse and the need for additional experimental approaches including cell-specific and reversible manipulation of PMCAs.

  5. Functional and structural deficits at accumbens synapses in a mouse model of Fragile X.

    Science.gov (United States)

    Neuhofer, Daniela; Henstridge, Christopher M; Dudok, Barna; Sepers, Marja; Lassalle, Olivier; Katona, István; Manzoni, Olivier J

    2015-01-01

    Fragile X is the most common cause of inherited intellectual disability and a leading cause of autism. The disease is caused by mutation of a single X-linked gene called fmr1 that codes for the Fragile X mental retardation protein (FMRP), a 71 kDa protein, which acts mainly as a translation inhibitor. Fragile X patients suffer from cognitive and emotional deficits that coincide with abnormalities in dendritic spines. Changes in spine morphology are often associated with altered excitatory transmission and long-term plasticity, the most prominent deficit in fmr1-/y mice. The nucleus accumbens, a central part of the mesocortico-limbic reward pathway, is now considered as a core structure in the control of social behaviors. Although the socio-affective impairments observed in Fragile X suggest dysfunctions in the accumbens, the impact of the lack of FMRP on accumbal synapses has scarcely been studied. Here we report for the first time a new spike timing-dependent plasticity paradigm that reliably triggers NMDAR-dependent long-term potentiation (LTP) of excitatory afferent inputs of medium spiny neurons (MSN) in the nucleus accumbens core region. Notably, we discovered that this LTP was completely absent in fmr1-/y mice. In the fmr1-/y accumbens intrinsic membrane properties of MSNs and basal excitatory neurotransmission remained intact in the fmr1-/y accumbens but the deficit in LTP was accompanied by an increase in evoked AMPA/NMDA ratio and a concomitant reduction of spontaneous NMDAR-mediated currents. In agreement with these physiological findings, we found significantly more filopodial spines in fmr1-/y mice by using an ultrastructural electron microscopic analysis of accumbens core medium spiny neuron spines. Surprisingly, spine elongation was specifically due to the longer longitudinal axis and larger area of spine necks, whereas spine head morphology and postsynaptic density size on spine heads remained unaffected in the fmr1-/y accumbens. These findings

  6. 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.

  7. The immunological synapse

    DEFF Research Database (Denmark)

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

    2003-01-01

    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 IS...

  8. Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses.

    Science.gov (United States)

    Gilman SR; Iossifov I; Levy D; Ronemus M; Wigler M; Vitkup D

    2011-06-09

    Identification of complex molecular networks underlying common human phenotypes is a major challenge of modern genetics. In this study, we develop a method for network-based analysis of genetic associations (NETBAG). We use NETBAG to identify a large biological network of genes affected by rare de novo CNVs in autism. The genes forming the network are primarily related to synapse development, axon targeting, and neuron motility. The identified network is strongly related to genes previously implicated in autism and intellectual disability phenotypes. Our results are also consistent with the hypothesis that significantly stronger functional perturbations are required to trigger the autistic phenotype in females compared to males. Overall, the presented analysis of de novo variants supports the hypothesis that perturbed synaptogenesis is at the heart of autism. More generally, our study provides proof of the principle that networks underlying complex human phenotypes can be identified by a network-based functional analysis of rare genetic variants.

  9. 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).

  10. Synapses and Memory Storage

    OpenAIRE

    Mayford, Mark; Siegelbaum, Steven A.; Kandel, Eric R.

    2012-01-01

    The synapse is the functional unit of the brain. During the last several decades we have acquired a great deal of information on its structure, molecular components, and physiological function. It is clear that synapses are morphologically and molecularly diverse and that this diversity is recruited to different functions. One of the most intriguing findings is that the size of the synaptic response in not invariant, but can be altered by a variety of homo- and heterosynaptic factors such as ...

  11. Diet and energy-sensing inputs affect TorC1-mediated axon misrouting but not TorC2-directed synapse growth in a Drosophila model of tuberous sclerosis.

    Directory of Open Access Journals (Sweden)

    Brian Dimitroff

    Full Text Available The Target of Rapamycin (TOR growth regulatory system is influenced by a number of different inputs, including growth factor signaling, nutrient availability, and cellular energy levels. While the effects of TOR on cell and organismal growth have been well characterized, this pathway also has profound effects on neural development and behavior. Hyperactivation of the TOR pathway by mutations in the upstream TOR inhibitors TSC1 (tuberous sclerosis complex 1 or TSC2 promotes benign tumors and neurological and behavioral deficits, a syndrome known as tuberous sclerosis (TS. In Drosophila, neuron-specific overexpression of Rheb, the direct downstream target inhibited by Tsc1/Tsc2, produced significant synapse overgrowth, axon misrouting, and phototaxis deficits. To understand how misregulation of Tor signaling affects neural and behavioral development, we examined the influence of growth factor, nutrient, and energy sensing inputs on these neurodevelopmental phenotypes. Neural expression of Pi3K, a principal mediator of growth factor inputs to Tor, caused synapse overgrowth similar to Rheb, but did not disrupt axon guidance or phototaxis. Dietary restriction rescued Rheb-mediated behavioral and axon guidance deficits, as did overexpression of AMPK, a component of the cellular energy sensing pathway, but neither was able to rescue synapse overgrowth. While axon guidance and behavioral phenotypes were affected by altering the function of a Tor complex 1 (TorC1 component, Raptor, or a TORC1 downstream element (S6k, synapse overgrowth was only suppressed by reducing the function of Tor complex 2 (TorC2 components (Rictor, Sin1. These findings demonstrate that different inputs to Tor signaling have distinct activities in nervous system development, and that Tor provides an important connection between nutrient-energy sensing systems and patterning of the nervous system.

  12. Functional and structural deficits at accumbens synapses in a mouse model of Fragile X

    Directory of Open Access Journals (Sweden)

    Daniela eNeuhofer

    2015-03-01

    Full Text Available Fragile X is the most common cause of inherited intellectual disability and a leading cause of autism. The disease is caused by mutation of a single X-linked gene called fmr1 that codes for the Fragile X mental retardation protein (FMRP, a 71 kDa protein, which acts mainly as a translation inhibitor. Fragile X patients suffer from cognitive and emotional deficits that coincide with abnormalities in dendritic spines. Changes in spine morphology are often associated with altered excitatory transmission and long-term plasticity, the most prominent deficit in fmr1-/y mice. The nucleus accumbens, a central part of the mesocortico-limbic reward pathway, is now considered as a core structure in the control of social behaviors. Although the socio-affective impairments observed in Fragile X suggest dysfunctions in the accumbens, the impact of the lack of FMRP on accumbal synapses has scarcely been studied. Here we report for the first time a new spike timing-dependent plasticity paradigm that reliably triggers NMDAR-dependent long-term potentiation (LTP of excitatory afferent inputs of medium spiny neurons (MSN in the nucleus accumbens core region. Notably, we discovered that this LTP was completely absent in fmr1-/y mice. In the fmr1-/y accumbens intrinsic membrane properties of MSNs and basal excitatory neurotransmission remained intact in the fmr1-/y accumbens but the deficit in LTP was accompanied by an increase in evoked AMPA/NMDA ratio and a concomitant reduction of spontaneous NMDAR-mediated currents. In agreement with these physiological findings, we found significantly more filopodial spines in fmr1-/y mice by using an ultrastructural electron microscopic analysis of accumbens core medium spiny neuron spines. Surprisingly, spine elongation was specifically due to the longer longitudinal axis and larger area of spine necks, whereas spine head morphology and postsynaptic density size on spine heads remained unaffected in the fmr1-/y accumbens

  13. Genetic targeting of NRXN2 in mice unveils role in excitatory cortical synapse function and social behaviors

    Directory of Open Access Journals (Sweden)

    Gesche eBorn

    2015-02-01

    Full Text Available Human genetics has identified rare copy number variations and deleterious mutations for all neurexin genes (NRXN1-3 in patients with neurodevelopmental diseases, and electrophysiological recordings in animal brains have shown that Nrxns are important for synaptic transmission. While several mouse models for Nrxn1α inactivation have previously been studied for behavioral changes, very little information is available for other variants. Here, we validate that mice lacking Nrxn2α exhibit behavioral abnormalities, characterized by social interaction deficits and increased anxiety-like behavior, which partially overlap, partially differ from Nrxn1α mutant behaviors. Using patch-clamp recordings in Nrxn2α knockout brains, we observe reduced spontaneous transmitter release at excitatory synapses in the neocortex. We also analyse at this cellular level a novel NRXN2 mouse model that carries a combined deletion of Nrxn2α and Nrxn2β. Electrophysiological analysis of this Nrxn2-mutant mouse shows surprisingly similar defects of excitatory release to Nrxn2α, indicating that the β-variant of Nrxn2 has no strong function in basic transmission at these synapses. Inhibitory transmission as well as synapse densities and ultrastructure remain unchanged in the neocortex of both models. Furthermore, at Nrxn2α and Nrxn2-mutant excitatory synapses we find an altered facilitation and N-methyl-D-aspartate receptor (NMDAR function because NMDAR-dependent decay time and NMDAR-mediated responses are reduced. As Nrxn can indirectly be linked to NMDAR via neuroligin and PSD-95, the trans-synaptic nature of this complex may help to explain occurrence of presynaptic and postsynaptic effects. Since excitatory/inhibitory imbalances and impairment of NMDAR function are alledged to have a role in autism and schizophrenia, our results support the idea of a related pathomechanism in these disorders.

  14. Dynamic Aspects of Synapse Formation

    OpenAIRE

    McAllister, A. Kimberley

    2007-01-01

    The mammalian central nervous system (CNS) requires the proper formation of exquisitely precise circuits to function correctly. These neuronal circuits are assembled during development by the formation of synaptic connections between thousands of differentiating neurons. Proper synapse formation during childhood provides the substrate for cognition while improper formation or function of these synapses leads to neurodevelopmental disorders, including mental retardation and autism. Recent work...

  15. A study of the role of presenilin (1) in regulating synaptic function at hippocampal synapses

    OpenAIRE

    Yu, L. M. Y.

    2010-01-01

    Synapse dysfunction is emerging as a major factor in the pathogenesis of Alzheimer’s disease (AD). Key insights into the pathological mechanisms have been provided through studies of familial AD (FAD) genes. Mutations in the PSEN1 gene account for the vast majority of FAD cases, which are typified by the formation of amyloid plaques, neurofibrillary tangles and neuronal loss. The PSEN1 gene encodes presenilin 1, a polytopic transmembrane protein, which is the catalytic core ...

  16. Gephyrin phosphorylation in the functional organization and plasticity of GABAergic synapses

    Directory of Open Access Journals (Sweden)

    Paola Zacchi

    2014-04-01

    Full Text Available Gephyrin is a multifunctional scaffold protein essential for the postsynaptic accumulation of inhibitory glycine and GABAA receptors at synaptic sites. The molecular events involved in gephyrin-dependent GABAA receptor clustering are still unclear. Evidence has been recently provided that gephyrin phosphorylation plays a key role in these processes. By impinging upon its post-synaptic scaffolding properties as well as its stability, gephyrin post-translational modifications have been shown to impact on the structural remodeling of GABAergic synapses leading to synaptic plasticity. In addition, not only gephyrin phosphorylation per se but also the subsequent phosphorylation-dependent recruitment of the chaperone molecule Pin1 represents an emerging mechanism to regulate GABAergic signaling. Extensively characterized as pivotal enzyme controlling cell proliferation and differentiation, the prolyl-isomerase activity of Pin1 has been shown to regulate protein synthesis necessary to sustain the late phase of long-term potentiation at excitatory synapses, thus suggesting its involvement at synaptic sites. In this review we will summarize the current state of knowledge on the signaling pathways responsible for gephyrin post-translational modifications. We will also outline future lines of research that might contribute to better unveil the molecular mechanisms by which gephyrin regulates synaptic plasticity processes at GABAergic synapses.

  17. Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses

    OpenAIRE

    Gilman, Sarah R; Iossifov, Ivan; Levy, Dan; Ronemus, Michael; Wigler, Michael; Vitkup, Dennis

    2011-01-01

    Identification of complex molecular networks underlying common human phenotypes is a major challenge of modern genetics. In this study we develop a method for NETwork-Based Analysis of Genetic associations (NETBAG). We use NETBAG to identify a large biological network of genes affected by rare de novo CNVs in autism. The genes forming the network are primarily related to synapse development, axon targeting and neuron motility. The identified network is strongly related to genes previously imp...

  18. Functional inactivation of a fraction of excitatory synapses in mice deficient for the active zone protein bassoon

    DEFF Research Database (Denmark)

    Altrock, Wilko D; tom Dieck, Susanne; Sokolov, Maxim;

    2003-01-01

    normal synaptic transmission, which can be attributed to the inactivation of a significant fraction of glutamatergic synapses. At these synapses, vesicles are clustered and docked in normal numbers but are unable to fuse. Phenotypically, the loss of Bassoon causes spontaneous epileptic seizures. These...... data show that Bassoon is not essential for synapse formation but plays an essential role in the regulated neurotransmitter release from a subset of glutamatergic synapses....

  19. Regulation of structural and functional synapse density by L-threonate through modulation of intraneuronal magnesium concentration.

    Science.gov (United States)

    Sun, Qifeng; Weinger, Jason G; Mao, Fei; Liu, Guosong

    2016-09-01

    Oral administration of the combination of L-threonate (threonate) and magnesium (Mg(2+)) in the form of L-Threonic acid Magnesium salt (L-TAMS) can enhance learning and memory in young rats and prevent memory decline in aging rats and in Alzheimer's disease model mice. Recent results from a human clinical trial demonstrate the efficacy of L-TAMS in restoring global cognitive abilities of older adults. Previously, we reported that neuronal intracellular Mg(2+) serves as a critical signaling molecule for controlling synapse density, a key factor that determines cognitive ability. The elevation of brain Mg(2+) by oral administration of L-TAMS in intact animals plays a significant role in mediating the therapeutic effects of L-TAMS. The current study sought to elucidate the unique role of threonate. We aimed to understand if threonate acts directly to elevate intraneuronal Mg(2+), and why Mg(2+) given without threonate is ineffective for enhancing learning and memory ability. We discovered that threonate is naturally present in cerebrospinal fluid (CSF) and oral treatment with L-TAMS elevated CSF threonate. In cultured hippocampal neurons, threonate treatment directly induced an increase in intracellular Mg(2+) concentration. Functionally, elevating threonate upregulated expression of NR2B-containing NMDAR, boosted mitochondrial membrane potential (ΔΨm), and increased functional synapse density in neuronal cultures. These effects are unique to threonate, as other common Mg(2+) anions failed to have the same results. Mechanistically, threonate's effects were specifically mediated through glucose transporters (GLUTs). We also evaluated the effects of threonate in human neural stem cell-derived neurons, and found it was equally effective at upregulating synapse density. The current study provides an explanation for why threonate is an essential component of L-TAMS and supports the use of L-TAMS to promote cognitive abilities in human. PMID:27178134

  20. Synapse Pathology in Psychiatric and Neurologic Disease

    OpenAIRE

    Spronsen, Myrrhe; 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 signals. In recent years, it has become evident that spine morphology is intimately linked to synapse function-smaller spines have smaller synapses and support reduced synaptic transmission. The relat...

  1. The guanine exchange factor Gartenzwerg and the small GTPase Arl1 function in the same pathway with Arfaptin during synapse growth

    Directory of Open Access Journals (Sweden)

    Leo Chang

    2015-08-01

    Full Text Available The generation of neuronal morphology requires transport vesicles originating from the Golgi apparatus (GA to deliver specialized components to the axon and dendrites. Drosophila Arfaptin is a membrane-binding protein localized to the GA that is required for the growth of the presynaptic nerve terminal. Here we provide biochemical, cellular and genetic evidence that the small GTPase Arl1 and the guanine-nucleotide exchange factor (GEF Gartenzwerg are required for Arfaptin function at the Golgi during synapse growth. Our data define a new signaling pathway composed of Arfaptin, Arl1, and Garz, required for the generation of normal synapse morphology.

  2. A Novel Topology of Proline-rich Transmembrane Protein 2 (PRRT2): HINTS FOR AN INTRACELLULAR FUNCTION AT THE SYNAPSE.

    Science.gov (United States)

    Rossi, Pia; Sterlini, Bruno; Castroflorio, Enrico; Marte, Antonella; Onofri, Franco; Valtorta, Flavia; Maragliano, Luca; Corradi, Anna; Benfenati, Fabio

    2016-03-18

    Proline-rich transmembrane protein 2 (PRRT2) has been identified as the single causative gene for a group of paroxysmal syndromes of infancy, including epilepsy, paroxysmal movement disorders, and migraine. On the basis of topology predictions, PRRT2 has been assigned to the recently characterized family of Dispanins, whose members share the two-transmembrane domain topology with a large N terminus and short C terminus oriented toward the outside of the cell. Because PRRT2 plays a role at the synapse, it is important to confirm the exact orientation of its N and C termini with respect to the plasma membrane to get clues regarding its possible function. Using a combination of different experimental approaches, including live immunolabeling, immunogold electron microscopy, surface biotinylation and computational modeling, we demonstrate a novel topology for this protein. PRRT2 is a type II transmembrane protein in which only the second hydrophobic segment spans the plasma membrane, whereas the first one is associated with the internal surface of the membrane and forms a helix-loop-helix structure without crossing it. Most importantly, the large proline-rich N-terminal domain is not exposed to the extracellular space but is localized intracellularly, and only the short C terminus is extracellular (Ncyt/Cexo topology). Accordingly, we show that PRRT2 interacts with the Src homology 3 domain-bearing protein Intersectin 1, an intracellular protein involved in synaptic vesicle cycling. These findings will contribute to the clarification of the role of PRRT2 at the synapse and the understanding of pathogenic mechanisms on the basis of PRRT2-related neurological disorders. PMID:26797119

  3. Structural dynamics of synapses in vivo correlate with functional changes during experience-dependent plasticity in visual cortex.

    Science.gov (United States)

    Tropea, Daniela; Majewska, Ania K; Garcia, Rodrigo; Sur, Mriganka

    2010-08-18

    The impact of activity on neuronal circuitry is complex, involving both functional and structural changes whose interaction is largely unknown. We have used optical imaging of mouse visual cortex responses and two-photon imaging of superficial layer spines on layer 5 neurons to monitor network function and synaptic structural dynamics in the mouse visual cortex in vivo. Total lack of vision due to dark-rearing from birth dampens visual responses and shifts spine dynamics and morphologies toward an immature state. The effects of vision after dark rearing are strongly dependent on the timing of exposure: over a period of days, functional and structural changes are temporally related such that light stabilizes spines while increasing visually driven activity. The effects of long-term light exposure can be partially mimicked by experimentally enhancing inhibitory signaling in the darkness. Brief light exposure, however, results in a rapid, transient, NMDA-dependent increase of cortical responses, accompanied by increased dynamics of dendritic spines. These findings indicate that visual experience induces rapid reorganization of cortical circuitry followed by a period of stabilization, and demonstrate a close relationship between dynamic changes at single synapses and cortical network function. PMID:20720116

  4. RNA-binding protein Hermes/RBPMS inversely affects synapse density and axon arbor formation in retinal ganglion cells in vivo.

    Science.gov (United States)

    Hörnberg, Hanna; Wollerton-van Horck, Francis; Maurus, Daniel; Zwart, Maarten; Svoboda, Hanno; Harris, William A; Holt, Christine E

    2013-06-19

    The RNA-binding protein Hermes [RNA-binding protein with multiple splicing (RBPMS)] is expressed exclusively in retinal ganglion cells (RGCs) in the CNS, but its function in these cells is not known. Here we show that Hermes protein translocates in granules from RGC bodies down the growing axons. Hermes loss of function in both Xenopus laevis and zebrafish embryos leads to a significant reduction in retinal axon arbor complexity in the optic tectum, and expression of a dominant acting mutant Hermes protein, defective in RNA-granule localization, causes similar defects in arborization. Time-lapse analysis of branch dynamics reveals that the decrease in arbor complexity is caused by a reduction in new branches rather than a decrease in branch stability. Surprisingly, Hermes depletion also leads to enhanced early visual behavior and an increase in the density of presynaptic puncta, suggesting that reduced arborization is accompanied by increased synaptogenesis to maintain synapse number. PMID:23785151

  5. MHCI promotes developmental synapse elimination and aging-related synapse loss at the vertebrate neuromuscular junction.

    Science.gov (United States)

    Tetruashvily, Mazell M; McDonald, Marin A; Frietze, Karla K; Boulanger, Lisa M

    2016-08-01

    Synapse elimination at the developing neuromuscular junction (NMJ) sculpts motor circuits, and synapse loss at the aging NMJ drives motor impairments that are a major cause of loss of independence in the elderly. Here we provide evidence that at the NMJ, both developmental synapse elimination and aging-related synapse loss are promoted by specific immune proteins, members of the major histocompatibility complex class I (MHCI). MHCI is expressed at the developing NMJ, and three different methods of reducing MHCI function all disrupt synapse elimination during the second postnatal week, leaving some muscle fibers multiply-innervated, despite otherwise outwardly normal synapse formation and maturation. Conversely, overexpressing MHCI modestly accelerates developmental synapse elimination. MHCI levels at the NMJ rise with aging, and reducing MHCI levels ameliorates muscle denervation in aged mice. These findings identify an unexpected role for MHCI in the elimination of neuromuscular synapses during development, and indicate that reducing MHCI levels can preserve youthful innervation of aging muscle. PMID:26802986

  6. Normal dynactin complex function during synapse growth in Drosophila requires membrane binding by Arfaptin

    OpenAIRE

    Chang, Leo; Kreko, Tabita; Davison, Holly; Cusmano, Tim; Wu, Yimin; Rothenfluh, Adrian; Eaton, Benjamin A.

    2013-01-01

    Mutations in DCTN1, a component of the dynactin complex, are linked to neurodegenerative diseases characterized by a broad collection of neuropathologies. Because of the pleiotropic nature of dynactin complex function within the neuron, defining the causes of neuropathology in DCTN1 mutants has been difficult. We combined a genetic screen with cellular assays of dynactin complex function to identify genes that are critical for dynactin complex function in the nervous system. This approach ide...

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

    Directory of Open Access Journals (Sweden)

    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

  8. The sticky synapse

    DEFF Research Database (Denmark)

    Owczarek, Sylwia Elzbieta; Kristiansen, Lars Villiam; Walmod, Peter Schledermann

    NCAM-type proteins modulate multiple neuronal functions, including the outgrowth and guidance of neurites, the formation, maturation, and plasticity of synapses, and the induction of both long-term potentiation and long-term depression. The ectodomains of NCAM proteins have a basic structure...... cleavage of their ectodomains. Although specific aspects of NCAM proteins have changed through evolution, core structural and functional features are conserved between NCAM-type proteins in vertebrates and invertebrates, demonstrating that the functions of this class of adhesive proteins are of general...

  9. Placebo Sleep Affects Cognitive Functioning

    Science.gov (United States)

    Draganich, Christina; Erdal, Kristi

    2014-01-01

    The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether…

  10. Proteomic studies of a single CNS synapse type: the parallel fiber/purkinje cell synapse.

    Directory of Open Access Journals (Sweden)

    Fekrije Selimi

    2009-04-01

    Full Text Available Precise neuronal networks underlie normal brain function and require distinct classes of synaptic connections. Although it has been shown that certain individual proteins can localize to different classes of synapses, the biochemical composition of specific synapse types is not known. Here, we have used a combination of genetically engineered mice, affinity purification, and mass spectrometry to profile proteins at parallel fiber/Purkinje cell synapses. We identify approximately 60 candidate postsynaptic proteins that can be classified into 11 functional categories. Proteins involved in phospholipid metabolism and signaling, such as the protein kinase MRCKgamma, are major unrecognized components of this synapse type. We demonstrate that MRCKgamma can modulate maturation of dendritic spines in cultured cortical neurons, and that it is localized specifically to parallel fiber/Purkinje cell synapses in vivo. Our data identify a novel synapse-specific signaling pathway, and provide an approach for detailed investigations of the biochemical complexity of central nervous system synapse types.

  11. Does Retirement Affect Cognitive Functioning?

    OpenAIRE

    Bonsang, E.D.M.; S. Adam; S Perelman

    2010-01-01

    This paper analyzes the effect of retirement on cognitive functioning using two large scale surveys. On the one hand the HRS, a longitudinal survey among individuals aged 50+ living in the United States, allows us to control for individual heterogeneity and endogeneity of the retirement decision by using the eligibility age for Social Security as an instrument. On the other hand, a comparable international European survey, SHARE, allows us to identify the causal effect of retirement on cognit...

  12. Does Retirement Affect Cognitive Functioning?

    OpenAIRE

    Bonsang, Eric; Adam, Stéphane; Perelman, Sergio

    2010-01-01

    This paper analyzes the effect of retirement on cognitive functioning using two large scale surveys. On the one hand the HRS, a longitudinal survey among individuals aged 50+ living in the United States, allows us to control for individual heterogeneity and endogeneity of the retirement decision by using the eligibility age for Social Security as an instrument. On the other hand, a comparable international European survey, SHARE, allows us to identify the causal effect of retir...

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

    OpenAIRE

    Rosemarie eGrantyn; Christian eHenneberger; Rene eJüttner; Meier, Jochen C.; Sergei eKirischuk

    2011-01-01

    Functional impairment of the adult brain can result from deficits in the ontogeny of GABAergic synaptic transmission. Gene defects underlying autism spectrum disorders, Rett’s syndrome or some forms of epilepsy, but also a diverse set of syndromes accompanying perinatal trauma, hormonal imbalances, intake of sleep-inducing or mood-improving drugs or, quite common, alcohol intake during pregnancy can alter GABA signaling early in life. The search for therapeutically relevant endogenous molecul...

  14. Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala.

    Science.gov (United States)

    Robinson, Stacey L; Alexander, Nancy J; Bluett, Rebecca J; Patel, Sachin; McCool, Brian A

    2016-09-01

    The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol. PMID:26707595

  15. Learning Discloses Abnormal Structural and Functional Plasticity at Hippocampal Synapses in the APP23 Mouse Model of Alzheimer's Disease

    Science.gov (United States)

    Middei, Silvia; Roberto, Anna; Berretta, Nicola; Panico, Maria Beatrice; Lista, Simone; Bernardi, Giorgio; Mercuri, Nicola B.; Ammassari-Teule, Martine; Nistico, Robert

    2010-01-01

    B6-Tg/Thy1APP23Sdz (APP23) mutant mice exhibit neurohistological hallmarks of Alzheimer's disease but show intact basal hippocampal neurotransmission and synaptic plasticity. Here, we examine whether spatial learning differently modifies the structural and electrophysiological properties of hippocampal synapses in APP23 and wild-type mice. While…

  16. SynDB: a Synapse protein DataBase based on synapse ontology

    OpenAIRE

    Zhang, Wuxue; Zhang, Yong; Zheng, Hui; Zhang, Chen; Xiong, Wei; Olyarchuk, John G.; Walker, Michael; Xu, Weifeng; Zhao, Min; Zhao, Shuqi; Zhou, Zhuan; Wei, Liping

    2006-01-01

    A synapse is the junction across which a nerve impulse passes from an axon terminal to a neuron, muscle cell or gland cell. The functions and building molecules of the synapse are essential to almost all neurobiological processes. To describe synaptic structures and functions, we have developed Synapse Ontology (SynO), a hierarchical representation that includes 177 terms with hundreds of synonyms and branches up to eight levels deep. associated 125 additional protein keywords and 109 InterPr...

  17. Preoperative liver functional volumetry performed by 3D-99mTc-GSA scintigraphy/vascular fusion imaging using SYNAPSE VINCENT:a preliminary study

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Yoshida; Hiroshi Makino; Tadashi Yokoyama; Hiroshi Maruyama; Atsushi Hirakata; Junji Ueda; Yasuhiro Mamada; Nobuhiko Taniai; Eiji Uchida

    2016-01-01

    Aim: The present study was designed to evaluate the feasibility of preoperative liver functional volumetry performed by 3D-technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) scintigraphy/vascular fusion imaging using SYNAPSE VINCENT and to examine the discrepancy between conventional and functional volumetry.Methods: The study group comprised 15 patients who underwent preoperative 3-dimensional (3D)-99mTc-GSA scintigraphy/vascular fusion imaging using SYNAPSE VINCENT software before hepatectomy between July 2014 and August 2015. The diagnosis was hepatocelular carcinoma (n = 4), metastatic liver tumor (n = 10), or intrahepatic cholangiocarcinoma (n = 1). Right hepatectomy was performed in 2 patients, left hepatectomy in 3 patients, right posterior sectionectomy in 3 patients, segmentectomy in 2 patients, and partial hepatectomy in 4 patients. 99mTc-GSA scintigraphy and computed tomography (CT) were performed to construct 3D-99mTc-GSA scintigraphy/vascular fused images. The conventional volume ratio of the planned resection region without tumor (% CT), and the functional volume ratio of the planned resection region without tumor (% GSA) were calculated. The discrepancy ratio was calculated as folows: discrepancy ratio = 100 - % GSA/ % CT × 100 (%).Results: The % GSA (17.9 ± 16.7%) was signiifcantly lower than the % CT (21.5 ± 17.6%) (P < 0.036). In al except 2 patients, the % GSA was lower than the % CT. The discrepancy ratio ranged from -4% to 75% (median, 20.7%).Conclusion: 3D-99mTc-GSA scintigraphy/vascular fused images constructed using SYNAPSE VINCENT were useful for noninvasively performing functional liver volumetry in patients scheduled to undergo various patterns of hepatectomy. In planned resection regions without tumor, the functional volume ratio was about 20% lower than the conventional volume ratio.

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

    Directory of Open Access Journals (Sweden)

    Pablo Mendez

    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.

  19. Activity-dependent plasticity of electrical synapses: increasing evidence for its presence and functional roles in the mammalian brain.

    Science.gov (United States)

    Haas, Julie S; Greenwald, Corey M; Pereda, Alberto E

    2016-01-01

    Gap junctions mediate electrical synaptic transmission between neurons. While the actions of neurotransmitter modulators on the conductance of gap junctions have been extensively documented, increasing evidence indicates they can also be influenced by the ongoing activity of neural networks, in most cases via local interactions with nearby glutamatergic synapses. We review here early evidence for the existence of activity-dependent regulatory mechanisms as well recent examples reported in mammalian brain. The ubiquitous distribution of both neuronal connexins and the molecules involved suggest this phenomenon is widespread and represents a property of electrical transmission in general. PMID:27230776

  20. The Nesprin family member ANC-1 regulates synapse formation and axon termination by functioning in a pathway with RPM-1 and β-Catenin.

    Directory of Open Access Journals (Sweden)

    Erik D Tulgren

    2014-07-01

    Full Text Available Mutations in Nesprin-1 and 2 (also called Syne-1 and 2 are associated with numerous diseases including autism, cerebellar ataxia, cancer, and Emery-Dreifuss muscular dystrophy. Nesprin-1 and 2 have conserved orthologs in flies and worms called MSP-300 and abnormal nuclear Anchorage 1 (ANC-1, respectively. The Nesprin protein family mediates nuclear and organelle anchorage and positioning. In the nervous system, the only known function of Nesprin-1 and 2 is in regulation of neurogenesis and neural migration. It remains unclear if Nesprin-1 and 2 regulate other functions in neurons. Using a proteomic approach in C. elegans, we have found that ANC-1 binds to the Regulator of Presynaptic Morphology 1 (RPM-1. RPM-1 is part of a conserved family of signaling molecules called Pam/Highwire/RPM-1 (PHR proteins that are important regulators of neuronal development. We have found that ANC-1, like RPM-1, regulates axon termination and synapse formation. Our genetic analysis indicates that ANC-1 functions via the β-catenin BAR-1, and the ANC-1/BAR-1 pathway functions cell autonomously, downstream of RPM-1 to regulate neuronal development. Further, ANC-1 binding to the nucleus is required for its function in axon termination and synapse formation. We identify variable roles for four different Wnts (LIN-44, EGL-20, CWN-1 and CWN-2 that function through BAR-1 to regulate axon termination. Our study highlights an emerging, broad role for ANC-1 in neuronal development, and unveils a new and unexpected mechanism by which RPM-1 functions.

  1. The Diversity of Cortical Inhibitory Synapses

    Directory of Open Access Journals (Sweden)

    Yoshiyuki eKubota

    2016-04-01

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

  2. 白细胞突触:结构、功能和意义%Leukocyte Synapse: Structure, Function and Significance

    Institute of Scientific and Technical Information of China (English)

    吴克复; 郑国光; 马小彤; 宋玉华

    2010-01-01

    神经突触是神经网络的关键性结构,免疫网络主要是无形网络.近年来的研究进展表明,免疫细胞在有些功能状态下形成白细胞突触,称为免疫学突触(immunological synapse,IS),构成局部暂时性结构网络,实际上是动态结构,有人将其分为synapse和kinapse.研究表明,不同白细胞的IS不尽相同,炎症细胞和白血病细胞的IS有其特点.在有些病毒感染的白细胞中也观察到类似结构,称为病毒学突触(virological synapse,VS),是病毒在细胞间传播的一种机制,它不仅提高了传染效率,还逃逸了抗体的中和作用,导致持续性感染.最近法国学者报道了呈花瓣样的多聚突触(polysynapses),即花瓣样的多个细胞膜纳米管道,病毒能从一个感染细胞同时传播给多个邻近细胞.本文作者显示了早期工作中观察到的感染EB病毒的人白血病细胞系J6-2中的类似结构.作者结合工作中的体会评述白细胞突触的结构和功能,探讨其生物学意义.

  3. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

    Science.gov (United States)

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

    2013-12-01

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

  4. A single-transistor silicon synapse

    OpenAIRE

    Diorio, Chris; Hasler, Paul; Minch, Bradley A.; Mead, Carver A.

    1996-01-01

    We have developed a new floating-gate silicon MOS transistor for analog learning applications. The memory storage is nonvolatile; hot-electron injection and electron tunneling permit bidirectional memory updates. Because these updates depend on both the stored memory value and the transistor terminal voltages, the synapse can implement a learning function. We have derived a memory-update rule from the physics of the tunneling and injection processes, and have investigated synapse learning in ...

  5. Artificial Synapse Network on Inorganic Proton Conductor for Neuromorphic Systems Applications

    OpenAIRE

    Zhu, Li Qiang; Wan, Chang Jin; Guo, Li Qiang; Shi, Yi; Wan, Qing

    2013-01-01

    The basic units in our brain are neurons and each neuron has more than 1000 synapse connections. Synapse is the basic structure for information transfer in an ever-changing manner, and short-term plasticity allows synapses to perform critical computational functions in neural circuits. Therefore the major challenge for the hardware implementation of neuromorphic computation is to develop artificial synapse. Here, in-plane oxide-based artificial synapse network coupled by proton neurotransmitt...

  6. Regulation of excitatory synapse development by the RhoGEF Ephexin5

    OpenAIRE

    Salogiannis, John

    2013-01-01

    The neuronal synapse is a specialized cell-cell junction that mediates communication between neurons. The formation of a synapse requires the coordinated activity of signaling molecules that can either promote or restrict synapse number and function. Tight regulation of these signaling molecules are critical to ensure that synapses form in the correct number, time and place during brain development. A number of molecular mechanisms that promote synapse formation have been elucidated, but s...

  7. Thyroid Functions and Bipolar Affective Disorder

    Directory of Open Access Journals (Sweden)

    Subho Chakrabarti

    2011-01-01

    Full Text Available Accumulating evidence suggests that hypothalamo-pituitary-thyroid (HPT axis dysfunction is relevant to the pathophysiology and clinical course of bipolar affective disorder. Hypothyroidism, either overt or more commonly subclinical, appears to the commonest abnormality found in bipolar disorder. The prevalence of thyroid dysfunction is also likely to be greater among patients with rapid cycling and other refractory forms of the disorder. Lithium-treatment has potent antithyroid effects and can induce hypothyroidism or exacerbate a preexisting hypothyroid state. Even minor perturbations of the HPT axis may affect the outcome of bipolar disorder, necessitating careful monitoring of thyroid functions of patients on treatment. Supplementation with high dose thyroxine can be considered in some patients with treatment-refractory bipolar disorder. Neurotransmitter, neuroimaging, and genetic studies have begun to provide clues, which could lead to an improved understanding of the thyroid-bipolar disorder connection, and more optimal ways of managing this potentially disabling condition.

  8. Does selenium supplementation affect thyroid function?

    DEFF Research Database (Denmark)

    Winther, Kristian Hillert; Bonnema, Steen Joop; Cold, Frederik;

    2015-01-01

    OBJECTIVE: Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake......, and after 6 months, and 5 years of supplementation. RESULTS: Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium (P<0.001). Serum TSH and FT4 concentrations decreased significantly and dose-dependently by 0.066 mIU/l (P=0.010) and 0.......11 pmol/l (P=0.015), respectively, per 100 μg/day increase, with insignificant differences between 6 months and 5 years. No significant effects were found for FT3 and FT3:FT4 ratio. CONCLUSIONS: In euthyroid subjects, selenium supplementation minutely and dose-dependently affects thyroid function, when...

  9. Aging of cholinergic synapses: fiction or reality?

    International Nuclear Information System (INIS)

    The authors make use of the ciliary ganglion iris preparation of the aging chicken as a model of senescent peripheral cholinergic synapses. Based on the studies performed on the iris, an hypothesis of aging of the cholinergic synapse has been suggested. In order to establish the nature of a deficit, the authors examine the ability of chloinergic synapses in the iris at various ages to take up the precursor tritium-choline and release the formed tritium-ACh in response to high K+ (115 mM) depolarization. A summary of preliminary results of morphometric analysis of nerve endings and synaptic components in the iris of young adult and aged chickens is shown. The experiments suggest that severe changes may occur at later stages of life. A specific functional defect in the cholinergic synapse during aging is found

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

    Directory of Open Access Journals (Sweden)

    S. Salucci

    2014-05-01

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

  11. Presenilin/γ-secretase regulates neurexin processing at synapses.

    Directory of Open Access Journals (Sweden)

    Carlos A Saura

    Full Text Available Neurexins are a large family of neuronal plasma membrane proteins, which function as trans-synaptic receptors during synaptic differentiation. The binding of presynaptic neurexins to postsynaptic partners, such as neuroligins, has been proposed to participate in a signaling pathway that regulates synapse formation/stabilization. The identification of mutations in neurexin genes associated with autism and mental retardation suggests that dysfunction of neurexins may underlie synaptic defects associated with brain disorders. However, the mechanisms that regulate neurexin function at synapses are still unclear. Here, we show that neurexins are proteolytically processed by presenilins (PS, the catalytic components of the γ-secretase complex that mediates the intramembraneous cleavage of several type I membrane proteins. Inhibition of PS/γ-secretase by using pharmacological and genetic approaches induces a drastic accumulation of neurexin C-terminal fragments (CTFs in cultured rat hippocampal neurons and mouse brain. Neurexin-CTFs accumulate mainly at the presynaptic terminals of PS conditional double knockout (PS cDKO mice lacking both PS genes in glutamatergic neurons of the forebrain. The fact that loss of PS function enhances neurexin accumulation at glutamatergic terminals mediated by neuroligin-1 suggests that PS regulate the processing of neurexins at glutamatergic synapses. Interestingly, presenilin 1 (PS1 is recruited to glutamatergic terminals mediated by neuroligin-1, thus concentrating PS1 at terminals containing β-neurexins. Furthermore, familial Alzheimer's disease (FAD-linked PS1 mutations differentially affect β-neurexin-1 processing. Expression of PS1 M146L and PS1 H163R mutants in PS-/- cells rescues the processing of β-neurexin-1, whereas PS1 C410Y and PS1 ΔE9 fail to rescue the processing defect. These results suggest that PS regulate the synaptic function and processing of neurexins at glutamatergic synapses, and that

  12. Neuron network activity scales exponentially with synapse density

    OpenAIRE

    Brewer, G. J.; Boehler, M D; Pearson, R. A.; DeMaris, A A; Ide, A. N.; Wheeler, B C

    2008-01-01

    Neuronal network output in the cortex as a function of synapse density during development has not been explicitly determined. Synaptic scaling in cortical brain networks seems to alter excitatory and inhibitory synaptic inputs to produce a representative rate of synaptic output. Here, we cultured rat hippocampal neurons over a three-week period to correlate synapse density with the increase in spontaneous spiking activity. We followed the network development as synapse formation and spike rat...

  13. Recruitment of dynein to the Jurkat immunological synapse

    OpenAIRE

    Combs, Jeffrey; Kim, Soo Jin; Tan, Sarah; Ligon, Lee A.; Holzbaur, Erika L.F.; Kuhn, Jeffrey; Poenie, Martin

    2006-01-01

    Binding of T cells to antigen-presenting cells leads to the formation of the immunological synapse, translocation of the microtubule-organizing center (MTOC) to the synapse, and focused secretion of effector molecules. Here, we show that upon activation of Jurkat cells microtubules project from the MTOC to a ring of the scaffolding protein ADAP, localized at the synapse. Loss of ADAP, but not lymphocyte function-associated antigen 1, leads to a severe defect in MTOC polarization at the immuno...

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

    OpenAIRE

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

    2009-01-01

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

  15. Pulmonary Function Affects Language Performance in Aging

    Directory of Open Access Journals (Sweden)

    Lewina O Lee

    2014-04-01

    associated with better ES performance (B = 6.64, SE = 2.43, p = .01. Higher FVC and FEV1 were related to better MN performance, but this did not reach statistical significance (FVC: B = 3.68, SE = 2.16, p = .09; FEV1: B = 4.92, SE = 2.64, p = .06. Higher FVC (B = 3.98, SE = 1.44, p = .01 and FEV1 (B = 4.79, SE = 1.75, p = .01 were associated with better ANT performance. The positive association between PF and BNT performance was marginally significant (FVC: B = 4.19, SE = 2.18, p = .06; FEV1: B = 3.51, SE = 2.66, p = .10. Discussion and Conclusion Better PF was associated with higher accuracy on sentence processing and naming-based lexical retrieval tasks, consistent with the conclusion that pulmonary function affects older adults’ language performance. Our findings support the emerging thesis that language changes in aging are influenced by health-related physiological and neural mechanisms (e.g., Albert et al., 2009; Cahana-Amitay et al., 2013. From a clinical perspective, these findings highlight the promise of targeting PF as an intervention for improving language abilities among the elderly.

  16. Back-Propagation Operation for Analog Neural Network Hardware with Synapse Components Having Hysteresis Characteristics

    OpenAIRE

    Ueda, Michihito; Nishitani, Yu; Kaneko, Yukihiro; Omote, Atsushi

    2014-01-01

    To realize an analog artificial neural network hardware, the circuit element for synapse function is important because the number of synapse elements is much larger than that of neuron elements. One of the candidates for this synapse element is a ferroelectric memristor. This device functions as a voltage controllable variable resistor, which can be applied to a synapse weight. However, its conductance shows hysteresis characteristics and dispersion to the input voltage. Therefore, the conduc...

  17. Structural dynamics of synapses in vivo correlate with functional changes during experience-dependent plasticity in visual cortex

    OpenAIRE

    Tropea, Daniela; Majewska, Ania K.; Garcia, Rodrigo; Sur, Mriganka

    2010-01-01

    The impact of activity on neuronal circuitry is complex, involving both functional and structural changes whose interaction is largely unknown. We have used optical imaging of mouse visual cortex responses and two-photon imaging of superficial layer spines on layer 5 neurons to monitor network function and synaptic structural dynamics in the mouse visual cortex in vivo. Total lack of vision due to dark-rearing from birth dampens visual responses and shifts spine dynamics and morphologies towa...

  18. Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

    OpenAIRE

    Kuhn, P.-H.; Colombo, A.V.; Schusser, B.; Dreymueller, D.; Wetzel, S.; Schepers, U.; Herber, J.; Ludwig, A.; Kremmer, E; Montag, D.; Müller, U; Schweizer, M.; Saftig, P; Bräse, S.; Lichtenthaler, S.F.

    2016-01-01

    Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM...

  19. Learning-guided automatic three dimensional synapse quantification for drosophila neurons

    OpenAIRE

    Sanders, Jonathan; Singh, Anil; Sterne, Gabriella; Ye, Bing; Zhou, Jie

    2015-01-01

    Background The subcellular distribution of synapses is fundamentally important for the assembly, function, and plasticity of the nervous system. Automated and effective quantification tools are a prerequisite to large-scale studies of the molecular mechanisms of subcellular synapse distribution. Common practices for synapse quantification in neuroscience labs remain largely manual or semi-manual. This is mainly due to computational challenges in automatic quantification of synapses, including...

  20. Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases

    OpenAIRE

    Yim, Yeong Shin; Kwon, Younghee; Nam, Jungyong; Yoon, Hong In; Lee, Kangduk; Kim, Dong Goo; Kim, Eunjoon; Kim, Chul Hoon; Ko, Jaewon

    2013-01-01

    The balance between excitatory and inhibitory synaptic inputs, which is governed by multiple synapse organizers, controls neural circuit functions and behaviors. Slit- and Trk-like proteins (Slitrks) are a family of synapse organizers, whose emerging synaptic roles are incompletely understood. Here, we report that Slitrks are enriched in postsynaptic densities in rat brains. Overexpression of Slitrks promoted synapse formation, whereas RNAi-mediated knockdown of Slitrks decreased synapse dens...

  1. Glimepiride protects neurons against amyloid-β-induced synapse damage.

    Science.gov (United States)

    Osborne, Craig; West, Ewan; Nolan, William; McHale-Owen, Harriet; Williams, Alun; Bate, Clive

    2016-02-01

    Alzheimer's disease is associated with the accumulation within the brain of amyloid-β (Aβ) peptides that damage synapses and affect memory acquisition. This process can be modelled by observing the effects of Aβ on synapses in cultured neurons. The addition of picomolar concentrations of soluble Aβ derived from brain extracts triggered the loss of synaptic proteins including synaptophysin, synapsin-1 and cysteine string protein from cultured neurons. Glimepiride, a sulphonylurea used for the treatment of diabetes, protected neurons against synapse damage induced by Aβ. The protective effects of glimepiride were multi-faceted. Glimepiride treatment was associated with altered synaptic membranes including the loss of specific glycosylphosphatidylinositol (GPI)-anchored proteins including the cellular prion protein (PrP(C)) that acts as a receptor for Aβ42, increased synaptic gangliosides and altered cell signalling. More specifically, glimepiride reduced the Aβ-induced increase in cholesterol and the Aβ-induced activation of cytoplasmic phospholipase A2 (cPLA2) in synapses that occurred within cholesterol-dense membrane rafts. Aβ42 binding to glimepiride-treated neurons was not targeted to membrane rafts and less Aβ42 accumulated within synapses. These studies indicate that glimepiride modified the membrane micro-environments in which Aβ-induced signalling leads to synapse damage. In addition, soluble PrP(C), released from neurons by glimepiride, neutralised Aβ-induced synapse damage. Such observations raise the possibility that glimepiride may reduce synapse damage and hence delay the progression of cognitive decline in Alzheimer's disease. PMID:26432105

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

    Directory of Open Access Journals (Sweden)

    Santiago Ruiz

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

  3. Hair cell ribbon synapses

    OpenAIRE

    Moser, Tobias; Brandt, Andreas; Lysakowski, Anna

    2006-01-01

    Hearing and balance rely on the faithful synaptic coding of mechanical input by the auditory and vestibular hair cells of the inner ear. Mechanical deflection of their stereocilia causes the opening of mechanosensitive channels, resulting in hair cell depolarization, which controls the release of glutamate at ribbon-type synapses. Hair cells have a compact shape with strong polarity. Mechanoelectrical transduction and active membrane turnover associated with stereociliar renewal dominate the ...

  4. SynDB: a Synapse protein DataBase based on synapse ontology.

    Science.gov (United States)

    Zhang, Wuxue; Zhang, Yong; Zheng, Hui; Zhang, Chen; Xiong, Wei; Olyarchuk, John G; Walker, Michael; Xu, Weifeng; Zhao, Min; Zhao, Shuqi; Zhou, Zhuan; Wei, Liping

    2007-01-01

    A synapse is the junction across which a nerve impulse passes from an axon terminal to a neuron, muscle cell or gland cell. The functions and building molecules of the synapse are essential to almost all neurobiological processes. To describe synaptic structures and functions, we have developed Synapse Ontology (SynO), a hierarchical representation that includes 177 terms with hundreds of synonyms and branches up to eight levels deep. associated 125 additional protein keywords and 109 InterPro domains with these SynO terms. Using a combination of automated keyword searches, domain searches and manual curation, we collected 14,000 non-redundant synapse-related proteins, including 3000 in human. We extensively annotated the proteins with information about sequence, structure, function, expression, pathways, interactions and disease associations and with hyperlinks to external databases. The data are stored and presented in the Synapse protein DataBase (SynDB, http://syndb.cbi.pku.edu.cn). SynDB can be interactively browsed by SynO, Gene Ontology (GO), domain families, species, chromosomal locations or Tribe-MCL clusters. It can also be searched by text (including Boolean operators) or by sequence similarity. SynDB is the most comprehensive database to date for synaptic proteins. PMID:17098931

  5. 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. PMID:26187063

  6. Activity-dependent synaptic plasticity of a chalcogenide electronic synapse for neuromorphic systems.

    Science.gov (United States)

    Li, Yi; Zhong, Yingpeng; Zhang, Jinjian; Xu, Lei; Wang, Qing; Sun, Huajun; Tong, Hao; Cheng, Xiaoming; Miao, Xiangshui

    2014-01-01

    Nanoscale inorganic electronic synapses or synaptic devices, which are capable of emulating the functions of biological synapses of brain neuronal systems, are regarded as the basic building blocks for beyond-Von Neumann computing architecture, combining information storage and processing. Here, we demonstrate a Ag/AgInSbTe/Ag structure for chalcogenide memristor-based electronic synapses. The memristive characteristics with reproducible gradual resistance tuning are utilised to mimic the activity-dependent synaptic plasticity that serves as the basis of memory and learning. Bidirectional long-term Hebbian plasticity modulation is implemented by the coactivity of pre- and postsynaptic spikes, and the sign and degree are affected by assorted factors including the temporal difference, spike rate and voltage. Moreover, synaptic saturation is observed to be an adjustment of Hebbian rules to stabilise the growth of synaptic weights. Our results may contribute to the development of highly functional plastic electronic synapses and the further construction of next-generation parallel neuromorphic computing architecture. PMID:24809396

  7. Nonlinear Synapses for Large-Scale Models: An Efficient Representation Enables Complex Synapse Dynamics Modeling in Large-Scale Simulations

    Directory of Open Access Journals (Sweden)

    Eric eHu

    2015-09-01

    Full Text Available Chemical synapses are comprised of a wide collection of intricate signaling pathways involving complex dynamics. These mechanisms are often reduced to simple spikes or exponential representations in order to enable computer simulations at higher spatial levels of complexity. However, these representations cannot capture important nonlinear dynamics found in synaptic transmission. Here, we propose an input-output (IO synapse model capable of generating complex nonlinear dynamics while maintaining low computational complexity. This IO synapse model is an extension of a detailed mechanistic glutamatergic synapse model capable of capturing the input-output relationships of the mechanistic model using the Volterra functional power series. We demonstrate that the IO synapse model is able to successfully track the nonlinear dynamics of the synapse up to the third order with high accuracy. We also evaluate the accuracy of the IO synapse model at different input frequencies and compared its performance with that of kinetic models in compartmental neuron models. Our results demonstrate that the IO synapse model is capable of efficiently replicating complex nonlinear dynamics that were represented in the original mechanistic model and provide a method to replicate complex and diverse synaptic transmission within neuron network simulations.

  8. Does Acquired Hypothyroidism Affect the Hearing Functions?

    Directory of Open Access Journals (Sweden)

    Ayşe Arduç

    2015-12-01

    Full Text Available Purpose: It is well known that congenital hypothyroidism can cause hearing loss. However, conflicting results were found in studies investigating hearing functions in acquired hypothyroidism. Therefore, we evaluated the audiometric findings in patients with acquired hypothyroidism. Material and Method: The study included 58 patients with hypothyroidism and age- and gender-matched 34 healthy controls. Twenty eight (48.27% patients had subclinical hypothyroidism, and 30 (51.73% had obvious hypothyroidism. All subjects had a normal otoscopic examination and tympanometry. Pure tone audiometry at 250, 500, 1000, 2000, 4000, 6000, and 8000 Hertz (Hz was performed in both groups. Blood pressure measurements and the levels of plasma electrolytes, lipids and vitamin B12 were available in all subjects. Results: Hypothyroidism group and control group were similar with respect to systolic and diastolic blood pressures and plasma glucose, lipid, vitamin B12, calcium, sodium, potassium, and chloride levels. Significantly higher audiometric thresholds (dB at 250 (10 (0-45 vs. 5 (0-15, p<0.001 and 500 Hz (10 (0-40 vs. 10 (-5-15, p=0.003 were recorded in hypothyroid patients compared to that in healthy controls. Hearing thresholds at 250 and 500 Hz correlated positively with thyroid-stimulating hormone (TSH, and negatively with free triiodothyronine and free thyroxine. Subclinical hypothyroid patients had a higher hearing threshold at 250 Hz than healthy controls (p=0.001. Discussion: Our study demonstrated that hearing ability decreases in hypothyroidism, even in subclinical hypothyroidism. The changes in TSH and thyroid hormone levels seem to be directly related to the hearing loss in this population of patients.

