Sample records for plasticity long-term potentiation
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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
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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
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Short-term plasticity and long-term potentiation mimicked in single inorganic synapses
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.
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Long-term potentiation and long-term depression: a clinical perspective
Directory of Open Access Journals (Sweden)
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.
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Directory of Open Access Journals (Sweden)
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.
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Synaptic Transmission Optimization Predicts Expression Loci of Long-Term Plasticity.
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.
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Short-term and long-term plasticity interaction in human primary motor cortex.
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.
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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.
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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.
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Critical neural networks with short- and long-term plasticity
Michiels van Kessenich, L.; Luković, M.; de Arcangelis, L.; Herrmann, H. J.
2018-03-01
In recent years self organized critical neuronal models have provided insights regarding the origin of the experimentally observed avalanching behavior of neuronal systems. It has been shown that dynamical synapses, as a form of short-term plasticity, can cause critical neuronal dynamics. Whereas long-term plasticity, such as Hebbian or activity dependent plasticity, have a crucial role in shaping the network structure and endowing neural systems with learning abilities. In this work we provide a model which combines both plasticity mechanisms, acting on two different time scales. The measured avalanche statistics are compatible with experimental results for both the avalanche size and duration distribution with biologically observed percentages of inhibitory neurons. The time series of neuronal activity exhibits temporal bursts leading to 1 /f decay in the power spectrum. The presence of long-term plasticity gives the system the ability to learn binary rules such as xor, providing the foundation of future research on more complicated tasks such as pattern recognition.
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Hu, Jiang-Yuan; Schacher, Samuel
2014-04-02
Short-term and long-term synaptic plasticity are cellular correlates of learning and memory of different durations. Little is known, however, how these two forms of plasticity interact at the same synaptic connection. We examined the reciprocal impact of short-term heterosynaptic or homosynaptic plasticity at sensorimotor synapses of Aplysia in cell culture when expressing persistent long-term facilitation (P-LTF) evoked by serotonin [5-hydroxytryptamine (5-HT)]. Short-term heterosynaptic plasticity induced by 5-HT (facilitation) or the neuropeptide FMRFa (depression) and short-term homosynaptic plasticity induced by tetanus [post-tetanic potentiation (PTP)] or low-frequency stimulation [homosynaptic depression (HSD)] of the sensory neuron were expressed in both control synapses and synapses expressing P-LTF in the absence or presence of protein synthesis inhibitors. All forms of short-term plasticity failed to significantly affect ongoing P-LTF in the absence of protein synthesis inhibitors. However, P-LTF reversed to control levels when either 5-HT or FMRFa was applied in the presence of rapamycin. In contrast, P-LTF was unaffected when either PTP or HSD was evoked in the presence of either rapamycin or anisomycin. These results indicate that synapses expressing persistent plasticity acquire a "new" baseline and functionally express short-term changes as naive synapses, but the new baseline becomes labile following selective activations-heterosynaptic stimuli that evoke opposite forms of plasticity-such that when presented in the presence of protein synthesis inhibitors produce a rapid reversal of the persistent plasticity. Activity-selective induction of a labile state at synapses expressing persistent plasticity may facilitate the development of therapies for reversing inappropriate memories.
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Long term potentiation, but not depression, in interlamellar hippocampus CA1.
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.
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Unified pre- and postsynaptic long-term plasticity enables reliable and flexible learning.
Costa, Rui Ponte; Froemke, Robert C; Sjöström, P Jesper; van Rossum, Mark Cw
2015-08-26
Although it is well known that long-term synaptic plasticity can be expressed both pre- and postsynaptically, the functional consequences of this arrangement have remained elusive. We show that spike-timing-dependent plasticity with both pre- and postsynaptic expression develops receptive fields with reduced variability and improved discriminability compared to postsynaptic plasticity alone. These long-term modifications in receptive field statistics match recent sensory perception experiments. Moreover, learning with this form of plasticity leaves a hidden postsynaptic memory trace that enables fast relearning of previously stored information, providing a cellular substrate for memory savings. Our results reveal essential roles for presynaptic plasticity that are missed when only postsynaptic expression of long-term plasticity is considered, and suggest an experience-dependent distribution of pre- and postsynaptic strength changes.
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Long-term plasticity in identified hippocampal GABAergic interneurons in the CA1 area in vivo.
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.
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Long-term plasticity is proportional to theta-activity.
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Marian Tsanov
Full Text Available BACKGROUND: Theta rhythm in the hippocampal formation is a main feature of exploratory behaviour and is believed to enable the encoding of new spatial information and the modification of synaptic weights. Cyclic changes of dentate gyrus excitability during theta rhythm are related to its function, but whether theta epochs per se are able to alter network properties of dentate gyrus for long time-periods is still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We used low-frequency stimulation protocols that amplify the power of endogenous theta oscillations, in order to estimate the plasticity effect of endogenous theta oscillations on a population level. We found that stimulation-induced augmentation of the theta rhythm is linked to a subsequent increase of neuronal excitability and decrease of the synaptic response. This EPSP-to-Spike uncoupling is related to an increased postsynaptic spiking on the positive phases of theta frequency oscillations. Parallel increase of the field EPSP slope and the population spike occurs only after concurrent pre- and postsynaptic activation. Furthermore, we observed that long-term potentiation (>24 h occurs in the dentate gyrus of freely behaving adult rats after phasic activity of entorhinal afferents in the theta-frequency range. This plasticity is proportional to the field bursting activity of granule cells during the stimulation, and may comprise a key step in spatial information transfer. Long-term potentiation of the synaptic component occurs only when the afferent stimulus precedes the evoked population burst, and is input-specific. CONCLUSIONS/SIGNIFICANCE: Our data confirm the role of the dentate gyrus in filtering information to the subsequent network during the activated state of the hippocampus.
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Directory of Open Access Journals (Sweden)
Wayne Croft
2015-01-01
Full Text Available The capacity of synaptic networks to express activity-dependent changes in strength and connectivity is essential for learning and memory processes. In recent years, glial cells (most notably astrocytes have been recognized as active participants in the modulation of synaptic transmission and synaptic plasticity, implicating these electrically nonexcitable cells in information processing in the brain. While the concept of bidirectional communication between neurons and glia and the mechanisms by which gliotransmission can modulate neuronal function are well established, less attention has been focussed on the computational potential of neuron-glial transmission itself. In particular, whether neuron-glial transmission is itself subject to activity-dependent plasticity and what the computational properties of such plasticity might be has not been explored in detail. In this review, we summarize current examples of plasticity in neuron-glial transmission, in many brain regions and neurotransmitter pathways. We argue that induction of glial plasticity typically requires repetitive neuronal firing over long time periods (minutes-hours rather than the short-lived, stereotyped trigger typical of canonical long-term potentiation. We speculate that this equips glia with a mechanism for monitoring average firing rates in the synaptic network, which is suited to the longer term roles proposed for astrocytes in neurophysiology.
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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).
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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.
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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.
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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
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Visual recognition memory, manifest as long-term habituation, requires synaptic plasticity in V1
Cooke, Sam F.; Komorowski, Robert W.; Kaplan, Eitan S.; Gavornik, Jeffrey P.; Bear, Mark F.
2015-01-01
Familiarity with stimuli that bring neither reward nor punishment, manifested through behavioural habituation, enables organisms to detect novelty and devote cognition to important elements of the environment. Here we describe in mice a form of long-term behavioural habituation to visual grating stimuli that is selective for stimulus orientation. Orientation-selective habituation (OSH) can be observed both in exploratory behaviour in an open arena, and in a stereotyped motor response to visual stimuli in head-restrained mice. We show that the latter behavioural response, termed a vidget, requires V1. Parallel electrophysiological recordings in V1 reveal that plasticity, in the form of stimulus-selective response potentiation (SRP), occurs in layer 4 of V1 as OSH develops. Local manipulations of V1 that prevent and reverse electrophysiological modifications likewise prevent and reverse memory demonstrated behaviourally. These findings suggest that a form of long-term visual recognition memory is stored via synaptic plasticity in primary sensory cortex. PMID:25599221
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Visual recognition memory, manifested as long-term habituation, requires synaptic plasticity in V1.
Cooke, Sam F; Komorowski, Robert W; Kaplan, Eitan S; Gavornik, Jeffrey P; Bear, Mark F
2015-02-01
Familiarity with stimuli that bring neither reward nor punishment, manifested through behavioral habituation, enables organisms to detect novelty and devote cognition to important elements of the environment. Here we describe in mice a form of long-term behavioral habituation to visual grating stimuli that is selective for stimulus orientation. Orientation-selective habituation (OSH) can be observed both in exploratory behavior in an open arena and in a stereotyped motor response to visual stimuli in head-restrained mice. We found that the latter behavioral response, termed a 'vidget', requires V1. Parallel electrophysiological recordings in V1 revealed that plasticity, in the form of stimulus-selective response potentiation (SRP), occurred in layer 4 of V1 as OSH developed. Local manipulations of V1 that prevented and reversed electrophysiological modifications likewise prevented and reversed memory demonstrated behaviorally. These findings suggest that a form of long-term visual recognition memory is stored via synaptic plasticity in primary sensory cortex.
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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.
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Lovelace, Jonathan W; Vieira, Philip A; Corches, Alex; Mackie, Ken; Korzus, Edward
2014-06-01
In addition to its central role in learning and memory, N-methyl D-aspartate receptor (NMDAR)-dependent signaling regulates central glutamatergic synapse maturation and has been implicated in schizophrenia. We have transiently induced NMDAR hypofunction in infant mice during postnatal days 7-11, followed by testing fear memory specificity and presynaptic plasticity in the prefrontal cortex (PFC) in adult mice. We show that transient NMDAR hypofunction during early brain development, coinciding with the maturation of cortical plasticity results in a loss of an endocannabinoid (eCB)-mediated form of long-term depression (eCB-LTD) at adult central glutamatergic synapses, while another form of presynaptic long-term depression mediated by the metabotropic glutamate receptor 2/3 (mGluR2/3-LTD) remains intact. Mice with this selective impairment of presynaptic plasticity also showed deficits in fear memory specificity. The observed deficit in cortical presynaptic plasticity may represent a neural maladaptation contributing to network instability and abnormal cognitive functioning.
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Directory of Open Access Journals (Sweden)
Mahua Chatterjee
2016-01-01
Full Text Available During odor sensing the activity of principal neurons of the mammalian olfactory bulb, the mitral and tufted cells (MTCs, occurs in repetitive bursts that are synchronized to respiration, reminiscent of hippocampal theta-gamma coupling. Axonless granule cells (GCs mediate self- and lateral inhibitory interactions between the excitatory MTCs via reciprocal dendrodendritic synapses. We have explored long-term plasticity at this synapse by using a theta burst stimulation (TBS protocol and variations thereof. GCs were excited via glomerular stimulation in acute brain slices. We find that TBS induces exclusively long-term depression in the majority of experiments, whereas single bursts (“single-sniff paradigm” can elicit both long-term potentiation and depression. Statistical analysis predicts that the mechanism underlying this bidirectional plasticity involves the proportional addition or removal of presynaptic release sites. Gamma stimulation with the same number of APs as in TBS was less efficient in inducing plasticity. Both TBS- and “single-sniff paradigm”-induced plasticity depend on NMDA receptor activation. Since the onset of plasticity is very rapid and requires little extra activity, we propose that these forms of plasticity might play a role already during an ongoing search for odor sources. Our results imply that components of both short-term and long-term olfactory memory may be encoded at this synapse.
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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.
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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.
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Gating of Long-Term Potentiation by Nicotinic Acetylcholine Receptors at the Cerebellum Input Stage
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
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Protein Phosphatase 1-Dependent Transcriptional Programs for Long-Term Memory and Plasticity
Graff, Johannes; Koshibu, Kyoko; Jouvenceau, Anne; Dutar, Patrick; Mansuy, Isabelle M.
2010-01-01
Gene transcription is essential for the establishment and the maintenance of long-term memory (LTM) and for long-lasting forms of synaptic plasticity. The molecular mechanisms that control gene transcription in neuronal cells are complex and recruit multiple signaling pathways in the cytoplasm and the nucleus. Protein kinases (PKs) and…
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Gur, Rotem; Tendler, Alex; Wagner, Shlomo
2014-09-01
Recognition of specific individuals is fundamental to mammalian social behavior and is mediated in most mammals by the main and accessory olfactory systems. Both these systems innervate the medial amygdala (MeA), where activity of the neuropeptide oxytocin is thought to mediate social recognition memory (SRM). The specific contribution of the MeA to SRM formation and the specific actions of oxytocin in the MeA are unknown. We used the social discrimination test to evaluate short-term and long-term SRM in adult Sprague-Dawley male rats (n = 38). The role of protein synthesis in the MeA was investigated by local application of the protein synthesis blocker anisomycin (n = 11). Synaptic plasticity was assessed in vivo by recording the MeA evoked field potential responses to stimulation of the main (n = 21) and accessory (n = 56) olfactory bulbs before and after theta burst stimulation. Intracerebroventricular administration of saline, oxytocin, or oxytocin receptor antagonist was used to measure the effect of oxytocin on synaptic plasticity. Anisomycin application to the MeA prevented the formation of long-term SRM. In addition, the responses of MeA neurons underwent long-term depression (LTD) after theta burst stimulation of the accessory olfactory bulb, but not the main accessory bulb, in an oxytocin-dependent manner. No LTD was found in socially isolated rats, which are known to lack long-term SRM. Finally, accessory olfactory bulb stimulation before SRM acquisition blocked long-term SRM, supporting the involvement of LTD in the MeA in formation of long-term SRM. Our results indicate that long-term SRM in rats involves protein synthesis and oxytocin-dependent LTD in the MeA. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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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.
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Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity
Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R.; Baldelli, Pietro; Benfenati, Fabio
2013-01-01
Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows. PMID:23970852
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Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity.
Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R; Baldelli, Pietro; Benfenati, Fabio
2013-01-01
Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows.
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Yang, Yi; Wen, Juan; Guo, Liqiang; Wan, Xiang; Du, Peifu; Feng, Ping; Shi, Yi; Wan, Qing
2016-11-09
Emulating neural behaviors at the synaptic level is of great significance for building neuromorphic computational systems and realizing artificial intelligence. Here, oxide-based electric double-layer (EDL) thin-film transistors were fabricated using 3-triethoxysilylpropylamine modified graphene oxide (KH550-GO) electrolyte as the gate dielectrics. Resulting from the EDL effect and electrochemical doping between mobile protons and the indium-zinc-oxide channel layer, long-term synaptic plasticity was emulated in our devices. Synaptic functions including long-term memory, synaptic temporal integration, and dynamic filters were successfully reproduced. In particular, spike rate-dependent plasticity (SRDP), one of the basic learning rules of long-term plasticity in the neural network where the synaptic weight changes according to the rate of presynaptic spikes, was emulated in our devices. Our results may facilitate the development of neuromorphic computational systems.
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Diversity in Long-Term Synaptic Plasticity at Inhibitory Synapses of Striatal Spiny Neurons
Rueda-Orozco, Pavel E.; Mendoza, Ernesto; Hernandez, Ricardo; Aceves, Jose J.; Ibanez-Sandoval, Osvaldo; Galarraga, Elvira; Bargas, Jose
2009-01-01
Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term…
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Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex.
Sale, Martin V; Nydam, Abbey S; Mattingley, Jason B
2017-03-01
Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis (APB) muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 min following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats
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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.
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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.
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Hu, Jiangyuan; Adler, Kerry; Farah, Carole Abi; Hastings, Margaret H; Sossin, Wayne S; Schacher, Samuel
2017-03-08
Multiple kinase activations contribute to long-term synaptic plasticity, a cellular mechanism mediating long-term memory. The sensorimotor synapse of Aplysia expresses different forms of long-term facilitation (LTF)-nonassociative and associative LTF-that require the timely activation of kinases, including protein kinase C (PKC). It is not known which PKC isoforms in the sensory neuron or motor neuron L7 are required to sustain each form of LTF. We show that different PKMs, the constitutively active isoforms of PKCs generated by calpain cleavage, in the sensory neuron and L7 are required to maintain each form of LTF. Different PKMs or calpain isoforms were blocked by overexpressing specific dominant-negative constructs in either presynaptic or postsynaptic neurons. Blocking either PKM Apl I in L7, or PKM Apl II or PKM Apl III in the sensory neuron 2 d after 5-hydroxytryptamine (5-HT) treatment reversed persistent nonassociative LTF. In contrast, blocking either PKM Apl II or PKM Apl III in L7, or PKM Apl II in the sensory neuron 2 d after paired stimuli reversed persistent associative LTF. Blocking either classical calpain or atypical small optic lobe (SOL) calpain 2 d after 5-HT treatment or paired stimuli did not disrupt the maintenance of persistent LTF. Soon after 5-HT treatment or paired stimuli, however, blocking classical calpain inhibited the expression of persistent associative LTF, while blocking SOL calpain inhibited the expression of persistent nonassociative LTF. Our data suggest that different stimuli activate different calpains that generate specific sets of PKMs in each neuron whose constitutive activities sustain long-term synaptic plasticity. SIGNIFICANCE STATEMENT Persistent synaptic plasticity contributes to the maintenance of long-term memory. Although various kinases such as protein kinase C (PKC) contribute to the expression of long-term plasticity, little is known about how constitutive activation of specific kinase isoforms sustains long-term
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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.
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Long-term potentiation expands information content of hippocampal dentate gyrus synapses.
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.
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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.
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Long-term potentiation (LTP) of human sensory-evoked potentials.
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.
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Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory.
Havekes, Robbert; Park, Alan J; Tolentino, Rosa E; Bruinenberg, Vibeke M; Tudor, Jennifer C; Lee, Yool; Hansen, Rolf T; Guercio, Leonardo A; Linton, Edward; Neves-Zaph, Susana R; Meerlo, Peter; Baillie, George S; Houslay, Miles D; Abel, Ted
2016-08-24
phosphodiesterase 4 (PDE4) family coordinates the degradation of cAMP, leading to the local attenuation of cAMP-dependent signaling pathways. Sleep deprivation leads to increased hippocampal expression of the PDE4A5 isoform. Here, we explored whether PDE4A5 overexpression mimics behavioral and synaptic plasticity phenotypes associated with sleep deprivation. Viral expression of PDE4A5 in hippocampal neurons impairs long-term potentiation and attenuates the formation of hippocampus-dependent long-term memories. Our findings suggest that PDE4A5 is a molecular constraint on cognitive processes and may contribute to the development of novel therapeutic approaches to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. Copyright © 2016 Havekes et al.
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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.
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Xie, Xiaoqiao
2011-01-01
In addition to synaptic communication between neurons, there is now strong evidence for neuron-to-astrocyte receptor signaling in the brain. During trains of action potentials or repetitive stimulation, neurotransmitter spills out of the synapse to activate astrocytic Gq protein-coupled receptors (Gq GPCRs). To date, very little is known about the ability of astrocytic receptors to exhibit plasticity as a result of long-term changes in neuronal firing rates. Here we describe for the first tim...
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Directory of Open Access Journals (Sweden)
Jonathan C. Lee
2017-05-01
Full Text Available ObjectiveThe objective of this study was to evaluate the feasibility of using paired-associative stimulation (PAS to study excitatory and inhibitory plasticity in adolescents while examining variables that may moderate plasticity (such as sex and environment.MethodsWe recruited 34 healthy adolescents (aged 13–19, 13 males, 21 females. To evaluate excitatory plasticity, we compared mean motor-evoked potentials (MEPs elicited by single-pulse transcranial magnetic stimulation (TMS before and after PAS at 0, 15, and 30 min. To evaluate inhibitory plasticity, we evaluated the cortical silent period (CSP elicited by single-pulse TMS in the contracted hand before and after PAS at 0, 15, and 30 min.ResultsAll participants completed PAS procedures. No adverse events occurred. PAS was well tolerated. PAS-induced significant increases in the ratio of post-PAS MEP to pre-PAS MEP amplitudes (p < 0.01 at all post-PAS intervals. Neither socioeconomic status nor sex was associated with post-PAS MEP changes. PAS induced significant CSP lengthening in males but not females.ConclusionPAS is a feasible, safe, and well-tolerated index of adolescent motor cortical plasticity. Gender may influence PAS-induced changes in cortical inhibition. PAS is safe and well tolerated by healthy adolescents and may be a novel tool with which to study adolescent neuroplasticity.
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Quantification of long term emission potential from landfills
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
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Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.
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.
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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.
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A single episode of high intensity sound inhibits long-term potentiation in the hippocampus of rats.
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.
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Penke, Zsuzsa; Morice, Elise; Veyrac, Alexandra; Gros, Alexandra; Chagneau, Carine; LeBlanc, Pascale; Samson, Nathalie; Baumgärtel, Karsten; Mansuy, Isabelle M; Davis, Sabrina; Laroche, Serge
2014-01-05
It is well established that Zif268/Egr1, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memory; however, it is as yet uncertain whether increasing expression of Zif268 in neurons can facilitate memory formation. Here, we used an inducible transgenic mouse model to specifically induce Zif268 overexpression in forebrain neurons and examined the effect on recognition memory and hippocampal synaptic transmission and plasticity. We found that Zif268 overexpression during the establishment of memory for objects did not change the ability to form a long-term memory of objects, but enhanced the capacity to form a long-term memory of the spatial location of objects. This enhancement was paralleled by increased long-term potentiation in the dentate gyrus of the hippocampus and by increased activity-dependent expression of Zif268 and selected Zif268 target genes. These results provide novel evidence that transcriptional mechanisms engaging Zif268 contribute to determining the strength of newly encoded memories.
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Crabtree, Gregg W.; Gogos, Joseph A.
2014-01-01
Synaptic plasticity alters the strength of information flow between presynaptic and postsynaptic neurons and thus modifies the likelihood that action potentials in a presynaptic neuron will lead to an action potential in a postsynaptic neuron. As such, synaptic plasticity and pathological changes in synaptic plasticity impact the synaptic computation which controls the information flow through the neural microcircuits responsible for the complex information processing necessary to drive adaptive behaviors. As current theories of neuropsychiatric disease suggest that distinct dysfunctions in neural circuit performance may critically underlie the unique symptoms of these diseases, pathological alterations in synaptic plasticity mechanisms may be fundamental to the disease process. Here we consider mechanisms of both short-term and long-term plasticity of synaptic transmission and their possible roles in information processing by neural microcircuits in both health and disease. As paradigms of neuropsychiatric diseases with strongly implicated risk genes, we discuss the findings in schizophrenia and autism and consider the alterations in synaptic plasticity and network function observed in both human studies and genetic mouse models of these diseases. Together these studies have begun to point toward a likely dominant role of short-term synaptic plasticity alterations in schizophrenia while dysfunction in autism spectrum disorders (ASDs) may be due to a combination of both short-term and long-term synaptic plasticity alterations. PMID:25505409
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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.
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Observation of long term potentiation in papain-based memory devices
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.
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Observation of long term potentiation in papain-based memory devices
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.
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Determination of plasticity and strength under long-term rupture of refractory materials
International Nuclear Information System (INIS)
Trunin, I.I.
1981-01-01
A possibility to obtain the equations of temperature- strength dependence of high-heat characteristics on the basis of previously obtained mechanical equation of state is studied, taking account of the accumulation of creep plastic strain. The calculation method of the resource of the material safe work with an account of fracture resistance and deformability at long-term rupture is considered. The 03Kh16N9M2 type steel used in power engeneering industry is examined [ru
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Hensbroek, R.A.; Kamal, A.; Baars, A.M.; Verhage, M.; Spruijt, B.M.
2003-01-01
The mossy fibers of the hippocampus display NMDA-receptor independent long-term plasticity. A number of studies addressed the role of mossy fiber long-term plasticity in memory, but have provided contrasting results. Here, we have exploited a genetic model, the rab3A null-mutant, which is
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Directory of Open Access Journals (Sweden)
Yun-Beom Choi
Full Text Available Patients with Huntington's disease exhibit memory and cognitive deficits many years before manifesting motor disturbances. Similarly, several studies have shown that deficits in long-term synaptic plasticity, a cellular basis of memory formation and storage, occur well before motor disturbances in the hippocampus of the transgenic mouse models of Huntington's disease. The autosomal dominant inheritance pattern of Huntington's disease suggests the importance of the mutant protein, huntingtin, in pathogenesis of Huntington's disease, but wild type huntingtin also has been shown to be important for neuronal functions such as axonal transport. Yet, the role of wild type huntingtin in long-term synaptic plasticity has not been investigated in detail. We identified a huntingtin homolog in the marine snail Aplysia, and find that similar to the expression pattern in mammalian brain, huntingtin is widely expressed in neurons and glial cells. Importantly the expression of mRNAs of huntingtin is upregulated by repeated applications of serotonin, a modulatory transmitter released during learning in Aplysia. Furthermore, we find that huntingtin expression levels are critical, not only in presynaptic sensory neurons, but also in the postsynaptic motor neurons for serotonin-induced long-term facilitation at the sensory-to-motor neuron synapse of the Aplysia gill-withdrawal reflex. These results suggest a key role for huntingtin in long-term memory storage.
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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
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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...
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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.
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Ataei, Negar; Sabzghabaee, Ali Mohammad; Movahedian, Ahmad
2015-01-01
Background: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. Methods: All of the observational, case–control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. Results: At the first search, it was fined 1015 articles which included “synaptic plasticity” OR “neuronal plasticity” OR “synaptic density” AND memory AND “molecular mechanism” AND “calcium/calmodulin-dependent protein kinase II” OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. Conclusions: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory. PMID:26445635
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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.
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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.
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Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons
Yang, Jiangyan; Ruchti, Evelyne; Petit, Jean Marie; Jourdain, Pascal; Grenningloh, Gabriele; Allaman, Igor; Magistretti, Pierre J.
2014-01-01
L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.
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Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons
Yang, Jiangyan
2014-07-28
L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.
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Rochman, Chelsea M; Hoh, Eunha; Hentschel, Brian T; Kaye, Shawn
2013-02-05
Concerns regarding marine plastic pollution and its affinity for chemical pollutants led us to quantify relationships between different types of mass-produced plastic and organic contaminants in an urban bay. At five locations in San Diego Bay, CA, we measured sorption of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) throughout a 12-month period to the five most common types of mass-produced plastic: polyethylene terephthalate (PET), high-density polyethylene (HDPE), polyvinyl chloride (PVC), low-density polyethylene (LDPE), and polypropylene (PP). During this long-term field experiment, sorption rates and concentrations of PCBs and PAHs varied significantly among plastic types and among locations. Our data suggest that for PAHs and PCBs, PET and PVC reach equilibrium in the marine environment much faster than HDPE, LDPE, and PP. Most importantly, concentrations of PAHs and PCBs sorbed to HDPE, LDPE, and PP were consistently much greater than concentrations sorbed to PET and PVC. These data imply that products made from HDPE, LDPE, and PP pose a greater risk than products made from PET and PVC of concentrating these hazardous chemicals onto fragmented plastic debris ingested by marine animals.
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Le Barillier, Léa; Léger, Lucienne; Luppi, Pierre-Hervé; Fort, Patrice; Malleret, Gaël; Salin, Paul-Antoine
2015-11-01
The cognitive role of melanin-concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero-lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long-term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal-dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long-term potentiation and depression in the CA1 area of the hippocampus. Post-tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre-synaptic forms of short-term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short-term memory T-maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short-term memory by impairing short-term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short-term synaptic plasticity in the hippocampus. © 2015 Wiley Periodicals, Inc.
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Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement
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...
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Directory of Open Access Journals (Sweden)
Alexander David Bird
2014-01-01
Full Text Available Synchrony in a presynaptic population leads to correlations in vesicle occupancy at the active sites for neurotransmitter release. The number of independent release sites per presynaptic neuron, a synaptic parameter recently shown to be modifed during long-term plasticity, will modulate these correlations and therefore have a significant effect on the firing rate of the postsynaptic neuron. To understand how correlations from synaptic dynamics and from presynaptic synchrony shape the postsynaptic response, we study a model of multiple release site short-term plasticity and derive exact results for the crosscorrelation function of vesicle occupancy and neurotransmitter release, as well as the postsynaptic voltage variance. Using approximate forms for the postsynaptic firing rate in the limits of low and high correlations, we demonstrate that short-term depression leads to a maximum response for an intermediate number of presynaptic release sites, and that this leads to a tuning-curve response peaked at an optimal presynaptic synchrony setby the number of neurotransmitter release sites per presynaptic neuron. These effects arise because, above a certain level of correlation, activity in the presynaptic population is overly strong resulting in wastage of the pool of releasable neurotransmitter. As the nervous system operates under constraints of efficient metabolism it is likely that this phenomenon provides an activity-dependent constraint on network architecture.
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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.
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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.
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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
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Hosang, Leon; Yusifov, Rashad; Löwel, Siegrid
2018-01-01
For routine behavioral tasks, mice predominantly rely on olfactory cues and tactile information. In contrast, their visual capabilities appear rather restricted, raising the question whether they can improve if vision gets more behaviorally relevant. We therefore performed long-term training using the visual water task (VWT): adult standard cage (SC)-raised mice were trained to swim toward a rewarded grating stimulus so that using visual information avoided excessive swimming toward nonrewarded stimuli. Indeed, and in contrast to old mice raised in a generally enriched environment (Greifzu et al., 2016), long-term VWT training increased visual acuity (VA) on average by more than 30% to 0.82 cycles per degree (cyc/deg). In an individual animal, VA even increased to 1.49 cyc/deg, i.e., beyond the rat range of VAs. Since visual experience enhances the spatial frequency threshold of the optomotor (OPT) reflex of the open eye after monocular deprivation (MD), we also quantified monocular vision after VWT training. Monocular VA did not increase reliably, and eye reopening did not initiate a decline to pre-MD values as observed by optomotry; VA values rather increased by continued VWT training. Thus, optomotry and VWT measure different parameters of mouse spatial vision. Finally, we tested whether long-term MD induced ocular dominance (OD) plasticity in the visual cortex of adult [postnatal day (P)162-P182] SC-raised mice. This was indeed the case: 40-50 days of MD induced OD shifts toward the open eye in both VWT-trained and, surprisingly, also in age-matched mice without VWT training. These data indicate that (1) long-term VWT training increases adult mouse VA, and (2) long-term MD induces OD shifts also in adult SC-raised mice.
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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.
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Chicca, E; Badoni, D; Dante, V; D'Andreagiovanni, M; Salina, G; Carota, L; Fusi, S; Del Giudice, P
2003-01-01
Electronic neuromorphic devices with on-chip, on-line learning should be able to modify quickly the synaptic couplings to acquire information about new patterns to be stored (synaptic plasticity) and, at the same time, preserve this information on very long time scales (synaptic stability). Here, we illustrate the electronic implementation of a simple solution to this stability-plasticity problem, recently proposed and studied in various contexts. It is based on the observation that reducing the analog depth of the synapses to the extreme (bistable synapses) does not necessarily disrupt the performance of the device as an associative memory, provided that 1) the number of neurons is large enough; 2) the transitions between stable synaptic states are stochastic; and 3) learning is slow. The drastic reduction of the analog depth of the synaptic variable also makes this solution appealing from the point of view of electronic implementation and offers a simple methodological alternative to the technological solution based on floating gates. We describe the full custom analog very large-scale integration (VLSI) realization of a small network of integrate-and-fire neurons connected by bistable deterministic plastic synapses which can implement the idea of stochastic learning. In the absence of stimuli, the memory is preserved indefinitely. During the stimulation the synapse undergoes quick temporary changes through the activities of the pre- and postsynaptic neurons; those changes stochastically result in a long-term modification of the synaptic efficacy. The intentionally disordered pattern of connectivity allows the system to generate a randomness suited to drive the stochastic selection mechanism. We check by a suitable stimulation protocol that the stochastic synaptic plasticity produces the expected pattern of potentiation and depression in the electronic network.
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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.
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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...
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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.
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Synaptic scaling enables dynamically distinct short- and long-term memory formation.
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.
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Directory of Open Access Journals (Sweden)
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.
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Enhanced hippocampal long-term potentiation and fear memory in Btbd9 mutant mice.
Directory of Open Access Journals (Sweden)
Mark P DeAndrade
Full Text Available Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS, a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS.
