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Sample records for long-term potentiation ltp

  1. Long-term potentiation (LTP) of human sensory-evoked potentials.

    Science.gov (United States)

    Kirk, Ian J; McNair, Nicolas A; Hamm, Jeffrey P; Clapp, Wesley C; Mathalon, Daniel H; Cavus, Idil; Teyler, Timothy J

    2010-09-01

    Long-term potentiation (LTP) is the principal candidate synaptic mechanism underlying learning and memory, and has been studied extensively at the cellular and molecular level in laboratory animals. Inquiry into the functional significance of LTP has been hindered by the absence of a human model as, until recently, LTP has only been directly demonstrated in humans in isolated cortical tissue obtained from patients undergoing surgery, where it displays properties identical to those seen in non-human preparations. In this brief review, we describe the results of paradigms recently developed in our laboratory for inducing LTP-like changes in visual-, and auditory-evoked potentials. We describe how rapid, repetitive presentation of sensory stimuli leads to a persistent enhancement of components of sensory-evoked potential in normal humans. Experiments to date, investigating the locus, stimulus specificity, and NMDA receptor dependence of these LTP-like changes suggest that they have the essential characteristics of LTP seen in experimental animals. The ability to elicit LTP from non-surgical patients will provide a human model system allowing the detailed examination of synaptic plasticity in normal subjects and may have future clinical applications in the assessment of cognitive disorders. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  2. Human sensory Long-Term Potentiation (LTP) predicts visual memory performance and is modulated by the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism

    OpenAIRE

    King, Rohan; Moreau, David; Russell, Bruce; Kirk, Ian; Wu, Carolyn; Antia, Ushtana; Lamb, Yvette; Spriggs, Meg; Thompson, Chris; Mckay, Nicole; Shelling, Andrew; Waldie, Karen; Teyler, Tim; Hamm, Jeff; Mcnair, Nicolas

    2018-01-01

    Background: Long-Term Potentiation (LTP) is recognised as a core neuronal process underlying long-term memory. However, a direct relationship between LTP and human memory performance is yet to be demonstrated. The first aim of the current study was thus to assess the relationship between LTP and human long-term memory performance. With this also comes an opportunity to explore factors thought to mediate the relationship between LTP and long-term memory, and to gain additional insight into var...

  3. Discovering long-term potentiation (LTP) - recollections and reflections on what came after.

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    Lømo, T

    2018-02-01

    Chance events led me to a lifelong career in scientific research. They paved the way for being the first to see long-term potentiation of synaptic efficiency (LTP) in Per Andersen's laboratory in Oslo in 1966. Here I describe my way to this discovery and the experiments with Tim Bliss in 1968-1969 that led to Bliss and Lømo, 1973. Surprisingly, we later failed to reproduce these results. I discuss possible reasons for this failure, which made us both leave LTP research, in my case for good, in Tim's case for several years. After 30 years of work in a different field, I renewed my interest in the hippocampus and LTP in the early 2000s and published, for the first time, results that I had obtained 40 years earlier. Here I present my take on how interest in and research on LTP evolved after the early years. This includes a discussion of the functions of hippocampus as seen in those early days, the case of patient H.M., Donald Hebb's place in the story, the search for 'memory molecules' such as PKMζ, and the primary site for LTP expression (pre- and/or post-synaptic?). Throughout, I reflect on my life in science, how science is done and what drives it. The reflections are quite personal and I admit to mixed feelings about broadcasting them. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  4. The effects of lindane and long-term potentiation (LTP) on pyramidal cell excitability in the rat hippocampal slice.

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    Albertson, T E; Walby, W F; Stark, L G; Joy, R M

    1997-01-01

    An in vitro orthodromic stimulation technique was used to examine the effects of lindane and long-term potentiation (LTP) inducing stimuli, alone or in combination, on the excitatory afferent terminal of CA1 pyramidal cells and on recurrent collateral evoked inhibition using the rat hippocampal slice model. Hippocampal slices of 400 microns thickness were perfused with oxygenated artificial cerebrospinal fluid. Stimulation of Schaffer collateral/commissural fibers produced extracellular excitatory postsynaptic potential (EPSP) and/or populations spike (PS) responses recorded from electrodes in the CA1 region. A paired-pulse technique was used to measure gamma-aminobutyric acid (GABAA)-mediated recurrent inhibition before and after treatments. After both lindane and LTP, larger PS amplitudes for a given stimulus intensity were seen. The resulting leftward shift in the curve of the PS amplitude versus stimulus intensity was larger after LTP than after 25 microM lindane. Both lindane and LTP treatments reduced PS thresholds and reduced or eliminated recurrent inhibition as measured by paired-pulse stimulation at the 15 msec interval. The reduction of recurrent inhibition after both treatments was more pronounced at lower stimulus intensities. When LTP stimuli were applied after lindane exposure a further large shift to the left was seen in the PS amplitude versus stimulus intensity curve. A smaller shift to the left was seen in the PS amplitude versus stimulus intensity curve only at the higher stimuli when lindane exposure occurred after LTP. Only at low stimulus intensities were further argumentations seen in PS amplitudes when the LTP stimuli was followed by a second LTP stimuli. Previous exposure to 25 microM lindane stimuli does not block the development of a further robust LTP in this in vitro model.

  5. Ischemic long-term-potentiation (iLTP: perspectives to set the threshold of neural plasticity toward therapy

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    Maximilian Lenz

    2015-01-01

    Full Text Available The precise role of neural plasticity under pathological conditions remains not well understood. It appears to be well accepted, however, that changes in the ability of neurons to express plasticity accompany neurological diseases. Here, we discuss recent experimental evidence, which suggests that synaptic plasticity induced by a pathological stimulus, i.e., ischemic long-term-potentiation (iLTP of excitatory synapses, could play an important role for post-stroke recovery by influencing the post-lesional reorganization of surviving neuronal networks.

  6. Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

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    Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

    2016-05-17

    PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

  7. Long-Term Potentiation in the Motor Cortex

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    Iriki, Atsushi; Pavlides, Constantine; Keller, Asaf; Asanuma, Hiroshi

    1989-09-01

    Long-term potentiation (LTP) is a model for learning and memory processes. Tetanic stimulation of the sensory cortex produces LTP in motor cortical neurons, whereas tetanization of the ventrolateral nucleus of the thalamus, which also projects to the motor cortex, does not. However, after simultaneous high-frequency stimulation of both the sensory cortex and the ventrolateral nucleus of the thalamus, LTP of thalamic input to motor cortical neurons is induced. This associative LTP occurs only in neurons in the superficial layers of the motor cortex that receive monosynaptic input from both the sensory cortex and the ventrolateral nucleus of the thalamus. Associative LTP in the motor cortex may constitute a basis for the retention of motor skills.

  8. GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories.

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    Hardt, Oliver; Nader, Karim; Wang, Yu-Tian

    2014-01-05

    The molecular processes involved in establishing long-term potentiation (LTP) have been characterized well, but the decay of early and late LTP (E-LTP and L-LTP) is poorly understood. We review recent advances in describing the mechanisms involved in maintaining LTP and homeostatic plasticity. We discuss how these phenomena could relate to processes that might underpin the loss of synaptic potentiation over time, and how they might contribute to the forgetting of short-term and long-term memories. We propose that homeostatic downscaling mediates the loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP, while both processes require the activity-dependent removal of postsynaptic GluA2-containing AMPA receptors.

  9. DEVELOPMENTAL LEAD (PB) EXPOSURE REDUCES THE ABILITY OF THE NNDA ANTAGONIST MK801 TO SUPPRESS LONG-TERM POTENTIATION (LTP) IN THE RAT DENTATE GYRUS, IN VIVO

    Science.gov (United States)

    Chronic developmental lead (Pb) exposure increases the threshold and enhances decay of long-term potentiation (LTP) in the dentate gyrus of the hippocampal formation. MK-801 and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype impair induction of LT...

  10. Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

    Science.gov (United States)

    Smolen, Paul; Baxter, Douglas A; Byrne, John H

    2012-01-01

    Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ) is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC) and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

  11. 长时程增强与长时程抑制的研究%Advances in long - term potentiation and long - term depression

    Institute of Scientific and Technical Information of China (English)

    张敬军; 夏作理

    2000-01-01

    The impairment of learning and memory function in the central nervous system(CNS)is one of the main features of aging and Alzheimer' s disease (AD). Many experimental results have showed that long- term memory(LTM) is related to long- term potentiation(LTP) and long- term depression (LTD). They intluenee each other. The relationship between LTP and LTD is complex. Therefore, it is important to study the learning and memory mechanism from LTP、LTD and gene expression in the CNS.

  12. Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

    Directory of Open Access Journals (Sweden)

    Paul Smolen

    Full Text Available Protein synthesis-dependent, late long-term potentiation (LTP and depression (LTD at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

  13. Exogenous glutamate induces short and long-term potentiation in the rat medial vestibular nuclei.

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    Grassi, S; Frondaroli, A; Pessia, M; Pettorossi, V E

    2001-08-08

    In rat brain stem slices, high concentrations of exogenous glutamate induce long-term potentiation (LTP) of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation. At low concentrations, glutamate can also induce short-term potentiation (STP), indicating that LTP and STP are separate events depending on the level of glutamatergic synapse activation. LTP and STP are prevented by blocking NMDA receptors and nitric oxide (NO) synthesis. Conversely, blocking platelet-activating factor (PAF) and group I metabotropic glutamate receptors only prevents the full development of LTP. Moreover, in the presence of blocking agents, glutamate causes transient inhibition, suggesting that when potentiation is impeded, exogenous glutamate can activate presynaptic mechanisms that reduce glutamate release.

  14. Long-term potentiation and depression after unilateral labyrinthectomy in the medial vestibular nucleus of rats.

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    Pettorossi, Vito Enrico; Dutia, Mayank; Frondaroli, Adele; Dieni, Cristina; Grassi, Silvarosa

    2003-01-01

    We previously demonstrated in rat brainstem slices that high-frequency stimulation (HFS) of the vestibular afferents induces long-term potentiation (LTP) in the ventral part (Vp) of the medial vestibular nucleus (MVN) and long-term depression (LTD) in the dorsal part (Dp). Both LTP and LTD depend on N-methyl-D-aspartate receptor activation, which increases synaptic efficacy; however, in the Dp, LTP reverses to LTD because of the activation of gamma-aminobutyric acid-ergic neurons. Here we show that the probability of inducing long-term effects in the MVN of rat brainstem slices is altered after unilateral labyrinthectomy (UL). In fact, LTP occurs less frequently in the ventral contra-lesional side compared with sham-operated rats. In the dorsal ipsi-lesional side, LTD is reduced and LTP enhanced, while the opposite occurs in the dorsal contra-lesional side. These changes in synaptic plasticity may be useful for re-balancing the tonic discharge of the MVN of the two sides during vestibular compensation, and for enhancing the dynamic responses of the deafferented MVN neurons in the long term.

  15. Anti-Hebbian long-term potentiation in the hippocampal feedback inhibitory circuit.

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    Lamsa, Karri P; Heeroma, Joost H; Somogyi, Peter; Rusakov, Dmitri A; Kullmann, Dimitri M

    2007-03-02

    Long-term potentiation (LTP), which approximates Hebb's postulate of associative learning, typically requires depolarization-dependent glutamate receptors of the NMDA (N-methyl-D-aspartate) subtype. However, in some neurons, LTP depends instead on calcium-permeable AMPA-type receptors. This is paradoxical because intracellular polyamines block such receptors during depolarization. We report that LTP at synapses on hippocampal interneurons mediating feedback inhibition is "anti-Hebbian":Itis induced by presynaptic activity but prevented by postsynaptic depolarization. Anti-Hebbian LTP may occur in interneurons that are silent during periods of intense pyramidal cell firing, such as sharp waves, and lead to their altered activation during theta activity.

  16. A Protein Synthesis and Nitric Oxide-Dependent Presynaptic Enhancement in Persistent Forms of Long-Term Potentiation

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    Johnstone, Victoria P. A.; Raymond, Clarke R.

    2011-01-01

    Long-term potentiation (LTP) is an important process underlying learning and memory in the brain. At CA3-CA1 synapses in the hippocampus, three discrete forms of LTP (LTP1, 2, and 3) can be differentiated on the basis of maintenance and induction mechanisms. However, the relative roles of pre- and post-synaptic expression mechanisms in LTP1, 2,…

  17. NF-κB p50 subunit knockout impairs late LTP and alters long term memory in the mouse hippocampus

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    Oikawa Kensuke

    2012-07-01

    Full Text Available Abstract Background Nuclear factor kappa B (NF-κB is a transcription factor typically expressed with two specific subunits (p50, p65. Investigators have reported that NF-κB is activated during the induction of in vitro long term potentiation (LTP, a paradigm of synaptic plasticity and correlate of memory, suggesting that NF-κB may be necessary for some aspects of memory encoding. Furthermore, NF-κB has been implicated as a potential requirement in behavioral tests of memory. Unfortunately, very little work has been done to explore the effects of deleting specific NF-κB subunits on memory. Studies have shown that NF-κB p50 subunit deletion (p50−/− leads to memory deficits, however some recent studies suggest the contrary where p50−/− mice show enhanced memory in the Morris water maze (MWM. To more critically explore the role of the NF-κB p50 subunit in synaptic plasticity and memory, we assessed long term spatial memory in vivo using the MWM, and synaptic plasticity in vitro utilizing high frequency stimuli capable of eliciting LTP in slices from the hippocampus of NF-κB p50−/− versus their controls (p50+/+. Results We found that the lack of the NF-κB p50 subunit led to significant decreases in late LTP and in selective but significant alterations in MWM tests (i.e., some improvements during acquisition, but deficits during retention. Conclusions These results support the hypothesis that the NF-κ p50 subunit is required in long term spatial memory in the hippocampus.

  18. The discovery of long-term potentiation.

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    Lømo, Terje

    2003-04-29

    This paper describes circumstances around the discovery of long-term potentiation (LTP). In 1966, I had just begun independent work for the degree of Dr medicinae (PhD) in Per Andersen's laboratory in Oslo after an eighteen-month apprenticeship with him. Studying the effects of activating the perforant path to dentate granule cells in the hippocampus of anaesthetized rabbits, I observed that brief trains of stimuli resulted in increased efficiency of transmission at the perforant path-granule cell synapses that could last for hours. In 1968, Tim Bliss came to Per Andersen's laboratory to learn about the hippocampus and field potential recording for studies of possible memory mechanisms. The two of us then followed up my preliminary results from 1966 and did the experiments that resulted in a paper that is now properly considered to be the basic reference for the discovery of LTP.

  19. Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.

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    Camera, Daria; Coleman, Harold A; Parkington, Helena C; Jenkins, Trisha A; Pow, David V; Boase, Natasha; Kumar, Sharad; Poronnik, Philip

    2016-04-15

    The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Induction of synaptic long-term potentiation after opioid withdrawal.

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    Drdla, Ruth; Gassner, Matthias; Gingl, Ewald; Sandkühler, Jürgen

    2009-07-10

    mu-Opioid receptor (MOR) agonists represent the gold standard for the treatment of severe pain but may paradoxically also enhance pain sensitivity, that is, lead to opioid-induced hyperalgesia (OIH). We show that abrupt withdrawal from MOR agonists induces long-term potentiation (LTP) at the first synapse in pain pathways. Induction of opioid withdrawal LTP requires postsynaptic activation of heterotrimeric guanine nucleotide-binding proteins and N-methyl-d-aspartate receptors and a rise of postsynaptic calcium concentrations. In contrast, the acute depression by opioids is induced presynaptically at these synapses. Withdrawal LTP can be prevented by tapered withdrawal and shares pharmacology and signal transduction pathways with OIH. These findings provide a previously unrecognized target to selectively combat pro-nociceptive effects of opioids without compromising opioid analgesia.

  1. Disinhibition mediates a form of hippocampal long-term potentiation in area CA1.

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    Jake Ormond

    Full Text Available The hippocampus plays a central role in memory formation in the mammalian brain. Its ability to encode information is thought to depend on the plasticity of synaptic connections between neurons. In the pyramidal neurons constituting the primary hippocampal output to the cortex, located in area CA1, firing of presynaptic CA3 pyramidal neurons produces monosynaptic excitatory postsynaptic potentials (EPSPs followed rapidly by feedforward (disynaptic inhibitory postsynaptic potentials (IPSPs. Long-term potentiation (LTP of the monosynaptic glutamatergic inputs has become the leading model of synaptic plasticity, in part due to its dependence on NMDA receptors (NMDARs, required for spatial and temporal learning in intact animals. Using whole-cell recording in hippocampal slices from adult rats, we find that the efficacy of synaptic transmission from CA3 to CA1 can be enhanced without the induction of classic LTP at the glutamatergic inputs. Taking care not to directly stimulate inhibitory fibers, we show that the induction of GABAergic plasticity at feedforward inhibitory inputs results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials. Like classic LTP, disinhibition-mediated LTP requires NMDAR activation, suggesting a role in types of learning and memory attributed primarily to the former and raising the possibility of a previously unrecognized target for therapeutic intervention in disorders linked to memory deficits, as well as a potentially overlooked site of LTP expression in other areas of the brain.

  2. Local establishment of repetitive long-term potentiation-induced synaptic enhancement in cultured hippocampal slices with divided input pathways.

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    Oe, Yuki; Tominaga-Yoshino, Keiko; Ogura, Akihiko

    2011-09-01

    Long-term potentiation (LTP) in the rodent hippocampus is a popular model for synaptic plasticity, which is considered the cellular basis for brain memory. Because most LTP analysis involves acutely prepared brain slices, however, the longevity of single LTP has not been well documented. Using stable hippocampal slice cultures for long-term examination, we previously found that single LTP disappeared within 1 day. In contrast, repeated induction of LTP led to the development of a distinct type of plasticity that lasted for more than 3 weeks and was accompanied by the formation of new synapses. Naming this novel plastic phenomenon repetitive LTP-induced synaptic enhancement (RISE), we proposed it as a model for the cellular processes involved in long-term memory formation. However, because in those experiments LTP was induced pharmacologically in the whole slice, it is not known whether RISE has input-pathway specificity, an essential property for memory. In this study, we divided the input pathway of CA1 pyramidal neurons by a knife cut and induced LTP three times, the third by tetanic stimulation in one of the divided pathways to express RISE specifically. Voltage-sensitive dye imaging and Golgi-staining performed 2 weeks after the three LTP inductions revealed both enhanced synaptic strength and increased dendritic spine density confined to the tetanized region. These results demonstrate that RISE is a feasible cellular model for long-term memory. Copyright © 2011 Wiley-Liss, Inc.

  3. Persistent inhibition of hippocampal long-term potentiation in vivo by learned helplessness stress.

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    Ryan, Benedict K; Vollmayr, Barbara; Klyubin, Igor; Gass, Peter; Rowan, Michael J

    2010-06-01

    The persistent cognitive disruptive effects of stress have been strongly implicated in the pathophysiology of depression and post-traumatic stress disorder. Here we examined factors influencing the time course of recovery from the inhibitory effect of acute inescapable stressors on the ability to induce long-term potentiation (LTP) in the dorsal hippocampus in vivo. We tested different forms of LTP, different stressors and different inbred strains of rats. Acute elevated platform stress completely, but transiently (learned helplessness, inhibited LTP for at least 4 weeks. Contrary to expectations, there was no clear relationship between the ability of the footshock to trigger helpless behavior, a model of stress-induced depression, and the magnitude of LTP inhibition. Moreover, LTP did not appear to be affected by genetic susceptibility to learned helplessness, a model of genetic vulnerability to depression. This long-lasting synaptic plasticity disruption may underlie persistent impairment of hippocampus-dependent cognition by excessive acute inescapable stress.

  4. Influence of visual experience on developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei.

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    Grassi, Silvarosa; Dieni, Cristina; Frondaroli, Adele; Pettorossi, Vito Enrico

    2004-11-01

    The influence of visual experience deprivation on changes in synaptic plasticity during postnatal development was studied in the ventral part of the rat medial vestibular nuclei (vMVN). We analysed the differences in the occurrence, expressed as a percentage, of long-term depression (LTD) and long-term potentiation (LTP) induced by high frequency stimulation (HFS) of the primary vestibular afferents in rats reared in the light (LR) and those in the dark (DR). In LR rats, HFS only induced LTD in the early stages of development, but the occurrence of LTD progressively decreased to zero before their eyes opened, while that of LTP enhanced from zero to about 50%. Once the rats' eyes had opened, LTD was no longer inducible while LTP occurrence gradually reached the normal adult value (70%). In DR rats, a similar shift from LTD to LTP was observed before their eyes opened, showing only a slightly slower LTD decay and LTP growth, and the LTD annulment was delayed by 1 day. By contrast, the time courses of LTD and LTP development in DR and LR rats showed remarkable differences following eye opening. In fact, LTD occurrence increased to about 50% in a short period of time and remained high until the adult stage. In addition, the occurrence of LTP slowly decreased to less than 20%. The effect of light-deprivation was reversible, since the exposure of DR rats to light, 5 days after eye opening, caused a sudden disappearance of LTD and a partial recover of LTP occurrence. In addition, we observed that a week of light deprivation in LR adult rats did not affect the normal adult LTP occurrence. These results provide evidence that in a critical period of development visual input plays a crucial role in shaping synaptic plasticity of the vMVN, and suggest that the visual guided shift from LTD to LTP during development may be necessary to refine and consolidate vestibular circuitry.

  5. Synaptic long-term potentiation realized in Pavlov's dog model based on a NiOx-based memristor

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    Hu, S. G.; Liu, Y.; Liu, Z.; Chen, T. P.; Yu, Q.; Deng, L. J.; Yin, Y.; Hosaka, Sumio

    2014-12-01

    Synaptic Long-Term Potentiation (LTP), which is a long-lasting enhancement in signal transmission between neurons, is widely considered as the major cellular mechanism during learning and memorization. In this work, a NiOx-based memristor is found to be able to emulate the synaptic LTP. Electrical conductance of the memristor is increased by electrical pulse stimulation and then spontaneously decays towards its initial state, which resembles the synaptic LTP. The lasting time of the LTP in the memristor can be estimated with the relaxation equation, which well describes the conductance decay behavior. The LTP effect of the memristor has a dependence on the stimulation parameters, including pulse height, width, interval, and number of pulses. An artificial network consisting of three neurons and two synapses is constructed to demonstrate the associative learning and LTP behavior in extinction of association in Pavlov's dog experiment.

  6. Melatonin administration impairs visuo-spatial performance and inhibits neocortical long-term potentiation in rats.

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    Soto-Moyano, Rubén; Burgos, Héctor; Flores, Francisco; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Pérez, Hernán; Hernández, Paula; Hernández, Alejandro

    2006-10-01

    Melatonin has been shown to inhibit long-term potentiation (LTP) in hippocampal slices of rats. Since LTP may be one of the main mechanisms by which memory traces are encoded and stored in the central nervous system, it is possible that melatonin could modulate cognitive performance by interfering with the cellular and/or molecular mechanisms involved in LTP. We investigated in rats the effects of intraperitoneally-administered melatonin (0.1, 1 and 10 mg/kg), its saline-ethanol solvent, or saline alone, on the acquisition of visuo-spatial memory as well as on the ability of the cerebral cortex to develop LTP in vivo. Visuo-spatial performance was assessed daily in rats, for 10 days, in an 8-arm radial maze, 30 min after they received a single daily dose of melatonin. Visual cortex LTP was determined in sodium pentobarbital anesthetized rats (65 mg/kg i.p.), by potentiating transcallosal evoked responses with a tetanizing train (312 Hz, 500 ms duration) 30 min after administration of a single dose of melatonin. Results showed that melatonin impaired visuo-spatial performance in rats, as revealed by the greater number of errors committed and time spent to solve the task in the radial maze. Melatonin also prevented the induction of neocortical LTP. It is concluded that melatonin, at the doses utilized in this study, could alter some forms of neocortical plasticity involved in short- and long-term visuo-spatial memories in rats.

  7. Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield.

    Directory of Open Access Journals (Sweden)

    Francisco J Rubio

    2013-05-01

    Full Text Available Antidepressant drugs are usually administered for long time for the treatment of major depressive disorder. However, they are also prescribed in several additional psychiatric conditions as well as during long term maintenance treatments. Antidepressants induce adaptive changes in several forebrain structures which include modifications at glutamatergic synapses. We recently found that repetitive administration of the selective serotonin reuptake inhibitor fluoxetine to naϊve adult male rats induced an increase of mature, mushroom-type dendritic spines in several forebrain regions. This was associated with an increase of GluA2-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPA-Rs in telencephalic postsynaptic densities. To unravel the functional significance of such a synaptic re-arrangement, we focused on glutamate neurotransmission in the hippocampus. We evaluated the effect of four weeks of treatment with 0.7 mg/kg of fluoxetine on long-term potentiation (LTP and long-term depression (LTD in the Schaffer collateral-CA1 synapses and the perforant path-CA1 synapses. Recordings in hippocampal slices revealed profound deficits in LTP and LTD at Schaffer collateral-CA1 synapses associated to increased spine density and enhanced presence of mushroom-type spines, as revealed by Golgi staining. However, the same treatment had neither an effect on spine morphology, nor on LTP and LTD at perforant path-CA1 synapses. Cobalt staining experiments revealed decreased AMPA-R Ca2+ permeability in the stratum radiatum together with increased GluA2-containing, Ca2+-impermeable AMPA-Rs. Therefore, 4 weeks of fluoxetine treatment promoted structural and functional adaptations in CA1 neurons in a pathway-specific manner that were selectively associated with impairment of activity-dependent plasticity at Schaffer collateral-CA1 synapses.

  8. Hypoxia-Induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons

    Science.gov (United States)

    Zhou, Chengwen; Bell, Jocelyn J. Lippman; Sun, Hongyu; Jensen, Frances E.

    2012-01-01

    Neonatal seizures can lead to epilepsy and long-term cognitive deficits in adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and “silent” N-methyl-D-aspartate receptor (NMDAR)-only synapses in hippocampal CA1. At 48-72 hours (hrs) post-HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, post-seizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early-life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits. PMID:22171027

  9. A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus.

    Science.gov (United States)

    Hunter, B E; de Fiebre, C M; Papke, R L; Kem, W R; Meyer, E M

    1994-02-28

    Long-term potentiation (LTP) can be modulated by a number of neurotransmitter receptors including muscarinic and GABAergic receptor types. We have found that a novel nicotinic agonist, 2,4-dimethoxybenzylidene anabaseine (DMXB), facilitated the induction of LTP in the hippocampus in a dose-dependent and mecamylamine-sensitive manner. DMXB displaced high affinity nicotinic [125I]alpha-bungarotoxin and [3H]acetylcholine binding in rat brain. Xenopus oocyte studies demonstrated that DMXB has agonist activity at alpha 7 but not alpha 4/beta 2 nicotinic receptor subtypes. These results indicated that DMXB is a novel nicotinic agonist with apparent specificity for the alpha 7/alpha-bungarotoxin nicotinic receptor subtype and indicate that nicotinic receptor activation is capable of modulating the induction of long-term potentiation.

  10. Correlating learning and memory improvements to long-term potentiation in patients with brain injury

    Institute of Scientific and Technical Information of China (English)

    Xingfu Peng; Qian Yu

    2008-01-01

    BACKGROUND:Brain injury patients often exhibit learning and memory functional deficits.Long-term potentiation(LTP)is a representative index for studying learning and memory cellular models; the LTP index correlates to neural plasticity. OBJECTIVE:This study was designed to investigate correlations of learning and memory functions to LTP in brain injury patients,and to summarize the research advancements in mechanisms underlying brain functional improvements after rehabilitation intervention. RETRIEVAL STRATEGY:Using the terms "brain injuries,rehabilitation,learning and memory,long-term potentiation",manuscripts that were published from 2000-2007 were retrieved from the PubMed database.At the same time,manuscripts published from 2000-2007 were also retrieved from the Database of Chinese Scientific and Technical Periodicals with the same terms in the Chinese language.A total of 64 manuscripts were obtained and primarily screened.Inclusion criteria:studies on learning and memory,as well as LTP in brain injury patients,and studies focused on the effects of rehabilitation intervention on the two indices; studies that were recently published or in high-impact journals.Exclusion criteria:repetitive studies.LITERATURE EVALUATION:The included manuscripts primarily focused on correlations between learning and memory and LTP,the effects of brain injury on learning and memory,as well as LTP,and the effects of rehabilitation intervention on learning and memory after brain injury.The included 39 manuscripts were clinical,basic experimental,or review studies. DATA SYNTHESIS:Learning and memory closely correlates to LTP.The neurobiological basis of learning and memory is central nervous system plasticity,which involves neural networks,neural circuits,and synaptic connections,in particular,synaptic plasticity.LTP is considered to be an ideal model for studying synaptic plasticity,and it is also a classic model for studying neural plasticity of learning and memory.Brain injury

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

    Science.gov (United States)

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

    2011-08-01

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

  12. Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory.

    Science.gov (United States)

    Palmeri, Agostino; Ricciarelli, Roberta; Gulisano, Walter; Rivera, Daniela; Rebosio, Claudia; Calcagno, Elisa; Tropea, Maria Rosaria; Conti, Silvia; Das, Utpal; Roy, Subhojit; Pronzato, Maria Adelaide; Arancio, Ottavio; Fedele, Ernesto; Puzzo, Daniela

    2017-07-19

    High levels of amyloid-β peptide (Aβ) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of Aβ are necessary for long-term potentiation (LTP) and memory. Because cGMP plays a key role in these processes, here we investigated whether the cyclic nucleotide cGMP influences Aβ levels and function during LTP and memory. We demonstrate that the increase of cGMP levels by the phosphodiesterase-5 inhibitors sildenafil and vardenafil induces a parallel release of Aβ due to a change in the approximation of amyloid precursor protein (APP) and the β-site APP cleaving enzyme 1. Moreover, electrophysiological and behavioral studies performed on animals of both sexes showed that blocking Aβ function, by using anti-murine Aβ antibodies or APP knock-out mice, prevents the cGMP-dependent enhancement of LTP and memory. Our data suggest that cGMP positively regulates Aβ levels in the healthy brain which, in turn, boosts synaptic plasticity and memory. SIGNIFICANCE STATEMENT Amyloid-β (Aβ) is a key pathogenetic factor in Alzheimer's disease. However, low concentrations of endogenous Aβ, mimicking levels of the peptide in the healthy brain, enhance hippocampal long-term potentiation (LTP) and memory. Because the second messenger cGMP exerts a central role in LTP mechanisms, here we studied whether cGMP affects Aβ levels and function during LTP. We show that cGMP enhances Aβ production by increasing the APP/BACE-1 convergence in endolysosomal compartments. Moreover, the cGMP-induced enhancement of LTP and memory was disrupted by blockade of Aβ, suggesting that the physiological effect of the cyclic nucleotide on LTP and memory is dependent upon Aβ. Copyright © 2017 the authors 0270-6474/17/376926-12$15.00/0.

  13. 12-lipoxygenase regulates hippocampal long-term potentiation by modulating L-type Ca2+ channels

    Science.gov (United States)

    DeCostanzo, Anthony J.; Voloshyna, Iryna; Rosen, Zev B.; Feinmark, Steven J.; Siegelbaum, Steven A.

    2010-01-01

    Although long-term potentiation (LTP) has been intensely studied, there is disagreement as to which molecules mediate and modulate LTP. This is partly due to the presence of mechanistically distinct forms of LTP that are induced by different patterns of stimulation and that depend on distinct Ca2+ sources. Here we report a novel role for the arachidonic acid-metabolizing enzyme 12-lipoxygenase (12-LO) in LTP at CA3-CA1 hippocampal synapses that is dependent on the pattern of tetanic stimulation. We find that 12-LO activity is required for the induction of LTP in response to a theta-burst stimulation (TBS) protocol, which depends on Ca2+ influx through both NMDA receptors and L-type voltage-gated Ca2+ channels. In contrast, LTP induced by 100 Hz tetanic stimulation, which requires Ca2+ influx through NMDA receptors but not L-type channels, does not require 12-LO. We find that 12-LO regulates LTP by enhancing postsynaptic somatodendritic Ca2+ influx through L-type channels during theta burst stimulation, an action exerted via 12(S)-HPETE, a downstream metabolite of 12-LO. These results help define the role of a long-disputed signaling enzyme in LTP. PMID:20130191

  14. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

    Directory of Open Access Journals (Sweden)

    Liu Xian-Guo

    2011-03-01

    Full Text Available Abstract Long-term potentiation (LTP in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.

  15. Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation

    NARCIS (Netherlands)

    van Beugen, Boeke J; Qiao, Xin; Simmons, Dana H; De Zeeuw, Chris I; Hansel, Christian

    2014-01-01

    Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory

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

    Science.gov (United States)

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

    2008-10-01

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

  17. Neural 17β-estradiol facilitates long-term potentiation in the hippocampal CA1 region.

    Science.gov (United States)

    Grassi, S; Tozzi, A; Costa, C; Tantucci, M; Colcelli, E; Scarduzio, M; Calabresi, P; Pettorossi, V E

    2011-09-29

    In the hippocampal formation many neuromodulators are possibly implied in the synaptic plasticity such as the long-term potentiation (LTP) induced by high-frequency stimulation (HFS) of afferent fibers. We investigated the involvement of locally synthesized neural 17β-estradiol (nE(2)) in the induction of HFS-LTP in hippocampal slices from male rats by stimulating the Schaffer collateral fibers and recording the evoked field excitatory postsynaptic potential (fEPSP) in the CA1 region. We demonstrated that either the blockade of nE(2) synthesis by the aromatase inhibitor letrozole, or the antagonism of E(2) receptors (ERs) by ICI 182,780 did not prevent the induction of HFS-LTP, but reduced its amplitude by ∼60%, without influencing its maintenance. Moreover, letrozole and ICI 182,780 did not affect the first short-term post-tetanic component of LTP and the paired-pulse facilitation (PPF). These findings demonstrate that nE(2) plays an important role in the induction phase of HFS-dependent LTP. Since the basal responses were not affected by the blocking agents, we suggest that the synthesis of nE(2) is induced or enhanced by HFS through aromatase activation. In this context, the local production of nE(2) seems to be a very effective mechanism to modulate the amplitude of LTP. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. LTP after Stress: Up or Down?

    Directory of Open Access Journals (Sweden)

    Marian Joëls

    2007-01-01

    Full Text Available When an organism is exposed to a stressful situation, corticosteroid levels in the brain rise. This rise has consequences for behavioral performance, including memory formation. Over the past decades, it has become clear that a rise in corticosteroid level is also accompanied by a reduction in hippocampal long-term potentiation (LTP. Recent studies, however, indicate that stress does not lead to a universal suppression of LTP. Many factors, including the type of stress, the phase of the stress response, the area of investigation, type of LTP, and the life history of the organism determine in which direction LTP will be changed.

  19. A single episode of high intensity sound inhibits long-term potentiation in the hippocampus of rats.

    Science.gov (United States)

    de Deus, J L; Cunha, A O S; Terzian, A L; Resstel, L B; Elias, L L K; Antunes-Rodrigues, J; Almeida, S S; Leão, R M

    2017-10-26

    Exposure to loud sounds has become increasingly common. The most common consequences of loud sound exposure are deafness and tinnitus, but emotional and cognitive problems are also associated with loud sound exposure. Loud sounds can activate the hipothalamic-pituitary-adrenal axis resulting in the secretion of corticosterone, which affects hippocampal synaptic plasticity. Previously we have shown that long-term exposure to short episodes of high intensity sound inhibited hippocampal long-term potentiation (LTP) without affecting spatial learning and memory. Here we aimed to study the impact of short term loud sound exposure on hippocampal synaptic plasticity and function. We found that a single minute of 110 dB sound inhibits hippocampal Schaffer-CA1 LTP for 24 hours. This effect did not occur with an 80-dB sound exposure, was not correlated with corticosterone secretion and was also observed in the perforant-dentate gyrus synapse. We found that despite the deficit in the LTP these animals presented normal spatial learning and memory and fear conditioning. We conclude that a single episode of high-intensity sound impairs hippocampal LTP, without impairing memory and learning. Our results show that the hippocampus is very responsive to loud sounds which can have a potential, but not yet identified, impact on its function.

  20. Cytokines and cytokine networks target neurons to modulate long-term potentiation.

    Science.gov (United States)

    Prieto, G Aleph; Cotman, Carl W

    2017-04-01

    Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Involvement of microglia activation in the lead induced long-term potentiation impairment.

    Directory of Open Access Journals (Sweden)

    Ming-Chao Liu

    Full Text Available Exposure of Lead (Pb, a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α, interleukin-1β (IL-1β and inducible nitric oxide synthase (iNOS in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits.

  2. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

    OpenAIRE

    Wen-bin He; Kazuho Abe; Tatsuhiro Akaishi

    2018-01-01

    To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to...

  3. Different contributions of platelet-activating factor and nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Pettorossi, V E; Grassi, S

    2001-01-01

    In rat brainstem slices, we investigated the differential role of nitric oxide (NO) and platelet-activating factor (PAF) in long-term potentiation (LTP) induced in the ventral portion of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferents. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and the PAF receptor antagonist ginkgolide B (BN-52021) were administered before and after induction of potentiation. The effect of carboxy-PTIO was to completely prevent LTP. By contrast, BN-52021 only reduced the amplitude of HFS potentiation, which could develop fully at the drug washout or decline to zero, becoming a short-term phenomenon, in the case of long-lasting PAF receptor block. Both drugs, when given after HFS, had no effect on the already established potentiation, but whilst BN-52021 showed an influence within 5 min of the LTP induction, carboxy-PTIO did not affect the response once HFS was delivered. Moreover, we showed that the NO donor, sodium nitroprusside, and methylcarbamyl PAF (mc-PAF) induced LTP which was associated with an increase in glutamate release as shown by reduction in the paired-pulse facilitation ratio. The mc-PAF LTP was prevented by the NO scavenger, while NO LTP was only reduced by BN-52021. We suggest that NO and PAF are implicated as retrograde messengers in two different phases of vestibular LTP: NO in the induction phase; and PAF in the full expression phase.

  4. Gating of Long-Term Potentiation by Nicotinic Acetylcholine Receptors at the Cerebellum Input Stage

    NARCIS (Netherlands)

    F. Prestori (Francesca); C. Bonardi (Claudia); L. Mapelli (Lisa); P. Lombardo (Paola); R. Goselink (Rianne); M.E. de Stefano (Maria Egle); D. Gandolfi (Daniela); J. Mapelli (Jonathan); D. Bertrand (Daniel); M. Schonewille (Martijn); C.I. de Zeeuw (Chris); E. D'Angelo (Egidio)

    2013-01-01

    textabstractThe brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD) between mossy fibres and granule cells can saturate synaptic

  5. BDNF Regains Function in Hippocampal Long-Term Potentiation Deficits Caused by Diencephalic Damage

    Science.gov (United States)

    Vedder, Lindsey C.; Savage, Lisa M.

    2017-01-01

    Thiamine deficiency (TD), commonly associated with chronic alcoholism, leads to diencephalic damage, hippocampal dysfunction, and spatial learning and memory deficits. We show a decrease in the magnitude of long-term potentiation (LTP) and paired-pulse facilitation (PPF) at CA3-CA1 synapses, independent of sex, following diencephalic damage…

  6. Complex modulation by stress of the effect of seizures on long term potentiation in mouse hippocampal slices.

    Science.gov (United States)

    Maggio, Nicola; Shavit Stein, Efrat; Segal, Menahem

    2017-08-01

    Stress has a profound effect on ability to express neuronal plasticity, learning, and memory. Likewise, epileptic seizures lead to massive changes in brain connectivity, and in ability to undergo long term changes in reactivity to afferent stimulation. In this study, we analyzed possible long lasting interactions between a stressful experience and reactivity to pilocarpine, on the ability to produce long term potentiation (LTP) in a mouse hippocampus. Pilocarpine lowers paired pulse potentiation as well as LTP in CA1 region of the mouse hippocampal slice. When stress experience precedes exposure to pilocarpine, it protects the brain from the lasting effect of pilocarpine. When stress follows pilocarpine, it exacerbates the effect of the drug, to produce a long lasting reduction in LTP. These changes are accompanied by a parallel change in blood corticosterone level. A single exposure to selective mineralo- or gluco-corticosterone (MR and GR, respectively) agonists and antagonists can mimic the stress effects, indicating that GR's underlie the lasting detrimental effects of stress whereas MRs are instrumental in counteracting the effects of stress. These studies open a new avenue of understanding of the interactive effects of stress and epileptic seizures on brain plasticity. © 2017 Wiley Periodicals, Inc.

  7. Reversal of long-term potentiation-like plasticity processes after motor learning disrupts skill retention.

    Science.gov (United States)

    Cantarero, Gabriela; Lloyd, Ashley; Celnik, Pablo

    2013-07-31

    Plasticity of synaptic connections in the primary motor cortex (M1) is thought to play an essential role in learning and memory. Human and animal studies have shown that motor learning results in long-term potentiation (LTP)-like plasticity processes, namely potentiation of M1 and a temporary occlusion of additional LTP-like plasticity. Moreover, biochemical processes essential for LTP are also crucial for certain types of motor learning and memory. Thus, it has been speculated that the occlusion of LTP-like plasticity after learning, indicative of how much LTP was used to learn, is essential for retention. Here we provide supporting evidence of it in humans. Induction of LTP-like plasticity can be abolished using a depotentiation protocol (DePo) consisting of brief continuous theta burst stimulation. We used transcranial magnetic stimulation to assess whether application of DePo over M1 after motor learning affected (1) occlusion of LTP-like plasticity and (2) retention of motor skill learning. We found that the magnitude of motor memory retention is proportional to the magnitude of occlusion of LTP-like plasticity. Moreover, DePo stimulation over M1, but not over a control site, reversed the occlusion of LTP-like plasticity induced by motor learning and disrupted skill retention relative to control subjects. Altogether, these results provide evidence of a link between occlusion of LTP-like plasticity and retention and that this measure could be used as a biomarker to predict retention. Importantly, attempts to reverse the occlusion of LTP-like plasticity after motor learning comes with the cost of reducing retention of motor learning.

  8. Persistent changes in ability to express long-term potentiation/depression in the rat hippocampus after juvenile/adult stress.

    Science.gov (United States)

    Maggio, Nicola; Segal, Menahem

    2011-04-15

    The ventral hippocampus (VH) was recently shown to express lower magnitude long-term potentiation (LTP) compared with the dorsal hippocampus (DH). Exposure to acute stress reversed this difference, and VH slices from stressed rats expressed larger LTP than that produced in the DH, which was reduced by stress. Stressful experience in adolescence has been shown to produce long-lasting effects on animal behavior and on ability to express LTP/long-term depression (LTD) of reactivity to afferent stimulation in the adult. We are interested in possible interactions between juvenile and adult stress in their effects of adult plasticity. We studied the effects of a composite juvenile (28-30 days) stress, followed by a reminder stressful experience in the young adult (60 days) rat, on the ability to produce LTP and LTD in CA1 region of slices of the VH and DH. Juvenile or adult stress produced a transient decrease in ability to express LTP in DH and a parallel increase in LTP in VH. Stress in the young adult after juvenile stress produced a striking prolongation of the DH/VH disparity with respect to the ability to express both LTP and LTD into the adulthood of the rat. These results have important implications for the impact of juvenile stress on adult neuronal plasticity and on the understanding the functions of the different sectors of the hippocampus. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. A juvenile form of postsynaptic hippocampal long-term potentiation in mice deficient for the AMPA receptor subunit GluR-A

    NARCIS (Netherlands)

    Jensen, V.; Kaiser, K.M.M.; Borchardt, T.; Adelmann, G.; Rozov, A.; Burnashev, N.; Brix, C.; Frotscher, M.; Anderson, P.; Hvalby, O.; Sakmann, B.; Seeburg, P.H.; Sprengel, R.

    2003-01-01

    In adult mice, long-term potentiation (LTP) of synaptic transmission at CA3-to-CA1 synapses induced by tetanic stimulation requires L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors containing GluR-A subunits. Here, we report a GluR-A-independent form of LTP, which is comparable in

  10. Prior Activation of Inositol 1,4,5-Trisphosphate Receptors Suppresses the Subsequent Induction of Long-Term Potentiation in Hippocampal CA1 Neurons

    Science.gov (United States)

    Fujii, Satoshi; Yamazaki, Yoshihiko; Goto, Jun-Ichi; Fujiwara, Hiroki; Mikoshiba, Katsuhiko

    2016-01-01

    We investigated the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) activated by preconditioning low-frequency afferent stimulation (LFS) in the subsequent induction of long-term potentiation (LTP) in CA1 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential or the population…

  11. Long-term potentiation of synaptic response and intrinsic excitability in neurons of the rat medial vestibular nuclei.

    Science.gov (United States)

    Pettorossi, V E; Dieni, C V; Scarduzio, M; Grassi, S

    2011-07-28

    Using intracellular recordings, we investigated the effects of high frequency stimulation (HFS) of the primary vestibular afferents on the evoked excitatory postsynaptic potential (EPSP) and intrinsic excitability (IE) of type-A and type-B neurons of the medial vestibular nucleus (MVN), in male rat brainstem slices. HFS induces long-term potentiation (LTP) of both EPSP and IE, which may occur in combination or separately. Synaptic LTP is characterized by an increase in the amplitude, slope and decay time constant of EPSP and IE-LTP through enhancements of spontaneous and evoked neuron firing and of input resistance (Rin). Moreover, IE-LTP is associated with a decrease in action potential afterhyperpolarization (AHP) amplitude and an increase in interspike slope steepness (ISS). The more frequent effects of HFS are EPSP-LTP in type-B neurons and IE-LTP in type-A neurons. In addition, the development of EPSP-LTP is fast in type-B neurons but slow in type-A, whereas IE-LTP develops slowly in both types. We have demonstrated that activation of N-methyl-d aspartate receptors (NMDARs) is only required for EPSP-LTP induction, whereas metabotropic glutamate receptors type-1 (mGluR1) are necessary for IE-LTP induction as well as the full development and maintenance of EPSP-LTP. Taken together, these findings demonstrate that brief and intense activation of vestibular afferent input to the MVN neurons may provoke synaptic LTP and/or IE-LTP that, induced in combination or separately, may assure the different selectivity of the MVN neuron response enhancement to the afferent signals. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Translating long-term potentiation from animals to humans: a novel method for noninvasive assessment of cortical plasticity.

    Science.gov (United States)

    Clapp, Wesley C; Hamm, Jeff P; Kirk, Ian J; Teyler, Timothy J

    2012-03-15

    Long-term potentiation (LTP) is a synaptic mechanism underlying learning and memory that has been studied extensively in laboratory animals. The study of LTP recently has been extended into humans with repetitive sensory stimulation to induce cortical LTP. In this review article, we will discuss past results from our group demonstrating that repetitive sensory stimulation (visual or auditory) induces LTP within the sensory cortex (visual/auditory, respectively) and can be measured noninvasively with electroencephalography or functional magnetic resonance imaging. We will discuss a number of studies that indicate that this form of LTP shares several characteristics with the synaptic LTP described in animals: it is frequency dependent, long-lasting (> 1 hour), input-specific, depotentiates with low-frequency stimulation, and is blocked by N-methyl-D-aspartate receptor blockers in rats. In this review, we also present new data with regard to the behavioral significance of human sensory LTP. These advances will permit enquiry into the functional significance of LTP that has been hindered by the absence of a human model. The ability to elicit LTP with a natural sensory stimulus noninvasively will provide a model system allowing the detailed examination of synaptic plasticity in normal subjects and might have future clinical applications in the diagnosis and assessment of neuropsychiatric and neurocognitive disorders. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Ryanodine receptors contribute to the induction of nociceptive input-evoked long-term potentiation in the rat spinal cord slice

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    Zhao Zhi-Qi

    2010-01-01

    Full Text Available Abstract Background Our previous study demonstrated that nitric oxide (NO contributes to long-term potentiation (LTP of C-fiber-evoked field potentials by tetanic stimulation of the sciatic nerve in the spinal cord in vivo. Ryanodine receptor (RyR is a downstream target for NO. The present study further explored the role of RyR in synaptic plasticity of the spinal pain pathway. Results By means of field potential recordings in the adult male rat in vivo, we showed that RyR antagonist reduced LTP of C-fiber-evoked responses in the spinal dorsal horn by tetanic stimulation of the sciatic nerve. Using spinal cord slice preparations and field potential recordings from superficial dorsal horn, high frequency stimulation of Lissauer's tract (LT stably induced LTP of field excitatory postsynaptic potentials (fEPSPs. Perfusion of RyR antagonists blocked the induction of LT stimulation-evoked spinal LTP, while Ins(1,4,5P3 receptor (IP3R antagonist had no significant effect on LTP induction. Moreover, activation of RyRs by caffeine without high frequency stimulation induced a long-term potentiation in the presence of bicuculline methiodide and strychnine. Further, in patch-clamp recordings from superficial dorsal horn neurons, activation of RyRs resulted in a large increase in the frequency of miniature EPSCs (mEPSCs. Immunohistochemical study showed that RyRs were expressed in the dorsal root ganglion (DRG neurons. Likewise, calcium imaging in small DRG neurons illustrated that activation of RyRs elevated [Ca2+]i in small DRG neurons. Conclusions These data indicate that activation of presynaptic RyRs play a crucial role in the induction of LTP in the spinal pain pathway, probably through enhancement of transmitter release.

  14. Pharmacological Modulation of Long-Term Potentiation-Like Activity in the Dorsolateral Prefrontal Cortex

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    Bahar Salavati

    2018-04-01

    Full Text Available Background: Long-term potentiation (LTP depends on glutamatergic neurotransmission and is modulated by cholinergic, dopaminergic and GABAergic inputs. Paired associative stimulation (PAS is a neurostimulation paradigm that, when combined with electroencephalography (EEG, assesses LTP-like activity (PAS-induced LTP in the dorsolateral prefrontal cortex (DLPFC. Thus, we conducted a study to assess the role of cholinergic, dopaminergic, GABAergic and glutamatergic neurotransmission on PAS-induced LTP in the DLPFC. We hypothesized that increasing the dopaminergic tone with L-DOPA and the cholinergic tone with rivastigmine will enhance PAS-induced LTP, while increasing the GABAergic tone with baclofen and inhibiting glutamatergic neurotransmission with dextromethorphan will reduce it compared to placebo.Methods: In this randomized controlled, double-blind cross-over within-subject study, 12 healthy participants received five sessions of PAS to the DLPFC in a random order, each preceded by the administration of placebo or one of the four active drugs. PAS-induced LTP was assessed after each drug administration and compared to PAS-induced LTP after placebo.Results: As predicted, L-DOPA and rivastigmine resulted in enhanced PAS-induced LTP in the DLPFC and dextromethorphan inhibited it compared to placebo. In contrast, baclofen did not significantly suppress PAS-induced LTP compared to placebo.Conclusions: This study provides a novel approach to study DLPFC neuroplasticity and its modulation in patients with brain disorders that are associated with abnormalities in these neurochemical systems. This study was based on a single dose administration of each drug. Given that these drugs are typically administered chronically, future studies should assess the effects of chronic administration.

  15. Alpha2-adrenoceptor modulation of long-term potentiation elicited in vivo in rat occipital cortex.

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    Mondaca, Mauricio; Hernández, Alejandro; Pérez, Hernán; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Soto-Moyano, Rubén

    2004-09-24

    Pretreatment with the alpha(2)-adrenoceptor agonist clonidine (31.25, 62.5, or 125 microg/kg, i.p.) dose-dependently reduced long-term potentiation (LTP) elicited in vivo in the occipital cortex of anesthetized rats, whereas pretreatment with the alpha(2)-adrenoceptor antagonist yohimbine (0.133, 0.4, or 1.2 mg/kg, i.p.) increased neocortical LTP in a dose-dependent fashion. These effects could be related to the reported disruptive and facilitatory actions induced on memory formation by pretreatment with alpha(2)-adrenoceptor agonists and antagonists, respectively.

  16. PKMζ inhibition prevents the metaplastic change induced by conditioned taste aversion on insular cortex long-term potentiation in vivo.

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    Ángeles-Durán, Sandybel; Ramos-Languren, Laura E; Escobar, Martha L

    2012-01-01

    The activity history of a given neuron or pathway has been suggested to influence its future responses to synaptic inputs. In particular, training in several learning tasks produces a metaplastic change, that is, a change in the ability to induce subsequent synaptic plasticity. Experimental evidence shows that the maintenance of long term memory and long-term potentiation (LTP) requires the persistent action of the atypical protein kinase Cisoform, protein kinase M ζ (PKM ζ ). Recent work has demonstrated that the inactivation of PKM ζ in the insular cortex (IC) abolishes conditioned taste aversion (CTA) long term memory. Our previous studies in the IC have demonstrated that the induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC projection previous to CTA training enhances the retention of this task. Moreover, recently, we have observed that CTA training blocks the subsequent induction of LTP in the Bla-IC projection. The aim of the present study was to investigate the participation of PKM ζon the CTA-dependent modification of the ability to induce subsequent LTP in the Bla-IC projection in vivo . Thus, we have delivered high-frequency stimulation in the Bla-IC projection in order to induce in vivo IC-LTP in the rats that underwent or did not have an impairment of CTA retention due to the intracortical administration of the selective PKM ζ pseudosubstrate inhibitory peptide, ZIP. Our results show that the microinfusion of ZIP into the IC of the behaving rats impairs long-term memory of CTA and prevents its effects on IC-LTP. These results indicate that PKM ζ is a key component of the cellular mechanisms necessary for the persistence of lasting memory traces as well as for those underlying metaplastic changes in neocortex, contributing to the persistence of aversive memories.

  17. Novel environments enhance the induction and maintenance of long-term potentiation in the dentate gyrus.

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    Davis, Cyndy D; Jones, Floretta L; Derrick, Brian E

    2004-07-21

    The induction of long-term potentiation (LTP) in the hippocampal formation can be modulated by different behavioral states. However, few studies have addressed modulation of LTP during behavioral states in which the animal is likely acquiring new information. Here, we demonstrate that both the induction and the longevity of LTP in the dentate gyrus are enhanced when LTP is induced during the initial exploration of a novel environment. These effects are independent from locomotor activity, changes in brain temperature, and theta rhythm. Previous exposure to the novel environment attenuated this enhancement, suggesting that the effects of novelty habituate with familiarity. LTP longevity also was enhanced when induced in familiar environments containing novel objects. Together, these data indicate that both LTP induction and maintenance are enhanced when LTP is induced while rats investigate novel stimuli. We suggest that novelty initiates a transition of the hippocampal formation to a mode that is particularly conducive to synaptic plasticity, a process that could allow for new learning while preserving the stability of previously stored information. In addition, LTP induced in novel environments elicited a sustained late LTP. This suggests that a single synaptic population can display distinct profiles of LTP maintenance and that this depends on the animal's behavioral state during its induction. Furthermore, the duration of LTP enhanced by novelty parallels the time period during which the hippocampal formation is thought necessary for memory, consistent with the view that dentate LTP is of a duration sufficient to sustain memory in the hippocampal formation.

  18. Long-term potentiation in the rat medial vestibular nuclei depends on locally synthesized 17beta-estradiol.

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    Grassi, Silvarosa; Frondaroli, Adele; Dieni, Cristina; Scarduzio, Mariangela; Pettorossi, Vito E

    2009-08-26

    In male rat brainstem slices, we investigated the involvement of locally synthesized 17beta-estradiol (E(2)) in the induction in the medial vestibular nucleus (MVN) of long-term potentiation (LTP) by high-frequency stimulation (HFS) of the primary vestibular afferents. We demonstrated that the blockade of aromatase by letrozole or of E(2) receptors (ERalpha and ERbeta) by ICI 182,780 prevented the HFS-induced LTP of the N1 wave of the evoked field potential (FP) without affecting baseline responses. Only prolonged afferent activation could induce low LTP. In contrast, HFS applied under a combined blockade of GABA(A) receptors and aromatase or ERs was still able to induce LTP, but it was significantly lower and slower. These findings demonstrate that E(2) does not have a tonic influence on the activity of the MVN neurons and provide the first evidence of the crucial role played by local synthesis of E(2) in inducing LTP. We suggest that the synthesis of E(2) occurs after aromatase activation during HFS and facilitates the development of vestibular synaptic plasticity by influencing glutamate and GABA transmission.

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

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

    2018-03-06

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

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

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    Wright, Brandon J; Jackson, Meyer B

    2014-07-16

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

  1. Long-term potentiation protects rat hippocampal slices from the effects of acute hypoxia.

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    Youssef, F F; Addae, J I; McRae, A; Stone, T W

    2001-07-13

    We have previously shown that long-term potentiation (LTP) decreases the sensitivity of glutamate receptors in the rat hippocampal CA1 region to exogenously applied glutamate agonists. Since the pathophysiology of hypoxia/ischemia involves increased concentration of endogenous glutamate, we tested the hypothesis that LTP could reduce the effects of hypoxia in the hippocampal slice. The effects of LTP on hypoxia were measured by the changes in population spike potentials (PS) or field excitatory post-synaptic potentials (fepsps). Hypoxia was induced by perfusing the slice with (i) artificial CSF which had been pre-gassed with 95%N2/5% CO2; (ii) artificial CSF which had not been pre-gassed with 95% O2/5% CO2; or (iii) an oxygen-glucose deprived (OGD) medium which was similar to (ii) and in which the glucose had been replaced with sucrose. Exposure of a slice to a hypoxic medium for 1.5-3.0 min led to a decrease in the PS or fepsps; the potentials recovered to control levels within 3-5 min. Repeat exposure, 45 min later, of the same slice to the same hypoxic medium for the same duration as the first exposure caused a reduction in the potentials again; there were no significant differences between the degree of reduction caused by the first or second exposure for all three types of hypoxic media (P>0.05; paired t-test). In some of the slices, two episodes of LTP were induced 25 and 35 min after the first hypoxic exposure; this caused inhibition of reduction in potentials caused by the second hypoxic insult which was given at 45 min after the first; the differences in reduction in potentials were highly significant for all the hypoxic media used (Peffects of LTP were not prevented by cyclothiazide or inhibitors of NO synthetase compounds that have been shown to be effective in blocking the effects of LTP on the actions of exogenously applied AMPA and NMDA, respectively. The neuroprotective effects of LTP were similar to those of propentofylline, a known neuroprotective

  2. Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.

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    Mariangela Scarduzio

    Full Text Available Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs and androgens (ARs. We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2 and 5α-dihydrotestosterone (DHT on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN. Long-term depression (LTD and long-term potentiation (LTP caused by different patterns of high frequency stimulation (HFS of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase and E2 (P450-aromatase from testosterone (T. We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

  3. Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.

    Science.gov (United States)

    Scarduzio, Mariangela; Panichi, Roberto; Pettorossi, Vito Enrico; Grassi, Silvarosa

    2013-01-01

    Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN). Long-term depression (LTD) and long-term potentiation (LTP) caused by different patterns of high frequency stimulation (HFS) of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase) and E2 (P450-aromatase) from testosterone (T). We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

  4. Dopamine Induces LTP Differentially in Apical and Basal Dendrites through BDNF and Voltage-Dependent Calcium Channels

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    Navakkode, Sheeja; Sajikumar, Sreedharan; Korte, Martin; Soong, Tuck Wah

    2012-01-01

    The dopaminergic modulation of long-term potentiation (LTP) has been studied well, but the mechanism by which dopamine induces LTP (DA-LTP) in CA1 pyramidal neurons is unknown. Here, we report that DA-LTP in basal dendrites is dependent while in apical dendrites it is independent of activation of L-type voltage-gated calcium channels (VDCC).…

  5. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

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    Wen-bin He

    2018-01-01

    Full Text Available To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood–brain barrier and promotes synaptic functions in the hippocampus.

  6. A computational simulation of long-term synaptic potentiation inducing protocol processes with model of CA3 hippocampal microcircuit.

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    Świetlik, D; Białowąs, J; Kusiak, A; Cichońska, D

    2018-01-01

    An experimental study of computational model of the CA3 region presents cog-nitive and behavioural functions the hippocampus. The main property of the CA3 region is plastic recurrent connectivity, where the connections allow it to behave as an auto-associative memory. The computer simulations showed that CA3 model performs efficient long-term synaptic potentiation (LTP) induction and high rate of sub-millisecond coincidence detection. Average frequency of the CA3 pyramidal cells model was substantially higher in simulations with LTP induction protocol than without the LTP. The entropy of pyramidal cells with LTP seemed to be significantly higher than without LTP induction protocol (p = 0.0001). There was depression of entropy, which was caused by an increase of forgetting coefficient in pyramidal cells simulations without LTP (R = -0.88, p = 0.0008), whereas such correlation did not appear in LTP simulation (p = 0.4458). Our model of CA3 hippocampal formation microcircuit biologically inspired lets you understand neurophysiologic data. (Folia Morphol 2018; 77, 2: 210-220).

  7. Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat.

    Science.gov (United States)

    Di Mauro, Michela; Tozzi, Alessandro; Calabresi, Paolo; Pettorossi, Vito Enrico; Grassi, Silvarosa

    2015-01-01

    Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD) and depotentiation (DP) by low frequency stimulation (LFS, 15 min-1 Hz) and of long-term potentiation (LTP) by high frequency stimulation (HFS, 1 s-100 Hz), medium (MFS, 1 s-50 Hz), or weak (WFS, 1 s-25 Hz) frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T) into DHT (5α-reductase) and T into E2 (P450-aromatase). We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

  8. Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat

    Directory of Open Access Journals (Sweden)

    Michela eDi Mauro

    2015-10-01

    Full Text Available Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17b-estradiol (E2 and 5a-dihydrotestosterone (DHT neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD and depotentiation (DP by low frequency stimulation (LFS, 15 min-1 Hz and of long-term potentiation (LTP by high (HFS, 1 s-100 Hz, medium (MFS, 1 s-50 Hz, or weak (WFS, 1 s-25 Hz frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T into DHT (5a-reductase and T into E2 (P450-aromatase. We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

  9. Long-term potentiation and olfactory memory formation in the carp (Cyprinus carpio L.) olfactory bulb.

    Science.gov (United States)

    Satou, M; Anzai, S; Huruno, M

    2005-05-01

    Long-term potentiation of synaptic transmission is considered to be an elementary process underlying the cellular mechanism of memory formation. In the present study we aimed to examine whether or not the dendrodendritic mitral-to-granule cell synapses in the carp olfactory bulb show plastic changes after their repeated activation. It was found that: (1) the dendrodendritic mitral-to-granule cell synapses showed three types of plasticity after tetanic electrical stimulation applied to the olfactory tract-long-term potentiation (potentiation lasting >1 h), short-term potentiation (potentiation lasting 1 h) of the odor-evoked bulbar response accompanied the electrically-induced LTP, and; (4) repeated olfactory stimulation enhanced dendrodendritic mitral-to-granule cell transmission. Based on these results, it was proposed that long-term potentiation (as well as olfactory memory) occurs at the dendrodendritic mitral-to-granule cell synapses after strong and long-lasting depolarization of granule cells, which follows repeated and simultaneous synaptic activation of both the peripheral and deep dendrites (or somata).

  10. Long term potentiation, but not depression, in interlamellar hippocampus CA1.

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    Sun, Duk-Gyu; Kang, Hyeri; Tetteh, Hannah; Su, Junfeng; Lee, Jihwan; Park, Sung-Won; He, Jufang; Jo, Jihoon; Yang, Sungchil; Yang, Sunggu

    2018-03-26

    Synaptic plasticity in the lamellar CA3 to CA1 circuitry has been extensively studied while interlamellar CA1 to CA1 connections have not yet received much attention. One of our earlier studies demonstrated that axons of CA1 pyramidal neurons project to neighboring CA1 neurons, implicating information transfer along a longitudinal interlamellar network. Still, it remains unclear whether long-term synaptic plasticity is present within this longitudinal CA1 network. Here, we investigate long-term synaptic plasticity between CA1 pyramidal cells, using in vitro and in vivo extracellular recordings and 3D holography glutamate uncaging. We found that the CA1-CA1 network exhibits NMDA receptor-dependent long-term potentiation (LTP) without direction or layer selectivity. By contrast, we find no significant long-term depression (LTD) under various LTD induction protocols. These results implicate unique synaptic properties in the longitudinal projection suggesting that the interlamellar CA1 network could be a promising structure for hippocampus-related information processing and brain diseases.

  11. Widespread promoter methylation of synaptic plasticity genes in long-term potentiation in the adult brain in vivo.

    Science.gov (United States)

    Maag, Jesper L V; Kaczorowski, Dominik C; Panja, Debabrata; Peters, Timothy J; Bramham, Clive R; Wibrand, Karin; Dinger, Marcel E

    2017-03-23

    DNA methylation is a key modulator of gene expression in mammalian development and cellular differentiation, including neurons. To date, the role of DNA modifications in long-term potentiation (LTP) has not been explored. To investigate the occurrence of DNA methylation changes in LTP, we undertook the first detailed study to describe the methylation status of all known LTP-associated genes during LTP induction in the dentate gyrus of live rats. Using a methylated DNA immunoprecipitation (MeDIP)-array, together with previously published matched RNA-seq and public histone modification data, we discover widespread changes in methylation status of LTP-genes. We further show that the expression of many LTP-genes is correlated with their methylation status. We show that these correlated genes are enriched for RNA-processing, active histone marks, and specific transcription factors. These data reveal that the synaptic activity-evoked methylation changes correlates with pre-existing activation of the chromatin landscape. Finally, we show that methylation of Brain-derived neurotrophic factor (Bdnf) CpG-islands correlates with isoform switching from transcripts containing exon IV to exon I. Together, these data provide the first evidence of widespread regulation of methylation status in LTP-associated genes.

