Cdk7 Is Required for Activity-Dependent Neuronal Gene Expression, Long-Lasting Synaptic Plasticity and Long-Term Memory

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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.

Transient inhibition and long-term facilitation of locomotion by phasic optogenetic activation of serotonin neurons

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Correia, Patrícia A; Lottem, Eran; Banerjee, Dhruba; Machado, Ana S; Carey, Megan R; Mainen, Zachary F

2017-01-01

Serotonin (5-HT) is associated with mood and motivation but the function of endogenous 5-HT remains controversial. Here, we studied the impact of phasic optogenetic activation of 5-HT neurons in mice over time scales from seconds to weeks. We found that activating dorsal raphe nucleus (DRN) 5-HT neurons induced a strong suppression of spontaneous locomotor behavior in the open field with rapid kinetics (onset ≤1 s). Inhibition of locomotion was independent of measures of anxiety or motor impairment and could be overcome by strong motivational drive. Repetitive place-contingent pairing of activation caused neither place preference nor aversion. However, repeated 15 min daily stimulation caused a persistent increase in spontaneous locomotion to emerge over three weeks. These results show that 5-HT transients have strong and opposing short and long-term effects on motor behavior that appear to arise from effects on the underlying factors that motivate actions. DOI: http://dx.doi.org/10.7554/eLife.20975.001 PMID:28193320

Short- and long-term memory in Drosophila require cAMP signaling in distinct neuron types.

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Blum, Allison L; Li, Wanhe; Cressy, Mike; Dubnau, Josh

2009-08-25

A common feature of memory and its underlying synaptic plasticity is that each can be dissected into short-lived forms involving modification or trafficking of existing proteins and long-term forms that require new gene expression. An underlying assumption of this cellular view of memory consolidation is that these different mechanisms occur within a single neuron. At the neuroanatomical level, however, different temporal stages of memory can engage distinct neural circuits, a notion that has not been conceptually integrated with the cellular view. Here, we investigated this issue in the context of aversive Pavlovian olfactory memory in Drosophila. Previous studies have demonstrated a central role for cAMP signaling in the mushroom body (MB). The Ca(2+)-responsive adenylyl cyclase RUTABAGA is believed to be a coincidence detector in gamma neurons, one of the three principle classes of MB Kenyon cells. We were able to separately restore short-term or long-term memory to a rutabaga mutant with expression of rutabaga in different subsets of MB neurons. Our findings suggest a model in which the learning experience initiates two parallel associations: a short-lived trace in MB gamma neurons, and a long-lived trace in alpha/beta neurons.

Consolidation of an olfactory memory trace in the olfactory bulb is required for learning-induced survival of adult-born neurons and long-term memory.

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Florence Kermen

Full Text Available BACKGROUND: It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days, but not a massed (within day, learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. CONCLUSION/SIGNIFICANCE: We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival during olfactory learning is governed by consolidation in the olfactory bulb strongly argues in favor of a role for bulbar adult-born neurons in supporting olfactory memory.

Consolidation of an olfactory memory trace in the olfactory bulb is required for learning-induced survival of adult-born neurons and long-term memory.

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Kermen, Florence; Sultan, Sébastien; Sacquet, Joëlle; Mandairon, Nathalie; Didier, Anne

2010-08-13

It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days), but not a massed (within day), learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival during olfactory learning is governed by consolidation in the olfactory bulb strongly argues in favor of a role for bulbar adult-born neurons in supporting olfactory memory.

Single whole-body exposure to sarin vapor in rats: Long-term neuronal and behavioral deficits

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Grauer, Ettie; Chapman, Shira; Rabinovitz, Ishai; Raveh, Lily; Weissman, Ben-Avi; Kadar, Tamar; Allon, Nahum

2008-01-01

Freely moving rats were exposed to sarin vapor (34.2 ± 0.8 μg/l) for 10 min. Mortality at 24 h was 35% and toxic sings in the surviving rats ranged from sever (prolonged convulsions) through moderate to almost no overt signs. Some of the surviving rats developed delayed, intermittent convulsions. All rats were evaluated for long-term functional deficits in comparison to air-exposed control rats. Histological analysis revealed typical cell loss at 1 week post inhalation exposure. Neuronal inflammation was demonstrated by a 20-fold increase in prostaglandin (PGE 2 ) levels 24 h following exposure that markedly decreased 6 days later. An additional, delayed increase in PGE 2 was detected at 1 month and continued to increase for up to 6 months post exposure. Glial activation following neural damage was demonstrated by an elevated level of peripheral benzodiazepine receptors (PBR) seen in the brain 4 and 6 months after exposure. At the same time muscarinic receptors were unaffected. Six weeks, four and six months post exposure behavioral evaluations were performed. In the open field, sarin-exposed rats showed a significant increase in overall activity with no habituation over days. In a working memory paradigm in the water maze, these same rats showed impaired working and reference memory processes with no recovery. Our data suggest long lasting impairment of brain functions in surviving rats following a single sarin exposure. Animals that seem to fully recover from the exposure, and even animals that initially show no toxicity signs, developed some adverse neural changes with time

Neuronal correlate of visual associative long-term memory in the primate temporal cortex

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Miyashita, Yasushi

1988-10-01

In human long-term memory, ideas and concepts become associated in the learning process1. No neuronal correlate for this cognitive function has so far been described, except that memory traces are thought to be localized in the cerebral cortex; the temporal lobe has been assigned as the site for visual experience because electric stimulation of this area results in imagery recall,2 and lesions produce deficits in visual recognition of objects3-9. We previously reported that in the anterior ventral temporal cortex of monkeys, individual neurons have a sustained activity that is highly selective for a few of the 100 coloured fractal patterns used in a visual working-memory task10. Here I report the development of this selectivity through repeated trials involving the working memory. The few patterns for which a neuron was conjointly selective were frequently related to each other through stimulus-stimulus association imposed during training. The results indicate that the selectivity acquired by these cells represents a neuronal correlate of the associative long-term memory of pictures.

Comparison of two voltage-sensitive dyes and their suitability for long-term imaging of neuronal activity.

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Stephanie Preuss

Full Text Available One of the key approaches for studying neural network function is the simultaneous measurement of the activity of many neurons. Voltage-sensitive dyes (VSDs simultaneously report the membrane potential of multiple neurons, but often have pharmacological and phototoxic effects on neuronal cells. Yet, to study the homeostatic processes that regulate neural network function long-term recordings of neuronal activities are required. This study aims to test the suitability of the VSDs RH795 and Di-4-ANEPPS for optically recording pattern generating neurons in the stomatogastric nervous system of crustaceans with an emphasis on long-term recordings of the pyloric central pattern generator. We demonstrate that both dyes stain pyloric neurons and determined an optimal concentration and light intensity for optical imaging. Although both dyes provided sufficient signal-to-noise ratio for measuring membrane potentials, Di-4-ANEPPS displayed a higher signal quality indicating an advantage of this dye over RH795 when small neuronal signals need to be recorded. For Di-4-ANEPPS, higher dye concentrations resulted in faster and brighter staining. Signal quality, however, only depended on excitation light strength, but not on dye concentration. RH795 showed weak and slowly developing phototoxic effects on the pyloric motor pattern as well as slow bleaching of the staining and is thus the better choice for long-term experiments. Low concentrations and low excitation intensities can be used as, in contrast to Di-4-ANEPPS, the signal-to-noise ratio was independent of excitation light strength. In summary, RH795 and Di-4-ANEPPS are suitable for optical imaging in the stomatogastric nervous system of crustaceans. They allow simultaneous recording of the membrane potential of multiple neurons with high signal quality. While Di-4-ANEPPS is better suited for short-term experiments that require high signal quality, RH795 is a better candidate for long-term experiments

Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate

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Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

2009-01-01

Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca 2+ permeability, we investigated whether Ca 2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca 2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate.

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Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

2009-10-15

Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca2+ permeability, we investigated whether Ca2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

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.

Diversity in Long-Term Synaptic Plasticity at Inhibitory Synapses of Striatal Spiny Neurons

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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…

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

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Mody, I.

1985-01-01

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

Long-term activation of group I metabotropic glutamate receptors increases functional TRPV1-expressing neurons in mouse dorsal root ganglia

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Takayoshi eMasuoka

2016-03-01

Full Text Available Damaged tissues release glutamate and other chemical mediators for several hours. These chemical mediators contribute to modulation of pruritus and pain. Herein, we investigated the effects of long-term activation of excitatory glutamate receptors on functional expression of transient receptor potential vaniloid type 1 (TRPV1 in dorsal root ganglion (DRG neurons and then on thermal pain behavior. In order to detect the TRPV1-mediated responses in cultured DRG neurons, we monitored intracellular calcium responses to capsaicin, a TRPV1 agonist, with Fura-2. Long-term (4 h treatment with glutamate receptor agonists (glutamate, quisqualate or DHPG increased the proportion of neurons responding to capsaicin through activation of metabotropic glutamate receptor mGluR1, and only partially through the activation of mGluR5; engagement of these receptors was evident in neurons responding to allylisothiocyanate (AITC, a transient receptor potential ankyrin type 1 (TRPA1 agonist. Increase in the proportion was suppressed by phospholipase C, protein kinase C, mitogen/extracellular signal-regulated kinase, p38 mitogen-activated protein kinase or transcription inhibitors. Whole-cell recording was performed to record TRPV1-mediated membrane current; TRPV1 current density significantly increased in the AITC-sensitive neurons after the quisqualate treatment. To elucidate the physiological significance of this phenomenon, a hot plate test was performed. Intraplantar injection of quisqualate or DHPG induced heat hyperalgesia that lasted for 4 h post injection. This chronic hyperalgesia was attenuated by treatment with either mGluR1 or mGluR5 antagonists. These results suggest that long-term activation of mGluR1/5 by peripherally released glutamate may increase the number of neurons expressing functional TRPV1 in DRG, which may be strongly associated with chronic hyperalgesia.

Functional Maturation of Human Stem Cell-Derived Neurons in Long-Term Cultures.

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Rebecca S Lam

Full Text Available Differentiated neurons can be rapidly acquired, within days, by inducing stem cells to express neurogenic transcription factors. We developed a protocol to maintain long-term cultures of human neurons, called iNGNs, which are obtained by inducing Neurogenin-1 and Neurogenin-2 expression in induced pluripotent stem cells. We followed the functional development of iNGNs over months and they showed many hallmark properties for neuronal maturation, including robust electrical and synaptic activity. Using iNGNs expressing a variant of channelrhodopsin-2, called CatCh, we could control iNGN activity with blue light stimulation. In combination with optogenetic tools, iNGNs offer opportunities for studies that require precise spatial and temporal resolution. iNGNs developed spontaneous network activity, and these networks had excitatory glutamatergic synapses, which we characterized with single-cell synaptic recordings. AMPA glutamatergic receptor activity was especially dominant in postsynaptic recordings, whereas NMDA glutamatergic receptor activity was absent from postsynaptic recordings but present in extrasynaptic recordings. Our results on long-term cultures of iNGNs could help in future studies elucidating mechanisms of human synaptogenesis and neurotransmission, along with the ability to scale-up the size of the cultures.

Plasticity of Neuron-Glial Transmission: Equipping Glia for Long-Term Integration of Network Activity

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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.

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

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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.

Critical neural networks with short- and long-term plasticity

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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.

Brief predator sound exposure elicits behavioral and neuronal long-term sensitization in the olfactory system of an insect

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Anton, S.; Evengaard, K.; Barrozo, R. B.

2011-01-01

later in the same way as exposure to the sex pheromone itself. The observed behavioral modification is accompanied by an increase in the sensitivity of olfactory neurons in the antennal lobe. Our data provide thus evidence for cross-modal experience-dependent plasticity not only on the behavioral level...... at the behavioral and central nervous level. Here we show that this effect is not confined to the same sensory modality: the sensitivity of olfactory neurons can also be modulated by exposure to a different sensory stimulus, i.e., a pulsed stimulus mimicking echolocating sounds from attacking insectivorous bats. We...... tested responses of preexposed male moths in a walking bioassay and recorded from neurons in the primary olfactory center, the antennal lobe. We show that brief exposure to a bat call, but not to a behaviorally irrelevant tone, increases the behavioral sensitivity of male moths to sex pheromone 24 h...

Long-term omega-3 supplementation modulates behavior, hippocampal fatty acid concentration, neuronal progenitor proliferation and central TNF-α expression in 7 month old unchallenged mice

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Grundy, Trent; Toben, Catherine; Jaehne, Emily J.; Corrigan, Frances; Baune, Bernhard T.

2014-01-01

Dietary polyunsaturated fatty acid (PUFA) manipulation is being investigated as a potential therapeutic supplement to reduce the risk of developing age-related cognitive decline (ARCD). Animal studies suggest that high omega (Ω)-3 and low Ω-6 dietary content reduces cognitive decline by decreasing central nervous system (CNS) inflammation and modifying neuroimmune activity. However, no previous studies have investigated the long term effects of Ω-3 and Ω-6 dietary levels in healthy aging mice leaving the important question about the preventive effects of Ω-3 and Ω-6 on behavior and underlying molecular pathways unaddressed. We aimed to investigate the efficacy of long-term Ω-3 and Ω-6 PUFA dietary supplementation in mature adult C57BL/6 mice. We measured the effect of low, medium, and high Ω-3:Ω-6 dietary ratio, given from the age of 3–7 months, on anxiety and cognition-like behavior, hippocampal tissue expression of TNF-α, markers of neuronal progenitor proliferation and gliogenesis and serum cytokine concentration. Our results show that a higher Ω-3:Ω-6 PUFA diet ratio increased hippocampal PUFA, increased anxiety, improved hippocampal dependent spatial memory and reduced hippocampal TNF-α levels compared to a low Ω-3:Ω-6 diet. Furthermore, serum TNF-α concentration was reduced in the higher Ω-3:Ω-6 PUFA ratio supplementation group while expression of the neuronal progenitor proliferation markers KI67 and doublecortin (DCX) was increased in the dentate gyrus as opposed to the low Ω-3:Ω-6 group. Conversely, Ω-3:Ω-6 dietary PUFA ratio had no significant effect on astrocyte or microglia number or cell death in the dentate gyrus. These results suggest that supplementation of PUFAs may delay aging effects on cognitive function in unchallenged mature adult C57BL/6 mice. This effect is possibly induced by increasing neuronal progenitor proliferation and reducing TNF-α. PMID:25484856

Phrenic long-term facilitation requires PKCθ activity within phrenic motor neurons.

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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.

Stable long-term chronic brain mapping at the single-neuron level.

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Fu, Tian-Ming; Hong, Guosong; Zhou, Tao; Schuhmann, Thomas G; Viveros, Robert D; Lieber, Charles M

2016-10-01

Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning. Properties of acquired signals suggest robust tracking of the same neurons over this period. This recording and stimulation platform allowed us to evoke stable single-neuron responses to chronic electrical stimulation and to carry out longitudinal studies of brain aging in freely behaving mice. Such advantages could open up future studies in mapping and modulating changes associated with learning, aging and neurodegenerative diseases.

Microscopic study of rock for estimating long-term behavior

International Nuclear Information System (INIS)

Ichikawa, Yasuaki

2002-03-01

Micro-structure of rock plays a essential role for their long-term behavior. For elucidating long-term characteristics of granite we here present the followings: 1) Conforcal Laser Scanning Microscope (LSM) observation of joint surfaces of granite and Fourier analysis, 2) characterization of the mechanism of microcrack initiation and propagation observed by stereoscopic microscope under uniaxial/triaxial compression and relaxation tests, 3) observation of microcrack initiation and propagation by LSM under uniaxial compression, and 4) a viscoelastic homogenization theory to predict the long-term behavior of micro/macro-level stress for granite. Rock image processing and analysis become a fundamental procedure to determine rock surface discontinuities. But the complexity of rock surface discontinuities seems beyond the manual image processing method. In Chapter 2 a Conforcal Laser Scanning Microscope that can acquire three-dimensional images is introduced to observe the rock roughness of a discontinuity. Then, scanning three-dimensional images are changed its data form in order to adapt various image analysis programs, and granitic rock roughness of discontinuities are displayed by graphic images. For example, these datas are analyzed by Discrete Fourier Transformation (DFT) program and Inverse Discrete Fourier Transformation (IDFT) program. Microcrack generation and propagation play an essential role to predict the long-term behavior of rock. In Chapter 3 a progressive development of cracking in granite is revealed by using stereoscopic microscope under triaxial compression condition and by using LSM under uniaxial compression condition. With a viscoelastic theory applied in homogenization method, we can calculate macro behavior of medium influenced by its micro structure by analyse the long-term time-dependent behavior of granite under the same condition to the relaxation experiment. (author)

Long term creep behavior of concrete

International Nuclear Information System (INIS)

Kennedy, T.W.

1975-01-01

This report presents the findings of an experimental investigation to evaluate the long term creep behavior of concrete subjected to sustained uniaxial loads for an extended period of time at 75 0 F. The factors investigated were (1) curing time (90, 183, and 365 days); (2) curing history (as-cast and air-dried); and (3) uniaxial stress (600 and 2400 psi). The experimental investigation applied uniaxial compressive loads to cylindrical concrete specimens and measured strains with vibrating wire strain gages that were cast in the concrete specimen along the axial and radial axes. Specimens cured for 90 days prior to loading were subjected to a sustained load for a period of one year, at which time the loads were removed; the specimens which were cured for 183 or 365 days, however, were not unloaded and have been under load for 5 and 4.5 years, respectively. The effect of each of the above factors on the instantaneous and creep behavior is discussed and the long term creep behavior of the specimens cured for 183 or 365 days is evaluated. The findings of these evaluations are summarized. (17 figures, 10 tables) (U.S.)

Immediate perception of a reward is distinct from the reward’s long-term salience

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McGinnis, John P; Jiang, Huoqing; Agha, Moutaz Ali; Sanchez, Consuelo Perez; Lange, Jeff; Yu, Zulin; Marion-Poll, Frederic; Si, Kausik

2016-01-01

Reward perception guides all aspects of animal behavior. However, the relationship between the perceived value of a reward, the latent value of a reward, and the behavioral response remains unclear. Here we report that, given a choice between two sweet and chemically similar sugars—L- and D-arabinose—Drosophila melanogaster prefers D- over L- arabinose, but forms long-term memories of L-arabinose more reliably. Behavioral assays indicate that L-arabinose-generated memories require sugar receptor Gr43a, and calcium imaging and electrophysiological recordings indicate that L- and D-arabinose differentially activate Gr43a-expressing neurons. We posit that the immediate valence of a reward is not always predictive of the long-term reinforcement value of that reward, and that a subset of sugar-sensing neurons may generate distinct representations of similar sugars, allowing for rapid assessment of the salient features of various sugar rewards and generation of reward-specific behaviors. However, how sensory neurons communicate information about L-arabinose quality and concentration—features relevant for long-term memory—remains unknown. DOI: http://dx.doi.org/10.7554/eLife.22283.001 PMID:28005005

Statins Promote Long-Term Recovery after Ischemic Stroke by Reconnecting Noradrenergic Neuronal Circuitry

Directory of Open Access Journals (Sweden)

Kyoung Joo Cho

2015-01-01

Full Text Available Inhibitors of HMG-CoA reductase (statins, widely used to lower cholesterol in coronary heart and vascular disease, are effective drugs in reducing the risk of stroke and improving its outcome in the long term. After ischemic stroke, cardiac autonomic dysfunction and psychological problems are common complications related to deficits in the noradrenergic (NA system. This study investigated the effects of statins on the recovery of NA neuron circuitry and its function after transient focal cerebral ischemia (tFCI. Using the wheat germ agglutinin (WGA transgene technique combined with the recombinant adenoviral vector system, NA-specific neuronal pathways were labeled, and were identified in the locus coeruleus (LC, where NA neurons originate. NA circuitry in the atorvastatin-treated group recovered faster than in the vehicle-treated group. The damaged NA circuitry was partly reorganized with the gradual recovery of autonomic dysfunction and neurobehavioral deficit. Newly proliferated cells might contribute to reorganizing NA neurons and lead anatomic and functional recovery of NA neurons. Statins may be implicated to play facilitating roles in the recovery of the NA neuron and its function.

Reconciling long-term cultural diversity and short-term collective social behavior.

Science.gov (United States)

Valori, Luca; Picciolo, Francesco; Allansdottir, Agnes; Garlaschelli, Diego

2012-01-24

An outstanding open problem is whether collective social phenomena occurring over short timescales can systematically reduce cultural heterogeneity in the long run, and whether offline and online human interactions contribute differently to the process. Theoretical models suggest that short-term collective behavior and long-term cultural diversity are mutually excluding, since they require very different levels of social influence. The latter jointly depends on two factors: the topology of the underlying social network and the overlap between individuals in multidimensional cultural space. However, while the empirical properties of social networks are intensively studied, little is known about the large-scale organization of real societies in cultural space, so that random input specifications are necessarily used in models. Here we use a large dataset to perform a high-dimensional analysis of the scientific beliefs of thousands of Europeans. We find that interopinion correlations determine a nontrivial ultrametric hierarchy of individuals in cultural space. When empirical data are used as inputs in models, ultrametricity has strong and counterintuitive effects. On short timescales, it facilitates a symmetry-breaking phase transition triggering coordinated social behavior. On long timescales, it suppresses cultural convergence by restricting it within disjoint groups. Moreover, ultrametricity implies that these results are surprisingly robust to modifications of the dynamical rules considered. Thus the empirical distribution of individuals in cultural space appears to systematically optimize the coexistence of short-term collective behavior and long-term cultural diversity, which can be realized simultaneously for the same moderate level of mutual influence in a diverse range of online and offline settings.

On the very long term delayed behavior of concrete

International Nuclear Information System (INIS)

Torrenti, J.M.; Benboudjema, F.; Barre, F.; Gallitre, E.

2015-01-01

The prediction of very long-term deformation of prestressed concrete structures is a major challenge considering the service life of these structures. It is therefore necessary to correctly model the delayed behavior of these structures. Using a review of laboratory tests and observations of the delayed behavior of structures (bridges and nuclear power plants), the main conclusions of this work are the following ones. First, very long term creep in laboratory or of real structures seems to be non asymptotic. In the actual Eurocode-2, creep is calculated by means of an asymptotic hyperbolic function while in the recent Model Code 2010 creep is expressed as a combination of an asymptotic and a logarithmic functions. In the latter case the logarithmic function corresponds to basic creep while drying creep is asymptotic. Secondly, using a long test (3 years) in a laboratory is not enough to assess the long term behaviour of a massive structure. We need physical relations for creep in codes in order to predict the delayed behavior of massive structures. Thirdly, the biaxial creep of nuclear power plant could be modelled but using data of the structure itself. This would allow to predict the delayed behavior of these structures. Further work is needed to improve the prediction in the design phase

Long-Term Plasticity of Astrocytic Metabotropic Neurotransmitter Receptors Driven by Changes in Neuronal Activity in Hippocampal Slices

OpenAIRE

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...

Genetic deletion of melanin-concentrating hormone neurons impairs hippocampal short-term synaptic plasticity and hippocampal-dependent forms of short-term memory.

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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.

Lithium prevents long-term neural and behavioral pathology induced by early alcohol exposure.

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Sadrian, B; Subbanna, S; Wilson, D A; Basavarajappa, B S; Saito, M

2012-03-29

Fetal alcohol exposure can cause developmental defects in offspring known as fetal alcohol spectrum disorder (FASD). FASD symptoms range from obvious facial deformities to changes in neuroanatomy and neurophysiology that disrupt normal brain function and behavior. Ethanol exposure at postnatal day 7 in C57BL/6 mice induces neuronal cell death and long-lasting neurobehavioral dysfunction. Previous work has demonstrated that early ethanol exposure impairs spatial memory task performance into adulthood and perturbs local and interregional brain circuit integrity in the olfacto-hippocampal pathway. Here we pursue these findings to examine whether lithium prevents anatomical, neurophysiological, and behavioral pathologies that result from early ethanol exposure. Lithium has neuroprotective properties that have been shown to prevent ethanol-induced apoptosis. Here we show that mice co-treated with lithium on the same day as ethanol exposure exhibit dramatically reduced acute neurodegeneration in the hippocampus and retain hippocampal-dependent spatial memory as adults. Lithium co-treatment also blocked ethanol-induced disruption in synaptic plasticity in slice recordings of hippocampal CA1 in the adult mouse brain. Moreover, long-lasting dysfunctions caused by ethanol in olfacto-hippocampal networks, including sensory-evoked oscillations and resting state coherence, were prevented in mice co-treated with lithium. Together, these results provide behavioral and physiological evidence that lithium is capable of preventing or reducing immediate and long-term deleterious consequences of early ethanol exposure on brain function. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Drosophila Neprilysins Are Involved in Middle-Term and Long-Term Memory.

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Turrel, Oriane; Lampin-Saint-Amaux, Aurélie; Préat, Thomas; Goguel, Valérie

2016-09-14

Neprilysins are type II metalloproteinases known to degrade and inactivate a number of small peptides. Neprilysins in particular are the major amyloid-β peptide-degrading enzymes. In mouse models of Alzheimer's disease, neprilysin overexpression improves learning and memory deficits, whereas neprilysin deficiency aggravates the behavioral phenotypes. However, whether these enzymes are involved in memory in nonpathological conditions is an open question. Drosophila melanogaster is a well suited model system with which to address this issue. Several memory phases have been characterized in this organism and the neuronal circuits involved are well described. The fly genome contains five neprilysin-encoding genes, four of which are expressed in the adult. Using conditional RNA interference, we show here that all four neprilysins are involved in middle-term and long-term memory. Strikingly, all four are required in a single pair of neurons, the dorsal paired medial (DPM) neurons that broadly innervate the mushroom bodies (MBs), the center of olfactory memory. Neprilysins are also required in the MB, reflecting the functional relationship between the DPM neurons and the MB, a circuit believed to stabilize memories. Together, our data establish a role for neprilysins in two specific memory phases and further show that DPM neurons play a critical role in the proper targeting of neuropeptides involved in these processes. Neprilysins are endopeptidases known to degrade a number of small peptides. Neprilysin research has essentially focused on their role in Alzheimer's disease and heart failure. Here, we use Drosophila melanogaster to study whether neprilysins are involved in memory. Drosophila can form several types of olfactory memory and the neuronal structures involved are well described. Four neprilysin genes are expressed in adult Drosophila Using conditional RNA interference, we show that all four are specifically involved in middle-term memory (MTM) and long-term

The requirement for enhanced CREB1 expression in consolidation of long-term synaptic facilitation and long-term excitability in sensory neurons of Aplysia

Science.gov (United States)

Liu, Rong-Yu; Cleary, Leonard J.; Byrne, John H.

2011-01-01

Accumulating evidence suggests that the transcriptional activator CREB1 is important for serotonin (5-HT)-induced long-term facilitation (LTF) of the sensorimotor synapse in Aplysia. Moreover, creb1 is among the genes activated by CREB1, suggesting a role for this protein beyond the induction phase of LTF. The time course of the requirement for CREB1 synthesis in the consolidation of long-term facilitation was examined using RNA interference (RNAi) techniques in sensorimotor co-cultures. Injection of CREB1 small-interfering RNA (siRNA) immediately or 10 h after 5-HT treatment blocked LTF when measured at 24 h and 48 h after treatment. In contrast, CREB1 siRNA did not block LTF when injected 16 h after 5-HT treatment. These results demonstrate that creb1 expression must be sustained for a relatively long time in order to support the consolidation of LTF. In addition, LTF is also accompanied by a long-term increase in the excitability (LTE) of sensory neurons (SNs). Because LTE was observed in the isolated SN after 5-HT treatment, this long-term change was intrinsic to that element of the circuit. LTE was blocked when CREB1 siRNA was injected into isolated SNs immediately after 5-HT treatment. These data suggest that 5-HT-induced CREB1 synthesis is required for consolidation of both LTF and LTE. PMID:21543617

Decoupling the short- and long-term behavior of stochastic volatility

DEFF Research Database (Denmark)

Bennedsen, Mikkel; Lunde, Asger; Pakkanen, Mikko

behavior) from long memory and persistence (long-term behavior) in a simple and parsimonious way, which allows us to successfully model volatility at all intraday time scales. Our prime model is based on the so-called Brownian semistationary process and we derive a number of theoretical properties...... measures of close to two thousand individual US equities, we find that both roughness and persistence appear to be universal properties of volatility. Inspired by the empirical findings, we introduce a new class of continuous-time stochastic volatility models, capable of decoupling roughness (short-term...

Dopamine Modulation of Reunion Behavior in Short and Long Term Marmoset Pairs

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Sarah B. Carp

2018-05-01

Full Text Available One major neurobiological substrate regulating social processes is dopamine (DA. DA is implicated in social behavior in species as diverse as fish and birds, and has an established role in regulating relationships between mates in socially monogamous rodents. Marmoset monkeys display traits associated with social monogamy including high rates of affiliation, biparental care, distress upon separation, and aggression toward strangers; several of these behavioral patterns change throughout the development of relationships. This temporal change may represent changing demands, as pairs are likely to jointly face new experiences (e.g., parenthood throughout pairing. We investigated the role of DA and pairing length on social behavior during reunion after separation from the mate. Marmosets were removed from their home environment and treated with agonists and antagonists for the D1 and D2 receptor subtypes. They were exposed to a novel environment containing an opposite-sex stranger and their pair mate, and then reunited with their mate in the home enclosure. Marmosets in long term pairs exhibited higher levels of food sharing during reunion than marmosets in short term pairs, with females in long term pairs sharing food more than males; no sex difference was observed in short term pairs. Subjects in short term pairs spent more time grooming their mate than receiving grooming during reunion, while marmosets in long term pairs displayed similar amounts of both initiated and received grooming. DA treatment altered pair-level behavior. When females received either a D2 agonist or antagonist, short term pairs spent less time in proximity, compared to when males received the same treatments. In long term pairs, treatment of females with either a D1 agonist or antagonist resulted in pairs spending less time in social proximity than when males were treated. These findings suggest that the function of the DA system in mate behavior may be similar between

Short-Term Depression, Temporal Summation, and Onset Inhibition Shape Interval Tuning in Midbrain Neurons

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Baker, Christa A.

2014-01-01

A variety of synaptic mechanisms can contribute to single-neuron selectivity for temporal intervals in sensory stimuli. However, it remains unknown how these mechanisms interact to establish single-neuron sensitivity to temporal patterns of sensory stimulation in vivo. Here we address this question in a circuit that allows us to control the precise temporal patterns of synaptic input to interval-tuned neurons in behaviorally relevant ways. We obtained in vivo intracellular recordings under multiple levels of current clamp from midbrain neurons in the mormyrid weakly electric fish Brienomyrus brachyistius during stimulation with electrosensory pulse trains. To reveal the excitatory and inhibitory inputs onto interval-tuned neurons, we then estimated the synaptic conductances underlying responses. We found short-term depression in excitatory and inhibitory pathways onto all interval-tuned neurons. Short-interval selectivity was associated with excitation that depressed less than inhibition at short intervals, as well as temporally summating excitation. Long-interval selectivity was associated with long-lasting onset inhibition. We investigated tuning after separately nullifying the contributions of temporal summation and depression, and found the greatest diversity of interval selectivity among neurons when both mechanisms were at play. Furthermore, eliminating the effects of depression decreased sensitivity to directional changes in interval. These findings demonstrate that variation in depression and summation of excitation and inhibition helps to establish tuning to behaviorally relevant intervals in communication signals, and that depression contributes to neural coding of interval sequences. This work reveals for the first time how the interplay between short-term plasticity and temporal summation mediates the decoding of temporal sequences in awake, behaving animals. PMID:25339741

Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons

NARCIS (Netherlands)

Reneman, L.; Booij, J.; de Bruin, K.; Reitsma, J. B.; de Wolff, F. A.; Gunning, W. B.; den Heeten, G. J.; van den Brink, W.

2001-01-01

BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug that has been shown to damage brain serotonin neurons in high doses. However, effects of moderate MDMA use on serotonin neurons have not been studied, and sex differences and the long-term effects of MDMA

Deleting HDAC3 Rescues Long-Term Memory Impairments Induced by Disruption of the Neuron-Specific Chromatin Remodeling Subunit BAF53b

Science.gov (United States)

Shu, Guanhua; Kramár, Enikö A.; López, Alberto J.; Huynh, Grace; Wood, Marcelo A.; Kwapis, Janine L.

2018-01-01

Multiple epigenetic mechanisms, including histone acetylation and nucleosome remodeling, are known to be involved in long-term memory formation. Enhancing histone acetylation by deleting histone deacetylases, like HDAC3, typically enhances long-term memory formation. In contrast, disrupting nucleosome remodeling by blocking the neuron-specific…

Long-term bedrock behavior research for soft rock

International Nuclear Information System (INIS)

Inoue, Hiroyuki; Noda, Kenji

2002-02-01

When a formation disposal system is thought about, it is important to evaluate long-term dynamics behavior of boundary condition and near field bedrock of an artificial barrier adequately. In this study, three matters were executed for improvement of a dependability of the evaluation as follows. (1) Creep test was executed as purpose by dependability improvement of evaluation technique of creep problem by Okubo model. Okubo model constant was calculated than the unconfined compression test which let strain rate change with true rock, and the creep test which the constant was used, and estimated breaking time was done. As a result, the estimation of breaking time by Okubo model almost suffered according to the estimation although a variation of test-piece influenced it. (2) A tunnel model apparatus was produced in the purpose which grasped near field bedrock behavior, and it was tested. Simulation rock test body of 1 m * 1 m * 0.5 m was used for a test, and 15 cm tunnel excavation was carried out in an initial stress bottom. Quantities of inner space displacement were measured in a test, and a hardness-test was done after dismantlement, and looseness area was grasped quantitatively. As a result, the looseness area was able to be estimated with about 17.5 cm than tunnel center position. (3) A test approach in deep underground laboratory was examined, and examination/the in situ test which took advantage of rock core analysis/borehole as purpose and done examination item by grip of long-term bedrock behavior (a bord is taken advantage of, and bord itself is used) was shown. In addition, layout of the deep underground laboratory which carried out various tests about long-term behavior in 3 depth was shown. (author)

Phrenic long-term facilitation following intrapleural CTB-SAP-induced respiratory motor neuron death.