  9. Maternal Dietary Loads of Alpha-Tocopherol Increase Synapse Density and Glial Synaptic Coverage in the Hippocampus of Adult Offspring

    Science.gov (United States)

    Salucci, S.; Ambrogini, P.; Lattanzi, D.; Betti, M.; Gobbi, P.; Galati, C.; Galli, F.; Cuppini, R.; Minelli, A.

    2014-01-01

    An increased intake of the antioxidant α-Tocopherol (vitamin E) is recommended in complicated pregnancies, to prevent free radical damage to mother and fetus. However, the anti-PKC and antimitotic activity of α-Tocopherol raises concerns about its potential effects on brain development. Recently, we found that maternal dietary loads of α-Tocopherol through pregnancy and lactation cause developmental deficit in hippocampal synaptic plasticity in rat offspring. The defect persisted into adulthood, with behavioral alterations in hippocampus-dependent learning. Here, using the same rat model of maternal supplementation, ultrastructural morphometric studies were carried out to provide mechanistic interpretation to such a functional impairment in adult offspring by the occurrence of long-term changes in density and morphological features of hippocampal synapses. Higher density of axo-spinous synapses was found in CA1 stratum radiatum of α-Tocopherol-exposed rats compared to controls, pointing to a reduced synapse pruning. No morphometric changes were found in synaptic ultrastructural features, i.e., perimeter of axon terminals, length of synaptic specializations, extension of bouton-spine contact. Gliasynapse anatomical relationship was also affected. Heavier astrocytic coverage of synapses was observed in Tocopherol-treated offspring, notably surrounding axon terminals; moreover, the percentage of synapses contacted by astrocytic endfeet at bouton-spine interface (tripartite synapses) was increased. These findings indicate that gestational and neonatal exposure to supranutritional Tocopherol intake can result in anatomical changes of offspring hippocampus that last through adulthood. These include a surplus of axo-spinous synapses and an aberrant gliasynapse relationship, which may represent the morphological signature of previously described alterations in synaptic plasticity and hippocampus-dependent learning. PMID:24998923

  10. 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.

  11. Synapse Loss in Olfactory Local Interneurons Modifies Perception

    OpenAIRE

    Acebes-Vindel, José Ángel; Martín-Peña, Alfonso; Chevalier, Valérie; Ferrús, Alberto

    2011-01-01

    Synapse loss correlates with cognitive decline in aging and most neurological pathologies. Sensory perception changes often represent subtle dysfunctions that precede the onset of a neurodegenerative disease. However, a cause–effect relationship between synapse loss and sensory perception deficits is difficult to prove and quantify due to functional and structural adaptation of neural systems. Here we modified a PI3K/AKT/GSK3 signaling pathway to reduce the number of synapses—without affectin...

  12. A New Efficient-Silicon Area MDAC Synapse

    OpenAIRE

    Zied Gafsi; Nejib Hassen; Mongia Mhiri; Kamel Besbes

    2007-01-01

    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 progr...

  13. Accounting for Human Polymorphisms Predicted to Affect Protein Function

    OpenAIRE

    Ng, Pauline C.; Henikoff, Steven

    2002-01-01

    A major interest in human genetics is to determine whether a nonsynonymous single-base nucleotide polymorphism (nsSNP) in a gene affects its protein product and, consequently, impacts the carrier's health. We used the SIFT (Sorting Intolerant From Tolerant) program to predict that 25% of 3084 nsSNPs from dbSNP, a public SNP database, would affect protein function. Some of the nsSNPs predicted to affect function were variants known to be associated with disease. Others were artifacts of SNP di...

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

    Directory of Open Access Journals (Sweden)

    Marta Esteves da Silva

    2015-11-01

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

  15. Cognitive function in unaffected twins discordant for affective disorder

    DEFF Research Database (Denmark)

    Christensen, Maj Vinberg; Kyvik, Kirsten Ohm; Kessing, Lars Vedel

    2006-01-01

    . Cognitive performance of 203 High-Risk and Low-Risk twins was compared. RESULTS: Healthy twins discordant for unipolar disorder showed lower performance on almost all measures of cognitive function: selective and sustained attention, executive function, language processing and working and declarative memory...... on language processing and episodic memory. CONCLUSIONS: The hypothesis that discrete cognitive impairment is present before the onset of the affective disorder and is genetically transmitted was supported. Thus, cognitive function may be a candidate endophenotype for affective disorders.......BACKGROUND: Patients may present with cognitive impairment in the euthymic phase of affective disorder, but it is unclear whether the impairment is prevalent before onset of the illness. The aim of the present study was to examine the hypothesis that genetic liability to affective disorder...

  16. How Does Maternal Employment Affect Children's Socioemotional Functioning?

    Science.gov (United States)

    Lam, Gigi

    2015-01-01

    The maternal employment becomes an irreversible trend across the globe. The effect of maternal employment on children's socioemotional functioning is so pervasive that it warrants special attention to investigate into the issue. A trajectory of analytical framework of how maternal employment affects children's socioemotional functioning originates…

  17. Advanced Fluorescence Protein-Based Synapse-Detectors.

    Science.gov (United States)

    Lee, Hojin; Oh, Won Chan; Seong, Jihye; Kim, Jinhyun

    2016-01-01

    The complex information-processing capabilities of the central nervous system emerge from intricate patterns of synaptic input-output relationships among various neuronal circuit components. Understanding these capabilities thus requires a precise description of the individual synapses that comprise neural networks. Recent advances in fluorescent protein engineering, along with developments in light-favoring tissue clearing and optical imaging techniques, have rendered light microscopy (LM) a potent candidate for large-scale analyses of synapses, their properties, and their connectivity. Optically imaging newly engineered fluorescent proteins (FPs) tagged to synaptic proteins or microstructures enables the efficient, fine-resolution illumination of synaptic anatomy and function in large neural circuits. Here we review the latest progress in fluorescent protein-based molecular tools for imaging individual synapses and synaptic connectivity. We also identify associated technologies in gene delivery, tissue processing, and computational image analysis that will play a crucial role in bridging the gap between synapse- and system-level neuroscience. PMID:27445785

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

    Directory of Open Access Journals (Sweden)

    Lijuan eShi

    2016-05-01

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

  19. Coding Deficits in Noise-Induced Hidden Hearing Loss May Stem from Incomplete Repair of Ribbon Synapses in the Cochlea

    Science.gov (United States)

    Shi, Lijuan; Chang, Yin; Li, Xiaowei; Aiken, Steven J.; Liu, Lijie; Wang, Jian

    2016-01-01

    Recent evidence has shown that noise-induced damage to the synapse between inner hair cells (IHCs) and type I afferent auditory nerve fibers (ANFs) may occur in the absence of permanent threshold shift (PTS), and that synapses connecting IHCs with low spontaneous rate (SR) ANFs are disproportionately affected. Due to the functional importance of low-SR ANF units for temporal processing and signal coding in noisy backgrounds, deficits in cochlear coding associated with noise-induced damage may result in significant difficulties with temporal processing and hearing in noise (i.e., “hidden hearing loss”). However, significant noise-induced coding deficits have not been reported at the single unit level following the loss of low-SR units. We have found evidence to suggest that some aspects of neural coding are not significantly changed with the initial loss of low-SR ANFs, and that further coding deficits arise in association with the subsequent reestablishment of the synapses. This suggests that synaptopathy in hidden hearing loss may be the result of insufficient repair of disrupted synapses, and not simply due to the loss of low-SR units. These coding deficits include decreases in driven spike rate for intensity coding as well as several aspects of temporal coding: spike latency, peak-to-sustained spike ratio and the recovery of spike rate as a function of click-interval. PMID:27252621

  20. Addictive drugs and plasticity of glutamatergic synapses on dopaminergic neurons: what have we learned from genetic mouse models?

    OpenAIRE

    Jan Rodriguez Parkitna; David Engblom

    2012-01-01

    Drug-induced changes in the functional properties of neurons in the mesolimbic dopaminergic system are attractive candidates for the molecular underpinnings of addiction. A central question in this context has been how drugs of abuse affect synaptic plasticity on dopaminergic cells in the ventral tegmental area. We now know that the intake of addictive drugs is accompanied by a complex sequence of alterations in the properties of excitatory synapses on dopaminergic neurons, mainly driven by s...

  1. Synapse-to-neuron ratio is inversely related to neuronal density in mature neuronal cultures

    OpenAIRE

    Cullen, D. Kacy; Gilroy, Meghan; Irons, Hillary R.; LaPlaca, Michelle C.

    2010-01-01

    Synapse formation is a fundamental process in neurons that occurs throughout development, maturity, and aging. Although these stages contain disparate and fluctuating numbers of mature neurons, tactics employed by neuronal networks to modulate synapse number as a function of neuronal density are not well understood. The goal of this study was to utilize an in vitro model to assess the influence of cell density and neuronal maturity on synapse number and distribution. Specifically, cerebral co...

  2. Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise

    OpenAIRE

    Valdez, G; Tapia, J; Kang, H; Clemenson, G.D.; Gage, F.H.; Lichtman, Jeff; Sanes, Joshua R.

    2010-01-01

    The cellular basis of age-related behavioral decline remains obscure but alterations in synapses are likely candidates. Accordingly, the beneficial effects on neural function of caloric restriction and exercise, which are among the most effective anti-aging treatments known, might also be mediated by synapses. As a starting point in testing these ideas, we studied the skeletal neuromuscular junction (NMJ), a large, accessible peripheral synapse. Comparison of NMJs in young adult and aged mice...

  3. Cortical synaptogenesis and excitatory synapse number are determined via a Neuroligin-1-dependent intercellular competition

    OpenAIRE

    Kwon, Hyung-Bae; Kozorovitskiy, Yevgenia; Oh, Won-Jong; Peixoto, Rui T.; Akhtar, Nazia; Saulnier, Jessica L.; Gu, Chenghua; Sabatini, Bernardo L.

    2012-01-01

    Members of the neuroligin (NL) family of cell-adhesion proteins are found at excitatory and inhibitory synapses and are mutated in some familial forms of autism spectrum disorders. Although they display synaptogenic properties in heterologous systems, a function of NLs in vivo in regulating synapse formation and synapse number has been difficult to establish. Here we show that neuroligin-1 (NL1), which is located at excitatory post-synaptic densities, does regulate activity-dependent synaptog...

  4. Activity-Dependent Synaptic Plasticity of a Chalcogenide Electronic Synapse for Neuromorphic Systems

    OpenAIRE

    Yi Li; Yingpeng Zhong; Jinjian Zhang; Lei Xu; Qing Wang; Huajun Sun; Hao Tong; Xiaoming Cheng; Xiangshui Miao

    2014-01-01

    Nanoscale inorganic electronic synapses or synaptic devices, which are capable of emulating the functions of biological synapses of brain neuronal systems, are regarded as the basic building blocks for beyond-Von Neumann computing architecture, combining information storage and processing. Here, we demonstrate a Ag/AgInSbTe/Ag structure for chalcogenide memristor-based electronic synapses. The memristive characteristics with reproducible gradual resistance tuning are utilised to mimic the act...

  5. Altered Disrupted-in-Schizophrenia-1 Function Affects the Development of Cortical Parvalbumin Interneurons by an Indirect Mechanism.

    Science.gov (United States)

    Borkowska, Malgorzata; Millar, J Kirsty; Price, David J

    2016-01-01

    Disrupted-in-Schizophrenia-1 (DISC1) gene has been linked to schizophrenia and related major mental illness. Mouse Disc1 has been implicated in brain development, mainly in the proliferation, differentiation, lamination, neurite outgrowth and synapse formation and maintenance of cortical excitatory neurons. Here, the effects of two loss-of-function point mutations in the mouse Disc1 sequence (Q31L and L100P) on cortical inhibitory interneurons were investigated. None of the mutations affected the overall number of interneurons. However, the 100P, but not the 31L, mutation resulted in a significant decrease in the numbers of interneurons expressing parvalbumin mRNA and protein across the sensory cortex. To investigate role of Disc1 in regulation of parvalbumin expression, mouse wild-type Disc-1 or the 100P mutant form were electroporated in utero into cortical excitatory neurons. Overexpression of wild-type Disc1 in these cells caused increased densities of parvalbumin-expressing interneurons in the electroporated area and in areas connected with it, whereas expression of Disc1-100P did not. We conclude that the 100P mutation prevents expression of parvalbumin by a normally sized cohort of interneurons and that altering Disc1 function in cortical excitatory neurons indirectly affects parvalbumin expression by cortical interneurons, perhaps as a result of altered functional input from the excitatory neurons. PMID:27244370

  6. Function if Cooperative Learning in Developing Positive Affect

    Institute of Scientific and Technical Information of China (English)

    佟玉平

    2008-01-01

    This paper focus on the function of cooperative learning in developing positive affect, Including reducing anxiety, increasing motivation, facilitating the development of positive attitudes toward learning and language learning, promoting serf- esteem, as well as supporting different learning styles and encouraging perseverance in the difficult and confusing process of learning a foreign language.

  7. Turnover of Synapse and Dynamic Nature of Synaptic Molecules In Vitro and In Vivo

    International Nuclear Information System (INIS)

    Recent advances of imaging techniques have enabled us to investigate the dynamics of synapses in living neurons. The synapse is constructed of presynaptic and postsynaptic elements which contain various kinds of structural and functional molecules. The postsynaptic density (PSD) is the most prominent structure among the excitatory postsynaptic elements. One of the main components of PSD is the scaffolding proteins which interact with multiple proteins in the synapse. Scaffolding proteins are suggested to play key roles in the emergence, maintenance, and remodeling of the excitatory synapses. Several kinds of scaffolding proteins are known to be present in the mammalian and also other vertebrate brains. These proteins were labeled with green fluorescent protein (GFP) and expressed in cultured neurons to analyze the dynamics and turnover of molecules in the synapses. In this review we describe how these molecules behave when the synapse is newly added or eliminated in the steady state and also when neuronal activity is changed

  8. A Synaptotagmin Isoform Switch during the Development of an Identified CNS Synapse.

    Science.gov (United States)

    Kochubey, Olexiy; Babai, Norbert; Schneggenburger, Ralf

    2016-06-01

    Various Synaptotagmin (Syt) isoform genes are found in mammals, but it is unknown whether Syts can function redundantly in a given nerve terminal, or whether isoforms can be switched during the development of a nerve terminal. Here, we investigated the possibility of a developmental Syt isoform switch using the calyx of Held as a model synapse. At mature calyx synapses, fast Ca(2+)-driven transmitter release depended entirely on Syt2, but the release phenotype of Syt2 knockout (KO) mice was weaker at immature calyces, and absent at pre-calyceal synapses early postnatally. Instead, conditional genetic inactivation shows that Syt1 mediates fast release at pre-calyceal synapses, as well as a fast release component resistant to Syt2 deletion in immature calyces. This demonstrates a developmental Syt1-Syt2 isoform switch at an identified synapse, a mechanism that could fine-tune the speed, reliability, and plasticity of transmitter release at fast releasing CNS synapses. PMID:27210552

  9. Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma

    OpenAIRE

    Wan, Guoqiang; Gómez-Casati, Maria E; Gigliello, Angelica R.; Liberman, M. Charles; Corfas, Gabriel

    2014-01-01

    Neurotrophin-3 (Ntf3) and brain derived neurotrophic factor (Bdnf) are critical for sensory neuron survival and establishment of neuronal projections to sensory epithelia in the embryonic inner ear, but their postnatal functions remain poorly understood. Using cell-specific inducible gene recombination in mice we found that, in the postnatal inner ear, Bbnf and Ntf3 are required for the formation and maintenance of hair cell ribbon synapses in the vestibular and cochlear epithelia, respective...

  10. cAMP-Inhibits Cytoplasmic Phospholipase A2 and Protects Neurons against Amyloid-β-Induced Synapse Damage

    OpenAIRE

    Clive Bate; Alun Williams

    2015-01-01

    A key event in Alzheimer’s disease (AD) is the production of amyloid-β (Aβ) peptides and the loss of synapses. In cultured neurons Aβ triggered synapse damage as measured by the loss of synaptic proteins. α-synuclein (αSN), aggregates of which accumulate in Parkinson’s disease, also caused synapse damage. Synapse damage was associated with activation of cytoplasmic phospholipase A2 (cPLA2), an enzyme that regulates synapse function and structure, and the production of prostaglandin (PG) E2. I...

  11. Does Subacromial Osteolysis Affect Shoulder Function after Clavicle Hook Plating?

    Science.gov (United States)

    Sun, Siwei; Gan, Minfeng; Sun, Han; Wu, Guizhong; Yang, Huilin; Zhou, Feng

    2016-01-01

    Purpose. To evaluate whether subacromial osteolysis, one of the major complications of the clavicle hook plate procedure, affects shoulder function. Methods. We had performed a retrospective study of 72 patients diagnosed with a Neer II lateral clavicle fracture or Degree-III acromioclavicular joint dislocation in our hospital from July 2012 to December 2013. All these patients had undergone surgery with clavicle hook plate and were divided into two groups based on the occurrence of subacromial osteolysis. By using the Constant-Murley at the first follow-up visit after plates removal, we evaluated patients' shoulder function to judge if it has been affected by subacromial osteolysis. Results. We have analyzed clinical data for these 72 patients, which shows that there is no significant difference between group A (39 patients) and group B (33 patients) in age, gender, injury types or side, and shoulder function (the Constant-Murley scores are 93.38 ± 3.56 versus 94.24 ± 3.60, P > 0.05). Conclusion. The occurrence of subacromial osteolysis is not rare, and also it does not significantly affect shoulder function. PMID:27034937

  12. Effects of curcumin on synapses in APPswe/PS1dE9 mice.

    Science.gov (United States)

    He, Yingkun; Wang, Pengwen; Wei, Peng; Feng, Huili; Ren, Ying; Yang, Jinduo; Rao, Yingxue; Shi, Jing; Tian, Jinzhou

    2016-06-01

    Significant losses of synapses have been demonstrated in studies of Alzheimer's disease (AD), but structural and functional changes in synapses that depend on alterations of the postsynaptic density (PSD) area occur prior to synaptic loss and play a crucial role in the pathology of AD. Evidence suggests that curcumin can ameliorate the learning and memory deficits of AD. To investigate the effects of curcumin on synapses, APPswe/PS1dE9 double transgenic mice (an AD model) were used, and the ultra-structures of synapses and synapse-associated proteins were observed. Six months after administration, few abnormal synapses were observed upon electron microscopy in the hippocampal CA1 areas of the APPswe/PS1dE9 double transgenic mice. The treatment of the mice with curcumin resulted in improvements in the quantity and structure of the synapses. Immunohistochemistry and western blot analyses revealed that the expressions of PSD95 and Shank1 were reduced in the hippocampal CA1 areas of the APPswe/PS1dE9 double transgenic mice, but curcumin treatment increased the expressions of these proteins. Our findings suggest that curcumin improved the structure and function of the synapses by regulating the synapse-related proteins PSD95 and Shank1. PMID:26957323

  13. Going Mobile: AMPA Receptors Move Synapse to Synapse In Vivo

    OpenAIRE

    Rongo, Christopher

    2013-01-01

    Plasticity models invoke the synaptic delivery of AMPARs, yet we know little about how receptors move in vivo. In this issue of Neuron, Hoerndli et al. show that lateral diffusion and kinesin-mediated transport move AMPARs between synapses in vivo.

  14. 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

  15. Childhood trauma and cognitive function in first-episode affective and non-affective psychosis.

    LENUS (Irish Health Repository)

    Aas, Monica

    2011-06-01

    A history of childhood trauma is reportedly more prevalent in people suffering from psychosis than in the general population. Childhood trauma has also been linked to cognitive abnormalities in adulthood, and cognitive abnormalities, in turn, are one of the key clinical features of psychosis. Therefore, this study investigated whether there was a relationship between childhood trauma and cognitive function in patients with first-episode psychosis. The potential impact of diagnosis (schizophrenia or affective psychosis) and gender on this association was also examined.

  16. Human NK Cell Subset Functions Are Differentially Affected by Adipokines

    OpenAIRE

    Huebner, Lena; Engeli, Stefan; Christiane D Wrann; Goudeva, Lilia; Laue, Tobias; Kielstein, Heike

    2013-01-01

    Background: Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines). Since natural killer (NK) cells are the host’s primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM) affects functions of two distinct human NK cell subsets. Methods: Isolated human peripheral blood mononuclear cell...

  17. Interplay between Subthreshold Oscillations and Depressing Synapses in Single Neurons.

    Directory of Open Access Journals (Sweden)

    Roberto Latorre

    Full Text Available In this paper we analyze the interplay between the subthreshold oscillations of a single neuron conductance-based model and the short-term plasticity of a dynamic synapse with a depressing mechanism. In previous research, the computational properties of subthreshold oscillations and dynamic synapses have been studied separately. Our results show that dynamic synapses can influence different aspects of the dynamics of neuronal subthreshold oscillations. Factors such as maximum hyperpolarization level, oscillation amplitude and frequency or the resulting firing threshold are modulated by synaptic depression, which can even make subthreshold oscillations disappear. This influence reshapes the postsynaptic neuron's resonant properties arising from subthreshold oscillations and leads to specific input/output relations. We also study the neuron's response to another simultaneous input in the context of this modulation, and show a distinct contextual processing as a function of the depression, in particular for detection of signals through weak synapses. Intrinsic oscillations dynamics can be combined with the characteristic time scale of the modulatory input received by a dynamic synapse to build cost-effective cell/channel-specific information discrimination mechanisms, beyond simple resonances. In this regard, we discuss the functional implications of synaptic depression modulation on intrinsic subthreshold dynamics.

  18. Factors affecting sexual function in menopause: A review article.

    Science.gov (United States)

    Nazarpour, Soheila; Simbar, Masoumeh; Tehrani, Fahimeh Ramezani

    2016-08-01

    This study aimed to systematically review the articles on factors affecting sexual function during menopause. Searching articles indexed in Pubmed, Science Direct, Iranmedex, EMBASE, Scopus, and Scientific Information Database databases, a total number of 42 studies published between 2003 and 2013 were selected. Age, estrogen deficiency, type of menopause, chronic medical problems, partner's sex problems, severity of menopause symptoms, dystocia history, and health status were the physical factors influencing sexual function of menopausal women. There were conflicting results regarding the amount of androgens, hormonal therapy, exercise/physical activity, and obstetric history. In the mental-emotional area, all studies confirmed the impact of depression and anxiety. Social factors, including smoking, alcohol consumption, the quality of relationship with husband, partner's loyalty, sexual knowledge, access to health care, a history of divorce or the death of a husband, living apart from a spouse, and a negative understanding of women's health were found to affect sexual function; however, there were conflicting results regarding the effects of education, occupation, socioeconomic status, marital duration, and frequency of sexual intercourse. PMID:27590367

  19. 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.

  20. 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%.

  1. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    Science.gov (United States)

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p Ramadan period of fasting group (p Ramadan compared to baseline (p Ramadan fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  2. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    Science.gov (United States)

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p fasting group (p fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  3. Can the hydrophilicity of functional monomers affect chemical interaction?

    Science.gov (United States)

    Feitosa, V P; Ogliari, F A; Van Meerbeek, B; Watson, T F; Yoshihara, K; Ogliari, A O; Sinhoreti, M A; Correr, A B; Cama, G; Sauro, S

    2014-02-01

    The number of carbon atoms and/or ester/polyether groups in spacer chains may influence the interaction of functional monomers with calcium and dentin. The present study assessed the chemical interaction and bond strength of 5 standard-synthesized phosphoric-acid ester functional monomers with different spacer chain characteristics, by atomic absorption spectroscopy (AAS), ATR-FTIR, thin-film x-ray diffraction (TF-XRD), scanning electron microscopy (SEM), and microtensile bond strength (μTBS). The tested functional monomers were 2-MEP (two-carbon spacer chain), 10-MDP (10-carbon), 12-MDDP (12-carbon), MTEP (more hydrophilic polyether spacer chain), and CAP-P (intermediate hydrophilicity ester spacer). The intensity of monomer-calcium salt formation measured by AAS differed in the order of 12-MDDP=10-MDP>CAP-P>MTEP>2-MEP. FTIR and SEM analyses of monomer-treated dentin surfaces showed resistance to rinsing for all monomer-dentin bonds, except with 2-MEP. TF-XRD confirmed the weaker interaction of 2-MEP. Highest µTBS was observed for 12-MDDP and 10-MDP. A shorter spacer chain (2-MEP) of phosphate functional monomers induced formation of unstable monomer-calcium salts, and lower chemical interaction and dentin bond strength. The presence of ester or ether groups within longer spacer carbon chains (CAP-P and MTEP) may affect the hydrophilicity, μTBS, and also the formation of monomer-calcium salts. PMID:24284259

  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. Quercetin Affects Erythropoiesis and Heart Mitochondrial Function in Mice

    Directory of Open Access Journals (Sweden)

    Lina M. Ruiz

    2015-01-01

    Full Text Available Quercetin, a dietary flavonoid used as a food supplement, showed powerful antioxidant effects in different cellular models. However, recent in vitro and in vivo studies in mammals have suggested a prooxidant effect of quercetin and described an interaction with mitochondria causing an increase in O2∙- production, a decrease in ATP levels, and impairment of respiratory chain in liver tissue. Therefore, because of its dual actions, we studied the effect of quercetin in vivo to analyze heart mitochondrial function and erythropoiesis. Mice were injected with 50 mg/kg of quercetin for 15 days. Treatment with quercetin decreased body weight, serum insulin, and ceruloplasmin levels as compared with untreated mice. Along with an impaired antioxidant capacity in plasma, quercetin-treated mice showed a significant delay on erythropoiesis progression. Heart mitochondrial function was also impaired displaying more protein oxidation and less activity for IV, respectively, than no-treated mice. In addition, a significant reduction in the protein expression levels of Mitofusin 2 and Voltage-Dependent Anion Carrier was observed. All these results suggest that quercetin affects erythropoiesis and mitochondrial function and then its potential use as a dietary supplement should be reexamined.

  6. Organic core-sheath nanowire artificial synapses with femtojoule energy consumption.

    Science.gov (United States)

    Xu, Wentao; Min, Sung-Yong; Hwang, Hyunsang; Lee, Tae-Woo

    2016-06-01

    Emulation of biological synapses is an important step toward construction of large-scale brain-inspired electronics. Despite remarkable progress in emulating synaptic functions, current synaptic devices still consume energy that is orders of magnitude greater than do biological synapses (~10 fJ per synaptic event). Reduction of energy consumption of artificial synapses remains a difficult challenge. We report organic nanowire (ONW) synaptic transistors (STs) that emulate the important working principles of a biological synapse. The ONWs emulate the morphology of nerve fibers. With a core-sheath-structured ONW active channel and a well-confined 300-nm channel length obtained using ONW lithography, ~1.23 fJ per synaptic event for individual ONW was attained, which rivals that of biological synapses. The ONW STs provide a significant step toward realizing low-energy-consuming artificial intelligent electronics and open new approaches to assembling soft neuromorphic systems with nanometer feature size. PMID:27386556

  7. 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.

  8. Can lifestyle modification affect men’s erectile function?

    Science.gov (United States)

    Hehemann, Marah C.

    2016-01-01

    Erectile dysfunction (ED) is a common condition affecting millions of men worldwide. The pathophysiology and epidemiologic links between ED and risk factors for cardiovascular disease (CVD) are well-established. Lifestyle modifications such as smoking cessation, weight reduction, dietary modification, physical activity, and psychological stress reduction have been increasingly recognized as foundational to the prevention and treatment of ED. The aim of this review is to outline behavioral choices which may increase ones risk of developing ED, to present relevant studies addressing lifestyle factors correlated with ED, and to highlight proposed mechanisms for intervention aimed at improving erectile function in men with ED. These recommendations can provide a framework for counseling patients with ED about lifestyle modification.

  9. Integrating Negative Affect Measures in a Measurement Model: Assessing the Function of Negative Affect as Interference to Self-Regulation

    Science.gov (United States)

    Magno, Carlo

    2010-01-01

    The present study investigated the composition of negative affect and its function as inhibitory to thought processes such as self-regulation. Negative affect in the present study were composed of anxiety, worry, thought suppression, and fear of negative evaluation. These four factors were selected based on the criteria of negative affect by…

  10. To what extent does urbanisation affect fragmented grassland functioning?

    Science.gov (United States)

    van der Walt, L; Cilliers, S S; Kellner, K; Du Toit, M J; Tongway, D

    2015-03-15

    Urbanisation creates altered environments characterised by increased human habitation, impermeable surfaces, artificial structures, landscape fragmentation, habitat loss, resulting in different resource loss pathways. The vulnerable Rand Highveld Grassland vegetation unit in the Tlokwe Municipal area, South Africa, has been extensively affected and transformed by urbanisation, agriculture, and mining. Grassland fragments in urban areas are often considered to be less species rich and less functional than in the more untransformed or "natural" exurban environments, and are therefore seldom a priority for conservation. Furthermore, urban grassland fragments are often being more intensely managed than exurban areas, such as consistent mowing in open urban areas. Four urbanisation measures acting as indicators for patterns and processes associated with urban areas were calculated for matrix areas surrounding each selected grassland fragment to quantify the position of each grassland remnant along an urbanisation gradient. The grassland fragments were objectively classified into two classes of urbanisation, namely "exurban" and "urban" based on the urbanisation measure values. Grazing was recorded in some exurban grasslands and mowing in some urban grassland fragments. Unmanaged grassland fragments were present in both urban and exurban areas. Fine-scale biophysical landscape function was determined by executing the Landscape Function Analysis (LFA) method. LFA assesses fine-scale landscape patchiness (entailing resource conserving potential and erosion resistance) and 11 soil surface indicators to produce three main LFA parameters (stability, infiltration, and nutrient cycling), which indicates how well a system is functioning in terms of fine-scale biophysical soil processes and characteristics. The aim of this study was to determine the effects of urbanisation and associated management practices on fine-scale biophysical landscape function of urban and exurban

  11. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    Directory of Open Access Journals (Sweden)

    Mahboubeh Ghayour Najafabadi

    2015-01-01

    Full Text Available We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n=9 and nonfasting (n=8 groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan. Digit span test (DST and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p<0.05. Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p<0.05. Group × week interaction was significant only for error numbers (p<0.05. Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p<0.05. The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes.

  12. Synapse: Synthetic Application Profiler and Emulator

    OpenAIRE

    Merzky, Andre; Jha, Shantenu

    2015-01-01

    We introduce Synapse motivated by the needs to estimate and emulate workload execution characteristics on high-performance and distributed heterogeneous resources. Synapse has a platform independent application profiler, and the ability to emulate profiled workloads on a variety of heterogeneous resources. Synapse is used as a proxy application (or "representative application") for real workloads, with the added advantage that it can be tuned at arbitrary levels of granularity in ways that ar...

  13. Analyzing the exhaustiveness of the synapse protocol

    OpenAIRE

    Marinkovic, Bojan; Ciancaglini, Vincenzo; Ognjanovic, Zoran; Glavan, Paola; Liquori, Luigi; Maksimovic, Petar

    2015-01-01

    International audience The Synapse protocol is a scalable protocol designed for information retrieval over inter-connected heterogeneous overlay networks. In this paper, we give a formal description of Synapse using the Abstract State Machines framework. The formal description pertains to Synapse actions that manipulate distributed keys. Based on this formal description, we present results concerning the expected exhaustiveness for a number of scenarios and systems maintained by the Synaps...

  14. The Biochemical Anatomy of Cortical Inhibitory Synapses

    OpenAIRE

    Heller, E.A.; Zhang, W.; Selimi, F.; Earnheart, J.C.; Slimak, M.A.; Santos-Torres, J.; Ibanez-Tallon, I.; Aoki, C; Chait, B. T.; Heintz, N

    2012-01-01

    Classical electron microscopic studies of the mammalian brain revealed two major classes of synapses, distinguished by the presence of a large postsynaptic density (PSD) exclusively at type 1, excitatory synapses. Biochemical studies of the PSD have established the paradigm of the synapse as a complex signal-processing machine that controls synaptic plasticity. We report here the results of a proteomic analysis of type 2, inhibitory synaptic complexes isolated by affinity purification from th...

  15. [Changes in the ultrastructure of neuromuscular synapses in rats under the effects of space flight factors].

    Science.gov (United States)

    Pozdniakov, O M; Babakova, L L; Demorzhi, M S; Il'ina-Kakueva, E I

    1988-06-01

    The influence of a 7-day space flight on board the biosputnik "Kosmos-1669" on the neuro-muscular synapses (NMS) of soleus, gastrocnemius and diaphragm muscles distinct in their functions has been studied. The synapse restructuring on the basis of destructive- regenerative process has been discovered. It is manifested to a great extent in the soleus muscle, to a lesser extent in the gastrocnemius muscle and the least of all in the diaphragm muscle. The changes observed in synapses may be caused by the attenuation of their function in weightlessness. PMID:3390600

  16. Human NK cell subset functions are differentially affected by adipokines.

    Directory of Open Access Journals (Sweden)

    Lena Huebner

    Full Text Available BACKGROUND: Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines. Since natural killer (NK cells are the host's primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM affects functions of two distinct human NK cell subsets. METHODS: Isolated human peripheral blood mononuclear cells (PBMCs were cultured with various concentrations of human and murine ACM harvested on two different days during adipogenesis and analyzed by fluorescent-activated cell sorting (FACS. RESULTS: FACS analyses showed that the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, granzyme A (GzmA and interferon (IFN-γ in NK cells was regulated in a subset-specific manner. ACM treatment altered IFN-γ expression in CD56(dim NK cells. The production of GzmA in CD56(bright NK cells was differentially affected by the distinct adipokine compositions harvested at different states of adipogenesis. Comparison of the treatment with either human or murine ACM revealed that adipokine-induced effects on NK cell expression of the leptin receptor (Ob-R, TRAIL and IFN-γ were species-specific. CONCLUSION: Considering the growing prevalence of obesity and the various disorders related to it, the present study provides further insights into the roles human NK cell subsets play in the obesity-associated state of chronic low-grade inflammation.

  17. The State of Synapses in Fragile X Syndrome

    OpenAIRE

    Pfeiffer, Brad E.; Huber, Kimberly M.

    2009-01-01

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

  18. IQ Motif and SEC7 Domain-containing Protein 3 (IQSEC3) Interacts with Gephyrin to Promote Inhibitory Synapse Formation.

    Science.gov (United States)

    Um, Ji Won; Choii, Gayoung; Park, Dongseok; Kim, Dongwook; Jeon, Sangmin; Kang, Hyeyeon; Mori, Takuma; Papadopoulos, Theofilos; Yoo, Taesun; Lee, Yeunkum; Kim, Eunjoon; Tabuchi, Katsuhiko; Ko, Jaewon

    2016-05-01

    Gephyrin is a central scaffold protein that mediates development, function, and plasticity of mammalian inhibitory synapses by interacting with various inhibitory synaptic proteins. Here, we show that IQSEC3, a guanine nucleotide exchange factor for ARF6, directly interacts with gephyrin, an interaction that is critical for the inhibitory synapse localization of IQSEC3. Overexpression of IQSEC3 increases inhibitory, but not excitatory, synapse density in a guanine nucleotide exchange factor activity-dependent manner. Conversely, knockdown of IQSEC3 decreases size of gephyrin cluster without altering gephyrin puncta density. Collectively, these data reveal that IQSEC3 acts together with gephyrin to regulate inhibitory synapse development. PMID:27002143

  19. The guanine exchange factor Gartenzwerg and the small GTPase Arl1 function in the same pathway with Arfaptin during synapse growth

    OpenAIRE

    Leo Chang; Tabita Kreko-Pierce; Eaton, Benjamin A.

    2015-01-01

    ABSTRACT The generation of neuronal morphology requires transport vesicles originating from the Golgi apparatus (GA) to deliver specialized components to the axon and dendrites. Drosophila Arfaptin is a membrane-binding protein localized to the GA that is required for the growth of the presynaptic nerve terminal. Here we provide biochemical, cellular and genetic evidence that the small GTPase Arl1 and the guanine-nucleotide exchange factor (GEF) Gartenzwerg are required for Arfaptin function ...

  20. Critical avalanches and subsampling in map-based neural networks coupled with noisy synapses.

    Science.gov (United States)

    Girardi-Schappo, M; Kinouchi, O; Tragtenberg, M H R

    2013-08-01

    Many different kinds of noise are experimentally observed in the brain. Among them, we study a model of noisy chemical synapse and obtain critical avalanches for the spatiotemporal activity of the neural network. Neurons and synapses are modeled by dynamical maps. We discuss the relevant neuronal and synaptic properties to achieve the critical state. We verify that networks of functionally excitable neurons with fast synapses present power-law avalanches, due to rebound spiking dynamics. We also discuss the measuring of neuronal avalanches by subsampling our data, shedding light on the experimental search for self-organized criticality in neural networks. PMID:24032969

  1. Astrocytic role in synapse formation after injury.

    Science.gov (United States)

    Li, Ying; Li, Daqing; Raisman, Geoffrey

    2016-08-15

    In 1969 a paper entitled Neuronal plasticity in the septal nuclei of the adult rat proposed that new synapses are formed in the adult brain after injury (Raisman, 1969). The quantitative electron microscopic study of the timed responses to selective partial denervation of the neuropil of the adult rat septal nuclei after distant transection of the hippocampal efferent axons in the fimbria showed that the new synapses arise by sprouting of surviving adjacent synapses which selectively take over the previously denervated sites and thus restore the number of synapses to normal. This article presents the evidence for the role of perisynaptic astrocytic processes in the removal and formation of synapses and considers its significance as one of the three major divisions of the astrocytic surface in terms of the axonal responses to injury and regeneration. This article is part of a Special Issue entitled SI:50th Anniversary Issue. PMID:26746338

  2. Morphological changes associated with the genesis and development of an excitatory glutemergic synapse: An integrated framework model

    Directory of Open Access Journals (Sweden)

    Venkateswaran Nagarajan

    2014-04-01

    Full Text Available The genesis of an excitatory synapse has its inception when a dendritic filopodium makes a tactile contact with a presynaptic specialisation (bouton. The subsequent maturation of the synapse takes place via a series of interrelated biochemical and biophysical signalling pathways which controls the actin polymerisation in the presynaptic and the postsynaptic sites. Although individual models of many of these signalling transductions have been proposed, a holistic model integrating the various signalling pathways to the morphological plasticity associated with the genesis and development of synapses has not. In this poster an attempt has been made towards establishing a framework for an integrated model such as the one aforementioned, encompassing several signalling pathways which control the morphology and the efficacy of the synapse. Predominant pathways include those triggered by NMDA and AMPA receptors, Trkb-BDNF, Integrin and Epherin. Also, steps towards a model that elucidates the change in shape of the synapse carried out by zonal actin polymerisation (ZAP governed by the "wastage" of neurotransmitters during exo cum endocytosis processes and the assimilation of the postsynaptic density (PSD and cell adhesion molecules with emphasis on Neurexin-Neuriligin, have been explored. The cannabinoid receptors in the PAZ have extracellular lipophilic domains. Endocannabinoid receptors are triggered by the retrograde signalling cues which negatively affect the cAMP dependent mechanisms. Apart from this, autoreceptors also pilot a feedback mechanism via secondary messengers with Ca 2+ ion concentration and neurotransmitter concentration in the synaptic cleft as its stakeholders. Feedback signals of autoreceptors which functions in accordance to “Lock and Key Mechanism” plays a vital role in fine-tuning the plasticity of the synapse and in controlling the presynaptic release probability by invoking PKA dependent pathways. In a future continuation

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

    International Nuclear Information System (INIS)

    Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABAA receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (Vd) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer's disease (AD), where synaptic loss tends indiscriminately to affect all cortical neurons, albeit more so in some areas than in others. In this pilot study we measured Vd in six patients with probable AD and in five age-matched controls using a brain-dedicated single-photon emission tomography scanner allowing all cortical levels to be sampled simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex Vd was significantly (Pd averaged 69 ml/ml in normals and 51 ml/ml in AD, and parietal Vd averaged 71 ml/ml in normals and 48 ml/ml in AD. These results accord well with emission tomographic studies of blood flow or labelled glucose. This supports the idea that while only measuring a subpopulation of synapses, the IMZ method reflects synaptic loss and hence functional loss in AD. The method constitutes an in vivo version of synaptic quantitation that in histopathological studies has been shown to correlated closely with the mental deterioration in AD. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Soricelli, A. [Dept. of Diagnostic Imaging, Univ. of Naples Federico II, Nuclear Medicine Center of the National Research Council (Italy); Postiglione, A. [Dept. of Clinical and Experimental Medicine, Univ. of Naples Federico II (Italy); Grivet-Fojaja, M.R. [Dept. of Diagnostic Imaging, Univ. of Naples Federico II, Nuclear Medicine Center of the National Research Council (Italy); Mainenti, P.P. [Dept. of Diagnostic Imaging, Univ. of Naples Federico II, Nuclear Medicine Center of the National Research Council (Italy); Discepolo, A. [Dept. of Diagnostic Imaging, Univ. of Naples Federico II, Nuclear Medicine Center of the National Research Council (Italy); Varrone, A. [Dept. of Diagnostic Imaging, Univ. of Naples Federico II, Nuclear Medicine Center of the National Research Council (Italy); Salvatore, M. [Dept. of Diagnostic Imaging, Univ. of Naples Federico II, Nuclear Medicine Center of the National Research Council (Italy); Lassen, N.A. [Dept. of Nuclear Medicine/Clinical Physiology, Bispebjerg Hospital, Copenhagen (Denmark)

    1996-10-01

    Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABA{sub A} receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (V{sub d}) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer`s disease (AD), where synaptic loss tends indiscriminately to affect all cortical neurons, albeit more so in some areas than in others. In this pilot study we measured V{sub d} in six patients with probable AD and in five age-matched controls using a brain-dedicated single-photon emission tomography scanner allowing all cortical levels to be sampled simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex V{sub d} was significantly (P<0.02) reduced: Temporal V{sub d} averaged 69 ml/ml in normals and 51 ml/ml in AD, and parietal V{sub d} averaged 71 ml/ml in normals and 48 ml/ml in AD. These results accord well with emission tomographic studies of blood flow or labelled glucose. This supports the idea that while only measuring a subpopulation of synapses, the IMZ method reflects synaptic loss and hence functional loss in AD. The method constitutes an in vivo version of synaptic quantitation that in histopathological studies has been shown to correlated closely with the mental deterioration in AD. (orig.)

  5. Families First-Keys to Successful Family Functioning. Affective Responsiveness

    OpenAIRE

    Peterson, Rick; Green, Stephen

    2009-01-01

    Affective responsiveness is the ability of an individual to respond to another with appropriate feelings . Affective (emotional) responsiveness is very important because family members interact with one another on a regular basis and often need to support each other during difficult times.

  6. The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Synapse formation is regulated by the signaling adaptor GIT1

    OpenAIRE

    Zhang, Huaye; Webb, Donna J.; Asmussen, Hannelore; Horwitz, Alan F.

    2003-01-01

    Dendritic spines in the central nervous system undergo rapid actin-based shape changes, making actin regulators potential modulators of spine morphology and synapse formation. Although several potential regulators and effectors for actin organization have been identified, the mechanisms by which these molecules assemble and localize are not understood. Here we show that the G protein–coupled receptor kinase–interacting protein (GIT)1 serves such a function by targeting actin regulators and lo...

  9. The Role of MuSK in Synapse Formation and Neuromuscular Disease

    OpenAIRE

    Burden, Steven J.; Yumoto, Norihiro; Zhang, Wei

    2013-01-01

    Muscle-specific kinase (MuSK) is essential for each step in neuromuscular synapse formation. Before innervation, MuSK initiates postsynaptic differentiation, priming the muscle for synapse formation. Approaching motor axons recognize the primed, or prepatterned, region of muscle, causing motor axons to stop growing and differentiate into specialized nerve terminals. MuSK controls presynaptic differentiation by causing the clustering of Lrp4, which functions as a direct retrograde signal for p...

  10. Giant ankyrin-G stabilizes somatodendritic GABAergic synapses through opposing endocytosis of GABAA receptors

    OpenAIRE

    Tseng, Wei Chou; Jenkins, Paul M.; Tanaka, Masashi; Mooney, Richard; Bennett, Vann

    2014-01-01

    GABAA-receptor-based interneuron circuitry is essential for higher order function of the human nervous system and is implicated in schizophrenia, depression, anxiety disorders, and autism. GABAergic synapses are located on neuronal cell bodies and dendritic shafts as well as axon initial segments. This study demonstrates that giant ankyrin-G forms micron-scale domains on neuronal cell bodies and dendritic shafts, and promotes somatodendritic GABAergic synapse stability through interaction wit...

  11. Pathogenic SYNGAP1 mutations impair cognitive development by disrupting the maturation of dendritic spine synapses

    OpenAIRE

    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

    2012-01-01

    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...

  12. 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. PMID:26599711

  13. Risk factors affecting somatosensory function after sagittal split osteotomy

    DEFF Research Database (Denmark)

    Thygesen, Torben Henrik; Jensen, Allan Bardow; Helleberg, M; Norholt, SE; Jensen, John; Svensson, Peter

    2008-01-01

    Purpose The aim of this study was to evaluate potential individual and intraoperative risk factors associated with bilateral sagittal split osteotomy (BSSO) and to correlate the findings with postoperative changes in somatosensory function. Patients and Methods A total of 18 men and 29 women (mean...... somatosensory function after BSSO is dependent on both intraoperative risk factors and preoperative sensation levels....

  14. Astrocytes Assemble Thalamocortical Synapses by Bridging NRX1α and NL1 via Hevin.

    Science.gov (United States)

    Singh, Sandeep K; Stogsdill, Jeff A; Pulimood, Nisha S; Dingsdale, Hayley; Kim, Yong Ho; Pilaz, Louis-Jan; Kim, Il Hwan; Manhaes, Alex C; Rodrigues, Wandilson S; Pamukcu, Arin; Enustun, Eray; Ertuz, Zeynep; Scheiffele, Peter; Soderling, Scott H; Silver, Debra L; Ji, Ru-Rong; Medina, Alexandre E; Eroglu, Cagla

    2016-01-14

    Proper establishment of synapses is critical for constructing functional circuits. Interactions between presynaptic neurexins and postsynaptic neuroligins coordinate the formation of synaptic adhesions. An isoform code determines the direct interactions of neurexins and neuroligins across the synapse. However, whether extracellular linker proteins can expand such a code is unknown. Using a combination of in vitro and in vivo approaches, we found that hevin, an astrocyte-secreted synaptogenic protein, assembles glutamatergic synapses by bridging neurexin-1alpha and neuroligin-1B, two isoforms that do not interact with each other. Bridging of neurexin-1alpha and neuroligin-1B via hevin is critical for the formation and plasticity of thalamocortical connections in the developing visual cortex. These results show that astrocytes promote the formation of synapses by modulating neurexin/neuroligin adhesions through hevin secretion. Our findings also provide an important mechanistic insight into how mutations in these genes may lead to circuit dysfunction in diseases such as autism. PMID:26771491

  15. 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.

  16. Dynamic changes in hair cell ribbon synapse induced by loss of spiral ganglion neurons in mice

    Institute of Scientific and Technical Information of China (English)

    Yuan Yasheng; Chi Fanglu

    2014-01-01

    Background Previous studies have suggested that primary degeneration of hair cells causes secondary degeneration of spiral ganglion neurons (SGNs),but the effect of SGN degeneration on hair cells has not been studied.In the adult mouse inner ear ouabain can selectively and permanently induce the degeneration of type 1 SGNs while leaving type 2 SGNs,efferent fibers,and sensory hair cells relatively intact.This study aimed to investigate the dynamic changes in hair cell ribbon synapse induced by loss of SGNs using ouabain application to the round window niche of adult mice.Methods In the analysis,24 CBA/CAJ mice aged 8-10 weeks,were used,of which 6 normal mice were used as the control group.After ouabain application in the round window niche 6 times in an hour,ABR threshold shifts at least 30 dB in the three experimental groups which had six mice for 1-week group,six for 1-month group,and six for 3-month group.All 24 animals underwent function test at 1 week and then immunostaining at 1 week,1 month,and 3 months.Results The loss of neurons was followed by degeneration of postsynaptic specializations at the afferent synapse with hair cells.One week after ouabain treatment,the nerve endings of type 1 SGNs and postsynaptic densities,as measured by Na/K ATPase and PSD-95,were affected but not entirely missing,but their partial loss had consequences for synaptic ribbons that form the presynaptic specialization at the synapse between hair cells and primary afferent neurons.Ribbon numbers in inner hair cells decreased (some of them broken and the ribbon number much decreased),and the arrangement of the synaptic ribbons had undergone a dynamic reorganization:ribbons with or without associated postsynaptic densities moved from their normal location in the basal membrane of the cell to a more apical location and the neural endings alone were also found at more apical locations without associated ribbons.After 1 month,when the neural postsynaptic densities had completed their

  17. Crossbar Nanoscale HfO2-Based Electronic Synapses.

    Science.gov (United States)

    Matveyev, Yury; Kirtaev, Roman; Fetisova, Alena; Zakharchenko, Sergey; Negrov, Dmitry; Zenkevich, Andrey

    2016-12-01

    Crossbar resistive switching devices down to 40 × 40 nm(2) in size comprising 3-nm-thick HfO2 layers are forming-free and exhibit up to 10(5) switching cycles. Four-nanometer-thick devices display the ability of gradual switching in both directions, thus emulating long-term potentiation/depression properties akin to biological synapses. Both forming-free and gradual switching properties are modeled in terms of oxygen vacancy generation in an ultrathin HfO2 layer. By applying the voltage pulses to the opposite electrodes of nanodevices with the shape emulating spikes in biological neurons, spike-timing-dependent plasticity functionality is demonstrated. Thus, the fabricated memristors in crossbar geometry are promising candidates for hardware implementation of hybrid CMOS-neuron/memristor-synapse neural networks. PMID:26979725

  18. 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...... the matrix is stored on-chip as differential voltages on capacitors. In principal any ANN configuration can be made using these chips. A neuron array of 4 neurons and a 4 × 4 matrix-vector multiplier has been fabricated in a standard 2.4 ¿m CMOS process for test purposes. The propagation time through...... the synapse and neuron chips is less than 4 ¿s and the weight matrix has a 10 bit resolution....

  19. Crossbar Nanoscale HfO2-Based Electronic Synapses

    Science.gov (United States)

    Matveyev, Yury; Kirtaev, Roman; Fetisova, Alena; Zakharchenko, Sergey; Negrov, Dmitry; Zenkevich, Andrey

    2016-03-01

    Crossbar resistive switching devices down to 40 × 40 nm2 in size comprising 3-nm-thick HfO2 layers are forming-free and exhibit up to 105 switching cycles. Four-nanometer-thick devices display the ability of gradual switching in both directions, thus emulating long-term potentiation/depression properties akin to biological synapses. Both forming-free and gradual switching properties are modeled in terms of oxygen vacancy generation in an ultrathin HfO2 layer. By applying the voltage pulses to the opposite electrodes of nanodevices with the shape emulating spikes in biological neurons, spike-timing-dependent plasticity functionality is demonstrated. Thus, the fabricated memristors in crossbar geometry are promising candidates for hardware implementation of hybrid CMOS-neuron/memristor-synapse neural networks.