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Enhanced hippocampal long-term potentiation and fear memory in Btbd9 mutant mice.
DeAndrade, Mark P; Zhang, Li; Doroodchi, Atbin; Yokoi, Fumiaki; Cheetham, Chad C; Chen, Huan-Xin; Roper, Steven N; Sweatt, J David; Li, Yuqing
2012-01-01
Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS), a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS.
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Synaptic Plasticity and Nociception
Institute of Scientific and Technical Information of China (English)
ChenJianguo
2004-01-01
Synaptic plasticity is one of the fields that progresses rapidly and has a lot of success in neuroscience. The two major types of synaptie plasticity: long-term potentiation ( LTP and long-term depression (LTD are thought to be the cellular mochanisms of learning and memory. Recently, accumulating evidence suggests that, besides serving as a cellular model for learning and memory, the synaptic plasticity involves in other physiological or pathophysiological processes, such as the perception of pain and the regulation of cardiovascular system. This minireview will focus on the relationship between synaptic plasticity and nociception.
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Persistent inhibition of hippocampal long-term potentiation in vivo by learned helplessness stress.
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.
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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.
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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.
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Directory of Open Access Journals (Sweden)
Jennifer L Helfer
Full Text Available Ethanol exposure during pregnancy can cause structural and functional changes in the brain that can impair cognitive capacity. The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of ethanol. In the present experiments we sought to determine if the functional effects of developmental ethanol exposure could be linked to ethanol exposure during any single trimester-equivalent. Ethanol exposure during the 1(st or 3(rd trimester-equivalent produced only minor changes in synaptic plasticity in adult offspring. In contrast, ethanol exposure during the 2(nd trimester equivalent resulted in a pronounced decrease in long-term potentiation, indicating that the timing of exposure influences the severity of the deficit. Together, the results from these experiments demonstrate long-lasting alterations in synaptic plasticity as the result of developmental ethanol exposure and dependent on the timing of exposure. Furthermore, these results allude to neural circuit malfunction within the hippocampal formation, perhaps relating to the learning and memory deficits observed in individuals with fetal alcohol spectrum disorders.
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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.
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Directory of Open Access Journals (Sweden)
Guiqin He
2017-11-01
Full Text Available In the brain, de novo gene expression driven by learning-associated neuronal activities is critical for the formation of long-term memories. However, the signaling machinery mediating neuronal activity-induced gene expression, especially the rapid transcription of immediate-early genes (IEGs remains unclear. Cyclin-dependent kinases (Cdks are a family of serine/threonine kinases that have been firmly established as key regulators of transcription processes underling coordinated cell cycle entry and sequential progression in nearly all types of proliferative cells. Cdk7 is a subunit of transcriptional initiation factor II-H (TFIIH and the only known Cdk-activating kinase (CAK in metazoans. Recent studies using a novel Cdk7 specific covalent inhibitor, THZ1, revealed important roles of Cdk7 in transcription regulation in cancer cells. However, whether Cdk7 plays a role in the regulation of transcription in neurons remains unknown. In this study, we present evidence demonstrating that, in post-mitotic neurons, Cdk7 activity is positively correlated with neuronal activities in cultured primary neurons, acute hippocampal slices and in the brain. Cdk7 inhibition by THZ1 significantly suppressed mRNA levels of IEGs, selectively impaired long-lasting synaptic plasticity induced by 4 trains of high frequency stimulation (HFS and prevented the formation of long-term memories.
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TACTILE STIMULATION EVOKES LONG-LASTING POTENTIATION OF PURKINJE CELL DISCHARGE IN VIVO
Directory of Open Access Journals (Sweden)
Ramakrishnan eKanchipuram
2016-02-01
Full Text Available In the cerebellar network, a precise relationship between plasticity and neuronal discharge has been predicted. However, the potential generation of persistent changes in PC spike discharge as a consequence of plasticity following natural stimulation patterns has not been clearly determined. Here we show that facial tactile stimuli organized in theta-patterns can induce stereotyped NMDA and GABA-A receptor-dependent changes in Purkinje cell (PCs and molecular layer interneuron (MLIs firing: invariably, all PCs showed a long-lasting increase (spike-related potentiation or SR-P and MLIs a long-lasting decrease (spike-related suppression or SR-S in baseline activity and spike response probability. These observations suggests that natural sensory stimulation engages multiple long-term plastic changes that are distributed along the mossy fiber – parallel fiber pathway and operate synergistically to potentiate spike generation in PCs. In contrast, theta-pattern electrical stimulation of PFs indistinctly induced SR-P and SR-S both in PCs and MLIs, suggesting that natural sensory stimulation preordinates plasticity upstream of the PF-PC synapse. All these effects occurred in the absence of complex spike changes, supporting the theoretical prediction that Purkinje cell activity is potentiated when the mossy fiber - parallel fiber system is activated in the absence of conjunctive climbing fiber activity.
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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.
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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
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Long-term potentiation in the amygdala: a cellular mechanism of fear learning and memory.
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.
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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.
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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.
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Hu, Jiangyuan; Schacher, Samuel
2015-12-09
Synapses express different forms of plasticity that contribute to different forms of memory, and both memory and plasticity can become labile after reactivation. We previously reported that a persistent form of nonassociative long-term facilitation (PNA-LTF) of the sensorimotor synapses in Aplysia californica, a cellular analog of long-term sensitization, became labile with short-term heterosynaptic reactivation and reversed when the reactivation was followed by incubation with the protein synthesis inhibitor rapamycin. Here we examined the reciprocal impact of different forms of short-term plasticity (reactivations) on a persistent form of associative long-term facilitation (PA-LTF), a cellular analog of classical conditioning, which was expressed at Aplysia sensorimotor synapses when a tetanic stimulation of the sensory neurons was paired with a brief application of serotonin on 2 consecutive days. The expression of short-term homosynaptic plasticity [post-tetanic potentiation or homosynaptic depression (HSD)], or short-term heterosynaptic plasticity [serotonin-induced facilitation or neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFa)-induced depression], at synapses expressing PA-LTF did not affect the maintenance of PA-LTF. The kinetics of HSD was attenuated at synapses expressing PA-LTF, which required activation of protein kinase C (PKC). Both PA-LTF and the attenuated kinetics of HSD were reversed by either a transient blockade of PKC activity or a homosynaptic, but not heterosynaptic, reactivation when paired with rapamycin. These results indicate that two different forms of persistent synaptic plasticity, PA-LTF and PNA-LTF, expressed at the same synapse become labile when reactivated by different stimuli. Activity-dependent changes in neural circuits mediate long-term memories. Some forms of long-term memories become labile and can be reversed with specific types of reactivations, but the mechanism is complex. At the cellular level, reactivations that induce a
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Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei.
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.
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The effect of heat and mass transfer on the cellular plastic insulation and the long-term aging
Energy Technology Data Exchange (ETDEWEB)
Fan Youchen [VTT Building Technology, Espoo (Finland). Building Physics, Building Services and Fire Technology
1997-12-31
To produce environmental-friendly products, foamed plastic industries are facing the challenge to replace the traditional blowing agents chlorofluorocarbons (CFCs) with zero ozone depletion potential (ODP) alternatives. After a series of studies were completed, more understandings and new findings have been achieved with respect to the rigid closed-cell cellular plastic insulations or foamed plastic insulations (FPIs). The mechanism of heat transfer within the FPIs was examined. A new formula for calculating the solid polymer matrix thermal conductivity has been deduced based on the law of energy conservation and Fourier equation of heat conduction. All the parameters involved in this formula can be easily measured. By comparing the simulation results with measurements, the Brokaw equation is recommended for the prediction of the thermal conductivity of a cell-gas mixture. The foamed plastic deformation was also discussed. A new model has been established for predicting the elastic modulus of the foamed plastics. In comparison to the published measurements, it was found that the new model gives fairly good results. A diffusion chamber has been designed and constructed for measuring the gaseous transport properties within the FPIs. To overcome the difficulties of the traditional method, a new measurement procedure and post test data treatment have been suggested. The measurement accuracy is equivalent to the traditional method with an exception of much short time being required. The diffusion coefficients of CO{sub 2}, O{sub 2}, and N{sub 2} within five n-pentane/CO{sub 2} based polyurethane (PUR) foams have been obtained from the diffusion chamber tests. Measurements showed that the relationship between the gaseous diffusion coefficients within FPIs and temperature follows the Arrhenius type. No identical relationship between diffusion coefficients and foam density was reached. To predict the long-term aging property of CFC-free foamed plastic insulations, a two
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Short-term synaptic plasticity and heterogeneity in neural systems
Mejias, J. F.; Kappen, H. J.; Longtin, A.; Torres, J. J.
2013-01-01
We review some recent results on neural dynamics and information processing which arise when considering several biophysical factors of interest, in particular, short-term synaptic plasticity and neural heterogeneity. The inclusion of short-term synaptic plasticity leads to enhanced long-term memory capacities, a higher robustness of memory to noise, and irregularity in the duration of the so-called up cortical states. On the other hand, considering some level of neural heterogeneity in neuron models allows neural systems to optimize information transmission in rate coding and temporal coding, two strategies commonly used by neurons to codify information in many brain areas. In all these studies, analytical approximations can be made to explain the underlying dynamics of these neural systems.
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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.
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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.
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Neuromodulation, development and synaptic plasticity.
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.
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Potentially inappropriate prescriptions for older patients in long-term care
Directory of Open Access Journals (Sweden)
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.
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The discovery of long-term potentiation.
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.
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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.
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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.)
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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.
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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.
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Long-term potentiation in hilar circuitry modulates gating by the dentate gyrus.
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.
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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.
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Neural 17β-estradiol facilitates long-term potentiation in the hippocampal CA1 region.
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.
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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
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Pick, Joseph E.; Malumbres, Marcos; Klann, Eric
2013-01-01
The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C-Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role of Cdh1 in synaptic plasticity and memory by generating…
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Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory
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
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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.
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Xu, Lin-Hao; Xie, Hui; Shi, Zhi-Hui; Du, Li-Da; Wing, Yun-Kwok; Li, Albert M; Ke, Ya; Yung, Wing-Ho
2015-09-20
This study examined the role of endoplasmic reticulum (ER) stress in mediating chronic intermittent hypoxia (IH)-induced neurocognitive deficits. We designed experiments to demonstrate that ER stress is initiated in the hippocampus under chronic IH and determined its role in apoptotic cell death, impaired synaptic structure and plasticity, and memory deficits. Two weeks of IH disrupted ER fine structure and upregulated ER stress markers, glucose-regulated protein 78, caspase-12, and C/EBP homologous protein, in the hippocampus, which could be suppressed by ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid. Meanwhile, ER stress induced apoptosis via decreased Bcl-2, promoted reactive oxygen species production, and increased malondialdehyde formation and protein carbonyl, as well as suppressed mitochondrial function. These effects were largely prevented by ER stress inhibitors. On the other hand, suppression of oxidative stress could reduce ER stress. In addition, the length of the synaptic active zone and number of mature spines were reduced by IH. Long-term recognition memory and spatial memory were also impaired, which was accompanied by reduced long-term potentiation in the Schaffer collateral pathway. These effects were prevented by coadministration of the TUDCA. These results show that ER stress plays a critical role in underlying memory deficits in obstructive sleep apnea (OSA)-associated IH. Attenuators of ER stress may serve as novel adjunct therapeutic agents for ameliorating OSA-induced neurocognitive impairment.
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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.
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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.
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Enhanced long term microcircuit plasticity in the valproic acid animal model of autism
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Guilherme T Silva
2009-06-01
Full Text Available A single intra-peritoneal injection of valproic acid (VPA on embryonic day (ED 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a mini-column (<50μm. In the present study, we explored whether Long Term Microcircuit Plasticity (LTMP was altered in this animal model. We performed multi-neuron patch-clamp recordings on clusters of layer V pyramidal cells in somatosensory cortex brain slices (PN 12-15, mapped the connectivity and characterized the synaptic properties for connected neurons. Pipettes were then withdrawn and the slice was perfused with 100μM sodium glutamate in artificial cerebrospinal fluid in the recording chamber for 12 h. When we re-patched the same cluster of neurons, we found enhanced LTMP only at inter-somatic distances beyond minicolumnar dimensions. These data suggest that hyperconnectivity is already near its peak within the dimensions of the minicolumn in the treated animals and that LTMP, which is normally restricted to within a minicolumn, spills over to drive hyperconnectivity across the dimensions of a minicolumn. This study provides further evidence to support the notion that the neocortex is highly plastic in response to new experiences in this animal model of autism.
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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.
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Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory.
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.
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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
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Directory of Open Access Journals (Sweden)
Ferdinando Fiumara
2015-06-01
Full Text Available The maintenance phase of memory-related long-term facilitation (LTF of synapses between sensory and motor neurons of the gill-withdrawal reflex of Aplysia depends on a serotonin (5-HT-triggered presynaptic upregulation of CPEB, a functional prion that regulates local protein synthesis at the synapse. The mechanisms whereby serotonin regulates CPEB levels in presynaptic sensory neurons are not known. Here, we describe a sensory neuron-specific microRNA 22 (miR-22 that has multiple binding sites on the mRNA of CPEB and inhibits it in the basal state. Serotonin triggers MAPK/Erk-dependent downregulation of miR-22, thereby upregulating the expression of CPEB, which in turn regulates, through functional CPE elements, the presynaptic expression of atypical PKC (aPKC, another candidate regulator of memory maintenance. Our findings support a model in which the neurotransmitter-triggered downregulation of miR-22 coordinates the regulation of genes contributing synergistically to the long-term maintenance of memory-related synaptic plasticity.
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Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation.
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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.
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Altered synaptic plasticity in Tourette's syndrome and its relationship to motor skill learning.
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Valerie Cathérine Brandt
Full Text Available Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by motor and phonic tics that can be considered motor responses to preceding inner urges. It has been shown that Tourette patients have inferior performance in some motor learning tasks and reduced synaptic plasticity induced by transcranial magnetic stimulation. However, it has not been investigated whether altered synaptic plasticity is directly linked to impaired motor skill acquisition in Tourette patients. In this study, cortical plasticity was assessed by measuring motor-evoked potentials before and after paired associative stimulation in 14 Tourette patients (13 male; age 18-39 and 15 healthy controls (12 male; age 18-33. Tic and urge severity were assessed using the Yale Global Tic Severity Scale and the Premonitory Urges for Tics Scale. Motor learning was assessed 45 minutes after inducing synaptic plasticity and 9 months later, using the rotary pursuit task. On average, long-term potentiation-like effects in response to the paired associative stimulation were present in healthy controls but not in patients. In Tourette patients, long-term potentiation-like effects were associated with more and long-term depression-like effects with less severe urges and tics. While motor learning did not differ between patients and healthy controls 45 minutes after inducing synaptic plasticity, the learning curve of the healthy controls started at a significantly higher level than the Tourette patients' 9 months later. Induced synaptic plasticity correlated positively with motor skills in healthy controls 9 months later. The present study confirms previously found long-term improvement in motor performance after paired associative stimulation in healthy controls but not in Tourette patients. Tourette patients did not show long-term potentiation in response to PAS and also showed reduced levels of motor skill consolidation after 9 months compared to healthy controls. Moreover
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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
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Long-Term Potentiation in the Motor Cortex
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.
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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.
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Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.
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
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Trillaud-Doppia, Emilie; Paradis-Isler, Nicolas; Boehm, Jannic
2016-07-01
Alzheimer disease (AD) is initially characterized as a disease of the synapse that affects synaptic transmission and synaptic plasticity. While amyloid-beta and tau have been traditionally implicated in causing AD, recent studies suggest that other factors, such as the intracellular domain of the amyloid-precursor protein (APP-ICD), can also play a role in the development of AD. Here, we show that the expression of APP-ICD induces synaptic depression, while the intracellular domain of its homolog amyloid-like precursor protein 2 (APLP2-ICD) does not. We are able to show that this effect by APP-ICD is due to a single alanine vs. proline difference between APP-ICD and APLP2-ICD. The alanine in APP-ICD and the proline in APLP2-ICD lie directly behind a conserved caspase cleavage site. Inhibition of caspase cleavage of APP-ICD prevents the induction of synaptic depression. Finally, we show that the expression of APP-ICD increases and facilitates long-term depression and blocks induction of long-term potentiation. The block in long-term potentiation can be overcome by mutating the aforementioned alanine in APP-ICD to the proline of APLP2. Based on our results, we propose the emergence of a new APP critical domain for the regulation of synaptic plasticity and in consequence for the development of AD. Copyright © 2016 Elsevier Inc. All rights reserved.
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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
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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.
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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.
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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.
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Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.
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.
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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
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Groussard, Mathilde; La Joie, Renaud; Rauchs, Géraldine; Landeau, Brigitte; Chételat, Gaël; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis; Platel, Hervé
2010-01-01
The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI) study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music). Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM) investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus. PMID:20957158
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Directory of Open Access Journals (Sweden)
Mathilde Groussard
Full Text Available The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music. Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus.
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Groussard, Mathilde; La Joie, Renaud; Rauchs, Géraldine; Landeau, Brigitte; Chételat, Gaël; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis; Platel, Hervé
2010-10-05
The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI) study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music). Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM) investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus.
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Distinct cerebellar engrams in short-term and long-term motor learning.
Wang, Wen; Nakadate, Kazuhiko; Masugi-Tokita, Miwako; Shutoh, Fumihiro; Aziz, Wajeeha; Tarusawa, Etsuko; Lorincz, Andrea; Molnár, Elek; Kesaf, Sebnem; Li, Yun-Qing; Fukazawa, Yugo; Nagao, Soichi; Shigemoto, Ryuichi
2014-01-07
Cerebellar motor learning is suggested to be caused by long-term plasticity of excitatory parallel fiber-Purkinje cell (PF-PC) synapses associated with changes in the number of synaptic AMPA-type glutamate receptors (AMPARs). However, whether the AMPARs decrease or increase in individual PF-PC synapses occurs in physiological motor learning and accounts for memory that lasts over days remains elusive. We combined quantitative SDS-digested freeze-fracture replica labeling for AMPAR and physical dissector electron microscopy with a simple model of cerebellar motor learning, adaptation of horizontal optokinetic response (HOKR) in mouse. After 1-h training of HOKR, short-term adaptation (STA) was accompanied with transient decrease in AMPARs by 28% in target PF-PC synapses. STA was well correlated with AMPAR decrease in individual animals and both STA and AMPAR decrease recovered to basal levels within 24 h. Surprisingly, long-term adaptation (LTA) after five consecutive daily trainings of 1-h HOKR did not alter the number of AMPARs in PF-PC synapses but caused gradual and persistent synapse elimination by 45%, with corresponding PC spine loss by the fifth training day. Furthermore, recovery of LTA after 2 wk was well correlated with increase of PF-PC synapses to the control level. Our findings indicate that the AMPARs decrease in PF-PC synapses and the elimination of these synapses are in vivo engrams in short- and long-term motor learning, respectively, showing a unique type of synaptic plasticity that may contribute to memory consolidation.
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Fiumara, Ferdinando; Rajasethupathy, Priyamvada; Antonov, Igor; Kosmidis, Stylianos; Sossin, Wayne S; Kandel, Eric R
2015-06-30
The maintenance phase of memory-related long-term facilitation (LTF) of synapses between sensory and motor neurons of the gill-withdrawal reflex of Aplysia depends on a serotonin (5-HT)-triggered presynaptic upregulation of CPEB, a functional prion that regulates local protein synthesis at the synapse. The mechanisms whereby serotonin regulates CPEB levels in presynaptic sensory neurons are not known. Here, we describe a sensory neuron-specific microRNA 22 (miR-22) that has multiple binding sites on the mRNA of CPEB and inhibits it in the basal state. Serotonin triggers MAPK/Erk-dependent downregulation of miR-22, thereby upregulating the expression of CPEB, which in turn regulates, through functional CPE elements, the presynaptic expression of atypical PKC (aPKC), another candidate regulator of memory maintenance. Our findings support a model in which the neurotransmitter-triggered downregulation of miR-22 coordinates the regulation of genes contributing synergistically to the long-term maintenance of memory-related synaptic plasticity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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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.
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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.
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Satb2 determines miRNA expression and long-term memory in the adult central nervous system.
Jaitner, Clemens; Reddy, Chethan; Abentung, Andreas; Whittle, Nigel; Rieder, Dietmar; Delekate, Andrea; Korte, Martin; Jain, Gaurav; Fischer, Andre; Sananbenesi, Farahnaz; Cera, Isabella; Singewald, Nicolas; Dechant, Georg; Apostolova, Galina
2016-11-29
SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.
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LENUS (Irish Health Repository)
Mitchell, Jacqueline C
2009-12-01
Increased production and deposition of amyloid beta-protein (Abeta) are believed to be key pathogenic events in Alzheimer\\'s disease. As such, routes for lowering cerebral Abeta levels represent potential therapeutic targets for Alzheimer\\'s disease. X11beta is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11beta inhibits Abeta production in a number of experimental systems. However, whether these changes to APP processing and Abeta production induced by X11beta overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11beta-mediated reduction in cerebral Abeta is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer\\'s disease. Overexpression of X11beta itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11beta function represents a therapeutic target for Abeta-mediated neuronal dysfunction in Alzheimer\\'s disease.
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International Nuclear Information System (INIS)
Pocock, D.C.; Worthington, J.C.; Oberpichler, R.; Van Exel, H.; Beukelmann, D.; Huth, R.; Rose, B.
1990-01-01
The objective of this research was to study the long-term performance of structures comprising nuclear power plants. The time period of interest for this study is 140 years (this figure is based on maximum periods of 40 years for operation and 100 years of storage). It was divided in two parts: - the first based on four UK nuclear power plants examine the principle deterioration mechanism of reinforced structure which is chloride ingress and carbonation penetration - the second based on 2 German nuclear power plants examine the long term behaviour of reinforced and prestressed concrete and also the corrosion of steel containments with particular reference on plastic seals and potential risk areas
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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.
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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.
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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.
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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
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Directory of Open Access Journals (Sweden)
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.
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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
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Phrenic long-term facilitation requires PKCθ activity within phrenic motor neurons.
Devinney, Michael J; Fields, Daryl P; Huxtable, Adrianne G; Peterson, Timothy J; Dale, Erica A; Mitchell, Gordon S
2015-05-27
Acute intermittent hypoxia (AIH) induces a form of spinal motor plasticity known as phrenic long-term facilitation (pLTF); pLTF is a prolonged increase in phrenic motor output after AIH has ended. In anesthetized rats, we demonstrate that pLTF requires activity of the novel PKC isoform, PKCθ, and that the relevant PKCθ is within phrenic motor neurons. Whereas spinal PKCθ inhibitors block pLTF, inhibitors targeting other PKC isoforms do not. PKCθ is highly expressed in phrenic motor neurons, and PKCθ knockdown with intrapleural siRNAs abolishes pLTF. Intrapleural siRNAs targeting PKCζ, an atypical PKC isoform expressed in phrenic motor neurons that underlies a distinct form of phrenic motor plasticity, does not affect pLTF. Thus, PKCθ plays a critical role in spinal AIH-induced respiratory motor plasticity, and the relevant PKCθ is localized within phrenic motor neurons. Intrapleural siRNA delivery has considerable potential as a therapeutic tool to selectively manipulate plasticity in vital respiratory motor neurons. Copyright © 2015 the authors 0270-6474/15/358107-11$15.00/0.
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Short-term immobilization influences use-dependent cortical plasticity and fine motor performance.
Opie, George M; Evans, Alexandra; Ridding, Michael C; Semmler, John G
2016-08-25
Short-term immobilization that reduces muscle use for 8-10h is known to influence cortical excitability and motor performance. However, the mechanisms through which this is achieved, and whether these changes can be used to modify cortical plasticity and motor skill learning, are not known. The purpose of this study was to investigate the influence of short-term immobilization on use-dependent cortical plasticity, motor learning and retention. Twenty-one adults were divided into control and immobilized groups, both of which underwent two experimental sessions on consecutive days. Within each session, transcranial magnetic stimulation (TMS) was used to assess motor-evoked potential (MEP) amplitudes, short- (SICI) and long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF) before and after a grooved pegboard task. Prior to the second training session, the immobilized group underwent 8h of left hand immobilization targeting the index finger, while control subjects were allowed normal limb use. Immobilization produced a reduction in MEP amplitudes, but no change in SICI, LICI or ICF. While motor performance improved for both groups in each session, the level of performance was greater 24-h later in control, but not immobilized subjects. Furthermore, training-related MEP facilitation was greater after, compared with before, immobilization. These results indicate that immobilization can modulate use-dependent plasticity and the retention of motor skills. They also suggest that changes in intracortical excitability are unlikely to contribute to the immobilization-induced modification of cortical excitability. Copyright © 2016. Published by Elsevier Ltd.
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Spike-timing dependent plasticity in the striatum
Directory of Open Access Journals (Sweden)
Elodie Fino
2010-06-01
Full Text Available The striatum is the major input nucleus of basal ganglia, an ensemble of interconnected sub-cortical nuclei associated with fundamental processes of action-selection and procedural learning and memory. The striatum receives afferents from the cerebral cortex and the thalamus. In turn, it relays the integrated information towards the basal ganglia output nuclei through which it operates a selected activation of behavioral effectors. The striatal output neurons, the GABAergic medium-sized spiny neurons (MSNs, are in charge of the detection and integration of behaviorally relevant information. This property confers to the striatum the ability to extract relevant information from the background noise and select cognitive-motor sequences adapted to environmental stimuli. As long-term synaptic efficacy changes are believed to underlie learning and memory, the corticostriatal long-term plasticity provides a fundamental mechanism for the function of the basal ganglia in procedural learning. Here, we reviewed the different forms of spike-timing dependent plasticity (STDP occurring at corticostriatal synapses. Most of the studies have focused on MSNs and their ability to develop long-term plasticity. Nevertheless, the striatal interneurons (the fast-spiking GABAergic, the NO synthase and cholinergic interneurons also receive monosynaptic afferents from the cortex and tightly regulated corticostriatal information processing. Therefore, it is important to take into account the variety of striatal neurons to fully understand the ability of striatum to develop long-term plasticity. Corticostriatal STDP with various spike-timing dependence have been observed depending on the neuronal sub-populations and experimental conditions. This complexity highlights the extraordinary potentiality in term of plasticity of the corticostriatal pathway.
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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.
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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.
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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.
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Grassi, S; Pettorossi, V E
2001-08-01
The analysis of cellular-molecular events mediating synaptic plasticity within vestibular nuclei is an attempt to explain the mechanisms underlying vestibular plasticity phenomena. The present review is meant to illustrate the main results, obtained in vitro, on the mechanisms underlying long-term changes in synaptic strength within the medial vestibular nuclei. The synaptic plasticity phenomena taking place at the level of vestibular nuclei could be useful for adapting and consolidating the efficacy of vestibular neuron responsiveness to environmental requirements, as during visuo-vestibular recalibration and vestibular compensation. Following a general introduction on the most salient features of vestibular compensation and visuo-vestibular adaptation, which are two plastic events involving neuronal circuitry within the medial vestibular nuclei, the second and third sections describe the results from rat brainstem slice studies, demonstrating the possibility to induce long-term potentiation and depression in the medial vestibular nuclei, following high frequency stimulation of the primary vestibular afferents. In particular the mechanisms sustaining the induction and expression of vestibular long-term potentiation and depression, such as the role of various glutamate receptors and retrograde messengers have been described. The relevant role of the interaction between the platelet-activating factor, acting as a retrograde messenger, and the presynaptic metabotropic glutamate receptors, in determining the full expression of vestibular long-term potentiation is also underlined. In addition, the mechanisms involved in vestibular long-term potentiation have been compared with those leading to long-term potentiation in the hippocampus to emphasize the most significant differences emerging from vestibular studies. The fourth part, describes recent results demonstrating the essential role of nitric oxide, another retrograde messenger, in the induction of vestibular
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International Nuclear Information System (INIS)
Lee, Eun Sun; Han, Joon Koo; Baek, Ji-Hyun; Suh, Suk-Won; Joo, Ijin; Yi, Nam-Joon; Lee, Kwang-Woong; Suh, Kyung-Suk
2016-01-01
PurposeWe aimed to evaluate the long-term efficacy of percutaneous management of non-anastomotic biliary stenosis after liver transplantation, using plastic internal biliary stents.Materials and MethodsThis study included 35 cases (28 men, 7 women; mean age: 52.09 ± 8.13 years, range 34–68) in 33 patients who needed repeated interventional procedures because of biliary strictures. After classification of the biliary strictures, we inserted percutaneous biliary plastic stents through the T-tube or percutaneous transhepatic biliary drainage tracts. Stents were exchanged according to percutaneous methods at regular 2- to 6-month intervals. The stents were removed if the condition improved, as observed on cholangiogram as well as based on clinical findings. The median patient follow-up period after initial diagnosis and treatment was 6.04 years (range 0.29–9.95 years). We assessed treatment success rate and patient and graft survival times.ResultsDuring the follow-up period, 14 patients (14/33, 42.42 %) were successfully treated and were tube-free. The median tube-free time, time without a stent, was 4.13 years (range 1.00–9.01). In contrast, internal plastic stents remained in 9 patients (9/33, 27.27 %) until the last follow-up. These patients had acceptable hepatic function. Among the remaining 10 patients, 3 (3/33, 9.09 %) were lost to regular follow-up and the other 7 (7/33, 21.21 %) patients died. The overall graft loss rate was 20.0 % (7/35). The median time from initial treatment to graft loss was 1.84 years (range 0.42–4.25).ConclusionsPercutaneous plastic stents placement is technically feasible and clinically useful in patients with multiple biliary stenoses following liver transplantation.
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Energy Technology Data Exchange (ETDEWEB)
Lee, Eun Sun, E-mail: seraph377@gmail.com; Han, Joon Koo, E-mail: hanjk@snu.ac.kr; Baek, Ji-Hyun, E-mail: 100paper@gmail.com [Seoul National University Hospital, Department of Radiology (Korea, Republic of); Suh, Suk-Won, E-mail: bomboy1@hanmail.net [Chung-Ang University Hospital, Department of Surgery (Korea, Republic of); Joo, Ijin, E-mail: hijijin@gmail.com [Seoul National University Hospital, Department of Radiology (Korea, Republic of); Yi, Nam-Joon, E-mail: gsleenj@hanmail.net; Lee, Kwang-Woong, E-mail: kwleegs@gmail.com; Suh, Kyung-Suk, E-mail: kssuh@snu.ac.kr [Seoul National University Hospital, Department of Surgery (Korea, Republic of)
2016-06-15
PurposeWe aimed to evaluate the long-term efficacy of percutaneous management of non-anastomotic biliary stenosis after liver transplantation, using plastic internal biliary stents.Materials and MethodsThis study included 35 cases (28 men, 7 women; mean age: 52.09 ± 8.13 years, range 34–68) in 33 patients who needed repeated interventional procedures because of biliary strictures. After classification of the biliary strictures, we inserted percutaneous biliary plastic stents through the T-tube or percutaneous transhepatic biliary drainage tracts. Stents were exchanged according to percutaneous methods at regular 2- to 6-month intervals. The stents were removed if the condition improved, as observed on cholangiogram as well as based on clinical findings. The median patient follow-up period after initial diagnosis and treatment was 6.04 years (range 0.29–9.95 years). We assessed treatment success rate and patient and graft survival times.ResultsDuring the follow-up period, 14 patients (14/33, 42.42 %) were successfully treated and were tube-free. The median tube-free time, time without a stent, was 4.13 years (range 1.00–9.01). In contrast, internal plastic stents remained in 9 patients (9/33, 27.27 %) until the last follow-up. These patients had acceptable hepatic function. Among the remaining 10 patients, 3 (3/33, 9.09 %) were lost to regular follow-up and the other 7 (7/33, 21.21 %) patients died. The overall graft loss rate was 20.0 % (7/35). The median time from initial treatment to graft loss was 1.84 years (range 0.42–4.25).ConclusionsPercutaneous plastic stents placement is technically feasible and clinically useful in patients with multiple biliary stenoses following liver transplantation.
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Directory of Open Access Journals (Sweden)
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.