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Nichols, Nicole L; Craig, Taylor A; Tanner, Miles A

2017-08-16

Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to progressive motor neuron degeneration and death by ventilatory failure. In a rat model of ALS (SOD1 G93A ), phrenic long-term facilitation (pLTF) following acute intermittent hypoxia (AIH) is enhanced greater than expected at disease end-stage but the mechanism is unknown. We suggest that one trigger for this enhancement is motor neuron death itself. Intrapleural injections of cholera toxin B fragment conjugated to saporin (CTB-SAP) selectively kill respiratory motor neurons and mimic motor neuron death observed in SOD1 G93A rats. This CTB-SAP model allows us to study the impact of respiratory motor neuron death on breathing without many complications attendant to ALS. Here, we tested the hypothesis that phrenic motor neuron death is sufficient to enhance pLTF. pLTF was assessed in anesthetized, paralyzed and ventilated Sprague Dawley rats 7 and 28days following bilateral intrapleural injections of: 1) CTB-SAP (25μg), or 2) un-conjugated CTB and SAP (control). CTB-SAP enhanced pLTF at 7 (CTB-SAP: 162±18%, n=8 vs. 63±3%; n=8; pSAP: 64±10%, n=10 vs. 60±13; n=8; p>0.05). Thus, pLTF at 7 (not 28) days post-CTB-SAP closely resembles pLTF in end-stage ALS rats, suggesting that processes unique to the early period of motor neuron death enhance pLTF. This project increases our understanding of respiratory plasticity and its implications for breathing in motor neuron disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Applying Psychological Theories to Promote Long-Term Maintenance of Health Behaviors

Science.gov (United States)

Joseph, Rodney P.; Daniel, Casey L.; Thind, Herpreet; Benitez, Tanya J.; Pekmezi, Dori

2014-01-01

Behavioral health theory provides a framework for researchers to design, implement, and evaluate the effects of health promotion programs. However, limited research has examined theories used in interventions to promote long-term maintenance of health behaviors. The purpose of this review was to evaluate the available literature and identify prominent behavioral health theories used in intervention research to promote maintenance of health behaviors. We reviewed theories used in intervention research assessing long-term maintenance (≥ 6 months post-intervention) of physical activity, weight loss, and smoking cessation. Five prominent behavioral theories were referenced by the 34 studies included in the review: Self-Determination Theory, Theory of Planned Behavior, Social Cognitive Theory, Transtheoretical Model, and Social Ecological Model. Descriptions and examples of applications of these theories are provided. Implications for future research are discussed. PMID:28217036

Phrenic motor neuron TrkB expression is necessary for acute intermittent hypoxia-induced phrenic long-term facilitation

OpenAIRE

Dale, Erica A.; Fields, Daryl P.; Devinney, Michael J.; Mitchell, Gordon S.

2016-01-01

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 n...

Phrenic motor neuron TrkB expression is necessary for acute intermittent hypoxia-induced phrenic long-term facilitation.

Science.gov (United States)

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.

Microscopic study of rock for estimating long-term behavior

International Nuclear Information System (INIS)

Ichikawa, Yasuaki

2004-02-01

Micro-structure of rock plays an essential role for their long-term behavior. For understanding long-term characteristics of granite we here present the followings: 1) observation of microcrack initiation and propagation by Conforcal Laser Scanning Microscope (CLSM) under uniaxial compression (before loading and at each loading stage), 2) characterization of the mechanism of microcrack initiation and propagation observed by stereoscopic microscope under uniaxial/triaxial compression and relaxation tests, and 3) a study of strong discontinuity analysis included in the homogenization theory to predict the long-term behavior of micro/macro-level stress for granite. First, CLSM was used to acquire clearly focused three-dimensional images of granite specimens, and observed the change of microscale structure including the mineral configuration under applying uniaxial compression stress. Then though microcracks have ever thought to be initiated and propagated on intergranular boundaries, we understand through the CLSM observation that new microcracks are generated from the ends of pre-existing cracks which are distributed in quartz and biotite. Second, we showed the results of stress-relaxation test of granite specimens observed by an optical microscope under water-saturated triaxial compression condition. Since microcrack generation and propagation play an essential role to predict the long-term behavior of rock, we managed the experiments with careful attention of 1) keeping constant edge-displacement and constant strain in the whole specimen accurately, and 2) measuring the relaxed stress exactly. Next, in order to simulate the experimental results which indicate that initiation and propagation of microcracks control the stress-relaxation phenomenon, we introduce a homogenization analysis procedure together with the strong discontinuity analysis which has recently established the mechanical implication and mathematical foundation. The numerical results show that we can

Controlled adhesion and growth of long term glial and neuronal cultures on Parylene-C.

Directory of Open Access Journals (Sweden)

Evangelos Delivopoulos

Full Text Available This paper explores the long term development of networks of glia and neurons on patterns of Parylene-C on a SiO(2 substrate. We harvested glia and neurons from the Sprague-Dawley (P1-P7 rat hippocampus and utilized an established cell patterning technique in order to investigate cellular migration, over the course of 3 weeks. This work demonstrates that uncontrolled glial mitosis gradually disrupts cellular patterns that are established early during culture. This effect is not attributed to a loss of protein from the Parylene-C surface, as nitrogen levels on the substrate remain stable over 3 weeks. The inclusion of the anti-mitotic cytarabine (Ara-C in the culture medium moderates glial division and thus, adequately preserves initial glial and neuronal conformity to underlying patterns. Neuronal apoptosis, often associated with the use of Ara-C, is mitigated by the addition of brain derived neurotrophic factor (BDNF. We believe that with the right combination of glial inhibitors and neuronal promoters, the Parylene-C based cell patterning method can generate structured, active neural networks that can be sustained and investigated over extended periods of time. To our knowledge this is the first report on the concurrent application of Ara-C and BDNF on patterned cell cultures.

Neuronal differentiation and long-term culture of the human neuroblastoma line SH-SY5Y.

Science.gov (United States)

Constantinescu, R; Constantinescu, A T; Reichmann, H; Janetzky, B

2007-01-01

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in industrialized countries. Present cell culture models for PD rely on either primary cells or immortal cell lines, neither of which allow for long-term experiments on a constant population, a crucial requisite for a realistic model of slowly progressing neurodegenerative diseases. We differentiated SH-SY5Y human dopaminergic neuroblastoma cells to a neuronal-like state in a perfusion culture system using a combination of retinoic acid and mitotic inhibitors. The cells could be cultivated for two months without the need for passage. We show, by various means, that the differentiated cells exhibit, at the molecular level, many neuronal properties not characteristic to the starting line. This approach opens the possibility to develop chronic models, in which the effect of perturbations and putative counteracting strategies can be monitored over long periods of time in a quasi-stable cell population.

Two Pairs of Mushroom Body Efferent Neurons Are Required for Appetitive Long-Term Memory Retrieval in Drosophila

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Pierre-Yves Plaçais

2013-11-01

Full Text Available One of the challenges facing memory research is to combine network- and cellular-level descriptions of memory encoding. In this context, Drosophila offers the opportunity to decipher, down to single-cell resolution, memory-relevant circuits in connection with the mushroom bodies (MBs, prominent structures for olfactory learning and memory. Although the MB-afferent circuits involved in appetitive learning were recently described, the circuits underlying appetitive memory retrieval remain unknown. We identified two pairs of cholinergic neurons efferent from the MB α vertical lobes, named MB-V3, that are necessary for the retrieval of appetitive long-term memory (LTM. Furthermore, LTM retrieval was correlated to an enhanced response to the rewarded odor in these neurons. Strikingly, though, silencing the MB-V3 neurons did not affect short-term memory (STM retrieval. This finding supports a scheme of parallel appetitive STM and LTM processing.

A Framework for Estimating Long Term Driver Behavior

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Vijay Gadepally

2017-01-01

Full Text Available We present a framework for estimation of long term driver behavior for autonomous vehicles and vehicle safety systems. The Hybrid State System and Hidden Markov Model (HSS+HMM system discussed in this article is capable of describing the hybrid characteristics of driver and vehicle coupling. In our model, driving observations follow a continuous trajectory that can be measured to create continuous state estimates. These continuous state estimates can then be used to estimate the most likely driver state using decision-behavior coupling inherent to the HSS+HMM system. The HSS+HMM system is encompassed in a HSS structure and intersystem connectivity is determined by using signal processing and pattern recognition techniques. The proposed method is suitable for a number of autonomous and vehicle safety scenarios such as estimating intent of other vehicles near intersections or avoiding hazardous driving events such as unexpected lane changes. The long term driver behavior estimation system involves an extended HSS+HMM structure that is capable of including external information in the estimation process. Through the grafting and pruning of metastates, the HSS+HMM system can be dynamically updated to best represent driver choices given external information. Three application examples are also provided to elucidate the theoretical system.

Long-term leaching behavior of vitrified high-level wastes

International Nuclear Information System (INIS)

Ishiguro, Katsuhiko; Sonobe, Hitoshi; Sasaki, Noriaki; Kashihara, Hidechiyo

1985-01-01

A long-term Soxhlet leaching test, long-term static leaching test, solubility evaluation test and actual-scale glass solid leaching test were carried out for simulated vitrified wastes. Under high flow-rate leachate conditions, the leaching of high-solubility substances such as B and Na increases almost linearly with time while that of Fe, Ni and rare earth metals strongly depends on their solubility. The overall leaching rate changes (tends to decrease) with time under static conditions. The elution or diffusion is the rate determining step in the earlier region of the leaching process while the solubilities of major components have greater effects in the latter region. The change of the dominant leaching mechanism is delayed more largely as the surface-area to leachate-volume (SA/V) ratio decreases. Actual-scale glass specimens showed almost the same leaching behaviors as small-scale ones. If cracks exist in glass solid, the leaching in them is slow causing little effects on the overall leaching rate. This may be due to the fact that solubility-dependent leaching is occuring in the cracks. The long-term static leaching observations were not satisfactorily explained by the MCC-3 type solubility test results. It is important to clarify the solubility-dependent leaching behaviors at large SA/V ratios. (Nogami, K.)

Neural plasticity in hypocretin neurons: the basis of hypocretinergic regulation of physiological and behavioral functions in animals

Directory of Open Access Journals (Sweden)

Xiao-Bing eGao

2015-10-01

Full Text Available The neuronal system that resides in the perifornical and lateral hypothalamus (Pf/LH and synthesizes the neuropeptide hypocretin/orexin participates in critical brain functions across species from fish to human. The hypocretin system regulates neural activity responsible for daily functions (such as sleep/wake homeostasis, energy balance, appetite, etc and long-term behavioral changes (such as reward seeking and addiction, stress response, etc in animals. The most recent evidence suggests that the hypocretin system undergoes substantial plastic changes in response to both daily fluctuations (such as food intake and sleep-wake regulation and long-term changes (such as cocaine seeking in neuronal activity in the brain. The understanding of these changes in the hypocretin system is essential in addressing the role of the hypocretin system in normal physiological functions and pathological conditions in animals and humans. In this review, the evidence demonstrating that neural plasticity occurs in hypocretin-containing neurons in the Pf/LH will be presented and possible physiological behavioral, and mental health implications of these findings will be discussed.

Neural plasticity in hypocretin neurons: the basis of hypocretinergic regulation of physiological and behavioral functions in animals

Science.gov (United States)

Gao, Xiao-Bing; Hermes, Gretchen

2015-01-01

The neuronal system that resides in the perifornical and lateral hypothalamus (Pf/LH) and synthesizes the neuropeptide hypocretin/orexin participates in critical brain functions across species from fish to human. The hypocretin system regulates neural activity responsible for daily functions (such as sleep/wake homeostasis, energy balance, appetite, etc.) and long-term behavioral changes (such as reward seeking and addiction, stress response, etc.) in animals. The most recent evidence suggests that the hypocretin system undergoes substantial plastic changes in response to both daily fluctuations (such as food intake and sleep-wake regulation) and long-term changes (such as cocaine seeking) in neuronal activity in the brain. The understanding of these changes in the hypocretin system is essential in addressing the role of the hypocretin system in normal physiological functions and pathological conditions in animals and humans. In this review, the evidence demonstrating that neural plasticity occurs in hypocretin-containing neurons in the Pf/LH will be presented and possible physiological, behavioral, and mental health implications of these findings will be discussed. PMID:26539086

PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons.

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Alison Wood-Kaczmar

2008-06-01

Full Text Available Parkinson's disease (PD is a common age-related neurodegenerative disease and it is critical to develop models which recapitulate the pathogenic process including the effect of the ageing process. Although the pathogenesis of sporadic PD is unknown, the identification of the mendelian genetic factor PINK1 has provided new mechanistic insights. In order to investigate the role of PINK1 in Parkinson's disease, we studied PINK1 loss of function in human and primary mouse neurons. Using RNAi, we created stable PINK1 knockdown in human dopaminergic neurons differentiated from foetal ventral mesencephalon stem cells, as well as in an immortalised human neuroblastoma cell line. We sought to validate our findings in primary neurons derived from a transgenic PINK1 knockout mouse. For the first time we demonstrate an age dependent neurodegenerative phenotype in human and mouse neurons. PINK1 deficiency leads to reduced long-term viability in human neurons, which die via the mitochondrial apoptosis pathway. Human neurons lacking PINK1 demonstrate features of marked oxidative stress with widespread mitochondrial dysfunction and abnormal mitochondrial morphology. We report that PINK1 plays a neuroprotective role in the mitochondria of mammalian neurons, especially against stress such as staurosporine. In addition we provide evidence that cellular compensatory mechanisms such as mitochondrial biogenesis and upregulation of lysosomal degradation pathways occur in PINK1 deficiency. The phenotypic effects of PINK1 loss-of-function described here in mammalian neurons provides mechanistic insight into the age-related degeneration of nigral dopaminergic neurons seen in PD.

Long-term deflection and flexural behavior of reinforced concrete beams with recycled aggregate

International Nuclear Information System (INIS)

Choi, Won-Chang; Yun, Hyun-Do

2013-01-01

Highlights: • Long-term deformation of recycled aggregate concrete beams was examined. • Three beams were monitored for over 380 days. • Influence of recycled aggregate on the long-term performance. • Comparison of that between normal and recycled aggregate concrete beams. - Abstract: This paper presents experimental results on the long-term deformations of recycled aggregate concrete (RAC) beams for over 1 year (380 days) and flexural behavior of RAC beams after exposure to sustained loading. Three reinforced concrete (RC) beam specimens were fabricated with replacement percentage of aggregate (100% natural aggregate, 100% recycled coarse aggregate, and 50% recycled fine aggregate) and subjected to sustained loading that is 50% of the nominal flexural capacity. During the sustained loading period (380 days), the long-term deflection due to creep and shrinkage was recorded and compared with predicted behavior that was determined based on current specifications (ACI 318 Code). After measuring the long-term deflection for 380 days, four-point bending tests were conducted to investigate the flexural behavior of RC beams after exposure to sustained loading and determine any reduction in flexural capacity. A modified equation to predict the long-term deflection values for RC beams with recycled aggregate is proposed, and the experimental results are compared with the predictions calculated using the ACI 318 Code provisions

Microscopic study of rock for estimating long-term behavior. Research document

International Nuclear Information System (INIS)

Ichikawa, Yasuaki

2003-02-01

Micro-structure of rock plays an essential role for their long-term behavior. For elucidating long-term characteristics of granite we here present the followings: 1) Conformal Lase Scanning Microscope (LSM) observation of configuration of a joint in granite, its Fourier analysis and the change under uniaxial stress condition, 2) characterization of the mechanism of microcrack initiation and propagation observed by stereoscopic microscope under uniaxial/triaxial compression and relaxation tests, 3) observation of microcrack initiation and propagation by LSM under uniaxial compression, and 4) a study of strong discontinuity analysis included in the homogenization theory to predict the long-term behavior of micro/macro-level stress for granite. Rock image processing and analysis become a fundamental procedure to determine rock surface discontinuities. In Chapter 2 LSM that can acquire three-dimensional images is introduced to observe the roughness of discontinuity in a rock specimen. Then, discontinuities appeared on circular sections are identified by LSM and characterized by a Discrete Fourier Transform (DFT) analysis. The change of discontinuities is observed under applying stress. Microcrack generation and propagation play an essential role to predict the long-term behavior of rock. In Chapter 3 a progressive development of cracking in granite is revealed by using stereoscopic microscope under water-saturated triaxial compression condition. Next by using LSM observe the procedure of micro-cracking under uniaxial compression condition. Obviously the micro-crack initiation and propagation controls the time-dependent behavior of granite. We have analysed the behavior by a viscoelastic theory applied in homogenization method. However since it is difficult to determine the inter-granular properties of constituent crystals and to represent the stress-dependent nonlinear characteristics by this method, we study a strong discontinuity analysis included in the

Inducible cAMP early repressor acts as a negative regulator for kindling epileptogenesis and long-term fear memory.

Science.gov (United States)

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.

A prediction method for long-term behavior of prestressed concrete containment vessels

International Nuclear Information System (INIS)

Ozaki, M.; Abe, T.; Watanabe, Y.; Kato, A.; Yamaguchi, T.; Yamamoto, M.

1995-01-01

This paper presents results of studies on the long-term behavior of PCCVs at Taruga Unit No 2 and Ohi Unit No 3/4 power stations. The objective of this study is to evaluate the measured strain in the concrete and reduction force in the tendons, and to establish the prediction methods for long-term PCCVs behavior. Comparing the measured strains with those calculated due to creep and shrinkage of the concrete, those in contrast were investigated. Furthermore, the reduced tendon forces are calculated considering losses in elasticity, relaxation, creep and shrinkage. The measured reduction in the tendon forces is compared with the calculated. Considering changes in temperature and humidity, the measured strains and tendon forces were in good agreement with those calculated. From the above results, it was confirmed that the residual pre stresses in the PCCVs maintain the predicted values at the design stage, and that the prediction method of long-term behaviors has sufficient reliability. (author). 10 refs., 8 figs., 3 tabs

Chaos in long-term behavior of some Bianchi-type VIII models

Energy Technology Data Exchange (ETDEWEB)

Halpern, P

1987-01-01

The long-term behavior of Bianchi-type VIII models with three different types of stress-energy tensors are examined and compared. The vacuum model, a matter-filled model, and a model with an electromagnetic field are considered. In each case the existence of chaotic behavior and transitions to chaotic behavior are discussed.

Fan-Shaped Body Neurons Are Involved in "Period"-Dependent Regulation of Long-Term Courtship Memory in "Drosophila"

Science.gov (United States)

Sakai, Takaomi; Inami, Show; Sato, Shoma; Kitamoto, Toshihiro

2012-01-01

In addition to its established function in the regulation of circadian rhythms, the "Drosophila" gene "period" ("per") also plays an important role in processing long-term memory (LTM). Here, we used courtship conditioning as a learning paradigm and revealed that (1) overexpression and knocking down of "per" in subsets of brain neurons enhance and…

Long term bending behavior of ultra-high performance concrete (UHPC beams

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Gheorghe-Alexandru BARBOS

2015-12-01

Full Text Available Unlike normal concrete (NC the behavior of ultra-high performance concrete (UHPC is different under long-term efforts, if we refer to creep, shrinkage or long-term deflections. It is well known that UHPC has special properties, like compressive strength higher than 150 MPa and tensile strength higher than 20 MPa - in case of UHPC reinforced with steel-fibers. Nevertheless, UHPC behavior is not completely elucidated in what concerns creep straining or serviceability behavior in case of structural elements. Some studies made on UHPC samples shown that creep is significantly reduced if the concrete is subjected to heat treatment and if it contains steel-fiber reinforcement. Relating thereto, it is important to know how does structural elements made of this type of concrete works in service life under long-term loadings. The results obtained on UHPC samples, regarding creep straining from tension or compression efforts may not be generalized in case of structural elements (e.g. beams, slabs, columns subjected to bending. By performing this study, it was aimed to understand the influence of heat treatment and steel-fiber addition on the rheological phenomena of UHPC bended beams.

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

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Hazem eToutounji

2014-05-01

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

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

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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.

Simulation of long-term dynamic behavior of runaway electrons

International Nuclear Information System (INIS)

Wang Yulei; Liu Jian; Zhang Ruili; He Yang

2015-01-01

The secular dynamics of runaway electrons in Tokamak electromagnetic field is studied. The radiation effect is added into a relativistic volume-preserving algorithm to gain long-term stability of calculation. The results shows that the method we used is able to reveal the behavior of a runaway electron in configuration space. (author)

A study on shear behavior of R/C beams subjected to long-term heating

International Nuclear Information System (INIS)

Maruta, M.; Yamazaki, M.

1993-01-01

In nuclear power plants, many structural members are subjected to long term heating. There are few experimental data available on the behavior especially in shear of reinforced concrete (R/C) members subjected to long term heating. This paper describes a study aimed at experimentally determining the shear behavior of R/C members in nuclear power plant facilities following sustained heating at high temperatures

Construction of implantable optical fibers for long-term optogenetic manipulation of neural circuits.

Science.gov (United States)

Sparta, Dennis R; Stamatakis, Alice M; Phillips, Jana L; Hovelsø, Nanna; van Zessen, Ruud; Stuber, Garret D

2011-12-08

In vivo optogenetic strategies have redefined our ability to assay how neural circuits govern behavior. Although acutely implanted optical fibers have previously been used in such studies, long-term control over neuronal activity has been largely unachievable. Here we describe a method to construct implantable optical fibers to readily manipulate neural circuit elements with minimal tissue damage or change in light output over time (weeks to months). Implanted optical fibers readily interface with in vivo electrophysiological arrays or electrochemical detection electrodes. The procedure described here, from implant construction to the start of behavioral experimentation, can be completed in approximately 2-6 weeks. Successful use of implantable optical fibers will allow for long-term control of mammalian neural circuits in vivo, which is integral to the study of the neurobiology of behavior.

Elongator complex is required for long-term olfactory memory formation in Drosophila.

Science.gov (United States)

Yu, Dinghui; Tan, Ying; Chakraborty, Molee; Tomchik, Seth; Davis, Ronald L

2018-04-01

The evolutionarily conserved Elongator Complex associates with RNA polymerase II for transcriptional elongation. Elp3 is the catalytic subunit, contains histone acetyltransferase activity, and is associated with neurodegeneration in humans. Elp1 is a scaffolding subunit and when mutated causes familial dysautonomia. Here, we show that elp3 and elp1 are required for aversive long-term olfactory memory in Drosophila RNAi knockdown of elp3 in adult mushroom bodies impairs long-term memory (LTM) without affecting earlier forms of memory. RNAi knockdown with coexpression of elp3 cDNA reverses the impairment. Similarly, RNAi knockdown of elp1 impairs LTM and coexpression of elp1 cDNA reverses this phenotype. The LTM deficit in elp3 and elp1 knockdown flies is accompanied by the abolishment of a LTM trace, which is registered as increased calcium influx in response to the CS+ odor in the α-branch of mushroom body neurons. Coexpression of elp1 or elp3 cDNA rescues the memory trace in parallel with LTM. These data show that the Elongator complex is required in adult mushroom body neurons for long-term behavioral memory and the associated long-term memory trace. © 2018 Yu et al.; Published by Cold Spring Harbor Laboratory Press.

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

Science.gov (United States)

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

2011-01-01

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

5-Bromo-2'-deoxyuridine impairs long-term food aversion memory in edible snail.

Science.gov (United States)

Efimova, O I; Anokhin, K V

2012-09-01

We studied the involvement of DNA synthesis into molecular mechanisms of long-term memory. Nucleoside analogue 5-bromo-2'-deoxyuridine (BrdU) is known to incorporate into synthesizing DNA and prevent subsequent DNA replication from this region. To investigate the effect of BrdU administration on long-term memory, terrestrial gastropods edible snails Helix lucorum were trained in the food aversion paradigm. Single-session training (carrot presentation combined with application of 10% quinine solution, three carrot presentations with 10-min intervals) resulted in the formation of long-term memory that persisted for at least 45° days. BrdU administration (250 mg/kg) 30 min before training impaired long-term memory tested 24 h later. Immunohistochemical study revealed BrdU incorporation in the nuclei of identified neurons of defensive behavior.

Delayed Dopamine Signaling of Energy Level Builds Appetitive Long-Term Memory in Drosophila

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Pierre-Yves Musso

2015-02-01

Full Text Available Sensory cues relevant to a food source, such as odors, can be associated with post-ingestion signals related either to food energetic value or toxicity. Despite numerous behavioral studies, a global understanding of the mechanisms underlying these long delay associations remains out of reach. Here, we demonstrate in Drosophila that the long-term association between an odor and a nutritious sugar depends on delayed post-ingestion signaling of energy level. We show at the neural circuit level that the activity of two pairs of dopaminergic neurons is necessary and sufficient to signal energy level to the olfactory memory center. Accordingly, we have identified in these dopaminergic neurons a delayed calcium trace that correlates with appetitive long-term memory formation. Altogether, these findings demonstrate that the Drosophila brain remembers food quality through a two-step mechanism that consists of the integration of olfactory and gustatory sensory information and then post-ingestion energetic value.

Delayed dopamine signaling of energy level builds appetitive long-term memory in Drosophila.

Science.gov (United States)

Musso, Pierre-Yves; Tchenio, Paul; Preat, Thomas

2015-02-24

Sensory cues relevant to a food source, such as odors, can be associated with post-ingestion signals related either to food energetic value or toxicity. Despite numerous behavioral studies, a global understanding of the mechanisms underlying these long delay associations remains out of reach. Here, we demonstrate in Drosophila that the long-term association between an odor and a nutritious sugar depends on delayed post-ingestion signaling of energy level. We show at the neural circuit level that the activity of two pairs of dopaminergic neurons is necessary and sufficient to signal energy level to the olfactory memory center. Accordingly, we have identified in these dopaminergic neurons a delayed calcium trace that correlates with appetitive long-term memory formation. Altogether, these findings demonstrate that the Drosophila brain remembers food quality through a two-step mechanism that consists of the integration of olfactory and gustatory sensory information and then post-ingestion energetic value. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Long-Term Sensitization Training in "Aplysia" Decreases the Excitability of a Decision-Making Neuron through a Sodium-Dependent Mechanism

Science.gov (United States)

Hernandez, John S.; Wainwright, Marcy L.; Mozzachiodi, Riccardo

2017-01-01

In "Aplysia," long-term sensitization (LTS) occurs concurrently with a suppression of feeding. At the cellular level, the suppression of feeding is accompanied by decreased excitability of decision-making neuron B51. We examined the contribution of voltage-gated Na[superscript +] and K[superscript +] channels to B51 decreased…

Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia.

Science.gov (United States)

Chen, Shanping; Cai, Diancai; Pearce, Kaycey; Sun, Philip Y-W; Roberts, Adam C; Glanzman, David L

2014-11-17

Long-term memory (LTM) is believed to be stored in the brain as changes in synaptic connections. Here, we show that LTM storage and synaptic change can be dissociated. Cocultures of Aplysia sensory and motor neurons were trained with spaced pulses of serotonin, which induces long-term facilitation. Serotonin (5HT) triggered growth of new presynaptic varicosities, a synaptic mechanism of long-term sensitization. Following 5HT training, two antimnemonic treatments-reconsolidation blockade and inhibition of PKM--caused the number of presynaptic varicosities to revert to the original, pretraining value. Surprisingly, the final synaptic structure was not achieved by targeted retraction of the 5HT-induced varicosities but, rather, by an apparently arbitrary retraction of both 5HT-induced and original synapses. In addition, we find evidence that the LTM for sensitization persists covertly after its apparent elimination by the same antimnemonic treatments that erase learning-related synaptic growth. These results challenge the idea that stable synapses store long-term memories.

Intratympanic steroid prevents long-term spiral ganglion neuron loss in experimental meningitis

DEFF Research Database (Denmark)

Worsøe, Lise Lotte; Brandt, C.T.; Lund, S.P.

2010-01-01

Hypothesis: Intratympanic steroid treatment prevents hearing loss and cochlear damage in a rat model of pneumococcal meningitis. Background: Sensorineural hearing loss is a long-term complication of meningitis affecting up to a third of survivors. Streptococcus pneumoniae is the bacterial species...... for 3 days. Hearing loss and cochlear damage were assessed by distortion product otoacoustic emissions, auditory brainstem response at 16 kHz, and spiral ganglion neuron density. Results: Fifty-six days after infection, auditory brainstem response showed no significant differences between groups...... in the spiral ganglion compared with both intratympanic and systemic saline (p = 0.0082 and p = 0.0089; Mann-Whitney test). Histology revealed fibrosis of the tympanic membrane and cavity in steroid-treated animals, which plausibly caused the low-frequency hearing loss. Conclusion: Intratympanic betamethasone...

BAF53b, a Neuron-Specific Nucleosome Remodeling Factor, Is Induced after Learning and Facilitates Long-Term Memory Consolidation.

Science.gov (United States)

Yoo, Miran; Choi, Kwang-Yeon; Kim, Jieun; Kim, Mujun; Shim, Jaehoon; Choi, Jun-Hyeok; Cho, Hye-Yeon; Oh, Jung-Pyo; Kim, Hyung-Su; Kaang, Bong-Kiun; Han, Jin-Hee

2017-03-29

Although epigenetic mechanisms of gene expression regulation have recently been implicated in memory consolidation and persistence, the role of nucleosome-remodeling is largely unexplored. Recent studies show that the functional loss of BAF53b, a postmitotic neuron-specific subunit of the BAF nucleosome-remodeling complex, results in the deficit of consolidation of hippocampus-dependent memory and cocaine-associated memory in the rodent brain. However, it is unclear whether BAF53b expression is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain site for fear memory encoding and storage. To address these questions, we used viral vector approaches to either decrease or increase BAF53b function specifically in the lateral amygdala of adult mice in auditory fear conditioning paradigm. Knockdown of Baf53b before training disrupted long-term memory formation with no effect on short-term memory, basal synaptic transmission, and spine structures. We observed in our qPCR analysis that BAF53b was induced in the lateral amygdala neurons at the late consolidation phase after fear conditioning. Moreover, transient BAF53b overexpression led to persistently enhanced memory formation, which was accompanied by increase in thin-type spine density. Together, our results provide the evidence that BAF53b is induced after learning, and show that such increase of BAF53b level facilitates memory consolidation likely by regulating learning-related spine structural plasticity. SIGNIFICANCE STATEMENT Recent works in the rodent brain begin to link nucleosome remodeling-dependent epigenetic mechanism to memory consolidation. Here we show that BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced in the lateral amygdala neurons at the late phase of consolidation after fear conditioning. Using specific gene knockdown or overexpression approaches, we identify the critical role of BAF53b in the lateral amygdala neurons for

Long-term oxytocin administration improves social behaviors in a girl with autistic disorder.

Science.gov (United States)

Kosaka, Hirotaka; Munesue, Toshio; Ishitobi, Makoto; Asano, Mizuki; Omori, Masao; Sato, Makoto; Tomoda, Akemi; Wada, Yuji

2012-08-13

Patients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs. We present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl's social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7. This case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs.

Long-term culture of rat hippocampal neurons at low density in serum-free medium: combination of the sandwich culture technique with the three-dimensional nanofibrous hydrogel PuraMatrix.

Science.gov (United States)

Kaneko, Ai; Sankai, Yoshiyuki

2014-01-01

The primary culture of neuronal cells plays an important role in neuroscience. There has long been a need for methods enabling the long-term culture of primary neurons at low density, in defined serum-free medium. However, the lower the cell density, the more difficult it is to maintain the cells in culture. Therefore, we aimed to develop a method for long-term culture of neurons at low density, in serum-free medium, without the need for a glial feeder layer. Here, we describe the work leading to our determination of a protocol for long-term (>2 months) primary culture of rat hippocampal neurons in serum-free medium at the low density of 3×10(4) cells/mL (8.9×10(3) cells/cm2) without a glial feeder layer. Neurons were cultured on a three-dimensional nanofibrous hydrogel, PuraMatrix, and sandwiched under a coverslip to reproduce the in vivo environment, including the three-dimensional extracellular matrix, low-oxygen conditions, and exposure to concentrated paracrine factors. We examined the effects of varying PuraMatrix concentrations, the timing and presence or absence of a coverslip, the timing of neuronal isolation from embryos, cell density at plating, medium components, and changing the medium or not on parameters such as developmental pattern, cell viability, neuronal ratio, and neurite length. Using our method of combining the sandwich culture technique with PuraMatrix in Neurobasal medium/B27/L-glutamine for primary neuron culture, we achieved longer neurites (≥3,000 µm), greater cell viability (≥30%) for 2 months, and uniform culture across the wells. We also achieved an average neuronal ratio of 97%, showing a nearly pure culture of neurons without astrocytes. Our method is considerably better than techniques for the primary culture of neurons, and eliminates the need for a glial feeder layer. It also exhibits continued support for axonal elongation and synaptic activity for long periods (>6 weeks).

Long-term culture of rat hippocampal neurons at low density in serum-free medium: combination of the sandwich culture technique with the three-dimensional nanofibrous hydrogel PuraMatrix.

Directory of Open Access Journals (Sweden)

Ai Kaneko

Full Text Available The primary culture of neuronal cells plays an important role in neuroscience. There has long been a need for methods enabling the long-term culture of primary neurons at low density, in defined serum-free medium. However, the lower the cell density, the more difficult it is to maintain the cells in culture. Therefore, we aimed to develop a method for long-term culture of neurons at low density, in serum-free medium, without the need for a glial feeder layer. Here, we describe the work leading to our determination of a protocol for long-term (>2 months primary culture of rat hippocampal neurons in serum-free medium at the low density of 3×10(4 cells/mL (8.9×10(3 cells/cm2 without a glial feeder layer. Neurons were cultured on a three-dimensional nanofibrous hydrogel, PuraMatrix, and sandwiched under a coverslip to reproduce the in vivo environment, including the three-dimensional extracellular matrix, low-oxygen conditions, and exposure to concentrated paracrine factors. We examined the effects of varying PuraMatrix concentrations, the timing and presence or absence of a coverslip, the timing of neuronal isolation from embryos, cell density at plating, medium components, and changing the medium or not on parameters such as developmental pattern, cell viability, neuronal ratio, and neurite length. Using our method of combining the sandwich culture technique with PuraMatrix in Neurobasal medium/B27/L-glutamine for primary neuron culture, we achieved longer neurites (≥3,000 µm, greater cell viability (≥30% for 2 months, and uniform culture across the wells. We also achieved an average neuronal ratio of 97%, showing a nearly pure culture of neurons without astrocytes. Our method is considerably better than techniques for the primary culture of neurons, and eliminates the need for a glial feeder layer. It also exhibits continued support for axonal elongation and synaptic activity for long periods (>6 weeks.

Development of a cell-based treatment for long-term neurotrophin expression and spiral ganglion neuron survival.

Science.gov (United States)

Zanin, M P; Hellström, M; Shepherd, R K; Harvey, A R; Gillespie, L N

2014-09-26

Spiral ganglion neurons (SGNs), the target cells of the cochlear implant, undergo gradual degeneration following loss of the sensory epithelium in deafness. The preservation of a viable population of SGNs in deafness can be achieved in animal models with exogenous application of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3. For translation into clinical application, a suitable delivery strategy that provides ongoing neurotrophic support and promotes long-term SGN survival is required. Cell-based neurotrophin treatment has the potential to meet the specific requirements for clinical application, and we have previously reported that Schwann cells genetically modified to express BDNF can support SGN survival in deafness for 4 weeks. This study aimed to investigate various parameters important for the development of a long-term cell-based neurotrophin treatment to support SGN survival. Specifically, we investigated different (i) cell types, (ii) gene transfer methods and (iii) neurotrophins, in order to determine which variables may provide long-term neurotrophin expression and which, therefore, may be the most effective for supporting long-term SGN survival in vivo. We found that fibroblasts that were nucleofected to express BDNF provided the most sustained neurotrophin expression, with ongoing BDNF expression for at least 30 weeks. In addition, the secreted neurotrophin was biologically active and elicited survival effects on SGNs in vitro. Nucleofected fibroblasts may therefore represent a method for safe, long-term delivery of neurotrophins to the deafened cochlea to support SGN survival in deafness. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Synthesis on the long term behavior of spent nuclear fuel. Vol.1,2

International Nuclear Information System (INIS)

Poinssot, Ch.; Toulhoat, P.; Grouiller, J.P.; Pavageau, J.; Piron, J.P.; Pelletier, M.; Dehaudt, Ph.; Cappelaere, Ch.; Limon, R.; Desgranges, L.; Jegou, Ch.; Corbel, C.; Maillard, S.; Faure, M.H.; Cicariello, J.C.; Masson, M.