  12. Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system

    Science.gov (United States)

    Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Giampà, Carmela; Di Mauro, Michela; Mazzocchetti, Petra; Costa, Cinzia; Di Filippo, Massimiliano; Grassi, Silvarosa; Pettorossi, Vito Enrico; Calabresi, Paolo

    2015-01-01

    17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson’s disease. PMID:26074768

  13. Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system.

    Science.gov (United States)

    Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Giampà, Carmela; Di Mauro, Michela; Mazzocchetti, Petra; Costa, Cinzia; Di Filippo, Massimiliano; Grassi, Silvarosa; Pettorossi, Vito Enrico; Calabresi, Paolo

    2015-01-01

    17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson's disease.

  14. Endogenous 17ß-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system

    Directory of Open Access Journals (Sweden)

    Alessandro eTozzi

    2015-05-01

    Full Text Available 17β-estradiol (E2, a neurosteroid synthesized by P450-aromatase (ARO, modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs and dopamine (DA receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP in both medium spiny neurons (MSNs and cholinergic interneurons (ChIs. Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson's disease.

  15. D-Serine rescues the deficits of hippocampal long-term potentiation and learning and memory induced by sodium fluoroacetate.

    Science.gov (United States)

    Han, Huili; Peng, Yan; Dong, Zhifang

    2015-06-01

    It is well known that bidirectional glia-neuron interactions play important roles in the neurophysiological and neuropathological processes. It is reported that impairing glial functions with sodium fluoroacetate (FAC) impaired hippocampal long-term depression (LTD) and spatial memory retrieval. However, it remains unknown whether FAC impairs hippocampal long-term potentiation (LTP) and learning and/or memory, and if so, whether pharmacological treatment with exogenous d-serine can recuse the impairment. Here, we reported that systemic administration of FAC (3mg/kg, i.p.) before training resulted in dramatic impairments of spatial learning and memory in water maze and fear memory in contextual fear conditioning. Furthermore, the behavioral deficits were accompanied by impaired LTP induction in the hippocampal CA1 area of brain slices. More importantly, exogenous d-serine treatment succeeded in recusing the deficits of hippocampal LTP and learning and memory induced by FAC. Together, these results suggest that astrocytic d-serine may be essential for hippocampal synaptic plasticity and memory, and that alteration of its levels may be relevant to the induction and potentially treatment of psychiatric and neurological disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Leptin attenuates the detrimental effects of β-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats.

    Science.gov (United States)

    Tong, Jia-Qing; Zhang, Jun; Hao, Ming; Yang, Ju; Han, Yu-Fei; Liu, Xiao-Jie; Shi, Hui; Wu, Mei-Na; Liu, Qing-Song; Qi, Jin-Shun

    2015-07-01

    β-Amyloid (Aβ) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Aβ in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Aβ-induced deficits in spatial memory and in vivo hippocampal late-phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1μg) effectively alleviated Aβ1-42 (20μg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Aβ1-42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Aβ-induced deficits in learning and memory and the maintenance of L-LTP. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Ammonia inhibits long-term potentiation via neurosteroid synthesis in hippocampal pyramidal neurons.

    Science.gov (United States)

    Izumi, Y; Svrakic, N; O'Dell, K; Zorumski, C F

    2013-03-13

    Neurosteroids are a class of endogenous steroids synthesized in the brain that are believed to be involved in the pathogenesis of neuropsychiatric disorders and memory impairment. Ammonia impairs long-term potentiation (LTP), a synaptic model of learning, in the hippocampus, a brain region involved in memory acquisition. Although mechanisms underlying ammonia-mediated LTP inhibition are not fully understood, we previously found that the activation of N-methyl-d-aspartate receptors (NMDARs) is important. Based on this, we hypothesize that metabolic stressors, including hyperammonemia, promote untimely NMDAR activation and result in neural adaptations that include the synthesis of allopregnanolone (alloP) and other GABA-potentiating neurosteroids that dampen neuronal activity and impair LTP and memory formation. Using an antibody against 5α-reduced neurosteroids, we found that 100 μM ammonia acutely enhanced neurosteroid immunostaining in pyramidal neurons in the CA1 region of rat hippocampal slices. The enhanced staining was blocked by finasteride, a selective inhibitor of 5α-reductase, a key enzyme required for alloP synthesis. Finasteride also overcame LTP inhibition by 100 μM ammonia, as did picrotoxin, an inhibitor of GABA-A receptors. These results indicate that GABA-enhancing neurosteroids, synthesized locally within pyramidal neurons, contribute significantly to ammonia-mediated synaptic dysfunction. These results suggest that the manipulation of neurosteroid synthesis could provide a strategy to improve cognitive function in individuals with hyperammonemia. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Basolateral amygdala inactivation impairs learning-induced long-term potentiation in the cerebellar cortex.

    Directory of Open Access Journals (Sweden)

    Lan Zhu

    Full Text Available Learning to fear dangerous situations requires the participation of basolateral amygdala (BLA. In the present study, we provide evidence that BLA is necessary for the synaptic strengthening occurring during memory formation in the cerebellum in rats. In the cerebellar vermis the parallel fibers (PF to Purkinje cell (PC synapse is potentiated one day following fear learning. Pretraining BLA inactivation impaired such a learning-induced long-term potentiation (LTP. Similarly, cerebellar LTP is affected when BLA is blocked shortly, but not 6 h, after training. The latter result shows that the effects of BLA inactivation on cerebellar plasticity, when present, are specifically related to memory processes and not due to an interference with sensory or motor functions. These data indicate that fear memory induces cerebellar LTP provided that a heterosynaptic input coming from BLA sets the proper local conditions. Therefore, in the cerebellum, learning-induced plasticity is a heterosynaptic phenomenon that requires inputs from other regions. Studies employing the electrically-induced LTP in order to clarify the cellular mechanisms of memory should therefore take into account the inputs arriving from other brain sites, considering them as integrative units. Based on previous and the present findings, we proposed that BLA enables learning-related plasticity to be formed in the cerebellum in order to respond appropriately to new stimuli or situations.

  19. The evidence for hippocampal long-term potentiation as a basis of memory for simple tasks

    Directory of Open Access Journals (Sweden)

    Iván Izquierdo

    2008-03-01

    Full Text Available Long-term potentiation (LTP is the enhancement of postsynaptic responses for hours, days or weeks following the brief repetitive afferent stimulation of presynaptic afferents. It has been proposed many times over the last 30 years to be the basis of long-term memory. Several recent findings finally supported this hypothesis: a memory formation of one-trial avoidance learning depends on a series of molecular steps in the CA1 region of the hippocampus almost identical to those of LTP in the same region; bhippocampal LTP in this region accompanies memory formation of that task and of another similar task. However, CA1 LTP and the accompanying memory processes can be dissociated, and in addition plastic events in several other brain regions(amygdala, entorhinal cortex, parietal cortex are also necessary for memory formation of the one-trial task, and perhaps of many others.A potenciação de longa duração (LTP é o aumento de respostas pós-sinápticas durante horas, dias ou semanas após a breve estimulação repetitiva de aferentes pre-sinápticos. Foi proposto durante 30 anos ser a base da memória de longa duração. Vários achados recentes finalmente apoiaram esta hipótese: a a formação da memória de esquiva inibitória adquirida numa sessão depende de uma cadeia de processos moleculares na região CA1 do hipocampo quase idêntica à da LTP nessa mesma região; b LTP hipocampal nessa região acompanha a formação da memóría dessa tarefa e de outra semelhante. No entanto, a LTP de CA1 e os processos de memória podem ser dissociados e, fora disso, processos plásticos em outras regiões cerebrais (amígdala, córtex entorrinal, córtex parietal também são necessários para a formação da memória da tarefa de uma sessão e talvez de muitas outras.

  20. Stimulus Intensity-dependent Modulations of Hippocampal Long-term Potentiation by Basolateral Amygdala Priming

    Directory of Open Access Journals (Sweden)

    Zexuan eLi

    2012-05-01

    Full Text Available There is growing realization that the relationship between memory and stress/emotionality is complicated, and may include both memory enhancing and memory impairing aspects. It has been suggested that the underlying mechanisms involve amygdalar modulation of hippocampal synaptic plasticity, such as long-term potentiation (LTP. We recently reported that while in CA1 basolateral amygdala (BLA priming impaired theta stimulation induced LTP, it enhanced LTP in the dentate gyrus (DG. However, emotional and stressfull experiences were found to activate synaptic plasticity within the BLA, rasing the possibility that BLA modulation of other brain regions may be altered as well, as it may depend on the way the BLA is activated or is responding. In previous studies BLA priming stimulation was relatively weak (1V, 50 µs pulse duration. In the present study we assessed the effects of two stronger levels of BLA priming stimulation (1V or 2V, 100 µs pulse duration on LTP induction in hippocampal DG and CA1, in anesthetized rats. Results show that 1V-BLA priming stimulation enhanced but 2V-BLA priming stimulation impaired DG LTP; however, both levels of BLA priming stimulation impaired CA1 LTP, suggesting that modulation of hippocampal synaptic plasticity by amygdala is dependent on the degree of amygdala activation. These findings suggest that plasticity induced within the amygdala, by stressful experiences induces a form of metaplasticity that would alter the way the amygdala may modulate memory-related processes in other brain areas, such as the hippocampus.

  1. Brevican-deficient mice display impaired hippocampal CA1 long-term potentiation but show no obvious deficits in learning and memory

    DEFF Research Database (Denmark)

    Brakebusch, Cord; Seidenbecher, Constanze I; Asztely, Fredrik

    2002-01-01

    to be less prominent in mutant than in wild-type mice. Brevican-deficient mice showed significant deficits in the maintenance of hippocampal long-term potentiation (LTP). However, no obvious impairment of excitatory and inhibitory synaptic transmission was found, suggesting a complex cause for the LTP defect....... Detailed behavioral analysis revealed no statistically significant deficits in learning and memory. These data indicate that brevican is not crucial for brain development but has restricted structural and functional roles....

  2. Effect of modafinil on learning performance and neocortical long-term potentiation in rats.

    Science.gov (United States)

    Burgos, Héctor; Castillo, Amparo; Flores, Osvaldo; Puentes, Gustavo; Morgan, Carlos; Gatica, Arnaldo; Cofré, Christian; Hernández, Alejandro; Laurido, Claudio; Constandil, Luis

    2010-10-30

    Modafinil is a novel wake-promoting agent whose effects on cognitive performance have begun to be addressed at both preclinical and clinical level. The present study was designed to investigate in rats the effects of chronic modafinil administration on cognitive performance by evaluating: (i) working and reference memories in an Olton 4×4 maze, and (ii) learning of a complex operant conditioning task in a Skinner box. In addition, the effect of modafinil on the ability of the rat frontal cortex to develop long-term potentiation (LTP) was also studied. Chronic modafinil did not significantly modify working memory errors but decreased long-term memory errors on the Olton 4×4 maze, meaning that the drug may have a favourable profile on performance of visuo-spatial tasks (typically, a hippocampus-dependent task) when chronically administered. On the other hand, chronic modafinil resulted in a marked decrease of successful responses in a complex operant conditioning learning, which means that repeated administration of the drug influences negatively problem-solving abilities when confronting the rat to a sequencing task (typically, a prefrontal cortex-dependent task). In addition, in vivo electrophysiology showed that modafinil resulted in impaired capacity of the rat prefrontal cortex to develop LTP following tetanization. It is concluded that modafinil can improve the performance of spatial tasks that depend almost exclusively on hippocampal functioning, but not the performance in tasks including a temporal factor where the prefrontal cortex plays an important role. The fact that modafinil together with preventing operant conditioning learning was also able to block LTP induction in the prefrontal cortex, suggests that the drug could interfere some critical component required for LTP can be developed, thereby altering neuroplastic capabilities of the prefrontal cortex. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Nutritional deficit and Long Term Potentiation alterations

    Directory of Open Access Journals (Sweden)

    M. Petrosino

    2009-01-01

    Full Text Available In the present work we examined the ability of prenatally malnourished offspring to produce and maintain long-term potentiation (LTP of the perforant path/dentate granule cell synapse in freely moving rats at 15,30, and 90 days of age. Population spike amplitude (PSA was calculated from dentate field potential recordings prior to and at 15, 30, 60 min. and 3, 5, 18 and 24 h following tetanization of the perforant pathway. All animals of both malnourished and well-nourished diet groups at 15 days of age showed potentiation of PSA measures but the measures obtained from 15-day-old prenatally malnourished animals were significantly less than that of age-matched, well-nourished controls. At 30 days of age, remarkable effect of tetanization was likely observed from PSA measures for this age group followed much the same pattern. At 90 days of age, PSA measures obtained from malnourished animals decreased from pretetanization levels immediately following tetanization. At this age, however, at three hours time recordings, this measure growing up to a level which did not differ significantly from that of the control group. These results indicate that the width of tetanization induced enhancement of dentate granule cell response in preweanling rats (15-day-old animals is signifacantly affected fromgestational protein malnutrition and this trend is kept in animals tested at 30 and 90 days of age. The fact, however, that considerable limitation in LTP generation was gained from prenatally malnourished animals at 90 days of age, implying that dietary rehabilitation starting at birth is an intervention strategy not capable to imbrove the effects of the gestational stress.

  4. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.

    Science.gov (United States)

    He, Wen-Bin; Abe, Kazuho; Akaishi, Tatsuhiro

    2018-01-01

    To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood-brain barrier and promotes synaptic functions in the hippocampus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  5. Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil's Amazon Rainforest.

    Science.gov (United States)

    Guimarães Marques, Marcia J; Reyes-Garcia, Selvin Z; Marques-Carneiro, José E; Lopes-Silva, Leonardo B; Andersen, Monica L; Cavalheiro, Esper A; Scorza, Fulvio A; Scorza, Carla A

    2018-01-01

    Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed

  6. Gating of long-term potentiation by nicotinic acetylcholine receptors at the cerebellum input stage.

    Directory of Open Access Journals (Sweden)

    Francesca Prestori

    Full Text Available The brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD between mossy fibres and granule cells can saturate synaptic capacity and impair cerebellar functioning, which suggests that neuromodulators are required to gate plasticity processes. Cholinergic systems innervating the cerebellum are thought to enhance procedural learning and memory. Here we show that a specific subtype of acetylcholine receptors, the α7-nAChRs, are distributed both in cerebellar mossy fibre terminals and granule cell dendrites and contribute substantially to synaptic regulation. Selective α7-nAChR activation enhances the postsynaptic calcium increase, allowing weak mossy fibre bursts, which would otherwise cause LTD, to generate robust LTP. The local microperfusion of α7-nAChR agonists could also lead to in vivo switching of LTD to LTP following sensory stimulation of the whisker pad. In the cerebellar flocculus, α7-nAChR pharmacological activation impaired vestibulo-ocular-reflex adaptation, probably because LTP was saturated, preventing the fine adjustment of synaptic weights. These results show that gating mechanisms mediated by specific subtypes of nicotinic receptors are required to control the LTD/LTP balance at the mossy fibre-granule cell relay in order to regulate cerebellar plasticity and behavioural adaptation.

  7. Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.

    Science.gov (United States)

    Zhu, G; Wang, Y; Li, J; Wang, J

    2015-04-30

    Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats.

    Science.gov (United States)

    Schuette, Sven R M; Fernández-Fernández, Diego; Lamla, Thorsten; Rosenbrock, Holger; Hobson, Scott

    2016-04-13

    The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing. Most of the literature investigating protein kinase Mζ (PKMζ) used inhibitors with selectivity that has been called into question or conventional knock-out animal

  9. Long-term potentiation in the amygdala: a cellular mechanism of fear learning and memory.

    Science.gov (United States)

    Sigurdsson, Torfi; Doyère, Valérie; Cain, Christopher K; LeDoux, Joseph E

    2007-01-01

    Much of the research on long-term potentiation (LTP) is motivated by the question of whether changes in synaptic strength similar to LTP underlie learning and memory. Here we discuss findings from studies on fear conditioning, a form of associative learning whose neural circuitry is relatively well understood, that may be particularly suited for addressing this question. We first review the evidence suggesting that fear conditioning is mediated by changes in synaptic strength at sensory inputs to the lateral nucleus of the amygdala. We then discuss several outstanding questions that will be important for future research on the role of synaptic plasticity in fear learning. The results gained from these studies may shed light not only on fear conditioning, but may also help unravel more general cellular mechanisms of learning and memory.

  10. Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest

    Directory of Open Access Journals (Sweden)

    Marcia J. Guimarães Marques

    2018-01-01

    Full Text Available Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials

  11. Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest

    Science.gov (United States)

    Guimarães Marques, Marcia J.; Reyes-Garcia, Selvin Z.; Marques-Carneiro, José E.; Lopes-Silva, Leonardo B.; Andersen, Monica L.; Cavalheiro, Esper A.; Scorza, Fulvio A.; Scorza, Carla A.

    2018-01-01

    Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed

  12. Developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei: role of group I metabotropic glutamate receptors.

    Science.gov (United States)

    Puyal, Julien; Grassi, Silvarosa; Dieni, Cristina; Frondaroli, Adele; Demêmes, Danielle; Raymond, Jaqueline; Pettorossi, Vito Enrico

    2003-12-01

    The effects of high frequency stimulation (HFS) of the primary vestibular afferents on synaptic transmission in the ventral part of the medial vestibular nuclei (vMVN) were studied during postnatal development and compared with the changes in the expression of the group I metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5. During the first stages of development, HFS always induced a mGluR5- and GABAA-dependent long-term depression (LTD) which did not require NMDA receptor and mGluR1 activation. The probability of inducing LTD decreased progressively throughout the development and it was zero at about the end of the second postnatal week. Conversely, long-term potentiation (LTP) appeared at the beginning of the second week and its occurrence increased to reach the adult value at the end of the third week. Of interest, the sudden change in the LTP frequency occurred at the time of eye opening, about the end of the second postnatal week. LTP depended on NMDA receptor and mGluR1 activation. In parallel with the modifications in synaptic plasticity, we observed that the expression patterns and localizations of mGluR5 and mGluR1 in the medial vestibular nuclei (MVN) changed during postnatal development. At the earlier stages the mGluR1 expression was minimal, then increased progressively. In contrast, mGluR5 expression was initially high, then decreased. While mGluR1 was exclusively localized in neuronal compartments and concentrated at the postsynaptic sites at all stages observed, mGluR5 was found mainly in neuronal compartments at immature stages, then preferentially in glial compartments at mature stages. These results provide the first evidence for a progressive change from LTD to LTP accompanied by a distinct maturation expression of mGluR1 and mGluR5 during the development of the MVN.

  13. Hippocampal NPY gene transfer attenuates seizures without affecting epilepsy-induced impairment of LTP

    DEFF Research Database (Denmark)

    Sørensen, Andreas T; Nikitidou, Litsa; Ledri, Marco

    2009-01-01

    (TLE). However, our previous studies show that recombinant adeno-associated viral (rAAV)-NPY treatment in naive rats attenuates long-term potentiation (LTP) and transiently impairs hippocampal learning process, indicating that negative effect on memory function could be a potential side effect of NPY...... is significantly attenuated in vitro. Importantly, transgene NPY overexpression has no effect on short-term synaptic plasticity, and does not further compromise LTP in kindled animals. These data suggest that epileptic seizure-induced impairment of memory function in the hippocampus may not be further affected...... injected with rAAV-NPY, we show that rapid kindling-induced hippocampal seizures in vivo are effectively suppressed as compared to rAAV-empty injected (control) rats. Six to nine weeks later, basal synaptic transmission and short-term synaptic plasticity are unchanged after rapid kindling, while LTP...

  14. Characterization of stress-induced suppression of long-term potentiation in the hippocampal CA1 field of freely moving rats.

    Science.gov (United States)

    Hirata, Riki; Togashi, Hiroko; Matsumoto, Machiko; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro

    2008-08-21

    Several lines of evidence have shown that exposure to stress impairs long-term potentiation (LTP) in the CA1 field of the hippocampus, but the detailed mechanisms for this effect remain to be clarified. The present study elucidated the synaptic mechanism of stress-induced LTP suppression in conscious, freely moving rats using electrophysiological approaches. Open field stress (i.e., novel environment stress) and elevated platform stress (i.e., uncontrollable stress) were employed. Basal synaptic transmission was significantly reduced during exposure to elevated platform stress but not during exposure to open field stress. LTP induction was blocked by elevated platform stress but not influenced by open field stress. Significant increases in serum corticosterone levels were observed in the elevated platform stress group compared with the open field stress group. Furthermore, LTP suppression induced by elevated platform stress was prevented by pretreatment with an anxiolytic drug diazepam (1 mg/kg, i.p.). These results suggest that stress-induced LTP suppression depends on the relative intensity of the stressor. The inhibitory synaptic response induced by an intense psychological stress, such as elevated platform stress, may be attributable to LTP impairment in the CA1 field of the hippocampus.

  15. mTORC2 controls actin polymerization required for consolidation of long-term memory

    Science.gov (United States)

    Huang, Wei; Zhu, Ping Jun; Zhang, Shixing; Zhou, Hongyi; Stoica, Loredana; Galiano, Mauricio; Krnjević, Krešimir; Roman, Gregg; Costa-Mattioli, Mauro

    2013-01-01

    A major goal of biomedical research has been the identification of molecular mechanisms that can enhance memory. Here we report a novel signaling pathway that regulates the conversion from short- to long-term memory. The mTOR complex 2 (mTORC2), which contains the key regulatory protein Rictor (Rapamycin-Insensitive Companion of mTOR), was discovered only recently, and little is known about its physiological role. We show that conditional deletion of rictor in the postnatal murine forebrain greatly reduces mTORC2 activity and selectively impairs both long-term memory (LTM) and the late (but not the early) phase of hippocampal long-term potentiation (LTP). Actin polymerization is reduced in the hippocampus of mTORC2-deficient mice and its restoration rescues both L-LTP and LTM. More importantly, a compound that selectively promotes mTORC2 activity converts early-LTP into late-LTP and enhances LTM. These findings indicate that mTORC2 could be a novel therapeutic target for the treatment of cognitive dysfunction. PMID:23455608

  16. The ethanol metabolite acetaldehyde inhibits the induction of long-term potentiation in the rat dentate gyrus in vivo

    Science.gov (United States)

    Abe, Kazuho; Yamaguchi, Shinichi; Sugiura, Minoru; Saito, Hiroshi

    1999-01-01

    Ethanol has been reported to inhibit the induction of long-term potentiation (LTP) in the hippocampus. However, the correlation between the effects of ethanol in vivo and in vitro remained unclear. In addition, previous works have little considered the possibility that the effect of ethanol is mediated by its metabolites. To solve these problems, we investigated the effects of ethanol and acetaldehyde, the first metabolite in the metabolism of ethanol, on the induction of LTP at medial perforant path-granule cell synapses in the dentate gyrus of anaesthetized rats in vivo.Oral administration of 1 g kg−1 ethanol significantly inhibited the induction of LTP, confirming the effectiveness of ethanol in vivo.A lower dose of ethanol (0.5 g kg−1) failed to inhibit the induction of LTP in intact rats, but significantly inhibited LTP in rats treated with disulfiram, an inhibitor of aldehyde dehydrogenase, demonstrating that LTP is inhibited by acetaldehyde accumulation following ethanol administration.Intravenous injection of acetaldehyde (0.06 g kg−1) significantly inhibited the induction of LTP.The inhibitory effect of acetaldehyde on LTP induction was also observed when it was injected into the cerebroventricules, suggesting that acetaldehyde has a direct effect on the brain. The intracerebroventricular dose of acetaldehyde effective in inhibiting LTP induction (0.1–0.15 mg brain−1) was approximately 10 fold lower than that of ethanol (1.0–1.5 mg brain−1).It is possible that acetaldehyde is partly responsible for memory impairments induced by ethanol intoxication. PMID:10482910

  17. Hippocampal network activity is transiently altered by induction of long-term potentiation in the dentate gyrus of freely behaving rats

    Directory of Open Access Journals (Sweden)

    Arthur Bikbaev

    2007-12-01

    Full Text Available A role for oscillatory activity in hippocampal neuronal networks has been proposed in sensory encoding, cognitive functions and synaptic plasticity. In the hippocampus, theta (5–10 Hz and gamma (30–100 Hz oscillations may provide a mechanism for temporal encoding of information, and the basis for formation and retrieval of memory traces. Long-term potentiation (LTP of synaptic transmission, a candidate cellular model of synaptic information storage, is typically induced by high-frequency tetanisation (HFT of afferent pathways. Taking into account the role of oscillatory activity in the processing of information, dynamic changes may occur in hippocampal network activity in the period during HFT and/or soon after it. These changes in rhythmic activity may determine or, at least, contribute to successful potentiation and, in general, to formation of memory. We have found that short-term potentiation (STP and LTP as well LTPfailure are characterised with different profiles of changes in theta and gamma frequencies. Potentiation of synaptic transmission was associated with a significant increase in the relative theta power and mean amplitude of theta cycles in the period encompassing 300 seconds after HFT. Where LTP or STP, but not failure of potentiation, occurred, this facilitation of theta was accompanied by transient increases in gamma power and in the mean amplitude of gamma oscillations within a single theta cycle. Our data support that specific, correlated changes in these parameters are associated with successful synaptic potentiation. These findings suggest that changes in theta-gamma activity associated with induction of LTP may enable synaptic information storage in the hippocampus.

  18. Conditioned taste aversion modifies persistently the subsequent induction of neocortical long-term potentiation in vivo.

    Science.gov (United States)

    Rodríguez-Durán, Luis F; Castillo, Diana V; Moguel-González, Minerva; Escobar, Martha L

    2011-05-01

    The ability of neurons to modify their synaptic strength in an activity-dependent manner has a crucial role in learning and memory processes. It has been proposed that homeostatic forms of plasticity might provide the global regulation necessary to maintain synaptic strength and plasticity within a functional dynamic range. Similarly, it is considered that the capacity of synapses to express plastic changes is itself subject to variation dependent on previous experience. In particular, training in several behavioral tasks modifies the possibility to induce long-term potentiation (LTP). Our previous studies in the insular cortex (IC) have shown that induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC projection previous to conditioned taste aversion (CTA) training enhances the retention of this task. The aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent LTP in the Bla-IC projection in vivo. Thus, CTA trained rats received high frequency stimulation in the Bla-IC projection in order to induce LTP 48, 72, 96 and 120 h after the aversion test. Our results show that CTA training prevents the subsequent induction of LTP in the Bla-IC projection, for at least 120 h after CTA training. We also showed that pharmacological inhibition of CTA consolidation with anisomycin (1 μl/side; 100 μg/μl) prevents the CTA effect on IC-LTP. These findings reveal that CTA training produces a persistent change in the ability to induce subsequent LTP in the Bla-IC projection in a protein-synthesis dependent manner, suggesting that changes in the ability to induce subsequent synaptic plasticity contribute to the formation and persistence of aversive memories. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Short-term and long-term plasticity interaction in human primary motor cortex.

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    Iezzi, Ennio; Suppa, Antonio; Conte, Antonella; Li Voti, Pietro; Bologna, Matteo; Berardelli, Alfredo

    2011-05-01

    Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short- and long-term forms of synaptic plasticity, resembling short-term potentiation (STP) and long-term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5-Hz rTMS interferes with LTP/LTD-like plasticity induced by intermittent and continuous theta-burst stimulation (iTBS and cTBS). The effects induced by 5-Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5-Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5-Hz rTMS. Interactions between 5-Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5-Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5-Hz rTMS and TBS, and delivering one and ten 5-Hz rTMS trains. We also investigated whether 5-Hz rTMS induces changes in intracortical excitability tested with paired-pulse transcranial magnetic stimulation. When given alone, 5-Hz rTMS induced short-lasting and iTBS/cTBS induced long-lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5-Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS-induced after-effects disappeared. The 5-Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5-Hz rTMS abolishes iTBS/cTBS-induced LTP/LTD-like plasticity through non-homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short-term and long-term rTMS-induced plasticity in human M1. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

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

    Science.gov (United States)

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

    2012-09-01

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

  1. A neuroligin-1-derived peptide stimulates phosphorylation of the NMDA receptor NR1 subunit and rescues MK-801-induced decrease in long-term potentiation and memory impairment

    DEFF Research Database (Denmark)

    Korshunova, Irina; Gjørlund, Michelle D; Jacobsen, Sylwia Owczarek

    2015-01-01

    neurolide-1 effects on short- and long-term social and spatial memory in social recognition, Morris water-maze, and Y-maze tests. We found that subcutaneous neurolide-1 administration, restored hippocampal LTP compromised by NMDA receptor inhibitor MK-801. It counteracted MK-801-induced memory deficit...... in the water-maze and Y-maze tests after long-term treatment (24 h and 1-2 h before the test), but not after short-term exposure (1-2 h). Long-term exposure to neurolide-1 also facilitated social recognition memory. In addition, neurolide-1-induced phosphorylation of the NMDA receptor NR1 subunit on a site...... receptor phosphorylation after treatment with NL1 or a mimetic peptide, neurolide-1, was quantified by immunoblotting. Subsequently, we investigated effects of neurolide-1 on long-term potentiation (LTP) induction in hippocampal slices compromised by NMDA receptor inhibitor MK-801. Finally, we investigated...

  2. NMDA and kainate receptor expression, long-term potentiation, and neurogenesis in the hippocampus of long-lived Ames dwarf mice.

    Science.gov (United States)

    Sharma, Sunita; Darland, Diane; Lei, Saobo; Rakoczy, Sharlene; Brown-Borg, Holly M

    2012-06-01

    In the current study, we investigated changes in N-methyl D-aspartate (NMDA) and kainate receptor expression, long-term potentiation (LTP), and neurogenesis in response to neurotoxic stress in long-living Ames dwarf mice. We hypothesized that Ames dwarf mice have enhanced neurogenesis that enables retention of spatial learning and memory with age and promotes neurogenesis in response to injury. Levels of the NMDA receptors (NR)1, NR2A, NR2B, and the kainate receptor (KAR)2 were increased in Ames dwarf mice, relative to wild-type littermates. Quantitative assessment of the excitatory postsynaptic potential in Schaffer collaterals in hippocampal slices from Ames dwarf mice showed an increased response in high-frequency induced LTP over time compared with wild type. Kainic acid (KA) injection was used to promote neurotoxic stress-induced neurogenesis. KA mildly increased the number of doublecortin-positive neurons in wild-type mice, but the response was significantly enhanced in the Ames dwarf mice. Collectively, these data support our hypothesis that the enhanced learning and memory associated with the Ames dwarf mouse may be due to elevated levels of NMDA and KA receptors in hippocampus and their ability to continue producing new neurons in response to neuronal damage.

  3. Persistent increased PKMζ in long-term and remote spatial memory.

    Science.gov (United States)

    Hsieh, Changchi; Tsokas, Panayiotis; Serrano, Peter; Hernández, A Iván; Tian, Dezhi; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

    2017-02-01

    PKMζ is an autonomously active PKC isoform that is thought to maintain both LTP and long-term memory. Whereas persistent increases in PKMζ protein sustain the kinase's action in LTP, the molecular mechanism for the persistent action of PKMζ during long-term memory has not been characterized. PKMζ inhibitors disrupt spatial memory when introduced into the dorsal hippocampus from 1day to 1month after training. Therefore, if the mechanisms of PKMζ's persistent action in LTP maintenance and long-term memory were similar, persistent increases in PKMζ would last for the duration of the memory, far longer than most other learning-induced gene products. Here we find that spatial conditioning by aversive active place avoidance or appetitive radial arm maze induces PKMζ increases in dorsal hippocampus that persist from 1day to 1month, coinciding with the strength and duration of memory retention. Suppressing the increase by intrahippocampal injections of PKMζ-antisense oligodeoxynucleotides prevents the formation of long-term memory. Thus, similar to LTP maintenance, the persistent increase in the amount of autonomously active PKMζ sustains the kinase's action during long-term and remote spatial memory maintenance. Copyright © 2016. Published by Elsevier Inc.

  4. Sustained increase of spontaneous input and spike transfer in the CA3-CA1 pathway following long term potentiation in vivo

    Directory of Open Access Journals (Sweden)

    Oscar eHerreras

    2012-10-01

    Full Text Available Long term potentiation (LTP is commonly used to study synaptic plasticity but the associated changes in the spontaneous activity of individual neurons or the computational properties of neural networks in vivo remain largely unclear. The multisynaptic origin of spontaneous spikes makes difficult estimating the impact of a particular potentiated input. Accordingly, we adopted an approach that isolates pathway-specific postsynaptic activity from raw local field potentials (LFPs in the rat hippocampus in order to study the effects of LTP on ongoing spike transfer between cell pairs in the CA3-CA1 pathway. CA1 Schaffer-specific LFPs elicited by spontaneous clustered firing of CA3 pyramidal cells involved a regular succession of elementary micro-field-EPSPs (gamma-frequency that fired spikes in CA1 units. LTP increased the amplitude but not the frequency of these ongoing excitatory quanta. Also, the proportion of Schaffer-driven spikes in both CA1 pyramidal cells and interneurons increased in a cell-specific manner only in previously connected CA3-CA1 cell pairs, i.e., when the CA3 pyramidal cell had shown pre-LTP significant correlation with firing of a CA1 unit and potentiated spike-triggered average of Schaffer LFPs following LTP. Moreover, LTP produced subtle reorganization of presynaptic CA3 cell assemblies. These findings show effective enhancement of pathway specific ongoing activity which leads to increased spike transfer in potentiated segments of a network. These indicate that plastic phenomena induced by external protocols may intensify spontaneous information flow across specific channels as proposed in transsynaptic propagation of plasticity and synfire chain hypotheses that may be the substrate for different types of memory involving multiple brain structures.

  5. Underlying Mechanisms of Cooperativity, Input Specificity, and Associativity of Long-Term Potentiation Through a Positive Feedback of Local Protein Synthesis

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    Lijie Hao

    2018-05-01

    Full Text Available Long-term potentiation (LTP is a specific form of activity-dependent synaptic plasticity that is a leading mechanism of learning and memory in mammals. The properties of cooperativity, input specificity, and associativity are essential for LTP; however, the underlying mechanisms are unclear. Here, based on experimentally observed phenomena, we introduce a computational model of synaptic plasticity in a pyramidal cell to explore the mechanisms responsible for the cooperativity, input specificity, and associativity of LTP. The model is based on molecular processes involved in synaptic plasticity and integrates gene expression involved in the regulation of neuronal activity. In the model, we introduce a local positive feedback loop of protein synthesis at each synapse, which is essential for bimodal response and synapse specificity. Bifurcation analysis of the local positive feedback loop of brain-derived neurotrophic factor (BDNF signaling illustrates the existence of bistability, which is the basis of LTP induction. The local bifurcation diagram provides guidance for the realization of LTP, and the projection of whole system trajectories onto the two-parameter bifurcation diagram confirms the predictions obtained from bifurcation analysis. Moreover, model analysis shows that pre- and postsynaptic components are required to achieve the three properties of LTP. This study provides insights into the mechanisms underlying the cooperativity, input specificity, and associativity of LTP, and the further construction of neural networks for learning and memory.

  6. Orexin 1 and orexin 2 receptor antagonism in the basolateral amygdala modulate long-term potentiation of the population spike in the perforant path-dentate gyrus-evoked field potential in rats.

    Science.gov (United States)

    Ardeshiri, Motahareh Rouhi; Hosseinmardi, Narges; Akbari, Esmaeil

    2018-03-01

    Involvement of amygdalo-hippocampal substructures in patients with narcolepsy due to deficiencies in the orexinergic system, and the presence of hippocampus-dependent memory impairments in this disorder, have led us to investigate the effects of orexin 1 and 2 receptor antagonism in the basolateral amygdala (BLA) on long-term potentiation (LTP) of dentate gyrus (DG) granular cells. We used a 200-Hz high-frequency stimulation protocol in anesthetized rats. We studied the long-term synaptic plasticity of perforant path-dentate gyrus granule cells following the inactivation of orexin receptors before and after tetanic stimulation. LTP of the DG population spike was attenuated in the presence of orexin 1 and 2 receptor antagonism (treatment with SB-334867-A and TCS-OX2-29, respectively) in the BLA when compared to that observed following treatment with dimethyl sulfoxide (DMSO). However, the population excitatory post-synaptic potentials were not affected. Moreover, when orexin 1 and 2 receptors in the BLA were blocked after LTP induction, there were no differences between the DMSO and treatment groups. Our findings suggest that the orexinergic system of the BLA plays a modulatory role in the regulation of hippocampal plasticity in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Rancillac, Armelle; Crépel, Francis

    2004-02-01

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

  8. Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Francescangeli, E; Goracci, G; Pettorossi, V E

    1998-06-01

    In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O- (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.

  9. CaMKII Requirement for in Vivo Insular Cortex LTP Maintenance and CTA Memory Persistence

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    Yectivani Juárez-Muñoz

    2017-11-01

    Full Text Available Calcium-calmodulin/dependent protein kinase II (CaMKII plays an essential role in LTP induction, but since it has the capacity to remain persistently activated even after the decay of external stimuli it has been proposed that it can also be necessary for LTP maintenance and therefore for memory persistence. It has been shown that basolateral amygdaloid nucleus (Bla stimulation induces long-term potentiation (LTP in the insular cortex (IC, a neocortical region implicated in the acquisition and retention of conditioned taste aversion (CTA. Our previous studies have demonstrated that induction of LTP in the Bla-IC pathway before CTA training increased the retention of this task. Although it is known that IC-LTP induction and CTA consolidation share similar molecular mechanisms, little is known about the molecular actors that underlie their maintenance. The purpose of the present study was to evaluate the role of CaMKII in the maintenance of in vivo Bla-IC LTP as well as in the persistence of CTA long-term memory (LTM. Our results show that acute microinfusion of myr-CaMKIINtide, a selective inhibitor of CaMKII, in the IC of adult rats during the late-phase of in vivo Bla-IC LTP blocked its maintenance. Moreover, the intracortical inhibition of CaMKII 24 h after CTA acquisition impairs CTA-LTM persistence. Together these results indicate that CaMKII is a central key component for the maintenance of neocortical synaptic plasticity as well as for persistence of CTA-LTM.

  10. Two organizational effects of pubertal testosterone in male rats: transient social memory and a shift away from long-term potentiation following a tetanus in hippocampal CA1.

    Science.gov (United States)

    Hebbard, Pamela C; King, Rebecca R; Malsbury, Charles W; Harley, Carolyn W

    2003-08-01

    The organizational role of pubertal androgen receptor (AR) activation in synaptic plasticity in hippocampal CA1 and in social memory was assessed. Earlier data suggest pubertal testosterone reduces adult hippocampal synaptic plasticity. Four groups were created following gonadectomy at the onset of puberty: rats given testosterone; rats given testosterone but with the AR antagonist flutamide, present during puberty; rats given testosterone at the end of puberty; and rats given cholesterol at the end of puberty. A tetanus normally inducing long-term potentiation (LTP) was used to stimulate CA1 in the urethane-anesthetized adults during the dark phase of their cycle. Social memory was assessed prior to electrophysiology. Social memory for a juvenile rat at 120 min was seen only in rats not exposed to AR activation during puberty. Pubertal AR activation may induce the reduced social memory of male rats. Early CA1 LTP occurred following tetanus in rats with no pubertal testosterone. Short-term potentiation occurred in rats exposed to pubertal testosterone. Unexpectedly, rats with pubertal AR activation developed long-term depression (LTD). The same pattern was seen in normal male rats. Lack of LTP during the dark phase is consistent with other data on circadian modulation of CA1 LTP. No correlations were seen among social memory scores and CA1 plasticity measures. These data argue for two organizational effects of pubertal testosterone: (1) CA1 synaptic plasticity shifts away from potentiation toward depression; (2) social memory is reduced. Enduring effects of pubertal androgen on limbic circuits may contribute to reorganized behaviors in the postpubertal period.

  11. Long-term plasticity in identified hippocampal GABAergic interneurons in the CA1 area in vivo.

    Science.gov (United States)

    Lau, Petrina Yau-Pok; Katona, Linda; Saghy, Peter; Newton, Kathryn; Somogyi, Peter; Lamsa, Karri P

    2017-05-01

    Long-term plasticity is well documented in synapses between glutamatergic principal cells in the cortex both in vitro and in vivo. Long-term potentiation (LTP) and -depression (LTD) have also been reported in glutamatergic connections to hippocampal GABAergic interneurons expressing parvalbumin (PV+) or nitric oxide synthase (NOS+) in brain slices, but plasticity in these cells has not been tested in vivo. We investigated synaptically-evoked suprathreshold excitation of identified hippocampal neurons in the CA1 area of urethane-anaesthetized rats. Neurons were recorded extracellularly with glass microelectrodes, and labelled with neurobiotin for anatomical analyses. Single-shock electrical stimulation of afferents from the contralateral CA1 elicited postsynaptic action potentials with monosynaptic features showing short delay (9.95 ± 0.41 ms) and small jitter in 13 neurons through the commissural pathway. Theta-burst stimulation (TBS) generated LTP of the synaptically-evoked spike probability in pyramidal cells, and in a bistratified cell and two unidentified fast-spiking interneurons. On the contrary, PV+ basket cells and NOS+ ivy cells exhibited either LTD or LTP. An identified axo-axonic cell failed to show long-term change in its response to stimulation. Discharge of the cells did not explain whether LTP or LTD was generated. For the fast-spiking interneurons, as a group, no correlation was found between plasticity and local field potential oscillations (1-3 or 3-6 Hz components) recorded immediately prior to TBS. The results demonstrate activity-induced long-term plasticity in synaptic excitation of hippocampal PV+ and NOS+ interneurons in vivo. Physiological and pathological activity patterns in vivo may generate similar plasticity in these interneurons.

  12. Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation.

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Szepesi

    Full Text Available Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs, a family of extracellularly acting and Zn(2+-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.

  13. Neuromodulatory neurotransmitters influence LTP-like plasticity in human cortex: a pharmaco-TMS study.

    Science.gov (United States)

    Korchounov, Alexei; Ziemann, Ulf

    2011-08-01

    Long-term potentiation (LTP) of synaptic efficacy is considered a fundamental mechanism of learning and memory. At the cellular level a large body of evidence demonstrated that the major neuromodulatory neurotransmitters dopamine (DA), norepinephrine (NE), and acetylcholine (ACh) influence LTP magnitude. Noninvasive brain stimulation protocols provide the opportunity to study LTP-like plasticity at the systems level of human cortex. Here we applied paired associative stimulation (PAS) to induce LTP-like plasticity in the primary motor cortex of eight healthy subjects. In a double-blind, randomized, placebo-controlled, crossover design, the acute effects of a single oral dose of the neuromodulatory drugs cabergoline (DA agonist), haloperidol (DA antagonist), methylphenidate (indirect NE agonist), prazosine (NE antagonist), tacrine (ACh agonist), and biperiden (ACh antagonist) on PAS-induced LTP-like plasticity were examined. The antagonists haloperidol, prazosine, and biperiden depressed significantly the PAS-induced LTP-like plasticity observed under placebo, whereas the agonists cabergoline, methylphenidate, and tacrine had no effect. Findings demonstrate that antagonists in major neuromodulatory neurotransmitter systems suppress LTP-like plasticity at the systems level of human cortex, in accord with evidence of their modulating action of LTP at the cellular level. This provides further supportive evidence for the known detrimental effects of these drugs on LTP-dependent mechanisms such as learning and memory.

  14. Inducing a long-term potentiation in the dentate gyrus is sufficient to produce rapid antidepressant-like effects.

    Science.gov (United States)

    Kanzari, A; Bourcier-Lucas, C; Freyssin, A; Abrous, D N; Haddjeri, N; Lucas, G

    2018-03-01

    Recent hypotheses propose that one prerequisite to obtain a rapid antidepressant (AD) effect would reside in processes of synaptic reinforcement occurring within the dentate gyrus (DG) of the hippocampus independently from neurogenesis. However, to date no relationship has been established between an increased DG synaptic plasticity, and rapid AD-like action. To the best of our knowledge, this study shows for the first time that inducing a long-term potentiation (LTP) within the DG by stimulating the perforant pathway (PP) is sufficient to induce such effects. Thus, Sprague-Dawley rats having undergone a successful LTP displayed a significant reduction of immobility when passed acutely 3 days thereafter in the forced swimming test (FST). Further, in a longitudinal paradigm using the pseudo-depressed Wistar-Kyoto rat strain, LTP elicited a decrease of FST immobility after only 2 days, whereas the AD desipramine was not effective before 16 days. In both models, the influence of LTP was transient, as it was no more observed after 8-9 days. No effects were observed on the locomotor activity or on anxiety-related behavior. Theta-burst stimulation of a brain region anatomically adjacent to the PP remained ineffective in the FST. Immunoreactivity of DG cells for phosphorylated histone H3 and doublecortin were not modified three days after LTP, indicating a lack of effect on both cell proliferation and neurogenesis. Finally, depleting brain serotonin contents reduced the success rate of LTP but did not affect its subsequent AD-like effects. These results confirm the 'plastic DG' theory of rapid AD efficacy. Beyond, they point out stimulations of the entorhinal cortex, from which the PP originates, as putative new approaches in AD research.

  15. Involvement of N-methyl-D-aspartate receptor subunits in zinc-mediated modification of CA1 long-term potentiation in the developing hippocampus.

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    Takeda, Atsushi; Itagaki, Kosuke; Ando, Masaki; Oku, Naoto

    2012-03-01

    Zinc is an endogenous N-methyl-D-aspartate (NMDA) receptor blocker. It is possible that zinc-mediated modification of hippocampal CA1 long-term potentiation (LTP) is linked to the expression of NMDA receptor subunits, which varies with postnatal development. In the present study, the effect of ZnCl(2) and CaEDTA, a membrane-impermeable zinc chelator, on CA1 LTP induction was examined in hippocampal slices from immature (3-week-old) and young (6-week-old) rats. Tetanus (10-100 Hz, 1 sec)-induced CA1 LTP was more greatly enhanced in 3-week-old rats. CA1 LTP was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, and CaEDTA in 3-week-old rats, as in the case of 6-week-old rats reported previously. In 3-week-old rats, on the other hand, 5 μM ZnCl(2) attenuated NMDA receptor-mediated EPSPs more than in 6-week-old rats and significantly attenuated CA1 LTP. Moreover, 5 μM ZnCl(2) significantly attenuated CA1 LTP in the presence of (2R,4S)-4-(3-phosphonopropyl)-2-piperidinecarboxylic acid (PPPA), an NR2A antagonist, in 3-week-old rats, but not that in the presence of ifenprodil, an NR2B antagonist, suggesting that zinc-mediated attenuation of CA1 LTP is associated with the preferential expression of NR2B subunit in 3-week-old rats. In 6-week-old rats, however, 5 μM ZnCl(2) significantly potentiated CA1 LTP and also CA1 LTP in the presence of PPPA. The present study demonstrates that endogenous zinc may participate in the induction of CA1 LTP. It is likely that the changes in expression of NMDA receptor subunits are involved in the zinc-mediated modification of CA1 LTP in the developing hippocampus. Copyright © 2011 Wiley Periodicals, Inc.

  16. Estradiol-induced increase in the magnitude of long-term potentiation is prevented by blocking NR2B-containing receptors.

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    Smith, Caroline C; McMahon, Lori L

    2006-08-16

    Estradiol, through activation of genomic estrogen receptors, induces changes in synaptic morphology and function in hippocampus, a brain region important for memory acquisition. Specifically, this hormone increases CA1 pyramidal cell dendritic spine density, NMDA receptor (NMDAR)-mediated transmission, and the magnitude of long-term potentiation (LTP) at CA3-CA1 synapses. We recently reported that the estradiol-induced increase in LTP magnitude occurs only when there is a simultaneous increase in the fractional contribution of NMDAR-mediated transmission relative to AMPA receptor transmission, suggesting a direct role for the increase in NMDAR transmission to the heightened LTP magnitude. Estradiol has been shown to increase expression of the NMDAR subunit NR2B, but whether this translates into an increase in function of NR2B-containing receptors remains to be determined. Here we show that not only is the estradiol-induced increase in NMDAR transmission mediated by NR2B-containing receptors, but blocking these receptors using RO25-6981 [R-(R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propranol] (0.5 microM), an NR2B selective antagonist, prevents the estradiol-induced increase in LTP magnitude. Thus, our data show a causal link between the estradiol-induced increase in transmission mediated by NR2B-containing NMDARs and the increase in LTP magnitude.

  17. Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats.

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    Dieni, Cristina V; Ferraresi, Aldo; Sullivan, Jacqueline A; Grassi, Sivarosa; Pettorossi, Vito E; Panichi, Roberto

    2018-03-01

    The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber-Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites.

  18. Preventive effect of theanine intake on stress-induced impairments of hippocamapal long-term potentiation and recognition memory.

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    Tamano, Haruna; Fukura, Kotaro; Suzuki, Miki; Sakamoto, Kazuhiro; Yokogoshi, Hidehiko; Takeda, Atsushi

    2013-06-01

    Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. On the basis of the preventive effect of theanine intake after birth on mild stress-induced attenuation of hippocamapal CA1 long-term potentiation (LTP), the present study evaluated the effect of theanine intake after weaning on stress-induced impairments of LTP and recognition memory. Young rats were fed water containing 0.3% theanine for 3 weeks after weaning and subjected to water immersion stress for 30min, which was more severe than tail suspension stress for 30s used previously. Serum corticosterone levels were lower in theanine-administered rats than in the control rats even after exposure to stress. CA1 LTP induced by a 100-Hz tetanus for 1s was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an N-methyl-d-aspartate (NMDA) receptor antagonist, in hippocampal slices from the control rats and was attenuated by water immersion stress. In contrast, CA1 LTP was not significantly inhibited in the presence of APV in hippocampal slices from theanine-administered rats and was not attenuated by the stress. Furthermore, object recognition memory was impaired in the control rats, but not in theanine-administered rats. The present study indicates the preventive effect of theanine intake after weaning on stress-induced impairments of hippocampal LTP and recognition memory. It is likely that the modification of corticosterone secretion after theanine intake is involved in the preventive effect. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Encoding of Discriminative Fear Memory by Input-Specific LTP in the Amygdala.

    Science.gov (United States)

    Kim, Woong Bin; Cho, Jun-Hyeong

    2017-08-30

    In auditory fear conditioning, experimental subjects learn to associate an auditory conditioned stimulus (CS) with an aversive unconditioned stimulus. With sufficient training, animals fear conditioned to an auditory CS show fear response to the CS, but not to irrelevant auditory stimuli. Although long-term potentiation (LTP) in the lateral amygdala (LA) plays an essential role in auditory fear conditioning, it is unknown whether LTP is induced selectively in the neural pathways conveying specific CS information to the LA in discriminative fear learning. Here, we show that postsynaptically expressed LTP is induced selectively in the CS-specific auditory pathways to the LA in a mouse model of auditory discriminative fear conditioning. Moreover, optogenetically induced depotentiation of the CS-specific auditory pathways to the LA suppressed conditioned fear responses to the CS. Our results suggest that input-specific LTP in the LA contributes to fear memory specificity, enabling adaptive fear responses only to the relevant sensory cue. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Effects of inhaled anesthetic isoflurane on long-term potentiation of CA3 pyramidal cell afferents in vivo

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    Ballesteros KA

    2012-11-01

    Full Text Available Kristen A Ballesteros,1 Angela Sikorski,2 James E Orfila,3 Joe L Martinez Jr41Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA; 2Texas A&M University Texarkana, Texarkana, TX, USA; 3University of Colorado in Denver, Denver, CO, USA; 4University of Illinois in Chicago, Chicago, IL, USAAbstract: Isoflurane is a preferred anesthetic, due to its properties that allow a precise concentration to be delivered continually during in vivo experimentation. The major mechanism of action of isoflurane is modulation of the γ-amino butyric acid (GABAA receptor-chloride channel, mediating inhibitory synaptic transmission. Animal studies have shown that isoflurane does not cause cell death, but it does inhibit cell growth and causes long-term hippocampal learning deficits. As there are no studies characterizing the effects of isoflurane on electrophysiological aspects of long-term potentiation (LTP in the hippocampus, it is important to determine whether isoflurane alters the characteristic responses of hippocampal afferents to cornu ammonis region 3 (CA3. We investigated the effects of isoflurane on adult male rats during in vivo induction of LTP, using the mossy fiber pathway, the lateral perforant pathway, the medial perforant pathway, and the commissural CA3 (cCA3 to CA3, with intracranial administration of Ringer’s solution, naloxone, RS-aminoindan-1, 5-dicarboxylic acid (AIDA, or 3-[(R-2-carboxypiperazin-4-yl]-propo-2-enyl-1-phosphonic acid (CPP. Then, we compared these responses to published electrophysiological data, using sodium pentobarbital as an anesthetic, under similar experimental conditions. Our results showed that LTP was exhibited in animals anesthetized with isoflurane under vehicle conditions. With the exception of AIDA in the lateral perforant pathway, the defining characteristics of the four pathways appeared to remain intact, except for the observation that LTP was markedly reduced in animals

  1. Lentiviral Modulation of Wnt/β-Catenin Signaling Affects In Vivo LTP.

    Science.gov (United States)

    Ivanova, Olga Ya; Dobryakova, Yulia V; Salozhin, Sergey V; Aniol, Viktor A; Onufriev, Mikhail V; Gulyaeva, Natalia V; Markevich, Vladimir A

    2017-10-01

    Wnt signaling is involved in hippocampal development and synaptogenesis. Numerous recent studies have been focused on the role of Wnt ligands in the regulation of synaptic plasticity. Inhibitors and activators of canonical Wnt signaling were demonstrated to decrease or increase, respectively, in vitro long-term potentiation (LTP) maintenance in hippocampal slices (Chen et al. in J Biol Chem 281:11910-11916, 2006; Vargas et al. in J Neurosci 34:2191-2202, 2014, Vargas et al. in Exp Neurol 264:14-25, 2015). Using lentiviral approach to down- and up-regulate the canonical Wnt signaling, we explored whether Wnt/β-catenin signaling is critical for the in vivo LTP. Chronic suppression of Wnt signaling induced an impairment of in vivo LTP expression 14 days after lentiviral suspension injection, while overexpression of Wnt3 was associated with a transient enhancement of in vivo LTP magnitude. Both effects were related to the early phase LTP and did not affect LTP maintenance. A loss-of-function study demonstrated decreased initial paired pulse facilitation ratio, β-catenin, and phGSK-3β levels. A gain-of-function study revealed not only an increase in PSD-95, β-catenin, and Cyclin D1 protein levels, but also a reduced phGSK-3β level and enhanced GSK-3β kinase activity. These results suggest a presynaptic dysfunction predominantly underlying LTP impairment while postsynaptic modifications are primarily involved in transient LTP amplification. This study is the first demonstration of the involvement of Wnt/β-catenin signaling in synaptic plasticity regulation in an in vivo LTP model.

  2. Priming stimulation of basal but not lateral amygdala affects long-term potentiation in the rat dentate gyrus in vivo.

    Science.gov (United States)

    Li, Z; Richter-Levin, G

    2013-08-29

    The amygdaloid complex, or amygdala, has been implicated in assigning emotional significance to sensory information and producing appropriate behavioral responses to external stimuli. The lateral and basal nuclei (lateral and basal amygdala), which are termed together as basolateral amygdala, play a critical role in emotional and motivational learning and memory. It has been established that the basolateral amygdala activation by behavioral manipulations or direct electrical stimulation can modulate hippocampal long-term potentiation (LTP), a putative cellular mechanism of memory. However, the specific functional role of each subnucleus in the modulation of hippocampal LTP has not been studied yet, even though studies have shown cytoarchitectural differences between the basal and lateral amygdala and differences in the connections of each one of them to other brain areas. In this study we have tested the effects of lateral or basal amygdala pre-stimulation on hippocampal dentate gyrus LTP, induced by theta burst stimulation of the perforant path, in anesthetized rats. We found that while priming stimulation of the lateral amygdala did not affect LTP of the dentate gyrus, priming stimulation of the basal amygdala enhanced the LTP response when the priming stimulation was relatively weak, but impaired it when it was relatively strong. These results show that the basal and lateral nuclei of the amygdala, which have been already shown to differ in their anatomy and connectivity, may also have different functional roles. These findings raise the possibility that the lateral and basal amygdala differentially modulate memory processes in the hippocampus under emotional and motivational situations. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. NMDA receptor expression and C terminus structure in the rotifer Brachionus plicatilis and long-term potentiation across the Metazoa.

    Science.gov (United States)

    Kenny, Nathan J; Dearden, Peter K

    2013-12-01

    The C termini of N-methyl-D-aspartate (NMDA) receptor NR2 subunits are thought to play a major role in the molecular establishment of memory across the Bilateria, via the phenomenon known as long-term potentiation (LTP). Despite their long history of use as models in the study of memory, the expression and structure of the NR2 subunit in the Lophotrochozoa has remained uncategorized. Here, we report the phylogenic relationships of NR subunits across the Bilateria, and the cloning and in situ analysis of expression of NMDA NR1 and NR2 subunits in the monogont rotifer Brachionus plicatilis. RNA in situ hybridization suggests expression of NMDA receptor subunits in B. plicatilis is neural, consistent with expression observed in other species, and ours is the first report confirming NR2 expression in the lophotrochozoan clade. However, the single NR2 subunit identified in B. plicatilis was found to lack the long C terminal domain found in vertebrates, which is believed to modulate LTP. Further investigation revealed that mollusc and annelid NR2 subunits possess long intracellular C terminal domains. As data from molluscs (and particularly Aplysia californica) are the basis for much of our understanding of LTP, understanding how these diverse lophotrochozoan C termini function in vivo will have many implications for how we consider the evolution of the molecular control of learning and memory across the Metazoa as a whole and interpret the results of experiments into this vital component of cognition.

  4. Fluoxetine Inhibits Natural Decay of Long-Term Memory via Akt/GSK-3β Signaling.

    Science.gov (United States)

    Yi, Jee Hyun; Zhang, JiaBao; Ko, Sang Yoon; Kwon, Huiyoung; Jeon, Se Jin; Park, Se Jin; Jung, Jiwook; Kim, Byung C; Lee, Young Choon; Kim, Dong Hyun; Ryu, Jong Hoon

    2018-02-09

    Understanding the mechanisms underlying the natural decay of long-term memory can help us find means of extending the duration of long-term memory. However, the neurobiological processes involved in the decay of long-term memory are poorly understood. In the present study, we examined the effect of acute and chronic treatment of fluoxetine on natural decay of long-term memory and the possible mechanism. Late administration of fluoxetine prolonged the persistence of long-term memory in mice, as demonstrated by object location recognition and Barnes maze tests. Fluoxetine altered Akt/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling in the hippocampus. Late short- and long-term pharmacological inhibition of GSK-3β mimicked the effect of fluoxetine on memory persistence. Pharmacological inhibition of Akt blocked the effect of fluoxetine on memory persistence. Finally, late infusion of fluoxetine increased hippocampal long-term potentiation (LTP) and pharmacological inhibition of GSK-3β blocked the natural decline in LTP. These results demonstrate that GSK-3β might be a key molecule in memory decay process, and fluoxetine extends the period of long-term memory maintenance via Akt/GSK-3β signaling.

  5. Bidirectional modulation of taste aversion extinction by insular cortex LTP and LTD.

    Science.gov (United States)

    Rodríguez-Durán, Luis F; Martínez-Moreno, Araceli; Escobar, Martha L

    2017-07-01

    The history of activity of a given neuron has been proposed to bidirectionally influence its future response to synaptic inputs. In particular, induction of synaptic plasticity expressions such as long-term potentiation (LTP) and long-term depression (LTD) modifies the performance of several behavioral tasks. Our previous studies in the insular cortex (IC), a neocortical region that has been related to acquisition and retention of conditioned taste aversion (CTA), have demonstrated that induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC pathway before CTA training enhances the retention of this task. In addition, we reported that CTA training triggers a persistent impairment in the ability to induce in vivo LTP in the IC. The aim of the present study was to investigate whether LTD can be induced in the Bla-IC projection in vivo, as well as, whether the extinction of CTA is bidirectionally modified by previous synaptic plasticity induction in this pathway. Thus, rats received 900 train pulses (five 250μs pulses at 250Hz) delivered at 1Hz in the Bla-IC projection in order to induce LTD or 10 trains of 100Hz/1s with an intertrain interval of 20s in order to induce LTP. Seven days after surgery, rats were trained in the CTA task including the extinction trials. Our results show that the Bla-IC pathway is able to express in vivo LTD in an N-Methyl-D-aspartate (NMDA) receptor-dependent manner. Induction of LTD in the Bla-IC projection previous to CTA training facilitates the extinction of this task. Conversely, LTP induction enhances CTA retention. The present results show the bidirectional modulation of CTA extinction in response to IC-LTP and LTD, providing evidence of the homeostatic adaptation of taste learning. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation.

    Science.gov (United States)

    Takeda, A; Suzuki, M; Tempaku, M; Ohashi, K; Tamano, H

    2015-09-24

    Physiological significance of synaptic Zn(2+) signaling was examined in the CA1 of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively, suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1 LTP induction. The increase in intracellular Zn(2+) was chelated with intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn(2+) signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1h after ZnAF-2DA injection. These data suggest that intracellular Zn(2+) signaling in the CA1 is required for object recognition memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with 0.1-1μM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in the presence of 1-5μM ZnCl2. The influx of extracellular Zn(2+) into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for LTP and cognitive performance. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Inhibition of long-term potentiation in the schaffer-CA1 pathway by repetitive high-intensity sound stimulation.

    Science.gov (United States)

    Cunha, A O S; de Oliveira, J A C; Almeida, S S; Garcia-Cairasco, N; Leão, R M

    2015-12-03

    High-intensity sound can induce seizures in susceptible animals. After repeated acoustic stimuli changes in behavioural seizure repertoire and epileptic EEG activity might be seen in recruited limbic and forebrain structures, a phenomenon known as audiogenic kindling. It is postulated that audiogenic kindling can produce synaptic plasticity events leading to the spread of epileptogenic activity to the limbic system. In order to test this hypothesis, we investigated if long-term potentiation (LTP) of hippocampal Schaffer-CA1 synapses and spatial navigation memory are altered by a repeated high-intensity sound stimulation (HISS) protocol, consisting of one-minute 120 dB broadband noise applied twice a day for 10 days, in normal Wistar rats and in audiogenic seizure-prone rats (Wistar Audiogenic Rats - WARs). After HISS all WARs exhibited midbrain seizures and 50% of these animals developed limbic recruitment, while only 26% of Wistar rats presented midbrain seizures and none of them had limbic recruitment. In naïve animals, LTP in hippocampal CA1 neurons was induced by 50- or 100-Hz high-frequency stimulation of Schaffer fibres in slices from both Wistar and WAR animals similarly. Surprisingly, HISS suppressed LTP in CA1 neurons in slices from Wistar rats that did not present any seizure, and inhibited LTP in slices from Wistar rats with only midbrain seizures. However HISS had no effect on LTP in CA1 neurons from slices of WARs. Interestingly HISS did not alter spatial navigation and memory in both strains. These findings show that repeated high-intensity sound stimulation prevent LTP of Schaffer-CA1 synapses from Wistar rats, without affecting spatial memory. This effect was not seen in hippocampi from audiogenic seizure-prone WARs. In WARs the link between auditory stimulation and hippocampal LTP seems to be disrupted which could be relevant for the susceptibility to seizures in this strain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Glutamate Receptor GluA1 Subunit Is Implicated in Capsaicin Induced Modulation of Amygdala LTP but Not LTD

    Science.gov (United States)

    Gebhardt, Christine; Albrecht, Doris

    2018-01-01

    Capsaicin has been shown to modulate synaptic plasticity in various brain regions including the amygdala. Whereas in the lateral amygdala the modulatory effect of capsaicin on long-term potentiation (LA-LTP) is mediated by TRPV1 channels, we have recently shown that capsaicin-induced enhancement of long term depression (LA-LTD) is mediated by…

  9. Layer 2/3 synapses in monocular and binocular regions of tree shrew visual cortex express mAChR-dependent long-term depression and long-term potentiation.

    Science.gov (United States)

    McCoy, Portia; Norton, Thomas T; McMahon, Lori L

    2008-07-01

    Acetylcholine is an important modulator of synaptic efficacy and is required for learning and memory tasks involving the visual cortex. In rodent visual cortex, activation of muscarinic acetylcholine receptors (mAChRs) induces a persistent long-term depression (LTD) of transmission at synapses recorded in layer 2/3 of acute slices. Although the rodent studies expand our knowledge of how the cholinergic system modulates synaptic function underlying learning and memory, they are not easily extrapolated to more complex visual systems. Here we used tree shrews for their similarities to primates, including a visual cortex with separate, defined regions of monocular and binocular innervation, to determine whether mAChR activation induces long-term plasticity. We find that the cholinergic agonist carbachol (CCh) not only induces long-term plasticity, but the direction of the plasticity depends on the subregion. In the monocular region, CCh application induces LTD of the postsynaptic potential recorded in layer 2/3 that requires activation of m3 mAChRs and a signaling cascade that includes activation of extracellular signal-regulated kinase (ERK) 1/2. In contrast, layer 2/3 postsynaptic potentials recorded in the binocular region express long-term potentiation (LTP) following CCh application that requires activation of m1 mAChRs and phospholipase C. Our results show that activation of mAChRs induces long-term plasticity at excitatory synapses in tree shrew visual cortex. However, depending on the ocular inputs to that region, variation exists as to the direction of plasticity, as well as to the specific mAChR and signaling mechanisms that are required.

  10. Dietary 2'-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication through the Vagus Nerve in Rodents.

    Directory of Open Access Journals (Sweden)

    Enrique Vazquez

    Full Text Available 2´-fucosyllactose (2´-FL is an abundant human milk oligosaccharide (HMO in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS function, such as hippocampal long term potentiation (LTP and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA, specifically the vagus nerve, and L-fucose (Fuc may play a role. This study had two aims: (1 determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2 confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2´-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2´-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2´-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2´-FL-mediated cognitive benefits.