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Li, Wei-Guang; Liu, Ming-Gang; Deng, Shining; Liu, Yan-Mei; Shang, Lin; Ding, Jing; Hsu, Tsan-Ting; Jiang, Qin; Li, Ying; Li, Fei; Zhu, Michael Xi; Xu, Tian-Le
2016-01-01
Acid-sensing ion channel 1a (ASIC1a) has been shown to play important roles in synaptic plasticity, learning and memory. Here we identify a crucial role for ASIC1a in long-term depression (LTD) at mouse insular synapses. Genetic ablation and pharmacological inhibition of ASIC1a reduced the induction probability of LTD without affecting that of long-term potentiation in the insular cortex. The disruption of ASIC1a also attenuated the extinction of established taste aversion memory without alte...
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Sanderson, David J; Good, Mark A; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H; Rawlins, J Nicholas P; Bannerman, David M
2009-06-01
The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of GluA1-dependent synaptic plasticity for short-term memory of recently visited places, but not for the ability to form long-term associations between a particular spatial location and an outcome. This hypothesis is in concordance with the theory that short-term and long-term memory depend on dissociable psychological processes. In this study we tested GluA1-/- mice on both short-term and long-term spatial memory using a simple novelty preference task. Mice were given a series of repeated exposures to a particular spatial location (the arm of a Y-maze) before their preference for a novel spatial location (the unvisited arm of the maze) over the familiar spatial location was assessed. GluA1-/- mice were impaired if the interval between the trials was short (1 min), but showed enhanced spatial memory if the interval between the trials was long (24 h). This enhancement was caused by the interval between the exposure trials rather than the interval prior to the test, thus demonstrating enhanced learning and not simply enhanced performance or expression of memory. This seemingly paradoxical enhancement of hippocampus-dependent spatial learning may be caused by GluA1 gene deletion reducing the detrimental effects of short-term memory on subsequent long-term learning. Thus, these results support a dual-process model of memory in which short-term and long-term memory are separate and sometimes competitive processes.
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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.
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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
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Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation
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
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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.
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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.
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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.
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Schaefer, Natascha; Rotermund, Carola; Blumrich, Eva-Maria; Lourenco, Mychael V; Joshi, Pooja; Hegemann, Regina U; Jamwal, Sumit; Ali, Nilufar; García Romero, Ezra Michelet; Sharma, Sorabh; Ghosh, Shampa; Sinha, Jitendra K; Loke, Hannah; Jain, Vishal; Lepeta, Katarzyna; Salamian, Ahmad; Sharma, Mahima; Golpich, Mojtaba; Nawrotek, Katarzyna; Paidi, Ramesh K; Shahidzadeh, Sheila M; Piermartiri, Tetsade; Amini, Elham; Pastor, Veronica; Wilson, Yvette; Adeniyi, Philip A; Datusalia, Ashok K; Vafadari, Benham; Saini, Vedangana; Suárez-Pozos, Edna; Kushwah, Neetu; Fontanet, Paula; Turner, Anthony J
2017-06-20
One of the most intriguing features of the brain is its ability to be malleable, allowing it to adapt continually to changes in the environment. Specific neuronal activity patterns drive long-lasting increases or decreases in the strength of synaptic connections, referred to as long-term potentiation and long-term depression, respectively. Such phenomena have been described in a variety of model organisms, which are used to study molecular, structural, and functional aspects of synaptic plasticity. This review originated from the first International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Alpbach, Austria (Sep 2016), and will use its curriculum and discussions as a framework to review some of the current knowledge in the field of synaptic plasticity. First, we describe the role of plasticity during development and the persistent changes of neural circuitry occurring when sensory input is altered during critical developmental stages. We then outline the signaling cascades resulting in the synthesis of new plasticity-related proteins, which ultimately enable sustained changes in synaptic strength. Going beyond the traditional understanding of synaptic plasticity conceptualized by long-term potentiation and long-term depression, we discuss system-wide modifications and recently unveiled homeostatic mechanisms, such as synaptic scaling. Finally, we describe the neural circuits and synaptic plasticity mechanisms driving associative memory and motor learning. Evidence summarized in this review provides a current view of synaptic plasticity in its various forms, offers new insights into the underlying mechanisms and behavioral relevance, and provides directions for future research in the field of synaptic plasticity. Read the Editorial Highlight for this article on doi: 10.1111/jnc.14102. © 2017 International Society for Neurochemistry.
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Directory of Open Access Journals (Sweden)
Daniela Hoeber
2016-01-01
Full Text Available Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg at the onset of hyperoxia (24 hours, 80% oxygen in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.
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Lau, Bonnie K; Ruggles, Dorea R; Katyal, Sucharit; Engel, Stephen A; Oxenham, Andrew J
2017-01-01
Short-term training can lead to improvements in behavioral discrimination of auditory and visual stimuli, as well as enhanced EEG responses to those stimuli. In the auditory domain, fluency with tonal languages and musical training has been associated with long-term cortical and subcortical plasticity, but less is known about the effects of shorter-term training. This study combined electroencephalography (EEG) and behavioral measures to investigate short-term learning and neural plasticity in both auditory and visual domains. Forty adult participants were divided into four groups. Three groups trained on one of three tasks, involving discrimination of auditory fundamental frequency (F0), auditory amplitude modulation rate (AM), or visual orientation (VIS). The fourth (control) group received no training. Pre- and post-training tests, as well as retention tests 30 days after training, involved behavioral discrimination thresholds, steady-state visually evoked potentials (SSVEP) to the flicker frequencies of visual stimuli, and auditory envelope-following responses simultaneously evoked and measured in response to rapid stimulus F0 (EFR), thought to reflect subcortical generators, and slow amplitude modulation (ASSR), thought to reflect cortical generators. Enhancement of the ASSR was observed in both auditory-trained groups, not specific to the AM-trained group, whereas enhancement of the SSVEP was found only in the visually-trained group. No evidence was found for changes in the EFR. The results suggest that some aspects of neural plasticity can develop rapidly and may generalize across tasks but not across modalities. Behaviorally, the pattern of learning was complex, with significant cross-task and cross-modal learning effects.
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Wnt Signaling Is Required for Long-Term Memory Formation
Directory of Open Access Journals (Sweden)
Ying Tan
2013-09-01
Full Text Available Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNAi approach. Interfering with β-catenin expression in adult mushroom body neurons specifically impaired long-term memory (LTM without altering short-term memory. The impairment was reversible, being rescued by expression of a wild-type β-catenin transgene, and correlated with disruption of a cellular LTM trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt coreceptor, also impaired LTM. Wingless expression in wild-type flies was transiently elevated in the brain after LTM conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in adult mushroom bodies impairs LTM, indicating that this pathway mechanistically underlies this specific form of memory.
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Mathiasen, Paula; Premoli, Andrea C
2016-06-01
Current climate change affects the competitive ability and reproductive success of many species, leading to local extinctions, adjustment to novel local conditions by phenotypic plasticity or rapid adaptation, or tracking their optima through range shifts. However, many species have limited ability to expand to suitable areas. Altitudinal gradients, with abrupt changes in abiotic conditions over short distances, represent "natural experiments" for the evaluation of ecological and evolutionary responses under scenarios of climate change. Nothofagus pumilio is the tree species which dominates as pure stands the montane forests of Patagonia. We evaluated the adaptive value of variation in quantitative traits of N. pumilio under contrasting conditions of the altitudinal gradient with a long-term reciprocal transplant experimental design. While high-elevation plants show little response in plant, leaf, and phenological traits to the experimental trials, low-elevation ones show greater plasticity in their responses to changing environments, particularly at high elevation. Our results suggest a relatively reduced potential for evolutionary adaptation of high-elevation genotypes, and a greater evolutionary potential of low-elevation ones. Under global warming scenarios of forest upslope migration, high-elevation variants may be outperformed by low-elevation ones during this process, leading to the local extinction and/or replacement of these genotypes. These results challenge previous models and predictions expected under global warming for altitudinal gradients, on which the leading edge is considered to be the upper treeline forests.
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Directory of Open Access Journals (Sweden)
Li Jian
2015-09-01
Full Text Available The dynamic strength and accumulated plastic strain are two important parameters for evaluating the dynamic response of soil. As a special clay, the remolded red clay is often used as the high speed railway subgrade filling, but studies on its dynamic characteristics are few. For a thorough analysis of the suitability of the remolded red clay as the subgrade filling, a series of long-term cyclic load triaxial test under different load histories are carried out. Considering the influence of compactness, confining pressure, consolidation ratio, vibration frequency and dynamic load to the remolded red clay dynamic property, the tests obtain the development curves of the dynamic strength and accumulated plastic strain under different test conditions. Then, through curve fitting method, two different hyperbolic models respectively for the dynamic strength and accumulated plastic strain are built, which can match the test datum well. By applying the dynamic strength model, the critical dynamic strength of the remolded red clay are gained. Meanwhile, for providing basic datum and reference for relevant projects, all key parameters for the dynamic strength and accumulated plastic strain of the remolded red clay are given in the paper.
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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.
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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.
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A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus.
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.
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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
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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
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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 ...
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Loss of long-term depression in the insular cortex after tail amputation in adult mice.
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.
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Virtual Models of Long-Term Care
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…
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Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation*
Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert
2016-01-01
Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein
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Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation.
Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert; Michaelevski, Izhak
2016-02-01
Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein
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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.
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Directory of Open Access Journals (Sweden)
Chelsea M Rochman
Full Text Available Concerns regarding plastic debris and its ability to accumulate large concentrations of priority pollutants in the aquatic environment led us to quantify relationships between different types of mass-produced plastic and metals in seawater. At three locations in San Diego Bay, we measured the accumulation of nine targeted metals (aluminum, chromium, manganese, iron, cobalt, nickel, zinc, cadmium and lead sampling at 1, 3, 6, 9 and 12 months, to five plastic types: polyethylene terephthalate (PET, high-density polyethylene (HDPE, polyvinyl chloride (PVC, low-density polyethylene (LDPE, and polypropylene (PP. Accumulation patterns were not consistent over space and time, and in general all types of plastic tended to accumulate similar concentrations of metals. When we did observe significant differences among concentrations of metals at a single sampling period or location in San Diego Bay, we found that HDPE typically accumulated lesser concentrations of metals than the other four polymers. Furthermore, over the 12-month study period, concentrations of all metals increased over time, and chromium, manganese, cobalt, nickel, zinc and lead did not reach saturation on at least one plastic type during the entire 12-month exposure. This suggests that plastic debris may accumulate greater concentrations of metals the longer it remains at sea. Overall, our work shows that a complex mixture of metals, including those listed as priority pollutants by the US EPA (Cd, Ni, Zn and Pb, can be found on plastic debris composed of various plastic types.
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Rochman, Chelsea M; Hentschel, Brian T; Teh, Swee J
2014-01-01
Concerns regarding plastic debris and its ability to accumulate large concentrations of priority pollutants in the aquatic environment led us to quantify relationships between different types of mass-produced plastic and metals in seawater. At three locations in San Diego Bay, we measured the accumulation of nine targeted metals (aluminum, chromium, manganese, iron, cobalt, nickel, zinc, cadmium and lead) sampling at 1, 3, 6, 9 and 12 months, to five plastic types: polyethylene terephthalate (PET), high-density polyethylene (HDPE), polyvinyl chloride (PVC), low-density polyethylene (LDPE), and polypropylene (PP). Accumulation patterns were not consistent over space and time, and in general all types of plastic tended to accumulate similar concentrations of metals. When we did observe significant differences among concentrations of metals at a single sampling period or location in San Diego Bay, we found that HDPE typically accumulated lesser concentrations of metals than the other four polymers. Furthermore, over the 12-month study period, concentrations of all metals increased over time, and chromium, manganese, cobalt, nickel, zinc and lead did not reach saturation on at least one plastic type during the entire 12-month exposure. This suggests that plastic debris may accumulate greater concentrations of metals the longer it remains at sea. Overall, our work shows that a complex mixture of metals, including those listed as priority pollutants by the US EPA (Cd, Ni, Zn and Pb), can be found on plastic debris composed of various plastic types.
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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.
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[Involvement of aquaporin-4 in synaptic plasticity, learning and memory].
Wu, Xin; Gao, Jian-Feng
2017-06-25
Aquaporin-4 (AQP-4) is the predominant water channel in the central nervous system (CNS) and primarily expressed in astrocytes. Astrocytes have been generally believed to play important roles in regulating synaptic plasticity and information processing. However, the role of AQP-4 in regulating synaptic plasticity, learning and memory, cognitive function is only beginning to be investigated. It is well known that synaptic plasticity is the prime candidate for mediating of learning and memory. Long term potentiation (LTP) and long term depression (LTD) are two forms of synaptic plasticity, and they share some but not all the properties and mechanisms. Hippocampus is a part of limbic system that is particularly important in regulation of learning and memory. This article is to review some research progresses of the function of AQP-4 in synaptic plasticity, learning and memory, and propose the possible role of AQP-4 as a new target in the treatment of cognitive dysfunction.
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Wang, Laiyuan; Wang, Zhiyong; Lin, Jinyi; Yang, Jie; Xie, Linghai; Yi, Mingdong; Li, Wen; Ling, Haifeng; Ou, Changjin; Huang, Wei
2016-10-01
Most simulations of neuroplasticity in memristors, which are potentially used to develop artificial synapses, are confined to the basic biological Hebbian rules. However, the simplex rules potentially can induce excessive excitation/inhibition, even collapse of neural activities, because they neglect the properties of long-term homeostasis involved in the frameworks of realistic neural networks. Here, we develop organic CuPc-based memristors of which excitatory and inhibitory conductivities can implement both Hebbian rules and homeostatic plasticity, complementary to Hebbian patterns and conductive to the long-term homeostasis. In another adaptive situation for homeostasis, in thicker samples, the overall excitement under periodic moderate stimuli tends to decrease and be recovered under intense inputs. Interestingly, the prototypes can be equipped with bio-inspired habituation and sensitization functions outperforming the conventional simplified algorithms. They mutually regulate each other to obtain the homeostasis. Therefore, we develop a novel versatile memristor with advanced synaptic homeostasis for comprehensive neural functions.
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Concept for a hyperspectral remote sensing algorithm for floating marine macro plastics
Goddijn-Murphy, Lonneke; Peters, Steef; van Sebille, Erik; James, Neil A.; Gibb, Stuart
2018-01-01
There is growing global concern over the chemical, biological and ecological impact of plastics in the ocean. Remote sensing has the potential to provide long-term, global monitoring but for marine plastics it is still in its early stages. Some progress has been made in hyperspectral remote sensing
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Exogenous glutamate induces short and long-term potentiation in the rat medial vestibular nuclei.
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.
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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.
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BDNF Regains Function in Hippocampal Long-Term Potentiation Deficits Caused by Diencephalic Damage
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…
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Short-term plasticity in auditory cognition.
Jääskeläinen, Iiro P; Ahveninen, Jyrki; Belliveau, John W; Raij, Tommi; Sams, Mikko
2007-12-01
Converging lines of evidence suggest that auditory system short-term plasticity can enable several perceptual and cognitive functions that have been previously considered as relatively distinct phenomena. Here we review recent findings suggesting that auditory stimulation, auditory selective attention and cross-modal effects of visual stimulation each cause transient excitatory and (surround) inhibitory modulations in the auditory cortex. These modulations might adaptively tune hierarchically organized sound feature maps of the auditory cortex (e.g. tonotopy), thus filtering relevant sounds during rapidly changing environmental and task demands. This could support auditory sensory memory, pre-attentive detection of sound novelty, enhanced perception during selective attention, influence of visual processing on auditory perception and longer-term plastic changes associated with perceptual learning.
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NF-κB p50 subunit knockout impairs late LTP and alters long term memory in the mouse hippocampus
Directory of Open Access Journals (Sweden)
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.
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Nunney, Leonard
2016-01-01
Human-induced habitat loss and fragmentation constrains the range of many species, making them unable to respond to climate change by moving. For such species to avoid extinction, they must respond with some combination of phenotypic plasticity and genetic adaptation. Haldane's "cost of natural selection" limits the rate of adaptation, but, although modeling has shown that in very large populations long-term adaptation can be maintained at rates substantially faster than Haldane's suggested limit, maintaining large populations is often an impossibility, so phenotypic plasticity may be crucial in enhancing the long-term survival of small populations. The potential importance of plasticity is in "buying time" for populations subject to directional environmental change: if genotypes can encompass a greater environmental range, then populations can maintain high fitness for a longer period of time. Alternatively, plasticity could be detrimental by lessening the effectiveness of natural selection in promoting genetic adaptation. Here, I modeled a directionally changing environment in which a genotype's adaptive phenotypic plasticity is centered around the environment where its fitness is highest. Plasticity broadens environmental tolerance and, provided it is not too costly, is favored by natural selection. However, a paradoxical result of the individually advantageous spread of plasticity is that, unless the adaptive trait is determined by very few loci, the long-term extinction risk of a population increases. This effect reflects a conflict between the short-term individual benefit of plasticity and a long-term detriment to population persistence, adding to the multiple threats facing small populations under conditions of climate change. © The American Genetic Association. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Transfer of a cold atmospheric pressure plasma jet through a long flexible plastic tube
International Nuclear Information System (INIS)
Kostov, Konstantin G; Prysiazhnyi, Vadym; Honda, Roberto Y; Machida, Munemasa
2015-01-01
This work proposes an experimental configuration for the generation of a cold atmospheric pressure plasma jet at the downstream end of a long flexible plastic tube. The device consists of a cylindrical dielectric chamber where an insulated metal rod that serves as high-voltage electrode is inserted. The chamber is connected to a long (up to 4 m) commercial flexible plastic tube, equipped with a thin floating Cu wire. The wire penetrates a few mm inside the discharge chamber, passes freely (with no special support) along the plastic tube and terminates a few millimeters before the tube end. The system is flushed with Ar and the dielectric barrier discharge (DBD) is ignited inside the dielectric chamber by a low frequency ac power supply. The gas flow is guided by the plastic tube while the metal wire, when in contact with the plasma inside the DBD reactor, acquires plasma potential. There is no discharge inside the plastic tube, however an Ar plasma jet can be extracted from the downstream tube end. The jet obtained by this method is cold enough to be put in direct contact with human skin without an electric shock. Therefore, by using this approach an Ar plasma jet can be generated at the tip of a long plastic tube far from the high-voltage discharge region, which provides the safe operation conditions and device flexibility required for medical treatment. (paper)
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Induction of synaptic long-term potentiation after opioid withdrawal.
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.
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Directory of Open Access Journals (Sweden)
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.
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Long-term variability of the thunderstorm and hail potential in Europe
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
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Directory of Open Access Journals (Sweden)
Yiu Chung Tse
Full Text Available Stress exerts a profound impact on learning and memory, in part, through the actions of adrenal corticosterone (CORT on synaptic plasticity, a cellular model of learning and memory. Increasing findings suggest that CORT exerts its impact on synaptic plasticity by altering the functional properties of glutamate receptors, which include changes in the motility and function of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype of glutamate receptor (AMPAR that are responsible for the expression of synaptic plasticity. Here we provide evidence that CORT could also regulate synaptic plasticity by modulating the function of synaptic N-methyl-D-aspartate receptors (NMDARs, which mediate the induction of synaptic plasticity. We found that stress level CORT applied to adult rat hippocampal slices potentiated evoked NMDAR-mediated synaptic responses within 30 min. Surprisingly, following this fast-onset change, we observed a slow-onset (>1 hour after termination of CORT exposure increase in synaptic expression of GluN2A-containing NMDARs. To investigate the consequences of the distinct fast- and slow-onset modulation of NMDARs for synaptic plasticity, we examined the formation of long-term potentiation (LTP and long-term depression (LTD within relevant time windows. Paralleling the increased NMDAR function, both LTP and LTD were facilitated during CORT treatment. However, 1-2 hours after CORT treatment when synaptic expression of GluN2A-containing NMDARs is increased, bidirectional plasticity was no longer facilitated. Our findings reveal the remarkable plasticity of NMDARs in the adult hippocampus in response to CORT. CORT-mediated slow-onset increase in GluN2A in hippocampal synapses could be a homeostatic mechanism to normalize synaptic plasticity following fast-onset stress-induced facilitation.
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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.
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Kojima, Nobuhiko; Borlikova, Gilyana; Sakamoto, Toshiro; Yamada, Kazuyuki; Ikeda, Toshio; Itohara, Shigeyoshi; Niki, Hiroaki; Endo, Shogo
2008-06-18
Long-lasting neuronal plasticity as well as long-term memory (LTM) requires de novo synthesis of proteins through dynamic regulation of gene expression. cAMP-responsive element (CRE)-mediated gene transcription occurs in an activity-dependent manner and plays a pivotal role in neuronal plasticity and LTM in a variety of species. To study the physiological role of inducible cAMP early repressor (ICER), a CRE-mediated gene transcription repressor, in neuronal plasticity and LTM, we generated two types of ICER mutant mice: ICER-overexpressing (OE) mice and ICER-specific knock-out (KO) mice. Both ICER-OE and ICER-KO mice show no apparent abnormalities in their development and reproduction. A comprehensive battery of behavioral tests revealed no robust changes in locomotor activity, sensory and motor functions, and emotional responses in the mutant mice. However, long-term conditioned fear memory was attenuated in ICER-OE mice and enhanced in ICER-KO mice without concurrent changes in short-term fear memory. Furthermore, ICER-OE mice exhibited retardation of kindling development, whereas ICER-KO mice exhibited acceleration of kindling. These results strongly suggest that ICER negatively regulates the neuronal processes required for long-term fear memory and neuronal plasticity underlying kindling epileptogenesis, possibly through suppression of CRE-mediated gene transcription.
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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).
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Near-Term Actions to Address Long-Term Climate Risk
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.
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Narp regulates long-term aversive effects of morphine withdrawal
Reti, Irving M.; Crombag, Hans S.; Takamiya, Kogo; Sutton, Jeffrey M.; Guo, Ning; Dinenna, Megan L.; Huganir, Richard L.; Holland, Peter C.; Baraban, Jay M.
2008-01-01
Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. As Narp is an immediate early gene product that is secreted at synaptic sites and binds to AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, we found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, we evaluated whether long-term aversive effects of morphine withdrawal are altered in Narp KO mice. We found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than WT controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. PMID:18729628
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BDNF Variants May Modulate Long-Term Visual Memory Performance in a Healthy Cohort.
Avgan, Nesli; Sutherland, Heidi G; Spriggens, Lauren K; Yu, Chieh; Ibrahim, Omar; Bellis, Claire; Haupt, Larisa M; Shum, David H K; Griffiths, Lyn R
2017-03-17
Brain-derived neurotrophic factor (BDNF) is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265) and long-term visual memory ( p -value = 0.003) in a small cohort ( n = 181) comprised of healthy individuals who had been phenotyped for various aspects of memory function. In this study, we have extended the cohort to 597 individuals and examined multiple genetic variants across both the BDNF and BDNF-AS genes for association with visual memory performance as assessed by the Wechsler Memory Scale-Fourth Edition subtests Visual Reproduction I and II (VR I and II). VR I assesses immediate visual memory, whereas VR II assesses long-term visual memory. Genetic association analyses were performed for 34 single nucleotide polymorphisms genotyped on Illumina OmniExpress BeadChip arrays with the immediate and long-term visual memory phenotypes. While none of the BDNF and BDNF-AS variants were shown to be significant for immediate visual memory, we found 10 variants (including the Val66Met polymorphism ( p -value = 0.006)) that were nominally associated, and three variants (two variants in BDNF and one variant in the BDNF-AS locus) that were significantly associated with long-term visual memory. Our data therefore suggests a potential role for BDNF , and its anti-sense transcript BDNF-AS , in long-term visual memory performance.
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BDNF Variants May Modulate Long-Term Visual Memory Performance in a Healthy Cohort
Directory of Open Access Journals (Sweden)
Nesli Avgan
2017-03-01
Full Text Available Brain-derived neurotrophic factor (BDNF is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265 and long-term visual memory (p-value = 0.003 in a small cohort (n = 181 comprised of healthy individuals who had been phenotyped for various aspects of memory function. In this study, we have extended the cohort to 597 individuals and examined multiple genetic variants across both the BDNF and BDNF-AS genes for association with visual memory performance as assessed by the Wechsler Memory Scale—Fourth Edition subtests Visual Reproduction I and II (VR I and II. VR I assesses immediate visual memory, whereas VR II assesses long-term visual memory. Genetic association analyses were performed for 34 single nucleotide polymorphisms genotyped on Illumina OmniExpress BeadChip arrays with the immediate and long-term visual memory phenotypes. While none of the BDNF and BDNF-AS variants were shown to be significant for immediate visual memory, we found 10 variants (including the Val66Met polymorphism (p-value = 0.006 that were nominally associated, and three variants (two variants in BDNF and one variant in the BDNF-AS locus that were significantly associated with long-term visual memory. Our data therefore suggests a potential role for BDNF, and its anti-sense transcript BDNF-AS, in long-term visual memory performance.
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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.
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Hu, Zhonghua; Yu, Danni; Gu, Qin-Hua; Yang, Yanqin; Tu, Kang; Zhu, Jun; Li, Zheng
2014-02-01
Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.
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Directory of Open Access Journals (Sweden)
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.
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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.
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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
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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.
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Tracking Plasticity: Effects of Long-Term Rehearsal in Expert Dancers Encoding Music to Movement
Bar, Rachel J.; DeSouza, Joseph F. X.
2016-01-01
Our knowledge of neural plasticity suggests that neural networks show adaptation to environmental and intrinsic change. In particular, studies investigating the neuroplastic changes associated with learning and practicing motor tasks have shown that practicing such tasks results in an increase in neural activation in several specific brain regions. However, studies comparing experts and non-experts suggest that experts employ less neuronal activation than non-experts when performing a familiar motor task. Here, we aimed to determine the long-term changes in neural networks associated with learning a new dance in professional ballet dancers over 34 weeks. Subjects visualized dance movements to music while undergoing fMRI scanning at four time points over 34-weeks. Results demonstrated that initial learning and performance at seven weeks led to increases in activation in cortical regions during visualization compared to the first week. However, at 34 weeks, the cortical networks showed reduced activation compared to week seven. Specifically, motor learning and performance over the 34 weeks showed the typical inverted-U-shaped function of learning. Further, our result demonstrate that learning of a motor sequence of dance movements to music in the real world can be visualized by expert dancers using fMRI and capture highly significant modeled fits of the brain network variance of BOLD signals from early learning to expert level performance. PMID:26824475
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Nicotinic mechanisms influencing synaptic plasticity in the hippocampus
Institute of Scientific and Technical Information of China (English)
Andon Nicholas PLACZEK; Tao A ZHANG; John Anthony DANI
2009-01-01
Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the hippocampus, and nicotinic signaling plays an important role in neuronal function. In the context of learning and memory related behaviors associated with hippocampal function, a potentially significant feature of nAChR activity is the impact it has on synaptic plasticity. Synaptic plasticity in hippocampal neurons has long been considered a contributing cellular mechanism of learning and memory. These same kinds of cellular mechanisms are a factor in the development of nicotine addiction. Nicotinic signaling has been demonstrated by in vitro studies to affect synaptic plasticity in hippocampal neurons via multiple steps, and the signaling has also been shown to evoke synaptic plasticity in vivo. This review focuses on the nAChRs subtypes that contribute to hippocampal synaptic plasticity at the cellular and circuit level. It also considers nicotinic influences over long-term changes in the hippocampus that may contribute to addiction.
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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.
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Intelligent power wheelchair use in long-term care: potential users' experiences and perceptions.
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.
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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
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Development of an evaluation method for long-term sealability of the spent fuel storage cask
International Nuclear Information System (INIS)
Kato, Osamu; Ito, Chihiro; Saegusa, Toshiari
1996-01-01
One of the characteristics of the cask storage method of spent fuel is that containment of radioactive materials is assured by the storage cask itself. Thus, the seal structure of the cask is designed to have a highly reliable multi-barrier system using metallic gaskets instead of the conventional rubber gaskets. Although, it has been reported that the containment feature of the metallic gaskets is influenced by the plastic deformation and stress relaxation of the gaskets for a short-term usage, no research report has been published on the containment feature of the metallic gaskets for a long-term usage. In this paper, the stress relaxation features of the metallic gaskets is investigated which will directly influence the long-term sealability of the storage cask, at first. Next, the relationship between the temperature/time dependence of the plastic deformation and the containment features of the metallic gaskets. Finally, an evaluation method of the long-term sealability from experimental data of a short-term behavior of the metallic gaskets is proposed. (author)
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Developmental plasticity and its relevance to assisted human reproduction
Roseboom, Tessa J.
2018-01-01
The advent of assisted reproduction has allowed the conception of millions of individuals who otherwise would not have existed. Although most ART children are born healthy, there is increasing awareness of the plasticity of the human embryo causing concerns about potential long-term consequences of
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Energy Technology Data Exchange (ETDEWEB)
Hagiwara, N.; Masuda, T.; Oguchi, N. [Tokyo Gas Co., Ltd. (Japan)
2000-07-01
For upgrading long-term integrity of transmission pipelines, two types of delayed fracture in regions of mechanical damage in pipelines were investigated. Experimental and numerical studies clarified factors affecting the fatigue behavior of line pipes containing an idealized flaw under fluctuating internal pressure. To investigate fatigue cracking at mechanical damage in pipelines, degradation of fracture toughness and fatigue properties due to plastic pre-strain was also evaluated. A fracture mechanics-based study revealed conditions necessarily for initiation of hydrogen stress cracking (HSC) at a surface defect in line pipes under cathodic protection. (authors)
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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.
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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.
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Research of long-term mechanical displaced behavior of soft rock
International Nuclear Information System (INIS)
Inoue, Hiroyuki; Minami, Kosuke
2003-01-01
When it thinks about a stratum disposition system of high-level radioactive waste, it is important to evaluate the long-term mechanical displaced behavior of the near field bedrock which is boundary condition of the engineered barrier that should be evaluated based on the reality. In this research, three following examination was carried out for reliability improvement of long-term dynamic deformation behavior estimate. 1) We evaluated the sedimentary rock of Horonobe where we used Okubo model as while changing hydraulic condition and temperature condition. 2) We carried out the model experiment that inner pressure acted on in order to grasp a movement of near field bedrock. 3) We examined model to evaluate that. As a result, the following things were provided. 1) Sedimentary rock of Horonobe is easy to cause strength degradation for being wet and dry cycles. When the rock is saturated after drying, it is broken along potential cracking. The rock reacts for a change of moisture content sensitively. In addition, a variation of the strength occurs in a little depth remainder. This diffuseness gave the strong influence on failure time. 2) Big plastic deformation may not do elasto-plasticity behavior according to theory for stress modification of rock mass. 3) We think with one of the factor that it produces remainder in prediction and real creep hour that these is as 'm = n (conatnt of Okubo model)' simply. Therefore we collect data after peak, and it is necessary to grasp 'm/n'. In addition, it is necessary to improve 'n' in the model which we can change by environment and stress state on the way. (author)
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Directory of Open Access Journals (Sweden)
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.
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Plasticity resembling spike-timing dependent synaptic plasticity: the evidence in human cortex
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Florian Müller-Dahlhaus
2010-07-01
Full Text Available Spike-timing dependent plasticity (STDP has been studied extensively in a variety of animal models during the past decade but whether it can be studied at the systems level of the human cortex has been a matter of debate. Only recently newly developed non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS have made it possible to induce and assess timing dependent plasticity in conscious human subjects. This review will present a critical synopsis of these experiments, which suggest that several of the principal characteristics and molecular mechanisms of TMS-induced plasticity correspond to those of STDP as studied at a cellular level. TMS combined with a second phasic stimulation modality can induce bidirectional long-lasting changes in the excitability of the stimulated cortex, whose polarity depends on the order of the associated stimulus-evoked events within a critical time window of tens of milliseconds. Pharmacological evidence suggests an NMDA receptor mediated form of synaptic plasticity. Studies in human motor cortex demonstrated that motor learning significantly modulates TMS-induced timing dependent plasticity, and, conversely, may be modulated bidirectionally by prior TMS-induced plasticity, providing circumstantial evidence that long-term potentiation-like mechanisms may be involved in motor learning. In summary, convergent evidence is being accumulated for the contention that it is now possible to induce STDP-like changes in the intact human central nervous system by means of TMS to study and interfere with synaptic plasticity in neural circuits in the context of behaviour such as learning and memory.