  20. Mammalian cadherins DCHS1-FAT4 affect functional cerebral architecture.

    Science.gov (United States)

    Beste, Christian; Ocklenburg, Sebastian; von der Hagen, Maja; Di Donato, Nataliya

    2016-06-01

    Cortical development is a complex process where a multitude of factors, including cadherins, plays an important role and where disruptions are known to have far reaching effects in neural development and cortical patterning. Cadherins play a central role in structural left-right differentiation during brain and body development, but their effect on a functional level remains elusive. We addressed this question by examining functional cerebral asymmetries in a patient with Van Maldergem Syndrome (VMS) (MIM#601390), which is caused by mutations in DCHS1-FAT4 cadherins, using a dichotic listening task. Using neurophysiological (EEG) data, we show that when key regulators during mammalian cerebral cortical development are disrupted due to DCHS1-FAT4 mutations, functional cerebral asymmetries are stronger. Basic perceptual processing of biaurally presented auditory stimuli was unaffected. This suggests that the strength and emergence of functional cerebral asymmetries is a direct function of proliferation and differentiation of neuronal stem cells. Moreover, these results support the recent assumption that the molecular mechanisms establishing early left-right differentiation are an important factor in the ontogenesis of functional lateralization. PMID:25930014

  1. Astrocytic mGluR5 and the tripartite synapse.

    Science.gov (United States)

    Panatier, A; Robitaille, R

    2016-05-26

    In the brain, astrocytes occupy a key position between vessels and synapses. Among their numerous functions, these glial cells are key partners of neurons during synaptic transmission. Astrocytes detect transmitter release through receptors and transporters at the level of their processes, which are in close proximity to the tow neuronal elements of synapses. In response to transmitter-mediated activation, glial cells in turn regulate synaptic transmission and neuronal excitability. This process has been reported to involve several glial receptors. One of the best known of such receptors is the metabotropic glutamatergic receptor subtype 5 (mGluR5). In the present review we will discuss the implication of mGluR5s as detectors of synaptic transmission. In particular, we will discuss how the functional properties and localization of these receptors permit the detection of the synaptic signal in a defined temporal window and a given spatial area around the synapse. Furthermore, we will review the impact of their activation on synaptic transmission. PMID:25847307

  2. Synapse geometry and receptor dynamics modulate synaptic strength.

    Directory of Open Access Journals (Sweden)

    Dominik Freche

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

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

    Science.gov (United States)

    Duman, Joseph G; Tu, Yen-Kuei; Tolias, Kimberley F

    2016-01-01

    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. PMID:26881134

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Investigating complex I deficiency in Purkinje cells and synapses in patients with mitochondrial disease

    Science.gov (United States)

    Chrysostomou, Alexia; Grady, John P.; Laude, Alex; Taylor, Robert W.; Turnbull, Doug M.

    2015-01-01

    Aims Cerebellar ataxia is common in patients with mitochondrial disease, and despite previous neuropathological investigations demonstrating vulnerability of the olivocerebellar pathway in patients with mitochondrial disease, the exact neurodegenerative mechanisms are still not clear. We use quantitative quadruple immunofluorescence to enable precise quantification of mitochondrial respiratory chain protein expression in Purkinje cell bodies and their synaptic terminals in the dentate nucleus. Methods We investigated NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 protein expression in 12 clinically and genetically defined patients with mitochondrial disease and ataxia and 10 age‐matched controls. Molecular genetic analysis was performed to determine heteroplasmy levels of mutated mitochondrial DNA in Purkinje cell bodies and inhibitory synapses. Results Our data reveal that complex I deficiency is present in both Purkinje cell bodies and their inhibitory synapses which surround dentate nucleus neurons. Inhibitory synapses are fewer and enlarged in patients which could represent a compensatory mechanism. Mitochondrial DNA heteroplasmy demonstrated similarly high levels of mutated mitochondrial DNA in cell bodies and synapses. Conclusions This is the first study to use a validated quantitative immunofluorescence technique to determine complex I expression in neurons and presynaptic terminals, evaluating the distribution of respiratory chain deficiencies and assessing the degree of morphological abnormalities affecting synapses. Respiratory chain deficiencies detected in Purkinje cell bodies and their synapses and structural synaptic changes are likely to contribute to altered cerebellar circuitry and progression of ataxia. PMID:26337858

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

    Directory of Open Access Journals (Sweden)

    Laurent Ladepeche

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

  7. A new measure for the strength of electrical synapses

    OpenAIRE

    Haas, Julie S.

    2015-01-01

    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 c...

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Drying process strongly affects probiotics viability and functionalities.

    Science.gov (United States)

    Iaconelli, Cyril; Lemetais, Guillaume; Kechaou, Noura; Chain, Florian; Bermúdez-Humarán, Luis G; Langella, Philippe; Gervais, Patrick; Beney, Laurent

    2015-11-20

    Probiotic formulations are widely used and are proposed to have a variety of beneficial effects, depending on the probiotic strains present in the product. The impact of drying processes on the viability of probiotics is well documented. However, the impact of these processes on probiotics functionality remains unclear. In this work, we investigated variations in seven different bacterial markers after various desiccation processes. Markers were composed of four different viability evaluation (combining two growth abilities and two cytometric measurements) and in three in vitro functionalities: stimulation of IL-10 and IL-12 production by PBMCs (immunomodulation) and bacterial adhesion to hexadecane. We measured the impact of three drying processes (air-drying, freeze-drying and spray-drying), without the use of protective agents, on three types of probiotic bacteria: Bifidobacterium bifidum, Lactobacillus plantarum and Lactobacillus zeae. Our results show that the bacteria respond differently to the three different drying processes, in terms of viability and functionality. Drying methods produce important variations in bacterial immunomodulation and hydrophobicity, which are correlated. We also show that adherence can be stimulated (air-drying) or inhibited (spray-drying) by drying processes. Results of a multivariate analysis show no direct correlation between bacterial survival and functionality, but do show a correlation between probiotic responses to desiccation-rewetting and the process used to dry the bacteria. PMID:26325197

  10. Factors affecting functional prognosis of patients with hip fracture

    DEFF Research Database (Denmark)

    Kristensen, M T

    2011-01-01

    Having a hip fracture is considered one of the most fatal fractures for elderly people, resulting in impaired function, and increased morbidity and mortality. This challenges clinicians in identifying patients at risk of worse outcome, in order to optimise and intensify treatment in these patient...

  11. Does vitamin C deficiency affect cognitive development and function?

    DEFF Research Database (Denmark)

    Hansen, Stine Normann; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-01-01

    Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(-/-) mice...

  12. Indoor Particles Affect Vascular Function in the Aged

    DEFF Research Database (Denmark)

    Bräuner, Elvira Vaclavik; Forchhammer, Lykke; Møller, Peter;

    2008-01-01

    , P-selectin, plasma amyloid A, C-reactive protein, fibrinogen, interleukin-6, tumor necrosis factor alpha, protein oxidation measured as 2-aminoadipic semialdehyde in plasma, urinary 8-iso-prostaglandin F2 and blood pressure. Indoor air filtration significantly improved microvascular function by 8......Rationale. Exposure to particulate matter is associated with risk of cardiovascular events, possibly through endothelial dysfunction and indoor air may be most important. Objective. We investigated effects of controlled exposure to indoor air particles on microvascular function as the primary...... endpoint and biomarkers of inflammation and oxidative stress as secondary endpoints in a healthy elderly population. Methods. Twenty-one non-smoking couples participated in a randomized, double-blind, cross-over study with two consecutive 48-h exposures to either particle filtered or non-filtered air (2533...

  13. Kinesthesia Is Not Affected by Functional Ankle Instability Status.

    Science.gov (United States)

    Hubbard, Tricia J; Kaminski, Thomas W

    2002-12-01

    OBJECTIVE: To determine whether subjects with functional ankle instability suffered kinesthetic deficits in the injured ankle compared with the healthy ankle and to examine the effect of prophylactic ankle bracing on kinesthesia in uninjured and functionally unstable ankles. DESIGN AND SETTING: We tested subjects over 4 consecutive days in a climate-controlled athletic training/sports medicine laboratory setting. A single-group time-series design enabled all subjects to serve as their own controls. A different bracing condition was tested on each of those occasions. SUBJECTS: Sixteen subjects (8 men, 8 women; age = 21.6 +/- 1.7 years; mass = 73.5 +/- 15.0 kg; height = 172.9 +/- 8.8 cm) with unilateral functional ankle instability participated in this study. MEASUREMENTS: Kinesthetic threshold-to-detection of passive motion (TTDPM) measurements were obtained during passive inversion and eversion movements (0.5 degrees.s(-1)) under 4 different bracing or taping conditions (unbraced, Swede-O Ankle Lok, Aircast Air-Stirrup, and tape). RESULTS: We analyzed the data using a 3-factor analysis of variance with repeated measures on the ankle and motion factors. Threshold-to-detection of passive motion scores in the unbraced condition were significantly better than the TTDPM scores in any of the other 3 test conditions. No significant differences were seen in TTDPM scores between the 2 ankles under any of the 4 conditions. CONCLUSIONS: Threshold-to-detection of passive motion scores did not differ in uninjured ankles and those with functional instability; however, bracing with either the Ankle Lok or Air-Stirrup decreased the ability to detect passive motion when compared with the no-tape (unbraced) condition. Further research is needed to determine the exact contributions of taping and bracing on ankle joint kinesthesia. PMID:12937571

  14. Does vitamin C deficiency affect cognitive development and function?

    OpenAIRE

    Stine Normann Hansen; Pernille Tveden-Nyborg; Jens Lykkesfeldt

    2014-01-01

    Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(-/-) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have sev...

  15. Seasonal Affective Disorder

    Science.gov (United States)

    ... transporter protein leaves less serotonin available at the synapse because the function of the transporter is to recycle neurotransmitter back into the pre-synaptic neuron. People with SAD may overproduce the hormone melatonin. ...

  16. The effect of negative affect on cognition: Anxiety, not anger, impairs executive function.

    Science.gov (United States)

    Shields, Grant S; Moons, Wesley G; Tewell, Carl A; Yonelinas, Andrew P

    2016-09-01

    It is often assumed that negative affect impairs the executive functions that underlie our ability to control and focus our thoughts. However, support for this claim has been mixed. Recent work has suggested that different negative affective states like anxiety and anger may reflect physiologically separable states with distinct effects on cognition. However, the effects of these 2 affective states on executive function have never been assessed. As such, we induced anxiety or anger in participants and examined the effects on executive function. We found that anger did not impair executive function relative to a neutral mood, whereas anxiety did. In addition, self-reports of induced anxiety, but not anger, predicted impairments in executive function. These results support functional models of affect and cognition, and highlight the need to consider differences between anxiety and anger when investigating the influence of negative affect on fundamental cognitive processes such as memory and executive function. (PsycINFO Database Record PMID:27100367

  17. cAMP-Inhibits Cytoplasmic Phospholipase A2 and Protects Neurons against Amyloid-β-Induced Synapse Damage

    Directory of Open Access Journals (Sweden)

    Clive Bate

    2015-09-01

    Full Text Available A key event in Alzheimer’s disease (AD is the production of amyloid-β (Aβ peptides and the loss of synapses. In cultured neurons Aβ triggered synapse damage as measured by the loss of synaptic proteins. α-synuclein (αSN, aggregates of which accumulate in Parkinson’s disease, also caused synapse damage. Synapse damage was associated with activation of cytoplasmic phospholipase A2 (cPLA2, an enzyme that regulates synapse function and structure, and the production of prostaglandin (PG E2. In synaptosomes PGE2 increased concentrations of cyclic adenosine monophosphate (cAMP which suppressed the activation of cPLA2 demonstrating an inhibitory feedback system. Thus, Aβ/αSN-induced activated cPLA2 produces PGE2 which increases cAMP which in turn suppresses cPLA2 and, hence, its own production. Neurons pre-treated with pentoxifylline and caffeine (broad spectrum phosphodiesterase (PDE inhibitors or the PDE4 specific inhibitor rolipram significantly increased the Aβ/αSN-induced increase in cAMP and consequently protected neurons against synapse damage. The addition of cAMP analogues also inhibited cPLA2 and protected neurons against synapse damage. These results suggest that drugs that inhibit Aβ-induced activation of cPLA2 and cross the blood–brain barrier may reduce synapse damage in AD.

  18. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    OpenAIRE

    Mahboubeh Ghayour Najafabadi; Laya Rahbar Nikoukar; Amir Memari; Hamed Ekhtiari; Sara Beygi

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whe...

  19. Factors affecting the decline of ventilatory function in chronic bronchitis.

    OpenAIRE

    Campbell, A H; Barter, C. E.; O'Connell, J M; Huggins, R

    1985-01-01

    Ninety six middle aged male patients with chronic bronchitis with relatively well preserved ventilatory function who were resident in Queensland, New South Wales, or Victoria took part in a prospective study to determine the relationship of various factors to the rate of decline of the FEV1. Thirty of the subjects withdrew, leaving 66 to be followed for four to six years. The mean rate of decline of the FEV1 was 58.6 (SD 51.4) ml/year. The subjects' ventilatory responses to bronchodilator and...

  20. The Dendritic Cell Synapse: A Life Dedicated to T Cell Activation.

    Science.gov (United States)

    Benvenuti, Federica

    2016-01-01

    T-cell activation within immunological synapses is a complex process whereby different types of signals are transmitted from antigen-presenting cells to T cells. The molecular strategies developed by T cells to interpret and integrate these signals have been systematically dissected in recent years and are now in large part understood. On the other side of the immune synapse, dendritic cells (DCs) participate actively in synapse formation and maintenance by remodeling of membrane receptors and intracellular content. However, the details of such changes have been only partially characterized. The DCs actin cytoskeleton has been one of the first systems to be identified as playing an important role in T-cell priming and some of the underlying mechanisms have been elucidated. Similarly, the DCs microtubule cytoskeleton undergoes major spatial changes during synapse formation that favor polarization of the DCs subcellular space toward the interacting T cell. Recently, we have begun to investigate the trafficking machinery that controls polarized delivery of endosomal vesicles at the DC-T immune synapse with the aim of understanding the functional relevance of polarized secretion of soluble factors during T-cell priming. Here, we will review the current knowledge of events occurring in DCs during synapse formation and discuss the open questions that still remain unanswered. PMID:27014259

  1. Artificial Synapses: Organometal Halide Perovskite Artificial Synapses (Adv. Mater. 28/2016).

    Science.gov (United States)

    Xu, Wentao; Cho, Himchan; Kim, Young-Hoon; Kim, Young-Tae; Wolf, Christoph; Park, Chan-Gyung; Lee, Tae-Woo

    2016-07-01

    A synapse-emulating electronic device based on organometal halide perovskite thin films is described by T.-W. Lee and co-workers on page 5916. The device successfully emulates important characteristics of a biological synapse. This work extends the application of organometal halide perovskites to bioinspired electronic devices, and contributes to the development of neuromorphic electronics. PMID:27442971

  2. Affected functional networks associated with sentence production in classic galactosemia.

    Science.gov (United States)

    Timmers, Inge; van den Hurk, Job; Hofman, Paul Am; Zimmermann, Luc Ji; Uludağ, Kâmil; Jansma, Bernadette M; Rubio-Gozalbo, M Estela

    2015-08-01

    Patients with the inherited metabolic disorder classic galactosemia have language production impairments in several planning stages. Here, we assessed potential deviations in recruitment and connectivity across brain areas responsible for language production that may explain these deficits. We used functional magnetic resonance imaging (fMRI) to study neural activity and connectivity while participants carried out a language production task. This study included 13 adolescent patients and 13 age- and gender-matched healthy controls. Participants passively watched or actively described an animated visual scene using two conditions, varying in syntactic complexity (single words versus a sentence). Results showed that patients recruited additional and more extensive brain regions during sentence production. Both groups showed modulations with syntactic complexity in left inferior frontal gyrus (IFG), a region associated with syntactic planning, and in right insula. In addition, patients showed a modulation with syntax in left superior temporal gyrus (STG), whereas the controls did not. Further, patients showed increased activity in right STG and right supplementary motor area (SMA). The functional connectivity data showed similar patterns, with more extensive connectivity with frontal and motor regions, and restricted and weaker connectivity with superior temporal regions. Patients also showed higher baseline cerebral blood flow (CBF) in right IFG and trends towards higher CBF in bilateral STG, SMA and the insula. Taken together, the data demonstrate that language abnormalities in classic galactosemia are associated with specific changes within the language network. These changes point towards impairments related to both syntactic planning and speech motor planning in these patients. PMID:25979518

  3. Gene Risk Factors for Age-Related Brain Disorders May Affect Immune System Function

    Science.gov (United States)

    ... factors for age-related brain disorders may affect immune system function June 17, 2014 Scientists have discovered gene ... risk factors for age-related neurological disorders to immune system functions, such as inflammation, offers new insights into ...

  4. Osmotic stress affects functional properties of human melanoma cell lines

    CERN Document Server

    La Porta, Caterina A M; Pasini, Maria; Laurson, Lasse; Alava, Mikko J; Zapperi, Stefano; Amar, Martine Ben

    2015-01-01

    Understanding the role of microenvironment in cancer growth and metastasis is a key issue for cancer research. Here, we study the effect of osmotic pressure on the functional properties of primary and metastatic melanoma cell lines. In particular, we experimentally quantify individual cell motility and transmigration capability. We then perform a circular scratch assay to study how a cancer cell front invades an empty space. Our results show that primary melanoma cells are sensitive to a low osmotic pressure, while metastatic cells are less. To better understand the experimental results, we introduce and study a continuous model for the dynamics of a cell layer and a stochastic discrete model for cell proliferation and diffusion. The two models capture essential features of the experimental results and allow to make predictions for a wide range of experimentally measurable parameters.

  5. Does Vitamin C Deficiency Affect Cognitive Development and Function?

    Directory of Open Access Journals (Sweden)

    Stine Normann Hansen

    2014-09-01

    Full Text Available Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(−/− mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies.

  6. Consumption of bee pollen affects rat ovarian functions.

    Science.gov (United States)

    Kolesarova, A; Bakova, Z; Capcarova, M; Galik, B; Juracek, M; Simko, M; Toman, R; Sirotkin, A V

    2013-12-01

    The aim of this study was to examine possible effects of bee pollen added to the feed mixture (FM) on rat ovarian functions (secretion activity and apoptosis). We evaluated the bee pollen effect on the release of insulin-like growth factor I (IGF-I) and steroid hormones (progesterone and estradiol), as well as on the expression of markers of apoptosis (Bcl-2, Bax and caspase-3) in rat ovarian fragments. Female rats (n = 15) were fed during 90 days by FM without or with rape seed bee pollen in dose either 3 kg/1000 kg FM or 5 kg/1000 kg FM. Fragments of ovaries isolated from rats of each group (totally 72 pieces) were incubated for 24 h. Hormonal secretion into the culture medium was detected by RIA. The markers of apoptosis were evaluated by Western blotting. It was observed that IGF-I release by rat ovarian fragments was significantly (p < 0.05) decreased; on the other hand, progesterone and estradiol secretion was increased after bee pollen treatment at dose 5 kg/1000 kg FM but not at 3 kg/1000 FM. Accumulation of Bcl-2 was increased by bee pollen added at 3 kg/1000 kg FM, but not at higher dose. Accumulation of Bax was increased in ovaries of rats fed by bee pollen at doses either 3 or 5 kg/1000 kg FM, whilst accumulation of caspase-3 increased after feeding with bee pollen at dose 5 kg/1000 kg FM, but not at 3 kg/1000 kg FM. Our results contribute to new insights regarding the effect of bee pollen on both secretion activity (release of growth factor IGF-I and steroid hormones progesterone and estradiol) and apoptosis (anti- and pro-apoptotic markers Bcl-2, Bax and caspase-3). Bee pollen is shown to be a potent regulator of rat ovarian functions. PMID:23137268

  7. DOES MEAN PERFUSION PRESSURE DURING CARDIOPULMONARY BYPASS AFFECT RENAL FUNCTION?

    Directory of Open Access Journals (Sweden)

    Ramesh

    2015-10-01

    Full Text Available BACKGROUND: After cardiac surgery acute kidney injury (AKI is a common and serious condition carrying significant costs and is independently associated with increased morbidity and mortality. During cardiopulmonary bypass (CPB surgery, modifiable factors may contri bute to post - operative AKI. Their prevention might be a potential target for nephroprotection and any other morbidity after cardiac surgery. METHODS AND MATERIAL : The objective of the present study was to identify and determine whether intraoperative hypot ension or any other cofactor are independent risk factors for postoperative AKI defined by the RIFLE (renal Risk, Injury, Failure, Loss of renal function and End - stage renal disease. On basis of this patients were divided into two groups according to rise in serum creatinine >0.3 mg/dl till 72 hrs postoperatively. Group B patients have developed AKI (n=34 and the remaining patients were in Group A. RESULT : In our study we have found that mean arterial pressure during CPB were less in group B patients compare to group A patients which was statistically significant (p<0.001. And in this group ICU stay and mortality rate were also high compare to group A pati ent who had not developed AKI. CONCLUSION: Lower MAP during CPB is associated with development of postoperative renal derangement, leads to increase ICU stay and mortality. Larger studies are required to further support the evidence

  8. Neurology of Affective Prosody and Its Functional-Anatomic Organization in Right Hemisphere

    Science.gov (United States)

    Ross, Elliott D.; Monnot, Marilee

    2008-01-01

    Unlike the aphasic syndromes, the organization of affective prosody in brain has remained controversial because affective-prosodic deficits may occur after left or right brain damage. However, different patterns of deficits are observed following left and right brain damage that suggest affective prosody is a dominant and lateralized function of…

  9. Modeling synaptic transmission of the tripartite synapse

    Science.gov (United States)

    Nadkarni, Suhita; Jung, Peter

    2007-03-01

    The tripartite synapse denotes the junction of a pre- and postsynaptic neuron modulated by a synaptic astrocyte. Enhanced transmission probability and frequency of the postsynaptic current-events are among the significant effects of the astrocyte on the synapse as experimentally characterized by several groups. In this paper we provide a mathematical framework for the relevant synaptic interactions between neurons and astrocytes that can account quantitatively for both the astrocytic effects on the synaptic transmission and the spontaneous postsynaptic events. Inferred from experiments, the model assumes that glutamate released by the astrocytes in response to synaptic activity regulates store-operated calcium in the presynaptic terminal. This source of calcium is distinct from voltage-gated calcium influx and accounts for the long timescale of facilitation at the synapse seen in correlation with calcium activity in the astrocytes. Our model predicts the inter-event interval distribution of spontaneous current activity mediated by a synaptic astrocyte and provides an additional insight into a novel mechanism for plasticity in which a low fidelity synapse gets transformed into a high fidelity synapse via astrocytic coupling.

  10. Endosome-mediated endocytic mechanism replenishes the majority of synaptic vesicles at mature CNS synapses in an activity-dependent manner.

    Science.gov (United States)

    Park, Joohyun; Cho, Oh Yeon; Kim, Jung Ah; Chang, Sunghoe

    2016-01-01

    Whether synaptic vesicles (SVs) are recovered via endosome-mediated pathways is a matter of debate; however, recent evidence suggests that clathrin-independent bulk endocytosis (CIE) via endosomes is functional and preferentially replenishes SV pools during strong stimulation. Here, using brefeldin-A (BFA) to block CIE, we found that CIE retrieved a minority of SVs at developing CNS synapses during strong stimulation, but its contribution increased up to 61% at mature CNS synapses. Contrary to previous views, BFA not only blocked SV formation from the endosome but also blocked the endosome formation at the plasma membrane. Adaptor protein 1 and 3 (AP-1/3) have key roles in SV reformation from endosomes during CIE, and AP-1 also affects bulk endosome formation from the plasma membrane. Finally, temporary blocking of chronic or acute neuronal activity with tetrodotoxin in mature neurons redirected most SV retrieval to endosome-independent pathways. These results show that during high neuronal activity, CIE becomes the major endocytic pathway at mature CNS synapses. Moreover, mature neurons use clathrin-mediated endocytosis and the CIE pathway to different extents depending on their previous activity; this may result in activity-dependent alterations of the SV composition which ultimately influence transmitter release and contribute to synaptic plasticity. PMID:27534442

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

    OpenAIRE

    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 the matrix is stored on-chip as differential voltages on capacitors. In principal any ANN configuration can be made using these chips. A neuron array of 4 neurons and a 4 × 4 matrix-vector multiplie...

  12. Synapse: a Scalable Protocol for Interconnecting Heterogeneous Overlay Networks

    OpenAIRE

    Liquori, Luigi; Tedeschi, Cédric; Vanni, Laurent; Ciancaglini, Vincenzo; Bongiovanni, Francesco; Marinkovic, Bojan

    2010-01-01

    International audience This paper presents Synapse, a scalable protocol for information retrieval over the inter-connection of heterogeneous overlay networks. Applications on top of Synapse see those intra-overlay networks as a unique inter-overlay network. Scalability in Synapse is achieved via co-located nodes, i.e. nodes that are part of multiple overlay networks at the same time. Co-located nodes, playing the role of neural synapses and connected to several overlay networks, give a lar...

  13. Flotillin-1 Promotes Formation of Glutamatergic Synapses in Hippocampal Neurons

    OpenAIRE

    Swanwick, Catherine Croft; Shapiro, Marietta E.; Vicini, Stefano; Wenthold, Robert J.

    2010-01-01

    Synapse malformation underlies numerous neurodevelopmental illnesses, including autism spectrum disorders. Here we identify the lipid raft protein flotillin-1 as a promoter of glutamatergic synapse formation. We cultured neurons from the hippocampus, a brain region important for learning and memory, and examined them at two weeks in vitro, a time period rich with synapse formation. Double-label immunocytochemistry of native flot-1 with glutamatergic and GABAergic synapse markers showed that f...

  14. Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking

    Science.gov (United States)

    Voelzmann, Andre; Okenve-Ramos, Pilar; Qu, Yue; Chojnowska-Monga, Monika; del Caño-Espinel, Manuela; Prokop, Andreas; Sanchez-Soriano, Natalia

    2016-01-01

    The mechanisms regulating synapse numbers during development and ageing are essential for normal brain function and closely linked to brain disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in regulating synapse numbers, thus unravelling an important cellular requirement of normal Tau. In this context, we find that Tau displays a strong functional overlap with microtubule-binding spectraplakins, establishing new links between two different neurodegenerative factors. Tau and the spectraplakin Short Stop act upstream of a three-step regulatory cascade ensuring adequate delivery of synaptic proteins. This cascade involves microtubule stability as the initial trigger, JNK signalling as the central mediator, and kinesin-3 mediated axonal transport as the key effector. This cascade acts during development (synapse formation) and ageing (synapse maintenance) alike. Therefore, our findings suggest novel explanations for intellectual disability in Tau deficient individuals, as well as early synapse loss in dementias including Alzheimer’s disease. DOI: http://dx.doi.org/10.7554/eLife.14694.001 PMID:27501441

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

    Science.gov (United States)

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

    2013-04-01

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

  16. Localization of mineralocorticoid receptors at mammalian synapses.

    Directory of Open Access Journals (Sweden)

    Eric M Prager

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

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

    Science.gov (United States)

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

    2011-01-01

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

  18. Both pre- and postsynaptic activity of Nsf prevents degeneration of hair-cell synapses.

    Directory of Open Access Journals (Sweden)

    Weike Mo

    Full Text Available Vesicle fusion contributes to the maintenance of synapses in the nervous system by mediating synaptic transmission, release of neurotrophic factors, and trafficking of membrane receptors. N-ethylmaleimide-sensitive factor (NSF is indispensible for dissociation of the SNARE-complex following vesicle fusion. Although NSF function has been characterized extensively in vitro, the in vivo role of NSF in vertebrate synaptogenesis is relatively unexplored. Zebrafish possess two nsf genes, nsf and nsfb. Here, we examine the function of either Nsf or Nsfb in the pre- and postsynaptic cells of the zebrafish lateral line organ and demonstrate that Nsf, but not Nsfb, is required for maintenance of afferent synapses in hair cells. In addition to peripheral defects in nsf mutants, neurodegeneration of glutamatergic synapses in the central nervous system also occurs in the absence of Nsf function. Expression of an nsf transgene in a null background indicates that stabilization of synapses requires Nsf function in both hair cells and afferent neurons. To identify potential targets of Nsf-mediated fusion, we examined the expression of genes implicated in stabilizing synapses and found that transcripts for multiple genes including brain-derived neurotrophic factor (bdnf were significantly reduced in nsf mutants. With regard to trafficking of BDNF, we observed a striking accumulation of BDNF in the neurites of nsf mutant afferent neurons. In addition, injection of recombinant BDNF protein partially rescued the degeneration of afferent synapses in nsf mutants. These results establish a role for Nsf in the maintenance of synaptic contacts between hair cells and afferent neurons, mediated in part via the secretion of trophic signaling factors.

  19. Quantitative study of the development of neurons and synapses in rats reared in the dark during early postnatal life. 1. Superior colliculus.

    OpenAIRE

    Fukui, Y; Bedi, K S

    1991-01-01

    Rearing animals in dark conditions during early postnatal life has been shown to affect both the morphology and the normal functioning of the visual system. We have investigated the effects on the synapse-to-neuron ratios in the superior colliculi of rearing male rats in the dark from birth until 30 days of age, followed in some cases by a 35 day period of rehabilitation in control lighting conditions. Control lighting conditions consisted of a room on a 12 hour light/12 hour dark cycle. Syna...

  20. Positive Affect in the Midst of Distress: Implications for Role Functioning

    OpenAIRE

    Moskowitz, Judith Tedlie; Shmueli-Blumberg, Dikla; Acree, Michael; Folkman, Susan

    2012-01-01

    Stress has been shown to deplete the self-regulation resources hypothesized to facilitate effective role functioning. However, recent research suggests that positive affect may help to replenish these vital self-regulation resources. Based on revised Stress and Coping theory and the Broaden-and-Build theory of positive emotion, three studies provide evidence of the potential adaptive function of positive affect in the performance of roles for participants experiencing stress. Participants wer...

  1. Fragile X Mental Retardation Protein is Required for Synapse Elimination by the Activity-Dependent Transcription Factor MEF2

    OpenAIRE

    Pfeiffer, Brad E.; Zang, Tong; Wilkerson, Julia R.; Taniguchi, Makoto; Maksimova, Marina A.; Smith, Laura N.; Cowan, Christopher W.; Huber, Kimberly M.

    2010-01-01

    Fragile X Syndrome (FXS), the most common genetic form of mental retardation and autism, is caused by loss of function mutations in an RNA binding protein, Fragile X Mental Retardation Protein (FMRP). Patients’ neurons, as well as those of the mouse model, Fmr1 knockout (KO), are characterized by an excess of dendritic spines, suggesting a deficit in excitatory synapse elimination. In response to neuronal activity, myocyte enhancing factor 2 (MEF2) transcription factors induce robust synapse ...

  2. Synaptic vesicle cycling is not impaired in a glutamatergic and a cholinergic synapse that exhibit deficits in acidification and filling

    OpenAIRE

    Bento João Abreu; Luciana Ferreira Leite; Débora Lopes Oliveira; Ernani Amaral

    2012-01-01

    The purpose of the present work was to investigate synaptic vesicle trafficking when vesicles exhibit alterations in filling and acidification in two different synapses: a cholinergic frog neuromuscular junction and a glutamatergic ribbon-type nerve terminal in the retina. These synapses display remarkable structural and functional differences, and the mechanisms regulating synaptic vesicle cycling might also differ between them. The lipophilic styryl dye FM1-43 was used to monitor vesicle tr...

  3. Synapse-specific inhibitory control of hippocampal feedback inhibitory circuit

    Directory of Open Access Journals (Sweden)

    Simon eChamberland

    2010-10-01

    Full Text Available Local circuit and long-range GABAergic projections provide powerful inhibitory control over the operation of hippocampal inhibitory circuits, yet little is known about the input- and target-specific organization of interacting inhibitory networks in relation to their specific functions. Using a combination of two-photon laser scanning photostimulation and whole-cell patch clamp recordings in mice hippocampal slices, we examined the properties of transmission at GABAergic synapses formed onto hippocampal CA1 stratum oriens – lacunosum moleculare (O–LM interneurons by two major inhibitory inputs: local projection originating from stratum radiatum interneurons and septohippocampal GABAergic terminals. Optical mapping of local inhibitory inputs to O–LM interneurons revealed that vasoactive intestinal polypeptide- and calretinine-positive neurons, with anatomical properties typical of type III interneuron-specific interneurons, provided the major local source of inhibition to O–LM cells. Inhibitory postsynaptic currents evoked by minimal stimulation of this input exhibited small amplitude and significant paired-pulse and multiple-pulse depression during repetitive activity. Moreover, these synapses failed to show any form of long-term synaptic plasticity. In contrast, synapses formed by septohippocampal projection produced higher amplitude and persistent inhibition and exhibited long-term potentiation induced by theta-like activity. These results indicate the input and target-specific segregation in inhibitory control, exerted by two types of GABAergic projections and responsible for distinct dynamics of inhibition in O–LM interneurons. The two inputs are therefore likely to support the differential activity- and brain state-dependent recruitment of hippocampal feedback inhibitory circuits in vivo, crucial for dendritic disinhibition and computations in CA1 pyramidal cells.

  4. Changes in rat hippocampal CA1 synapses following imipramine treatment

    DEFF Research Database (Denmark)

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

    2008-01-01

    synapses) in subregions of the hippocampus by quantifying number of neurons and synapses. Adult male Sprague-Dawley rats were injected with imipramine or saline (i.p.) daily for 14 days. Unbiased stereological methods were used to quantify the number of neurons and synapses. No differences in the volume...... and number of neurons of hippocampal subregions following imipramine treatment were found. However, the number and percentage of CA1 asymmetric spine synapses increased significantly and, conversely, the percentage of asymmetric shaft synapses significantly decreased in the imipramine treated group....... Our results indicate that administration of imipramine for 14 days in normal rats could significantly increase the excitatory spine synapses, and change the relative distribution of spine and shaft synapses. We speculate that the present findings may be explained by the establishment of new synaptic...

  5. Mild Maternal Iron Deficiency Anemia Induces Hearing Impairment Associated with Reduction of Ribbon Synapse Density and Dysregulation of VGLUT3, Myosin VIIa, and Prestin Expression in Young Guinea Pigs.

    Science.gov (United States)

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Zhang, Wenyue; Yang, Jun

    2016-05-01

    Mild maternal iron deficiency anemia (IDA) adversely affects the development of cochlear hair cells of the young offspring, but the mechanisms underlying the association are incompletely understood. The aim of this study was to evaluate whether mild maternal IDA in guinea pigs could interrupt inner hair cell (IHC) ribbon synapse density and outer hair cell motility of the offspring. Here, we established a dietary restriction model that allows us to study quantitative changes in the number of IHC ribbon synapses and hearing impairment in response to mild maternal IDA in young guinea pig. The offspring were weaned on postnatal day (PND) 9 and then were given the iron-sufficient diet. On PND 24, pups were examined the hearing function by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements. Then, the cochleae were harvested for assessment of the number of IHC ribbon synapses by immunofluorescence, the morphology of cochlear hair cells, and spiral ganglion cells (SGCs) by scanning electron microscope and hematoxylin-eosin staining, the location, and expression of vesicular glutamate transporter (VGLUT) 3, myosin VIIa, and prestin by immunofluorescence and blotting. Here, we show that mild maternal IDA in guinea pigs induced elevated ABR threshold shifts, declined DPOAE level shifts, and reduced the number of ribbon synapses, impaired the morphology of cochlear hair cells and SGCs in offsprings. In addition, downregulation of VGLUT3 and myosin VIIa, and upregulation of prestin were observed in the cochlea of offsprings from mild maternal IDA in guinea pigs. These data indicate that mild maternal IDA in guinea pigs induced hearing impairment in offsprings, and this deficit may be attributed to the reduction of ribbon synapse density and dysregulation of VGLUT3, myosin VIIa, and prestin. PMID:26913517

  6. Power-law forgetting in synapses with metaplasticity

    International Nuclear Information System (INIS)

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

  7. Short-Term Plasticity and Long-Term Potentiation in Magnetic Tunnel Junctions: Towards Volatile Synapses

    Science.gov (United States)

    Sengupta, Abhronil; Roy, Kaushik

    2016-02-01

    Synaptic memory is considered to be the main element responsible for learning and cognition in humans. Although traditionally nonvolatile long-term plasticity changes are implemented in nanoelectronic synapses for neuromorphic applications, recent studies in neuroscience reveal that biological synapses undergo metastable volatile strengthening followed by a long-term strengthening provided that the frequency of the input stimulus is sufficiently high. Such "memory strengthening" and "memory decay" functionalities can potentially lead to adaptive neuromorphic architectures. In this paper, we demonstrate the close resemblance of the magnetization dynamics of a magnetic tunnel junction (MTJ) to short-term plasticity and long-term potentiation observed in biological synapses. We illustrate that, in addition to the magnitude and duration of the input stimulus, the frequency of the stimulus plays a critical role in determining long-term potentiation of the MTJ. Such MTJ synaptic memory arrays can be utilized to create compact, ultrafast, and low-power intelligent neural systems.

  8. Nanogranular SiO2 proton gated silicon layer transistor mimicking biological synapses

    Science.gov (United States)

    Liu, M. J.; Huang, G. S.; Feng, P.; Guo, Q. L.; Shao, F.; Tian, Z. A.; Li, G. J.; Wan, Q.; Mei, Y. F.

    2016-06-01

    Silicon on insulator (SOI)-based transistors gated by nanogranular SiO2 proton conducting electrolytes were fabricated to mimic synapse behaviors. This SOI-based device has both top proton gate and bottom buried oxide gate. Electrical transfer properties of top proton gate show hysteresis curves different from those of bottom gate, and therefore, excitatory post-synaptic current and paired pulse facilitation (PPF) behavior of biological synapses are mimicked. Moreover, we noticed that PPF index can be effectively tuned by the spike interval applied on the top proton gate. Synaptic behaviors and functions, like short-term memory, and its properties are also experimentally demonstrated in our device. Such SOI-based electronic synapses are promising for building neuromorphic systems.

  9. Effects of the Geometry of the Immunological Synapse on the Delivery of Effector Molecules

    OpenAIRE

    Coombs, Daniel; Goldstein, Byron

    2004-01-01

    Recent experiments focusing on the function of the immunological synapse formed between a T cell and an antigen-presenting cell raise many questions about its purpose. We examine the proposal that the close apposition of the cell membranes in the central region of the synapse acts to focus T-cell secretions on the target cell, thus reducing the effect on nearby cells. We show that the efficiency of targeted T-cell responses to closely apposed cells is only weakly dependent on the distance bet...

  10. The role of affect in attentional functioning for younger and older adults

    Directory of Open Access Journals (Sweden)

    Soo RimNoh

    2012-08-01

    Full Text Available Although previous research has shown that positive affect (PA and negative affect (NA modulate attentional functioning in distinct ways, few studies have considered whether the links between affect and attentional functioning may vary as a function of age. Using the Attention Network Test (Fan, McCandliss, Sommer, Raz, & Posner, 2002, we tested whether participants’ current state of PA and NA influenced distinct attentional functions (i.e., alerting, orienting, and executive attention and how the relationships between affective states and attentional functioning differ in younger (18-25 yrs and older (60-85 yrs age groups. The results revealed that higher PA was associated with lower alerting efficiency; however, this pattern did not vary by age group. While there were age differences in alerting efficiency, these age differences were mediated by PA, indicating that the higher state PA found in older adults may contribute to age differences in alerting. Furthermore, age group moderated the relationship between PA and orienting as well as NA and orienting. That is, higher levels of PA and lower levels of NA were associated with enhanced orienting efficiency in older adults. Neither PA nor NA had any influence on executive attention. The current results suggest that positive and negative affect may influence attentional functioning in distinct ways, but that these patterns may depend on age groups.

  11. Factors Affecting Consumers' Willingness to Pay for Functional Foods in Vietnam

    OpenAIRE

    Tra, Pham Van; Moritaka, Masahiro; Fukuda, Susumu

    2011-01-01

    Ordered probit model is used to analyze 11 independent factors, socio?demographic characteristics, family health condition, experience of functional food consumption and mass media impact those are presumed to affect the willingness to pay for functional food by Vietnamese consumers. Contingent valuation using the payment card method was used to elicit the premium that respondents are willing to pay for 2 popular functional food items which is selected from the pilot survey, Diabetes milk?fun...

  12. 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.

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

    OpenAIRE

    Belmeguenai, A.; Botta, Paolo; Weber, John; Carta, Mario; De Ruiter, Martijn; De Zeeuw, Chris; Valenzuela, Fernando; Hansel, Christian

    2008-01-01

    textabstractAcute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor learning. It has previously been shown that ethanol modulates inhibitory transmission in the cerebellum and affects synaptic transmission and plasticity at excitatory climbing fiber (CF) to Purkinje cell synapses. However, it has not been examined thus far how acute ethanol application affects...

  14. Structure, Distribution, and Function of Neuronal/Synaptic Spinules and Related Invaginating Projections.

    Science.gov (United States)

    Petralia, Ronald S; Wang, Ya-Xian; Mattson, Mark P; Yao, Pamela J

    2015-09-01

    Neurons and especially their synapses often project long thin processes that can invaginate neighboring neuronal or glial cells. These "invaginating projections" can occur in almost any combination of postsynaptic, presynaptic, and glial processes. Invaginating projections provide a precise mechanism for one neuron to communicate or exchange material exclusively at a highly localized site on another neuron, e.g., to regulate synaptic plasticity. The best-known types are postsynaptic projections called "spinules" that invaginate into presynaptic terminals. Spinules seem to be most prevalent at large very active synapses. Here, we present a comprehensive review of all kinds of invaginating projections associated with both neurons in general and more specifically with synapses; we describe them in all animals including simple, basal metazoans. These structures may have evolved into more elaborate structures in some higher animal groups exhibiting greater synaptic plasticity. In addition to classic spinules and filopodial invaginations, we describe a variety of lesser-known structures such as amphid microvilli, spinules in giant mossy terminals and en marron/brush synapses, the highly specialized fish retinal spinules, the trophospongium, capitate projections, and fly gnarls, as well as examples in which the entire presynaptic or postsynaptic process is invaginated. These various invaginating projections have evolved to modify the function of a particular synapse, or to channel an effect to one specific synapse or neuron, without affecting those nearby. We discuss how they function in membrane recycling, nourishment, and cell signaling and explore how they might change in aging and disease. PMID:26007200

  15. Cooperative synapse formation in the neocortex

    OpenAIRE

    Stepanyants Armen; Fares Tarec

    2009-01-01

    Neuron morphology plays an important role in defining synaptic connectivity. Clearly, only pairs of neurons with closely positioned axonal and dendritic branches can be synaptically coupled. For excitatory neurons in the cerebral cortex, such axo-dendritic oppositions, termed potential synapses, must be bridged by dendritic spines to form synaptic connections. To explore the rules by which synaptic connections are formed within the constraints imposed by neuron morphology, we compared the dis...

  16. 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.

  17. Comparative Anatomy of Phagocytic and immunological Synapses

    OpenAIRE

    Niedergang, Florence; Di Bartolo, Vincenzo; Alcover, Andrés

    2016-01-01

    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 ...

  18. Plant Species and Functional Group Combinations Affect Green Roof Ecosystem Functions

    OpenAIRE

    Lundholm, Jeremy; MacIvor, J. Scott; MacDougall, Zachary; Ranalli, Melissa

    2010-01-01

    Background Green roofs perform ecosystem services such as summer roof temperature reduction and stormwater capture that directly contribute to lower building energy use and potential economic savings. These services are in turn related to ecosystem functions performed by the vegetation layer such as radiation reflection and transpiration, but little work has examined the role of plant species composition and diversity in improving these functions. Methodology/Principal Findings We used a repl...

  19. Plant Species and Functional Group Combinations Affect Green Roof Ecosystem Functions

    OpenAIRE

    Jeremy Lundholm; J Scott Macivor; Zachary Macdougall; Melissa Ranalli

    2010-01-01

    BACKGROUND: Green roofs perform ecosystem services such as summer roof temperature reduction and stormwater capture that directly contribute to lower building energy use and potential economic savings. These services are in turn related to ecosystem functions performed by the vegetation layer such as radiation reflection and transpiration, but little work has examined the role of plant species composition and diversity in improving these functions. METHODOLOGY/PRINCIPAL FINDINGS: We used a re...

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

    Science.gov (United States)

    West, Ewan; Osborne, Craig; Nolan, William; Bate, Clive

    2015-01-01

    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. PMID:26043272

  1. 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.

  2. Sex-specific pruning of neuronal synapses in Caenorhabditis elegans.

    Science.gov (United States)

    Oren-Suissa, Meital; Bayer, Emily A; Hobert, Oliver

    2016-05-12

    Whether and how neurons that are present in both sexes of the same species can differentiate in a sexually dimorphic manner is not well understood. A comparison of the connectomes of the Caenorhabditis elegans hermaphrodite and male nervous systems reveals the existence of sexually dimorphic synaptic connections between neurons present in both sexes. Here we demonstrate sex-specific functions of these sex-shared neurons and show that many neurons initially form synapses in a hybrid manner in both the male and hermaphrodite pattern before sexual maturation. Sex-specific synapse pruning then results in the sex-specific maintenance of subsets of these connections. Reversal of the sexual identity of either the pre- or postsynaptic neuron alone transforms the patterns of synaptic connectivity to that of the opposite sex. A dimorphically expressed and phylogenetically conserved transcription factor is both necessary and sufficient to determine sex-specific connectivity patterns. Our studies reveal new insights into sex-specific circuit development. PMID:27144354

  3. Impairment of executive function and attention predicts onset of affective disorder in healthy high-risk twins

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla W; Kessing, Lars Vedel

    2013-01-01

    To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk.......To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk....

  4. Plant Species and Functional Group Combinations Affect Green Roof Ecosystem Functions

    Science.gov (United States)

    Lundholm, Jeremy; MacIvor, J. Scott; MacDougall, Zachary; Ranalli, Melissa

    2010-01-01

    Background Green roofs perform ecosystem services such as summer roof temperature reduction and stormwater capture that directly contribute to lower building energy use and potential economic savings. These services are in turn related to ecosystem functions performed by the vegetation layer such as radiation reflection and transpiration, but little work has examined the role of plant species composition and diversity in improving these functions. Methodology/Principal Findings We used a replicated modular extensive (shallow growing- medium) green roof system planted with monocultures or mixtures containing one, three or five life-forms, to quantify two ecosystem services: summer roof cooling and water capture. We also measured the related ecosystem properties/processes of albedo, evapotranspiration, and the mean and temporal variability of aboveground biomass over four months. Mixtures containing three or five life-form groups, simultaneously optimized several green roof ecosystem functions, outperforming monocultures and single life-form groups, but there was much variation in performance depending on which life-forms were present in the three life-form mixtures. Some mixtures outperformed the best monocultures for water capture, evapotranspiration, and an index combining both water capture and temperature reductions. Combinations of tall forbs, grasses and succulents simultaneously optimized a range of ecosystem performance measures, thus the main benefit of including all three groups was not to maximize any single process but to perform a variety of functions well. Conclusions/Significance Ecosystem services from green roofs can be improved by planting certain life-form groups in combination, directly contributing to climate change mitigation and adaptation strategies. The strong performance by certain mixtures of life-forms, especially tall forbs, grasses and succulents, warrants further investigation into niche complementarity or facilitation as mechanisms

  5. Plant species and functional group combinations affect green roof ecosystem functions.

    Directory of Open Access Journals (Sweden)

    Jeremy Lundholm

    Full Text Available BACKGROUND: Green roofs perform ecosystem services such as summer roof temperature reduction and stormwater capture that directly contribute to lower building energy use and potential economic savings. These services are in turn related to ecosystem functions performed by the vegetation layer such as radiation reflection and transpiration, but little work has examined the role of plant species composition and diversity in improving these functions. METHODOLOGY/PRINCIPAL FINDINGS: We used a replicated modular extensive (shallow growing- medium green roof system planted with monocultures or mixtures containing one, three or five life-forms, to quantify two ecosystem services: summer roof cooling and water capture. We also measured the related ecosystem properties/processes of albedo, evapotranspiration, and the mean and temporal variability of aboveground biomass over four months. Mixtures containing three or five life-form groups, simultaneously optimized several green roof ecosystem functions, outperforming monocultures and single life-form groups, but there was much variation in performance depending on which life-forms were present in the three life-form mixtures. Some mixtures outperformed the best monocultures for water capture, evapotranspiration, and an index combining both water capture and temperature reductions. Combinations of tall forbs, grasses and succulents simultaneously optimized a range of ecosystem performance measures, thus the main benefit of including all three groups was not to maximize any single process but to perform a variety of functions well. CONCLUSIONS/SIGNIFICANCE: Ecosystem services from green roofs can be improved by planting certain life-form groups in combination, directly contributing to climate change mitigation and adaptation strategies. The strong performance by certain mixtures of life-forms, especially tall forbs, grasses and succulents, warrants further investigation into niche complementarity or

  6. Tree functional diversity affects litter decomposition and arthropod community composition in a tropical forest

    OpenAIRE

    Laird-Hopkins, Benita

    2016-01-01

    The crucial role of tropical forests in the global carbon balance is determined by tree growth and the rapid turnover of organic material. Land-use change and forest recovery from disturbance alters species- and functional diversity, which in turn can modify decomposition processes and affect ecosystem carbon and nutrient cycling. Despite numerous studies on tropical litter decomposition, the links among plant- and invertebrate diversity and microbial function are far from clear. I investigat...

  7. Aging Impairs the Late Phase of Long-Term Potentiation at the Medial Perforant Path-CA3 Synapse in Awake Rats

    OpenAIRE

    Dieguez, Dario; Barea-Rodriguez, Edwin J.

    2004-01-01

    The effects of aging on long-term potentiation (LTP) in the dentate gyrus (DG) and CA1 are well documented, but LTP at the medial perforant path (MPP)-CA3 synapse of aged animals has remained unexplored. Because the MPP-DG and Schaffer-collateral-CA1 synapses account for only about 20% of total hippocampal synapses, global understanding of how aging affects hippocampal plasticity has remained limited. Much is known about LTP induction in the hippocampal formation, whereas the mechanisms that ...

  8. 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.

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

    Science.gov (United States)

    Dong, Yan

    2016-05-01

    Exposure to cocaine, and likely other drugs of abuse, generates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-silent glutamatergic synapses in the nucleus accumbens. These immature synaptic contacts evolve after drug withdrawal to redefine the neurocircuital properties. These results raise at least three critical questions: (1) what are the molecular and cellular mechanisms that mediate drug-induced generation of silent synapses; (2) how are neurocircuits remodeled upon generation and evolution of drug-generated silent synapses; and (3) what behavioral consequences are produced by silent synapse-based circuitry remodeling? This short review analyzes related experimental results, and extends them to some speculations. PMID:26721952

  10. Handgrip Strength, Positive Affect, and Perceived Health Are Prospectively Associated with Fewer Functional Limitations among Centenarians

    Science.gov (United States)

    Franke, Warren D.; Margrett, Jennifer A.; Heinz, Melinda; Martin, Peter

    2012-01-01

    This study assessed the association between perceived health, fatigue, positive and negative affect, handgrip strength, objectively measured physical activity, body mass index, and self-reported functional limitations, assessed 6 months later, among 11 centenarians (age = 102 plus or minus 1). Activities of daily living, assessed 6 months prior to…

  11. Metacognitive Awareness of Facial Affect in Higher-Functioning Children and Adolescents with Autism Spectrum Disorder

    Science.gov (United States)

    McMahon, Camilla M.; Henderson, Heather A.; Newell, Lisa; Jaime, Mark; Mundy, Peter

    2016-01-01

    Higher-functioning participants with and without autism spectrum disorder (ASD) viewed a series of face stimuli, made decisions regarding the affect of each face, and indicated their confidence in each decision. Confidence significantly predicted accuracy across all participants, but this relation was stronger for participants with typical…

  12. Full-thickness cartilage lesion do not affect knee function in patients with ACL injury

    OpenAIRE

    2011-01-01

    Full-thickness cartilage lesion do not affect knee function in patients with ACL injury Abstract There is debate in the literature regarding the impact of full-thickness cartilage lesion on knee function in patients with ACL injury. The hypothesis of this study is that a full-thickness cartilage lesion at the time of ACL reconstruction does not influence knee function as measured by the Knee injury and Osteoarthritis Outcome Score (KOOS) in patients with ACL injury. Of the 4,849 prim...

  13. 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.

  14. 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...