2001-01-01

The aim of this report is to present the major objectives, the key scientific issues, and the preliminary results of the research conducted in France in the framework of the third line of the 1991 Law, on the topic of the long term behavior of spent nuclear fuel in view of long term storage or geological disposal. Indeed, CEA launched in 1998 the Research Program on the Long Term Behavior of Spent Nuclear Fuel (abbreviated and referred to as PRECCI in French; Poinssot, 1998) the aim of which is to study and assess the ability of spent nuclear fuel packages to keep their initially allocated functions in interim storage and geological disposal: total containment and recovery functions for duration up to hundreds of years (long term or short-term interim storage and/or first reversible stages of geological disposal) and partial confinement function (controlled fluxes of RN) for thousands of years in geological disposal. This program has to allow to obtain relevant and reliable data concerning the long term behavior of the spent fuel packages so that feasibility of interim storage and/or geological disposal can be assessed and demonstrated as well as optimized. Within this framework, this report presents for every possible scenario of evolution (closed system, in Presence of water in presence of gases) what are estimated to be the most relevant evolution mechanism. For the most relevant scientific issues hence defined, a complete scientific review of the best state of knowledge is subsequently here given thus allowing to draw a clear guideline of the major R and D issues for the next years. (authors)

Whole-Body Exposure to 28Si-Radiation Dose-Dependently Disrupts Dentate Gyrus Neurogenesis and Proliferation in the Short Term and New Neuron Survival and Contextual Fear Conditioning in the Long Term.

Science.gov (United States)

Whoolery, Cody W; Walker, Angela K; Richardson, Devon R; Lucero, Melanie J; Reynolds, Ryan P; Beddow, David H; Clark, K Lyles; Shih, Hung-Ying; LeBlanc, Junie A; Cole, Mara G; Amaral, Wellington Z; Mukherjee, Shibani; Zhang, Shichuan; Ahn, Francisca; Bulin, Sarah E; DeCarolis, Nathan A; Rivera, Phillip D; Chen, Benjamin P C; Yun, Sanghee; Eisch, Amelia J

2017-11-01

in male and female mice, although only male mice showed fewer surviving BrdU + cells in the long-term group. Fluorescent immunolabeling and confocal phenotypic analysis revealed that most surviving BrdU + cells in the long-term group expressed the neuronal marker NeuN, definitively confirming that exposure to 1 Gy 28 Si radiation decreased the number of surviving adult-generated neurons in male mice relative to both 0- and 0.2-Gy-irradiated mice. For hippocampal function assessment, 9-week-old male C57BL/6J mice received whole-body 28 Si-particle exposure and were then assessed long-term for performance on contextual and cued fear conditioning. In the context test the animals that received 0.2 Gy froze less relative to control animals, suggesting decreased hippocampal-dependent function. However, in the cued fear conditioning test, animals that received 1 Gy froze more during the pretone portion of the test, relative to controls and 0.2-Gy-irradiated mice, suggesting enhanced anxiety. Compared to previously reported studies, these data suggest that 28 Si-radiation exposure damages neurogenesis, but to a lesser extent than 56 Fe radiation and that low-dose 28 Si exposure induces abnormalities in hippocampal function, disrupting fear memory but also inducing anxiety-like behavior. Furthermore, exposure to 28 Si radiation decreased new neuron survival in long-term male groups but not females suggests that sex may be an important factor when performing brain health risk assessment for astronauts traveling in space.

Effects of long-term inhibition of neuronal nitric oxide synthase on blood pressure and renin release

DEFF Research Database (Denmark)

Ollerstam, A.; Skøtt, O.; Ek, J.

2001-01-01

Nitric oxide (NO) produced by neuronal NO-synthase (nNOS) in macula densa cells may be involved in the control of renin release. 7-Nitro indazole (7-NI) inhibits nNOS, and we investigated the effect of short- (4 days) and long-term (4 weeks) 7-NI treatment on blood pressure (BP), plasma renin...... LS rats (107 +/- 15 vs. 56 +/- 1 mGU mL(-1)). Stimulation of PRC in LS rats was further enhanced by 7-NI after 4 days of treatment, but not affected in rats treated for 4 weeks. This suggests that inhibition of nNOS stimulates renin release but that this stimulatory effect in the long run might...

Protective effects of long-term lithium administration in a slowly progressive SMA mouse model.

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Biagioni, Francesca; Ferrucci, Michela; Ryskalin, Larisa; Fulceri, Federica; Lazzeri, Gloria; Calierno, Maria Teresa; Busceti, Carla L; Ruffoli, Riccardo; Fornai, Francesco

2017-12-01

In the present study we evaluated the long-term effects of lithium administration to a knock-out double transgenic mouse model (Smn-/-; SMN1A2G+/-; SMN2+/+) of Spinal Muscle Atrophy type III (SMA-III). This model is characterized by very low levels of the survival motor neuron protein, slow disease progression and motor neuron loss, which enables to detect disease-modifying effects at delayed time intervals. Lithium administration attenuates the decrease in motor activity and provides full protection from motor neuron loss occurring in SMA-III mice, throughout the disease course. In addition, lithium prevents motor neuron enlargement and motor neuron heterotopy and suppresses the occurrence of radial-like glial fibrillary acidic protein immunostaining in the ventral white matter of SMA-III mice. In SMA-III mice long-term lithium administration determines a dramatic increase of survival motor neuron protein levels in the spinal cord. These data demonstrate that long-term lithium administration during a long-lasting motor neuron disorder attenuates behavioural deficit and neuropathology. Since low level of survival motor neuron protein is bound to disease severity in SMA, the robust increase in protein level produced by lithium provides solid evidence which calls for further investigations considering lithium in the long-term treatment of spinal muscle atrophy.

Effects of long-term elevated temperature on covering, sheltering and righting behaviors of the sea urchin Strongylocentrotus intermedius

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Zhang, Lisheng; Zhang, Lingling; Shi, Dongtao; Wei, Jing; Chang, Yaqing

2017-01-01

Increases in ocean temperature due to climate change are predicted to change the behaviors of marine invertebrates. Altered behaviors of keystone ecosystem engineers such as echinoderms will have consequences for the fitness of individuals, which are expected to flow on to the local ecosystem. Relatively few studies have investigated the behavioral responses of echinoderms to long-term elevated temperature. We investigated the effects of exposure to long-term (∼31 weeks) elevated temperature (∼3 °C above the ambient water temperature) on covering, sheltering and righting behaviors of the sea urchin Strongylocentrotus intermedius. Long-term elevated temperature showed different effects on the three behaviors. It significantly decreased covering behavior, including both covering behavior reaction (time to first covering) and ability (number of covered sea urchins and number of shells used for covering). Conversely, exposure to long-term elevated temperature significantly increased sheltering behavior. Righting response in S. intermedius was not significantly different between temperature treatments. The results provide new information into behavioral responses of echinoderms to ocean warming. PMID:28348933

Prenatal alcohol exposure results in long-term serotonin neuron deficits in female rats: modulatory role of ovarian steroids.

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Sliwowska, Joanna H; Song, Hyun Jung; Bodnar, Tamara; Weinberg, Joanne

2014-01-01

Previous studies on male rodents found that prenatal alcohol exposure (PAE) decreases the number of serotonin immunoreactive (5-HT-ir) neurons in the brainstem. However, data on the effects of PAE in females are lacking. In light of known sex differences in responsiveness of the 5-HT system and known effects of estrogen (E2 ) and progesterone (P4 ) in the brain, we hypothesized that sex steroids will modulate the adverse effects of PAE on 5-HT neurons in adult females. Adult females from 3 prenatal groups (Prenatal alcohol-exposed [PAE], Pair-fed [PF], and ad libitum-fed Controls [C]) were ovariectomized (OVX), with or without hormone replacement, or underwent Sham OVX. 5-HT-ir cells were examined in key brainstem areas. Our data support the hypothesis that PAE has long-term effects on the 5-HT system of females and that ovarian steroids have a modulatory role in these effects. Intact (Sham OVX) PAE females had marginally lower numbers of 5-HT-ir neurons in the dorsal raphe nucleus of the brainstem compared with PF and C females. This marginal difference became significant following removal of hormones by OVX. Replacement with E2 restored the number of 5-HT-ir neurons in PAE females to control levels, while P4 reversed the effects of E2 . Importantly, despite these differential responses of the 5-HT system to ovarian steroids, there were no differences in E2 and P4 levels among prenatal treatment groups. These data demonstrate long-term, adverse effects of PAE on the 5-HT system of females, as well as differential sensitivity of PAE compared with control females to the modulatory effects of ovarian steroids on 5-HT neurons. Our findings have important implications for understanding sex differences in 5-HT dysfunction in depression/anxiety disorders and the higher rates of these mental health problems in individuals with fetal alcohol spectrum disorder. Copyright © 2013 by the Research Society on Alcoholism.

Activation of the Akt/mTOR signaling pathway: A potential response to long-term neuronal loss in the hippocampus after sepsis

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Jia-nan Guo

2017-01-01

Full Text Available Survivors of sepsis may suffer chronic cognitive impairment as a long-term sequela. However, the precise mechanisms of cognitive dysfunction after sepsis are not well understood. We employed the cecal ligation-and-puncture-induced septic mouse model. We observed elevated phosphorylation of Akt, mammalian target of rapamycin (mTOR and p70S6K on days 14 and 60, progressive neuronal loss in the cornu ammonis 1 region, and abnormal neuronal morphology in the hippocampus in the sepsis mouse model. These findings indicate that changes in neuronal morphology and number in the hippocampus after sepsis were associated with strong activation of the Akt/mTOR signaling pathway, and may reflect a “self-rescuing” feedback response to neuronal loss after sepsis.

Failure of delayed nonsynaptic neuronal plasticity underlies age-associated long-term associative memory impairment

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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

Phenomenological study on crystalline rock for evaluating of long-term behavior (Contract research)

International Nuclear Information System (INIS)

Okubo, Seisuke; Fukui, Katsunori; Hashiba, Kimihiro; Hikima, Ryoichi; Tanno, Takeo; Sanada, Hiroyuki; Matsui, Hiroya; Sato, Toshinori

2012-02-01

Rock, under in situ conditions, shows time-dependent behavior such as creep/relaxation. With respect to high-level radioactive waste disposal, knowledge of the long-term mechanical stability of shafts and galleries excavated in rock is required, not only during construction and operation but also over a period of thousands of years after closure. Therefore, it is very important to understand the time-dependent behavior of rock for evaluating long-term mechanical stability. The purpose of this study is determining the mechanisms of time-dependent behavior of rock by precise testing, observation and measurement in order to develop methods for evaluating long-term mechanical stability of a rock mass. In the previous work, testing techniques have been established and basic evaluation methods were developed. Recently, some parameters needed for simulation of time-dependent behavior were determined at the Mizunami underground research facilities. However, sufficient data to check the reliability of the evaluation method for these parameters were not available. This report describes the results of the activities in fiscal year 2010. In Chapter 1, we provide an overview and the background to this study. In Chapter 2, the results of a long-term creep test on Tage tuff, started in fiscal year 1997 are described. In Chapter 3, the relation of loading-rate dependency of strength and stress dependency of creep life, the relation of time dependency, probability distribution and size effects are discussed to indicate more clearly the meaning of the value of 'n' to express the degree of time dependency of the rock. Furthermore, past studies concerning the value of 'n' are reviewed and the tests that could be carried out in future studies of mechanical properties and time dependency of Toki granite are considered in this Chapter. In Chapter 4, failure criterions of a rock mass considering time dependency are discussed. In Chapter 5, the FEM analysis implemented with a generalized

Retrosplenial Cortex and Long-Term Memory: Molecules to Behavior

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Travis P. Todd

2015-01-01

Full Text Available The retrosplenial cortex (RSC is reciprocally connected with the hippocampus and various parahippocampal cortical regions, suggesting that RSC is well-positioned to contribute to hippocampal-dependent memory. Consistent with this, substantial behavioral evidence indicates that RSC is essential for consolidating and/or retrieving contextual and spatial memories. In addition, there is growing evidence that RSC neurons undergo activity-dependent plastic changes during memory formation and retrieval. In this paper we review both the behavioral and cellular/molecular data and posit that the RSC has a particularly important role in the storage and retrieval of spatial and contextual memories perhaps due its involvement in binding together multiple cues in the environment. We identify remaining questions and avenues for future research that take advantage of emerging methods to selectively manipulate RSC neurons both spatially and temporally and to image the RSC in awake, behaving animals.

How Do You Motivate Long-Term Behavior Change to Prevent Cancer?

Science.gov (United States)

John P. Pierce PhD, a professor in the Department of Family and Preventive Medicine at the University of California, San Diego and Director of Population Science at Moores Cancer Center, presented "How Do You Motivate Long-Term Behavior Change to Prevent Cancer?" 

CREB binding protein is required for both short-term and long-term memory formation.

Science.gov (United States)

Chen, Guiquan; Zou, Xiaoyan; Watanabe, Hirotaka; van Deursen, Jan M; Shen, Jie

2010-09-29

CREB binding protein (CBP) is a transcriptional coactivator with histone acetyltransferase activity. Our prior study suggested that CBP might be a key target of presenilins in the regulation of memory formation and neuronal survival. To elucidate the role of CBP in the adult brain, we generated conditional knock-out (cKO) mice in which CBP is completely inactivated in excitatory neurons of the postnatal forebrain. Histological analysis revealed normal neuronal morphology and absence of age-dependent neuronal degeneration in the CBP cKO cerebral cortex. CBP cKO mice exhibited robust impairment in the formation of spatial, associative, and object-recognition memory. In addition to impaired long-term memory, CBP cKO mice also displayed deficits in short-term associative and object-recognition memory. Administration of a histone deacetylase inhibitor, trichostatin A, rescued the reduction of acetylated histones in the CBP cKO cortex but failed to rescue either short- or long-term memory deficits, suggesting that the memory impairment may not be caused by general reduction of histone acetyltransferase activity in CBP cKO mice. Further microarray and Western analysis showed decreased expression of calcium-calmodulin-dependent kinase isoforms and NMDA and AMPA receptor subunits in the cerebral cortex of CBP cKO mice. Collectively, these findings suggest a crucial role for CBP in the formation of both short- and long-term memory.

Social Stairs : taking the Piano Staircase towards long-term behavioral change

NARCIS (Netherlands)

Peeters, M.M.R.; Megens, C.J.P.G.; Hoven, van den E.A.W.H.; Hummels, C.C.M.; Brombacher, A.C.; Berkovsky, S.; Freyne, J.

2013-01-01

This paper addresses the development of Social Stairs, an intelligent musical staircase to change people’s behavior in the long-term to take the stairs in favor of the elevator. Through designing with the Experiential Design Landscape (EDL) method, a design opportunity was found that social

Propofol causes neuronal degeneration in neonatal mice and long ...

African Journals Online (AJOL)

Propofol causes neuronal degeneration in neonatal mice and long-term ... of 2.5 and 5.0 mg/kg (treatment group) or normal saline (control) on postnatal day 7. ... PO2, glucose and lactate), among which decreased blood glucose might be ...

Creep deformation behavior at long-term in P23/T23 steels

Energy Technology Data Exchange (ETDEWEB)

Sawada, K.; Tabuchi, M.; Kimura, K. [National Institute for Materials Science (Japan)

2008-07-01

Creep behavior of ASME P23/T23 steels was investigated and analyzed, focusing on creep strength degradation at long-term. Creep rupture strength at 625 C and 650 C dropped at long-term in both P23 and T23 steels. The stress exponent of minimum creep rate at 625 C and 650 C was 7.8-13 for higher stresses and 3.9-5.3 for lower stresses in the P23/T23 steels. The change of stress exponent with stress levels was consistent with the drop in creep rupture strength at long-term. The Monkman-Grant rule was confirmed in the range examined in P23 steel, while the data points deviated from the rule at long-term in the case of T23 steel. The creep ductility of P23 steel was high over a wide stress and temperature range. On the other hand, in T23 steel, creep ductility at 625 C and 650 C decreased as time to rupture increased. The change in ductility may cause the deviation from the Monkman-Grant rule. Fracture mode changed from transgranular to intergranular fracture in the long-term at 625 C and 650 C. (orig.)

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

Science.gov (United States)

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.

Phospholipase A₂: the key to reversing long-term memory impairment in a gastropod model of aging.

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Watson, Shawn N; Wright, Natasha; Hermann, Petra M; Wildering, Willem C

2013-02-01

Memory failure associated with changes in neuronal circuit functions rather than cell death is a common feature of normal aging in diverse animal species. The (neuro)biological foundations of this phenomenon are not well understood although oxidative stress, particularly in the guise of lipid peroxidation, is suspected to play a key role. Using an invertebrate model system of age-associated memory impairment that supports direct correlation between behavioral deficits and changes in the underlying neural substrate, we show that inhibition of phospholipase A(2) (PLA(2)) abolishes both long-term memory (LTM) and neural defects observed in senescent subjects and subjects exposed to experimental oxidative stress. Using a combination of behavioral assessments and electrophysiological techniques, we provide evidence for a close link between lipid peroxidation, provocation of phospholipase A(2)-dependent free fatty acid release, decline of neuronal excitability, and age-related long-term memory impairments. This supports the view that these processes suspend rather than irreversibly extinguish the aging nervous system's intrinsic capacity for plasticity. Copyright © 2013 Elsevier Inc. All rights reserved.

Behavioral Specifications of Reward-Associated Long-Term Memory Enhancement in Humans

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Wittmann, Bianca C.; Dolan, Raymond J.; Duzel, Emrah

2011-01-01

Recent functional imaging studies link reward-related activation of the midbrain substantia nigra-ventral tegmental area (SN/VTA), the site of origin of ascending dopaminergic projections, with improved long-term episodic memory. Here, we investigated in two behavioral experiments how (1) the contingency between item properties and reward, (2) the…

Upregulation of T-type Ca2+ channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons.

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Duzhyy, Dmytro E; Viatchenko-Karpinski, Viacheslav Y; Khomula, Eugen V; Voitenko, Nana V; Belan, Pavel V

2015-05-20

Previous studies have shown that increased excitability of capsaicin-sensitive DRG neurons and thermal hyperalgesia in rats with short-term (2-4 weeks) streptozotocin-induced diabetes is mediated by upregulation of T-type Ca(2+) current. In longer-term diabetes (after the 8th week) thermal hyperalgesia is changed to hypoalgesia that is accompanied by downregulation of T-type current in capsaicin-sensitive small-sized nociceptors. At the same time pain symptoms of diabetic neuropathy other than thermal persist in STZ-diabetic animals and patients during progression of diabetes into later stages suggesting that other types of DRG neurons may be sensitized and contribute to pain. In this study, we examined functional expression of T-type Ca(2+) channels in capsaicin-insensitive DRG neurons and excitability of these neurons in longer-term diabetic rats and in thermally hypoalgesic diabetic rats. Here we have demonstrated that in STZ-diabetes T-type current was upregulated in capsaicin-insensitive low-pH-sensitive small-sized nociceptive DRG neurons of longer-term diabetic rats and thermally hypoalgesic diabetic rats. This upregulation was not accompanied by significant changes in biophysical properties of T-type channels suggesting that a density of functionally active channels was increased. Sensitivity of T-type current to amiloride (1 mM) and low concentration of Ni(2+) (50 μM) implicates prevalence of Cav3.2 subtype of T-type channels in the capsaicin-insensitive low-pH-sensitive neurons of both naïve and diabetic rats. The upregulation of T-type channels resulted in the increased neuronal excitability of these nociceptive neurons revealed by a lower threshold for action potential initiation, prominent afterdepolarizing potentials and burst firing. Sodium current was not significantly changed in these neurons during long-term diabetes and could not contribute to the diabetes-induced increase of neuronal excitability. Capsaicin-insensitive low-pH-sensitive type

Cellular activation of hypothalamic hypocretin/orexin neurons facilitates short-term spatial memory in mice.

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Aitta-Aho, Teemu; Pappa, Elpiniki; Burdakov, Denis; Apergis-Schoute, John

2016-12-01

The hypothalamic hypocretin/orexin (HO) system holds a central role in the regulation of several physiological functions critical for food-seeking behavior including mnemonic processes for effective foraging behavior. It is unclear however whether physiological increases in HO neuronal activity can support such processes. Using a designer rM3Ds receptor activation approach increasing HO neuronal activity resulted in improved short-term memory for novel locations. When tested on a non-spatial novelty object recognition task no significant difference was detected between groups indicating that hypothalamic HO neuronal activation can selectively facilitate short-term spatial memory for potentially supporting memory for locations during active exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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

2011-07-28

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

Reconsolidation of long-term memory in Aplysia.

Science.gov (United States)

Cai, Diancai; Pearce, Kaycey; Chen, Shanping; Glanzman, David L

2012-10-09

When an animal is reminded of a prior experience and shortly afterward treated with a protein synthesis inhibitor, the consolidated memory for the experience can be disrupted; by contrast, protein synthesis inhibition without prior reminding commonly does not disrupt long-term memory [1-3]. Such results imply that the reminding triggers reconsolidation of the memory. Here, we asked whether the behavioral and synaptic changes associated with the memory for long-term sensitization (LTS) of the siphon-withdrawal reflex in the marine snail Aplysia californica [4, 5] could undergo reconsolidation. In support of this idea, we found that when sensitized animals were given abbreviated reminder sensitization training 48-96 hr after the original sensitization training, followed by treatment with the protein synthesis inhibitor anisomycin, LTS was disrupted. We also found that long-term (≥ 24 hr) facilitation (LTF) [6], which can be induced in the monosynaptic connection between Aplysia sensory and motor neurons in dissociated cell culture by multiple spaced pulses of the endogenous facilitatory transmitter serotonin (5-HT) [7, 8], could be eliminated by treating the synapses with one reminder pulse of 5-HT, followed by anisomycin, at 48 hr after the original training. Our results provide a simple model system for understanding the synaptic basis of reconsolidation. Copyright © 2012 Elsevier Ltd. All rights reserved.

3D Holographic Observatory for Long-term Monitoring of Complex Behaviors in Drosophila

Science.gov (United States)

Kumar, S. Santosh; Sun, Yaning; Zou, Sige; Hong, Jiarong

2016-09-01

Drosophila is an excellent model organism towards understanding the cognitive function, aging and neurodegeneration in humans. The effects of aging and other long-term dynamics on the behavior serve as important biomarkers in identifying such changes to the brain. In this regard, we are presenting a new imaging technique for lifetime monitoring of Drosophila in 3D at spatial and temporal resolutions capable of resolving the motion of limbs and wings using holographic principles. The developed system is capable of monitoring and extracting various behavioral parameters, such as ethograms and spatial distributions, from a group of flies simultaneously. This technique can image complicated leg and wing motions of flies at a resolution, which allows capturing specific landing responses from the same data set. Overall, this system provides a unique opportunity for high throughput screenings of behavioral changes in 3D over a long term in Drosophila.

Involvement of translation and transcription processes into neurophysiological mechanisms of long-term memory reconsolidation.

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Kozyrev, S A; Nikitin, V P

2013-03-01

We studied the involvement of translation and transcription processes into behavioral and neuronal mechanisms of reconsolidation of the long-term memory of the conditioned taste aversion in edible snails. Injection of cycloheximide (an inhibitor of protein synthesis) to the snails in 48 h after training combined with subsequent reminder and presentation of the conditional stimulus resulted in the development of persistent amnesia and depression of the responses of the defensive behavior command neurons LPl1 and RPl1 to the conditional stimulus. Injection of mRNA synthesis inhibitors actinomycin D or DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidasole) in 48 h after conditioning with subsequent reminding procedure produced no effects on memory retention and on the responses of the command neurons to the conditional stimulus. The study suggests that the proteins translated from previously synthesized and stored mRNA were involved in the mechanisms of reconsolidation of the memory responsible for conditioned taste aversion.

Short-term memory in networks of dissociated cortical neurons.

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Dranias, Mark R; Ju, Han; Rajaram, Ezhilarasan; VanDongen, Antonius M J

2013-01-30

Short-term memory refers to the ability to store small amounts of stimulus-specific information for a short period of time. It is supported by both fading and hidden memory processes. Fading memory relies on recurrent activity patterns in a neuronal network, whereas hidden memory is encoded using synaptic mechanisms, such as facilitation, which persist even when neurons fall silent. We have used a novel computational and optogenetic approach to investigate whether these same memory processes hypothesized to support pattern recognition and short-term memory in vivo, exist in vitro. Electrophysiological activity was recorded from primary cultures of dissociated rat cortical neurons plated on multielectrode arrays. Cultures were transfected with ChannelRhodopsin-2 and optically stimulated using random dot stimuli. The pattern of neuronal activity resulting from this stimulation was analyzed using classification algorithms that enabled the identification of stimulus-specific memories. Fading memories for different stimuli, encoded in ongoing neural activity, persisted and could be distinguished from each other for as long as 1 s after stimulation was terminated. Hidden memories were detected by altered responses of neurons to additional stimulation, and this effect persisted longer than 1 s. Interestingly, network bursts seem to eliminate hidden memories. These results are similar to those that have been reported from similar experiments in vivo and demonstrate that mechanisms of information processing and short-term memory can be studied using cultured neuronal networks, thereby setting the stage for therapeutic applications using this platform.

On the effect of long-term electrical stimulation on three-dimensional cell cultures: Hen embryo brain spheroids

OpenAIRE

Uroukov, Ivan S; Bull, Larry

2008-01-01

A comprehensive dataset of multielectrode array recordings was collected from three-dimensional hen embryo brain cell cultures, termed spheroids, under long-term electrical stimulation. The aim is to understand the ongoing changes in the spiking activity under electrical stimulation within the lifetime of 14–72DIV of the neuronal networks contained therein. The spiking dynamics were analyzed and behavioral characteristics derived. Some effects on spiking patterns and exhaustion were followed ...

Transcriptional regulation of long-term memory in the marine snail Aplysia

Directory of Open Access Journals (Sweden)

Lee Yong-Seok

2008-06-01

Full Text Available Abstract Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF. The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT, a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT induce a transcription- and translation-dependent long-term facilitation (LTF lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced

Transcriptional regulation of long-term memory in the marine snail Aplysia.

Science.gov (United States)

Lee, Yong-Seok; Bailey, Craig H; Kandel, Eric R; Kaang, Bong-Kiun

2008-06-17

Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF). The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB) acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT), a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT) induce a transcription- and translation-dependent long-term facilitation (LTF) lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced by different

Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

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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

Learning-dependent neurogenesis in the olfactory bulb determines long-term olfactory memory.

Science.gov (United States)

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.

Hypertension impairs hippocampus-related adult neurogenesis, CA1 neuron dendritic arborization and long-term memory.

Science.gov (United States)

Shih, Y-H; Tsai, S-F; Huang, S-H; Chiang, Y-T; Hughes, M W; Wu, S-Y; Lee, C-W; Yang, T-T; Kuo, Y-M

2016-05-13

Hypertension is associated with neurodegenerative diseases and cognitive impairment. Several studies using spontaneous hypertensive rats to study the effect of hypertension on memory performance and adult hippocampal neurogenesis have reached inconsistent conclusions. The contradictory findings may be related to the genetic variability of spontaneous hypertensive rats due to the conventional breeding practices. The objective of this study is to examine the effect of hypertension on hippocampal structure and function in isogenic mice. Hypertension was induced by the '2 kidneys, 1 clip' method (2K1C) which constricted one of the two renal arteries. The blood pressures of 2K1C mice were higher than the sham group on post-operation day 7 and remained high up to day 28. Mice with 2K1C-induced hypertension had impaired long-term, but not short-term, memory. Dendritic complexity of CA1 neurons and hippocampal neurogenesis were reduced by 2K1C-induced hypertension on post-operation day 28. Furthermore, 2K1C decreased the levels of hippocampal brain-derived neurotrophic factor, while blood vessel density and activation status of astrocytes and microglia were not affected. In conclusion, hypertension impairs hippocampus-associated long-term memory, dendritic arborization and neurogenesis, which may be caused by down-regulation of brain-derived neurotrophic factor signaling pathways. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Study on crystalline rock for evaluating method of long-term behavior. FY2012 (Contract research)

International Nuclear Information System (INIS)

Fukui, Katsunori; Hashiba, Kimihiro; Tanno, Takeo; Hikima, Ryoichi; Sanada, Hiroyuki; Sato, Toshinori

2013-12-01

Rock shows time-dependent behavior such as creep/relaxation. With respect to high-level radioactive waste disposal, knowledge of the long-term mechanical stability of shafts and galleries excavated in rock are required, over a period of thousands of years after closure as well as during construction and operation. Therefore, it is very important to understand the time-dependent behavior of rock for evaluating long-term mechanical stability. The purpose of this study is to determine the mechanisms of time-dependent behavior of rock by the precise test (e.g. laboratory creep test), observation and measurement and to develop methods for evaluating long-term mechanical stability. In previous works, testing techniques were established and basic evaluation methods were developed. Recently, some parameters, which required for simulation of time-dependent behavior, were determined for the modeling of biotite granite (Toki granite) distributed around the Mizunami underground research laboratory. However, we were not able to obtain enough data to assess the reliability of the method to evaluate these parameters. This report describes the results of the research activities carried out in fiscal year 2012. In Chapter 1, we provide background and an overview of this study. In Chapter 2, the results of a long-term creep test on Tage tuff, started in fiscal year 1997, are described. In Chapter 3, the experimental results concerning the loading-rate dependency of rock strength were examined to understand the time-dependent behavior of rock. In Chapter 4, the stability of tunnels, under conditions which rock stress is larger than that around a circular tunnel, were examined to obtain useful information on the future plan for in-situ tests in the underground research laboratory. (author)

Long-term behavior of aortic intramural hematomas and penetrating ulcers.

Science.gov (United States)

Chou, Alan S; Ziganshin, Bulat A; Charilaou, Paris; Tranquilli, Maryann; Rizzo, John A; Elefteriades, John A

2016-02-01

For intramural hematoma and penetrating atherosclerotic ulcer, long-term behavior and treatment are controversial. This study evaluates the long-term behavior of intramural hematoma and penetrating atherosclerotic ulcer, including radiologic follow-up and survival analysis. Between 1995 and 2014, 108 patients (mean age, 70.8 ± 10 years; 56% female) presented with intramural hematoma or penetrating atherosclerotic ulcer to Yale-New Haven Hospital (New Haven, Conn). We reviewed the medical records, radiology, and online mortality databases. Ten of 55 patients (18%) with intramural hematoma and 17 of 53 patients (32%) with penetrating atherosclerotic ulcer had rupture state symptoms on admission, both greater than type A (8%) or type B dissection (4%) (P hematoma with follow-up imaging, 8 of 14 (57%) worsened (mean follow-up, 9.4 months) and 6 (43%) underwent late surgery. For patients with penetrating atherosclerotic ulcer with follow-up imaging, 6 of 20 (30%) worsened and underwent late surgery, and 11 (55%) showed no change (mean follow-up, 34.3 months). Overall survivals were 77%, 70%, 58%, and 33% at 1, 3, 5, and 10 years, respectively. No operative deaths occurred for patients with nonrupture state. Patients with penetrating atherosclerotic ulcer with initial surgical treatment had better long-term survival than patients treated medically (P = .037). In the intramural hematoma group, no such difference was observed (P = .10). At presentation, the incidence of early rupture of intramural hematoma and penetrating atherosclerotic ulcer was higher than for typical dissection. For branch vessels, intramural hematoma never occludes branch arteries. On imaging follow-up, patients with intramural hematoma and penetrating atherosclerotic ulcer rarely improved, with late surgery commonly needed. Better survival was observed for the initial surgical management of patients with penetrating atherosclerotic ulcer compared with initial medical management. Copyright © 2016

Long-term estradiol-17β administration changes the population of paracervical ganglion neurons supplying the ovary in adult gilts.

Science.gov (United States)

Jana, Barbara; Palus, Katarzyna; Czarzasta, Joanna; Całka, Jarosław

2013-07-01

The aim of this study was to determine the influence of estradiol-17β (E(2)) overdose on the number and distribution of ovarian parasympathetic neurons in the paracervical ganglion (PCG) in adult pigs. To identify the neurons innervating gonads on day 3 of the estrous cycle, the ovaries of both the control and experimental gilts were injected with retrograde neuronal tracer Fast Blue. From next day to the expected day 20 of the second studied cycle, experimental gilts were injected with E(2), while control gilts received oil. The PCG were then collected and processed for double-labeling immunofluorescence. Injections of E(2) increased the E(2) level in the peripheral blood approximately four- to fivefold and reduced the following in the PCG: the total number of Fast Blue-positive neurons; the number of perikarya in the lateral part of the PCG; the numbers of vesicular acetylcholine transporter (VAChT)(+)/somatostatin(+), VAChT(+)/vasoactive intestinal polypeptide (VIP)(+), VAChT(+)/neuronal isoform of nitric oxide synthase(+), VAChT(+)/VIP(-), VAChT(+)/dopamine β-hydroxylase (DβH)(-), VAChT(-)/VIP(-), and VAChT(-)/DβH(-) perikarya; and the total number of perikarya expressing estrogen receptors (ERs) subtype α and/or β. In summary, long-term E(2) treatment of adult gilts downregulates the population of both cholinergic and ERs expressing the PCG ovary-projecting neurons. Our results suggest that elevated E(2) levels occurring during pathological states may regulate gonadal function(s) by affecting ovary-supplying neurons.

Network reconfiguration and neuronal plasticity in rhythm-generating networks.

Science.gov (United States)

Koch, Henner; Garcia, Alfredo J; Ramirez, Jan-Marino

2011-12-01

Neuronal networks are highly plastic and reconfigure in a state-dependent manner. The plasticity at the network level emerges through multiple intrinsic and synaptic membrane properties that imbue neurons and their interactions with numerous nonlinear properties. These properties are continuously regulated by neuromodulators and homeostatic mechanisms that are critical to maintain not only network stability and also adapt networks in a short- and long-term manner to changes in behavioral, developmental, metabolic, and environmental conditions. This review provides concrete examples from neuronal networks in invertebrates and vertebrates, and illustrates that the concepts and rules that govern neuronal networks and behaviors are universal.

Purinergic modulation of adult guinea pig cardiomyocytes in long term cultures and co-cultures with extracardiac or intrinsic cardiac neurones.

Science.gov (United States)

Horackova, M; Huang, M H; Armour, J A

1994-05-01

To determine the capacity of ATP to modify cardiomyocytes directly or indirectly via peripheral autonomic neurones, the effects of various purinergic agents were studied on long term cultures of adult guinea pig ventricular myocytes and their co-cultures with extracardiac (stellate ganglion) or intrinsic cardiac neurones. Ventricular myocytes and cardiac neurones were enzymatically dissociated and plated together or alone (myocytes only). Myocyte cultures were used for experiments after three to six weeks. The electrical and contractile properties of cultured myocytes and myocyte-neuronal networks were investigated. The spontaneous beating frequency of ventricular myocytes co-cultured with stellate ganglion neurones increased by approximately 140% (p under control conditions, but when beta adrenergic receptors of tetrodotoxin sensitive neural responses were blocked, ATP induced greater augmentation (> 100%). In contrast, ATP induced much smaller effects in non-innervated myocyte cultures (approximately 26%, p UTP > MSATP > beta gamma ATP > alpha beta ATP. Adenosine (10(-4) M) attenuated the beating frequency of myocytes in both types of co-culture, while not significantly affecting non-innervated myocyte cultures. The experimental model used in this study showed that extrinsic and intrinsic cardiac neurones which possess P2 receptors can greatly enhance cardiac myocyte contractile rate when activated by ATP. Since adenosine reduced contractile rate in both types of co-cultures while not affecting non-innervated myocytes, it is concluded that some of these neurones possess P1 receptors.