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Osinga, Rik; Babst, Doris; Bodmer, Elvira S; Link, Bjoern C; Fritsche, Elmar; Hug, Urs
2017-12-01
This work assessed both subjective and objective postoperative parameters after breast reduction surgery and compared between patients and plastic surgeons. After an average postoperative observation period of 6.7 ± 2.7 (2 - 13) years, 159 out of 259 patients (61 %) were examined. The mean age at the time of surgery was 37 ± 14 (15 - 74) years. The postoperative anatomy of the breast and other anthropometric parameters were measured in cm with the patient in an upright position. The visual analogue scale (VAS) values for symmetry, size, shape, type of scar and overall satisfaction both from the patient's and from four plastic surgeons' perspectives were assessed and compared. Patients rated the postoperative result significantly better than surgeons. Good subjective ratings by patients for shape, symmetry and sensitivity correlated with high scores for overall assessment. Shape had the strongest influence on overall satisfaction (regression coefficient 0.357; p reduction surgery, long-term outcome is rated significantly better by patients than by plastic surgeons. Good subjective ratings by patients for shape, symmetry and sensitivity correlated with high scores for overall assessment. Shape had the strongest influence on overall satisfaction, followed by symmetry and sensitivity of the breast. Postoperative size of the breast, resection weight, type of scar, age or BMI was not of significant influence. Symmetry was the only assessed subjective parameter of this study that could be objectified by postoperative measurements. Georg Thieme Verlag KG Stuttgart · New York.
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Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity
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
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Long-term antibiotic delivery by chitosan-based composite coatings with bone regenerative potential
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.
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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
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Anti-Hebbian long-term potentiation in the hippocampal feedback inhibitory circuit.
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.
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Grassi, S; Malfagia, C; Pettorossi, V E
1998-11-01
In rat brainstem slices, we investigated the possible role of metabotropic glutamate receptors in modulating the synaptic transmission within the medial vestibular nuclei, under basal and plasticity inducing conditions. We analysed the effect of the metabotropic glutamate receptor antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine on the amplitude of the field potentials and latency of unitary potentials evoked in the ventral portion of the medial vestibular nuclei by primary vestibular afferent stimulation, and on the induction and maintenance of long-term potentiation, after high-frequency stimulation. Two effects were observed, consisting of a slight increase of the field potentials and reduction of unit latency during the drug infusion, and a further long-lasting development of these modifications after the drug wash-out. The long-term effect depended on N-methyl-D-aspartate receptor activation, as D,L-2-amino-5-phosphonopentanoic acid prevented its development. We suggest that (R,S)-alpha-methyl-4carboxyphenylglycine enhances the vestibular responses and induces N-methyl-D-aspartate-dependent long-term potentiation by increasing glutamate release, through the block of presynaptic metabotropic glutamate receptors which actively inhibit it. The block of these receptors was indirectly supported by the fact that the agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid reduced the vestibular responses and blocked the induction of long-term potentiation by high-frequency stimulation. The simultaneous block of metabotropic glutamate receptors facilitating synaptic plasticity, impedes the full expression of the long-term effect throughout the (R,S)-alpha-methyl-4-carboxyphenylglycine infusion. The involvement of such a facilitatory mechanism in the potentiation is supported by its reversible reduction following a second (R,S)-alpha-methyl-4-carboxyphenylglycine infusion. The drug also reduced the expression of potentiation induced by high-frequency stimulation
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Late protein synthesis-dependent phases in CTA long-term memory: BDNF requirement
Directory of Open Access Journals (Sweden)
Araceli eMartínez-Moreno
2011-09-01
Full Text Available 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 memory when protein synthesis was inhibited. Our previous studies on the insular cortex (IC, a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA, have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis dependent in different time-windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 hours after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes.
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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.
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Presynaptic protein synthesis required for NT-3-induced long-term synaptic modulation
Directory of Open Access Journals (Sweden)
Je H
2011-01-01
Full Text Available Abstract Background Neurotrophins elicit both acute and long-term modulation of synaptic transmission and plasticity. Previously, we demonstrated that the long-term synaptic modulation requires the endocytosis of neurotrophin-receptor complex, the activation of PI3K and Akt, and mTOR mediated protein synthesis. However, it is unclear whether the long-term synaptic modulation by neurotrophins depends on protein synthesis in pre- or post-synaptic cells. Results Here we have developed an inducible protein translation blocker, in which the kinase domain of protein kinase R (PKR is fused with bacterial gyrase B domain (GyrB-PKR, which could be dimerized upon treatment with a cell permeable drug, coumermycin. By genetically targeting GyrB-PKR to specific cell types, we show that NT-3 induced long-term synaptic modulation requires presynaptic, but not postsynaptic protein synthesis. Conclusions Our results provide mechanistic insights into the cell-specific requirement for protein synthesis in the long-term synaptic modulation by neurotrophins. The GyrB-PKR system may be useful tool to study protein synthesis in a cell-specific manner.
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Short-term ionic plasticity at GABAergic synapses
Directory of Open Access Journals (Sweden)
Joseph Valentino Raimondo
2012-10-01
Full Text Available Fast synaptic inhibition in the brain is mediated by the pre-synaptic release of the neurotransmitter γ-Aminobutyric acid (GABA and the post-synaptic activation of GABA-sensitive ionotropic receptors. As with excitatory synapses, it is being increasinly appreciated that a variety of plastic processes occur at inhibitory synapses, which operate over a range of timescales. Here we examine a form of activity-dependent plasticity that is somewhat unique to GABAergic transmission. This involves short-lasting changes to the ionic driving force for the postsynaptic receptors, a process referred to as short-term ionic plasticity. These changes are directly related to the history of activity at inhibitory synapses and are influenced by a variety of factors including the location of the synapse and the post-synaptic cell’s ion regulation mechanisms. We explore the processes underlying this form of plasticity, when and where it can occur, and how it is likely to impact network activity.
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Directory of Open Access Journals (Sweden)
James W Grau
2014-09-01
Full Text Available Research has shown that spinal circuits have the capacity to adapt in response to training, nociceptive stimulation and peripheral inflammation. These changes in neural function are mediated by physiological and neurochemical systems analogous to those that support plasticity within the hippocampus (e.g., long-term potentiation and the NMDA receptor. As observed in the hippocampus, engaging spinal circuits can have a lasting impact on plastic potential, enabling or inhibiting the capacity to learn. These effects are related to the concept of metaplasticity. Behavioral paradigms are described that induce metaplastic effects within the spinal cord. Uncontrollable/unpredictable stimulation, and peripheral inflammation, induce a form of maladaptive plasticity that inhibits spinal learning. Conversely, exposure to controllable or predictable stimulation engages a form of adaptive plasticity that counters these maladaptive effects and enables learning. Adaptive plasticity is tied to an up-regulation of brain derived neurotrophic factor (BDNF. Maladaptive plasticity is linked to processes that involve kappa opioids, the metabotropic glutamate (mGlu receptor, glia, and the cytokine tumor necrosis factor (TNF. Uncontrollable nociceptive stimulation also impairs recovery after a spinal contusion injury and fosters the development of pain (allodynia. These adverse effects are related to an up-regulation of TNF and a down-regulation of BDNF and its receptor (TrkB. In the absence of injury, brain systems quell the sensitization of spinal circuits through descending serotonergic fibers and the serotonin 1A (5HT 1A receptor. This protective effect is blocked by surgical anesthesia. Disconnected from the brain, intracellular Cl- concentrations increase (due to a down-regulation of the cotransporter KCC2, which causes GABA to have an excitatory effect. It is suggested that BDNF has a restorative effect because it up-regulates KCC2 and re-establishes GABA
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Devaraju, P; Yu, J; Eddins, D; Mellado-Lagarde, M M; Earls, L R; Westmoreland, J J; Quarato, G; Green, D R; Zakharenko, S S
2017-09-01
Hemizygous deletion of a 1.5- to 3-megabase region on chromosome 22 causes 22q11.2 deletion syndrome (22q11DS), which constitutes one of the strongest genetic risks for schizophrenia. Mouse models of 22q11DS have abnormal short-term synaptic plasticity that contributes to working-memory deficiencies similar to those in schizophrenia. We screened mutant mice carrying hemizygous deletions of 22q11DS genes and identified haploinsufficiency of Mrpl40 (mitochondrial large ribosomal subunit protein 40) as a contributor to abnormal short-term potentiation (STP), a major form of short-term synaptic plasticity. Two-photon imaging of the genetically encoded fluorescent calcium indicator GCaMP6, expressed in presynaptic cytosol or mitochondria, showed that Mrpl40 haploinsufficiency deregulates STP via impaired calcium extrusion from the mitochondrial matrix through the mitochondrial permeability transition pore. This led to abnormally high cytosolic calcium transients in presynaptic terminals and deficient working memory but did not affect long-term spatial memory. Thus, we propose that mitochondrial calcium deregulation is a novel pathogenic mechanism of cognitive deficiencies in schizophrenia.
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Long-term performance potential of concentrated photovoltaic (CPV) systems
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
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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...
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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.
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Rocchetti, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; Tronche, François; Levesque, Daniel; Moquin, Luc; Gratton, Alain; Wong, Tak Pan; Rubinstein, Marcelo; Giros, Bruno
2015-03-15
Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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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.
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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...
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Directory of Open Access Journals (Sweden)
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.
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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.
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Auditory-Cortex Short-Term Plasticity Induced by Selective Attention
Jääskeläinen, Iiro P.; Ahveninen, Jyrki
2014-01-01
The ability to concentrate on relevant sounds in the acoustic environment is crucial for everyday function and communication. Converging lines of evidence suggests that transient functional changes in auditory-cortex neurons, “short-term plasticity”, might explain this fundamental function. Under conditions of strongly focused attention, enhanced processing of attended sounds can take place at very early latencies (~50 ms from sound onset) in primary auditory cortex and possibly even at earlier latencies in subcortical structures. More robust selective-attention short-term plasticity is manifested as modulation of responses peaking at ~100 ms from sound onset in functionally specialized nonprimary auditory-cortical areas by way of stimulus-specific reshaping of neuronal receptive fields that supports filtering of selectively attended sound features from task-irrelevant ones. Such effects have been shown to take effect in ~seconds following shifting of attentional focus. There are findings suggesting that the reshaping of neuronal receptive fields is even stronger at longer auditory-cortex response latencies (~300 ms from sound onset). These longer-latency short-term plasticity effects seem to build up more gradually, within tens of seconds after shifting the focus of attention. Importantly, some of the auditory-cortical short-term plasticity effects observed during selective attention predict enhancements in behaviorally measured sound discrimination performance. PMID:24551458
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Li, Wei-Guang; Liu, Ming-Gang; Deng, Shining; Liu, Yan-Mei; Shang, Lin; Ding, Jing; Hsu, Tsan-Ting; Jiang, Qin; Li, Ying; Li, Fei; Zhu, Michael Xi; Xu, Tian-Le
2016-12-07
Acid-sensing ion channel 1a (ASIC1a) has been shown to play important roles in synaptic plasticity, learning and memory. Here we identify a crucial role for ASIC1a in long-term depression (LTD) at mouse insular synapses. Genetic ablation and pharmacological inhibition of ASIC1a reduced the induction probability of LTD without affecting that of long-term potentiation in the insular cortex. The disruption of ASIC1a also attenuated the extinction of established taste aversion memory without altering the initial associative taste learning or its long-term retention. Extinction of taste aversive memory led to the reduced insular synaptic efficacy, which precluded further LTD induction. The impaired LTD and extinction learning in ASIC1a null mice were restored by virus-mediated expression of wild-type ASIC1a, but not its ion-impermeable mutant, in the insular cortices. Our data demonstrate the involvement of an ASIC1a-mediated insular synaptic depression mechanism in extinction learning, which raises the possibility of targeting ASIC1a to manage adaptive behaviours.
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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...
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Mateika, Jason H; Syed, Ziauddin
2013-09-15
This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. Published by Elsevier B.V.
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Mateika, Jason H.; Syed, Ziauddin
2013-01-01
This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. PMID:23587570
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Recycling potential of post-consumer plastic packaging waste in Finland.
Dahlbo, Helena; Poliakova, Valeria; Mylläri, Ville; Sahimaa, Olli; Anderson, Reetta
2018-01-01
Recycling of plastics is urged by the need for closing material loops to maintain our natural resources when striving towards circular economy, but also by the concern raced by observations of plastic scrap in oceans and lakes. Packaging industry is the sector using the largest share of plastics, hence packaging dominates in the plastic waste flow. The aim of this paper was to sum up the recycling potential of post-consumer plastic packaging waste in Finland. This potential was evaluated based on the quantity, composition and mechanical quality of the plastic packaging waste generated by consumers and collected as a source-separated fraction, within the mixed municipal solid waste (MSW) or within energy waste. Based on the assessment 86,000-117,000 tons (18 kg/person/a) of post-consumer plastic packaging waste was generated in Finland in 2014. The majority, 84% of the waste was in the mixed MSW flow in 2014. Due to the launching of new sorting facilities and separate collections for post-consumer plastic packaging in 2016, almost 40% of the post-consumer plastic packaging could become available for recycling. However, a 50% recycling rate for post-consumer plastic packaging (other than PET bottles) would be needed to increase the overall MSW recycling rate from the current 41% by around two percentage points. The share of monotype plastics in the overall MSW plastics fraction was 80%, hence by volume the recycling potential of MSW plastics is high. Polypropylene (PP) and low density polyethylene (LDPE) were the most common plastic types present in mixed MSW, followed by polyethylene terephthalate (PET), polystyrene (PS) and high density polyethylene (HDPE). If all the Finnish plastic packaging waste collected through the three collection types would be available for recycling, then 19,000-25,000 tons of recycled PP and 6000-8000 tons of recycled HDPE would be available on the local market. However, this assessment includes uncertainties due to performing the
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What Legislators Need to Know about Long-Term Care Insurance.
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…
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Long-Term Memory Performance in Adult ADHD.
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.
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Long Term Depression in Rat Hippocampus and the Effect of Ethanol during Fetal Life
Directory of Open Access Journals (Sweden)
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.
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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.
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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.
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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
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Long-term performance potential of concentrated photovoltaic (CPV) systems
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.
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Directory of Open Access Journals (Sweden)
Melanie Hüttenrauch
2016-08-01
Full Text Available There is ample evidence that physical activity exerts positive effects on a variety of brain functions by facilitating neuroprotective processes and influencing neuroplasticity. Accordingly, numerous studies have shown that continuous exercise can successfully diminish or prevent the pathology of neurodegenerative diseases such as Alzheimer’s disease in transgenic mouse models. However, the long-term effect of physical activity on brain health of aging WT mice has not been studied in detail yet. Here, we show that prolonged physical and cognitive stimulation, mediated by an enriched environment (EE paradigm for a duration of eleven months, leads to reduced anxiety and improved spatial reference memory in C57BL6 wildtype (WT mice. While the number of CA1 pyramidal neurons remained unchanged between standard housed (SH and EE mice, the number of dentate gyrus (DG neurons, as well as the CA1 and DG volume were significantly increased in EE mice. A whole-brain deep sequencing transcriptome analysis, carried out to better understand the molecular mechanisms underlying the observed effects, revealed an up-regulation of a variety of genes upon EE, mainly associated with synaptic plasticity and transcription regulation. The present findings corroborate the impact of continuous physical activity as a potential prospective route in the prevention of age-related cognitive decline and neurodegenerative disorders.
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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.
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Abnormal cortical synaptic plasticity in primary motor area in progressive supranuclear palsy.
Conte, Antonella; Belvisi, Daniele; Bologna, Matteo; Ottaviani, Donatella; Fabbrini, Giovanni; Colosimo, Carlo; Williams, David R; Berardelli, Alfredo
2012-03-01
No study has yet investigated whether cortical plasticity in primary motor area (M1) is abnormal in patients with progressive supranuclear palsy (PSP). We studied M1 plasticity in 15 PSP patients and 15 age-matched healthy subjects. We used intermittent theta-burst stimulation (iTBS) to investigate long-term potentiation (LTP) and continuous TBS (cTBS) to investigate long-term depression (LTD)-like cortical plasticity in M1. Ten patients underwent iTBS again 1 year later. We also investigated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in M1 with paired-pulse transcranial magnetic stimulation, tested H reflex from upper limb flexor muscles before and after iTBS, and measured motor evoked potential (MEP) input-output (I/O) curves before and after iTBS. iTBS elicited a significantly larger MEP facilitation after iTBS in patients than in healthy subjects. Whereas in healthy subjects, cTBS inhibited MEP, in patients it significantly facilitated MEPs. In patients, SICI was reduced, whereas ICF was normal. H reflex size remained unchanged after iTBS. Patients had steeper MEP I/O slopes than healthy subjects at baseline and became even more steeper after iTBS only in patients. The iTBS-induced abnormal MEP facilitation in PSP persisted at 1-year follow-up. In conclusion, patients with PSP have abnormal M1 LTP/LTD-like plasticity. The enhanced LTP-like cortical synaptic plasticity parallels disease progression.
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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
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The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex.
Pulimood, Nisha S; Rodrigues, Wandilson Dos Santos; Atkinson, Devon A; Mooney, Sandra M; Medina, Alexandre E
2017-07-12
The transcription factors CREB (cAMP response element binding factor), SRF (serum response factor), and MEF2 (myocyte enhancer factor 2) play critical roles in the mechanisms underlying neuronal plasticity. However, the role of the activation of these transcription factors in the different components of plasticity in vivo is not well known. In this study, we tested the role of CREB, SRF, and MEF2 in ocular dominance plasticity (ODP), a paradigm of activity-dependent neuronal plasticity in the visual cortex. These three proteins bind to the synaptic activity response element (SARE), an enhancer sequence found upstream of many plasticity-related genes (Kawashima et al., 2009; Rodríguez-Tornos et al., 2013), and can act cooperatively to express Arc , a gene required for ODP (McCurry et al., 2010). We used viral-mediated gene transfer to block the transcription function of CREB, SRF, and MEF2 in the visual cortex, and measured visually evoked potentials in awake male and female mice before and after a 7 d monocular deprivation, which allowed us to examine both the depression component (Dc-ODP) and potentiation component (Pc-ODP) of plasticity independently. We found that CREB, SRF, and MEF2 are all required for ODP, but have differential effects on Dc-ODP and Pc-ODP. CREB is necessary for both Dc-ODP and Pc-ODP, whereas SRF and MEF2 are only needed for Dc-ODP. This finding supports previous reports implicating SRF and MEF2 in long-term depression (required for Dc-ODP), and CREB in long-term potentiation (required for Pc-ODP). SIGNIFICANCE STATEMENT Activity-dependent neuronal plasticity is the cellular basis for learning and memory, and it is crucial for the refinement of neuronal circuits during development. Identifying the mechanisms of activity-dependent neuronal plasticity is crucial to finding therapeutic interventions in the myriad of disorders where it is disrupted, such as Fragile X syndrome, Rett syndrome, epilepsy, major depressive disorder, and autism
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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...
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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...
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Plastic surgery improves long-term weight control after bariatric surgery.
Balagué, Nicolas; Combescure, Christophe; Huber, Olivier; Pittet-Cuénod, Brigitte; Modarressi, Ali
2013-10-01
The positive impact of Roux-en-Y gastric bypass on weight, comorbidities, and health-related quality of life is well documented. However, 50 percent of patients regain some of the lost weight after 2 years with Roux-en-Y gastric bypass and present a mean weight regain of 10 to 15 percent after several years, partially losing the previously obtained benefits. The authors hypothesize that body contouring could decrease weight regain, leading to better long-term weight control after Roux-en-Y gastric bypass. In a matched control study, variations in weight for 98 patients with body contouring after Roux-en-Y gastric bypass were compared with those of 102 matched control patients with Roux-en-Y gastric bypass alone. Data were collected prospectively at 1, 3, 6, 9, 12, and 18 months after Roux-en-Y gastric bypass and then yearly until 7 years. After a massive mean weight loss of 45.2 kg during the first 2 years after Roux-en-Y gastric bypass, patients with Roux-en-Y gastric bypass alone presented a higher continuous mean weight regain than those with Roux-en-Y gastric bypass and body contouring (1.78 kg/year versus 0.51 kg/year of weight regain, respectively; p = 0.001). After 7 years, patients with Roux-en-Y gastric bypass presented significantly higher mean weight regain than patients with Roux-en-Y gastric bypass and body contouring (i.e., 10.8 percent versus 3.6 percent mean weight gain, respectively; p weight of 2.04 kg by body contouring, the weight regain was 22.9 kg for patients with Roux-en-Y gastric bypass alone and only 6.2 kg for those with Roux-en-Y gastric bypass and body contouring. The authors demonstrated that patients with body contouring present better long-term weight control after Roux-en-Y gastric bypass. Therefore, body contouring must be considered as a reconstructive operation in the treatment of morbid obesity. Therapeutic, III.
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O'Mara, S M; Commins, S; Anderson, M
2000-01-01
This paper reviews investigations of synaptic plasticity in the major, and underexplored, pathway from hippocampal area CA1 to the subiculum. This brain area is the major synaptic relay for the majority of hippocampal area CA1 neurons, making the subiculum the last relay of the hippocampal formation prior to the cortex. The subiculum thus has a very major role in mediating hippocampal-cortical interactions. We demonstrate that the projection from hippocampal area CA1 to the subiculum sustains plasticity on a number of levels. We show that this pathway is capable of undergoing both long-term potentiation (LTP) and paired-pulse facilitation (PPF, a short-term plastic effect). Although we failed to induce long-term depression (LTD) of this pathway with low-frequency stimulation (LFS) and two-pulse stimulation (TPS), both protocols can induce a "late-developing" potentiation of synaptic transmission. We further demonstrate that baseline synaptic transmission can be dissociated from paired-pulse stimulation of the same pathway; we also show that it is possible, using appropriate protocols, to change PPF to paired-pulse depression, thus revealing subtle and previously undescribed mechanisms which regulate short-term synaptic plasticity. Finally, we successfully recorded from individual subicular units in the freely-moving animal, and provide a description of the characteristics of such neurons in a pellet-chasing task. We discuss the implications of these findings in relation to theories of the biological consolidation of memory.
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Suppression of synaptic plasticity by fullerenol in rat hippocampus in vitro
Directory of Open Access Journals (Sweden)
Wang XX
2016-09-01
Full Text Available Xin-Xing Wang,1,2,* Ying-Ying Zha,3,* Bo Yang,1 Lin Chen,1,2 Ming Wang1,2 1CAS Key Laboratory of Brain Function and Diseases, 2Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 3Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu, Anhui, People’s Republic of China *These authors contributed equally to this work Abstract: Fullerenol, a water-soluble fullerene derivative, has attracted much attention due to its bioactive properties, including the antioxidative properties and free radical scavenging ability. Due to its superior nature, fullerenol represents a promising diagnostic, therapeutic, and protective agent. Therefore, elucidation of the possible side effects of fullerenol is important in determining its potential role. In the present study, we investigated the acute effects of 5 µM fullerenol on synaptic plasticity in hippocampal brain slices of rats. Incubation with fullerenol for 20 minutes significantly decreased the peak of paired-pulse facilitation and long-term potentiation, indicating that fullerenol suppresses the short- and long-term synaptic plasticity of region I of hippocampus. We found that fullerenol depressed the activity and the expression of nitric oxide (NO synthase in hippocampus. In view of the important role of NO in synaptic plasticity, the inhibition of fullerenol on NO synthase may contribute to the suppression of synaptic plasticity. These findings may facilitate the evaluation of the side effects of fullerenol. Keywords: fullerenol, hippocampal slice, nitric oxide synthase, synaptic plasticity, oxidative stress
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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.
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The Chemokine MIP-1α/CCL3 impairs mouse hippocampal synaptic transmission, plasticity and memory.
Marciniak, Elodie; Faivre, Emilie; Dutar, Patrick; Alves Pires, Claire; Demeyer, Dominique; Caillierez, Raphaëlle; Laloux, Charlotte; Buée, Luc; Blum, David; Humez, Sandrine
2015-10-29
Chemokines are signaling molecules playing an important role in immune regulations. They are also thought to regulate brain development, neurogenesis and neuroendocrine functions. While chemokine upsurge has been associated with conditions characterized with cognitive impairments, their ability to modulate synaptic plasticity remains ill-defined. In the present study, we specifically evaluated the effects of MIP1-α/CCL3 towards hippocampal synaptic transmission, plasticity and spatial memory. We found that CCL3 (50 ng/ml) significantly reduced basal synaptic transmission at the Schaffer collateral-CA1 synapse without affecting NMDAR-mediated field potentials. This effect was ascribed to post-synaptic regulations, as CCL3 did not impact paired-pulse facilitation. While CCL3 did not modulate long-term depression (LTD), it significantly impaired long-term potentiation (LTP), an effect abolished by Maraviroc, a CCR5 specific antagonist. In addition, sub-chronic intracerebroventricular (icv) injections of CCL3 also impair LTP. In accordance with these electrophysiological findings, we demonstrated that the icv injection of CCL3 in mouse significantly impaired spatial memory abilities and long-term memory measured using the two-step Y-maze and passive avoidance tasks. These effects of CCL3 on memory were inhibited by Maraviroc. Altogether, these data suggest that the chemokine CCL3 is an hippocampal neuromodulator able to regulate synaptic plasticity mechanisms involved in learning and memory functions.
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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.
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Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement
Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.
2011-01-01
It has been proposed that long-term memory (LTM) 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 LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes. PMID:21960964
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Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement.
Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L
2011-01-01
It has been proposed that long-term memory (LTM) 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 LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes.
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Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D
2016-03-15
Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity. Copyright © 2015 Elsevier B.V. All rights reserved.
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Brain plasticity, memory, and aging: a discussion
Energy Technology Data Exchange (ETDEWEB)
Bennett, E.L.; Rosenzweig, M.R.
1977-12-01
It is generally assumed that memory faculties decline with age. A discussion of the relationship of memory and aging and the possibility of retarding the potential decline is hampered by the fact that no satisfactory explanation of memory is available in either molecular or anatomical terms. However, this lack of description of memory does not mean that there is a lack of suggested mechanisms for long-term memory storage. Present theories of memory usually include first, neurophysiological or electrical events, followed by a series of chemical events which ultimately lead to long-lasting anatomical changes in the brain. Evidence is increasing for the biochemical and anatomical plasticity of the nervous system and its importance in the normal functioning of the brain. Modification of this plasticity may be an important factor in senescence. This discussion reports experiments which indicate that protein synthesis and anatomical changes may be involved in long-term memory storage. Environmental influences can produce quantitative differences in brain anatomy and in behavior. In experimental animals, enriched environments lead to more complex anatomical patterns than do colony or impoverished environments. This raises fundamental questions about the adequacy of the isolated animal which is frequently being used as a model for aging research. A more important applied question is the role of social and intellectual stimulation in influencing aging of the human brain.
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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...
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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,...
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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
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Space ventures and society long-term perspectives
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.
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Endogenous BDNF Is Required for Long-Term Memory Formation in the Rat Parietal Cortex
Alonso, Mariana; Bekinschtein, Pedro, Cammarota, Martin; Vianna, Monica R. M.; Izquierdo, Ivan; Medina, Jorge H.
2005-01-01
Information storage in the brain is a temporally graded process involving different memory phases as well as different structures in the mammalian brain. Cortical plasticity seems to be essential to store stable long-term memories, although little information is available at the moment regarding molecular and cellular events supporting memory…
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Plasticity of cortical excitatory-inhibitory balance.
Froemke, Robert C
2015-07-08
Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior.
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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,…
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Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo
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...
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Da Cunha, Claudio; McKimm, Eric; Da Cunha, Rafael M; Boschen, Suelen L; Redgrave, Peter; Blaha, Charles D
2017-07-15
Repeated electrical stimulation of dopamine (dopamine) fibers can cause variable effects on further dopamine release; sometimes there are short-term decreases while in other cases short-term increases have been reported. Previous studies have failed to discover what factors determine in which way dopamine neurons will respond to repeated stimulation. The aim of the present study was therefore to investigate what determines the direction and magnitude of this particular form of short-term plasticity. Fixed potential amperometry was used to measure dopamine release in the nucleus accumbens in response to two trains of electrical pulses administered to the ventral tegmental area of anesthetized mice. When the pulse trains were of equal magnitude we found that low magnitude stimulation was associated with short-term suppression and high magnitude stimulation with short-term facilitation of dopamine release. Secondly, we found that the magnitude of the second pulse train was critical for determining the sign of the plasticity (suppression or facilitation), while the magnitude of the first pulse train determined the extent to which the response to the second train was suppressed or facilitated. This form of bidirectional plasticity might provide a mechanism to enhance signal-to-noise ratio of dopamine neurotransmission. Copyright © 2017 Elsevier B.V. All rights reserved.
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Epigenetic Basis of Neuronal and Synaptic Plasticity.
Karpova, Nina N; Sales, Amanda J; Joca, Samia R
2017-01-01
Neuronal network and plasticity change as a function of experience. Altered neural connectivity leads to distinct transcriptional programs of neuronal plasticity-related genes. The environmental challenges throughout life may promote long-lasting reprogramming of gene expression and the development of brain disorders. The modifications in neuronal epigenome mediate gene-environmental interactions and are required for activity-dependent regulation of neuronal differentiation, maturation and plasticity. Here, we highlight the latest advances in understanding the role of the main players of epigenetic machinery (DNA methylation and demethylation, histone modifications, chromatin-remodeling enzymes, transposons, and non-coding RNAs) in activity-dependent and long- term neural and synaptic plasticity. The review focuses on both the transcriptional and post-transcriptional regulation of gene expression levels, including the processes of promoter activation, alternative splicing, regulation of stability of gene transcripts by natural antisense RNAs, and alternative polyadenylation. Further, we discuss the epigenetic aspects of impaired neuronal plasticity and the pathogenesis of neurodevelopmental (Rett syndrome, Fragile X Syndrome, genomic imprinting disorders, schizophrenia, and others), stressrelated (mood disorders) and neurodegenerative Alzheimer's, Parkinson's and Huntington's disorders. The review also highlights the pharmacological compounds that modulate epigenetic programming of gene expression, the potential treatment strategies of discussed brain disorders, and the questions that should be addressed during the development of effective and safe approaches for the treatment of brain disorders.
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Low Doses of Ethanol Enhance LTD-like Plasticity in Human Motor Cortex.
Fuhl, Anna; Müller-Dahlhaus, Florian; Lücke, Caroline; Toennes, Stefan W; Ziemann, Ulf
2015-12-01
Humans liberally use ethanol for its facilitating effects on social interactions but its effects on central nervous system function remain underexplored. We have recently described that very low doses of ethanol abolish long-term potentiation (LTP)-like plasticity in human cortex, most likely through enhancement of tonic inhibition [Lücke et al, 2014, Neuropsychopharmacology 39:1508-18]. Here, we studied the effects of low-dose ethanol on long-term depression (LTD)-like plasticity. LTD-like plasticity was induced in human motor cortex by paired associative transcranial magnetic stimulation (PASLTD), and measured as decreases of motor evoked potential input-output curve (IO-curve). In addition, sedation was measured by decreases in saccade peak velocity (SPV). Ethanol in two low doses (EtOH<10mM, EtOH<20mM) was compared to single oral doses of alprazolam (APZ, 1mg) a classical benzodiazepine, and zolpidem (ZLP, 10 mg), a non-benzodiazepine hypnotic, in a double-blinded randomized placebo-controlled crossover design in ten healthy human subjects. EtOH<10mM and EtOH<20mM but not APZ or ZLP enhanced the PASLTD-induced LTD-like plasticity, while APZ and ZLP but not EtOH<10mM or EtOH<20mM decreased SPV. Non-sedating low doses of ethanol, easily reached during social drinking, enhance LTD-like plasticity in human cortex. This effect is most likely explained by the activation of extrasynaptic α4-subunit containing gamma-aminobutyric type A receptors by low-dose EtOH, resulting in increased tonic inhibition. Findings may stimulate cellular research on the role of tonic inhibition in regulating excitability and plasticity of cortical neuronal networks.