  11. The taurine transporter substrate guanidinoethyl sulfonate mimics the action of taurine on long-term synaptic potentiation.

    Science.gov (United States)

    Suárez, Luz M; Muñoz, María-Dolores; González, José C; Bustamante, Julián; Del Río, Rafael Martín; Solís, José M

    2016-11-01

    Taurine is especially abundant in rodent brain where it appears to be involved in osmoregulation and synaptic plasticity mechanisms. The demonstration of a physiological role for taurine has been hampered by the difficulty in modifying taurine levels in most tissues, including the brain. We used an experimental strategy to reduce taurine levels, involving treatment with guanidinoethyl sulfonate (GES), a structural analogue of taurine that, among other properties, acts as a competitive inhibitor of taurine transport. GES delivered in the drinking water of rats for 1 month effectively reduced taurine levels in brain structures (hippocampus, cerebellum and cortex) and outside the brain (heart, muscle, kidney, liver and plasma) by between 50 and 80 %, depending on the tissue. This partial taurine depletion did not affect either basal synaptic transmission or the late phase of long-term potentiation (late-LTP) in hippocampal slices. In vivo microdialysis studies in the hippocampus revealed that GES treatment reduced extracellular taurine levels and the magnitude of taurine released in response to the application of either N-methyl-D-aspartate (NMDA) or a hypoosmotic solution, without affecting release mechanisms. Finally, we demonstrated in hippocampal slices that a brief GES application can mimic taurine action on the conversion of a decremental LTP into a perdurable late-LTP, concluding that GES might replace taurine function in some mechanisms such as those implicated in synaptic plasticity.

  12. Erythropoietin enhances hippocampal long-term potentiation and memory

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    El-Kordi Ahmed

    2008-09-01

    Full Text Available Abstract Background Erythropoietin (EPO improves cognition of human subjects in the clinical setting by as yet unknown mechanisms. We developed a mouse model of robust cognitive improvement by EPO to obtain the first clues of how EPO influences cognition, and how it may act on hippocampal neurons to modulate plasticity. Results We show here that a 3-week treatment of young mice with EPO enhances long-term potentiation (LTP, a cellular correlate of learning processes in the CA1 region of the hippocampus. This treatment concomitantly alters short-term synaptic plasticity and synaptic transmission, shifting the balance of excitatory and inhibitory activity. These effects are accompanied by an improvement of hippocampus dependent memory, persisting for 3 weeks after termination of EPO injections, and are independent of changes in hematocrit. Networks of EPO-treated primary hippocampal neurons develop lower overall spiking activity but enhanced bursting in discrete neuronal assemblies. At the level of developing single neurons, EPO treatment reduces the typical increase in excitatory synaptic transmission without changing the number of synaptic boutons, consistent with prolonged functional silencing of synapses. Conclusion We conclude that EPO improves hippocampus dependent memory by modulating plasticity, synaptic connectivity and activity of memory-related neuronal networks. These mechanisms of action of EPO have to be further exploited for treating neuropsychiatric diseases.

  13. Effect of Prenatal Protein Malnutrition on Long-Term Potentiation and BDNF Protein Expression in the Rat Entorhinal Cortex after Neocortical and Hippocampal Tetanization

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    Alejandro Hernández

    2008-01-01

    Full Text Available Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC in the adult progeny. Unlike normal eutrophic controls, 55–60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

  14. Effect of prenatal protein malnutrition on long-term potentiation and BDNF protein expression in the rat entorhinal cortex after neocortical and hippocampal tetanization.

    Science.gov (United States)

    Hernández, Alejandro; Burgos, Héctor; Mondaca, Mauricio; Barra, Rafael; Núñez, Héctor; Pérez, Hernán; Soto-Moyano, Rubén; Sierralta, Walter; Fernández, Victor; Olivares, Ricardo; Valladares, Luis

    2008-01-01

    Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP) of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC) in the adult progeny. Unlike normal eutrophic controls, 55-60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF) in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

  15. Age-Dependent Long-Term Potentiation Deficits in the Prefrontal Cortex of the Fmr1 Knockout Mouse Model of Fragile X Syndrome.

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    Martin, Henry G S; Lassalle, Olivier; Brown, Jonathan T; Manzoni, Olivier J

    2016-05-01

    The most common inherited monogenetic cause of intellectual disability is Fragile X syndrome (FXS). The clinical symptoms of FXS evolve with age during adulthood; however, neurophysiological data exploring this phenomenon are limited. The Fmr1 knockout (Fmr1KO) mouse models FXS, but studies in these mice of prefrontal cortex (PFC) function are underrepresented, and aging linked data are absent. We studied synaptic physiology and activity-dependent synaptic plasticity in the medial PFC of Fmr1KO mice from 2 to 12 months. In young adult Fmr1KO mice, NMDA receptor (NMDAR)-mediated long-term potentiation (LTP) is intact; however, in 12-month-old mice this LTP is impaired. In parallel, there was an increase in the AMPAR/NMDAR ratio and a concomitant decrease of synaptic NMDAR currents in 12-month-old Fmr1KO mice. We found that acute pharmacological blockade of mGlu5 receptor in 12-month-old Fmr1KO mice restored a normal AMPAR/NMDAR ratio and LTP. Taken together, the data reveal an age-dependent deficit in LTP in Fmr1KO mice, which may correlate to some of the complex age-related deficits in FXS. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Beta-Adrenergic Receptor Activation during Distinct Patterns of Stimulation Critically Modulates the PKA-Dependence of LTP in the Mouse Hippocampus

    Science.gov (United States)

    Gelinas, Jennifer N.; Tenorio, Gustavo; Lemon, Neal; Abel, Ted; Nguyen, Peter V.

    2008-01-01

    Activation of Beta-adrenergic receptors (Beta-ARs) enhances hippocampal memory consolidation and long-term potentiation (LTP), a likely mechanism for memory storage. One signaling pathway linked to Beta-AR activation is the cAMP-PKA pathway. PKA is critical for the consolidation of hippocampal long-term memory and for the expression of some forms…

  17. Sauroxine reduces memory retention in rats and impairs hippocampal long-term potentiation generation.

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    Vallejo, Mariana; Carlini, Valeria; Gabach, Laura; Ortega, M G; L Cabrera, José; de Barioglio, Susana Rubiales; Pérez, Mariela; Agnese, Alicia M

    2017-07-01

    In the present paper it was investigated the role of sauroxine, an alkaloid of Phlegmariurus saururus, as a modulator of some types of learning and memory, considering the potential nootropic properties previously reported for the alkaloid extract and the main alkaloid sauroine. Sauroxine was isolated by means of an alkaline extraction, purified by several chromatographic techniques, and assayed in electrophysiological experiments on rat hippocampus slices, tending towards the elicitation of the long-term potentiation (LTP) phenomena. It was also studied the effects of intrahippocampal administration of sauroxine on memory retention in vivo using a Step-down test. Being the bio distribution of a drug an important parameter to be considered, the concentration of sauroxine in rat brain was determined by GLC-MS. Sauroxine blocked LTP generation at both doses used, 3.65 and 3.610 -2 μM. In the behavioral test, the animals injected with this alkaloid (3.6510 -3 nmol) exhibited a significant decrease on memory retention compared with control animals. It was also showed that sauroxine reached the brain (3.435μg/g tissue), after an intraperitoneal injection, displaying its ability to cross the blood-brain barrier. Thus, sauroxine demonstrated to exert an inhibition on these mnemonic phenomena. The effect here established for 1 is defeated by other constituents according to the excellent results obtained for P. saururus alkaloid extract as well as for the isolated alkaloid sauroine. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Long Term Depression in Rat Hippocampus and the Effect of Ethanol during Fetal Life

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    Olivier Pierrefiche

    2017-11-01

    Full Text Available Alcohol (ethanol disturbs cognitive functions including learning and memory in humans, non-human primates, and laboratory animals such as rodents. As studied in animals, cellular mechanisms for learning and memory include bidirectional synaptic plasticity, long-term potentiation (LTP, and long-term depression (LTD, primarily in the hippocampus. Most of the research in the field of alcohol has analyzed the effects of ethanol on LTP; however, with recent advances in the understanding of the physiological role of LTD in learning and memory, some authors have examined the effects of ethanol exposure on this particular signal. In the present review, I will focus on hippocampal LTD recorded in rodents and the effects of fetal alcohol exposure on this signal. A synthesis of the findings indicates that prenatal ethanol exposure disturbs LTD concurrently with LTP in offspring and that both glutamatergic and γ-aminobutyric acid (GABA neurotransmissions are altered and contribute to LTD disturbances. Although the ultimate mode of action of ethanol on these two transmitter systems is not yet clear, novel suggestions have recently appeared in the literature.

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

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

    2015-05-19

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

  20. Global estimation of long-term persistence in annual river runoff

    Science.gov (United States)

    Markonis, Y.; Moustakis, Y.; Nasika, C.; Sychova, P.; Dimitriadis, P.; Hanel, M.; Máca, P.; Papalexiou, S. M.

    2018-03-01

    Long-term persistence (LTP) of annual river runoff is a topic of ongoing hydrological research, due to its implications to water resources management. Here, we estimate its strength, measured by the Hurst coefficient H, in 696 annual, globally distributed, streamflow records with at least 80 years of data. We use three estimation methods (maximum likelihood estimator, Whittle estimator and least squares variance) resulting in similar mean values of H close to 0.65. Subsequently, we explore potential factors influencing H by two linear (Spearman's rank correlation, multiple linear regression) and two non-linear (self-organizing maps, random forests) techniques. Catchment area is found to be crucial for medium to larger watersheds, while climatic controls, such as aridity index, have higher impact to smaller ones. Our findings indicate that long-term persistence is weaker than found in other studies, suggesting that enhanced LTP is encountered in large-catchment rivers, were the effect of spatial aggregation is more intense. However, we also show that the estimated values of H can be reproduced by a short-term persistence stochastic model such as an auto-regressive AR(1) process. A direct consequence is that some of the most common methods for the estimation of H coefficient, might not be suitable for discriminating short- and long-term persistence even in long observational records.

  1. Redistribution of ionotropic glutamate receptors detected by laser microdissection of the rat dentate gyrus 48 h following LTP induction in vivo.

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    Jeremy T T Kennard

    Full Text Available The persistence and input specificity of long-term potentiation (LTP make it attractive as a mechanism of information storage. In its initial phase, both in vivo and in vitro studies have shown that LTP is associated with increased membrane localization of AMPA receptor subunits, but the molecular basis of LTP maintenance over the long-term is still unclear. We have previously shown that expression of AMPA and NMDA receptor subunits is elevated in whole homogenates prepared from dentate gyrus 48 h after LTP induction in vivo. In the present study, we utilized laser microdissection (LMD techniques to determine whether AMPA and NMDA receptor upregulation occurs specifically in the stimulated regions of the dentate gyrus dendritic arbor. Receptor proteins GluN1, GluA1 and GluA2, as well as postsynaptic density protein of 95 kDa and tubulin were detected by Western blot analysis in microdissected samples. Gradients of expression were observed for GluN1 and GluA2, decreasing from the inner to the outer zones of the molecular layer, and were independent of LTP. When induced at medial perforant path synapses, LTP was associated with an apparent specific redistribution of GluA1 and GluN1 to the middle molecular layer that contains these synapses. These data indicate that glutamate receptor proteins are delivered specifically to dendritic regions possessing LTP-expressing synapses, and that these changes are preserved for at least 48 h.

  2. Cholinergic pairing with visual activation results in long-term enhancement of visual evoked potentials.

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    Jun Il Kang

    Full Text Available Acetylcholine (ACh contributes to learning processes by modulating cortical plasticity in terms of intensity of neuronal activity and selectivity properties of cortical neurons. However, it is not known if ACh induces long term effects within the primary visual cortex (V1 that could sustain visual learning mechanisms. In the present study we analyzed visual evoked potentials (VEPs in V1 of rats during a 4-8 h period after coupling visual stimulation to an intracortical injection of ACh analog carbachol or stimulation of basal forebrain. To clarify the action of ACh on VEP activity in V1, we individually pre-injected muscarinic (scopolamine, nicotinic (mecamylamine, alpha7 (methyllycaconitine, and NMDA (CPP receptor antagonists before carbachol infusion. Stimulation of the cholinergic system paired with visual stimulation significantly increased VEP amplitude (56% during a 6 h period. Pre-treatment with scopolamine, mecamylamine and CPP completely abolished this long-term enhancement, while alpha7 inhibition induced an instant increase of VEP amplitude. This suggests a role of ACh in facilitating visual stimuli responsiveness through mechanisms comparable to LTP which involve nicotinic and muscarinic receptors with an interaction of NMDA transmission in the visual cortex.

  3. The effect of acute swim stress and training in the water maze on hippocampal synaptic activity as well as plasticity in the dentate gyrus of freely moving rats: revisiting swim-induced LTP reinforcement.

    Science.gov (United States)

    Tabassum, Heena; Frey, Julietta U

    2013-12-01

    Hippocampal long-term potentiation (LTP) is a cellular model of learning and memory. An early form of LTP (E-LTP) can be reinforced into its late form (L-LTP) by various behavioral interactions within a specific time window ("behavioral LTP-reinforcement"). Depending on the type and procedure used, various studies have shown that stress differentially affects synaptic plasticity. Under low stress, such as novelty detection or mild foot shocks, E-LTP can be transformed into L-LTP in the rat dentate gyrus (DG). A reinforcing effect of a 2-min swim, however, has only been shown in (Korz and Frey (2003) J Neurosci 23:7281-7287; Korz and Frey (2005) J Neurosci 25:7393-7400; Ahmed et al. (2006) J Neurosci 26:3951-3958; Sajikumar et al., (2007) J Physiol 584.2:389-400) so far. We have reinvestigated these studies using the same as well as an improved recording technique which allowed the recording of field excitatory postsynaptic potentials (fEPSP) and the population spike amplitude (PSA) at their places of generation in freely moving rats. We show that acute swim stress led to a long-term depression (LTD) in baseline values of PSA and partially fEPSP. In contrast to earlier studies a LTP-reinforcement by swimming could never be reproduced. Our results indicate that 2-min swim stress influenced synaptic potentials as well as E-LTP negatively. Copyright © 2013 Wiley Periodicals, Inc.

  4. MGluR5 mediates the interaction between late-LTP, network activity, and learning.

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    Arthur Bikbaev

    2008-05-01

    Full Text Available Hippocampal synaptic plasticity and learning are strongly regulated by metabotropic glutamate receptors (mGluRs and particularly by mGluR5. Here, we investigated the mechanisms underlying mGluR5-modulation of these phenomena. Prolonged pharmacological blockade of mGluR5 with MPEP produced a profound impairment of spatial memory. Effects were associated with 1 a reduction of mGluR1a-expression in the dentate gyrus; 2 impaired dentate gyrus LTP; 3 enhanced CA1-LTP and 4 suppressed theta (5-10 Hz and gamma (30-100 Hz oscillations in the dentate gyrus. Allosteric potentiation of mGluR1 after mGluR5 blockade significantly ameliorated dentate gyrus LTP, as well as suppression of gamma oscillatory activity. CA3-lesioning prevented MPEP effects on CA1-LTP, suggesting that plasticity levels in CA1 are driven by mGluR5-dependent synaptic and network activity in the dentate gyrus. These data support the hypothesis that prolonged mGluR5-inactivation causes altered hippocampal LTP levels and network activity, which is mediated in part by impaired mGluR1-expression in the dentate gyrus. The consequence is impairment of long-term learning.

  5. Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area

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    Vladimir O. Pustylnyak

    2015-01-01

    Full Text Available Gene expression plays an important role in the mechanisms of long-term potentiation (LTP, which is a widely accepted experimental model of synaptic plasticity. We have studied the expression of at least 50 genes that are transcriptionally regulated by p53, as well as other genes that are related to p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer collaterals (SC tetanization, increases in the mRNA and protein levels of Bax, which are upregulated by p53, and a decrease in the mRNA and protein levels of Bcl2, which are downregulated by p53, were observed. The inhibition of Mdm2 by nutlin-3 increased the basal p53 protein level and rescued its tetanization-induced depletion, which suggested the involvement of Mdm2 in the control over p53 during LTP. Furthermore, nutlin-3 caused an increase in the basal expression of Bax and a decrease in the basal expression of Bcl2, whereas tetanization-induced changes in their expression were occluded. These results support the hypothesis that p53 may be involved in transcriptional regulation during the early phase of LTP. We hope that the presented data may aid in the understanding of the contribution of p53 and related genes in the processes that are associated with synaptic plasticity.

  6. Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats

    International Nuclear Information System (INIS)

    Wu Chuanyun; Liu Bing; Wang Huili; Ruan Diyun

    2011-01-01

    Lead (Pb) exposure during development has been associated with impaired long-term potentiation (LTP). Hypothyroidism happening upon subjects with occupational exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis, leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis. Hippocampus is one of the targets of Pb exposure, and is sensitive to and dependent on thyroid hormones, leading us to explore whether levothyroxine (L-T 4 ) administration could alter the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb exposure. Our results show that Pb exposure caused a decrease in triiodothyronine (T 3 ) and tetraiodothyronine (T 4 ) levels accompanied by a dramatic decrease of TSH and application of L-T 4 restored these changes to about control levels. Hippocampal and blood Pb concentration were significantly reduced following L-T 4 treatment. L-T 4 treatment rescued the impairment of LTP induced by the Pb exposure. These results suggest that Pb exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a direct electrophysiological proof that L-T 4 relieves chronic Pb exposure-induced impairment of synaptic plasticity. - Highlights: → Lead may interfere with thyroid hormone homeostasis and induce hypothyroidism. → Levothyroxine decreases the hippocampal and blood Pb concentration. → Levothyroxine amends the T 3 , T 4 and TSH levels in blood. → Levothyroxine rescues the impaired LTP in CA1.

  7. Nucleolar integrity is required for the maintenance of long-term synaptic plasticity.

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    Kim D Allen

    Full Text Available Long-term memory (LTM formation requires new protein synthesis and new gene expression. Based on our work in Aplysia, we hypothesized that the rRNA genes, stimulation-dependent targets of the enzyme Poly(ADP-ribose polymerase-1 (PARP-1, are primary effectors of the activity-dependent changes in synaptic function that maintain synaptic plasticity and memory. Using electrophysiology, immunohistochemistry, pharmacology and molecular biology techniques, we show here, for the first time, that the maintenance of forskolin-induced late-phase long-term potentiation (L-LTP in mouse hippocampal slices requires nucleolar integrity and the expression of new rRNAs. The activity-dependent upregulation of rRNA, as well as L-LTP expression, are poly(ADP-ribosylation (PAR dependent and accompanied by an increase in nuclear PARP-1 and Poly(ADP ribose molecules (pADPr after forskolin stimulation. The upregulation of PARP-1 and pADPr is regulated by Protein kinase A (PKA and extracellular signal-regulated kinase (ERK--two kinases strongly associated with long-term plasticity and learning and memory. Selective inhibition of RNA Polymerase I (Pol I, responsible for the synthesis of precursor rRNA, results in the segmentation of nucleoli, the exclusion of PARP-1 from functional nucleolar compartments and disrupted L-LTP maintenance. Taken as a whole, these results suggest that new rRNAs (28S, 18S, and 5.8S ribosomal components--hence, new ribosomes and nucleoli integrity--are required for the maintenance of long-term synaptic plasticity. This provides a mechanistic link between stimulation-dependent gene expression and the new protein synthesis known to be required for memory consolidation.

  8. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

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    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China); Teng, Weiping, E-mail: twpendocrine@yahoo.com.cn [Liaoning Provincial Key Laboratory of Endocrine Diseases, the First Hospital of China Medical University, Shenyang (China); Chen, Jie, E-mail: chenjie@mail.cmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China)

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  9. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

    International Nuclear Information System (INIS)

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

    2013-01-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  10. Impaired induction of long-term potentiation-like plasticity in patients with high-functioning autism and Asperger syndrome.

    Science.gov (United States)

    Jung, Nikolai H; Janzarik, Wibke G; Delvendahl, Igor; Münchau, Alexander; Biscaldi, Monica; Mainberger, Florian; Bäumer, Tobias; Rauh, Reinhold; Mall, Volker

    2013-01-01

    We aimed to investigate the induction of long-term potentiation (LTP)-like plasticity by paired associative stimulation (PAS) in patients with high-functioning autism and Asperger syndrome (HFA/AS). PAS with an interstimulus interval between electrical and transcranial magnetic stimulation of 25 ms (PAS(25)) was performed in patients with HFA/AS (n=9; eight males, one female; mean age 17 y 11 mo, SD 4 y 5 mo) and in typically developing age-matched volunteers (n=9; five males, four females; mean age 22 y 4 mo, SD 5 y 2 mo). The amplitude of motor-evoked potentials was measured before PAS(25), immediately after stimulation, and 30 minutes and 60 minutes later. A PAS protocol adapted to individual N20 latency (PAS(N20+2)) was performed in six additional patients with HFA/AS. Short-interval intracortical inhibition was measured using paired-pulse stimulation. In contrast to the typically developing participants, the patients with HFA/AS did not show a significant increase in motor-evoked potentials after PAS(25). This finding could also be demonstrated after adaptation for N20 latency. Short-interval intracortical inhibition of patients with HFA/AS was normal compared with the comparison group and did not correlate with PAS effect. Our results show a significant impairment of LTP-like plasticity induced by PAS in individuals with HFA/AS compared with typically developing participants. This finding is in accordance with results from animal studies as well as human studies. Impaired LTP-like plasticity in patients with HFA/AS points towards reduced excitatory synaptic connectivity and deficits in sensory-motor integration in these patients. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

  11. Unilateral lesion of dorsal hippocampus in adult rats impairs contralateral long-term potentiation in vivo and spatial memory in the early postoperative phase.

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    Li, Hongjie; Wu, Xiaoyan; Bai, Yanrui; Huang, Yan; He, Wenting; Dong, Zhifang

    2012-05-01

    It is well documented that bilateral hippocampal lesions or unilateral hippocampal lesion at birth causes impairment of contralateral LTP and long-term memory. However, effects of unilateral hippocampal lesion in adults on contralateral in vivo LTP and memory are not clear. We here examined the influence of unilateral electrolytic dorsal hippocampal lesion in adult rats on contralateral LTP in vivo and spatial memory during different postoperative phases. We found that acute unilateral hippocampal lesion had no effect on contralateral LTP. However, contralateral LTP was impaired at 1 week after lesion, and was restored to the control level at postoperative week 4. Similarly, spatial memory was also impaired at postoperative week 1, and was restored at postoperative week 4. In addition, the rats at postoperative week 1 showed stronger spatial exploratory behavior in a novel open-field environment. The sham operation had no effects on contralateral LTP, spatial memory and exploration at either postoperative week 1 or week 4. These results suggest that unilateral dorsal hippocampal lesion in adult rats causes transient contralateral LTP impairment and spatial memory deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Improvement in Memory and Brain Long-term Potentiation Deficits Due to Permanent Hypoperfusion/Ischemia by Grape Seed Extract in Rats

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    Alireza Sarkaki

    2013-09-01

    Full Text Available   Objective(s: Cerebral hypoperfusion/ischemia (CHI is a neurological disease where impaired hippocampus electrical activity and cognition caused by a serial pathophysiological events. This study aimed to evaluate the effects of chronic oral administration of grape seed extract (GSE on passive avoidance memory and long-term potentiation (LTP after permanent bilateral common carotid arteries occlusion (2CCAO in male adult rats.   Materials and Methods: Thirty-two adult male Wistar rats were randomly divided into: 1 Sham+Veh, 2 Isch+Veh, 3 Sham+GSE, 4 Isch+GSE. In order to make 2CCAO as an animal model of CHI, carotid arteries were ligatured and then cut bilaterally. To evaluation of passive avoidance memory, step-down latency (STL was measured and LTP was recorded from hippocampal dentate gyrus (DG after high frequency stimulation (HFS in all rats. Results: We found that memory was significantly impaired in rats after CHI (P

  13. Cholinergic induction of input-specific late-phase LTP via localized Ca2+ release in the visual cortex.

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    Cho, Kwang-Hyun; Jang, Hyun-Jong; Jo, Yang-Hyeok; Singer, Wolf; Rhie, Duck-Joo

    2012-03-28

    Acetylcholine facilitates long-term potentiation (LTP) and long-term depression (LTD), substrates of learning, memory, and sensory processing, in which acetylcholine also plays a crucial role. Ca(2+) ions serve as a canonical regulator of LTP/LTD but little is known about the effect of acetylcholine on intracellular Ca(2+) dynamics. Here, we investigated dendritic Ca(2+) dynamics evoked by synaptic stimulation and the resulting LTP/LTD in layer 2/3 pyramidal neurons of the rat visual cortex. Under muscarinic stimulation, single-shock electrical stimulation (SES) inducing ∼20 mV EPSP, applied via a glass electrode located ∼10 μm from the basal dendrite, evoked NMDA receptor-dependent fast Ca(2+) transients and the subsequent Ca(2+) release from the inositol 1,4,5-trisphosphate (IP(3))-sensitive stores. These secondary dendritic Ca(2+) transients were highly localized within 10 μm from the center (SD = 5.0 μm). The dendritic release of Ca(2+) was a prerequisite for input-specific muscarinic LTP (LTPm). Without the secondary Ca(2+) release, only muscarinic LTD (LTDm) was induced. D(-)-2-amino-5-phosphopentanoic acid and intracellular heparin blocked LTPm as well as dendritic Ca(2+) release. A single burst consisting of 3 EPSPs with weak stimulus intensities instead of the SES also induced secondary Ca(2+) release and LTPm. LTPm and LTDm were protein synthesis-dependent. Furthermore, LTPm was confined to specific dendritic compartments and not inducible in distal apical dendrites. Thus, cholinergic activation facilitated selectively compartment-specific induction of late-phase LTP through IP(3)-dependent Ca(2+) release.

  14. NR2B subunit-dependent long-term potentiation enhancement in the rat cortical auditory system in vivo following masking of patterned auditory input by white noise exposure during early postnatal life.

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    Hogsden, Jennifer L; Dringenberg, Hans C

    2009-08-01

    The composition of N-methyl-D-aspartate (NMDA) receptor subunits influences the degree of synaptic plasticity expressed during development and into adulthood. Here, we show that theta-burst stimulation of the medial geniculate nucleus reliably induced NMDA receptor-dependent long-term potentiation (LTP) of field postsynaptic potentials recorded in the primary auditory cortex (A1) of urethane-anesthetized rats. Furthermore, substantially greater levels of LTP were elicited in juvenile animals (30-37 days old; approximately 55% maximal potentiation) than in adult animals (approximately 30% potentiation). Masking patterned sound via continuous white noise exposure during early postnatal life (from postnatal day 5 to postnatal day 50-60) resulted in enhanced, juvenile-like levels of LTP (approximately 70% maximal potentiation) relative to age-matched controls reared in unaltered acoustic environments (approximately 30%). Rats reared in white noise and then placed in unaltered acoustic environments for 40-50 days showed levels of LTP comparable to those of adult controls, indicating that white noise rearing results in a form of developmental arrest that can be overcome by subsequent patterned sound exposure. We explored the mechanisms mediating white noise-induced plasticity enhancements by local NR2B subunit antagonist application in A1. NR2B subunit antagonists (Ro 25-6981 or ifenprodil) completely reversed white noise-induced LTP enhancement at concentrations that did not affect LTP in adult or age-matched controls. We conclude that white noise exposure during early postnatal life results in the maintenance of juvenile-like, higher levels of plasticity in A1, an effect that appears to be critically dependent on NR2B subunit activation.

  15. Long-term potentiation and long-term depression: a clinical perspective

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    Timothy V.P. Bliss

    2011-01-01

    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  16. A Voltage-Based STDP Rule Combined with Fast BCM-Like Metaplasticity Accounts for LTP and Concurrent "Heterosynaptic" LTD in the Dentate Gyrus In Vivo.

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    Peter Jedlicka

    2015-11-01

    Full Text Available Long-term potentiation (LTP and long-term depression (LTD are widely accepted to be synaptic mechanisms involved in learning and memory. It remains uncertain, however, which particular activity rules are utilized by hippocampal neurons to induce LTP and LTD in behaving animals. Recent experiments in the dentate gyrus of freely moving rats revealed an unexpected pattern of LTP and LTD from high-frequency perforant path stimulation. While 400 Hz theta-burst stimulation (400-TBS and 400 Hz delta-burst stimulation (400-DBS elicited substantial LTP of the tetanized medial path input and, concurrently, LTD of the non-tetanized lateral path input, 100 Hz theta-burst stimulation (100-TBS, a normally efficient LTP protocol for in vitro preparations produced only weak LTP and concurrent LTD. Here we show in a biophysically realistic compartmental granule cell model that this pattern of results can be accounted for by a voltage-based spike-timing-dependent plasticity (STDP rule combined with a relatively fast Bienenstock-Cooper-Munro (BCM-like homeostatic metaplasticity rule, all on a background of ongoing spontaneous activity in the input fibers. Our results suggest that, at least for dentate granule cells, the interplay of STDP-BCM plasticity rules and ongoing pre- and postsynaptic background activity determines not only the degree of input-specific LTP elicited by various plasticity-inducing protocols, but also the degree of associated LTD in neighboring non-tetanized inputs, as generated by the ongoing constitutive activity at these synapses.

  17. LTP in Hippocampal Area CA1 Is Induced by Burst Stimulation over a Broad Frequency Range Centered around Delta

    Science.gov (United States)

    Grover, Lawrence M.; Kim, Eunyoung; Cooke, Jennifer D.; Holmes, William R.

    2009-01-01

    Long-term potentiation (LTP) is typically studied using either continuous high-frequency stimulation or theta burst stimulation. Previous studies emphasized the physiological relevance of theta frequency; however, synchronized hippocampal activity occurs over a broader frequency range. We therefore tested burst stimulation at intervals from 100…

  18. 5-HT4-receptors modulate induction of long-term depression but not potentiation at hippocampal output synapses in acute rat brain slices.

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    Matthias Wawra

    Full Text Available The subiculum is the principal target of CA1 pyramidal cells and mediates hippocampal output to various cortical and subcortical regions of the brain. The majority of subicular pyramidal cells are burst-spiking neurons. Previous studies indicated that high frequency stimulation in subicular burst-spiking cells causes presynaptic NMDA-receptor dependent long-term potentiation (LTP whereas low frequency stimulation induces postsynaptic NMDA-receptor-dependent long-term depression (LTD. In the present study, we investigate the effect of 5-hydroxytryptamine type 4 (5-HT4 receptor activation and blockade on both forms of synaptic plasticity in burst-spiking cells. We demonstrate that neither activation nor block of 5-HT4 receptors modulate the induction or expression of LTP. In contrast, activation of 5-HT4 receptors facilitates expression of LTD, and block of the 5-HT4 receptor prevents induction of short-term depression and LTD. As 5-HT4 receptors are positively coupled to adenylate cyclase 1 (AC1, 5-HT4 receptors might modulate PKA activity through AC1. Since LTD is blocked in the presence of 5-HT4 receptor antagonists, our data are consistent with 5-HT4 receptor activation by ambient serotonin or intrinsically active 5-HT4 receptors. Our findings provide new insight into aminergic modulation of hippocampal output.

  19. Motor learning interference is proportional to occlusion of LTP-like plasticity.

    Science.gov (United States)

    Cantarero, Gabriela; Tang, Byron; O'Malley, Rebecca; Salas, Rachel; Celnik, Pablo

    2013-03-13

    Learning interference occurs when learning something new causes forgetting of an older memory (retrograde interference) or when learning a new task disrupts learning of a second subsequent task (anterograde interference). This phenomenon, described in cognitive, sensory, and motor domains, limits our ability to learn multiple tasks in close succession. It has been suggested that the source of interference is competition of neural resources, although the neuronal mechanisms are unknown. Learning induces long-term potentiation (LTP), which can ultimately limit the ability to induce further LTP, a phenomenon known as occlusion. In humans we quantified the magnitude of occlusion of anodal transcranial direct current stimulation-induced increased excitability after learning a skill task as an index of the amount of LTP-like plasticity used. We found that retention of a newly acquired skill, as reflected by performance in the second day of practice, is proportional to the magnitude of occlusion. Moreover, the degree of behavioral interference was correlated with the magnitude of occlusion. Individuals with larger occlusion after learning the first skill were (1) more resilient to retrograde interference and (2) experienced larger anterograde interference when training a second task, as expressed by decreased performance of the learned skill in the second day of practice. This effect was not observed if sufficient time elapsed between training the two skills and LTP-like occlusion was not present. These findings suggest competition of LTP-like plasticity is a factor that limits the ability to remember multiple tasks trained in close succession.

  20. The fatty acid amide hydrolase inhibitor URB597 exerts anti-inflammatory effects in hippocampus of aged rats and restores an age-related deficit in long-term potentiation

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    Murphy Niamh

    2012-04-01

    Full Text Available Abstract Background Several factors contribute to the deterioration in synaptic plasticity which accompanies age and one of these is neuroinflammation. This is characterized by increased microglial activation associated with increased production of proinflammatory cytokines like interleukin-1β (IL-1β. In aged rats these neuroinflammatory changes are associated with a decreased ability of animals to sustain long-term potentiation (LTP in the dentate gyrus. Importantly, treatment of aged rats with agents which possess anti-inflammatory properties to decrease microglial activation, improves LTP. It is known that endocannabinoids, such as anandamide (AEA, have anti-inflammatory properties and therefore have the potential to decrease the age-related microglial activation. However, endocannabinoids are extremely labile and are hydrolyzed quickly after production. Here we investigated the possibility that inhibiting the degradation of endocannabinoids with the fatty acid amide hydrolase (FAAH inhibitor, URB597, could ameliorate age-related increases in microglial activation and the associated decrease in LTP. Methods Young and aged rats received subcutaneous injections of the FAAH inhibitor URB597 every second day and controls which received subcutaneous injections of 30% DMSO-saline every second day for 28 days. Long-term potentiation was recorded on day 28 and the animals were sacrificed. Brain tissue was analyzed for markers of microglial activation by PCR and for levels of endocannabinoids by liquid chromatography coupled to tandem mass spectrometry. Results The data indicate that expression of markers of microglial activation, MHCII, and CD68 mRNA, were increased in the hippocampus of aged, compared with young, rats and that these changes were associated with increased expression of the proinflammatory cytokines interleukin (IL-1β and tumor necrosis factor-α (TNFα which were attenuated by treatment with URB597. Coupled with these changes, we

  1. Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.

    Science.gov (United States)

    Shetty, Mahesh Shivarama; Sharma, Mahima; Sajikumar, Sreedharan

    2017-02-01

    Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear. Zinc deficiency and the resultant adverse effects on cognition have been well studied. However, the role of excess of zinc in synaptic plasticity, especially in aging, is not addressed well. Here, we have investigated the hippocampal zinc levels and the impairments in synaptic plasticity, such as LTP and synaptic tagging and capture (STC), in the CA1 region of acute hippocampal slices from 82- to 84-week-old male Wistar rats. We report increased zinc levels in the hippocampus of aged rats and also deficits in the tetani-induced and dopaminergic agonist-induced late-LTP and STC. The observed deficits in synaptic plasticity were restored upon chelation of zinc using a cell-permeable chelator. These data suggest that functional plasticity and associativity can be successfully established in aged neural networks by chelating zinc with cell-permeable chelating agents. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  2. Calcium regulation in long-term changes of neuronal excitability in the hippocampal formation

    Energy Technology Data Exchange (ETDEWEB)

    Mody, I.

    1985-01-01

    The regulation of calcium (Ca/sup 2 +/) was examined during long-term changes of neuronal excitability in the mammalian CNS. The preparations under investigation included the kindling model of epilepsy, a genetic form of epilepsy and long-term potentiation (LTP) of neuronal activity. The study also includes a discussion of the possible roles of a neuron-specific calcium-binding protein (CaBP). The findings are summarized as follows: (1) CaBP was found to have an unequal distribution in various cortical areas of the rat with higher levels in ventral structures. (2) The decline in CaBP was correlated to the number of evoked afterdischarges (AD's) during kindling-induced epilepsy. (3) Marked changes in CaBP levels were also found in the brains of the epileptic strain of mice (El). The induction of seizures further decreased the levels of CaBP in the El mice, indicating a possible genetic impairment of neuronal Ca/sup 2 +/ homeostasis in the El strain. (4) The levels of total hippocampal Ca/sup 2 +/ and Zn/sup 2 +/ were measured by atomic absorption spectrophotometry in control and commissural-kindled animals. (5) To measure Ca/sup 2 +/-homeostasis, the kinetic analysis of /sup 45/Ca uptake curves was undertaken in the in vitro hippocampus. (6) The kinetic analysis of /sup 45/Ca uptake curves revealed that Ca/sup 2 +/-regulation of the hippocampus is impaired following amygdala- and commissural kindling. (7). A novel form of long-term potentiation (LTP) of neuronal activity in the CA1 region of the hippocampus is described. The findings raise the possibility that the Ca/sup 2 +/ necessary for induction of LTP may be derived from an intraneuronal storage site.

  3. α1-Adrenoceptors in the hippocampal dentate gyrus involved in learning-dependent long-term potentiation during active-avoidance learning in rats.

    Science.gov (United States)

    Lv, Jing; Zhan, Su-Yang; Li, Guang-Xie; Wang, Dan; Li, Ying-Shun; Jin, Qing-Hua

    2016-11-09

    The hippocampus is the key structure for learning and memory in mammals and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. The influences of norepinephrine (NE) on the modulation of learning and memory, as well as LTP, through β-adrenoceptors are well documented, whereas the role of α1-adrenoceptors in learning-dependent LTP is not yet clear. In the present study, we measured extracellular concentrations of NE in the hippocampal dentate gyrus (DG) region using an in-vivo brain microdialysis and high-performance liquid chromatography techniques during the acquisition and extinction of active-avoidance behavior in freely moving conscious rats. Next, the effects of prazosin (an antagonist of α1-adrenoceptor) and phenylephrine (an agonist of the α1-adrenoceptor) on amplitudes of field excitatory postsynaptic potential were measured in the DG region during the active-avoidance behavior. Our results showed that the extracellular concentration of NE in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to the baseline level following extinction training. A local microinjection of prazosin into the DG significantly accelerated the acquisition of the active-avoidance behavior, whereas a local microinjection of phenylephrine retarded the acquisition of the active-avoidance behavior. Furthermore, in all groups, the changes in field excitatory postsynaptic potential amplitude were accompanied by corresponding changes in active-avoidance behavior. Our results suggest that NE activation of α1-adrenoceptors in the hippocampal DG inhibits active-avoidance learning by modulation of synaptic efficiency in rats.

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

    Science.gov (United States)

    Liu, Kang; Lisman, John; Hagan, Michael

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

  5. Signaling through cGMP-dependent protein kinase I in the amygdala is critical for auditory-cued fear memory and long-term potentiation.

    Science.gov (United States)

    Paul, Cindy; Schöberl, Florian; Weinmeister, Pascal; Micale, Vincenzo; Wotjak, Carsten T; Hofmann, Franz; Kleppisch, Thomas

    2008-12-24

    Long-term potentiation (LTP) of inputs relaying sensory information from cortical and thalamic neurons to principal neurons in the lateral amygdala (LA) is thought to serve as a cellular mechanism for associative fear learning. Nitric oxide (NO), a messenger molecule widely implicated in synaptic plasticity and behavior, has been shown to enhance LTP in the LA as well as consolidation of associative fear memory. Additional evidence suggests that NO-induced enhancement of LTP and amygdala-dependent learning requires signaling through soluble guanylyl cyclase (sGC) and cGMP-dependent protein kinase (cGK). Mammals possess two genes for cGK: the prkg1 gene gives rise to the cGK type I isoforms, cGKIalpha and cGKIbeta, and the prkg2 gene encodes the cGK type II. Reportedly, both cGKI and cGKII are expressed in the amygdala, and cGKII is involved in controlling anxiety-like behavior. Because selective pharmacological tools for individual cGK isoforms are lacking, we used different knock-out mouse models to examine the function of cGKI and cGKII for LTP in the LA and pavlovian fear conditioning. We found robust expression of the cGKI specifically in the LA with cGKIbeta as the prevailing isoform. We further show a marked reduction of LTP at both thalamic and cortical inputs to the LA and a selective impairment of auditory-cued fear memory in cGKI-deficient mutants. In contrast, cGKII null mutants lack these phenotypes. Our data suggest a function of cGKI, likely the beta isoform, in the LA, supporting synaptic plasticity and consolidation of fear memory.

  6. Optimised purification and characterisation of lipid transfer protein 1 (LTP1) and its lipid-bound isoform LTP1b from barley malt.

    Science.gov (United States)

    Nieuwoudt, Melanie; Lombard, Nicolaas; Rautenbach, Marina

    2014-08-15

    In beer brewing, brewers worldwide strive to obtain product consistency in terms of flavour, colour and foam. Important proteins contributing to beer foam are lipid transfer proteins (LTPs), in particular LTP1 and its lipid-bound isoform LTP1b, which are known to transport lipids in vivo and prevent lipids from destabilising the beer foam. LTP1 and LTP1b were successfully purified using only five purification steps with a high purified protein yield (160 mg LTP1 and LTP1b from 200 g barley). Circular dichroism of LTP1 and LTP1b confirmed that both proteins are highly tolerant to high temperatures (>90 °C) and are pH stable, particularly at a neutral to a more basic pH. Only LTP1 exhibited antiyeast and thermo-stable lytic activity, while LTP1b was inactive, indicating that the fatty acid moiety compromised the antimicrobial activity of LTP1. This lack in antiyeast activity and the positive foam properties of LTP1b would benefit beer fermentation and quality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Learning, memory and hippocampal LTP in genetically obese rodents

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    We have found that leptin, at physiological concentrations of 10-12 mol/L, facilitates learning and memory and LTP maintenance in Wistar rats. To explore the role of leptin recepors in learning, memory and synaptic plasticity, experiments were carried out using Zucker rats (Z), db/db mice (db), and ob/ob mice(ob). The former two have defects in leptin receptors and the latter cannot produce normal leptin. Unlike the effects observed in normal rats, high or low frequency stimulation of Schaffer collateral-CA1 synapses in hippocampal slices prepared from Z, db and ob animals failed to induce the learning and memory relevant long-term potentiation or depression in CA1 neurons. However, LTP in ob CA1 synapses was facilitated by leptin at 10-12 mol/L concentration. Moreover, the paired-pulse facilitation of CA1 synaptic potentials and intracellularly recorded postsynaptic responses to the neurotransmitters AMPA, NMDA and GABA, applied electrophoretically to the apical dendrites of CA1 neurons, were approximately the same compared to the control lean animals. In addition, unlike the second messenger responses observed in Wistar rats, calmodulin kinase Ⅱ activity in the CA1 area of Z and db animals was not activated after tetanic stimulation of the Schaffer collaterals. It has been shown that all three strains, Z, db and ob display impaired spatial learning and memory when tested in the Morris water maze. The results of these experiments indicate a close relationship between spatial learning and memory, facilitation of LTP, and calmodulin kinase Ⅱ activity.

  8. Cystathionine-β-synthase-derived hydrogen sulfide is required for amygdalar long-term potentiation and cued fear memory in rats.

    Science.gov (United States)

    Chen, Hai-Bo; Wu, Wen-Ning; Wang, Wei; Gu, Xun-Hu; Yu, Bin; Wei, Bo; Yang, Yuan-Jian

    2017-04-01

    Hydrogen sulfide (H 2 S) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that H 2 S regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous H 2 S is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-β-synthase (CBS), the predominant H 2 S-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of H 2 S in the lateral amygdala (LA) region. Incubating brain slices with CBS inhibitor significantly prevented the induction of NMDA receptors (NMDARs)-dependent LTP in the thalamo-LA pathway, and intra-LA infusion of CBS inhibitor impaired cued fear memory in rats. Notably, treatment with H 2 S donor, but not CBS activator, significantly reversed the impairments of LTP and fear memory caused by CBS inhibition. Mechanismly, inhibition of CBS activity led to a reduction in NMDAR-mediated synaptic response in the thalamo-LA pathway, and treatment with H 2 S donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived H 2 S is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous H 2 S might involve the regulation of NMDAR function. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. D1/D5 Receptors and Histone Deacetylation Mediate the Gateway Effect of LTP in Hippocampal Dentate Gyrus

    Science.gov (United States)

    Huang, Yan-You; Lavine, Amir; Kandel, Denise B.; Yin, Deqi; Colnaghi, Luca; Drisaldi, Bettina; Kandel, Eric R.

    2014-01-01

    The dentate gyrus (DG) of the hippocampus is critical for spatial memory and is also thought to be involved in the formation of drug-related associative memory. Here, we attempt to test an aspect of the Gateway Hypothesis, by studying the effect of consecutive exposure to nicotine and cocaine on long-term synaptic potentiation (LTP) in the DG. We…

  10. Social Isolation During Adolescence Strengthens Retention of Fear Memories and Facilitates Induction of Late-Phase Long-Term Potentiation.

    Science.gov (United States)

    Liu, Ji-Hong; You, Qiang-Long; Wei, Mei-Dan; Wang, Qian; Luo, Zheng-Yi; Lin, Song; Huang, Lang; Li, Shu-Ji; Li, Xiao-Wen; Gao, Tian-Ming

    2015-12-01

    Social isolation during the vulnerable period of adolescence produces emotional dysregulation that often manifests as abnormal behavior in adulthood. The enduring consequence of isolation might be caused by a weakened ability to forget unpleasant memories. However, it remains unclear whether isolation affects unpleasant memories. To address this, we used a model of associative learning to induce the fear memories and evaluated the influence of isolation mice during adolescence on the subsequent retention of fear memories and its underlying cellular mechanisms. Following adolescent social isolation, we found that mice decreased their social interaction time and had an increase in anxiety-related behavior. Interestingly, when we assessed memory retention, we found that isolated mice were unable to forget aversive memories when tested 4 weeks after the original event. Consistent with this, we observed that a single train of high-frequency stimulation (HFS) enabled a late-phase long-term potentiation (L-LTP) in the hippocampal CA1 region of isolated mice, whereas only an early-phase LTP was observed with the same stimulation in the control mice. Social isolation during adolescence also increased brain-derived neurotrophic factor (BDNF) expression in the hippocampus, and application of a tropomyosin-related kinase B (TrkB) receptor inhibitor ameliorated the facilitated L-LTP seen after isolation. Together, our results suggest that adolescent isolation may result in mental disorders during adulthood and that this may stem from an inability to forget the unpleasant memories via BDNF-mediated synaptic plasticity. These findings may give us a new strategy to prevent mental disorders caused by persistent unpleasant memories.

  11. Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs Long-Term Potentiation in Adulthood.

    Science.gov (United States)

    DeAngeli, Nicole E; Todd, Travis P; Chang, Stephen E; Yeh, Hermes H; Yeh, Pamela W; Bucci, David J

    2014-01-01

    Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with L-kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing) when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value) as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst of high-frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during adolescence.

  12. Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs Long-Term Potentiation in Adulthood

    Science.gov (United States)

    DeAngeli, Nicole E.; Todd, Travis P.; Chang, Stephen E.; Yeh, Hermes H.; Yeh, Pamela W.; Bucci, David J.

    2015-01-01

    Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with L-kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing) when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value) as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst of high-frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during adolescence

  13. Exposure to Kynurenic Acid during Adolescence Increases Sign-tracking and Impairs Long-term Potentiation in Adulthood

    Directory of Open Access Journals (Sweden)

    Nicole eDeAngeli

    2015-01-01

    Full Text Available Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently there are few treatments for persons with a dual-diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA, a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with l-kynurenine (L-KYN, the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP. Rats treated with L-KYN exhibited no LTP after a burst of high frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during

  14. GABAergic activities control spike timing- and frequency-dependent long-term depression at hippocampal excitatory synapses

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    Makoto Nishiyama

    2010-06-01

    Full Text Available GABAergic interneuronal network activities in the hippocampus control a variety of neural functions, including learning and memory, by regulating θ and γ oscillations. How these GABAergic activities at pre- and post-synaptic sites of hippocampal CA1 pyramidal cells differentially contribute to synaptic function and plasticity during their repetitive pre- and post-synaptic spiking at θ and γ oscillations is largely unknown. We show here that activities mediated by postsynaptic GABAARs and presynaptic GABABRs determine, respectively, the spike timing- and frequency-dependence of activity-induced synaptic modifications at Schaffer collateral-CA1 excitatory synapses. We demonstrate that both feedforward and feedback GABAAR-mediated inhibition in the postsynaptic cell controls the spike timing-dependent long-term depression of excitatory inputs (“e-LTD” at the θ frequency. We also show that feedback postsynaptic inhibition specifically causes e-LTD of inputs that induce small postsynaptic currents (<70 pA with LTP timing, thus enforcing the requirement of cooperativity for induction of long-term potentiation at excitatory inputs (“e-LTP”. Furthermore, under spike-timing protocols that induce e-LTP and e-LTD at excitatory synapses, we observed parallel induction of LTP and LTD at inhibitory inputs (“i-LTP” and “i-LTD” to the same postsynaptic cells. Finally, we show that presynaptic GABABR-mediated inhibition plays a major role in the induction of frequency-dependent e-LTD at α and β frequencies. These observations demonstrate the critical influence of GABAergic interneuronal network activities in regulating the spike timing and frequency dependences of long-term synaptic modifications in the hippocampus.

  15. Costs and Benefits of a Shared Digital Long-Term Preservation System

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    Esa-Pekka Keskitalo

    2011-10-01

    Full Text Available This paper describes the cost-benefit analysis of digital long-term preservation (LTP that was carried out in the context of the Finnish National Digital Library Project (NDL in 2010. The analysis was based on the assumption that as many as 200 archives, libraries, and museums will share an LTP system. The term ‘system’ shall be understood as encompassing not only information technology, but also human resources, organizational structures, policies and funding mechanisms. The cost analysis shows that an LTP system will incur, over the first 12 years, cumulative costs of €42 million, i.e. an average of €3.5 million per annum. Human resources and investments in information technology are the major cost factors. After the initial stages, the analysis predicts annual costs of circa €4 million. The analysis compared scenarios with and without a shared LTP system. The results indicate that a shared system will have remarkable benefits. At the development and implementation stages, a shared system shows an advantage of €30 million against the alternative scenario consisting of five independent LTP solutions. During the later stages, the advantage is estimated at €10 million per annum. The cumulative cost benefit over the first 12 years would amount to circa €100 million.

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

    Science.gov (United States)

    Tamano, Haruna; Nishio, Ryusuke; Takeda, Atsushi

    2017-07-01

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

  17. Long-term potentiation in the CA1 hippocampus induced by NR2A subunit-containing NMDA glutamate receptors is mediated by Ras-GRF2/Erk map kinase signaling.

    Directory of Open Access Journals (Sweden)

    Shan-xue Jin

    Full Text Available BACKGROUND: NMDA-type glutamate receptors (NMDARs are major contributors to long-term potentiation (LTP, a form of synaptic plasticity implicated in the process of learning and memory. These receptors consist of calcium-permeating NR1 and multiple regulatory NR2 subunits. A majority of studies show that both NR2A and NR2B-containing NMDARs can contribute to LTP, but their unique contributions to this form of synaptic plasticity remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that NR2A and NR2B-containing receptors promote LTP differently in the CA1 hippocampus of 1-month old mice, with the NR2A receptors functioning through Ras-GRF2 and its downstream effector, Erk Map kinase, and NR2B receptors functioning independently of these signaling molecules. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that NR2A-, but not NR2B, containing NMDA receptors induce LTP in pyramidal neurons of the CA1 hippocampus from 1 month old mice through Ras-GRF2 and Erk. This difference add new significance to the observation that the relative levels of these NMDAR subtypes is regulated in neurons, such that NR2A-containing receptors become more prominent late in postnatal development, after sensory experience and synaptic activity.

  18. Acupuncture Prevents the Impairment of Hippocampal LTP Through β1-AR in Vascular Dementia Rats.

    Science.gov (United States)

    Xiao, Ling-Yong; Wang, Xue-Rui; Yang, Jing-Wen; Ye, Yang; Zhu, Wen; Cao, Yan; Ma, Si-Ming; Liu, Cun-Zhi

    2018-02-13

    It is widely accepted that the synaptic dysfunction and synapse loss contribute to the cognitive deficits of vascular dementia (VD) patients. We have previously reported that acupuncture improved cognitive function in rats with VD. However, the mechanisms involved in acupuncture improving cognitive ability remain to be elucidated. The present study aims to investigate the pathways and molecules involved in the neuroprotective effect of acupuncture. We assessed the effects of acupuncture on hippocampal long-term potentiation (LTP), the most prominent cellular model of memory formation. Acupuncture enhanced LTP and norepinephrine (NE) levels in the hippocampus. Inhibition of the β-adrenergic receptor (AR), but not the α-AR, was able to block the effects of acupuncture on hippocampal LTP. Furthermore, inhibition of β1-AR, not β2-AR, abolished the enhanced LTP induced by acupuncture. The expression analysis revealed a significant upregulation of β1-AR and unchanged β2-AR with acupuncture, which supported the above findings. Specifically, increased β1-ARs in the dentate gyrus were expressed on neurons exclusively. Taken together, the present data supports a beneficial role of acupuncture in synaptic plasticity challenged with VD. A likely mechanism is the increase of NE and activation of β1-AR in the hippocampus.

  19. The effects of prolonged administration of norepinephrine reuptake inhibitors on long-term potentiation in dentate gyrus, and on tests of spatial and object recognition memory in rats.

    Science.gov (United States)

    Walling, Susan G; Milway, J Stephen; Ingram, Matthew; Lau, Catherine; Morrison, Gillian; Martin, Gerard M

    2016-02-01

    Phasic norepinephrine (NE) release events are involved in arousal, novelty detection and in plasticity processes underlying learning and memory in mammalian systems. Although the effects of phasic NE release events on plasticity and memory are prevalently documented, it is less understood what effects chronic NE reuptake inhibition and sustained increases in noradrenergic tone, might have on plasticity and cognitive processes in rodent models of learning and memory. This study investigates the effects of chronic NE reuptake inhibition on hippocampal plasticity and memory in rats. Rats were administered NE reuptake inhibitors (NRIs) desipramine (DMI; 0, 3, or 7.5mg/kg/day) or nortriptyline (NTP; 0, 10 or 20mg/kg/day) in drinking water. Long-term potentiation (LTP; 200 Hz) of the perforant path-dentate gyrus evoked potential was examined in urethane anesthetized rats after 30-32 days of DMI treatment. Short- (4-h) and long-term (24-h) spatial memory was tested in separate rats administered 0 or 7.5mg/kg/day DMI (25-30 days) using a two-trial spatial memory test. Additionally, the effects of chronically administered DMI and NTP were tested in rats using a two-trial, Object Recognition Test (ORT) at 2- and 24-h after 45 and 60 days of drug administration. Rats administered 3 or 7.5mg/kg/day DMI had attenuated LTP of the EPSP slope but not the population spike at the perforant path-dentate gyrus synapse. Short- and long-term memory for objects is differentially disrupted in rats after prolonged administration of DMI and NTP. Rats that were administered 7.5mg/kg/day DMI showed decreased memory for a two-trial spatial task when tested at 4-h. In the novel ORT, rats receiving 0 or 7.5mg/kg/day DMI showed a preference for the arm containing a Novel object when tested at both 2- and 24-h demonstrating both short- and long-term memory retention of the Familiar object. Rats that received either dose of NTP or 3mg/kg/day DMI showed impaired memory at 2-h, however this

  20. Alzheimer's Disease Brain-Derived Amyloid-{beta}-Mediated Inhibition of LTP In Vivo Is Prevented by Immunotargeting Cellular Prion Protein.

    LENUS (Irish Health Repository)

    Barry, Andrew E

    2011-05-18

    Synthetic amyloid-β protein (Aβ) oligomers bind with high affinity to cellular prion protein (PrP(C)), but the role of this interaction in mediating the disruption of synaptic plasticity by such soluble Aβ in vitro is controversial. Here we report that intracerebroventricular injection of Aβ-containing aqueous extracts of Alzheimer\\'s disease (AD) brain robustly inhibits long-term potentiation (LTP) without significantly affecting baseline excitatory synaptic transmission in the rat hippocampus in vivo. Moreover, the disruption of LTP was abrogated by immunodepletion of Aβ. Importantly, intracerebroventricular administration of antigen-binding antibody fragment D13, directed to a putative Aβ-binding site on PrP(C), prevented the inhibition of LTP by AD brain-derived Aβ. In contrast, R1, a Fab directed to the C terminus of PrP(C), a region not implicated in binding of Aβ, did not significantly affect the Aβ-mediated inhibition of LTP. These data support the pathophysiological significance of SDS-stable Aβ dimer and the role of PrP(C) in mediating synaptic plasticity disruption by soluble Aβ.

  1. Aluminium chloride impairs long-term memory and downregulates cAMP-PKA-CREB signalling in rats.

    Science.gov (United States)

    Zhang, Lifeng; Jin, Cuihong; Lu, Xiaobo; Yang, Jinghua; Wu, Shengwen; Liu, Qiufang; Chen, Rong; Bai, Chunyu; Zhang, Di; Zheng, Linlin; Du, Yanqiu; Cai, Yuan

    2014-09-02

    Epidemiological investigations have indicated that aluminium (Al) is an important environmental neurotoxicant that may be involved in the aetiology of the cognitive dysfunction associated with neurodegenerative diseases. Additionally, exposure to Al is known to cause neurobehavioural abnormalities in animals. Previous studies demonstrated that Al impaired early-phase long-term potentiation (E-LTP) in vivo and in vitro. Our previous research revealed that Al could impair long-term memory via the impairment of late-phase long-term potentiation (L-LTP) in vivo. However, the exact mechanism by which Al impairs long-term memory has been poorly studied thus far. This study was designed not only to observe the effects of subchronic Al treatment on long-term memory and hippocampal ultrastructure but also to explore a possible underlying mechanism (involving the cAMP-PKA-CREB signalling pathway) in the hippocampus of rats.. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation for 3 weeks and then fed with distilled water containing 0, 0.2%, 0.4% or 0.6% Al chloride (AlCl3) for 3 postnatal months. The levels of Al in the blood and hippocampus were quantified by atomic absorption spectrophotometry. The shuttle-box test was performed to detect long-term memory. The hippocampus was collected for ultrastructure observation, and the level of cAMP-PKA-CREB signalling was examined. The results showed that the Al concentrations in the blood and hippocampus of Al-treated rats were higher than those of the control rats. Al may impair the long-term memory of rats. Hippocampal cAMP, cPKA, pCREB, BDNF and c-jun expression decreased significantly, and the neuronal and synaptic ultrastructure exhibited pathological changes after Al treatment. These results indicated that Al may induce long-term memory damage in rats by inhibiting cAMP-PKA-CREB signalling and altering the synaptic and neuronal ultrastructure in the hippocampus. Copyright

  2. Aluminium chloride impairs long-term memory and downregulates cAMP-PKA-CREB signalling in rats

    International Nuclear Information System (INIS)

    Zhang, Lifeng; Jin, Cuihong; Lu, Xiaobo; Yang, Jinghua; Wu, Shengwen; Liu, Qiufang; Chen, Rong; Bai, Chunyu; Zhang, Di; Zheng, Linlin; Du, Yanqiu; Cai, Yuan

    2014-01-01

    Epidemiological investigations have indicated that aluminium (Al) is an important environmental neurotoxicant that may be involved in the aetiology of the cognitive dysfunction associated with neurodegenerative diseases. Additionally, exposure to Al is known to cause neurobehavioural abnormalities in animals. Previous studies demonstrated that Al impaired early-phase long-term potentiation (E-LTP) in vivo and in vitro. Our previous research revealed that Al could impair long-term memory via the impairment of late-phase long-term potentiation (L-LTP) in vivo. However, the exact mechanism by which Al impairs long-term memory has been poorly studied thus far. This study was designed not only to observe the effects of subchronic Al treatment on long-term memory and hippocampal ultrastructure but also to explore a possible underlying mechanism (involving the cAMP-PKA-CREB signalling pathway) in the hippocampus of rats.. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation for 3 weeks and then fed with distilled water containing 0, 0.2%, 0.4% or 0.6% Al chloride (AlCl 3 ) for 3 postnatal months. The levels of Al in the blood and hippocampus were quantified by atomic absorption spectrophotometry. The shuttle–box test was performed to detect long-term memory. The hippocampus was collected for ultrastructure observation, and the level of cAMP-PKA-CREB signalling was examined. The results showed that the Al concentrations in the blood and hippocampus of Al-treated rats were higher than those of the control rats. Al may impair the long-term memory of rats. Hippocampal cAMP, cPKA, pCREB, BDNF and c-jun expression decreased significantly, and the neuronal and synaptic ultrastructure exhibited pathological changes after Al treatment. These results indicated that Al may induce long-term memory damage in rats by inhibiting cAMP-PKA-CREB signalling and altering the synaptic and neuronal ultrastructure in the hippocampus

  3. Mild prenatal protein malnutrition increases alpha2C-adrenoceptor density in the cerebral cortex during postnatal life and impairs neocortical long-term potentiation and visuo-spatial performance in rats.

    Science.gov (United States)

    Soto-Moyano, Rubén; Valladares, Luis; Sierralta, Walter; Pérez, Hernán; Mondaca, Mauricio; Fernández, Victor; Burgos, Héctor; Hernández, Alejandro

    2005-06-01

    Mild reduction in the protein content of the mother's diet from 25 to 8% casein, calorically compensated by carbohydrates, does not alter body and brain weights of rat pups at birth, but leads to significant enhancements in the concentration and release of cortical noradrenaline during early postnatal life. Since central noradrenaline and some of its receptors are critically involved in long-term potentiation (LTP) and memory formation, this study evaluated the effect of mild prenatal protein malnutrition on the alpha2C-adrenoceptor density in the frontal and occipital cortices, induction of LTP in the same cortical regions and the visuo-spatial memory. Pups born from rats fed a 25% casein diet throughout pregnancy served as controls. At day 8 of postnatal age, prenatally malnourished rats showed a threefold increase in neocortical alpha2C-adrenoceptor density. At 60 days-of-age, alpha2C-adrenoceptor density was still elevated in the neocortex, and the animals were unable to maintain neocortical LTP and presented lower visuo-spatial memory performance. Results suggest that overexpression of neocortical alpha2C-adrenoceptors during postnatal life, subsequent to mild prenatal protein malnutrition, could functionally affect the synaptic networks subserving neocortical LTP and visuo-spatial memory formation.

  4. Functional optical probing of the hippocampal trisynaptic circuit in vitro: network dynamics, filter properties, and polysynaptic induction of CA1 LTP.

    Science.gov (United States)

    Stepan, Jens; Dine, Julien; Eder, Matthias

    2015-01-01

    Decades of brain research have identified various parallel loops linking the hippocampus with neocortical areas, enabling the acquisition of spatial and episodic memories. Especially the hippocampal trisynaptic circuit [entorhinal cortex layer II → dentate gyrus (DG) → cornu ammonis (CA)-3 → CA1] was studied in great detail because of its seemingly simple connectivity and characteristic structures that are experimentally well accessible. While numerous researchers focused on functional aspects, obtained from a limited number of cells in distinct hippocampal subregions, little is known about the neuronal network dynamics which drive information across multiple synapses for subsequent long-term storage. Fast voltage-sensitive dye imaging in vitro allows real-time recording of activity patterns in large/meso-scale neuronal networks with high spatial resolution. In this way, we recently found that entorhinal theta-frequency input to the DG most effectively passes filter mechanisms of the trisynaptic circuit network, generating activity waves which propagate across the entire DG-CA axis. These "trisynaptic circuit waves" involve high-frequency firing of CA3 pyramidal neurons, leading to a rapid induction of classical NMDA receptor-dependent long-term potentiation (LTP) at CA3-CA1 synapses (CA1 LTP). CA1 LTP has been substantially evidenced to be essential for some forms of explicit learning in mammals. Here, we review data with particular reference to whole network-level approaches, illustrating how activity propagation can take place within the trisynaptic circuit to drive formation of CA1 LTP.

  5. Extinction of aversive taste memory homeostatically prevents the maintenance of in vivo insular cortex LTP: Calcineurin participation.

    Science.gov (United States)

    Rivera-Olvera, Alejandro; Nelson-Mora, Janikua; Gonsebatt, María E; Escobar, Martha L

    2018-04-06

    Accumulating evidence indicates that homeostatic plasticity mechanisms dynamically adjust synaptic strength to promote stability that is crucial for memory storage. Our previous studies have shown that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of long-term potentiation (LTP) in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) in vivo. We have also reported that induction of LTP in the Bla-IC pathway modifies the CTA extinction. Memoryextinction involves the formation of a new associativememorythat inhibits a previously conditioned association. The aim of the present study was to analyze the effect of CTA extinction on the ability to induce subsequent LTP in the Bla-IC projection in vivo. Thus, 48 h after CTA extinction animals received high frequency stimulation in order to induce IC-LTP. Our results show that extinction training allows the induction but not the maintenance of IC-LTP. In addition, with the purpose of exploring part of the mechanisms involved in this process and since a body of evidence suggests that protein phosphatase calcineurin (CaN) is involved in the extinction of some behavioral tasks, we analyzed the participation of this phosphatase. The present results show that extinction training increases the CaN expression in the IC, as well as that the inhibition of this phosphatase reverts the effects of the CTA-extinction on the IC-LTP. These findings reveal that CTA extinction promotes a homeostatic regulation of subsequent IC synaptic plasticity maintenance through increases in CaN levels. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Quantification of long term emission potential from landfills

    NARCIS (Netherlands)

    Heimovaara, T.J.