Short-term memory and critical clusterization in brain neurons spike series

Science.gov (United States)

Bershadskii, A.; Dremencov, E.; Yadid, G.

2003-06-01

A new phenomenon: critical clusterization, is observed in the neuron firing of a genetically defined rat model of depression. The critical clusterization is studied using a multiscaling analysis of the data obtained from the neurons belonging to the Red Nucleus area of the depressive brains. It is suggested that this critical phenomenon can be partially responsible for the observed ill behavior of the depressive brains: loss of short-term motor memory and slow motor reaction.

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

Science.gov (United States)

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

2016-01-01

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

Long-Term Clock Behavior of GPS IIR Satellites

National Research Council Canada - National Science Library

Epstein, Marvin; Dass, Todd; Rajan, John; Gilmour, Paul

2007-01-01

.... Rubidium clocks, as opposed to cesium clocks, have significant long-term drift. The current literature describes an initial model of drift aging for rubidium atomic clocks followed by a long-term characteristic...

Neuronal antibodies in pediatric epilepsy: Clinical features and long-term outcomes of a historical cohort not treated with immunotherapy.

Science.gov (United States)

Wright, Sukhvir; Geerts, Ada T; Jol-van der Zijde, Cornelia Maria; Jacobson, Leslie; Lang, Bethan; Waters, Patrick; van Tol, Maarten J D; Stroink, Hans; Neuteboom, Rinze F; Brouwer, Oebele F; Vincent, Angela

2016-05-01

In autoimmune encephalitis the etiologic role of neuronal cell-surface antibodies is clear; patients diagnosed and treated early have better outcomes. Neuronal antibodies have also been described in patients with pediatric epilepsy without encephalitis. The aim was to assess whether antibody presence had any effect on long-term outcomes in these patients. Patients (n = 178) were recruited between 1988 and 1992 as part of the prospective Dutch Study of Epilepsy in Childhood; none received immunotherapy. Healthy age-matched bone-marrow donors served as controls (n = 112). All sera were tested for serum N-methyl-d-aspartate receptor (NMDAR), alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, leucine rich glioma inactivated 1, contactin associated protein like 2 (CASPR2), contactin-2, glutamic acid decarboxylase, and voltage gated potassium channel (VGKC)-complex antibodies by standard techniques. No cerebrospinal fluid (CSF) samples were available. Results were correlated with clinical data collected over 15 years. Seventeen patients (9.5%) were positive for VGKC complex (n = 3), NMDAR (n = 7), CASPR2 (n = 4), and contactin-2 (n = 3), compared to three (3/112; 2.6%) healthy controls (VGKC complex [n = 1], NMDAR [n = 2]; p = 0.03; Fisher's exact test). Titers were relatively low (≤1:100 for cell-surface antibodies), but 8 (47%) of the 17 positive samples bound to the surface of live hippocampal neurons consistent with a potential pathogenic antibody. Preexisting cognitive impairment was more frequent in antibody-positive patients (9/17 vs. 33/161; p = 0.01). Fourteen antibody-positive patients were treated with standard antiepileptic drugs (AEDs); three (17%) became intractable but this was not different from the 16 (10%) of 161 antibody-negative patients. In 96 patients with available follow-up samples at 6 and/or 12 months, 6 of 7 positive antibodies had disappeared and, conversely, antibodies had appeared for the first time in a further 7 patients

Magnetic Behavior of Sintered NdFeB Magnets on a Long-Term Timescale

Directory of Open Access Journals (Sweden)

Minna Haavisto

2014-01-01

Full Text Available Stable polarization of permanent magnets over the lifetime of the application is an important aspect in electrical machine design. Specification of the long-term stability of magnet material is difficult, since knowledge of the phenomenon is incomplete. To be able to optimize magnet material selection, the long-term magnetic behavior of the material must also be understood. This study shows that material with a very square JH curve is stable until a certain critical operating temperature is reached. Major losses are detected as the critical temperature is exceeded. Material with a rounder JH curve does not show a well-defined critical temperature, but increasing losses over a large temperature range. The critical temperature of a material is also dependent on the field conditions. Results differ whether the tests are performed in an open or closed magnetic circuit. In open-circuit tests, the opposing field is not homogeneously distributed throughout the volume of the magnet and thus the long-term behavior is different than that in closed-circuit conditions. Open-circuit tests seem to give bigger losses than closed-circuit tests in cases where the permeance coefficient of the open-circuit sample is considered to be the average permeance coefficient, calculated according to the dimensions of the magnet.

Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APPswe/PS1dE9 transgenic mice: Effect of long-term treatment with paroxetine.

Science.gov (United States)

Olesen, Louise Ørum; Sivasaravanaparan, Mithula; Severino, Maurizio; Babcock, Alicia A; Bouzinova, Elena V; West, Mark J; Wiborg, Ove; Finsen, Bente

2017-08-01

Altered neurogenesis may influence hippocampal functions such as learning and memory in Alzheimer's disease. Selective serotonin reuptake inhibitors enhance neurogenesis and have been reported to reduce cerebral amyloidosis in both humans and transgenic mice. We have used stereology to assess the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APP swe /PS1 dE9 transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis, and spontaneous alternation behaviour, a measure of spatial working memory, in transgenic mice. We observed no difference in granular neurons between transgenic and wild type mice up till 18months of age, and no differences with age in wild type mice. The number of neuroblasts and the performance in the spontaneous alternation task was reduced in aged transgenic mice. Paroxetine treatment from 9 to 18months of age reduced hippocampal amyloidosis without affecting the number of neuroblasts or granular neurons. These findings suggest that the amyloidosis affects the differentiation of neuroblasts and spatial working memory, independent of changes in total granular neurons. Furthermore, while long-term paroxetine treatment may be able to reduce hippocampal amyloidosis, it appears to have no effect on total number of granular neurons or spatial working memory. Copyright © 2017 Elsevier Inc. All rights reserved.

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)

Sevoflurane exposure during the neonatal period induces long-term memory impairment but not autism-like behaviors.

Science.gov (United States)

Chung, Woosuk; Park, Saegeun; Hong, Jiso; Park, Sangil; Lee, Soomin; Heo, Junyoung; Kim, Daesoo; Ko, Youngkwon

2015-10-01

To examine whether neonatal exposure to sevoflurane induces autism-like behaviors in mice. There are continuing reports regarding the potential negative effects of anesthesia on the developing brain. Recently, several studies suggest that neurotoxicity caused by anesthesia may lead to neurodevelopmental impairments. However, unlike reports focusing on learning and memory, there are only a few animal studies focusing on neurodevelopmental disorders after general anesthesia. Therefore, we have focused on autism, a representative neurodevelopmental disorder. Neonatal mice (P6-7) were exposed to a titrated dose of sevoflurane for 6 h. Apoptosis was evaluated by assessing the expression level of cleaved (activated) caspase-3. Autism-like behaviors, general activity, anxiety level, and long-term memory were evaluated with multiple behavioral assays. Western blotting confirmed that neonatal exposure to sevoflurane increased the expression level of activated caspase-3, indicative of apoptosis. Mice exposed to sevoflurane also showed impaired long-term memory in fear tests. However, sevoflurane-exposed mice did not exhibit autism-like features in all of the following assays: social interaction (three-chamber test, caged social interaction), social communication (ultrasonic vocalization test), or repetitive behavior (self-grooming test, digging). There were also no differences in general activity (open field test, home cage activity) and anxiety (open field test, light-dark box) after sevoflurane exposure. Our results confirm previous studies that neonatal sevoflurane exposure causes neurodegeneration and long-term memory impairment in mice. However, sevoflurane did not induce autism-like features. Our study suggests that mice are more vulnerable to long-term memory deficits than autism-like behaviors after exposure to sevoflurane. © 2015 John Wiley & Sons Ltd.

Electroconvulsive stimulation results in long-term survival of newly generated hippocampal neurons in rats

DEFF Research Database (Denmark)

Olesen, Mikkel Vestergaard; Wörtwein, Gitta; Folke, Jonas

2017-01-01

Electroconvulsive stimulation (ECS) is one of the strongest stimulators of hippocampal neurogenesis in rodents that represents a plausible mechanism for the efficacy of electroconvulsive therapy (ECT) in major depressive disorder. Using design-based stereological cell counting, we recently...... in neurogenesis facilitates the behavioral outcome of the forced swim test (FST), an animal model of depression. The results showed that ECS in conjunction with CRS stimulates hippocampal neurogenesis, and that a significant quantity of the newly formed hippocampal neurons survives up to 12 months. The new Brd......U-positive neurons showed time-dependent attrition of ∼40% from day 1 to 3 months, with no further decline between 3 and 12 months. ECS did not affect the number of pre-existing dentate granule neurons or the volume of the dentate granule cell layer, suggesting no damaging effect of the treatment. Finally, we found...

Synthesis on the long term behavior of spent nuclear fuel. Vol.1,2; Synthese sur l'evolution a long terme des colis de combustibles irradies. Tome 1,2

Energy Technology Data Exchange (ETDEWEB)

Poinssot, Ch.; Toulhoat, P.; Grouiller, J.P.; Pavageau, J.; Piron, J.P.; Pelletier, M.; Dehaudt, Ph.; Cappelaere, Ch.; Limon, R.; Desgranges, L.; Jegou, Ch.; Corbel, C.; Maillard, S.; Faure, M.H.; Cicariello, J.C.; Masson, M. [CEA Saclay, DEN/DDIN/DPRGD, 91 - Gif sur Yvette (France)

2001-07-01

The aim of this report is to present the major objectives, the key scientific issues, and the preliminary results of the research conducted in France in the framework of the third line of the 1991 Law, on the topic of the long term behavior of spent nuclear fuel in view of long term storage or geological disposal. Indeed, CEA launched in 1998 the Research Program on the Long Term Behavior of Spent Nuclear Fuel (abbreviated and referred to as PRECCI in French; Poinssot, 1998) the aim of which is to study and assess the ability of spent nuclear fuel packages to keep their initially allocated functions in interim storage and geological disposal: total containment and recovery functions for duration up to hundreds of years (long term or short-term interim storage and/or first reversible stages of geological disposal) and partial confinement function (controlled fluxes of RN) for thousands of years in geological disposal. This program has to allow to obtain relevant and reliable data concerning the long term behavior of the spent fuel packages so that feasibility of interim storage and/or geological disposal can be assessed and demonstrated as well as optimized. Within this framework, this report presents for every possible scenario of evolution (closed system, in Presence of water in presence of gases) what are estimated to be the most relevant evolution mechanism. For the most relevant scientific issues hence defined, a complete scientific review of the best state of knowledge is subsequently here given thus allowing to draw a clear guideline of the major R and D issues for the next years. (authors)

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.

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

Science.gov (United States)

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.

Long-term lithium treatment increases intracellular and extracellular brain-derived neurotrophic factor (BDNF) in cortical and hippocampal neurons at subtherapeutic concentrations.

Science.gov (United States)

De-Paula, Vanessa J; Gattaz, Wagner F; Forlenza, Orestes V

2016-12-01

The putative neuroprotective effects of lithium treatment rely on the fact that it modulates several homeostatic mechanisms involved in the neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function. Lithium is a well-established therapeutic option for the acute and long-term management of bipolar disorder and major depression. The aim of this study was to evaluate the effects of subtherapeutic and therapeutic concentrations of chronic lithium treatment on brain-derived neurotrophic factor (BDNF) synthesis and secretion. Primary cultures of cortical and hippocampal neurons were treated with different subtherapeutic (0.02 and 0.2 mM) and therapeutic (2 mM) concentrations of chronic lithium treatment in cortical and hippocampal cell culture. Lithium treatment increased the intracellular protein expression of cortical neurons (10% at 0.02 mM) and hippocampal neurons (28% and 14% at 0.02 mM and 0.2 mM, respectively). Extracellular BDNF of cortical neurons increased 30% and 428% at 0.02 and 0.2 mM, respectively and in hippocampal neurons increased 44% at 0.02 mM. The present study indicates that chronic, low-dose lithium treatment up-regulates BDNF production in primary neuronal cell culture. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mode-locking behavior of Izhikevich neurons under periodic external forcing

Science.gov (United States)

Farokhniaee, AmirAli; Large, Edward W.

2017-06-01

Many neurons in the auditory system of the brain must encode periodic signals. These neurons under periodic stimulation display rich dynamical states including mode locking and chaotic responses. Periodic stimuli such as sinusoidal waves and amplitude modulated sounds can lead to various forms of n :m mode-locked states, in which a neuron fires n action potentials per m cycles of the stimulus. Here, we study mode-locking in the Izhikevich neurons, a reduced model of the Hodgkin-Huxley neurons. The Izhikevich model is much simpler in terms of the dimension of the coupled nonlinear differential equations compared with other existing models, but excellent for generating the complex spiking patterns observed in real neurons. We obtained the regions of existence of the various mode-locked states on the frequency-amplitude plane, called Arnold tongues, for the Izhikevich neurons. Arnold tongue analysis provides useful insight into the organization of mode-locking behavior of neurons under periodic forcing. We find these tongues for both class-1 and class-2 excitable neurons in both deterministic and noisy regimes.

Versatile Networks of Simulated Spiking Neurons Displaying Winner-Take-All Behavior

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Yanqing eChen

2013-03-01

Full Text Available We describe simulations of large-scale networks of excitatory and inhibitory spiking neurons that can generate dynamically stable winner-take-all (WTA behavior. The network connectivity is a variant of center-surround architecture that we call center-annular-surround (CAS. In this architecture each neuron is excited by nearby neighbors and inhibited by more distant neighbors in an annular-surround region. The neural units of these networks simulate conductance-based spiking neurons that interact via mechanisms susceptible to both short-term synaptic plasticity and STDP. We show that such CAS networks display robust WTA behavior unlike the center-surround networks and other control architectures that we have studied. We find that a large-scale network of spiking neurons with separate populations of excitatory and inhibitory neurons can give rise to smooth maps of sensory input. In addition, we show that a humanoid Brain-Based-Device (BBD under the control of a spiking WTA neural network can learn to reach to target positions in its visual field, thus demonstrating the acquisition of sensorimotor coordination.

Versatile networks of simulated spiking neurons displaying winner-take-all behavior.

Science.gov (United States)

Chen, Yanqing; McKinstry, Jeffrey L; Edelman, Gerald M

2013-01-01

We describe simulations of large-scale networks of excitatory and inhibitory spiking neurons that can generate dynamically stable winner-take-all (WTA) behavior. The network connectivity is a variant of center-surround architecture that we call center-annular-surround (CAS). In this architecture each neuron is excited by nearby neighbors and inhibited by more distant neighbors in an annular-surround region. The neural units of these networks simulate conductance-based spiking neurons that interact via mechanisms susceptible to both short-term synaptic plasticity and STDP. We show that such CAS networks display robust WTA behavior unlike the center-surround networks and other control architectures that we have studied. We find that a large-scale network of spiking neurons with separate populations of excitatory and inhibitory neurons can give rise to smooth maps of sensory input. In addition, we show that a humanoid brain-based-device (BBD) under the control of a spiking WTA neural network can learn to reach to target positions in its visual field, thus demonstrating the acquisition of sensorimotor coordination.

Neural Rhythms of Change: Long-Term Improvement after Successful Treatment in Children with Disruptive Behavior Problems

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Steven Woltering

2015-01-01

Full Text Available Neural changes were investigated for children with disruptive behavior problems one year after a treatment program ended. Thirty-nine children and their parents visited the research lab before, after, and a year after treatment ended. During those lab visits, electroencephalography (EEG was recorded during a challenging Go/No-go task. Treatment consisted of intensive 14-week combined cognitive behavioral therapy and parent management training sessions. For the analysis, participants were divided into long-term improvers (IMPs and long-term nonimprovers (NIMPs based on changes in their externalizing problem scores. The results showed early no-go theta power (4–8 Hz, 100–250 ms decreased for long-term IMPs compared to NIMPs. When participants were divided based on changes in their comorbid internalizing symptoms, effects were stronger and reductions in theta power were found for early as well as later phases (250–650 ms. We provided preliminary evidence that theta power is a useful neural measure to trace behavioral change linked to improved self-regulation even up to a year after treatment ended. Results may have implications for the characterization of children with disruptive behavior problems and may lead to the development of novel markers of treatment success.

Establishment of a long-term spiral ganglion neuron culture with reduced glial cell number: Effects of AraC on cell composition and neurons.

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Schwieger, Jana; Esser, Karl-Heinz; Lenarz, Thomas; Scheper, Verena

2016-08-01

Sensorineural deafness is mainly caused by damage to hair cells and degeneration of the spiral ganglion neurons (SGN). Cochlear implants can functionally replace lost hair cells and stimulate the SGN electrically. The benefit from cochlear implantation depends on the number and excitability of these neurons. To identify potential therapies for SGN protection, in vitro tests are carried out on spiral ganglion cells (SGC). A glial cell-reduced and neuron-enhanced culture of neonatal rat SGC under mitotic inhibition (cytarabine (AraC)) for up to seven days is presented. Serum containing and neurotrophin-enriched cultures with and without AraC-addition were analyzed after 4 and 7 days. The total number of cells was significantly reduced, while the proportion of neurons was greatly increased by AraC-treatment. Cell type-specific labeling demonstrated that nearly all fibroblasts and most of the glial cells were removed. Neither the neuronal survival, nor the neurite outgrowth or soma diameter were negatively affected. Additionally neurites remain partly free of surrounding non-neuronal cells. Recent culture conditions allow only for short-term cultivation of neonatal SGC and lack information on the influence of non-neuronal cells on SGN and of direct contact of neurites with test-materials. AraC-addition reduces the number of non-neuronal cells and increases the ratio of SGN in culture, without negative impact on neuronal viability. This treatment allows longer-term cultivation of SGC and provides deeper insight into SGN-glial cell interaction and the attachment of neurites on test-material surfaces. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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

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Tomoko Inagaki

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

Long-Term Mechanical Behavior of Yucca Mountain Tuff and its Variability, Final Technical Report for Task ORD-FY04-021

International Nuclear Information System (INIS)

Daemen, Jaak J.K.; Ma, Lumin; Zhao, Guohua

2006-01-01

The study of the long term mechanical behavior of Yucca Mountain tuffs is important for several reasons. Long term stability of excavations will affect accessibility (e.g. for inspection purposes), and retrievability. Long term instabilities may induce loading of drip shields and/or emplaced waste, thus affecting drip shield and/or waste package corrosion. Failure of excavations will affect airflow, may affect water flow, and may affect temperature distributions. The long term mechanical behavior of rocks remains an elusive topic, loaded with uncertainties. A variety of approaches have been used to improve the understanding of this complex subject, but it is doubtful that it has reached a stage where firm predictions can be considered feasible. The long term mechanical behavior of ''soft'' rocks, especially evaporites, and in particular rock salt, has been the subject of numerous investigations (e.g. Cristescu and Hunsche, 1998, Cristescu et al, 2002), and basic approaches towards engineering taking into account the long term behavior of such materials have long been well established (e.g. Dreyer, 1972, 1982). The same is certainly not true of ''hard'' rocks. While it long has been recognized that the long term strength of ''hard'' rocks almost certainly is significantly less than that measured during ''short'', i.e. standard (ASTM D 2938), ISRM suggested (Bieniawski et al, 1978) and conventionally used test procedures (e.g. Bieniawski, 1970, Wawersik, 1972, Hoek and Brown, 1980, p. 150), what limited approaches have been taken to develop strategies toward determining the long term mechanical behavior of ''hard'' rock remain in the early research and investigation stage, at best. One early model developed specifically for time dependent analysis of underground ''hard'' rock structures is the phenomenological model by Kaiser and Morgenstern (1981). Brady and Brown (1985, p. 93) state that over a wide range of strain rates, from 10 -8 to 10 2 /s the difference in

Long-Term Potentiation in the Motor Cortex

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

1989-09-01

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

Long-term Behavior of Hydrocarbon Production Curves

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Lovell, A.; Karra, S.; O'Malley, D.; Viswanathan, H. S.; Srinivasan, G.

2017-12-01

Recovering hydrocarbons (such as natural gas) from naturally-occurring formations with low permeability has had a huge impact on the energy sector, however, recovery rates are low due to poor understanding of recovery and transport mechanisms [1]. The physical mechanisms that control the production of hydrocarbon are only partially understood. Calculations have shown that the short-term behavior in the peak of the production curve is understood to come from the free hydrocarbons in the fracture networks, but the long-term behavior of these curves is often underpredicted [2]. This behavior is thought to be due to small scale processes - such as matrix diffusion, desorption, and connectivity in the damage region around the large fracture network. In this work, we explore some of these small-scale processes using discrete fracture networks (DFN) and the toolkit dfnWorks [3], the matrix diffusion, size of the damage region, and distribution of free gas between the fracture networks and rock matrix. Individual and combined parameter spaces are explored, and comparisons of the resulting production curves are made to experimental site data from the Haynesville formation [4]. We find that matrix diffusion significantly controls the shape of the tail of the production curve, while the distribution of free gas impacts the relative magnitude of the peak to the tail. The height of the damage region has no effect on the shape of the tail. Understanding the constrains of the parameter space based on site data is the first step in rigorously quantifying the uncertainties coming from these types of systems, which can in turn optimize and improve hydrocarbon recovery. [1] C. McGlade, et. al., (2013) Methods of estimating shale gas resources - comparison, evaluation, and implications, Energy, 59, 116-125 [2] S. Karra, et. al., (2015) Effect of advective flow in fractures and matrix diffusion on natural gas production, Water Resources Research, 51(10), 8646-8657 [3] J.D. Hyman, et

Temporal-pattern recognition by single neurons in a sensory pathway devoted to social communication behavior.

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Carlson, Bruce A

2009-07-29

Sensory systems often encode stimulus information into the temporal pattern of action potential activity. However, little is known about how the information contained within these patterns is extracted by postsynaptic neurons. Similar to temporal coding by sensory neurons, social information in mormyrid fish is encoded into the temporal patterning of an electric organ discharge. In the current study, sensitivity to temporal patterns of electrosensory stimuli was found to arise within the midbrain posterior exterolateral nucleus (ELp). Whole-cell patch recordings from ELp neurons in vivo revealed three patterns of interpulse interval (IPI) tuning: low-pass neurons tuned to long intervals, high-pass neurons tuned to short intervals, and bandpass neurons tuned to intermediate intervals. Many neurons within each class also responded preferentially to either increasing or decreasing IPIs. Playback of electric signaling patterns recorded from freely behaving fish revealed that the IPI and direction tuning of ELp neurons resulted in selective responses to particular social communication displays characterized by distinct IPI patterns. The postsynaptic potential responses of many neurons indicated a combination of excitatory and inhibitory synaptic input, and the IPI tuning of ELp neurons was directly related to rate-dependent changes in the direction and amplitude of postsynaptic potentials. These results suggest that differences in the dynamics of short-term synaptic plasticity in excitatory and inhibitory pathways may tune central sensory neurons to particular temporal patterns of presynaptic activity. This may represent a general mechanism for the processing of behaviorally relevant stimulus information encoded into temporal patterns of activity by sensory neurons.

Nerve growth factor (NGF) immunoreactive neurons in the juvenile rat hippocampus: response to acute and long-term high-light open-field (HL-OF) or forced swim (FS) stress stimulation.

Science.gov (United States)

Badowska-Szalewska, E; Spodnik, E; Ludkiewicz, B; Klejbor, I; Moryś, J

2011-12-29

This study aimed at examining and comparing the influence of two different stress stimuli on the density (number of cells/mm²) of nerve growth factor (NGF) containing neurons in the hippocampal CA1 and CA3 pyramidal cell layers and the dentate gyrus (DG) granule cell layer in juvenile rats (P28; P-postnatal day). The high-light open-field (HL-OF) test and forced swim (FS) test were employed to investigate the effects of a single, 15-min acute exposure and repeated (15 min daily for 21 days) long-term exposure to stress. In order to detect NGF-ir neurons, immunohistochemical (-ir) techniques were used. In comparison with nonstressed animals, acute and long-term HL-OF or FS stimulation resulted in a marked increase (P<0.001) in the density of NGF-ir containing cells in all the hippocampal structures. The frequency of stress application (acute vs. long-term), however, did not have a substantial impact on the studied parameter, with the exception of the CA3 sector, where a decreased density (P<0.001) of NGF-ir neurons was observed after long-term exposure to FS. It may be concluded that a rise in the density of NGF-ir neurons in the juvenile rat hippocampus after exposure to HL-OF or FS stressors could have affected the activity of the hypothalamic-pituitary-adrenocortical (HPA) stress axis. Prolonged HL-OF or FS stress was probably aggravating enough not to trigger the habituation process. The type of stressor applied (HL-OF vs. FS) was not essentially a factor determining the density of NGF-ir cells in the hippocampus. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

A VLSI recurrent network of integrate-and-fire neurons connected by plastic synapses with long-term memory.

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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.

An expectancy-value theory approach to the long-term modification of smoking behavior.

Science.gov (United States)

Rogers, R W; Deckner, C W; Mewborn, C R

1978-04-01

Despite the research interest in modifying smoking behavior, therapeutic treatments that can produce long-term cessation have not been demonstrated rigorously. A follow-up study of two attitude change experiments (N = 173) examined the effects of a fear appeal, that is, increasing smokers' awareness and appreciation of the highly noxious consequences of smoking. Although this familiar type of information may be an integral component of many smoking treatment programs, its long-term suppressive effect has not been demonstrated in well-controlled experiments. The results disclosed that 3 months and also 1 year after treatment, a high-fear manipulation had increased significantly the percentage of smokers who were able to stop smoking completely.

Microscopic study of rock for estimating long-term behavior

International Nuclear Information System (INIS)

Ichikawa, Yasuaki

1997-03-01

One must consider micro-structures of rock and rock mass in order to predict the long-term behavior for more than ten thousand years. First we observe the micro-crack distribution of granite which is commonly distributed in Japan, and is widely used for several structures. The creep under constant load and the relaxation under constant displacement are typical time dependent phenomena, and we performed a series of relaxation tests under microscope observation in laboratory. The specimen that is preserved in water is granite as mentioned above. The aim of this experiment is to observe the sequential propagation of micro-cracks and its affect to the macroscopic response of the rock material under relaxation state. Next, a viscoelastic homogenization method is applied for analyzing the behavior of granite that is composed of several kinds of minerals (i.e., a polycrystalline material). The homogenization method developed for analyzing mechanics of composite materials is a mathematical theory that can describe the macroscopic behavior accounting for the microscopic characteristics with periodic microstructures. In this study, it is applied to a polycrystalline rock which involves a few minerals and micro-cracks. Furthermore, it is required to apply the homogenization analysis for rock materials which show a nonlinear time dependent behavior, so we develop a new elasto-visco-plastic homogenization theory, and its validity is checked for some ground structures made by clay. (author)

Long-Term Bending Creep Behavior of Thin-Walled CFRP Tendon Pretensioned Spun Concrete Poles

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Giovanni P. Terrasi

2014-07-01

Full Text Available This paper discusses the long-term behavior of a series of highly-loaded, spun concrete pole specimens prestressed with carbon fiber-reinforced polymer (CFRP tendons, which were subjected to outdoor four-point bending creep tests since 1996 in the frame of collaboration with the Swiss precast concrete producer, SACAC (Società Anonima Cementi Armati Centrifugati. The 2 m span cylindrical beams studied are models for lighting poles produced for the last 10 years and sold on the European market. Five thin-walled pole specimens were investigated (diameter: 100 mm; wall-thickness: 25–27 mm. All specimens were produced in a pretensioning and spinning technique and were prestressed by pultruded CFRP tendons. Initially, two reference pole specimens were tested in quasi-static four-point bending to determine the short-term failure moment and to model the short-term flexural behavior. Then, three pole specimens were loaded to different bending creep moments: while the lowest loaded specimen was initially uncracked, the second specimen was loaded with 50% of the short-term bending failure moment and exhibited cracking immediately after load introduction. The highest loaded pole specimen sustained a bending moment of 72% of the short-term bending failure moment for 16.5 years before failing in July 2013, due to the bond failure of the tendons, which led to local crushing of the high-performance spun concrete (HPSC. Besides this, long-term monitoring of the creep tests has shown a limited time- and temperature-dependent increase of the deflections over the years, mainly due to the creep of the concrete. A concrete creep-based model allowed for the calculation of the long-term bending curvatures with reasonable accuracy. Furthermore, the pole specimens showed crack patterns that were stable over time and minimal slippage of the tendons with respect to the pole’s end-faces for the two lower load levels. The latter proves the successful and durable

Modeling long-term dynamics of electricity markets

International Nuclear Information System (INIS)

Olsina, Fernando; Garces, Francisco; Haubrich, H.-J.

2006-01-01

In the last decade, many countries have restructured their electricity industries by introducing competition in their power generation sectors. Although some restructuring has been regarded as successful, the short experience accumulated with liberalized power markets does not allow making any founded assertion about their long-term behavior. Long-term prices and long-term supply reliability are now center of interest. This concerns firms considering investments in generation capacity and regulatory authorities interested in assuring the long-term supply adequacy and the stability of power markets. In order to gain significant insight into the long-term behavior of liberalized power markets, in this paper, a simulation model based on system dynamics is proposed and the underlying mathematical formulations extensively discussed. Unlike classical market models based on the assumption that market outcomes replicate the results of a centrally made optimization, the approach presented here focuses on replicating the system structure of power markets and the logic of relationships among system components in order to derive its dynamical response. The simulations suggest that there might be serious problems to adjust early enough the generation capacity necessary to maintain stable reserve margins, and consequently, stable long-term price levels. Because of feedback loops embedded in the structure of power markets and the existence of some time lags, the long-term market development might exhibit a quite volatile behavior. By varying some exogenous inputs, a sensitivity analysis is carried out to assess the influence of these factors on the long-run market dynamics

Provision or Good Genes? Menstrual Cycle Shifts in Women's Preferences for Short-Term and Long-Term Mates' Altruistic Behavior

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Ryo Oda

2014-04-01

Full Text Available Men's altruism may have evolved, via female choice, as a signal of either their genetic quality or their willingness to allocate resources to offspring. The possibility that men display altruism to signal their genetic quality may be tested by examining women's preference for men's altruism across the stages of the menstrual cycle. Because women can maximize reproductive benefits by mating with men who have “good genes” on high-fertility versus low-fertility days, women should show a heightened preference for male altruism on high-fertility days compared to low-fertility days, and this heightened preference should be more apparent when women evaluate men for short-term sexual relationships than for long-term committed relationships. The possibility that men display altruism to signal their willingness to provision, as opposed to their genetic quality, may be tested by examining women's preference for men's altruism toward different recipients. More specifically, altruistic behavior toward family members may reflect a willingness to provide resources for kin and, hence, willingness to provision, whereas altruistic behavior toward strangers may function as an honest signal of genetic quality. In two samples of young women (TVs = 131 and 481, we found no differences between high- and low-fertility participants in preference for men's altruism, and women preferred men's altruism more in long-term than short-term relationships. The findings suggest that men's altruistic behavior functions as a signal of willingness to provide resources rather than genetic quality.

Bidirectional Long Short-Term Memory Network for Vehicle Behavior Recognition

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Jiasong Zhu

2018-06-01

Full Text Available Vehicle behavior recognition is an attractive research field which is useful for many computer vision and intelligent traffic analysis tasks. This paper presents an all-in-one behavior recognition framework for moving vehicles based on the latest deep learning techniques. Unlike traditional traffic analysis methods which rely on low-resolution videos captured by road cameras, we capture 4K ( 3840 × 2178 traffic videos at a busy road intersection of a modern megacity by flying a unmanned aerial vehicle (UAV during the rush hours. We then manually annotate locations and types of road vehicles. The proposed method consists of the following three steps: (1 vehicle detection and type recognition based on deep neural networks; (2 vehicle tracking by data association and vehicle trajectory modeling; (3 vehicle behavior recognition by nearest neighbor search and by bidirectional long short-term memory network, respectively. This paper also presents experimental results of the proposed framework in comparison with state-of-the-art approaches on the 4K testing traffic video, which demonstrated the effectiveness and superiority of the proposed method.

Nonverbal behavior observation : collaborative gaming method for prediction of conflicts during long-term missions

NARCIS (Netherlands)

Voynarovskaya, N.; Gorbunov, R.D.; Barakova, E.I.; Ahn, R.M.C.; Rauterberg, G.W.M.; Yang, H.S.; et al., xx

2010-01-01

This paper presents a method for monitoring mental state of small isolated crews during long-term missions (such as space mission, polar expeditions, submarine crews, meteorological stations, and etc). It combines the records of negotiation game with monitoring of the nonverbal behavior of the

Long-Term Dynamics of Autonomous Fractional Differential Equations

Science.gov (United States)

Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

Near-Term Actions to Address Long-Term Climate Risk

Science.gov (United States)

Lempert, R. J.

2014-12-01

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

Long-term performance and behavior of sows fed high levels of non-starch polysaccharides

NARCIS (Netherlands)

Peet-Schwering, van der C.M.C.

2004-01-01

The main objective of this thesis was to investigate the long-term effects of feeding sows high levels of dietary fermentable non-starch polysaccharides CNSP) (i.e., NSP from sugar beet pulp) restrictedly or ad libitum during gestation or ad libitum during lactation on behavior, reproductive

Requirement for nuclear calcium signaling in Drosophila long-term memory.

Science.gov (United States)

Weislogel, Jan-Marek; Bengtson, C Peter; Müller, Michaela K; Hörtzsch, Jan N; Bujard, Martina; Schuster, Christoph M; Bading, Hilmar

2013-05-07

Calcium is used throughout evolution as an intracellular signal transducer. In the mammalian central nervous system, calcium mediates the dialogue between the synapse and the nucleus that is required for transcription-dependent persistent neuronal adaptations. A role for nuclear calcium signaling in similar processes in the invertebrate brain has yet to be investigated. Here, we show by in vivo calcium imaging of adult brain neurons of the fruit fly Drosophila melanogaster, that electrical foot shocks used in olfactory avoidance conditioning evoked transient increases in cytosolic and nuclear calcium concentrations in neurons. These calcium signals were detected in Kenyon cells of the flies' mushroom bodies, which are sites of learning and memory related to smell. Acute blockade of nuclear calcium signaling during conditioning selectively and reversibly abolished the formation of long-term olfactory avoidance memory, whereas short-term, middle-term, or anesthesia-resistant olfactory memory remained unaffected. Thus, nuclear calcium signaling is required in flies for the progression of memories from labile to transcription-dependent long-lasting forms. These results identify nuclear calcium as an evolutionarily conserved signal needed in both invertebrate and vertebrate brains for transcription-dependent memory consolidation.

Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice

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Mark A. Smith

2015-04-01

Full Text Available Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC and agouti-related protein (AgRP neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons.