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Seabirds, gyres and global trends in plastic pollution
International Nuclear Information System (INIS)
Franeker, Jan A. van; Law, Kara Lavender
2015-01-01
Fulmars are effective biological indicators of the abundance of floating plastic marine debris. Long-term data reveal high plastic abundance in the southern North Sea, gradually decreasing to the north at increasing distance from population centres, with lowest levels in high-arctic waters. Since the 1980s, pre-production plastic pellets in North Sea fulmars have decreased by ∼75%, while user plastics varied without a strong overall change. Similar trends were found in net-collected floating plastic debris in the North Atlantic subtropical gyre, with a ∼75% decrease in plastic pellets and no obvious trend in user plastic. The decreases in pellets suggest that changes in litter input are rapidly visible in the environment not only close to presumed sources, but also far from land. Floating plastic debris is rapidly “lost” from the ocean surface to other as-yet undetermined sinks in the marine environment. - Highlights: • Seabirds are effective biological monitors of floating plastic marine debris. • Plastics in fulmar stomachs and in the North Atlantic gyre show similar trends. • Pre-production plastic pellets show strong decreases in fulmars and in the gyre. • These data show that floating plastics rapidly disappear from the ocean surface. - Long term studies give evidence that reduced input of plastic debris into the ocean becomes rapidly visible. Floating plastics disappear to as-yet undetermined sinks
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Potential long-term storage of the predatory mite Phytoseiulus persimilis
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...
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Murakami, Jun; Okada, Ryuichi; Sadamoto, Hisayo; Kobayashi, Suguru; Mita, Koichi; Sakamoto, Yuki; Yamagishi, Miki; Hatakeyama, Dai; Otsuka, Emi; Okuta, Akiko; Sunada, Hiroshi; Takigami, Satoshi; Sakakibara, Manabu; Fujito, Yutaka; Awaji, Masahiko; Moriyama, Shunsuke; Lukowiak, Ken; Ito, Etsuro
2013-01-02
The pond snail Lymnaea stagnalis is capable of learning taste aversion and consolidating this learning into long-term memory (LTM) that is called conditioned taste aversion (CTA). Previous studies showed that some molluscan insulin-related peptides (MIPs) were upregulated in snails exhibiting CTA. We thus hypothesized that MIPs play an important role in neurons underlying the CTA-LTM consolidation process. To examine this hypothesis, we first observed the distribution of MIP II, a major peptide of MIPs, and MIP receptor and determined the amounts of their mRNAs in the CNS. MIP II was only observed in the light green cells in the cerebral ganglia, but the MIP receptor was distributed throughout the entire CNS, including the buccal ganglia. Next, when we applied exogenous mammalian insulin, secretions from MIP-containing cells or partially purified MIPs, to the isolated CNS, we observed a long-term change in synaptic efficacy (i.e., enhancement) of the synaptic connection between the cerebral giant cell (a key interneuron for CTA) and the B1 motor neuron (a buccal motor neuron). This synaptic enhancement was blocked by application of an insulin receptor antibody to the isolated CNS. Finally, injection of the insulin receptor antibody into the snail before CTA training, while not blocking the acquisition of taste aversion learning, blocked the memory consolidation process; thus, LTM was not observed. These data suggest that MIPs trigger changes in synaptic connectivity that may be correlated with the consolidation of taste aversion learning into CTA-LTM in the Lymnaea CNS.
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Developmental Plasticity in Child Growth and Maturation
Directory of Open Access Journals (Sweden)
Ze'ev eHochberg
2011-09-01
Full Text Available The ability of a given genotype to produce different phenotypes in response to different environments is termed "plasticity", and is part of the organism's "adaptability" to environmental cues. The expressions of suites of genes, particularly during development or life-history transitions, probably underlie the fundamental plasticity of an organism. Plasticity in developmental programming has evolved in order to provide the best chances of survival and reproductive success to organisms under changing environments. Environmental conditions that are experienced in early life can profoundly influence human biology, child growth and maturation, and long-term health and longevity. Developmental origins of health and disease and life history transitions are purported to use placental, nutritional, and endocrine cues for setting long-term biological, mental, and behavioral strategies for child growth and maturation in response to local ecological and/or social conditions. The window of developmental plasticity extends from conception to early childhood, and even beyond to the transition from juvenility to adoelscence, and could be transmitted transgenerationally. It involves epigenetic responses to environmental changes, which exert their effects during life history phase-transitions.
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Differential functions of NR2A and NR2B in short-term and long-term memory in rats.
Jung, Ye-Ha; Suh, Yoo-Hun
2010-08-23
N-methyl-D-aspartate receptors (NMDARs) are glutamate receptors implicated in synaptic plasticity and memory function. The specific functions of NMDA receptor subunits NR2A and NR2B have not yet been fully determined in the different types of memory. Nine Wistar rats (8-weeks-old) were subjected to the Morris water maze task to evaluate the memory behaviorally. Quantitative analysis of NR1, NR2A, and NR2B levels in the right and left forebrain of rats was performed and subunit associations with different types of memory were investigated using the Morris water maze task. Right forebrain NR2A expression was significantly increased and correlated with faster escape time onto a hidden platform, indicating involvement of short-term memory, because of the training time interval. Right forebrain NR2B expression was positively associated with long-term memory lasting 24-h (h). In the left forebrain, NR2B expression was positively related to 72-h long-term memory. In conclusion, the functions of NR2A and NR2B receptors were differentially specialized in short-term and long-term memory, depending on the right or left forebrain.
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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.
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Chen, Xudong; Xi, Fengming; Geng, Yong; Fujita, Tsuyoshi
2011-01-01
With the increasing attention on developing a low-carbon economy, it is necessary to seek appropriate ways on reducing greenhouse gas (GHG) emissions through innovative municipal solid waste management (MSWM), such as urban symbiosis. However, quantitative assessments on the environmental benefits of urban symbiosis, especially in developing countries, are limited because only a limited number of planned synergistic activities have been successful and it is difficult to acquire detailed inventory data from private companies. This paper modifies and applies a two-step simulation system and used it to assess the potential environmental benefits, including the reduction of GHG emissions and saving of fossil fuels, by employing various Japanese plastics recycling/energy-recovery technologies in Shenyang, China. The results showed that among various recycling/energy-recovery technologies, the mechanical waste plastics recycling technology, which produces concrete formwork boards (NF boards), has the greatest potential in terms of reducing GHG emissions (1.66 kg CO(2)e/kg plastics), whereas the technology for the production of refuse plastic fuel (RPF) has the greatest potential on saving fossil fuel consumption (0.77 kg ce/kg-plastics). Additional benefits can be gained by applying combined technologies that cascade the utilization of waste plastics. Moreover, the development of clean energy in conjunction with the promotion of new waste plastics recycling programs could contribute to additional reductions in GHG emissions and fossil fuel consumption. Copyright © 2010 Elsevier Ltd. All rights reserved.
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The organization of plasticity in the cerebellar cortex: from synapses to control.
D'Angelo, Egidio
2014-01-01
The cerebellum is thought to play a critical role in procedural learning, but the relationship between this function and the underlying cellular and synaptic mechanisms remains largely speculative. At present, at least nine forms of long-term synaptic and nonsynaptic plasticity (some of which are bidirectional) have been reported in the cerebellar cortex and deep cerebellar nuclei. These include long-term potentiation (LTP) and long-term depression at the mossy fiber-granule cell synapse, at the synapses formed by parallel fibers, climbing fibers, and molecular layer interneurons on Purkinje cells, and at the synapses formed by mossy fibers and Purkinje cells on deep cerebellar nuclear cells, as well as LTP of intrinsic excitability in granule cells, Purkinje cells, and deep cerebellar nuclear cells. It is suggested that the complex properties of cerebellar learning would emerge from the distribution of plasticity in the network and from its dynamic remodeling during the different phases of learning. Intrinsic and extrinsic factors may hold the key to explain how the different forms of plasticity cooperate to select specific transmission channels and to regulate the signal-to-noise ratio through the cerebellar cortex. These factors include regulation of neuronal excitation by local inhibitory networks, engagement of specific molecular mechanisms by spike bursts and theta-frequency oscillations, and gating by external neuromodulators. Therefore, a new and more complex view of cerebellar plasticity is emerging with respect to that predicted by the original "Motor Learning Theory," opening issues that will require experimental and computational testing. © 2014 Elsevier B.V. All rights reserved.
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Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons
Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington
2016-01-01
Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals. PMID:27833531
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BDNF-induced local protein synthesis and synaptic plasticity.
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.
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Arshavsky, Yuri I
2006-10-01
Memorizing new facts and events means that entering information produces specific physical changes within the brain. According to the commonly accepted view, traces of memory are stored through the structural modifications of synaptic connections, which result in changes of synaptic efficiency and, therefore, in formations of new patterns of neural activity (the hypothesis of synaptic plasticity). Most of the current knowledge on learning and initial stages of memory consolidation ("synaptic consolidation") is based on this hypothesis. However, the hypothesis of synaptic plasticity faces a number of conceptual and experimental difficulties when it deals with potentially permanent consolidation of declarative memory ("system consolidation"). These difficulties are rooted in the major intrinsic self-contradiction of the hypothesis: stable declarative memory is unlikely to be based on such a non-stable foundation as synaptic plasticity. Memory that can last throughout an entire lifespan should be "etched in stone." The only "stone-like" molecules within living cells are DNA molecules. Therefore, I advocate an alternative, genomic hypothesis of memory, which suggests that acquired information is persistently stored within individual neurons through modifications of DNA, and that these modifications serve as the carriers of elementary memory traces.
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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.
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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.
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Hosang, Leon; Yusifov, Rashad; Löwel, Siegrid
2018-01-01
Abstract For routine behavioral tasks, mice predominantly rely on olfactory cues and tactile information. In contrast, their visual capabilities appear rather restricted, raising the question whether they can improve if vision gets more behaviorally relevant. We therefore performed long-term training using the visual water task (VWT): adult standard cage (SC)-raised mice were trained to swim toward a rewarded grating stimulus so that using visual information avoided excessive swimming toward ...
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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
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Tokuda, Kazuhiro; O'Dell, Kazuko A; Izumi, Yukitoshi; Zorumski, Charles F
2010-12-15
Benzodiazepines (BDZs) enhance GABA(A) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors [translocator protein (18 kDa) (TSPO)] and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ, with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition after stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA [17-phenyl-(3α,5α)-androst-16-en-3-ol], a blocker of neurosteroid effects on GABA(A) receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN (2-[2-(4-fluorophenyl)-1H-indol-3-yl]-N,N-dihexylacetamide), a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated 1 d before midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity.
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Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition.
Basu, Jayeeta; Zaremba, Jeffrey D; Cheung, Stephanie K; Hitti, Frederick L; Zemelman, Boris V; Losonczy, Attila; Siegelbaum, Steven A
2016-01-08
The cortico-hippocampal circuit is critical for storage of associational memories. Most studies have focused on the role in memory storage of the excitatory projections from entorhinal cortex to hippocampus. However, entorhinal cortex also sends inhibitory projections, whose role in memory storage and cortico-hippocampal activity remains largely unexplored. We found that these long-range inhibitory projections enhance the specificity of contextual and object memory encoding. At the circuit level, these γ-aminobutyric acid (GABA)-releasing projections target hippocampal inhibitory neurons and thus act as a disinhibitory gate that transiently promotes the excitation of hippocampal CA1 pyramidal neurons by suppressing feedforward inhibition. This enhances the ability of CA1 pyramidal neurons to fire synaptically evoked dendritic spikes and to generate a temporally precise form of heterosynaptic plasticity. Long-range inhibition from entorhinal cortex may thus increase the precision of hippocampal-based long-term memory associations by assessing the salience of mnemonormation to the immediate sensory input. Copyright © 2016, American Association for the Advancement of Science.
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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.
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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.
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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
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Excitability decreasing central motor plasticity is retained in multiple sclerosis patients
Directory of Open Access Journals (Sweden)
Zeller Daniel
2012-09-01
Full Text Available Abstract Background Compensation of brain injury in multiple sclerosis (MS may in part work through mechanisms involving neuronal plasticity on local and interregional scales. Mechanisms limiting excessive neuronal activity may have special significance for retention and (re-acquisition of lost motor skills in brain injury. However, previous neurophysiological studies of plasticity in MS have investigated only excitability enhancing plasticity and results from neuroimaging are ambiguous. Thus, the aim of this study was to probe long-term depression-like central motor plasticity utilizing continuous theta-burst stimulation (cTBS, a non-invasive brain stimulation protocol. Because cTBS also may trigger behavioral effects through local interference with neuronal circuits, this approach also permitted investigating the functional role of the primary motor cortex (M1 in force control in patients with MS. Methods We used cTBS and force recordings to examine long-term depression-like central motor plasticity and behavioral consequences of a M1 lesion in 14 patients with stable mild-to-moderate MS (median EDSS 1.5, range 0 to 3.5 and 14 age-matched healthy controls. cTBS consisted of bursts (50 Hz of three subthreshold biphasic magnetic stimuli repeated at 5 Hz for 40 s over the hand area of the left M1. Corticospinal excitability was probed via motor-evoked potentials (MEP in the abductor pollicis brevis muscle over M1 before and after cTBS. Force production performance was assessed in an isometric right thumb abduction task by recording the number of hits into a predefined force window. Results cTBS reduced MEP amplitudes in the contralateral abductor pollicis brevis muscle to a comparable extent in control subjects (69 ± 22% of baseline amplitude, p Conclusions Long-term depression-like plasticity remains largely intact in mild-to-moderate MS. Increasing brain injury may render the neuronal networks less responsive toward lesion
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Anticipatory eye movements and long-term memory in early infancy.
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.
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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.
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Artinian, Julien; Lacaille, Jean-Claude
2017-11-23
Neural circuit functions involve finely controlled excitation/inhibition interactions that allow complex neuronal computations and support high order brain functions such as learning and memory. Disinhibition, defined as a transient brake on inhibition that favors excitation, recently appeared to be a conserved circuit mechanism implicated in various functions such as sensory processing, learning and memory. Although vasoactive intestinal polypeptide (VIP) interneurons are considered to be the main disinhibitory cells, recent studies highlighted a pivotal role of somatostatin (SOM) interneurons in inhibiting GABAergic interneurons and promoting principal cell activation. Interestingly, long-term potentiation of excitatory input synapses onto hippocampal SOM interneurons is proposed as a lasting mechanism for regulation of disinhibition of principal neurons. Such regulation of network metaplasticity may be important for hippocampal-dependent learning and memory. Copyright © 2017 Elsevier Inc. All rights reserved.
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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.
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Visual attentional load influences plasticity in the human motor cortex.
Kamke, Marc R; Hall, Michelle G; Lye, Hayley F; Sale, Martin V; Fenlon, Laura R; Carroll, Timothy J; Riek, Stephan; Mattingley, Jason B
2012-05-16
Neural plasticity plays a critical role in learning, memory, and recovery from injury to the nervous system. Although much is known about the physical and physiological determinants of plasticity, little is known about the influence of cognitive factors. In this study, we investigated whether selective attention plays a role in modifying changes in neural excitability reflecting long-term potentiation (LTP)-like plasticity. We induced LTP-like effects in the hand area of the human motor cortex using transcranial magnetic stimulation (TMS). During the induction of plasticity, participants engaged in a visual detection task with either low or high attentional demands. Changes in neural excitability were assessed by measuring motor-evoked potentials in a small hand muscle before and after the TMS procedures. In separate experiments plasticity was induced either by paired associative stimulation (PAS) or intermittent theta-burst stimulation (iTBS). Because these procedures induce different forms of LTP-like effects, they allowed us to investigate the generality of any attentional influence on plasticity. In both experiments reliable changes in motor cortex excitability were evident under low-load conditions, but this effect was eliminated under high-attentional load. In a third experiment we investigated whether the attentional task was associated with ongoing changes in the excitability of motor cortex, but found no difference in evoked potentials across the levels of attentional load. Our findings indicate that in addition to their role in modifying sensory processing, mechanisms of attention can also be a potent modulator of cortical plasticity.
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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...
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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.
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Directory of Open Access Journals (Sweden)
Watson Shawn N
2012-08-01
Full Text Available Abstract Background Cognitive impairment associated with subtle changes in neuron and neuronal network function rather than widespread neuron death is a feature of the normal aging process in humans and animals. Despite its broad evolutionary conservation, the etiology of this aging process is not well understood. However, recent evidence suggests the existence of a link between oxidative stress in the form of progressive membrane lipid peroxidation, declining neuronal electrical excitability and functional decline of the normal aging brain. The current study applies a combination of behavioural and electrophysiological techniques and pharmacological interventions to explore this hypothesis in a gastropod model (Lymnaea stagnalis feeding system that allows pinpointing the molecular and neurobiological foundations of age-associated long-term memory (LTM failure at the level of individual identified neurons and synapses. Results Classical appetitive reward-conditioning induced robust LTM in mature animals in the first quartile of their lifespan but failed to do so in animals in the last quartile of their lifespan. LTM failure correlated with reduced electrical excitability of two identified serotonergic modulatory interneurons (CGCs critical in chemosensory integration by the neural network controlling feeding behaviour. Moreover, while behavioural conditioning induced delayed-onset persistent depolarization of the CGCs known to underlie appetitive LTM formation in this model in the younger animals, it failed to do so in LTM-deficient senescent animals. Dietary supplementation of the lipophilic anti-oxidant α-tocopherol reversed the effect of age on CGCs electrophysiological characteristics but failed to restore appetitive LTM function. Treatment with the SSRI fluoxetine reversed both the neurophysiological and behavioural effects of age in senior animals. Conclusions The results identify the CGCs as cellular loci of age-associated appetitive
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Premi, Enrico; Benussi, Alberto; La Gatta, Antonio; Visconti, Stefano; Costa, Angelo; Gilberti, Nicola; Cantoni, Valentina; Padovani, Alessandro; Borroni, Barbara; Magoni, Mauro
2018-06-13
Non-depolarizing magnetic fields, like low frequency-pulsed electromagnetic fields (LF-PEMFs) have shown the ability to modulate living structures, principally by influencing synaptic activity and ion channels on cellular membranes. Recently, the CTU Mega 20 device was presented as a molecular accelerator, using energy up to 200 J and providing high-power (2 Tesla) pulsating fields with a water-repulsive (diamagnetic) action and tissue biostimulation. We tested the hypothesis that LF-PEMFs could modulate long-term corticospinal excitability in healthy brains by applying CTU Mega 20 ® . Ten healthy subjects without known neurological and/or psychiatric diseases entered the study. A randomized double-blind sham-controlled crossover design was employed, recording TMS parameters (amplitude variation of the motor evoked potential as index of cortical excitability perturbations of the motor system) before (pre) and after (post + 0, + 15, + 30 min) a single CTU Mega 20 session on the corresponding primary right-hand motor area, using a real (magnetic field = 2 Tesla; intensity = 90 J; impulse frequency = 7 Hz; duration = 15 min) or sham device. A two-way repeated measures ANOVA with TIME (pre, post + 0, + 15, + 30 min) and TREATMENT (real vs. sham stimulation) as within-subjects factor was applied. A significant TIME × TREATMENT interaction was found (p < 0.001). Post hoc comparisons showed a significant effect of TIME, with significant differences at + 0, + 15 and + 30 min compared to baseline after real stimulation (all p < 0.05) but not after sham stimulation (all p < 0.05) and significant effects of TREATMENT, with significant differences at + 0, + 15 and + 30 min for real stimulation compared to sham stimulation (all p < 0.005). No significant depolarizing effects were detected throughout the (real) stimulation. Our proof-of-concept study in healthy subjects supports the idea that non-ionizing LF
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Directory of Open Access Journals (Sweden)
Saeed Ismaeilimoghadam
2016-09-01
Full Text Available The objective of this study was to investigate the effect of nano SiO2 on long-term water absorption and thickness swelling, humidity coefficient diffusion and thickness swelling rate of wood plastic composite. For this purpose, 60% wood flour, 40% polypropylene, 2 per hundred compound (phc MAPP in internal mixer (HAAKE were mixed. Nano SiO2 with 0, 1, 3 and 5 (phc ratios as a reinforcing was used too. Finally test samples were fabricated by using the injection molding machine. Then long-term water absorption and thickness swelling for 1848 hours according to the ASTM standard on the samples were measured. Humidity coefficient diffusion and thickness swelling rate for closer look long-term water absorption and thickness swelling behavior in wood plastic nanocomposite were calculated too. For ensure to the formation of hydrogen bonds between hydroxyl grope of SiO2 nanoparticles with hydroxyl grope of wood flour form Fourier transform infrared (FTIR spectroscopy tests was used. The results showed that water absorption behavior of nanocomposite is according to Fick's law, in addition with increasing to SiO2 nanoparticles, long-term water absorption and thickness swelling and humidity coefficient diffusion in wood plastic nanocomposite decreased. The results of infrared spectroscopy showed that hydrogen bond between the nano SiO2 and wood flour confirmed. Statistical analysis showed that after 1848 hours of immersion, nano SiO2 showed a significant effect at a confidence level of 99% on water absorption and thickness swelling, so the sample with 5% silica nanoparticles was chosen as the best treatment.
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Clinical trials with rasagiline: evidence for short-term and long-term effects.
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.
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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.
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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.
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Jin, Iksung; Kandel, Eric R.; Hawkins, Robert D.
2011-01-01
Whereas short-term plasticity involves covalent modifications that are generally restricted to either presynaptic or postsynaptic structures, long-term plasticity involves the growth of new synapses, which by its nature involves both pre- and postsynaptic alterations. In addition, an intermediate-term stage of plasticity has been identified that…
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Global long-term cost dynamics of offshore wind electricity generation
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
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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.
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Valic, Maja; Pecotic, Renata; Pavlinac Dodig, Ivana; Valic, Zoran; Stipica, Ivona; Dogas, Zoran
2016-02-01
What is the central question of this study? Intermittent hypercapnia is a concomitant feature of breathing disorders. Hypercapnic stimuli evoke a form of respiratory plasticity known as phrenic long-term depression in experimental animals. This study was performed to investigate the putative role of serotonin receptors in the initiation of phrenic long-term depression in anaesthetized rats. What is the main finding and its importance? Phrenic nerve long-term depression was revealed in animals pretreated with the serotonin broad-spectrum antagonist, methysergide. This study highlights that serotonin receptors modulate respiratory plasticity evoked by acute intermittent hypercapnia in anaesthetized rats. This study was performed to test the hypothesis that intermittent hypercapnia can evoke a form of respiratory plasticity known as long-term depression of the phrenic nerve (pLTD) and that 5-HT receptors play a role in the initiation of pLTD. Adult male urethane-anaesthetized, vagotomized, paralysed, mechanically ventilated Sprague-Dawley rats were exposed to an acute intermittent hypercapnia protocol. One group received i.v. injection of the non-selective 5-HT receptor antagonist methysergide and another group received i.v. injection of the selective 5-HT1A receptor antagonist WAY-100635 20 min before exposure to intermittent hypercapnia. A control group received i.v. injection of saline. Peak phrenic nerve activity and respiratory rhythm parameters were analysed at baseline (T0), during each of five hypercapnic episodes, and 15, 30 and 60 min (T60) after the last hypercapnia. Intravenous injection of methysergide before exposure to acute intermittent hypercapnia induced development of amplitude pLTD at T60 (decreased by 46.1 ± 6.9%, P = 0.003). Conversely, in control and WAY-100635-pretreated animals, exposure to acute intermittent hypercapnia did not evoke amplitude pLTD. However, a long-term decrease in phrenic nerve frequency was evoked both in control (42 ± 4
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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.
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Learning of spiking networks with different forms of long-term synaptic plasticity
International Nuclear Information System (INIS)
Vlasov, D.S.; Sboev, A.G.; Serenko, A.V.; Rybka, R.B.; Moloshnikov, I.A.
2016-01-01
The possibility of modeling the learning process based on different forms of spike timing-dependent plasticity (STDP) has been studied. It has been shown that the learnability depends on the choice of the spike pairing scheme in the STDP rule and the type of the input signal used during learning [ru
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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.
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Seabirds, gyres and global trends in plastic pollution
Franeker, van J.A.; Law, K.L.
2015-01-01
Fulmars are effective biological indicators of the abundance of floating plastic marine debris. Long-term data reveal high plastic abundance in the southern North Sea, gradually decreasing to the north at increasing distance from population centres, with lowest levels in high-arctic waters. Since
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Spatial olfactory learning facilitates long-term depression in the hippocampus.
André, Marion Agnès Emma; Manahan-Vaughan, Denise
2013-10-01
Recently, it has emerged that visual spatial exploration facilitates synaptic plasticity at different synapses within the trisynaptic network. Particularly striking is the finding that visuospatial contexts facilitate hippocampal long-term depression (LTD), raising the possibility that this form of plasticity may be important for memory formation. It is not known whether other sensory modalities elicit similar permissive effects on LTD. Here, we explored if spatial olfactory learning facilitates LTD in the hippocampus region of freely behaving rats. Patterned afferent stimulation of the Schaffer collaterals elicited short-term depression (STD) (<1 h) of evoked responses in the Stratum radiatum of the CA1 region. Coupling of this protocol with novel exploration of a spatial constellation of olfactory cues facilitated short-term depression into LTD that lasted for over 24 h. Facilitation of LTD did not occur when animals were re-exposed 1 week later to the same odors in the same spatial constellation. Evaluation of learning behavior revealed that 1 week after the 1st odor exposure, the animals remembered the odors and their relative positions. These data support that the hippocampus can use nonvisuospatial resources, and specifically can use spatial olfactory information, to facilitate LTD and to generate spatial representations. The data also support that a tight relationship exists between the processing of spatial contextual information and the expression of LTD in the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.
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Long-term ecological research in a human-dominated world
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 todayâs most difficult environmental challenges. The networkâs potential for tackling emergent...
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Global change and the evolution of phenotypic plasticity in plants.
Matesanz, Silvia; Gianoli, Ernesto; Valladares, Fernando
2010-09-01
Global change drivers create new environmental scenarios and selective pressures, affecting plant species in various interacting ways. Plants respond with changes in phenology, physiology, and reproduction, with consequences for biotic interactions and community composition. We review information on phenotypic plasticity, a primary means by which plants cope with global change scenarios, recommending promising approaches for investigating the evolution of plasticity and describing constraints to its evolution. We discuss the important but largely ignored role of phenotypic plasticity in range shifts and review the extensive literature on invasive species as models of evolutionary change in novel environments. Plasticity can play a role both in the short-term response of plant populations to global change as well as in their long-term fate through the maintenance of genetic variation. In new environmental conditions, plasticity of certain functional traits may be beneficial (i.e., the plastic response is accompanied by a fitness advantage) and thus selected for. Plasticity can also be relevant in the establishment and persistence of plants in novel environments that are crucial for populations at the colonizing edge in range shifts induced by climate change. Experimental studies show taxonomically widespread plastic responses to global change drivers in many functional traits, though there is a lack of empirical support for many theoretical models on the evolution of phenotypic plasticity. Future studies should assess the adaptive value and evolutionary potential of plasticity under complex, realistic global change scenarios. Promising tools include resurrection protocols and artificial selection experiments. © 2010 New York Academy of Sciences.
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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
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Disruption in proprioception from long-term thalamic deep brain stimulation: A pilot study
Directory of Open Access Journals (Sweden)
Jennifer A Semrau
2015-05-01
Full Text Available Deep brain stimulation (DBS is an excellent treatment for tremor and is generally thought to be reversible by turning off stimulation. For tremor, DBS is implanted in the ventrointermedius (Vim nucleus of the thalamus, a region that relays proprioceptive information for movement sensation (kinaesthesia. Gait disturbances have been observed with bilateral Vim DBS, but the long-term effects on proprioceptive processing are unknown. We aimed to determine whether Vim DBS surgical implantation or stimulation leads to proprioceptive deficits in the upper limb. We assessed two groups of tremor subjects on measures of proprioception (kinaesthesia, position sense and motor function using a robotic exoskeleton. In the first group (Surgery, we tested patients before and after implantation of Vim DBS, but before DBS was turned on to determine if proprioceptive deficits were inherent to tremor or caused by DBS implantation. In the second group (Stim, we tested subjects with chronically implanted Vim DBS ON and OFF stimulation. Compared to controls, there were no proprioceptive deficits before or after DBS implantation in the Surgery group. Surprisingly, those that received chronic long-term stimulation (LT-stim, 3-10 years displayed significant proprioceptive deficits ON and OFF stimulation not present in subjects with chronic short-term stimulation (ST-stim, 0.5-2 years. LT-stim had significantly larger variability and reduced workspace area during the position sense assessment. During the kinesthetic assessment, LT-stim made significantly larger directional errors and consistently underestimated the speed of the robot, despite generating normal movement speeds during motor assessment. Chronic long-term Vim DBS may potentially disrupt proprioceptive processing, possibly inducing irreversible plasticity in the Vim nucleus and/or its network connections. Our findings in the upper limb may help explain some of the gait disturbances seen by others following Vim
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Alpha2-adrenoceptor modulation of long-term potentiation elicited in vivo in rat occipital cortex.
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.
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Spike-timing dependent plasticity in a transistor-selected resistive switching memory
International Nuclear Information System (INIS)
Ambrogio, S; Balatti, S; Nardi, F; Facchinetti, S; Ielmini, D
2013-01-01
In a neural network, neuron computation is achieved through the summation of input signals fed by synaptic connections. The synaptic activity (weight) is dictated by the synchronous firing of neurons, inducing potentiation/depression of the synaptic connection. This learning function can be supported by the resistive switching memory (RRAM), which changes its resistance depending on the amplitude, the pulse width and the bias polarity of the applied signal. This work shows a new synapse circuit comprising a MOS transistor as a selector and a RRAM as a variable resistance, displaying spike-timing dependent plasticity (STDP) similar to the one originally experienced in biological neural networks. We demonstrate long-term potentiation and long-term depression by simulations with an analytical model of resistive switching. Finally, the experimental demonstration of the new STDP scheme is presented. (paper)
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International Nuclear Information System (INIS)
Chen Xudong; Xi Fengming; Geng Yong; Fujita, Tsuyoshi
2011-01-01
Research highlights: → Urban symbiosis creates compatibility of industrial development and waste management. → Mechanical technology leads to more CO 2 emission reduction. → Energy recovery technology leads to more fossil fuel saving. → Clean energy makes recycling technologies cleaner. → Demand management is crucial for realizing potential environmental gains of recycling. - Abstract: With the increasing attention on developing a low-carbon economy, it is necessary to seek appropriate ways on reducing greenhouse gas (GHG) emissions through innovative municipal solid waste management (MSWM), such as urban symbiosis. However, quantitative assessments on the environmental benefits of urban symbiosis, especially in developing countries, are limited because only a limited number of planned synergistic activities have been successful and it is difficult to acquire detailed inventory data from private companies. This paper modifies and applies a two-step simulation system and used it to assess the potential environmental benefits, including the reduction of GHG emissions and saving of fossil fuels, by employing various Japanese plastics recycling/energy-recovery technologies in Shenyang, China. The results showed that among various recycling/energy-recovery technologies, the mechanical waste plastics recycling technology, which produces concrete formwork boards (NF boards), has the greatest potential in terms of reducing GHG emissions (1.66 kg CO 2 e/kg plastics), whereas the technology for the production of refuse plastic fuel (RPF) has the greatest potential on saving fossil fuel consumption (0.77 kgce/kg-plastics). Additional benefits can be gained by applying combined technologies that cascade the utilization of waste plastics. Moreover, the development of clean energy in conjunction with the promotion of new waste plastics recycling programs could contribute to additional reductions in GHG emissions and fossil fuel consumption.
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International Nuclear Information System (INIS)
Stefanik, J.
2001-01-01
Processes are developed for the immobilization of radionuclides by solidification of radioactive wastes. The resulting solidification products are characterized by strong resistance to leaching aimed at low release rates of the radionuclides to the environment. To measure this resistance to leaching of the solidified materials: glass, glass-ceramics, bitumen, cement, concrete, plastics, a long-term leach test is presented. The long-term leach test is aimed at: a) the comparison of different kinds or compositions of solidified waste forms; b) the intercomparison between leach test results from different laboratories on one product; c) the intercomparison between leach test results on products from different processes
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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.
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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
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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
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Concept for a hyperspectral remote sensing algorithm for floating marine macro plastics.