  15. Spin switches for compact implementation of neuron and synapse

    International Nuclear Information System (INIS)

    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

  16. Circadian rhythmicity of synapses in mouse somatosensory cortex.

    Science.gov (United States)

    Jasinska, Malgorzata; Grzegorczyk, Anna; Woznicka, Olga; Jasek, Ewa; Kossut, Malgorzata; Barbacka-Surowiak, Grazyna; Litwin, Jan A; Pyza, Elzbieta

    2015-10-01

    The circadian rhythmicity displayed by motor behavior of mice: activity at night and rest during the day; and the associated changes in the sensory input are reflected by cyclic synaptic plasticity in the whisker representations located in the somatosensory (barrel) cortex. It was not clear whether diurnal rhythmic changes in synapse density previously observed in the barrel cortex resulted from changes in the activity of the animals, from daily light/dark (LD) rhythm or are driven by an endogenous clock. These changes were investigated in the barrel cortex of C57BL/6 mouse strain kept under LD 12 : 12 h conditions and in constant darkness (DD). Stereological analysis of serial electron microscopic sections was used to assess numerical density of synapses. In mice kept under LD conditions, the total density of synapses and the density of excitatory synapses located on dendritic spines was higher during the light period (rest phase). In contrast, the density of inhibitory synapses located on dendritic spines increased during the dark period (activity phase). Under DD conditions, the upregulation of the inhibitory synapses during the activity phase was retained, but the cyclic changes in the density of excitatory synapses were not observed. The results show that the circadian plasticity concerns only synapses located on spines (and not those on dendritic shafts), and that excitatory and inhibitory synapses are differently regulated during the 24 h cycle: the excitatory synapses are influenced by light, whilst the inhibitory synapses are driven by the endogenous circadian clock. PMID:26274013

  17. Independent origins of neurons and synapses: insights from ctenophores.

    Science.gov (United States)

    Moroz, Leonid L; Kohn, Andrea B

    2016-01-01

    There is more than one way to develop neuronal complexity, and animals frequently use different molecular toolkits to achieve similar functional outcomes. Genomics and metabolomics data from basal metazoans suggest that neural signalling evolved independently in ctenophores and cnidarians/bilaterians. This polygenesis hypothesis explains the lack of pan-neuronal and pan-synaptic genes across metazoans, including remarkable examples of lineage-specific evolution of neurogenic and signalling molecules as well as synaptic components. Sponges and placozoans are two lineages without neural and muscular systems. The possibility of secondary loss of neurons and synapses in the Porifera/Placozoa clades is a highly unlikely and less parsimonious scenario. We conclude that acetylcholine, serotonin, histamine, dopamine, octopamine and gamma-aminobutyric acid (GABA) were recruited as transmitters in the neural systems in cnidarian and bilaterian lineages. By contrast, ctenophores independently evolved numerous secretory peptides, indicating extensive adaptations within the clade and suggesting that early neural systems might be peptidergic. Comparative analysis of glutamate signalling also shows numerous lineage-specific innovations, implying the extensive use of this ubiquitous metabolite and intercellular messenger over the course of convergent and parallel evolution of mechanisms of intercellular communication. Therefore: (i) we view a neuron as a functional character but not a genetic character, and (ii) any given neural system cannot be considered as a single character because it is composed of different cell lineages with distinct genealogies, origins and evolutionary histories. Thus, when reconstructing the evolution of nervous systems, we ought to start with the identification of particular cell lineages by establishing distant neural homologies or examples of convergent evolution. In a corollary of the hypothesis of the independent origins of neurons, our analyses

  18. In vivo knockdown of Piccolino disrupts presynaptic ribbon morphology in mouse photoreceptor synapses

    Directory of Open Access Journals (Sweden)

    Hanna Regus-Leidig

    2014-09-01

    Full Text Available Piccolo is the largest known cytomatrix protein at active zones of chemical synapses. A growing number of studies on conventional chemical synapses assign Piccolo a role in the recruitment and integration of molecules relevant for both endo- and exocytosis of synaptic vesicles, the dynamic assembly of presynaptic F-actin, as well as the proteostasis of presynaptic proteins, yet a direct function in the structural organization of the active zone has not been uncovered in part due to the expression of multiple alternatively spliced isoforms. We recently identified Piccolino, a Piccolo splice variant specifically expressed in sensory ribbon synapses of the eye and ear. Here we down regulated Piccolino in vivo via an adeno-associated virus-based RNA interference approach and explored the impact on the presynaptic structure of mouse photoreceptor ribbon synapses. Detailed immunocytochemical light and electron microscopical analysis of Piccolino knockdown in photoreceptors revealed a hitherto undescribed photoreceptor ribbon synaptic phenotype with striking morphological changes of synaptic ribbon ultrastructure.

  19. 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.

  20. Aplysia synapse associated protein (APSAP): identification, characterization, and selective interactions with Shaker-type potassium channels

    OpenAIRE

    Reissner, Kathryn J.; Boyle, Heather D.; Ye, Xiaojing; Carew, Thomas J.

    2007-01-01

    The vertebrate post-synaptic density (PSD) is a region of high molecular complexity in which dynamic protein interactions modulate receptor localization and synaptic function. Members of the membrane-associated guanylate kinase (MAGUK) family of proteins represent a major structural and functional component of the vertebrate PSD. In order to investigate the expression and significance of orthologous PSD components associated with the Aplysia sensory neuron-motor neuron synapse, we have cloned...

  1. The complete synchronization of coupled Morris-Lecar neurons with chemical synapses

    Science.gov (United States)

    Wang, Guanping; Jin, Wuyin; Wang, An

    2016-05-01

    Based on the basic principles of stability theory and Lyapunov function, the condition of complete synchronization in coupled Morris-Lecar (ML) neuronal system with chemical synapses is studied in this work. The boundedness of the model solution is proved by analytical approach, the sufficient condition of the complete synchronization is proposed based on the quadratic of the constructed Lyapunov function and the result is verified by simulations.

  2. MET Receptor Tyrosine Kinase Controls Dendritic Complexity, Spine Morphogenesis, and Glutamatergic Synapse Maturation in the Hippocampus

    OpenAIRE

    Qiu, Shenfeng; Lu, Zhongming; Levitt, Pat

    2014-01-01

    The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation ont...

  3. Back-propagation operation for analog neural network hardware with synapse components having hysteresis characteristics.

    Science.gov (United States)

    Ueda, Michihito; Nishitani, Yu; Kaneko, Yukihiro; Omote, Atsushi

    2014-01-01

    To realize an analog artificial neural network hardware, the circuit element for synapse function is important because the number of synapse elements is much larger than that of neuron elements. One of the candidates for this synapse element is a ferroelectric memristor. This device functions as a voltage controllable variable resistor, which can be applied to a synapse weight. However, its conductance shows hysteresis characteristics and dispersion to the input voltage. Therefore, the conductance values vary according to the history of the height and the width of the applied pulse voltage. Due to the difficulty of controlling the accurate conductance, it is not easy to apply the back-propagation learning algorithm to the neural network hardware having memristor synapses. To solve this problem, we proposed and simulated a learning operation procedure as follows. Employing a weight perturbation technique, we derived the error change. When the error reduced, the next pulse voltage was updated according to the back-propagation learning algorithm. If the error increased the amplitude of the next voltage pulse was set in such way as to cause similar memristor conductance but in the opposite voltage scanning direction. By this operation, we could eliminate the hysteresis and confirmed that the simulation of the learning operation converged. We also adopted conductance dispersion numerically in the simulation. We examined the probability that the error decreased to a designated value within a predetermined loop number. The ferroelectric has the characteristics that the magnitude of polarization does not become smaller when voltages having the same polarity are applied. These characteristics greatly improved the probability even if the learning rate was small, if the magnitude of the dispersion is adequate. Because the dispersion of analog circuit elements is inevitable, this learning operation procedure is useful for analog neural network hardware. PMID:25393715

  4. Shank–cortactin interactions control actin dynamics to maintain flexibility of neuronal spines and synapses

    Science.gov (United States)

    MacGillavry, Harold D.; Kerr, Justin M.; Kassner, Josh; Frost, Nicholas A.; Blanpied, Thomas A.

    2016-01-01

    The family of Shank scaffolding molecules (comprising Shank1, 2 and 3) are core components of the postsynaptic density (PSD) in neuronal synapses. Shanks link surface receptors to other scaffolding molecules within the PSD, as well as to the actin cytoskeleton. However, determining the function of Shank proteins in neurons has been complicated because the different Shank isoforms share a very high degree of sequence and domain homology. Therefore, to control Shank content while minimizing potential compensatory effects, a miRNA-based knockdown strategy was developed to reduce the expression of all synaptically targeted Shank isoforms simultaneously in rat hippocampal neurons. Using this approach, a strong (>75%) reduction in total Shank protein levels was achieved at individual dendritic spines, prompting an approximately 40% decrease in mushroom spine density. Furthermore, Shank knockdown reduced spine actin levels and increased sensitivity to the actin depolymerizing agent Latrunculin A. A SHANK2 mutant lacking the proline-rich cortactin-binding motif (SHANK2-ΔPRO) was unable to rescue these defects. Furthermore, Shank knockdown reduced cortactin levels in spines and increased the mobility of spine cortactin as measured by single-molecule tracking photoactivated localization microscopy, suggesting that Shank proteins recruit and stabilize cortactin at the synapse. Furthermore, it was found that Shank knockdown significantly reduced spontaneous remodelling of synapse morphology that could not be rescued by the SHANK2-ΔPRO mutant. It was concluded that Shank proteins are key intermediates between the synapse and the spine interior that, via cortactin, permit the actin cytoskeleton to dynamically regulate synapse morphology and function. PMID:26547831

  5. Back-propagation operation for analog neural network hardware with synapse components having hysteresis characteristics.

    Directory of Open Access Journals (Sweden)

    Michihito Ueda

    Full Text Available To realize an analog artificial neural network hardware, the circuit element for synapse function is important because the number of synapse elements is much larger than that of neuron elements. One of the candidates for this synapse element is a ferroelectric memristor. This device functions as a voltage controllable variable resistor, which can be applied to a synapse weight. However, its conductance shows hysteresis characteristics and dispersion to the input voltage. Therefore, the conductance values vary according to the history of the height and the width of the applied pulse voltage. Due to the difficulty of controlling the accurate conductance, it is not easy to apply the back-propagation learning algorithm to the neural network hardware having memristor synapses. To solve this problem, we proposed and simulated a learning operation procedure as follows. Employing a weight perturbation technique, we derived the error change. When the error reduced, the next pulse voltage was updated according to the back-propagation learning algorithm. If the error increased the amplitude of the next voltage pulse was set in such way as to cause similar memristor conductance but in the opposite voltage scanning direction. By this operation, we could eliminate the hysteresis and confirmed that the simulation of the learning operation converged. We also adopted conductance dispersion numerically in the simulation. We examined the probability that the error decreased to a designated value within a predetermined loop number. The ferroelectric has the characteristics that the magnitude of polarization does not become smaller when voltages having the same polarity are applied. These characteristics greatly improved the probability even if the learning rate was small, if the magnitude of the dispersion is adequate. Because the dispersion of analog circuit elements is inevitable, this learning operation procedure is useful for analog neural network hardware.

  6. Efferent synapses return to inner hair cells in the aging cochlea

    OpenAIRE

    Lauer, Amanda M.; Fuchs, Paul; Ryugo, David K.; Francis, Howard W.

    2012-01-01

    Efferent innervation of the cochlea undergoes extensive modification early in development, but it is unclear if efferent synapses are modified by age, hearing loss, or both. Structural alterations in the cochlea affecting information transfer from the auditory periphery to the brain may contribute to age-related hearing deficits. We investigated changes to efferent innervation in the vicinity of inner hair cells (IHC) in young and old C57BL/6 mice using transmission electron microscopy to rev...

  7. An investigation on pharmacy functions and services affecting satisfaction of patients with prescriptions in community pharmacies.

    Science.gov (United States)

    Sakurai, Hidehiko; Nakajima, Fumio; Tada, Yuichirou; Yoshikawa, Emi; Iwahashi, Yoshiki; Fujita, Kenji; Hayase, Yukitoshi

    2009-05-01

    Various functions expected by patient expects are needed with progress in the system for separation of dispensing and prescribing functions. In this investigation, the relationship between patient satisfaction and pharmacy function were analyzed quantitatively. A questionnaire survey was conducted in 178 community pharmacies. Questions on pharmacy functions and services totaled 87 items concerning information service, amenities, safety, personnel training, etc. The questionnaires for patients had five-grade scales and composed 11 items (observed variables). Based on the results, "the percentage of satisfied patients" was determined. Multivariate analysis was performed to investigate the relationship between patient satisfaction and pharmacy functions or services provided, to confirm patient's evaluation of the pharmacy, and how factors affected comprehensive satisfaction. In correlation analysis, "the number of pharmacists" and "comprehensive satisfaction" had a negative correlation. Other interesting results were obtained. As a results of factor analysis, three latent factors were obtained: the "human factor," "patients' convenience," and "environmental factor," Multiple regression analysis showed that the "human factor" affected "comprehensive satisfaction" the most. Various pharmacy functions and services influence patient satisfaction, and improvement in their quality increases patient satisfaction. This will result in the practice of patient-centered medicine. PMID:19420889

  8. Cognitive Function in Adolescent Patients with Anorexia Nervosa and Unipolar Affective Disorders.

    Science.gov (United States)

    Sarrar, Lea; Holzhausen, Martin; Warschburger, Petra; Pfeiffer, Ernst; Lehmkuhl, Ulrike; Schneider, Nora

    2016-05-01

    Studies have shown impairments in cognitive function among adult patients with anorexia nervosa (AN) and affective disorders (AD). The association between cognitive dysfunctions, AN and AD as well as the specificity for these psychiatric diagnoses remains unclear. Therefore, we examined cognitive flexibility and processing speed in 47 female adolescent patients with AN, 21 female adolescent patients with unipolar affective disorders and 48 female healthy adolescents. All participants completed a neuropsychological test battery. There were no significant group differences regarding cognitive function, except for psychomotor processing speed with poorer performance in patients with AN. A further analysis revealed that all groups performed with the normal range, although patients with AN were over represented in the poorest performing quartile. We found no severe cognitive impairments in either patient group. Nevertheless, belonging to the AN group contributed significantly to poor performances in neuropsychological tasks. Therefore, we conclude that the risk for cognitive impairments is slightly higher for patients with AN. PMID:26695683

  9. Fish oil affects immune function in 9 to 12 month old infants

    DEFF Research Database (Denmark)

    Damsgaard, Camilla Trab; Lauritzen, Lotte; Kjær, Tanja;

    Background - n-3 Polyunsaturated fatty acids (PUFA) are thought to affect immune function and may affect immune maturation in early life. Objective - To examine if fish oil supplementation in late infancy could modify immune function. Design - A 2×2 intervention with fish oil (3.4 ± 1.1 ml/day) or...... no fish oil and cow’s milk or infant formula from 9 to 12 month of age in 64 healthy Danish infants. Before and after the intervention we measured the fatty acid composition of erythrocyte (RBC) membranes, plasma IgE levels, C-reactive protein and soluble IL-2 receptors (sIL-2R) as well as cytokine...

  10. DISC1 gene and affective psychopathology: a combined structural and functional MRI study.

    Science.gov (United States)

    Opmeer, Esther M; van Tol, Marie-José; Kortekaas, Rudie; van der Wee, Nic J A; Woudstra, Saskia; van Buchem, Mark A; Penninx, Brenda W; Veltman, Dick J; Aleman, André

    2015-02-01

    The gene Disrupted-In-Schizophrenia-1 (DISC1) has been indicated as a determinant of psychopathology, including affective disorders, and shown to influence prefrontal cortex (PFC) and hippocampus functioning, regions of major interest for affective disorders. We aimed to investigate whether DISC1 differentially modulates brain function during executive and memory processing, and morphology in regions relevant for depression and anxiety disorders (affective disorders). 128 participants, with (n = 103) and without (controls; n = 25) affective disorders underwent genotyping for Ser704Cys (with Cys-allele considered as risk-allele) and structural and functional (f) Magnetic Resonance Imaging (MRI) during visuospatial planning and emotional episodic memory tasks. For both voxel-based morphometry and fMRI analyses, we investigated the effect of genotype in controls and explored genotypeXdiagnosis interactions. Results are reported at p < 0.05 FWE small volume corrected. In controls, Cys-carriers showed smaller bilateral (para)hippocampal volumes compared with Ser-homozygotes, and lower activation in the anterior cingulate cortex (ACC) and dorsolateral PFC during visuospatial planning. In anxiety patients, Cys-carriers showed larger (para)hippocampal volumes and more ACC activation during visuospatial planning. In depressive patients, no effect of genotype was observed and overall, no effect of genotype on episodic memory processing was detected. We demonstrated that Ser704Cys-genotype influences (para)hippocampal structure and functioning the dorsal PFC during executive planning, most prominently in unaffected controls. Results suggest that presence of psychopathology moderates Ser704Cys effects. PMID:25533973

  11. Breakfast Staple Types Affect Brain Gray Matter Volume and Cognitive Function in Healthy Children

    OpenAIRE

    Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Takeuchi, Hikaru; Asano, Michiko; Asano, Kohei; Kawashima, Ryuta

    2010-01-01

    Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ) in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry. We divided subjects into rice, bread, and both groups according to their breakfast staple. We showed that the rice group had a si...

  12. Affective response to a loved one's pain: insula activity as a function of individual differences.

    Directory of Open Access Journals (Sweden)

    Viridiana Mazzola

    Full Text Available Individual variability in emotion processing may be associated with genetic variation as well as with psychological predispositions such as dispositional affect styles. Our previous fMRI study demonstrated that amygdala reactivity was independently predicted by affective-cognitive styles (phobic prone or eating disorders prone and genotype of the serotonin transporter in a discrimination task of fearful facial expressions. Since the insula is associated with the subjective evaluation of bodily states and is involved in human feelings, we explored whether its activity could also vary in function of individual differences. In the present fMRI study, the association between dispositional affects and insula reactivity has been examined in two groups of healthy participants categorized according to affective-cognitive styles (phobic prone or eating disorders prone. Images of the faces of partners and strangers, in both painful and neutral situations, were used as visual stimuli. Interaction analyses indicate significantly different activations in the two groups in reaction to a loved one's pain: the phobic prone group exhibited greater activation in the left posterior insula. These results demonstrate that affective-cognitive style is associated with insula activity in pain empathy processing, suggesting a greater involvement of the insula in feelings for a certain cohort of people. In the mapping of individual differences, these results shed new light on variability in neural networks of emotion.

  13. SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3–LAR adhesion

    Science.gov (United States)

    Lie, Eunkyung; Ko, Ji Seung; Choi, Su-Yeon; Roh, Junyeop Daniel; Cho, Yi Sul; Noh, Ran; Kim, Doyoun; Li, Yan; Kang, Hyeyeon; Choi, Tae-Yong; Nam, Jungyong; Mah, Won; Lee, Dongmin; Lee, Seong-Gyu; Kim, Ho Min; Kim, Hyun; Choi, Se-Young; Um, Ji Won; Kang, Myoung-Goo; Bae, Yong Chul; Ko, Jaewon; Kim, Eunjoon

    2016-01-01

    Synaptic adhesion molecules regulate various aspects of synapse development, function and plasticity. These functions mainly involve trans-synaptic interactions and positive regulations, whereas cis-interactions and negative regulation are less understood. Here we report that SALM4, a member of the SALM/Lrfn family of synaptic adhesion molecules, suppresses excitatory synapse development through cis inhibition of SALM3, another SALM family protein with synaptogenic activity. Salm4-mutant (Salm4−/−) mice show increased excitatory synapse numbers in the hippocampus. SALM4 cis-interacts with SALM3, inhibits trans-synaptic SALM3 interaction with presynaptic LAR family receptor tyrosine phosphatases and suppresses SALM3-dependent presynaptic differentiation. Importantly, deletion of Salm3 in Salm4−/− mice (Salm3−/−; Salm4−/−) normalizes the increased excitatory synapse number. These results suggest that SALM4 negatively regulates excitatory synapses via cis inhibition of the trans-synaptic SALM3–LAR adhesion. PMID:27480238

  14. The mature activating natural killer cell immunologic synapse is formed in distinct stages.

    Science.gov (United States)

    Orange, Jordan S; Harris, K Eliza; Andzelm, Milena M; Valter, Markus M; Geha, Raif S; Strominger, Jack L

    2003-11-25

    Natural killer (NK) cells form a structure at their interface with a susceptible target cell called the activating NK cell immunologic synapse (NKIS). The mature activating NKIS contains a central and peripheral supramolecular activation cluster (SMAC), and includes polarized surface receptors, filamentous actin (F-actin) and perforin. Evaluation of the NKIS in human NK cells revealed CD2, CD11a, CD11b and F-actin in the peripheral SMAC (pSMAC) with perforin in the central SMAC. The accumulation of F-actin and surface receptors was rapid and depended on Wiskott-Aldrich syndrome protein-driven actin polymerization. The accumulation at and arrangement of these molecules in the pSMAC was not affected by microtubule depolymerization. The polarization of perforin, however was slower and required intact actin, Wiskott-Aldrich syndrome protein, and microtubule function. Thus the process of CD2, CD11a, CD11b, and F-actin accumulation in the pSMAC and perforin accumulation in the central SMAC of the NKIS are sequential processes with distinct cytoskeletal requirements. PMID:14612578

  15. Psychosocial Functioning in Depressive Patients: A Comparative Study between Major Depressive Disorder and Bipolar Affective Disorder

    Directory of Open Access Journals (Sweden)

    Shubham Mehta

    2014-01-01

    Full Text Available Introduction. Major depressive disorder (MDD and bipolar affective disorder (BAD are among the leading causes of disability. These are often associated with widespread impairments in all domains of functioning including relational, occupational, and social. The main aim of the study was to examine and compare nature and extent of psychosocial impairment of patients with MDD and BAD during depressive phase. Methodology. 96 patients (48 in MDD group and 48 in BAD group were included in the study. Patients were recruited in depressive phase (moderate to severe depression. Patients having age outside 18–45 years, psychotic symptoms, mental retardation, and current comorbid medical or axis-1 psychiatric disorder were excluded. Psychosocial functioning was assessed using Range of Impaired Functioning Tool (LIFE-RIFT. Results. Domains of work, interpersonal relationship, life satisfaction, and recreation were all affected in both groups, but the groups showed significant difference in global psychosocial functioning score only (P=0.031 with BAD group showing more severe impairment. Conclusion. Bipolar depression causes higher global psychosocial impairment than unipolar depression.

  16. GA-Binding Protein Is Dispensable for Neuromuscular Synapse Formation and Synapse-Specific Gene Expression▿

    OpenAIRE

    Jaworski, Alexander; Smith, Cynthia L.; Burden, Steven J.

    2007-01-01

    The mRNAs encoding postsynaptic components at the neuromuscular junction are concentrated in the synaptic region of muscle fibers. Accumulation of these RNAs in the synaptic region is mediated, at least in part, by selective transcription of the corresponding genes in synaptic myofiber nuclei. The transcriptional mechanisms that are responsible for synapse-specific gene expression are largely unknown, but an Ets site in the promoter regions of acetylcholine receptor (AChR) subunit genes and o...

  17. Proteomic studies of a single CNS synapse type: the parallel fiber/purkinje cell synapse.

    OpenAIRE

    Fekrije Selimi; Cristea, Ileana M.; Elizabeth Heller; Brian T Chait; Nathaniel Heintz

    2009-01-01

    Author Summary The brain is composed of many different types of neurons that form very specific connections: synapses are formed with specific cellular partners and on precise subcellular domains. It has been proposed that different combinations of molecules encode the specificity of neuronal connections, implying the existence of a “molecular synaptic code.” To test this hypothesis, we describe a new experimental strategy that allows systematic identification of the protein composition for i...

  18. The protective function of personal growth initiative among a genocide-affected population in Rwanda.

    Science.gov (United States)

    Blackie, Laura E R; Jayawickreme, Eranda; Forgeard, Marie J C; Jayawickreme, Nuwan

    2015-07-01

    The aim of the current study was to investigate the extent to which individual differences in personal growth initiative (PGI) were associated with lower reports of functional impairment of daily activities among a genocide-affected population in Rwanda. PGI measures an individual's motivation to develop as a person and the extent to which he or she is active in setting goals that work toward achieving self-improvement. We found that PGI was negatively associated with functional impairment when controlling for depression, posttraumatic stress disorder, and other demographic factors. Our results suggest that PGI may constitute an important mindset for facilitating adaptive functioning in the aftermath of adversity and in the midst of psychological distress, and as such they might have practical applications for the development of intervention programs. PMID:26147518

  19. Plant diversity and functional groups affect Si and Ca pools in aboveground biomass of grassland systems.

    Science.gov (United States)

    Schaller, Jörg; Roscher, Christiane; Hillebrand, Helmut; Weigelt, Alexandra; Oelmann, Yvonne; Wilcke, Wolfgang; Ebeling, Anne; Weisser, Wolfgang W

    2016-09-01

    Plant diversity is an important driver of nitrogen and phosphorus stocks in aboveground plant biomass of grassland ecosystems, but plant diversity effects on other elements also important for plant growth are less understood. We tested whether plant species richness, functional group richness or the presence/absence of particular plant functional groups influences the Si and Ca concentrations (mmol g(-1)) and stocks (mmol m(-2)) in aboveground plant biomass in a large grassland biodiversity experiment (Jena Experiment). In the experiment including 60 temperate grassland species, plant diversity was manipulated as sown species richness (1, 2, 4, 8, 16) and richness and identity of plant functional groups (1-4; grasses, small herbs, tall herbs, legumes). We found positive species richness effects on Si as well as Ca stocks that were attributable to increased biomass production. The presence of particular functional groups was the most important factor explaining variation in aboveground Si and Ca stocks (mmol m(-2)). Grass presence increased the Si stocks by 140 % and legume presence increased the Ca stock by 230 %. Both the presence of specific plant functional groups and species diversity altered Si and Ca stocks, whereas Si and Ca concentration were affected mostly by the presence of specific plant functional groups. However, we found a negative effect of species diversity on Si and Ca accumulation, by calculating the deviation between mixtures and mixture biomass proportions, but in monoculture concentrations. These changes may in turn affect ecosystem processes such as plant litter decomposition and nutrient cycling in grasslands. PMID:27164912

  20. Phthalate esters affect maturation and function of primate testis tissue ectopically grafted in mice

    Science.gov (United States)

    Rodriguez-Sosa, Jose R; Bondareva, Alla; Tang, Lin; Avelar, Gleide F.; Coyle, Krysta M.; Modelski, Mark; Alpaugh, Whitney; Conley, Alan; Wynne-Edwards, Katherine; França, Luiz R; Meyers, Stuart; Dobrinski, Ina

    2014-01-01

    Di-n-Butyl (DBP) and Di-(2-EthylHexyl) (DEHP) phthalates can leach from daily-use products resulting in environmental exposure. In male rodents, phthalate exposure results in reproductive effects. To evaluate effects on the immature primate testis, testis fragments from 6-month-old rhesus macaques were grafted subcutaneously to immune-deficient mice, which were exposed to 0, 10, or 500 mg/kg of DBP or DEHP for 14 weeks or 28 weeks (DBP only). DBP exposure reduced the expression of key steroidogenic genes, indicating that Leydig cell function was compromised. Exposure to 500 mg/kg impaired tubule formation and germ cell differentiation and reduced numbers of spermatogonia. Exposure to 10 mg/kg did not affect development, but reduced Sertoli cell number and resulted in increased expression of inhibin B. Exposure to DEHP for 14 week also affected steroidogenic genes expression. Therefore, long-term exposure to phthalate esters affected development and function of the primate testis in a time and dosage dependent manner. PMID:25450860

  1. A newly recognized autosomal recessive syndrome affecting neurologic function and vision.

    Science.gov (United States)

    Salih, Mustafa A; Tzschach, Andreas; Oystreck, Darren T; Hassan, Hamdy H; AlDrees, Abdulmajeed; Elmalik, Salah A; El Khashab, Heba Y; Wienker, Thomas F; Abu-Amero, Khaled K; Bosley, Thomas M

    2013-06-01

    Genetic factors represent an important etiologic group in the causation of intellectual disability. We describe a Saudi Arabian family with closley related parents in which four of six children were affected by a congenital cognitive disturbance. The four individuals (aged 18, 16, 13, and 2 years when last examined) had motor and cognitive delay with seizures in early childhood, and three of the four (sparing only the youngest child) had progressive, severe cognitive decline with spasticity. Two affected children had ocular malformations, and the three older children had progressive visual loss. The youngest had normal globes with good functional vision when last examined but exhibited the oculodigital sign, which may signify a subclinical visual deficit. A potentially deleterious nucleotide change (c.1A>G; p.Met1Val) in the C12orf57 gene was homozygous in all affected individuals, heterozygous in the parents, and absent in an unaffected sibling and >350 normal individuals. This gene has no known function. This family manifests a autosomal recessive syndrome with some phenotypic variability that includes abnormal development of brain and eyes, delayed cognitive and motor milestones, seizures, and a severe cognitive and visual decline that is associated with a homozygous variant in a newly identified gene. PMID:23633300

  2. Functional connectivity of pain-mediated affect regulation in Borderline Personality Disorder.

    Directory of Open Access Journals (Sweden)

    Inga Niedtfeld

    Full Text Available Affective instability and self-injurious behavior are important features of Borderline Personality Disorder. Whereas affective instability may be caused by a pattern of limbic hyperreactivity paired with dysfunctional prefrontal regulation mechanisms, painful stimulation was found to reduce affective arousal at the neural level, possibly underlying the soothing effect of pain in BPD.We used psychophysiological interactions to analyze functional connectivity of (para- limbic brain structures (i.e. amygdala, insula, anterior cingulate cortex in Borderline Personality Disorder in response to painful stimulation. Therefore, we re-analyzed a dataset from 20 patients with Borderline Personality Disorder and 23 healthy controls who took part in an fMRI-task inducing negative (versus neutral affect and subsequently applying heat pain (versus warmth perception.Results suggest an enhanced negative coupling between limbic as well as paralimbic regions and prefrontal regions, specifically with the medial and dorsolateral prefrontal cortex, when patients experienced pain in addition to emotional arousing pictures. When neutral pictures were combined with painful heat sensation, we found positive connectivity in Borderline Personality Disorder between (para-limbic brain areas and parts of the basal ganglia (lentiform nucleus, putamen, as well areas involved in self-referential processing (precuneus and posterior cingulate.We found further evidence for alterations in the emotion regulation process in Borderline Personality Disorder, in the way that pain improves the inhibition of limbic activity by prefrontal areas. This study provides new insights in pain processing in BPD, including enhanced coupling of limbic structures and basal ganglia.

  3. Is there an association between subjective and objective measures of cognitive function in patients with affective disorders?

    DEFF Research Database (Denmark)

    Svendsen, Anne M; Kessing, Lars V; Munkholm, Klaus;

    2012-01-01

    Background: Patients with affective disorders experience cognitive dysfunction in addition to their affective symptoms. The relationship between subjectively experienced and objectively measured cognitive function is controversial with several studies reporting no correlation between subjective...... and objective deficits. Aims: To investigate whether there is a correlation between subjectively reported and objectively measured cognitive function in patients with affective disorders, and whether subjective complaints predict objectively measured dysfunction. Methods: The study included 45 participants; 15...... with bipolar disorder (BD), 15 with unipolar disorder (UD) and 15 healthy individuals. Participants' subjectively experienced cognitive function and objective cognitive function were assessed with the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) and the Screen...

  4. Neuromorhic Silicon Neuron and Synapse: Analog VLSI Implemetation of Biological Structures

    OpenAIRE

    Ms. Pooja Verma; Ms. Neha Verma

    2014-01-01

    Neuromorphic Silicon neurons and synapses are very large scale integration (VLSI) circuits that emulate or mimic the electrophysiological behavior of their biological counterparts. These analog circuits can be used for the qualitative analysis of the functioning of neural circuits; and also for making intelligent systems that can perform the tasks that can be easily performed by biolological organisms but are very difficult to be performed by any traditionally engineered syste...

  5. Changes in input strength and number are driven by distinct mechanisms at the retinogeniculate synapse

    OpenAIRE

    Lin, David J.; Kang, Erin; Chen, Chinfei

    2014-01-01

    Recent studies have demonstrated that vision influences the functional remodeling of the mouse retinogeniculate synapse, the connection between retinal ganglion cells and thalamic relay neurons in the dorsal lateral geniculate nucleus (LGN). Initially, each relay neuron receives a large number of weak retinal inputs. Over a 2- to 3-wk developmental window, the majority of these inputs are eliminated, and the remaining inputs are strengthened. This period of refinement is followed by a critica...

  6. Sensory experience shapes the development of the visual system’s first synapse

    OpenAIRE

    Dunn, Felice A.; Santina, Luca Della; Parker, Edward D.; Wong, Rachel O.L.

    2013-01-01

    Specific connectivity patterns among neurons create the basic architecture underlying parallel processing in our nervous system. Here we focus on the visual system’s first synapse to examine the structural and functional consequences of sensory deprivation on the establishment of parallel circuits. Dark rearing reduces synaptic strength between cones and cone bipolar cells, a previously unappreciated effect of sensory deprivation. In contrast, rod bipolar cells, which utilize the same glutama...

  7. Interaction between autism-linked MDGAs and neuroligins suppresses inhibitory synapse development

    OpenAIRE

    Pettem, Katherine L.; Yokomaku, Daisaku; Takahashi, Hideto; Ge, Yuan; Craig, Ann Marie

    2013-01-01

    Rare variants in MDGAs (MAM domain–containing glycosylphosphatidylinositol anchors), including multiple protein-truncating deletions, are linked to autism and schizophrenia, but the function of these genes is poorly understood. Here, we show that MDGA1 and MDGA2 bound to neuroligin-2 inhibitory synapse–organizing protein, also implicated in neurodevelopmental disorders. MDGA1 inhibited the synapse-promoting activity of neuroligin-2, without altering neuroligin-2 surface trafficking, by inhibi...

  8. A matter of balance: role of neurexin and neuroligin at the synapse

    DEFF Research Database (Denmark)

    Bang, Marie Louise; Owczarek, Sylwia

    2013-01-01

    Neurexins and neuroligins are synaptic cell adhesion molecules. Neurexins are primary located on the presynaptic membrane, whereas neuroligins are strictly postsynaptic proteins. Since their discovery, the knowledge of neurexins and neuroligins has expanded, implicating them in various neuronal p...... processes, including the differentiation, maturation, stabilization, and plasticity of both inhibitory and excitatory synapses. Here, we review the most recent results regarding the structure and function of these cell adhesion molecules....

  9. Bipolar affective disorders: Assessment of functional brain changes by means of Tc99m HMPAO neurospect

    International Nuclear Information System (INIS)

    Affective Bipolar Disorder (ABD) is observed in all countries of the world with a prevalence fluctuating between 3 and 6.5%. The nature of its clinical manifestations and clinical evolution constitute a diagnostic and therapeutic challenge even for the most experienced clinician. We have analysed by means of NeuroSPECT the neuro functional cortical and subcortical expression of a cohort of 44 eutimic patients with DSM IV criteria compatible with the diagnosis of ABD. The results were expressed in functional 3 dimensional images normalized for volume and compared to a normal data base matched for the age of the patient. Quantitative analyses considered the maximal regional perfusion in each Brodmann area with behavioral significance. The results were expressed in standard deviations with respect to the control population and we considered these findings as a continual variable susceptible to statistical analyses. In the cortex we report the presence of increased perfusion in subregions of areas 8, 9 and 10 of Brodmann (executive area) also in area 7 of Brodmann (posterior parietal lobe). We describe also relative decreased perfusion in areas 24 and 32 (internal frontal lobe), area 25 (affective area), area 21, 22 and 38 (temporal lobe). In subcortical structures we report increased perfusion in thalamus, caudate, and lentiform nucleous with values superior to 3 standard deviations above the normal controls. These findings can constitute neurofunctional markers of ABD that can be used as a clinical diagnostic tool. These findings suggest the participation of cortical/subcortical circuits as the probable etiologic substratum in affective bipolar disorders. Keys: Affective Bipolar Disorders (Au)

  10. The Functional Effect of Teacher Positive and Neutral Affect on Task Performance of Students with Significant Disabilities

    Science.gov (United States)

    Park, Sungho; Singer, George H. S.; Gibson, Mary

    2005-01-01

    The study uses an alternating treatment design to evaluate the functional effect of teacher's affect on students' task performance. Tradition in special education holds that teachers should engage students using positive and enthusiastic affect for task presentations and praise. To test this assumption, we compared two affective conditions. Three…

  11. The Interplay between Synaptic Activity and Neuroligin Function in the CNS

    OpenAIRE

    2015-01-01

    Neuroligins (NLs) are postsynaptic transmembrane cell-adhesion proteins that play a key role in the regulation of excitatory and inhibitory synapses. Previous in vitro and in vivo studies have suggested that NLs contribute to synapse formation and synaptic transmission. Consistent with their localization, NL1 and NL3 selectively affect excitatory synapses, whereas NL2 specifically affects inhibitory synapses. Deletions or mutations in NL genes have been found in patients with autism spectrum ...

  12. Ultra-endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function.

    Science.gov (United States)

    Stelzer, I; Kröpfl, J M; Fuchs, R; Pekovits, K; Mangge, H; Raggam, R B; Gruber, H-J; Prüller, F; Hofmann, P; Truschnig-Wilders, M; Obermayer-Pietsch, B; Haushofer, A C; Kessler, H H; Mächler, P

    2015-10-01

    Although amateur sports have become increasingly competitive within recent decades, there are as yet few studies on the possible health risks for athletes. This study aims to determine the impact of ultra-endurance exercise-induced stress on the number and function of circulating hematopoietic progenitor cells (CPCs) and hematological, inflammatory, clinical, metabolic, and stress parameters in moderately trained amateur athletes. Following ultra-endurance exercise, there were significant increases in leukocytes, platelets, interleukin-6, fibrinogen, tissue enzymes, blood lactate, serum cortisol, and matrix metalloproteinase-9. Ultra-endurance exercise did not influence the number of CPCs but resulted in a highly significant decline of CPC functionality after the competition. Furthermore, Epstein-Barr virus was seen to be reactivated in one of seven athletes. The link between exercise-induced stress and decline of CPC functionality is supported by a negative correlation between cortisol and CPC function. We conclude that ultra-endurance exercise induces metabolic stress and an inflammatory response that affects not only mature hematopoietic cells but also the function of the immature hematopoietic stem and progenitor cell fraction, which make up the immune system and provide for regeneration. PMID:25438993

  13. Antioxidant and functional properties of tea protein as affected by the different tea processing methods

    OpenAIRE

    Zhang, Yu; Chen, Haixia; Ning ZHANG; Ma, Lishuai

    2013-01-01

    The Box-Behnken design combined with response surface methodology was used to optimize alkali extraction of protein from tea. Three independent extraction variables (extraction time: X1; extraction temperature: X2; alkali concentration: X3) were evaluated. The antioxidant and functional properties of tea protein as affected by different tea processing were compared. The optimum conditions were: extraction time of 85 min, extraction temperature of 80 °C, and alkali concentration of 0.15 M. Und...

  14. Aging. Aging-induced type I interferon signaling at the choroid plexus negatively affects brain function

    Science.gov (United States)

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M.; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2016-01-01

    Age-associated cognitive decline is affected by factors produced inside and outside the brain. We found in aged mice and humans, that the choroid plexus (CP), an epithelial interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent expression profile, often associated with anti-viral responses. This signature was induced by brain-derived signals present in the cerebrospinal fluid of aged mice. Blocking IFN-I signaling within the brain of cognitively-impaired aged mice, using IFN-I receptor neutralizing antibody, led to partial restoration of cognitive function and hippocampal neurogenesis, and reestablished IFN-II-dependent CP activity, lost in aging. Our data identify an aging-induced IFN-I signature at the CP, and demonstrate its negative influence on brain function, thereby suggesting a potential target for therapeutic intervention for age-related cognitive decline. PMID:25147279

  15. Developing fragility functions for the areas affected by the 2009 Samoa earthquake and tsunami

    Directory of Open Access Journals (Sweden)

    H. Gokon

    2014-01-01

    Full Text Available Fragility functions in terms of flow depth, flow velocity and hydrodynamic force are developed to evaluate structural vulnerability in the areas affected by the 2009 Samoa earthquake and tsunami. First, numerical simulations of tsunami propagation and inundation are conducted to reproduce the features of tsunami inundation. To validate the results, flow depths measured in field surveys and waveforms measured by Deep-ocean Assessment and Reporting of Tsunamis (DART gauges are utilized. Next, building damage is investigated by manually detecting changes between pre- and post-tsunami high-resolution satellite images. Finally, the data related to tsunami features and building damage are integrated using GIS, and tsunami fragility functions are developed based on the statistical analyses.

  16. Rate dynamics of leaky integrate-and-fire neurons with strong synapses

    Directory of Open Access Journals (Sweden)

    Eilen Nordlie

    2010-12-01

    Full Text Available Firing-rate models provide a practical tool for studying the dynamics of trial- or population-averaged neuronal signals. A wealth of theoretical and experimental studies has been dedicated to the derivation or extraction of such models by investigating the firing-rate response characteristics of ensembles of neurons. The majority of these studies assumes that neurons receive input spikes at a high rate through weak synapses (diffusion approximation. For many biological neural systems, however, this assumption cannot be justified. So far, it is unclear how time-varying presynaptic firing rates are transmitted by a population of neurons if the diffusion assumption is dropped. Here, we numerically investigate the stationary and non-stationary firing-rate response properties of leaky integrate-and-fire (LIF neurons receiving input spikes through excitatory synapses with alpha-function shaped postsynaptic currents for strong synaptic weights. Input spike trains are modelled by inhomogeneous Poisson point-processes with sinusoidal rate. Average rates, modulation amplitudes and phases of the period-averaged spike responses are measured for a broad range of stimulus, synapse and neuron parameters. Across wide parameter regions, the resulting transfer functions can be approximated by a linear 1st-order low-pass filter. Below a critical synaptic weight, the cutoff frequencies are approximately constant and determined by the synaptic time constants. Only for synapses with unrealistically strong weights are the cutoff frequencies significantly increased. To account for stimuli with larger modulation depths, we combine the measured linear transfer function with the nonlinear response characteristics obtained for stationary inputs. The resulting linear-nonlinear model accurately predicts the population response for a variety of non-sinusoidal stimuli.

  17. The subcellular localization of IGFBP5 affects its cell growth and migration functions in breast cancer

    Directory of Open Access Journals (Sweden)

    Sahin Aysegul

    2009-04-01

    Full Text Available Abstract Background Insulin-like growth factor binding protein 5 (IGFBP5 has been shown to be associated with breast cancer metastasis in clinical marker studies. However, a major difficulty in understanding how IGFBP5 functions in this capacity is the paradoxical observation that ectopic overexpression of IGFBP5 in breast cancer cell lines results in suppressed cellular proliferation. In cancer tissues, IGFBP5 resides mainly in the cytoplasm; however, in transfected cells, IGFBP5 is mainly located in the nucleus. We hypothesized that subcellular localization of IGFBP5 affects its functions in host cells. Methods To test this hypothesis, we generated wild-type and mutant IGFBP5 expression constructs. The mutation occurs within the nuclear localization sequence (NLS of the protein and is generated by site-directed mutagenesis using the wild-type IGFBP5 expression construct as a template. Next, we transfected each expression construct into MDA-MB-435 breast cancer cells to establish stable clones overexpressing either wild-type or mutant IGFBP5. Results Functional analysis revealed that cells overexpressing wild-type IGFBP5 had significantly lower cell growth rate and motility than the vector-transfected cells, whereas cells overexpressing mutant IGFBP5 demonstrated a significantly higher ability to proliferate and migrate. To illustrate the subcellular localization of the proteins, we generated wild-type and mutant IGFBP5-pDsRed fluorescence fusion constructs. Fluorescence microscopy imaging revealed that mutation of the NLS in IGFBP5 switched the accumulation of IGFBP5 from the nucleus to the cytoplasm of the protein. Conclusion Together, these findings imply that the mutant form of IGFBP5 increases proliferation and motility of breast cancer cells and that mutation of the NLS in IGFBP5 results in localization of IGFBP5 in the cytoplasm, suggesting that subcellular localization of IGFBP5 affects its cell growth and migration functions in the

  18. Functional Connectivity under Anticipation of Shock: Correlates of Trait Anxious Affect versus Induced Anxiety.

    Science.gov (United States)

    Bijsterbosch, Janine; Smith, Stephen; Bishop, Sonia J

    2015-09-01

    Sustained anxiety about potential future negative events is an important feature of anxiety disorders. In this study, we used a novel anticipation of shock paradigm to investigate individual differences in functional connectivity during prolonged threat of shock. We examined the correlates of between-participant differences in trait anxious affect and induced anxiety, where the latter reflects changes in self-reported anxiety resulting from the shock manipulation. Dissociable effects of trait anxious affect and induced anxiety were observed. Participants with high scores on a latent dimension of anxious affect showed less increase in ventromedial pFC-amygdala connectivity between periods of safety and shock anticipation. Meanwhile, lower levels of induced anxiety were linked to greater augmentation of dorsolateral pFC-anterior insula connectivity during shock anticipation. These findings suggest that ventromedial pFC-amygdala and dorsolateral pFC-insula networks might both contribute to regulation of sustained fear responses, with their recruitment varying independently across participants. The former might reflect an evolutionarily old mechanism for reducing fear or anxiety, whereas the latter might reflect a complementary mechanism by which cognitive control can be implemented to diminish fear responses generated due to anticipation of aversive stimuli or events. These two circuits might provide complementary, alternate targets for exploration in future pharmacological and cognitive intervention studies. PMID:25961638

  19. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xujie [State key laboratory of new ceramics and fine processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Feng, Qingling, E-mail: biomater@mail.tsinghua.edu.cn [State key laboratory of new ceramics and fine processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Bachhuka, Akash [Mawson Institute, University of South Australia, Mawson Lakes 5095 (Australia); Vasilev, Krasimir [Mawson Institute, University of South Australia, Mawson Lakes 5095 (Australia); School of Advanced Manufacturing, University of South Australia, Mawson Lakes 5095 (Australia)

    2013-04-01

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (-NH{sub 2}), carboxyl (-COOH) and methyl (-CH{sub 3}), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (-COOH and -NH{sub 2}) can absorb more proteins than these modified with more hydrophobic functional group (-CH{sub 3}). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the -NH{sub 2} modified surfaces encourage osteogenic differentiation; the -COOH modified surfaces promote cell adhesion and spreading and the -CH{sub 3} modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  20. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    Science.gov (United States)

    Liu, Xujie; Feng, Qingling; Bachhuka, Akash; Vasilev, Krasimir

    2013-04-01

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (sbnd NH2), carboxyl (sbnd COOH) and methyl (sbnd CH3), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (sbnd COOH and sbnd NH2) can absorb more proteins than these modified with more hydrophobic functional group (sbnd CH3). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the sbnd NH2 modified surfaces encourage osteogenic differentiation; the sbnd COOH modified surfaces promote cell adhesion and spreading and the sbnd CH3 modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  1. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    International Nuclear Information System (INIS)

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (-NH2), carboxyl (-COOH) and methyl (-CH3), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (-COOH and -NH2) can absorb more proteins than these modified with more hydrophobic functional group (-CH3). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the -NH2 modified surfaces encourage osteogenic differentiation; the -COOH modified surfaces promote cell adhesion and spreading and the -CH3 modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  2. Japanese encephalitis virus disrupts cell-cell junctions and affects the epithelial permeability barrier functions.

    Directory of Open Access Journals (Sweden)

    Tanvi Agrawal

    Full Text Available Japanese encephalitis virus (JEV is a neurotropic flavivirus, which causes viral encephalitis leading to death in about 20-30% of severely-infected people. Although JEV is known to be a neurotropic virus its replication in non-neuronal cells in peripheral tissues is likely to play a key role in viral dissemination and pathogenesis. We have investigated the effect of JEV infection on cellular junctions in a number of non-neuronal cells. We show that JEV affects the permeability barrier functions in polarized epithelial cells at later stages of infection. The levels of some of the tight and adherens junction proteins were reduced in epithelial and endothelial cells and also in hepatocytes. Despite the induction of antiviral response, barrier disruption was not mediated by secreted factors from the infected cells. Localization of tight junction protein claudin-1 was severely perturbed in JEV-infected cells and claudin-1 partially colocalized with JEV in intracellular compartments and targeted for lysosomal degradation. Expression of JEV-capsid alone significantly affected the permeability barrier functions in these cells. Our results suggest that JEV infection modulates cellular junctions in non-neuronal cells and compromises the permeability barrier of epithelial and endothelial cells which may play a role in viral dissemination in peripheral tissues.

  3. Arabidopsis AtADF1 is Functionally Affected by Mutations on Actin Binding Sites

    Institute of Scientific and Technical Information of China (English)

    Chun-Hai Dong; Wei-Ping Tang; Jia-Yao Liu

    2013-01-01

    The plant actin depolymerizing factor (ADF) binds to both monomeric and filamentous actin,and is directly involved in the depolymerization of actin filaments.To better understand the actin binding sites of the Arabidopsis thaliana L.AtADF1,we generated mutants of AtADF1 and investigated their functions in vitro and in vivo.Analysis of mutants harboring amino acid substitutions revealed that charged residues (Arg98 and Lys100) located at the α-helix 3 and forming an actin binding site together with the N-terminus are essential for both G-and F-actin binding.The basic residues on the β-strand 5 (K82/A) and the α-helix 4 (R135/A,R137/A) form another actin binding site that is important for F-actin binding.Using transient expression of CFP-tagged AtADF1 mutant proteins in onion (Allium cepa) peel epidermal cells and transgenic Arabidopsis thaliana L.plants overexpressing these mutants,we analyzed how these mutant proteins regulate actin organization and affect seedling growth.Our results show that the ADF mutants with a lower affinity for actin filament binding can still be functional,unless the affinity foractin monomers is also affected.The G-actin binding activity of the ADF plays an essential role in actin binding,depolymerization of actin polymers,and therefore in the control of actin organization.

  4. Relationship of mercury to cognitive, affective and perceptual motor functioning in a normal sample in Hawaii

    Energy Technology Data Exchange (ETDEWEB)

    Sine, L.F.

    1983-01-01

    Although the effects of toxic levels of mercury have been well documented, the effects of subclinical levels of mercury on normal populations have generally not been studied. The purpose of this investigation was to assess the impact of mercury risk factors on cognition, affect, psychopathology, and known mercury-related symptoms in a normal sample in Hawaii exposed to subclinical although elevated levels of elemental mercury through inhalation associated with volcanic activity and of methylmercury mostly through ingestion of large ocean species fish. The following summarizes the findings and conclusions of the study: 1) a four week test-retest reliability using 41 of the subjects showed that the 41 measures used in the study exhibited an average correlation of .78. Using all 413 subjects, the average internal consistency measured by Cronbach's ..cap alpha.. was .82 for the 17 affect, psychopathology, and symptom measures; 2) nine mercury source variables were used to predict the amount of total mercury in hair. Interestingly, none of the source variables predicted hair total mercury; 3) the source variables in addition to hair total mercury and statistical control variables were used to predict the twenty-two functioning variables in the four domains cited above with a relative absence of relationships noted. This finding indicates that the normal population in Hawaii appears not to be at risk; and 4) one historical mercury source variable, reported fish intake when young, related to six functioning variables - the psychopathology measures of Somatization, Obsessive-Compulsive and Anxiety as well as the Sensory, Affect and Mental symptoms - with Beta weights in the .15 to .20 range. The implications of the findings were discussed and suggestions offered for future research especially with respect to specific high risk subgroups.

  5. Breakfast staple types affect brain gray matter volume and cognitive function in healthy children.

    Directory of Open Access Journals (Sweden)

    Yasuyuki Taki

    Full Text Available Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry. We divided subjects into rice, bread, and both groups according to their breakfast staple. We showed that the rice group had a significantly larger gray matter ratio (gray matter volume percentage divided by intracranial volume and significantly larger regional gray matter volumes of several regions, including the left superior temporal gyrus. The bread group had significantly larger regional gray and white matter volumes of several regions, including the right frontoparietal region. The perceptual organization index (POI; IQ subcomponent of the rice group was significantly higher than that of the bread group. All analyses were adjusted for age, gender, intracranial volume, socioeconomic status, average weekly frequency of having breakfast, and number of side dishes eaten for breakfast. Although several factors may have affected the results, one possible mechanism underlying the difference between the bread and the rice groups may be the difference in the glycemic index (GI of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI. Our study suggests that breakfast staple type affects brain gray and white matter volumes and cognitive function in healthy children; therefore, a diet of optimal nutrition is important for brain maturation during childhood and adolescence.