Long-Term Sensitization Training Primes "Aplysia" for Further Learning

Science.gov (United States)

Cleary, Leonard J.; Byrne, John H.; Antzoulatos, Evangelos G.; Wainwright, Marcy L.

2006-01-01

Repetitive, unilateral stimulation of "Aplysia" induces long-term sensitization (LTS) of ipsilaterally elicited siphon-withdrawal responses. Whereas some morphological effects of training appear only on ipsilateral sensory neurons, others appear bilaterally. We tested the possibility that contralateral morphological modifications may have…

Monosynaptic connections made by the sensory neurons of the gill- and siphon-withdrawal reflex in Aplysia participate in the storage of long-term memory for sensitization

OpenAIRE

Frost, William N.; Castellucci, Vincent F.; Hawkins, Robert D.; Kandel, Eric R.

1985-01-01

We have found that in the gill- and siphon- withdrawal reflex of Aplysia, the memory for short-term sensitization grades smoothly into long-term memory with increased amounts of sensitization training. One cellular locus for the storage of the memory underlying short-term sensitization is the set of monosynaptic connections between the siphon sensory cells and the gill and siphon motor neurons. We have now also found that these same monosynaptic connections participate in the storage of the m...

Accumulation and long term behavior of radiocesium in tropical plants

Energy Technology Data Exchange (ETDEWEB)

Anjos, R.M.; Carvalho, C.; Mosquera, B.; Macario, K.; Veiga, R.; Sanches, N.; Bastos, J.; Saavedra, R.; Iguatemy, M. [Universidade Federal Fluminense, Niteroi (Brazil)

2006-07-01

Full text of publication follows: In recent years, there has been a growing interest in the evaluation of nutrient fluxes and radioactive contaminants in forest and agricultural ecosystems. Several studies on forest ecosystems have been carried out, mostly in Europe, after the Chernobyl accident. Japanese forest sites and native plant species of the Marshall Islands have also been extensively investigated. These studies have been used for various purposes, including the development of models for predicting plant concentrations from soil concentration measurements or the long term of dietary contamination by radiocesium following a fallout nuclear. Cesium is an alkali metal just like potassium and its behavior in nature, as well as in the human body, is similar to that of potassium. Uptake of 137 Cs from contaminated soil represents a significant pathway of human radiation exposure, either due to the direct consumption of cereals, fruits and vegetables or, indirectly, following consumption of milk and meat from animals fed on contaminated vegetable matter. The decline of 137 Cs levels as function of time of fruit trees is of interest given its long life in the field. Therefore, the cesium behavior is important in the design of management strategies to mitigate any negative health effects of radioactivity on the environment. It is also important to apply the current knowledge of the transport and distribution of salts derived from forest ecosystems in agricultural ecosystems, especially for tropical fruit trees. So far, in the South hemisphere there have been only a few studies on this subject, without conclusive results. With this aim, the Laboratory of Radioecology (L.A.R.A.) of the Universidade Federal Fluminense has been performing analyzes of 137 Cs and 40 K concentrations in several tropical plants (guava, mango, avocado, pomegranate, papaya, manioc and chili pepper trees) in order to determine the accumulation of these radionuclides throughout these trees and

Accumulation and long term behavior of radiocesium in tropical plants

International Nuclear Information System (INIS)

Anjos, R.M.; Carvalho, C.; Mosquera, B.; Macario, K.; Veiga, R.; Sanches, N.; Bastos, J.; Saavedra, R.; Iguatemy, M.

2006-01-01

Full text of publication follows: In recent years, there has been a growing interest in the evaluation of nutrient fluxes and radioactive contaminants in forest and agricultural ecosystems. Several studies on forest ecosystems have been carried out, mostly in Europe, after the Chernobyl accident. Japanese forest sites and native plant species of the Marshall Islands have also been extensively investigated. These studies have been used for various purposes, including the development of models for predicting plant concentrations from soil concentration measurements or the long term of dietary contamination by radiocesium following a fallout nuclear. Cesium is an alkali metal just like potassium and its behavior in nature, as well as in the human body, is similar to that of potassium. Uptake of 137 Cs from contaminated soil represents a significant pathway of human radiation exposure, either due to the direct consumption of cereals, fruits and vegetables or, indirectly, following consumption of milk and meat from animals fed on contaminated vegetable matter. The decline of 137 Cs levels as function of time of fruit trees is of interest given its long life in the field. Therefore, the cesium behavior is important in the design of management strategies to mitigate any negative health effects of radioactivity on the environment. It is also important to apply the current knowledge of the transport and distribution of salts derived from forest ecosystems in agricultural ecosystems, especially for tropical fruit trees. So far, in the South hemisphere there have been only a few studies on this subject, without conclusive results. With this aim, the Laboratory of Radioecology (L.A.R.A.) of the 'Universidade Federal Fluminense' has been performing analyzes of 137 Cs and 40 K concentrations in several tropical plants (guava, mango, avocado, pomegranate, papaya, manioc and chili pepper trees) in order to determine the accumulation of these radionuclides throughout these trees

Huntingtin is critical both pre- and postsynaptically for long-term learning-related synaptic plasticity in Aplysia.

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.

SAD kinases sculpt axonal arbors of sensory neurons through long and short-term responses to neurotrophin signals

Science.gov (United States)

Lilley, Brendan N.; Pan, Y. Albert; Sanes, Joshua R.

2013-01-01

SUMMARY Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex, but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short duration signals from extrinsic cues to sculpt axon arbors within the CNS. PMID:23790753

Synaptic Mechanisms of Induction and Maintenance of Long-Term Sensitization Memory in Aplysia

OpenAIRE

Glanzman, DL

2013-01-01

The marine snail Aplysia californica exhibits a simple defensive withdrawal reflex that can undergo several forms of learning. In particular, the reflex can exhibit long-term sensitization (LTS), a form of nonassociative memory. LTS is mediated by long-term facilitation (LTF) of the monosynaptic connection between the sensory and motor neurons that mediate the withdrawal reflex. LTS and LTF represent one of the best understood model systems of long-term memory extent. Furthermore, discoveries...

Presynaptic learning and memory with a persistent firing neuron and a habituating synapse: a model of short term persistent habituation.

Science.gov (United States)

Ramanathan, Kiruthika; Ning, Ning; Dhanasekar, Dhiviya; Li, Guoqi; Shi, Luping; Vadakkepat, Prahlad

2012-08-01

Our paper explores the interaction of persistent firing axonal and presynaptic processes in the generation of short term memory for habituation. We first propose a model of a sensory neuron whose axon is able to switch between passive conduction and persistent firing states, thereby triggering short term retention to the stimulus. Then we propose a model of a habituating synapse and explore all nine of the behavioral characteristics of short term habituation in a two neuron circuit. We couple the persistent firing neuron to the habituation synapse and investigate the behavior of short term retention of habituating response. Simulations show that, depending on the amount of synaptic resources, persistent firing either results in continued habituation or maintains the response, both leading to longer recovery times. The effectiveness of the model as an element in a bio-inspired memory system is discussed.

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors

Directory of Open Access Journals (Sweden)

Anne Teissier

2015-12-01

Full Text Available Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood. Using a pharmacogenetic approach, we find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim test, whereas inhibition has no effect on the same measures. In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphé and increased median raphé serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition. Furthermore, we identify opposing consequences of dorsal versus median raphé serotonergic neuron inhibition on floating behavior, together suggesting that median raphé hyperactivity increases anxiety, whereas a low dorsal/median raphé serotonergic activity ratio increases depression-like behavior. Thus, we find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphé function.

Npas4: Linking Neuronal Activity to Memory.

Science.gov (United States)

Sun, Xiaochen; Lin, Yingxi

2016-04-01

Immediate-early genes (IEGs) are rapidly activated after sensory and behavioral experience and are believed to be crucial for converting experience into long-term memory. Neuronal PAS domain protein 4 (Npas4), a recently discovered IEG, has several characteristics that make it likely to be a particularly important molecular link between neuronal activity and memory: it is among the most rapidly induced IEGs, is expressed only in neurons, and is selectively induced by neuronal activity. By orchestrating distinct activity-dependent gene programs in different neuronal populations, Npas4 affects synaptic connections in excitatory and inhibitory neurons, neural circuit plasticity, and memory formation. It may also be involved in circuit homeostasis through negative feedback and psychiatric disorders. We summarize these findings and discuss their implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory.

Science.gov (United States)

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.

Sustainable Change Sequence: a framework for developing behavior change interventions for patients with long-term conditions

OpenAIRE

Elwyn, Glyn; Marrin, Katy; Frosch, Dominick; White, James

2014-01-01

Objective\\ud \\ud Interactive interventions are increasingly advocated to support behavior change for patients who have long-term conditions. Such interventions are most likely to achieve behavior change when they are based on appropriate theoretical frameworks. Developers of interventions are faced with a diverse set of behavioral theories that do not specifically address intervention development. The aim of our work was to develop a framework to guide the developers of interactive healthcare...

The use of natural and archaeological analogues for understanding the long-term behavior of nuclear glasses; L'utilisation des analogues naturels et archeologiques pour la comprehension de l'evolution a long terme des verres nucleaires

Energy Technology Data Exchange (ETDEWEB)

Libourel, G.; Verney-Carron, A.; Morlok, A. [CNRS UPR2300, centre de recherches petrographiques et geochimiques (CRPG), Nancy-universite, 15, rue Notre-Dame-des-Pauvres, BP 20, 54501 Vandoeuvre-les-Nancy (France); Libourel, G. [INPL, Ecole nationale superieure de geologie (ENSG), Nancy-universite, rue du Doyen-Marcel-Roubault, BP 20, 54501 Vandoeuvre-les-Nancy (France); Gin, St. [CEA Marcoule, DEN/SECM/LCLT, 30 (France); Sterpenich, J. [G2R, CNRS-UMR 7566, Nancy-universite, BP 70239, 54506 Vandoeuvre-les-Nancy cedex (France); Michelin, A.; Neff, D.; Dillmann, Ph. [Laboratoire archeomateriaux et prevision de l' alteration LAPA/SIS2 M, CEA and CNRS, Bat 637, CEA Saclay, 91191 Gif/Yvette cedex (France); Michelin, A.; Dillmann, Ph. [LMC IRAMAT UMR5060 CNRS (France)

2011-02-15

The knowledge of the long-term behavior of nuclear waste in anticipation of ultimate disposal in a deep geological formation is of prime importance in a waste management strategy. If phenomenological models have been developed to predict the long-term behavior of these materials, validating these models remains a challenge, when considering the time scale of radioactive decay of radionuclides of environmental concern, typically 10{sup 4}-10{sup 5} yrs. Here we show how natural or archaeological analogues provide critical constraints not only on the phenomenology of glass alteration and the mechanisms involved, but also on the ability of experimental short-term data to predict long-term alteration in complex environments. (authors)

Long-Term Orientation in Trade

NARCIS (Netherlands)

Hofstede, G.J.; Jonker, C.M.; Verwaart, D.

2008-01-01

Trust does not work in the same way across cultures. This paper presents an agent model of behavior in trade across Hofstedes cultural dimension of long-term vs. short-term orientation. The situation is based on a gaming simulation, the Trust and Tracing game. The paper investigates the

Synchronous behavior of two coupled electronic neurons

International Nuclear Information System (INIS)

Pinto, R. D.; Varona, P.; Volkovskii, A. R.; Szuecs, A.; Abarbanel, Henry D. I.; Rabinovich, M. I.

2000-01-01

We report on experimental studies of synchronization phenomena in a pair of analog electronic neurons (ENs). The ENs were designed to reproduce the observed membrane voltage oscillations of isolated biological neurons from the stomatogastric ganglion of the California spiny lobster Panulirus interruptus. The ENs are simple analog circuits which integrate four-dimensional differential equations representing fast and slow subcellular mechanisms that produce the characteristic regular/chaotic spiking-bursting behavior of these cells. In this paper we study their dynamical behavior as we couple them in the same configurations as we have done for their counterpart biological neurons. The interconnections we use for these neural oscillators are both direct electrical connections and excitatory and inhibitory chemical connections: each realized by analog circuitry and suggested by biological examples. We provide here quantitative evidence that the ENs and the biological neurons behave similarly when coupled in the same manner. They each display well defined bifurcations in their mutual synchronization and regularization. We report briefly on an experiment on coupled biological neurons and four-dimensional ENs, which provides further ground for testing the validity of our numerical and electronic models of individual neural behavior. Our experiments as a whole present interesting new examples of regularization and synchronization in coupled nonlinear oscillators. (c) 2000 The American Physical Society

Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury

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.

Long-term behavior of nuclear glass: the r(t) operational model

International Nuclear Information System (INIS)

Ribet, I.; Gin, S.; Minet, Y.; Vernaz, E.; Chaix, P.; Do Quang, R.

2001-01-01

Predicting the long-term behavior of vitrified waste packages requires the development of models incorporating knowledge of the aqueous alteration mechanisms of nuclear glass. The r(t) model allows for the formation of a protective gel layer during leaching, and is thus able to account for the major drops in the glass alteration rate that are observed experimentally. This article describes the model hypotheses, the methodology implemented to determine its three internal parameters, and the results obtained from about fifty leaching experiments performed under various conditions. The orders of magnitude of the internal parameter values are indicated according to the alteration conditions. (author)

Short-term and long-term effects of violent media on aggression in children and adults.

Science.gov (United States)

Bushman, Brad J; Huesmann, L Rowell

2006-04-01

To test whether the results of the accumulated studies on media violence and aggressive behavior are consistent with the theories that have evolved to explain the effects. We tested for the existence of both short-term and long-term effects for aggressive behavior. We also tested the theory-driven hypothesis that short-term effects should be greater for adults and long-term effects should be greater for children. Meta-analysis. Children younger than 18 years and adults. Violent media, including TV, movies, video games, music, and comic books. Measures of aggressive behavior, aggressive thoughts, angry feelings, physiological arousal (eg, heart rate, blood pressure), and helping behavior. Effect size estimates were combined using meta-analytic procedures. As expected, the short-term effects of violent media were greater for adults than for children whereas the long-term effects were greater for children than for adults. The results also showed that there were overall modest but significant effect sizes for exposure to media violence on aggressive behaviors, aggressive thoughts, angry feelings, arousal levels, and helping behavior. The results are consistent with the theory that short-term effects are mostly due to the priming of existing well-encoded scripts, schemas, or beliefs, which adults have had more time to encode. In contrast, long-term effects require the learning (encoding) of scripts, schemas, or beliefs. Children can encode new scripts, schemas, and beliefs via observational learning with less interference and effort than adults.

Cell-Specific PKM Isoforms Contribute to the Maintenance of Different Forms of Persistent Long-Term Synaptic Plasticity.

Science.gov (United States)

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

Behavioral plasticity through the modulation of switch neurons.

Science.gov (United States)

Vassiliades, Vassilis; Christodoulou, Chris

2016-02-01

A central question in artificial intelligence is how to design agents capable of switching between different behaviors in response to environmental changes. Taking inspiration from neuroscience, we address this problem by utilizing artificial neural networks (NNs) as agent controllers, and mechanisms such as neuromodulation and synaptic gating. The novel aspect of this work is the introduction of a type of artificial neuron we call "switch neuron". A switch neuron regulates the flow of information in NNs by selectively gating all but one of its incoming synaptic connections, effectively allowing only one signal to propagate forward. The allowed connection is determined by the switch neuron's level of modulatory activation which is affected by modulatory signals, such as signals that encode some information about the reward received by the agent. An important aspect of the switch neuron is that it can be used in appropriate "switch modules" in order to modulate other switch neurons. As we show, the introduction of the switch modules enables the creation of sequences of gating events. This is achieved through the design of a modulatory pathway capable of exploring in a principled manner all permutations of the connections arriving on the switch neurons. We test the model by presenting appropriate architectures in nonstationary binary association problems and T-maze tasks. The results show that for all tasks, the switch neuron architectures generate optimal adaptive behaviors, providing evidence that the switch neuron model could be a valuable tool in simulations where behavioral plasticity is required. Copyright © 2015 Elsevier Ltd. All rights reserved.

Long Term Effectiveness of Cognitive Behavioral Group Therapy for Treatment of Major Depressive Disorder: A Systematic Review

Directory of Open Access Journals (Sweden)

Ceren Gokdag

2016-03-01

Full Text Available The aim of the study was to conduct systematic review the articles on long term effectiveness of cognitive-behavioral group therapy for treatment of major depressive disorder. Articles in English and Turkish published between the years of 2000 and 2015 (January were searched in national and international databases. The articles that did not include follow-up studies were excluded. Although the main aim of this study is to evaluate permanent effect of the cognitive behavioral group therapy, 21 articles that met the criteria were examined also in terms of some other variables such as research method, therapy characteristics and post test results. The findings of the articles revealed that cognitive-behavioral group therapy is effective for major depressive disorder and post therapy gains are maintained for a long time. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(Supplement 1: 23-38

Selection of Hidden Layer Neurons and Best Training Method for FFNN in Application of Long Term Load Forecasting

Science.gov (United States)

Singh, Navneet K.; Singh, Asheesh K.; Tripathy, Manoj

2012-05-01

For power industries electricity load forecast plays an important role for real-time control, security, optimal unit commitment, economic scheduling, maintenance, energy management, and plant structure planning etc. A new technique for long term load forecasting (LTLF) using optimized feed forward artificial neural network (FFNN) architecture is presented in this paper, which selects optimal number of neurons in the hidden layer as well as the best training method for the case study. The prediction performance of proposed technique is evaluated using mean absolute percentage error (MAPE) of Thailand private electricity consumption and forecasted data. The results obtained are compared with the results of classical auto-regressive (AR) and moving average (MA) methods. It is, in general, observed that the proposed method is prediction wise more accurate.

Erythropoietin enhances hippocampal long-term potentiation and memory

Directory of Open Access Journals (Sweden)

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.

SAD kinases sculpt axonal arbors of sensory neurons through long- and short-term responses to neurotrophin signals.

Science.gov (United States)

Lilley, Brendan N; Pan, Y Albert; Sanes, Joshua R

2013-07-10

Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A, and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here, we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short-duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short-duration signals from extrinsic cues to sculpt axon arbors within the CNS. Copyright © 2013 Elsevier Inc. All rights reserved.

Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice.

Science.gov (United States)

Smith, Mark A; Katsouri, Loukia; Irvine, Elaine E; Hankir, Mohammed K; Pedroni, Silvia M A; Voshol, Peter J; Gordon, Matthew W; Choudhury, Agharul I; Woods, Angela; Vidal-Puig, Antonio; Carling, David; Withers, Dominic J

2015-04-21

Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors.

Science.gov (United States)

Teissier, Anne; Chemiakine, Alexei; Inbar, Benjamin; Bagchi, Sneha; Ray, Russell S; Palmiter, Richard D; Dymecki, Susan M; Moore, Holly; Ansorge, Mark S

2015-12-01

Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood. Using a pharmacogenetic approach, we find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim test, whereas inhibition has no effect on the same measures. In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphé and increased median raphé serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition. Furthermore, we identify opposing consequences of dorsal versus median raphé serotonergic neuron inhibition on floating behavior, together suggesting that median raphé hyperactivity increases anxiety, whereas a low dorsal/median raphé serotonergic activity ratio increases depression-like behavior. Thus, we find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphé function. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Communication Behaviors as Predictors of Long-Term Dyadic Adjustment: Personality as a Moderator

OpenAIRE

Ariane Lazaridès; Claude Bélanger; Stéphane Sabourin

2010-01-01

In this longitudinal study, we examined the moderating role of personality in the relationship between communication behaviors and long-term dyadic adjustment. A sample of 82 couples completed the NEO Five-Factor Inventory and the Dyadic Adjustment Scale. These couples were also videotaped during a 15-minute problem-solving discussion. Approximately 2.5 years later, these couples completed again the Dyadic Adjustment Scale. Results show that personality of both men and women moderates the rel...

Long-term relationships between cholinergic tone, synchronous bursting and synaptic remodeling.

Directory of Open Access Journals (Sweden)

Maya Kaufman

Full Text Available Cholinergic neuromodulation plays key roles in the regulation of neuronal excitability, network activity, arousal, and behavior. On longer time scales, cholinergic systems play essential roles in cortical development, maturation, and plasticity. Presumably, these processes are associated with substantial synaptic remodeling, yet to date, long-term relationships between cholinergic tone and synaptic remodeling remain largely unknown. Here we used automated microscopy combined with multielectrode array recordings to study long-term relationships between cholinergic tone, excitatory synapse remodeling, and network activity characteristics in networks of cortical neurons grown on multielectrode array substrates. Experimental elevations of cholinergic tone led to the abrupt suppression of episodic synchronous bursting activity (but not of general activity, followed by a gradual growth of excitatory synapses over hours. Subsequent blockage of cholinergic receptors led to an immediate restoration of synchronous bursting and the gradual reversal of synaptic growth. Neither synaptic growth nor downsizing was governed by multiplicative scaling rules. Instead, these occurred in a subset of synapses, irrespective of initial synaptic size. Synaptic growth seemed to depend on intrinsic network activity, but not on the degree to which bursting was suppressed. Intriguingly, sustained elevations of cholinergic tone were associated with a gradual recovery of synchronous bursting but not with a reversal of synaptic growth. These findings show that cholinergic tone can strongly affect synaptic remodeling and synchronous bursting activity, but do not support a strict coupling between the two. Finally, the reemergence of synchronous bursting in the presence of elevated cholinergic tone indicates that the capacity of cholinergic neuromodulation to indefinitely suppress synchronous bursting might be inherently limited.

Long-term Relationships between Cholinergic Tone, Synchronous Bursting and Synaptic Remodeling

Science.gov (United States)

Kaufman, Maya; Corner, Michael A.; Ziv, Noam E.

2012-01-01

Cholinergic neuromodulation plays key roles in the regulation of neuronal excitability, network activity, arousal, and behavior. On longer time scales, cholinergic systems play essential roles in cortical development, maturation, and plasticity. Presumably, these processes are associated with substantial synaptic remodeling, yet to date, long-term relationships between cholinergic tone and synaptic remodeling remain largely unknown. Here we used automated microscopy combined with multielectrode array recordings to study long-term relationships between cholinergic tone, excitatory synapse remodeling, and network activity characteristics in networks of cortical neurons grown on multielectrode array substrates. Experimental elevations of cholinergic tone led to the abrupt suppression of episodic synchronous bursting activity (but not of general activity), followed by a gradual growth of excitatory synapses over hours. Subsequent blockage of cholinergic receptors led to an immediate restoration of synchronous bursting and the gradual reversal of synaptic growth. Neither synaptic growth nor downsizing was governed by multiplicative scaling rules. Instead, these occurred in a subset of synapses, irrespective of initial synaptic size. Synaptic growth seemed to depend on intrinsic network activity, but not on the degree to which bursting was suppressed. Intriguingly, sustained elevations of cholinergic tone were associated with a gradual recovery of synchronous bursting but not with a reversal of synaptic growth. These findings show that cholinergic tone can strongly affect synaptic remodeling and synchronous bursting activity, but do not support a strict coupling between the two. Finally, the reemergence of synchronous bursting in the presence of elevated cholinergic tone indicates that the capacity of cholinergic neuromodulation to indefinitely suppress synchronous bursting might be inherently limited. PMID:22911726

Long-term relationships between cholinergic tone, synchronous bursting and synaptic remodeling.

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Kaufman, Maya; Corner, Michael A; Ziv, Noam E

2012-01-01

Cholinergic neuromodulation plays key roles in the regulation of neuronal excitability, network activity, arousal, and behavior. On longer time scales, cholinergic systems play essential roles in cortical development, maturation, and plasticity. Presumably, these processes are associated with substantial synaptic remodeling, yet to date, long-term relationships between cholinergic tone and synaptic remodeling remain largely unknown. Here we used automated microscopy combined with multielectrode array recordings to study long-term relationships between cholinergic tone, excitatory synapse remodeling, and network activity characteristics in networks of cortical neurons grown on multielectrode array substrates. Experimental elevations of cholinergic tone led to the abrupt suppression of episodic synchronous bursting activity (but not of general activity), followed by a gradual growth of excitatory synapses over hours. Subsequent blockage of cholinergic receptors led to an immediate restoration of synchronous bursting and the gradual reversal of synaptic growth. Neither synaptic growth nor downsizing was governed by multiplicative scaling rules. Instead, these occurred in a subset of synapses, irrespective of initial synaptic size. Synaptic growth seemed to depend on intrinsic network activity, but not on the degree to which bursting was suppressed. Intriguingly, sustained elevations of cholinergic tone were associated with a gradual recovery of synchronous bursting but not with a reversal of synaptic growth. These findings show that cholinergic tone can strongly affect synaptic remodeling and synchronous bursting activity, but do not support a strict coupling between the two. Finally, the reemergence of synchronous bursting in the presence of elevated cholinergic tone indicates that the capacity of cholinergic neuromodulation to indefinitely suppress synchronous bursting might be inherently limited.

Chronic dietary chlorpyrifos causes long-term spatial memory impairment and thigmotaxic behavior.

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López-Granero, Caridad; Ruiz-Muñoz, Ana M; Nieto-Escámez, Francisco A; Colomina, María T; Aschner, Michael; Sánchez-Santed, Fernando

2016-03-01

Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity. In addition, we assessed the chronic effects of CPF on glutamatergic and gamma-aminobutyric acid (GABAergic) function using pharmacological challenges with dizocilpine (MK801) and diazepam. Impaired performance related to altered search patterns, including thigmotaxis and long-term spatial memory was noted in the MWM in animals exposed to CPF, pointing to dietary CPF-induced behavioral disturbances, such as anxiety. Twenty-four hours after the 31st session of repeated acquisition task, 0.1mg/kg MK801, an N-methyl-d-aspartate (NMDA) antagonist was intraperitoneally (i.p.) injected for 4 consecutive days. Decreased latencies in the MWM in the control group were noted after two sessions with MK801 treatment. Once the MWM assessment was completed, animals were administered 0.1 or 0.2mg/kg of MK801 and 1 or 3mg/kg of diazepam i.p., and tested for locomotor activity. Both groups, the CPF dietary and control, displayed analogous performance in motor activity. In conclusion, our data point to a connection between the long-term spatial memory, thigmotaxic response and CPF long after the exposure ended. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-Term Cognitive and Behavioral Outcomes following Resolution of Sleep Disordered Breathing in Preschool Children.

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Sarah N Biggs

Full Text Available This study aimed to determine the long term effects of resolution of SDB in preschool children, either following treatment or spontaneous recovery, on cognition and behavior. Children diagnosed with SDB at 3-5y (N = 35 and non-snoring controls (N = 25, underwent repeat polysomnography (PSG and cognitive and behavioral assessment 3 years following a baseline study. At follow-up, children with SDB were grouped into Resolved and Unresolved. Resolution was defined as: obstructive apnea hypopnea index (OAHI ≤1 event/h; no snoring detected on PSG; and no parental report of habitual snoring. 57% (20/35 of children with SDB received treatment, with SDB resolving in 60% (12/20. 43% (15/35 were untreated, of whom 40% (6/15 had spontaneous resolution of SDB. Cognitive reduced between baseline and follow-up, however this was not related to persistent disease, with no difference in cognitive outcomes between Resolved, Unresolved or Control groups. Behavioral functioning remained significantly worse in children originally diagnosed with SDB compared to control children, regardless of resolution. Change in OAHI did not predict cognitive or behavioral outcomes, however a reduction in nocturnal arousals, irrespective of full resolution, was associated with improvement in attention and aggressive behavior. These results suggest that resolution of SDB in preschool children has little effect on cognitive or behavioral outcomes over the long term. The association between sleep fragmentation and behavior appears independent of SDB, however may be moderated by concomitant SDB. This challenges the assumption that treatment of SDB will ameliorate associated cognitive and behavioural deficits and supports the possibility of a SDB phenotype.

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats.

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Spiga, Saturnino; Talani, Giuseppe; Mulas, Giovanna; Licheri, Valentina; Fois, Giulia R; Muggironi, Giulia; Masala, Nicola; Cannizzaro, Carla; Biggio, Giovanni; Sanna, Enrico; Diana, Marco

2014-09-02

Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence.

Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory.

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Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi; Tanaka, Teruyuki

2018-01-01

Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the

Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory.

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Kosuke Okuda

Full Text Available Mutations in the Cyclin-dependent kinase-like 5 (CDKL5 gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be

Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory

Science.gov (United States)

Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi

2018-01-01

Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the

Long-Term Retardation of Uranium in the KURT Environment

International Nuclear Information System (INIS)

Baik, Min Hoon; Shin, Joo Do; Park, Tae Jin

2016-01-01

One of possibilities resolving this issue is to study the migration and retardation processes of radionuclides in the subsurface environments by using naturally occurring radionuclides as analogues of radioactive waste. To date, however, the long-term behavior of radionuclides in a granitic groundwater system is not yet fully understood. The ubiquitous presence of uranium (U) in rocks makes it an ideal natural analogue for studying the behaviors of radionuclides in a deep geological repository for the final disposal of HLW. In this study, long-term retardation behavior of natural uranium was investigated using granite rock samples taken from the KURT (KAERI Underground Research Tunnel), located in Daejeon city. The distribution of uranium and its binding mechanism in granite samples were investigated using the sequential chemical extraction (SCE) technique combined with X-ray diffraction (XRD) and ICP-MS methods. In this study, the long-term retardation of uranium in the KURT environment was investigated using SCE and EPMA techniques combined with ICP-MS and XRD. Results showed that long-term interaction of rock with groundwater can change U species and mineralize dissolved U, which can consequently contribute to the retardation of U in the fractured granitic rock environment. This study will help us to understand the long-term behavior of radionuclides migrating through the fractured granite rock and then enhance the reliability of the safety assessment for a HLW repository

Protein Phosphatase 1-Dependent Transcriptional Programs for Long-Term Memory and Plasticity

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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…

Long-term aging behaviors in a model soft colloidal system.

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Li, Qi; Peng, Xiaoguang; McKenna, Gregory B

2017-02-15

Colloidal and molecular systems share similar behaviors near to the glass transition volume fraction or temperature. Here, aging behaviors after volume fraction up-jump (induced by performing temperature down-jumps) conditions for a PS-PNIPAM/AA soft colloidal system were investigated using light scattering (diffusing wave spectroscopy, DWS). Both aging responses and equilibrium dynamics were investigated. For the aging responses, long-term experiments (100 000 s) were performed, and both equilibrium and non-equilibrium behaviors of the system were obtained. In the equilibrium state, as effective volume fraction increases (or temperature decreases), the colloidal dispersion displays a transition from the liquid to a glassy state. The equilibrium α-relaxation dynamics strongly depend on both the effective volume fraction and the initial mass concentration for the studied colloidal systems. Compared with prior results from our lab [X. Di, X. Peng and G. B. McKenna, J. Chem. Phys., 2014, 140, 054903], the effective volume fractions investigated spanned a wider range, to deeper into the glassy domain. The results show that the α-relaxation time τ α of the samples aged into equilibrium deviate from the classical Vogel-Fulcher-Tammann (VFT)-type expectations and the super-Arrhenius signature disappears above the glass transition volume fraction. The non-equilibrium aging response shows that the time for the structural evolution into equilibrium and the α-relaxation time are decoupled. The DWS investigation of the aging behavior after different volume fraction jumps reveals a different non-equilibrium or aging behavior for the considered colloidal systems compared with either molecular glasses or the macroscopic rheology of a similar colloidal dispersions.

The effects of long-term dopaminergic treatment on locomotor behavior in rats.

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Oliveira de Almeida, Welinton Alessandro; Maculano Esteves, Andrea; Leite de Almeida-Júnior, Canuto; Lee, Kil Sun; Kannebley Frank, Miriam; Oliveira Mariano, Melise; Frussa-Filho, Roberto; Tufik, Sergio; Tulio de Mello, Marco

2014-12-01

Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Augmentation consists of an exacerbation of restless legs syndrome (a sleep-related movement disorder) symptoms during treatment compared to those experienced during the period before therapy was initiated. The objective of this study was to examine locomotor activity in rats after long-term dopaminergic treatment and its relationship with expression of the D2 receptor, in addition to demonstrating possible evidence of augmentation. The rats were divided into control (CTRL) and drug (Pramipexole-PPX) groups that received daily saline vehicle and PPX treatments, respectively, for 71 days. The locomotor behavior of the animals was evaluated weekly in the Open Field test for 71 days. The expression of the dopamine D2 receptor was evaluated by Western Blot analysis. The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days. No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist. This study suggests changes in locomotor activity in rats after long-term PPX treatment that include an immediate reduction of locomotion and an increase in immobilization, and after 64 days, these values returned to baseline levels without evidence of augmentation. In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions.

The effects of long-term dopaminergic treatment on locomotor behavior in rats

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Oliveira de Almeida, Welinton Alessandro; Maculano Esteves, Andrea; Leite de Almeida-Júnior, Canuto; Lee, Kil Sun; Kannebley Frank, Miriam; Oliveira Mariano, Melise; Frussa-Filho, Roberto; Tufik, Sergio; Tulio de Mello, Marco

2014-01-01

Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Augmentation consists of an exacerbation of restless legs syndrome (a sleep-related movement disorder) symptoms during treatment compared to those experienced during the period before therapy was initiated. The objective of this study was to examine locomotor activity in rats after long-term dopaminergic treatment and its relationship with expression of the D2 receptor, in addition to demonstrating possible evidence of augmentation. The rats were divided into control (CTRL) and drug (Pramipexole—PPX) groups that received daily saline vehicle and PPX treatments, respectively, for 71 days. The locomotor behavior of the animals was evaluated weekly in the Open Field test for 71 days. The expression of the dopamine D2 receptor was evaluated by Western Blot analysis. The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days. No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist. This study suggests changes in locomotor activity in rats after long-term PPX treatment that include an immediate reduction of locomotion and an increase in immobilization, and after 64 days, these values returned to baseline levels without evidence of augmentation. In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions. PMID:26483930

The effects of long-term dopaminergic treatment on locomotor behavior in rats

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Welinton Alessandro Oliveira de Almeida

2014-12-01

Full Text Available Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Augmentation consists of an exacerbation of restless legs syndrome (a sleep-related movement disorder symptoms during treatment compared to those experienced during the period before therapy was initiated. The objective of this study was to examine locomotor activity in rats after long-term dopaminergic treatment and its relationship with expression of the D2 receptor, in addition to demonstrating possible evidence of augmentation. The rats were divided into control (CTRL and drug (Pramipexole—PPX groups that received daily saline vehicle and PPX treatments, respectively, for 71 days. The locomotor behavior of the animals was evaluated weekly in the Open Field test for 71 days. The expression of the dopamine D2 receptor was evaluated by Western Blot analysis. The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days. No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist. This study suggests changes in locomotor activity in rats after long-term PPX treatment that include an immediate reduction of locomotion and an increase in immobilization, and after 64 days, these values returned to baseline levels without evidence of augmentation. In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions.

Long-Term Outcomes of Cognitive-Behavioral Therapy for Adolescent Body Dysmorphic Disorder.