    2011-01-01

    Novel approaches for the after-care of Municipal Solid Waste (MSW) landfills are based on technological measures to reduce the long term emission potential in a short time period. Biological degradation in landfills is a means to significantly reduce the long term emission potential. Leachate

  7. Afferent input selects NMDA receptor subtype to determine the persistency of hippocampal LTP in freely behaving mice

    Directory of Open Access Journals (Sweden)

    Jesús Javier Ballesteros

    2016-10-01

    Full Text Available The glutamatergic N-methyl-D-aspartate receptor (NMDAR is critically involved in many forms of hippocampus-dependent memory that may be enabled by synaptic plasticity. Behavioral studies with NMDAR antagonists and NMDAR subunit (GluN2 mutants revealed distinct contributions from GluN2A- and GluN2B-containing NMDARs to rapidly and slowly acquired memory performance. Furthermore, studies of synaptic plasticity, in genetically modified mice in vitro, suggest that GluN2A and GluN2B may contribute in different ways to the induction and longevity of synaptic plasticity. In contrast to the hippocampal slice preparation, in behaving mice, the afferent frequencies that induce synaptic plasticity are very restricted and specific. In fact, it is the stimulus pattern, and not variations in afferent frequency that determine the longevity of long-term potentiation (LTP. Here, we explored the contribution of GluN2A and GluN2B to LTP of differing magnitudes and persistencies in freely behaving mice. We applied differing high-frequency stimulation (HFS patterns at 100 Hz to the hippocampal CA1 region, to induce NMDAR-dependent LTP in wild-type (WT mice, that endured for 24h (late (L-LTP. In GluN2A-KO mice, E-LTP (HFS, 50 pulses was significantly reduced in magnitude and duration, whereas LTP (HFS, 2 x 50 pulses and L-LTP (HFS, 4 x 50 pulses were unaffected compared to responses in WT animals. By contrast, pharmacological antagonism of GluN2B in WT had no effect on E-LTP but significantly prevented LTP. E- LTP and LTP were significantly impaired by GluN2B antagonism in GluN2A-KO mice. These data indicate that the pattern of afferent stimulation is decisive for the recruitment of distinct GluN2A and GluN2B signaling pathways that in turn determine the persistency of hippocampal LTP. Whereas brief bursts of patterned stimulation preferentially recruit GluN2A and lead to weak and short-lived forms of LTP, prolonged, more intense, afferent activation recruits GluN2B

  8. NMDA receptor activation and PKC but not PKA lead to the modification of the long-term potentiation in the insular cortex induced by conditioned taste aversion: differential role of kinases in metaplasticity.

    Science.gov (United States)

    Rodríguez-Durán, Luis F; Escobar, Martha L

    2014-06-01

    It has been reported that training in behavioral tasks modifies the ability to induce long-term potentiation (LTP) in an N-methyl-D-aspartate receptor (NMDAR)-dependent manner. This receptor leads to calcium entry into neuronal cells, promoting the activation of protein kinases as protein kinase A (PKA) and protein kinase C (PKC), which contribute significantly to the formation of different types of memories and play a pivotal role in the expression of LTP. Our previous studies involving the insular cortex (IC) have demonstrated that induction of LTP in the basolateral amygdaloid nucleus (BLA)-IC projection prior to conditioned taste aversion (CTA) training enhances the retention of this task. Recently, we showed that CTA training triggers a persistent impairment in the ability to induce subsequent synaptic plasticity on the BLA-IC pathway in a protein synthesis-dependent manner, but the underlying molecular mechanisms remain unclear. In the present study we investigated whether the blockade of NMDAR, as well as the inhibition of PKC and PKA affects the CTA-dependent impairment of the IC-LTP. Thus, CTA-trained rats received high frequency stimulation in the Bla-IC projection in order to induce LTP 48 h after the aversion test. The NMDAR antagonist CPP and the specific inhibitors for PKC (chelerythrine) and PKA (KT-5720) were intracortically administered during the acquisition session. Our results show that the blockade of NMDAR and the inhibition of PKC activity prevent the CTA memory-formation as well as the IC-LTP impairment. Nevertheless, PKA inhibition prevents the memory formation of taste aversion but produces no interference with the CTA-dependent impairment of the IC-LTP. These findings reveal the differential roles of protein kinases on CTA-dependent modification of IC-LTP enhancing our understanding of the effects of memory-related changes on synaptic function. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Anisomycin Injection in Area CA3 of the Hippocampus Impairs Both Short-Term and Long-Term Memories of Contextual Fear

    Science.gov (United States)

    Remaud, Jessica; Ceccom, Johnatan; Carponcy, Julien; Dugué, Laura; Menchon, Gregory; Pech, Stéphane; Halley, Helene; Francés, Bernard; Dahan, Lionel

    2014-01-01

    Protein synthesis is involved in the consolidation of short-term memory into long-term memory. Previous electrophysiological data concerning LTP in CA3 suggest that protein synthesis in that region might also be necessary for short-term memory. We tested this hypothesis by locally injecting the protein synthesis inhibitor anisomycin in hippocampal…

  10. Nuclear protein phosphatase-1: an epigenetic regulator of fear memory and amygdala long-term potentiation.

    Science.gov (United States)

    Koshibu, K; Gräff, J; Mansuy, I M

    2011-01-26

    Complex brain diseases and neurological disorders in human generally result from the disturbance of multiple genes and signaling pathways. These disturbances may derive from mutations, deletions, translocations or rearrangements of specific gene(s). However, over the past years, it has become clear that such disturbances may also derive from alterations in the epigenome affecting several genes simultaneously. Our work recently demonstrated that epigenetic mechanisms in the adult brain are in part regulated by protein phosphatase 1 (PP1), a protein Ser/Thr phosphatase that negatively regulates hippocampus-dependent long-term memory (LTM) and synaptic plasticity. PP1 is abundant in brain structures involved in emotional processing like the amygdala, it may therefore be involved in the regulation of fear memory, a form of memory related to post-traumatic stress disorder (PTSD) in human. Here, we demonstrate that PP1 is a molecular suppressor of fear memory and synaptic plasticity in the amygdala that can control chromatin remodeling in neurons. We show that the selective inhibition of the nuclear pool of PP1 in amygdala neurons significantly alters posttranslational modifications (PTMs) of histones and the expression of several memory-associated genes. These alterations correlate with enhanced fear memory, and with an increase in long-term potentiation (LTP) that is transcription-dependent. Our results underscore the importance of nuclear PP1 in the amygdala as an epigenetic regulator of emotional memory, and the relevance of protein phosphatases as potential targets for therapeutic treatment of brain disorders like PTSD. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Effects of a human milk oligosaccharide, 2'-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents.

    Science.gov (United States)

    Vázquez, Enrique; Barranco, Alejandro; Ramírez, Maria; Gruart, Agnes; Delgado-García, José M; Martínez-Lara, Esther; Blanco, Santos; Martín, María Jesús; Castanys, Esther; Buck, Rachael; Prieto, Pedro; Rueda, Ricardo

    2015-05-01

    Human milk oligosaccharides (HMOs) are unique with regard to their diversity, quantity and complexity, particularly in comparison to bovine milk oligosaccharides. HMOs are associated with functional development during early life, mainly related to immunity and intestinal health. Whether HMOs elicit a positive effect on cognitive capabilities of lactating infants remains an open question. This study evaluated the role of the most abundant HMO, 2'-fucosyllactose (2'-FL), in synaptic plasticity and learning capabilities in rodents. Mice and rats were prepared for the chronic recording of field excitatory postsynaptic potentials evoked at the hippocampal CA3-CA1 synapse. Following chronic oral administration of 2'-FL, both species showed improvements in input/output curves and in long-term potentiation (LTP) evoked experimentally in alert behaving animals. This effect on LTP was related to better performance of animals in various types of learning behavioral tests. Mice were tested for spatial learning, working memory and operant conditioning using the IntelliCage system, while rats were submitted to a fixed-ratio schedule in the Skinner box. In both cases, 2'-FL-treated animals performed significantly better than controls. In addition, chronic administration of 2'-FL increased the expression of different molecules involved in the storage of newly acquired memories, such as the postsynaptic density protein 95, phosphorylated calcium/calmodulin-dependent kinase II and brain-derived neurotrophic factor in cortical and subcortical structures. Taken together, the data show that dietary 2'-FL affects cognitive domains and improves learning and memory in rodents. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Activation of the CREB/c-Fos Pathway during Long-Term Synaptic Plasticity in the Cerebellum Granular Layer

    Directory of Open Access Journals (Sweden)

    Daniela Gandolfi

    2017-06-01

    Full Text Available The induction of long-term potentiation and depression (LTP and LTD is thought to trigger gene expression and protein synthesis, leading to consolidation of synaptic and neuronal changes. However, while LTP and LTD have been proposed to play important roles for sensori-motor learning in the cerebellum granular layer, their association with these mechanisms remained unclear. Here, we have investigated phosphorylation of the cAMP-responsive element binding protein (CREB and activation of the immediate early gene c-Fos pathway following the induction of synaptic plasticity by theta-burst stimulation (TBS in acute cerebellar slices. LTP and LTD were localized using voltage-sensitive dye imaging (VSDi. At two time points following TBS (15 min and 120 min, corresponding to the early and late phases of plasticity, slices were fixed and processed to evaluate CREB phosphorylation (P-CREB and c-FOS protein levels, as well as Creb and c-Fos mRNA expression. High levels of P-CREB and Creb/c-Fos were detected before those of c-FOS, as expected if CREB phosphorylation triggered gene expression followed by protein synthesis. No differences between control slices and slices stimulated with TBS were observed in the presence of an N-methyl-D-aspartate receptor (NMDAR antagonist. Interestingly, activation of the CREB/c-Fos system showed a relevant degree of colocalization with long-term synaptic plasticity. These results show that NMDAR-dependent plasticity at the cerebellum input stage bears about transcriptional and post-transcriptional processes potentially contributing to cerebellar learning and memory consolidation.

  13. Wild-Type, but Not Mutant N296H, Human Tau Restores Aβ-Mediated Inhibition of LTP in Tau−/− mice

    Directory of Open Access Journals (Sweden)

    Mariana Vargas-Caballero

    2017-04-01

    Full Text Available Microtubule associated protein tau (MAPT is involved in the pathogenesis of Alzheimer's disease and many forms of frontotemporal dementia (FTD. We recently reported that Aβ-mediated inhibition of hippocampal long-term potentiation (LTP in mice requires tau. Here, we asked whether expression of human MAPT can restore Aβ-mediated inhibition on a mouse Tau−/− background and whether human tau with an FTD-causing mutation (N296H can interfere with Aβ-mediated inhibition of LTP. We used transgenic mouse lines each expressing the full human MAPT locus using bacterial artificial chromosome technology. These lines expressed all six human tau protein isoforms on a Tau−/− background. We found that the human wild-type MAPT H1 locus was able to restore Aβ42-mediated impairment of LTP. In contrast, Aβ42 did not reduce LTP in slices in two independently generated transgenic lines expressing tau protein with the mutation N296H associated with frontotemporal dementia (FTD. Basal phosphorylation of tau measured as the ratio of AT8/Tau5 immunoreactivity was significantly reduced in N296H mutant hippocampal slices. Our data show that human MAPT is able to restore Aβ42-mediated inhibition of LTP in Tau−/− mice. These results provide further evidence that tau protein is central to Aβ-induced LTP impairment and provide a valuable tool for further analysis of the links between Aβ, human tau and impairment of synaptic function.

  14. Brief environmental enrichment elicits metaplasticity of hippocampal synaptic potentiation in vivo

    Directory of Open Access Journals (Sweden)

    Denise eManahan-Vaughan

    2012-12-01

    Full Text Available Long-term environmental enrichment (EE elicits enduring effects on the adult brain, including altered synaptic plasticity. Synaptic plasticity may underlie memory formation and includes robust (>24h and weak (<2h forms of long-term potentiation (LTP and long-term depression (LTD. Most studies of the effect of EE on synaptic efficacy have examined the consequences of very prolonged EE-exposure. It is unclear whether brief exposure to EE can alter synaptic plasticity. Clarifying this issue could help develop strategies to address cognitive deficits arising from neglect in children or adults.We assessed whether short-term EE elicits alterations in hippocampal synaptic plasticity and if social context may play a role. Adult mice were exposed to EE for 14 consecutive days. We found that robust late-LTP (>24h and short-term depression (<2h at Schaffer-collateral-CA1 synapses in freely behaving mice were unaltered, whereas early-LTP (E-LTP, <2h was significantly enhanced by EE. Effects were transient: E-LTP returned to control levels 1 week after cessation of EE. Six weeks later animals were re-exposed to EE for 14d. Under these conditions, E-LTP was facilitated into L-LTP (>24h, suggesting that metaplasticity was induced during the first EE experience and that EE-mediated modifications are cumulative. Effects were absent in mice that underwent solitary enrichment or were group-housed without EE. These data suggest that EE in naïve animals strengthens E-LTP, and also promotes L-LTP in animals that underwent EE in the past. This indicates that brief exposure to EE, particularly under social conditions can elicit lasting positive effects on synaptic strength that may have beneficial consequences for cognition that depends on synaptic plasticity.

  15. Modulation of Long-term Potentiation of Cortico-amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid

    Directory of Open Access Journals (Sweden)

    Daisuke Yamada

    2016-08-01

    Full Text Available Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala. However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP of optogenetically–evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed a diet with a high ω3 to ω6 PUFA ratio (0.97, compared with mice fed a diet with a low ω3 to ω6 PUFA ratio (0.14. Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol, in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner.

  16. Nano-CuO impairs spatial cognition associated with inhibiting hippocampal long-term potentiation via affecting glutamatergic neurotransmission in rats.

    Science.gov (United States)

    Li, Xiaoliang; Sun, Wei; An, Lei

    2018-06-01

    Manufactured metal nanoparticles and their applications are continuously expanding because of their unique characteristics while their increasing use may predispose to potential health problems. Several studies have reported the adverse effects of copper oxide nanoparticles (nano-CuO) relative to ecotoxicity and cell toxicity, whereas little is known about the neurotoxicity of nano-CuO. The present study aimed to examine its effects on spatial cognition, hippocampal function, and the possible mechanisms. Male Wistar rats were used to establish an animal model, and nano-CuO was administered at a dose of 0.5 mg/kg/day for 2 weeks. The Morris water maze (MWM) test was employed to evaluate learning and memory. The long-term potentiation (LTP) from Schaffer collaterals to the hippocampal CA1 region, and the effects of nano-CuO on synases were recorded in the hippocampal CA1 neurons of rats. MWM test showed that learning and memory abilities were impaired significantly by nano-CuO ( p nano-CuO-treated groups compared with the control group ( p nano-CuO markedly depressed the frequencies of both spontaneous excitatory postsynaptic currents (sEPSCs) and miniature EPSCs (mEPSCs), indicating an effect of nano-CuO on inhibiting the release frequency of glutamate presynapticly ( p nano-CuO-treated animals, which suggested that the effect of nano-CuO modulates postsynaptic receptor kinetics ( p nano-CuO impaired glutamate transmission presynapticly and postsynapticly, which may contribute importantly to diminished LTP and other induced cognitive deficits.

  17. Observation of long term potentiation in papain-based memory devices

    KAUST Repository

    Bag, A.; Hota, Mrinal Kanti; Mallik, Sandipan B.; Maì ti, Chinmay Kumar

    2014-01-01

    Biological synaptic behavior in terms of long term potentiation has been observed in papain-based (plant protein) memory devices (memristors) for the first time. Improvement in long term potentiation depends on pulse amplitude and width (duration). Continuous/repetitive dc voltage sweep leads to an increase in memristor conductivity leading to a long term memory in the 'learning' processes.

  18. Observation of long term potentiation in papain-based memory devices

    KAUST Repository

    Bag, A.

    2014-06-01

    Biological synaptic behavior in terms of long term potentiation has been observed in papain-based (plant protein) memory devices (memristors) for the first time. Improvement in long term potentiation depends on pulse amplitude and width (duration). Continuous/repetitive dc voltage sweep leads to an increase in memristor conductivity leading to a long term memory in the \\'learning\\' processes.

  19. Daily acclimation handling does not affect hippocampal long-term potentiation or cause chronic sleep deprivation in mice.

    Science.gov (United States)

    Vecsey, Christopher G; Wimmer, Mathieu E J; Havekes, Robbert; Park, Alan J; Perron, Isaac J; Meerlo, Peter; Abel, Ted

    2013-04-01

    Gentle handling is commonly used to perform brief sleep deprivation in rodents. It was recently reported that daily acclimation handling, which is often used before behavioral assays, causes alterations in sleep, stress, and levels of N-methyl-D-aspartate receptor subunits prior to the actual period of sleep deprivation. It was therefore suggested that acclimation handling could mediate some of the observed effects of subsequent sleep deprivation. Here, we examine whether acclimation handling, performed as in our sleep deprivation studies, alters sleep/wake behavior, stress, or forms of hippocampal synaptic plasticity that are impaired by sleep deprivation. Adult C57BL/6J mice were either handled daily for 6 days or were left undisturbed in their home cages. On the day after the 6(th) day of handling, long-term potentiation (LTP) was induced in hippocampal slices with spaced four-train stimulation, which we previously demonstrated to be impaired by brief sleep deprivation. Basal synaptic properties were also assessed. In three other sets of animals, activity monitoring, polysomnography, and stress hormone measurements were performed during the 6 days of handling. Daily gentle handling alone does not alter LTP, rest/activity patterns, or sleep/wake architecture. Handling initially induces a minimal stress response, but by the 6(th) day, stress hormone levels are unaltered by handling. It is possible to handle mice daily to accustom them to the researcher without causing alterations in sleep, stress, or synaptic plasticity in the hippocampus. Therefore, effects of acclimation handling cannot explain the impairments in signaling mechanisms, synaptic plasticity, and memory that result from brief sleep deprivation.

  20. Studies in Optimal Configuration of the LTP

    International Nuclear Information System (INIS)

    McKinney, Wayne R.; Anders, Mark; Barber, Samuel K.; Domning, Edward E.; Lou, Yunian; Morrison, Gregory Y.; Salmassi, Farhad; Smith, Brian V.; Yashchuk, Valeriy V.

    2010-01-01

    Brightness preservation requirements for ever brighter synchrotron radiation and free electron laser beamlines require surface slope tolerances of x-ray optics on the order of 0.2 mu rad, or better. Hence, the accuracy of dedicated surface slope metrology must be 0.1 mu rad, or even less. Achieving this level of measurement accuracy with the flagship instrument at synchrotron radiation metrology laboratories, the Long Trace Profiler (LTP), requires all significant sources of systematic, random, and instrumental drift errors to be identified, and reduced or eliminated. In this respect, the performance of certain components of the Advanced Light Source LTP-II design [Kirschman, et al., Proc. SPIE, 7077, 70770A-12 (2008)] is analyzed, considering the principal justification for inclusion of each component, possible systematic error due to the quality of its optical material, and drift effects due to generated heat, etc. We investigate the effects of replacement of the existing diode laser with a fiber-coupled laser light source, and demonstrate that reducing the number of components by using a single beam on the surface under test (SUT), rather than an original double beam maintains, or even improves the accuracy of measurement with our LTP. Based on the performance of the upgraded LTP, we trace the further steps for improving of the LTP optical system.

  1. Parameter estimation techniques for LTP system identification

    Science.gov (United States)

    Nofrarias Serra, Miquel

    LISA Pathfinder (LPF) is the precursor mission of LISA (Laser Interferometer Space Antenna) and the first step towards gravitational waves detection in space. The main instrument onboard the mission is the LTP (LISA Technology Package) whose scientific goal is to test LISA's drag-free control loop by reaching a differential acceleration noise level between two masses in √ geodesic motion of 3 × 10-14 ms-2 / Hz in the milliHertz band. The mission is not only challenging in terms of technology readiness but also in terms of data analysis. As with any gravitational wave detector, attaining the instrument performance goals will require an extensive noise hunting campaign to measure all contributions with high accuracy. But, opposite to on-ground experiments, LTP characterisation will be only possible by setting parameters via telecommands and getting a selected amount of information through the available telemetry downlink. These two conditions, high accuracy and high reliability, are the main restrictions that the LTP data analysis must overcome. A dedicated object oriented Matlab Toolbox (LTPDA) has been set up by the LTP analysis team for this purpose. Among the different toolbox methods, an essential part for the mission are the parameter estimation tools that will be used for system identification during operations: Linear Least Squares, Non-linear Least Squares and Monte Carlo Markov Chain methods have been implemented as LTPDA methods. The data analysis team has been testing those methods with a series of mock data exercises with the following objectives: to cross-check parameter estimation methods and compare the achievable accuracy for each of them, and to develop the best strategies to describe the physics underlying a complex controlled experiment as the LTP. In this contribution we describe how these methods were tested with simulated LTP-like data to recover the parameters of the model and we report on the latest results of these mock data exercises.

  2. Forebrain-specific knockout of B-raf kinase leads to deficits in hippocampal long-term potentiation, learning, and memory.

    Science.gov (United States)

    Chen, Adele P; Ohno, Masuo; Giese, K Peter; Kühn, Ralf; Chen, Rachel L; Silva, Alcino J

    2006-01-01

    Raf kinases are downstream effectors of Ras and upstream activators of the MEK-ERK cascade. Ras and MEK-ERK signaling play roles in learning and memory (L&M) and neural plasticity, but the roles of Raf kinases in L&M and plasticity are unclear. Among Raf isoforms, B-raf is preferentially expressed in the brain. To determine whether B-raf has a role in synaptic plasticity and L&M, we used the Cre-LoxP gene targeting system to derive forebrain excitatory neuron B-raf knockout mice. This conditional knockout resulted in deficits in ERK activation and hippocampal long-term potentiation (LTP) and impairments in hippocampus-dependent L&M, including spatial learning and contextual discrimination. Despite the widespread expression of B-raf, this mutation did not disrupt other forms of L&M, such as cued fear conditioning and conditioned taste aversion. Our findings demonstrate that B-raf plays a role in hippocampal ERK activation, synaptic plasticity, and L&M.

  3. Lack of LTP-like plasticity in primary motor cortex in Parkinson's disease.

    Science.gov (United States)

    Suppa, A; Marsili, L; Belvisi, D; Conte, A; Iezzi, E; Modugno, N; Fabbrini, G; Berardelli, A

    2011-02-01

    In this study in patients with Parkinson's disease (PD), off and on dopaminergic therapy, with and without L-dopa-induced dyskinesias (LIDs), we tested intermittent theta-burst stimulation (iTBS), a technique currently used for non-invasively inducing long-term potentiation (LTP)-like plasticity in primary motor cortex (M1). The study group comprised 20 PD patients on and off dopaminergic therapy (11 patients without and 9 patients with LIDs), and 14 age-matched healthy subjects. Patients had mild-to-moderate PD, and no additional neuropsychiatric disorders. We clinically evaluated patients using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The left M1 was conditioned with iTBS at 80% active motor threshold intensity. Twenty motor evoked potentials (MEPs) were recorded from right first interosseous muscle before and at 5, 15 and 30 min after iTBS. Between-group analysis of variance (ANOVA) testing healthy subjects versus patients with and without LIDs, on and off therapy showed a significant interaction between factors "Group" and "Time". After iTBS, MEP amplitudes in healthy subjects increased significantly at 5, 15 and 30 min (piTBS fails to increase MEP responses. This finding suggests lack of iTBS-induced LTP-like plasticity in M1 in PD regardless of patients' clinical features. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. High-Frequency Stimulation-Induced Synaptic Potentiation in Dorsal and Ventral CA1 Hippocampal Synapses: The Involvement of NMDA Receptors, mGluR5, and (L-Type) Voltage-Gated Calcium Channels

    Science.gov (United States)

    Papatheodoropoulos, Costas; Kouvaros, Stylianos

    2016-01-01

    The ability of the ventral hippocampus (VH) for long-lasting long-term potentiation (LTP) and the mechanisms underlying its lower ability for shortlasting LTP compared with the dorsal hippocampus (DH) are unknown. Using recordings of field excitatory postsynaptic potentials (EPSPs) from the CA1 field of adult rat hippocampal slices, we found that…

  5. Methamphetamine reduces LTP and increases baseline synaptic transmission in the CA1 region of mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Jarod Swant

    2010-06-01

    Full Text Available Methamphetamine (METH is an addictive psychostimulant whose societal impact is on the rise. Emerging evidence suggests that psychostimulants alter synaptic plasticity in the brain--which may partly account for their adverse effects. While it is known that METH increases the extracellular concentration of monoamines dopamine, serotonin, and norepinephrine, it is not clear how METH alters glutamatergic transmission. Within this context, the aim of the present study was to investigate the effects of acute and systemic METH on basal synaptic transmission and long-term potentiation (LTP; an activity-induced increase in synaptic efficacy in CA1 sub-field in the hippocampus. Both the acute ex vivo application of METH to hippocampal slices and systemic administration of METH decreased LTP. Interestingly, the acute ex vivo application of METH at a concentration of 30 or 60 microM increased baseline synaptic transmission as well as decreased LTP. Pretreatment with eticlopride (D2-like receptor antagonist did not alter the effects of METH on synaptic transmission or LTP. In contrast, pretreatment with D1/D5 dopamine receptor antagonist SCH23390 or 5-HT1A receptor antagonist NAN-190 abrogated the effect of METH on synaptic transmission. Furthermore, METH did not increase baseline synaptic transmission in D1 dopamine receptor haploinsufficient mice. Our findings suggest that METH affects excitatory synaptic transmission via activation of dopamine and serotonin receptor systems in the hippocampus. This modulation may contribute to synaptic maladaption induced by METH addiction and/or METH-mediated cognitive dysfunction.

  6. Pharmacological Activators of the NR4A Nuclear Receptors Enhance LTP in a CREB/CBP-Dependent Manner.

    Science.gov (United States)

    Bridi, Morgan S; Hawk, Joshua D; Chatterjee, Snehajyoti; Safe, Stephen; Abel, Ted

    2017-05-01

    Nr4a nuclear receptors contribute to long-term memory formation and are required for long-term memory enhancement by a class of broad-acting drugs known as histone deacetylase (HDAC) inhibitors. Understanding the molecular mechanisms that regulate these genes and identifying ways to increase their activity may provide novel therapeutic approaches for ameliorating cognitive dysfunction. In the present study, we find that Nr4a gene expression after learning requires the cAMP-response element binding (CREB) interaction domain of the histone acetyltransferase CREB-binding protein (CBP). These gene expression deficits emerge at a time after learning marked by promoter histone acetylation in wild-type mice. Further, mutation of the CREB-CBP interaction domain reduces Nr4a promoter acetylation after learning. As memory enhancement by HDAC inhibitors requires CREB-CBP interaction and Nr4a gene function, these data support the notion that the balance of histone acetylation at the Nr4a promoters is critical for memory formation. NR4A ligands have recently been described, but the effect of these drugs on synaptic plasticity or memory has not been investigated. We find that the 'C-DIM' NR4A ligands, para-phenyl substituted di-indolylmethane compounds, enhance long-term contextual fear memory and increase the duration of long-term potentiation (LTP), a form of hippocampal synaptic plasticity. LTP enhancement by these drugs is eliminated in mice expressing a dominant negative form of NR4A and attenuated in mice with mutation of the CREB-CBP interaction domain. These data define the molecular connection between histone acetylation and Nr4a gene expression after learning. In addition, they suggest that NR4A-activating C-DIM compounds may serve as a potent and selective means to enhance memory and synaptic plasticity.

  7. Switching On Depression and Potentiation in the Cerebellum

    Directory of Open Access Journals (Sweden)

    Andrew R. Gallimore

    2018-01-01

    Full Text Available Long-term depression (LTD and long-term potentiation (LTP in the cerebellum are important for motor learning. However, the signaling mechanisms controlling whether LTD or LTP is induced in response to synaptic stimulation remain obscure. Using a unified model of LTD and LTP at the cerebellar parallel fiber-Purkinje cell (PF-PC synapse, we delineate the coordinated pre- and postsynaptic signaling that determines the direction of plasticity. We show that LTP is the default response to PF stimulation above a well-defined frequency threshold. However, if the calcium signal surpasses the threshold for CaMKII activation, then an ultrasensitive “on switch” activates an extracellular signal-regulated kinase (ERK-based positive feedback loop that triggers LTD instead. This postsynaptic feedback loop is sustained by another, trans-synaptic, feedback loop that maintains nitric oxide production throughout LTD induction. When full depression is achieved, an automatic “off switch” inactivates the feedback loops, returning the network to its basal state and demarcating the end of the early phase of LTD.

  8. Stress enhances fear by forming new synapses with greater capacity for long-term potentiation in the amygdala.

    Science.gov (United States)

    Suvrathan, Aparna; Bennur, Sharath; Ghosh, Supriya; Tomar, Anupratap; Anilkumar, Shobha; Chattarji, Sumantra

    2014-01-05

    Prolonged and severe stress leads to cognitive deficits, but facilitates emotional behaviour. Little is known about the synaptic basis for this contrast. Here, we report that in rats subjected to chronic immobilization stress, long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated synaptic responses are enhanced in principal neurons of the lateral amygdala, a brain area involved in fear memory formation. This is accompanied by electrophysiological and morphological changes consistent with the formation of 'silent synapses', containing only NMDARs. In parallel, chronic stress also reduces synaptic inhibition. Together, these synaptic changes would enable amygdalar neurons to undergo further experience-dependent modifications, leading to stronger fear memories. Consistent with this prediction, stressed animals exhibit enhanced conditioned fear. Hence, stress may leave its mark in the amygdala by generating new synapses with greater capacity for plasticity, thereby creating an ideal neuronal substrate for affective disorders. These findings also highlight the unique features of stress-induced plasticity in the amygdala that are strikingly different from the stress-induced impairment of structure and function in the hippocampus.

  9. Methylprednisolone as a memory enhancer in rats: Effects on aversive memory, long-term potentiation and calcium influx.

    Science.gov (United States)

    de Vargas, Liane da Silva; Gonçalves, Rithiele; Lara, Marcus Vinícius S; Costa-Ferro, Zaquer S M; Salamoni, Simone Denise; Domingues, Michelle Flores; Piovesan, Angela Regina; de Assis, Dênis Reis; Vinade, Lucia; Corrado, Alexandre P; Alves-Do-Prado, Wilson; Correia-de-Sá, Paulo; da Costa, Jaderson Costa; Izquierdo, Ivan; Dal Belo, Cháriston A; Mello-Carpes, Pâmela B

    2017-09-01

    It is well recognized that stress or glucocorticoids hormones treatment can modulate memory performance in both directions, either impairing or enhancing it. Despite the high number of studies aiming at explaining the effects of glucocorticoids on memory, this has not yet been completely elucidated. Here, we demonstrate that a low daily dose of methylprednisolone (MP, 5mg/kg, i.p.) administered for 10-days favors aversive memory persistence in adult rats, without any effect on the exploring behavior, locomotor activity, anxiety levels and pain perception. Enhanced performance on the inhibitory avoidance task was correlated with long-term potentiation (LTP), a phenomenon that was strengthen in hippocampal slices of rats injected with MP (5mg/kg) during 10days. Additionally, in vitro incubation with MP (30-300µM) concentration-dependently increased intracellular [Ca 2+ ] i in cultured hippocampal neurons depolarized by KCl (35mM). In conclusion, a low daily dose of MP for 10days may promote aversive memory persistence in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Depotentiation from potentiated synaptic strength in a tristable system of coupled phosphatase and kinase

    Directory of Open Access Journals (Sweden)

    Mengjiao Chen

    2016-10-01

    Full Text Available Long-term potentiation (LTP of synaptic strength is strongly implicated in learning and memory. On the other hand, depotentiation, the reversal of synaptic strength from potentiated LTP state to the pre-LTP level, is required in extinction of the obsolete memory. A generic tristable system, which couples the phosphatase and kinase switches, exclusively explains how moderate and high elevation of intracellular calcium concentration triggers long-term depression (LTD and LTP, respectively. The present study, introducing calcium influx and calcium release from internal store into the tristable system, further show that significant elevation of cytoplasmic calcium concentration switches activation of both kinase and phosphatase to their basal states, thereby depotentiate the synaptic strength. A phase-plane analysis of the combined model was employed to explain the previously reported depotentiation in experiments and predict a threshold-like effect with calcium concentration. The results not only reveal a mechanism of NMDAR- and mGluR-dependent depotentiation, but also predict further experiments about the role of internal calcium store in induction of depotentiation and extinction of established memories.

  11. The effects of CCK-8S on spatial memory and long-term potentiation at CA1 during induction of stress in rats

    Directory of Open Access Journals (Sweden)

    Malihe Sadeghi

    2017-12-01

    Full Text Available Objective(s: Cholecystokinin (CCK has been proposed as a mediator in stress. However, it is still not fully documented what are its effects. We aimed to evaluate the effects of systemic administration of CCK exactly before induction of stress on spatial memory and synaptic plasticity at CA1 in rats. Materials and Methods: Male Wistar rats were divided into 4 groups: the control, the control-CCK, the stress and the stress-CCK. Restraint stress was induced 6 hr per day, for 24 days. Cholecystokinin sulfated octapeptide (CCK-8S was injected (1.6 µg/kg, IP before each session of stress induction. Spatial memory was evaluated by Morris water maze test. Long term potentiation (LTP in Schaffer collateral-CA1 synapses was assessed (by 100 Hz tetanization in order to investigate synaptic plasticity. Results: Stress impaired spatial memory significantly (P

  12. The upgraded LTP-V at SLS

    Energy Technology Data Exchange (ETDEWEB)

    Flechsig, U., E-mail: uwe.flechsig@psi.ch [Paul Scherrer Institut, Swiss Light Source, 5232 Villigen-PSI (Switzerland); Jaggi, A.; Krempaský, J.; Spielmann, S.; Thominet, V. [Paul Scherrer Institut, Swiss Light Source, 5232 Villigen-PSI (Switzerland)

    2013-05-11

    Since 2005 the Swiss Light Source (SLS) has been operating a Long Trace Profiler (LTP)-V from Ocean Optics in its metrology laboratory to measure the synchrotron optics for SLS. In 2012 we finished a significant upgrade to improve the accuracy, reliability and measurement efficiency in particular for the calibration of adaptive optics. Folding mirrors with figure errors <λ/100 and an additional linear encoder have been installed, the 1d CCD detector with 2048 pixels has been replaced by a 16 mega-pixel CCD camera with gigabit ethernet interface GigE, the monolithic software has been replaced by a modular, full- EPICS compatible system based on a new LTP plugin for the areaDetector software for image processing. The plugin allows slope determination in real time i.e. per frame.

  13. SNAP-25 in hippocampal CA3 region is required for long-term memory formation

    International Nuclear Information System (INIS)

    Hou Qiuling; Gao Xiang; Lu Qi; Zhang Xuehan; Tu Yanyang; Jin Meilei; Zhao Guoping; Yu Lei; Jing Naihe; Li Baoming

    2006-01-01

    SNAP-25 is a synaptosomal protein of 25 kDa, a key component of synaptic vesicle-docking/fusion machinery, and plays a critical role in exocytosis and neurotransmitter release. We previously reported that SNAP-25 in the hippocampal CA1 region is involved in consolidation of contextual fear memory and water-maze spatial memory (Hou et al. European J Neuroscience, 20: 1593-1603, 2004). SNAP-25 is expressed not only in the CA1 region, but also in the CA3 region, and the SNAP-25 mRNA level in the CA3 region is higher than in the CA1 region. Here, we provide evidence that SNAP-25 in the CA3 region is also involved in learning/memory. Intra-CA3 infusion of SNAP-25 antisense oligonucleotide impaired both long-term contextual fear memory and water-maze spatial memory, with short-term memory intact. Furthermore, the SNAP-25 antisense oligonucleotide suppressed the long-term potentiation (LTP) of field excitatory post-synaptic potential (fEPSP) in the mossy-fiber pathway (DG-CA3 pathway), with no effect on paired-pulse facilitation of the fEPSP. These results are consistent with the notion that SNAP-25 in the hippocampal CA3 region is required for long-term memory formation

  14. Weakened Intracellular Zn2+-Buffering in the Aged Dentate Gyrus and Its Involvement in Erasure of Maintained LTP.

    Science.gov (United States)

    Takeda, Atsushi; Tamano, Haruna; Murakami, Taku; Nakada, Hiroyuki; Minamino, Tatsuya; Koike, Yuta

    2018-05-01

    Memory is lost by the increased influx of extracellular Zn 2+ into neurons. It is possible that intracellular Zn 2+ dynamics is modified even at non-zincergic medial perforant pathway-dentate granule cell synapses along with aging and that vulnerability to the modification is linked to age-related cognitive decline. To examine these possibilities, vulnerability of long-term potentiation (LTP) maintenance, which underlies memory retention, to modification of synaptic Zn 2+ dynamics was compared between young and aged rats. The influx of extracellular Zn 2+ into dentate granule cells was increased in aged rats after injection of high K + into the dentate gyrus, but not in young rats. This increase impaired maintained LTP in aged rats. However, the impairment was rescued by co-injection of CaEDTA, an extracellular Zn 2+ chelator, or CNQX, an AMPA receptor antagonist, which suppressed the Zn 2+ influx. Maintained LTP was also impaired in aged rats after injection of ZnAF-2DA into the dentate gyrus that chelates intracellular Zn 2+ , but not in young rats. Interestingly, the capacity of chelating intracellular Zn 2+ with intracellular ZnAF-2 was almost lost in the aged dentate gyrus 2 h after injection of ZnAF-2DA into the dentate gyrus, suggesting that intracellular Zn 2+ -buffering is weakened in the aged dentate gyrus, compared to the young dentate gyrus. In the dentate gyrus of aged rats, maintained LTP is more vulnerable to modification of intracellular Zn 2+ dynamics than in young rats, probably due to weakened intracellular Zn 2+ -buffering.

  15. Anodal tDCS over the Primary Motor Cortex Facilitates Long-Term Memory Formation Reflecting Use-Dependent Plasticity.

    Directory of Open Access Journals (Sweden)

    Orjon Rroji

    Full Text Available Previous research suggests that anodal transcranial direct current stimulation (tDCS over the primary motor cortex (M1 modulates NMDA receptor dependent processes that mediate synaptic plasticity. Here we test this proposal by applying anodal versus sham tDCS while subjects practiced to flex the thumb as fast as possible (ballistic movements. Repetitive practice of this task has been shown to result in performance improvements that reflect use-dependent plasticity resulting from NMDA receptor mediated, long-term potentiation (LTP-like processes. Using a double-blind within-subject cross-over design, subjects (n=14 participated either in an anodal or a sham tDCS session which were at least 3 months apart. Sham or anodal tDCS (1 mA was applied for 20 min during motor practice and retention was tested 30 min, 24 hours and one week later. All subjects improved performance during each of the two sessions (p < 0.001 and learning gains were similar. Our main result is that long term retention performance (i.e. 1 week after practice was significantly better when practice was performed with anodal tDCS than with sham tDCS (p < 0.001. This effect was large (Cohen's d=1.01 and all but one subject followed the group trend. Our data strongly suggest that anodal tDCS facilitates long-term memory formation reflecting use-dependent plasticity. Our results support the notion that anodal tDCS facilitates synaptic plasticity mediated by an LTP-like mechanism, which is in accordance with previous research.

  16. Excess influx of Zn(2+) into dentate granule cells affects object recognition memory via attenuated LTP.

    Science.gov (United States)

    Suzuki, Miki; Fujise, Yuki; Tsuchiya, Yuka; Tamano, Haruna; Takeda, Atsushi

    2015-08-01

    The influx of extracellular Zn(2+) into dentate granule cells is nonessential for dentate gyrus long-term potentiation (LTP) and the physiological significance of extracellular Zn(2+) dynamics is unknown in the dentate gyrus. Excess increase in extracellular Zn(2+) in the hippocampal CA1, which is induced with excitation of zincergic neurons, induces memory deficit via excess influx of Zn(2+) into CA1 pyramidal cells. In the present study, it was examined whether extracellular Zn(2+) induces object recognition memory deficit via excess influx of Zn(2+) into dentate granule cells. KCl (100 mM, 2 µl) was locally injected into the dentate gyrus. The increase in intracellular Zn(2+) in dentate granule cells induced with high K(+) was blocked by co-injection of CaEDTA and CNQX, an extracellular Zn(2+) chelator and an AMPA receptor antagonist, respectively, suggesting that high K(+) increases the influx of Zn(2+) into dentate granule cells via AMPA receptor activation. Dentate gyrus LTP induction was attenuated 1 h after KCl injection into the dentate gyrus and also attenuated when KCl was injected 5 min after the induction. Memory deficit was induced when training of object recognition test was performed 1 h after KCl injection into the dentate gyrus and also induced when KCl was injected 5 min after the training. High K(+)-induced impairments of LTP and memory were rescued by co-injection of CaEDTA. These results indicate that excess influx of Zn(2+) into dentate granule cells via AMPA receptor activation affects object recognition memory via attenuated LTP induction. Even in the dentate gyrus where is scarcely innervated by zincergic neurons, it is likely that extracellular Zn(2+) homeostasis is strictly regulated for cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-03-01

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

  18. Ginsenoside Rg1 ameliorates hippocampal long-term potentiation and memory in an Alzheimer's disease model.

    Science.gov (United States)

    Li, Fengling; Wu, Xiqing; Li, Jing; Niu, Qingliang

    2016-06-01

    The complex etiopathogenesis of Alzheimer's disease (AD) has limited progression in the identification of effective therapeutic agents. Amyloid precursor protein (APP) and presenilin‑1 (PS1) are always overexpressed in AD, and are considered to be the initiators of the formation of β‑amyloid plaques and the symptoms of AD. In the present study, a transgenic AD model, constructed via the overexpression of APP and PS1, was used to verify the protective effects of ginsenoside Rg1 on memory performance and synaptic plasticity. AD mice (6‑month‑old) were treated via intraperitoneal injection of 0.1‑10 mg/kg ginsenoside Rg1. Long‑term memory, synaptic plasticity, and the levels of AD‑associated and synaptic plasticity‑associated proteins were measured following treatment. Memory was measured using a fear conditioning task and protein expression levels were investigated using western blotting. All the data was analyzed by one-way analysis of variance or t‑test. Following 30 days of consecutive treatment, memory in the AD mouse model was ameliorated in the 10 mg/kg ginsenoside Rg1 treatment group. As demonstrated by biochemical experiments, ginsenoside Rg1 treatment reduced the accumulations of β‑amyloid 1‑42 and phosphorylated (p)‑Tau in the AD model. Additionally, brain-derived neurotrophic factor (BDNF) and p‑TrkB synaptic plasticity‑associated proteins were upregulated following ginsenoside Rg1 application. Correspondingly, long‑term potentiation (LTP) was restored following ginsenoside Rg1 application in the AD mice model. Taken together, ginsenoside Rg1 repaired hippocampal LTP and memory, likely through facilitating the clearance of AD‑associated proteins and through activation of the BDNF‑TrkB pathway. Therefore, ginsenoside Rg1 may be a candidate drug for the treatment of AD.

  19. Two-Stage Translational Control of Dentate Gyrus LTP Consolidation Is Mediated by Sustained BDNF-TrkB Signaling to MNK

    Directory of Open Access Journals (Sweden)

    Debabrata Panja

    2014-11-01

    Full Text Available BDNF signaling contributes to protein-synthesis-dependent synaptic plasticity, but the dynamics of TrkB signaling and mechanisms of translation have not been defined. Here, we show that long-term potentiation (LTP consolidation in the dentate gyrus of live rodents requires sustained (hours BDNF-TrkB signaling. Surprisingly, this sustained activation maintains an otherwise labile signaling pathway from TrkB to MAP-kinase-interacting kinase (MNK. MNK activity promotes eIF4F translation initiation complex formation and protein synthesis in mechanistically distinct early and late stages. In early-stage translation, MNK triggers release of the CYFIP1/FMRP repressor complex from the 5′-mRNA cap. In late-stage translation, MNK regulates the canonical translational repressor 4E-BP2 in a synapse-compartment-specific manner. This late stage is coupled to MNK-dependent enhanced dendritic mRNA translation. We conclude that LTP consolidation in the dentate gyrus is mediated by sustained BDNF signaling to MNK and MNK-dependent regulation of translation in two functionally and mechanistically distinct stages.

  20. Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

    Science.gov (United States)

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

    2011-01-01

    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

  1. HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner

    Science.gov (United States)

    Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

    2011-01-01

    Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory. PMID:21224411

  2. Calcitonin gene-related peptide erases the fear memory and facilitates long-term potentiation in the central nucleus of the amygdala in rats.

    Science.gov (United States)

    Wu, Xin; Zhang, Jie-Ting; Liu, Jue; Yang, Si; Chen, Tao; Chen, Jian-Guo; Wang, Fang

    2015-11-01

    Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide, which plays a critical role in the central nervous system. CGRP binds to G protein-coupled receptors, including CGRP1, which couples positively to adenylyl cyclase (AC) and protein kinase A (PKA) activation. CGRP and CGRP1 receptors are enriched in central nucleus of the amygdala (CeA), the main part of the amygdala, which regulates conditioned fear memories. Here, we reported the importance of CGRP and CGRP1 receptor for synaptic plasticity in the CeA and the extinction of fear memory in rats. Our electrophysiological and behavioral in vitro and in vivo results showed exogenous application of CGRP induced an immediate and lasting long-term potentiation in the basolateral nucleus of amygdala-CeA pathway, but not in the lateral nucleus of amygdala-CeA pathway, while bilateral intra-CeA infusion CGRP (0, 5, 13 and 21 μM/side) dose dependently enhanced fear memory extinction. The effects were blocked by CGRP1 receptor antagonist (CGRP8-37 ), N-methyl-d-aspartate receptors antagonist MK801 and PKA inhibitor H89. These results demonstrate that CGRP can lead to long-term potentiation of basolateral nucleus of amygdala-CeA pathway through a PKA-dependent postsynaptic mechanism that involved N-methyl-d-aspartate receptors and enhance the extinction of fear memory in rats. Together, the results strongly support a pivotal role of CGRP in the synaptic plasticity of CeA and extinction of fear memory. Calcitonin gene-related peptide (CGRP) plays an essential role in synaptic plasticity in the amygdala and fear memory. We found that CGRP-induced chemical long-term potentiation (LTP) in a dose-dependent way in the BLA-CeA (basolateral and central nucleus of amygdala, respectively) pathway and enhanced fear memory extinction in rats through a protein kinase A (PKA)-dependent postsynaptic mechanism that involved NMDA receptors. These results support a pivotal role of CGRP in amygdala. © 2015 International

  3. Deficits in LTP induction by 5-HT2A receptor antagonist in a mouse model for fragile X syndrome.

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    Zhao-hui Xu

    Full Text Available Fragile X syndrome is a common inherited form of mental retardation caused by the lack of fragile X mental retardation protein (FMRP because of Fmr1 gene silencing. Serotonin (5-HT is significantly increased in the null mutants of Drosophila Fmr1, and elevated 5-HT brain levels result in cognitive and behavioral deficits in human patients. The serotonin type 2A receptor (5-HT2AR is highly expressed in the cerebral cortex; it acts on pyramidal cells and GABAergic interneurons to modulate cortical functions. 5-HT2AR and FMRP both regulate synaptic plasticity. Therefore, the lack of FMRP may affect serotoninergic activity. In this study, we determined the involvement of FMRP in the 5-HT modulation of synaptic potentiation with the use of primary cortical neuron culture and brain slice recording. Pharmacological inhibition of 5-HT2AR by R-96544 or ketanserin facilitated long-term potentiation (LTP in the anterior cingulate cortex (ACC of WT mice. The prefrontal LTP induction was dependent on the activation of NMDARs and elevation of postsynaptic Ca(2+ concentrations. By contrast, inhibition of 5-HT2AR could not restore the induction of LTP in the ACC of Fmr1 knock-out mice. Furthermore, 5-HT2AR inhibition induced AMPA receptor GluR1 subtype surface insertion in the cultured ACC neurons of Fmr1 WT mice, however, GluR1 surface insertion by inhibition of 5-HT2AR was impaired in the neurons of Fmr1KO mice. These findings suggested that FMRP was involved in serotonin receptor signaling and contributed in GluR1 surface expression induced by 5-HT2AR inactivation.

  4. LTP-like plasticity in the visual system and in the motor system appear related in young and healthy subjects

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    Stefan eKlöppel

    2015-09-01

    Full Text Available LTP-like plasticity measured by visual evoked potentials (VEP can be induced in the intact human brain by presenting checkerboard reversals. Also associated with LTP-like plasticity, around two third of participants respond to transcranial magnetic stimulation with a paired-associate stimulation (PAS protocol with a potentiation of their motor evoked potentials. LTP-like processes are also required for verbal and motor learning tasks. We compared effect sizes, responder rates and intercorrelations as well as the potential influence of attention between these four assessments in a group of 37 young and healthy volunteers. We observed a potentiation effect of the N75 and P100 VEP component which positively correlated with plasticity induced by PAS. Subjects with a better subjective alertness were more likely to show PAS and VEP potentiation. No correlation was found between the other assessments. Effect sizes and responder rates of VEP potentiation were higher compared to PAS. Our results indicate a high variability of LTP-like effects and no evidence for a system-specific nature. As a consequence, studies wishing to assess individual levels of LTP-like plasticity should employ a combination of multiple assessments.

  5. PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.

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    Peter Serrano

    2008-12-01

    Full Text Available How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta, an autonomously active atypical protein kinase C (PKC isoform critical for the maintenance of long-term potentiation (LTP. PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH and basolateral amygdala (BLA on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise

  6. PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.

    Science.gov (United States)

    Serrano, Peter; Friedman, Eugenia L; Kenney, Jana; Taubenfeld, Stephen M; Zimmerman, Joshua M; Hanna, John; Alberini, Cristina; Kelley, Ann E; Maren, Stephen; Rudy, Jerry W; Yin, Jerry C P; Sacktor, Todd C; Fenton, André A

    2008-12-23

    How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta), an autonomously active atypical protein kinase C (PKC) isoform critical for the maintenance of long-term potentiation (LTP). PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP) by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH) and basolateral amygdala (BLA) on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US) associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise, or

  7. Boosting the LTP-like plasticity effect of intermittent theta-burst stimulation using gamma transcranial alternating current stimulation.

    Science.gov (United States)

    Guerra, Andrea; Suppa, Antonio; Bologna, Matteo; D'Onofrio, Valentina; Bianchini, Edoardo; Brown, Peter; Di Lazzaro, Vincenzo; Berardelli, Alfredo

    2018-03-24

    Transcranial Alternating Current Stimulation (tACS) consists in delivering electric current to the brain using an oscillatory pattern that may entrain the rhythmic activity of cortical neurons. When delivered at gamma frequency, tACS modulates motor performance and GABA-A-ergic interneuron activity. Since interneuronal discharges play a crucial role in brain plasticity phenomena, here we co-stimulated the primary motor cortex (M1) in healthy subjects by means of tACS during intermittent theta-burst stimulation (iTBS), a transcranial magnetic stimulation paradigm known to induce long-term potentiation (LTP)-like plasticity. We measured and compared motor evoked potentials before and after gamma, beta and sham tACS-iTBS. While we delivered gamma-tACS, we also measured short-interval intracortical inhibition (SICI) to detect any changes in GABA-A-ergic neurotransmission. Gamma, but not beta and sham tACS, significantly boosted and prolonged the iTBS-induced after-effects. Interestingly, the extent of the gamma tACS-iTBS after-effects correlated directly with SICI changes. Overall, our findings point to a link between gamma oscillations, interneuronal GABA-A-ergic activity and LTP-like plasticity in the human M1. Gamma tACS-iTBS co-stimulation might represent a new strategy to enhance and prolong responses to plasticity-inducing protocols, thereby lending itself to future applications in the neurorehabilitation setting. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Potentially inappropriate prescriptions for older patients in long-term care

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    Laurin Danielle

    2004-10-01

    Full Text Available Abstract Background Inappropriate medication use is a major healthcare issue for the elderly population. This study explored the prevalence of potentially inappropriate prescriptions (PIPs in long-term care in metropolitan Quebec. Methods A cross sectional chart review of 2,633 long-term care older patients of the Quebec City area was performed. An explicit criteria list for PIPs was developed based on the literature and validated by a modified Delphi method. Medication orders were reviewed to describe prescribing patterns and to determine the prevalence of PIPs. A multivariate analysis was performed to identify predictors of PIPs. Results Almost all residents (94.0% were receiving one or more prescribed medication; on average patients had 4.8 prescribed medications. A majority (54.7% of treated patients had a potentially inappropriate prescription (PIP. Most common PIPs were drug interactions (33.9% of treated patients, followed by potentially inappropriate duration (23.6%, potentially inappropriate medication (14.7% and potentially inappropriate dosage (9.6%. PIPs were most frequent for medications of the central nervous system (10.8% of prescribed medication. The likelihood of PIP increased significantly as the number of drugs prescribed increased (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.33 – 1.43 and with the length of stay (OR: 1.78, CI: 1.43 – 2.20. On the other hand, the risk of receiving a PIP decreased with age. Conclusion Potentially inappropriate prescribing is a serious problem in the highly medicated long-term care population in metropolitan Quebec. Use of explicit criteria lists may help identify the most critical issues and prioritize interventions to improve quality of care and patient safety.

  9. Loss of long-term depression in the insular cortex after tail amputation in adult mice.

    Science.gov (United States)

    Liu, Ming-Gang; Zhuo, Min

    2014-01-08

    The insular cortex (IC) is an important forebrain structure involved in pain perception and taste memory formation. Using a 64-channel multi-electrode array system, we recently identified and characterized two major forms of synaptic plasticity in the adult mouse IC: long-term potentiation (LTP) and long-term depression (LTD). In this study, we investigate injury-related metaplastic changes in insular synaptic plasticity after distal tail amputation. We found that tail amputation in adult mice produced a selective loss of low frequency stimulation-induced LTD in the IC, without affecting (RS)-3,5-dihydroxyphenylglycine (DHPG)-evoked LTD. The impaired insular LTD could be pharmacologically rescued by priming the IC slices with a lower dose of DHPG application, a form of metaplasticity which involves activation of protein kinase C but not protein kinase A or calcium/calmodulin-dependent protein kinase II. These findings provide important insights into the synaptic mechanisms of cortical changes after peripheral amputation and suggest that restoration of insular LTD may represent a novel therapeutic strategy against the synaptic dysfunctions underlying the pathophysiology of phantom pain.

  10. Enhanced sensitivity to ethanol-induced inhibition of LTP in CA1 pyramidal neurons of socially isolated C57BL/6J mice: role of neurosteroids

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    Giuseppe eTalani

    2011-10-01

    Full Text Available Ethanol (EtOH–induced impairment of long-term potentiation (LTP in the rat hippocampus is prevented by the 5α-reductase inhibitor finasteride, suggesting that this effect of EtOH is dependent on the increased local release of neurosteroids such as 3α,5α-THP that promote GABA–mediated transmission. Given that social isolation (SI in rodents is associated with altered plasma and brain levels of such neurosteroids as well as with an enhanced neurosteroidogenic action of EtOH, we examined whether the inhibitory effect of EtOH on LTP at CA3-CA1 hippocampal excitatory synapses is altered in C57BL/6J mice subjected to SI for 6 weeks in comparison with group-housed (GH animals. Extracellular recording of fEPSPs as well as patch-clamp analysis were performed in hippocampal slices prepared from both SI and GH mice. Consistent with previous observations, recording of fEPSPs revealed that the extent of LTP induced in the CA1 region of SI mice was significantly reduced compared with that in GH animals. EtOH (40 mM inhibited LTP in slices from SI mice but not in those from GH mice, and this effect of EtOH was abolished by co-application of 1 µM finasteride. Current-clamp analysis of CA1 pyramidal neurons revealed a decrease in action potential frequency and an increase in the intensity of injected current required to evoke the first action potential in SI mice compared with GH mice, indicative of a decrease in neuronal excitability associated with SI. Together, our data suggest that SI results in reduced levels of neuronal excitability and synaptic plasticity in the hippocampus. Furthermore, the increased sensitivity to the neurosteroidogenic effect of EtOH associated with SI likely accounts for the greater inhibitory effect of EtOH on LTP in SI mice. The increase in EtOH sensitivity induced by SI may be important for the changes in the effects of EtOH on anxiety and on learning and memory associated with the prolonged stress attributable to social

  11. Elevation of endogenous anandamide impairs LTP, learning, and memory through CB1 receptor signaling in mice.

    Science.gov (United States)

    Basavarajappa, Balapal S; Nagre, Nagaraja N; Xie, Shan; Subbanna, Shivakumar

    2014-07-01

    In rodents, many exogenous and endogenous cannabinoids, such as anandamide (AEA) and 2-arachidonyl glycerol (2-AG), have been shown to play an important role in certain hippocampal memory processes. However, the mechanisms by which endogenous AEA regulate this processes are not well understood. Here the effects of AEA on long-term potentiation (LTP), hippocampal-dependent learning and memory tasks, pERK1/2, pCaMKIV, and pCREB signaling events in both cannabinoid receptor type 1 (CB1R) wild-type (WT) and knockout (KO) mice were assessed following administration of URB597, an inhibitor of the fatty acid amide hydrolase (FAAH). Acute administration of URB597 enhanced AEA levels without affecting the levels of 2-AG or CB1R in the hippocampus and neocortex as compared to vehicle. In hippocampal slices, URB597 impaired LTP in CB1R WT but not in KO littermates. URB597 impaired object recognition, spontaneous alternation and spatial memory in the Y-maze test in CB1R WT mice but not in KO mice. Furthermore, URB597 enhanced ERK phosphorylation in WT without affecting total ERK levels in WT or KO mice. URB597 impaired CaMKIV and CREB phosphorylation in WT but not in KO mice. CB1R KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio as compared to WT littermates. Our results indicate that pharmacologically elevated AEA impair LTP, learning and memory and inhibit CaMKIV and CREB phosphorylation, via the activation of CB1Rs. Collectively, these findings also suggest that pharmacological elevation of AEA beyond normal concentrations is also detrimental for the underlying physiological responses. © 2014 Wiley Periodicals, Inc.

  12. SPIN90 Modulates Long-Term Depression and Behavioral Flexibility in the Hippocampus

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    Dae Hwan Kim

    2017-09-01

    Full Text Available The importance of actin-binding proteins (ABPs in the regulation of synapse morphology and plasticity has been well established. SH3 protein interacting with Nck, 90 kDa (SPIN90, an Nck-interacting protein highly expressed in synapses, is essential for actin remodeling and dendritic spine morphology. Synaptic targeting of SPIN90 to spine heads or dendritic shafts depends on its phosphorylation state, leading to blockage of cofilin-mediated actin depolymerization and spine shrinkage. However, the physiological role of SPIN90 in long-term plasticity, learning and memory are largely unknown. In this study, we demonstrate that Spin90-knockout (KO mice exhibit substantial deficits in synaptic plasticity and behavioral flexibility. We found that loss of SPIN90 disrupted dendritic spine density in CA1 neurons of the hippocampus and significantly impaired long-term depression (LTD, leaving basal synaptic transmission and long-term potentiation (LTP intact. These impairments were due in part to deficits in AMPA receptor endocytosis and its pre-requisites, GluA1 dephosphorylation and postsynaptic density (PSD 95 phosphorylation, but also by an intrinsic activation of Akt-GSK3β signaling as a result of Spin90-KO. In accordance with these defects, mice lacking SPIN90 were found to carry significant deficits in object-recognition and behavioral flexibility, while learning ability was largely unaffected. Collectively, these findings demonstrate a novel modulatory role for SPIN90 in hippocampal LTD and behavioral flexibility.

  13. Long term effects on potential repository sites: occurrence and diagenesis of anhydrite

    International Nuclear Information System (INIS)

    Bath, A.H.; George, I.A.; Milodowski, A.E.; Darling, W.G.

    1985-10-01

    The report deals with the long-term behaviour of anhydrite as a potential host rock for deep disposal of intermediate-level radioactive wastes. The principal long-term effect on the integrity of such a repository is the possibility of penetration of groundwater and consequent transformation to gypsum. Therefore, in order to assess the chydrological and geochemical processes of hydration in detail, mineralogical and geochemical analyses have been carried out on anhydrite samples in a drillcore taken near Darlington, United Kingdom. The results are discussed in terms of the long-term integrity of anhydrite as a repository site. (U.K.)

  14. Short- and long-term cognitive effects of chronic cannabinoids administration in late-adolescence rats.

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    Hila Abush

    Full Text Available The use of cannabis can impair cognitive function, especially short-term memory. A controversial question is whether long-term cannabis use during the late-adolescence period can cause irreversible deficits in higher brain function that persist after drug use stops. In order to examine the short- and long-term effects of chronic exposure to cannabinoids, rats were administered chronic i.p. treatment with the CB1/CB2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg for two weeks during the late adolescence period (post-natal days 45-60 and tested for behavioral and electrophysiological measures of cognitive performance 24 hrs, 10 and 30 days after the last drug injection. The impairing effects of chronic WIN on short-term memory in the water maze and the object recognition tasks as well as long-term potentiation (LTP in the ventral subiculum (vSub-nucleus accumbens (NAc pathway were temporary as they lasted only 24 h or 10 d after withdrawal. However, chronic WIN significantly impaired hippocampal dependent short-term memory measured in the object location task 24 hrs, 10, 30, and 75 days after the last drug injection. Our findings suggest that some forms of hippocampal-dependent short-term memory are sensitive to chronic cannabinoid administration but other cognitive impairments are temporary and probably result from a residue of cannabinoids in the brain or acute withdrawal effects from cannabinoids. Understanding the effects of cannabinoids on cognitive function may provide us with tools to overcome these impairments and for cannabinoids to be more favorably considered for clinical use.

  15. NMDA receptor subunits in the adult rat hippocampus undergo similar changes after 5 minutes in an open field and after LTP induction.

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    Maria Veronica Baez

    Full Text Available NMDA receptor subunits change during development and their synaptic expression is modified rapidly after synaptic plasticity induction in hippocampal slices. However, there is scarce information on subunits expression after synaptic plasticity induction or memory acquisition, particularly in adults. GluN1, GluN2A and GluN2B NMDA receptor subunits were assessed by western blot in 1 adult rats that had explored an open field (OF for 5 minutes, a time sufficient to induce habituation, 2 mature rat hippocampal neuron cultures depolarized by KCl and 3 hippocampal slices from adult rats where long term potentiation (LTP was induced by theta-burst stimulation (TBS. GluN1 and GluN2A, though not GluN2B, were significantly higher 70 minutes--but not 30 minutes--after a 5 minutes session in an OF. GluN1 and GluN2A total immunofluorescence and puncta in neurites increased in cultures, as evaluated 70 minutes after KCl stimulation. Similar changes were found in hippocampal slices 70 minutes after LTP induction. To start to explore underlying mechanisms, hippocampal slices were treated either with cycloheximide (a translation inhibitor or actinomycin D (a transcription inhibitor during electrophysiological assays. It was corroborated that translation was necessary for LTP induction and expression. The rise in GluN1 depends on transcription and translation, while the increase in GluN2A appears to mainly depend on translation, though a contribution of some remaining transcriptional activity during actinomycin D treatment could not be rouled out. LTP effective induction was required for the subunits to increase. Although in the three models same subunits suffered modifications in the same direction, within an apparently similar temporal course, further investigation is required to reveal if they are related processes and to find out whether they are causally related with synaptic plasticity, learning and memory.

  16. Harmonic Enhancement in Low Bitrate Audio Coding Using an Efficient Long-Term Predictor

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    Song Jeongook

    2010-01-01

    Full Text Available This paper proposes audio coding using an efficient long-term prediction method to enhance the perceptual quality of audio codecs to speech input signals at low bit-rates. The MPEG-4 AAC-LTP exploited a similar concept, but its improvement was not significant because of small prediction gain due to long prediction lags and aliased components caused by the transformation with a time-domain aliasing cancelation (TDAC technique. The proposed algorithm increases the prediction gain by employing a deharmonizing predictor and a long-term compensation filter. The look-back memory elements are first constructed by applying the de-harmonizing predictor to the input signal, then the prediction residual is encoded and decoded by transform audio coding. Finally, the long-term compensation filter is applied to the updated look-back memory of the decoded prediction residual to obtain synthesized signals. Experimental results show that the proposed algorithm has much lower spectral distortion and higher perceptual quality than conventional approaches especially for harmonic signals, such as voiced speech.

  17. LTP - LISA technology package: Development challenges of a spaceborne fundamental physics experiment

    International Nuclear Information System (INIS)

    Gerndt, R

    2009-01-01

    The LISA Technology Package (LTP) is the main payload onboard the LISA Pathfinder Spacecraft. The LTP Instrument together with the Drag-Free Attitude Control System (DFACS) and the respective LTP and DFACS operational software forms the LTP Experiment. It is completed by the FEEPs of the LPF spacecraft that are controlled by DFACS in order to control the spacecraft's attitude along with the experiment's needs. This article concentrates on aspects of the Industrial development of the LTP Instrument items and on essential performance issues of LTP. Examples of investigations on specific issue will highlight the kind of special problems to be solved for LTP in close cooperation with the Scientific Community.