  6. Application of Synapses Dilution Method for Pattern Recognition Optimation Using Hopfield Model Neural Network

    International Nuclear Information System (INIS)

    Human's neural network consist of thousands of neurons, each of which has only one input, and more than one output. these neurons are linked together through junctions called synapses, which have different strength from one to another, to configure specific information pattern. Using their functions and capabilities, we are able to improve the performance of neuman-type computers in the future. This is because of the capabilities to parallely process information, especially for voice and image pattern recognitions, instead of serial process as in Neuman-type computers. This paper explains how to simplify hopfield model neural network by using synapse dilution without reducing the capability of its pattern recognition. the dilution is done by using two ways: sequence, and random. Both ways are followed by either intact or distorted pattern recognitions

  7. Physical aspects of low power synapses based on phase change memory devices

    Science.gov (United States)

    Suri, Manan; Bichler, Olivier; Querlioz, Damien; Traoré, Boubacar; Cueto, Olga; Perniola, Luca; Sousa, Veronique; Vuillaume, Dominique; Gamrat, Christian; DeSalvo, Barbara

    2012-09-01

    In this work, we demonstrate how phase change memory (PCM) devices can be used to emulate biologically inspired synaptic functions in particular, potentiation and depression, important for implementing neuromorphic hardware. PCM devices with different chalcogenide materials are fabricated and characterized. The asymmetry between the potentiation and depression behaviors of the PCM is stressed. Detailed multi-physical simulations are performed to study the underlying physics of the synaptic behavior of PCM. A versatile behavioral model and a multi-level circuit-compatible model are developed for system and circuit-level neuromorphic simulations. We propose a unique low-power methodology named the 2-PCM Synapse, to use PCM devices as synapses in large scale neuromorphic systems. To show the strength of our proposed solution, we efficiently simulated fully connected feed-forward spiking neural network capable of complex visual pattern extraction from real world data.

  8. Synapses, synaptic activity and intraneuronal Aβ in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Davide Tampellini

    2010-05-01

    Full Text Available β-amyloid peptide accumulation plays a central role in the pathogenesis of Alzheimer’s disease. Aberrant β-amyloid buildup in the brain has been shown to be present both in the extracellular space and within neurons. Synapses are important targets of β-amyloid, and alterations in synapses better correlate with cognitive impairment than amyloid plaques or neurofibrillary tangles. The link between β-amyloid and synapses became even tighter when it was discovered that β-amyloid accumulates within synapses and that synaptic activity modulates β-amyloid secretion. Currently, a central question in Alzheimer’s disease research is what role synaptic activity plays in the disease process, and how specifically β-amyloid is involved in the synaptic dysfunction that characterizes the disease.

  9. Direct imaging of lateral movements of AMPA receptors inside synapses

    CERN Document Server

    Tardin, Catherine; Bats, Cécile; Lounis, Brahim; Choquet, Daniel

    2003-01-01

    Trafficking of AMPA receptors in and out of synapses is crucial for synaptic plasticity. Previous studies have focused on the role of endo/exocytosis processes or that of lateral diffusion of extra-synaptic receptors. We have now directly imaged AMPAR movements inside and outside synapses of live neurons using single-molecule fluorescence microscopy. Inside individual synapses, we found immobile and mobile receptors, which display restricted diffusion. Extra-synaptic receptors display free diffusion. Receptors could also exchange between these membrane compartments through lateral diffusion. Glutamate application increased both receptor mobility inside synapses and the fraction of mobile receptors present in a juxtasynaptic region. Block of inhibitory transmission to favor excitatory synaptic activity induced a transient increase in the fraction of mobile receptors and a decrease in the proportion of juxtasynaptic receptors. Altogether, our data show that rapid exchange of receptors between a synaptic and ext...

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

    Science.gov (United States)

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

    2015-12-01

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

  11. The role of MuSK in synapse formation and neuromuscular disease.

    Science.gov (United States)

    Burden, Steven J; Yumoto, Norihiro; Zhang, Wei

    2013-05-01

    Muscle-specific kinase (MuSK) is essential for each step in neuromuscular synapse formation. Before innervation, MuSK initiates postsynaptic differentiation, priming the muscle for synapse formation. Approaching motor axons recognize the primed, or prepatterned, region of muscle, causing motor axons to stop growing and differentiate into specialized nerve terminals. MuSK controls presynaptic differentiation by causing the clustering of Lrp4, which functions as a direct retrograde signal for presynaptic differentiation. Developing synapses are stabilized by neuronal Agrin, which is released by motor nerve terminals and binds to Lrp4, a member of the low-density lipoprotein receptor family, stimulating further association between Lrp4 and MuSK and increasing MuSK kinase activity. In addition, MuSK phosphorylation is stimulated by an inside-out ligand, docking protein-7 (Dok-7), which is recruited to tyrosine-phosphorylated MuSK and increases MuSK kinase activity. Mutations in MuSK and in genes that function in the MuSK signaling pathway, including Dok-7, cause congenital myasthenia, and autoantibodies to MuSK, Lrp4, and acetylcholine receptors are responsible for myasthenia gravis. PMID:23637281

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

    Directory of Open Access Journals (Sweden)

    Lisa eMapelli

    2015-05-01

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

  13. Opposite actions of nitric oxide on cholinergic synapses: which pathways?

    OpenAIRE

    Mothet, J P; Fossier, P; Tauc, L; Baux, G

    1996-01-01

    Nitric oxide (NO) produced opposite effects on acetylcholine (ACh) release in identified neuroneuronal Aplysia synapses depending on the excitatory or the inhibitory nature of the synapse. Extracellular application of the NO donor, SIN-1, depressed the inhibitory postsynaptic currents (IPSCs) and enhanced the excitatory postsynaptic currents (EPSCs) evoked by presynaptic action potentials (1/60 Hz). Application of a membrane-permeant cGMP analog mimicked the effect of SIN-1 suggesting the par...

  14. Low voltage and time constant organic synapse-transistor

    OpenAIRE

    Desbief, Simon; Kyndiah, Adrica; Guerin, David; Gentili, Denis; Murgia, Mauro; Lenfant, Stéphane; Alibart, Fabien; Cramer, Tobias; Biscarini, Fabio; Vuillaume, Dominique

    2015-01-01

    We report on an artificial synapse, an organic synapse-transistor (synapstor) working at 1 volt and with a typical response time in the range 100-200 ms. This device (also called NOMFET, Nanoparticle Organic Memory Field Effect Transistor) combines a memory and a transistor effect in a single device. We demonstrate that short-term plasticity (STP), a typical synaptic behavior, is observed when stimulating the device with input spikes of 1 volt. Both significant facilitating and depressing beh...

  15. Memory-Relevant Mushroom Body Output Synapses Are Cholinergic

    OpenAIRE

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

    2016-01-01

    Summary Memories are stored in the fan-out fan-in neural architectures of the mammalian cerebellum and hippocampus and the insect mushroom bodies. However, whereas key plasticity occurs at glutamatergic synapses in mammals, the neurochemistry of the memory-storing mushroom body Kenyon cell output synapses is unknown. Here we demonstrate a role for acetylcholine (ACh) in Drosophila. Kenyon cells express the ACh-processing proteins ChAT and VAChT, and reducing their expression impairs learned o...

  16. Imaging Structural Plasticity Of Synapses In The Brain

    OpenAIRE

    Yu, Xinzhu

    2012-01-01

    Synapses are the sites where neurons contact each other and exchange information in the brain. Experience-dependent changes in synaptic connections are fundamental for numerous neurological processes, ranging from the development of neuronal circuitry to learning and memory. Dendritic spines are the postsynaptic sites of the majority of excitatory synapses in the mammalian central nervous system. The morphology and dynamics of dendritic spines change throughout the lifespan of animals, espe...

  17. Silent Synapse-Based Circuitry Remodeling in Drug Addiction

    OpenAIRE

    Dong, Yan

    2015-01-01

    Exposure to cocaine, and likely other drugs of abuse, generates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-silent glutamatergic synapses in the nucleus accumbens. These immature synaptic contacts evolve after drug withdrawal to redefine the neurocircuital properties. These results raise at least three critical questions: (1) what are the molecular and cellular mechanisms that mediate drug-induced generation of silent synapses; (2) how are neurocircuits remodeled upon genera...

  18. Earthworm-mycorrhiza interactions can affect the diversity, structure and functioning of establishing model grassland communities.

    Directory of Open Access Journals (Sweden)

    Johann G Zaller

    Full Text Available Both earthworms and arbuscular mycorrhizal fungi (AMF are important ecosystem engineers co-occurring in temperate grasslands. However, their combined impacts during grassland establishment are poorly understood and have never been studied. We used large mesocosms to study the effects of different functional groups of earthworms (i.e., vertically burrowing anecics vs. horizontally burrowing endogeics and a mix of four AMF taxa on the establishment, diversity and productivity of plant communities after a simulated seed rain of 18 grassland species comprising grasses, non-leguminous forbs and legumes. Moreover, effects of earthworms and/or AMF on water infiltration and leaching of ammonium, nitrate and phosphate were determined after a simulated extreme rainfall event (40 l m(-2. AMF colonisation of all three plant functional groups was altered by earthworms. Seedling emergence and diversity was reduced by anecic earthworms, however only when AMF were present. Plant density was decreased in AMF-free mesocosms when both anecic and endogeic earthworms were active; with AMF also anecics reduced plant density. Plant shoot and root biomass was only affected by earthworms in AMF-free mesocosms: shoot biomass increased due to the activity of either anecics or endogeics; root biomass increased only when anecics were active. Water infiltration increased when earthworms were present in the mesocosms but remained unaffected by AMF. Ammonium leaching was increased only when anecics or a mixed earthworm community was active but was unaffected by AMF; nitrate and phosphate leaching was neither affected by earthworms nor AMF. Ammonium leaching decreased with increasing plant density, nitrate leaching decreased with increasing plant diversity and density. In order to understand the underlying processes of these interactions further investigations possibly under field conditions using more diverse belowground communities are required. Nevertheless, this study

  19. Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

    Science.gov (United States)

    Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

    2016-03-01

    Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood

  20. 沉默突触的激活机制及其功能意义%Silent Synapse:A Review

    Institute of Scientific and Technical Information of China (English)

    蔡靓; 苏朝芬; 罗焕敏

    2012-01-01

    沉默突触(silent synapse)是指具有突触结构,但在生理情况下没有传递功能的突触。沉默突触在某些情况下能转变为功能性突触并能增加突触联系(即能与其他末梢形成新的突触),突触功能与结构上的变化统称为突触的可塑性,它的这一性质与神经修复、记忆改善等过程密切相关。所以,研究沉默突触的形成、功能、激活机制等意义重大。%Silent synapse is defined as a synapse that is incapable of exerting neurotransmission in physiological conditions but could be activated under certain conditions. The change of function and structure of synapses are defined as plasticity of synapse, and this property of synapses is related to restoration of the neurons and memory improvement. It is essential to understand the mechanisms of formation, function and activation of silent synapse.

  1. 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. PMID:26929363

  2. Rett syndrome: genes, synapses, circuits and therapeutics

    Directory of Open Access Journals (Sweden)

    Abhishek eBanerjee

    2012-05-01

    Full Text Available Development of the nervous system proceeds through a set of complex checkpoints which arise from a combination of sequential gene expression and early neural activity sculpted by the environment. Genetic and environmental insults lead to neurodevelopmental disorders which encompass a large group of diseases that result from anatomical and physiological abnormalities during maturation and development of brain circuits. Rett syndrome (RTT is a postnatal neurological disorder of genetic origin, caused by mutations in the X-linked gene MECP2. It features neuropsychiatric abnormalities like motor dysfunctions and mild to severe cognitive impairment. This review discusses several key questions and attempts to evaluate recently developed animal models, cell-type specific function of MeCP2, defects in neural circuit plasticity and possible therapeutic strategies. Finally, we also discuss how genes, proteins and overlapping signaling pathways affect the molecular etiology of apparently unrelated neuropsychiatric disorders, an understanding of which can offer novel therapeutic strategies.

  3. Noise-induced damage to ribbon synapses without permanent threshold shifts in neonatal mice.

    Science.gov (United States)

    Shi, L; Guo, X; Shen, P; Liu, L; Tao, S; Li, X; Song, Q; Yu, Z; Yin, S; Wang, J

    2015-09-24

    Recently, ribbon synapses to the hair cells (HCs) in the cochlea have become a novel site of interest in the investigation of noise-induced cochlear lesions in adult rodents (Kujawa and Liberman, 2009; Lin et al., 2011; Liu et al., 2012; Shi et al., 2013). Permanent noise-induced damage to this type of synapse can result in subsequent degeneration of spiral ganglion neurons (SGNs) in the absence of permanent changes to hearing sensitivity. To verify whether noise exposure during an early developmental period produces a similar impact on ribbon synapses, the present study examined the damaging effects of noise exposure in neonatal Kunming mice. The animals received exposure to broadband noise at 105-decibel (dB) sound pressure level (SPL) for 2h on either postnatal day 10 (P10d) or postnatal day 14 (P14d), and then hearing function (based on the auditory brainstem response (ABR)) and cochlear morphology were evaluated during either postnatal weeks 3-4 (P4w) or postnatal weeks 7-8 (P8w). There were no significant differences in the hearing threshold between noise-exposed and control animals, which suggests that noise did not cause permanent loss of hearing sensitivity. However, noise exposure did produce a significant loss of ribbon synapses, particularly in P14d mice, which continued to increase from P4w to P8w. Additionally, a corresponding reduction in the amplitude of compound action potential (CAP) was observed in the noise-exposed groups at P4w and P8w, and the CAP latency was elongated, indicating a change in synaptic function. PMID:26232715

  4. Vulnerability-Based Critical Neurons, Synapses, and Pathways in the Caenorhabditis elegans Connectome

    Science.gov (United States)

    Kim, Seongkyun; Kim, Hyoungkyu; Kralik, Jerald D.; Jeong, Jaeseung

    2016-01-01

    Determining the fundamental architectural design of complex nervous systems will lead to significant medical and technological advances. Yet it remains unclear how nervous systems evolved highly efficient networks with near optimal sharing of pathways that yet produce multiple distinct behaviors to reach the organism’s goals. To determine this, the nematode roundworm Caenorhabditis elegans is an attractive model system. Progress has been made in delineating the behavioral circuits of the C. elegans, however, many details are unclear, including the specific functions of every neuron and synapse, as well as the extent the behavioral circuits are separate and parallel versus integrative and serial. Network analysis provides a normative approach to help specify the network design. We investigated the vulnerability of the Caenorhabditis elegans connectome by performing computational experiments that (a) “attacked” 279 individual neurons and 2,990 weighted synaptic connections (composed of 6,393 chemical synapses and 890 electrical junctions) and (b) quantified the effects of each removal on global network properties that influence information processing. The analysis identified 12 critical neurons and 29 critical synapses for establishing fundamental network properties. These critical constituents were found to be control elements—i.e., those with the most influence over multiple underlying pathways. Additionally, the critical synapses formed into circuit-level pathways. These emergent pathways provide evidence for (a) the importance of backward locomotion, avoidance behavior, and social feeding behavior to the organism; (b) the potential roles of specific neurons whose functions have been unclear; and (c) both parallel and serial design elements in the connectome—i.e., specific evidence for a mixed architectural design. PMID:27540747

  5. Fmr1 KO and Fenobam Treatment Differentially Impact Distinct Synapse Populations of Mouse Neocortex

    OpenAIRE

    Wang, Gordon X.; Smith, Stephen J.; MOURRAIN, PHILIPPE

    2014-01-01

    Cognitive deficits in fragile X syndrome (FXS) are attributed to molecular abnormalities of the brain’s vast and heterogeneous synapse populations. Unfortunately, the density of synapses coupled with their molecular heterogeneity presents formidable challenges in understanding the specific contribution of synapse changes in FXS. We demonstrate powerful new methods for the large-scale molecular analysis of individual synapses that allow quantification of numerous specific changes in synapse po...

  6. Synapse- and Stimulus-Specific Local Translation During Long-Term Neuronal Plasticity

    OpenAIRE

    Wang, Dan Ohtan; Kim, Sang Mok; Zhao, Yali; Hwang, Hongik; Miura, Satoru K.; Sossin, Wayne S.; Martin, Kelsey C.

    2009-01-01

    Long-term memory and synaptic plasticity require changes in gene expression and yet can occur in a synapse-specific manner. mRNA localization and regulated translation at synapses are thus critical for establishing synapse specificity. Using live cell microscopy of photoconvertible fluorescent protein translational reporters, we directly visualized local translation at synapses during long-term facilitation of Aplysia sensory-motor synapses. Translation of the reporter required multiple appli...

  7. Daily rhythm of synapse turnover in mouse somatosensory cortex.

    Science.gov (United States)

    Jasinska, Malgorzata; Grzegorczyk, Anna; Jasek, Ewa; Litwin, Jan A; Kossut, Malgorzata; Barbacka-Surowiak, Grazyna; Pyza, Elzbieta

    2014-01-01

    The whisker representations in the somatosensory barrel cortex of mice are modulated by sensory inputs associated with animal motor behavior which shows circadian rhythmicity. In a C57/BL mouse strain kept under a light/dark (LD 12:12) regime, we observed daily structural changes in the barrel cortex, correlated with the locomotor activity level. Stereological analysis of serial electron microscopic sections of the barrel cortex of mice sacrificed during their active or rest period, revealed an increase in the total numerical density of synapses and in the density of excitatory synapses located on dendritic spines during the rest, as well as an increase in the density of inhibitory synapses located on double-synapse spines during the active period. This is the first report demonstrating a daily rhythm in remodeling of the mammalian somatosensory cortex, manifested by changes in the density of synapses and dendritic spines. Moreover, we have found that the excitatory and inhibitory synapses are differently regulated during the day/night cycle. PMID:24718049

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

    Directory of Open Access Journals (Sweden)

    Nawal Zabouri

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

  9. Plant species richness and functional traits affect community stability after a flood event.

    Science.gov (United States)

    Fischer, Felícia M; Wright, Alexandra J; Eisenhauer, Nico; Ebeling, Anne; Roscher, Christiane; Wagg, Cameron; Weigelt, Alexandra; Weisser, Wolfgang W; Pillar, Valério D

    2016-05-19

    Climate change is expected to increase the frequency and magnitude of extreme weather events. It is therefore of major importance to identify the community attributes that confer stability in ecological communities during such events. In June 2013, a flood event affected a plant diversity experiment in Central Europe (Jena, Germany). We assessed the effects of plant species richness, functional diversity, flooding intensity and community means of functional traits on different measures of stability (resistance, resilience and raw biomass changes from pre-flood conditions). Surprisingly, plant species richness reduced community resistance in response to the flood. This was mostly because more diverse communities grew more immediately following the flood. Raw biomass increased over the previous year; this resulted in decreased absolute value measures of resistance. There was no clear response pattern for resilience. We found that functional traits drove these changes in raw biomass: communities with a high proportion of late-season, short-statured plants with dense, shallow roots and small leaves grew more following the flood. Late-growing species probably avoided the flood, whereas greater root length density might have allowed species to better access soil resources brought from the flood, thus growing more in the aftermath. We conclude that resource inputs following mild floods may favour the importance of traits related to resource acquisition and be less associated with flooding tolerance. PMID:27114578

  10. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Maria Carolina Salomé Marquezin

    2015-01-01

    Full Text Available The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child’s psychosocial development.

  11. Aesthetic and functional rehabilitation of the primary dentition affected by amelogenesis imperfecta.

    Science.gov (United States)

    Marquezin, Maria Carolina Salomé; Zancopé, Bruna Raquel; Pacheco, Larissa Ferreira; Gavião, Maria Beatriz Duarte; Pascon, Fernanda Miori

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child's psychosocial development. PMID:25705526

  12. Nonlinear Synapses for Large-Scale Models: An Efficient Representation Enables Complex Synapse Dynamics Modeling in Large-Scale Simulations

    OpenAIRE

    Eric eHu; Jean-Marie Charles Bouteiller; Dong eSong; Michel eBaudry; Theodore W. Berger

    2015-01-01

    Chemical synapses are comprised of a wide collection of intricate signaling pathways involving complex dynamics. These mechanisms are often reduced to simple spikes or exponential representations in order to enable computer simulations at higher spatial levels of complexity. However, these representations cannot capture important nonlinear dynamics found in synaptic transmission. Here, we propose an input-output (IO) synapse model capable of generating complex nonlinear dynamics while maintai...

  13. Metacognitive Awareness of Facial Affect in Higher-Functioning Children and Adolescents with Autism Spectrum Disorder.

    Science.gov (United States)

    McMahon, Camilla M; Henderson, Heather A; Newell, Lisa; Jaime, Mark; Mundy, Peter

    2016-03-01

    Higher-functioning participants with and without autism spectrum disorder (ASD) viewed a series of face stimuli, made decisions regarding the affect of each face, and indicated their confidence in each decision. Confidence significantly predicted accuracy across all participants, but this relation was stronger for participants with typical development than participants with ASD. In the hierarchical linear modeling analysis, there were no differences in face processing accuracy between participants with and without ASD, but participants with ASD were more confident in their decisions. These results suggest that individuals with ASD have metacognitive impairments and are overconfident in face processing. Additionally, greater metacognitive awareness was predictive of better face processing accuracy, suggesting that metacognition may be a pivotal skill to teach in interventions. PMID:26496991

  14. How measurement artifacts affect cerebral autoregulation outcomes: A technical note on transfer function analysis.

    Science.gov (United States)

    Meel-van den Abeelen, Aisha S S; de Jong, Daan L K; Lagro, Joep; Panerai, Ronney B; Claassen, Jurgen A H R

    2016-05-01

    Cerebral autoregulation (CA) is the mechanism that aims to maintain adequate cerebral perfusion during changes in blood pressure (BP). Transfer function analysis (TFA), the most reported method in literature to quantify CA, shows large between-study variability in outcomes. The aim of this study is to investigate the role of measurement artifacts in this variation. Specifically, the role of distortion in the BP and/or CBFV measurementon TFA outcomes was investigated. The influence of three types of artifacts on TFA outcomes was studied: loss of signal, motion artifacts, and baseline drifts. TFA metrics of signals without the simulated artifacts were compared with those of signals with artifacts. TFA outcomes scattered highly when more than 10% of BP signal or over 8% of the CBFV signal was lost, or when measurements contained one or more artifacts resulting from head movement. Furthermore, baseline drift affected interpretation of TFA outcomes when the power in the BP signal was 5 times the power in the LF band. In conclusion, loss of signal in BP and loss in CBFV, affects interpretation of TFA outcomes. Therefore, it is vital to validate signal quality to the defined standards before interpreting TFA outcomes. PMID:26935320

  15. In vitro study on human cytomegalovirus affecting early pregnancy villous EVT's invasion function

    Directory of Open Access Journals (Sweden)

    Juan Xiao

    2011-03-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most common pathogen in uterus during pregnancy, which may lead to some serious results such as miscarriage, stillbirth, cerebellar malformation, fetus developmental retardation, but its pathogenesis has not been fully explained. The hypofunction of extravillous cytotrophoblast (EVT invasion is the essential pathologic base of some complications of pregnancy. c-erbB-2 is a kind of oncogene protein and closely linked with embryogenesis, tissue repair and regeneration. Matrix metalloproteinase (MMP is one of the key enzymes which affect EVT migration and invasion function. The expression level changes of c-erbB-2, MMP-2 and MMP-9 can reflect the changes of EVT invasion function. Results To explore the influence of HCMV on the invasion function of EVT, we tested the protein expression level changes of c-erbB-2, MMP-2 and MMP-9 in villous explant cultured in vitro infected by HCMV, with the use of immunohistochemistry SP method and western blot. We confirmed that HCMV can reproduce and spread in early pregnancy villus; c-erbB-2 protein mainly expressed in normal early pregnancy villous syncytiotrophoblast (ST remote plasma membrane and EVT, especially remote EVT cell membrane in villous stem cell column, little expressed in ST proximal end cell membrane and interstitial cells; MMP-2 protein primarily expressed in early pregnancy villous EVT endochylema and rarely in villous trophoblast (VT, ST and interstitial cells; MMP-9 protein largely expressed in early pregnancy villous mesenchyme, EVT and VT endochylema. Compared with control group, the three kinds of protein expression level in early pregnancy villus of virus group significantly decreased (P Conclusion HCMV can infect villus in vitro and cause the decrease of early pregnancy villous EVT's invasion function.

  16. Macrofauna assemblage composition and soil moisture interact to affect soil ecosystem functions

    Science.gov (United States)

    Collison, E. J.; Riutta, T.; Slade, E. M.

    2013-02-01

    Changing climatic conditions and habitat fragmentation are predicted to alter the soil moisture conditions of temperate forests. It is not well understood how the soil macrofauna community will respond to changes in soil moisture, and how changes to species diversity and community composition may affect ecosystem functions, such as litter decomposition and soil fluxes. Moreover, few studies have considered the interactions between the abiotic and biotic factors that regulate soil processes. Here we attempt to disentangle the interactive effects of two of the main factors that regulate soil processes at small scales - moisture and macrofauna assemblage composition. The response of assemblages of three common temperate soil invertebrates (Glomeris marginata Villers, Porcellio scaber Latreille and Philoscia muscorum Scopoli) to two contrasting soil moisture levels was examined in a series of laboratory mesocosm experiments. The contribution of the invertebrates to the leaf litter mass loss of two common temperate tree species of contrasting litter quality (easily decomposing Fraxinus excelsior L. and recalcitrant Quercus robur L.) and to soil CO2 fluxes were measured. Both moisture conditions and litter type influenced the functioning of the invertebrate assemblages, which was greater in high moisture conditions compared with low moisture conditions and on good quality vs. recalcitrant litter. In high moisture conditions, all macrofauna assemblages functioned at equal rates, whereas in low moisture conditions there were pronounced differences in litter mass loss among the assemblages. This indicates that species identity and assemblage composition are more important when moisture is limited. We suggest that complementarity between macrofauna species may mitigate the reduced functioning of some species, highlighting the importance of maintaining macrofauna species richness.

  17. Synapse function of neuron-like cells differentiated from bone marrow stromal stem cells by rehmannia glutinosa polysaccharide%地黄多糖诱导骨髓间充质干细胞为神经样细胞后的突触功能

    Institute of Scientific and Technical Information of China (English)

    刘宇卓; 王霞; 杜红阳; 包翠芬; 秦书俭

    2013-01-01

    Objective:To study the synapse function of the neuron-like cells induced by rehmannia glutinosa polysaccharide.Methods:The bone marrow strornal stem cells (BMSCs) were cultured and purified by their characteristic of plastic adhesion,then induced by rehmannia glutinosa polysaccharide for 24 hours,and were cultured for 7 days.The membrane potential (MP),Ca2+ influx,synapse function were detected with laser-scanning confocal microscope.Results:BMSCs were induced for 24h,and cultured for 7 days,than neuron-like cells were observed to stretch out bumps and interact into complex network; Immunofluorescence cytochemistry demonstrated that the rate of nestin expression was 97.9%±1.3%,NSE expression 95.4%±1.9% and the synaptophysin expression 94.2% ±2.2%; the neuron-like cells were stimulated with high concentration KCl; the physiology chart showed that the curve rose shapely,Ca2+ influx increased and endocytosis and exocytosis happened.Conclusion:Rehmannia glutinosa polysaccharide can induce BMSCs to differentiate into the neuron-like cells with synaptic function.%目的:探讨地黄多糖诱导大鼠骨髓间充质干细胞(BMSCs)分化为神经元样细胞后是否具有神经突触功能.方法:贴壁筛选法分离纯化BMSCs,地黄多糖进行诱导,激光共聚焦显微镜检测细胞在高钾刺激下细胞膜电位的变化,细胞内钙流变化及细胞突触循环功能.结果:地黄多糖诱导24 h,连续培养7d后,光学显微镜下显示诱导后的细胞伸出突起交互成复杂网状;免疫荧光细胞化学显示诱导后的细胞神经元巢蛋白阳性表达率为97.9%±1.3%,神经元特异性烯醇化酶阳性率95.4%±1.9%,突触小泡蛋白阳性率为94.2%±2.2%;激光共聚焦显微镜显示诱导后细胞在高钾刺激下细胞膜电位迅速升高,细胞内钙离子流增加,细胞突触发生了胞吞胞吐现象.结论:地黄多糖可以诱导BMSCs分化为神经样细胞,此细胞具有神经细胞的神经生理功能.

  18. Chronic Exposure to Bisphenol A Affects Uterine Function During Early Pregnancy in Mice.

    Science.gov (United States)

    Li, Quanxi; Davila, Juanmahel; Kannan, Athilakshmi; Flaws, Jodi A; Bagchi, Milan K; Bagchi, Indrani C

    2016-05-01

    Environmental and occupational exposure to bisphenol A (BPA), a chemical widely used in polycarbonate plastics and epoxy resins, has received much attention in female reproductive health due to its widespread toxic effects. Although BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In this study, we addressed the effect of prolonged exposure to an environmental relevant dose of BPA on embryo implantation and establishment of pregnancy. Our studies revealed that treatment of mice with BPA led to improper endometrial epithelial and stromal functions thus affecting embryo implantation and establishment of pregnancy. Upon further analyses, we found that the expression of progesterone receptor (PGR) and its downstream target gene, HAND2 (heart and neural crest derivatives expressed 2), was markedly suppressed in BPA-exposed uterine tissues. Previous studies have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor and the MAPK signaling pathways and inhibiting epithelial proliferation. Interestingly, we observed that down-regulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with enhanced activation of fibroblast growth factor and MAPK signaling in the epithelium, thus contributing to aberrant proliferation and lack of uterine receptivity. Further, the differentiation of endometrial stromal cells to decidual cells, an event critical for the establishment and maintenance of pregnancy, was severely compromised in response to BPA. In summary, our studies revealed that chronic exposure to BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy. PMID:27022677

  19. Role of primary afferents in the developmental regulation of motor axon synapse numbers on Renshaw cells.

    Science.gov (United States)

    Siembab, Valerie C; Gomez-Perez, Laura; Rotterman, Travis M; Shneider, Neil A; Alvarez, Francisco J

    2016-06-15

    Motor function in mammalian species depends on the maturation of spinal circuits formed by a large variety of interneurons that regulate motoneuron firing and motor output. Interneuron activity is in turn modulated by the organization of their synaptic inputs, but the principles governing the development of specific synaptic architectures unique to each premotor interneuron are unknown. For example, Renshaw cells receive, at least in the neonate, convergent inputs from sensory afferents (likely Ia) and motor axons, raising the question of whether they interact during Renshaw cell development. In other well-studied neurons, such as Purkinje cells, heterosynaptic competition between inputs from different sources shapes synaptic organization. To examine the possibility that sensory afferents modulate synaptic maturation on developing Renshaw cells, we used three animal models in which afferent inputs in the ventral horn are dramatically reduced (ER81(-/-) knockout), weakened (Egr3(-/-) knockout), or strengthened (mlcNT3(+/-) transgenic). We demonstrate that increasing the strength of sensory inputs on Renshaw cells prevents their deselection and reduces motor axon synaptic density, and, in contrast, absent or diminished sensory afferent inputs correlate with increased densities of motor axons synapses. No effects were observed on other glutamatergic inputs. We conclude that the early strength of Ia synapses influences their maintenance or weakening during later development and that heterosynaptic influences from sensory synapses during early development regulates the density and organization of motor inputs on mature Renshaw cells. J. Comp. Neurol. 524:1892-1919, 2016. © 2016 Wiley Periodicals, Inc. PMID:26660356

  20. Specific disruption of hippocampal mossy fiber synapses in a mouse model of familial Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Scott A Wilke

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

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

    Directory of Open Access Journals (Sweden)

    Zhongqiang eWang

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Richard eMiles

    2014-01-01

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

  3. Physical Realization of a Supervised Learning System Built with Organic Memristive Synapses

    Science.gov (United States)

    Lin, Yu-Pu; Bennett, Christopher H.; Cabaret, Théo; Vodenicarevic, Damir; Chabi, Djaafar; Querlioz, Damien; Jousselme, Bruno; Derycke, Vincent; Klein, Jacques-Olivier

    2016-01-01

    Multiple modern applications of electronics call for inexpensive chips that can perform complex operations on natural data with limited energy. A vision for accomplishing this is implementing hardware neural networks, which fuse computation and memory, with low cost organic electronics. A challenge, however, is the implementation of synapses (analog memories) composed of such materials. In this work, we introduce robust, fastly programmable, nonvolatile organic memristive nanodevices based on electrografted redox complexes that implement synapses thanks to a wide range of accessible intermediate conductivity states. We demonstrate experimentally an elementary neural network, capable of learning functions, which combines four pairs of organic memristors as synapses and conventional electronics as neurons. Our architecture is highly resilient to issues caused by imperfect devices. It tolerates inter-device variability and an adaptable learning rule offers immunity against asymmetries in device switching. Highly compliant with conventional fabrication processes, the system can be extended to larger computing systems capable of complex cognitive tasks, as demonstrated in complementary simulations. PMID:27601088

  4. Physical Realization of a Supervised Learning System Built with Organic Memristive Synapses.

    Science.gov (United States)

    Lin, Yu-Pu; Bennett, Christopher H; Cabaret, Théo; Vodenicarevic, Damir; Chabi, Djaafar; Querlioz, Damien; Jousselme, Bruno; Derycke, Vincent; Klein, Jacques-Olivier

    2016-01-01

    Multiple modern applications of electronics call for inexpensive chips that can perform complex operations on natural data with limited energy. A vision for accomplishing this is implementing hardware neural networks, which fuse computation and memory, with low cost organic electronics. A challenge, however, is the implementation of synapses (analog memories) composed of such materials. In this work, we introduce robust, fastly programmable, nonvolatile organic memristive nanodevices based on electrografted redox complexes that implement synapses thanks to a wide range of accessible intermediate conductivity states. We demonstrate experimentally an elementary neural network, capable of learning functions, which combines four pairs of organic memristors as synapses and conventional electronics as neurons. Our architecture is highly resilient to issues caused by imperfect devices. It tolerates inter-device variability and an adaptable learning rule offers immunity against asymmetries in device switching. Highly compliant with conventional fabrication processes, the system can be extended to larger computing systems capable of complex cognitive tasks, as demonstrated in complementary simulations. PMID:27601088

  5. Temporal dynamics in an immunological synapse: Role of thermal fluctuations in signaling

    Science.gov (United States)

    Bush, Daniel R.; Chattopadhyay, Amit K.

    2015-07-01

    The article analyzes the contribution of stochastic thermal fluctuations in the attachment times of the immature T-cell receptor TCR: peptide-major-histocompatibility-complex pMHC immunological synapse bond. The key question addressed here is the following: how does a synapse bond remain stabilized in the presence of high-frequency thermal noise that potentially equates to a strong detaching force? Focusing on the average time persistence of an immature synapse, we show that the high-frequency nodes accompanying large fluctuations are counterbalanced by low-frequency nodes that evolve over longer time periods, eventually leading to signaling of the immunological synapse bond primarily decided by nodes of the latter type. Our analysis shows that such a counterintuitive behavior could be easily explained from the fact that the survival probability distribution is governed by two distinct phases, corresponding to two separate time exponents, for the two different time regimes. The relatively shorter timescales correspond to the cohesion:adhesion induced immature bond formation whereas the larger time reciprocates the association:dissociation regime leading to TCR:pMHC signaling. From an estimate of the bond survival probability, we show that, at shorter timescales, this probability PΔ(τ ) scales with time τ as a universal function of a rescaled noise amplitude D/Δ2, such that PΔ(τ ) ˜τ-(Δ/√{D }+1/2 ) ,Δ being the distance from the mean intermembrane (T cell:Antigen Presenting Cell) separation distance. The crossover from this shorter to a longer time regime leads to a universality in the dynamics, at which point the survival probability shows a different power-law scaling compared to the one at shorter timescales. In biological terms, such a crossover indicates that the TCR:pMHC bond has a survival probability with a slower decay rate than the longer LFA-1:ICAM-1 bond justifying its stability.

  6. Anatomically Detailed and Large-Scale Simulations Studying Synapse Loss and Synchrony Using NeuroBox.

    Science.gov (United States)

    Breit, Markus; Stepniewski, Martin; Grein, Stephan; Gottmann, Pascal; Reinhardt, Lukas; Queisser, Gillian

    2016-01-01

    The morphology of neurons and networks plays an important role in processing electrical and biochemical signals. Based on neuronal reconstructions, which are becoming abundantly available through databases such as NeuroMorpho.org, numerical simulations of Hodgkin-Huxley-type equations, coupled to biochemical models, can be performed in order to systematically investigate the influence of cellular morphology and the connectivity pattern in networks on the underlying function. Development in the area of synthetic neural network generation and morphology reconstruction from microscopy data has brought forth the software tool NeuGen. Coupling this morphology data (either from databases, synthetic, or reconstruction) to the simulation platform UG 4 (which harbors a neuroscientific portfolio) and VRL-Studio, has brought forth the extendible toolbox NeuroBox. NeuroBox allows users to perform numerical simulations on hybrid-dimensional morphology representations. The code basis is designed in a modular way, such that e.g., new channel or synapse types can be added to the library. Workflows can be specified through scripts or through the VRL-Studio graphical workflow representation. Third-party tools, such as ImageJ, can be added to NeuroBox workflows. In this paper, NeuroBox is used to study the electrical and biochemical effects of synapse loss vs. synchrony in neurons, to investigate large morphology data sets within detailed biophysical simulations, and used to demonstrate the capability of utilizing high-performance computing infrastructure for large scale network simulations. Using new synapse distribution methods and Finite Volume based numerical solvers for compartment-type models, our results demonstrate how an increase in synaptic synchronization can compensate synapse loss at the electrical and calcium level, and how detailed neuronal morphology can be integrated in large-scale network simulations. PMID:26903818

  7. Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus.

    Science.gov (United States)

    Kitahara, Yosuke; Ohta, Keisuke; Hasuo, Hiroshi; Shuto, Takahide; Kuroiwa, Mahomi; Sotogaku, Naoki; Togo, Akinobu; Nakamura, Kei-ichiro; Nishi, Akinori

    2016-01-01

    A selective serotonin reuptake inhibitor is the most commonly prescribed antidepressant for the treatment of major depression. However, the mechanisms underlying the actions of selective serotonin reuptake inhibitors are not fully understood. In the dentate gyrus, chronic fluoxetine treatment induces increased excitability of mature granule cells (GCs) as well as neurogenesis. The major input to the dentate gyrus is the perforant path axons (boutons) from the entorhinal cortex (layer II). Through voltage-sensitive dye imaging, we found that the excitatory neurotransmission of the perforant path synapse onto the GCs in the middle molecular layer of the mouse dentate gyrus (perforant path-GC synapse) is enhanced after chronic fluoxetine treatment (15 mg/kg/day, 14 days). Therefore, we further examined whether chronic fluoxetine treatment affects the morphology of the perforant path-GC synapse, using FIB/SEM (focused ion beam/scanning electron microscopy). A three-dimensional reconstruction of dendritic spines revealed the appearance of extremely large-sized spines after chronic fluoxetine treatment. The large-sized spines had a postsynaptic density with a large volume. However, chronic fluoxetine treatment did not affect spine density. The presynaptic boutons that were in contact with the large-sized spines were large in volume, and the volumes of the mitochondria and synaptic vesicles inside the boutons were correlated with the size of the boutons. Thus, the large-sized perforant path-GC synapse induced by chronic fluoxetine treatment contains synaptic components that correlate with the synapse size and that may be involved in enhanced glutamatergic neurotransmission. PMID:26788851

  8. Key soil functional properties affected by soil organic matter - evidence from published literature

    Science.gov (United States)

    Murphy, Brian

    2015-07-01

    The effect of varying the amount of soil organic matter on a range of individual soil properties was investigated using a literature search of published information largely from Australia, but also included relevant information from overseas. Based on published pedotransfer functions, soil organic matter was shown to increase plant available water by 2 to 3 mm per 10 cm for each 1% increase in soil organic carbon, with the largest increases being associated with sandy soils. Aggregate stability increased with increasing soil organic carbon, with aggregate stability decreasing rapidly when soil organic carbon fell below 1.2 to 1.5 5%. Soil compactibility, friability and soil erodibility were favourably improved by increasing the levels of soil organic carbon. Nutrient cycling was a major function of soil organic matter. Substantial amounts of N, P and S become available to plants when the soil organic matter is mineralised. Soil organic matter also provides a food source for the microorganisms involved in the nutrient cycling of N, P, S and K. In soils with lower clay contents, and less active clays such as kaolinites, soil organic matter can supply a significant amount of the cation exchange capacity and buffering capacity against acidification. Soil organic matter can have a cation exchange capacity of 172 to 297 cmol(+)/kg. As the cation exchange capacity of soil organic matter varies with pH, the effectiveness of soil organic matter to contribute to cation exchange capacity below pH 5.5 is often minimal. Overall soil organic matter has the potential to affect a range of functional soil properties.

  9. PARP1 gene knock-out increases resistance to retinal degeneration without affecting retinal function.

    Directory of Open Access Journals (Sweden)

    Ayse Sahaboglu

    Full Text Available Retinitis pigmentosa (RP is a group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness in humans. Previously, excessive activation of enzymes belonging to the poly-ADP-ribose polymerase (PARP group was shown to be involved in photoreceptor degeneration in the human homologous rd1 mouse model for RP. Since there are at least 16 different PARP isoforms, we investigated the exact relevance of the predominant isoform - PARP1 - for photoreceptor cell death using PARP1 knock-out (KO mice. In vivo and ex vivo morphological analysis using optic coherence tomography (OCT and conventional histology revealed no major alterations of retinal phenotype when compared to wild-type (wt. Likewise, retinal function as assessed by electroretinography (ERG was normal in PARP1 KO animals. We then used retinal explant cultures derived from wt, rd1, and PARP1 KO animals to test their susceptibility to chemically induced photoreceptor degeneration. Since photoreceptor degeneration in the rd1 retina is triggered by a loss-of-function in phosphodiesterase-6 (PDE6, we used selective PDE6 inhibition to emulate the rd1 situation on non-rd1 genotypes. While wt retina subjected to PDE6 inhibition showed massive photoreceptor degeneration comparable to rd1 retina, in the PARP1 KO situation, cell death was robustly reduced. Together, these findings demonstrate that PARP1 activity is in principle dispensable for normal retinal function, but is of major importance for photoreceptor degeneration under pathological conditions. Moreover, our results suggest that PARP dependent cell death or PARthanatos may play a major role in retinal degeneration and highlight the possibility to use specific PARP inhibitors for the treatment of RP.

  10. Sensory integration dysfunction affects efficacy of speech therapy on children with functional articulation disorders

    Directory of Open Access Journals (Sweden)

    Tung LC

    2013-01-01

    = 70.393; P > 0.001 and interaction between the pre/post speech therapy treatment and groups (F = 11.119; P = 0.002.Conclusions: Speech therapy can improve the articulation performance of children who have functional articulation disorders whether or not they have SID, but it results in significantly greater improvement in children without SID. SID may affect the treatment efficiency of speech therapy in young children with articulation disorders.Keywords: children, functional articulation disorders, sensory integration dysfunction, speech therapy, efficacy

  11. Cationic influences upon synaptic transmission at the hair cell-afferent fiber synapse of the frog

    Science.gov (United States)

    Cochran, S. L.

    1995-01-01

    vertebrate neuromuscular junction. The major differences between these two synapses are the neurotransmitters and the higher resting release rate and higher sensitivity of release to increased K+ concentrations of the hair cells over that of motor nerve terminals. These differences reflect the functional roles of the two synapses: the motor nerve terminal response in an all-or-nothing signal consequent from action potential invasion, while the hair cell releases transmitter in a graded fashion, proportionate to the extent of stereocilial deflection. Despite these differences between the two junctions, the similar actions of these elemental cations upon synaptic function at each implies that these ions may participate similarly in the operations of other synapses, independent of the neurotransmitter type.(ABSTRACT TRUNCATED AT 400 WORDS).

  12. Structure-mechanical function relations at nano-scale in heat-affected human dental tissue.

    Science.gov (United States)

    Sui, Tan; Sandholzer, Michael A; Le Bourhis, Eric; Baimpas, Nikolaos; Landini, Gabriel; Korsunsky, Alexander M

    2014-04-01

    The knowledge of the mechanical properties of dental materials related to their hierarchical structure is essential for understanding and predicting the effect of microstructural alterations on the performance of dental tissues in the context of forensic and archaeological investigation as well as laser irradiation treatment of caries. So far, few studies have focused on the nano-scale structure-mechanical function relations of human teeth altered by chemical or thermal treatment. The response of dental tissues to thermal treatment is thought to be strongly affected by the mineral crystallite size, their spatial arrangement and preferred orientation. In this study, synchrotron-based small and wide angle X-ray scattering (SAXS/WAXS) techniques were used to investigate the micro-structural alterations (mean crystalline thickness, crystal perfection and degree of alignment) of heat-affected dentine and enamel in human dental teeth. Additionally, nanoindentation mapping was applied to detect the spatial and temperature-dependent nano-mechanical properties variation. The SAXS/WAXS results revealed that the mean crystalline thickness distribution in dentine was more uniform compared with that in enamel. Although in general the mean crystalline thickness increased both in dentine and enamel as the temperature increased, the local structural variations gradually reduced. Meanwhile, the hardness and reduced modulus in enamel decreased as the temperature increased, while for dentine, the tendency reversed at high temperature. The analysis of the correlation between the ultrastructure and mechanical properties coupled with the effect of temperature demonstrates the effect of mean thickness and orientation on the local variation of mechanical property. This structural-mechanical property alteration is likely to be due to changes of HAp crystallites, thus dentine and enamel exhibit different responses at different temperatures. Our results enable an improved understanding of

  13. Accelerated intoxication of GABAergic synapses by botulinum neurotoxin A disinhibits stem cell-derived neuron networks prior to network silencing

    Directory of Open Access Journals (Sweden)

    Phillip H Beske

    2015-04-01

    Full Text Available Botulinum neurotoxins (BoNTs are extremely potent toxins that specifically cleave SNARE proteins in peripheral synapses, preventing neurotransmitter release. Neuronal responses to BoNT intoxication are traditionally studied by quantifying SNARE protein cleavage in vitro or monitoring physiological paralysis in vivo. Consequently, the dynamic effects of intoxication on synaptic behaviors are not well understood. We have reported that mouse embryonic stem cell-derived neurons (ESNs are highly sensitive to BoNT based on molecular readouts of intoxication. Here we study the time-dependent changes in synapse- and network-level behaviors following addition of BoNT/A to spontaneously active networks of glutamatergic and GABAergic ESNs. Whole-cell patch-clamp recordings indicated that BoNT/A rapidly blocked synaptic neurotransmission, confirming that ESNs replicate the functional pathophysiology responsible for clinical botulism. Quantitation of spontaneous neurotransmission in pharmacologically isolated synapses revealed accelerated silencing of GABAergic synapses compared to glutamatergic synapses, which was consistent with the selective accumulation of cleaved SNAP-25 at GAD1+ presynaptic terminals at early timepoints. Different latencies of intoxication resulted in complex network responses to BoNT/A addition, involving rapid disinhibition of stochastic firing followed by network silencing. Synaptic activity was found to be highly sensitive to SNAP-25 cleavage, reflecting the functional consequences of the localized cleavage of the small subpopulation of SNAP-25 that is engaged in neurotransmitter release in the nerve terminal. Collectively these findings illustrate that use of synaptic function assays in networked neurons cultures offers a novel and highly sensitive approach for mechanistic studies of toxin:neuron interactions and synaptic responses to BoNT.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Effects of propofol on glycinergic neurotransmission in a single spinal nerve synapse preparation.

    Science.gov (United States)

    Wakita, Masahito; Kotani, Naoki; Akaike, Norio

    2016-01-15

    The effects of the intravenous anesthetic, propofol, on glycinergic transmission and on glycine receptor-mediated whole-cell currents (IGly) were examined in the substantia gelatinosa (SG) neuronal cell body, mechanically dissociated from the rat spinal cord. This "synaptic bouton" preparation, which retains functional native nerve endings, allowed us to evaluate glycinergic inhibitory postsynaptic currents (IPSCs) and whole-cell currents in a preparation in which experimental solution could rapidly access synaptic terminals. Synaptic IPSCs were measured as spontaneous (s) and evoked (e) IPSCs. The eIPSCs were elicited by applying paired-pulse focal electrical stimulation, while IGly was evoked by a bath application of glycine. A concentration-dependent enhancement of IGly was observed for ≥10µM propofol. Propofol (≥3µM) significantly increased the frequency of sIPSCs and prolonged the decay time without altering the current amplitude. However, propofol (≥3µM) also significantly increased the mean amplitude of eIPSCs and decreased the failure rate (Rf). A decrease in the paired-pulse ratio (PPR) was noted at higher concentrations (≥10µM). The decay time of eIPSCs was prolonged only at the maximum concentration tested (30µM). Propofol thus acts at both presynaptic glycine release machinery and postsynaptic glycine receptors. At clinically relevant concentrations (<1μM) there was no effect on IGly, sIPSCs or eIPSCs suggesting that at anesthetic doses propofol does not affect inhibitory glycinergic synapses in the spinal cord. PMID:26616339

  16. How the type of input function affects the dynamic response of conducting polymer actuators

    International Nuclear Information System (INIS)

    There has been a growing interest in smart actuators typified by conducting polymer actuators, especially in their (i) fabrication, modeling and control with minimum external data and (ii) applications in bio-inspired devices, robotics and mechatronics. Their control is a challenging research problem due to the complex and nonlinear properties of these actuators, which cannot be predicted accurately. Based on an input-shaping technique, we propose a new method to improve the conducting polymer actuators’ command-following ability, while minimizing their electric power consumption. We applied four input functions with smooth characteristics to a trilayer conducting polymer actuator to experimentally evaluate its command-following ability under an open-loop control strategy and a simulated feedback control strategy, and, more importantly, to quantify how the type of input function affects the dynamic response of this class of actuators. We have found that the four smooth inputs consume less electrical power than sharp inputs such as a step input with discontinuous higher-order derivatives. We also obtained an improved transient response performance from the smooth inputs, especially under the simulated feedback control strategy, which we have proposed previously [X Xiang, R Mutlu, G Alici, and W Li, 2014 “Control of conducting polymer actuators without physical feedback: simulated feedback control approach with particle swarm optimization’, Journal of Smart Materials and Structure, 23]. The idea of using a smooth input command, which results in lower power consumption and better control performance, can be extended to other smart actuators. Consuming less electrical energy or power will have a direct effect on enhancing the operational life of these actuators. (paper)

  17. How the type of input function affects the dynamic response of conducting polymer actuators

    Science.gov (United States)

    Xiang, Xingcan; Alici, Gursel; Mutlu, Rahim; Li, Weihua

    2014-10-01

    There has been a growing interest in smart actuators typified by conducting polymer actuators, especially in their (i) fabrication, modeling and control with minimum external data and (ii) applications in bio-inspired devices, robotics and mechatronics. Their control is a challenging research problem due to the complex and nonlinear properties of these actuators, which cannot be predicted accurately. Based on an input-shaping technique, we propose a new method to improve the conducting polymer actuators’ command-following ability, while minimizing their electric power consumption. We applied four input functions with smooth characteristics to a trilayer conducting polymer actuator to experimentally evaluate its command-following ability under an open-loop control strategy and a simulated feedback control strategy, and, more importantly, to quantify how the type of input function affects the dynamic response of this class of actuators. We have found that the four smooth inputs consume less electrical power than sharp inputs such as a step input with discontinuous higher-order derivatives. We also obtained an improved transient response performance from the smooth inputs, especially under the simulated feedback control strategy, which we have proposed previously [X Xiang, R Mutlu, G Alici, and W Li, 2014 “Control of conducting polymer actuators without physical feedback: simulated feedback control approach with particle swarm optimization’, Journal of Smart Materials and Structure, 23]. The idea of using a smooth input command, which results in lower power consumption and better control performance, can be extended to other smart actuators. Consuming less electrical energy or power will have a direct effect on enhancing the operational life of these actuators.

  18. Role of Affective Self-Regulatory Efficacy in Diverse Spheres of Psychosocial Functioning.

    Science.gov (United States)

    Bandura, Albert; Caprara, Gian Vittorio; Barbaranelli, Claudio; Gerbino, Maria; Pastorelli, Concetta

    2003-01-01

    Examined influence of perceived self-efficacy for affect regulation with older adolescents. Found that self-efficacy to regulate affect related to high efficacy to manage academic development, resist social pressures for antisocial activities, and engage with empathy in others' emotional experiences. Perceived self-efficacy for affect regulation…

  19. Novel function of perforin in negatively regulating CD4+T cell activation by affecting calcium signaling

    Institute of Scientific and Technical Information of China (English)

    Enguang Bi; Kairui Mao; Jia Zou; Yuhan Zheng; Bing Sun; Chunjian Huang; Yu Hu; Xiaodong Wu; Weiwen Deng; Guomei Lin; Zhiduo Liu; Lin Tian; Shuhui Sun

    2009-01-01

    Perforin is a pore-forming protein engaged mainly in mediating target T cell death and is employed by cytotoxic Tlymphocytes (CTLs) and natural killer cells. However, whether it also plays a role in conventional CD4+ T cell func-tion remains unclear. Here we report that in perforin-deficient (PKO) mice, CD4+ T cells are hyperproliferative in response to T cell receptor (TCR) stimulation. This feature of hyperproliferation is accompanied by the enhancement both in cell division and in IL-2 secretion. It seems that the perforin deficiency does not influence T cell development in thymus spleen and lymph node. In vivo, perforin deficiency results in increased antigen-specific T cell prolifera-tion and antibody production. Furthermore, PKO mice are more susceptible to experimental autoimmune uveitis. To address the molecular mechanism, we found that after TCR stimulation, CD44 T cells from PKO mice display an increased intracellular calcium flux and subsequently enhance activation of transcription factor NFATI. Our results indicate that perforin plays a negative role in regulating CD4+ T cell activation and immune response by affecting TCR-dependent Ca2+ signaling.