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Krebs, Georgina; de la Cruz, Lorena Fernández; Monzani, Benedetta; Bowyer, Laura; Anson, Martin; Cadman, Jacinda; Heyman, Isobel; Turner, Cynthia; Veale, David; Mataix-Cols, David

2017-07-01

Emerging evidence suggests that cognitive-behavioral therapy (CBT) is an efficacious treatment for adolescent body dysmorphic disorder (BDD) in the short term, but longer-term outcomes remain unknown. The current study aimed to follow up a group of adolescents who had originally participated in a randomized controlled trial of CBT for BDD to determine whether treatment gains were maintained. Twenty-six adolescents (mean age = 16.2, SD = 1.6) with a primary diagnosis of BDD received a course of developmentally tailored CBT and were followed up over 12 months. Participants were assessed at baseline, midtreatment, posttreatment, 2-, 6-, and 12-month follow-up. The primary outcome measure was the clinician-rated Yale-Brown Obsessive-Compulsive Scale Modified for BDD. Secondary outcomes included measures of insight, depression, quality of life, and global functioning. BDD symptoms decreased significantly from pre- to posttreatment and remained stable over the 12-month follow-up. At this time point, 50% of participants were classified as responders and 23% as remitters. Participants remained significantly improved on all secondary outcomes at 12-month follow-up. Neither baseline insight nor baseline depression predicted long-term outcomes. The positive effects of CBT appear to be durable up to 12-month follow-up. However, the majority of patients remained symptomatic and vulnerable to a range of risks at 12-month follow-up, indicating that longer-term monitoring is advisable in this population. Future research should focus on enhancing the efficacy of CBT in order to improve long-term outcomes. Copyright © 2017. Published by Elsevier Ltd.

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

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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.

Long-term corrosion behaviors of Hastelloy-N and Hastelloy-B3 in moisture-containing molten FLiNaK salt environments

International Nuclear Information System (INIS)

Ouyang, Fan-Yi; Chang, Chi-Hung; Kai, Ji-Jung

2014-01-01

Highlights: •Corrosion behaviors of Hastelloy-N and -B3 in molten FLiNaK salt at 700 °C. •The alleviated corrosion rate of alloys was observed after long-hour immersion. •Long-term corrosion rate was limited by diffusion from matrix to alloy surface. •Corrosion pattern transferred from intergranular corrosion into general corrosion. •Presence of minor H 2 O did not greatly influence the long-term corrosion behavior. -- Abstract: This study investigated long-term corrosion behaviors of Ni-based Hastelloy-N and Hastelloy-B3 under moisture-containing molten alkali fluoride salt (LiF–NaF–KF: 46.5–11.5–42%) environment at an ambient temperature of 700 °C. The Hastelloy-N and Hastelloy-B3 experienced similar weight losses for tested duration of 100–1000 h, which was caused by aggregate dissolution of Cr and Mo into FLiNaK salts. The corrosion rate of both alloys was high initially, but then reduced during the course of the test. The alleviated corrosion rate was due to the depletion of Cr and Mo near surface of the alloys and thus the long-term corrosion rate was controlled by diffusion of Cr and Mo outward to the alloy surface. The results of microstructural characterization revealed that the corrosion pattern for both alloys tended to be intergranular corrosion at early stage of corrosion test, and then transferred to general corrosion for longer immersion hours

Effect of nerve injury on the number of dorsal root ganglion neurons and autotomy behavior in adult Bax-deficient mice

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Lyu C

2017-08-01

Full Text Available Chuang Lyu,1,2 Gong-Wei Lyu,3 Aurora Martinez,4 Tie-Jun Sten Shi4 1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of China; 2Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; 3Department of Neurology, 1st Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Biomedicine, University of Bergen, Bergen, Norway Background: The proapoptotic molecule BAX, plays an important role in mitochondrial apoptotic pathway. Dorsal root ganglion (DRG neurons depend on neurotrophic factors for survival at early developmental stages. Withdrawal of neurotrophic factors will induce apoptosis in DRG neurons, but this type of cell death can be delayed or prevented in neonatal Bax knockout (KO mice. In adult animals, evidence also shows that DRG neurons are less dependent upon neurotrophic factors for survival. However, little is known about the effect of Bax deletion on the survival of normal and denervated DRG neurons in adult mice. Methods: A unilateral sciatic nerve transection was performed in adult Bax KO mice and wild-type (WT littermates. Stereological method was employed to quantify the number of lumbar-5 DRG neurons 1 month post-surgery. Nerve injury-induced autotomy behavior was also examined on days 1, 3, and 7 post-surgery. Results: There were significantly more neurons in contralateral DRGs of KO mice as compared with WT mice. The number of neurons was reduced in ipsilateral DRGs in both KO and WT mice. No changes in size distributions of DRG neuron profiles were detected before or after nerve injury. Injury-induced autotomy behavior developed much earlier and was more serious in KO mice. Conclusion: Although postnatal death or loss of DRG neurons is partially prevented by Bax deletion, this effect cannot interfere with long-term nerve injury-induced neuronal loss. The exaggerated self

Behavioral tagging is a general mechanism of long-term memory formation.

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Ballarini, Fabricio; Moncada, Diego; Martinez, Maria Cecilia; Alen, Nadia; Viola, Haydée

2009-08-25

In daily life, memories are intertwined events. Little is known about the mechanisms involved in their interactions. Using two hippocampus-dependent (spatial object recognition and contextual fear conditioning) and one hippocampus-independent (conditioned taste aversion) learning tasks, we show that in rats subjected to weak training protocols that induce solely short term memory (STM), long term memory (LTM) is promoted and formed only if training sessions took place in contingence with a novel, but not familiar, experience occurring during a critical time window around training. This process requires newly synthesized proteins induced by novelty and reveals a general mechanism of LTM formation that begins with the setting of a "learning tag" established by a weak training. These findings represent the first comprehensive set of evidences indicating the existence of a behavioral tagging process that in analogy to the synaptic tagging and capture process, need the creation of a transient, protein synthesis-independent, and input specific tag.

Involvement of insulin-like peptide in long-term synaptic plasticity and long-term memory of the pond snail Lymnaea stagnalis.

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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.

Long-term dependence in exchange rates

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A. Karytinos

2000-01-01

Full Text Available The extent to which exchange rates of four major currencies against the Greek Drachma exhibit long-term dependence is investigated using a R/S analysis testing framework. We show that both classic R/S analysis and the modified R/S statistic if enhanced by bootstrapping techniques can be proven very reliable tools to this end. Our findings support persistence and long-term dependence with non-periodic cycles for the Deutsche Mark and the French Franc series. In addition a noisy chaos explanation is favored over fractional Brownian motion. On the contrary, the US Dollar and British Pound were found to exhibit a much more random behavior and lack of any long-term structure.

MicroRNA-128 governs neuronal excitability and motor behavior in mice

DEFF Research Database (Denmark)

Tan, Chan Lek; Plotkin, Joshua L.; Venø, Morten Trillingsgaard

2013-01-01

The control of motor behavior in animals and humans requires constant adaptation of neuronal networks to signals of various types and strengths. We found that microRNA-128 (miR-128), which is expressed in adult neurons, regulates motor behavior by modulating neuronal signaling networks and excita...

The Sleeper Effect of Intimate Partner Violence Exposure: Long-Term Consequences on Young Children's Aggressive Behavior

Science.gov (United States)

Holmes, Megan R.

2013-01-01

Background: Children who have been exposed to intimate partner violence (IPV) experience a wide variety of short-term social adjustment and emotional difficulties, including externalizing behavioral problems such as aggression. While children are affected by IPV at all ages, little is known about the long-term consequences of IPV exposure at…

Long-term subregion-specific encoding of enhanced ethanol intake by D1DR medium spiny neurons of the nucleus accumbens.

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Renteria, Rafael; Buske, Tavanna R; Morrisett, Richard A

2018-03-01

The nucleus accumbens (NAc) is a critical component of the mesocorticolimbic system and is involved in mediating the motivational and reinforcing aspects of ethanol consumption. Chronic intermittent ethanol (CIE) exposure is a reliable model to induce ethanol dependence and increase volitional ethanol consumption in mice. Following a CIE-induced escalation of ethanol consumption, NMDAR (N-methyl-D-aspartate receptor)-dependent long-term depression in D1 dopamine receptor expressing medium spiny neurons of the NAc shell was markedly altered with no changes in plasticity in D1 dopamine receptor medium spiny neurons from the NAc core. This disruption of plasticity persisted for up to 2 weeks after cessation of ethanol access. To determine if changes in AMPA receptor (AMPAR) composition contribute to this ethanol-induced neuroadaptation, we monitored the rectification of AMPAR excitatory postsynaptic currents (EPSCs). We observed a marked decrease in the rectification index in the NAc shell, suggesting the presence of GluA2-lacking AMPARs. There was no change in the amplitude of spontaneous EPSCs (sEPSCs), but there was a transient increase in sEPSC frequency in the NAc shell. Using the paired pulse ratio, we detected a similar transient increase in the probability of neurotransmitter release. With no change in sEPSC amplitude, the change in the rectification index suggests that GluA2-containing AMPARs are removed and replaced with GluA2-lacking AMPARs in the NAc shell. This CIE-induced alteration in AMPAR subunit composition may contribute to the loss of NMDAR-dependent long-term depression in the NAc shell and therefore may constitute a critical neuroadaptive response underlying the escalation of ethanol intake in the CIE model. © 2017 Society for the Study of Addiction.

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

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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.

Synaptic remodeling, synaptic growth and the storage of long-term memory in Aplysia.

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Bailey, Craig H; Kandel, Eric R

2008-01-01

Synaptic remodeling and synaptic growth accompany various forms of long-term memory. Storage of the long-term memory for sensitization of the gill-withdrawal reflex in Aplysia has been extensively studied in this respect and is associated with the growth of new synapses by the sensory neurons onto their postsynaptic target neurons. Recent time-lapse imaging studies of living sensory-to-motor neuron synapses in culture have monitored both functional and structural changes simultaneously so as to follow remodeling and growth at the same specific synaptic connections continuously over time and to examine the functional contribution of these learning-related structural changes to the different time-dependent phases of memory storage. Insights provided by these studies suggest the synaptic differentiation and growth induced by learning in the mature nervous system are highly dynamic and often rapid processes that can recruit both molecules and mechanisms used for de novo synapse formation during development.

Qualitative and quantitative estimation of comprehensive synaptic connectivity in short- and long-term cultured rat hippocampal neurons with new analytical methods inspired by Scatchard and Hill plots

Energy Technology Data Exchange (ETDEWEB)

Tanamoto, Ryo; Shindo, Yutaka; Niwano, Mariko [Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University (Japan); Matsumoto, Yoshinori [Department of Applied Physics and Physico-Informatics, Faculty of Science and Technology, Keio University (Japan); Miki, Norihisa [Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522 (Japan); Hotta, Kohji [Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University (Japan); Oka, Kotaro, E-mail: oka@bio.keio.ac.jp [Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University (Japan)

2016-03-18

To investigate comprehensive synaptic connectivity, we examined Ca{sup 2+} responses with quantitative electric current stimulation by indium-tin-oxide (ITO) glass electrode with transparent and high electro-conductivity. The number of neurons with Ca{sup 2+} responses was low during the application of stepwise increase of electric current in short-term cultured neurons (less than 17 days in-vitro (DIV)). The neurons cultured over 17 DIV showed two-type responses: S-shaped (sigmoid) and monotonous saturated responses, and Scatchard plots well illustrated the difference of these two responses. Furthermore, sigmoid like neural network responses over 17 DIV were altered to the monotonous saturated ones by the application of the mixture of AP5 and CNQX, specific blockers of NMDA and AMPA receptors, respectively. This alternation was also characterized by the change of Hill coefficients. These findings indicate that the neural network with sigmoid-like responses has strong synergetic or cooperative synaptic connectivity via excitatory glutamate synapses. - Highlights: • We succeed to evaluate the maturation of neural network by Scathard and Hill Plots. • Long-term cultured neurons showed two-type responses: sigmoid and monotonous. • The sigmoid-like increase indicates the cooperatevity of neural networks. • Excitatory glutamate synapses cause the cooperatevity of neural networks.

A causal link between prediction errors, dopamine neurons and learning.

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Steinberg, Elizabeth E; Keiflin, Ronald; Boivin, Josiah R; Witten, Ilana B; Deisseroth, Karl; Janak, Patricia H

2013-07-01

Situations in which rewards are unexpectedly obtained or withheld represent opportunities for new learning. Often, this learning includes identifying cues that predict reward availability. Unexpected rewards strongly activate midbrain dopamine neurons. This phasic signal is proposed to support learning about antecedent cues by signaling discrepancies between actual and expected outcomes, termed a reward prediction error. However, it is unknown whether dopamine neuron prediction error signaling and cue-reward learning are causally linked. To test this hypothesis, we manipulated dopamine neuron activity in rats in two behavioral procedures, associative blocking and extinction, that illustrate the essential function of prediction errors in learning. We observed that optogenetic activation of dopamine neurons concurrent with reward delivery, mimicking a prediction error, was sufficient to cause long-lasting increases in cue-elicited reward-seeking behavior. Our findings establish a causal role for temporally precise dopamine neuron signaling in cue-reward learning, bridging a critical gap between experimental evidence and influential theoretical frameworks.

Neurons That Underlie Drosophila melanogaster Reproductive Behaviors: Detection of a Large Male-Bias in Gene Expression in fruitless-Expressing Neurons

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Nicole R. Newell

2016-08-01

Full Text Available Male and female reproductive behaviors in Drosophila melanogaster are vastly different, but neurons that express sex-specifically spliced fruitless transcripts (fru P1 underlie these behaviors in both sexes. How this set of neurons can generate such different behaviors between the two sexes is an unresolved question. A particular challenge is that fru P1-expressing neurons comprise only 2–5% of the adult nervous system, and so studies of adult head tissue or whole brain may not reveal crucial differences. Translating Ribosome Affinity Purification (TRAP identifies the actively translated pool of mRNAs from fru P1-expressing neurons, allowing a sensitive, cell-type-specific assay. We find four times more male-biased than female-biased genes in TRAP mRNAs from fru P1-expressing neurons. This suggests a potential mechanism to generate dimorphism in behavior. The male-biased genes may direct male behaviors by establishing cell fate in a similar context of gene expression observed in females. These results suggest a possible global mechanism for how distinct behaviors can arise from a shared set of neurons.

Observation of long term potentiation in papain-based memory devices

KAUST Repository

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

2014-01-01

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

Observation of long term potentiation in papain-based memory devices

KAUST Repository

Bag, A.

2014-06-01

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

Changes in the female arcuate nucleus morphology and neurochemistry after chronic ethanol consumption and long-term withdrawal.

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Rebouças, Elce C C; Leal, Sandra; Silva, Susana M; Sá, Susana I

2016-11-01

Ethanol is a macronutrient whose intake is a form of ingestive behavior, sharing physiological mechanisms with food intake. Chronic ethanol consumption is detrimental to the brain, inducing gender-dependent neuronal damage. The hypothalamic arcuate nucleus (ARN) is a modulator of food intake that expresses feeding-regulatory neuropeptides, such as alpha melanocyte-stimulating hormone (α-MSH) and neuropeptide Y (NPY). Despite its involvement in pathways associated with eating disorders and ethanol abuse, the impact of ethanol consumption and withdrawal in the ARN structure and neurochemistry in females is unknown. We used female rat models of 20% ethanol consumption for six months and of subsequent ethanol withdrawal for two months. Food intake and body weights were measured. ARN morphology was stereologically analyzed to estimate its volume, total number of neurons and total number of neurons expressing NPY, α-MSH, tyrosine hydroxylase (TH) and estrogen receptor alpha (ERα). Ethanol decreased energy intake and body weights. However, it did not change the ARN morphology or the expression of NPY, α-MSH and TH, while increasing ERα expression. Withdrawal induced a significant volume and neuron loss that was accompanied by an increase in NPY expression without affecting α-MSH and TH expression. These findings indicate that the female ARN is more vulnerable to withdrawal than to excess alcohol. The data also support the hypothesis that the same pathways that regulate the expression of NPY and α-MSH in long-term ethanol intake may regulate food intake. The present model of long-term ethanol intake and withdrawal induces new physiological conditions with adaptive responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Behavior Change Strategies for Successful Long-Term Weight Loss: Focusing on Dietary and Physical Activity Adherence, Not Weight Loss

Science.gov (United States)

Hongu, Nobuko; Kataura, Martha P.; Block, Linda M.

2011-01-01

This article helps Extension professionals guide individuals in a successful long-term weight loss program. A program should focus on behavioral changes (improving eating habits and physical activity), not just weight loss. In order to do this, Extension professionals should implement behavior change strategies that motivate individuals to…

Long-term behavior of glass-ceramic zirconolite

International Nuclear Information System (INIS)

Martin, Ch.

2003-01-01

This work is a part of the investigation of new containment matrices considered for specific conditioning of radionuclides after separation. The aim was to demonstrate the long-term aqueous corrosion resistance of the glass-ceramic zirconolite considered for the conditioning of plutonium and the minor actinides. This material is composed of crystals of zirconolite (CaZrTi 2 O 7 ) dispersed in a residual vitreous phase. It appears that glass-ceramic zirconolite presents a better kinetic behavior than the nuclear glass R 7T7. This is mainly due to a more important rate decrease that occurs more rapidly, that induces a quantity of glass altered at least 10 times as small as for R 7T7 glass. This high slowdown of the alteration rate is attributed to the formation of an alteration film that has been the subject of a specific study. We have demonstrated that the rate decrease was controlled as for the R7T7 glass by the amorphous phase of the alteration film forming a diffusion barrier for reactive species. It seems that the porosity is not the single parameter that explains the protective effect of the gel. The main differences compared with R7T7 glass are that silicon does not control the alteration of the material and that the gel is composed of two distinct phases. We have in particular identified a dense phase enriched in titanium and neodymium that probably influences deeply the kinetics. (author)

Arm injury produces long-term behavioral and neural hypersensitivity in octopus.

Science.gov (United States)

Alupay, Jean S; Hadjisolomou, Stavros P; Crook, Robyn J

2014-01-13

Cephalopod molluscs are the most neurally and behaviorally complex invertebrates, with brains rivaling those of some vertebrates in size and complexity. This has fostered the opinion that cephalopods, particularly octopuses, may experience vertebrate-like pain when injured. However, it is not known whether octopuses possess nociceptors or if their somatic sensory neurons exhibit sensitization after injury. Here we show that the octopus Abdopus aculeatus expresses nocifensive behaviors including arm autotomy, and displays marked neural hyperexcitability both in injured and uninjured arms for at least 24h after injury. These findings do not demonstrate that octopuses experience pain-like states; instead they add to the minimal existing literature on how cephalopods receive, process, and integrate noxious sensory information, potentially informing and refining regulations governing use of cephalopods in scientific research. Published by Elsevier Ireland Ltd.

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

Science.gov (United States)

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.

Long-term changes in neurocognition and behavior following treatment of sleep disordered breathing in school-aged children.

Science.gov (United States)

Biggs, Sarah N; Vlahandonis, Anna; Anderson, Vicki; Bourke, Robert; Nixon, Gillian M; Davey, Margot J; Horne, Rosemary S C

2014-01-01

Sleep disordered breathing (SDB) in children is associated with detrimental neurocognitive and behavioral consequences. The long term impact of treatment on these outcomes is unknown. This study examined the long-term effect of treatment of SDB on neurocognition, academic ability, and behavior in a cohort of school-aged children. Four-year longitudinal study. Children originally diagnosed with SDB and healthy non-snoring controls underwent repeat polysomnography and age-standardized neurocognitive and behavioral assessment 4y following initial testing. Melbourne Children's Sleep Centre, Melbourne, Australia. Children 12-16 years of age, originally assessed at 7-12 years, were categorized into Treated (N = 12), Untreated (N = 26), and Control (N = 18) groups. Adenotonsillectomy, Tonsillectomy, Nasal Steroids. Decision to treat was independent of this study. Changes in sleep and respiratory parameters over time were assessed. A decrease in obstructive apnea hypopnea index (OAHI) from Time 1 to Time 2 was seen in 63% and 100% of the Untreated and Treated groups, respectively. The predictive relationship between change in OAHI and standardized neurocognitive, academic, and behavioral scores over time was examined. Improvements in OAHI were predictive of improvements in Performance IQ, but not Verbal IQ or academic measures. Initial group differences in behavioral assessment on the Child Behavior Checklist did not change over time. Children with SDB at baseline continued to exhibit significantly poorer behavior than Controls at follow-up, irrespective of treatment. After four years, improvements in SDB are concomitant with improvements in some areas of neurocognition, but not academic ability or behavior in school-aged children.

Long-Term Impairment of Sound Processing in the Auditory Midbrain by Daily Short-Term Exposure to Moderate Noise

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Liang Cheng

2017-01-01

Full Text Available Most citizen people are exposed daily to environmental noise at moderate levels with a short duration. The aim of the present study was to determine the effects of daily short-term exposure to moderate noise on sound level processing in the auditory midbrain. Sound processing properties of auditory midbrain neurons were recorded in anesthetized mice exposed to moderate noise (80 dB SPL, 2 h/d for 6 weeks and were compared with those from age-matched controls. Neurons in exposed mice had a higher minimum threshold and maximum response intensity, a longer first spike latency, and a higher slope and narrower dynamic range for rate level function. However, these observed changes were greater in neurons with the best frequency within the noise exposure frequency range compared with those outside the frequency range. These sound processing properties also remained abnormal after a 12-week period of recovery in a quiet laboratory environment after completion of noise exposure. In conclusion, even daily short-term exposure to moderate noise can cause long-term impairment of sound level processing in a frequency-specific manner in auditory midbrain neurons.

Wave-processing of long-scale information by neuronal chains.

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José Antonio Villacorta-Atienza

Full Text Available Investigation of mechanisms of information handling in neural assemblies involved in computational and cognitive tasks is a challenging problem. Synergetic cooperation of neurons in time domain, through synchronization of firing of multiple spatially distant neurons, has been widely spread as the main paradigm. Complementary, the brain may also employ information coding and processing in spatial dimension. Then, the result of computation depends also on the spatial distribution of long-scale information. The latter bi-dimensional alternative is notably less explored in the literature. Here, we propose and theoretically illustrate a concept of spatiotemporal representation and processing of long-scale information in laminar neural structures. We argue that relevant information may be hidden in self-sustained traveling waves of neuronal activity and then their nonlinear interaction yields efficient wave-processing of spatiotemporal information. Using as a testbed a chain of FitzHugh-Nagumo neurons, we show that the wave-processing can be achieved by incorporating into the single-neuron dynamics an additional voltage-gated membrane current. This local mechanism provides a chain of such neurons with new emergent network properties. In particular, nonlinear waves as a carrier of long-scale information exhibit a variety of functionally different regimes of interaction: from complete or asymmetric annihilation to transparent crossing. Thus neuronal chains can work as computational units performing different operations over spatiotemporal information. Exploiting complexity resonance these composite units can discard stimuli of too high or too low frequencies, while selectively compress those in the natural frequency range. We also show how neuronal chains can contextually interpret raw wave information. The same stimulus can be processed differently or identically according to the context set by a periodic wave train injected at the opposite end of the

Phenomenological study on crystalline rock for evaluating of long-term behavior (Contract research)

International Nuclear Information System (INIS)

Okubo, Seisuke; Seno, Yasuhiro; Hirano, Toru; Matsui, Hiroya; Nakama, Shigeo

2008-08-01

The Japan Atomic Energy Agency (JAEA) is conducting the Mizunami Underground Research Laboratory (MIU) Project in order to develop comprehensive geological investigation and engineering techniques for deep underground applications (e.g. repository of HLW). The purpose of this study is to contribute to the evaluation of the mechanical stability of a research drift and to plan the future studies. Rock shows time-dependent behavior such as creep/relaxation. For the shaft and gallery of the geological disposal for the radioactive waste, the mechanical stability over a period of thousands of years is demanded not only during construction and operation but also after back-filling. So, to understand the time-dependent behavior of rock is very important for evaluating the long-term mechanical stability. This study is aiming to find out the mechanism of time-dependent behavior of rock such as creep by the precision test, observation and measurement, to develop the evaluating method of long-term behavior of rock mass, and to get the information for planning the study of the Phase III (Operation Phase) at the Mizunami URL. In the previous work conducted before this fiscal year 2007, we improved the testing technique and started test of Toki granite sampled from target site. Furthermore we studied the in-situ measurement method for evaluating the scatter of rock properties. This report describes the results of the works in the fiscal year 2007. In Chapter 1, we described the overview and background of this study. In Chapter 2, the result of continuing creep test of Tage tuff which was started from the fiscal year 1997 was described. Although there was some annual variability, the precious data were obtained. In Chapter 3, the control program for the generalized relaxation test was developed. The generalized relaxation test of Toki granite was conducted in order to get basically data. In Chapter 4, the extended constitutive equation of variable compliance was analytically

C. elegans positive butanone learning, short-term, and long-term associative memory assays.

Science.gov (United States)

Kauffman, Amanda; Parsons, Lance; Stein, Geneva; Wills, Airon; Kaletsky, Rachel; Murphy, Coleen

2011-03-11

The memory of experiences and learned information is critical for organisms to make choices that aid their survival. C. elegans navigates its environment through neuron-specific detection of food and chemical odors, and can associate nutritive states with chemical odors, temperature, and the pathogenicity of a food source. Here, we describe assays of C. elegans associative learning and short- and long-term associative memory. We modified an aversive olfactory learning paradigm to instead produce a positive response; the assay involves starving ~400 worms, then feeding the worms in the presence of the AWC neuron-sensed volatile chemoattractant butanone at a concentration that elicits a low chemotactic index (similar to Toroyama et al.). A standard population chemotaxis assay1 tests the worms' attraction to the odorant immediately or minutes to hours after conditioning. After conditioning, wild-type animals' chemotaxis to butanone increases ~0.6 Chemotaxis Index units, its "Learning Index". Associative learning is dependent on the presence of both food and butanone during training. Pairing food and butanone for a single conditioning period ("massed training") produces short-term associative memory that lasts ~2 hours. Multiple conditioning periods with rest periods between ("spaced training") yields long-term associative memory (long-term memory across species. Our protocol also includes image analysis methods for quick and accurate determination of chemotaxis indices. High-contrast images of animals on chemotaxis assay plates are captured and analyzed by worm counting software in MatLab. The software corrects for uneven background using a morphological tophat transformation. Otsu's method is then used to determine a threshold to separate worms from the background. Very small particles are removed automatically and larger non-worm regions (plate edges or agar punches) are removed by manual selection. The software then estimates the size of single worm by ignoring

Curcumin Prevents Acute Neuroinflammation and Long-Term Memory Impairment Induced by Systemic Lipopolysaccharide in Mice

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Vincenzo Sorrenti

2018-03-01

Full Text Available Systemic lipopolysaccharide (LPS induces an acute inflammatory response in the central nervous system (CNS (“neuroinflammation” characterized by altered functions of microglial cells, the major resident immune cells of the CNS, and an increased inflammatory profile that can result in long-term neuronal cell damage and severe behavioral and cognitive consequences. Curcumin, a natural compound, exerts CNS anti-inflammatory and neuroprotective functions mainly after chronic treatment. However, its effect after acute treatment has not been well investigated. In the present study, we provide evidence that 50 mg/kg of curcumin, orally administered for 2 consecutive days before a single intraperitoneal injection of a high dose of LPS (5 mg/kg in young adult mice prevents the CNS immune response. Curcumin, able to enter brain tissue in biologically relevant concentrations, reduced acute and transient microglia activation, pro-inflammatory mediator production, and the behavioral symptoms of sickness. In addition, short-term treatment with curcumin, administered at the time of LPS challenge, anticipated the recovery from memory impairments observed 1 month after the inflammatory stimulus, when mice had completely recovered from the acute neuroinflammation. Together, these results suggest that the preventive effect of curcumin in inhibiting the acute effects of neuroinflammation could be of value in reducing the long-term consequences of brain inflammation, including cognitive deficits such as memory dysfunction.

Long-term effect of September 11 on the political behavior of victims’ families and neighbors

Science.gov (United States)

Hersh, Eitan D.

2013-01-01

This article investigates the long-term effect of September 11, 2001 on the political behaviors of victims’ families and neighbors. Relative to comparable individuals, family members and residential neighbors of victims have become—and have stayed—significantly more active in politics in the last 12 years, and they have become more Republican on account of the terrorist attacks. The method used to demonstrate these findings leverages the random nature of the terrorist attack to estimate a causal effect and exploits new techniques to link multiple, individual-level, governmental databases to measure behavioral change without relying on surveys or aggregate analysis. PMID:24324145

Long-term effect of September 11 on the political behavior of victims' families and neighbors.

Science.gov (United States)

Hersh, Eitan D

2013-12-24

This article investigates the long-term effect of September 11, 2001 on the political behaviors of victims' families and neighbors. Relative to comparable individuals, family members and residential neighbors of victims have become--and have stayed--significantly more active in politics in the last 12 years, and they have become more Republican on account of the terrorist attacks. The method used to demonstrate these findings leverages the random nature of the terrorist attack to estimate a causal effect and exploits new techniques to link multiple, individual-level, governmental databases to measure behavioral change without relying on surveys or aggregate analysis.

ASIC1A in neurons is critical for fear-related behaviors.

Science.gov (United States)

Taugher, R J; Lu, Y; Fan, R; Ghobbeh, A; Kreple, C J; Faraci, F M; Wemmie, J A

2017-11-01

Acid-sensing ion channels (ASICs) have been implicated in fear-, addiction- and depression-related behaviors in mice. While these effects have been attributed to ASIC1A in neurons, it has been reported that ASICs may also function in nonneuronal cells. To determine if ASIC1A in neurons is indeed required, we generated neuron-specific knockout (KO) mice with floxed Asic1a alleles disrupted by Cre recombinase driven by the neuron-specific synapsin I promoter (SynAsic1a KO mice). We confirmed that Cre expression occurred in neurons, but not all neurons, and not in nonneuronal cells including astrocytes. Consequent loss of ASIC1A in some but not all neurons was verified by western blotting, immunohistochemistry and electrophysiology. We found ASIC1A was disrupted in fear circuit neurons, and SynAsic1a KO mice exhibited prominent deficits in multiple fear-related behaviors including Pavlovian fear conditioning to cue and context, predator odor-evoked freezing and freezing responses to carbon dioxide inhalation. In contrast, in the nucleus accumbens ASIC1A expression was relatively normal in SynAsic1a KO mice, and consistent with this observation, cocaine conditioned place preference (CPP) was normal. Interestingly, depression-related behavior in the forced swim test, which has been previously linked to ASIC1A in the amygdala, was also normal. Together, these data suggest neurons are an important site of ASIC1A action in fear-related behaviors, whereas other behaviors likely depend on ASIC1A in other neurons or cell types not targeted in SynAsic1a KO mice. These findings highlight the need for further work to discern the roles of ASICs in specific cell types and brain sites. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Thermal behavior of neutron shielding material, NS-4-FR, under long term storage conditions

International Nuclear Information System (INIS)

Yamada, N.; O-iwa, A.; Asano, R.; Horita, R.; Kusunoki, K.

2004-01-01

NS-4-FR, Epoxy-Resin, has been widely used as a neutron shielding material for casks. It is recognized that the resin will degrade during storage and loose weight under high temperature conditions. Most of the examinations for the resin degrading behavior were conducted with rather small bare resin specimens. However, the actual quantity of neutron shielding is quite large and is covered by the cask body. To confirm the degrading behavior of the resin under the long-term storage conditions, we performed the test on the specimen with the same cross-section as the actual design, Hitz B69. The resin test vessels were made out of stainless steel and equipped with flange

Neuronal representations of stimulus associations develop in the temporal lobe during learning.

Science.gov (United States)

Messinger, A; Squire, L R; Zola, S M; Albright, T D

2001-10-09

Visual stimuli that are frequently seen together become associated in long-term memory, such that the sight of one stimulus readily brings to mind the thought or image of the other. It has been hypothesized that acquisition of such long-term associative memories proceeds via the strengthening of connections between neurons representing the associated stimuli, such that a neuron initially responding only to one stimulus of an associated pair eventually comes to respond to both. Consistent with this hypothesis, studies have demonstrated that individual neurons in the primate inferior temporal cortex tend to exhibit similar responses to pairs of visual stimuli that have become behaviorally associated. In the present study, we investigated the role of these areas in the formation of conditional visual associations by monitoring the responses of individual neurons during the learning of new stimulus pairs. We found that many neurons in both area TE and perirhinal cortex came to elicit more similar neuronal responses to paired stimuli as learning proceeded. Moreover, these neuronal response changes were learning-dependent and proceeded with an average time course that paralleled learning. This experience-dependent plasticity of sensory representations in the cerebral cortex may underlie the learning of associations between objects.

Long-term social recognition memory is mediated by oxytocin-dependent synaptic plasticity in the medial amygdala.

Science.gov (United States)

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.

Short-Term Expectation Formation Versus Long-Term Equilibrium Conditions: The Danish Housing Market

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Andreas Hetland

2017-09-01

Full Text Available The primary contribution of this paper is to establish that the long-swings behavior observed in the market price of Danish housing since the 1970s can be understood by studying the interplay between short-term expectation formation and long-run equilibrium conditions. We introduce an asset market model for housing based on uncertainty rather than risk, which under mild assumptions allows for other forms of forecasting behavior than rational expectations. We test the theory via an I(2 cointegrated VAR model and find that the long-run equilibrium for the housing price corresponds closely to the predictions from the theoretical framework. Additionally, we corroborate previous findings that housing markets are well characterized by short-term momentum forecasting behavior. Our conclusions have wider relevance, since housing prices play a role in the wider Danish economy, and other developed economies, through wealth effects.

Long-term effects of a single exposure to stress in adult rats on behavior and hypothalamic-pituitary-adrenal responsiveness: comparison of two outbred rat strains.

Science.gov (United States)

Belda, Xavier; Márquez, Cristina; Armario, Antonio

2004-10-05

We have previously observed that a single exposure to immobilization (IMO), a severe stressor, caused long-term (days to weeks) desensitization of the response of the hypothalamic-pituitary-adrenal (HPA) axis to the homotypic stressor, with no changes in behavioral reactivity to novel environments. In contrast, other laboratories have reported that a single exposure to footshock induced a long-term sensitization of both HPA and behavioral responses to novel environments. To test whether these apparent discrepancies can be explained by the use of different stressors or different strains of rats, we studied in the present work the long-term effects of a single exposure to two different stressors (footshock or IMO) in two different strains of rats (Sprague-Dawley from Iffa-Credo and Wistar rats from Harlan). We found that both strains showed desensitization of the HPA response to the same (homotypic) stressor after a previous exposure to either shock or IMO. The long-term effects were higher after IMO than shock. No major changes in behavior in two novel environments (circular corridor, CC and elevated plus-maze, EPM) were observed after a single exposure to shock or IMO in neither strain, despite the fact that shocked rats showed a conditioned freezing response to the shock boxes. The present results demonstrate that long-term stress-induced desensitization of the HPA axis is a reliable phenomenon that can be observed with different stressors and strains. However, only behavioral changes related to shock-induced conditioned fear were found, which suggests that so far poorly characterized factors are determining the long-term behavioral consequences of a single exposure to stress.