Goddijn-Murphy, Lonneke; Peters, Steef; van Sebille, Erik; James, Neil A; Gibb, Stuart
2018-01-01
There is growing global concern over the chemical, biological and ecological impact of plastics in the ocean. Remote sensing has the potential to provide long-term, global monitoring but for marine plastics it is still in its early stages. Some progress has been made in hyperspectral remote sensing of marine macroplastics in the visible (VIS) to short wave infrared (SWIR) spectrum. We present a reflectance model of sunlight interacting with a sea surface littered with macro plastics, based on geometrical optics and the spectral signatures of plastic and seawater. This is a first step towards the development of a remote sensing algorithm for marine plastic using light reflectance measurements in air. Our model takes the colour, transparency, reflectivity and shape of plastic litter into account. This concept model can aid the design of laboratory, field and Earth observation measurements in the VIS-SWIR spectrum and explain the results. Copyright © 2017 Elsevier Ltd. All rights reserved.
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[Long-term psychiatric hospitalizations].
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
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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.
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Long term durability of wood-plastic composites made with chemically modified wood
Rebecca E. Ibach; Craig M. Clemons
2017-01-01
Wood-plastic composites (WPCs) have slower moisture sorption than solid wood, but over time moisture can impact the strength, stiffness, and decay of the composite. These changes will become increasingly important if WPCs are used in more challenging environments such as in ground-contact applications. There are several options for mitigating the moisture sorption of...
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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
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Enhanced long term microcircuit plasticity in the valproic acid animal model of autism
Guilherme T Silva; Guilherme T Silva; Jean-Vincent Le Bé; Imad Riachi; Tania Rinaldi; Kamila Markram; Henry Markram
2009-01-01
A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a mini-column (<50μm). In the present study, we explored whether Long Term Microcircuit ...
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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.
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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.
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Sui, Li; Huang, SiJia; Peng, BinBin; Ren, Jie; Tian, FuYing; Wang, Yan
2014-07-01
Deep brain stimulation (DBS) of the amygdala has been demonstrated to modulate hyperactivity of the amygdala, which is responsible for the symptoms of post-traumatic stress disorder (PTSD), and thus might be used for the treatment of PTSD. However, the underlying mechanism of DBS of the amygdala in the modulation of the amygdala is unclear. The present study investigated the effects of DBS of the amygdala on synaptic transmission and synaptic plasticity at cortical inputs to the amygdala, which is critical for the formation and storage of auditory fear memories, and fear memories. The results demonstrated that auditory fear conditioning increased single-pulse-evoked field excitatory postsynaptic potentials in the cortical-amygdala pathway. Furthermore, auditory fear conditioning decreased the induction of paired-pulse facilitation and long-term potentiation, two neurophysiological models for studying short-term and long-term synaptic plasticity, respectively, in the cortical-amygdala pathway. In addition, all these auditory fear conditioning-induced changes could be reversed by DBS of the amygdala. DBS of the amygdala also rescued auditory fear conditioning-induced enhancement of long-term retention of fear memory. These findings suggested that DBS of the amygdala alleviating fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory may underlie the neuromodulatory role of DBS of the amygdala in activities of the amygdala.
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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.)
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Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains.
Sudhakaran, Indulekha P; Ramaswami, Mani
2017-05-04
Long-term and short-term memories differ primarily in the duration of their retention. At a molecular level, long-term memory (LTM) is distinguished from short-term memory (STM) by its requirement for new gene expression. In addition to transcription (nuclear gene expression) the translation of stored mRNAs is necessary for LTM formation. The mechanisms and functions for temporal and spatial regulation of mRNAs required for LTM is a major contemporary problem, of interest from molecular, cell biological, neurobiological and clinical perspectives. This review discusses primary evidence in support for translational regulatory events involved in LTM and a model in which different phases of translation underlie distinct phases of consolidation of memories. However, it focuses largely on mechanisms of memory persistence and the role of prion-like domains in this defining aspect of long-term memory. We consider primary evidence for the concept that Cytoplasmic Polyadenylation Element Binding (CPEB) protein enables the persistence of formed memories by transforming in prion-like manner from a soluble monomeric state to a self-perpetuating and persistent polymeric translationally active state required for maintaining persistent synaptic plasticity. We further discuss prion-like domains prevalent on several other RNA-binding proteins involved in neuronal translational control underlying LTM. Growing evidence indicates that such RNA regulatory proteins are components of mRNP (RiboNucleoProtein) granules. In these proteins, prion-like domains, being intrinsically disordered, could mediate weak transient interactions that allow the assembly of RNP granules, a source of silenced mRNAs whose translation is necessary for LTM. We consider the structural bases for RNA granules formation as well as functions of disordered domains and discuss how these complicate the interpretation of existing experimental data relevant to general mechanisms by which prion-domain containing RBPs
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The potential benefits of a new poliovirus vaccine for long-term poliovirus risk management.
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.
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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.
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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.
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Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.
Directory of Open Access Journals (Sweden)
Christian Albers
Full Text Available Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP. Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious and strong (teacher spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.
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Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.
Albers, Christian; Westkott, Maren; Pawelzik, Klaus
2016-01-01
Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.
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Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis.
Directory of Open Access Journals (Sweden)
Robert Nisticò
Full Text Available Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS and its mouse model, experimental autoimmune encephalomyelitis (EAE. In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP induction was favored over long-term depression (LTD in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS.
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Inflammation Subverts Hippocampal Synaptic Plasticity in Experimental Multiple Sclerosis
Mandolesi, Georgia; Piccinin, Sonia; Berretta, Nicola; Pignatelli, Marco; Feligioni, Marco; Musella, Alessandra; Gentile, Antonietta; Mori, Francesco; Bernardi, Giorgio; Nicoletti, Ferdinando; Mercuri, Nicola B.; Centonze, Diego
2013-01-01
Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE). In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP) induction was favored over long-term depression (LTD) in EAE, as shown by a significant rightward shift in the frequency–synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β) perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS. PMID:23355887
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The Plastic Potential, Double-slip, Double-spin and Viscoplasticity
Harris, David
2010-05-01
In this paper we describe two classical models for rate-independent behaviour of granular materials, namely the plastic potential and the double shearing model, emphasising their ill-posedness. We then describe a model, called the doubleslip and double-spin model which generalises the plastic potential model and is closely related to the double shearing model. This new model eliminates the causes of the ill-posedness in the classical models and provides a suitable basis for the analysis of the deformation and flow of granular materials in the rate-independent regime. There has been considerable recent interest in the intermediate regime between densely-packed, rate-independent, quasistatic flow and the rate-dependent dilute gaseous regime. In this intermediate regime the material also exhibits a degree of ratedependence. The natural extension of a rate-independent plasticity model to incorporate rate-dependent material behaviour is by way of viscoplasticity. The archetypal example here is the Bingham material which generalises a von Mises type plasticity model and introduces a viscosity parameter into the model. We propose an extension of the double-slip and double-spin model to incorporate viscosity, thereby extending the range of the model to incorporate rate-dependent behaviour. The new model is then applied to a simplified problem of pipe flow.
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NPY gene transfer in the hippocampus attenuates synaptic plasticity and learning
DEFF Research Database (Denmark)
Sørensen, Andreas T; Kanter-Schlifke, Irene; Carli, Mirjana
2008-01-01
-mediated mechanisms. In addition, transgene NPY seems to be released during high frequency neuronal activity, leading to decreased glutamate release in excitatory synapses. Importantly, memory consolidation appears to be affected by the treatment. We found that long-term potentiation (LTP) in the CA1 area...... processing. Here we show, by electrophysiological recordings in CA1 of the hippocampal formation of rats, that hippocampal NPY gene transfer into the intact brain does not affect basal synaptic transmission, but slightly alters short-term synaptic plasticity, most likely via NPY Y2 receptor....... Future clinical progress, however, requires more detailed evaluation of possible side effects of this treatment. Until now it has been unknown whether rAAV vector-based NPY overexpression in the hippocampus alters normal synaptic transmission and plasticity, which could disturb learning and memory...
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Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.
Monte-Silva, Katia; Liebetanz, David; Grundey, Jessica; Paulus, Walter; Nitsche, Michael A
2010-09-15
The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.
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Endogenous BDNF is required for long-term memory formation in the rat parietal cortex.
Alonso, Mariana; Bekinschtein, Pedro; Cammarota, Martín; Vianna, Monica R M; Izquierdo, Iván; Medina, Jorge H
2005-01-01
Information storage in the brain is a temporally graded process involving different memory phases as well as different structures in the mammalian brain. Cortical plasticity seems to be essential to store stable long-term memories, although little information is available at the moment regarding molecular and cellular events supporting memory consolidation in the neocortex. Brain-derived neurotrophic factor (BDNF) modulates both short-term synaptic function and activity-dependent synaptic plasticity in hippocampal and cortical neurons. We have recently demonstrated that endogenous BDNF in the hippocampus is involved in memory formation. Here we examined the role of BDNF in the parietal cortex (PCx) in short-term (STM) and long-term memory (LTM) formation of a one-trial fear-motivated learning task in rats. Bilateral infusions of function-blocking anti-BDNF antibody into the PCx impaired both STM and LTM retention scores and decreased the phosphorylation state of cAMP response element-binding protein (CREB). In contrast, intracortical administration of recombinant human BDNF facilitated LTM and increased CREB activation. Moreover, inhibitory avoidance training is associated with a rapid and transient increase in phospho-CREB/total CREB ratio in the PCx. Thus, our results indicate that endogenous BDNF is required for both STM and LTM formation of inhibitory avoidance learning, possibly involving CREB activation-dependent mechanisms. The present data support the idea that early sensory areas constitute important components of the networks subserving memory formation and that information processing in neocortex plays an important role in memory formation.
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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.
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POTENTIAL PRODUCTION OF OIL FROM WASTE PLASTIC PYROLIYSIS IN GEOSTECH BUILDING
Kristyawan, I Putu Angga
2017-01-01
Office waste is produced from activity that carried in the office area. In Geostech office area, 18.05 % composition of the waste is plastic waste. Plastic waste total in Geostech is 17.1 kg/week. The highest of plastic waste type is PP (Polypropylene). plastic waste. From the waste total is known that that the potential of oil produced through pyrolysis is 11.6 kg/week or 13.7 L/week. Pirolysis oil can be used as substitute for diesel fuel because of the calorific value equal with the calori...
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Fiber breakage phenomena in long fiber reinforced plastic preparation
International Nuclear Information System (INIS)
Huang, Chao-Tsai; Tseng, Huan-Chang; Chang, Rong-Yeu; Vlcek, Jiri
2015-01-01
Due to the high demand of smart green, the lightweight technologies have become the driving force for the development of automotives and other industries in recent years. Among those technologies, using short and long fiber-reinforced plastics (FRP) to replace some metal components can reduce the weight of an automotive significantly. However, the microstructures of fibers inside plastic matrix are too complicated to manage and control during the injection molding through the screw, the runner, the gate, and then into the cavity. This study focuses on the fiber breakage phenomena during the screw plastification. Results show that fiber breakage is strongly dependent on screw design and operation. When the screw geometry changes, the fiber breakage could be larger even with lower compression ratio. (paper)
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Banerjee, A.; Meredith, R.M.; Rodriguez-Moreno, A.; Mierau, S.B.; Auberson, Y.P.; Paulsen, O.
2009-01-01
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
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Transformative art: art as means for long-term neurocognitive change.
Preminger, Son
2012-01-01
Every artwork leads to a unique experience by the observer or participant, may it be sensory, emotional, cognitive, interactive, or spiritual experience. At the neurobiological level, such experiences are manifested as activation of the corresponding neural networks. Neuroscience has demonstrated that experience, in particular repeated experience, can cause a long-term change in the involved brain circuits (experience-dependent plasticity). This review will discuss the molding and transformative aspect of arts, examining how repeated and on-going experience of arts may alter cognitive, emotional, and behavioral patterns as well as their underlying neural circuits. The application of this approach to cognitive training and neuropsychological rehabilitation methods will be addressed as well. In addition, it will be suggested that this approach to art, as a long-term transformative medium, may lead to a novel viewpoint on art and a different approach to its creation. Artists can design artworks that aspire to form, in addition to one-shot influencing experience, on-going experiences which gradually create a lasting change, possibly improving audiences' neuropsychological functions.
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Transformative Art:Art as Means for Long-term Neurocognitive Change
Directory of Open Access Journals (Sweden)
Son ePreminger
2012-04-01
Full Text Available Every artwork leads to a unique experience by the observer or participant, may it be sensory, emotional, cognitive, interactive or spiritual experience. At the neurobiological level, such experiences are manifested as activation of the corresponding neural networks. Neuroscience has demonstrated that experience, in particular repeated experience, can cause a long-term change in the involved brain circuits (experience-dependent plasticity. This review will discuss the molding and transformative aspect of arts, examining how repeated and on-going experience of arts may alter cognitive, emotional and behavioral patterns as well as their underlying neural circuits. The application of this approach to cognitive training and neuropsychological rehabilitation methods will be addressed as well. In addition, it will be suggested that this approach to art, as long-term transformative, may lead to a novel viewpoint on art and a different approach to its creation. Artists can design artworks that aspire to form, in addition to one-shot influencing experience, on-going experiences which gradually create a lasting change, possibly improving audiences' neuropsychological functions.
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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...
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International Nuclear Information System (INIS)
Sera, Takehiko; Hirano, Shinro; Chigusa, Naoki; Okano, Shigetaka; Saida, Kazuyoshi; Mochizuki, Masahito; Nishimoto, Kazutoshi
2012-01-01
Surface finishing methods, such as Water Jet Peening (WJP), have been applied to welds in some major components of nuclear power plants as a counter measure to Primary Water Stress Corrosion Cracking (PWSCC). In addition, the methods of surface finishing (buffing treatment) is being standardized, and thus the buffing treatment has been also recognized as the well-established method of improving stress. On the other hand, the long-term stability of peening techniques has been confirmed by accelerated test. However, the effectiveness of stress improvement by surface treatment is limited to thin layers and the effect of complicated residual stress distribution in the weld metal beneath the surface is not strictly taken into account for long-term stability. This paper, therefore, describes the accelerated tests, which confirmed that the long-term stability of the layer subjected to buffing treatment was equal to that subjected to WJP. The long-term reliability of very thin stress improved layer was also confirmed through a trial evaluation by thermal elastic-plastic creep analysis, even if the effect of complicated residual stress distribution in the weld metal was excessively taken into account. Considering the above findings, an approach is proposed for constructing the prediction method of the long-term reliability of stress improvement by surface finishing. (author)
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Long-Term Prognosis of Ischemic Stroke in Young Adults
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...
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Pediatric polytrauma : Short-term and long-term outcomes
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
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Ren, Weibo; Hu, Ningning; Hou, Xiangyang; Zhang, Jize; Guo, Huiqin; Liu, Zhiying; Kong, Lingqi; Wu, Zinian; Wang, Hui; Li, Xiliang
2017-01-01
Previous studies of transgenerational plasticity have demonstrated that long-term overgrazing experienced by Leymus chinensis , an ecologically dominant, rhizomatous grass species in eastern Eurasian temperate grassland, significantly affects its clonal growth in subsequent generations. However, there is a dearth of information on the reasons underlying this overgrazing-induced memory effect in plant morphological plasticity. We characterized the relationship between a dwarf phenotype and photosynthesis function decline of L. chinensis from the perspective of leaf photosynthesis by using both field measurement and rhizome buds culture cultivated in a greenhouse. Leaf photosynthetic functions (net photosynthetic rate, stomatal conductance, intercellular carbon dioxide concentration, and transpiration rate) were significantly decreased in smaller L. chinensis individuals that were induced to have a dwarf phenotype by being heavily grazed in the field. This decreased photosynthetic function was maintained a generation after greenhouse tests in which grazing was excluded. Both the response of L. chinensis morphological traits and photosynthetic functions in greenhouse were deceased relative to those in the field experiment. Further, there were significant decreases in leaf chlorophyll content and Rubisco enzyme activities of leaves between bud-cultured dwarf and non-dwarf L. chinensis in the greenhouse. Moreover, gene expression patterns showed that the bud-cultured dwarf L. chinensis significantly down-regulated (by 1.86- to 5.33-fold) a series of key genes that regulate photosynthetic efficiency, stomata opening, and chloroplast development compared with the non-dwarf L. chinensis . This is among the first studies revealing a linkage between long-term overgrazing affecting the transgenerational morphological plasticity of clonal plants and physiologically adaptive photosynthesis function. Overall, clonal transgenerational effects in L. chinensis phenotypic traits
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Directory of Open Access Journals (Sweden)
Xiangyang Hou
2017-04-01
Full Text Available Previous studies of transgenerational plasticity have demonstrated that long-term overgrazing experienced by Leymus chinensis, an ecologically dominant, rhizomatous grass species in eastern Eurasian temperate grassland, significantly affects its clonal growth in subsequent generations. However, there is a dearth of information on the reasons underlying this overgrazing-induced memory effect in plant morphological plasticity. We characterized the relationship between a dwarf phenotype and photosynthesis function decline of L. chinensis from the perspective of leaf photosynthesis by using both field measurement and rhizome buds culture cultivated in a greenhouse. Leaf photosynthetic functions (net photosynthetic rate, stomatal conductance, intercellular carbon dioxide concentration, and transpiration rate were significantly decreased in smaller L. chinensis individuals that were induced to have a dwarf phenotype by being heavily grazed in the field. This decreased photosynthetic function was maintained a generation after greenhouse tests in which grazing was excluded. Both the response of L. chinensis morphological traits and photosynthetic functions in greenhouse were deceased relative to those in the field experiment. Further, there were significant decreases in leaf chlorophyll content and Rubisco enzyme activities of leaves between bud-cultured dwarf and non-dwarf L. chinensis in the greenhouse. Moreover, gene expression patterns showed that the bud-cultured dwarf L. chinensis significantly down-regulated (by 1.86- to 5.33-fold a series of key genes that regulate photosynthetic efficiency, stomata opening, and chloroplast development compared with the non-dwarf L. chinensis. This is among the first studies revealing a linkage between long-term overgrazing affecting the transgenerational morphological plasticity of clonal plants and physiologically adaptive photosynthesis function. Overall, clonal transgenerational effects in L. chinensis
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International Nuclear Information System (INIS)
Yang, Rui; Terabe, Kazuya; Yao, Yiping; Tsuruoka, Tohru; Hasegawa, Tsuyoshi; Gimzewski, James K; Aono, Masakazu
2013-01-01
A compact neuromorphic nanodevice with inherent learning and memory properties emulating those of biological synapses is the key to developing artificial neural networks rivaling their biological counterparts. Experimental results showed that memorization with a wide time scale from volatile to permanent can be achieved in a WO 3−x -based nanoionics device and can be precisely and cumulatively controlled by adjusting the device’s resistance state and input pulse parameters such as the amplitude, interval, and number. This control is analogous to biological synaptic plasticity including short-term plasticity, long-term potentiation, transition from short-term memory to long-term memory, forgetting processes for short- and long-term memory, learning speed, and learning history. A compact WO 3−x -based nanoionics device with a simple stacked layer structure should thus be a promising candidate for use as an inorganic synapse in artificial neural networks due to its striking resemblance to the biological synapse. (paper)
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Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo
Directory of Open Access Journals (Sweden)
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.
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High prevalence of parental delivery of plastic debris in Cory's shearwaters (Calonectris diomedea).
Rodríguez, Airam; Rodríguez, Beneharo; Nazaret Carrasco, María
2012-10-01
Plastic ingestion by adult Procellariiformes has been widely recorded, but few studies have evaluated intergenerational transfer. We assessed the prevalence of plastic particles, as well as their basic characteristics, in the gut content of dead Cory's shearwater fledglings stranded by light pollution on Canary Islands. Eighty-three percent of birds were affected, containing on average 8.0 plastic pieces per bird. The average plastic weight per bird was low (2.97±3.97mg) compared with other petrel species. We found no relationships between plastic loads and body condition or body size, but negative effects may be hidden or delayed. We propose to use the fledglings stranded by light pollution to carry out more precise studies to understand the potential hidden costs of plastic ingestion; and to monitor in a long-term the marine debris to develop management actions for the control of pollution at the marine environment. Copyright © 2012 Elsevier Ltd. All rights reserved.
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A compact cyclic plasticity model with parameter evolution
DEFF Research Database (Denmark)
Krenk, Steen; Tidemann, L.
2017-01-01
The paper presents a compact model for cyclic plasticity based on energy in terms of external and internal variables, and plastic yielding described by kinematic hardening and a flow potential with an additive term controlling the nonlinear cyclic hardening. The model is basically described by five...... parameters: external and internal stiffness, a yield stress and a limiting ultimate stress, and finally a parameter controlling the gradual development of plastic deformation. Calibration against numerous experimental results indicates that typically larger plastic strains develop than predicted...
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Phenotypic plasticity, costs of phenotypes, and costs of plasticity
DEFF Research Database (Denmark)
Callahan, Hilary S; Maughan, Heather; Steiner, Uli
2008-01-01
Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...
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Long-term Morbidity of Testicular Cancer Treatment.
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.
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Long-term preservation of bacon by high energy electrons
International Nuclear Information System (INIS)
Hannah, K.W.; Simic, M.G.
1985-01-01
Extra long-term storage of frozen, vacuum packed, cured bacon can be achieved by electronation, using 3 MeV electrons generated by an electron accelerator. A combination process consisting of low nitrite curing (40 ppm), smoking, vacuum packaging in Saran plastic, electronation (1 to 3 Mrad), and freezing (-10 C) allows storage for at least 2 1/2 years without any noticeable loss in quality, e.g. color, appearance, smell, or taste. This process also eliminates microbiological hazards associated with Salmonella and C. botulinum. Six Mrad tons/hour throughput of a 3 MeV 50 kw electron beam accelerator for standard sliced bacon packaging indicates a practical and economic commercial use for this combination process. (author)
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Binks, Oliver; Meir, Patrick; Rowland, Lucy; da Costa, Antonio Carlos Lola; Vasconcelos, Steel Silva; de Oliveira, Alex Antonio Ribeiro; Ferreira, Leandro; Christoffersen, Bradley; Nardini, Andrea; Mencuccini, Maurizio
2016-07-01
The tropics are predicted to become warmer and drier, and understanding the sensitivity of tree species to drought is important for characterizing the risk to forests of climate change. This study makes use of a long-term drought experiment in the Amazon rainforest to evaluate the role of leaf-level water relations, leaf anatomy and their plasticity in response to drought in six tree genera. The variables (osmotic potential at full turgor, turgor loss point, capacitance, elastic modulus, relative water content and saturated water content) were compared between seasons and between plots (control and through-fall exclusion) enabling a comparison between short- and long-term plasticity in traits. Leaf anatomical traits were correlated with water relation parameters to determine whether water relations differed among tissues. The key findings were: osmotic adjustment occurred in response to the long-term drought treatment; species resistant to drought stress showed less osmotic adjustment than drought-sensitive species; and water relation traits were correlated with tissue properties, especially the thickness of the abaxial epidermis and the spongy mesophyll. These findings demonstrate that cell-level water relation traits can acclimate to long-term water stress, and highlight the limitations of extrapolating the results of short-term studies to temporal scales associated with climate change. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.
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Wan, Chang Jin; Liu, Yang Hui; Zhu, Li Qiang; Feng, Ping; Shi, Yi; Wan, Qing
2016-04-20
In the biological nervous system, synaptic plasticity regulation is based on the modulation of ionic fluxes, and such regulation was regarded as the fundamental mechanism underlying memory and learning. Inspired by such biological strategies, indium-gallium-zinc-oxide (IGZO) electric-double-layer (EDL) transistors gated by aqueous solutions were proposed for synaptic behavior emulations. Short-term synaptic plasticity, such as paired-pulse facilitation, high-pass filtering, and orientation tuning, was experimentally emulated in these EDL transistors. Most importantly, we found that such short-term synaptic plasticity can be effectively regulated by alcohol (ethyl alcohol) and salt (potassium chloride) additives. Our results suggest that solution gated oxide-based EDL transistors could act as the platforms for short-term synaptic plasticity emulation.
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Plasticity in thermal tolerance has limited potential to buffer ectotherms from global warming
Gunderson, Alex R.; Stillman, Jonathon H.
2015-01-01
Global warming is increasing the overheating risk for many organisms, though the potential for plasticity in thermal tolerance to mitigate this risk is largely unknown. In part, this shortcoming stems from a lack of knowledge about global and taxonomic patterns of variation in tolerance plasticity. To address this critical issue, we test leading hypotheses for broad-scale variation in ectotherm tolerance plasticity using a dataset that includes vertebrate and invertebrate taxa from terrestrial, freshwater and marine habitats. Contrary to expectation, plasticity in heat tolerance was unrelated to latitude or thermal seasonality. However, plasticity in cold tolerance is associated with thermal seasonality in some habitat types. In addition, aquatic taxa have approximately twice the plasticity of terrestrial taxa. Based on the observed patterns of variation in tolerance plasticity, we propose that limited potential for behavioural plasticity (i.e. behavioural thermoregulation) favours the evolution of greater plasticity in physiological traits, consistent with the ‘Bogert effect’. Finally, we find that all ectotherms have relatively low acclimation in thermal tolerance and demonstrate that overheating risk will be minimally reduced by acclimation in even the most plastic groups. Our analysis indicates that behavioural and evolutionary mechanisms will be critical in allowing ectotherms to buffer themselves from extreme temperatures. PMID:25994676
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Adiponectin modulates synaptic plasticity in hippocampal dentate gyrus.
Pousti, Farideh; Ahmadi, Ramesh; Mirahmadi, Fatemeh; Hosseinmardi, Narges; Rohampour, Kambiz
2018-01-01
Recent studies have suggested the involvement of some metabolic hormones in memory formation and synaptic plasticity. Insulin dysfunction is known as an essential process in the pathogenesis of sporadic Alzheimer's disease (AD). In this study we examined whether adiponectin (ADN), as an insulin-sensitizing adipokine, could affect hippocampal synaptic plasticity. Field potential recordings were performed on intracerebroventricular (icv) cannulated urethane anesthetized rats. After baseline recording from dentate gyrus (DG) and 10min prior to high/low frequency stimulation (HFS/LFS), 10μl icv ADN (600nm) were injected. The slope of field excitatory postsynaptic potentials (fEPSP) and the amplitude of population spikes (PS) were recorded in response to perforanth path (PP) stimulation. Paired pulse stimuli and ADN injection without any stimulation protocols were also evaluated. Application of ADN before HFS increased PS amplitude recorded in DG significantly (P≤0.05) in comparison to HFS only group. ADN suppressed the potency of LFS to induce long-term depression (LTD), causing a significant difference between fEPSP slope (P≤0.05) and PS amplitude (P≤0.01) between ADN+LFS and ADN group. Paired pulse stimuli applied at 20ms intervals showed more paired pulse facilitation (PPF), when applied after ADN (P≤0.05). ADN induced a chemical long-term potentiation (LTP) in which fEPSP slope and PS amplitude increased significantly (P≤0.01 and P≤0.05, respectively). It is concluded that ADN is able to potentiate the HFS-induced LTP and suppress LFS-induced LTD. ADN caused a chemical LTP, when applied without any tetanic protocol. ADN may enhance the presynaptic release probability. Copyright © 2017. Published by Elsevier B.V.
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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.
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Directory of Open Access Journals (Sweden)
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.
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Monitoring the abundance of plastic debris in the marine environment
Ryan, Peter G.; Moore, Charles J.; van Franeker, Jan A.; Moloney, Coleen L.
2009-01-01
Plastic debris has significant environmental and economic impacts in marine systems. Monitoring is crucial to assess the efficacy of measures implemented to reduce the abundance of plastic debris, but it is complicated by large spatial and temporal heterogeneity in the amounts of plastic debris and by our limited understanding of the pathways followed by plastic debris and its long-term fate. To date, most monitoring has focused on beach surveys of stranded plastics and other litter. Infreque...
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Randomized trial of plastic bags to prevent term neonatal hypothermia in a resource-poor setting.
Belsches, Theodore C; Tilly, Alyssa E; Miller, Tonya R; Kambeyanda, Rohan H; Leadford, Alicia; Manasyan, Albert; Chomba, Elwyn; Ramani, Manimaran; Ambalavanan, Namasivayam; Carlo, Waldemar A
2013-09-01
Term infants in resource-poor settings frequently develop hypothermia during the first hours after birth. Plastic bags or wraps are a low-cost intervention for the prevention of hypothermia in preterm and low birth weight infants that may also be effective in term infants. Our objective was to test the hypothesis that placement of term neonates in plastic bags at birth reduces hypothermia at 1 hour after birth in a resource-poor hospital. This parallel-group randomized controlled trial was conducted at University Teaching Hospital, the tertiary referral center in Zambia. Inborn neonates with both a gestational age ≥37 weeks and a birth weight ≥2500 g were randomized 1:1 to either a standard thermoregulation protocol or to a standard thermoregulation protocol with placement of the torso and lower extremities inside a plastic bag within 10 minutes after birth. The primary outcome was hypothermia (plastic bag (n = 135) or to standard thermoregulation care (n = 136) had similar baseline characteristics (birth weight, gestational age, gender, and baseline temperature). Neonates in the plastic bag group had a lower rate of hypothermia (60% vs 73%, risk ratio 0.76, confidence interval 0.60-0.96, P = .026) and a higher axillary temperature (36.4 ± 0.5°C vs 36.2 ± 0.7°C, P plastic bag at birth reduced the incidence of hypothermia at 1 hour after birth in term neonates born in a resource-poor setting, but most neonates remained hypothermic.
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Cytokines and cytokine networks target neurons to modulate long-term potentiation.
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.
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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
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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.
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Hawkins, Robert D
2013-09-18
Recent studies in Aplysia have identified a new variation of synaptic plasticity in which modulatory transmitters enhance spontaneous release of glutamate, which then acts on postsynaptic receptors to recruit mechanisms of intermediate- and long-term plasticity. In this review I suggest the hypothesis that similar plasticity occurs in mammals, where it may contribute to reward, memory, and their dysfunctions in several psychiatric disorders. In Aplysia, spontaneous release is enhanced by activation of presynaptic serotonin receptors, but presynaptic D1 dopamine receptors or nicotinic acetylcholine receptors could play a similar role in mammals. Those receptors enhance spontaneous release of glutamate in hippocampus, entorhinal cortex, prefrontal cortex, ventral tegmental area, and nucleus accumbens. In all of those brain areas, glutamate can activate postsynaptic receptors to elevate Ca(2+) and engage mechanisms of early-phase long-term potentiation (LTP), including AMPA receptor insertion, and of late-phase LTP, including protein synthesis and growth. Thus, presynaptic receptors and spontaneous release may contribute to postsynaptic mechanisms of plasticity in brain regions involved in reward and memory, and could play roles in disorders that affect plasticity in those regions, including addiction, Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD).
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A Spiking Working Memory Model Based on Hebbian Short-Term Potentiation
Fiebig, Florian
2017-01-01
A dominant theory of working memory (WM), referred to as the persistent activity hypothesis, holds that recurrently connected neural networks, presumably located in the prefrontal cortex, encode and maintain WM memory items through sustained elevated activity. Reexamination of experimental data has shown that prefrontal cortex activity in single units during delay periods is much more variable than predicted by such a theory and associated computational models. Alternative models of WM maintenance based on synaptic plasticity, such as short-term nonassociative (non-Hebbian) synaptic facilitation, have been suggested but cannot account for encoding of novel associations. Here we test the hypothesis that a recently identified fast-expressing form of Hebbian synaptic plasticity (associative short-term potentiation) is a possible mechanism for WM encoding and maintenance. Our simulations using a spiking neural network model of cortex reproduce a range of cognitive memory effects in the classical multi-item WM task of encoding and immediate free recall of word lists. Memory reactivation in the model occurs in discrete oscillatory bursts rather than as sustained activity. We relate dynamic network activity as well as key synaptic characteristics to electrophysiological measurements. Our findings support the hypothesis that fast Hebbian short-term potentiation is a key WM mechanism. SIGNIFICANCE STATEMENT Working memory (WM) is a key component of cognition. Hypotheses about the neural mechanism behind WM are currently under revision. Reflecting recent findings of fast Hebbian synaptic plasticity in cortex, we test whether a cortical spiking neural network model with such a mechanism can learn a multi-item WM task (word list learning). We show that our model can reproduce human cognitive phenomena and achieve comparable memory performance in both free and cued recall while being simultaneously compatible with experimental data on structure, connectivity, and
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Partial diel migration: A facultative migration underpinned by long-term inter-individual variation.