  18. Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory

    Science.gov (United States)

    Maher, Pamela; Akaishi, Tatsuhiro; Abe, Kazuho

    2006-01-01

    Small molecules that activate signaling pathways used by neurotrophic factors could be useful for treating CNS disorders. Here we show that the flavonoid fisetin activates ERK and induces cAMP response element-binding protein (CREB) phosphorylation in rat hippocampal slices, facilitates long-term potentiation in rat hippocampal slices, and enhances object recognition in mice. Together, these data demonstrate that the natural product fisetin can facilitate long-term memory, and therefore it may be useful for treating patients with memory disorders. PMID:17050681

  19. LTP - LISA technology package: Development challenges of a spaceborne fundamental physics experiment

    Energy Technology Data Exchange (ETDEWEB)

    Gerndt, R, E-mail: ruediger.gerndt@astrium.eads.ne [Astrium Satellites GmbH, Claude-Dornier-Str., 88090 Immenstaad (Germany)

    2009-03-01

    The LISA Technology Package (LTP) is the main payload onboard the LISA Pathfinder Spacecraft. The LTP Instrument together with the Drag-Free Attitude Control System (DFACS) and the respective LTP and DFACS operational software forms the LTP Experiment. It is completed by the FEEPs of the LPF spacecraft that are controlled by DFACS in order to control the spacecraft's attitude along with the experiment's needs. This article concentrates on aspects of the Industrial development of the LTP Instrument items and on essential performance issues of LTP. Examples of investigations on specific issue will highlight the kind of special problems to be solved for LTP in close cooperation with the Scientific Community.

  20. Screening of agrochemicals in foodstuffs using low-temperature plasma (LTP) ambient ionization mass spectrometry.

    Science.gov (United States)

    Wiley, Joshua S; García-Reyes, Juan F; Harper, Jason D; Charipar, Nicholas A; Ouyang, Zheng; Cooks, R Graham

    2010-05-01

    Low-temperature plasma (LTP) permits direct ambient ionization and mass analysis of samples in their native environment with minimal or no prior preparation. LTP utilizes dielectric barrier discharges (DBDs) to create a low power plasma which is guided by gas flow onto the sample from which analytes are desorbed and ionized. In this study, the potential of LTP-MS for the detection of pesticide residues in food is demonstrated. Thirteen multi-class agricultural chemicals were studied (ametryn, amitraz, atrazine, buprofezin, DEET, diphenylamine, ethoxyquin, imazalil, isofenphos-methyl, isoproturon, malathion, parathion-ethyl and terbuthylazine). To evaluate the potential of the proposed approach, LTP-MS experiments were performed directly on fruit peels as well as on fruit/vegetable extracts. Most of the agrochemicals examined displayed remarkable sensitivity in the positive ion mode, giving limits of detection (LOD) for the direct measurement in the low picogram range. Tandem mass spectrometry (MS/MS) was used to confirm identification of selected pesticides by using for these experiments spiked fruit/vegetable extracts (QuEChERS, a standard sample treatment protocol) at levels as low as 1 pg, absolute, for some of the analytes. Comparisons of the data obtained by direct LTP-MS were made with the slower but more accurate conventional LC-MS/MS procedure. Herbicides spiked in aqueous solutions were detectable at LODs as low as 0.5 microg L(-1) without the need for any sample preparation. The results demonstrate that ambient LTP-MS can be applied for the detection and confirmation of traces of agrochemicals in actual market-purchased produce and in natural water samples. Quantitative analysis was also performed in a few selected cases and displayed a relatively high degree of linearity over four orders of magnitude.

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

    Science.gov (United States)

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

    2016-04-01

    Homeostatic plasticity mechanisms dynamically adjust synaptic strengths to promote stability that is crucial for memory storage. Metaplasticity is an example of these forms of plasticity that modify the capacity of synapses to experience subsequent Hebbian modifications. In particular, training in several behavioral tasks modifies the ability to induce long-term potentiation (LTP). Recently, we have reported that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP generated by high frequency stimulation in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC). One of the key molecular players that underlie long-term synaptic plasticity is brain-derived neurotrophic factor (BDNF). Previous studies from our group reported that acute microinfusion of BDNF in the IC induces a lasting potentiation of synaptic efficacy at the Bla-IC projection. Thus, the aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent BDNF-induced potentiation of synaptic transmission in the Bla-IC projection in vivo. Accordingly, CTA trained rats received intracortical microinfusion of BDNF in order to induce lasting potentiation 48h after the aversion test. Our results show that CTA training prevents the induction of in vivo BDNF-LTP in the Bla-IC projection. The present results provide evidence that CTA modulates BDNF-dependent changes in IC synaptic strength. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Dopamine D1-like receptor in lateral habenula nucleus affects contextual fear memory and long-term potentiation in hippocampal CA1 in rats.

    Science.gov (United States)

    Chan, Jiangping; Guan, Xin; Ni, Yiling; Luo, Lilu; Yang, Liqiang; Zhang, Pengyue; Zhang, Jichuan; Chen, Yanmei

    2017-03-15

    The Lateral Habenula (LHb) plays an important role in emotion and cognition. Recent experiments suggest that LHb has functional interaction with the hippocampus and plays an important role in spatial learning. LHb is reciprocally connected with midbrain monoaminergic brain areas such as the ventral tegmental area (VTA). However, the role of dopamine type 1 receptor (D1R) in LHb in learning and memory is not clear yet. In the present study, D1R agonist or antagonist were administered bilaterally into the LHb in rats. We found that both D1R agonist and antagonist impaired the acquisition of contextual fear memory in rats. D1R agonist or antagonist also impaired long term potentiation (LTP) in hippocampal CA3-CA1 synapses in freely moving rats and attenuated learning induced phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) at Ser831 and Ser845 in hippocampus. Taken together, our results suggested that dysfunction of D1R in LHb affected the function of hippocampus. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Performance of the upgraded LTP-II at the ALS Optical Metrology Laboratory

    International Nuclear Information System (INIS)

    Advanced Light Source; Yashchuk, Valeriy V; Kirschman, Jonathan L.; Domning, Edward E.; McKinney, Wayne R.; Morrison, Gregory Y.; Smith, Brian V.; Yashchuk, Valeriy V.

    2008-01-01

    The next generation of synchrotrons and free electron laser facilities requires x-ray optical systems with extremely high performance, generally of diffraction limited quality. Fabrication and use of such optics requires adequate, highly accurate metrology and dedicated instrumentation. Previously, we suggested ways to improve the performance of the Long Trace Profiler (LTP), a slope measuring instrument widely used to characterize x-ray optics at long spatial wavelengths. The main way is use of a CCD detector and corresponding technique for calibration of photo-response non-uniformity [J. L. Kirschman, et al., Proceedings of SPIE 6704, 67040J (2007)]. The present work focuses on the performance and characteristics of the upgraded LTP-II at the ALS Optical Metrology Laboratory. This includes a review of the overall aspects of the design, control system, the movement and measurement regimes for the stage, and analysis of the performance by a slope measurement of a highly curved super-quality substrate with less than 0.3 microradian (rms)slope variation

  4. Temperate Streptococcus thermophilus phages expressing superinfection exclusion proteins of the Ltp type

    Directory of Open Access Journals (Sweden)

    Yahya eAli

    2014-03-01

    Full Text Available Lipoprotein Ltp encoded by temperate Streptococcus thermophilus phage TP-J34 is the prototype of the wide-spread family of host cell surface-exposed lipoproteins involved in superinfection exclusion. When screening for other S. thermophilus phages expressing this type of lipoprotein, three temperate phages - TP-EW, TP-DSM20617 and TP-778 - were isolated. In this communication we present the total nucleotide sequences of TP-J34 and TP-778L. For TP-EW, a phage almost identical to TP-J34, besides the ltp gene only the two regions of deviation from TP-J34 DNA were analyzed: the gene encoding the tail protein causing an assembly defect in TP-J34 and the gene encoding the lysin, which in TP-EW contains an intron. For TP-DSM20617 only the sequence of the lysogeny module containing the ltp gene was determined. The region showed high homology to the same region of TP-778. For TP-778 we could show that absence of the attR region resulted in aberrant excision of phage DNA. The amino acid sequence of mature LtpTP-EW was shown to be identical to that of mature LtpTP-J34, whereas the amino acid sequence of mature LtpTP-778 was shown to differ from mature LtpTP-J34 in eight amino acid positions. LtpTP-DSM20617 was shown to differ from LtpTP-778 in just one amino acid position. In contrast to LtpTP-J34, LtpTP-778 did not affect infection of lactococcal phage P008 instead increased activity against phage P001 was noticed.

  5. Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Pettorossi, V E

    2000-01-01

    In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a

  6. Mark I containment long-term program safety evaluation report, resolution of generic technical activity A-7. Report for February 1977-December 1979

    International Nuclear Information System (INIS)

    1980-07-01

    During testing for an advanced Boiling Water Reactor (BWR) containment system design (Mark III), suppression pool hydrodynamic loads were identified which had not been considered in the original design of the Mark I containment system. To address this issue, a Mark I Owners Group was formed and the assessment was divided into a short-term and long-term program. The results of the NRC staff's review of the Mark I Containment Short Term Program are described in NUREG-0408. This report describes the results of the NRC staff's review of the generic Mark I Containment Long Term Program (LTP). The LTP was conducted to provide a generic basis to define suppression pool hydrodynamic loads and the related structural acceptance criteria, such that a comprehensive reassessment of each Mark I containment system would be performed. A series of experimental and analytical programs were conducted by the Mark I Owners Group to provide the necessary bases for the generic load definition and structural assessment techniques. The generic methods proposed by the Mark I Owners Group, as modified by the NRC staff's requirements, will be used to perform plant-unique analyses, which will identify the plant modifications, if any, that will be needed to restore the originally intended margin of safety in the Mark I containment designs

  7. Assessing the Quality and Potential Efficacy of Commercial Extracts of Rhodiola rosea L. by Analyzing the Salidroside and Rosavin Content and the Electrophysiological Activity in Hippocampal Long-Term Potentiation, a Synaptic Model of Memory

    Directory of Open Access Journals (Sweden)

    Wilfried Dimpfel

    2018-05-01

    Full Text Available Rhodiola rosea L. roots and rhizome extracts are active ingredients in adaptogenic herbal medicinal products (HMP and dietary supplements for temporary relief of symptoms of stress, such as fatigue and weakness. R. rosea extract has a stimulating effect on the CNS, suggesting potential benefits on cognitive functions, memory, learning, and attention. The reproducible efficacy and quality of preparations of the underground parts of R. rosea depend on the highly variable content of the active markers, salidroside and rosavin, which affect the quality of HMP and dietary supplements. However, it is not clear which analytical markers are important for assessing the efficacy of R. rosea preparations intended for use in aging-induced mild cognitive disorders, such as attenuated memory, attention, and learning. Furthermore, the activity of various commercial R. rosea extracts has not been correlated with their content. Here, the biological activities of salidroside, rosavin, and seven commercial extracts of underground parts of R. rosea were assessed using a synaptic model of memory: long-term potentiation (LTP of synaptic transmission in hippocampus slices. A high degree of variation in the content of all active markers was observed. One extract from China lacked rosavin, and there was even variation in the extracts from the Altai geographic region. In vitro, rosavin, salidroside and all tested R. rosea extracts potentiated electric stimulation of an intra-hippocampal electric circuit, which resulted in higher responses of the pyramidal cells in isolated hippocampus slices. Rosavin was more active at higher concentrations than salidroside; while, salidroside was more effective at lower concentrations. The highest content of both active markers was found in the extracts that were active at the lowest concentrations tested; while, some extracts contained some other compounds that presumably reduced the efficacy due to antagonistic interactions

  8. The effect of chronic stimulation of serotonin receptor type 7 on recognition, passive avoidance memory, hippocampal long-term potentiation, and neuronal apoptosis in the amyloid β protein treated rat.

    Science.gov (United States)

    Shahidi, Siamak; Asl, Sara Soleimani; Komaki, Alireza; Hashemi-Firouzi, Nasrin

    2018-05-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairment, neuronal death, and synaptic loss in the hippocampus. Long-term potentiation (LTP), a type of synaptic plasticity, occurs during learning and memory. Serotonin receptor type 7 (5-HTR7) activation is suggested as a possible therapeutic target for AD. The aim of the present study was to examine the effects of chronic treatment with the 5-HTR7 agonist, AS19, on cognitive function, memory, hippocampal plasticity, amyloid beta (Aβ) plaque accumulation, and apoptosis in an adult rat model of AD. AD was induced in rats using Aβ (single 1 μg/μL intracerebroventricular (icv) injection during surgery). The following experimental groups were included: control, sham-operated, Aβ + saline (1 μL icv for 30 days), and Aβ + AS19 (1 μg/μL icv for 30 days) groups. The animals were tested for cognition and memory performance using the novel object recognition and passive avoidance tests, respectively. Next, anesthetized rats were placed in a stereotaxic apparatus for electrode implantation, and field potentials were recorded in the hippocampal dentate gyrus. Lastly, brains were removed and Aβ plaques and neuronal apoptosis were evaluated using Congo red staining and TUNEL assay, respectively. Administration of AS19 in the Aβ rats increased the discrimination index of the novel object recognition test. Furthermore, AS19 treatment decreased time spent in the dark compartment during the passive avoidance test. AS19 also enhanced both the population spike (PS) amplitude and the field excitatory postsynaptic potential (fEPSP) slope evoked potentials of the LTP components. Aβ plaques and neuronal apoptosis were decreased in the AS19-treated Aβ rats. These results indicate that chronic treatment with a 5-HTR7 agonist can prevent Aβ-related impairments in cognition and memory performance by alleviating Aβ plaque accumulation and neuronal apoptosis, hence improving neuronal

  9. Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits.

    Science.gov (United States)

    Bhagya, Venkanna Rao; Srikumar, Bettadapura N; Veena, Jayagopalan; Shankaranarayana Rao, Byrathnahalli S

    2017-08-01

    Exposure to prolonged stress results in structural and functional alterations in the hippocampus including reduced long-term potentiation (LTP), neurogenesis, spatial learning and working memory impairments, and enhanced anxiety-like behavior. On the other hand, enriched environment (EE) has beneficial effects on hippocampal structure and function, such as improved memory, increased hippocampal neurogenesis, and progressive synaptic plasticity. It is unclear whether exposure to short-term EE for 10 days can overcome restraint stress-induced cognitive deficits and impaired hippocampal plasticity. Consequently, the present study explored the beneficial effects of short-term EE on chronic stress-induced impaired LTP, working memory, and anxiety-like behavior. Male Wistar rats were subjected to chronic restraint stress (6 hr/day) over a period of 21 days, and then they were exposed to EE (6 hr/day) for 10 days. Restraint stress reduced hippocampal CA1-LTP, increased anxiety-like symptoms in elevated plus maze, and impaired working memory in T-maze task. Remarkably, EE facilitated hippocampal LTP, improved working memory performance, and completely overcame the effect of chronic stress on anxiety behavior. In conclusion, exposure to EE can bring out positive effects on synaptic plasticity in the hippocampus and thereby elicit its beneficial effects on cognitive functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. The effects of CCK-8S on spatial memory and long-term potentiation at CA1 during induction of stress in rats.

    Science.gov (United States)

    Sadeghi, Malihe; Reisi, Parham; Radahmadi, Maryam

    2017-12-01

    Cholecystokinin (CCK) has been proposed as a mediator in stress. However, it is still not fully documented what are its effects. We aimed to evaluate the effects of systemic administration of CCK exactly before induction of stress on spatial memory and synaptic plasticity at CA1 in rats. Male Wistar rats were divided into 4 groups: the control, the control-CCK, the stress and the stress-CCK. Restraint stress was induced 6 hr per day, for 24 days. Cholecystokinin sulfated octapeptide (CCK-8S) was injected (1.6 µg/kg, IP) before each session of stress induction. Spatial memory was evaluated by Morris water maze test. Long-term potentiation (LTP) in Schaffer collateral-CA1 synapses was assessed (by 100 Hz tetanization) in order to investigate synaptic plasticity. Stress impaired spatial memory significantly ( P stress group. With respect to the control group, both fEPSP amplitude and slope were significantly ( P stress group. However, there were no differences between responses of the control-CCK and Stress-CCK groups compared to the control group. The present results suggest that high levels of CCK-8S during induction of stress can modulate the destructive effects of stress on hippocampal synaptic plasticity and memory. Therefore, the mediatory effects of CCK in stress are likely as compensatory responses.

  11. Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala.

    Science.gov (United States)

    Krishnan, Balaji; Scott, Michael T; Pollandt, Sebastian; Schroeder, Bradley; Kurosky, Alexander; Shinnick-Gallagher, Patricia

    2016-02-01

    Long-term memory (LTM) of fear stores activity dependent modifications that include changes in amygdala signaling. Previously, we identified an enhanced probability of release of glutamate mediated signaling to be important in rat fear potentiated startle (FPS), a well-established translational behavioral measure of fear. Here, we investigated short- and long-term synaptic plasticity in FPS involving metabotropic glutamate receptors (mGluRs) and associated downstream proteomic changes in the thalamic-lateral amygdala pathway (Th-LA). Aldolase A, an inhibitor of phospholipase D (PLD), expression was reduced, concurrent with significantly elevated PLD protein expression. Blocking the PLD-mGluR signaling significantly reduced PLD activity. While transmitter release probability increased in FPS, PLD-mGluR agonist and antagonist actions were occluded. In the unpaired group (UNP), blocking the PLD-mGluR increased while activating the receptor decreased transmitter release probability, consistent with decreased synaptic potentials during tetanic stimulation. FPS Post-tetanic potentiation (PTP) immediately following long-term potentiation (LTP) induction was significantly increased. Blocking PLD-mGluR signaling prevented PTP and reduced cumulative PTP probability but not LTP maintenance in both groups. These effects are similar to those mediated through mGluR7, which is co-immunoprecipitated with PLD in FPS. Lastly, blocking mGluR-PLD in the rat amygdala was sufficient to prevent behavioral expression of fear memory. Thus, our study in the Th-LA pathway provides the first evidence for PLD as an important target of mGluR signaling in amygdala fear-associated memory. Importantly, the PLD-mGluR provides a novel therapeutic target for treating maladaptive fear memories in posttraumatic stress and anxiety disorders. Published by Elsevier Inc.

  12. Radiofrequency Ablation of Hepatocellular Carcinoma with a “Nodule-in-Nodule” Appearance: Long-Term Follow-up and Clinical Implications

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Tae Wook; Rhim, Hyunchul, E-mail: rhimhc@skku.edu; Song, Kyoung Doo; Lee, Min Woo; Cha, Dong Ik [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center (Korea, Republic of); Ha, Sang Yun [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center (Korea, Republic of); Ahn, Joong Hyun [Samsung Biomedical Research Institute, Biostatics Team, Samsung Medical Center (Korea, Republic of)

    2017-03-15

    PurposeHepatocellular carcinoma (HCC) with a “nodule-in-nodule” (NIN) appearance has unique histological characteristics as an early HCC. We assessed long-term therapeutic outcomes of radiofrequency ablation (RFA) in HCC patients considering this appearance.Materials and MethodsOur Institutional Review Board approved this retrospective study, and the requirement for written informed consent was waived. Between May 2006 and April 2012, a total of 572 patients underwent RFA for single HCC as a first-line treatment. Patients were divided into a NIN HCC group (n = 22) and a non-NIN HCC group (n = 550), according to the NIN feature on pretreatment imaging studies. Local tumor progression (LTP) and disease-free survival (DFS) were compared. Prognostic factors for LTP and DFS were assessed using a Cox proportional hazards model.ResultsThe cumulative LTP rates were 4.6 and 4.6% at 3 and 5 years, respectively, in the NIN HCC group, and 15.9 and 20.5% in the non-NIN HCC group, with borderline statistical significance (p = 0.085). The corresponding DFS rates were 53.8 and 37.7% in the NIN HCC group and 44.0 and 31.7% in the non-NIN HCC group, with no significant difference (p = 0.318). Although on multivariate analysis only tumor size was a significant prognostic factor for LTP, there was a trend bordering on the significance for the NIN feature [hazard ratio (HR) = 0.19; p = 0.099]. However, it was not a significant factor for DFS (HR = 0.18; p = 0.682).ConclusionsThe NIN appearance, a rare (4%, 22/550) but unique feature of early HCC, may be a favorable prognostic factor for RFA in terms of local tumor control.

  13. Radiofrequency Ablation of Hepatocellular Carcinoma with a “Nodule-in-Nodule” Appearance: Long-Term Follow-up and Clinical Implications

    International Nuclear Information System (INIS)

    Kang, Tae Wook; Rhim, Hyunchul; Song, Kyoung Doo; Lee, Min Woo; Cha, Dong Ik; Ha, Sang Yun; Ahn, Joong Hyun

    2017-01-01

    PurposeHepatocellular carcinoma (HCC) with a “nodule-in-nodule” (NIN) appearance has unique histological characteristics as an early HCC. We assessed long-term therapeutic outcomes of radiofrequency ablation (RFA) in HCC patients considering this appearance.Materials and MethodsOur Institutional Review Board approved this retrospective study, and the requirement for written informed consent was waived. Between May 2006 and April 2012, a total of 572 patients underwent RFA for single HCC as a first-line treatment. Patients were divided into a NIN HCC group (n = 22) and a non-NIN HCC group (n = 550), according to the NIN feature on pretreatment imaging studies. Local tumor progression (LTP) and disease-free survival (DFS) were compared. Prognostic factors for LTP and DFS were assessed using a Cox proportional hazards model.ResultsThe cumulative LTP rates were 4.6 and 4.6% at 3 and 5 years, respectively, in the NIN HCC group, and 15.9 and 20.5% in the non-NIN HCC group, with borderline statistical significance (p = 0.085). The corresponding DFS rates were 53.8 and 37.7% in the NIN HCC group and 44.0 and 31.7% in the non-NIN HCC group, with no significant difference (p = 0.318). Although on multivariate analysis only tumor size was a significant prognostic factor for LTP, there was a trend bordering on the significance for the NIN feature [hazard ratio (HR) = 0.19; p = 0.099]. However, it was not a significant factor for DFS (HR = 0.18; p = 0.682).ConclusionsThe NIN appearance, a rare (4%, 22/550) but unique feature of early HCC, may be a favorable prognostic factor for RFA in terms of local tumor control.

  14. LTP interferometer-noise sources and performance

    International Nuclear Information System (INIS)

    Robertson, David; Killow, Christian; Ward, Harry; Hough, Jim; Heinzel, Gerhard; Garcia, Antonio; Wand, Vinzenz; Johann, Ulrich; Braxmaier, Claus

    2005-01-01

    The LISA Technology Package (LTP) uses laser interferometry to measure the changes in relative displacement between two inertial test masses. The goals of the mission require a displacement measuring precision of 10 pm Hz -1/2 at frequencies in the 3-30 mHz band. We report on progress with a prototype LTP interferometer optical bench in which fused silica mirrors and beamsplitters are fixed to a ZERODUR (registered) substrate using hydroxide catalysis bonding to form a rigid interferometer. The couplings to displacement noise of this interferometer of two expected noise sources-laser frequency noise and ambient temperature fluctuations-have been investigated, and an additional, unexpected, noise source has been identified. The additional noise is due to small amounts of signal at the heterodyne frequency arriving at the photodiode preamplifiers with a phase that quasistatically changes with respect to the optical signal. The phase shift is caused by differential changes in the external optical paths the beams travel before they reach the rigid interferometer. Two different external path length stabilization systems have been demonstrated and these allowed the performance of the overall system to meet the LTP displacement noise requirement

  15. Potential breeding distributions of U.S. birds predicted with both short-term variability and long-term average climate data.

    Science.gov (United States)

    Bateman, Brooke L; Pidgeon, Anna M; Radeloff, Volker C; Flather, Curtis H; VanDerWal, Jeremy; Akçakaya, H Resit; Thogmartin, Wayne E; Albright, Thomas P; Vavrus, Stephen J; Heglund, Patricia J

    2016-12-01

    Climate conditions, such as temperature or precipitation, averaged over several decades strongly affect species distributions, as evidenced by experimental results and a plethora of models demonstrating statistical relations between species occurrences and long-term climate averages. However, long-term averages can conceal climate changes that have occurred in recent decades and may not capture actual species occurrence well because the distributions of species, especially at the edges of their range, are typically dynamic and may respond strongly to short-term climate variability. Our goal here was to test whether bird occurrence models can be predicted by either covariates based on short-term climate variability or on long-term climate averages. We parameterized species distribution models (SDMs) based on either short-term variability or long-term average climate covariates for 320 bird species in the conterminous USA and tested whether any life-history trait-based guilds were particularly sensitive to short-term conditions. Models including short-term climate variability performed well based on their cross-validated area-under-the-curve AUC score (0.85), as did models based on long-term climate averages (0.84). Similarly, both models performed well compared to independent presence/absence data from the North American Breeding Bird Survey (independent AUC of 0.89 and 0.90, respectively). However, models based on short-term variability covariates more accurately classified true absences for most species (73% of true absences classified within the lowest quarter of environmental suitability vs. 68%). In addition, they have the advantage that they can reveal the dynamic relationship between species and their environment because they capture the spatial fluctuations of species potential breeding distributions. With this information, we can identify which species and guilds are sensitive to climate variability, identify sites of high conservation value where climate

  16. Double dissociation of spike timing-dependent potentiation and depression by subunit-preferring NMDA receptor antagonists in mouse barrel cortex.

    Science.gov (United States)

    Banerjee, Abhishek; Meredith, Rhiannon M; Rodríguez-Moreno, Antonio; Mierau, Susanna B; Auberson, Yves P; Paulsen, Ole

    2009-12-01

    Spike timing-dependent plasticity (STDP) is a strong candidate for an N-methyl-D-aspartate (NMDA) receptor-dependent form of synaptic plasticity that could underlie the development of receptive field properties in sensory neocortices. Whilst induction of timing-dependent long-term potentiation (t-LTP) requires postsynaptic NMDA receptors, timing-dependent long-term depression (t-LTD) requires the activation of presynaptic NMDA receptors at layer 4-to-layer 2/3 synapses in barrel cortex. Here we investigated the developmental profile of t-LTD at layer 4-to-layer 2/3 synapses of mouse barrel cortex and studied their NMDA receptor subunit dependence. Timing-dependent LTD emerged in the first postnatal week, was present during the second week and disappeared in the adult, whereas t-LTP persisted in adulthood. An antagonist at GluN2C/D subunit-containing NMDA receptors blocked t-LTD but not t-LTP. Conversely, a GluN2A subunit-preferring antagonist blocked t-LTP but not t-LTD. The GluN2C/D subunit requirement for t-LTD appears to be synapse specific, as GluN2C/D antagonists did not block t-LTD at horizontal cross-columnar layer 2/3-to-layer 2/3 synapses, which was blocked by a GluN2B antagonist instead. These data demonstrate an NMDA receptor subunit-dependent double dissociation of t-LTD and t-LTP mechanisms at layer 4-to-layer 2/3 synapses, and suggest that t-LTD is mediated by distinct molecular mechanisms at different synapses on the same postsynaptic neuron.

  17. Long-term Ameliorative Effects of the Antidepressant Fluoxetine Exposure on Cognitive Deficits in 3 × TgAD Mice.

    Science.gov (United States)

    Jin, Li; Gao, Li-Feng; Sun, Dong-Sheng; Wu, Hao; Wang, Qun; Ke, Dan; Lei, Hao; Wang, Jian-Zhi; Liu, Gong-Ping

    2017-08-01

    Fluoxetine, a selective serotonin reuptake inhibitor, is neuroprotective; therefore, it has been applied to treat some neurodegenerative disorders. For instance, chronic fluoxetine exposure has short-term effects on Alzheimer's disease (AD). However, the long-term ameliorative effects of fluoxetine exposure on AD have not been reported. In the present study, 6-month-old 3 × TgAD mice were treated with fluoxetine for 15 days, and then the influence of fluoxetine was detected at 20 days after the drug withdrawal. We found that chronic fluoxetine treatment ameliorated cognitive deficits of 3 × TgAD mice and increased the volume of the hippocampal CA1 and dentate gyrus (DG) with increased neuron number and dendritic spine density. Meanwhile, fluoxetine exposure also stimulated the long-term potentiation (LTP) in hippocampal DG. The synaptic-related protein expression increased via activation of the cyclic AMP response element binding (CREB) protein/brain-derived neurotrophic factor (BDNF) signaling pathway induced by fluoxetine exposure. Lastly, we found that fluoxetine treatment decreased beta-amyloid (Aβ) levels. These results further certified that fluoxetine may be a potent effective drug for AD.

  18. Metabotropic action of postsynaptic kainate receptors triggers hippocampal long-term potentiation

    Czech Academy of Sciences Publication Activity Database

    Petrovič, Miloš; da Silva, S. V.; Clement, J. P.; Vyklický ml., Ladislav; Mulle, C.; González-González, I. M.; Henley, J. M.

    2017-01-01

    Roč. 20, č. 4 (2017), s. 529-539 ISSN 1097-6256 R&D Projects: GA ČR(CZ) GA17-02300S Institutional support: RVO:67985823 Keywords : hippocampus * long-term potentiation * membrane proteins Subject RIV: FH - Neurology OBOR OECD: Neuroscience s (including psychophysiology Impact factor: 17.839, year: 2016

  19. p-Coumaric acid enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments.

    Science.gov (United States)

    Kim, Hyun-Bum; Lee, Seok; Hwang, Eun-Sang; Maeng, Sungho; Park, Ji-Ho

    2017-10-21

    Due to the improvement of medical level, life expectancy increased. But the increased incidence of cognitive disorders is an emerging social problem. Current drugs for dementia treatment can only delay the progress rather than cure. p-Coumaric acid is a phenylpropanoic acid derived from aromatic amino acids and known as a precursor for flavonoids such as resveratrol and naringenin. It was shown to reduce oxidative stress, inhibit genotoxicity and exert neuroprotection. Based on these findings, we evaluated whether p-coumaric acid can protect scopolamine induced learning and memory impairment by measuring LTP in organotypic hippocampal slice and cognitive behaviors in rats. p-Coumaric acid dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In addition, while scopolamine shortened the step-through latency in the passive avoidance test and prolonged the latency as well as reduced the latency in the target quadrant in the Morris water maze test, co-treatment of p-coumaric acid improved avoidance memory and long-term retention of spatial memory in behavioral tests. Since p-coumaric acid improved electrophysiological and cognitive functional deterioration by scopolamine, it may have regulatory effects on central cholinergic synapses and is expected to improve cognitive problems caused by abnormality of the cholinergic nervous system. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Somatostatin-positive interneurons in the dentate gyrus of mice provide local- and long-range septal synaptic inhibition.

    Science.gov (United States)

    Yuan, Mei; Meyer, Thomas; Benkowitz, Christoph; Savanthrapadian, Shakuntala; Ansel-Bollepalli, Laura; Foggetti, Angelica; Wulff, Peer; Alcami, Pepe; Elgueta, Claudio; Bartos, Marlene

    2017-04-03

    Somatostatin-expressing-interneurons (SOMIs) in the dentate gyrus (DG) control formation of granule cell (GC) assemblies during memory acquisition. Hilar-perforant-path-associated interneurons (HIPP cells) have been considered to be synonymous for DG-SOMIs. Deviating from this assumption, we show two functionally contrasting DG-SOMI-types. The classical feedback-inhibitory HIPPs distribute axon fibers in the molecular layer. They are engaged by converging GC-inputs and provide dendritic inhibition to the DG circuitry. In contrast, SOMIs with axon in the hilus, termed hilar interneurons (HILs), provide perisomatic inhibition onto GABAergic cells in the DG and project to the medial septum. Repetitive activation of glutamatergic inputs onto HIPP cells induces long-lasting-depression (LTD) of synaptic transmission but long-term-potentiation (LTP) of synaptic signals in HIL cells. Thus, LTD in HIPPs may assist flow of spatial information from the entorhinal cortex to the DG, whereas LTP in HILs may facilitate the temporal coordination of GCs with activity patterns governed by the medial septum.

  1. Activation of PAF-synthesizing enzymes in rat brain stem slices after LTP induction in the medial vestibular nuclei.

    Science.gov (United States)

    Francescangeli, Ermelinda; Grassi, Silvarosa; Pettorossi, Vito E; Goracci, Gianfrancesco

    2002-11-01

    LysoPAF acetyltransferase (lysoPAF-AT) and PAF-synthesizing phosphocholinetransferase (PAF-PCT) are the two enzymes which catalyze the final reactions for the synthesis of PAF. Their activities, assayed in the homogenate of rat brain stem slices and under their optimal conditions, increased 5 min after high frequency stimulation of vestibular afferents, inducing LTP in the medial vestibular nuclei. The activity of phosphatidylcholine-synthesizing phosphocholinetransferase, was not affected. Sixty minutes from the induction of LTP, PAF-PCT activity, but not that of lysoPAF-AT, was still significantly higher with respect to 5 min test stimulated control. We used AP-5 to verify whether this increase was strictly dependent upon LTP induction, which requires NMDA receptor activation. In AP-5 treated slices, lysoPAF-acetyltransferase and PAF-synthesizing phosphocholinetransferase activities increased, but they were reduced after high frequency stimulation under AP-5. In conclusion, we have demonstrated that the activities of PAF-synthesizing enzymes are activated soon after the induction of LTP and that this effect is linked to the activation of NMDA-receptors. We suggest that the enzyme activation by AP-5, preventing LTP, might be due to glutamate enhancement but, in neurons showing LTP and under normal conditions, the activation of potentiation mechanisms is critical for the enhancement of enzyme activities.

  2. Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats

    Directory of Open Access Journals (Sweden)

    Yonglu Tian

    2017-08-01

    Full Text Available Fragile X syndrome (FXS is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP. In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated protein 9 (Cas9 technology to generate Fmr1 knockout (KO rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1exon4-KO. Electrophysiological analysis revealed that the theta-burst stimulation (TBS–induced long-term potentiation (LTP and the low-frequency stimulus (LFS–induced long-term depression (LTD were decreased in the hippocampal Schaffer collateral pathway of the Fmr1exon4-KO rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR was also impaired. Consistent with previous reports, the Fmr1exon4-KO rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG–induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1exon4-KO rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1exon4-KO rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1exon4-KO rats constitute a novel rat model of FXS that complements existing mouse models.

  3. Detection of some safe plant-derived foods for LTP-allergic patients.

    Science.gov (United States)

    Asero, Riccardo; Mistrello, Gianni; Roncarolo, Daniela; Amato, Stefano

    2007-01-01

    Lipid transfer protein (LTP) is a widely cross-reacting plant pan-allergen. Adverse reactions to Rosaceae, tree nuts, peanut, beer, maize, mustard, asparagus, grapes, mulberry, cabbage, dates, orange, fig, kiwi, lupine, fennel, celery, tomato, eggplant, lettuce, chestnut and pineapple have been recorded. To detect vegetable foods to be regarded as safe for LTP-allergic patients. Tolerance/intolerance to a large spectrum of vegetable foods other than Rosaceae, tree nuts and peanut was assessed by interview in 49 subjects monosensitized to LTP and in three distinct groups of controls monosensitized to Bet v 1 (n = 24) or Bet v 2 (n = 18), or sensitized to both LTP and birch pollen (n = 16), all with a history of vegetable food allergy. Patients and controls underwent skin prick test (SPT) with a large spectrum of vegetable foods. The absence of IgE reactivity to foods that were negative in both clinical history and SPT was confirmed by immunoblot analysis and their clinical tolerance was finally assessed by open oral challenge (50 g per food). All patients reported tolerance and showed negative SPT to carrot, potato, banana and melon; these foods scored positive in SPT and elicited clinical symptoms in a significant proportion of patients from all three control groups. All patients tolerated these four foods on oral challenge. Immunoblot analysis confirmed the lack of IgE reactivity to these foods by LTP-allergic patients. Carrot, potato, banana and melon seem safe for LTP-allergic patients. This finding may be helpful for a better management of allergy to LTP.

  4. The LTP interferometer and phasemeter

    International Nuclear Information System (INIS)

    Heinzel, G; Wand, V; GarcIa, A; Jennrich, O; Braxmaier, C; Robertson, D; Middleton, K; Hoyland, D; Ruediger, A; Schilling, R; Johann, U; Danzmann, K

    2004-01-01

    The LISA Technology Package (LTP), to be launched by ESA in 2006/2007, is a technology demonstration mission in preparation for the LISA space-borne gravitational wave detector. A central part of the LTP is the optical metrology package (heterodyne interferometer with phasemeter) which monitors the distance between two test masses with a noise level of 10 pm Hz -1/2 between 3 mHz and 30 mHz. It has a dynamic range of >100 μm without any actuators for the pathlength. In addition to the longitudinal measurements, it provides alignment measurements with an expected noise level of -1/2 . While the basic design has been described previously by Heinzel et al (2003 Class. Quantum Grav. 20 S153-61), this paper gives new details on the laser stabilization, the phasemeter and recent prototype results

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

    Directory of Open Access Journals (Sweden)

    Tomoko Inagaki

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

  6. LISA and the LTP

    International Nuclear Information System (INIS)

    Jennrich, O.

    2002-01-01

    The primary objective of the LISA (Laser Interferometer Space Antenna mission is the detection and observation of gravitational waves from massive black holes (MBH) and galactic binaries in the frequency range 10 -4 Hz ... 10 -1 Hz. This low-frequency range is inaccessible to ground-based interferometers due to the background of local gravitational noise and because ground-based interferometers are limited in length to a few kilometres. LISA is envisaged as an ESA/NASA collaborative project, selected an ESA cornerstone mission and included in NASA's strategic plan and with a nominal launch date in 2011. SMART-2 is primarily intended to demonstrate the key technologies for the ESA/NASA collaborative LISA cornerstone mission. The synergy with the technology being used for Darwin motivates the utilization of SMART-2 for both missions. To this end, SMART-2 will accommodate a LISA technology package (LTP), provided by European institutes and industry and possibly also a Disturbance Reduction System (DRS) that is very similar to the LTP and has the same goals but is provided by US institutes and industry

  7. Astrocyte, the star avatar: redefined

    Indian Academy of Sciences (India)

    Srinivas

    LIF, leukaemia inhibitory factor; LTP, long-term potentiation; MBP, myelin basic protein; MCP, ... In short, astrocytes are multifunctional, efficient housekeeping cells that help neurons become ..... memory, synaptic plasticity and induction of LTP.

  8. LTP fibre injector qualification and status

    International Nuclear Information System (INIS)

    Bogenstahl, J; Cunningham, L; Fitzsimons, E D; Hough, J; Killow, C J; Perreur-Lloyd, M; Robertson, D; Rowan, S; Ward, H

    2009-01-01

    This paper presents the current state of the LISA Technology Package (LTP) fibre injector qualification project in terms of vibration and shock tests. The fibre injector is a custom built part and therefore must undergo a full space qualification process. The mounting structure and method for sinusoidal vibration and random vibration tests as well as shock tests will be presented. Furthermore a proposal will be presented to use the fibre injector pair qualification model to build an optical prototype bench. The optical prototype bench is a full-scale model of the flight model. It will be used for development and rehearsal of all the assembly stages of the flight model and will provide an on-ground simulator for investigation as an updated engineering model.

  9. Blockade of intracellular Zn2+ signaling in the basolateral amygdala affects object recognition memory via attenuation of dentate gyrus LTP.

    Science.gov (United States)

    Fujise, Yuki; Kubota, Mitsuyasu; Suzuki, Miki; Tamano, Haruna; Takeda, Atsushi

    2017-09-01

    Hippocampus-dependent memory is modulated by the amygdala. However, it is unknown whether intracellular Zn 2+ signaling in the amygdala is involved in hippocampus-dependent memory. On the basis of the evidence that intracellular Zn 2+ signaling in dentate granule cells (DGC) is necessary for object recognition memory via LTP at medial perforant pathway (PP)-DGC synapses, the present study examined whether intracellular Zn 2+ signaling in the amygdala influences object recognition memory via modulation of LTP at medial PP-DGC synapses. When ZnAF-2DA (100 μM, 2 μl) was injected into the basolateral amygdala (BLA), intracellular ZnAF-2 locally chelated intracellular Zn 2+ in the amygdala. Recognition memory was affected when training of object recognition test was performed 20 min after ZnAF-2DA injection into the BLA. Twenty minutes after injection of ZnAF-2DA into the BLA, LTP induction at medial PP-DGC synapses was attenuated, while LTP induction at PP-BLA synapses was potentiated and LTP induction at BLA-DGC synapses was attenuated. These results suggest that intracellular Zn 2+ signaling in the BLA is involved in BLA-associated LTP and modulates LTP at medial PP-DGC synapses, followed by modulation of object recognition memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Potential Long-Term Complications of Endovascular Stent Grafting for Blunt Thoracic Aortic Injury

    Directory of Open Access Journals (Sweden)

    Larry E. Miller

    2012-01-01

    Full Text Available Blunt thoracic aortic injury (BTAI is a rare, but lethal, consequence of rapid deceleration events. Most victims of BTAI die at the scene of the accident. Of those who arrive to the hospital alive, expedient aortic intervention significantly improves survival. Thoracic endovascular aortic repair (TEVAR has been accepted as the standard of care for BTAI at many centers, primarily due to the convincing evidence of lower mortality and morbidity in comparison to open surgery. However, less attention has been given to potential long-term complications of TEVAR for BTAI. This paper focuses on these complications, which include progressive aortic expansion with aging, inadequate stent graft characteristics, device durability concerns, long-term radiation exposure concerns from follow-up computed tomography scans, and the potential for (Victims of Modern Imaging Technology VOMIT.

  11. Long-term effect of set potential on biocathodes in microbial fuel cells: electrochemical and phylogenetic characterization.

    Science.gov (United States)

    Xia, Xue; Sun, Yanmei; Liang, Peng; Huang, Xia

    2012-09-01

    The long-term effect of set potential on oxygen reducing biocathodes was investigated in terms of electrochemical and biological characteristics. Three biocathodes were poised at 200, 60 and -100 mV vs. saturated calomel electrode (SCE) for 110 days, including the first 17 days for startup. Electrochemical analyses showed that 60 mV was the optimum potential during long-term operation. The performance of all the biocathodes kept increasing after startup, suggesting a period longer than startup time needed to make potential regulation more effective. The inherent characteristics without oxygen transfer limitation were studied. Different from short-term regulation, the amounts of biomass were similar while the specific electrochemical activity was significantly influenced by potential. Moreover, potential showed a strong selection for cathode bacteria. Clones 98% similar with an uncultured Bacteroidetes bacterium clone CG84 accounted for 75% to 80% of the sequences on the biocathodes that showed higher electrochemical activity (60 and -100 mV). Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Different synaptic stimulation patterns influence the local androgenic and estrogenic neurosteroid availability triggering hippocampal synaptic plasticity in the male rat.

    Science.gov (United States)

    Di Mauro, Michela; Tozzi, Alessandro; Calabresi, Paolo; Pettorossi, Vito Enrico; Grassi, Silvarosa

    2017-02-01

    Electrophysiological recordings were used to investigate the role of the local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on synaptic long-term effects induced in the hippocampal CA1 region of male rat slices. Long-term depression (LTD) and long-term potentiation (LTP), induced by different stimulation patterns, were examined under the block of the DHT synthesis by finasteride (FIN), and the E2 synthesis by letrozole (LET). We used low frequency stimulation (LFS) for LTD, high frequency stimulation (HFS) for LTP, and intermediate patterns differing in duration or frequency. We found that FIN reverted the LFS-LTD into LTP and enhanced LTP induced by intermediate and HFSs. These effects were abolished by exogenous DHT at concentration higher than the basal one, suggesting a stimulus dependent increase in DHT availability. No effect on the synaptic responses was observed giving DHT alone. Moreover, we found that the inhibition of E2 synthesis influenced the HFS-LTP by reducing its amplitude, and the exogenous E2 either enhanced HFS-LTP or reverted the LFS-LTD into LTP. The equivalence of the E2 concentration for rescuing the full HFS-LTP under LET and reverting the LFS-LTD into LTP suggests an enhancement of the endogenous E2 availability that is specifically driven by the HFS. No effect of FIN or LET was observed on the responses to stimuli that did not induce either LTD or LTP. This study provides evidence that the E2 and DHT availability combined with specific stimulation patterns is determinant for the sign and amplitude of the long-term effects. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

    Directory of Open Access Journals (Sweden)

    Eric J. Neuberger

    2017-09-01

    Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

  14. Potentials of short term and long term cryopreserved sperm of the ...

    African Journals Online (AJOL)

    To service the growing demand for male African giant catfish (Clarias gariepinus) broodstock for aquaculture in Nigeria, and to conserve valuable genetic resources, we improved both short-term (in deep freezer at -35°C) and long-term cryopreservation (in liquid nitrogen at -296°C) of catfish sperm. Catfish sperm ...

  15. Virtual Models of Long-Term Care

    Science.gov (United States)

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  16. Cyclic estrogenic fluctuation influences synaptic transmission of the medial vestibular nuclei in female rats.

    Science.gov (United States)

    Pettorossi, Vito E; Frondaroli, Adele; Grassi, Silvarosa

    2011-04-01

    The estrous cycle in female rats influences the basal synaptic responsiveness and plasticity of the medial vestibular nucleus (MVN) neurons through different levels of circulating 17β-estradiol (cE(2)). The aim of this study was to verify, in the female rat, whether cyclic fluctuations of cE(2) influence long-term synaptic effects induced by high frequency afferent stimulation (HFS) in the MVN, since we found that HFS in the male rat induces fast long-term potentiation (fLTP), which depends on the neural synthesis of E(2) (nE(2)) from testosterone (T). We analyzed the field potential (FP) evoked in the MVN by vestibular afferent stimulation, under basal conditions, and after HFS, in brainstem slices of female rats during high levels (proestrus, PE) and low levels (diestrus, DE) of cE(2). Selective blocking agents of converting T enzymes were used. Unlike in the male rat, HFS induced three effects: fLTP through T conversion into E(2), and slow LTP (sLTP) and long-term depression (LTD), through T conversion into DHT. The occurrence of these effects depended on the estrous cycle phase: the frequency of fLTP was higher in DE, and those of sLTP and LTD were higher in PE. Conversely, the basal FP was also higher in PE than in DE.

  17. Long-trace profiler for neutron focusing mirrors

    International Nuclear Information System (INIS)

    Puzyrev, Yevgeniy S.; Ice, Gene E.; Takacs, Peter Z.

    2009-01-01

    A long-trace profiler (LTP) optimized for measuring the shape of large neutron supermirrors has been designed and built. This LTP can measure 1.6 m long mirrors in both vertically and horizontally deflecting geometries, which is essential to achieve best performance from bendable mirrors. The LTP suppresses the influence of angular deviations of the linear-stage carriage during translation with a pentaprism and a cylindrical lens. The stationary optical head and the carriage-mounted pentaprism are precisely aligned to rotate about the optical axis between the two components. This feature allows measurements to be made on mirrors mounted vertically, horizontally or at any angle in between. The LTP software allows for rapid optimization of parameters for dynamically bent elliptical mirrors. Here we describe the motivation for the LTP, the design, and a first application of the LTP to study the effect of gravity on a bent microfocusing neutron supermirror.

  18. Manifestations and possible sources of lunar transient phenomena (LTP)

    International Nuclear Information System (INIS)

    Cameron, W.S.

    1975-01-01

    Several different manifestations of lunar transient phenomena (LTP) have been reported. These include: (1) brightenings--both sudden and slow, (2) reddish--both bright and dull, (3) bluish--both bright and dull, (4) fairly abrupt dimmings or darkenings, and (5) obscurations, which may be accompanied by any of the other four manifestations. Approximately 200 lunar features exhibiting such anomalies have been reported at least once, but 80% of all observations are found in less than a dozen sites and 60% are found in about one-half dozen sites. An observing program is being conducted for the Association of Lunar and Planetary Observers which is designed to monitor the LTP sites, the seismic epicenter sites and non-LTP comparison sites. It addresses the ''brightenings'' category of observations and is designed to establish normal brightness of each observed feature for all phases of a lunation. It also seeks to establish a quantified ''seeing'' scale. About one-half dozen observers have reported albedo measures (estimated from an albedo scale set up by each observer). The most extensive new data on albedo versus age (phase of Moon) are for the crater Dawes. Several LTP effects have been discerned in Dawes. In addition, seeing estimates, based on the behavior of a star's diffraction disk, provided some unexpected results when disk behavior is compared with other subjective estimates of seeing

  19. Factors associated with conversion of long-term non-progressors to progressors: A prospective study of HIV perinatally infected paediatric survivors

    Directory of Open Access Journals (Sweden)

    Muttineni Radhakrishna

    2013-01-01

    Full Text Available Background & objectives : Survival pattern among children infected with the human immune deficiency virus (HIV follows a bimodel distribution. Some children survive beyond 9 years age and are known as long term survivers (LTS while others had a more rapid course to death during the first few years of life. In the LTS group of children, two sub-populations have emerged, the long term non-progressors (LTNP who have remained asymptomatic over a period of years and those who have survived despite clinical and laboratory evidence of disease progression, the long term progressors (LTP. The aim of the present study was to determine the factors influencing the conversion of LTNPs to LTPs in a group of perinatally HIV infected children who were followed up for five years. Methods : A total of 26 HIV seropositive paediatric patients were monitored from 2006 to 2011 with CD4 cell counts, onset of clinical manifestations, body weight, biochemical, haematological and immunological parameters. Statistical analyses, both qualitative and quantitative, were used to determine the degree of conversion of non-progressors to progressors. Results : All 26 (13 female and 13 male perinatally HIV infected children, born during1991-1996 were healthy until 2006. But by 2011, 18 were placed in progressors group with antiretroviral therapy (ART, while six remained in non progressors group and two died. As per the Kaplan-Meier survival analysis, AIDS free median survival period (years in LTP group (CD4 count of the cohort was 10΁0.66 (350, P=<0.05. Intercurrent and opportunistic infections (OIs were observed in LTPs only. The incidence of OI in LTPs was higher when compared to general paediatric population. Interpretation & conclusions : Our findings show that CD4 counts and OIs play an important role in influencing the survival chances of perinatally HIV infected children.

  20. 转录因子Egr-1参与长期性恐惧记忆和焦虑%Transcription factor Egr-1 is required for long-term fear memory and anxiety

    Institute of Scientific and Technical Information of China (English)

    Shanelle; W.Ko; 敖虎山; Amelia; Gallitano-Mendel; 邱长申; 魏峰; Jeffrey; Milbrandt; 卓敏

    2005-01-01

    The zinc finger transcription factor Egr-1 is critical for coupling extracellular signals to changes in cellular gene expression.In the hippocampus and amygdala, two major central regions for memory formation and storage, Egr-1 is up-regulated by long-term potentiation (LTP) and learning paradigms. Using Egr-1 knockout mice, we showed that Egr-1 was selectively required for late auditory fear memory while short term, trace and contextual memory were not affected. Additionally, synaptic potentiation induced by theta burst stimulation in the amygdala and auditory cortex was significantly reduced or blocked in Egr-1 knockout mice. Our study suggests that the transcription factor Egr-1 plays a selective role in late auditory fear memory.%锌指转录因子Egr-1在将细胞外信号和胞内基因表达的变化相耦联过程中发挥重要的作用.海马和杏仁体是记忆形成和储存的两个主要的脑区.在海马和杏仁体中,Egr-1可被长时程增强(long-term potentiation,LTP)和学习过程上调.在Egr-1敲除小鼠上观察到晚时相声音恐惧记忆受损,而短时的痕迹和场景记忆却不受影响;另外,在Egr-1敲除小鼠上,用thetaburst刺激杏仁体和听觉皮层所引起的突触增强被明显减弱或完全阻断.因此,我们的研究表明,转录因子Egr-1选择性地在晚时相听觉恐惧记忆中发挥作用.

  1. Long-term variability of the thunderstorm and hail potential in Europe

    Science.gov (United States)

    Mohr, Susanna; Kunz, Michael; Speidel, Johannes; Piper, David

    2016-04-01

    Severe thunderstorms and associated hazardous weather events such as hail frequently cause considerable damage to buildings, crops, and automobiles, resulting in large monetary costs in many parts of Europe and the world. To relate single extreme hail events to the historic context and to estimate their return periods and possible trends related to climate change, long-term statistics of hail events are required. Due to the local-scale nature of hail and a lack of suitable observation systems, however, hailstorms are not captured reliably and comprehensively for a long period of time. In view of this fact, different proxies (indirect climate data) obtained from sounding stations and regional climate models can be used to infer the probability and intensity of thunderstorms or hailstorms. In contrast to direct observational data, such proxies are available homogeneously over a long time period. The aim of the study is to investigate the potential for severe thunderstorms and their changes over past decades. Statistical analyses of sounding data show that the convective potential over the past 20 - 30 years has significantly increased over large parts of Central Europe, making severe thunderstorms more likely. A similar picture results from analyses of weather types that are most likely associated with damaging hailstorms. These weather patterns have increased, even if only slightly but nevertheless statistically significantly, in the time period from 1971 to 2000. To improve the diagnostics of hail events in regional climate models, a logistic hail model has been developed by means of a multivariate analysis method. The model is based on a combination of appropriate hail-relevant meteorological parameters. The output of the model is a new index that estimates the potential of the atmosphere for hailstorm development, referred to as potential hail index (PHI). Applied to a high-resolved reanalysis run for Europe driven by NCEP/NCAR1, long-term changes of the PHI for

  2. Blockade of intracellular Zn2+ signaling in the dentate gyrus erases recognition memory via impairment of maintained LTP.

    Science.gov (United States)

    Tamano, Haruna; Minamino, Tatsuya; Fujii, Hiroaki; Takada, Shunsuke; Nakamura, Masatoshi; Ando, Masaki; Takeda, Atsushi

    2015-08-01

    There is no evidence on the precise role of synaptic Zn2+ signaling on the retention and recall of recognition memory. On the basis of the findings that intracellular Zn2+ signaling in the dentate gyrus is required for object recognition, short-term memory, the present study deals with the effect of spatiotemporally blocking Zn2+ signaling in the dentate gyrus after LTP induction and learning. Three-day-maintained LTP was impaired 1 day after injection of clioquinol into the dentate gyrus, which transiently reduced intracellular Zn2+ signaling in the dentate gyrus. The irreversible impairment was rescued not only by co-injection of ZnCl2 , which ameliorated the loss of Zn2+ signaling, but also by pre-injection of Jasplakinolide, a stabilizer of F-actin, prior to clioquinol injection. Simultaneously, 3-day-old space recognition memory was impaired 1 day after injection of clioquinol into the dentate gyrus, but not by pre-injection of Jasplakinolide. Jasplakinolide also rescued both impairments of 3-day-maintained LTP and 3-day-old memory after injection of ZnAF-2DA into the dentate gyrus, which blocked intracellular Zn2+ signaling in the dentate gyrus. The present paper indicates that the blockade and/or loss of intracellular Zn2+ signaling in the dentate gyrus coincidently impair maintained LTP and recognition memory. The mechanism maintaining LTP via intracellular Zn2+ signaling in dentate granule cells, which may be involved in the formation of F-actin, may retain space recognition memory. © 2015 Wiley Periodicals, Inc.

  3. Hippocampal long-term depression is facilitated by the acquisition and updating of memory of spatial auditory content and requires mGlu5 activation.

    Science.gov (United States)

    Dietz, Birte; Manahan-Vaughan, Denise

    2017-03-15

    Long-term potentiation (LTP) and long-term depression (LTD) are key cellular processes that support memory formation. Whereas increases of synaptic strength by means of LTP may support the creation of a spatial memory 'engram', LTD appears to play an important role in refining and optimising experience-dependent encoding. A differentiation in the role of hippocampal subfields is apparent. For example, LTD in the dentate gyrus (DG) is enabled by novel learning about large visuospatial features, whereas in area CA1, it is enabled by learning about discrete aspects of spatial content, whereby, both discrete visuospatial and olfactospatial cues trigger LTD in CA1. Here, we explored to what extent local audiospatial cues facilitate information encoding in the form of LTD in these subfields. Coupling of low frequency afferent stimulation (LFS) with discretely localised, novel auditory tones in the sonic hearing, or ultrasonic range, facilitated short-term depression (STD) into LTD (>24 h) in CA1, but not DG. Re-exposure to the now familiar audiospatial configuration ca. 1 week later failed to enhance STD. Reconfiguration of the same audiospatial cues resulted anew in LTD when ultrasound, but not non-ultrasound cues were used. LTD facilitation that was triggered by novel exposure to spatially arranged tones, or to spatial reconfiguration of the same tones were both prevented by an antagonism of the metabotropic glutamate receptor, mGlu5. These data indicate that, if behaviourally salient enough, the hippocampus can use audiospatial cues to facilitate LTD that contributes to the encoding and updating of spatial representations. Effects are subfield-specific, and require mGlu5 activation, as is the case for visuospatial information processing. These data reinforce the likelihood that LTD supports the encoding of spatial features, and that this occurs in a qualitative and subfield-specific manner. They also support that mGlu5 is essential for synaptic encoding of spatial

  4. Long term hydrogen production potential of concentrated photovoltaic (CPV) system in tropical weather of Singapore

    KAUST Repository

    Burhan, Muhammad

    2016-08-23

    Concentrated photovoltaic (CPV) system provides highest solar energy conversion efficiency among all the photovoltaic technologies and provides the most suitable option to convert solar energy into hydrogen, as future sustainable energy carrier. So far, only conventional flat plate PV systems are being used for almost all of the commercial applications. However, most of the studies have only shown the maximum efficiency of hydrogen production using CPV. In actual field conditions, the performance of CPV-Hydrogen system is affected by many parameter and it changes continuously during whole day operation. In this paper, the daily average and long term performances are proposed to analyze the real field potential of the CPV-Hydrogen system, which is of main interest for designers and consumers. An experimental setup is developed and a performance model is proposed to investigate the average and long term production potential of CPV-Hydrogen system. The study is carried out in tropical weather of Singapore. The maximum CPV efficiency of 27-28% and solar to hydrogen (STH) efficiency of 18%, were recorded. In addition, the CPV-Hydrogen system showed the long term average efficiency of 15.5%, for period of one year (12-months), with electrolyser rating of 47 kWh/kg and STH production potential of 218 kWh/kg. Based upon the DNI availability, the system showed hydrogen production potential of 0.153-0.553 kg/m/month, with average production of 0.43 kg/m/month. However, CPV-Hydrogen system has shown annual hydrogen production potential of 5.162 kg/m/year in tropical weather of Singapore.

  5. Long-Term Visuo-Gustatory Appetitive and Aversive Conditioning Potentiate Human Visual Evoked Potentials

    Directory of Open Access Journals (Sweden)

    Gert R. J. Christoffersen

    2017-09-01

    Full Text Available Human recognition of foods and beverages are often based on visual cues associated with flavors. The dynamics of neurophysiological plasticity related to acquisition of such long-term associations has only recently become the target of investigation. In the present work, the effects of appetitive and aversive visuo-gustatory conditioning were studied with high density EEG-recordings focusing on late components in the visual evoked potentials (VEPs, specifically the N2-P3 waves. Unfamiliar images were paired with either a pleasant or an unpleasant juice and VEPs evoked by the images were compared before and 1 day after the pairings. In electrodes located over posterior visual cortex areas, the following changes were observed after conditioning: the amplitude from the N2-peak to the P3-peak increased and the N2 peak delay was reduced. The percentage increase of N2-to-P3 amplitudes was asymmetrically distributed over the posterior hemispheres despite the fact that the images were bilaterally symmetrical across the two visual hemifields. The percentage increases of N2-to-P3 amplitudes in each experimental subject correlated with the subject’s evaluation of positive or negative hedonic valences of the two juices. The results from 118 scalp electrodes gave surface maps of theta power distributions showing increased power over posterior visual areas after the pairings. Source current distributions calculated from swLORETA revealed that visual evoked currents rose as a result of conditioning in five cortical regions—from primary visual areas and into the inferior temporal gyrus (ITG. These learning-induced changes were seen after both appetitive and aversive training while a sham trained control group showed no changes. It is concluded that long-term visuo-gustatory conditioning potentiated the N2-P3 complex, and it is suggested that the changes are regulated by the perceived hedonic valence of the US.

  6. Near-Term Actions to Address Long-Term Climate Risk

    Science.gov (United States)

    Lempert, R. J.

    2014-12-01

    Addressing climate change requires effective long-term policy making, which occurs when reflecting on potential events decades or more in the future causes policy makers to choose near-term actions different than those they would otherwise pursue. Contrary to some expectations, policy makers do sometimes make such long-term decisions, but not as commonly and successfully as climate change may require. In recent years however, the new capabilities of analytic decision support tools, combined with improved understanding of cognitive and organizational behaviors, has significantly improved the methods available for organizations to manage longer-term climate risks. In particular, these tools allow decision makers to understand what near-term actions consistently contribute to achieving both short- and long-term societal goals, even in the face of deep uncertainty regarding the long-term future. This talk will describe applications of these approaches for infrastructure, water, and flood risk management planning, as well as studies of how near-term choices about policy architectures can affect long-term greenhouse gas emission reduction pathways.

  7. PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory.

    Science.gov (United States)

    Volk, Lenora J; Bachman, Julia L; Johnson, Richard; Yu, Yilin; Huganir, Richard L

    2013-01-17

    Long-term potentiation (LTP), a well-characterized form of synaptic plasticity, has long been postulated as a cellular correlate of learning and memory. Although LTP can persist for long periods of time, the mechanisms underlying LTP maintenance, in the midst of ongoing protein turnover and synaptic activity, remain elusive. Sustained activation of the brain-specific protein kinase C (PKC) isoform protein kinase M-ζ (PKM-ζ) has been reported to be necessary for both LTP maintenance and long-term memory. Inhibiting PKM-ζ activity using a synthetic zeta inhibitory peptide (ZIP) based on the PKC-ζ pseudosubstrate sequence reverses established LTP in vitro and in vivo. More notably, infusion of ZIP eliminates memories for a growing list of experience-dependent behaviours, including active place avoidance, conditioned taste aversion, fear conditioning and spatial learning. However, most of the evidence supporting a role for PKM-ζ in LTP and memory relies heavily on pharmacological inhibition of PKM-ζ by ZIP. To further investigate the involvement of PKM-ζ in the maintenance of LTP and memory, we generated transgenic mice lacking PKC-ζ and PKM-ζ. We find that both conventional and conditional PKC-ζ/PKM-ζ knockout mice show normal synaptic transmission and LTP at Schaffer collateral-CA1 synapses, and have no deficits in several hippocampal-dependent learning and memory tasks. Notably, ZIP still reverses LTP in PKC-ζ/PKM-ζ knockout mice, indicating that the effects of ZIP are independent of PKM-ζ.

  8. Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons.

    Science.gov (United States)

    Díez-García, Andrea; Barros-Zulaica, Natali; Núñez, Ángel; Buño, Washington; Fernández de Sevilla, David

    2017-01-01

    According to Hebb's original hypothesis (Hebb, 1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic input causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol. Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca 2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca 2+ spike and Ca 2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor information.

  9. Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons

    Science.gov (United States)

    Díez-García, Andrea; Barros-Zulaica, Natali; Núñez, Ángel; Buño, Washington; Fernández de Sevilla, David

    2017-01-01

    According to Hebb's original hypothesis (Hebb, 1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic input causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol. Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca2+ spike and Ca2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor information. PMID:28203145

  10. Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity.

    Science.gov (United States)

    Shoshan, Noa; Segev, Amir; Abush, Hila; Mizrachi Zer-Aviv, Tomer; Akirav, Irit

    2017-10-01

    Exposure to excessive or uncontrolled stress is a major factor associated with various diseases including posttraumatic stress disorder (PTSD). The consequences of exposure to trauma are affected not only by aspects of the event itself, but also by the frequency and severity of trauma reminders. It was suggested that in PTSD, hippocampal-dependent memory is compromised while amygdala-dependent memory is strengthened. Several lines of evidence support the role of the endocannabinoid (eCB) system as a modulator of the stress response. In this study we aimed to examine cannabinoids modulation of the long-term effects (i.e., 1 month) of exposure to a traumatic event on memory and plasticity in the hippocampus and amygdala. Following exposure to the shock and reminders model of PTSD in an inhibitory avoidance light-dark apparatus rats demonstrated: (i) enhanced fear retrieval and impaired inhibitory extinction (Ext), (ii) no long-term potentiation (LTP) in the CA1, (iii) impaired hippocampal-dependent short-term memory in the object location task, (iv) enhanced LTP in the amygdala, and (v) enhanced amygdala-dependent conditioned taste aversion memory. The cannabinoid CB1/2 receptor agonist WIN55-212,2 (0.5mg/kg, i.p.) and the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.), administered 2 hr after shock exposure prevented these opposing effects on hippocampal- and amygdala-dependent processes. Moreover, the effects of WIN55-212,2 and URB597 on Ext and acoustic startle were prevented by co-administration of a low dose of the CB1 receptor antagonist AM251 (0.5mg/kg, i.p.), suggesting that the preventing effects of both drugs are mediated by CB1 receptors. Exposure to shock and reminders increased CB1 receptor levels in the CA1 and basolateral amygdala 1 month after shock exposure and this increase was also prevented by administering WIN55-212,2 or URB597. Taken together, these findings suggest the involvement of the eCB system, and specifically CB1

  11. Inter-subject and Inter-session Variability of Plasticity Induction by Non-invasive Brain Stimulation

    DEFF Research Database (Denmark)

    Ziemann, Ulf; Siebner, Hartwig R

    2015-01-01

    in human cortex well beyond the time of stimulation. These aftereffects have been termed long-term potentiation (LTP)-like and long-term depression (LTD)-like plasticity because indirect evidence supported the notion that synaptic strengthening or weakening similar to LTP/D at the cellular level underlies......Non-invasive brain stimulation (NIBS) protocols such as regular repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), paired associative stimulation (PAS) and transcranial direct current stimulation (tDCS) can change the excitability of the stimulated neuronal network...