Self-guided Change: The most common form of long-term, maintained health behavior change

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Bishop, F Michler

2018-01-01

Millions of people change risky, health-related behaviors and maintain those changes. However, they often take years to change, and their unhealthy behaviors may harm themselves and others and constitute a significant cost to society. A review—similar in nature to a scoping review—was done of the literature related to long-term health behavior change in six areas: alcohol, cocaine and heroin misuse, gambling, smoking, and overeating. Based on the limited research available, reasons for change and strategies for changing and for maintaining change were also reviewed. Fifty years of research clearly indicate that as people age, in the case of alcohol, heroin and cocaine misuse, smoking, and gambling, 80–90 percent moderate or stop their unhealthy behaviors. The one exception is overeating; only 20 percent maintain their weight loss. Most of these changes, when they occur, appear to be the result of self-guided change. More ways to accelerate self-guided, health-related behavior change need to be developed and disseminated. PMID:29375888

Molecular Correlates of Cortical Network Modulation by Long-Term Sensory Experience in the Adult Rat Barrel Cortex

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Vallès, Astrid; Granic, Ivica; De Weerd, Peter; Martens, Gerard J. M.

2014-01-01

Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment…

A Simple Account of the Behavior of Long-Term Interest Rates.

OpenAIRE

Campbell, John Y; Shiller, Robert J

1984-01-01

Recent empirical research on the term structure of interest rates has shown that the long-term interest rate is well described by a distributed lag on short-term interest rates, but does not conform to the expectations theory of the term structure. It has been suggested that the long rate "overreacts" to the short rate. This paper presents aunified taxonomy of risk premia, or deviations from the expectations theory. This enables the hypothesis of overreaction to be formally stated. It is show...

Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability

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Speca, David J.; Ogata, Genki; Mandikian, Danielle; Bishop, Hannah I.; Wiler, Steve W.; Eum, Kenneth; Wenzel, H. Jürgen; Doisy, Emily T.; Matt, Lucas; Campi, Katharine L.; Golub, Mari S.; Nerbonne, Jeanne M.; Hell, Johannes W.; Trainor, Brian C.; Sack, Jon T.; Schwartzkroin, Philip A.; Trimmer, James S.

2014-01-01

The Kv2.1 delayed rectifier potassium channel exhibits high-level expression in both principal and inhibitory neurons throughout the central nervous system, including prominent expression in hippocampal neurons. Studies of in vitro preparations suggest that Kv2.1 is a key yet conditional regulator of intrinsic neuronal excitability, mediated by changes in Kv2.1 expression, localization and function via activity-dependent regulation of Kv2.1 phosphorylation. Here we identify neurological and behavioral deficits in mutant (Kv2.1−/−) mice lacking this channel. Kv2.1−/− mice have grossly normal characteristics. No impairment in vision or motor coordination was apparent, although Kv2.1−/− mice exhibit reduced body weight. The anatomic structure and expression of related Kv channels in the brains of Kv2.1−/− mice appears unchanged. Delayed rectifier potassium current is diminished in hippocampal neurons cultured from Kv2.1−/− animals. Field recordings from hippocampal slices of Kv2.1−/− mice reveal hyperexcitability in response to the convulsant bicuculline, and epileptiform activity in response to stimulation. In Kv2.1−/− mice, long-term potentiation at the Schaffer collateral – CA1 synapse is decreased. Kv2.1−/− mice are strikingly hyperactive, and exhibit defects in spatial learning, failing to improve performance in a Morris Water Maze task. Kv2.1−/− mice are hypersensitive to the effects of the convulsants flurothyl and pilocarpine, consistent with a role for Kv2.1 as a conditional suppressor of neuronal activity. Although not prone to spontaneous seizures, Kv2.1−/− mice exhibit accelerated seizure progression. Together, these findings suggest homeostatic suppression of elevated neuronal activity by Kv2.1 plays a central role in regulating neuronal network function. PMID:24494598

Multimethod Behavioral Treatment of Long-Term Selective Mutism.

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Watson, T. Steuart; Kramer, Jack J.

1992-01-01

Conducted single-subject, experimental research to examine efficacy of treating severe, long-term selective mutism in nine-year-old male using shaping, multiple reinforcers, natural consequences, stimulus fading, and mild aversives. Implemented different treatment regimens in home and school environments. Home intervention resulted in increase in…

Short-term and long-term effects of violent media on aggression in children and adults

NARCIS (Netherlands)

Bushman, B.J.; Huesmann, L.R.

2006-01-01

Objectives: To test whether the results of the accumulated studies on media violence and aggressive behavior are consistent with the theories that have evolved to explain the effects. We tested for the existence of both short-term and long-term effects for aggressive behavior. We also tested the

Rapamycin inhibits mTOR/p70S6K activation in CA3 region of the hippocampus of the rat and impairs long term memory.

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Lana, D; Di Russo, J; Mello, T; Wenk, G L; Giovannini, M G

2017-01-01

The present study was aimed at establishing whether the mTOR pathway and its downstream effector p70S6K in CA3 pyramidal neurons are under the modulation of the cholinergic input to trigger the formation of long term memories, similar to what we demonstrated in CA1 hippocampus. We performed in vivo behavioral experiments using the step down inhibitory avoidance test in adult Wistar rats to evaluate memory formation under different conditions. We examined the effects of rapamycin, an inhibitor of mTORC1 formation, scopolamine, a muscarinic receptor antagonist or mecamylamine, a nicotinic receptor antagonist, on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition was conducted 30min after i.c.v. injection of rapamycin. Recall testing was performed 1h, 4h or 24h after acquisition. We found that (1) mTOR and p70S6K activation in CA3 pyramidal neurons were involved in long term memory formation; (2) rapamycin significantly inhibited mTOR and of p70S6K activation at 4h, and long term memory impairment 24h after acquisition; (3) scopolamine impaired short but not long term memory, with an early increase of mTOR/p70S6K activation at 1h followed by stabilization at longer times; (4) mecamylamine and scopolamine co-administration impaired short term memory at 1h and 4h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1h and 4h; (5) mecamylamine and scopolamine treatment did not impair long term memory formation; (6) unexpectedly, rapamycin increased mTORC2 activation in microglial cells. Our results demonstrate that in CA3 pyramidal neurons the mTOR/p70S6K pathway is under the modulation of the cholinergic system and is involved in long-term memory encoding, and are consistent with the hypothesis that the CA3 region of the hippocampus is involved in memory mechanisms based on rapid, one-trial object-place learning and recall. Furthermore, our results are in accordance with previous reports that selective

Concurrent and robust regulation of feeding behaviors and metabolism by orexin neurons.

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Inutsuka, Ayumu; Inui, Azusa; Tabuchi, Sawako; Tsunematsu, Tomomi; Lazarus, Michael; Yamanaka, Akihiro

2014-10-01

Orexin neurons in the hypothalamus regulate energy homeostasis by coordinating various physiological responses. Past studies have shown the role of the orexin peptide itself; however, orexin neurons contain not only orexin but also other neurotransmitters such as glutamate and dynorphin. In this study, we examined the physiological role of orexin neurons in feeding behavior and metabolism by pharmacogenetic activation and chronic ablation. We generated novel orexin-Cre mice and utilized Cre-dependent adeno-associated virus vectors to express Gq-coupled modified GPCR, hM3Dq or diphtheria toxin fragment A in orexin neurons. By intraperitoneal injection of clozapine-N oxide in orexin-Cre mice expressing hM3Dq in orexin neurons, we could selectively manipulate the activity of orexin neurons. Pharmacogenetic stimulation of orexin neurons simultaneously increased locomotive activity, food intake, water intake and the respiratory exchange ratio (RER). Elevation of blood glucose levels and RER persisted even after locomotion and feeding behaviors returned to basal levels. Accordantly, 83% ablation of orexin neurons resulted in decreased food and water intake, while 70% ablation had almost no effect on these parameters. Our results indicate that orexin neurons play an integral role in regulation of both feeding behavior and metabolism. This regulation is so robust that greater than 80% of orexin neurons were ablated before significant changes in feeding behavior emerged. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Long-term post-stroke changes include myelin loss, specific deficits in sensory and motor behaviors and complex cognitive impairment detected using active place avoidance.

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Jin Zhou

Full Text Available Persistent neurobehavioral deficits and brain changes need validation for brain restoration. Two hours middle cerebral artery occlusion (tMCAO or sham surgery was performed in male Sprague-Dawley rats. Neurobehavioral and cognitive deficits were measured over 10 weeks included: (1 sensory, motor, beam balance, reflex/abnormal responses, hindlimb placement, forepaw foot fault and cylinder placement tests, and (2 complex active place avoidance learning (APA and simple passive avoidance retention (PA. Electroretinogram (ERG, hemispheric loss (infarction, hippocampus CA1 neuronal loss and myelin (Luxol Fast Blue staining in several fiber tracts were also measured. In comparison to Sham surgery, tMCAO surgery produced significant deficits in all behavioral tests except reflex/abnormal responses. Acute, short lived deficits following tMCAO were observed for forelimb foot fault and forelimb cylinder placement. Persistent, sustained deficits for the whole 10 weeks were exhibited for motor (p<0.001, sensory (p<0.001, beam balance performance (p<0.01 and hindlimb placement behavior (p<0.01. tMCAO produced much greater and prolonged cognitive deficits in APA learning (maximum on last trial of 604±83% change, p<0.05 but only a small, comparative effect on PA retention. Hemispheric loss/atrophy was measured 10 weeks after tMCAO and cross-validated by two methods (e.g., almost identical % ischemic hemispheric loss of 33.4±3.5% for H&E and of 34.2±3.5% for TTC staining. No visual dysfunction by ERG and no hippocampus neuronal loss were detected after tMCAO. Fiber tract damage measured by Luxol Fast Blue myelin staining intensity was significant (p<0.01 in the external capsule and striatum but not in corpus callosum and anterior commissure. In summary, persistent neurobehavioral deficits were validated as important endpoints for stroke restorative research in the future. Fiber myelin loss appears to contribute to these long term behavioral dysfunctions and

Prediction of rat behavior outcomes in memory tasks using functional connections among neurons.

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Hu Lu

Full Text Available BACKGROUND: Analyzing the neuronal organizational structures and studying the changes in the behavior of the organism is key to understanding cognitive functions of the brain. Although some studies have indicated that spatiotemporal firing patterns of neuronal populations have a certain relationship with the behavioral responses, the issues of whether there are any relationships between the functional networks comprised of these cortical neurons and behavioral tasks and whether it is possible to take advantage of these networks to predict correct and incorrect outcomes of single trials of animals are still unresolved. METHODOLOGY/PRINCIPAL FINDINGS: This paper presents a new method of analyzing the structures of whole-recorded neuronal functional networks (WNFNs and local neuronal circuit groups (LNCGs. The activity of these neurons was recorded in several rats. The rats performed two different behavioral tasks, the Y-maze task and the U-maze task. Using the results of the assessment of the WNFNs and LNCGs, this paper describes a realization procedure for predicting the behavioral outcomes of single trials. The methodology consists of four main parts: construction of WNFNs from recorded neuronal spike trains, partitioning the WNFNs into the optimal LNCGs using social community analysis, unsupervised clustering of all trials from each dataset into two different clusters, and predicting the behavioral outcomes of single trials. The results show that WNFNs and LNCGs correlate with the behavior of the animal. The U-maze datasets show higher accuracy for unsupervised clustering results than those from the Y-maze task, and these datasets can be used to predict behavioral responses effectively. CONCLUSIONS/SIGNIFICANCE: The results of the present study suggest that a methodology proposed in this paper is suitable for analysis of the characteristics of neuronal functional networks and the prediction of rat behavior. These types of structures in cortical

Effects of Long-Term Representations on Free Recall of Unrelated Words

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Katkov, Mikhail; Romani, Sandro; Tsodyks, Misha

2015-01-01

Human memory stores vast amounts of information. Yet recalling this information is often challenging when specific cues are lacking. Here we consider an associative model of retrieval where each recalled item triggers the recall of the next item based on the similarity between their long-term neuronal representations. The model predicts that…

Long-term cognitive and behavioral consequences of neonatal encephalopathy following perinatal asphyxia: a review

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Swaab, Hanna; de Vries, Linda S.; Jongmans, Marian J.

2007-01-01

Neonatal encephalopathy (NE) following perinatal asphyxia (PA) is considered an important cause of later neurodevelopmental impairment in infants born at term. This review discusses long-term consequences for general cognitive functioning, educational achievement, neuropsychological functioning and behavior. In all areas reviewed, the outcome of children with mild NE is consistently positive and the outcome of children with severe NE consistently negative. However, children with moderate NE form a more heterogeneous group with respect to outcome. On average, intelligence scores are below those of children with mild NE and age-matched peers, but within the normal range. With respect to educational achievement, difficulties have been found in the domains reading, spelling and arithmetic/mathematics. So far, studies of neuropsychological functioning have yielded ambiguous results in children with moderate NE. A few studies suggest elevated rates of hyperactivity in children with moderate NE and autism in children with moderate and severe NE. Conclusion: Behavioral monitoring is required for all children with NE. In addition, systematic, detailed neuropsychological examination is needed especially for children with moderate NE. PMID:17426984

Remote memory and cortical synaptic plasticity require neuronal CCCTC-binding factor (CTCF).

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Kim, Somi; Yu, Nam-Kyung; Shim, Kyu-Won; Kim, Ji-Il; Kim, Hyopil; Han, Dae Hee; Choi, Ja Eun; Lee, Seung-Woo; Choi, Dong Il; Kim, Myung Won; Lee, Dong-Sung; Lee, Kyungmin; Galjart, Niels; Lee, Yong-Seok; Lee, Jae-Hyung; Kaang, Bong-Kiun

2018-04-30

The molecular mechanism of long-term memory has been extensively studied in the context of the hippocampus-dependent recent memory examined within several days. However, months-old remote memory maintained in the cortex for long-term has not been investigated much at the molecular level yet. Various epigenetic mechanisms are known to be important for long-term memory, but how the three-dimensional (3D) chromatin architecture and its regulator molecules contribute to neuronal plasticity and systems consolidation are still largely unknown. CCCTC-binding factor (CTCF) is an eleven-zinc finger protein well known for its role as a genome architecture molecule. Male conditional knockout (cKO) mice in which CTCF is lost in excitatory neurons during adulthood showed normal recent memory in the contextual fear conditioning and spatial water maze tasks. However, they showed remarkable impairments in remote memory in both tasks. Underlying the remote memory-specific phenotypes, we observed that female CTCF cKO mice exhibit disrupted cortical long-term potentiation (LTP), but not hippocampal LTP. Similarly, we observed that CTCF deletion in inhibitory neurons caused partial impairment of remote memory. Through RNA-sequencing, we observed that CTCF knockdown in cortical neuron culture caused altered expression of genes that are highly involved in cell adhesion, synaptic plasticity, and memory. These results suggest that remote memory storage in the cortex requires CTCF-mediated gene regulation in neurons while recent memory formation in the hippocampus does not. SIGNIFICANCE STATEMENT CTCF is a well-known 3D genome architectural protein that regulates gene expression. Here, we use two different CTCF conditional knockout mouse lines and reveal for the first time that CTCF is critically involved in the regulation of remote memory. We also show that CTCF is necessary for appropriate expression of genes, many of which we found to be involved in the learning and memory related

Long term treadmill exercise performed to chronic social isolated rats regulate anxiety behavior without improving learning.

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Cevik, Ozge Selin; Sahin, Leyla; Tamer, Lulufer

2018-05-01

The type and duration of exposure to stress is an important influence on emotional and cognitive functions. Learning is the adaptive response of the central nervous system that occurs in hippocampus which affects from environmental factors like exercise. In this study, we investigated effects of long term treadmill exercise on learning and behavior on chronic social isolated rat. Male Wistar rats (n = 32) randomly assigned into four groups: control, exercised, social isolation, social isolation + exercise during postnatal days (PNDs) 21-34. Social isolation protocol was applied during 14 days by placing rat in a cage one by one. Rats were exercised during 5 days, days were chosen randomly for overall 4 weeks (20, 30, 50, 60 min respectively). Finally, learning performance was evaluated by Morris water maze (MWM). Anxiety behavior was evaluated by Open field and elevated plus maze test. At the end of learning and behavior tests, the rats were decapitated to collect blood samples via intracardiac puncture and corticosterone analysis was performed with ELISA method. Animal weights and water consumption did not change significantly but food intake differed among groups. Corticosterone level did not change between groups. The frequency of entering to the target quadrant increased in exercised rat significantly. However, there was no difference in learning and memory in rats. Treadmill exercise reduced anxiety behavior significantly. Taken together these findings may point out that, long term treadmill exercise did not change learning and memory but reduced anxiety level of rat without changing corticosterone level. Copyright © 2018 Elsevier Inc. All rights reserved.

Exchange Protein Activated by cAMP Enhances Long-Term Memory Formation Independent of Protein Kinase A

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Ma, Nan; Abel, Ted; Hernandez, Pepe J.

2009-01-01

It is well established that cAMP signaling within neurons plays a major role in the formation of long-term memories--signaling thought to proceed through protein kinase A (PKA). However, here we show that exchange protein activated by cAMP (Epac) is able to enhance the formation of long-term memory in the hippocampus and appears to do so…

Long-Term Cyclic Oxidation Behavior of Wrought Commercial Alloys at High Temperatures

Energy Technology Data Exchange (ETDEWEB)

Li, Bingtao [Iowa State Univ., Ames, IA (United States)

2003-01-01

The oxidation resistance of a high-temperature alloy is dependent upon sustaining the formation of a protective scale, which is strongly related to the alloying composition and the oxidation condition. The protective oxide scale only provides a finite period of oxidation resistance owing to its eventual breakdown, which is especially accelerated under thermal cycling conditions. This current study focuses on the long-term cyclic oxidation behavior of a number of commercial wrought alloys. The alloys studied were Fe- and Ni-based, containing different levels of minor elements, such as Si, Al, Mn, and Ti. Oxidation testing was conducted at 1000 and 1100 C in still air under both isothermal and thermal cycling conditions (1-day and 7-days). The specific aspects studied were the oxidation behavior of chromia-forming alloys that are used extensively in industry. The current study analyzed the effects of alloying elements, especially the effect of minor element Si, on cyclic oxidation resistance. The behavior of oxide scale growth, scale spallation, subsurface changes, and chromium interdiffusion in the alloy were analyzed in detail. A novel model was developed in the current study to predict the life-time during cyclic oxidation by simulating oxidation kinetics and chromium interdiffusion in the subsurface of chromia-forming alloys.

Immature doublecortin-positive hippocampal neurons are important for learning but not for remembering.

Science.gov (United States)

Vukovic, Jana; Borlikova, Gilyana G; Ruitenberg, Marc J; Robinson, Gregory J; Sullivan, Robert K P; Walker, Tara L; Bartlett, Perry F

2013-04-10

It is now widely accepted that hippocampal neurogenesis underpins critical cognitive functions, such as learning and memory. To assess the behavioral importance of adult-born neurons, we developed a novel knock-in mouse model that allowed us to specifically and reversibly ablate hippocampal neurons at an immature stage. In these mice, the diphtheria toxin receptor (DTR) is expressed under control of the doublecortin (DCX) promoter, which allows for specific ablation of immature DCX-expressing neurons after administration of diphtheria toxin while leaving the neural precursor pool intact. Using a spatially challenging behavioral test (a modified version of the active place avoidance test), we present direct evidence that immature DCX-expressing neurons are required for successful acquisition of spatial learning, as well as reversal learning, but are not necessary for the retrieval of stored long-term memories. Importantly, the observed learning deficits were rescued as newly generated immature neurons repopulated the granule cell layer upon termination of the toxin treatment. Repeat (or cyclic) depletion of immature neurons reinstated behavioral deficits if the mice were challenged with a novel task. Together, these findings highlight the potential of stimulating neurogenesis as a means to enhance learning.

A supplementary circuit rule-set for the neuronal wiring

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Kunjumon I Vadakkan

2013-05-01

Full Text Available Limitations of known anatomical circuit rules necessitate the identification of supplementary rules. This is essential for explaining how associative sensory stimuli induce nervous system changes that generate internal sensations of memory, concurrent with triggering specific motor activities in response to specific cue stimuli. A candidate mechanism is rapidly reversible, yet stabilizable membrane hemi-fusion formed between the closely apposed postsynaptic membranes of different neurons at locations of convergence of sensory inputs during associative learning. The lateral entry of activity from the cue stimulus-activated postsynapse re-activates the opposite postsynapse through the hemi-fused area and induces the basic units of internal sensation (namely, semblions as a systems property. Working, short-term and long-term memories can be viewed as functions of the number of re-activatible hemi-fusions present at the time of memory retrieval. Blocking membrane hemi-fusion either by the insertion of the herpes simplex virus glycoproteins or by the deposition of insoluble intermediates of amyloid and tau proteins in the inter-postsynaptic extracellular matrix space leads to cognitive impairments, supporting this mechanism. The introduction of membrane fusion blockers into the postsynaptic cell cytoplasm that attenuates long-term potentiation, a correlate of behavioral motor activities in response to memory retrieval, provides further support. The lateral spread of activity through the inter-postsynaptic membrane is capable of contributing to oscillating neuronal activity at certain neuronal orders. At the resting state these oscillations provide sub-threshold activation to many neurons at higher orders, including motor neurons maintaining them at a low initiation threshold for motor activity.

Physicochemical properties and long-term behavior of french R7T7 nuclear waste glass

International Nuclear Information System (INIS)

Vernaz, E.

1990-01-01

The French R7T7 nuclear glass composition was carefully selected to allow incorporation of some thirty different oxides found in fission product solutions. The resulting glass exhibits very low crystallization, and its physical and chemical properties are very similar to those of standard industrial glasses. Nuclear glasses have been shown to withstand α doses corresponding to several hundred thousand years under repository conditions. Predicting the long-term behavior of fission product glasses subjected to aqueous corrosion is no doubt the most difficult aspect of the problem. Predictions are necessarily based on mathematical models. A substantial research effort has been undertaken to identify all the basic corrosion mechanisms liable to control long-term alteration. These mechanisms are now relatively well understood, and provide the basis for developing the indispensable models. Realistic storage conditions exist under which glass alteration occurs at a very slow rate, and can fulfill its role as the first containment barrier for several tens of thousands of years

Automated analysis of long-term grooming behavior in Drosophila using a k-nearest neighbors classifier

Science.gov (United States)

Allen, Victoria W; Shirasu-Hiza, Mimi

2018-01-01

Despite being pervasive, the control of programmed grooming is poorly understood. We addressed this gap by developing a high-throughput platform that allows long-term detection of grooming in Drosophila melanogaster. In our method, a k-nearest neighbors algorithm automatically classifies fly behavior and finds grooming events with over 90% accuracy in diverse genotypes. Our data show that flies spend ~13% of their waking time grooming, driven largely by two major internal programs. One of these programs regulates the timing of grooming and involves the core circadian clock components cycle, clock, and period. The second program regulates the duration of grooming and, while dependent on cycle and clock, appears to be independent of period. This emerging dual control model in which one program controls timing and another controls duration, resembles the two-process regulatory model of sleep. Together, our quantitative approach presents the opportunity for further dissection of mechanisms controlling long-term grooming in Drosophila. PMID:29485401

Enteric Neuronal Damage, Intramuscular Denervation and Smooth Muscle Phenotype Changes as Mechanisms of Chagasic Megacolon: Evidence from a Long-Term Murine Model of Trypanosoma cruzi Infection.

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Camila França Campos

Full Text Available We developed a novel murine model of long-term infection with Trypanosoma cruzi with the aim to elucidate the pathogenesis of megacolon and the associated adaptive and neuromuscular intestinal disorders. Our intent was to produce a chronic stage of the disease since the early treatment should avoid 100% mortality of untreated animals at acute phase. Treatment allowed animals to be kept infected and alive in order to develop the chronic phase of infection with low parasitism as in human disease. A group of Swiss mice was infected with the Y strain of T. cruzi. At the 11th day after infection, a sub-group was euthanized (acute-phase group and another sub-group was treated with benznidazole and euthanized 15 months after infection (chronic-phase group. Whole colon samples were harvested and used for studying the histopathology of the intestinal smooth muscle and the plasticity of the enteric nerves. In the acute phase, all animals presented inflammatory lesions associated with intense and diffuse parasitism of the muscular and submucosa layers, which were enlarged when compared with the controls. The occurrence of intense degenerative inflammatory changes and increased reticular fibers suggests inflammatory-induced necrosis of muscle cells. In the chronic phase, parasitism was insignificant; however, the architecture of Aüerbach plexuses was focally affected in the inflamed areas, and a significant decrease in the number of neurons and in the density of intramuscular nerve bundles was detected. Other changes observed included increased thickness of the colon wall, diffuse muscle cell hypertrophy, and increased collagen deposition, indicating early fibrosis in the damaged areas. Mast cell count significantly increased in the muscular layers. We propose a model for studying the long-term (15 months pathogenesis of Chagasic megacolon in mice that mimics the human disease, which persists for several years and has not been fully elucidated. We

PKA-CREB-BDNF signaling pathway mediates propofol-induced long-term learning and memory impairment in hippocampus of rats.

Science.gov (United States)

Zhong, Yu; Chen, Jing; Li, Li; Qin, Yi; Wei, Yi; Pan, Shining; Jiang, Yage; Chen, Jialin; Xie, Yubo

2018-04-20

Studies have found that propofol can induce widespread neuroapoptosis in developing brains, which leads to cause long-term learning and memory abnormalities. However, the specific cellular and molecular mechanisms underlying propofol-induced neuroapoptosis remain elusive. The aim of the present study was to explore the role of PKA-CREB-BDNF signaling pathway in propofol-induced long-term learning and memory impairment during brain development. Seven-day-old rats were randomly assigned to control, intralipid and three treatment groups (n = 5). Rats in control group received no treatment. Intralipid (10%, 10 mL/kg) for vehicle control and different dosage of propofol for three treatment groups (50, 100 and 200 mg/kg) were administered intraperitoneally. FJB staining, immunohistochemistry analysis for neuronal nuclei antigen and transmission electron microscopy were used to detect neuronal apoptosis and structure changes. MWM test examines the long-term spatial learning and memory impairment. The expression of PKA, pCREB and BDNF was quantified using western blots. Propofol induced significant increase of FJB-positive cells and decrease of PKA, pCREB and BDNF protein levels in the immature brain of P7 rats. Using the MWM test, propofol-treated rats demonstrated long-term spatial learning and memory impairment. Moreover, hippocampal NeuN-positive cell loss, long-lasting ultrastructural abnormalities of the neurons and synapses, and long-term down-regulation of PKA, pCREB and BDNF protein expression in adult hippocampus were also found. Our results indicated that neonatal propofol exposure can significantly result in long-term learning and memory impairment in adulthood. The possible mechanism involved in the propofol-induced neuroapoptosis was related to down-regulation of PKA-CREB-BDNF signaling pathway. Copyright © 2018. Published by Elsevier B.V.

Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

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Kathrin Hemmer

2014-09-01

Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

Reforming Management of Behavior Symptoms and Psychiatric Conditions in Long-Term Care Facilities: A Different Perspective.

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Levenson, Steven A; Desai, Abhilash K

2017-04-01

Despite much attention including national initiatives, concerns remain about the approaches to managing behavior symptoms and psychiatric conditions across all settings, including in long-term care settings such as nursing homes and assisted living facilities. One key reason why problems persist is because most efforts to "reform" and "correct" the situation have failed to explore or address root causes and instead have promoted inadequate piecemeal "solutions." Further improvement requires jumping off the bandwagon and rethinking the entire issue, including recognizing and applying key concepts of clinical reasoning and the care delivery process to every situation. The huge negative impact of cognitive biases and rote approaches on related clinical problem solving and decision making and patient outcomes also must be addressed. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Long-term avoidance memory formation is associated with a transient increase in mushroom body synaptic complexes in leaf-cutting ants

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Agustina eFalibene

2015-04-01

Full Text Available Long-term behavioral changes related to learning and experience have been shown to be associated with structural remodeling in the brain. Leaf-cutting ants learn to avoid previously preferred plants after they have proved harmful for their symbiotic fungus, a process that involves long-term olfactory memory. We studied the dynamics of brain microarchitectural changes after long-term olfactory memory formation following avoidance learning in Acromyrmex ambiguus. After performing experiments to control for possible neuronal changes related to age and body size, we quantified synaptic complexes (microglomeruli, MG in olfactory regions of the mushroom bodies (MB at different times after learning. Long-term avoidance memory formation was associated with a transient change in MG densities. Two days after learning, MG density was higher than before learning. At days 4 and 15 after learning — when ants still showed plant avoidance — MG densities had decreased to the initial state. The structural reorganization of MG triggered by long-term avoidance memory formation clearly differed from changes promoted by pure exposure to and collection of novel plants with distinct odors. Sensory exposure by the simultaneous collection of several, instead of one, non-harmful plant species resulted in a decrease in MG densities in the olfactory lip. We hypothesize that while sensory exposure leads to MG pruning in the MB olfactory lip, the formation of long-term avoidance memory involves an initial growth of new MG followed by subsequent pruning.

Long-term avoidance memory formation is associated with a transient increase in mushroom body synaptic complexes in leaf-cutting ants.

Science.gov (United States)

Falibene, Agustina; Roces, Flavio; Rössler, Wolfgang

2015-01-01

Long-term behavioral changes related to learning and experience have been shown to be associated with structural remodeling in the brain. Leaf-cutting ants learn to avoid previously preferred plants after they have proved harmful for their symbiotic fungus, a process that involves long-term olfactory memory. We studied the dynamics of brain microarchitectural changes after long-term olfactory memory formation following avoidance learning in Acromyrmex ambiguus. After performing experiments to control for possible neuronal changes related to age and body size, we quantified synaptic complexes (microglomeruli, MG) in olfactory regions of the mushroom bodies (MBs) at different times after learning. Long-term avoidance memory formation was associated with a transient change in MG densities. Two days after learning, MG density was higher than before learning. At days 4 and 15 after learning-when ants still showed plant avoidance-MG densities had decreased to the initial state. The structural reorganization of MG triggered by long-term avoidance memory formation clearly differed from changes promoted by pure exposure to and collection of novel plants with distinct odors. Sensory exposure by the simultaneous collection of several, instead of one, non-harmful plant species resulted in a decrease in MG densities in the olfactory lip. We hypothesize that while sensory exposure leads to MG pruning in the MB olfactory lip, the formation of long-term avoidance memory involves an initial growth of new MG followed by subsequent pruning.

Time-series modeling of long-term weight self-monitoring data.

Science.gov (United States)

Helander, Elina; Pavel, Misha; Jimison, Holly; Korhonen, Ilkka

2015-08-01

Long-term self-monitoring of weight is beneficial for weight maintenance, especially after weight loss. Connected weight scales accumulate time series information over long term and hence enable time series analysis of the data. The analysis can reveal individual patterns, provide more sensitive detection of significant weight trends, and enable more accurate and timely prediction of weight outcomes. However, long term self-weighing data has several challenges which complicate the analysis. Especially, irregular sampling, missing data, and existence of periodic (e.g. diurnal and weekly) patterns are common. In this study, we apply time series modeling approach on daily weight time series from two individuals and describe information that can be extracted from this kind of data. We study the properties of weight time series data, missing data and its link to individuals behavior, periodic patterns and weight series segmentation. Being able to understand behavior through weight data and give relevant feedback is desired to lead to positive intervention on health behaviors.

Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards.

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Miyazaki, Kayoko W; Miyazaki, Katsuhiko; Tanaka, Kenji F; Yamanaka, Akihiro; Takahashi, Aki; Tabuchi, Sawako; Doya, Kenji

2014-09-08

Serotonin is a neuromodulator that is involved extensively in behavioral, affective, and cognitive functions in the brain. Previous recording studies of the midbrain dorsal raphe nucleus (DRN) revealed that the activation of putative serotonin neurons correlates with the levels of behavioral arousal [1], rhythmic motor outputs [2], salient sensory stimuli [3-6], reward, and conditioned cues [5-8]. The classic theory on serotonin states that it opposes dopamine and inhibits behaviors when aversive events are predicted [9-14]. However, the therapeutic effects of serotonin signal-enhancing medications have been difficult to reconcile with this theory [15, 16]. In contrast, a more recent theory states that serotonin facilitates long-term optimal behaviors and suppresses impulsive behaviors [17-21]. To test these theories, we developed optogenetic mice that selectively express channelrhodopsin in serotonin neurons and tested how the activation of serotonergic neurons in the DRN affects animal behavior during a delayed reward task. The activation of serotonin neurons reduced the premature cessation of waiting for conditioned cues and food rewards. In reward omission trials, serotonin neuron stimulation prolonged the time animals spent waiting. This effect was observed specifically when the animal was engaged in deciding whether to keep waiting and was not due to motor inhibition. Control experiments showed that the prolonged waiting times observed with optogenetic stimulation were not due to behavioral inhibition or the reinforcing effects of serotonergic activation. These results show, for the first time, that the timed activation of serotonin neurons during waiting promotes animals' patience to wait for a delayed reward. Copyright © 2014 Elsevier Ltd. All rights reserved.

Glucose-responsive neurons of the paraventricular thalamus control sucrose-seeking behavior.

Science.gov (United States)

Labouèbe, Gwenaël; Boutrel, Benjamin; Tarussio, David; Thorens, Bernard

2016-08-01

Feeding behavior is governed by homeostatic needs and motivational drive to obtain palatable foods. Here, we identify a population of glutamatergic neurons in the paraventricular thalamus of mice that express the glucose transporter Glut2 (encoded by Slc2a2) and project to the nucleus accumbens. These neurons are activated by hypoglycemia and, in freely moving mice, their activation by optogenetics or Slc2a2 inactivation increases motivated sucrose-seeking but not saccharin-seeking behavior. These neurons may control sugar overconsumption in obesity and diabetes.

Behavioral sensitivity of temporally modulated striatal neurons

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George ePortugal

2011-07-01

Full Text Available Recent investigations into the neural mechanisms that underlie temporal perception have revealed that the striatum is an important contributor to interval timing processes, and electrophysiological recording studies have shown that the firing rates of striatal neurons are modulated by the time in a trial at which an operant response is made. However, it remains unclear whether striatal firing rate modulations are related to the passage of time alone (i.e., whether temporal information is represented in an abstract manner independent of other attributes of biological importance, or whether this temporal information is embedded within striatal activity related to co-occurring contextual information, such as motor behaviors. This study evaluated these two hypotheses by recording from striatal neurons while rats performed a temporal production task. Rats were trained to respond at different nosepoke apertures for food reward under two simultaneously active reinforcement schedules: a variable-interval (VI-15 sec schedule and a fixed-interval (FI-15 sec schedule of reinforcement. Responding during a trial occurred in a sequential manner composing 3 phases; VI responding, FI responding, VI responding. The vast majority of task-sensitive striatal neurons (95% varied their firing rates associated with equivalent behaviors (e.g., periods in which their snout was held within the nosepoke across these behavioral phases, and 96% of cells varied their firing rates for the same behavior within a phase, thereby demonstrating their sensitivity to time. However, in a direct test of the abstract timing hypothesis, 91% of temporally modulated hold cells were further modulated by the overt motor behaviors associated with transitioning between nosepokes. As such, these data are inconsistent with the striatum representing time in an abstract’ manner, but support the hypothesis that temporal information is embedded within contextual and motor functions of the

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

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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.

Comparison of the long-term behavioral effects of neonatal exposure to retigabine or phenobarbital in rats.