Harrison, Philip M; Gutowsky, Lee F G; Martins, Eduardo G; Patterson, David A; Cooke, Steven J; Power, Michael
2017-09-01
The variations in migration that comprise partial diel migrations, putatively occur entirely as a consequence of behavioural flexibility. However, seasonal partial migrations are increasingly recognised to be mediated by a combination of reversible plasticity in response to environmental variation and individual variation due to genetic and environmental effects. Here, we test the hypothesis that while partial diel migration heterogeneity occurs primarily due to short-term within-individual flexibility in behaviour, long-term individual differences in migratory behaviour also underpin this migration variation. Specifically, we use a hierarchical behavioural reaction norm approach to partition within- and among-individual variation in depth use and diel plasticity in depth use, across short- and long-term time-scales, in a group of 47 burbot (Lota lota) tagged with depth-sensing acoustic telemetry transmitters. We found that within-individual variation at the among-dates-within-seasons and among-seasons scale, explained the dominant proportion of phenotypic variation. However, individuals also repeatedly differed in their expression of migration behaviour over the 2 year study duration. These results reveal that diel migration variation occurs primarily due to short-term within-individual flexibility in depth use and diel migration behaviour. However, repeatable individual differences also played a key role in mediating partial diel migration. These findings represent a significant advancement of our understanding of the mechanisms generating the important, yet poorly understood phenomena of partial diel migration. Moreover, given the pervasive occurrence of diel migrations across aquatic taxa, these findings indicate that individual differences have an important, yet previously unacknowledged role in structuring the temporal and vertical dynamics of aquatic ecosystems. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.
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Neurotrophins play differential roles in short and long-term recognition memory.
Callaghan, Charlotte K; Kelly, Aine M
2013-09-01
The neurotrophin family of proteins are believed to mediate various forms of synaptic plasticity in the adult brain. Here we have assessed the roles of these proteins in object recognition memory in the rat, using icv infusions of function-blocking antibodies or the tyrosine kinase antagonist, tyrphostin AG879, to block Trk receptors. We report that tyrphostin AG879 impairs both short-term and long-term recognition memory, indicating a requirement for Trk receptor activation in both processes. The effect of inhibition of each of the neurotrophins with activity-blocking neutralising antibodies was also tested. Treatment with anti-BDNF, anti-NGF or anti-NT4 had no effect on short-term memory, but blocked long-term recognition memory. Treatment with anti-NT3 had no effect on either process. We also assessed changes in expression of neurotrophins and their respective receptors in the hippocampus, dentate gyrus and perirhinal cortex over a 24 h period following training in the object recognition task. We observed time-dependent changes in expression of the Trk receptors and their ligands in the dentate gyrus and perirhinal cortex. The data are consistent with a pivotal role for neurotrophic factors in the expression of recognition memory. Copyright © 2013 Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
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
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CaMKII knockdown affects both early and late phases of olfactory long-term memory in the honeybee.
Scholl, Christina; Kübert, Natalie; Muenz, Thomas S; Rössler, Wolfgang
2015-12-01
Honeybees are able to solve complex learning tasks and memorize learned information for long time periods. The molecular mechanisms mediating long-term memory (LTM) in the honeybee Apis mellifera are, to a large part, still unknown. We approached this question by investigating the potential function of the calcium/calmodulin-dependent protein kinase II (CaMKII), an enzyme known as a 'molecular memory switch' in vertebrates. CaMKII is able to switch to a calcium-independent constitutively active state, providing a mechanism for a molecular memory and has further been shown to play an essential role in structural synaptic plasticity. Using a combination of knockdown by RNA interference and pharmacological manipulation, we disrupted the function of CaMKII during olfactory learning and memory formation. We found that learning, memory acquisition and mid-term memory were not affected, but all manipulations consistently resulted in an impaired LTM. Both early LTM (24 h after learning) and late LTM (72 h after learning) were significantly disrupted, indicating the necessity of CaMKII in two successive stages of LTM formation in the honeybee. © 2015. Published by The Company of Biologists Ltd.
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Long Term Financing of Infrastructure
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...
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Short-term cortical plasticity induced by conditioning pain modulation
DEFF Research Database (Denmark)
Egsgaard, Line Lindhardt; Buchgreitz, Line; Wang, Li
2012-01-01
To investigate the effects of homotopic and heterotopic conditioning pain modulation (CPM) on short-term cortical plasticity. Glutamate (tonic pain) or isotonic saline (sham) was injected in the upper trapezius (homotopic) and in the thenar (heterotopic) muscles. Intramuscular electrical stimulat......To investigate the effects of homotopic and heterotopic conditioning pain modulation (CPM) on short-term cortical plasticity. Glutamate (tonic pain) or isotonic saline (sham) was injected in the upper trapezius (homotopic) and in the thenar (heterotopic) muscles. Intramuscular electrical......, and after homotopic and heterotopic CPM versus control. Peak latencies at N100, P200, and P300 were extracted and the location/strength of corresponding dipole current sources and multiple dipoles were estimated. Homotopic CPM caused hypoalgesia (P = 0.032, 30.6% compared to baseline) to electrical...... stimulation. No cortical changes were found for homotopic CPM. A positive correlation at P200 between electrical pain threshold after tonic pain and the z coordinate after tonic pain (P = 0.032) was found for homotopic CPM. For heterotopic CPM, no significant hypoalgesia was found and a dipole shift of the P...
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Long-term use of short- and long-acting nitrates in stable angina pectoris.
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.
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Directory of Open Access Journals (Sweden)
Laura eMaggi
2011-10-01
Full Text Available In recent years several evidence demonstrated that some features of hippocampal biology, like neurogenesis, synaptic transmission, learning and memory performances are deeply modulated by social, motor and sensorial experiences. Fractalkine/CX3CL1 is a transmembrane chemokine abundantly expressed in the brain by neurons, where it modulates glutamatergic transmission and long-term plasticity processes regulating the intercellular communication between glia and neurons, being its specific receptor CX3CR1 expressed by microglia. In this paper we investigated the role of CX3CL1/CX3CR1 signaling on experience-dependent hippocampal plasticity processes. At this aim wt and CX3CR1GFP/GFP mice were exposed to long-lasting-enriched environment (EE and the effects on hippocampal functions were studied by electrophysiological recordings of long-term potentiation (LTP of synaptic activity, behavioral tests of learning and memory in the Morris water maze paradigm and analysis of neurogenesis in the subgranular zone of the dentate gyrus (DG.We found that CX3CR1 deficiency increases hippocampal plasticity and spatial memory blunting the potentiating effects of EE. In contrast, exposure to EE increased the number and migration of neural progenitors in the DG of both wt and CX3CR1GFP/GFP mice. These data indicate that CX3CL1/CX3CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.
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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.
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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.
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Long-lasting antifog plasma modification of transparent plastics.
Di Mundo, Rosa; d'Agostino, Riccardo; Palumbo, Fabio
2014-10-08
Antifog surfaces are necessary for any application requiring optical efficiency of transparent materials. Surface modification methods aimed toward increasing solid surface energy, even when supposed to be permanent, in fact result in a nondurable effect due to the instability in air of highly hydrophilic surfaces. We propose the strategy of combining a hydrophilic chemistry with a nanotextured topography, to tailor a long-lasting antifog modification on commercial transparent plastics. In particular, we investigated a two-step process consisting of self-masked plasma etching followed by plasma deposition of a silicon-based film. We show that the deposition of the silicon-based coatings on the flat (pristine) substrates allows a continuous variation of wettability from hydrophobic to superhydrophilic, due to a continuous reduction of carbon-containing groups, as assessed by Fourier transform infrared and X-ray photoelectron spectroscopies. By depositing these different coatings on previously nanotextured substrates, the surface wettability behavior is changed consistently, as well as the condensation phenomenon in terms of microdroplets/liquid film appearance. This variation is correlated with advancing and receding water contact angle features of the surfaces. More importantly, in the case of the superhydrophilic coating, though its surface energy decreases with time, when a nanotextured surface underlies it, the wetting behavior is maintained durably superhydrophilic, thus durably antifog.
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Cabezas, Carolina; Buño, Washington
2006-05-01
Recent evidence suggests that functional and silent synapses are not only postsynaptically different but also presynaptically distinct. The presynaptic differences may be of functional importance in memory formation because a proposed mechanism for long-term potentiation is the conversion of silent synapses into functional ones. However, there is little direct experimentally evidence of these differences. We have investigated the transmitter release properties of functional and silent Schaffer collateral synapses and show that on the average functional synapses displayed a lower percentage of failures and higher excitatory postsynaptic current (EPSC) amplitudes than silent synapses at +60 mV. Moreover, functional but not silent synapses show paired-pulse facilitation (PPF) at +60 mV and thus presynaptic short-term plasticity will be distinct in the two types of synapse. We examined whether intraterminal endoplasmic reticulum Ca2+ stores influenced the release properties of these synapses. Ryanodine (100 microM) and thapsigargin (1 microM) increased the percentage of failures and decreased both the EPSC amplitude and PPF in functional synapses. Caffeine (10 mM) had the opposite effects. In contrast, silent synapses were insensitive to both ryanodine and caffeine. Hence we have identified differences in the release properties of functional and silent synapses, suggesting that synaptic terminals of functional synapses express regulatory molecular mechanisms that are absent in silent synapses.
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Directory of Open Access Journals (Sweden)
Seungsoo Chung
2017-06-01
Full Text Available Recent work has shown that thalamocortical (TC inputs can be plastic after the developmental critical period has closed, but the mechanism that enables re-establishment of plasticity is unclear. Here, we find that long-term potentiation (LTP at TC inputs is transiently restored in spared barrel cortex following either a unilateral infra-orbital nerve (ION lesion, unilateral whisker trimming, or unilateral ablation of the rodent barrel cortex. Restoration of LTP is associated with increased potency at TC input and reactivates anatomical map plasticity induced by whisker follicle ablation. The reactivation of TC LTP is accompanied by reappearance of silent synapses. Both LTP and silent synapse formation are preceded by transient re-expression of synaptic GluN2B-containing N-methyl-D-aspartate (NMDA receptors, which are required for the reappearance of TC plasticity. These results clearly demonstrate that peripheral sensory deprivation reactivates synaptic plasticity in the mature layer 4 barrel cortex with features similar to the developmental critical period.
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Directory of Open Access Journals (Sweden)
Christian Bonansco
2016-01-01
Full Text Available Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks.
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A systematic review of potential long-term effects of sport-related concussion
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
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Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin
2015-07-01
Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood. © 2014 Society for the Study of Addiction.
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Venezia, Andrew C.; Guth, Lisa M.; Sapp, Ryan M.; Spangenburg, Espen E.; Roth, Stephen M.
2016-01-01
The beneficial effects of physical activity on brain health (synaptogenesis, neurogenesis, enhanced synaptic plasticity, improved learning and memory) appear to be mediated through changes in region-specific expression of neurotrophins, transcription factors, and postsynaptic receptors, though investigations of sex differences in response to long-term voluntary wheel running are limited.
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Synaptic long-term potentiation realized in Pavlov's dog model based on a NiOx-based memristor
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.
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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
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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)
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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…
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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
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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.
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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.
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Vogel-Ciernia, Annie; Wood, Marcelo A
2014-05-01
Long-term memory formation requires the coordinated regulation of gene expression. Until recently nucleosome remodeling, one of the major epigenetic mechanisms for controlling gene expression, had been largely unexplored in the field of neuroscience. Nucleosome remodeling is carried out by chromatin remodeling complexes (CRCs) that interact with DNA and histones to physically alter chromatin structure and ultimately regulate gene expression. Human exome sequencing and gene wide association studies have linked mutations in CRC subunits to intellectual disability disorders, autism spectrum disorder and schizophrenia. However, how mutations in CRC subunits were related to human cognitive disorders was unknown. There appears to be both developmental and adult specific roles for the neuron specific CRC nBAF (neuronal Brg1/hBrm Associated Factor). nBAF regulates gene expression required for dendritic arborization during development, and in the adult, contributes to long-term potentiation, a form of synaptic plasticity, and long-term memory. We propose that the nBAF complex is a novel epigenetic mechanism for regulating transcription required for long-lasting forms of synaptic plasticity and memory processes and that impaired nBAF function may result in human cognitive disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.
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HIV-related politics in long-term perspective.
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?
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Color change, phenotypic plasticity, and camouflage
Directory of Open Access Journals (Sweden)
Martin eStevens
2016-05-01
Full Text Available The ability to change appearance over a range of timescales is widespread in nature, existing in many invertebrate and vertebrate groups. This can include color change occurring in seconds, minutes, and hours, to longer term changes associated with phenotypic plasticity and development. A major function is for camouflage against predators because color change and plasticity enables animals to match their surroundings and potentially reduce the risk of predation. Recently, we published findings (Stevens et al. 2014a showing how shore crabs can change their appearance and better match the background to predator vision in the short term. This, coupled with a number of past studies, emphasizes the potential that animals have to modify their appearance for camouflage. However, the majority of studies on camouflage and color plasticity have focused on a small number of species capable of unusually rapid changes. There are many broad questions that remain about the nature, mechanisms, evolution, and adaptive value of color change and plasticity for concealment. Here, I discuss past work and outline six questions relating to color change and plasticity, as well as major avenues for future work.
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Effect of modafinil on learning performance and neocortical long-term potentiation in rats.
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.
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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
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Behavior of high burnup fuel rod cladding during long-term dry storage in CASTOR casks
International Nuclear Information System (INIS)
Schaberg, A.; Spilker, H.; Goll, W.
2000-01-01
Short-time creep and rupture tests were performed to assess the strain potential of cladding of high burnt rods under conditions of dry storage. The tests comprised optimized Zr y-4 cladding samples from fuel rods irradiated to burnups of up to 64 MWd/kg U and were carried out at temperatures of 573 and 643 K at cladding stresses of about 400 and 600 MPa. The stresses, much higher than those occurring in a fuel rod, were chosen to reach circumferential elongations of about 2% within an envisaged testing time of 3-4 days. The creep tests were followed by a low temperature test at 423 K and 100 MPa to assess the long-term behavior of the cladding ductility especially with regard to the effect of a higher hydrogen content in the cladding due to the high burnup. The creep tests showed considerable uniform plastic elongations at these high burnups. It was demonstrated that around 600 K a uniform plastic strain of a least 2% is reached without cladding failure. The low temperature tests at 423 K for up to 5 days revealed no cladding failure under these conditions of reduced cladding ductility. It can be concluded that the increased hydrogen content has no adverse effect on cladding performance. (Authors)
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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.)
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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
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Learning-dependent neurogenesis in the olfactory bulb determines long-term olfactory memory.
Sultan, S; Mandairon, N; Kermen, F; Garcia, S; Sacquet, J; Didier, A
2010-07-01
Inhibitory interneurons of the olfactory bulb are subjected to permanent adult neurogenesis. Their number is modulated by learning, suggesting that they could play a role in plastic changes of the bulbar network associated with olfactory memory. Adult male C57BL/6 mice were trained in an associative olfactory task, and we analyzed long-term retention of the task 5, 30, and 90 d post-training. In parallel, we assessed the fate of these newborn cells, mapped their distribution in the olfactory bulb and measured their functional implication using the immediate early gene Zif268. In a second set of experiments, we pharmacologically modulated glutamatergic transmission and using the same behavioral task assessed the consequences on memory retention and neurogenesis. Finally, by local infusion of an antimitotic drug, we selectively blocked neurogenesis during acquisition of the task and looked at the effects on memory retention. First we demonstrated that retrieval of an associative olfactory task recruits the newborn neurons in odor-specific areas of the olfactory bulb selected to survive during acquisition of the task and that it does this in a manner that depends on the strength of learning. We then demonstrated that acquisition is not dependent on neurogenesis if long-term retention of the task is abolished by blocking neurogenesis. Adult-born neurons are thus involved in changes in the neural representation of an odor; this underlies long-term olfactory memory as the strength of learning is linked to the duration of this memory. Neurogenesis thus plays a crucial role in long-term olfactory memory.
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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
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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.
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Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.
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.
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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…
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A systematic review of potential long-term effects of sport-related concussion.
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.
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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
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Cannabinoids modulate hippocampal memory and plasticity.
Abush, Hila; Akirav, Irit
2010-10-01
Considerable evidence demonstrates that cannabinoid agonists impair whereas cannabinoid antagonists improve memory and plasticity. However, recent studies suggest that the effects of cannabinoids on learning do not necessarily follow these simple patterns, particularly when emotional memory processes are involved. We investigated the involvement of the cannabinoid system in hippocampal learning and plasticity using the fear-related inhibitory avoidance (IA) and the non-fear-related spatial learning paradigms, and cellular models of learning and memory, i.e., long-term potentiation (LTP) and long-term depression (LTD). We found that microinjection into the CA1 of the CB1/CB2 receptor agonist WIN55,212-2 (5 μg/side) and an inhibitor of endocannabinoid reuptake and breakdown AM404 (200 ng/side) facilitated the extinction of IA, while the CB1 receptor antagonist AM251 (6 ng/side) impaired it. WIN55,212-2 and AM251 did not affect IA conditioning, while AM404 enhanced it, probably due to a drug-induced increase in pain sensitivity. However, in the water maze, systemic or local CA1 injections of AM251, WIN55,212-2, and AM404 all impaired spatial learning. We also found that i.p. administration of WIN55,212-2 (0.5 mg/kg), AM404 (10 mg/kg), and AM251 (2 mg/kg) impaired LTP in the Schaffer collateral-CA1 projection, whereas AM404 facilitated LTD. Our findings suggest diverse effects of the cannabinoid system on CA1 memory and plasticity that cannot be categorized simply into an impairing or an enhancing effect of cannabinoid activation and deactivation, respectively. Moreover, they provide preclinical support for the suggestion that targeting the endocannabinoid system may aid in the treatment of disorders associated with impaired extinction-like processes, such as post-traumatic stress disorder. © 2009 Wiley-Liss, Inc.
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Long-term urethral catheterisation.
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.
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Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review.
Balk, Ethan M; Earley, Amy; Avendano, Esther A; Raman, Gowri
2016-02-02
Silicone gel breast implants were removed from the U.S. market for cosmetic use in 1992 owing to safety concerns. They were reintroduced in 2006, with a call for improved surveillance of clinical outcomes. To systematically review the literature regarding specific long-term health outcomes in women with silicone gel breast implants, including cancer; connective tissue, rheumatologic, and autoimmune diseases; neurologic diseases; reproductive issues, including lactation; offspring issues; and mental health issues (depression and suicide). MEDLINE, EMBASE, and Ovid Healthstar (inception through 30 June 2015), and the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the first quarter of 2015). 4 researchers double-screened articles for longitudinal studies that compared women with and without breast implants and reported long-term health outcomes of interest. 4 researchers extracted data on participant and implant characteristics, analytic methods, and results. 32 studies (in 58 publications) met eligibility criteria. Random-effects model meta-analyses of effect sizes were conducted when feasible. For most outcomes, there was at most only a single adequately adjusted study, which usually found no significant associations. There were possible associations with decreased risk for primary breast and endometrial cancers and increased risks for lung cancer, rheumatoid arthritis, Sjögren syndrome, and Raynaud syndrome. Evidence on breast implants and other outcomes either was limited or did not exist. The evidence was most frequently not specific to silicone gel implants, and studies were rarely adequately adjusted for potential confounders. The evidence remains inconclusive about any association between silicone gel implants and long-term health outcomes. Better evidence is needed from existing large studies, which can be reanalyzed to clarify the strength of associations between silicone gel implants and health outcomes
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Chang, C T; Zeng, F; Li, X J; Dong, W S; Lu, S H; Gao, S; Pan, F
2016-01-07
The simulation of synaptic plasticity using new materials is critical in the study of brain-inspired computing. Devices composed of Ba(CF3SO3)2-doped polyethylene oxide (PEO) electrolyte film were fabricated and with pulse responses found to resemble the synaptic short-term plasticity (STP) of both short-term depression (STD) and short-term facilitation (STF) synapses. The values of the charge and discharge peaks of the pulse responses did not vary with input number when the pulse frequency was sufficiently low(~1 Hz). However, when the frequency was increased, the charge and discharge peaks decreased and increased, respectively, in gradual trends and approached stable values with respect to the input number. These stable values varied with the input frequency, which resulted in the depressed and potentiated weight modifications of the charge and discharge peaks, respectively. These electrical properties simulated the high and low band-pass filtering effects of STD and STF, respectively. The simulations were consistent with biological results and the corresponding biological parameters were successfully extracted. The study verified the feasibility of using organic electrolytes to mimic STP.
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Cyclic plastic hinges with degradation effects for frame structures
DEFF Research Database (Denmark)
Tidemann, Lasse; Krenk, Steen
2017-01-01
A model of cyclic plastic hinges in frame structures including degradation effects for stiffness and strength is developed. The model is formulated via potentials in terms of section forces. It consists of a yield surface, described in a generic format permitting representation of general convex...... shapes including corners, and a set of evolution equations based on an internal energy potential and a plastic flow potential. The form of these potentials is specified by five parameters for each generalized stress-strain component describing yield level, ultimate stress capacity, elastic...... and stiffness parameters. The cyclic plastic hinges are introduced into a six-component equilibrium-based beam element, using additive element and hinge flexibilities. When converted to stiffness format the plastic hinges are incorporated into the element stiffness matrix. The cyclic plastic hinge model...
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Energy Technology Data Exchange (ETDEWEB)
Shen, Chen [GE Global Research, NIskayuna, NY (United States); Gupta, Vipul [GE Global Research, NIskayuna, NY (United States); Huang, Shenyan [GE Global Research, NIskayuna, NY (United States); Soare, Monica [GE Global Research, NIskayuna, NY (United States); Zhao, Pengyang [GE Global Research, NIskayuna, NY (United States); Wang, Yunzhi [GE Global Research, NIskayuna, NY (United States)
2017-02-28
The goal of this project is to model long-term creep performance for nickel-base superalloy weldments in high temperature power generation systems. The project uses physics-based modeling methodologies and algorithms for predicting alloy properties in heterogeneous material structures. The modeling methodology will be demonstrated on a gas turbine combustor liner weldment of Haynes 282 precipitate-strengthened nickel-base superalloy. The major developments are: (1) microstructure-property relationships under creep conditions and microstructure characterization (2) modeling inhomogeneous microstructure in superalloy weld (3) modeling mesoscale plastic deformation in superalloy weld and (4) a constitutive creep model that accounts for weld and base metal microstructure and their long term evolution. The developed modeling technology is aimed to provide a more efficient and accurate assessment of a material’s long-term performance compared with current testing and extrapolation methods. This modeling technology will also accelerate development and qualification of new materials in advanced power generation systems. This document is a final technical report for the project, covering efforts conducted from October 2014 to December 2016.
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Short-term versus long-term approaches to the development of tourism-related policies
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...
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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.
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Noack, Marko; Partzsch, Johannes; Mayr, Christian G; Hänzsche, Stefan; Scholze, Stefan; Höppner, Sebastian; Ellguth, Georg; Schüffny, Rene
2015-01-01
Synaptic dynamics, such as long- and short-term plasticity, play an important role in the complexity and biological realism achievable when running neural networks on a neuromorphic IC. For example, they endow the IC with an ability to adapt and learn from its environment. In order to achieve the millisecond to second time constants required for these synaptic dynamics, analog subthreshold circuits are usually employed. However, due to process variation and leakage problems, it is almost impossible to port these types of circuits to modern sub-100nm technologies. In contrast, we present a neuromorphic system in a 28 nm CMOS process that employs switched capacitor (SC) circuits to implement 128 short term plasticity presynapses as well as 8192 stop-learning synapses. The neuromorphic system consumes an area of 0.36 mm(2) and runs at a power consumption of 1.9 mW. The circuit makes use of a technique for minimizing leakage effects allowing for real-time operation with time constants up to several seconds. Since we rely on SC techniques for all calculations, the system is composed of only generic mixed-signal building blocks. These generic building blocks make the system easy to port between technologies and the large digital circuit part inherent in an SC system benefits fully from technology scaling.
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Orlando, Marta
2017-10-17
Both excitatory and inhibitory synaptic contacts display activity dependent dynamic changes in their efficacy that are globally termed synaptic plasticity. Although the molecular mechanisms underlying glutamatergic synaptic plasticity have been extensively investigated and described, those responsible for inhibitory synaptic plasticity are only beginning to be unveiled. In this framework, the ultrastructural changes of the inhibitory synapses during plasticity have been poorly investigated. Here we combined confocal fluorescence microscopy (CFM) with high resolution scanning electron microscopy (HRSEM) to characterize the fine structural rearrangements of post-synaptic GABAA Receptors (GABAARs) at the nanometric scale during the induction of inhibitory long-term potentiation (iLTP). Additional electron tomography (ET) experiments on immunolabelled hippocampal neurons allowed the visualization of synaptic contacts and confirmed the reorganization of post-synaptic GABAAR clusters in response to chemical iLTP inducing protocol. Altogether, these approaches revealed that, following the induction of inhibitory synaptic potentiation, GABAAR clusters increase in size and number at the post-synaptic membrane with no other major structural changes of the pre- and post-synaptic elements.
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Orlando, Marta; Ravasenga, Tiziana; Petrini, Enrica Maria; Falqui, Andrea; Marotta, Roberto; Barberis, Andrea
2017-01-01
Both excitatory and inhibitory synaptic contacts display activity dependent dynamic changes in their efficacy that are globally termed synaptic plasticity. Although the molecular mechanisms underlying glutamatergic synaptic plasticity have been extensively investigated and described, those responsible for inhibitory synaptic plasticity are only beginning to be unveiled. In this framework, the ultrastructural changes of the inhibitory synapses during plasticity have been poorly investigated. Here we combined confocal fluorescence microscopy (CFM) with high resolution scanning electron microscopy (HRSEM) to characterize the fine structural rearrangements of post-synaptic GABAA Receptors (GABAARs) at the nanometric scale during the induction of inhibitory long-term potentiation (iLTP). Additional electron tomography (ET) experiments on immunolabelled hippocampal neurons allowed the visualization of synaptic contacts and confirmed the reorganization of post-synaptic GABAAR clusters in response to chemical iLTP inducing protocol. Altogether, these approaches revealed that, following the induction of inhibitory synaptic potentiation, GABAAR clusters increase in size and number at the post-synaptic membrane with no other major structural changes of the pre- and post-synaptic elements.
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Orlando, Marta; Ravasenga, Tiziana; Petrini, Enrica Maria; Falqui, Andrea; Marotta, Roberto; Barberis, Andrea
2017-10-23
Both excitatory and inhibitory synaptic contacts display activity dependent dynamic changes in their efficacy that are globally termed synaptic plasticity. Although the molecular mechanisms underlying glutamatergic synaptic plasticity have been extensively investigated and described, those responsible for inhibitory synaptic plasticity are only beginning to be unveiled. In this framework, the ultrastructural changes of the inhibitory synapses during plasticity have been poorly investigated. Here we combined confocal fluorescence microscopy (CFM) with high resolution scanning electron microscopy (HRSEM) to characterize the fine structural rearrangements of post-synaptic GABA A Receptors (GABA A Rs) at the nanometric scale during the induction of inhibitory long-term potentiation (iLTP). Additional electron tomography (ET) experiments on immunolabelled hippocampal neurons allowed the visualization of synaptic contacts and confirmed the reorganization of post-synaptic GABA A R clusters in response to chemical iLTP inducing protocol. Altogether, these approaches revealed that, following the induction of inhibitory synaptic potentiation, GABA A R clusters increase in size and number at the post-synaptic membrane with no other major structural changes of the pre- and post-synaptic elements.
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Ammonia inhibits long-term potentiation via neurosteroid synthesis in hippocampal pyramidal neurons.
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.
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Long-term memory shapes the primary olfactory center of an insect brain.
Hourcade, Benoît; Perisse, Emmanuel; Devaud, Jean-Marc; Sandoz, Jean-Christophe
2009-10-01
The storage of stable memories is generally considered to rely on changes in the functional properties and/or the synaptic connectivity of neural networks. However, these changes are not easily tractable given the complexity of the learning procedures and brain circuits studied. Such a search can be narrowed down by studying memories of specific stimuli in a given sensory modality and by working on networks with a modular and relatively simple organization. We have therefore focused on associative memories of individual odors and the possible related changes in the honeybee primary olfactory center, the antennal lobe (AL). As this brain structure is organized in well-identified morpho-functional units, the glomeruli, we looked for evidence of structural and functional plasticity in these units in relation with the bees' ability to store long-term memories (LTMs) of specific odors. Restrained bees were trained to form an odor-specific LTM in an appetitive Pavlovian conditioning protocol. The stability and specificity of this memory was tested behaviorally 3 d after conditioning. At that time, we performed both a structural and a functional analysis on a subset of 17 identified glomeruli by measuring glomerular volume under confocal microscopy, and odor-evoked activity, using in vivo calcium imaging. We show that long-term olfactory memory for a given odor is associated with volume increases in a subset of glomeruli. Independent of these structural changes, odor-evoked activity was not modified. Lastly, we show that structural glomerular plasticity can be predicted based on a putative model of interglomerular connections.
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A kinetic model of dopamine- and calcium-dependent striatal synaptic plasticity.
Directory of Open Access Journals (Sweden)
Takashi Nakano
2010-02-01
Full Text Available Corticostriatal synapse plasticity of medium spiny neurons is regulated by glutamate input from the cortex and dopamine input from the substantia nigra. While cortical stimulation alone results in long-term depression (LTD, the combination with dopamine switches LTD to long-term potentiation (LTP, which is known as dopamine-dependent plasticity. LTP is also induced by cortical stimulation in magnesium-free solution, which leads to massive calcium influx through NMDA-type receptors and is regarded as calcium-dependent plasticity. Signaling cascades in the corticostriatal spines are currently under investigation. However, because of the existence of multiple excitatory and inhibitory pathways with loops, the mechanisms regulating the two types of plasticity remain poorly understood. A signaling pathway model of spines that express D1-type dopamine receptors was constructed to analyze the dynamic mechanisms of dopamine- and calcium-dependent plasticity. The model incorporated all major signaling molecules, including dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP32, as well as AMPA receptor trafficking in the post-synaptic membrane. Simulations with dopamine and calcium inputs reproduced dopamine- and calcium-dependent plasticity. Further in silico experiments revealed that the positive feedback loop consisted of protein kinase A (PKA, protein phosphatase 2A (PP2A, and the phosphorylation site at threonine 75 of DARPP-32 (Thr75 served as the major switch for inducing LTD and LTP. Calcium input modulated this loop through the PP2B (phosphatase 2B-CK1 (casein kinase 1-Cdk5 (cyclin-dependent kinase 5-Thr75 pathway and PP2A, whereas calcium and dopamine input activated the loop via PKA activation by cyclic AMP (cAMP. The positive feedback loop displayed robust bi-stable responses following changes in the reaction parameters. Increased basal dopamine levels disrupted this dopamine-dependent plasticity. The
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Potential of Electronic Plastic Waste as a Source of Raw Material and Energy Recovery
International Nuclear Information System (INIS)
Norazli Othman; Nor Ezlin Ahmad Basri; Lariyah Mohd Sidek
2009-01-01
Nowadays, the production of electronic equipment is one of the fastest growing industrial activities in this world. The increase use of plastic in this sector resulted in an increase of electronic plastic waste. Basically, electronic plastic material contains various chemical elements which act as a flame retardant when electronic equipment is operated. In general, the concept of recycling electronic plastic waste should be considered in order to protect the environment. For this purpose, research has been conducted to different resins of electronic plastic waste to identify the potential of electronic plastic waste as a source of raw material and energy recovery. This study was divided into two part for example determination of physical and chemical characteristics of plastic resins and calculation of heating value for plastic resins based on Dulong formula. Results of this research show that the average calorific value of electronic waste is 30,872.42 kJ/ kg (7,375 kcal/ kg). The emission factor analysis showed that the concentration of emission value that might occur during waste management activities is below the standard set by the Environment Quality Act 1974. Basically, this research shows that electronic plastic waste has the potential to become the source of raw material and energy recovery. (author)
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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
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Nitsche, Michael A.; Wobrock, Thomas; Bunse, Tilmann; Rein, Bettina; Herrmann, Maximiliane; Schmitt, Andrea; Nieratschker, Vanessa; Witt, Stephanie H.; Rietschel, Marcella; Falkai, Peter; Hasan, Alkomiet
2015-01-01
Background: Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients. Methods: Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied. Results: Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS. Conclusions: These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory
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International Nuclear Information System (INIS)
Mozharovskaya, T.N.