  12. Thermal diagnostics for LTP

    International Nuclear Information System (INIS)

    Lobo, Alberto; Nofrarias, M; Sanjuan, J

    2005-01-01

    This is a short note reporting on the current state of development of the temperature sensors which are part of the LTP Diagnostics Subsystem on board the LISA Pathfinder mission (LPF). A thermal insulator has been designed which ensures sufficient stability of a set of eight NTC sensors (negative temperature coefficient of resistance or thermistors), and the front-end electronics has also been designed and manufactured. Tests have been performed which nearly approach the goal of a global stability of 10 -5 K Hz -1/2

  13. A comparative study of long-term energy demand and potential greenhouse gas emission control in Bangladesh

    International Nuclear Information System (INIS)

    Khalaquazzaman, Mohammad

    2005-02-01

    This report presents a comparative study of long-term energy demand and potential greenhouse gas emissions projections from energy demand and supply sectors in Bangladesh covering the period 2000 to 2020. The study was conducted employing the IAEA's tool ENPEP- BALANCE model. This study presents a reliable energy system plan with minimal carbon emission for the country. Primary energy demands distributed by energy carriers and electricity demand have been projected based on macro-economic growth scenarios constructed for national energy policy of 1996. The conservation of indigenous energy resources was emphasized to build a long-term secured energy supply system. The potential energy supply options including nuclear energy and prospective greenhouse gas mitigation options were analyzed

  14. Persistent deficits in hippocampal synaptic plasticity accompany losses of hippocampus-dependent memory in a rodent model of psychosis

    Directory of Open Access Journals (Sweden)

    Valentina eWiescholleck

    2013-03-01

    Full Text Available Irreversible N-methyl-D-aspartate receptor (NMDAR antagonism is known to provoke symptoms of psychosis and schizophrenia in healthy humans. NMDAR hypofunction is believed to play a central role in the pathophysiology of both disorders and in an animal model of psychosis, that is based on irreversible antagonism of NMDARs, pronounced deficits in hippocampal synaptic plasticity have been reported shortly after antagonist treatment. Here, we examined the long-term consequences for long-term potentiation (LTP of a single acute treatment with an irreversible antagonist and investigated whether deficits are associated with memory impairments.The ability to express long-term potentiation (LTP at the perforant pathway – dentate gyrus synapse, as well as object recognition memory was assessed 1, 2, 3 and 4 weeks after a single -treatment of the antagonist, MK801. Here, LTP in freely behaving rats was significantly impaired at all time-points compared to control LTP before treatment. Object recognition memory was also significantly poorer in MK801-treated compared to vehicle-treated animals for several weeks after treatment. Histological analysis revealed no changes in brain tissue.Taken together, these data support that acute treatment with an irreversible NMDAR antagonist persistently impairs hippocampal functioning on behavioral, as well as synaptic levels. The long-term deficits in synaptic plasticity may underlie the cognitive impairments that are associated with schizophrenia-spectrum disorders.

  15. Intelligent power wheelchair use in long-term care: potential users' experiences and perceptions.

    Science.gov (United States)

    Rushton, Paula W; Mortenson, Ben W; Viswanathan, Pooja; Wang, Rosalie H; Miller, William C; Hurd Clarke, Laura

    2017-10-01

    Long-term care (LTC) residents with cognitive impairments frequently experience limited mobility and participation in preferred activities. Although a power wheelchair could mitigate some of these mobility and participation challenges, this technology is often not prescribed for this population due to safety concerns. An intelligent power wheelchair (IPW) system represents a potential intervention that could help to overcome these concerns. The purpose of this study was to explore a) how residents experienced an IPW that used three different modes of control and b) what perceived effect the IPW would have on their daily lives. We interviewed 10 LTC residents with mild or moderate cognitive impairment twice, once before and once after testing the IPW. Interviews were conducted using a semi-structured interview guide, audio recorded and transcribed verbatim for thematic analyses. Our analyses identified three overarching themes: (1) the difference an IPW would make, (2) the potential impact of the IPW on others and (3) IPW-related concerns. Findings from this study confirm the need for and potential benefits of IPW use in LTC. Future studies will involve testing IPW improvements based on feedback and insights from this study. Implications for rehabilitation Intelligent power wheelchairs may enhance participation and improve safety and feelings of well-being for long-term care residents with cognitive impairments. Intelligent power wheelchairs could potentially have an equally positive impact on facility staff, other residents, and family and friends by decreasing workload and increasing safety.

  16. Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory.

    Science.gov (United States)

    Abush, Hila; Akirav, Irit

    2013-07-01

    Repeated stress is one of the environmental factors that precipitates and exacerbates mental illnesses like depression and anxiety as well as cognitive impairments. We have previously shown that cannabinoids can prevent the effects of acute stress on learning and memory. Here we aimed to find whether chronic cannabinoid treatment would alleviate the long-term effects of exposure to chronic restraint stress on memory and plasticity as well as on behavioral and neuroendocrine measures of anxiety and depression. Late adolescent rats were exposed to chronic restraint stress for 2 weeks followed each day by systemic treatment with vehicle or with the CB1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). Thirty days after the last exposure to stress, rats demonstrated impaired long-term potentiation (LTP) in the ventral subiculum-nucleus accumbens (NAc) pathway, impaired performance in the prefrontal cortex (PFC)-dependent object-recognition task and the hippocampal-dependent spatial version of this task, increased anxiety levels, and significantly reduced expression of glucocorticoid receptors (GRs) in the amygdala, hippocampus, PFC, and NAc. Chronic WIN55,212-2 administration prevented the stress-induced impairment in LTP levels and in the spatial task, with no effect on stress-induced alterations in unconditioned anxiety levels or GR levels. The CB1 antagonist AM251 (0.3 mg/kg) prevented the ameliorating effects of WIN55,212-2 on LTP and short-term memory. Hence, the beneficial effects of WIN55,212-2 on memory and plasticity are mediated by CB1 receptors and are not mediated by alterations in GR levels in the brain areas tested. Our findings suggest that cannabinoid receptor activation could represent a novel approach to the treatment of cognitive deficits that accompany a variety of stress-related neuropsychiatric disorders.

  17. Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells

    International Nuclear Information System (INIS)

    Chen, P.-Y.; Huang, Lynn L.H.; Hsieh, H.-J.

    2007-01-01

    For long-term culture, murine adipose-derived stromal cells (mADSCs) at latter passages demonstrated a marked decline in proliferative activity, exhibited senescent morphology and reduced differentiation potentials, particularly osteogenesis. To extend the lifespan of mADSCs, two culture conditions containing hyaluronan (HA) was compared in our study, one as a culture medium supplement (SHA), and the other where HA was pre-coated on culture surface (CHA). mADSCs cultivated with SHA exhibited a prolonged lifespan, reduced cellular senescence, and enhanced osteogenic potential compared to regular culture condition (control). Upon CHA treatment, mADSCs tended to form cell aggregates with gradual growth profiles, while their differentiation activities remained similar to SHA groups. After transferring mADSCs from CHA to control surface, they were shown to have an extended lifespan and an increase of osteogenic potential. Our results suggested that HA can be useful for preserving the proliferation and differentiation potentials of long-term cultured mADSCs

  18. Long term storage of explosively erupted magma at Nevado de Toluca volcano, Mexico

    Science.gov (United States)

    Arce, J. L.; Gardner, J.; Macias, J. L.

    2007-12-01

    Dacitic magmas production is common in subduction-related volcanoes, occurring in those with a long period of activity as a result of the magmatic evolution. However, in this evolution many factors (i.e. crystal fractionation, assimilation, magma mixing) can interact to produce dacites. Nevado de Toluca volcano (4,680 masl; 19°09'N; 99°45'W) Central Mexico has recorded a long period of time producing dacites explosively, at least during 42 ka of activity, involving several km3 of magma, with two important Plinian-type eruptions occurred at ~21.7 ka (Lower Toluca Pumice) and ~10.5 ka (Upper Toluca Pumice). Questions like, what was the mechanism responsible to produce voluminous dacitic magma and how the volatiles and pressure changed in the Nevado de Toluca system, remain without answers. Dacites from the Lower Toluca Pumice (LTP) contain plagioclase, amphibole, iron-titanium oxides, and minor resorbed biotite, set in a glassy-vesicular matrix and the Upper Toluca Pumice (UTP) dacites contain the same mineral phases plus orthopyroxene. Ilmenite- ulvospinel geothermometry yielded a temperature of ~860°C for the LTP dacite, a little hotter than the UTP (~ 840°C). Based on hydrothermal experiments data, amphibole is stable above 100 MPa under 900°C, while plagioclase crystallizes up to 250-100 MPa at temperatures of 850-900°C. Pyroxene occurs only at pressures of 200-100 MPa with its respective temperatures of 825-900°C. Water contents in the LTP magma (2-3.5 wt %) are similar to that calculated for the UTP magma (1.3-3.6 wt %). So, there are only small changes in temperature and pressure from ~21.7 ka to 10.5 ka. It is noteworthy that orthopyroxene is absent in the LTP, however reaction-rimmed biotite (probably xenocrystic) is commonly observed in all dacites. Hence, almost all dacitic magmas seem to be stored at relatively similar pressures, water contents, and temperatures. All of these data could suggest repetitive basic magma injections producing the

  19. Piracetam prevents memory deficit induced by postnatal propofol exposure in mice.

    Science.gov (United States)

    Wang, Yuan-Lin; Li, Feng; Chen, Xin

    2016-05-15

    Postnatal propofol exposure impairs hippocampal synaptic development and memory. However, the effective agent to alleviate the impairments was not verified. In this study, piracetam, a positive allosteric modulator of AMPA receptor was administered following a seven-day propofol regime. Two months after propofol administration, hippocampal long-term potentiation (LTP) and long-term memory decreased, while intraperitoneal injection of piracetam at doses of 100mg/kg and 50mg/kg following last propofol exposure reversed the impairments of memory and LTP. Mechanically, piracetam reversed propofol exposure-induced decrease of BDNF and phosphorylation of mTor. Similar as piracetam, BDNF supplementary also ameliorated propofol-induced abnormalities of synaptic plasticity-related protein expressions, hippocampal LTP and long-term memory. These results suggest that piracetam prevents detrimental effects of propofol, likely via activating BDNF synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Involvement of glucocorticoid-mediated Zn2+ signaling in attenuation of hippocampal CA1 LTP by acute stress.

    Science.gov (United States)

    Takeda, Atsushi; Suzuki, Miki; Tamano, Haruna; Takada, Shunsuke; Ide, Kazuki; Oku, Naoto

    2012-03-01

    Glucocorticoid-glutamatergic interactions have been proposed as a potential model to explain stress-mediated impairment of cognition. However, it is unknown whether glucocorticoid-zincergic interactions are involved in this impairment. Histochemically reactive zinc (Zn(2+)) is co-released with glutamate from zincergic neurons. In the present study, involvement of synaptic Zn(2+) in stress-induced attenuation of CA1 LTP was examined in hippocampal slices from young rats after exposure to tail suspension stress for 30s, which significantly increased serum corticosterone. Stress-induced attenuation of CA1 LTP was ameliorated by administration of clioquinol, a membrane permeable zinc chelator, to rats prior to exposure to stress, implying that the reduction of synaptic Zn(2+) by clioquinol participates in this amelioration. To pursue the involvement of corticosterone-mediated Zn(2+) signal in the attenuated CA1 LTP by stress, dynamics of synaptic Zn(2+) was checked in hippocampal slices exposed to corticosterone. Corticosterone increased extracellular Zn(2+) levels measured with ZnAF-2 dose-dependently, as well as the intracellular Ca(2+) levels measured with calcium orange AM, suggesting that corticosterone excites zincergic neurons in the hippocampus and increases Zn(2+) release from the neuron terminals. Intracellular Zn(2+) levels measured with ZnAF-2DA were also increased dose-dependently, but not in the coexistence of CaEDTA, a membrane-impermeable zinc chelator, suggesting that intracellular Zn(2+) levels is increased by the influx of extracellular Zn(2+). Furthermore, corticosterone-induced attenuation of CA1 LTP was abolished in the coexistence of CaEDTA. The present study suggests that corticosterone-mediated increase in postsynaptic Zn(2+) signal in the cytosolic compartment is involved in the attenuation of CA1 LTP after exposure to acute stress. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Long-term antibiotic delivery by chitosan-based composite coatings with bone regenerative potential

    Science.gov (United States)

    Ordikhani, F.; Simchi, A.

    2014-10-01

    Composite coatings with bone-bioactivity and drug-eluting capacity are considered as promising materials for titanium bone implants. In this work, drug-eluting chitosan-bioactive glass coatings were fabricated by a single-step electrophoretic deposition technique. Drug-loading and -releasing capacity of the composite coatings were carried out using the vancomycin antibiotic. Uniform coatings with a thickness of ∼55 μm containing 23.7 wt% bioactive glass particles and various amounts of the antibiotic (380-630 μg/cm2) were produced. The coatings were bioactive in terms of apatite-forming ability in simulated body fluid and showed favorable cell adhesion and growth. In vitro biological tests also indicated that the composite coatings had better cellular affinity than pristine chitosan coatings. The in vitro elution kinetics of the composite coating revealed an initial burst release of around 40% of the drug within the first elution step of 1 h and following by a continuous eluting over 4 weeks, revealing long-term drug-delivering potential. Antibacterial tests using survival assay against Gram-positive Staphylococcus aureus bacteria determined the effect of vancomycin release on reduction of infection risk. Almost no bacteria were survived on the coatings prepared from the EPD suspension containing ≥0.5 g/l vancomycin. The developed chitosan-based composite coatings with bone bioactivity and long-term drug-delivery ability may be potentially useful for metallic implants to reduce infection risk.

  2. Role of mast cell- and non-mast cell-derived inflammatory mediators in immunologic induction of synaptic plasticity

    Directory of Open Access Journals (Sweden)

    A.A.C. Albuquerque

    1997-07-01

    Full Text Available We have previously discovered a long-lasting enhancement of synaptic transmission in mammal autonomic ganglia caused by immunological activation of ganglionic mast cells. Subsequent to mast cell activation, lipid and peptide mediators are released which may modulate synaptic function. In this study we determined whether some mast cell-derived mediators, prostaglandin D2 (PGD2; 1.0 µM, platelet aggregating factor (PAF; 0.3 µM and U44619 (a thromboxane analogue; 1.0 µM, and also endothelin-1 (ET-1; 0.5 µM induce synaptic potentiation in the guinea pig superior cervical ganglion (SCG, and compared their effects on synaptic transmission with those induced by a sensitizing antigen, ovalbumin (OVA; 10 µg/ml. The experiments were carried out on SCGs isolated from adult male guinea pigs (200-250 g actively sensitized to OVA, maintained in oxygenated Locke solution at 37oC. Synaptic potentiation was measured through alterations of the integral of the post-ganglionic compound action potential (CAP. All agents tested caused long-term (LTP; duration ³30 min or short-term (STP; <30 min potentiation of synaptic efficacy, as measured by the increase in the integral of the post-ganglionic CAP. The magnitude of mediator-induced potentiation was never the same as the antigen-induced long-term potentiation (A-LTP. The agent that best mimicked the antigen was PGD2, which induced a 75% increase in CAP integral for LTP (antigen: 94% and a 34% increase for STP (antigen: 91%. PAF-, U44619-, and ET-1-induced increases in CAP integral ranged for LTP from 34 to 47%, and for STP from 0 to 26%. These results suggest that the agents investigated may participate in the induction of A-LTP

  3. Alterations in synaptic curvature in the dentate gyrus following induction of long-term potentiation, long-term depression, and treatment with the N-methyl-D-aspartate receptor antagonist CPP

    Czech Academy of Sciences Publication Activity Database

    Medvedev, N. I.; Popov, V. I.; Dallerac, G.; Davies, H.A.; Laroche, S.; Kraev, I. V.; Rodríguez Arellano, Jose Julio; Doyere, V.; Stewart, M.G.

    2010-01-01

    Roč. 171, č. 2 (2010), s. 390-397 ISSN 0306-4522 Institutional research plan: CEZ:AV0Z50390703 Keywords : D synaptic ultrastructure * hippocampus * long term potentiation and depression Subject RIV: FH - Neurology Impact factor: 3.215, year: 2010

  4. Adult onset-hypothyroidism increases response latency and long-term potentiation (LTP) in rat hippocampus

    Science.gov (United States)

    Thyroid hormones (TH) influence central nervous system (CNS) function during both development and in adulthood. The hippocampus is critical for some types of learning and memory and is particularly sensitive to thyroid hormone deficiency. Hypothyroidism in adulthood has been ass...

  5. Long-term visuo-gustatory appetitive and aversive conditioning potentiate human visual evoked potentials

    DEFF Research Database (Denmark)

    Christoffersen, Gert R.J.; Laugesen, Jakob L.; Møller, Per

    2017-01-01

    Human recognition of foods and beverages are often based on visual cues associated with flavors. The dynamics of neurophysiological plasticity related to acquisition of such long-term associations has only recently become the target of investigation. In the present work, the effects of appetitive...... and aversive visuo-gustatory conditioning were studied with high density EEG-recordings focusing on late components in the visual evoked potentials (VEPs), specifically the N2-P3 waves. Unfamiliar images were paired with either a pleasant or an unpleasant juice and VEPs evoked by the images were compared...... before and 1 day after the pairings. In electrodes located over posterior visual cortex areas, the following changes were observed after conditioning: the amplitude from the N2-peak to the P3-peak increased and the N2 peak delay was reduced. The percentage increase of N2-to-P3 amplitudes...

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

    Science.gov (United States)

    Myoga, Michael H.; Regehr, Wade G.

    2011-01-01

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

  7. Long-term performance potential of concentrated photovoltaic (CPV) systems

    KAUST Repository

    Burhan, Muhammad; Shahzad, Muhammad Wakil; Ng, Kim Choon

    2017-01-01

    estimation of a large PV field, the long term performance as electrical output is a more rational approach over the conventional testing methods, such as at Standard Testing Conditions (STC) and at the Nominal Operating Cell Temperature (NOCT) available

  8. Long-term potential and actual evapotranspiration of two different forests on the Atlantic Coastal Plain

    Science.gov (United States)

    Devendra Amatya; S. Tian; Z. Dai; Ge Sun

    2016-01-01

    A reliable estimate of potential evapotranspiration (PET) for a forest ecosystem is critical in ecohydrologic modeling related with water supply, vegetation dynamics, and climate change and yet is a challenging task due to its complexity. Based on long-term on-site measured hydro-climatic data and predictions from earlier validated hydrologic modeling studies...

  9. Amine Neurotransmitter Regulation of Long-Term Snyaptic Plasticity in Hippocampus

    Science.gov (United States)

    1988-06-14

    conductance, or the membrane properties of the postsynaptic neuron. During the first and second years oi4AIpga, we explored the neuromodulation of LTP by...ladrenoceptors and cyclic AMP, increased the activity of single calcium chaj el. During the third year -of 4IW gisirt, we explored the neuromodulation ...the postsynaptic neuron. During the first and second years of the grant, we explored the neuromodulation of LTP by norepinephrine (NE). We found that NE

  10. The ltp gene of temperate Streptococcus thermophilus phage TP-J34 confers superinfection exclusion to Streptococcus thermophilus and Lactococcus lactis

    International Nuclear Information System (INIS)

    Sun Xingmin; Goehler, Andre; Heller, Knut J.; Neve, Horst

    2006-01-01

    The ltp gene, located within the lysogeny module of temperate Streptococcus thermophilus phage TP-J34, has been shown to be expressed in lysogenic strain S. thermophilus J34. It codes for a lipoprotein, as demonstrated by inhibition of cleavage of the signal sequence by globomycin. Exposure of Ltp on the surface of Lactococcus lactis protoplasts bearing a plasmid-encoded copy of ltp has been demonstrated by immunogold labeling and electron microscopy. Expression of ltp in prophage- and plasmid-cured S. thermophilus J34-6f interfered with TP-J34 infection. While plating efficiency was reduced by a factor of about 40 and lysis of strain J34-6f in liquid medium was delayed considerably, phage adsorption was not affected at all. Intracellular accumulation of phage DNA was shown to be inhibited by Ltp. This indicates interference of Ltp with infection at the stage of triggering DNA release and injection into the cell, indicating a role of Ltp in superinfection exclusion. Expression of ltp in L. lactis Bu2-60 showed that the same superinfection exclusion mechanism was strongly effective against phage P008, a member of the lactococcal 936 phage species: no plaque-formation was detectable with even 10 9 phage per ml applied, and lysis in liquid medium did not occur. In Lactococcus also, Ltp apparently inhibited phage DNA release and/or injection. Ltp appears to be a member of a family of small, secreted proteins with a 42 amino acids repeat structure encoded by genes of Gram-positive bacteria. Some of these homologous genes are part of the genomes of prophages

  11. Opposite long-term synaptic effects of 17β-estradiol and 5α-dihydrotestosterone and localization of their receptors in the medial vestibular nucleus of rats.

    Science.gov (United States)

    Grassi, Silvarosa; Scarduzio, Mariangela; Panichi, Roberto; Dall'Aglio, Cecilia; Boiti, Cristiano; Pettorossi, Vito E

    2013-08-01

    In brainstem slices of male rats, we examined in single neurons of the medial vestibular nucleus (MVN) the effect of exogenous administration of estrogenic (17β-estradiol, E2) and androgenic (5α-dihydrotestosterone, DHT) steroids on the synaptic response to vestibular afferent stimulation. By whole cell patch clamp recordings we showed that E2 induced synaptic long-term potentiation (LTP) that was cancelled by the subsequent administration of DHT. Conversely, DHT induced synaptic long-term depression (LTD) that was partially reversed by E2. The electrophysiological findings were supported by immunohistochemical analysis showing the presence of estrogen (ER: α and β) and androgen receptors (AR) in the MVN neurons. We found that a large number of neurons were immunoreactive for ERα, ERβ, and AR and most of them co-localized ERβ and AR. We also showed the presence of P450-aromatase (ARO) in the MVN neurons, clearly proving that E2 can be locally synthesized in the MVN. On the whole, these results demonstrate a role of estrogenic and androgenic signals in modulating vestibular synaptic plasticity and suggest that the enhancement or depression of vestibular synaptic response may depend on the local conversion of T into E2 or DHT. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training

    OpenAIRE

    Shields, Richard K.; Dudley-Javoroski, Shauna; Littmann, Andrew E.

    2006-01-01

    Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potent...

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

    Directory of Open Access Journals (Sweden)

    Amber Kerkhofs

    2018-03-01

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

  14. Net sulfur mineralization potential in Swedish arable soils in relation to long-term treatment history and soil properties

    DEFF Research Database (Denmark)

    Boye, Kristin; Nilsson, S Ingvar; Eriksen, Jørgen

    2009-01-01

    accumulated net S mineralization (SAccMin) and a number of soil physical and chemical properties were determined. Treatments and soil differences in SAccMin, as well as correlations with soil variables, were tested with single and multivariate analyses. Long-term FYM application resulted in a significantly (p......The long-term treatment effect (since 1957-1966) of farmyard manure (FYM) application compared with crop residue incorporation was investigated in five soils (sandy loam to silty clay) with regards to the net sulfur (S) mineralization potential. An open incubation technique was used to determine...... = 0.012) higher net S mineralization potential, although total amounts of C, N, and S were not significantly (p soils within this treatment. The measured soil variables were not significantly correlated...

  15. Modulatory role of androgenic and estrogenic neurosteroids in determining the direction of synaptic plasticity in the CA1 hippocampal region of male rats.

    Science.gov (United States)

    Pettorossi, Vito Enrico; Di Mauro, Michela; Scarduzio, Mariangela; Panichi, Roberto; Tozzi, Alessandro; Calabresi, Paolo; Grassi, Silvarosa

    2013-12-01

    Estrogenic and androgenic neurosteroids can rapidly modulate synaptic plasticity in the brain through interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used electrophysiological recordings in slices of young and adolescent male rats to explore the influence of sex neurosteroids on synaptic plasticity in the CA1 hippocampal region, by blocking ARs or ERs during induction of long-term depression (LTD) and depotentiation (DP) by low-frequency stimulation (LFS) and long-term potentiation (LTP) by high-frequency stimulation (HFS). We found that LTD and DP depend on ARs, while LTP on ERs in both age groups. Accordingly, the AR blocker flutamide affected induction of LTD reverting it into LTP, and prevented DP, while having no effect on HFS-dependent LTP. Conversely, ER blockade with ICI 182,780 (ICI) markedly reduced LTP, but did not influence LTD and DP. However, the receptor blockade did not affect the maintenance of either LTD or LTP. Moreover, we found that similar to LTP and LTD induced in control condition, the LTP unveiled by flutamide during LFS and residual LTP induced by HFS under ICI depended on N-methyl-d aspartate receptor (NMDAR) activation. Furthermore, as the synaptic paired-pulse facilitation (PPF) was not affected by either AR or ER blockade, we suggest that sex neurosteroids act primarily at a postsynaptic level. This study demonstrates for the first time the crucial role of estrogenic and androgenic neurosteroids in determining the sign of hippocampal synaptic plasticity in male rat and the activity-dependent recruitment of androgenic and estrogenic pathways leading to LTD and LTP, respectively.

  16. What Legislators Need to Know about Long-Term Care Insurance.

    Science.gov (United States)

    Landes, David

    This booklet discusses the potential importance to states of long-term care insurance, describes general policy characteristics, and summarizes state actions to both regulate and promote long-term care insurance. It is intended as a resource for legislators and others involved in long-term care financing and public policy formulation. Long-term…

  17. Long-Term Memory Performance in Adult ADHD.

    Science.gov (United States)

    Skodzik, Timo; Holling, Heinz; Pedersen, Anya

    2017-02-01

    Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

  18. Overexpression of wheat lipid transfer protein gene TaLTP5 increases resistances to Cochliobolus sativus and Fusarium graminearum in transgenic wheat.

    Science.gov (United States)

    Zhu, Xiuliang; Li, Zhao; Xu, Huijun; Zhou, Miaoping; Du, Lipu; Zhang, Zengyan

    2012-08-01

    The fungus Cochliobolus sativus is the main pathogen of common root rot, a serious soil-borne disease of wheat (Triticum aestivum L.). The fungus Fusarium graminearum is the primary pathogen of Fusarium head blight, a devastating disease of wheat worldwide. In this study, the wheat lipid transfer protein gene, TaLTP5, was cloned and evaluated for its ability to suppress disease development in transgenic wheat. TaLTP5 expression was induced after C. sativus infection. The TaLTP5 expression vector, pA25-TaLTP5, was constructed and bombarded into Chinese wheat variety Yangmai 18. Six TaLTP5 transgenic wheat lines were established and characterized. PCR and Southern blot analyses indicated that the introduced TaLTP5 gene was integrated into the genomes of six transgenic wheat lines by distinct patterns, and heritable. RT-PCR and real-time quantitative RT-PCR revealed that the TaLTP5 gene was over-expressed in the transgenic wheat lines compared to segregants lacking the transgene and wild-type wheat plants. Following challenge with C. sativus or F. graminearum, all six transgenic lines overexpressing TaLTP5 exhibited significantly enhanced resistance to both common root rot and Fusarium head blight compared to the untransformed wheat Yangmai 18.

  19. Do studies on cortical plasticity provide a rationale for using non invasive brain stimulation as a treatment for Parkinson’s disease patients?

    Directory of Open Access Journals (Sweden)

    Giacomo eKoch

    2013-11-01

    Full Text Available Animal models of Parkinson’s disease (PD have shown that key mechanisms of cortical plasticity such as long-term potentiation (LTP and long-term depression (LTD can be impaired by the PD pathology. In humans protocols of non-invasive brain stimulation, such as paired associative stimulation (PAS and theta burst stimulation (TBS, can be used to investigate cortical plasticity of the primary motor cortex. Through the amplitude of the motor evoked potential (MEP these transcranial magnetic stimulation methods allow to measure both LTP-like and LTD-like mechanisms of cortical plasticity. So far these protocols have reported some controversial findings when tested in PD patients. While various studies described evidence for reduced LTP- and LTD-like plasticity, others showed different results, demonstrating increased LTP-like and normal LTD-like plasticity. Recent evidence provided support to the hypothesis that these different patterns of cortical plasticity likely depend on the stage of the disease and on the concomitant administration of levo-dopa. However, it still unclear how and if these altered mechanisms of cortical plasticity can be taken as a reliable model to build appropriate protocols aimed at treating PD symptoms b

  20. Training the integrate-and-fire model with the informax principle: I

    Energy Technology Data Exchange (ETDEWEB)

    Feng Jianfeng; Buxton, Hilary [COGS, Sussex University, Brighton (United Kingdom); Deng Yingchun [Department of Mathematics, Hunan Normal University, Changsha (China)

    2002-03-15

    In terms of the informax principle, and the input-output relationship of the integrate-and-fire (IF) model, IF neuron learning rules are developed. For supervised learning and with uniform weight of synapses (the theoretically tractable case), we show that the derived learning rule is stable and the stable state is unique. For unsupervised learning, within physiologically reasonable parameter regions, both long-term potentiation (LTP) and long-term depression (LTD) could happen when the inhibitory input is weak, but LTD cannot be observed when inhibitory input is strong enough. When both LTP and LTD occur, LTD is observable when the output of the postsynaptic neuron is faster than pre-synaptic inputs, otherwise LTP is observable, as observed in recent experiments. Learning rules of general cases are also studied and numerical examples show that the derived learning rule tends to equalize the contribution of different inputs to the output firing rates. (author)

  1. Long-term performance potential of concentrated photovoltaic (CPV) systems

    KAUST Repository

    Burhan, Muhammad

    2017-07-17

    Owing to the diverse photovoltaic (PV) systems’ design and technology, as well as the dynamic nature of insolation data received on the aperture surfaces, the instantaneous output from a PV system fluctuates greatly. For accurate performance estimation of a large PV field, the long term performance as electrical output is a more rational approach over the conventional testing methods, such as at Standard Testing Conditions (STC) and at the Nominal Operating Cell Temperature (NOCT) available hitherto. In this paper, the long-term performances of concentrated PVs (Cassegrain reflectors and Fresnel lens) with 2-axes tracking and a variety of PV systems, namely the stationary flat-plate PV (mono-crystalline, poly-crystalline and thin-films CIS types), is presented over a period of one year for the merit comparison of system design, under the tropical weather conditions of Singapore. From the measured field performances, the total energy output of 240.2 kW h/m/year is recorded for CPV operation in Singapore, which is nearly two folds higher than the stationary PV panels.

  2. Chronic Methamphetamine Exposure Produces a Delayed, Long-Lasting Memory Deficit

    OpenAIRE

    North, Ashley; Swant, Jarod; Salvatore, Michael F.; Gamble-George, Joyonna; Prins, Petra; Butler, Brittany; Mittal, Mukul K.; Heltsley, Rebecca; Clark, John T.; Khoshbouei, Habibeh

    2013-01-01

    Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment. Whether this is due to long-term deficits in short-term memory and/or hippocampal plasticity remains unclear. Recently, we reported that METH increases baseline synaptic transmission and reduces LTP in an ex vivo preparation of the hippocampal CA1 region from young mice. In the current study, we tested the hypothesis that a repeated neurotoxic regi...

  3. The repetition timing of high frequency afferent stimulation drives the bidirectional plasticity at central synapses in the rat medial vestibular nuclei.

    Science.gov (United States)

    Scarduzio, M; Panichi, R; Pettorossi, V E; Grassi, S

    2012-10-25

    In this study we show that high frequency stimulation (HFS, 100Hz) of afferent fibers to the medial vestibular nucleus (MVN) can induce opposite long-term modifications of synaptic responses in the type B neurons depending upon the stimulation pattern. Long burst stimulation (LBS: 2s) and short burst stimulation (SBS: 0.55s) were applied with different burst number (BN) and inter-burst intervals (IBI). It results that both LBS and SBS can induce either N-methyl-d aspartate receptors (NMDARs)-mediated long-term potentiation (LTP) or long-term depression (LTD), depending on temporal organization of repetitive bursts. In particular, the IBI plays a relevant role in guiding the shift from LTP to LTD since by using both LBS and SBS LTP is induced by shorter IBI than LTD. By contrast, the sign of long-term effect does not depend on the mean impulse frequency evaluated within the entire stimulation period. Therefore, the patterns of repetitive vestibular activation with different ratios between periods of increased activity and periods of basal activity may lead to LTP or LTD probably causing different levels of postsynaptic Ca(2+). On the whole, this study demonstrates that glutamatergic vestibular synapse in the MVN can undergo NMDAR-dependent bidirectional plasticity and puts forward a new aspect for understanding the adaptive and compensatory plasticity of the oculomotor responses. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. iTBS-induced LTP-like plasticity parallels oscillatory activity changes in the primary sensory and motor areas of macaque monkeys.

    Science.gov (United States)

    Papazachariadis, Odysseas; Dante, Vittorio; Verschure, Paul F M J; Del Giudice, Paolo; Ferraina, Stefano

    2014-01-01

    Recently, neuromodulation techniques based on the use of repetitive transcranial magnetic stimulation (rTMS) have been proposed as a non-invasive and efficient method to induce in vivo long-term potentiation (LTP)-like aftereffects. However, the exact impact of rTMS-induced perturbations on the dynamics of neuronal population activity is not well understood. Here, in two monkeys, we examine changes in the oscillatory activity of the sensorimotor cortex following an intermittent theta burst stimulation (iTBS) protocol. We first probed iTBS modulatory effects by testing the iTBS-induced facilitation of somatosensory evoked potentials (SEP). Then, we examined the frequency information of the electrocorticographic signal, obtained using a custom-made miniaturised multi-electrode array for electrocorticography, after real or sham iTBS. We observed that iTBS induced facilitation of SEPs and influenced spectral components of the signal, in both animals. The latter effect was more prominent on the θ band (4-8 Hz) and the high γ band (55-90 Hz), de-potentiated and potentiated respectively. We additionally found that the multi-electrode array uniformity of β (13-26 Hz) and high γ bands were also afflicted by iTBS. Our study suggests that enhanced cortical excitability promoted by iTBS parallels a dynamic reorganisation of the interested neural network. The effect in the γ band suggests a transient local modulation, possibly at the level of synaptic strength in interneurons. The effect in the θ band suggests the disruption of temporal coordination on larger spatial scales.

  5. iTBS-induced LTP-like plasticity parallels oscillatory activity changes in the primary sensory and motor areas of macaque monkeys.

    Directory of Open Access Journals (Sweden)

    Odysseas Papazachariadis

    Full Text Available Recently, neuromodulation techniques based on the use of repetitive transcranial magnetic stimulation (rTMS have been proposed as a non-invasive and efficient method to induce in vivo long-term potentiation (LTP-like aftereffects. However, the exact impact of rTMS-induced perturbations on the dynamics of neuronal population activity is not well understood. Here, in two monkeys, we examine changes in the oscillatory activity of the sensorimotor cortex following an intermittent theta burst stimulation (iTBS protocol. We first probed iTBS modulatory effects by testing the iTBS-induced facilitation of somatosensory evoked potentials (SEP. Then, we examined the frequency information of the electrocorticographic signal, obtained using a custom-made miniaturised multi-electrode array for electrocorticography, after real or sham iTBS. We observed that iTBS induced facilitation of SEPs and influenced spectral components of the signal, in both animals. The latter effect was more prominent on the θ band (4-8 Hz and the high γ band (55-90 Hz, de-potentiated and potentiated respectively. We additionally found that the multi-electrode array uniformity of β (13-26 Hz and high γ bands were also afflicted by iTBS. Our study suggests that enhanced cortical excitability promoted by iTBS parallels a dynamic reorganisation of the interested neural network. The effect in the γ band suggests a transient local modulation, possibly at the level of synaptic strength in interneurons. The effect in the θ band suggests the disruption of temporal coordination on larger spatial scales.

  6. BraLTP1, a lipid transfer protein gene involved in epicuticular wax deposition, cell proliferation and flower development in Brassica napus.

    Directory of Open Access Journals (Sweden)

    Fang Liu

    Full Text Available Plant non-specific lipid transfer proteins (nsLTPs constitute large multigene families that possess complex physiological functions, many of which remain unclear. This study isolated and characterized the function of a lipid transfer protein gene, BraLTP1 from Brassica rapa, in the important oilseed crops Brassica napus. BraLTP1 encodes a predicted secretory protein, in the little known VI Class of nsLTP families. Overexpression of BnaLTP1 in B. napus caused abnormal green coloration and reduced wax deposition on leaves and detailed wax analysis revealed 17-80% reduction in various major wax components, which resulted in significant water-loss relative to wild type. BnaLTP1 overexpressing leaves exhibited morphological disfiguration and abaxially curled leaf edges, and leaf cross-sections revealed cell overproliferation that was correlated to increased cytokinin levels (tZ, tZR, iP, and iPR in leaves and high expression of the cytokinin biosynthsis gene IPT3. BnaLTP1-overexpressing plants also displayed morphological disfiguration of flowers, with early-onset and elongated carpel development and outwardly curled stamen. This was consistent with altered expression of a a number of ABC model genes related to flower development. Together, these results suggest that BraLTP1 is a new nsLTP gene involved in wax production or deposition, with additional direct or indirect effects on cell division and flower development.

  7. Short-Term Success versus Long-Term Failure: A Simulation-Based Approach for Understanding the Potential of Zambia’s Fertilizer Subsidy Program in Enhancing Maize Availability

    Directory of Open Access Journals (Sweden)

    Andreas Gerber

    2016-10-01

    Full Text Available In Sub-Saharan Africa, food-related policies such as fertilizer subsidy programs (FSPs have undergone a revival and triggered a controversy about their impact. In this article I applied a simulation-based approach to examine the FSPs’ short- and long-term potential for increasing maize availability in Zambia. The study revealed that FSPs are an effective policy measure to enhance maize availability in the short-term. However, in the long-term, the food system becomes dependent on the government’s annual expenses. The dependency occurs because FSPs fail to build up adequate stock levels of soil organic matter (SOM, which is an important source of resilience and productivity, and thus represents a long-term leverage point in Zambia’s maize production system. For this reason, alternative policies that combine increasing productivity and building up SOM stock levels were analyzed. They were found to be a viable means for enhancing long-term maize availability. The study concludes that gradually reducing investments in FSPs while simultaneously promoting farming practices that build up SOM stock levels is a promising strategy to enhance maize availability sustainably.

  8. The long-term benefits of director stock ownership

    Directory of Open Access Journals (Sweden)

    Brian Bolton

    2009-11-01

    Full Text Available In October 2009, the United States Treasury Department and Congress considered new regulations requiring executives and directors to receive much of their compensation in the form of long-term stock. One concern with this is that it may have negative consequences by entrenching managers and directors over the long term. This study compares the potential benefits of long-term director ownership with the potential costs of entrenchment. Using the dollar amount of stock owned by independent directors, the results suggest that the incentive effect dominates any costs related to entrenchment: firms with greater stock ownership outperform other firms, regardless of the degree of managerial entrenchment that may be present. The implication for policy-makers is that providing directors with incentives through stock ownership can be a very effective corporate governance mechanism.

  9. Pomegranate ( Punica granatum L.) expresses several nsLTP isoforms characterized by different immunoglobulin E-binding properties.

    Science.gov (United States)

    Bolla, Michela; Zenoni, Sara; Scheurer, Stephan; Vieths, Stefan; San Miguel Moncin, Maria Del Mar; Olivieri, Mario; Antico, Andrea; Ferrer, Marta; Berroa, Felicia; Enrique, Ernesto; Avesani, Linda; Marsano, Francesco; Zoccatelli, Gianni

    2014-01-01

    Pomegranate allergy is associated with sensitization to non-specific lipid transfer proteins (nsLTPs). Our aim was to identify and characterize the non-specific nsLTPs expressed in pomegranate at the molecular level and to study their allergenic properties in terms of immunoglobulin E (IgE)-binding and cross-reactivity with peach nsLTP (Pru p 3). A non-equilibrium two-dimensional (2-D) electrophoretic approach based on acid-urea PAGE and sodium dodecyl sulfate PAGE was set up to separate pomegranate nsLTPs. Their immunoreactivity was tested by immunoblotting carried out with anti-Pru p 3 polyclonal antibodies and sera from pomegranate-allergic patients. For final identification, pomegranate nsLTPs were purified by chromatography and subjected to trypsin digestion and mass spectrometry (MS) analysis. For this purpose, the sequences obtained by cDNA cloning of three pomegranate nsLTPs were integrated in the database that was subsequently searched for MS data interpretation. Four nsLTPs were identified by 2-D immunoblotting. The detected proteins showed different IgE-binding capacity and partial cross-reactivity with Pru p 3. cDNA cloning and MS analyses led to the identification of three nsLTP isoforms with 66-68% amino acid sequence identity named Pun g 1.0101, Pun g 1.0201 and Pun g 1.0301. By 2-D electrophoresis, we could separate different nsLTP isoforms possessing different IgE-binding properties, which might reflect peculiar allergenic potencies. The contribution of Pru p 3 to prime sensitization is not central as in other plant nsLTPs. © 2014 S. Karger AG, Basel.

  10. Effect of Insulin on Visuo-Spatial Memory and Histology of Cerebral ...

    African Journals Online (AJOL)

    olayemitoyin

    the neuronal networks, based on long-term potentiation (LTP) ... insulin syringe daily between the hours of 8:00 – 9:00 am. The mice ... findings. Assessment of long-term visuo-spatial learning and ... (Handycam, SONY, Japan) recorded movement of the mice for later .... laboratory methods, and which this work did not seek.

  11. A least squares approach for efficient and reliable short-term versus long-term optimization

    DEFF Research Database (Denmark)

    Christiansen, Lasse Hjuler; Capolei, Andrea; Jørgensen, John Bagterp

    2017-01-01

    The uncertainties related to long-term forecasts of oil prices impose significant financial risk on ventures of oil production. To minimize risk, oil companies are inclined to maximize profit over short-term horizons ranging from months to a few years. In contrast, conventional production...... optimization maximizes long-term profits over horizons that span more than a decade. To address this challenge, the oil literature has introduced short-term versus long-term optimization. Ideally, this problem is solved by a posteriori multi-objective optimization methods that generate an approximation...... the balance between the objectives, leaving an unfulfilled potential to increase profits. To promote efficient and reliable short-term versus long-term optimization, this paper introduces a natural way to characterize desirable Pareto points and proposes a novel least squares (LS) method. Unlike hierarchical...

  12. Long-term no-till and stover retention each decrease the global warming potential of irrigated continuous corn

    Science.gov (United States)

    Over the last 50 years, the most increase in cultivated land area globally has been due to a doubling of irrigated land. Long-term agronomic management impacts on soil organic carbon (SOC) stocks, soil greenhouse gas (GHG) emis-sions, and global warming potential (GWP) in irrigated systems, however,...

  13. Long-range terms in atomic collisions

    International Nuclear Information System (INIS)

    McGuire, J.H.; Weaver, O.L.

    1986-01-01

    Various separations, or ''gauge choices,'' are possible for the decomposition of the total Hamiltonian into electronic and internuclear terms. We show that, for one particular choice, all long-range Coulomb terms are associated with the internuclear motion. The potential then associated with electronic transitions is non-Coulombic. Some practical consequences of this gauge choice are discussed

  14. IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning.

    Science.gov (United States)

    Liu, Zhihui; Chen, Zijun; Shang, Congping; Yan, Fei; Shi, Yingchao; Zhang, Jiajing; Qu, Baole; Han, Hailin; Wang, Yanying; Li, Dapeng; Südhof, Thomas C; Cao, Peng

    2017-07-05

    During social transmission of food preference (STFP), mice form long-term memory of food odors presented by a social partner. How does the brain associate a social context with odor signals to promote memory encoding? Here we show that odor exposure during STFP, but not unconditioned odor exposure, induces glomerulus-specific long-term potentiation (LTP) of synaptic strength selectively at the GABAergic component of dendrodendritic synapses of granule and mitral cells in the olfactory bulb. Conditional deletion of synaptotagmin-10, the Ca 2+ sensor for IGF1 secretion from mitral cells, or deletion of IGF1 receptor in the olfactory bulb prevented the socially relevant GABAergic LTP and impaired memory formation after STFP. Conversely, the addition of IGF1 to acute olfactory bulb slices elicited the GABAergic LTP in mitral cells by enhancing postsynaptic GABA receptor responses. Thus, our data reveal a synaptic substrate for a socially conditioned long-term memory that operates at the level of the initial processing of sensory information. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Space ventures and society long-term perspectives

    Science.gov (United States)

    Brown, W. M.

    1985-01-01

    A futuristic evaluation of mankind's potential long term future in space is presented. Progress in space will not be inhibited by shortages of the Earth's physical resources, since long term economic growth will be focused on ways to constrain industrial productivity by changing social values, management styles, or government competence. Future technological progress is likely to accelerate with an emphasis on international cooperation, making possible such large joint projects as lunar colonies or space stations on Mars. The long term future in space looks exceedingly bright even in relatively pessimistic scenarios. The principal driving forces will be technological progress, commercial and public-oriented satellites, space industrialization, space travel, and eventually space colonization.

  16. DCC Expression by Neurons Regulates Synaptic Plasticity in the Adult Brain

    Directory of Open Access Journals (Sweden)

    Katherine E. Horn

    2013-01-01

    Full Text Available The transmembrane protein deleted in colorectal cancer (DCC and its ligand, netrin-1, regulate synaptogenesis during development, but their function in the mature central nervous system is unknown. Given that DCC promotes cell-cell adhesion, is expressed by neurons, and activates proteins that signal at synapses, we hypothesized that DCC expression by neurons regulates synaptic function and plasticity in the adult brain. We report that DCC is enriched in dendritic spines of pyramidal neurons in wild-type mice, and we demonstrate that selective deletion of DCC from neurons in the adult forebrain results in the loss of long-term potentiation (LTP, intact long-term depression, shorter dendritic spines, and impaired spatial and recognition memory. LTP induction requires Src activation of NMDA receptor (NMDAR function. DCC deletion severely reduced Src activation. We demonstrate that enhancing NMDAR function or activating Src rescues LTP in the absence of DCC. We conclude that DCC activation of Src is required for NMDAR-dependent LTP and certain forms of learning and memory.

  17. Potential long-term storage of the predatory mite Phytoseiulus persimilis

    Science.gov (United States)

    Increasing the ability to store mass-reared natural enemies during periods or seasons of low demand is a critical need of the biocontrol industry. We tested the hypothesis that cryoprotectant or carbohydrate molecules can enhance long-term cold storage of a predatory mite Phytoseiulus persimilis At...

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

    Directory of Open Access Journals (Sweden)

    Katharine L. Dobson

    2015-01-01

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

  19. Audit of long-term and short-term liabilities

    Directory of Open Access Journals (Sweden)

    Korinko M.D.

    2017-03-01

    Full Text Available The article determines the importance of long-term and short-term liabilities for the management of financial and material resources of an enterprise. It reviews the aim, objects and information generators for realization of audit of short-term and long-term obligations. The organizing and methodical providing of audit of long-term and short-term liabilities of an enterprise are generalized. The authors distinguish the stages of realization of audit of long-term and short-term liabilities, the aim of audit on each of the presented stages, and recommend methodical techniques. It is fixed that it is necessary to conduct the estimation of the systems of internal control and record-keeping of an enterprise by implementation of public accountant procedures for determination of volume and maintenance of selection realization. After estimating the indicated systems, a public accountant determines the methodology for realization of public accountant verification of long-term and short-term liabilities. The analytical procedures that public accountants are expedient to use for realization of audit of short-term and long-term obligations are determined. The authors suggest the classification of the educed defects on the results of the conducted public accountant verification of short-term and long-term obligations.

  20. Group I mGluR antagonist rescues the deficit of D1-induced LTP in a mouse model of fragile X syndrome

    Directory of Open Access Journals (Sweden)

    Xu Zhao-Hui

    2012-05-01

    Full Text Available Abstract Background Fragile X syndrome (FXS is caused by the absence of the mRNA-binding protein Fragile X mental retardation protein (FMRP, encoded by the Fmr1 gene. Overactive signaling by group 1 metabotropic glutamate receptor (Grp1 mGluR could contribute to slowed synaptic development and other symptoms of FXS. Our previous study has identified that facilitation of synaptic long-term potentiation (LTP by D1 receptor is impaired in Fmr1 knockout (KO mice. However, the contribution of Grp1 mGluR to the facilitation of synaptic plasticity by D1 receptor stimulation in the prefrontal cortex has been less extensively studied. Results Here we demonstrated that DL-AP3, a Grp1 mGluR antagonist, rescued LTP facilitation by D1 receptor agonist SKF81297 in Fmr1KO mice. Grp1 mGluR inhibition restored the GluR1-subtype AMPA receptors surface insertion by D1 activation in the cultured Fmr1KO neurons. Simultaneous treatment of Grp1 mGluR antagonist with D1 agonist recovered the D1 receptor signaling by reversing the subcellular redistribution of G protein-coupled receptor kinase 2 (GRK2 in the Fmr1KO neurons. Treatment of SKF81297 alone failed to increase the phosphorylation of NR2B-containing N-methyl D-aspartate receptors (NMDARs at Tyr-1472 (p-NR2B-Tyr1472 in the cultures from KO mice. However, simultaneous treatment of DL-AP3 could rescue the level of p-NR2B-Tyr1472 by SKF81297 in the cultures from KO mice. Furthermore, behavioral tests indicated that simultaneous treatment of Grp1 mGluR antagonist with D1 agonist inhibited hyperactivity and improved the learning ability in the Fmr1KO mice. Conclusion The findings demonstrate that mGluR1 inhibition is a useful strategy to recover D1 receptor signaling in the Fmr1KO mice, and combination of Grp1 mGluR antagonist and D1 agonist is a potential drug therapy for the FXS.

  1. Chronic caffeine treatment prevents sleep deprivation-induced impairment of cognitive function and synaptic plasticity.

    Science.gov (United States)

    Alhaider, Ibrahim A; Aleisa, Abdulaziz M; Tran, Trinh T; Alzoubi, Karem H; Alkadhi, Karim A

    2010-04-01

    This study was undertaken to provide a detailed account of the effect of chronic treatment with a small dose of caffeine on the deleterious effects of sleep loss on brain function in rats. We investigated the effects of chronic (4 weeks) caffeine treatment (0.3 g/L in drinking water) on memory impairment in acutely (24 h) sleep-deprived adult male Wistar rats. Sleep deprivation was induced using the modified multiple platform model. The effects of caffeine on sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by 3 approaches: learning and memory performance in the radial arm water maze task, electrophysiological recording of early long-term potentiation (E-LTP) in area CA1 of the hippocampus, and levels of memory- and synaptic plasticity-related signaling molecules after E-LTP induction. The results showed that chronic caffeine treatment prevented impairment of hippocampus-dependent learning, shortterm memory and E-LTP of area CA1 in the sleep-deprived rats. In correlation, chronic caffeine treatment prevented sleep deprivation-associated decrease in the levels of phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) during expression of E-LTP. The results suggest that long-term use of a low dose of caffeine prevents impairment of short-term memory and E-LTP in acutely sleep-deprived rats.

  2. The effect of extensive reading and paired-associate learning on long-term vocabulary retention: an event-related potential study.

    Science.gov (United States)

    Chun, Eunjin; Choi, Sungmook; Kim, Junsoo

    2012-07-19

    We investigated the relative efficacy of extensive reading (ER) and paired-associate learning (PAL) in the ability of second language (L2) learners to retain new vocabulary words. To that end, we combined behavioral measures (i.e., vocabulary tests) and an event-related potential (ERP) investigation with a focus on the N400 ERP component to track short- and long-term vocabulary retention as a consequence of the two different approaches. Behavioral results indicated that both ER and PAL led to substantial short-term retention of the target words. In contrast, on a long-term basis, ER was more effective than PAL to a considerable degree as indicated by a large-size effect (d=1.35). Evidence from the N400 effects (d=1.70) observed in the parietal electrode group (P3, Pz, P4) provided further support for the superior effects of ER over PAL on long-term vocabulary retention. The converging evidence challenges the assumptions of some L2 researchers and makes a significant contribution to the literature of vocabulary acquisition, because it provides the first ERP evidence that ER is more conducive to long-term vocabulary retention than PAL. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Long-term follow-up study and long-term care of childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Hyeon Jin Park

    2010-04-01

    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  4. Maintained LTP and Memory Are Lost by Zn2+ Influx into Dentate Granule Cells, but Not Ca2+ Influx.

    Science.gov (United States)

    Takeda, Atsushi; Tamano, Haruna; Hisatsune, Marie; Murakami, Taku; Nakada, Hiroyuki; Fujii, Hiroaki

    2018-02-01

    The idea that maintained LTP and memory are lost by either increase in intracellular Zn 2+ in dentate granule cells or increase in intracellular Ca 2+ was examined to clarify significance of the increases induced by excess synapse excitation. Both maintained LTP and space memory were impaired by injection of high K + into the dentate gyrus, but rescued by co-injection of CaEDTA, which blocked high K + -induced increase in intracellular Zn 2+ but not high K + -induced increase in intracellular Ca 2+ . High K + -induced disturbances of LTP and intracellular Zn 2+ are rescued by co-injection of 6-cyano-7-nitroquinoxakine-2,3-dione, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, but not by co-injection of blockers of NMDA receptors, metabotropic glutamate receptors, and voltage-dependent calcium channels. Furthermore, AMPA impaired maintained LTP and the impairment was also rescued by co-injection of CaEDTA, which blocked increase in intracellular Zn 2+ , but not increase in intracellular Ca 2+ . NMDA and glucocorticoid, which induced Zn 2+ release from the internal stores, did not impair maintained LTP. The present study indicates that increase in Zn 2+ influx into dentate granule cells through AMPA receptors loses maintained LTP and memory. Regulation of Zn 2+ influx into dentate granule cells is more critical for not only memory acquisition but also memory retention than that of Ca 2+ influx.

  5. Long-term biodosimetry Redux

    International Nuclear Information System (INIS)

    Simon, Steven L.; Bouville, Andre

    2016-01-01

    This paper revisits and reiterates the needs, purposes and requirements of bio-dosimetric assays for long-term dose and health risk assessments. While the most crucial need for bio-dosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure

  6. Status Epilepticus Impairs Synaptic Plasticity in Rat Hippocampus and Is Followed by Changes in Expression of NMDA Receptors.

    Science.gov (United States)

    Postnikova, T Y; Zubareva, O E; Kovalenko, A A; Kim, K K; Magazanik, L G; Zaitsev, A V

    2017-03-01

    Cognitive deficits and memory loss are frequent in patients with temporal lobe epilepsy. Persistent changes in synaptic efficacy are considered as a cellular substrate underlying memory processes. Electrophysiological studies have shown that the properties of short-term and long-term synaptic plasticity in the cortex and hippocampus may undergo substantial changes after seizures. However, the neural mechanisms responsible for these changes are not clear. In this study, we investigated the properties of short-term and long-term synaptic plasticity in rat hippocampal slices 24 h after pentylenetetrazole (PTZ)-induced status epilepticus. We found that the induction of long-term potentiation (LTP) in CA1 pyramidal cells is reduced compared to the control, while short-term facilitation is increased. The experimental results do not support the hypothesis that status epilepticus leads to background potentiation of hippocampal synapses and further LTP induction becomes weaker due to occlusion, as the dependence of synaptic responses on the strength of input stimulation was not different in the control and experimental animals. The decrease in LTP can be caused by impairment of molecular mechanisms of neuronal plasticity, including those associated with NMDA receptors and/or changes in their subunit composition. Real-time PCR demonstrated significant increases in the expression of GluN1 and GluN2A subunits 3 h after PTZ-induced status epilepticus. The overexpression of obligate GluN1 subunit suggests an increase in the total number of NMDA receptors in the hippocampus. A 3-fold increase in the expression of the GluN2B subunit observed 24 h after PTZ-induced status epilepticus might be indicative of an increase in the proportion of GluN2B-containing NMDA receptors. Increased expression of the GluN2B subunit may be a cause for reducing the magnitude of LTP at hippocampal synapses after status epilepticus.

  7. Repetitive transcranial magnetic stimulation as a neuropsychiatric tool: present status and future potential.

    Science.gov (United States)

    Post, R M; Kimbrell, T A; McCann, U D; Dunn, R T; Osuch, E A; Speer, A M; Weiss, S R

    1999-03-01

    Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising therapeutic intervention in the treatment of affective disorders. The differences in the type of electrical stimulation required for therapeutic efficacy by rTMS and electroconvulsive therapy (ECT) are discussed. In contrast to ECT, rTMS would not appear to require the generation of a major motor seizure to achieve therapeutic efficacy. Accordingly, it carries the potentially important clinical advantages of not requiring anesthesia and of avoiding side effects such as transient memory loss. Preclinical studies on long-term potentiation (LTP) and long-term depression (LTD) in hippocampal and amygdala slices, as well as clinical data from neuroimaging studies, have provided encouraging clues for potential frequency-dependent effects of rTMS. Preliminary evidence from position emission tomography (PET) scans suggests that higher frequency (20 Hz) stimulation may increase brain glucose metabolism in a transsynaptic fashion, whereas lower frequency (1 Hz) stimulation may decrease it. Therefore, the ability of rTMS to control the frequency as well as the location of stimulation, in addition to its other advantages, has opened up new possibilities for clinical explorations and treatments of neuropsychiatric conditions.

  8. Anticipatory eye movements and long-term memory in early infancy.

    Science.gov (United States)

    Wong-Kee-You, Audrey M B; Adler, Scott A

    2016-11-01

    Advances in our understanding of long-term memory in early infancy have been made possible by studies that have used the Rovee-Collier's mobile conjugate reinforcement paradigm and its variants. One function that has been attributed to long-term memory is the formation of expectations (Rovee-Collier & Hayne, 1987); consequently, a long-term memory representation should be established during expectation formation. To examine this prediction and potentially open the door on a new paradigm for exploring infants' long-term memory, using the Visual Expectation Paradigm (Haith, Hazan, & Goodman, 1988), 3-month-old infants were trained to form an expectation for predictable color and spatial information of picture events and emit anticipatory eye movements to those events. One day later, infants' anticipatory eye movements decreased in number relative to the end of training when the predictable colors were changed but not when the spatial location of the predictable color events was changed. These findings confirm that information encoded during expectation formation are stored in long-term memory, as hypothesized by Rovee-Collier and colleagues. Further, this research suggests that eye movements are potentially viable measures of long-term memory in infancy, providing confirmatory evidence for early mnemonic processes. © 2016 Wiley Periodicals, Inc.

  9. CLIMATE CHANGE: LONG-TERM TRENDS AND SHORT-TERM OSCILLATIONS

    Institute of Scientific and Technical Information of China (English)

    GAO Xin-quan; ZHANG Xin; QIAN Wei-hong

    2006-01-01

    Identifying the Northern Hemisphere (NH) temperature reconstruction and instrumental data for the past 1000 years shows that climate change in the last millennium includes long-term trends and various oscillations. Two long-term trends and the quasi-70-year oscillation were detected in the global temperature series for the last 140 years and the NH millennium series. One important feature was emphasized that temperature decreases slowly but it increases rapidly based on the analysis of different series. Benefits can be obtained of climate change from understanding various long-term trends and oscillations. Millennial temperature proxies from the natural climate system and time series of nonlinear model system are used in understanding the natural climate change and recognizing potential benefits by using the method of wavelet transform analysis. The results from numerical modeling show that major oscillations contained in numerical solutions on the interdecadal timescale are consistent with that of natural proxies. It seems that these oscillations in the climate change are not directly linked with the solar radiation as an external forcing. This investigation may conclude that the climate variability at the interdecadal timescale strongly depends on the internal nonlinear effects in the climate system.

  10. Involvement of TrkB- and p75NTR-signaling pathways in two contrasting forms of long-lasting synaptic plasticity

    Science.gov (United States)

    Sakuragi, Shigeo; Tominaga-Yoshino, Keiko; Ogura, Akihiko

    2013-11-01

    The repetition of experience is often necessary to establish long-lasting memory. However, the cellular mechanisms underlying this repetition-dependent consolidation of memory remain unclear. We previously observed in organotypic slice cultures of the rodent hippocampus that repeated inductions of long-term potentiation (LTP) led to a slowly developing long-lasting synaptic enhancement coupled with synaptogenesis. We also reported that repeated inductions of long-term depression (LTD) produced a long-lasting synaptic suppression coupled with synapse elimination. We proposed these phenomena as useful in vitro models for analyzing repetition-dependent consolidation. Here, we hypothesized that the enhancement and suppression are mediated by the brain-derived neurotrophic factor (BDNF)-TrkB signaling pathway and the proBDNF-p75NTR pathway, respectively. When we masked the respective pathways, reversals of the enhancement and suppression resulted. These results suggest the alternative activation of the p75NTR pathway by BDNF under TrkB-masking conditions and of the TrkB pathway by proBDNF under p75NTR-masking conditions, thus supporting the aforementioned hypothesis.

  11. Portable long trace profiler: Concept and solution

    Science.gov (United States)

    Qian, Shinan; Takacs, Peter; Sostero, Giovanni; Cocco, Daniele

    2001-08-01

    Since the early development of the penta-prism long trace profiler (LTP) and the in situ LTP, and following the completion of the first in situ distortion profile measurements at Sincrotrone Trieste (ELETTRA) in Italy in 1995, a concept was developed for a compact, portable LTP with the following characteristics: easily installed on synchrotron radiation beam lines, easily carried to different laboratories around the world for measurements and calibration, convenient for use in evaluating the LTP as an in-process tool in the optical workshop, and convenient for use in temporarily installation as required by other special applications. The initial design of a compact LTP optical head was made at ELETTRA in 1995. Since 1997 further efforts to reduce the optical head size and weight, and to improve measurement stability have been made at Brookhaven National Laboratory. This article introduces the following solutions and accomplishments for the portable LTP: (1) a new design for a compact and very stable optical head, (2) the use of a small detector connected to a laptop computer directly via an enhanced parallel port, and there is no extra frame grabber interface and control box, (3) a customized small mechanical slide that uses a compact motor with a connector-sized motor controller, and (4) the use of a laptop computer system. These solutions make the portable LTP able to be packed into two laptop-size cases: one for the computer and one for the rest of the system.

  12. Portable long trace profiler: Concept and solution

    International Nuclear Information System (INIS)

    Qian, Shinan; Takacs, Peter; Sostero, Giovanni; Cocco, Daniele

    2001-01-01

    Since the early development of the penta-prism long trace profiler (LTP) and the in situ LTP, and following the completion of the first in situ distortion profile measurements at Sincrotrone Trieste (ELETTRA) in Italy in 1995, a concept was developed for a compact, portable LTP with the following characteristics: easily installed on synchrotron radiation beam lines, easily carried to different laboratories around the world for measurements and calibration, convenient for use in evaluating the LTP as an in-process tool in the optical workshop, and convenient for use in temporarily installation as required by other special applications. The initial design of a compact LTP optical head was made at ELETTRA in 1995. Since 1997 further efforts to reduce the optical head size and weight, and to improve measurement stability have been made at Brookhaven National Laboratory. This article introduces the following solutions and accomplishments for the portable LTP: (1) a new design for a compact and very stable optical head, (2) the use of a small detector connected to a laptop computer directly via an enhanced parallel port, and there is no extra frame grabber interface and control box, (3) a customized small mechanical slide that uses a compact motor with a connector-sized motor controller, and (4) the use of a laptop computer system. These solutions make the portable LTP able to be packed into two laptop-size cases: one for the computer and one for the rest of the system

  13. Clinical trials with rasagiline: evidence for short-term and long-term effects.

    Science.gov (United States)

    Siderowf, Andrew; Stern, Matthew

    2006-05-23

    Rasagiline (N-propargyl-1 (R)-aminoindan) is a selective, potent irreversible inhibitor of MAO-B that possesses neuroprotective and anti-apoptotic properties in a variety of in vitro and in vivo animal models relevant to Parkinson's disease (PD). Several randomized controlled clinical trials have demonstrated the safety and efficacy of rasagiline as monotherapy in PD and as adjunctive therapy for patients receiving levodopa. In addition, the 1-year randomized, delayed-start analysis of the TEMPO study suggests that rasagiline may slow the rate of progression of PD. The randomized delayed-start paradigm has potential to differentiate short-term symptomatic effects from long-term effects of anti-parkinsonian agents. In the future, long-term trials to examine the potential disease-modifying effects of rasagiline, which incorporate biological markers as well as clinical endpoints, may further elucidate the role of rasagiline in the treatment of both early and advanced PD.

  14. Group long-term care insurance: decision-making factors and implications for financing long-term care.

    Science.gov (United States)

    Stum, Marlene S

    2008-01-01

    This study proposes and tests a systemic family decision-making framework to understand group long-term care insurance (LTCI) enrollment decisions. A random sample of public employees who were offered group LTCI as a workplace benefit were examined. Findings reveal very good predictive efficacy for the overall conceptual framework with a pseudo R2 value of .687, and reinforced the contributions of factors within the family system. Enrollees were more likely to have discussed the decision with others, used information sources, and had prior experience when compared to non-enrollees. Perceived health status, financial knowledge, attitudes regarding the role of private insurance, risk taking, and coverage features were additional factors related to enrollment decisions. The findings help to inform policymakers about the potential of LTCI as one strategy for financing long-term care.

  15. Using OpenTarget to Generate Potential Countermeasures for Long-Term Space Exposure from Data Available on GeneLab

    Science.gov (United States)

    Beheshti, Afshin

    2018-01-01

    GeneLab as a general tool for the scientific community; Utilizing GeneLab datasets to generate hypothesis and determining potential biological targets against health risks due to long-term space missions; How can OpenTarget be used to discover novel drugs to test as countermeasures that can be utilized by astronauts.

  16. Global long-term cost dynamics of offshore wind electricity generation

    NARCIS (Netherlands)

    Gernaat, David E H J; Van Vuuren, Detlef P.; Van Vliet, Jasper; Sullivan, Patrick; Arent, Douglas J.

    2014-01-01

    Using the IMAGE/TIMER (The Targets IMage Energy Regional) long-term integrated assessment model, this paper explores the regional and global potential of offshore wind to contribute to global electricity production. We develop long-term cost supply curve for offshore wind, a representation of the

  17. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    Science.gov (United States)

    Gosz, J.