  20. Identification of archaeal proteins that affect the exosome function in vitro

    Directory of Open Access Journals (Sweden)

    Palhano Fernando L

    2010-05-01

    Full Text Available Abstract Background The archaeal exosome is formed by a hexameric RNase PH ring and three RNA binding subunits and has been shown to bind and degrade RNA in vitro. Despite extensive studies on the eukaryotic exosome and on the proteins interacting with this complex, little information is yet available on the identification and function of archaeal exosome regulatory factors. Results Here, we show that the proteins PaSBDS and PaNip7, which bind preferentially to poly-A and AU-rich RNAs, respectively, affect the Pyrococcus abyssi exosome activity in vitro. PaSBDS inhibits slightly degradation of a poly-rA substrate, while PaNip7 strongly inhibits the degradation of poly-A and poly-AU by the exosome. The exosome inhibition by PaNip7 appears to depend at least partially on its interaction with RNA, since mutants of PaNip7 that no longer bind RNA, inhibit the exosome less strongly. We also show that FITC-labeled PaNip7 associates with the exosome in the absence of substrate RNA. Conclusions Given the high structural homology between the archaeal and eukaryotic proteins, the effect of archaeal Nip7 and SBDS on the exosome provides a model for an evolutionarily conserved exosome control mechanism.

  1. Fish functional traits are affected by hydrodynamics at small spatial scale.

    Science.gov (United States)

    Bracciali, C; Guzzo, G; Giacoma, C; Dean, J M; Sarà, G

    2016-02-01

    The Mediterranean damselfish Chromis chromis is a species with a broad distribution found both in the Mediterranean Sea and Eastern Atlantic as far south as the coast of Angola. We hypothesized that the species may have significant functional morphological plasticity to adapt along a gradient of environmental conditions. It is a non-migratory zooplanktivorous species and spends the daytime searching for food in the middle of the water column. Therefore, local hydrodynamics could be one of the environmental factors affecting traits of C. chromis with repercussions at the population level. We compared the body condition, individual growth and body shapes of damselfish collected under two different hydrodynamic conditions (low ∼10 cm s(-1) vs. high ∼20 cm s(-1)). Specimens showed higher body condition under high-hydrodynamics, where conditions offered greater amounts of food, which were able to support larger individuals. Individuals smaller than 60-mm were more abundant under low-hydrodynamics. Morphometric analysis revealed that high-hydrodynamics were favored by fish with a more fusiform body shape and body traits developed for propellant swimming. PMID:26707883

  2. 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.

  3. 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.

  4. GABABR-Dependent Long-Term Depression at Hippocampal Synapses between CB1-Positive Interneurons and CA1 Pyramidal Cells.

    Science.gov (United States)

    Jappy, Dave; Valiullina, Fliza; Draguhn, Andreas; Rozov, Andrei

    2016-01-01

    Activity induced long lasting modifications of synaptic efficacy have been extensively studied in excitatory synapses, however, long term plasticity is also a property of inhibitory synapses. Inhibitory neurons in the hippocampal CA1 region can be subdivided according to the compartment they target on the pyramidal cell. Some interneurons preferentially innervate the perisomatic area and axon hillock of the pyramidal cells while others preferentially target dendritic branches and spines. Another characteristic feature allowing functional classification of interneurons is cell type specific expression of different neurochemical markers and receptors. In the hippocampal CA1 region, nearly 90% of the interneurons expressing cannabinoid type 1 receptors (CB1R) also express cholecystokinin (CCK). Therefore, the functional presence of CB1 receptors can be used for identification of the inhibitory input from CCK positive (CCK+) interneurons to CA1 pyramidal cells. The goal of this study was to explore the nature of long term plasticity at the synapses between interneurons expressing CB1Rs (putative CCK+) and pyramidal neurons in the CA1 region of the hippocampus in vitro. We found that theta burst stimulation triggered robust long-term depression (LTD) at this synapse. The locus of LTD induction was postsynaptic and required activation of GABAB receptors. We also showed that LTD at this synaptic connection involves GABABR-dependent suppression of adenylyl cyclase and consequent reduction of PKA activity. In this respect, CB1+ to pyramidal cell synapses differ from the majority of the other hippocampal inhibitory connections where theta burst stimulation results in long-term potentiation. PMID:26858602

  5. 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.

  6. Meet the players: local translation at the synapse

    Directory of Open Access Journals (Sweden)

    Michael A Kiebler

    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.

  7. 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.

  8. The Relationship between Sleep-Wake Cycle and Cognitive Functioning in Young People with Affective Disorders

    OpenAIRE

    Carpenter, Joanne S.; Rébecca Robillard; Rico S C Lee; Hermens, Daniel F.; Naismith, Sharon L.; Django White; Bradley Whitwell; Scott, Elizabeth M; Ian B Hickie

    2015-01-01

    Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disord...

  9. Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.

    Science.gov (United States)

    Thibault, Dominic; Giguère, Nicolas; Loustalot, Fabien; Bourque, Marie-Josée; Ducrot, Charles; El Mestikawy, Salah; Trudeau, Louis-Éric

    2016-05-01

    Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit. PMID:25782435

  10. Functional SNP in stem of mir-146a affects Her2 status and breast cancer survival.

    Science.gov (United States)

    Meshkat, Mahboobeh; Tanha, Hamzeh Mesrian; Naeini, Marjan Mojtabavi; Ghaedi, Kamran; Sanati, Mohammad H; Meshkat, Marzieh; Bagheri, Fatemeh

    2016-07-01

    In-silico investigation suggested a common variant within stem of miR-146a-5p precursor (rs2910164, n.60C>G) associated with breast cancer (BC) phenotypes. Our aim was computationally predicting possible targets of miR-146a-5p and probable rs2910164 mechanism of action in expression of phenotypes in BC. Additionally, a case-control study was designated to examine experimentally the correlation of mir-146a rs2910164 variant and BC phenotypes. In this study, 152 BC subjects and healthy controls were genotyped using RFLP-PCR. Allelic and genotypic association and Armitage's trend tests were run to investigate the correlation between the alleles and genotypes and expressed phenotypes of BC. Bioinformatics analyses introduce regulatory function of miR-146a-5p in numerous signaling pathways and impact of allele substitution upon mir-146a stem-loop stability. Logistic regression data represented the C allele of rs2910164 (OR = 4.00, p= 0.0037) as the risk allele and associated with Her2-positive phenotype. In a similar vein, data revealed the correlation of the C allele and cancer death less than two years in BC patients (OR = 2.65, p= 0.0217). Ultimately, unconditional logistical regression models suggested log-additive model for inheritance manner of rs2910164 in either Her2 status or BC survival (OR = 5.64, p= 0.0025 and OR = 3.13, p= 0.019, respectively). Using bioinformatics connected association of Her2 status to altered function of miR-146a-5p in regulation of focal adhesion and Ras pathway. Furthermore, computations inferred the association between death phenotype and studied SNP upon specific target genes of miR-146a-5p involved in focal adhesion, EGF receptor, Ras, ErbB, interleukin, Toll-like receptor, NGF, angiogenesis, and p53 feedback loops 2 signaling pathways. These verdicts may enhance our perceptions of how mir-146a rs2910164 affect expressed phenotypes in BC, and might have potential implications to develop BC treatment in future. PMID:27434289

  11. Land-use systems affect Archaeal community structure and functional diversity in western Amazon soils

    Directory of Open Access Journals (Sweden)

    Acácio Aparecido Navarrete

    2011-10-01

    Full Text Available The study of the ecology of soil microbial communities at relevant spatial scales is primordial in the wide Amazon region due to the current land use changes. In this study, the diversity of the Archaea domain (community structure and ammonia-oxidizing Archaea (richness and community composition were investigated using molecular biology-based techniques in different land-use systems in western Amazonia, Brazil. Soil samples were collected in two periods with high precipitation (March 2008 and January 2009 from Inceptisols under primary tropical rainforest, secondary forest (5-20 year old, agricultural systems of indigenous people and cattle pasture. Denaturing gradient gel electrophoresis of polymerase chain reaction-amplified DNA (PCR-DGGE using the 16S rRNA gene as a biomarker showed that archaeal community structures in crops and pasture soils are different from those in primary forest soil, which is more similar to the community structure in secondary forest soil. Sequence analysis of excised DGGE bands indicated the presence of crenarchaeal and euryarchaeal organisms. Based on clone library analysis of the gene coding the subunit of the enzyme ammonia monooxygenase (amoA of Archaea (306 sequences, the Shannon-Wiener function and Simpson's index showed a greater ammonia-oxidizing archaeal diversity in primary forest soils (H' = 2.1486; D = 0.1366, followed by a lower diversity in soils under pasture (H' = 1.9629; D = 0.1715, crops (H' = 1.4613; D = 0.3309 and secondary forest (H' = 0.8633; D = 0.5405. All cloned inserts were similar to the Crenarchaeota amoA gene clones (identity > 95 % previously found in soils and sediments and distributed primarily in three major phylogenetic clusters. The findings indicate that agricultural systems of indigenous people and cattle pasture affect the archaeal community structure and diversity of ammonia-oxidizing Archaea in western Amazon soils.

  12. The Pathophysiology of Fragile X (and What It Teaches Us about Synapses)

    OpenAIRE

    Bhakar, Asha L.; Dölen, Gül; Bear, Mark F.

    2012-01-01

    Fragile X is the most common known inherited cause of intellectual disability and autism, and it typically results from transcriptional silencing of FMR1 and loss of the encoded protein, FMRP (fragile X mental retardation protein). FMRP is an mRNA-binding protein that functions at many synapses to inhibit local translation stimulated by metabotropic glutamate receptors (mGluRs) 1 and 5. Recent studies on the biology of FMRP and the signaling pathways downstream of mGluR1/5 have yielded deeper...

  13. Chronic desipramine prevents acute stress-induced reorganization of medial prefrontal cortex architecture by blocking glutamate vesicle accumulation and excitatory synapse increase

    DEFF Research Database (Denmark)

    Nava, Nicoletta; Treccani, Giulia; Liebenberg, Nico;

    2014-01-01

    acute foot-shock (FS)-stress. By means of serial section electron microscopy, the structural remodeling of medial prefrontal cortex (mPFC) glutamate synapses was assessed soon after acute stressor cessation and stress hormone levels were measured. FS-stress induced a remarkable increase in the number of...... docked vesicles and small excitatory synapses, partially and strongly prevented by DMI pretreatment, respectively. Acute stress-induced corticosterone elevation was not affected by drug treatment. Since DMI pretreatment prevented the stress-induced structural plasticity but not the hormone level increase...

  14. No longer falling on deaf ears: mechanisms of degeneration and regeneration of cochlear ribbon synapses.

    Science.gov (United States)

    Wan, Guoqiang; Corfas, Gabriel

    2015-11-01

    Cochlear ribbon synapses are required for the rapid and precise neural transmission of acoustic signals from inner hair cells to the spiral ganglion neurons. Emerging evidence suggests that damage to these synapses represents an important form of cochlear neuropathy that might be highly prevalent in sensorineural hearing loss. In this review, we discuss our current knowledge on how ribbon synapses are damaged by noise and during aging, as well as potential strategies to promote ribbon synapse regeneration for hearing restoration. PMID:25937135

  15. A strategic analysis of synapse and Canada health infoway’s electronic health record solution blueprint

    OpenAIRE

    Labrosse, Chadwick Andre

    2007-01-01

    Synapse is a currently deployed software application that collects and presents clinical and administrative information about Mental Health & Addictions patients, in the form of an Electronic Health Record (EHR). Synapse was jointly developed by regional health authorities, federal and provincial governments and research institutions. While Synapse has enjoyed limited regional success in British Columbia, the Synapse Project Steering Committee seeks to expand its adoption with clinicians ...

  16. Cadherin-9 Regulates Synapse-Specific Differentiation in the Developing Hippocampus

    OpenAIRE

    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

    2011-01-01

    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 downre...

  17. Predicting the Accuracy of Facial Affect Recognition: The Interaction of Child Maltreatment and Intellectual Functioning

    Science.gov (United States)

    Shenk, Chad E.; Putnam, Frank W.; Noll, Jennie G.

    2013-01-01

    Previous research demonstrates that both child maltreatment and intellectual performance contribute uniquely to the accurate identification of facial affect by children and adolescents. The purpose of this study was to extend this research by examining whether child maltreatment affects the accuracy of facial recognition differently at varying…

  18. Addictive drugs and plasticity of glutamatergic synapses on dopaminergic neurons: what have we learned from genetic mouse models?

    Directory of Open Access Journals (Sweden)

    Jan Rodriguez Parkitna

    2012-08-01

    Full Text Available Drug-induced changes in the functional properties of neurons in the mesolimbic dopaminergic system are attractive candidates for the molecular underpinnings of addiction. A central question in this context has been how drugs of abuse affect synaptic plasticity on dopaminergic cells in the ventral tegmental area. We now know that the intake of addictive drugs is accompanied by a complex sequence of alterations in the properties of excitatory synapses on dopaminergic neurons, mainly driven by signaling and redistribution of NMDA- and AMPA-receptors. It has, however, been unclear how these molecular changes are related to the behavioral effects of addictive drugs. Recently, new genetic tools have permitted researchers to perform genetic intervention with plasticity-related molecules selectively in dopaminergic cells and to subsequently study the behaviors of genetically modified mice. These studies have started to reveal how plasticity and drug-induced behavior are connected as well as what role plasticity in dopaminergic cells may have in general reward learning. The findings thus far show that there is not a one-to-one relation between plastic events and specific behaviors and that the early responses to drugs of abuse are to a large extent independent of the types of synaptic plasticity so far targeted. In contrast, plasticity in dopaminergic cells indeed is an important regulator of the persistence of behaviors driven by drug associations, making synaptic plasticity in dopaminergic cells an important field of study for understanding the mechanisms behind relapse.

  19. Occupational functioning in early non-affective psychosis: the role of attributional biases, symptoms and executive functioning.

    Science.gov (United States)

    Fornells-Ambrojo, M; Craig, T; Garety, P

    2014-03-01

    Aims. Occupational functioning is severely impaired in people with psychosis. Social cognition has recently been found to be a stronger predictor of functioning than neurocognition. This study is the first to investigate if externalizing attributional biases that are typically associated with psychosis play a role in the vocational pathways of people with early psychosis. Methods. A cross-sectional design was used. Fifty participants with early psychosis were recruited from a cohort of 144 participants of the Lambeth Early Onset randomized control trial at 18-month follow-up. Information on occupational functioning was obtained using case notes and interview. Severity of symptoms was assessed and participants completed measures on attributional style and executive functioning. Results. Although executive functioning and positive symptoms were associated with poor occupational functioning, an externalizing attributional style for failures and reduced engagement in occupational activities during the previous 18 months emerged as the only predictors of poor occupational functioning at 18-month follow-up. Conclusions. An externalizing attributional bias is associated with poor occupational functioning. Further research is needed to investigate the direction of this relationship and whether attributional biases mediate the impact of symptoms and cognitive impairment on functioning. PMID:23510839

  20. Auditory nerve synapses persist in ventral cochlear nucleus long after loss of acoustic input in mice with early-onset progressive hearing loss.

    Science.gov (United States)

    McGuire, Brian; Fiorillo, Benjamin; Ryugo, David K; Lauer, Amanda M

    2015-04-24

    Perceptual performance in persons with hearing loss, especially those using devices to restore hearing, is not fully predicted by traditional audiometric measurements designed to evaluate the status of peripheral function. The integrity of auditory brainstem synapses may vary with different forms of hearing loss, and differential effects on the auditory nerve-brain interface may have particularly profound consequences for the transfer of sound from ear to brain. Loss of auditory nerve synapses in ventral cochlear nucleus (VCN) has been reported after acoustic trauma, ablation of the organ of Corti, and administration of ototoxic compounds. The effects of gradually acquired forms deafness on these synapses are less well understood. We investigated VCN gross morphology and auditory nerve synapse integrity in DBA/2J mice with early-onset progressive sensorineural hearing loss. Hearing status was confirmed using auditory brainstem response audiometry and acoustic startle responses. We found no change in VCN volume, number of macroneurons, or number of VGLUT1-positive auditory nerve terminals between young adult and older, deaf DBA/2J. Cell-type specific analysis revealed no difference in the number of VGLUT1 puncta contacting bushy and multipolar cell body profiles, but the terminals were smaller in deaf DBA/2J mice. Transmission electron microscopy confirmed the presence of numerous healthy, vesicle-filled auditory nerve synapses in older, deaf DBA/2J mice. The present results suggest that synapses can be preserved over a relatively long time-course in gradually acquired deafness. Elucidating the mechanisms supporting survival of central auditory nerve synapses in models of acquired deafness may reveal new opportunities for therapeutic intervention. PMID:25686750

  1. Synapse-Specific Metaplasticity: To Be Silenced Is Not to Silence 2B

    OpenAIRE

    Philpot, Benjamin D.; Zukin, R. Suzanne

    2010-01-01

    What happens to a single, presynaptically quiescent synapse among a population of active synapses? In this issue of Neuron, Ehlers and colleagues show that, far from being eliminated, these inactive synapses are primed for potentiation and incorporation into a new neural circuit through an upregulation of NR2B-containing NMDA receptors.

  2. 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. PMID:27035941

  3. Human post-mortem synapse proteome integrity screening for proteomic studies of postsynaptic complexes

    OpenAIRE

    Bayés, Alex; Collins, Mark O; Galtrey, Clare M; Simonnet, Clémence; Roy, Marcia; Croning, Mike; Gou, Gemma; van de Lagemaat, Louie N.; Milward, David; Whittle, Ian R.; Smith, Colin; Choudhary, Jyoti S.; Grant, Seth

    2014-01-01

    BackgroundSynapses are fundamental components of brain circuits and are disrupted in over 100 neurological and psychiatric diseases. The synapse proteome is physically organized into multiprotein complexes and polygenic mutations converge on postsynaptic complexes in schizophrenia, autism and intellectual disability. Directly characterising human synapses and their multiprotein complexes from post-mortem tissue is essential to understanding disease mechanisms. However, multiprotein complexes ...

  4. Human post-mortem synapse proteome integrity screening for proteomic studies of postsynaptic complexes

    OpenAIRE

    Bayés, Àlex; Collins, Mark O; Galtrey, Clare M; Simonnet, Clémence; Roy, Marcia; Croning, Mike DR; Gou, Gemma; van de Lagemaat, Louie N.; Milward, David; Whittle, Ian R.; Smith, Colin; Choudhary, Jyoti S.; Grant, Seth GN

    2014-01-01

    Background Synapses are fundamental components of brain circuits and are disrupted in over 100 neurological and psychiatric diseases. The synapse proteome is physically organized into multiprotein complexes and polygenic mutations converge on postsynaptic complexes in schizophrenia, autism and intellectual disability. Directly characterising human synapses and their multiprotein complexes from post-mortem tissue is essential to understanding disease mechanisms. However, multiprotein complexes...

  5. Short-term ionic plasticity at GABAergic synapses

    Directory of Open Access Journals (Sweden)

    Joseph Valentino Raimondo

    2012-10-01

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

  6. Activity-dependent acceleration of endocytosis at a central synapse.

    Science.gov (United States)

    Wu, Wei; Xu, Jianhua; Wu, Xin-Sheng; Wu, Ling-Gang

    2005-12-14

    Accumulated evidence indicates the existence of rapid and slow endocytosis at many synapses. It has been proposed that rapid endocytosis is activated by intense stimulation when vesicle recycling needs to be speeded up to supply vesicles at hippocampal synapses. However, the evidence, as obtained with imaging techniques, which are somewhat indirect in indicating rapid endocytosis, is controversial. Furthermore, a slower time course of endocytosis is often found after more intense nerve activity, casting doubt on the role of rapid endocytosis at synapses. Here, we addressed this issue at a mammalian central synapse, the calyx of Held, using a capacitance measurement technique that provides a higher time resolution than imaging techniques. We found that rapid endocytosis with a time constant of approximately 1-2 s was activated during intense nerve activity. Reducing the presynaptic calcium current or buffering the intracellular calcium with EGTA significantly inhibited rapid endocytosis, suggesting that calcium triggers rapid endocytosis. During intense stimulation, rapid endocytosis retrieved up to approximately eight vesicles per second per active zone, approximately eightfold larger than reported in the hippocampus, and thus played a dominant role during and within 3 s after intense stimulation. Slow endocytosis became dominant 3 s after intense stimulation likely because of the fall of the intracellular calcium level that deactivated rapid endocytosis. These results underscore the importance of calcium-triggered rapid endocytosis, which offers the nerve terminal the plasticity to speed up vesicle cycling during intense nerve activity. PMID:16354926

  7. 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.

  8. 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...

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

    Science.gov (United States)

    Touzet, Claude

    2015-09-01

    Sleep is ubiquitous among the animal realm, and represents about 30% of our lives. Despite numerous efforts, the reason behind our need for sleep is still unknown. The Theory of neuronal Cognition (TnC) proposes that sleep is the period of time during which the local inhibitory synapses (in particular the cortical ones) are replenished. Indeed, as long as the active brain stays awake, hebbian learning guarantees that efficient inhibitory synapses lose their efficiency – just because they are efficient at avoiding the activation of the targeted neurons. Since hebbian learning is the only known mechanism of synapse modification, it follows that to replenish the inhibitory synapses' efficiency, source and targeted neurons must be activated together. This is achieved by a local depolarization that may travel (wave). The period of time during which such slow waves are experienced has been named the "slow-wave sleep" (SWS). It is cut into several pieces by shorter periods of paradoxical sleep (REM) which activity resembles that of the awake state. Indeed, SWS – because it only allows local neural activation – decreases the excitatory long distance connections strength. To avoid losing the associations built during the awake state, these long distance activations are played again during the REM sleep. REM and SWS sleeps act together to guarantee that when the subject awakes again, his inhibitory synaptic efficiency is restored and his (excitatory) long distance associations are still there. PMID:26138624

  10. Learning Spike Time Codes Through Morphological Learning With Binary Synapses.

    Science.gov (United States)

    Roy, Subhrajit; San, Phyo Phyo; Hussain, Shaista; Wei, Lee Wang; Basu, Arindam

    2016-07-01

    In this brief, a neuron with nonlinear dendrites (NNLDs) and binary synapses that is able to learn temporal features of spike input patterns is considered. Since binary synapses are considered, learning happens through formation and elimination of connections between the inputs and the dendritic branches to modify the structure or morphology of the NNLD. A morphological learning algorithm inspired by the tempotron, i.e., a recently proposed temporal learning algorithm is presented in this brief. Unlike tempotron, the proposed learning rule uses a technique to automatically adapt the NNLD threshold during training. Experimental results indicate that our NNLD with 1-bit synapses can obtain accuracy similar to that of a traditional tempotron with 4-bit synapses in classifying single spike random latency and pairwise synchrony patterns. Hence, the proposed method is better suited for robust hardware implementation in the presence of statistical variations. We also present results of applying this rule to real-life spike classification problems from the field of tactile sensing. PMID:26173221

  11. Supporting shared care for diabetes patients. The synapses solution.

    Science.gov (United States)

    Toussaint, P. J.; Kalshoven, M.; Ros, M.; van der Kolk, H.; Weier, O.

    1997-01-01

    In this paper we discuss the construction of a Federated Health Care Record server within the context of the European R&D project Synapses. We describe the system using the five ODP viewpoints. From an analysis of the business process to be supported by the distributed system (the shared care for diabetes patients) requirements for the server are derived. PMID:9357655

  12. Organizational Perspective on Cognitive Control Functioning and Cognitive-Affective Balance in Maltreated Children.

    Science.gov (United States)

    Rieder, Carolyn; Cicchetti, Dante

    1989-01-01

    Examined the relation between a history of maltreatment and cognitive control functioning in two groups of preschool and early school-age maltreated and nonmaltreated children. Maltreated children showed developmentally impaired cognitive control functioning on a number of tasks. (RH)

  13. Developing a functional model for cities impacted by a natural hazard: application to a city affected by flooding

    OpenAIRE

    Bambara, G.; Peyras, L.; Felix, H.; Serre, D.

    2015-01-01

    The experience feedback on a crisis that hit a city is frequently used as a "recollection" tool. To capitalize information about an experience feedback from the cities that have been affected by a natural hazard, the authors propose in this study a functional model to model scenarios of city crises. In this model, the city, considered as a complex system, was modelled using a functional analysis method. Based on such modelling, two risk analysis methods (Failure Mode and Eff...

  14. What Affects Academic Functioning in Secondary Special Education Students with Serious Emotional and/or Behavioral Problems?

    Science.gov (United States)

    Mattison, Richard E.; Blader, Joseph C.

    2013-01-01

    Concern is growing over the limited academic progress in special education students with emotional and/or behavioral disorders (EBD). We know little about how academic and behavioral factors interact in these students to affect their academic functioning. Therefore, potential associations were investigated over the course of one school year for…

  15. Factors Affecting the Functionality of Postgraduate Programs in Natural Sciences and Engineering in a Northwest State in Mexico

    Science.gov (United States)

    Valdés Cuervo, Angel Alberto; Estévez Nenninger, Etty Haydeé; Wendlandt Amezaga, Teodoro Rafael; Vera Noriega, José Ángel

    2015-01-01

    From the researchers' perspective, the study aimed to identify factors affecting the functionality of postgraduate programs in natural sciences and engineering in a north-western Mexican state. Through the typical cases method, 25 researchers who worked in six doctorate programs in the region were selected. From the perception of these…

  16. Factors That Affect Function Capacity in Patients With Musculoskeletal Pain : A Delphi Study Among Scientists, Clinicians, and Patients

    NARCIS (Netherlands)

    Lakke, Sandra E.; Wittink, Harriet; Geertzen, Jan H.; van der Schans, Cees P.; Reneman, Michiel F.

    2012-01-01

    Lakke SE. Wittink H, Geertzen JH, van der Schans CP, Reneman MF. Factors that affect functional capacity in patients with musculoskeletal pain: a Delphi study among scientists, clinicians, and patients. Arch Phys Med Rehabil 2012;93:446-57. Objective: To reach consensus on the most important biopsyc

  17. Adolescent Heavy Drinking Does Not Affect Maturation of Basic Executive Functioning : Longitudinal Findings from the TRAILS Study

    NARCIS (Netherlands)

    Boelema, Sarai R.; Harakeh, Zeena; van Zandvoort, Martine J. E.; Reijneveld, Sijmen A.; Verhulst, Frank C.; Ormel, Johan; Vollebergh, Wilma A. M.

    2015-01-01

    Background and Aims Excessive alcohol use is assumed to affect maturation of cognitive functioning in adolescence. However, most existing studies that have tested this hypothesis are seriously flawed due to the use of selective groups and/or cross-sectional designs, which limits the ability to draw

  18. Adolescent Heavy Drinking Does Not Affect Maturation of Basic Executive Functioning: Longitudinal Findings from the TRAILS Study

    NARCIS (Netherlands)

    S.R. Boelema (Sarai R.); Z. Harakeh (Zeena); M.J.E. Van Zandvoort (Martine J. E.); S.A. Reijneveld (Sijmen); F.C. Verhulst (Frank); J. Ormel (Johan); W.A.M. Vollebergh (Wilma)

    2015-01-01

    textabstractBackground and Aims Excessive alcohol use is assumed to affect maturation of cognitive functioning in adolescence. However, most existing studies that have tested this hypothesis are seriously flawed due to the use of selective groups and/or cross-sectional designs, which limits the abil

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

    OpenAIRE

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

    2002-01-01

    International audience 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 a...

  20. Repetitive activation of the corticospinal tract by means of rTMS may reduce the efficiency of corticomotoneuronal synapses

    DEFF Research Database (Denmark)

    Taube, Wolfgang; Leukel, Christian; Schubert, Martin;

    Repetitive transcranial magnetic stimulation (rTMS) is extensively used to study cognitive and motor function in humans and might be of value in the treatment of various disorders. For a better understanding of the effects of rTMS and its more efficient application it is crucial to identify...... is the synapses of the corticomotoneuronal neurones on the spinal motoneurones. Perez et al. (2005). Exp Brain Res 162, 202-212. Speer et al. (2003). Biol Psychiatry 54, 818-825....

  1. Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea.

    Science.gov (United States)

    Barclay, M; Constable, R; James, N R; Thorne, P R; Montgomery, J M

    2016-06-14

    Neural activity during early development is known to alter innervation pathways in the central and peripheral nervous systems. We sought to examine how reduced sound-induced sensory activity in the cochlea affected the consolidation of glutamatergic synapses between inner hair cells (IHC) and the primary auditory neurons as these synapses play a primary role in transmitting sound information to the brain. A unilateral conductive hearing loss was induced prior to the onset of sound-mediated stimulation of the sensory hair cells, by rupturing the tympanic membrane and dislocating the auditory ossicles in the left ear of P11 mice. Auditory brainstem responses at P15 and P21 showed a 40-50-dB increase in thresholds for frequencies 8-32kHz in the dislocated ear relative to the control ear. Immunohistochemistry and confocal microscopy were subsequently used to examine the effect of this attenuation of sound stimulation on the expression of RIBEYE, which comprises the presynaptic ribbons, Shank-1, a postsynaptic scaffolding protein, and the GluA2/3 and 4 subunits of postsynaptic AMPA receptors. Our results show that dislocation did not alter the number of pre- or postsynaptic protein puncta. However, dislocation did increase the size of RIBEYE, GluA4, GluA2/3 and Shank-1 puncta, with postsynaptic changes preceding presynaptic changes. Our data suggest that a reduction in sound stimulation during auditory development induces plasticity in the molecular make-up of IHC glutamatergic synapses, but does not affect the number of these synapses. Up-regulation of synaptic proteins with sound attenuation may facilitate a compensatory increase in synaptic transmission due to the reduced sensory stimulation of the IHC. PMID:27012610

  2. The therapeutic effect of memantine through the stimulation of synapse formation and dendritic spine maturation in autism and fragile X syndrome.

    Directory of Open Access Journals (Sweden)

    Hongen Wei

    Full Text Available Although the pathogenic mechanisms that underlie autism are not well understood, there is evidence showing that metabotropic and ionotropic glutamate receptors are hyper-stimulated and the GABAergic system is hypo-stimulated in autism. Memantine is an uncompetitive antagonist of NMDA receptors and is widely prescribed for treatment of Alzheimer's disease treatment. Recently, it has been shown to improve language function, social behavior, and self-stimulatory behaviors of some autistic subjects. However the mechanism by which memantine exerts its effect remains to be elucidated. In this study, we used cultured cerebellar granule cells (CGCs from Fmr1 knockout (KO mice, a mouse model for fragile X syndrome (FXS and syndromic autism, to examine the effects of memantine on dendritic spine development and synapse formation. Our results show that the maturation of dendritic spines is delayed in Fmr1-KO CGCs. We also detected reduced excitatory synapse formation in Fmr1-KO CGCs. Memantine treatment of Fmr1-KO CGCs promoted cell adhesion properties. Memantine also stimulated the development of mushroom-shaped mature dendritic spines and restored dendritic spine to normal levels in Fmr1-KO CGCs. Furthermore, we demonstrated that memantine treatment promoted synapse formation and restored the excitatory synapses to a normal range in Fmr1-KO CGCs. These findings suggest that memantine may exert its therapeutic capacity through a stimulatory effect on dendritic spine maturation and excitatory synapse formation, as well as promoting adhesion of CGCs.

  3. KCC2 knockdown impairs glycinergic synapse maturation in cultured spinal cord neurons.

    Science.gov (United States)

    Schwale, Chrysovalandis; Schumacher, Stefanie; Bruehl, Claus; Titz, Stefan; Schlicksupp, Andrea; Kokocinska, Mirka; Kirsch, Joachim; Draguhn, Andreas; Kuhse, Jochen

    2016-06-01

    Synaptic inhibition in the spinal cord is mediated mainly by strychnine-sensitive glycine (GlyRs) and by γ-aminobutyric acid type A receptors (GABAAR). During neuronal maturation, neonatal GlyRs containing α2 subunits are replaced by adult-type GlyRs harboring α1 and α3 subunits. At the same time period of postnatal development, the transmembrane chloride gradient is changed due to increased expression of the potassium-chloride cotransporter (KCC2), thereby shifting the GABA- and glycine-mediated synaptic currents from mostly excitatory depolarization to inhibitory hyperpolarization. Here, we used RNA interference to suppress KCC2 expression during in vitro maturation of spinal cord neurons. Morphological analysis revealed reduced numbers and size of dendritic GlyR clusters containing α1 subunits but not of clusters harboring neonatal α2 subunits. The morphological changes were accompanied by decreased frequencies and amplitudes of glycinergic miniature inhibitory currents, whereas GABAergic synapses appeared functionally unaltered. Our data indicate that KCC2 exerts specific functions for the maturation of glycinergic synapses in cultured spinal cord neurons. PMID:26780567

  4. How Do Cognitive Function and Knowledge Affect Heart Failure Self-Care?

    Science.gov (United States)

    Dickson, Victoria Vaughan; Lee, Christopher S.; Riegel, Barbara

    2011-01-01

    Despite extensive patient education, few heart failure (HF) patients master self-care. Impaired cognitive function may explain why patient education is ineffective. A concurrent triangulation mixed methods design was used to explore how knowledge and cognitive function influence HF self-care. A total of 41 adults with HF participated in interviews…

  5. Good vibrations switch attention: an affective function for network oscillations in evolutionary simulations

    NARCIS (Netherlands)

    B.T. Heerebout; R.H. Phaf

    2010-01-01

    In the present study, a new hypothesis on the neural mechanisms linking affect to attention was brought forward by evolutionary simulations on agents navigating a virtual environment while collecting food and avoiding predation. The connection strengths between nodes in the networks controlling the

  6. Child Internalizing Symptoms: Contributions of Child Temperament, Maternal Negative Affect, and Family Functioning

    Science.gov (United States)

    Crawford, Nicole A.; Schrock, Matthew; Woodruff-Borden, Janet

    2011-01-01

    Research has traditionally focused on the role of genetic and environmental variables in the development and maintenance of childhood internalizing disorders. Temperament variables, such as negative affect and effortful control have gained considerable interest within the field of developmental psychopathology. Environmental factors such as…

  7. The affects of contrast medium on renal function in selective coronary angiography and intervention

    International Nuclear Information System (INIS)

    Selective coronary angiography and intervention with injection of contrast medium into the coronary arteries has become very common in dealing with coronary cardiac diseases. The excretion of contrast medium through kidneys may lead to acute renal functional insufficiency, especially for those suffering from chronic nephropathy, diabetes and cardiac functional disorder to form the so called 'contrast medium nephropathy' which is considered as the number second drug induced acute renal functional failure. Although routine preventive measure including low osmotic contrast medium and fine hydrotherapy have been taken, 14% incidences still occur with renal functional damage. The majority could be reversible but the minority needs emergent hemodialysis or even with persistent renal functional damage in a few ones. (authors)

  8. New functional sites in MutS affect DNA mismatch repair

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The MutS protein plays an important role in the DNA mismatch repair system. Mutations in the mutS gene can lead to genome instability and ultimately cell malfunction. Here we have established a method for identifying functional defective mutants of MutS by random mutation and rifampicin screening. Some novel functional sites in MutS were identified. The MutS mutant strains were analyzed using surface plasmon resonance, gel filtration and far-western methods to determine the molecular mechanisms behind the DNA mismatch repair function of MutS.

  9. Cannabinoids inhibit network-driven synapse loss between hippocampal neurons in culture.

    Science.gov (United States)

    Kim, Hee Jung; Waataja, Jonathan J; Thayer, Stanley A

    2008-06-01

    Dendritic pruning and loss of synaptic contacts are early events in many neurodegenerative diseases. These effects are dynamic and seem to differ mechanistically from the cell death process. Cannabinoids modulate synaptic activity and afford protection in some neurotoxicity models. We investigated the effects of cannabinoids on activity-induced changes in the number of synapses between rat hippocampal neurons in culture. Morphology and synapses were visualized by confocal imaging of neurons expressing DsRed2 and postsynaptic density protein 95 (PSD95) fused to enhanced green fluorescent protein (GFP). Reducing the extracellular Mg2+ concentration to 0.1 mM for 4 h induced intense synaptic activity, which decreased the number of PSD95-GFP puncta by 45 +/- 13%. Synapse loss was an early event, required activation of N-methyl-D-aspartate receptors, and was mediated by the ubiquitin-proteasome pathway. The cannabinoid receptor full agonist WIN55,212-2 [(R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)-methyl] pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-napthalenyl)-methanone monomethanesulfonate] (EC(50) = 2.5 +/- 0.5 nM) and the partial agonist Delta(9)-tetrahydrocannabinol (THC; EC(50) = 9 +/- 3 nM) inhibited PSD loss in a manner reversed by the CB1 receptor antagonist rimonabant [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide]. The protection was mimicked by inhibition of presynaptic Ca2+ channels, and WIN55,212-2 did not prevent PSD loss elicited by direct application of glutamate, suggesting a presynaptic mechanism. Prolonged exposure to WIN55,212-2, but not THC, desensitized the protective effect. Treating cells that had undergone PSD loss with WIN55,212-2 reversed the loss and enabled recovery of a full compliment of synapses. The modulation of synaptic number by acute and prolonged exposure to cannabinoids may account for some of the effects of these drugs on the plasticity, survival, and function of neural networks. PMID

  10. Restoration of hip architecture with bipolar hemiarthroplasty in the elderly : does it affect early functional outcome?

    NARCIS (Netherlands)

    Hartel, Maximilian; Arndt, Marius; Eulenburg, Christine Zu; Petersen, Jan Philipp; Rueger, Johannes M.; Hoffmann, Michael

    2014-01-01

    Reconstruction of the anatomic architecture correlates with functional outcome in patients receiving elective total hip arthroplasty. In theory similar rules should apply for bipolar hemiarthroplasty in femoral neck fractures. The influence of anatomic restoration after bipolar hemiarthroplasty on s

  11. miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function

    Directory of Open Access Journals (Sweden)

    Maude Giroud

    2016-08-01

    Conclusion: Collectively, our results demonstrate that miR-125b-5p plays an important role in the repression of brite adipocyte function by modulating oxygen consumption and mitochondrial gene expression.

  12. Maternal early-life trauma and affective parenting style: the mediating role of HPA-axis function.

    Science.gov (United States)

    Juul, Sarah H; Hendrix, Cassandra; Robinson, Brittany; Stowe, Zachary N; Newport, D Jeffrey; Brennan, Patricia A; Johnson, Katrina C

    2016-02-01

    A history of childhood trauma is associated with increased risk for psychopathology and interpersonal difficulties in adulthood and, for those who have children, impairments in parenting and increased risk of negative outcomes in offspring. Physiological and behavioral mechanisms are poorly understood. In the current study, maternal history of childhood trauma was hypothesized to predict differences in maternal affect and HPA axis functioning. Mother-infant dyads (N = 255) were assessed at 6 months postpartum. Mothers were videotaped during a 3-min naturalistic interaction, and their behavior was coded for positive, neutral, and negative affect. Maternal salivary cortisol was measured six times across the study visit, which also included an infant stressor paradigm. Results showed that childhood trauma history predicted increased neutral affect and decreased mean cortisol in the mothers and that cortisol mediated the association between trauma history and maternal affect. Maternal depression was not associated with affective measures or cortisol. Results suggest that early childhood trauma may disrupt the development of the HPA axis, which in turn impairs affective expression during mother-infant interactions in postpartum women. Interventions aimed at treating psychiatric illness in postpartum women may benefit from specific components to assess and treat trauma-related symptoms and prevent secondary effects on parenting. PMID:25956587

  13. Good vibrations switch attention: an affective function for network oscillations in evolutionary simulations.

    Science.gov (United States)

    Heerebout, Bram T; Phaf, R Hans

    2010-05-01

    In the present study, a new hypothesis on the neural mechanisms linking affect to attention was brought forward by evolutionary simulations on agents navigating a virtual environment while collecting food and avoiding predation. The connection strengths between nodes in the networks controlling the agents were subjected to random variation, and the fittest agents were selected for reproduction. Unexpectedly, oscillations of node activations emerged, which drastically enhanced the agent's fitness. We analyzed the mechanisms involved in the modulation of attention and found that oscillations acted on competitive networks. Response selection depended on the connection structure, but the speed and efficacy of switching between selections was modulated by oscillation frequency. The main focus of the present study was the differential emergence of stimulus-specific oscillation frequencies. Oscillations had a higher frequency in an appetitive motivational state than in an aversive state. We suggest that oscillations in biological networks also mediate the affective modulation of attention. PMID:20498346

  14. HoLEP does not affect the overall sexual function of BPH patients: a prospective study

    Directory of Open Access Journals (Sweden)

    Sung Han Kim

    2014-12-01

    Full Text Available We aimed to prospectively evaluate the influence of holmium laser enucleation of the prostate (HoLEP on the overall postoperative sexual function of benign prostatic hyperplasia (BPH patients with lower urinary tract symptoms (LUTS and to explore the relationship between sexual function and LUTS. From January 2010 to December 2011, sixty sexually active consecutive patients with BPH who underwent HoLEP were prospectively enrolled in the study. All patients filled out the Male Sexual Health Questionnaire (MSHQ for evaluation of their overall sexual function and the International Prostatic Symptom Score (IPSS for pre- and post-operative 6 months evaluation of their voiding symptoms. The LUTS and sexual function changes were statistically analyzed. The preoperative and 6 months postoperative status of the patients was compared using uroflowmetry and IPSS questionnaires. The analysis revealed significant improvements following HoLEP. Among the sub-domains of the MSHQ, postoperative sexual function, including erection, ejaculation, sexual satisfaction, anxiety or sexual desire, did not significantly change after HoLEP (P > 0.05, whereas satisfaction scores decreased slightly due to retrograde ejaculation in 38 patients (63.3%. Sexual satisfaction improved significantly and was correlated with the improvements of all LUTS and the quality-of-life (QoL domains in IPSS after surgery (QoL; relative risk [RR]: −0.293; total symptoms, RR: −0.411; P < 0.05. The nocturia score was associated with the erectile function score (odds ratio 0.318, P = 0.029. The change in ejaculatory scores did not show significant association with IPSS scores. HoLEP did not influence overall sexual function, including erectile function. In addition, sexual satisfaction improved in proportion with the improvement of LUTS.

  15. Functional Dissection of Sugar Signals Affecting Gene Expression in Arabidopsis thaliana

    OpenAIRE

    Sabine Kunz; Edouard Pesquet; Kleczkowski, Leszek A.

    2014-01-01

    Background: Sugars modulate expression of hundreds of genes in plants. Previous studies on sugar signaling, using intact plants or plant tissues, were hampered by tissue heterogeneity, uneven sugar transport and/or inter-conversions of the applied sugars. This, in turn, could obscure the identity of a specific sugar that acts as a signal affecting expression of given gene in a given tissue or cell-type. Methodology/Principal Findings: To bypass those biases, we have developed a novel biologic...

  16. A newly recognized autosomal recessive syndrome affecting neurologic function and vision

    OpenAIRE

    Salih, M.; A. Tzschach; Oystreck, D.; Hassan, H.; AlDrees, A.; Elmalik, S.; El Khashab, H.; Wienker, T; Abu-Amero, K; Bosley, T.

    2013-01-01

    Genetic factors represent an important etiologic group in the causation of intellectual disability. We describe a Saudi Arabian family with closley related parents in which four of six children were affected by a congenital cognitive disturbance. The four individuals (aged 18, 16, 13, and 2 years when last examined) had motor and cognitive delay with seizures in early childhood, and three of the four (sparing only the youngest child) had progressive, severe cognitive decline with spasticity. ...

  17. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    OpenAIRE

    Maria Carolina Salomé Marquezin; Bruna Raquel Zancopé; Larissa Ferreira Pacheco; Maria Beatriz Duarte Gavião; Fernanda Miori Pascon

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars wit...

  18. Affective symptoms and cognitive functions in the acute phase of Graves' thyrotoxicosis

    DEFF Research Database (Denmark)

    Vogel, Asmus; Elberling, Tina V; Hørding, Merete;

    2007-01-01

    problems. No significant differences between the patient and the control group on neuropsychological test performances were found. Thyroid levels did not correlate with the neuropsychological test performances or psychiatric ratings. After reaching euthyroidism the level of affective symptoms (including......In the acute phase of Graves' thyrotoxicosis patients often have subjective cognitive complaints. Continuing controversy exists about the nature of these symptoms and whether they persist after treatment. This prospective study included 31 consecutively referred, newly diagnosed, and untreated...

  19. Diverse Short-Term Dynamics of Inhibitory Synapses Converging on Striatal Projection Neurons: Differential Changes in a Rodent Model of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Janet Barroso-Flores

    2015-01-01

    Full Text Available Most neurons in the striatum are projection neurons (SPNs which make synapses with each other within distances of approximately 100 µm. About 5% of striatal neurons are GABAergic interneurons whose axons expand hundreds of microns. Short-term synaptic plasticity (STSP between fast-spiking (FS interneurons and SPNs and between SPNs has been described with electrophysiological and optogenetic techniques. It is difficult to obtain pair recordings from some classes of interneurons and due to limitations of actual techniques, no other types of STSP have been described on SPNs. Diverse STSPs may reflect differences in presynaptic release machineries. Therefore, we focused the present work on answering two questions: Are there different identifiable classes of STSP between GABAergic synapses on SPNs? And, if so, are synapses exhibiting different classes of STSP differentially affected by dopamine depletion? Whole-cell voltage-clamp recordings on SPNs revealed three classes of STSPs: depressing, facilitating, and biphasic (facilitating-depressing, in response to stimulation trains at 20 Hz, in a constant ionic environment. We then used the 6-hydroxydopamine (6-OHDA rodent model of Parkinson’s disease to show that synapses with different STSPs are differentially affected by dopamine depletion. We propose a general model of STSP that fits all the dynamics found in our recordings.

  20. Combined standard and novel immunosuppressive substances affect B-lymphocyte function.

    Science.gov (United States)

    Matz, Mareen; Lehnert, Martin; Lorkowski, Christine; Fabritius, Katharina; Weber, Ulrike A; Mashreghi, Mir-Farzin; Neumayer, Hans-H; Budde, Klemens

    2013-04-01

    A considerable fraction of renal transplanted patients is susceptible to humoral rejection. Today well-established therapy regimens are available to control antibody-mediated rejection in the short term. Nevertheless, donor-specific antibodies persist and graft function deteriorates over time. This might be due to insufficient maintenance immunosuppression - which always consists of two to three drugs with different mechanisms of action. Since T- and B-cell functions always depend on each other in the alloimmune response it is of interest to analyze the effects of combined standard and new immunosuppressive substances with T-cell inhibitory properties on B-cell function. The effectiveness of complementary administrations of sotrastaurin, mycophenolic acid and everolimus on the activation and function of human primary B-lymphocytes was tested. Everolimus and mycophenolic acid alone and in combination proved to be highly effective in suppressing B-cell activation, whereas the proteinkinase C inhibitor sotrastaurin had an unexpected and reverse impact on various B-cell functions when applied in combination with the mammalian target of rapamycin and the inosine monophosphate dehydrogenase inhibitor. PMID:23499640

  1. Stimulus-specific adaptation at the synapse level in vitro

    OpenAIRE

    Haitao Wang; Yi-Fan Han; Ying-Shing Chan; Jufang He

    2014-01-01

    Stimulus-specific adaptation (SSA) is observed in many brain regions in humans and animals. SSA of cortical neurons has been proposed to accumulate through relays in ascending pathways. Here, we examined SSA at the synapse level using whole-cell patch-clamp recordings of primary cultured cortical neurons of the rat. First, we found that cultured neurons had high firing capability with 100-Hz current injection. However, neuron firing started to adapt to repeated electrically activated synaptic...

  2. A Mathematical Model of Tripartite Synapse: Astrocyte Induced Synaptic Plasticity

    OpenAIRE

    Tewari, Shivendra; Majumdar, Kaushik

    2011-01-01

    In this paper we present a biologically detailed mathematical model of tripartite synapses, where astrocytes modulate short-term synaptic plasticity. The model consists of a pre-synaptic bouton, a post-synaptic dendritic spine-head, a synaptic cleft and a peri-synaptic astrocyte controlling Ca2+ dynamics inside the synaptic bouton. This in turn controls glutamate release dynamics in the cleft. As a consequence of this, glutamate concentration in the cleft has been modeled, in which glutamate ...

  3. Experience-driven brain plasticity: beyond the synapse

    OpenAIRE

    Markham, Julie A.; Greenough, William T.

    2004-01-01

    The brain is remarkably responsive to its interactions with the environment, and its morphology is altered by experience in measurable ways. Histological examination of the brains of animals exposed to either a complex (‘enriched’) environment or learning paradigm, compared with appropriate controls, has illuminated the nature of experience-induced morphological plasticity in the brain. For example, this research reveals that changes in synapse number and morphology are associated with learni...

  4. Storage capacity of attractor neural networks with depressing synapses

    International Nuclear Information System (INIS)

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

  5. Laser programmable integrated curcuit for forming synapses in neural networks

    Science.gov (United States)

    Fu, Chi Y.

    1997-01-01

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

  6. Laser programmable integrated circuit for forming synapses in neural networks

    Science.gov (United States)

    Fu, C.Y.

    1997-02-11

    Customizable neural network in which one or more resistors form each synapse is disclosed. All the resistors in the synaptic array are identical, thus simplifying the processing issues. Highly doped, amorphous silicon is used as the resistor material, to create extremely high resistances occupying very small spaces. Connected in series with each resistor in the array is at least one severable conductor whose uppermost layer has a lower reflectivity of laser energy than typical metal conductors at a desired laser wavelength. 5 figs.

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

    Science.gov (United States)

    Fu, Chi Y.

    1996-01-01

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

  8. Affecting Rhomboid-3 function causes a dilated heart in adult Drosophila.

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2010-05-01

    Full Text Available Drosophila is a well recognized model of several human diseases, and recent investigations have demonstrated that Drosophila can be used as a model of human heart failure. Previously, we described that optical coherence tomography (OCT can be used to rapidly examine the cardiac function in adult, awake flies. This technique provides images that are similar to echocardiography in humans, and therefore we postulated that this approach could be combined with the vast resources that are available in the fly community to identify new mutants that have abnormal heart function, a hallmark of certain cardiovascular diseases. Using OCT to examine the cardiac function in adult Drosophila from a set of molecularly-defined genomic deficiencies from the DrosDel and Exelixis collections, we identified an abnormally enlarged cardiac chamber in a series of deficiency mutants spanning the rhomboid 3 locus. Rhomboid 3 is a member of a highly conserved family of intramembrane serine proteases and processes Spitz, an epidermal growth factor (EGF-like ligand. Using multiple approaches based on the examination of deficiency stocks, a series of mutants in the rhomboid-Spitz-EGF receptor pathway, and cardiac-specific transgenic rescue or dominant-negative repression of EGFR, we demonstrate that rhomboid 3 mediated activation of the EGF receptor pathway is necessary for proper adult cardiac function. The importance of EGF receptor signaling in the adult Drosophila heart underscores the concept that evolutionarily conserved signaling mechanisms are required to maintain normal myocardial function. Interestingly, prior work showing the inhibition of ErbB2, a member of the EGF receptor family, in transgenic knock-out mice or individuals that received herceptin chemotherapy is associated with the development of dilated cardiomyopathy. Our results, in conjunction with the demonstration that altered ErbB2 signaling underlies certain forms of mammalian cardiomyopathy, suggest

  9. The effect of STDP temporal kernel structure on the learning dynamics of single excitatory and inhibitory synapses.

    Directory of Open Access Journals (Sweden)

    Yotam Luz

    Full Text Available Spike-Timing Dependent Plasticity (STDP is characterized by a wide range of temporal kernels. However, much of the theoretical work has focused on a specific kernel - the "temporally asymmetric Hebbian" learning rules. Previous studies linked excitatory STDP to positive feedback that can account for the emergence of response selectivity. Inhibitory plasticity was associated with negative feedback that can balance the excitatory and inhibitory inputs. Here we study the possible computational role of the temporal structure of the STDP. We represent the STDP as a superposition of two processes: potentiation and depression. This allows us to model a wide range of experimentally observed STDP kernels, from Hebbian to anti-Hebbian, by varying a single parameter. We investigate STDP dynamics of a single excitatory or inhibitory synapse in purely feed-forward architecture. We derive a mean-field-Fokker-Planck dynamics for the synaptic weight and analyze the effect of STDP structure on the fixed points of the mean field dynamics. We find a phase transition along the Hebbian to anti-Hebbian parameter from a phase that is characterized by a unimodal distribution of the synaptic weight, in which the STDP dynamics is governed by negative feedback, to a phase with positive feedback characterized by a bimodal distribution. The critical point of this transition depends on general properties of the STDP dynamics and not on the fine details. Namely, the dynamics is affected by the pre-post correlations only via a single number that quantifies its overlap with the STDP kernel. We find that by manipulating the STDP temporal kernel, negative feedback can be induced in excitatory synapses and positive feedback in inhibitory. Moreover, there is an exact symmetry between inhibitory and excitatory plasticity, i.e., for every STDP rule of inhibitory synapse there exists an STDP rule for excitatory synapse, such that their dynamics is identical.