1984-01-01
A programme and procedure are given to study 08Kh18N9 steel at 600 deg C and 15Kh2MFA steel at 550 deg C for creep and long-term strength at different parameters of proportional loading as well as at different parameters under loading in two-link irregular trajectories. This makes it possible to estimate the effect of the kind of a stress deviator, history and prehistory of loading on plastic deformation in creep and on failure under long-term loading
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Energy Technology Data Exchange (ETDEWEB)
Mozharovskaya, T N [AN Ukrainskoj SSR, Kiev. Inst. Problem Prochnosti
1984-11-01
A programme and procedure are given to study 08Kh18N9 steel at 600 deg C and 15Kh2MFA steel at 550 deg C for creep and long-term strength at different parameters of proportional loading as well as at different parameters under loading in two-link irregular trajectories. This makes it possible to estimate the effect of the kind of a stress deviator, history and prehistory of loading on plastic deformation in creep and on failure under long-term loading.
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Enhancing neural activity to drive respiratory plasticity following cervical spinal cord injury
Hormigo, Kristiina M.; Zholudeva, Lyandysha V.; Spruance, Victoria M.; Marchenko, Vitaliy; Cote, Marie-Pascale; Vinit, Stephane; Giszter, Simon; Bezdudnaya, Tatiana; Lane, Michael A.
2016-01-01
Cervical spinal cord injury (SCI) results in permanent life-altering sensorimotor deficits, among which impaired breathing is one of the most devastating and life-threatening. While clinical and experimental research has revealed that some spontaneous respiratory improvement (functional plasticity) can occur post-SCI, the extent of the recovery is limited and significant deficits persist. Thus, increasing effort is being made to develop therapies that harness and enhance this neuroplastic potential to optimize long-term recovery of breathing in injured individuals. One strategy with demonstrated therapeutic potential is the use of treatments that increase neural and muscular activity (e.g. locomotor training, neural and muscular stimulation) and promote plasticity. With a focus on respiratory function post-SCI, this review will discuss advances in the use of neural interfacing strategies and activity-based treatments, and highlights some recent results from our own research. PMID:27582085
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Frequency dependent changes in NMDAR-dependent synaptic plasticity
Directory of Open Access Journals (Sweden)
Arvind eKumar
2011-09-01
Full Text Available The NMDAR-dependent synaptic plasticity is thought to mediate several forms of learning, and can be induced by spike trains containing a small number of spikes occurring with varying rates and timing, as well as with oscillations. We computed the influence of these variables on the plasticity induced at a single NMDAR containing synapse using a reduced model that was analytically tractable, and these findings were confirmed using detailed, multi-compartment model. In addition to explaining diverse experimental results about the rate and timing dependence of synaptic plasticity, the model made several novel and testable predictions. We found that there was a preferred frequency for inducing long-term potentiation (LTP such that higher frequency stimuli induced lesser LTP, decreasing as 1/f when the number of spikes in the stimulus was kept fixed. Among other things, the preferred frequency for inducing LTP varied as a function of the distance of the synapse from the soma. In fact, same stimulation frequencies could induce LTP or LTD depending on the dendritic location of the synapse. Next, we found that rhythmic stimuli induced greater plasticity then irregular stimuli. Furthermore, brief bursts of spikes significantly expanded the timing dependence of plasticity. Finally, we found that in the ~5-15Hz frequency range both rate- and timing-dependent plasticity mechanisms work synergistically to render the synaptic plasticity most sensitive to spike-timing. These findings provide computational evidence that oscillations can have a profound influence on the plasticity of an NMDAR-dependent synapse, and show a novel role for the dendritic morphology in this process.
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Assessing the associative deficit of older adults in long-term and short-term/working memory.
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.
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Dale, Erica A; Fields, Daryl P; Devinney, Michael J; Mitchell, Gordon S
2017-01-01
Phrenic long-term facilitation (pLTF) is a form of hypoxia-induced spinal respiratory motor plasticity that requires new synthesis of brain derived neurotrophic factor (BDNF) and activation of its high-affinity receptor, tropomyosin receptor kinase B (TrkB). Since the cellular location of relevant TrkB receptors is not known, we utilized intrapleural siRNA injections to selectively knock down TrkB receptor protein within phrenic motor neurons. TrkB receptors within phrenic motor neurons are necessary for BDNF-dependent acute intermittent hypoxia-induced pLTF, demonstrating that phrenic motor neurons are a critical site of respiratory motor plasticity. Copyright © 2016 Elsevier Inc. All rights reserved.
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Long-term associative learning predicts verbal short-term memory performance.
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.
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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.
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Small-Scale Testing Rig for Long-Term Cyclically Loaded Monopiles in Cohesionless Soil
DEFF Research Database (Denmark)
Roesen, Hanne Ravn; Ibsen, Lars Bo; Andersen, Lars Vabbersgaard
2012-01-01
, and the period of the cyclic loading. However, the design guidance on these issues is limited. Thus, in order to investigate the pile behaviour for cyclically long-term loaded monopiles, a test setup for small-scale tests in saturated dense cohesionless soil is constructed and presented in here. The cyclic...... loading is applied mechanically by means of a testing rig, where the important input parameters: mean level, amplitude, number of cycles, and period of the loading can be varied. The results from a monotonic and a cyclic loading test on an open-ended aluminium pile with diameter = 100 mm and embedded...... length = 600 mm proves that the test setup is capable of applying the cyclic long-term loading. The plastic deformations during loading depend not only on the loading applied but also of the relative density of the soil and, thus, the tests are carried out with relative densities of 77-88%, i.e. similar...
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Leroy, Felix; Brann, David H; Meira, Torcato; Siegelbaum, Steven A
2017-08-30
Input-timing-dependent plasticity (ITDP) is a circuit-based synaptic learning rule by which paired activation of entorhinal cortical (EC) and Schaffer collateral (SC) inputs to hippocampal CA1 pyramidal neurons (PNs) produces a long-term enhancement of SC excitation. We now find that paired stimulation of EC and SC inputs also induces ITDP of SC excitation of CA2 PNs. However, whereas CA1 ITDP results from long-term depression of feedforward inhibition (iLTD) as a result of activation of CB1 endocannabinoid receptors on cholecystokinin-expressing interneurons, CA2 ITDP results from iLTD through activation of δ-opioid receptors on parvalbumin-expressing interneurons. Furthermore, whereas CA1 ITDP has been previously linked to enhanced specificity of contextual memory, we find that CA2 ITDP is associated with enhanced social memory. Thus, ITDP may provide a general synaptic learning rule for distinct forms of hippocampal-dependent memory mediated by distinct hippocampal regions. Copyright © 2017 Elsevier Inc. All rights reserved.
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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
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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)
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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.
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Directory of Open Access Journals (Sweden)
Sabine Conrad
2014-01-01
Full Text Available This study aimed to provide a molecular signature for enriched adult human stem/progenitor spermatogonia during short-term (<2 weeks and long-term culture (up to more than 14 months in comparison to human testicular fibroblasts and human embryonic stem cells. Human spermatogonia were isolated by CD49f magnetic activated cell sorting and collagen−/laminin+ matrix binding from primary testis cultures obtained from ten adult men. For transcriptomic analysis, single spermatogonia-like cells were collected based on their morphology and dimensions using a micromanipulation system from the enriched germ cell cultures. Immunocytochemical, RT-PCR and microarray analyses revealed that the analyzed populations of cells were distinct at the molecular level. The germ- and pluripotency-associated genes and genes of differentiation/spermatogenesis pathway were highly expressed in enriched short-term cultured spermatogonia. After long-term culture, a proportion of cells retained and aggravated the “spermatogonial” gene expression profile with the expression of germ and pluripotency-associated genes, while in the majority of long-term cultured cells this molecular profile, typical for the differentiation pathway, was reduced and more genes related to the extracellular matrix production and attachment were expressed. The approach we provide here to study the molecular status of in vitro cultured spermatogonia may be important to optimize the culture conditions and to evaluate the germ cell plasticity in the future.
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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.
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Bailey, C H; Chen, M
1988-01-01
The morphological consequences of long-term habituation and sensitization of the gill withdrawal reflex in Aplysia california were explored by examining the total number of presynaptic varicosities of single identified sensory neurons (a critical site of plasticity for the biochemical and biophysical changes that underlie both types of learning) in control and behaviorally trained animals. Sensory neurons from habituated animals had 35% fewer synaptic varicosities than did sensory neurons fro...
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A Spiking Working Memory Model Based on Hebbian Short-Term Potentiation.
Fiebig, Florian; Lansner, Anders
2017-01-04
A dominant theory of working memory (WM), referred to as the persistent activity hypothesis, holds that recurrently connected neural networks, presumably located in the prefrontal cortex, encode and maintain WM memory items through sustained elevated activity. Reexamination of experimental data has shown that prefrontal cortex activity in single units during delay periods is much more variable than predicted by such a theory and associated computational models. Alternative models of WM maintenance based on synaptic plasticity, such as short-term nonassociative (non-Hebbian) synaptic facilitation, have been suggested but cannot account for encoding of novel associations. Here we test the hypothesis that a recently identified fast-expressing form of Hebbian synaptic plasticity (associative short-term potentiation) is a possible mechanism for WM encoding and maintenance. Our simulations using a spiking neural network model of cortex reproduce a range of cognitive memory effects in the classical multi-item WM task of encoding and immediate free recall of word lists. Memory reactivation in the model occurs in discrete oscillatory bursts rather than as sustained activity. We relate dynamic network activity as well as key synaptic characteristics to electrophysiological measurements. Our findings support the hypothesis that fast Hebbian short-term potentiation is a key WM mechanism. Working memory (WM) is a key component of cognition. Hypotheses about the neural mechanism behind WM are currently under revision. Reflecting recent findings of fast Hebbian synaptic plasticity in cortex, we test whether a cortical spiking neural network model with such a mechanism can learn a multi-item WM task (word list learning). We show that our model can reproduce human cognitive phenomena and achieve comparable memory performance in both free and cued recall while being simultaneously compatible with experimental data on structure, connectivity, and neurophysiology of the underlying
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CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory.
Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha; Cai, Denise J; Lee, Yong-Seok; Fox, Kevin; Silva, Alcino J
2016-12-20
Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV.
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Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop
Directory of Open Access Journals (Sweden)
Ling-ling Shen
2015-01-01
Full Text Available Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca 2+ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.
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Biodegradable Plastic Mulch Films: Impacts on Soil Microbial Communities and Ecosystem Functions
Directory of Open Access Journals (Sweden)
Sreejata Bandopadhyay
2018-04-01
Full Text Available Agricultural plastic mulch films are widely used in specialty crop production systems because of their agronomic benefits. Biodegradable plastic mulches (BDMs offer an environmentally sustainable alternative to conventional polyethylene (PE mulch. Unlike PE films, which need to be removed after use, BDMs are tilled into soil where they are expected to biodegrade. However, there remains considerable uncertainty about long-term impacts of BDM incorporation on soil ecosystems. BDMs potentially influence soil microbial communities in two ways: first, as a surface barrier prior to soil incorporation, indirectly affecting soil microclimate and atmosphere (similar to PE films and second, after soil incorporation, as a direct input of physical fragments, which add carbon, microorganisms, additives, and adherent chemicals. This review summarizes the current literature on impacts of plastic mulches on soil biological and biogeochemical processes, with a special emphasis on BDMs. The combined findings indicated that when used as a surface barrier, plastic mulches altered soil microbial community composition and functioning via microclimate modification, though the nature of these alterations varied between studies. In addition, BDM incorporation into soil can result in enhanced microbial activity and enrichment of fungal taxa. This suggests that despite the fact that total carbon input from BDMs is minuscule, a stimulatory effect on microbial activity may ultimately affect soil organic matter dynamics. To address the current knowledge gaps, long term studies and a better understanding of impacts of BDMs on nutrient biogeochemistry are needed. These are critical to evaluating BDMs as they relate to soil health and agroecosystem sustainability.
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Biodegradable Plastic Mulch Films: Impacts on Soil Microbial Communities and Ecosystem Functions.
Bandopadhyay, Sreejata; Martin-Closas, Lluis; Pelacho, Ana M; DeBruyn, Jennifer M
2018-01-01
Agricultural plastic mulch films are widely used in specialty crop production systems because of their agronomic benefits. Biodegradable plastic mulches (BDMs) offer an environmentally sustainable alternative to conventional polyethylene (PE) mulch. Unlike PE films, which need to be removed after use, BDMs are tilled into soil where they are expected to biodegrade. However, there remains considerable uncertainty about long-term impacts of BDM incorporation on soil ecosystems. BDMs potentially influence soil microbial communities in two ways: first, as a surface barrier prior to soil incorporation, indirectly affecting soil microclimate and atmosphere (similar to PE films) and second, after soil incorporation, as a direct input of physical fragments, which add carbon, microorganisms, additives, and adherent chemicals. This review summarizes the current literature on impacts of plastic mulches on soil biological and biogeochemical processes, with a special emphasis on BDMs. The combined findings indicated that when used as a surface barrier, plastic mulches altered soil microbial community composition and functioning via microclimate modification, though the nature of these alterations varied between studies. In addition, BDM incorporation into soil can result in enhanced microbial activity and enrichment of fungal taxa. This suggests that despite the fact that total carbon input from BDMs is minuscule, a stimulatory effect on microbial activity may ultimately affect soil organic matter dynamics. To address the current knowledge gaps, long term studies and a better understanding of impacts of BDMs on nutrient biogeochemistry are needed. These are critical to evaluating BDMs as they relate to soil health and agroecosystem sustainability.
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Axonal plasticity elicits long-term changes in oligodendroglia and myelinated fibers
DEFF Research Database (Denmark)
Drøjdahl, Nina; Nielsen, Helle Hvilsted; Gardi, Jonathan E
2010-01-01
Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly...... formed axonal sprouts are able to induce a protracted myelination response in adult CNS. We show that newly formed axonal sprouts, induced by lesion of the entorhino-hippocampal perforant pathway, have the ability to induce a myelination response in stratum radiatum and lucidum CA3. The lesion resulted...... in significant recruitment of newly formed myelinating cells, documented by incorporation of the proliferation marker bromodeoxyuridine into chondroitin sulphate NG2 expressing cells in stratum radiatum and lucidum CA3 early after lesion, and the occurrence of a 28% increase in the number of oligodendrocytes...
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Short-term plasticity as a neural mechanism supporting memory and attentional functions.
Jääskeläinen, Iiro P; Ahveninen, Jyrki; Andermann, Mark L; Belliveau, John W; Raij, Tommi; Sams, Mikko
2011-11-08
Based on behavioral studies, several relatively distinct perceptual and cognitive functions have been defined in cognitive psychology such as sensory memory, short-term memory, and selective attention. Here, we review evidence suggesting that some of these functions may be supported by shared underlying neuronal mechanisms. Specifically, we present, based on an integrative review of the literature, a hypothetical model wherein short-term plasticity, in the form of transient center-excitatory and surround-inhibitory modulations, constitutes a generic processing principle that supports sensory memory, short-term memory, involuntary attention, selective attention, and perceptual learning. In our model, the size and complexity of receptive fields/level of abstraction of neural representations, as well as the length of temporal receptive windows, increases as one steps up the cortical hierarchy. Consequently, the type of input (bottom-up vs. top down) and the level of cortical hierarchy that the inputs target, determine whether short-term plasticity supports purely sensory vs. semantic short-term memory or attentional functions. Furthermore, we suggest that rather than discrete memory systems, there are continuums of memory representations from short-lived sensory ones to more abstract longer-duration representations, such as those tapped by behavioral studies of short-term memory. Copyright © 2011 Elsevier B.V. All rights reserved.
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How long-term dynamics of sediment subduction controls short-term dynamics of seismicity
Brizzi, S.; van Zelst, I.; van Dinther, Y.; Funiciello, F.; Corbi, F.
2017-12-01
Most of the world's greatest earthquakes occur along the subduction megathrust. Weak and porous sediments have been suggested to homogenize the plate interface and thereby promote lateral rupture propagation and great earthquakes. However, the importance of sediment thickness, let alone their physical role, is not yet unequivocally established. Based on a multivariate statistical analysis of a global database of 62 subduction segments, we confirm that sediment thickness is one of the key parameters controlling the maximum magnitude a megathrust can generate. Moreover, Monte Carlo simulations highlighted that the occurrence of great earthquakes on sediment-rich subduction segments is very unlikely (p-value≪0.05) related to pure chance. To understand how sediments in the subduction channel regulate earthquake size, this study extends and demystifies multivariate, spatiotemporally limited data through numerical modeling. We use the 2D Seismo-Thermo-Mechanical modeling approach to simulate both the long- and short-term dynamics of subduction and related seismogenesis (van Dinther et al., JGR, 2013). These models solve for the conservation of mass, momentum and energy using a visco-elasto-plastic rheology with rate-dependent friction. Results show that subducted sediments have a strong influence on the long-term evolution of the convergent margin. Increasing the sediment thickness on the incoming plate from 0 to 6 km causes a decrease of slab dip from 23° to 10°. This, in addition to increased radiogenic heating, extends isotherms, thereby widening the seismogenic portion of the megathrust from 80 to 150 km. Consequently, over tens of thousands of years, we observe that the maximum moment magnitude of megathrust earthquakes increases from 8.2 to 9.2 for these shallower and warmer interfaces. In addition, we observe more and larger splay faults, which could enhance vertical seafloor displacements. These results highlight the primary role of subducted sediments in
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Applications and societal benefits of plastics.
Andrady, Anthony L; Neal, Mike A
2009-07-27
This article explains the history, from 1600 BC to 2008, of materials that are today termed 'plastics'. It includes production volumes and current consumption patterns of five main commodity plastics: polypropylene, polyethylene, polyvinyl chloride, polystyrene and polyethylene terephthalate. The use of additives to modify the properties of these plastics and any associated safety, in use, issues for the resulting polymeric materials are described. A comparison is made with the thermal and barrier properties of other materials to demonstrate the versatility of plastics. Societal benefits for health, safety, energy saving and material conservation are described, and the particular advantages of plastics in society are outlined. Concerns relating to littering and trends in recycling of plastics are also described. Finally, we give predictions for some of the potential applications of plastic over the next 20 years.
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A Presynaptic Role for FMRP during Protein Synthesis-Dependent Long-Term Plasticity in "Aplysia"
Till, Sally M.; Li, Hsiu-Ling; Miniaci, Maria Concetta; Kandel, Eric R.; Choi, Yun-Beom
2011-01-01
Loss of the Fragile X mental retardation protein (FMRP) is associated with presumed postsynaptic deficits in mouse models of Fragile X syndrome. However, the possible presynaptic roles of FMRP in learning-related plasticity have received little attention. As a result, the mechanisms whereby FMRP influences synaptic function remain poorly…
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12-lipoxygenase regulates hippocampal long-term potentiation by modulating L-type Ca2+ channels
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
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Wearing, Oliver H; Eme, John; Rhen, Turk; Crossley, Dane A
2016-01-15
Studies of embryonic and hatchling reptiles have revealed marked plasticity in morphology, metabolism, and cardiovascular function following chronic hypoxic incubation. However, the long-term effects of chronic hypoxia have not yet been investigated in these animals. The aim of this study was to determine growth and postprandial O2 consumption (V̇o2), heart rate (fH), and mean arterial pressure (Pm, in kPa) of common snapping turtles (Chelydra serpentina) that were incubated as embryos in chronic hypoxia (10% O2, H10) or normoxia (21% O2, N21). We hypothesized that hypoxic development would modify posthatching body mass, metabolic rate, and cardiovascular physiology in juvenile snapping turtles. Yearling H10 turtles were significantly smaller than yearling N21 turtles, both of which were raised posthatching in normoxic, common garden conditions. Measurement of postprandial cardiovascular parameters and O2 consumption were conducted in size-matched three-year-old H10 and N21 turtles. Both before and 12 h after feeding, H10 turtles had a significantly lower fH compared with N21 turtles. In addition, V̇o2 was significantly elevated in H10 animals compared with N21 animals 12 h after feeding, and peak postprandial V̇o2 occurred earlier in H10 animals. Pm of three-year-old turtles was not affected by feeding or hypoxic embryonic incubation. Our findings demonstrate that physiological impacts of developmental hypoxia on embryonic reptiles continue into juvenile life. Copyright © 2016 the American Physiological Society.
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Energy Technology Data Exchange (ETDEWEB)
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
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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
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Long-term care financing: lessons from France.
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
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Energy Technology Data Exchange (ETDEWEB)
Gao Xiaoyan [Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf (Germany); Tang Mingliang [Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (China); Li Zhifeng; Zha Yingying [University of Science and Technology of China, CAS Key Laboratory of Brain Function and Disease, and School of Life Sciences (China); Cheng Guosheng [Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (China); Yin Shuting [Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf (Germany); Chen Jutao; Ruan Diyun; Chen Lin; Wang Ming, E-mail: wming@ustc.edu.cn [University of Science and Technology of China, CAS Key Laboratory of Brain Function and Disease, and School of Life Sciences (China)
2013-04-15
Studies reported that quantum dots (QDs), as a novel probe, demonstrated a promising future for in vivo imaging, but also showed potential toxicity. This study is mainly to investigate in vivo response in the central nervous system (CNS) after exposure to QDs in a rat model of synaptic plasticity and spatial memory. Adult rats were exposed to streptavidin-conjugated CdSe/ZnS QDs (Qdots 525, purchased from Molecular Probes Inc.) by intraperitoneal injection for 7 days, followed by behavioral, electrophysiological, and biochemical examinations. The electrophysiological results show that input/output (I/O) functions were increased, while the peak of paired-pulse reaction and long-term potentiation were decreased after QDs insult, indicating synaptic transmission was enhanced and synaptic plasticity in the hippocampus was impaired. Meanwhile, behavioral experiments provide the evidence that QDs could impair rats' spatial memory process. All the results present evidences of interference of synaptic transmission and plasticity in rat hippocampal dentate gyrus area by QDs insult and suggest potential adverse issues which should be considered in QDs applications.
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Gao, Xiaoyan; Tang, Mingliang; Li, Zhifeng; Zha, Yingying; Cheng, Guosheng; Yin, Shuting; Chen, Jutao; Ruan, Di-yun; Chen, Lin; Wang, Ming
2013-04-01
Studies reported that quantum dots (QDs), as a novel probe, demonstrated a promising future for in vivo imaging, but also showed potential toxicity. This study is mainly to investigate in vivo response in the central nervous system (CNS) after exposure to QDs in a rat model of synaptic plasticity and spatial memory. Adult rats were exposed to streptavidin-conjugated CdSe/ZnS QDs (Qdots 525, purchased from Molecular Probes Inc.) by intraperitoneal injection for 7 days, followed by behavioral, electrophysiological, and biochemical examinations. The electrophysiological results show that input/output ( I/ O) functions were increased, while the peak of paired-pulse reaction and long-term potentiation were decreased after QDs insult, indicating synaptic transmission was enhanced and synaptic plasticity in the hippocampus was impaired. Meanwhile, behavioral experiments provide the evidence that QDs could impair rats' spatial memory process. All the results present evidences of interference of synaptic transmission and plasticity in rat hippocampal dentate gyrus area by QDs insult and suggest potential adverse issues which should be considered in QDs applications.
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International Nuclear Information System (INIS)
Gao Xiaoyan; Tang Mingliang; Li Zhifeng; Zha Yingying; Cheng Guosheng; Yin Shuting; Chen Jutao; Ruan Diyun; Chen Lin; Wang Ming
2013-01-01
Studies reported that quantum dots (QDs), as a novel probe, demonstrated a promising future for in vivo imaging, but also showed potential toxicity. This study is mainly to investigate in vivo response in the central nervous system (CNS) after exposure to QDs in a rat model of synaptic plasticity and spatial memory. Adult rats were exposed to streptavidin-conjugated CdSe/ZnS QDs (Qdots 525, purchased from Molecular Probes Inc.) by intraperitoneal injection for 7 days, followed by behavioral, electrophysiological, and biochemical examinations. The electrophysiological results show that input/output (I/O) functions were increased, while the peak of paired-pulse reaction and long-term potentiation were decreased after QDs insult, indicating synaptic transmission was enhanced and synaptic plasticity in the hippocampus was impaired. Meanwhile, behavioral experiments provide the evidence that QDs could impair rats’ spatial memory process. All the results present evidences of interference of synaptic transmission and plasticity in rat hippocampal dentate gyrus area by QDs insult and suggest potential adverse issues which should be considered in QDs applications.
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Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity
Directory of Open Access Journals (Sweden)
Lemtiri-Chlieh Fouad
2011-12-01
Full Text Available Abstract Background Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response 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 enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7, a Rho GDP/GTP exchange factor (Rho-GEF localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7KO have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments. Results We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7. Conclusions These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus.
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Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity
Lemtiri-Chlieh, Fouad
2011-12-19
Background: Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response 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 enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7 KO) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments.Results: We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7.Conclusions: These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus. 2011 Lemtiri-Chlieh et al; licensee BioMed Central Ltd.
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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.
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International Nuclear Information System (INIS)
Wu, Gui-Yi; Smith, David J.; Pavier, Martyn J.
2013-01-01
Structural integrity assessments of pressurised pipes include plastic collapse as a potential failure mode. This paper uses analytical and numerical models to explore the effect of the end conditions of the pipe on the collapse pressure. The pipe is open-ended and two bounding conditions are addressed: one where axial loading is applied to the ends of the pipe and the other where a fixed axial displacement is applied. The fixed axial displacement condition represents long-range or fit-up residual stress. It is common practice to treat long-range residual stress in the same way as axial loading, leading to the conclusion that such long-range residual stress reduces the collapse pressure. Pipes in a number of states are considered: pipes with no flaws, pipes with fully circumferential flaws and pipes with part circumferential flaws. The flaws consist of either a crack or a slot on the external surface of the pipe. For the axial load condition, the collapse pressure for a flawed pipe is reduced when higher magnitudes of tensile or compressive axial loads are applied. For the fixed displacement condition however, the magnitude of the displacement may have little or no effect on the collapse pressure. The results of the work indicate that substantially conservative assessments may be made of the collapse pressures of pipes containing flaws, when long-range residual stress is taken to be a form of axial loading. -- Highlights: • The effect of end conditions on the collapse pressure of a pipe has been explored. • Fixed displacement conditions represent long-range residual stress. • Long-range residual stress is commonly thought to contribute to plastic collapse. • We show long-range residual stress has no influence on collapse for flawed pipes. • It is therefore possible to reduce conservatism in structural integrity assessment
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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
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High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity.
Directory of Open Access Journals (Sweden)
Zhigang Liu
Full Text Available High-fat diet (HFD-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, learning, and memory. The experimental model consisted of 3 month-old C57BL/6J mice fed either a normal chow diet (control group or a HFD (60% of calorie from fat; HFD group for 12 weeks. This model was characterized as a function of time in terms of body weight, fasting blood glucose and insulin levels, HOMA-IR values, and plasma triglycerides. IRS-1/Akt pathway was assessed in primary hepatocytes and brain homogenates. The effect of HFD in brain was assessed by electrophysiology, input/output responses and long-term potentiation. HFD-fed mice exhibited a significant increase in body weight, higher fasting glucose- and insulin levels in plasma, lower glucose tolerance, and higher HOMA-IR values. In liver, HFD elicited (a a significant decrease of insulin receptor substrate (IRS-1 phosphorylation on Tyr608 and increase of Ser307 phosphorylation, indicative of IRS-1 inactivation; (b these changes were accompanied by inflammatory responses in terms of increases in the expression of NFκB and iNOS and activation of the MAP kinases p38 and JNK; (c primary hepatocytes from mice fed a HFD showed decreased cellular oxygen consumption rates (indicative of mitochondrial functional impairment; this can be ascribed partly to a decreased expression of PGC1α and mitochondrial biogenesis. In brain, HFD feeding elicited (a an inactivation of the IRS-1 and, consequentially, (b a decreased expression and plasma membrane localization of the insulin-sensitive neuronal glucose transporters GLUT3/GLUT4; (c a suppression of the ERK/CREB pathway, and (d a substantial decrease in long-term potentiation in the CA1 region of hippocampus (indicative of impaired synaptic plasticity. It may be surmised that 12 weeks fed with HFD induce a systemic insulin resistance that impacts
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Rousset, Baptiste; Lasserre, Cécile; Cubas, Nadaya; Graham, Shannon; Radiguet, Mathilde; DeMets, Charles; Socquet, Anne; Campillo, Michel; Kostoglodov, Vladimir; Cabral-Cano, Enrique; Cotte, Nathalie; Walpersdorf, Andrea
2016-10-01
Although patterns of interseismic strain accumulation above subduction zones are now routinely characterised using geodetic measurements, their physical origin, persistency through time, and relationships to seismic hazard and long-term deformation are still debated. Here, we use GPS and morphological observations from southern Mexico to explore potential mechanical links between variations in inter-SSE (in between slow slip events) coupling along the Mexico subduction zone and the long-term topography of the coastal regions from Guerrero to Oaxaca. Inter-SSE coupling solutions for two different geometries of the subduction interface are derived from an inversion of continuous GPS time series corrected from slow slip events. They reveal strong along-strike variations in the shallow coupling (i.e. at depths down to 25 km), with high-coupling zones (coupling >0.7) alternating with low-coupling zones (coupling 0.7) and transitions to uncoupled, steady slip at a relatively uniform ˜ 175-km inland from the trench. Along-strike variations in the coast-to-trench distances are strongly correlated with the GPS-derived forearc coupling variations. To explore a mechanical explanation for this correlation, we apply Coulomb wedge theory, constrained by local topographic, bathymetric, and subducting-slab slopes. Critical state areas, i.e. areas where the inner subduction wedge deforms, are spatially correlated with transitions at shallow depth between uncoupled and coupled areas of the subduction interface. Two end-member models are considered to explain the correlation between coast-to-trench distances and along-strike variations in the inter-SSE coupling. The first postulates that the inter-SSE elastic strain is partitioned between slip along the subduction interface and homogeneous plastic permanent deformation of the upper plate. In the second, permanent plastic deformation is postulated to depend on frictional transitions along the subduction plate interface. Based on the
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Short- and long-term antidepressant effects of ketamine in a rat chronic unpredictable stress model.
Jiang, Yinghong; Wang, Yiqiang; Sun, Xiaoran; Lian, Bo; Sun, Hongwei; Wang, Gang; Du, Zhongde; Li, Qi; Sun, Lin
2017-08-01
This research was aimed to evaluate the behaviors of short- or long-term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS). Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory. After 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43-75). The influence of ketamine on behavioral reactivity was assessed 24 hr (short-term) or 7 weeks after ketamine treatment (long-term). Behavioral tests used to assess the effects of these treatments included the sucrose preference (SP), open field (OF), elevated plus maze (EPM), forced swimming (FS), and water maze (WM) to detect anxiety-like behavior (OF and EPM), forced swimming (FS), and water maze (WM). Results: Short-term ketamine administration resulted in increases of body weight gain, higher sensitivity to sucrose, augmented locomotor activity in the OF, more entries into the open arms of the EPM, along increased activity in the FS test; all responses indicative of reductions in depression/despair in anxiety-eliciting situations. No significant differences in these behaviors were obtained under conditions of long-term ketamine administration ( p > .05). The CUS + Ketamine group showed significantly increased activity as compared with the CUS + Vehicle group for analysis of the long-term effects of ketamine (* p .05). Taken together these findings demonstrate that a short-term administration of ketamine induced rapid antidepressant-like effects in adult male rats exposed to CUS conditions, effects that were not observed in response to the long-term treatment regime.