    2001-12-01

    estuaries below by removing all incoming freshwater. At Toolik Lake, long-term experiments of removing top predators from the good web of lakes showed dramatic alterations of lake populations of small fish and zooplankton. In New Mexico, LTER research on small mammal populations is successfully predicting rodent increases and the potential for increased zoonotic diseases such as Hantavirus and bubonic plague. This ability to forecast based on El Nino prediction is being used to increase scientific awareness and public health awareness through media based communication with the public. In Oregon, the Andrews Forest LTER program has had long, strong links with natural resource policy and management. Basic understanding of forest-stream interactions, characteristics of old-growth forests, roles of woody debris in temperate forest ecosystems, invertebrate biodiversity and ecosystem function have been incorporated in management guidelines, plans and regulations for public and private lands throughout the Pacific Northwest. Other examples of the values of long-term research and monitoring will be presented.

  18. Interferometry for the LISA technology package LTP: an update

    International Nuclear Information System (INIS)

    Heinzel, G; Bogenstahl, J; Braxmaier, C; Danzmann, K; Garcia, A; Guzman, F; Hough, J; Hoyland, D; Jennrich, O; Killow, C; Robertson, D; Sodnik, Z; Steier, F; Ward, H; Wand, V

    2006-01-01

    This paper gives an update on the status of the LISA technology package (LTP) which is to be launched in 2009 by ESA as a technology demonstration mission for the spaceborne gravitational wave observatory LISA. The dominant noise source in the interferometer prototype has been investigated and improved such that it is now comfortably below its budget at all frequencies

  19. Long-term ecological research in a human-dominated world

    Science.gov (United States)

    G. Philip Robertson; Scott L. Collins; David R. Foster; Nicholas Brokaw; Hugh W. Ducklow; Ted L. Gragson; Corinna Gries; Stephen K. Hamilton; A. David McGuire; John C. Moore; Emily H. Stanley; Robert B. Waide; Mark W. Williams

    2012-01-01

    The US Long Term Ecological Research (LTER) Network enters its fourth decade with a distinguished record of achievement in ecological science. The value of long-term observations and experiments has never been more important for testing ecological theory and for addressing today’s most difficult environmental challenges. The network’s potential for tackling emergent...

  20. Deleting Both PHLPP1 and CANP1 Rescues Impairments in Long-Term Potentiation and Learning in Both Single Knockout Mice

    Science.gov (United States)

    Liu, Yan; Sun, Jiandong; Wang, Yubin; Lopez, Dulce; Tran, Jennifer; Bi, Xiaoning; Baudry, Michel

    2016-01-01

    Calpain-1 (CANP1) has been shown to play a critical role in synaptic plasticity and learning and memory, as its deletion in mice results in impairment in theta-burst stimulation (TBS)-induced LTP and various forms of learning and memory. Likewise, PHLPP1 (aka SCOP) has also been found to participate in learning and memory, as PHLPP1 overexpression…

  1. Base cation depletion and potential long-term acidification of Norwegian catchments

    International Nuclear Information System (INIS)

    Kirchner, J.W.; Lydersen, E.

    1995-01-01

    Long-term monitoring data from Norwegian catchments show that since the late 1970s, sulfate deposition and runoff sulfate concentrations have declined significantly. However, water quality has not significantly improved, because reductions in runoff sulfate have been matched by equal declines in calcium and magnesium concentrations. Long-term declines in runoff Ca and Mg are most pronounced at catchments subject to highly acidic deposition; the observed rates of decline are quantitatively consistent with depletion of exchangeable bases by accelerated leaching under high acid loading. Even though water quality has not recovered, reductions in acid deposition have been valuable because they have prevented significant acidification that would otherwise have occurred under constant acid deposition. Ongoing depletion of exchangeable bases from these catchments implies that continued deposition reductions will be needed to avoid further acidification and that recovery from acidification will be slow. 31 refs., 2 figs., 4 tabs

  2. [Long-term psychiatric hospitalizations].

    Science.gov (United States)

    Plancke, L; Amariei, A

    2017-02-01

    Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

  3. Platelet-activating factor and group I metabotropic glutamate receptors interact for full development and maintenance of long-term potentiation in the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Francescangeli, E; Goracci, G; Pettorossi, V E

    1999-01-01

    In rat brainstem slices, we investigated the interaction between platelet-activating factor and group I metabotropic glutamate receptors in mediating long-term potentiation within the medial vestibular nuclei. We analysed the N1 field potential wave evoked in the ventral portion of the medial vestibular nuclei by primary vestibular afferent stimulation. The group I metabotropic glutamate receptor antagonist, (R,S)-1-aminoindan-1,5-dicarboxylic acid, prevented long-term potentiation induced by a platelet-activating factor analogue [1-O-hexadecyl-2-O-(methylcarbamyl)-sn-glycero-3-phosphocholine], as well as the full development of potentiation, induced by high-frequency stimulation under the blocking agent for synaptosomal platelet-activating factor receptors (ginkolide B), at drug washout. However, potentiation directly induced by the group I glutamate metabotropic receptor agonist, (R,S)-3,5-dihydroxyphenylglycine, was reduced by ginkolide B. These findings suggest that platelet-activating factor, whether exogenous or released following potentiation induction, exerts its effect through presynaptic group I metabotropic glutamate receptors, mediating the increase of glutamate release. In addition, we found that this mechanism, which led to full potentiation through presynaptic group I metabotropic glutamate receptor activation, was inactivated soon after application of potentiation-inducing stimulus. In fact, the long-lasting block of the platelet-activating factor and metabotropic glutamate receptors prevented the full potentiation development and the induced potentiation progressively declined to null. Moreover, ginkolide B, given when high-frequency-dependent potentiation was established, only reduced it within 5 min after potentiation induction. We conclude that to fully develop vestibular long-term potentiation requires presynaptic events. Platelet-activating factor, released after the activation of postsynaptic mechanisms which induce potentiation, is necessary

  4. Long-term potentiation and memory processes in the psychological works of Sigmund Freud and in the formation of neuropsychiatric symptoms.

    Science.gov (United States)

    Centonze, D; Siracusano, A; Calabresi, P; Bernardi, G

    2005-01-01

    Far from disproving the model of mind functioning proposed by psychoanalysis, the recent advances in neuropsychiatrical research confirmed the crucial ideas of Sigmund Freud. The hypothesis that the origin of mental illnesses lies in the impossibility for a subject to erase the long-term effects of a remote adverse event is in tune with the view that several psychiatric disturbances reflect the activation of aberrant unconscious memory processes. Freud's insights did not stop here, but went on to describe in an extremely precise manner the neural mechanisms of memory formation almost a century before the description of long-term synaptic potentiation.

  5. Impact of long-term and short-term therapies on seminal parameters

    Directory of Open Access Journals (Sweden)

    Jlenia Elia

    2013-04-01

    Full Text Available Aim: The aim of this work was: i to evaluate the prevalence of male partners of subfertile couples being treated with long/short term therapies for non andrological diseases; ii to study their seminal profile for the possible effects of their treatments on spermatogenesis and/or epididymal maturation. Methods: The study group was made up of 723 subjects, aged between 25 and 47 years. Semen analysis was performed according to World Health Organization (WHO guidelines (1999. The Superimposed Image Analysis System (SIAS, which is based on the computerized superimposition of spermatozoa images, was used to assess sperm motility parameters. Results: The prevalence of subjects taking pharmacological treatments was 22.7% (164/723. The prevalence was 3.7% (27/723 for the Short-Term Group and 18.9% (137/723 for the Long-Term Group. The subjects of each group were also subdivided into subgroups according to the treatments being received. Regarding the seminal profile, we did not observe a significant difference between the Long-Term, Short-Term or the Control Group. However, regarding the subgroups, we found a significant decrease in sperm number and progressive motility percentage in the subjects receiving treatment with antihypertensive drugs compared with the other subgroups and the Control Group. Conclusions: In the management of infertile couples, the potential negative impact on seminal parameters of any drugs being taken as Long-Term Therapy should be considered. The pathogenic mechanism needs to be clarified.

  6. Comparison of LTI and LTP Models for Stability Analysis of Grid Converters

    DEFF Research Database (Denmark)

    Kwon, Jun Bum; Wang, Xiongfei; Blaabjerg, Frede

    2016-01-01

    The stability analysis of grid-connected converters have attracted increasing attentions, due to the oscillations arising in wind power plants, micro-grids, and other emerging power electronics based power systems. The modeling tool of converters thus becomes essential to faithfully reveal...... oscillations without any hidden regions. This paper presents a detailed comparison of two linearized modeling methods, which are, respectively, developed in the Linear Time-Invariant (LTI) and the Linear Time-Periodic (LTP) frameworks. The LTP model can consider the effect of frequency-coupling dynamics, which...... are occurred by the time-varying behavior, while the conventional LTI model can not capture this behavior. The advantages and limits of two models are then illustrated with examples. The compared results are verified in the frequency domain and time domain as well....

  7. Long term storage techniques for 85Kr

    International Nuclear Information System (INIS)

    Foster, B.A.; Pence, D.T.; Staples, B.A.

    1975-01-01

    As new nuclear fuel reprocessing plants go on stream, the collection of fission product 85 Kr will be required to avoid potential local release problems and long-term atmospheric buildup. Storage of the collected 85 Kr for a period of at least 100 years will be necessary to allow approximately 99.9 percent decay before it is released. A program designed to develop and evaluate proposed methods for long-term storage of 85 Kr is discussed, and the results of a preliminary evaluation of three methods, high pressure steel cylinders, zeolite encapsulation, and clathrate inclusion are presented. (U.S.)

  8. The potential benefits of a new poliovirus vaccine for long-term poliovirus risk management.

    Science.gov (United States)

    Duintjer Tebbens, Radboud J; Thompson, Kimberly M

    2016-12-01

    To estimate the incremental net benefits (INBs) of a hypothetical ideal vaccine with all of the advantages and no disadvantages of existing oral and inactivated poliovirus vaccines compared with current vaccines available for future outbreak response. INB estimates based on expected costs and polio cases from an existing global model of long-term poliovirus risk management. Excluding the development costs, an ideal poliovirus vaccine could offer expected INBs of US$1.6 billion. The ideal vaccine yields small benefits in most realizations of long-term risks, but great benefits in low-probability-high-consequence realizations. New poliovirus vaccines may offer valuable insurance against long-term poliovirus risks and new vaccine development efforts should continue as the world gathers more evidence about polio endgame risks.

  9. 46 - 57 Badamasi and Lawal

    African Journals Online (AJOL)

    User

    memory, learning and asymptomatic level of performance(ALOP). The design of the study ... especially like it can be accomplished in a short period of time with a relatively ... their ability to maintain long term potentiation (LTP). (Giampaoloet al.

  10. Synaptic Plasticity in the Bed Nucleus of the Stria Terminalis: Underlying Mechanisms and Potential Ramifications for Reinstatement of Drug- and Alcohol-Seeking Behaviors.

    Science.gov (United States)

    Harris, Nicholas A; Winder, Danny G

    2018-06-13

    The bed nucleus of the stria terminalis (BNST) is a component of the extended amygdala that shows significant changes in activity and plasticity through chronic exposure to drugs and stress. The region is critical for stress- and cue-induced reinstatement of drug-seeking behaviors and is thus a candidate region for the plastic changes that occur in abstinence that prime addicted patients for reinstatement behaviors. Here, we discuss the various forms of long-term potentiation (LTP) and long-term depression (LTD) in the rodent BNST and highlight the way that these changes in excitatory transmission interact with exposure to alcohol and other drugs of abuse, as well as other stressors. In addition, we highlight potential areas for future research in this area, including investigating input- and cell-specific bidirectional changes in activity. As we continue to accrue foundational knowledge in the mechanisms and effects of plasticity in the BNST, molecular targets and treatment strategies that are relevant to reinstatement behaviors will also begin to emerge. Here, we briefly discuss the effects of catecholamine receptor modulators on synaptic plasticity in the BNST due to the role of norepinephrine in LTD and dopamine on the short-term component of LTP as well as the role that signaling at these receptors plays in reinstatement of drug- and alcohol-seeking behaviors. We hope that insights gained on the specific changes in plasticity that occur within the BNST during abstinence from alcohol and other drugs of abuse will provide insight into the biological underpinnings of relapse behavior in human addicts and inform future treatment modalities for addiction that tackle this complex biological problem.

  11. Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

    OpenAIRE

    Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.

    2011-01-01

    It has been proposed that long-term memory persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related long-term memo...

  12. Clipboard

    Indian Academy of Sciences (India)

    2015-04-17

    Apr 17, 2015 ... environment; learning; long term potentiation; LTP; memory; neuroepigenetics; plasticity ... axon of cell A is near enough to excite cell B, and repeatedly and .... education of children with DS and prevention of AD in this group; ...

  13. Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

    KAUST Repository

    Lemtiri-Chlieh, Fouad; Zhao, Liangfang; Kiraly, Drew D; Eipper, Betty A; Mains, Richard E; Levine, Eric S

    2011-01-01

    to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine

  14. Acute Effects of the Ampakine Farampator on Memory and Information Processing in Healthy Elderly Volunteers

    NARCIS (Netherlands)

    Wezenberg, E.; Verkes, R.J.; Ruigt, G.S.F.; Hulstijn, W.; Sabbe, B.G.C.

    2007-01-01

    Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl)

  15. Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers.

    NARCIS (Netherlands)

    Wezenberg, E.; Verkes, R.J.; Ruigt, G.S.F.; Hulstijn, W.; Sabbe, B.G.C.

    2007-01-01

    Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl)

  16. Long-Term Symbolic Learning

    National Research Council Canada - National Science Library

    Kennedy, William G; Trafton, J. G

    2007-01-01

    What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

  17. Long-Term Prognosis of Ischemic Stroke in Young Adults

    OpenAIRE

    Varona, Jose F.

    2010-01-01

    There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emotional aspects of an ischemic stroke in young people, providing early accurate long-term prognostic information is very important in this clinical setting. Moreover, detection of factors associated with bad outcomes (death, recurrence, moderate-to-severe disability) help physicians in optimizing secondary prevention strategies. The prese...

  18. Pediatric polytrauma : Short-term and long-term outcomes

    NARCIS (Netherlands)

    vanderSluis, CK; Kingma, J; Eisma, WH; tenDuis, HJ

    Objective: To assess the short-term and long-term outcomes of pediatric polytrauma patients and to analyze the extent to which short-term outcomes can predict long-term outcomes. Materials and Methods: Ail pediatric polytrauma patients (Injury Severity Score of greater than or equal to 16, less than

  19. Influence of sex and estrous cycle on synaptic responses of the medial vestibular nuclei in rats: role of circulating 17β-estradiol.

    Science.gov (United States)

    Grassi, Silvarosa; Frondaroli, Adele; Scarduzio, Mariangela; Dieni, Cristina V; Brecchia, Gabriele; Boiti, Cristiano; Pettorossi, Vito E

    2012-02-10

    We investigated the possible influence of sex and estrous cycle on the synaptic responses of neurons in the medial vestibular nucleus (MVN) and their long-term modifications. In brain stem slices of male and female rats during proestrus (PE) and diestrus (DE), we evaluated the field potential evoked in the MVN by vestibular afferent stimulation. Here we find that in PE females the field potential had a lower threshold and higher amplitude than in DE females and in males and also that the stimulus-response curve was shifted to the left. Such difference is related to the level and cyclic fluctuation of circulating 17β-estradiol (E(2)). This is supported by the exogenous administration of E(2) in DE females and males, with low levels of circulating E(2) that enhanced the field potential amplitude to values close to those of PE females. Sex and estrous cycle also influence the MVN synaptic plasticity. This has been shown by investigating the effect of testosterone (T) on the induction of long-term effects, since T is the precursor for the neural synthesis of E(2) (estrogenic pathway), which is involved in the induction of fast long-term potentiation (LTP), or of 5α-dihydrotestosterone (DHT, androgenic pathway) which mediates slow LTP and long-term depression (LTD). We found that T mostly induced LTD in PE females and no effect in DE females, while it only provoked fast LTP in males. We suggest that high level of circulating E(2) may interfere with the conversion of T, by inhibiting the neural estrogenic pathway and facilitating the androgenic one. On the whole these results demonstrate an influence of circulating E(2) on vestibular synaptic transmission and plasticity that in some cases may contribute to the sex and menstrual cycle dependence of symptoms in human vestibular pathology. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Long-term Morbidity of Testicular Cancer Treatment.

    Science.gov (United States)

    Fung, Chunkit; Fossa, Sophie D; Williams, Annalynn; Travis, Lois B

    2015-08-01

    Second malignant neoplasms, cardiovascular disease, neurotoxicity and ototoxicity, pulmonary complications, hypogonadism, and nephrotoxicity are potentially life-threatening long-term complications of testicular cancer and its therapy. This article describes the pathogenesis, risks, and management of these late effects experienced by long-term testicular cancer survivors, who are defined as individuals who are disease free 5 years or more after primary treatment. Testicular cancer survivors should follow applicable national guidelines for cancer screening and management of cardiovascular disease risk factors. In addition, health care providers should capitalize on the time of cancer diagnosis as a teachable moment to introduce and promote lifestyle changes. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Plastic mulching in agriculture. Trading short-term agronomic benefits for long-term soil degradation?

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Zacharias; Wollmann, Claudia; Schaefer, Miriam; Buchmann, Christian; David, Jan [Institute for Environmental Sciences, Group of Environmental and Soil Chemistry, University of Koblenz-Landau, Fortstraße 7, 76829 Landau (Germany); Tröger, Josephine [Department of Psychology, University of Koblenz-Landau, Fortstraße 7, 76829 Landau (Germany); Interdisciplinary Research Group on Environmental Issues, University of Koblenz-Landau, Fortstraße 7, 76829 Landau (Germany); Muñoz, Katherine [Institute for Environmental Sciences, Group of Environmental and Soil Chemistry, University of Koblenz-Landau, Fortstraße 7, 76829 Landau (Germany); Interdisciplinary Research Group on Environmental Issues, University of Koblenz-Landau, Fortstraße 7, 76829 Landau (Germany); Frör, Oliver [Institute for Environmental Sciences, Group of Environmental Economics, University of Koblenz-Landau, Fortstraße 7, 76829 Landau (Germany); Schaumann, Gabriele Ellen, E-mail: schaumann@uni-landau.de [Institute for Environmental Sciences, Group of Environmental and Soil Chemistry, University of Koblenz-Landau, Fortstraße 7, 76829 Landau (Germany)

    2016-04-15

    Plastic mulching has become a globally applied agricultural practice for its instant economic benefits such as higher yields, earlier harvests, improved fruit quality and increased water-use efficiency. However, knowledge of the sustainability of plastic mulching remains vague in terms of both an environmental and agronomic perspective. This review critically discusses the current understanding of the environmental impact of plastic mulch use by linking knowledge of agricultural benefits and research on the life cycle of plastic mulches with direct and indirect implications for long-term soil quality and ecosystem services. Adverse effects may arise from plastic additives, enhanced pesticide runoff and plastic residues likely to fragment into microplastics but remaining chemically intact and accumulating in soil where they can successively sorb agrochemicals. The quantification of microplastics in soil remains challenging due to the lack of appropriate analytical techniques. The cost and effort of recovering and recycling used mulching films may offset the aforementioned benefits in the long term. However, comparative and long-term agronomic assessments have not yet been conducted. Furthermore, plastic mulches have the potential to alter soil quality by shifting the edaphic biocoenosis (e.g. towards mycotoxigenic fungi), accelerate C/N metabolism eventually depleting soil organic matter stocks, increase soil water repellency and favour the release of greenhouse gases. A substantial process understanding of the interactions between the soil microclimate, water supply and biological activity under plastic mulches is still lacking but required to estimate potential risks for long-term soil quality. Currently, farmers mostly base their decision to apply plastic mulches rather on expected short-term benefits than on the consideration of long-term consequences. Future interdisciplinary research should therefore gain a deeper understanding of the incentives for farmers

  2. Plastic mulching in agriculture. Trading short-term agronomic benefits for long-term soil degradation?

    International Nuclear Information System (INIS)

    Steinmetz, Zacharias; Wollmann, Claudia; Schaefer, Miriam; Buchmann, Christian; David, Jan; Tröger, Josephine; Muñoz, Katherine; Frör, Oliver; Schaumann, Gabriele Ellen

    2016-01-01

    Plastic mulching has become a globally applied agricultural practice for its instant economic benefits such as higher yields, earlier harvests, improved fruit quality and increased water-use efficiency. However, knowledge of the sustainability of plastic mulching remains vague in terms of both an environmental and agronomic perspective. This review critically discusses the current understanding of the environmental impact of plastic mulch use by linking knowledge of agricultural benefits and research on the life cycle of plastic mulches with direct and indirect implications for long-term soil quality and ecosystem services. Adverse effects may arise from plastic additives, enhanced pesticide runoff and plastic residues likely to fragment into microplastics but remaining chemically intact and accumulating in soil where they can successively sorb agrochemicals. The quantification of microplastics in soil remains challenging due to the lack of appropriate analytical techniques. The cost and effort of recovering and recycling used mulching films may offset the aforementioned benefits in the long term. However, comparative and long-term agronomic assessments have not yet been conducted. Furthermore, plastic mulches have the potential to alter soil quality by shifting the edaphic biocoenosis (e.g. towards mycotoxigenic fungi), accelerate C/N metabolism eventually depleting soil organic matter stocks, increase soil water repellency and favour the release of greenhouse gases. A substantial process understanding of the interactions between the soil microclimate, water supply and biological activity under plastic mulches is still lacking but required to estimate potential risks for long-term soil quality. Currently, farmers mostly base their decision to apply plastic mulches rather on expected short-term benefits than on the consideration of long-term consequences. Future interdisciplinary research should therefore gain a deeper understanding of the incentives for farmers

  3. Synchrotron radiation and precision mirror metrology with a long trace profiler

    International Nuclear Information System (INIS)

    Qian, S.; Takacs, P.Z.

    1997-08-01

    The Long Trace Profiler (LTP) is in use at several synchrotron radiation (SR) laboratories throughout the world and by a number of manufacturers who specialize in making grazing incidence mirrors for SR customers. Recent improvements in the design and operation of the LTP system have reduced the slope profile error bar to the level of 0.3 microradians RMS over measurement lengths of 0.5 meter. This corresponds to a height error bar on the order of 20 nanometers. This level of performance allows one to measure with confidence the shape of large cylinders and spheres that have kilometer radii of curvature in the axial direction. The LTP is versatile enough to make measurements of a mirror in the face up, sideways, and face down configurations. The authors will illustrate the versatility of the current version of the instrument, the LTP II, and present results from two new versions of the instrument: the in-situ LTP (ISLTP) and the Vertical Scan LTP (VSLTP). Both of them are based on the penta-prism LTP (ppLTP) principle with a stationary optical head and moving penta-prism. The ISLTP is designed to measure the distortion of high heat load mirrors during actual operation in SR beam lines. The VSLTP is designed to measure the complete 3-dimensional shape of x-ray telescope cylinder mirrors and mandrels in a vertical configuration. Scans are done both in the axial direction and in the azimuthal direction

  4. Yield gap analysis in long-term experiments with intensive rice cultivation

    International Nuclear Information System (INIS)

    Laureles, E.V.; Correa, T. Jr.; Buresh, R.J.

    2007-01-01

    The long-term continuous cropping experiment at IRRI is cultivated with three rice crops in a year, making it the world's most intensively cropped long-term rice experiment. The availability of comprehensive rice production records, compiled weather data, and tested crop models provides a means to evaluate long-term trends in measured and potential yields and yield gaps in this rice production system. Yield trends were assessed using the highest yielding cultivar in each cropping season from 1979 to 2005. Potential yield of the highest yielding cultivar in each season was determined using three rice models (ORYZA, TERM, and CERES) run with the actual transplanting and harvest dates for the cultivar. The yield gap was determined from the difference between the simulated potential grain yield and the measured grain yield. Measured and potential yields and the yield gap varied across seasons and years. Measured yields were higher in the dry season than in the early and late wet seasons. The yield gap tended to be higher in the wet season than in the dry season. Climatic parameters, particularly solar radiation, influenced the performance of rice cultivars. The relatively larger yield gaps in the late wet season than in the dry season were associated with increased spikelet sterility. The cumulative measured yield for the three annual rice crop was near 80 percent of the annual yield potential in years with best practices for fertilizer N and crop management. The long term trends suggest that effective timing and rates of N fertilization and effective control of diseases were critical in achieving 80 percent of the annual yield potential

  5. Associative stimulation of the supraorbital nerve fails to induce timing-specific plasticity in the human blink reflex

    DEFF Research Database (Denmark)

    Zeuner, Kirsten E; Knutzen, Arne; Al-Ali, Asmaa

    2010-01-01

    Associative high-frequency electrical stimulation (HFS) of the supraorbital nerve in five healthy individuals induced long-term potentiation (LTP)-like or depression (LTD)-like changes in the human blink reflex circuit according to the rules of spike timing-dependent plasticity (Mao and Evinger...

  6. Characterization of a new antifungal non-specific lipid transfer protein (nsLTP) from sugar beet leaves

    DEFF Research Database (Denmark)

    Kristensen, A K; Brunstedt, J; Madsen, M T

    2000-01-01

    A novel protein (IWF5) comprising 92 amino acids has been purified from the intercellular washing fluid of sugar beet leaves using cation exchange chromatography and reversed phase high performance liquid chromatography. Based on amino acid sequence homology, including the presence of eight...... cysteines at conserved positions, the protein can be classified as a member of the plant family of non-specific lipid transfer proteins (nsLTPs). The protein is 47% identical to IWF1, an antifungal nsLTP previously isolated from leaves of sugar beet. A potential site for N-linked glycosylation present...

  7. Long Term Financing of Infrastructure

    OpenAIRE

    Sinha, Sidharth

    2014-01-01

    Infrastructure projects, given their long life, require long term financing. The main sources of long term financings are insurance and pension funds who seek long term investments with low credit risk. However, in India household financial savings are mainly invested in bank deposits. Insurance and pension funds account for only a small percentage of household financial savings. In addition most infrastructure projects do not qualify for investment by insurance and pension funds because of t...

  8. Long-term use of short- and long-acting nitrates in stable angina pectoris.

    Science.gov (United States)

    Kosmicki, Marek Antoni

    2009-05-01

    Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

  9. Neuromodulation, development and synaptic plasticity.

    Science.gov (United States)

    Foehring, R C; Lorenzon, N M

    1999-03-01

    We discuss parallels in the mechanisms underlying use-dependent synaptic plasticity during development and long-term potentiation (LTP) and long-term depression (LTD) in neocortical synapses. Neuromodulators, such as norepinephrine, serotonin, and acetylcholine have also been implicated in regulating both developmental plasticity and LTP/LTD. There are many potential levels of interaction between neuromodulators and plasticity. Ion channels are substrates for modulation in many cell types. We discuss examples of modulation of voltage-gated Ca2+ channels and Ca(2+)-dependent K+ channels and the consequences for neocortical pyramidal cell firing behaviour. At the time when developmental plasticity is most evident in rat cortex, the substrate for modulation is changing as the densities and relative proportions of various ion channels types are altered during ontogeny. We discuss examples of changes in K+ and Ca2+ channels and the consequence for modulation of neuronal activity.

  10. Long term stability of power systems

    Energy Technology Data Exchange (ETDEWEB)

    Kundur, P; Gao, B [Powertech Labs. Inc., Surrey, BC (Canada)

    1994-12-31

    Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

  11. Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains

    Directory of Open Access Journals (Sweden)

    Schouenborg Jens

    2008-05-01

    Full Text Available Abstract Background Previous studies in the rat have shown that the spatial organisation of the receptive fields of nociceptive withdrawal reflex (NWR system are functionally adapted through experience dependent mechanisms, termed somatosensory imprinting, during postnatal development. Here we wanted to clarify 1 if mice exhibit a similar spatial encoding of sensory input to NWR as previously found in the rat and 2 if mice strains with a poor learning capacity in various behavioural tests, associated with deficient long term potention, also exhibit poor adaptation of NWR. The organisation of the NWR system in two adult wild type mouse strains with normal long term potentiation (LTP in hippocampus and two adult wild type mouse strains exhibiting deficiencies in corresponding LTP were used and compared to previous results in the rat. Receptive fields of reflexes in single hindlimb muscles were mapped with CO2 laser heat pulses. Results While the spatial organisation of the nociceptive receptive fields in mice with normal LTP were very similar to those in rats, the LTP impaired strains exhibited receptive fields of NWRs with aberrant sensitivity distributions. However, no difference was found in NWR thresholds or onset C-fibre latencies suggesting that the mechanisms determining general reflex sensitivity and somatosensory imprinting are different. Conclusion Our results thus confirm that sensory encoding in mice and rat NWR is similar, provided that mice strains with a good learning capability are studied and raise the possibility that LTP like mechanisms are involved in somatosensory imprinting.

  12. A systematic review of potential long-term effects of sport-related concussion

    Science.gov (United States)

    Gardner, Andrew J; Schneider, Kathryn J; Guskiewicz, Kevin M; Bailes, Julian; Cantu, Robert C; Castellani, Rudolph J; Turner, Michael; Jordan, Barry D; Randolph, Christopher; Dvořák, Jiří; Hayden, K. Alix; Tator, Charles H; McCrory, Paul; Iverson, Grant L

    2017-01-01

    Objective Systematic review of possible long-term effects of sports-related concussion in retired athletes. Data sources Ten electronic databases. Study selection Original research; incidence, risk factors or causation related to long-term mental health or neurological problems; individuals who have suffered a concussion; retired athletes as the subjects and possible long-term sequelae defined as >10 years after the injury. Data extraction Study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors. Results Following review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes. Conclusion Multiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports. PMID:28455362

  13. Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Kulangara, Karina; Antoniello, Katia

    2007-01-01

    as the commonly linked kinase calcium/calmodulin-dependent protein kinase II. Synaptic plasticity experiments between pairs of pyramidal neurons revealed an augmented postsynaptic form of long-term potentiation. These results indicate that VPA significantly enhances NMDA receptor-mediated transmission and causes......Valproic acid (VPA) is a powerful teratogen causing birth defects in humans, including autism spectrum disorder (ASD), if exposure occurs during the first trimester of embryogenesis. Learning and memory alterations are common symptoms of ASD, but underlying molecular and synaptic alterations remain...

  14. Analysis of the potential impact of capillarity on long-term geochemical processes in sulphidic waste-rock dumps

    International Nuclear Information System (INIS)

    Pedretti, Daniele; Lassin, Arnault; Beckie, Roger D.

    2015-01-01

    Highlights: • Capillarity may affect geochemical reactions generating acid-rock drainage. • We studied its impact in a simplified, synthetic WRD. • Capillarity mainly affects the formation of secondary minerals. • It can strongly control long-term formation of gypsum and in turn sulfate release. • Capillarity can be also important for the analysis of calcite passivation. - Abstract: Assessing long-term production of acid rock drainage (ARD) from waste-rock dumps (WRDs) requires a careful analysis of the processes controlling acid-generating geochemical reactions under unsaturated conditions. In this work, we focus on the potential control of capillarity on these reactions, as previous studies showed that capillarity affects the activity of water and solutes in the unsaturated zone through the pore water pressure. We used capillarity-corrected thermodynamic databases and compared calculated speciation and solubility results with those from databases that do not account for capillarity. We developed a simple dynamic model with reduced geochemical components to analyze in detail the effect of capillarity. Results indicate that under low pH conditions simulations with capillarity-controlled reactions generate relatively larger dissolved sulfate concentrations from the WRDs over longer time scales, when compared against simulations without capillarity control. This occurs because capillarity strongly controls the formation of secondary sulfate-bearing minerals such as gypsum. When sufficient oxygen and carbon dioxide partial pressures are maintained within WRDs (such as in well-ventilated systems) and calcite content is insufficient to buffer acidity, the amount of secondary gypsum was calculated to be much larger in capillarity-corrected models. No appreciable effects of capillarity were observed under conditions where gypsum was not generated. Model results are also insensitive to temperature changes in typical climatic ranges. These results indicate some of

  15. Loss of catecholaminergic neuromodulation of persistent forms of hippocampal synaptic plasticity with increasing age

    Directory of Open Access Journals (Sweden)

    Hannah Twarkowski

    2016-09-01

    Full Text Available Neuromodulation by means of the catecholaminergic system is a key component of motivation-driven learning and behaviorally modulated hippocampal synaptic plasticity. In particular, dopamine acting on D1/D5 receptors and noradrenaline acting on beta-adrenergic receptors exert a very potent regulation of forms of hippocampal synaptic plasticity that last for very long-periods of time (>24h, and occur in conjunction with novel spatial learning. Antagonism of these receptors not only prevents long-term potentiation (LTP and long-term depression (LTD, but prevents the memory of the spatial event that, under normal circumstances, leads to the perpetuation of these plasticity forms. Spatial learning behavior that normally comes easily to rats, such as object-place learning and spatial reference learning, becomes increasingly impaired with aging. Middle-aged animals display aging-related deficits of specific, but not all, components of spatial learning, and one possibility is that this initial manifestation of decrements in learning ability that become manifest in middle-age relate to changes in motivation, attention and/or the regulation by neuromodulatory systems of these behavioral states.Here, we compared the regulation by dopaminergic D1/D5 and beta-adrenergic receptors of persistent LTP in young (2-4 month old and middle-aged (8-14 month old rats. We observed in young rats, that weak potentiation that typically lasts for ca. 2h could be strengthened into persistent (>24h LTP by pharmacological activation of either D1/D5 or beta-adrenergic receptors. By contrast, no such facilitation occurred in middle-aged rats. This difference was not related to an ostensible learning deficit: a facilitation of weak potentiation into LTP by spatial learning was possible both in young and middle-aged rats. It was also not directly linked to deficits in LTP: strong afferent stimulation resulted in equivalent LTP in both age groups. We postulate that this change in

  16. proBDNF Negatively Regulates Neuronal Remodeling, Synaptic Transmission, and Synaptic Plasticity in Hippocampus

    Directory of Open Access Journals (Sweden)

    Jianmin Yang

    2014-05-01

    Full Text Available Experience-dependent plasticity shapes postnatal development of neural circuits, but the mechanisms that refine dendritic arbors, remodel spines, and impair synaptic activity are poorly understood. Mature brain-derived neurotrophic factor (BDNF modulates neuronal morphology and synaptic plasticity, including long-term potentiation (LTP via TrkB activation. BDNF is initially translated as proBDNF, which binds p75NTR. In vitro, recombinant proBDNF modulates neuronal structure and alters hippocampal long-term plasticity, but the actions of endogenously expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates hippocampal dendritic complexity and spine density through p75NTR. Hippocampal slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, and enhanced long-term depression (LTD in area CA1. These results suggest that proBDNF acts in vivo as a biologically active factor that regulates hippocampal structure, synaptic transmission, and plasticity, effects that are distinct from those of mature BDNF.

  17. Risk assessment in long-term storage of spent nuclear fuel

    International Nuclear Information System (INIS)

    Ahn, T.; Guttmann, J.; Mohseni, A.

    2013-01-01

    This paper presents probabilistic risk-informed approaches that the Nuclear Regulatory Commission (NRC) staff is planning to consider in preparing regulatory bases for long-term storage of spent nuclear fuel (SNF) for up to 300 years. Due to uncertainties associated with long-term SNF storage, the NRC is considering a probabilistic risk-informed approach as well as a deterministic design-based approach. The uncertainties considered here are primarily associated with materials aging of the canister and SNF in the cask system during long-term storage of SNF. This paper discusses some potential risk contributors involved in long-term SNF storage. Methods of performance evaluation are presented that assess the various types of risks involved. They include deterministic evaluation, probabilistic evaluation, and consequence assessment under normal conditions and the conditions of accidents and natural hazards. Some potentially important technical issues resulting from the consideration of a probabilistic risk-informed evaluation of the cask system performance are discussed for the canister and SNF integrity. These issues are also discussed in comparison with the deterministic approach for comparison purposes, as appropriate. Probabilistic risk-informed methods can provide insights that deterministic methods may not capture. Two specific examples include stress corrosion cracking of the canister and hydrogen-induced cladding failure. These examples are discussed in more detail, in terms of their effects on radionuclide release and nuclear subcriticality associated with the failure. The plan to consider the probabilistic risk-informed approaches is anticipated to provide helpful regulatory insights for long-term storage of SNF that provide reasonable assurance for public health and safety. (authors)

  18. Synaptic activity regulates AMPA receptor trafficking through different recycling pathways

    Science.gov (United States)

    Zheng, Ning; Jeyifous, Okunola; Munro, Charlotte; Montgomery, Johanna M; Green, William N

    2015-01-01

    Changes in glutamatergic synaptic strength in brain are dependent on AMPA-type glutamate receptor (AMPAR) recycling, which is assumed to occur through a single local pathway. In this study, we present evidence that AMPAR recycling occurs through different pathways regulated by synaptic activity. Without synaptic stimulation, most AMPARs recycled in dynamin-independent endosomes containing the GTPase, Arf6. Few AMPARs recycled in dynamin-dependent endosomes labeled by transferrin receptors (TfRs). AMPAR recycling was blocked by alterations in the GTPase, TC10, which co-localized with Arf6 endosomes. TC10 mutants that reduced AMPAR recycling had no effect on increased AMPAR levels with long-term potentiation (LTP) and little effect on decreased AMPAR levels with long-term depression. However, internalized AMPAR levels in TfR-containing recycling endosomes increased after LTP, indicating increased AMPAR recycling through the dynamin-dependent pathway with synaptic plasticity. LTP-induced AMPAR endocytosis is inconsistent with local recycling as a source of increased surface receptors, suggesting AMPARs are trafficked from other sites. DOI: http://dx.doi.org/10.7554/eLife.06878.001 PMID:25970033

  19. Why does serotonergic activity drastically decrease during REM sleep?

    Science.gov (United States)

    Sato, Kohji

    2013-10-01

    Here, I postulate two hypotheses that can explain the missing link between sleep and the serotonergic system in terms of spine homeostasis and memory consolidation. As dendritic spines contain many kinds of serotonin receptors, and the activation of serotonin receptors generally increases the number of spines in the cortex and hippocampus, I postulate that serotonin neurons are down-regulated during sleep to decrease spine number, which consequently maintains the total spine number at a constant level. Furthermore, since synaptic consolidation during REM sleep needs long-term potentiation (LTP), and serotonin is reported to inhibit LTP in the cortex, I postulate that serotonergic activity must drastically decrease during REM sleep to induce LTP and do memory consolidation. Until now, why serotonergic neurons show these dramatic changes in the sleep-wake cycle remains unexplained; however, making these hypotheses, I can confer physiological meanings on these dramatic changes of serotonergic neurons in terms of spine homeostasis and memory consolidation. Copyright © 2013. Published by Elsevier Ltd.

  20. Designing indicators of long-term energy supply security

    International Nuclear Information System (INIS)

    Jansen, J.C.; Van Arkel, W.G.; Boots, M.G.

    2004-01-01

    To our knowledge, so far amazingly little research work has been undertaken to construct meaningful indicators of long-run energy supply security for a particular nation or region. Currently, in addressing energy supply security, policy makers tend to emphasise short-term supply disruptions. In contrast, this pre-study accords with the broader Sustainability Outlook in considering the long-term perspective. This report starts with taking stock, in a concise way, of the official EU energy outlook and issues related to the opportunities to administer changes in the energy mix at the level of major energy use categories. Then a brief survey of relevant literature is made on long-term strategies to ensure survival of systems - be it biological, social, etc. - in an environment largely characterised by high uncertainty and a lot of unchartered territory. We found the work of Andrew Stirling very inspiring in this context. Based on his work and considering the limitations of the present research activity, we retained the Shannon index as the best 'simple' indicator of diversity. In the core of the report, the Shannon index is elaborated into four indicators of long-term energy supply security. Stepwise, additional aspects of long-term energy supply security are introduced. These aspects are: Diversification of energy sources in energy supply; Diversification of imports with respect to imported energy sources; Long-term political stability in regions of origin; The resource base in regions of origin, including the home region/country itself. After small adjustments to allow for data availability, these indicators were applied to the reference year 2030 of four long-term scenarios with data of base year 1995 and projections for underlying variables provided by the Netherlands Environmental Assessment Agency (MNP). Preliminary interpretation of the results suggests the usefulness of the indicators presented in this report. A second activity undertaken in this report was

  1. Long term testing of PSI-membranes

    Energy Technology Data Exchange (ETDEWEB)

    Huslage, J; Brack, H P; Geiger, F; Buechi, F N; Tsukada, A; Scherer, G G [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    Long term tests of PSI membranes based on radiation-grafted FEP and ETFE films were carried out and FEP-based membranes were evaluated by monitoring the in-situ membrane area resistance measured by a current pulse method. By modifying our irradiation procedure and using the double crosslinking concept we obtain reproducible membrane cell lifetimes (in term of in-situ membrane resistance) of greater than 5000 hours at 60-65{sup o}C. Preliminary tests at 80-85{sup o}C with lifetimes of greater than 2500 demonstrate the potential long term stability of PSI proton exchange membranes based on FEP over the whole operating temperature range of low-temperature polymer electrolyte fuel cells. Radiation grafted PSI membranes based on ETFE have better mechanical properties than those of the FEP membranes. Mechanical properties are particularly important in large area cells and fuel cell stacks. ETFE membranes have been tested successfully for approximately 1000 h in a 2-cell stack (100 cm{sup 2} active area each cell). (author) 4 figs., 4 refs.

  2. Waste transmutation with minimal fuel cycle long-term risk

    Energy Technology Data Exchange (ETDEWEB)

    Slessarev, I.; Salvatores, M.; Uematsu, M. [Direction des Reacteurs Nucleaires, Cadarache (France)

    1995-10-01

    Hybrid systems (source-driven subcritical reactors), are investigated at CEA, mainly from a conceptual point of view, in order to assess their potential to transmute radioactive wastes (mainly long-lived fission products, LLFP) and their potential to insure a minimal long-term radiological risk related both to the fuel inventory inside the system and to the full fuel cycle (mass flows, reprocessing transport, waste disposal). The physics of these systems has been explored and work is in progress both in the field of basic data and INC code validation, in the frame of international collaborations and in the field of conceptual design studies. The most interesting feature of subcritical source-driven system is related to the possibility to obtain an {open_quotes}excess{close_quotes} of neutrons per fission, which can be used to reduce the long-term radiological risk. A specific example will be discussed here.

  3. HIV-related politics in long-term perspective.

    Science.gov (United States)

    Friedman, S R

    1998-06-01

    Some long-term, large-scale socio-economic changes may affect the politics of HIV and other emerging viruses such as hepatitis C. It is useful to ask why the potential peace dividend of the early 1990s failed to provide adequate resources for HIV-related social and medical service delivery in developed or developing nations. This failure can be understood by looking at long-term global economic trends and the pressures they put on governments and corporations. They have produced a period in which fundamental issues of political and economic structure are at stake and, often, the response is a divide-and-rule politics to promote stability. National politics differ in terms of the extent to which such a 'politics of scapegoating' is institutionalized and in terms of which groups are scapegoated. Groups such as drug injectors, gay and bisexual men and sex traders are particularly likely to be targeted both by the scapegoaters and by HIV. Given this framework, how should public health professionals and activists engaged in HIV-related issues respond? Under what circumstances should we orient efforts upwards towards corporate, political or bureaucratic leaders? Under what circumstances, and how, should we orient towards popular forces? Relatedly, we need to consider an issue we often ignore: What do we have to offer potential allies? That is, in terms of their goals, philosophies and needs, why should they ally with us?

  4. Long term effects on potential repository sites: the alteration of the Lower Oxford Clay during weathering

    International Nuclear Information System (INIS)

    Milowdowski, A.E.; Bloodworth, A.J.; Wilmot, R.D.

    1985-09-01

    The report is one of a short series describing work carried out to investigate the long-term effects of various geological processes on the performance of both shallow and deep repositories for low and intermediate-level radioactive wastes. This paper deals with the alteration as a result of weathering of the Lower Oxford Clay, a potential host rock for shallow disposal of wastes. A description of the Lower Oxford Clay is given, along with the weathering of argillaceous rocks. Investigations of the weathering at the Elstow Storage Depot are described, as well as the implications for radioactive waste disposal. (U.K.)

  5. Long-term monitoring for closed special sites

    International Nuclear Information System (INIS)

    Golchert, N.W.; Sedlet, J.

    1987-01-01

    A methodology is presented for planning and implementing a long-term environmental monitoring program for closed special radioactive waste disposal sites. The steps in the method involve collection of the available background information on the site history, site and area characteristics, waste inventory, pathway analysis, prior monitoring programs, applicable standards, and the legal/regulatory requirements. This information is coupled with factors such as experience, half-life, radionuclide migration rates, and potential hazard to develop a monitoring program. As an example, a site-specific long-term monitoring program is described for the AMAX site using the available information. Sampling techniques and practices for the monitoring program are discussed and techniques and practices expected to be available in the future are considered. 7 references, 2 tables

  6. Risk assessment for long-term post-accident sequences

    International Nuclear Information System (INIS)

    Ellia-Hervy, A.; Ducamp, F.

    1987-11-01

    Probabilistic risk analysis, currently conducted by the CEA (French Atomic Energy Commission) for the French replicate series of 900 MWe power plants, has identified accident sequences requiring long-term operation of some systems after the initiating event. They have been named long-term sequences. Quantification of probabilities of such sequences cannot rely exclusively on equipment failure-on-demand data: it must also take into account operating failures, the probability of which increase with time. Specific studies have therefore been conducted for a number of plant systems actuated during these long-term sequences. This has required: - Definition of the most realistic equipment utilization strategies based on existing emergency procedures for 900 MWe French plants. - Evaluation of the potential to repair failed equipment, given accessibility, repair time, and specific radiation conditions for the given sequence. - Definition of the event bringing the long-term sequence to an end. - Establishment of an appropriate quantification method, capable of taking into account the evolution of assumptions concerning equipment utilization strategies or repair conditions over time. The accident sequence quantification method based on realistic scenarios has been used in the risk assessment of the initiating event loss of reactor coolant accident occurring at power and at shutdown. Compared with the results obtained from conventional methods, this method redistributes the relative weight of accident sequences and also demonstrates that the long term can be a significant contribution to the probability of core melt

  7. Long- and Short-Term Cryptocurrency Volatility Components: A GARCH-MIDAS Analysis

    Directory of Open Access Journals (Sweden)

    Christian Conrad

    2018-05-01

    Full Text Available We use the GARCH-MIDAS model to extract the long- and short-term volatility components of cryptocurrencies. As potential drivers of Bitcoin volatility, we consider measures of volatility and risk in the US stock market as well as a measure of global economic activity. We find that S&P 500 realized volatility has a negative and highly significant effect on long-term Bitcoin volatility. The finding is atypical for volatility co-movements across financial markets. Moreover, we find that the S&P 500 volatility risk premium has a significantly positive effect on long-term Bitcoin volatility. Finally, we find a strong positive association between the Baltic dry index and long-term Bitcoin volatility. This result shows that Bitcoin volatility is closely linked to global economic activity. Overall, our findings can be used to construct improved forecasts of long-term Bitcoin volatility.

  8. Attention Problems, Phonological Short-Term Memory, and Visuospatial Short-Term Memory: Differential Effects on Near- and Long-Term Scholastic Achievement

    Science.gov (United States)

    Sarver, Dustin E.; Rapport, Mark D.; Kofler, Michael J.; Scanlan, Sean W.; Raiker, Joseph S.; Altro, Thomas A.; Bolden, Jennifer

    2012-01-01

    The current study examined individual differences in children's phonological and visuospatial short-term memory as potential mediators of the relationship among attention problems and near- and long-term scholastic achievement. Nested structural equation models revealed that teacher-reported attention problems were associated negatively with…

  9. A systematic review of potential long-term effects of sport-related concussion.

    Science.gov (United States)

    Manley, Geoff; Gardner, Andrew J; Schneider, Kathryn J; Guskiewicz, Kevin M; Bailes, Julian; Cantu, Robert C; Castellani, Rudolph J; Turner, Michael; Jordan, Barry D; Randolph, Christopher; Dvořák, Jiří; Hayden, K Alix; Tator, Charles H; McCrory, Paul; Iverson, Grant L

    2017-06-01

    Systematic review of possible long-term effects of sports-related concussion in retired athletes. Ten electronic databases. Original research; incidence, risk factors or causation related to long-term mental health or neurological problems; individuals who have suffered a concussion; retired athletes as the subjects and possible long-term sequelae defined as > 10 years after the injury. Study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors. Following review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes. Multiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Assessment of the potential for long-term toxicological effects of the Exxon Valdez oil spill on birds and mammals

    International Nuclear Information System (INIS)

    Hartung, R.

    1995-01-01

    This paper assesses the potential for direct long-term toxicological effects of exposures to oils in birds and mammals by tracing exposures and effects form the initial cute phases through the sub-chronic to the eventual long-term exposures. The immediate effects of oil spills are physical, the oil acting on the plumage of birds or the fur of mammals. This causes a loss of entrained air and a concomitant reduction in buoyancy and thermal insulation. Animals that escape the immediate impacts may be isolated from their food supply and often ingest large amounts of oil while attempting to clean themselves. At the comparatively high dose levels involved, these exposures can result in toxicologically significant responses in many organ systems. In the course of an oil pollution incident, the amounts of biologically available oils decrease steadily, and simultaneously the composition of the oils shifts towards those components that have low volatility, and that resist photo- and bio-degradation. As this occurs, the primary pathways of exposure change from direct intakes to indirect routes involving the food supply. Although laboratory studies often report finding some adverse effects, the dose rates employed in many of these studies are extremely high when compared with those that are potentially available to animals in the wild, and very few actually use weathered oils. An assessment of the toxicological literature and of the available empirical data on the Exxon Valdez oil spill leads to the conclusion that long-term sub-lethal toxic effects of crude oils on wildlife in such marine spills appear to be very unlikely. 111 refs., 4 figs., 1 tab

  11. Long-term urethral catheterisation.

    Science.gov (United States)

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  12. Assessment of short- and long-term memory in trends of major climatic variables over Iran: 1966-2015

    Science.gov (United States)

    Mianabadi, Ameneh; Shirazi, Pooya; Ghahraman, Bijan; Coenders-Gerrits, A. M. J.; Alizadeh, Amin; Davary, Kamran

    2018-02-01

    In arid and semi-arid regions, water scarcity is the crucial issue for crop production. Identifying the spatial and temporal trends in aridity, especially during the crop-growing season, is important for farmers to manage their agricultural practices. This will become especially relevant when considering climate change projections. To reliably determine the actual trends, the influence of short- and long-term memory should be removed from the trend analysis. The objective of this study is to investigate the effect of short- and long-term memory on estimates of trends in two aridity indicators—the inverted De Martonne (ϕ IDM ) and Budyko (ϕ B ) indices. The analysis is done using precipitation and temperature data over Iran for a 50-year period (1966-2015) at three temporal scales: annual, wheat-growing season (October-June), and maize-growing season (May-November). For this purpose, the original and the modified Mann-Kendall tests (i.e., modified by three methods of trend free pre-whitening (TFPT), effective sample size (ESS), and long-term persistence (LTP)) are used to investigate the temporal trends in aridity indices, precipitation, and temperature by taking into account the effect of short- and long-term memory. Precipitation and temperature data were provided by the Islamic Republic of Iran Meteorological Organization (IRIMO). The temporal trend analysis showed that aridity increased from 1966 to 2015 at the annual and wheat-growing season scales, which is due to a decreasing trend in precipitation and an increasing trend in mean temperature at these two timescales. The trend in aridity indices was decreasing in the maize-growing season, since precipitation has an increasing trend for most parts of Iran in that season. The increasing trend in aridity indices is significant in Western Iran, which can be related to the significantly more negative trend in precipitation in the West. This increasing trend in aridity could result in an increasing crop water

  13. Biphasic somatic A-type K channel downregulation mediates intrinsic plasticity in hippocampal CA1 pyramidal neurons.

    Directory of Open Access Journals (Sweden)

    Sung-Cherl Jung

    2009-08-01

    Full Text Available Since its original description, the induction of synaptic long-term potentiation (LTP has been known to be accompanied by a lasting increase in the intrinsic excitability (intrinsic plasticity of hippocampal neurons. Recent evidence shows that dendritic excitability can be enhanced by an activity-dependent decrease in the activity of A-type K(+ channels. In the present manuscript, we examined the role of A-type K(+ channels in regulating intrinsic excitability of CA1 pyramidal neurons of the hippocampus after synapse-specific LTP induction. In electrophysiological recordings we found that LTP induced a potentiation of excitability which was accompanied by a two-phased change in A-type K(+ channel activity recorded in nucleated patches from organotypic slices of rat hippocampus. Induction of LTP resulted in an immediate but short lasting hyperpolarization of the voltage-dependence of steady-state A-type K(+ channel inactivation along with a progressive, long-lasting decrease in peak A-current density. Blocking clathrin-mediated endocytosis prevented the A-current decrease and most measures of intrinsic plasticity. These results suggest that two temporally distinct but overlapping mechanisms of A-channel downregulation together contribute to the plasticity of intrinsic excitability. Finally we show that intrinsic plasticity resulted in a global enhancement of EPSP-spike coupling.

  14. Short-term versus long-term approaches to the development of tourism-related policies

    OpenAIRE

    Dredge, Dianne

    2015-01-01

    Tourism policy development is an increasingly complex activity involving multiple public sector agencies, industry and community stakeholders and non-government organisations at different scales. This discussion paper examines the implications for tourism of governments adopting short- term versus long-term approaches to the development of tourism related policies and identifies policy considerations to maximize the growth potential of tourism. The key issue is to understand how governments c...

  15. Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation.

    Directory of Open Access Journals (Sweden)

    Aline Rideau Batista Novais

    Full Text Available Maternal inflammation during pregnancy is associated with the later development of cognitive and behavioral impairment in the offspring, reminiscent of the traits of schizophrenia or autism spectrum disorders. Hippocampal long-term potentiation and long-term depression of glutamatergic synapses are respectively involved in memory formation and consolidation. In male rats, maternal inflammation with lipopolysaccharide (LPS led to a premature loss of long-term depression, occurring between 12 and 25 postnatal days instead of after the first postnatal month, and aberrant occurrence of long-term potentiation. We hypothesized this would be related to GABAergic system impairment. Sprague Dawley rats received either LPS or isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between 12 and 25 postnatal days. Morphological and functional analyses demonstrated that prenatal LPS triggered a deficit of hippocampal GABAergic interneurons, associated with presynaptic GABAergic transmission deficiency in male offspring. Increasing ambient GABA by impairing GABA reuptake with tiagabine did not interact with the low frequency-induced long-term depression in control animals but fully prevented its impairment in male offspring of LPS-challenged dams. Tiagabine furthermore prevented the aberrant occurrence of paired-pulse triggered long-term potentiation in these rats. Deficiency in GABA seems to be central to the dysregulation of synaptic plasticity observed in juvenile in utero LPS-challenged rats. Modulating GABAergic tone may be a possible therapeutic strategy at this developmental stage.

  16. Mechanisms of translation control underlying long-lasting synaptic plasticity and the consolidation of long-term memory.

    Science.gov (United States)

    Santini, Emanuela; Huynh, Thu N; Klann, Eric

    2014-01-01

    The complexity of memory formation and its persistence is a phenomenon that has been studied intensely for centuries. Memory exists in many forms and is stored in various brain regions. Generally speaking, memories are reorganized into broadly distributed cortical networks over time through systems level consolidation. At the cellular level, storage of information is believed to initially occur via altered synaptic strength by processes such as long-term potentiation. New protein synthesis is required for long-lasting synaptic plasticity as well as for the formation of long-term memory. The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of cap-dependent protein synthesis and is required for numerous forms of long-lasting synaptic plasticity and long-term memory. As such, the study of mTORC1 and protein factors that control translation initiation and elongation has enhanced our understanding of how the process of protein synthesis is regulated during memory formation. Herein we discuss the molecular mechanisms that regulate protein synthesis as well as pharmacological and genetic manipulations that demonstrate the requirement for proper translational control in long-lasting synaptic plasticity and long-term memory formation. © 2014 Elsevier Inc. All rights reserved.

  17. Impact of short-term severe accident management actions in a long-term perspective. Final Report

    International Nuclear Information System (INIS)

    2000-03-01

    The present systems for severe accident management are focused on mitigating the consequences of special severe accident phenomena and to reach a safe plant state. However, in the development of strategies and procedures for severe accident management, it is also important to consider the long-term perspective of accident management and especially to secure the safe state of the plant. The main reason for this is that certain short-term actions have an impact on the long-term scenario. Both positive and negative effects from short-term actions on the accident management in the long-term perspective have been included in this paper. Short-term actions are accident management measures taken within about 24 hours after the initiating event. The purpose of short-term actions is to reach a stable status of the plant. The main goal in the long-term perspective is to maintain the reactor in a stable state and prevent uncontrolled releases of activity. The purpose of this short Technical Note, deliberately limited in scope, is to draw attention to potential long-term problems, important to utilities and regulatory authorities, arising from the way a severe accident would be managed during the first hours. Its objective is to encourage discussions on the safest - and maybe also most economical - way to manage a severe accident in the long term by not making the situation worse through inappropriate short-term actions, and on the identification of short-term actions likely to make long-term management easier and safer. The Note is intended as a contribution to the knowledge base put at the disposal of Member countries through international collaboration. The scope of the work has been limited to a literature search. Useful further activities have been identified. However, there is no proposal, at this stage, for more detailed work to be undertaken under the auspices of the CSNI. Plant-specific applications would need to be developed by utilities

  18. New twist in the optical schematic of surface slope measuring long trace profiler

    Science.gov (United States)

    Nikitin, Sergey M.; Gevorkyan, Gevork S.; McKinney, Wayne R.; Lacey, Ian; Takacs, Peter Z.; Yashchuk, Valeriy V.

    2017-09-01

    The advents of fully coherent free electron lasers and diffraction limited synchrotron storage ring sources of x-rays are catalyzing the development of new, ultra-high accuracy metrology methods. To fully exploit the potential of these sources, metrology needs to be capable of determining the figure of an optical element with sub-nanometer height accuracy. Currently, the two most prevalent slope measuring instruments used for characterization of x-ray optics are the auto-collimator based nanometer optical measuring device (NOM) and the long trace profiler (LTP) using pencil beam interferometry (PBI). These devices have been consistently improved upon by the x-ray optics metrology community, but appear to be approaching their metrological limits. Here, we revise the traditional optical schematic of the LTP. We experimentally show that, for the level of accuracy desired for metrology with state-of-the-art x-ray optics, the Dove prism in the LTP reference channel appears to be one of the major sources of instrumental error. Therefore, we suggest returning back to the original PBI LTP schematics with no Dove prism in the reference channel. In this case, the optimal scanning strategies [Yashchuk, Rev. Sci. Instrum. 80, 115101 (2009)] used to suppress the instrumental drift error have to be used to suppress a possible drift error associated with laser beam pointing instability. We experimentally and by numerical simulation demonstrate the usefulness of the suggested approach for measurements with x-ray optics with both face up and face down orientations.

  19. Synaptic plasticity and the analysis of the field-EPSP as well as the population spike using separate recording electrodes in the dentate gyrus in freely moving rats.

    Science.gov (United States)

    Frey, Sabine; Frey, Julietta U

    2009-10-30

    Commonly, synaptic plasticity events such as long-term potentiation (LTP) are investigated by using a stimulation electrode and a single, monopolar field recording electrode in the dentate gyrus in intact, freely moving rats. The recording electrode is mostly positioned in the granular cell layer, or the hilar region of the dentate gyrus, i.e. far away from the place of generation of monosynaptic postsynaptic excitatory potentials (EPSP). Since LTP is a synaptic phenomenon and field recordings far away from the activated synapses do not guarantee a specific interpretation of the overlaid, mixture of complex potentials of several different electrical fields it is often difficult or even impossible to interpret the data obtained by such a single recording electrode. Therefore, at least a separate or two recording electrodes should be used to record the EPSP as well as the spike, respectively, ideally at their places of generation. Here, we describe a method by implanting a chronic bipolar recording electrode which fulfils the above requirements by recording the field-EPSP as well as the population spike at their places of generation and describe the time course of LTP measured using this "double-recording" electrode. We show that different tetanization protocols resulted in EPSP- or population spike-LTP but only if the potentials were recorded by electrodes positioned within adequate places of potential generation. Interestingly, the commonly used recording in the hilus of a distinct part of a potential, mistakenly analyzed as an "EPSP" did not reveal any LTP.

  20. Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

    Directory of Open Access Journals (Sweden)

    Atsushi Takeda

    Full Text Available We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ concentration. A single injection of Aβ (25 pmol into the dentate gyrus affected dentate gyrus long-term potentiation (LTP 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.

  1. Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

    Science.gov (United States)

    Takeda, Atsushi; Nakamura, Masatoshi; Fujii, Hiroaki; Uematsu, Chihiro; Minamino, Tatsuya; Adlard, Paul A; Bush, Ashley I; Tamano, Haruna

    2014-01-01

    We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.

  2. Assessing the associative deficit of older adults in long-term and short-term/working memory.

    Science.gov (United States)

    Chen, Tina; Naveh-Benjamin, Moshe

    2012-09-01

    Older adults exhibit a deficit in associative long-term memory relative to younger adults. However, the literature is inconclusive regarding whether this deficit is attenuated in short-term/working memory. To elucidate the issue, three experiments assessed younger and older adults' item and interitem associative memory and the effects of several variables that might potentially contribute to the inconsistent pattern of results in previous studies. In Experiment 1, participants were tested on item and associative recognition memory with both long-term and short-term retention intervals in a single, continuous recognition paradigm. There was an associative deficit for older adults in the short-term and long-term intervals. Using only short-term intervals, Experiment 2 utilized mixed and blocked test designs to examine the effect of test event salience. Blocking the test did not attenuate the age-related associative deficit seen in the mixed test blocks. Finally, an age-related associative deficit was found in Experiment 3, under both sequential and simultaneous presentation conditions. Even while accounting for some methodological issues, the associative deficit of older adults is evident in short-term/working memory.

  3. Long-term associative learning predicts verbal short-term memory performance.

    Science.gov (United States)

    Jones, Gary; Macken, Bill

    2018-02-01

    Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting.

  4. Short-term treatment with flumazenil restores long-term object memory in a mouse model of Down syndrome.

    Science.gov (United States)

    Colas, Damien; Chuluun, Bayarsaikhan; Garner, Craig C; Heller, H Craig

    2017-04-01

    Down syndrome (DS) is a common genetic cause of intellectual disability yet no pro-cognitive drug therapies are approved for human use. Mechanistic studies in a mouse model of DS (Ts65Dn mice) demonstrate that impaired cognitive function is due to excessive neuronal inhibitory tone. These deficits are normalized by chronic, short-term low doses of GABA A receptor (GABA A R) antagonists in adult animals, but none of the compounds investigated are approved for human use. We explored the therapeutic potential of flumazenil (FLUM), a GABA A R antagonist working at the benzodiazepine binding site that has FDA approval. Long-term memory was assessed by the Novel Object Recognition (NOR) testing in Ts65Dn mice after acute or short-term chronic treatment with FLUM. Short-term, low, chronic dose regimens of FLUM elicit long-lasting (>1week) normalization of cognitive function in both young and aged mice. FLUM at low dosages produces long lasting cognitive improvements and has the potential of fulfilling an unmet therapeutic need in DS. Copyright © 2017. Published by Elsevier Inc.

  5. Expression of NMDA receptor-dependent LTP in the hippocampus: bridging the divide

    Directory of Open Access Journals (Sweden)

    Bliss Tim VP

    2013-01-01

    Full Text Available Abstract A consensus has famously yet to emerge on the locus and mechanisms underlying the expression of the canonical NMDA receptor-dependent form of LTP. An objective assessment of the evidence leads us to conclude that both presynaptic and postsynaptic expression mechanisms contribute to this type of synaptic plasticity.

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

    Science.gov (United States)

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

    2017-09-27

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

  7. Long-term stabilization considerations for decommissioned and reclaimed uranium sites

    International Nuclear Information System (INIS)

    Abt, S.R.; Nelson, J.D.; Johnson, T.L.

    1988-01-01

    The long-term stabilization of decommissioned uranium mill sites and of reclaimed uranium mill tailings sites encompass a broad spectrum of design capabilities. This paper presents a few of the quantitative methodologies recently developed or refined to evaluate physical factors (i.e. precipitation, fluvial geomorphology, stable slope, slope stabilization with riprap and riprap selection) that influence long-term stabilization of uranium mill and mill tailings sites. It is acknowledged that the degree of refinement of these methodologies are in their infancy and that extensive research and development are warranted to increase the level of assurance. However, these methodologies provide an initial guideline for evaluating long-term stabilization that has not been previously existed. The purpose of this paper is to present a review of currently available state-of-the-art engineering techniques and methodologies for the evaluation of reclamation plans designed to provide long-term stability against potential failure modes. In some cases, evaluative techniques have been developed for long-term stabilization where methodologies have not previously existed. Each methodology to be presented represents a starting point upon which additional research and/or development may be warranted

  8. Long term adequacy of uranium resources

    International Nuclear Information System (INIS)

    Steyn, J.

    1990-01-01

    This paper examines the adequacy of world economic uranium resources to meet requirements in the very long term, that is until at least 2025 and beyond. It does so by analysing current requirements forecasts, existing and potential production centre supply capability schedules and national resource estimates. It takes into account lead times from resource discovery to production and production rate limitations. The institutional and political issues surrounding the question of adequacy are reviewed. (author)

  9. Upgrade of long trace profiler for characterization of high-precision X-ray mirrors at SPring-8

    International Nuclear Information System (INIS)

    Senba, Y.; Kishimoto, H.; Ohashi, H.; Yumoto, H.; Zeschke, T.; Siewert, F.; Goto, S.; Ishikawa, T.