  10. Presynaptic size of associational/commissural CA3 synapses is controlled by fibroblast growth factor 22 in adult mice.

    Science.gov (United States)

    Pasaoglu, Taliha; Schikorski, Thomas

    2016-02-01

    Associational/commissural CA3-CA3 synapses define the recurrent CA3 network that generates the input to CA1 pyramidal neurons. We quantified the fine structure of excitatory synapses in the stratum radiatum of the CA3d area in adult wild type (WT) and fibroblast growth factor 22 knock-out (FGF22KO) mice by using serial 3D electron microscopy. WT excitatory CA3 synapses are rather small yet range 10 fold in size. Spine size, however, was small and uniform and did not correlate with the size of the synaptic junction. To reveal mechanisms that regulate presynaptic structure, we investigated the role of FGF22, a target-derived signal specific for the distal part of area CA3 (CA3d). In adult FGF22KO mice, postsynaptic properties of associational CA3 synapses were unaltered. Presynaptically, the number of synaptic vesicles (SVs), the bouton volume, and the number of vesicles in axonal regions (the super pool) were reduced. This concurrent decrease suggests concerted control by FGF22 of presynaptic size. This hypothesis is supported by the finding that WT presynapses in the proximal part of area CA3 (CA3p) that do not receive FGF22 signaling in WT mice were smaller than presynapses in CA3d in WT but of comparable size in CA3d of FGF22KO mice. Docked SV density was decreased in CA1, CA3d, and CA3p in FGF22KO mice. Because CA1 and CA3p are not directly affected by the loss of FGF22, the smaller docked SV density may be an adaptation to activity changes in the CA3 network. Thus, docked SV density potentially is a long-term regulator for the synaptic release probability and/or the strength of short-term depression in vivo. PMID:26222899

  11. Deficient fear conditioning in psychopathy as a function of interpersonal and affective disturbances

    Directory of Open Access Journals (Sweden)

    Ralf eVeit

    2013-10-01

    Full Text Available The diminished fear reactivity is one of the most valid physiological findings in psychopathy research. In a fear conditioning paradigm, with faces as conditioned stimulus (CS and electric shock as unconditioned stimulus (US, we investigated a sample of 14 high psychopathic violent offenders. Event related potentials, skin conductance responses (SCR as well as subjective ratings of the CSs were collected. This study assessed to which extent the different facets of the psychopathy construct contribute to the fear conditioning deficits observed in psychopaths. Participants with high scores on the affective facet subscale of the Psychopathy Checklist-Revised (PCL-R showed weaker conditioned fear responses and lower N100 amplitudes compared to low scorers. In contrast, high scorers on the affective facet rated the CS+ (paired more negatively than low scorers regarding the CS- (unpaired. Regarding the P300, high scores on the interpersonal facet were associated with increased amplitudes to the CS+ compared to the CS-, while the opposed pattern was found with the antisocial facet. Both, the initial and terminal contingent negative variation indicated a divergent pattern: participants with pronounced interpersonal deficits, showed increased cortical negativity to the CS+ compared to the CS-, whereas a reversed CS+/CS- differentiation was found in offenders scoring high on the antisocial facet. The present study revealed that deficient fear conditioning in psychopathy was most pronounced in offenders with high scores on the affective facet. Event related potentials suggest that participants with distinct interpersonal deficits showed increased information processing, whereas the antisocial facet was linked to decreased attention and interest to the CS+. These data indicate that an approach to the facets of psychopathy can help to resolve ambiguous findings in psychopathy research and enables a more precise and useful description of this disorder.

  12. Affective symptoms and cognitive functions in the acute phase of Graves' thyrotoxicosis

    DEFF Research Database (Denmark)

    Vogel, Asmus; Elberling, Tina V; Hørding, Merete;

    2007-01-01

    In the acute phase of Graves' thyrotoxicosis patients often have subjective cognitive complaints. Continuing controversy exists about the nature of these symptoms and whether they persist after treatment. This prospective study included 31 consecutively referred, newly diagnosed, and untreated...... of cognitive deficits) had decreased significantly, with further normalisation 1-year after treatment initiation. In conclusion, patients had subjective reports of cognitive deficits in the toxic phase of Graves' thyrotoxicosis but comprehensive neuropsychological testing revealed no cognitive impairment....... Reports of cognitive dysfunction may reflect affective and somatic manifestations of thyrotoxicosis and in most patients these symptoms disappear after treatment of Graves' thyrotoxicosis....

  13. Visualizing Presynaptic Calcium Dynamics and Vesicle Fusion with a Single Genetically Encoded Reporter at Individual Synapses.

    Science.gov (United States)

    Jackson, Rachel E; Burrone, Juan

    2016-01-01

    Synaptic transmission depends on the influx of calcium into the presynaptic compartment, which drives neurotransmitter release. Genetically encoded reporters are widely used tools to understand these processes, particularly pHluorin-based reporters that report vesicle exocytosis and endocytosis through pH dependent changes in fluorescence, and genetically encoded calcium indicators (GECIs) that exhibit changes in fluorescence upon binding to calcium. The recent expansion of the color palette of available indicators has made it possible to image multiple probes simultaneously within a cell. We have constructed a single molecule reporter capable of concurrent imaging of both presynaptic calcium influx and exocytosis, by fusion of sypHy, the vesicle associated protein synaptophysin containing a GFP-based pHluorin sensor, with the red-shifted GECI R-GECO1. Due to the fixed stoichiometry of the two probes, the ratio of the two responses can also be measured, providing an all optical correlate of the calcium dependence of release. Here, we have characterized stimulus-evoked sypHy-RGECO responses of hippocampal synapses in vitro, exploring the effects of different stimulus strengths and frequencies as well as variations in external calcium concentrations. By combining live sypHy-RGECO imaging with post hoc fixation and immunofluorescence, we have also investigated correlations between structural and functional properties of synapses. PMID:27507942

  14. Astrocyte-secreted thrombospondin-1 modulates synapse and spine defects in the fragile X mouse model.

    Science.gov (United States)

    Cheng, Connie; Lau, Sally K M; Doering, Laurie C

    2016-01-01

    Astrocytes are key participants in various aspects of brain development and function, many of which are executed via secreted proteins. Defects in astrocyte signaling are implicated in neurodevelopmental disorders characterized by abnormal neural circuitry such as Fragile X syndrome (FXS). In animal models of FXS, the loss in expression of the Fragile X mental retardation 1 protein (FMRP) from astrocytes is associated with delayed dendrite maturation and improper synapse formation; however, the effect of astrocyte-derived factors on the development of neurons is not known. Thrombospondin-1 (TSP-1) is an important astrocyte-secreted protein that is involved in the regulation of spine development and synaptogenesis. In this study, we found that cultured astrocytes isolated from an Fmr1 knockout (Fmr1 KO) mouse model of FXS displayed a significant decrease in TSP-1 protein expression compared to the wildtype (WT) astrocytes. Correspondingly, Fmr1 KO hippocampal neurons exhibited morphological deficits in dendritic spines and alterations in excitatory synapse formation following long-term culture. All spine and synaptic abnormalities were prevented in the presence of either astrocyte-conditioned media or a feeder layer derived from FMRP-expressing astrocytes, or following the application of exogenous TSP-1. Importantly, this work demonstrates the integral role of astrocyte-secreted signals in the establishment of neuronal communication and identifies soluble TSP-1 as a potential therapeutic target for Fragile X syndrome. PMID:27485117

  15. Does Gender-Specific Differential Item Functioning Affect the Structure in Vocational Interest Inventories?

    Science.gov (United States)

    Beinicke, Andrea; Pässler, Katja; Hell, Benedikt

    2014-01-01

    The study investigates consequences of eliminating items showing gender-specific differential item functioning (DIF) on the psychometric structure of a standard RIASEC interest inventory. Holland's hexagonal model was tested for structural invariance using a confirmatory methodological approach (confirmatory factor analysis and randomization…

  16. Functional Measurement Analysis of Brand Equity: Does Brand Name Affect Perceptions of Quality?

    Science.gov (United States)

    Hilgenkamp, Heather; Shanteau, James

    2010-01-01

    This research project used Functional Measurement to examine how the brand name of consumer products impacts intended purchasing decisions. Thirty undergraduate students tested actual products from three different product categories (crayons, tissues, and tortilla chips). Each product category consisted of three different brands; one with high…

  17. The parasitic copepod Lernaeocera branchialis negatively affects cardiorespiratory function in Gadus morhua

    DEFF Research Database (Denmark)

    Behrens, Jane W.; Seth, H.; Axelsson, M.; Buchmann, K.

    2014-01-01

    The parasitic copepod Lernaeocera branchialis had a negative effect on cardiorespiratory function in Atlantic cod Gadus morhua such that it caused pronounced cardiac dysfunction with irregular rhythm and reduced stroke amplitude compared with uninfected fish. In addition, parasite infection...... depressed the postprandial cardiac output and oxygen consumption...

  18. Enrichment of SNPs in Functional Categories Reveals Genes Affecting Complex Traits.

    Science.gov (United States)

    Zhao, Huiying; Fan, Dongsheng; Nyholt, Dale R; Yang, Yuedong

    2016-08-01

    Genome-wide association studies (GWAS) have indicated potential to identify heritability of common complex phenotypes, but traditional approaches have limited ability to detect hiding signals because single SNP has weak effect size accounting for only a small fraction of overall phenotypic variations. To improve the power of GWAS, methods have been developed to identify truly associated genes by jointly testing effects of all SNPs. However, equally considering all SNPs within a gene might dilute strong signals of SNPs in real functional categories. Here, we observed a consistent pattern on enrichment of significant SNPs in eight functional categories across six phenotypes, with the highest enrichment in coding and both UTR regions while the lowest enrichment in the intron. Based on the pattern of SNP enrichment in functional categories, we developed a new approach for detecting gene associations on traits (DGAT) by selecting the most significant functional category and then using SNPs within it to assess gene associations. The method was found to be robust in type I error rate on simulated data, and to have mostly higher power in detecting associated genes for three different diseases than other methods. Further analysis indicated ability of the DGAT to detect novel genes. The DGAT is available by http://sparks-lab.org/server/DGAT. PMID:27113629

  19. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R;

    2007-01-01

    The uPAR and its ligand uPA are expressed by both osteoblasts and osteoclasts. Their function in bone remodeling is unknown. We report that uPAR-lacking mice display increased BMD, increased osteogenic potential of osteoblasts, decreased osteoclasts formation, and altered cytoskeletal reorganizat...

  20. Acute Physical Exercise Affects Cognitive Functioning in Children With Cerebral Palsy.

    Science.gov (United States)

    Maltais, Désirée B; Gane, Claire; Dufour, Sophie-Krystale; Wyss, Dominik; Bouyer, Laurent J; McFadyen, Bradford J; Zabjek, Karl; Andrysek, Jan; Voisen, Julien I

    2016-05-01

    Little is known about the effects of acute exercise on the cognitive functioning of children with cerebral palsy (CP). Selected cognitive functions were thus measured using a pediatric version of the Stroop test before and after maximal, locomotor based aerobic exercise in 16 independently ambulatory children (8 children with CP), 6-15 years old. Intense exercise had: 1) a significant, large, positive effect on reaction time (RT) for the CP group (preexercise: 892 ± 56.5 ms vs. postexercise: 798 ± 45.6 ms, p effect on the interference effect for the CP group (preexercise: 4.5 ± 2.5%RT vs. postexercise: 13 ± 2.9%RT, p effect for the TD group (preexercise: 7.2 ± 2.5%RT vs. postexercise: 6.9 ± 2.9%RT, p > .4, d = 0.03). Response accuracy was high in both groups pre- and postexercise (>96%). In conclusion, intense exercise impacts cognitive functioning in children with CP, both by increasing processing speed and decreasing executive function. PMID:26502458

  1. Neuronal glutamate transporters regulate synaptic transmission in single synapses on CA1 hippocampal neurons.

    Science.gov (United States)

    Kondratskaya, Elena; Shin, Min-Chul; Akaike, Norio

    2010-01-15

    Glutamate is the major excitatory transmitter in CNS although it causes severe brain damage by pathologic excitotoxicity. Efficient neurotransmission is controlled by powerful protection and support afforded by specific high-affinity glutamate transporters in neurons and glia, clearing synaptic glutamate. While the role of glial cells in glutamate uptake is well defined, the role of neuronal transporters remains poorly understood. The evaluation of impact of neuronal transporters on spontaneous and evoked EPSC in hippocampal CA1 neurons within a model 'single bouton preparation' by pre- and postsynaptic uptake was addressed. In whole-cell patch clamp experiments the influence of blocking, pre- or both pre- and postsynaptic glutamate transporters (GluT) on spontaneous and evoked postsynaptic currents (sEPSC and eEPSC), was examined by manipulating the content of intracellular solution. Suppressing GluT by non-transportable inhibitor TBOA (10 microM) led to remarkable alteration of glutamate uptake process and was reflected in measurable changes of general properties of synaptic currents. Elimination of intracellular K(+) concentration required for glutamate transporter operation by using Cs(+)-based internal solution (postsynaptic GluTs are non-functional apriori), causes the deficient of presynaptic glutamate transporters. Applied in such conditions glutamate transporter inhibitor TBOA (10 microM) affected the occurrence of synaptic event and thus unregulated the transmitter release. eEPSCs were generally suppressed both in amplitude (to 48.73+/-7.03% vs. control) and in success rate (R(suc)) by TBOA (from 91.1+/-7.5% in control to 79.57+/-13.2%). In contrast, with K(+)-based solution in patch pipette (pre- and postsynaptic GluT are intact), amplitude of eEPSC was substantially potentiated by pre-treatment with TBOA (152.1+/-11%), whereas (R(suc)) was reduced to 79.8+/-8.3% in average. The identical reduction of event success rate as well as increased pair

  2. Plant sterols: factors affecting their efficacy and safety as functional food ingredients

    Directory of Open Access Journals (Sweden)

    Abumweis Suhad S

    2004-04-01

    Full Text Available Abstract Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8–1.0 g of equivalents per day and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status.

  3. Association between Lung Function and Vocal Affections Arising from Tobacco Consumption

    Directory of Open Access Journals (Sweden)

    Santos, Karoline Weber dos

    2014-01-01

    Full Text Available Introduction Smoking is a major risk factor for numerous diseases; it is necessary to analyze the impact that the habit can have on vocal health. Objectives To determine the influence of smoking on changes in vocal production and lung vital capacity compared with nonsmokers. Methods This cross-sectional study compared smokers and nonsmokers (24 subjects each. Each participant underwent a vocal and spirometric evaluation to measure vital lung capacity. Results The results showed a worsening in lung vital capacity and other parameters of voice in smokers compared with nonsmokers. Furthermore, the decreased pulmonary vital capacity affected the evaluated voice parameters, and decreased carrying capacity was closely related to smoking. The time and amount of consumption had a direct relationship with the vocal and maximum phonation time. Conclusions This study showed that smoking causes voice disorders due to lung weakness. Thus, voice changes are affected both directly by interference of smoking on vocal structures and indirectly by increased weakness, which impairs lung vocal production.

  4. Association between Lung Function and Vocal Affections Arising from Tobacco Consumption.

    Science.gov (United States)

    Santos, Karoline Weber Dos; Echeveste, Simone Soares; Vidor, Deisi Cristina Gollo Marques

    2014-01-01

    Introduction Smoking is a major risk factor for numerous diseases; it is necessary to analyze the impact that the habit can have on vocal health. Objectives To determine the influence of smoking on changes in vocal production and lung vital capacity compared with nonsmokers. Methods This cross-sectional study compared smokers and nonsmokers (24 subjects each). Each participant underwent a vocal and spirometric evaluation to measure vital lung capacity. Results The results showed a worsening in lung vital capacity and other parameters of voice in smokers compared with nonsmokers. Furthermore, the decreased pulmonary vital capacity affected the evaluated voice parameters, and decreased carrying capacity was closely related to smoking. The time and amount of consumption had a direct relationship with the vocal and maximum phonation time. Conclusions This study showed that smoking causes voice disorders due to lung weakness. Thus, voice changes are affected both directly by interference of smoking on vocal structures and indirectly by increased weakness, which impairs lung vocal production. PMID:25992056

  5. In vitro atrazine exposure affects the phenotypic and functional maturation of dendritic cells

    International Nuclear Information System (INIS)

    Recent data suggest that some of the immunotoxic effects of the herbicide atrazine, a very widely used pesticide, may be due to perturbations in dendritic cell (DC) function. As consequences of atrazine exposure on the phenotypic and functional maturation of DC have not been studied, our objective was, using the murine DC line, JAWSII, to determine whether atrazine will interfere with DC maturation. First, we characterized the maturation of JAWSII cells in vitro by inducing them to mature in the presence of growth factors and selected maturational stimuli in vitro. Next, we exposed the DC cell line to a concentration range of atrazine and examined its effects on phenotypic and functional maturation of DC. Atrazine exposure interfered with the phenotypic and functional maturation of DC at non-cytotoxic concentrations. Among the phenotypic changes caused by atrazine exposure was a dose-dependent removal of surface MHC-I with a significant decrease being observed at 1 μM concentration. In addition, atrazine exposure decreased the expression of the costimulatory molecule CD86 and it downregulated the expression of the CD11b and CD11c accessory molecules and the myeloid developmental marker CD14. When, for comparative purposes, we exposed primary thymic DC to atrazine, MHC-I and CD11c expression was also decreased. Phenotypic changes in JAWSII DC maturation were associated with functional inhibition of maturation as, albeit at higher concentrations, receptor-mediated antigen uptake was increased by atrazine. Thus, our data suggest that atrazine directly targets DC maturation and that toxicants such as atrazine that efficiently remove MHC-I molecules from the DC surface are likely to contribute to immune evasion

  6. Representations of modality-specific affective processing for visual and auditory stimuli derived from functional magnetic resonance imaging data.

    Science.gov (United States)

    Shinkareva, Svetlana V; Wang, Jing; Kim, Jongwan; Facciani, Matthew J; Baucom, Laura B; Wedell, Douglas H

    2014-07-01

    There is converging evidence that people rapidly and automatically encode affective dimensions of objects, events, and environments that they encounter in the normal course of their daily routines. An important research question is whether affective representations differ with sensory modality. This research examined the nature of the dependency of affect and sensory modality at a whole-brain level of analysis in an incidental affective processing paradigm. Participants were presented with picture and sound stimuli that differed in positive or negative valence in an event-related functional magnetic resonance imaging experiment. Global statistical tests, applied at a level of the individual, demonstrated significant sensitivity to valence within modality, but not valence across modalities. Modality-general and modality-specific valence hypotheses predict distinctly different multidimensional patterns of the stimulus conditions. Examination of lower dimensional representation of the data demonstrated separable dimensions for valence processing within each modality. These results provide support for modality-specific valence processing in an incidental affective processing paradigm at a whole-brain level of analysis. Future research should further investigate how stimulus-specific emotional decoding may be mediated by the physical properties of the stimuli. PMID:24302696

  7. Intermittent hypoxia leads to functional reorganization of mitochondria and affects cellular bioenergetics in marine molluscs.

    Science.gov (United States)

    Ivanina, Anna V; Nesmelova, Irina; Leamy, Larry; Sokolov, Eugene P; Sokolova, Inna M

    2016-06-01

    Fluctuations in oxygen (O2) concentrations represent a major challenge to aerobic organisms and can be extremely damaging to their mitochondria. Marine intertidal molluscs are well-adapted to frequent O2 fluctuations, yet it remains unknown how their mitochondrial functions are regulated to sustain energy metabolism and prevent cellular damage during hypoxia and reoxygenation (H/R). We used metabolic control analysis to investigate the mechanisms of mitochondrial responses to H/R stress (18 h at recovery, combined with the ability to suppress ATP-demanding cellular functions during hypoxia, may contribute to high resilience of clams to H/R stress and help maintain energy homeostasis during frequent H/R cycles in the intertidal zone. PMID:27252455

  8. Altered CD45 isoform expression affects lymphocyte function in CD45 Tg mice.

    Science.gov (United States)

    Tchilian, Elma Z; Dawes, Ritu; Hyland, Lisa; Montoya, Maria; Le Bon, Agnes; Borrow, Persephone; Hou, Sam; Tough, David; Beverley, Peter C L

    2004-09-01

    Transgenic mice have been constructed expressing high (CD45RABC) and low (CD45R0) molecular weight CD45 isoforms on a CD45-/- background. Phenotypic analysis and in vivo challenge of these mice with influenza and lymphocytic choriomeningitis viruses shows that T cell differentiation and peripheral T cell function are related to the level of CD45 expression but not to which CD45 isoform is expressed. In contrast, B cell differentiation is not restored, irrespective of the level of expression of a single isoform. All CD45 trangenic mice have T cells with an activated phenotype and increased T cell turnover. These effects are more prominent in CD8 than CD4 cells. The transgenic mice share several properties with humans expressing variant CD45 alleles and provide a model to understand immune function in variant individuals. PMID:15302847

  9. The new PR of states: How nation branding practices affect the security function of public diplomacy

    DEFF Research Database (Denmark)

    Rasmussen, Rasmus Kjærgaard; Merkelsen, Henrik

    2012-01-01

    This paper investigates how the role of public relations practice in public diplomacy is undergoing a transformation as a consequence of the influence from nation branding. A case study of the Danish government's response to the so-called Cartoon Crisis illustrates how the threat from international...... terrorism to national security initially served as a catalyst for new public diplomacy initiatives. But as the initiatives were implemented within a framework of nation branding the focus on risk reduction became subjected to a marketing logic and a new focus on economic objectives took over. The paper...... points to a possible future status of public diplomacy under the influence of nation branding: Public diplomacy may maintain a function pertinent to national security but as this function is incapable of managing real risks it will only serve as auto-communication that legitimizes security policy towards...

  10. Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen

    OpenAIRE

    Mendes-Pereira, Ana M.; Sims, David; Dexter, Tim; Fenwick, Kerry; Assiotis, Ioannis; Kozarewa, Iwanka; Mitsopoulos, Costas; Hakas, Jarle; Zvelebil, Marketa; Lord, Christopher J; Ashworth, Alan

    2011-01-01

    Therapies that target estrogen signaling have made a very considerable contribution to reducing mortality from breast cancer. However, resistance to tamoxifen remains a major clinical problem. Here we have used a genome-wide functional profiling approach to identify multiple genes that confer resistance or sensitivity to tamoxifen. Combining whole-genome shRNA screening with massively parallel sequencing, we have profiled the impact of more than 56,670 RNA interference reagents targeting 16,4...

  11. Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo

    OpenAIRE

    Hesselink, M.K.C.; Greenhaff, P L; Constantin-Teodosu, D.; Hultman, E; Saris, W. H. M.; Nieuwlaat, R.; Schaart, G.; Kornips, C.F.P.; P. Schrauwen

    2003-01-01

    Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (L...

  12. The subcellular localization of IGFBP5 affects its cell growth and migration functions in breast cancer

    OpenAIRE

    Sahin Aysegul; Hu Limei; Akkiprik Mustafa; Hao Xishan; Zhang Wei

    2009-01-01

    Abstract Background Insulin-like growth factor binding protein 5 (IGFBP5) has been shown to be associated with breast cancer metastasis in clinical marker studies. However, a major difficulty in understanding how IGFBP5 functions in this capacity is the paradoxical observation that ectopic overexpression of IGFBP5 in breast cancer cell lines results in suppressed cellular proliferation. In cancer tissues, IGFBP5 resides mainly in the cytoplasm; however, in transfected cells, IGFBP5 is mainly ...

  13. Neonatal oxygen adversely affects lung function in adult mice without altering surfactant composition or activity

    OpenAIRE

    Yee, Min; Chess, Patricia R.; McGrath-Morrow, Sharon A.; Wang, Zhengdong; Gelein, Robert; Zhou, Rui; Dean, David A.; Notter, Robert H.; O'Reilly, Michael A.

    2009-01-01

    Despite its potentially adverse effects on lung development and function, supplemental oxygen is often used to treat premature infants in respiratory distress. To understand how neonatal hyperoxia can permanently disrupt lung development, we previously reported increased lung compliance, greater alveolar simplification, and disrupted epithelial development in adult mice exposed to 100% inspired oxygen fraction between postnatal days 1 and 4. Here, we investigate whether oxygen-induced changes...

  14. Elementary Neurocognitive Function, Facial Affect Recognition and Social-skills in Schizophrenia

    OpenAIRE

    Meyer, Melissa B.; Kurtz, Matthew M.

    2009-01-01

    Social-skill deficits are pervasive in schizophrenia and negatively impact many key aspects of functioning. Prior studies have found that measures of elementary neurocognition and social cognition are related to social-skills. In the present study we selected a range of neurocognitive measures and examined their relationship with identification of happy and sad faces and performance-based social-skills. Fifty-three patients with schizophrenia or schizoaffective disorder participated. Results ...

  15. Adolescent Heavy Drinking Does Not Affect Maturation of Basic Executive Functioning: Longitudinal Findings from the TRAILS Study.

    Directory of Open Access Journals (Sweden)

    Sarai R Boelema

    Full Text Available Excessive alcohol use is assumed to affect maturation of cognitive functioning in adolescence. However, most existing studies that have tested this hypothesis are seriously flawed due to the use of selective groups and/or cross-sectional designs, which limits the ability to draw firm conclusions. This longitudinal study investigated whether patterns of alcohol use predicted differences in maturation of executive functioning in adolescence. Additionally, gender was tested as a possible moderator.We used data from the Tracking Adolescents' Individual Lives Survey (TRAILS, which comprises a cohort of 2,230 Dutch adolescents. Maturation of executive functioning was measured by assessing the standardized improvement on each of four basic executive functions (i.e., inhibition, working memory, and shift- and sustained attention between ages 11 and 19. Participants were assigned to one of six (heavy drinking groups (i.e., non-drinkers, light drinkers, infrequent heavy drinkers, increased heavy drinkers, decreased heavy drinkers, and chronic heavy drinkers. We conducted linear regression analyses, and adjusted for relevant confounders.The six drinking groups did not reveal significant differences in maturation between drinking groups. E.g., maturation executive functioning of chronic heavy drinkers in comparison to non-drinkers; inhibition: B = -0.14, 95% CI [-0.41 to 0.14], working memory: B = -0.03, 95% CI [-0.26 to 0.21], shift attention: B = 0.13, 95% CI [-0.17 to 0.41], sustained attention: B = 0.12, 95% CI [-0.60 to 0.36]. Furthermore, gender was not found to be a significant moderator.Four years of weekly heavy drinking (i.e., chronic heavy drinkers did not result in measurable impairments in four basic executive functions. Thus, regular heavy drinking in adolescence does not seem to affect these basic behavioural measures of executive functioning.

  16. Tree species and functional traits but not species richness affect interrill erosion processes in young subtropical forests

    Science.gov (United States)

    Seitz, S.; Goebes, P.; Song, Z.; Bruelheide, H.; Härdtle, W.; Kühn, P.; Li, Y.; Scholten, T.

    2016-01-01

    Soil erosion is seriously threatening ecosystem functioning in many parts of the world. In this context, it is assumed that tree species richness and functional diversity of tree communities can play a critical role in improving ecosystem services such as erosion control. An experiment with 170 micro-scale run-off plots was conducted to investigate the influence of tree species and tree species richness as well as functional traits on interrill erosion in a young forest ecosystem. An interrill erosion rate of 47.5 Mg ha-1 a-1 was calculated. This study provided evidence that different tree species affect interrill erosion differently, while tree species richness did not affect interrill erosion in young forest stands. Thus, different tree morphologies have to be considered, when assessing soil erosion under forest. High crown cover and leaf area index reduced interrill erosion in initial forest ecosystems, whereas rising tree height increased it. Even if a leaf litter cover was not present, the remaining soil surface cover by stones and biological soil crusts was the most important driver for soil erosion control. Furthermore, soil organic matter had a decreasing influence on interrill erosion. Long-term monitoring of soil erosion under closing tree canopies is necessary, and a wide range of functional tree traits should be considered in future research.

  17. Class IIa histone deacetylases affect neuronal remodeling and functional outcome after stroke.

    Science.gov (United States)

    Kassis, Haifa; Shehadah, Amjad; Li, Chao; Zhang, Yi; Cui, Yisheng; Roberts, Cynthia; Sadry, Neema; Liu, Xianshuang; Chopp, Michael; Zhang, Zheng Gang

    2016-06-01

    We have previously demonstrated that stroke induces nuclear shuttling of class IIa histone deacetylase 4 (HDAC4). Stroke-induced nuclear shuttling of HDAC4 is positively and significantly correlated with improved indices of neuronal remodeling in the peri-infarct cortex. In this study, using a rat model for middle cerebral artery occlusion (MCAO), we tested the effects of selective inhibition of class IIa HDACs on functional recovery and neuronal remodeling when administered 24hr after stroke. Adult male Wistar rats (n = 15-17/group) were subjected to 2 h MCAO and orally gavaged with MC1568 (a selective class IIa HDAC inhibitor), SAHA (a non-selective HDAC inhibitor), or vehicle-control for 7 days starting 24 h after MCAO. A battery of behavioral tests was performed. Lesion volume measurement and immunohistochemistry were performed 28 days after MCAO. We found that stroke increased total HDAC activity in the ipsilateral hemisphere compared to the contralateral hemisphere. Stroke-increased HDAC activity was significantly decreased by the administration of SAHA as well as by MC1568. However, SAHA significantly improved functional outcome compared to vehicle control, whereas selective class IIa inhibition with MC1568 increased mortality and lesion volume and did not improve functional outcome. In addition, MC1568 decreased microtubule associated protein 2 (MAP2, dendrites), phosphorylated neurofilament heavy chain (pNFH, axons) and myelin basic protein (MBP, myelination) immunoreactivity in the peri-infarct cortex. Quantitative RT-PCR of cortical neurons isolated by laser capture microdissection revealed that MC1568, but not SAHA, downregulated CREB and c-fos expression. Additionally, MC1568 decreased the expression of phosphorylated CREB (active) in neurons. Taken together, these findings demonstrate that selective inhibition of class IIa HDACs impairs neuronal remodeling and neurological outcome. Inactivation of CREB and c-fos by MC1568 likely contributes to

  18. Cerebellar mutism syndrome and its relation to cerebellar cognitive and affective function: Review of the literature

    Directory of Open Access Journals (Sweden)

    Yildiz Ozlem

    2010-01-01

    Full Text Available Tumors of the cerebellum and brainstem account for half of all brain tumors in children. The realization that cerebellar lesions produce clinically relevant intellectual disability makes it important to determine whether neuropsychological abnormalities occur in long-term survivors of pediatric cerebellar tumors. Little is known about the neurobehavioral sequale resulting specifically from the resection of these tumors in this population. We therefore reviewed neuropsychological findings associated with postoperative cerebellar mutism syndrome and discuss the further implications for cerebellar cognitive function.

  19. Exposure to grass pollen – but not birch pollen – affects lung function in Swedish children

    OpenAIRE

    Gruzieva, O.; Pershagen, G; Wickman, M; Melén, E; Hallberg, J.; Bellander, T; Lõhmus, M.

    2015-01-01

    Abstract Allergic response to pollen is increasing worldwide, leading to high medical and social costs. However, the effect of pollen exposure on lung function has rarely been investigated. Over 1800 children in the Swedish birth cohort BAMSE were lung‐function‐ and IgE‐tested at the age of 8 and 16 years old. Daily concentrations for 9 pollen types together with measurements for ozone, NO 2, PM 10, PM 2.5 were estimated for the index day as well as up to 6 days before the testing. Exposure t...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Differentiation of autonomic reflex control begins with cellular mechanisms at the first synapse within the nucleus tractus solitarius

    Directory of Open Access Journals (Sweden)

    M.C. Andresen

    2004-04-01

    Full Text Available Visceral afferents send information via cranial nerves to the nucleus tractus solitarius (NTS. The NTS is the initial step of information processing that culminates in homeostatic reflex responses. Recent evidence suggests that strong afferent synaptic responses in the NTS are most often modulated by depression and this forms a basic principle of central integration of these autonomic pathways. The visceral afferent synapse is uncommonly powerful at the NTS with large unitary response amplitudes and depression rather than facilitation at moderate to high frequencies of activation. Substantial signal depression occurs through multiple mechanisms at this very first brainstem synapse onto second order NTS neurons. This review highlights new approaches to the study of these basic processes featuring patch clamp recordings in NTS brain slices and optical techniques with fluorescent tracers. The vanilloid receptor agonist, capsaicin, distinguishes two classes of second order neurons (capsaicin sensitive or capsaicin resistant that appear to reflect unmyelinated and myelinated afferent pathways. The differences in cellular properties of these two classes of NTS neurons indicate clear functional differentiation at both the pre- and postsynaptic portions of these first synapses. By virtue of their position at the earliest stage of these pathways, such mechanistic differences probably impart important differentiation in the performance over the entire reflex pathways.

  2. Does Speaking Two Dialects in Daily Life Affect Executive Functions? An Event-Related Potential Study.

    Science.gov (United States)

    Wu, Yan Jing; Zhang, Haoyun; Guo, Taomei

    2016-01-01

    Whether using two languages enhances executive functions is a matter of debate. Here, we take a novel perspective to examine the bilingual advantage hypothesis by comparing bi-dialect with mono-dialect speakers' performance on a non-linguistic task that requires executive control. Two groups of native Chinese speakers, one speaking only the standard Chinese Mandarin and the other also speaking the Southern-Min dialect, which differs from the standard Chinese Mandarin primarily in phonology, performed a classic Flanker task. Behavioural results showed no difference between the two groups, but event-related potentials recorded simultaneously revealed a number of differences, including an earlier P2 effect in the bi-dialect as compared to the mono-dialect group, suggesting that the two groups engage different underlying neural processes. Despite differences in the early ERP component, no between-group differences in the magnitude of the Flanker effects, which is an index of conflict resolution, were observed in the N2 component. Therefore, these findings suggest that speaking two dialects of one language does not enhance executive functions. Implications of the current findings for the bilingual advantage hypothesis are discussed. PMID:26991456

  3. IL-6 signaling blockade increases inflammation but does not affect muscle function in the mdx mouse

    Directory of Open Access Journals (Sweden)

    Kostek Matthew C

    2012-06-01

    Full Text Available Abstract Background IL-6 is a pleiotropic cytokine that modulates inflammatory responses and plays critical roles in muscle maintenance and remodeling. In the mouse model (mdx of Duchenne Muscular Dystrophy, IL-6 and muscle inflammation are elevated, which is believed to contribute to the chronic inflammation and failure of muscle regeneration in DMD. The purpose of the current study was to examine the effect of blocking IL-6 signaling on the muscle phenotype including muscle weakness and pathology in the mdx mouse. Methods A monoclonal antibody against the IL-6 receptor (IL-6r mAb that blocks local and systemic IL-6 signaling was administered to mdx and BL-10 mice for 5 weeks and muscle function, histology, and inflammation were examined. Results IL-6r mAb treatment increased mdx muscle inflammation including total inflammation score and ICAM-1 positive lumens in muscles. There was no significant improvement in muscle strength nor muscle pathology due to IL-6r mAb treatment in mdx mice. Conclusions These results showed that instead of reducing inflammation, IL-6 signaling blockade for 5 weeks caused an increase in muscle inflammation, with no significant change in indices related to muscle regeneration and muscle function. The results suggest a potential anti-inflammatory instead of the original hypothesized pro-inflammatory role of IL-6 signaling in the mdx mice.

  4. Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

    International Nuclear Information System (INIS)

    Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17β-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca2+ delaying the opening of the permeability transition pore. The presence of 25 μM E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H2O2 in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered

  5. MicroRNA-155 negatively affects blood-brain barrier function during neuroinflammation.

    Science.gov (United States)

    Lopez-Ramirez, Miguel Alejandro; Wu, Dongsheng; Pryce, Gareth; Simpson, Julie E; Reijerkerk, Arie; King-Robson, Josh; Kay, Oliver; de Vries, Helga E; Hirst, Mark C; Sharrack, Basil; Baker, David; Male, David Kingsley; Michael, Gregory J; Romero, Ignacio Andres

    2014-06-01

    Blood-brain barrier (BBB) dysfunction is a hallmark of neurological conditions such as multiple sclerosis (MS) and stroke. However, the molecular mechanisms underlying neurovascular dysfunction during BBB breakdown remain elusive. MicroRNAs (miRNAs) have recently emerged as key regulators of pathogenic responses, although their role in central nervous system (CNS) microvascular disorders is largely unknown. We have identified miR-155 as a critical miRNA in neuroinflammation at the BBB. miR-155 is expressed at the neurovascular unit of individuals with MS and of mice with experimental autoimmune encephalomyelitis (EAE). In mice, loss of miR-155 reduced CNS extravasation of systemic tracers, both in EAE and in an acute systemic inflammation model induced by lipopolysaccharide. In cultured human brain endothelium, miR-155 was strongly and rapidly upregulated by inflammatory cytokines. miR-155 up-regulation mimicked cytokine-induced alterations in junctional organization and permeability, whereas inhibition of endogenous miR-155 partially prevented a cytokine-induced increase in permeability. Furthermore, miR-155 modulated brain endothelial barrier function by targeting not only cell-cell complex molecules such as annexin-2 and claudin-1, but also focal adhesion components such as DOCK-1 and syntenin-1. We propose that brain endothelial miR-155 is a negative regulator of BBB function that may constitute a novel therapeutic target for CNS neuroinflammatory disorders. PMID:24604078

  6. Does Dietary Mitigation of Enteric Methane Production Affect Rumen Function and Animal Productivity in Dairy Cows?

    Science.gov (United States)

    Veneman, Jolien B.; Muetzel, Stefan; Hart, Kenton J.; Faulkner, Catherine L.; Moorby, Jon M.; Perdok, Hink B.; Newbold, Charles J.

    2015-01-01

    It has been suggested that the rumen microbiome and rumen function might be disrupted if methane production in the rumen is decreased. Furthermore concerns have been voiced that geography and management might influence the underlying microbial population and hence the response of the rumen to mitigation strategies. Here we report the effect of the dietary additives: linseed oil and nitrate on methane emissions, rumen fermentation, and the rumen microbiome in two experiments from New Zealand (Dairy 1) and the UK (Dairy 2). Dairy 1 was a randomized block design with 18 multiparous lactating cows. Dairy 2 was a complete replicated 3 x 3 Latin Square using 6 rumen cannulated, lactating dairy cows. Treatments consisted of a control total mixed ration (TMR), supplementation with linseed oil (4% of feed DM) and supplementation with nitrate (2% of feed DM) in both experiments. Methane emissions were measured in open circuit respiration chambers and rumen samples were analyzed for rumen fermentation parameters and microbial population structure using qPCR and next generation sequencing (NGS). Supplementation with nitrate, but not linseed oil, decreased methane yield (g/kg DMI; Pmethane emissions can be significantly decreased with nitrate supplementation with only minor, but consistent, effects on the rumen microbial population and its function, with no evidence that the response to dietary additives differed due to geography and different underlying microbial populations. PMID:26509835

  7. Does Congenital Deafness Affect the Structural and Functional Architecture of Primary Visual Cortex?

    Science.gov (United States)

    Smittenaar, C R; MacSweeney, M; Sereno, M I; Schwarzkopf, D S

    2016-01-01

    Deafness results in greater reliance on the remaining senses. It is unknown whether the cortical architecture of the intact senses is optimized to compensate for lost input. Here we performed widefield population receptive field (pRF) mapping of primary visual cortex (V1) with functional magnetic resonance imaging (fMRI) in hearing and congenitally deaf participants, all of whom had learnt sign language after the age of 10 years. We found larger pRFs encoding the peripheral visual field of deaf compared to hearing participants. This was likely driven by larger facilitatory center zones of the pRF profile concentrated in the near and far periphery in the deaf group. pRF density was comparable between groups, indicating pRFs overlapped more in the deaf group. This could suggest that a coarse coding strategy underlies enhanced peripheral visual skills in deaf people. Cortical thickness was also decreased in V1 in the deaf group. These findings suggest deafness causes structural and functional plasticity at the earliest stages of visual cortex. PMID:27014392

  8. Does Speaking Two Dialects in Daily Life Affect Executive Functions? An Event-Related Potential Study

    Science.gov (United States)

    Wu, Yan Jing; Zhang, Haoyun; Guo, Taomei

    2016-01-01

    Whether using two languages enhances executive functions is a matter of debate. Here, we take a novel perspective to examine the bilingual advantage hypothesis by comparing bi-dialect with mono-dialect speakers’ performance on a non-linguistic task that requires executive control. Two groups of native Chinese speakers, one speaking only the standard Chinese Mandarin and the other also speaking the Southern-Min dialect, which differs from the standard Chinese Mandarin primarily in phonology, performed a classic Flanker task. Behavioural results showed no difference between the two groups, but event-related potentials recorded simultaneously revealed a number of differences, including an earlier P2 effect in the bi-dialect as compared to the mono-dialect group, suggesting that the two groups engage different underlying neural processes. Despite differences in the early ERP component, no between-group differences in the magnitude of the Flanker effects, which is an index of conflict resolution, were observed in the N2 component. Therefore, these findings suggest that speaking two dialects of one language does not enhance executive functions. Implications of the current findings for the bilingual advantage hypothesis are discussed. PMID:26991456

  9. Functional Measurement Analysis of Brand Equity: Does Brand Name affect Perceptions of Quality?

    Directory of Open Access Journals (Sweden)

    James Shanteau

    2010-01-01

    Full Text Available This research project used Functional Measurement to examine how the brand name of consumer products impacts intended purchasing decisions. Thirty undergraduate students tested actual products from three different product categories (crayons, tissues, and tortilla chips. Each product category consisted of three different brands; one with high brand value, one with medium, and one with low brand (generic value. For each brand, there were five conditions: 1 the product with the correct brand name; 2 the product with a switched brand name; 3 the product with another switched brand name; 4 the product alone with no brand name; and 5 the brand name alone with no product. Participants were unaware that products had been switched. After trying each product, participants rated their likelihood to purchase on a 9-point Likert scale: 1 being "definitely would not buy" and 9 being "definitely would buy." Results revealed that perceptions of quality were dependent on both perceived product quality and brand name. Unexpectedly, results also showed that the strength of the brand equity effect is dependent on product type, e.g., chips showed the strongest brand effect. For most product categories, main effects and interactions were significant. Functional measurement analyses revealed that brand name effects were independent of product quality. In conclusion, the brand name associated with a product led people to evaluate quality of that product as either higher or lower depending on the strength of the brand name.

  10. Land Management Effects on Biogeochemical Functioning of Salt-Affected Paddy Soils

    Institute of Scientific and Technical Information of China (English)

    C.QUANTIN; O.GRUNBERGER; N.SUVANNANG; E.BOURDON

    2008-01-01

    Most lowlands in Northeast Thailand (Isaan region) are cultivated with rice and large areas are affected by salinity,which drastically limits rice production.A field experiment was conducted during the 2003 rainy season to explore the interactions between salinity and land management in two fields representative of two farming practices:an intensively managed plot with organic inputs and efficient water management,and one without organic matter addition.Field measurements,including pH,Eh,electrical conductivity (EC),and soil solution chemistry,were performed at three depths,with a particular focus on Fe dynamics,inside and outside saline patches.High reducing conditions appeared after flooding particularly in plots receiving organic matter and reduction processes leading to oxide reduction and to the release of Fe and,to a lesser extend,Mn to the soil solution.Oxide reduction led to the consumption of H+ and the more the Fe reduction was,the higher the pH was,up to 6.5.Formation of hydroxy-green rust were likely to be at the origin of the pH stabilization.In the absence of organic amendments,high salinity prevented the establishment of the reduction processes and pH value remained around 4.Even under high reduction conditions,the Fe concentrations in the soil solution were below commonly observed toxic values and the amended plot had better rice production yield.

  11. Technical parameters affecting differential renal function estimation using Tc 99m MAG3 scintigraphy

    International Nuclear Information System (INIS)

    Introduction: Differential renal function (DRF) is an important parameter that is assessed from virtually every dynamic renal scintigraphy. Standardization of DRF estimation is very important, as this is a measurement of individual kidney function used in gamma camera based techniques for estimating Tc99m MAG3 clearance. The aim of this study was to assess the effect of different acquisition and processing parameters on the estimation of DRF. Material and methods: Retrospective study of 24 patients (2.5-73 yrs). The patients were divided into 3 groups: 1)Normal renogram pattern (DRF within 45/55). 2) Abnormal renogram patterns (DRF>20%). 3) One kidney with DRF<20% (poor functioning). In each group we investigated the effect on DRF of the following parameters in all patients: renal ROIs (rectangular or fitting), background ROIs (manual subrenal, perirenal, lateral and automated elliptical), with and without correction for kidneys depth attenuation, time interval (1-2, 2-3 min) for calculation of renal counts, and matrix size (128 x 128, 64 x 64). Results: Two experienced readers evaluated the results: 1. DRF did not differ among the two time intervals. 2. DRF calculated in group 1 using subrenal background ROI was significantly different from that of perirenal and flanking background ROI's on 64x64 matrix (p= 0.0095, 0.055 respectively), whereas no difference was found in 128x128 where all types of background ROI's gave almost the same results. 3. Mean left kidney depth from height and weight formula (7.6+ 2.57 cm)was significantly different (p= 0.000237,t test) from formula of age, height and weight ( 8.7±3.18 cm), yet DRF did not change significantly, when attenuation correction was applied using these formulas. 4. Good correlation (r = 0.98) was observed between the two readers. Conclusion: Matrix size of 128x128 increased the reliability and accuracy for drawing ROIs. It eliminated the differences found within different locations and size of background (ROI

  12. Maternal separation affects dopamine transporter function in the Spontaneously Hypertensive Rat: An in vivo electrochemical study

    Directory of Open Access Journals (Sweden)

    Womersley Jacqueline S

    2011-12-01

    Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT in ways that distinguish SHR from control rat strains. Methods SHR and control Wistar-Kyoto (WKY rats were subjected to maternal separation for 3 hours per day from postnatal day 2 to 14. Rats were tested for separation-induced anxiety-like behaviour followed by in vivo chronoamperometry to determine whether changes had occurred in striatal clearance of dopamine by DAT. The rate of disappearance of ejected dopamine was used as a measure of DAT function. Results Consistent with a model for ADHD, SHR were more active than WKY in the open field. SHR entered the inner zone more frequently and covered a significantly greater distance than WKY. Maternal separation increased the time that WKY spent in the closed arms and latency to enter the open arms of the elevated plus maze, consistent with other rat strains. Of note is that, maternal separation failed to produce anxiety-like behaviour in SHR. Analysis of the chronoamperometric data revealed that there was no difference in DAT function in the striatum of non-separated SHR and WKY. Maternal separation decreased the rate of dopamine clearance (k-1 in SHR striatum. Consistent with this observation, the dopamine clearance time (T100 was increased in SHR. These results suggest that the chronic mild stress of

  13. Allelic and copy-number variations of FcγRs affect granulocyte function and susceptibility for autoimmune blistering diseases.

    Science.gov (United States)

    Recke, Andreas; Vidarsson, Gestur; Ludwig, Ralf J; Freitag, Miriam; Möller, Steffen; Vonthein, Reinhard; Schellenberger, Julia; Haase, Ozan; Görg, Siegfried; Nebel, Almut; Flachsbart, Friederike; Schreiber, Stefan; Lieb, Wolfgang; Gläser, Regine; Benoit, Sandrine; Sárdy, Miklós; Eming, Rüdiger; Hertl, Michael; Zillikens, Detlef; König, Inke R; Schmidt, Enno; Ibrahim, Saleh

    2015-07-01

    Low-affinity Fcγ receptors (FcγR) bridge innate and adaptive immune responses. In many autoimmune diseases, these receptors act as key mediators of the pathogenic effects of autoantibodies. Genes encoding FcγR exhibit frequent variations in sequence and gene copy number that influence their functional properties. FcγR variations also affect the susceptibility to systemic autoimmunity, e.g. systemic lupus erythematosus and rheumatoid arthritis. This raises the question whether FcγR variations are also associated with organ-specific autoimmunity, particularly autoantibody-mediated diseases, such as subepidermal autoimmune blistering diseases (AIBD). A multitude of evidence suggests a pathogenic role of neutrophil granulocyte interaction with autoantibodies via FcγR. In a two-stage study, we analyzed whether the FcγR genotype affects neutrophil function and mRNA expression, and consequently, bullous pemphigoid (BP) disease risk. We compared this to findings in pemphigus vulgaris/foliaceus (PV/PF), two Fc-independent AIBDs. Our results indicate that both allele and copy number variation of FcγR genes affect FcγR mRNA expression and reactive oxygen species (ROS) release by granulocytes. Susceptibility of BP was associated with FcγR genotypes that led to a decreased ROS release by neutrophils, indicating an unexpected protective role for these cells. BP and PV/PF differed substantially regarding the FcγR genotype association patterns, pointing towards different disease etiologies. PMID:26032265

  14. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R;

    2007-01-01

    reorganization in mature osteoclasts. INTRODUCTION: Urokinase receptor (uPAR) is actively involved in the regulation of important cell functions, such as proliferation, adhesion, and migration. It was previously shown that the major players in bone remodeling, osteoblasts and osteoclasts, express uPAR and...... to mechanical tests. UPAR KO calvaria osteoblasts were characterized by proliferation assays, RT-PCR for important proteins secreted during differentiation, and immunoblot for activator protein 1 (AP-1) family members. In vitro osteoclast formation was tested with uPAR KO bone marrow monocytes in the...... osteoblasts showed a proliferative advantage with no difference in apoptosis, higher matrix mineralization, and earlier appearance of alkaline phosphatase (ALP). Surface RANKL expression at different stages of differentiation was not altered. AP-1 components, such as JunB and Fra-1, were upregulated in u...

  15. Subject-specific geometrical detail rather than cost function formulation affects hip loading calculation.

    Science.gov (United States)

    Wesseling, Mariska; De Groote, Friedl; Bosmans, Lode; Bartels, Ward; Meyer, Christophe; Desloovere, Kaat; Jonkers, Ilse

    2016-11-01

    This study assessed the relative importance of introducing an increasing level of medical image-based subject-specific detail in bone and muscle geometry in the musculoskeletal model, on calculated hip contact forces during gait. These forces were compared to introducing minimization of hip contact forces in the optimization criterion. With an increasing level of subject-specific detail, specifically MRI-based geometry and wrapping surfaces representing the hip capsule, hip contact forces decreased and were more comparable to contact forces measured using instrumented prostheses (average difference of 0.69 BW at the first peak compared to 1.04 BW for the generic model). Inclusion of subject-specific wrapping surfaces in the model had a greater effect than altering the cost function definition. PMID:26930478

  16. Indoor particles affect vascular function in the aged - An air filtration-based intervention study

    DEFF Research Database (Denmark)

    Brauner, E.V.; Forchhammer, L.; Moller, P.;

    2008-01-01

    factors, P-selectin, plasma amyloid A, C-reactive protein, fibrinogen, IL-6, tumor necrosis factor-alpha, protein oxidation measured as 2-aminoadipic semialdehyde in plasma, urinary 8-iso-prostaglandin F-2 alpha, and blood pressure. Indoor air filtration significantly improved MVF by 8.1% (95% confidence......Rationale: Exposure to particulate matter is associated with risk of cardiovascular events, possibly through endothelial dysfunction, and indoor air may be most important. Objectives: We investigated effects of controlled exposure to indoor air particles on microvascular function (MVF) as the...... nonfiltered air (2,533-4,058 and 7,718-12,988 particles/cm(3), respectively) in their homes. Measurements and Main Results: MVF was assessed noninvasively by measuring digital peripheral artery tone after arm ischemia. Secondary endpoints included hemoglobin, red blood cells, platelet count, coagulation...

  17. Blood withdrawal affects iron store dynamics in primates with consequences on monoaminergic system function.

    Science.gov (United States)

    Hyacinthe, C; De Deurwaerdere, P; Thiollier, T; Li, Q; Bezard, E; Ghorayeb, I

    2015-04-01

    Iron homeostasis is essential for the integrity of brain monoaminergic functions and its deregulation might be involved in neurological movement disorders such as the restless legs syndrome (RLS). Although iron metabolism breakdown concomitantly appears with monoaminergic system dysfunction in iron-deficient rodents and in RLS patients, the direct consequences of peripheral iron deficiency in the central nervous system (CNS) of non-human primates have received little attention. Here, we evaluated the peripheral iron-depletion impact on brain monoamine levels in macaque monkeys. After documenting circadian variations of iron and iron-related proteins (hemoglobin, ferritin and transferrin) in both serum and cerebrospinal fluid (CSF) of normal macaques, repeated blood withdrawals (RBW) were used to reduce peripheral iron-related parameter levels. Decreased serum iron levels were paradoxically associated with increased CSF iron concentrations. Despite limited consequences on tissue monoamine contents (dopamine - DA, 3, 4-dihydroxyphenylacetic acid - DOPAC, homovanillic acid, L-3, 4-dihydroxyphenylalanine - L-DOPA, 5-8 hydroxytryptamine - 5-HT, 5-hydroxyindoleacetic acid - 5-HIAA and noradrenaline) measured with post-mortem chromatography, we found distinct and region-dependent relationships of these tissue concentrations with CSF iron and/or serum iron and/or blood hemoglobin. Additionally, striatal extracellular DA, DOPAC and 5-HIAA levels evaluated by in vivo microdialysis showed a substantial increase, suggesting an overall increase in both DA and 5-HT tones. Finally, a trending increase in general locomotor activity, measured by actimetry, was observed in the most serum iron-depleted macaques. Taken together, our data are compatible with an increase in nigrostriatal DAergic function in the event of iron deficiency and point to a specific alteration of the 5-HT/DA interaction in the CNS that is possibly involved in the etiology of RLS. PMID:25662508

  18. Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.

    Directory of Open Access Journals (Sweden)

    Ding Wang

    Full Text Available OBJECTIVE: Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs that may be associated with sepsis. METHODS: A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation and SOFA (sepsis-related organ failure assessment scores and discharge rate. Four functional SNPs, -1616T/C (rs2069705, -764G/C (rs2069707, +874A/T (rs2430561 and +3234C/T (rs2069718, were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson's chi-square test or Fisher's exact test were used to analyze the distribution of the SNPs, and the probability values (P values, odds ratios (OR and 95% confidence intervals (CIs were calculated. RESULTS: No mutations in the IFN-γ -764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD (r(2 = 0.894. The -1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of -1616 TT wasn't only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either. CONCLUSION: Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.

  19. Prolonged synaptic currents increase relay neuron firing at the developing retinogeniculate synapse

    OpenAIRE

    Hauser, Jessica L.; Liu, Xiaojin; Litvina, Elizabeth Y.; Chen, Chinfei

    2014-01-01

    The retinogeniculate synapse, the connection between retinal ganglion cells (RGC) and thalamic relay neurons, undergoes robust changes in connectivity over development. This process of synapse elimination and strengthening of remaining inputs is thought to require synapse specificity. Here we show that glutamate spillover and asynchronous release are prominent features of retinogeniculate synaptic transmission during this period. The immature excitatory postsynaptic currents exhibit a slow de...

  20. Neuronal pentraxins mediate silent synapse conversion in the developing visual system

    OpenAIRE

    Koch, Selina; Ullian, Erik M.

    2010-01-01

    Neuronal pentraxins (NPs) are hypothesized to play important roles in the recruitment of AMPA receptors (AMPARs) to immature synapses, yet a physiological role for NPs at nascent synapses in vivo has remained elusive. Here we report that the loss of NP1 and NP2 (NP1/2) leads to a dramatic and specific reduction in AMPAR-mediated transmission at developing visual system synapses. In thalamic slices taken from early postnatal mice (

  1. ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse formation

    OpenAIRE

    Sol-Foulon, Nathalie; Sourisseau, Marion; Porrot, Françoise; Thoulouze, Maria-Isabel; Trouillet, Céline; Nobile, Cinzia; Blanchet, Fabien; Di Bartolo, Vincenzo; Noraz, Nelly; Taylor, Naomi; Alcover, Andres; Hivroz, Claire; Schwartz, Olivier

    2007-01-01

    HIV efficiently spreads in lymphocytes, likely through virological synapses (VSs). These cell–cell junctions share some characteristics with immunological synapses, but cellular proteins required for their constitution remain poorly characterized. We have examined here the role of ZAP-70, a key kinase regulating T-cell activation and immunological synapse formation, in HIV replication. In lymphocytes deficient for ZAP-70, or expressing a kinase-dead mutant of the protein, HIV replication was ...

  2. Antibody to a molecular marker of cell position inhibits synapse formation in retina.

    OpenAIRE

    Trisler, D.; Bekenstein, J; Daniels, M P

    1986-01-01

    A topographic gradient of TOP molecules in retina can be used to identify neuron position. Antibody to TOP from hybridoma cells that were injected into in vivo embryo eyes diffused into the retina and bound in a topographic gradient of [antibody.TOP] ([Ab.TOP]) complexes. Synapse formation in retina was inhibited in the presence of anti-TOP antibody. This suggests that TOP is involved in synapse formation and that recognition of position by neurons is necessary for normal synapse formation.

  3. A Novel, Noncanonical BMP Pathway Modulates Synapse Maturation at the Drosophila Neuromuscular Junction

    OpenAIRE

    Sulkowski, Mikolaj J.; Tae Hee Han; Carolyn Ott; Qi Wang; Verheyen, Esther M.; Jennifer Lippincott-Schwartz; Mihaela Serpe

    2016-01-01

    Author Summary Synaptic activity and synapse development are intimately linked, but our understanding of the coupling mechanisms remains limited. Anterograde and retrograde signals together with trans-synaptic complexes enable intercellular communications. How synapse activity status is monitored and relayed across the synaptic cleft remains poorly understood. The Drosophila NMJ is a very powerful genetic system to study synapse development. BMP signaling modulates NMJ growth via a canonical,...

  4. NK cell survival mediated through the regulatory synapse with human DCs requires IL-15Rα

    OpenAIRE

    Brilot, Fabienne; Strowig, Till; Roberts, Susanne M.; Arrey, Frida; Münz, Christian

    2007-01-01

    DCs activate NK cells during innate immune responses to viral infections. However, the composition and kinetics of the immunological synapse mediating this interaction are largely unknown. Here, we report the rapid formation of an immunological synapse between human resting NK cells and mature DCs. Although inhibitory NK cell receptors were polarized to this synapse, where they are known to protect mature DCs from NK cell lysis, the NK cell also received activation signals that induced mobili...

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

    OpenAIRE

    Duman, Joseph G.; Yen-Kuei Tu; Tolias, Kimberley F.

    2016-01-01

    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...

  6. 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.

  7. Structure and function of the liver in conditions of chrome-isoniazid-rifampicin affection of rats after applying of sorbex

    Directory of Open Access Journals (Sweden)

    N. I. Burmas

    2014-09-01

    Full Text Available The aim of this research was to assess the activity of marker enzymes of the liver and its biliary formation function in conditions of the affection of animals by hexavalent chromium compounds, isoniazid and rifampicin, after applying of sorbex. The experimental affection of rats of different age was carried in the conditions of combined injection of hexavalent chromium compounds (solution of potassium dichromate, 3 mg/kg, isoniazid (0.05 g/kg and rifampicin (0.25 g/kg during the 7th and 14th days, and sorbex enterosorbent was introduced in quantity of 150 mg/kg. The activity of marker enzymes of the liver was evaluated by the activity of alanine and aspartate aminotransferases (ALT and AST and alkaline phosphatase (ALP. The state of biliary formation function of the liver was evaluated by the content of total bilirubin (TB and bile acids (BA in blood. The most significant changes in ALT activity were observed in the liver of old animals by the combined effects of the abovementioned xenobiotics – the activity of ALT was decreased by the end of the experiment by 58% compared with the animals of intact control. Using of sorbex led to decreasing in blood serum and increasing in the liver of affected animals of the different age of ALT activity throughout the experiment. AST activity in blood serum increased, and it was the highest in old animals upon chrome-isoniazid-rifampicin affection on the 14th day of the research. With the use of sorbex, there was a tendency to normalization of this index in blood serum and liver of affected animals on the 7th day from the beginning of the experiment. It was found that the largest increase in ALP took place in blood serum of immature animals by the combined effects of toxicants. In the liver of affected animals the activity of ALP decreased throughout the experiment in all age groups of animals. Maximum corrective effect on the activity of ALP was shown by the enterosorbent in the liver of mature animals on

  8. Sialic Acid within the Glycosylphosphatidylinositol Anchor Targets the Cellular Prion Protein to Synapses.

    Science.gov (United States)

    Bate, Clive; Nolan, William; McHale-Owen, Harriet; Williams, Alun

    2016-08-12

    Although the cellular prion protein (PrP(C)) is concentrated at synapses, the factors that target PrP(C) to synapses are not understood. Here we demonstrate that exogenous PrP(C) was rapidly targeted to synapses in recipient neurons derived from Prnp knock-out((0/0)) mice. The targeting of PrP(C) to synapses was dependent upon both neuronal cholesterol concentrations and the lipid and glycan composition of its glycosylphosphatidylinositol (GPI) anchor. Thus, the removal of either an acyl chain or sialic acid from the GPI anchor reduced the targeting of PrP(C) to synapses. Isolated GPIs (derived from PrP(C)) were also targeted to synapses, as was IgG conjugated to these GPIs. The removal of sialic acid from GPIs prevented the targeting of either the isolated GPIs or the IgG-GPI conjugate to synapses. Competition studies showed that pretreatment with sialylated GPIs prevented the targeting of PrP(C) to synapses. These results are consistent with the hypothesis that the sialylated GPI anchor attached to PrP(C) acts as a synapse homing signal. PMID:27325697

  9. Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen

    Science.gov (United States)

    Mendes-Pereira, Ana M.; Sims, David; Dexter, Tim; Fenwick, Kerry; Assiotis, Ioannis; Kozarewa, Iwanka; Mitsopoulos, Costas; Hakas, Jarle; Zvelebil, Marketa; Lord, Christopher J.; Ashworth, Alan

    2012-01-01

    Therapies that target estrogen signaling have made a very considerable contribution to reducing mortality from breast cancer. However, resistance to tamoxifen remains a major clinical problem. Here we have used a genome-wide functional profiling approach to identify multiple genes that confer resistance or sensitivity to tamoxifen. Combining whole-genome shRNA screening with massively parallel sequencing, we have profiled the impact of more than 56,670 RNA interference reagents targeting 16,487 genes on the cellular response to tamoxifen. This screen, along with subsequent validation experiments, identifies a compendium of genes whose silencing causes tamoxifen resistance (including BAP1, CLPP, GPRC5D, NAE1, NF1, NIPBL, NSD1, RAD21, RARG, SMC3, and UBA3) and also a set of genes whose silencing causes sensitivity to this endocrine agent (C10orf72, C15orf55/NUT, EDF1, ING5, KRAS, NOC3L, PPP1R15B, RRAS2, TMPRSS2, and TPM4). Multiple individual genes, including NF1, a regulator of RAS signaling, also correlate with clinical outcome after tamoxifen treatment. PMID:21482774

  10. Marine Toxin Okadaic Acid Affects the Immune Function of Bay Scallop (Argopecten irradians).

    Science.gov (United States)

    Chi, Cheng; Giri, Sib Sankar; Jun, Jin Woo; Kim, Hyoun Joong; Yun, Saekil; Kim, Sang Guen; Park, Se Chang

    2016-01-01

    Okadaic acid (OA) is produced by dinoflagellates during harmful algal blooms and is a diarrhetic shellfish poisoning toxin. This toxin is particularly problematic for bivalves that are cultured for human consumption. This study aimed to reveal the effects of exposure to OA on the immune responses of bay scallop, Argopecten irradians. Various immunological parameters were assessed (total hemocyte counts (THC), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), lactate dehydrogenase (LDH), and nitric oxide (NO) in the hemolymph of scallops at 3, 6, 12, 24, and 48 h post-exposure (hpe) to different concentrations of OA (50, 100, and 500 nM). Moreover, the expression of immune-system-related genes (CLT-6, FREP, HSP90, MT, and Cu/ZnSOD) was also measured. Results showed that ROS, MDA, and NO levels and LDH activity were enhanced after exposure to different concentrations of OA; however, both THC and GSH decreased between 24-48 hpe. The expression of immune-system-related genes was also assessed at different time points during the exposure period. Overall, our results suggest that exposure to OA had negative effects on immune system function, increased oxygenic stress, and disrupted metabolism of bay scallops. PMID:27563864

  11. Does bovine besnoitiosis affect the sexual function of chronically infected bulls?

    Science.gov (United States)

    Esteban-Gil, A; Jacquiet, P; Florentin, S; Decaudin, A; Berthelot, X; Ronsin, P; Grisez, C; Prevot, F; Alzieu, J P; Marois, M; Corboz, N; Peglion, M; Vilardell, C; Liénard, E; Bouhsira, E; Castillo, J A; Franc, M; Picard-Hagen, N

    2016-09-15

    Bovine besnoitiosis is a reemerging disease in Europe. The clinically Besnoitia besnoiti infection in bulls is characterized by fever, nasal discharge, and orchitis in the acute phase and by scleroderma in the chronic phase. However, in many bulls, B besnoiti infection remains at a subclinical stage. Bull infertility is an economically relevant consequence of besnoitiosis infection. It is not clear, however, if semen quality returns to normal levels when infected animals have clinically recovered. The aim of this study was to examine the relationship between chronic besnoitiosis and bull sexual function in a region of eastern France, where the disease is reemerging, by comparing semen quality and genital lesions in 11 uninfected, 17 subclinically infected, and 12 clinically infected bulls. The presence of anti-B besnoiti antibodies was detected by Western blot test. Semen was collected by electroejaculation. Bulls clinically infected with B besnoiti showed significantly more genital tract alterations than uninfected or subclinically infected bulls. No relationship was evidenced between besnoitiosis infectious status and semen quality, whereas a significant relationship was noted between genital lesions and semen score. This means that in the absence of moderate to severe genital lesions, chronic bovine besnoitiosis is unlikely to alter semen quality. However, as the presence of infected animals could lead to spread of the disease, culling or separation of clinically infected bulls from the remaining healthy animals is strongly recommended. PMID:27264738

  12. Deiodinase knockdown affects zebrafish eye development at the level of gene expression, morphology and function.

    Science.gov (United States)

    Houbrechts, Anne M; Vergauwen, Lucia; Bagci, Enise; Van Houcke, Jolien; Heijlen, Marjolein; Kulemeka, Bernard; Hyde, David R; Knapen, Dries; Darras, Veerle M

    2016-03-15

    Retinal development in vertebrates relies extensively on thyroid hormones. Their local availability is tightly controlled by several regulators, including deiodinases (Ds). Here we used morpholino technology to explore the roles of Ds during eye development in zebrafish. Transcriptome analysis at 3 days post fertilization (dpf) revealed a pronounced effect of knockdown of both T4-activating Ds (D1D2MO) or knockdown of T3-inactivating D3 (D3bMO) on phototransduction and retinoid recycling. This was accompanied by morphological defects (studied from 1 to 7 dpf) including reduced eye size, disturbed retinal lamination and strong reduction in rods and all four cone types. Defects were more prominent and persistent in D3-deficient fish. Finally, D3-deficient zebrafish larvae had disrupted visual function at 4 dpf and were less sensitive to a light stimulus at 5 dpf. These data demonstrate the importance of TH-activating and -inactivating Ds for correct zebrafish eye development, and point to D3b as a central player. PMID:26802877

  13. How the choice of safety performance function affects the identification of important crash prediction variables.

    Science.gov (United States)

    Wang, Ketong; Simandl, Jenna K; Porter, Michael D; Graettinger, Andrew J; Smith, Randy K

    2016-03-01

    Across the nation, researchers and transportation engineers are developing safety performance functions (SPFs) to predict crash rates and develop crash modification factors to improve traffic safety at roadway segments and intersections. Generalized linear models (GLMs), such as Poisson or negative binomial regression, are most commonly used to develop SPFs with annual average daily traffic as the primary roadway characteristic to predict crashes. However, while more complex to interpret, data mining models such as boosted regression trees have improved upon GLMs crash prediction performance due to their ability to handle more data characteristics, accommodate non-linearities, and include interaction effects between the characteristics. An intersection data inventory of 36 safety relevant parameters for three- and four-legged non-signalized intersections along state routes in Alabama was used to study the importance of intersection characteristics on crash rate and the interaction effects between key characteristics. Four different SPFs were investigated and compared: Poisson regression, negative binomial regression, regularized generalized linear model, and boosted regression trees. The models did not agree on which intersection characteristics were most related to the crash rate. The boosted regression tree model significantly outperformed the other models and identified several intersection characteristics as having strong interaction effects. PMID:26710265

  14. Adsorption of sulfamethoxazole on functionalized carbon nanotubes as affected by cations and anions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Di; Pan Bo; Wu Min; Wang Bin; Zhang Huang; Peng Hongbo; Wu Di [Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650093 (China); Ning Ping, E-mail: pingning58@gmail.com [Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650093 (China)

    2011-10-15

    The environmental risks of antibiotics have attracted lots of research attention, but their environmental behavior is not clear yet. Functionalized carbon nanotubes (CNTs) were used as model adsorbents and sulfamethoxazole (SMX) was used as a model antibiotic to investigate the effect of both cations (Ca{sup 2+}, Cs{sup +}) and anions (phosphate) on antibiotics adsorption. Various mechanisms (such as electrostatic interaction, hydrophobic interaction, {pi}-{pi} and hydrogen bonds) play roles in SMX adsorption. Cations and anions could 'wedge into' these mechanisms and thus alter SMX adsorption. This study emphasized that both increased and decreased SMX adsorption could be observed with the addition of cations/anions, depending on environmental conditions (such as pH in this current study). The net effect is the balance between the increased and decreased effects. The contribution of different mechanisms to the overall antibiotic adsorption on solid particles should be identified to accurately predict the apparent effect by cations and anions. - Highlights: > Various mechanisms play role in SMX sorption on CNTs. > The presence of cations and anions may decrease or increase SMX sorption. > The net effect is dependent on the balance among different mechanisms. > It is essential to identify the contribution of different mechanisms. - The balance between decreasing and increasing roles determines the apparent sulfamethoxazole adsorption on carbon nanotubes depending on environmental conditions.

  15. Adsorption of sulfamethoxazole on functionalized carbon nanotubes as affected by cations and anions

    International Nuclear Information System (INIS)

    The environmental risks of antibiotics have attracted lots of research attention, but their environmental behavior is not clear yet. Functionalized carbon nanotubes (CNTs) were used as model adsorbents and sulfamethoxazole (SMX) was used as a model antibiotic to investigate the effect of both cations (Ca2+, Cs+) and anions (phosphate) on antibiotics adsorption. Various mechanisms (such as electrostatic interaction, hydrophobic interaction, π-π and hydrogen bonds) play roles in SMX adsorption. Cations and anions could 'wedge into' these mechanisms and thus alter SMX adsorption. This study emphasized that both increased and decreased SMX adsorption could be observed with the addition of cations/anions, depending on environmental conditions (such as pH in this current study). The net effect is the balance between the increased and decreased effects. The contribution of different mechanisms to the overall antibiotic adsorption on solid particles should be identified to accurately predict the apparent effect by cations and anions. - Highlights: → Various mechanisms play role in SMX sorption on CNTs. → The presence of cations and anions may decrease or increase SMX sorption. → The net effect is dependent on the balance among different mechanisms. → It is essential to identify the contribution of different mechanisms. - The balance between decreasing and increasing roles determines the apparent sulfamethoxazole adsorption on carbon nanotubes depending on environmental conditions.

  16. Absence of system xc- in mice decreases anxiety and depressive-like behavior without affecting sensorimotor function or spatial vision.

    Science.gov (United States)

    Bentea, Eduard; Demuyser, Thomas; Van Liefferinge, Joeri; Albertini, Giulia; Deneyer, Lauren; Nys, Julie; Merckx, Ellen; Michotte, Yvette; Sato, Hideyo; Arckens, Lutgarde; Massie, Ann; Smolders, Ilse

    2015-06-01

    There is considerable preclinical and clinical evidence indicating that abnormal changes in glutamatergic signaling underlie the development of mood disorders. Astrocytic glutamate dysfunction, in particular, has been recently linked with the pathogenesis and treatment of mood disorders, including anxiety and depression. System xc- is a glial cystine/glutamate antiporter that is responsible for nonvesicular glutamate release in various regions of the brain. Although system xc- is involved in glutamate signal transduction, its possible role in mediating anxiety or depressive-like behaviors is currently unknown. In the present study, we phenotyped adult and aged system xc- deficient mice in a battery of tests for anxiety and depressive-like behavior (open field, light/dark test, elevated plus maze, novelty suppressed feeding, forced swim test, tail suspension test). Concomitantly, we evaluated the sensorimotor function of system xc- deficient mice, using motor and sensorimotor based tests (rotarod, adhesive removal test, nest building test). Finally, due to the presence and potential functional relevance of system xc- in the eye, we investigated the visual acuity of system xc- deficient mice (optomotor test). Our results indicate that loss of system xc- does not affect motor or sensorimotor function, in either adult or aged mice, in any of the paradigms investigated. Similarly, loss of system xc- does not affect basic visual acuity, in either adult or aged mice. On the other hand, in the open field and light/dark tests, and forced swim and tail suspension tests respectively, we could observe significant anxiolytic and antidepressive-like effects in system xc- deficient mice that in certain cases (light/dark, forced swim) were age-dependent. These findings indicate that, under physiological conditions, nonvesicular glutamate release via system xc- mediates aspects of higher brain function related to anxiety and depression, but does not influence sensorimotor function

  17. Plectin isoform P1b and P1d deficiencies differentially affect mitochondrial morphology and function in skeletal muscle

    Science.gov (United States)

    Winter, Lilli; Kuznetsov, Andrey V.; Grimm, Michael; Zeöld, Anikó; Fischer, Irmgard; Wiche, Gerhard

    2015-01-01

    Plectin, a versatile 500-kDa cytolinker protein, is essential for muscle fiber integrity and function. The most common disease caused by mutations in the human plectin gene, epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), is characterized by severe skin blistering and progressive muscular dystrophy. Besides displaying pathological desmin-positive protein aggregates and degenerative changes in the myofibrillar apparatus, skeletal muscle specimens of EBS-MD patients and plectin-deficient mice are characterized by massive mitochondrial alterations. In this study, we demonstrate that structural and functional alterations of mitochondria are a primary aftermath of plectin deficiency in muscle, contributing to myofiber degeneration. We found that in skeletal muscle of conditional plectin knockout mice (MCK-Cre/cKO), mitochondrial content was reduced, and mitochondria were aggregated in sarcoplasmic and subsarcolemmal regions and were no longer associated with Z-disks. Additionally, decreased mitochondrial citrate synthase activity, respiratory function and altered adenosine diphosphate kinetics were characteristic of plectin-deficient muscles. To analyze a mechanistic link between plectin deficiency and mitochondrial alterations, we comparatively assessed mitochondrial morphology and function in whole muscle and teased muscle fibers of wild-type, MCK-Cre/cKO and plectin isoform-specific knockout mice that were lacking just one isoform (either P1b or P1d) while expressing all others. Monitoring morphological alterations of mitochondria, an isoform P1b-specific phenotype affecting the mitochondrial fusion–fission machinery and manifesting with upregulated mitochondrial fusion-associated protein mitofusin-2 could be identified. Our results show that the depletion of distinct plectin isoforms affects mitochondrial network organization and function in different ways. PMID:26019234

  18. Cannabinoid agonists rearrange synaptic vesicles at excitatory synapses and depress motoneuron activity in vivo.

    Science.gov (United States)

    García-Morales, Victoria; Montero, Fernando; Moreno-López, Bernardo

    2015-05-01

    Impairment of motor skills is one of the most common acute adverse effects of cannabis. Related studies have focused mainly on psychomotor alterations, and little is known about the direct impact of cannabinoids (CBs) on motoneuron physiology. As key modulators of synaptic function, CBs regulate multiple neuronal functions and behaviors. Presynaptic CB1 mediates synaptic strength depression by inhibiting neurotransmitter release, via a poorly understood mechanism. The present study examined the effect of CB agonists on excitatory synaptic inputs incoming to hypoglossal motoneurons (HMNs) in vitro and in vivo. The endocannabinoid anandamide (AEA) and the synthetic CB agonist WIN 55,212-2 rapidly and reversibly induced short-term depression (STD) of glutamatergic synapses on motoneurons by a presynaptic mechanism. Presynaptic effects were fully reversed by the CB1-selective antagonist AM281. Electrophysiological and electron microscopy analysis showed that WIN 55,212-2 reduced the number of synaptic vesicles (SVs) docked to active zones in excitatory boutons. Given that AM281 fully abolished depolarization-induced depression of excitation, motoneurons can be feasible sources of CBs, which in turn act as retrograde messengers regulating synaptic function. Finally, microiontophoretic application of the CB agonist O-2545 reversibly depressed, presumably via CB1, glutamatergic inspiratory-related activity of HMNs in vivo. Therefore, evidence support that CBs, via presynaptic CB1, induce excitatory STD by reducing the readily releasable pool of SVs at excitatory synapses, then attenuating motoneuron activity. These outcomes contribute a possible mechanistic basis for cannabis-associated motor performance disturbances such as ataxia, dysarthria and dyscoordination. PMID:25595101

  19. Deletion of TDO2, IDO-1 and IDO-2 differentially affects mouse behavior and cognitive function.

    Science.gov (United States)

    Too, Lay Khoon; Li, Kong M; Suarna, Cacang; Maghzal, Ghassan J; Stocker, Roland; McGregor, Iain S; Hunt, Nicholas H

    2016-10-01

    Tryptophan, an amino acid involved in routine energy metabolism, is a key modulator of sickness behaviors associated with inflammatory states and also plays roles in some psychiatric disorders. Tissue concentrations of tryptophan are regulated primarily by the enzymes indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO, encoded by TDO2). Altered IDO1 and TDO activities have been linked to the perturbed serotonergic neurotransmission that may underlie certain psychopathologies. Here we assessed mice genetically modified to be deficient in IDO1, IDO2 or TDO2 for their behavior and cognitive function using an automated home cage system, the IntelliCage™. A well-established behavioural and cognitive test battery was applied during two periods (Runs 1 and 2, "R1" and "R2") separated by one month. Various tryptophan-related neurochemicals also were measured in brain extracts. IDO1(-/-) mice displayed remarkable reductions of early diurnal exploration in the IntelliCage and this persisted in R2. In contrast, early diurnal hyperactivity was observed in IDO2(-/-) mice in both R1 and R2. TDO2(-/-) mice displayed increased diurnal and nocturnal exploration, but only in R2. Cognitive assessment suggested enhanced reference memory in IDO2(-/-) mice in a complex patrolling task, while TDO deficiency was associated with enhanced performance in complex patrolling and discrimination reversal tasks. Neurochemical measures showed attenuated brain serotonin levels in IDO1(-/-) mice and augmented tryptophan and serotonin levels in TDO2(-/-) animals, respectively. No neurochemical alterations were detected in IDO2(-/-) mice. Taken together, these findings reveal complex and dissimilar patterns of behavioral and cognitive changes induced by knockout of three different tryptophan-metabolizing enzymes. PMID:27316339

  20. Diffuse traumatic brain injury affects chronic corticosterone function in the rat

    Directory of Open Access Journals (Sweden)

    Rachel K Rowe

    2016-07-01

    Full Text Available As many as 20–55% of patients with a history of traumatic brain injury (TBI experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration–deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic–pituitary endocrine (HPE dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT, a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI. At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain, neuropathology (silver stain and activated astrocytes (GFAP in the paraventricular nucleus (PVN of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI.

  1. Diffuse traumatic brain injury affects chronic corticosterone function in the rat.

    Science.gov (United States)

    Rowe, Rachel K; Rumney, Benjamin M; May, Hazel G; Permana, Paska; Adelson, P David; Harman, S Mitchell; Lifshitz, Jonathan; Thomas, Theresa C

    2016-07-01

    As many as 20-55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration-deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic-pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI. PMID:27317610

  2. Factors affecting characterization and localization of interindividual differences in functional connectivity using MRI.

    Science.gov (United States)

    Airan, Raag D; Vogelstein, Joshua T; Pillai, Jay J; Caffo, Brian; Pekar, James J; Sair, Haris I

    2016-05-01

    Much recent attention has been paid to quantifying anatomic and functional neuroimaging on the individual subject level. For optimal individual subject characterization, specific acquisition and analysis features need to be identified that maximize interindividual variability while concomitantly minimizing intra-subject variability. We delineate the effect of various acquisition parameters (length of acquisition, sampling frequency) and analysis methods (time course extraction, region of interest parcellation, and thresholding of connectivity-derived network graphs) on characterizing individual subject differentiation. We utilize a non-parametric statistical metric that quantifies the degree to which a parameter set allows this individual subject differentiation by both maximizing interindividual variance and minimizing intra-individual variance. We apply this metric to analysis of four publicly available test-retest resting-state fMRI (rs-fMRI) data sets. We find that for the question of maximizing individual differentiation, (i) for increasing sampling, there is a relative tradeoff between increased sampling frequency and increased acquisition time; (ii) for the sizes of the interrogated data sets, only 3-4 min of acquisition time was sufficient to maximally differentiate each subject with an algorithm that utilized no a priori information regarding subject identification; and (iii) brain regions that most contribute to this individual subject characterization lie in the default mode, attention, and executive control networks. These findings may guide optimal rs-fMRI experiment design and may elucidate the neural bases for subject-to-subject differences. Hum Brain Mapp 37:1986-1997, 2016. © 2016 Wiley Periodicals, Inc. PMID:27012314

  3. Interaction of Berberine derivative with protein POT1 affect telomere function in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Nannan; Chen, Siqi; Ma, Yan; Qiu, Jun; Tan, Jia-Heng; Ou, Tian-Miao; Gu, Lian-Quan; Huang, Zhi-Shu [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, Waihuan East Road 132, Guangzhou 510006 (China); Li, Ding, E-mail: liding@mail.sysu.edu.cn [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, Waihuan East Road 132, Guangzhou 510006 (China)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer The protein POT1 plays an important role in telomere protection. Black-Right-Pointing-Pointer Functional POT1 was overexpressed in Escherichia coli for the first time, and purified. Black-Right-Pointing-Pointer Compound Sysu-00692 was found to be the first POT1-binding ligand. Black-Right-Pointing-Pointer Sysu-00692 could interfere with the binding activity of POT1 in vivo. Black-Right-Pointing-Pointer Sysu-00692 had inhibition on telomerase and cell proliferation. -- Abstract: The protein POT1 plays an important role in telomere protection, which is related with telomere elongation and cell immortality. The protein has been recognized as a promising drug target for cancer treatment. In the present study, we cloned, overexpressed in Escherichia coli for the first time, and purified recombinant human POT1. The protein was proved to be active through filter binding assay, FRET and CD experiments. In the initial screening for protein binding ligands using SPR, compound Sysu-00692 was found to bind well with the POT1, which was confirmed with EMSA. Its in vivo activity study showed that compound Sysu-00692 could interfere with the binding between human POT1 and the telomeric DNA through chromatin immunoprecipitation. Besides, the compound showed mild inhibition on telomerase and cell proliferation. As we know, compound Sysu-00692 is the first reported POT1-binding ligand, which could serve as a lead compound for further improvement. This work offered a potentially new approach for drug design for the treatment of cancers.

  4. Microbial Functional Diversity, Biomass and Activity as Affected by Soil Surface Mulching in a Semiarid Farmland.

    Science.gov (United States)

    Shen, Yufang; Chen, Yingying; Li, Shiqing

    2016-01-01

    Mulching is widely used to increase crop yield in semiarid regions in northwestern China, but little is known about the effect of different mulching systems on the microbial properties of the soil, which play an important role in agroecosystemic functioning and nutrient cycling. Based on a 4-year spring maize (Zea mays L.) field experiment at Changwu Agricultural and Ecological Experimental Station, Shaanxi, we evaluated the responses of soil microbial activity and crop to various management systems. The treatments were NMC (no mulching with inorganic N fertilizer), GMC (gravel mulching with inorganic N fertilizer), FMC (plastic-film mulching with inorganic N fertilizer) and FMO (plastic-film mulching with inorganic N fertilizer and organic manure addition). The results showed that the FMO soil had the highest contents of microbial biomass carbon and nitrogen, dehydrogenase activity, microbial activity and Shannon diversity index. The relative use of carbohydrates and amino acids by microbes was highest in the FMO soil, whereas the relative use of polymers, phenolic compounds and amines was highest in the soil in the NMC soil. Compared with the NMC, an increased but no significant trend of biomass production and nitrogen accumulation was observed under the GMC treatment. The FMC and FMO led a greater increase in biomass production than GMC and NMC. Compare with the NMC treatment, FMC increased grain yield, maize biomass and nitrogen accumulation by 62.2, 62.9 and 86.2%, but no significant difference was found between the FMO and FMC treatments. Some soil biological properties, i.e. microbial biomass carbon, microbial biomass nitrogen, being sensitive to the mulching and organic fertilizer, were significant correlated with yield and nitrogen availability. Film mulching over gravel mulching can serve as an effective measure for crop production and nutrient cycling, and plus organic fertilization additions may thus have improvements in the biological quality of the

  5. Microbial Functional Diversity, Biomass and Activity as Affected by Soil Surface Mulching in a Semiarid Farmland

    Science.gov (United States)

    Shen, Yufang; Chen, Yingying; Li, Shiqing

    2016-01-01

    Mulching is widely used to increase crop yield in semiarid regions in northwestern China, but little is known about the effect of different mulching systems on the microbial properties of the soil, which play an important role in agroecosystemic functioning and nutrient cycling. Based on a 4-year spring maize (Zea mays L.) field experiment at Changwu Agricultural and Ecological Experimental Station, Shaanxi, we evaluated the responses of soil microbial activity and crop to various management systems. The treatments were NMC (no mulching with inorganic N fertilizer), GMC (gravel mulching with inorganic N fertilizer), FMC (plastic-film mulching with inorganic N fertilizer) and FMO (plastic-film mulching with inorganic N fertilizer and organic manure addition). The results showed that the FMO soil had the highest contents of microbial biomass carbon and nitrogen, dehydrogenase activity, microbial activity and Shannon diversity index. The relative use of carbohydrates and amino acids by microbes was highest in the FMO soil, whereas the relative use of polymers, phenolic compounds and amines was highest in the soil in the NMC soil. Compared with the NMC, an increased but no significant trend of biomass production and nitrogen accumulation was observed under the GMC treatment. The FMC and FMO led a greater increase in biomass production than GMC and NMC. Compare with the NMC treatment, FMC increased grain yield, maize biomass and nitrogen accumulation by 62.2, 62.9 and 86.2%, but no significant difference was found between the FMO and FMC treatments. Some soil biological properties, i.e. microbial biomass carbon, microbial biomass nitrogen, being sensitive to the mulching and organic fertilizer, were significant correlated with yield and nitrogen availability. Film mulching over gravel mulching can serve as an effective measure for crop production and nutrient cycling, and plus organic fertilization additions may thus have improvements in the biological quality of the

  6. Interleukins Affect Equine Endometrial Cell Function: Modulatory Action of Ovarian Steroids

    Directory of Open Access Journals (Sweden)

    Anna Z. Szóstek

    2014-01-01

    Full Text Available The aim of the present study was to investigate the interaction between ovarian steroids, interleukins and prostaglandins (PG in equine epithelial and stromal cells in vitro. In Experiment 1, cells were exposed to IL-1α (10 ng/mL, IL-1β (10 ng/mL or IL-6 (10 ng/mL for 24 h and cell proliferation was determined using MTT. In Experiment 2, cells were exposed to progesterone (P4; 10−7 M; 17-β estradiol (E2; 10−9 M or P4+E2 for 24 h and later medium was replaced with a fresh one treated with IL-1α, IL-1β or IL-6 (10 ng/mL, each for 24 h. The oxytocin (OT; 10−7 M was used as a positive control. In Experiment 3, cells were exposed to P4 (10−7 M, E2 (10−9 M or P4+E2 for 24 h and the IL receptor mRNAs transcription was determined using Real-time PCR. Prostaglandins concentration was determined using the direct enzyme immunoassay (EIA method. Our findings reveal a functional linking between ovarian steroids and IL-stimulated PG secretion by equine endometrial cells. This interaction could be one of the mechanisms responsible for endometrial local orchestrating events during the estrous cycle and early pregnancy.

  7. Microbial Functional Diversity, Biomass and Activity as Affected by Soil Surface Mulching in a Semiarid Farmland.

    Directory of Open Access Journals (Sweden)

    Yufang Shen

    Full Text Available Mulching is widely used to increase crop yield in semiarid regions in northwestern China, but little is known about the effect of different mulching systems on the microbial properties of the soil, which play an important role in agroecosystemic functioning and nutrient cycling. Based on a 4-year spring maize (Zea mays L. field experiment at Changwu Agricultural and Ecological Experimental Station, Shaanxi, we evaluated the responses of soil microbial activity and crop to various management systems. The treatments were NMC (no mulching with inorganic N fertilizer, GMC (gravel mulching with inorganic N fertilizer, FMC (plastic-film mulching with inorganic N fertilizer and FMO (plastic-film mulching with inorganic N fertilizer and organic manure addition. The results showed that the FMO soil had the highest contents of microbial biomass carbon and nitrogen, dehydrogenase activity, microbial activity and Shannon diversity index. The relative use of carbohydrates and amino acids by microbes was highest in the FMO soil, whereas the relative use of polymers, phenolic compounds and amines was highest in the soil in the NMC soil. Compared with the NMC, an increased but no significant trend of biomass production and nitrogen accumulation was observed under the GMC treatment. The FMC and FMO led a greater increase in biomass production than GMC and NMC. Compare with the NMC treatment, FMC increased grain yield, maize biomass and nitrogen accumulation by 62.2, 62.9 and 86.2%, but no significant difference was found between the FMO and FMC treatments. Some soil biological properties, i.e. microbial biomass carbon, microbial biomass nitrogen, being sensitive to the mulching and organic fertilizer, were significant correlated with yield and nitrogen availability. Film mulching over gravel mulching can serve as an effective measure for crop production and nutrient cycling, and plus organic fertilization additions may thus have improvements in the biological

  8. Neuroligins and Neurexins Link Synaptic Function to Cognitive Disease

    OpenAIRE

    Südhof, Thomas C.

    2008-01-01

    The brain processes information by transmitting signals at synapses, which connect neurons into vast networks of communicating cells. In these networks, synapses not only transmit, but also process and refine information. Neurexins and neuroligins are synaptic cell-adhesion molecules that connect pre- and postsynaptic neurons at synapses, mediate trans-synaptic signaling, and shape neural network properties by specifying synaptic functions. In humans, alterations in neurexin or neuroligin gen...

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

    Energy Technology Data Exchange (ETDEWEB)

    Muller, C.; Mangeas, M.; Perrot, N.

    1994-08-01

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

  10. Baclofen and adenosine inhibition of synaptic transmission at CA3-CA1 synapses display differential sensitivity to K+ channel blockade.

    Science.gov (United States)

    Skov, Jane; Andreasen, Mogens; Hablitz, John J; Nedergaard, Steen

    2011-05-01

    The metabotropic GABA(B) and adenosine A(1) receptors mediate presynaptic inhibition through regulation of voltage-dependent Ca(2+) channels, whereas K(+) channel regulation is believed to have no role at the CA3-CA1 synapse. We show here that the inhibitory effect of baclofen (20 μM) and adenosine (300 μM) on field EPSPs are differentially sensitive to Cs(+) (3.5 mM) and Ba(2+) (200 μM), but not 4-aminopyridine (100 μM). Barium had no effect on paired-pulse facilitation (PPF) in itself, but gave significant reduction (14 ± 5%) when applied in the presence of baclofen, but not adenosine, suggesting that the effect is presynaptic and selective on the GABA(B) receptor-mediated response. The effect of Ba(2+) on PPF was not mimicked by tertiapin (30 nM), indicating that the underlying mechanism does not involve GIRK channels. Barium did not affect PPF in slices from young rats (P7-P8), suggesting developmental regulation. The above effects of Ba(2+) on adult tissue were reproduced when measuring evoked whole-cell EPSCs from CA1 pyramidal neurons: PPF was reduced by 22 ± 3% in the presence of baclofen and unaltered in adenosine. In contrast, Ba(2+) caused no significant change in frequency or amplitude of miniature EPSCs. The Ba(2+)-induced reduction of PPF was antagonized by LY341495, suggesting metabotropic glutamate receptor involvement. We propose that these novel effects of Ba(2+) and Cs(+) are exerted through blockade of inwardly rectifying K(+) channels in glial cells, which are functionally interacting with the GABA(B) receptor-dependent glutamate release that generates heterosynaptic depression. PMID:21274618

  11. Foundation species loss affects vegetation structure more than ecosystem function in a northeastern USA forest

    Directory of Open Access Journals (Sweden)

    David A. Orwig

    2013-02-01

    ecological processes underlying patterns observed consistently in region-wide studies of adelgid-infested hemlock stands. Mechanisms of T. canadensis loss determine rates, magnitudes, and trajectories of ecological changes in hemlock forests. Logging causes abrupt, large changes in vegetation structure whereas girdling (and by inference, A. tsugae causes sustained, smaller changes. Ecosystem processes depend more on vegetation cover per se than on species composition. We conclude that the loss of this late-successional foundation species will have long-lasting impacts on forest structure but subtle impacts on ecosystem function.

  12. Cromakalin pretreatment affects mitochondrial structure and function in a rat model of ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shilei Wang; Peng Wang; Qingxian Chang; Yu Li; Yan Jiang; Shiduan Wang

    2008-01-01

    BACKGROUND: Mitochondrial structural changes and energy dysmetabolism frequently occur subsequent to cerebral ischemia. Adenosine triphosphate (ATP)-sensitive potassium channel openers exhibit protective effects on cerebral ischemia/reperfusion injury. OBJECTIVE: To validate the effects of cromakalin on mitochondrial structure and function in ischemic penumbra brain tissue in a rat model of middle cerebral artery occlusion (MCAO). DESIGN, TIME AND SETTING: The present single-factor analysis of variance, randomized, controlled, animal experiment was performed at the Institute of Brain Science, Affiliated Hospital of Qingdao University Medical College between October 2007 and March 2008. MATERIALS: Forty male, Wistar rats were randomly divided into four groups, with 10 rats per group: sham-operated, MCAO, MCAO+ATP-sensitive potassium channel opener (cromakalin), and MCAO+eromakalin+ATP-sensitive potassium channel blocking agent (glibenclamide). METHODS: Focal cerebral ischemia/reperfusion injury was induced by MCAO in all groups except the sham-operated group. The MCAO cromakalin group was administered 10 mg/kg cromakalin (i.p.) prior to MCAO induction. The MCAO+cromakalin+glibenclamide group received an injection of 10 mg/kg cromakalin (i.v.), and subsequently an injection of 10 mg/kg cromakalin (i.p.) prior to MCAO induction. MAIN OUTCOME MEASURES: At 24 hours after cerebral ischemia/reperfusion injury, cellular apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labeling technique. Cytochrome C expression was measured by immunohistochemistry. In addition, mitochondrial swelling, membrane fluidity, membrane phospholipid and malonaldehyde (MDA) contents, as well as Na+-K+-ATPase, Ca2+-ATPase, and superoxide dismutase (SOD) activities were determined. RESULTS: Compared with the sham-operated group, the three ischemia groups exhibited significantly elevated mitochondrial MDA content, reduced membrane

  13. Phagocytic function of monocyte-derived macrophages is not affected by human immunodeficiency virus type 1 infection.

    Science.gov (United States)

    Nottet, H S; de Graaf, L; de Vos, N M; Bakker, L J; van Strijp, J A; Visser, M R; Verhoef, J

    1993-07-01

    The immunopathogenesis of human immunodeficiency virus (HIV) infection is characterized by the failure to control opportunistic infections. Here, the direct effect of HIV on macrophage phagocytic function was studied. HIV-1-infected monocyte-derived macrophages expressed as many Fc gamma and complement receptors as did control macrophages. The function of these receptors was not affected by HIV-1 infection since binding and internalization of opsonized Escherichia coli and Staphylococcus aureus were not impaired. Production of reactive oxygen species induced by stimulation of the HIV-1-infected macrophages with opsonized E. coli, zymosan, or PMA was intact. HIV-1-infected macrophages killed opsonized E. coli and Candida albicans as effectively as did control macrophages. These results, therefore, do not support the hypothesis that HIV-1 infection of macrophages causes phagocytic dysfunction and suggest that HIV-induced abnormalities outside the mononuclear phagocyte system may lead to the inability to control opportunistic pathogens. PMID:8390549

  14. Visual input controls the functional activity of goldfish Mauthner neuron through the reciprocal synaptic mechanism.

    Science.gov (United States)

    Moshkov, Dmitry A; Shtanchaev, Rashid S; Mikheeva, Irina B; Bezgina, Elena N; Kokanova, Nadezhda A; Mikhailova, Gulnara Z; Tiras, Nadezhda R; Pavlik, Lyubov' L

    2013-03-01

    Goldfish are known to exhibit motor asymmetry due to functional asymmetry of their Mauthner neurons that induce the turns to the right or left during free swimming. It has been previously found that if the less active neuron is subjected to prolonged aimed visual stimulation via its ventral dendrite, the motor asymmetry of goldfish is inverted, testifying that this neuron becomes functionally dominant, while the size of the ventral dendrite under these conditions is reduced 2-3 times compared to its counterpart in mirror neuron. Earlier it has been also revealed that training optokinetic stimulation induces adaptation, a substantial resistance of both fish motor asymmetry and morphofunctional state of Mauthner neurons against prolonged optokinetic stimulation. The aim of this work was to study the cellular mechanisms of the effect of an unusual visual afferent input on goldfish motor asymmetry and Mauthner neuron function in norm and under adaptation. It was shown that serotonin applied onto Mauthner neurons greatly reduces their activity whereas its antagonist ondansetron increases it. Against the background of visual stimulation, serotonin strengthens functional asymmetry between neurons whereas ondansetron smoothes it. Taken together these data suggest the involvement of serotonergic excitatory synaptic transmission in the regulation of Mauthner neurons by vision. Ultrastructural study of the ventral dendrites after prolonged optokinetic stimulation has revealed depletions of numeral axo-axonal synapses with specific morphology, identified by means of immunogold label as serotonergic ones. These latter in turn are situated mainly on shaft boutons, which according to specific ultrastructural features are assigned to axo-dendritic inhibitory synapses. Thus, the excitatory serotonergic synapses seem to affect Mauthner neuron indirectly through inhibitory synapses. Further, it was morphometrically established that adaptation is accompanied by the significant

  15. STRUCTURE AND FUNCTION OF SUBSURFACE MICROBIAL COMMUNITIES AFFECTING RADIONUCLIDE TRANSPORT AND BIOIMMOBILIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Joel E. Kostka; Lee Kerkhof; Kuk-Jeong Chin; Martin Keller; Joseph W. Stucki

    2011-06-15

    (comprising 50% to 100% of rRNA detected). (2) We demonstrated for the first time that the function of microbial communities can be quantified in subsurface sediments using messenger RNA assays (molecular proxies) under in situ conditions. (3) Active Geobacteraceae were identified and phylogenetically characterized from the cDNA of messenger RNA extracted from ORFRC subsurface sediment cores. Multiple clone sequences were retrieved from G. uraniireducens, G. daltonii, and G. metallireducens. (4) Results show that Geobacter strain FRC-32 is capable of growth on benzoate, toluene and benzene as the electron donor, thereby providing evidence that this strain is physiologically distinct from other described members of the subsurface Geobacter clade. (5) Fe(III)-reducing bacteria transform structural Fe in clay minerals from their layer edges rather than from their basal surfaces.

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

    Directory of Open Access Journals (Sweden)

    Guilherme T Silva

    2010-07-01

    Full Text Available Throughout our lifetime, activity-dependent changes in neuronal connection strength enable the brain to refine neural circuits and learn based on experience. Synapses can bi-directionally alter strength and the magnitude and sign depend on the millisecond timing of presynaptic and postsynaptic action potential firing. Recent findings on laboratory animals have shown that neurons can show a variety of temporal windows for spike-timing-dependent plasticity (STDP. It is unknown what synaptic learning rules exist in human synapses and whether similar temporal windows for STDP at synapses hold true for the human brain. Here, we directly tested in human slices cut from hippocampal tissue removed for surgical treatment of deeper brain structures in drug-resistant epilepsy patients, whether adult human synapses can change strength in response to millisecond timing of pre- and postsynaptic firing. We find that adult human hippocampal synapses can alter synapse strength in response to timed pre- and postsynaptic activity. In contrast to rodent hippocampal synapses, the sign of plasticity does not sharply switch around 0 millisecond timing. Instead, both positive timing intervals, in which presynaptic firing preceded the postsynaptic action potential, and negative timing intervals, in which postsynaptic firing preceded presynaptic activity down to -80 ms, increase synapse strength (tLTP. Negative timing intervals between -80 to -130 ms induce a lasting reduction of synapse strength (tLTD. Thus, similar to rodent synapses, adult human synapses can show spike-timing-dependent changes in strength. The timing rules of STDP in human hippocampus, however, seem to differ from rodent hippocampus, and suggest a less strict interpretation of Hebb’s predictions.

  17. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Changlian [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Gao, Jianfeng [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Department of Physiology, Henan Traditional Medical University (China); Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Kuhn, Hans-Georg [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Blomgren, Klas, E-mail: klas.blomgren@neuro.gu.se [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatric Oncology, The Queen Silvia Children' s Hospital, Gothenburg (Sweden)

    2011-01-07

    Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  18. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

    International Nuclear Information System (INIS)

    Research highlights: → The effect of MRI on the developing brain is a matter of debate. → Repeated exposure to MRI did not affect neurogenesis. → Memory function was not affected by repeated MRI during development. → Neither late gestation nor young postnatal brains were affected by MRI. → Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 oC. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  19. Development of an auditory emotion recognition function using psychoacoustic parameters based on the International Affective Digitized Sounds.

    Science.gov (United States)

    Choi, Youngimm; Lee, Sungjun; Jung, SungSoo; Choi, In-Mook; Park, Yon-Kyu; Kim, Chobok

    2015-12-01

    The purpose of this study was to develop an auditory emotion recognition function that could determine the emotion caused by sounds coming from the environment in our daily life. For this purpose, sound stimuli from the International Affective Digitized Sounds (IADS-2), a standardized database of sounds intended to evoke emotion, were selected, and four psychoacoustic parameters (i.e., loudness, sharpness, roughness, and fluctuation strength) were extracted from the sounds. Also, by using an emotion adjective scale, 140 college students were tested to measure three basic emotions (happiness, sadness, and negativity). From this discriminant analysis to predict basic emotions from the psychoacoustic parameters of sound, a discriminant function with overall discriminant accuracy of 88.9% was produced from training data. In order to validate the discriminant function, the same four psychoacoustic parameters were extracted from 46 sound stimuli collected from another database and substituted into the discriminant function. The results showed that an overall discriminant accuracy of 63.04% was confirmed. Our findings provide the possibility that daily-life sounds, beyond voice and music, can be used in a human-machine interface. PMID:25319038

  20. Tree species identity and functional traits but not species richness affect interrill erosion processes in young subtropical forests

    Science.gov (United States)

    Seitz, S.; Goebes, P.; Song, Z.; Bruelheide, H.; Härdtle, W.; Kühn, P.; Li, Y.; Scholten, T.

    2015-06-01

    Soil erosion is seriously threatening ecosystem functioning in many parts of the world. In this context, it is assumed that tree species richness and functional diversity of tree communities can play a critical role in improving ecosystem services such as erosion control. An experiment with 170 micro-scale runoff plots was conducted to investigate the influence of tree species richness and identity as well as tree functional traits on interrill erosion in a young forest ecosystem. An interrill erosion rate of 47.5 t ha-1 a-1 was calculated. This study provided evidence that different tree species affect interrill erosion, but higher tree species richness did not mitigate soil losses in young forest stands. Thus, different tree morphologies have to be considered, when assessing erosion under forest. High crown cover and leaf area index reduced soil losses in initial forest ecosystems, whereas rising tree height increased them. Even if a leaf litter cover was not present, remaining soil surface cover by stones and biological soil crusts was the most important driver for soil erosion control. Furthermore, soil organic matter had a decreasing influence on soil loss. Long-term monitoring of soil erosion under closing tree canopies is necessary and a wide range of functional tree traits should be taken into consideration in future research.