    2010-01-01

    The long trace profiler (LTP) at SPring-8 has been upgraded to improve stability and resolution of slope measurement. The performances of the upgraded LTP at SPring-8 are presented by cross-checking measurements on a flat mirror with data obtained using Nanometer Optical Component Measuring Machine (NOM) at the Helmholtz Zentrum Berlin/BESSY-II.

  10. NMDA receptor-mediated long term modulation of electrically evoked field potentials in the rat medial vestibular nuclei.

    Science.gov (United States)

    Capocchi, G; Della Torre, G; Grassi, S; Pettorossi, V E; Zampolini, M

    1992-01-01

    The effect of high frequency stimulation (HFS) of the primary vestibular afferents on field potentials recorded in the ipsilateral Medial Vestibular Nuclei (MVN) was studied. Our results show that potentiation and depression can be induced in different portions of MVN, which are distinguishable by their anatomical organization. HFS induces potentiation of the monosynaptic component in the ventral portion of the MVN, whereas it provokes depression of the polysynaptic component in the dorsal portion of the same nucleus. The induction of both potentiation and depression was blocked under AP5 perfusion, thus demonstrating that NMDA receptor activation mediates both phenomena. Furthermore, the finding that the field potentials were not modified during perfusion with DL-AP5, as previously reported, supports the hypothesis that NMDA receptors are not involved in the normal synaptic transmission from the primary vestibular afferent fibres, but are only activated following hyperstimulation of this afferent system. Our results suggest that the mechanisms of long term modification of synaptic efficacy observed in MVN may underlie the plasticity phenomena occurring in vestibular nuclei.

  11. A simple way of characterizing X-ray downwards-deflecting mirror-bender assemblies using the long trace profiler

    International Nuclear Information System (INIS)

    Assoufid, L.; Her, P.

    1999-01-01

    A simple device composed of a modular double-pentaprism system that enables the long trace profiler (LTP) to measure mirrors in nonconventional ways, i.e., in the vertical-downward and sideways positions, has been devised and implemented in the Advanced Photon Source (APS) long trace profiler (LTP II). The systems is very useful in calibrating mirror-bender assemblies. This paper describes the system and gives results of measurements performed with it on a mirror used at the APS

  12. Error reduction techniques for measuring long synchrotron mirrors

    International Nuclear Information System (INIS)

    Irick, S.

    1998-07-01

    Many instruments and techniques are used for measuring long mirror surfaces. A Fizeau interferometer may be used to measure mirrors much longer than the interferometer aperture size by using grazing incidence at the mirror surface and analyzing the light reflected from a flat end mirror. Advantages of this technique are data acquisition speed and use of a common instrument. Disadvantages are reduced sampling interval, uncertainty of tangential position, and sagittal/tangential aspect ratio other than unity. Also, deep aspheric surfaces cannot be measured on a Fizeau interferometer without a specially made fringe nulling holographic plate. Other scanning instruments have been developed for measuring height, slope, or curvature profiles of the surface, but lack accuracy for very long scans required for X-ray synchrotron mirrors. The Long Trace Profiler (LTP) was developed specifically for long x-ray mirror measurement, and still outperforms other instruments, especially for aspheres. Thus, this paper focuses on error reduction techniques for the LTP

  13. Metrology of variable-line-spacing x-ray gratings using the APS Long Trace Profiler

    Science.gov (United States)

    Sheung, Janet; Qian, Jun; Sullivan, Joseph; Thomasset, Muriel; Manton, Jonathan; Bean, Sunil; Takacs, Peter; Dvorak, Joseph; Assoufid, Lahsen

    2017-09-01

    As resolving power targets have increased with each generation of beamlines commissioned in synchrotron radiation facilities worldwide, diffraction gratings are quickly becoming crucial optical components for meeting performance targets. However, the metrology of variable-line-spacing (VLS) gratings for high resolution beamlines is not widespread; in particular, no metrology facility at any US DOE facility is currently equipped to fully characterize such gratings. To begin to address this issue, the Optics Group at the Advanced Photon Source at Argonne, in collaboration with SOLEIL and with support from Brookhaven National Laboratory (BNL), has developed an alternative beam path addition to the Long Trace Profiler (LTP) at Argonne's Advanced Photon Source. This significantly expands the functionality of the LTP not only to measure mirrors surface slope profile at normal incidence, but also to characterize the groove density of VLS diffraction gratings in the Littrow incidence up to 79°, which covers virtually all diffraction gratings used at synchrotrons in the first order. The LTP light source is a 20mW HeNe laser, which yields enough signal for diffraction measurements to be performed on low angle blazed gratings optimized for soft X-ray wavelengths. We will present the design of the beam path, technical requirements for the optomechanics, and our data analysis procedure. Finally, we discuss challenges still to be overcome and potential limitations with use of the LTP to perform metrology on diffraction gratings.

  14. Long-term care financing: lessons from France.

    Science.gov (United States)

    Doty, Pamela; Nadash, Pamela; Racco, Nathalie

    2015-06-01

    POLICY POINTS: France's model of third-party coverage for long-term services and supports (LTSS) combines a steeply income-adjusted universal public program for people 60 or older with voluntary supplemental private insurance. French and US policies differ: the former pay cash; premiums are lower; and take-up rates are higher, in part because employer sponsorship, with and without subsidization, is more common-but also because coverage targets higher levels of need and pays a smaller proportion of costs. Such inexpensive, bare-bones private coverage, especially if marketed as a supplement to a limited public benefit, would be more affordable to those Americans currently most at risk of "spending down" to Medicaid. An aging population leads to a growing demand for long-term services and supports (LTSS). In 2002, France introduced universal, income-adjusted, public long-term care coverage for adults 60 and older, whereas the United States funds means-tested benefits only. Both countries have private long-term care insurance (LTCI) markets: American policies create alternatives to out-of-pocket spending and protect purchasers from relying on Medicaid. Sales, however, have stagnated, and the market's viability is uncertain. In France, private LTCI supplements public coverage, and sales are growing, although its potential to alleviate the long-term care financing problem is unclear. We explore whether France's very different approach to structuring public and private financing for long-term care could inform the United States' long-term care financing reform efforts. We consulted insurance experts and conducted a detailed review of public reports, academic studies, and other documents to understand the public and private LTCI systems in France, their advantages and disadvantages, and the factors affecting their development. France provides universal public coverage for paid assistance with functional dependency for people 60 and older. Benefits are steeply income

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Long-term sealing of openings in salt formations

    International Nuclear Information System (INIS)

    Walter, F.; Stockmann, N.; Yaramanci, U.; Laurens, J.F.

    1993-01-01

    Radioactive wastes can be disposed of in deep salt formations. Rock salt is a suitable geologic medium because of its unique characteristics. Open boreholes, shafts and drifts are created to provide physical access to the repository. Long-term seals must be emplaced in those potential pathways to prevent radioactive release to the biosphere. The sealing materials must be mechanically and, most important, geochemically stable within the host rock. Salt bricks made of compressed salt-powder are understood to be the first choice long-term sealing material. Seals built from salt bricks will be ductile. The permeability of the salt bricks is assumed to be in the order of 2*10 -15 m 2 . Large sealing systems are built by combining the individual bricks with mortar. Raw materials for mortar are fine-grained halite powder and ground saliferous clay. The permeability of the mortar decreases with its salt content to approx. 2*10 -14 m 2 . Moistened saliferous clay may show temporary swelling. Sealing experiments will be carried out in the Asse salt mine. Long-term seals will be built into holes of 1 m diameter. The contact and merging of the brick-wall with the surrounding rock salt will be investigated in long-term tests. Within the in situ sealing program a number of geophysical methods are applied. Acoustic emission measurements are used to study the effects of high pressure gas injection and a geoelectrical observation program is aiming to estimate the permeability in and around the long-term seal. High frequency electromagnetic methods contribute to the knowledge of the petrophysical rock properties. 11 refs., 12 figs

  17. Ketamine Protects Gamma Oscillations by Inhibiting Hippocampal LTD

    Science.gov (United States)

    Huang, Lanting; Yang, Xiu-Juan; Huang, Ying; Sun, Eve Y.

    2016-01-01

    NMDA receptors have been widely reported to be involved in the regulation of synaptic plasticity through effects on long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD have been implicated in learning and memory processes. Besides synaptic plasticity, it is known that the phenomenon of gamma oscillations is critical in cognitive functions. Synaptic plasticity has been widely studied, however it is still not clear, to what degree synaptic plasticity regulates the oscillations of neuronal networks. Two NMDA receptor antagonists, ketamine and memantine, have been shown to regulate LTP and LTD, to promote cognitive functions, and have even been reported to bring therapeutic effects in major depression and Alzheimer’s disease respectively. These compounds allow us to investigate the putative interrelationship between network oscillations and synaptic plasticity and to learn more about the mechanisms of their therapeutic effects. In the present study, we have identified that ketamine and memantine could inhibit LTD, without impairing LTP in the CA1 region of mouse hippocampus, which may underlie the mechanism of these drugs’ therapeutic effects. Our results suggest that NMDA-induced LTD caused a marked loss in the gamma power, and pretreatment with 10 μM ketamine prevented the oscillatory loss via its inhibitory effect on LTD. Our study provides a new understanding of the role of NMDA receptors on hippocampal plasticity and oscillations. PMID:27467732

  18. New Developments in Long-Term Downhole Monitoring Arrays

    Directory of Open Access Journals (Sweden)

    Jochem Kück

    2006-03-01

    Full Text Available The long-term observation of active geological processes is a major research goal in an increasing number of scientific drilling projects. An extended monitoring phase within a potentially hostile environment (e.g., temperature, pressure, salinity requires new long-lasting and robust instrumentation currently unavailable from either industry or academia. Extended exposure of instrument packages to extreme conditions will typically cause seals to weaken and fail,electronic parts to break under permanent load, and sensors to degrade or develop strong drift. In the framework of scientific exploration, there are currently several major research projects targeting fault zone drilling and in situ measurements to monitor physical and chemical conditions before, during, and after seismic events. Planning has now begun for tool development, testing, and continuous long-term monitoring for the San Andreas Fault Zone Observatory at Depth, SAFOD (Parkfi eld, Calif., U.S.A.; See article on page 32..

  19. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

    Science.gov (United States)

    Soheili, Masoud; Tavirani, Mostafa Rezaei; Salami, Mahmoud

    2015-01-01

    Objective(s): Neurodegenerative Alzheimer’s disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area. Materials and Methods: The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON) and lavender (CE) treated rats and two Alzheimeric groups including the vehicle (ALZ) and lavender (AE) treated animals. Results: The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. Conclusion: The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals. PMID:26949505

  20. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer's disease.

    Science.gov (United States)

    Soheili, Masoud; Tavirani, Mostafa Rezaei; Salami, Mahmoud

    2015-11-01

    Neurodegenerative Alzheimer's disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area. The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON) and lavender (CE) treated rats and two Alzheimeric groups including the vehicle (ALZ) and lavender (AE) treated animals. The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals.

  1. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Masoud Soheili

    2015-11-01

    Full Text Available Objective(s:Neurodegenerative Alzheimer’s disease (AD is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP, an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs were recorded in the CA1 area. Materials and Methods: The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON and lavender (CE treated rats and two Alzheimeric groups including the vehicle (ALZ and lavender (AE treated animals. Results: The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. Conclusion:The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals.

  2. Reforming Long-Term Care Funding in Alberta.

    Science.gov (United States)

    Crump, R Trafford; Repin, Nadya; Sutherland, Jason M

    2015-01-01

    Like many provinces across Canada, Alberta is facing growing demand for long-term care. Issues with the mixed funding model used to pay long-term care providers had Alberta Health Services concerned that it was not efficiently meeting the demand for long-term care. Consequently, in 2010, Alberta Health Services introduced the patient/care-based funding (PCBF) model. PCBF is similar to activity-based funding in that it directly ties the complexity and care needs of long-term care residents to the payment received by long-term care providers. This review describes PCBF and discusses some of its strengths and weaknesses. In doing so, this review is intended to inform other provinces faced with similar long-term care challenges and contemplating their own funding reforms.

  3. Protein kinase M ζ and the maintenance of long-term memory.

    Science.gov (United States)

    Zhang, Yang; Zong, Wei; Zhang, Lei; Ma, Yuanye; Wang, Jianhong

    2016-10-01

    Although various molecules have been found to mediate the processes of memory acquisition and consolidation, the molecular mechanism to maintain memory still remains elusive. In recent years, a molecular pathway focusing on protein kinase Mζ (PKMζ) has become of interest to researchers because of its potential role in long-term memory maintenance. PKMζ is an isoform of protein kinase C (PKC) and has a related structure that influences its function in maintaining memory. Considerable evidence has been gathered on PKMζ activity, including loss of function studies using PKMζ inhibitors, such as PKMζ inhibitory peptide (ZIP), suggesting PKMζ plays an important role in long-term memory maintenance. This review provides an overview of the role of PKMζ in long-term memory and outlines the molecular structure of PKMζ, the molecular mechanism of PKMζ in long-term memory maintenance and future directions of PKMζ research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Individual decision making in the non-purchase of long-term care insurance.

    Science.gov (United States)

    Curry, Leslie A; Robison, Julie; Shugrue, Noreen; Keenan, Patricia; Kapp, Marshall B

    2009-08-01

    Although prior research suggests that economic, behavioral, and psychosocial factors influence decisions not to purchase long-term care insurance, few studies have examined the interplay among these factors in depth and from the consumer's point of view. This study was intended to further illuminate these considerations, generate hypotheses about non-purchasing decisions, and inform the design of policies that are responsive to concerns and preferences of potential purchasers. Qualitative study using 32 in-depth interviews and 6 focus groups, following a grounded theory approach. Five themes characterize decisions not to purchase long-term care insurance: (a) the determination that a policy is "too costly" reflects highly individualized and complex trade-offs not solely economic in nature, (b) non-purchasers are skeptical about the viability and integrity of private insurance companies and seek an unbiased source of information, (c) family dynamics play an important role in insurance decisions, (d) contemplating personal risk for long-term care triggers psychological responses that have implications for decision making, and (e) non-purchasers feel inadequately informed and overwhelmed by the process of deciding whether to purchase long-term care insurance. States are seeking to offset escalating Medicaid long-term care expenditures through a variety of policy mechanisms, including stimulating individual purchase of long-term care insurance. Findings suggest that economic incentives such as lowering premiums will be necessary but not sufficient to attract appropriate candidates. Attention to behavioral and psychosocial factors is essential to designing incentives that are responsive to concerns and preferences of potential purchasers.

  5. Environmental enrichment improves learning and memory and long-term potentiation in young adult rats through a mechanism requiring mGluR5 signaling and sustained activation of p70s6k.

    Science.gov (United States)

    Hullinger, Rikki; O'Riordan, Kenneth; Burger, Corinna

    2015-11-01

    Previous studies from our lab have demonstrated that mild cognitive impairments identified early in life are predictive of cognitive deficits that develop with age, suggesting that enhancements in cognition at an early age can provide a buffer against age-related cognitive decline. Environmental enrichment has been shown to improve learning and memory in the rodent, but the impact of enrichment on synaptic plasticity and the molecular mechanisms behind enrichment are not completely understood. To address these unresolved issues, we have housed 2-month old rats in environmentally enriched (EE), socially enriched (SE), or standard housing (SC) and conducted tests of learning and memory formation at various time intervals. Here we demonstrate that animals that have been exposed to one month of social or environmental enrichment demonstrate enhanced learning and memory relative to standard housed controls. However, we have found that after 4months EE animals perform better than both SE and SC groups and demonstrate an enhanced hippocampal LTP. Our results demonstrate that this LTP is dependent on mGluR5 signaling, activation of ERK and mTOR signaling cascades, and sustained phosphorylation of p70s6 kinase, thus providing a potential target mechanism for future studies of cognitive enhancement in the rodent. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Mechanism and treatment for the learning and memory deficits associated with mouse models of Noonan syndrome

    Science.gov (United States)

    Lee, Yong-Seok; Ehninger, Dan; Zhou, Miou; Oh, Jun-Young; Kang, Minkyung; Kwak, Chuljung; Ryu, Hyun-Hee; Butz, Delana; Araki, Toshiyuki; Cai, Ying; Balaji, J.; Sano, Yoshitake; Nam, Christine I.; Kim, Hyong Kyu; Kaang, Bong-Kiun; Burger, Corinna; Neel, Benjamin G.; Silva, Alcino J.

    2015-01-01

    In Noonan Syndrome (NS) 30% to 50% of subjects show cognitive deficits of unknown etiology and with no known treatment. Here, we report that knock-in mice expressing either of two NS-associated Ptpn11 mutations show hippocampal-dependent spatial learning impairments and deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of the PTPN11D61G in adult hippocampus results in increased baseline excitatory synaptic function, deficits in LTP and spatial learning, which can all be reversed by a MEK inhibitor. Furthermore, brief treatment with lovastatin reduces Ras-Erk activation in the brain, and normalizes the LTP and learning deficits in adult Ptpn11D61G/+ mice. Our results demonstrate that increased basal Erk activity and corresponding baseline increases in excitatory synaptic function are responsible for the LTP impairments and, consequently, the learning deficits in mouse models of NS. These data also suggest that lovastatin or MEK inhibitors may be useful for treating the cognitive deficits in NS. PMID:25383899

  7. PKMzeta Maintains Spatial, Instrumental, and Classically Conditioned Long-Term Memories

    Czech Academy of Sciences Publication Activity Database

    Serrano, P.; Friedman, E.L.; Kenney, Jana; Taubenfeld, S.M.; Zimmerman, J.M.; Hanna, J.; Alberini, C.; Kelley, A.E.; Maren, S.; Rudy, J.W.; Yin, J.C.P.; Sacktor, T.C.; Fenton, A.A.

    2008-01-01

    Roč. 6, č. 12 (2008), s. 2698-2706 ISSN 1544-9173 R&D Projects: GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GA309/06/1231 Institutional research plan: CEZ:AV0Z50110509 Keywords : PKMzeta * memory * LTP Subject RIV: FH - Neurology Impact factor: 12.683, year: 2008

  8. Industrial Foundations as Long-Term Owners

    DEFF Research Database (Denmark)

    Thomsen, Steen; Poulsen, Thomas; Børsting, Christa Winther

    Short-termism has become a serious concern for corporate governance, and this has inspired a search for institutional arrangements to promote long-term decision-making. In this paper, we call attention to long-term ownership by industrial foundations, which is common in Northern Europe but little...... known in the rest of the world. We use a unique Danish data set to document that industrial foundations are long-term owners that practice long-term governance. We show that foundation ownership is highly stable compared to other ownership structures. Foundation-owned companies replace managers less...... frequently. They have conservative capital structures with low financial leverage. They score higher on an index of long-termism in finance, investment, and employment. They survive longer. Overall, our paper supports the hypothesis that corporate time horizons are influenced by ownership structures...

  9. Long-term associative learning predicts verbal short-term memory performance

    OpenAIRE

    Jones, Gary; Macken, Bill

    2017-01-01

    Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term...

  10. Low-fat, high-carbohydrate parenteral nutrition (PN) may potentially reverse liver disease in long-term PN-dependent infants

    DEFF Research Database (Denmark)

    Jakobsen, Marianne Skytte; Jørgensen, Marianne Hørby; Husby, Steffen

    2015-01-01

    INTRODUCTION: Parenteral nutrition-associated cholestasis (PNAC) is a complication of long-term parenteral nutrition (PN). Removal of lipids may reverse PNAC but compromises the energy to ensure infant growth. The purpose of this study was to test whether a low-fat, high-carbohydrate PN regimen......, which prevents and reverses PNAC in adults, could do the same in infants. This regimen could potentially avoid the problem of diminished energy input after removing nutritional lipids. METHODS: Infants developing PNAC over a 2-year period were started on a low-fat PN regimen with calories primarily from...

  11. Going Solar Yields Long-Term Economical, Educational Benefits

    Science.gov (United States)

    von Moos, Brian

    2009-01-01

    Going solar is not an easy decision, but a long-term investment with a potentially substantial up-front cost. While some schools have enough capital in reserve, can raise bond money, or can solicit sufficient donations, many schools rely on creative financial programs to make a solar energy system economically feasible. Thinking about going solar…

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

    Directory of Open Access Journals (Sweden)

    Hardy Hagena

    2016-09-01

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

  13. The long-term psychiatric and medical prognosis of perinatal mental illness.

    Science.gov (United States)

    Meltzer-Brody, Samantha; Stuebe, Alison

    2014-01-01

    The perinatal period provides an important window into a woman's long-term health. Perinatal mental illness is a common condition conferring potential serious long-term psychiatric and medical consequences for the mother and family. It is known that childbirth acts as a powerful trigger for depressive episodes in some women, and that women with histories of a mood disorder are particularly vulnerable. Some evidence links perinatal mental illness with obstetrical complications and reduced lactation initiation and duration. Therefore, perinatal mental illness may be a marker for long-term risk, and may contribute directly to subsequent cardiometabolic disease through both neuroendocrine mechanisms and the effects of mental illness on health behaviours. In clinical practice, these associations underscore the importance of screening and treating women with perinatal mental illness to ensure best possible long-term outcomes. Early screening and treatment may both mitigate the primary disease process and reduce the risk of comorbid medical conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Complete long-term corrosion protection with chemical vapor deposited graphene

    DEFF Research Database (Denmark)

    Yu, Feng; Camilli, Luca; Wang, Ting

    2018-01-01

    Despite numerous reports regarding the potential of graphene for corrosion protection, examples of chemical vapor deposited (CVD) graphene-based anticorrosive coatings able to provide long-term protection (i.e. several months) of metals have so far been absent. Here, we present a polymer-graphene......Despite numerous reports regarding the potential of graphene for corrosion protection, examples of chemical vapor deposited (CVD) graphene-based anticorrosive coatings able to provide long-term protection (i.e. several months) of metals have so far been absent. Here, we present a polymer......-graphene hybrid coating, comprising two single layers of CVD graphene sandwiched by three layers of polyvinyl butyral, which provides complete corrosion protection of commercial aluminum alloys even after 120 days of exposure to simulated seawater. The essential role played by graphene in the hybrid coating...

  15. Possible relationship between the stress-induced synaptic response and metaplasticity in the hippocampal CA1 field of freely moving rats.

    Science.gov (United States)

    Hirata, Riki; Matsumoto, Machiko; Judo, Chika; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro; Togashi, Hiroko

    2009-07-01

    Hippocampal long-term potentiation (LTP) is suppressed not only by stress paradigms but also by low frequency stimulation (LFS) prior to LTP-inducing high frequency stimulation (HFS; tetanus), termed metaplasticity. These synaptic responses are dependent on N-methyl-D-aspartate receptors, leading to speculations about the possible relationship between metaplasticity and stress-induced LTP impairment. However, the functional significance of metaplasticity has been unclear. The present study elucidated the electrophysiological and neurochemical profiles of metaplasticity in the hippocampal CA1 field, with a focus on the synaptic response induced by the emotional stress, contextual fear conditioning (CFC). The population spike amplitude in the CA1 field was decreased during exposure to CFC, and LTP induction was suppressed after CFC in conscious rats. The synaptic response induced by CFC was mimicked by LFS, i.e., LFS impaired the synaptic transmission and subsequent LTP. Plasma corticosterone levels were increased by both CFC and LFS. Extracellular levels of gamma-aminobutyric acid (GABA), but not glutamate, in the hippocampus increased during exposure to CFC or LFS. Furthermore, electrical stimulation of the medial prefrontal cortex (mPFC), which caused decreases in freezing behavior during exposure to CFC, counteracted the LTP impairment induced by LFS. These findings suggest that metaplasticity in the rat hippocampal CA1 field is related to the neural basis of stress experience-dependent fear memory, and that hippocampal synaptic response associated stress-related processes is under mPFC regulation.

  16. Long-term collections

    CERN Multimedia

    Collectes à long terme

    2007-01-01

    The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

  17. Mark I containment, short term program. Safety evaluation report

    International Nuclear Information System (INIS)

    1977-12-01

    Presented is a Safety Evaluation Report (SER) prepared by the Office of Nuclear Reactor Regulation addressing the Short Term Program (STP) reassessment of the containment systems of operating Boiler Water Reactor (BWR) facilities with the Mark I containment system design. The information presented in this SER establishes the basis for the NRC staff's conclusion that licensed Mark I BWR facilities can continue to operate safely, without undue risk to the health and safety of the public, during an interim period of approximately two years while a methodical, comprehensive Long Term Program (LTP) is conducted. This SER also provides one of the basic foundations for the NRC staff review of the Mark I containment systems for facilities not yet licensed for operation

  18. Archiving Primary Data: Solutions for Long-Term Studies.

    Science.gov (United States)

    Mills, James A; Teplitsky, Céline; Arroyo, Beatriz; Charmantier, Anne; Becker, Peter H; Birkhead, Tim R; Bize, Pierre; Blumstein, Daniel T; Bonenfant, Christophe; Boutin, Stan; Bushuev, Andrey; Cam, Emmanuelle; Cockburn, Andrew; Côté, Steeve D; Coulson, John C; Daunt, Francis; Dingemanse, Niels J; Doligez, Blandine; Drummond, Hugh; Espie, Richard H M; Festa-Bianchet, Marco; Frentiu, Francesca; Fitzpatrick, John W; Furness, Robert W; Garant, Dany; Gauthier, Gilles; Grant, Peter R; Griesser, Michael; Gustafsson, Lars; Hansson, Bengt; Harris, Michael P; Jiguet, Frédéric; Kjellander, Petter; Korpimäki, Erkki; Krebs, Charles J; Lens, Luc; Linnell, John D C; Low, Matthew; McAdam, Andrew; Margalida, Antoni; Merilä, Juha; Møller, Anders P; Nakagawa, Shinichi; Nilsson, Jan-Åke; Nisbet, Ian C T; van Noordwijk, Arie J; Oro, Daniel; Pärt, Tomas; Pelletier, Fanie; Potti, Jaime; Pujol, Benoit; Réale, Denis; Rockwell, Robert F; Ropert-Coudert, Yan; Roulin, Alexandre; Sedinger, James S; Swenson, Jon E; Thébaud, Christophe; Visser, Marcel E; Wanless, Sarah; Westneat, David F; Wilson, Alastair J; Zedrosser, Andreas

    2015-10-01

    The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Baroreflexes of the rat. V. Tetanus-induced potentiation of ADN A-fiber responses at the NTS.

    Science.gov (United States)

    Tang, Xiaorui; Dworkin, Barry R

    2007-12-01

    In a long-term neuromuscular blocked (NMB) rat preparation, tetanic stimulation of the aortic depressor nerve (ADN) enhanced the A-fiber evoked responses (ERs) in the cardiovascular region, the nucleus of the solitary tract (dmNTS). The potentiation persisted for at least several hours and may be a mechanism for adaptive adjustment of the gain of the baroreflex, with functional implications for blood pressure regulation. Using a capacitance electrode, we selectively stimulated A-fibers and acquired a stable 10-h "A-fiber only" ER baseline at the dmNTS. Following baseline, an A+C-fiber activating tetanus was applied to the ADN. The tetanus consisted of 1,000 "high current" pulses (10 trains; 300 mus, 100 Hz, 1 s), with intertrain interval of 9 s. A 10-h A-fiber only posttetanic test phase repeated the stimulus pattern of the baseline. Fourteen tetanus experiments were done in 12 rats. Compared with the baseline before tetanus, the A-fiber ER magnitudes of posttetanus hours were larger [F(13, 247) = 3.407, P ADN A+C fiber-activating tetanus produced increases in the magnitude of the A-fiber ERs in the dmNTS that persisted for several hours. In an additional rat, application of an NMDA receptor antagonist, prior to the tetanus, blocked the potentiation effect. The stimulus protocols, magnitude and duration of the effect, and pharmacology resemble associative long-term potentiation (LTP).

  20. Birds choose long-term partners years before breeding

    Science.gov (United States)

    Teitelbaum, Claire S.; Converse, Sarah J.; Mueller, Thomas

    2017-01-01

    Pair bonds can provide social benefits to long-term monogamous species alongside their benefits for reproduction. However, little is known about when these bonds form, in particular how long they are present before breeding. Previous studies of pair formation in long-term monogamous birds have been rather data-limited, but for many migratory birds they report pair formation on the wintering grounds. We provide the first systematic investigation of prebreeding association patterns of long-term monogamous pairs by examining entire life histories based on tracking data of migratory whooping cranes, Grus americana. We found that a substantial portion (62%) of breeding pairs started associating at least 12 months before first breeding, with 16 of 58 breeding pairs beginning to associate over 2 years before first breeding. For most pairs, these associations with future breeding partners also became unique and distinguishable from association patterns with nonpartner individuals 12 months before first breeding. In addition, 60% of pair associations began before at least one partner had reached nominal sexual maturity. Most pairs began associating in the late spring upon arrival at the summer grounds, while associations beginning at other times of the year were rare. Patterns in the associations of pairs prior to breeding can point to the potential benefits of prebreeding relationships, for instance providing support in competitive interactions or increasing partner familiarity.

  1. Diacylglycerol kinases in the coordination of synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Dongwon Lee

    2016-08-01

    Full Text Available Synaptic plasticity is activity-dependent modification of the efficacy of synaptic transmission. Although detailed mechanisms underlying synaptic plasticity are diverse and vary at different types of synapses, diacylglycerol (DAG-associated signaling has been considered as an important regulator of many forms of synaptic plasticity, including long-term potentiation (LTP and long-term depression (LTD. Recent evidence indicate that DAG kinases (DGKs, which phosphorylate DAG to phosphatidic acid to terminate DAG signaling, are important regulators of LTP and LTD, as supported by the results from mice lacking specific DGK isoforms. This review will summarize these studies and discuss how specific DGK isoforms distinctly regulate different forms of synaptic plasticity at pre- and postsynaptic sites. In addition, we propose a general role of DGKs as coordinators of synaptic plasticity that make local synaptic environments more permissive for synaptic plasticity by regulating DAG concentration and interacting with other synaptic proteins.

  2. MOLECULAR BASIS OF LEARNING IN THE HIPPOCAMPUS AND THE AMYGDALA

    Directory of Open Access Journals (Sweden)

    Łukasz BIJOCH

    2015-12-01

    Full Text Available The hippocampus and the amygdala are structures of mammalian brain both involved in memorizing. However, they are responsible for different types of memory: the hippocampus is involved in creating and storing declarative engrams and the amygdala is engaged in some of non-declarative learning. During memorization, changes of synapses appear and it is believed that they encode information. Long-Term Potentiation (LTP and Long-Term Depression (LTD are two processes which provide to these changes which are called synaptic plasticity. LTP strengthens connections between neurons and because of that it is traditionally linked with learning. LTD as an opposite state is usually treated as forgetting. However, there are some evidences that it is true only for few types of non-declarative engrams. More sophisticated learning (like declarative learning requires cooperation of these processes. Review is focused on functions and detailed signaling pathways of processes of synaptic plasticity.

  3. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma

    DEFF Research Database (Denmark)

    Jacobsen, L; Niggemann, B; Dreborg, S

    2007-01-01

    BACKGROUND: 3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT. OBJECTIVE: We......: Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination....

  4. Peripheral arteriovenous fistula as vascular access for long-term chemotherapy.

    Science.gov (United States)

    Kovalyov, Oleksiy O; Kostyuk, Oleksandr G; Tkachuk, Tetyana V

    To provide long-term vascular access in clinical oncology peripheral forearm veins (up to 95% of patients in Ukraine), central venous access and "complete implanted vascular systems" are used most often. Many oncology patients have contraindications to catheterization of superior vena cava. Besides, exploitation of central veins is associated with potential technical and infectious complications. The aim - to study short-term and long-term results of arteriovenous fistula exploitation as vascular access for continuous anticancer therapy. Peripheral venous bed status in 41 oncology patients taking long-term chemotherapy treatment is analyzed in the article. Doppler sonography, morphologic and immune histochemical analyses were used in the study. Doppler sonography found qualitative and quantitative changes in forearm veins at different time periods after initiation of chemotherapy in the majority of patients. The major morphologic manifestations of venous wall damage were chemical phlebitis, local or extended hardening of venous wall, venous thrombosis and extravasations with necrosis and subsequent paravasal tissue sclerosis. Alternative vascular access created in 12 patients completely met the adequacy criteria (safety, multiple use, longevity, realization of the designed therapy program). The conclusion was made about inapplicability of forearm veins for long-term administration of cytostatic agents. If it is impossible to use central veins, arteriovenous fistula can become an alternative vascular access.

  5. Long term warranty and after sales service concept, policies and cost models

    CERN Document Server

    Rahman, Anisur

    2015-01-01

    This volume presents concepts, policies and cost models for various long-term warranty and maintenance contracts. It offers several numerical examples for estimating costs to both the manufacturer and consumer. Long-term warranties and maintenance contracts are becoming increasingly popular, as these types of aftersales services provide assurance to consumers that they can enjoy long, reliable service, and protect them from defects and the potentially high costs of repairs. Studying long-term warranty and service contracts is important to manufacturers and consumers alike, as offering long-term warranty and maintenance contracts produce additional costs for manufacturers / service providers over the product’s service life. These costs must be factored into the price, or the manufacturer / dealer will incur losses instead of making a profit. On the other hand, the buyer / consumer needs to weigh the cost of maintaining it over its service life and to decide whether or not these policies are worth purchasing....

  6. Sexuality and Physical Intimacy in Long Term Care: Sexuality, long term care, capacity assessment

    OpenAIRE

    Lichtenberg, Peter A.

    2014-01-01

    Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long term care settings. Because older adults in medical rehabilitation and long term care beds present with significant frailties, and often significant neurocognitive disorders it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literatur...

  7. Light exposure before learning improves memory consolidation at night

    Science.gov (United States)

    Shan, Li-Li; Guo, Hao; Song, Ning-Ning; Jia, Zheng-Ping; Hu, Xin-Tian; Huang, Jing-Fei; Ding, Yu-Qiang; Richter-Levine, Gal; Zhou, Qi-Xin; Xu, Lin

    2015-01-01

    Light is recently recognized as a modulator able to activate the hippocampus and modulate memory processing, but little is known about the molecular mechanisms. Here, we report that in mice, a short pulse of white light before learning dramatically improves consolidation of contextual fear memory during the night. The light exposure increases hippocampal active p21-activated kinase 1 (PAK1) and CA1 long-term potentiation (LTP). These light effects are abolished in PAK1 knockout and dominant-negative transgenic mice, but preserved by expression of constitutively active PAK1 in the hippocampus. Our results indicate that light can act as a switch of PAK1 activity that modulate CA1 LTP and thereby memory consolidation without affecting learning and short-term memory. PMID:26493375

  8. Differences in health status between long-term and short-term benzodiazepine users.

    NARCIS (Netherlands)

    Zandstra, S.M.; Furer, J.W.; Lisdonk, E.H. van de; Bor, J.H.J.; Zitman, F.G.; Weel, C. van

    2002-01-01

    BACKGROUND: Despite generally accepted advice to keep treatment short, benzodiazepines are often prescibed for more than six months. Prevention of long-term benzodiazepine use could be facilitated by the utilisation of risk indicators for long-term use. However, the characteristics of long-term

  9. The epidemiology of long- and short-term cancer survivors

    DEFF Research Database (Denmark)

    Jarlbæk, Lene; Christensen, Linda; Bruera, Eduardo

    2014-01-01

    Introduction. In this study, we present data from a population-based cohort of incident cancer patients separated in long- and short-term survivors. Our aim was to procure denominators for use in the planning of rehabilitation and palliative care programs. Material and methods. A registry......-linkage cohort study. All cancer patients, diagnosed from 1993 to 2003 from a 470 000 large population, were followed individually from diagnosis to death or until 31 December 2008. Long-term survivors lived five years or more after the time of the cancer diagnosis (TOCD). Short-term survivors died less than...... and sex. Two-year crude cancer survival seems as a clinically relevant cut point for characterizing potential "denominators" for rehabilitation or palliative care programs. From this cohort of incident cancer patients, and using two-year survival as a cut point, it could be estimated that 54% would...

  10. Advantages of the in-situ LTP distortion profile test on high-heat-load mirrors and applications

    International Nuclear Information System (INIS)

    Qian, S.; Jark, W.; Sostero, G.; Gambitta, A.; Mazzolini, F.; Savoia, A.

    1996-01-01

    The first in-situ distortion profile measurement of a high heat load mirror by use of the penta-prism LTP is presented. A maximum height distortion of 0.47 micron in tangential direction over a length of 180 mm was measured for an internally water-cooled mirror of a undulator beam line at ELETTRA while exposed to a total emitted power of 600 W (undulator gap 30 mm and current 180 mA). The experiment has an accuracy and repeatability of 0.04 micron. The test schematic and the test equipment are presented. Two measuring methods to scan a penta-prism being installed either outside or inside the vacuum chamber are introduced. Advantages and some possible applications of adopting the penta-prism LTP to make the in-situ profile test are explained

  11. Atypical PKCs in Memory Maintenance: The Roles of Feedback and Redundancy

    Science.gov (United States)

    Jalil, Sajiya J.; Sacktor, Todd Charlton; Shouval, Harel Z.

    2015-01-01

    Memories that last a lifetime are thought to be stored, at least in part, as persistent enhancement of the strength of particular synapses. The synaptic mechanism of these persistent changes, late long-term potentiation (L-LTP), depends on the state and number of specific synaptic proteins. Synaptic proteins, however, have limited dwell times due…

  12. Long-term deconditioning of gas-filled surge arresters

    Science.gov (United States)

    Stanković, Koviljka; Brajović, Dragan; Alimpijević, Mališa; Lončar, Boris

    2016-07-01

    pressure that is as high as possible (with pd = const), and that the electrode active surface should have a marked microscopic topography. In addition to this, an essential conclusion for GFSA manufacturers is that long-term system deconditioning is caused by impurities and adsorbed gases that appear at electrode during the state of rest. Out of these two causes, the influence of impurities is probably the dominant one, which is proved by considerably reduced long-term deconditioning in the case of noble metal electrodes, not susceptible to corrosion. This has also been confirmed by a less distinct effect of long-term deconditioning in the case of sandblasted electrodes that have a stronger tendency towards gas adsorption and a weaker tendency towards corrosion. However, it has been shown that adding of the third electrode (that is concentric to the main electrode system) on a free floating potential along with usage of sandblasted electrodes and with smaller interelectrode distance significantly reduces the effects of the long-term deconditioning.

  13. Chronic methamphetamine exposure produces a delayed, long-lasting memory deficit.

    Science.gov (United States)

    North, Ashley; Swant, Jarod; Salvatore, Michael F; Gamble-George, Joyonna; Prins, Petra; Butler, Brittany; Mittal, Mukul K; Heltsley, Rebecca; Clark, John T; Khoshbouei, Habibeh

    2013-05-01

    Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment. Whether this is due to long-term deficits in short-term memory and/or hippocampal plasticity remains unclear. Recently, we reported that METH increases baseline synaptic transmission and reduces LTP in an ex vivo preparation of the hippocampal CA1 region from young mice. In the current study, we tested the hypothesis that a repeated neurotoxic regimen of METH exposure in adolescent mice decreases hippocampal synaptic plasticity and produces a deficit in short-term memory. Contrary to our prediction, there was no change in the hippocampal plasticity or short-term memory when measured after 14 days of METH exposure. However, we found that at 7, 14, and 21 days of drug abstinence, METH-exposed mice exhibited a deficit in spatial memory, which was accompanied by a decrease in hippocampal plasticity. Our results support the interpretation that the deleterious cognitive consequences of neurotoxic levels of METH exposure may manifest and persist after drug abstinence. Therefore, therapeutic strategies should consider short-term as well as long-term consequences of methamphetamine exposure. Copyright © 2012 Wiley Periodicals, Inc.

  14. Acute mastoiditis in children: presentation and long term consequences.

    LENUS (Irish Health Repository)

    Glynn, F

    2008-03-01

    Acute mastoiditis, a destructive bacterial infection of the mastoid bone and air cell system, is relatively uncommon today but remains a potentially serious condition. There is a lack of information in the literature regarding the long term otological problems that children may face following an episode of this condition.

  15. Synaptic characteristics with strong analog potentiation, depression, and short-term to long-term memory transition in a Pt/CeO2/Pt crossbar array structure

    Science.gov (United States)

    Kim, Hyung Jun; Park, Daehoon; Yang, Paul; Beom, Keonwon; Kim, Min Ju; Shin, Chansun; Kang, Chi Jung; Yoon, Tae-Sik

    2018-06-01

    A crossbar array of Pt/CeO2/Pt memristors exhibited the synaptic characteristics such as analog, reversible, and strong resistance change with a ratio of ∼103, corresponding to wide dynamic range of synaptic weight modulation as potentiation and depression with respect to the voltage polarity. In addition, it presented timing-dependent responses such as paired-pulse facilitation and the short-term to long-term memory transition by increasing amplitude, width, and repetition number of voltage pulse and reducing the interval time between pulses. The memory loss with a time was fitted with a stretched exponential relaxation model, revealing the relation of memory stability with the input stimuli strength. The resistance change was further enhanced but its stability got worse as increasing measurement temperature, indicating that the resistance was changed as a result of voltage- and temperature-dependent electrical charging and discharging to alter the energy barrier for charge transport. These detailed synaptic characteristics demonstrated the potential of crossbar array of Pt/CeO2/Pt memristors as artificial synapses in highly connected neuron-synapse network.

  16. Long-term memory of heterospecific vocalizations by African lions

    Science.gov (United States)

    Grinnell, Jon; van Dyk, Gus; Slotow, Rob

    2005-09-01

    Animals that use and evaluate long-distance signals have the potential to glean valuable information about others in their environment via eavesdropping. In those areas where they coexist, African lions (Panthera leo) are a significant eavesdropper on spotted hyenas (Crocuta crocuta), often using hyena vocalizations to locate and scavenge from hyena kills. This relationship was used to test African lions' long-term memory of the vocalizations of spotted hyenas via playback experiments. Hyena whoops and a control sound (Canis lupus howls) were played to three populations of lions in South Africa: (1) lions with past experience of spotted hyenas; (2) lions with current experience; and (3) lions with no experience. The results strongly suggest that lions have the cognitive ability to remember the vocalizations of spotted hyenas even after 10 years with no contact of any kind with them. Such long-term memory of heterospecific vocalizations may be widespread in species that gain fitness benefits from eavesdropping on others, but where such species are sympatric and often interact it may pass unrecognized as short-term memory instead.

  17. Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Weili; Xiao, Linlin; Dong, Chen; He, Mingyuan; Pan, Yan; Xie, Yuexia; Tu, Wenzhi; Fu, Jiamei; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

    2014-05-09

    Highlights: • Multi-exposures of 25 mGy α-ray enhanced cell proliferation, adhesion, and invasion. • MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. • LDR of α-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway.

  18. Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

    International Nuclear Information System (INIS)

    Liu, Weili; Xiao, Linlin; Dong, Chen; He, Mingyuan; Pan, Yan; Xie, Yuexia; Tu, Wenzhi; Fu, Jiamei; Shao, Chunlin

    2014-01-01

    Highlights: • Multi-exposures of 25 mGy α-ray enhanced cell proliferation, adhesion, and invasion. • MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. • LDR of α-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway

  19. Biochemical principles underlying the stable maintenance of LTP by the CaMKII/NMDAR complex.

    Science.gov (United States)

    Lisman, John; Raghavachari, Sridhar

    2015-09-24

    Memory involves the storage of information at synapses by an LTP-like process. This information storage is synapse specific and can endure for years despite the turnover of all synaptic proteins. There must, therefore, be special principles that underlie the stability of LTP. Recent experimental results suggest that LTP is maintained by the complex of CaMKII with the NMDAR. Here we consider the specifics of the CaMKII/NMDAR molecular switch, with the goal of understanding the biochemical principles that underlie stable information storage by synapses. Consideration of a variety of experimental results suggests that multiple principles are involved. One switch requirement is to prevent spontaneous transitions from the off to the on state. The highly cooperative nature of CaMKII autophosphorylation by Ca(2+) (Hill coefficient of 8) and the fact that formation of the CaMKII/NMDAR complex requires release of CaMKII from actin are mechanisms that stabilize the off state. The stability of the on state depends critically on intersubunit autophosphorylation, a process that restores any loss of pT286 due to phosphatase activity. Intersubunit autophosphorylation is also important in explaining why on state stability is not compromised by protein turnover. Recent evidence suggests that turnover occurs by subunit exchange. Thus, stability could be achieved if a newly inserted unphosphorylated subunit was autophosphorylated by a neighboring subunit. Based on other recent work, we posit a novel mechanism that enhances the stability of the on state by protection of pT286 from phosphatases. We posit that the binding of the NMNDAR to CaMKII forces pT286 into the catalytic site of a neighboring subunit, thereby protecting pT286 from phosphatases. A final principle concerns the role of structural changes. The binding of CaMKII to the NMDAR may act as a tag to organize the binding of further proteins that produce the synapse enlargement that underlies late LTP. We argue that these

  20. Space Life Sciences Research: The Importance of Long-Term Space Experiments

    Science.gov (United States)

    1993-01-01

    This report focuses on the scientific importance of long-term space experiments for the advancement of biological science and the benefit of humankind. It includes a collection of papers that explore the scientific potential provided by the capability to manipulate organisms by removing a force that has been instrumental in the evolution and development of all organisms. Further, it provides the scientific justification for why the long-term space exposure that can be provided by a space station is essential to conduct significant research.

  1. Synaptic scaling enables dynamically distinct short- and long-term memory formation.

    Directory of Open Access Journals (Sweden)

    Christian Tetzlaff

    2013-10-01

    Full Text Available Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling - a slow process usually associated with the maintenance of activity homeostasis - combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The interaction between plasticity and scaling provides also an explanation for an established paradox where memory consolidation critically depends on the exact order of learning and recall. These results indicate that scaling may be fundamental for stabilizing memories, providing a dynamic link between early and late memory formation processes.

  2. Synaptic scaling enables dynamically distinct short- and long-term memory formation.

    Science.gov (United States)

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

    2013-10-01

    Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling - a slow process usually associated with the maintenance of activity homeostasis - combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The interaction between plasticity and scaling provides also an explanation for an established paradox where memory consolidation critically depends on the exact order of learning and recall. These results indicate that scaling may be fundamental for stabilizing memories, providing a dynamic link between early and late memory formation processes.

  3. Very long-term sequelae of craniopharyngioma.

    Science.gov (United States)

    Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

    2017-06-01

    Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after

  4. Effects of Ethanol Exposure during Distinct Periods of Brain Development on Hippocampal Synaptic Plasticity

    Directory of Open Access Journals (Sweden)

    Brian R. Christie

    2013-07-01

    Full Text Available Fetal alcohol spectrum disorders occur when a mother drinks during pregnancy and can greatly influence synaptic plasticity and cognition in the offspring. In this study we determined whether there are periods during brain development that are more susceptible to the effects of ethanol exposure on hippocampal synaptic plasticity. In particular, we evaluated how the ability to elicit long-term potentiation (LTP in the hippocampal dentate gyrus (DG was affected in young adult rats that were exposed to ethanol during either the 1st, 2nd, or 3rd trimester equivalent. As expected, the effects of ethanol on young adult DG LTP were less severe when exposure was limited to a particular trimester equivalent when compared to exposure throughout gestation. In males, ethanol exposure during the 1st, 2nd or 3rd trimester equivalent did not significantly reduce LTP in the DG. In females, ethanol exposure during either the 1st or 2nd trimester equivalents did not impact LTP in early adulthood, but following exposure during the 3rd trimester equivalent alone, LTP was significantly increased in the female DG. These results further exemplify the disparate effects between the ability to elicit LTP in the male and female brain following perinatal ethanol exposure (PNEE.

  5. Spine formation pattern of adult-born neurons is differentially modulated by the induction timing and location of hippocampal plasticity.

    Directory of Open Access Journals (Sweden)

    Noriaki Ohkawa

    Full Text Available In the adult hippocampus dentate gyrus (DG, newly born neurons are functionally integrated into existing circuits and play important roles in hippocampus-dependent memory. However, it remains unclear how neural plasticity regulates the integration pattern of new neurons into preexisting circuits. Because dendritic spines are major postsynaptic sites for excitatory inputs, spines of new neurons were visualized by retrovirus-mediated labeling to evaluate integration. Long-term potentiation (LTP was induced at 12, 16, or 21 days postinfection (dpi, at which time new neurons have no, few, or many spines, respectively. The spine expression patterns were investigated at one or two weeks after LTP induction. Induction at 12 dpi increased later spinogenesis, although the new neurons at 12 dpi didn't respond to the stimulus for LTP induction. Induction at 21 dpi transiently mediated spine enlargement. Surprisingly, LTP induction at 16 dpi reduced the spine density of new neurons. All LTP-mediated changes specifically appeared within the LTP-induced layer. Therefore, neural plasticity differentially regulates the integration of new neurons into the activated circuit, dependent on their developmental stage. Consequently, new neurons at different developmental stages may play distinct roles in processing the acquired information by modulating the connectivity of activated circuits via their integration.

  6. Long-term prisoner in prison isolation

    Directory of Open Access Journals (Sweden)

    Karolina Grudzińska

    2013-06-01

    Full Text Available Long-term prisoner belongs to a particular category of people who are imprisoned in prisons. On the one hand in this group are often heavily demoralized people who committed the most serious crimes, on the other hand it is a group of prisoners, who should be well thought out and programmed the impact of rehabilitation. The situation of man trapped for years poses in a complicated situation not only the prisoners, but also the entire prison staff. They have to take care of the fact that the prison isolation did not cause the state in which convicts form itself in learned helplessness and lack of skills for self-planning and decision-making. In addition, planning the rehabilitation impact of long-term prisoners should not be forgotten that these prisoners in the short or the long term will return to the libertarian environment therefore, should prevent any negative effects of long-term imprisonment. This article presents the main issues related to the execution of imprisonment against long-term prisoners. It is an attempt to systematize the knowledge of this category of people living in prison isolation.

  7. Long-term no-till and stover retention each decrease the global warming potential of irrigated continuous corn.

    Science.gov (United States)

    Jin, Virginia L; Schmer, Marty R; Stewart, Catherine E; Sindelar, Aaron J; Varvel, Gary E; Wienhold, Brian J

    2017-07-01

    Over the last 50 years, the most increase in cultivated land area globally has been due to a doubling of irrigated land. Long-term agronomic management impacts on soil organic carbon (SOC) stocks, soil greenhouse gas (GHG) emissions, and global warming potential (GWP) in irrigated systems, however, remain relatively unknown. Here, residue and tillage management effects were quantified by measuring soil nitrous oxide (N 2 O) and methane (CH 4 ) fluxes and SOC changes (ΔSOC) at a long-term, irrigated continuous corn (Zea mays L.) system in eastern Nebraska, United States. Management treatments began in 2002, and measured treatments included no or high stover removal (0 or 6.8 Mg DM ha -1  yr -1 , respectively) under no-till (NT) or conventional disk tillage (CT) with full irrigation (n = 4). Soil N 2 O and CH 4 fluxes were measured for five crop-years (2011-2015), and ΔSOC was determined on an equivalent mass basis to ~30 cm soil depth. Both area- and yield-scaled soil N 2 O emissions were greater with stover retention compared to removal and for CT compared to NT, with no interaction between stover and tillage practices. Methane comprised <1% of total emissions, with NT being CH 4 neutral and CT a CH 4 source. Surface SOC decreased with stover removal and with CT after 14 years of management. When ΔSOC, soil GHG emissions, and agronomic energy usage were used to calculate system GWP, all management systems were net GHG sources. Conservation practices (NT, stover retention) each decreased system GWP compared to conventional practices (CT, stover removal), but pairing conservation practices conferred no additional mitigation benefit. Although cropping system, management equipment/timing/history, soil type, location, weather, and the depth to which ΔSOC is measured affect the GWP outcomes of irrigated systems at large, this long-term irrigated study provides valuable empirical evidence of how management decisions can impact soil GHG emissions and surface

  8. Long-term athletic development- part 1: a pathway for all youth.

    Science.gov (United States)

    Lloyd, Rhodri S; Oliver, Jon L; Faigenbaum, Avery D; Howard, Rick; De Ste Croix, Mark B A; Williams, Craig A; Best, Thomas M; Alvar, Brent A; Micheli, Lyle J; Thomas, D Phillip; Hatfield, Disa L; Cronin, John B; Myer, Gregory D

    2015-05-01

    The concept of developing talent and athleticism in youth is the goal of many coaches and sports systems. Consequently, an increasing number of sporting organizations have adopted long-term athletic development models in an attempt to provide a structured approach to the training of youth. It is clear that maximizing sporting talent is an important goal of long-term athletic development models. However, ensuring that youth of all ages and abilities are provided with a strategic plan for the development of their health and physical fitness is also important to maximize physical activity participation rates, reduce the risk of sport- and activity-related injury, and to ensure long-term health and well-being. Critical reviews of independent models of long-term athletic development are already present within the literature; however, to the best of our knowledge, a comprehensive examination and review of the most prominent models does not exist. Additionally, considerations of modern day issues that may impact on the success of any long-term athletic development model are lacking, as are proposed solutions to address such issues. Therefore, within this 2-part commentary, Part 1 provides a critical review of existing models of practice for long-term athletic development and introduces a composite youth development model that includes the integration of talent, psychosocial and physical development across maturation. Part 2 identifies limiting factors that may restrict the success of such models and offers potential solutions.

  9. Representativeness of shorter measurement sessions in long-term indoor air monitoring.

    Science.gov (United States)

    Maciejewska, M; Szczurek, A

    2015-02-01

    Indoor air quality (IAQ) considerably influences health, comfort and the overall performance of people who spend most of their lives in confined spaces. For this reason, there is a strong need to develop methods for IAQ assessment. The fundamental issue in the quantitative determination of IAQ is the duration of measurements. Its inadequate choice may result in providing incorrect information and this potentially leads to wrong conclusions. The most complete information may be acquired through long-term monitoring. However it is typically perceived as impractical due to time and cost load. The aim of this study was to determine whether long-term monitoring can be adequately represented by a shorter measurement session. There were considered three measurable quantities: temperature, relative humidity and carbon dioxide concentration. They are commonly recognized as indicatives for IAQ and may be readily monitored. Scaled Kullback-Leibler divergence, also called relative entropy, was applied as a measure of data representativeness. We considered long-term monitoring in a range from 1 to 9 months. Based on our work, the representative data on CO2 concentration may be acquired while performing measurements during 20% of time dedicated to long-term monitoring. In the case of temperature and relative humidity the respective time demand was 50% of long-term monitoring. From our results, in indoor air monitoring strategies, there could be considered shorter measurement sessions, while still collecting data which are representative for long-term monitoring.

  10. Competitive short-term and long-term memory processes in spatial habituation.

    Science.gov (United States)

    Sanderson, David J; Bannerman, David M

    2011-04-01

    Exposure to a spatial location leads to habituation of exploration such that, in a novelty preference test, rodents subsequently prefer exploring a novel location to the familiar location. According to Wagner's (1981) theory of memory, short-term and long-term habituation are caused by separate and sometimes opponent processes. In the present study, this dual-process account of memory was tested. Mice received a series of exposure training trials to a location before receiving a novelty preference test. The novelty preference was greater when tested after a short, rather than a long, interval. In contrast, the novelty preference was weaker when exposure training trials were separated by a short, rather than a long interval. Furthermore, it was found that long-term habituation was determined by the independent effects of the amount of exposure training and the number of exposure training trials when factors such as the intertrial interval and the cumulative intertrial interval were controlled. A final experiment demonstrated that a long-term reduction of exploration could be caused by a negative priming effect due to associations formed during exploration. These results provide evidence against a single-process account of habituation and suggest that spatial habituation is determined by both short-term, recency-based memory and long-term, incrementally strengthened memory.

  11. Long term results of kissing stents in the aortic bifurcation

    NARCIS (Netherlands)

    Hinnen, J.W.; Konickx, M.A.; Meerwaldt, Robbert; Kolkert, J.L.P.; van der Palen, Jacobus Adrianus Maria; Huisman, A.B.

    2015-01-01

    BACKGROUND: To evaluate the long-term outcome after aortoiliac kissing stent placement and to analyze variables, which potentially influence the outcome of endovascular reconstruction of the aortic bifurcation. METHODS: All patients treated with aortoiliac kissing stents at our institution between

  12. Long-term climate monitoring by the global climate observing system

    International Nuclear Information System (INIS)

    Karl, T.R.

    1995-12-01

    Is the climate warming? Is the hydrologic cycle changing? Is the atmospheric/oceanic circulation changing? Is the climate becoming more variable or extreme? Is radiative forcing of the climate changing? are complex questions not only from the standpoint of a multi-variate problem, but because of the various aspects of spatial and temporal sampling that must be considered on a global scale. The development of a Global Climate Observing System (GCOS) offers the opportunity for scientists to do something about existing observing deficiencies in light of the importance of documenting long-term climate changes that may already be affected by anthropogenic changes of atmospheric composition and land use as well as other naturally occurring changes. As an important step toward improving the present inadequacies, a workshop was held to help define the long-term monitoring requirements minimally needed to address the five questions posed above, with special emphasis on detecting anthropogenic climate change and its potential impact on managed and unmanaged systems The workshop focussed on three broad areas related to long-term climate monitoring: (a) the scientific rationale for the long-term climate products (including their accuracy, resolution, and homogeneity) required from our observing systems as related to climate monitoring and climate change detection and attribution; (b) the status of long-term climate products and the observing systems from which these data are derived; and (c) implementation strategies necessary to fulfill item (a) in light of existing systems. Item (c) was treated more in terms of feasibility rather than as a specific implementation plan. figs., tabs., refs

  13. Long-term storage of Greater-Than-Class C Low-Level Waste

    International Nuclear Information System (INIS)

    Magleby, M.T.

    1990-01-01

    Under Federal law, the Department of Energy (DOE) is responsible for safe disposal of Greater-Than-Class C Low-Level Waste (GTCC LLW) generated by licenses of the Nuclear Regulatory commission (NRC) or Agreement States. Such waste must be disposed of in a facility licensed by the NRC. It is unlikely that licensed disposal of GTCC LLW will be available prior to the year 2010. Pending availability of disposal capacity, DOE is assessing the need for collective, long-term storage of GTCC LLW. Potential risks to public health and safety caused by long-term storage of GTCC LLW at the place of generation will be evaluated to determine if alternative facilities are warranted. If warranted, several options will be investigated to determine the preferred alternative for long-term storage. These options include modification of an existing DOE facility, development of a new DOE facility, or development of a facility by the private sector with or without DOE support. Reasonable costs for long-term storage would be borne by the waste generators. 5 refs., 1 fig

  14. Early Adolescent MK-801 Exposure Impairs the Maturation of Ventral Hippocampal Control of Basolateral Amygdala Drive in the Adult Prefrontal Cortex

    Science.gov (United States)

    Thomases, Daniel R.; Cass, Daryn K.; Meyer, Jacqueline D.; Caballero, Adriana

    2014-01-01

    The adolescent susceptibility to the onset of psychiatric disorders is only beginning to be understood when factoring in the development of the prefrontal cortex (PFC). The functional maturation of the PFC is dependent upon proper integration of glutamatergic inputs from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA). Here we assessed how transient NMDAR blockade during adolescence alters the functional interaction of vHipp–BLA inputs in regulating PFC plasticity. Local field potential recordings were used to determine changes in long-term depression (LTD) and long-term potentiation (LTP) of PFC responses resulting from vHipp and BLA high-frequency stimulation in adult rats that received repeated injections of saline or the NMDAR antagonist MK-801 from postnatal day 35 (P35) to P40. We found that early adolescent MK-801 exposure elicited an age- and input-specific dysregulation of vHipp–PFC plasticity, characterized by a shift from LTD to LTP without altering the BLA-induced LTP. Data also showed that the vHipp normally resets the LTP state of BLA transmission; however, this inhibitory regulation is absent following early adolescent MK-801 treatment. This deficit was reminiscent of PFC responses seen in drug-naive juveniles. Notably, local prefrontal upregulation of GABAAα1 function completely restored vHipp functionality and its regulation of BLA plasticity in MK-801-treated rats. Thus, NMDAR signaling is critical for the periadolescent acquisition of a GABA-dependent hippocampal control of PFC plasticity, which enables the inhibitory control of the prefrontal output by the vHipp. A dysregulation of this pathway can alter PFC processing of other converging afferents such as those from the BLA. PMID:24990926

  15. Fatigue and quality of life in breast cancer survivors: temporal courses and long-term pattern

    NARCIS (Netherlands)

    Schmidt, M.E.; Chang-Claude, J.; Vrieling, A.; Heinz, J.; Flesch-Janys, D.; Steindorf, K.

    2012-01-01

    INTRODUCTION: Fatigue is a frequent problem during and after cancer treatment. We investigated different courses of fatigue from pre-diagnosis, through therapy, to long-term survivorship and evaluated potential implications on long-term quality of life (QoL). METHODS: Breast cancer patients

  16. Long term liquidity analysis of the firm

    Directory of Open Access Journals (Sweden)

    Jaroslav Gonos

    2009-09-01

    Full Text Available Liquidity control is a very difficult and important function. If the business is not liquid in the long term, it is under threatof bankruptcy, and on the other hand surplus of the cash in hand threaten its future efficiency, because the cash in hand is a sourceof only limited profitability. Long term liquidity is related to the ability of the short term and long term liabilities payment. Articleis trying to point out to the monitoring and analyzing of the long term liquidity in the concrete business, in this case the printing industrycompany. Hereby at the end of the article mentioned monitored and analyzed liquidity is evaluated in the five years time period.

  17. Synaptic plasticity in the hippocampus of a APP/PS1 mouse model of Alzheimer's disease is impaired in old but not young mice.

    Directory of Open Access Journals (Sweden)

    Simon Gengler

    Full Text Available BACKGROUND: Alzheimer disease (AD is a neurodegenerative disorder for which there is no cure. We have investigated synaptic plasticity in area CA1 in a novel AD mouse model (APPPS1-21 which expresses the Swedish mutation of APP and the L166P mutation of human PS-1. This model shows initial plaque formation at 2 months in the neocortex and 4 months in the hippocampus and displays beta-amyloid-associated pathologies and learning impairments. METHODOLOGY/PRINCIPAL FINDINGS: We tested long-term potentiation (LTP and short term potentiation (paired-pulse facilitation, PPF of synaptic transmission in vivo in area CA1 of the hippocampus. There was no difference in LTP or PPF at 4-5 months of age in APPPS1-21 mice compared to littermate controls. At 6 months of age there was also no difference in LTP but APPPS1-21 mice showed slightly increased PPF (p<0.03. In 8 months old mice, LTP was greatly impaired in APPPS-21 animals (p<0.0001 while PPF was not changed. At 15 months of age, APPPS1-21 mice showed again impaired LTP compared to littermate controls (p<0.005, and PPF was also significantly reduced at 80 ms (p<0.005 and 160 ms (p<0.01 interstimulus interval. Immunohistological analysis showed only modest amyloid deposition in the hippocampus at 4 and 6 months with a robust increase up to 15 months of age. CONCLUSIONS: Our results suggest that increased formation and aggregation of beta amyloid with aging is responsible for the impaired LTP with aging in this mouse model, while the transient increase of PPF at 6 months of age is caused by some other mechanism.

  18. Brain amyloid β protein and memory disruption in Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Weiming Xia

    2010-09-01

    Full Text Available Weiming XiaCenter for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USAAbstract: The development of amyloid-containing neuritic plaques is an invariable characteristic of Alzheimer’s diseases (AD. The conversion from monomeric amyloid β protein (Aβ to oligomeric Aβ and finally neuritic plaques is highly dynamic. The specific Aß species that is correlated with disease severity remains to be discovered. Oligomeric Aβ has been detected in cultured cells, rodent and human brains, as well as human cerebrospinal fluid. Synthetic, cell, and brain derived Aβ oligomers have been found to inhibit hippocampal long-term potentiation (LTP and this effect can be suppressed by the blockage of Aβ oligomer formation. A large body of evidence suggests that Aβ oligomers inhibit N-methyl-D-aspartate receptor dependent LTP; additional receptors have also been found to elicit downstream pathways upon binding to Aβ oligomers. Amyloid antibodies and small molecular compounds that reduce brain Aβ levels and block Aβ oligomer formation are capable of reversing synaptic dysfunction and these approaches hold a promising therapeutic potential to rescue memory disruption.Keywords: Alzheimer, amyloid, oligomer, long-term potentiation, NMDA

  19. Effects of Joint Attention on Long-Term Memory in 9-Month-Old Infants: An Event-Related Potentials Study

    Science.gov (United States)

    Kopp, Franziska; Lindenberger, Ulman

    2011-01-01

    Joint attention develops during the first year of life but little is known about its effects on long-term memory. We investigated whether joint attention modulates long-term memory in 9-month-old infants. Infants were familiarized with visually presented objects in either of two conditions that differed in the degree of joint attention (high…

  20. Toward a Neurocentric View of Learning.

    Science.gov (United States)

    Titley, Heather K; Brunel, Nicolas; Hansel, Christian

    2017-07-05

    Synaptic plasticity (e.g., long-term potentiation [LTP]) is considered the cellular correlate of learning. Recent optogenetic studies on memory engram formation assign a critical role in learning to suprathreshold activation of neurons and their integration into active engrams ("engram cells"). Here we review evidence that ensemble integration may result from LTP but also from cell-autonomous changes in membrane excitability. We propose that synaptic plasticity determines synaptic connectivity maps, whereas intrinsic plasticity-possibly separated in time-amplifies neuronal responsiveness and acutely drives engram integration. Our proposal marks a move away from an exclusively synaptocentric toward a non-exclusive, neurocentric view of learning. Copyright © 2017 Elsevier Inc. All rights reserved.