Science.gov (United States)

Frankel, Sari; Medvedeva, Natalia; Gutherz, Samuel; Kulick, Catherine; Kondratyev, Alexei; Forcelli, Patrick A

2016-04-01

Anticonvulsant drugs, when given during vulnerable periods of brain development, can have long-lasting consequences on nervous system function. In rats, the second postnatal week approximately corresponds to the late third trimester of gestation/early infancy in humans. Exposure to phenobarbital during this period has been associated with deficits in learning and memory, anxiety-like behavior, and social behavior, among other domains. Phenobarbital is the most common anticonvulsant drug used in neonatology. Several other drugs, such as lamotrigine, phenytoin, and clonazepam, have also been reported to trigger behavioral changes. A new generation anticonvulsant drug, retigabine, has not previously been evaluated for long-term effects on behavior. Retigabine acts as an activator of KCNQ channels, a mechanism that is unique among anticonvulsants. Here, we examined the effects retigabine exposure from postnatal day (P)7 to P14 on behavior in adult rats. We compared these effects with those produced by phenobarbital (as a positive control) and saline (as a negative control). Motor behavior was assessed by using the open field and rotarod, anxiety-like behavior by the open field, elevated plus maze, and light-dark transition task, and learning/memory by the passive avoidance task; social interactions were assessed in same-treatment pairs, and nociceptive sensitivity was assessed via the tail-flick assay. Motor behavior was unaltered by exposure to either drug. We found that retigabine exposure and phenobarbital exposure both induced increased anxiety-like behavior in adult animals. Phenobarbital, but not retigabine, exposure impaired learning and memory. These drugs also differed in their effects on social behavior, with retigabine-exposed animals displaying greater social interaction than phenobarbital-exposed animals. These results indicate that neonatal retigabine induces a subset of behavioral alterations previously described for other anticonvulsant drugs and extend

GnRH neurons of young and aged female rhesus monkeys co-express GPER but are unaffected by long-term hormone replacement.

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Naugle, Michelle M; Gore, Andrea C

2014-01-01

Menopause is caused by changes in the function of the hypothalamic-pituitary-gonadal axis that controls reproduction. Hypophysiotropic gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus orchestrate the activity of this axis and are regulated by hormonal feedback loops. The mechanisms by which GnRH responds to the primary regulatory sex steroid hormone, estradiol (E2), are still poorly understood in the context of menopause. Our goal was to determine whether the G protein-coupled estrogen receptor (GPER) is co-expressed in adult primate GnRH neurons and whether this changes with aging and/or E2 treatment. We used immunofluorescence double-labeling to characterize the co-expression of GPER in GnRH perikarya and terminals in the hypothalamus. Young and aged rhesus macaques were ovariectomized and given long-term (~2-year) hormone treatments (E2, E2 + progesterone, or vehicle) selected to mimic currently prescribed hormone replacement therapies used for the alleviation of menopausal symptoms in women. We found that about half of GnRH perikarya co-expressed GPER, while only about 12% of GnRH processes and terminals in the median eminence (ME) were double-labeled. Additionally, many GPER-labeled processes were in direct contact with GnRH neurons, often wrapped around the perikarya and processes and in close proximity in the ME. These results extend prior work by showing robust co-localization of GPER in GnRH in a clinically relevant model, and they support the possibility that GPER-mediated E2 regulation of GnRH occurs both in the soma and terminals in nonhuman primates.

The more you play, the more aggressive you become: A long-term experimental study of cumulative violent video game effects on hostile expectations and aggressive behavior

NARCIS (Netherlands)

Hasan, Y.; Bègue, L.; Scharkow, M.; Bushman, B.J.

2012-01-01

It is well established that violent video games increase aggression. There is a stronger evidence of short-term violent video game effects than of long-term effects. The present experiment tests the cumulative long-term effects of violent video games on hostile expectations and aggressive behavior

Long-term Consequences of Childhood ADHD on Criminal Activities*

OpenAIRE

Fletcher, Jason; Wolfe, Barbara

2009-01-01

The question of whether childhood mental illness has long term consequences in terms of criminal behavior has been little studied, yet it could have major consequences for both the individual and society more generally. In this paper, we focus on Attention-Deficit/Hyperactivity Disorder (ADHD), one of the most prevalent mental conditions in school-age children, to examine the long-term effects of childhood mental illness on criminal activities, controlling for a rich set of individual, family...

Long-term plasticity determines the postsynaptic response to correlated afferents with multivesicular short-term synaptic depression

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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.

PRENATAL HYPOXIA IN DIFFERENT PERIODS OF EMBRYOGENESIS DIFFERENTIALLY AFFECTS CELL MIGRATION, NEURONAL PLASTICITY AND RAT BEHAVIOR IN POSTNATAL ONTOGENESIS

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Dmitrii S Vasilev

2016-03-01

Full Text Available Long-term effects of prenatal hypoxia on embryonic days E14 or E18 on the number, type and localization of cortical neurons, density of labile synaptopodin-positive dendritic spines and parietal cortex-dependent behavioral tasks were examined in the postnatal ontogenesis of rats. An injection of 5’ethynyl-2’deoxyuridine to pregnant rats was used to label neurons generated on E14 or E18 in the fetuses. In control rat pups a majority of cells labeled on E14 were localized in the lower cortical layers V-VI while the cells labeled on E18 were mainly found in the superficial cortical layers II-III. It was shown that hypoxia both on E14 and E18 results in disruption of neuroblast generation and migration but affects different cell populations. In rat pups subjected to hypoxia on E14, the total number of labeled cells in the parietal cortex was decreased while the number of labeled neurons scattered within the superficial cortical layers was increased. In rat pups subjected to hypoxia on E18, the total number of labeled cells in the parietal cortex was also decreased but the number of scattered labeled neurons was higher in the lower cortical layers. It can be suggested that prenatal hypoxia both on E14 and E18 causes a disruption in neuroblast migration but with a different outcome. Only in rats subjected to hypoxia on E14 did we observe a reduction in the total number of pyramidal cortical neurons and the density of labile synaptopodin-positive dendritic spines in the molecular cortical layer during the first month after birth which affected development of the cortical functions. As a result, rats subjected to hypoxia on E14, but not on E18, had impaired development of the whisker-placing reaction and reduced ability to learn reaching by a forepaw. The data obtained suggest that hypoxia on E14 in the period of generation of the cells, which later differentiate into the pyramidal cortical neurons of the V-VI layers and form cortical minicolumns

Short-term treatment with flumazenil restores long-term object memory in a mouse model of Down syndrome.

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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.

[Changes of the neuronal membrane excitability as cellular mechanisms of learning and memory].

Science.gov (United States)

Gaĭnutdinov, Kh L; Andrianov, V V; Gaĭnutdinova, T Kh

2011-01-01

In the presented review given literature and results of own studies of dynamics of electrical characteristics of neurons, which change are included in processes both an elaboration of learning, and retention of the long-term memory. Literary datas and our results allow to conclusion, that long-term retention of behavioural reactions during learning is accompanied not only by changing efficiency of synaptic transmission, as well as increasing of excitability of command neurons of the defensive reflex. This means, that in the process of learning are involved long-term changes of the characteristics a membrane of certain elements of neuronal network, dependent from the metabolism of the cells. see text). Thou phenomena possible mark as cellular (electrophysiological) correlates of long-term plastic modifications of the behaviour. The analyses of having results demonstrates an important role of membrane characteristics of neurons (their excitability) and parameters an synaptic transmission not only in initial stage of learning, as well as in long-term modifications of the behaviour (long-term memory).

Dynamics of Time Delay-Induced Multiple Synchronous Behaviors in Inhibitory Coupled Neurons

Science.gov (United States)

Gu, Huaguang; Zhao, Zhiguo

2015-01-01

The inhibitory synapse can induce synchronous behaviors different from the anti-phase synchronous behaviors, which have been reported in recent studies. In the present paper, synchronous behaviors are investigated in the motif model composed of reciprocal inhibitory coupled neurons with endogenous bursting and time delay. When coupling strength is weak, synchronous behavior appears at a single interval of time delay within a bursting period. When coupling strength is strong, multiple synchronous behaviors appear at different intervals of time delay within a bursting period. The different bursting patterns of synchronous behaviors, and time delays and coupling strengths that can induce the synchronous bursting patterns can be well interpreted by the dynamics of the endogenous bursting pattern of isolated neuron, which is acquired by the fast-slow dissection method, combined with the inhibitory coupling current. For an isolated neuron, when a negative impulsive current with suitable strength is applied at different phases of the bursting, multiple different bursting patterns can be induced. For a neuron in the motif, the inhibitory coupling current, of which the application time and strength is modulated by time delay and coupling strength, can cause single or multiple synchronous firing patterns like the negative impulsive current when time delay and coupling strength is suitable. The difference compared to the previously reported multiple synchronous behaviors that appear at time delays wider than a period of the endogenous firing is discussed. The results present novel examples of synchronous behaviors in the neuronal network with inhibitory synapses and provide a reasonable explanation. PMID:26394224

Long-term creep behavior of high-temperature gas turbine materials under constant and variable stress

International Nuclear Information System (INIS)

Granacher, J.; Preussler, T.

1987-01-01

Within the framework of the documented research project, extensive creep rupture tests were carried out with characteristic, high-temperature gas turbine materials for establishment of improved design data. In the range of the main application temperatures and in stress ranges down to application-relevant values the tests extended over a period of about 40,000 hours. In addition, long-term annealing tests were carried out in the most important temperature ranges for the measurement of the density-dependent straim, which almost always manifested itself as a material contraction. Furthermore, hot tensile tests were carried out for the description of the elastoplastic short-term behavior. Several creep curves were derived from the results of the different tests with a differentiated evaluation method. On the basis of these creep curves, creep equations were set up for a series of materials which are valid in the entire examined temperature range and stress range and up to the end of the secondary creep range. Also, equations for the time-temperature-dependent description of the material contraction behavior were derived. With these equations, the high-temperature deformation behavior of the examined materials under constant creep stress can be described simply and application-oriented. (orig.) With 109 figs., 19 tabs., 77 refs [de

The family environment predicts long-term academic achievement and classroom behavior following traumatic brain injury in early childhood.

Science.gov (United States)

Durber, Chelsea M; Yeates, Keith Owen; Taylor, H Gerry; Walz, Nicolay Chertkoff; Stancin, Terry; Wade, Shari L

2017-07-01

This study examined how the family environment predicts long-term academic and behavioral functioning in school following traumatic brain injury (TBI) in early childhood. Using a concurrent cohort, prospective design, 15 children with severe TBI, 39 with moderate TBI, and 70 with orthopedic injury (OI) who were injured when they were 3-7 years of age were compared on tests of academic achievement and parent and teacher ratings of school performance and behavior on average 6.83 years postinjury. Soon after injury and at the longer term follow-up, families completed measures of parental psychological distress, family functioning, and quality of the home environment. Hierarchical linear regression analyses examined group differences in academic outcomes and their associations with measures of the early and later family environment. The severe TBI group, but not the moderate TBI group, performed worse than did the OI group on all achievement tests, parent ratings of academic performance, and teacher ratings of internalizing problems. Higher quality early and late home environments predicted stronger academic skills and better classroom behavior for children with both TBI and OI. The early family environment more consistently predicted academic achievement, whereas the later family environment more consistently predicted classroom functioning. The quality of the home environment predicted academic outcomes more strongly than did parental psychological distress or family functioning. TBI in early childhood has long-term consequences for academic achievement and school performance and behavior. Higher quality early and later home environments predict better school outcomes for both children with TBI and children with OI. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Super long-term creep tests of advanced HP and IP rotor steels

Energy Technology Data Exchange (ETDEWEB)

Tchizhik, A A [The Polzunov Central Boiler and Turbine Institute, Department the Fatigue Life of Materials for Power Plans Equipment, St. Petersburg (Russian Federation)

1999-12-31

A creep model has been developed for predicting the long-term creep behavior, in excess of 200,000 h for advanced materials.The new creep theory is based on a continuum microdamage model and is used to calculate the fields of stress and strain and wedge and cavities damage in critical components of steam and gas turbines. The application of this new model increases the reliability and service life of modern turbines. The accuracy of the model to predict long - term creep behavior, creep ductility was verified using the data bank of super long-term creep tests of advanced materials. (orig.) 12 refs.

Super long-term creep tests of advanced HP and IP rotor steels

Energy Technology Data Exchange (ETDEWEB)

Tchizhik, A.A. [The Polzunov Central Boiler and Turbine Institute, Department the Fatigue Life of Materials for Power Plans Equipment, St. Petersburg (Russian Federation)

1998-12-31

A creep model has been developed for predicting the long-term creep behavior, in excess of 200,000 h for advanced materials.The new creep theory is based on a continuum microdamage model and is used to calculate the fields of stress and strain and wedge and cavities damage in critical components of steam and gas turbines. The application of this new model increases the reliability and service life of modern turbines. The accuracy of the model to predict long - term creep behavior, creep ductility was verified using the data bank of super long-term creep tests of advanced materials. (orig.) 12 refs.

Prefrontal Neuronal Excitability Maintains Cocaine-Associated Memory During Retrieval

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James M. Otis

2018-06-01

Full Text Available Presentation of drug-associated cues provokes craving and drug seeking, and elimination of these associative memories would facilitate recovery from addiction. Emotionally salient memories are maintained during retrieval, as particular pharmacologic or optogenetic perturbations of memory circuits during retrieval, but not after, can induce long-lasting memory impairments. For example, in rats, inhibition of noradrenergic beta-receptors, which control intrinsic neuronal excitability, in the prelimbic medial prefrontal cortex (PL-mPFC can cause long-term memory impairments that prevent subsequent cocaine-induced reinstatement. The physiologic mechanisms that allow noradrenergic signaling to maintain drug-associated memories during retrieval, however, are unclear. Here we combine patch-clamp electrophysiology ex vivo and behavioral neuropharmacology in vivo to evaluate the mechanisms that maintain drug-associated memory during retrieval in rats. Consistent with previous studies, we find that cocaine experience increases the intrinsic excitability of pyramidal neurons in PL-mPFC. In addition, we now find that this intrinsic plasticity positively predicts the retrieval of a cocaine-induced conditioned place preference (CPP memory, suggesting that such plasticity may contribute to drug-associated memory retrieval. In further support of this, we find that pharmacological blockade of a cAMP-dependent signaling cascade, which allows noradrenergic signaling to elevate neuronal excitability, is required for memory maintenance during retrieval. Thus, inhibition of PL-mPFC neuronal excitability during memory retrieval not only leads to long-term deficits in the memory, but this memory deficit provides protection against subsequent cocaine-induced reinstatement. These data reveal that PL-mPFC intrinsic neuronal excitability maintains a cocaine-associated memory during retrieval and suggest a unique mechanism whereby drug-associated memories could be targeted

Later Life Changes in Hippocampal Neurogenesis and Behavioral Functions After Low-Dose Prenatal Irradiation at Early Organogenesis Stage

International Nuclear Information System (INIS)

Ganapathi, Ramya; Manda, Kailash

2017-01-01

Purpose: To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. Methods and Materials: Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. Results: Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significant changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. Conclusion: Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female.

Later Life Changes in Hippocampal Neurogenesis and Behavioral Functions After Low-Dose Prenatal Irradiation at Early Organogenesis Stage

Energy Technology Data Exchange (ETDEWEB)

Ganapathi, Ramya; Manda, Kailash, E-mail: kailashmanda@gmail.com

2017-05-01

Purpose: To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. Methods and Materials: Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. Results: Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significant changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. Conclusion: Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female.

Localization of molecular correlates of memory consolidation to buccal ganglia mechanoafferent neurons after learning that food is inedible in Aplysia.

Science.gov (United States)

Levitan, David; Saada-Madar, Ravit; Teplinsky, Anastasiya; Susswein, Abraham J

2012-10-15

Training paradigms affecting Aplysia withdrawal reflexes cause changes in gene expression leading to long-term memory formation in primary mechanoafferents that initiate withdrawal. Similar mechanoafferents are also found in the buccal ganglia that control feeding behavior, raising the possibility that these mechanoafferents are a locus of memory formation after a training paradigm affecting feeding. Buccal ganglia mechanoafferent neurons expressed increases in mRNA expression for the transcription factor ApC/EBP, and for the growth factor sensorin-A, within the first 2 h after training with an inedible food. No increases in expression were detected in the rest of the buccal ganglia. Increased ApC/EBP expression was not elicited by food and feeding responses not causing long-term memory. Increased ApC/EBP expression was directly related to a measure of the efficacy of training in causing long-term memory, suggesting that ApC/EBP expression is necessary for the expression of aspects of long-term memory. In behaving animals, memory is expressed as a decrease in the likelihood to respond to food, and a decrease in the amplitude of protraction, the first phase of consummatory feeding behaviors. To determine how changes in the properties of mechanoafferents could cause learned changes in feeding behavior, synaptic contacts were mapped from the mechanoafferents to the B31/B32 neurons, which have a key role in initiating consummatory behaviors and also control protractions. Many mechanoafferents monosynaptically and polysynaptically connect with B31/B32. Monosynaptic connections were complex combinations of fast and slow excitation and/or inhibition. Changes in the response of B31/B32 to stimuli sensed by the mechanoafferent could underlie aspects of long-term memory expression.

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

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

2014-09-02

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Engineering Circular Gliding of Actin Filaments Along Myosin-Patterned DNA Nanotube Rings To Study Long-Term Actin-Myosin Behaviors.

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Hariadi, Rizal F; Appukutty, Abhinav J; Sivaramakrishnan, Sivaraj

2016-09-27

Nature has evolved molecular motors that are critical in cellular processes occurring over broad time scales, ranging from seconds to years. Despite the importance of the long-term behavior of molecular machines, topics such as enzymatic lifetime are underexplored due to the lack of a suitable approach for monitoring motor activity over long time periods. Here, we developed an "O"-shaped Myosin Empowered Gliding Assay (OMEGA) that utilizes engineered micron-scale DNA nanotube rings with precise arrangements of myosin VI to trap gliding actin filaments. This circular gliding assay platform allows the same individual actin filament to glide over the same myosin ensemble (50-1000 motors per ring) multiple times. First, we systematically characterized the formation of DNA nanotubes rings with 4, 6, 8, and 10 helix circumferences. Individual actin filaments glide along the nanotube rings with high processivity for up to 12.8 revolutions or 11 min in run time. We then show actin gliding speed is robust to variation in motor number and independent of ring curvature within our sample space (ring diameter of 0.5-4 μm). As a model application of OMEGA, we then analyze motor-based mechanical influence on "stop-and-go" gliding behavior of actin filaments, revealing that the stop-to-go transition probability is dependent on motor flexibility. Our circular gliding assay may provide a closed-loop platform for monitoring long-term behavior of broad classes of molecular motors and enable characterization of motor robustness and long time scale nanomechanical processes.

Immediate and persistent transcriptional correlates of long-term sensitization training at different CNS loci in Aplysia californica.

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Samantha Herdegen

Full Text Available Repeated noxious stimulation produces long-term sensitization of defensive withdrawal reflexes in Aplysia californica, a form of long-term memory that requires changes in both transcription and translation. Previous work has identified 10 transcripts which are rapidly up-regulated after long-term sensitization training in the pleural ganglia. Here we use quantitative PCR to begin examining how these transcriptional changes are expressed in different CNS loci related to defensive withdrawal reflexes at 1 and 24 hours after long-term sensitization training. Specifically, we sample from a the sensory wedge of the pleural ganglia, which exclusively contains the VC nociceptor cell bodies that help mediate input to defensive withdrawal circuits, b the remaining pleural ganglia, which contain withdrawal interneurons, and c the pedal ganglia, which contain many motor neurons. Results from the VC cluster show different temporal patterns of regulation: 1 rapid but transient up-regulation of Aplysia homologs of C/EBP, C/EBPγ, and CREB1, 2 delayed but sustained up-regulation of BiP, Tolloid/BMP-1, and sensorin, 3 rapid and sustained up-regulation of Egr, GlyT2, VPS36, and an uncharacterized protein (LOC101862095, and 4 an unexpected lack of regulation of Aplysia homologs of calmodulin (CaM and reductase-related protein (RRP. Changes in the remaining pleural ganglia mirror those found in the VC cluster at 1 hour but with an attenuated level of regulation. Because these samples had almost no expression of the VC-specific transcript sensorin, our data suggests that sensitization training likely induces transcriptional changes in either defensive withdrawal interneurons or neurons unrelated to defensive withdrawal. In the pedal ganglia, we observed only a rapid but transient increase in Egr expression, indicating that long-term sensitization training is likely to induce transcriptional changes in motor neurons but raising the possibility of different

Behavioral and Single-Neuron Sensitivity to Millisecond Variations in Temporally Patterned Communication Signals.

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Baker, Christa A; Ma, Lisa; Casareale, Chelsea R; Carlson, Bruce A

2016-08-24

In many sensory pathways, central neurons serve as temporal filters for timing patterns in communication signals. However, how a population of neurons with diverse temporal filtering properties codes for natural variation in communication signals is unknown. Here we addressed this question in the weakly electric fish Brienomyrus brachyistius, which varies the time intervals between successive electric organ discharges to communicate. These fish produce an individually stereotyped signal called a scallop, which consists of a distinctive temporal pattern of ∼8-12 electric pulses. We manipulated the temporal structure of natural scallops during behavioral playback and in vivo electrophysiology experiments to probe the temporal sensitivity of scallop encoding and recognition. We found that presenting time-reversed, randomized, or jittered scallops increased behavioral response thresholds, demonstrating that fish's electric signaling behavior was sensitive to the precise temporal structure of scallops. Next, using in vivo intracellular recordings and discriminant function analysis, we found that the responses of interval-selective midbrain neurons were also sensitive to the precise temporal structure of scallops. Subthreshold changes in membrane potential recorded from single neurons discriminated natural scallops from time-reversed, randomized, and jittered sequences. Pooling the responses of multiple neurons improved the discriminability of natural sequences from temporally manipulated sequences. Finally, we found that single-neuron responses were sensitive to interindividual variation in scallop sequences, raising the question of whether fish may analyze scallop structure to gain information about the sender. Collectively, these results demonstrate that a population of interval-selective neurons can encode behaviorally relevant temporal patterns with millisecond precision. The timing patterns of action potentials, or spikes, play important roles in representing

Study on effects of coupled phenomenon on long-term behavior for crystalline rock (Joint research)

International Nuclear Information System (INIS)

Kimoto, Kazushi; Ichikawa, Yasuaki; Matsui, Hiroya

2017-11-01

It is important to evaluate the stability of a repository for high-level radioactive waste not only during the design, construction and operation phases, but also during the post-closure period, for time frames likely exceeding several millennia or longer. The rock mass around the tunnels could be deformed through time in response to time dependent behavior such as creep and stress relaxation. On the other hand, it was revealed that chemical reaction of groundwater in rock has an influence on the long-term behavior. Therefore, an evaluation of the microcracks influencing on rock mechanical and chemical coupled phenomena is the issue to understand the past long-term behavior of rock mass. In view of above points, this study has been started as joint research with Okayama University from Fiscal Year 2016. In Fiscal Year 2016, several kinds of elastic wave velocity were measured using ultra sonic sensors and laser Doppler vibrometer to evaluate the anisotropy of different elastic wave in granite. The velocity measurements were carried out focused on transmitted wave and surface wave. The results showed that strong anisotropy was observed in transmitted P-wave velocity while weak anisotropy was observed in transmitted S-wave and group velocity estimated by surface velocity measurement. In addition, data obtained from surface velocity measurement was partitioned into transmitted and reflected waves and analyzed them in detail. It resulted that elastic wave due to mineral particles to compose granite was dispersed; however, significant dispersion was only observed at specific location. For the future study, understanding of the relationship between density and anisotropy of micro cracks also anisotropy and strong dispersion of group velocity is important subject to estimate the geometrical distribution of micro cracks in granitic rock. (author)

Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

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Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

2014-09-09

Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Few long-term consequences after prolonged maternal separation in female Wistar rats.

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Stina Lundberg

Full Text Available Environmental factors during the early-life period are known to have long-term consequences for the adult phenotype. An intimate interplay between genes and environment shape the individual and may affect vulnerability for psychopathology in a sex-dependent manner. A rodent maternal separation model was here used to study the long-term effects of different early-life rearing conditions on adult behavior, HPA axis activity and long-term voluntary alcohol intake in female rats. Litters were subjected to 15 min (MS15 or 360 min (MS360 of daily maternal separation during postnatal day 1-21. In adulthood, the behavioral profiles were investigated using the multivariate concentric square field™ (MCSF test or examined for HPA axis reactivity by cat-odor exposure with subsequent characterization of voluntary alcohol intake and associated changes in HPA axis activity. Adult female MS360 offspring showed mostly no, or only minor, effects on behavior, HPA axis reactivity and long-term alcohol intake relative to MS15. Instead, more pronounced effects were found dependent on changes in the natural hormonal cycle or by the choice of animal supplier. However, changes were revealed in corticosterone load after long-term alcohol access, as females subjected to MS360 had higher concentrations of fecal corticosterone. The present findings are in line with and expand on previous studies on the long-term effects of maternal separation in female rats with regard to behavior, HPA axis activity and voluntary alcohol intake. It can also be a window into further studies detailing how early-life experiences interact with other risk and protective factors to impact the adult phenotype and how possible sex differences play a role.

Complex Behavior in a Selective Aging Neuron Model Based on Small World Networks

International Nuclear Information System (INIS)

Zhang Guiqing; Chen Tianlun

2008-01-01

Complex behavior in a selective aging simple neuron model based on small world networks is investigated. The basic elements of the model are endowed with the main features of a neuron function. The structure of the selective aging neuron model is discussed. We also give some properties of the new network and find that the neuron model displays a power-law behavior. If the brain network is small world-like network, the mean avalanche size is almost the same unless the aging parameter is big enough.

SHORT-TERM AND LONG-TERM WATER LEVEL PREDICTION AT ONE RIVER MEASUREMENT LOCATION

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Rudolf Scitovski

2012-12-01

Full Text Available Global hydrological cycles mainly depend on climate changes whose occurrence is predominantly triggered by solar and terrestrial influence, and the knowledge of the high water regime is widely applied in hydrology. Regular monitoring and studying of river water level behavior is important from several perspectives. On the basis of the given data, by using modifications of general approaches known from literature, especially from investigation in hydrology, the problem of long- and short-term water level forecast at one river measurement location is considered in the paper. Long-term forecasting is considered as the problem of investigating the periodicity of water level behavior by using linear-trigonometric regression and short-term forecasting is based on the modification of the nearest neighbor method. The proposed methods are tested on data referring to the Drava River level by Donji Miholjac, Croatia, in the period between the beginning of 1900 and the end of 2012.

Loners, Groupies, and Long-term Eccentricity (and Inclination) Behavior: Insights from Secular Theory

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Van Laerhoven, Christa L.

2015-05-01

Considering the secular dynamics of multi-planet systems provides substantial insight into the interactions between planets in those systems. Secular interactions are those that don't involve knowing where a planet is along its orbit, and they dominate when planets are not involved in mean motion resonances. These interactions exchange angular momentum among the planets, evolving their eccentricities and inclinations. To second order in the planets' eccentricities and inclinations, the eccentricity and inclination perturbations are decoupled. Given the right variable choice, the relevant differential equations are linear and thus the eccentricity and inclination behaviors can be described as a sum of eigenmodes. Since the underlying structure of the secular eigenmodes can be calculated using only the planets' masses and semi-major axes, one can elucidate the eccentricity and inclination behavior of planets in exoplanet systems even without knowing the planets' current eccentricities and inclinations. I have calculated both the eccentricity and inclination secular eigenmodes for the population of known multi-planet systems whose planets have well determined masses and periods. Using this catalog of secular character, I will discuss the prevalence of dynamically grouped planets ('groupies') versus dynamically uncoupled planets ('loners') and how this relates to the exoplanets' long-term eccentricity and inclination behavior. I will also touch on the distribution of the secular eigenfreqiencies.

Sweet taste and nutrient value subdivide rewarding dopaminergic neurons in Drosophila.

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Huetteroth, Wolf; Perisse, Emmanuel; Lin, Suewei; Klappenbach, Martín; Burke, Christopher; Waddell, Scott

2015-03-16

Dopaminergic neurons provide reward learning signals in mammals and insects [1-4]. Recent work in Drosophila has demonstrated that water-reinforcing dopaminergic neurons are different to those for nutritious sugars [5]. Here, we tested whether the sweet taste and nutrient properties of sugar reinforcement further subdivide the fly reward system. We found that dopaminergic neurons expressing the OAMB octopamine receptor [6] specifically convey the short-term reinforcing effects of sweet taste [4]. These dopaminergic neurons project to the β'2 and γ4 regions of the mushroom body lobes. In contrast, nutrient-dependent long-term memory requires different dopaminergic neurons that project to the γ5b regions, and it can be artificially reinforced by those projecting to the β lobe and adjacent α1 region. Surprisingly, whereas artificial implantation and expression of short-term memory occur in satiated flies, formation and expression of artificial long-term memory require flies to be hungry. These studies suggest that short-term and long-term sugar memories have different physiological constraints. They also demonstrate further functional heterogeneity within the rewarding dopaminergic neuron population. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Calibrating and validating a FE model for long-term behavior of RC beams

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Tošić Nikola D.

2014-01-01

Full Text Available This study presents the research carried out in finding an optimal finite element (FE model for calculating the long-term behavior of reinforced concrete (RC beams. A multi-purpose finite element software DIANA was used. A benchmark test in the form of a simply supported beam loaded in four point bending was selected for model calibration. The result was the choice of 3-node beam elements, a multi-directional fixed crack model with constant stress cut-off, nonlinear tension softening and constant shear retention and a creep and shrinkage model according to CEB-FIP Model Code 1990. The model was then validated on 14 simply supported beams and 6 continuous beams. Good agreement was found with experimental results (within ±15%.

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization

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Thanos Manos

2018-04-01

Full Text Available In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization.

Science.gov (United States)

Manos, Thanos; Zeitler, Magteld; Tass, Peter A

2018-01-01

In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long-term

Long-term consequences of adolescent cannabinoid exposure in adult psychopathology

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Justine eRenard

2014-11-01

Full Text Available Marijuana is the most widely used illicit drug among adolescents and young adults. Unique cognitive, emotional, and social changes occur during this critical period of development from childhood into adulthood. The adolescent brain is in a state of transition and differs from the adult brain with respect to both anatomy (e.g., neuronal connections and morphology and neurochemistry (e.g., dopamine, GABA, and glutamate. These changes are thought to support the emergence of adult cerebral processes and behaviors. The endocannabinoid system plays an important role in development by acting on synaptic plasticity, neuronal cell proliferation, migration, and differentiation. Delta-9-tetrahydrocanabinol (THC, the principal psychoactive component in marijuana, acts as an agonist of the cannabinoid type 1 receptor (CB1R. Thus, over-activation of the endocannabinoid system by chronic exposure to CB1R agonists (e.g. THC, CP-55,940, and WIN55,212-2 during adolescence can dramatically alter brain maturation and cause long-lasting neurobiological changes that ultimately affect the function and behavior of the adult brain. Indeed, emerging evidence from both human and animal studies demonstrates that early-onset marijuana use has long-lasting consequences on cognition; moreover, in humans, this use is associated with a two-fold increase in the risk of developing a psychotic disorder. Here, we review the relationship between cannabinoid exposure during adolescence and the increased risk of neuropsychiatric disorders, focusing on both clinical and animal studies.

Relative phase asynchrony and long-range correlation of long-term solar magnetic activity

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Deng, Linhua

2017-07-01

Statistical signal processing is one of the most important tasks in a large amount of areas of scientific studies, such as astrophysics, geophysics, and space physics. Phase recurrence analysis and long-range persistence are the two dynamical structures of the underlying processes for the given natural phenomenon. Linear and nonlinear time series analysis approaches (cross-correlation analysis, cross-recurrence plot, wavelet coherent transform, and Hurst analysis) are combined to investigate the relative phase interconnection and long-range correlation between solar activity and geomagnetic activity for the time interval from 1932 January to 2017 January. The following prominent results are found: (1) geomagnetic activity lags behind sunspot numbers with a phase shift of 21 months, and they have a high level of asynchronous behavior; (2) their relative phase interconnections are in phase for the periodic scales during 8-16 years, but have a mixing behavior for the periodic belts below 8 years; (3) both sunspot numbers and geomagnetic activity can not be regarded as a stochastic phenomenon because their dynamical behaviors display a long-term correlation and a fractal nature. We believe that the presented conclusions could provide further information on understanding the dynamical coupling of solar dynamo process with geomagnetic activity variation, and the crucial role of solar and geomagnetic activity in the long-term climate change.

Human Albumin Improves Long-Term Behavioral Sequelae After Subarachnoid Hemorrhage Through Neurovascular Remodeling.

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Xie, Yi; Liu, Wenhua; Zhang, Xiaohao; Wang, Liumin; Xu, Lili; Xiong, Yunyun; Yang, Lian; Sang, Hongfei; Ye, Ruidong; Liu, Xinfeng

2015-10-01

Subarachnoid hemorrhage results in significant long-lasting neurologic sequelae. Here, we investigated whether human albumin improves long-term outcomes in experimental subarachnoid hemorrhage and whether neurovascular remodeling is involved in the protection of albumin. Laboratory investigation. Hospital research laboratory. Male Sprague-Dawley rats. Rats underwent subarachnoid hemorrhage by endovascular perforation. Albumin of either 0.63 or 1.25 g/kg was injected IV immediately after the surgery. Modified Garcia test, beam-walking test, novel object recognition, and Morris water maze were employed to determine the behavioral deficits. The effects of albumin on early neurovascular dysfunction and chronic synaptic plasticity were also studied. Both doses of albumin significantly improved the sensorimotor scores (F = 31.277; p = 0.001) and cognitive performance (F = 7.982; p = 0.001 in novel object recognition test; and F = 3.431; p = 0.026 in the latency analysis of Morris water maze test) for at least 40 days after subarachnoid hemorrhage. There were remarkable microvasculature hypoperfusion, intracranial pressure rise, early vasoconstriction, neural apoptosis, and degeneration in subarachnoid hemorrhage rats, with albumin significantly attenuating such neurovascular dysfunction. Furthermore, albumin markedly prevented blood-brain barrier disruption, as indicated by less blood-brain barrier leakage, preserved blood-brain barrier-related proteins, and dampened gelatinase activities. The expressions of key synaptic elements were up-regulated with albumin supplementation in both acute and chronic phases. Accordingly, a higher dendritic spine density was observed in the prefrontal and hippocampal areas of albumin-treated subarachnoid hemorrhage animals. Albumin at low-to-moderate doses markedly improves long-term neurobehavioral sequelae after subarachnoid hemorrhage, which may involve an integrated process of neurovascular remodeling.

Simulation of ultra-long term behavior in HLW near-field by centrifugal model test. Part 1. Development of centrifugal equipment and centrifuge model test method

International Nuclear Information System (INIS)

Nishimoto, Soshi; Okada, Tetsuji; Sawada, Masataka

2011-01-01

The objective of this paper is to develop a centrifugal equipment which can continuously be run for a long time and a model test method in order to evaluate a long term behavior which is a coupled thermo-hydro-mechanical processes in the high level wastes geological disposal repository and the neighborhood (called 'near-field'). The centrifugal equipment of CRIEPI, 'CENTURY5000-THM', developed in the present study is able to run continuously up to six months. Therefore, a long term behavior in the near-field can be simulated in a short term, for instance, the behavior for 5000 equivalent years can be simulated in six months by centrifugalizing 100 G using a 1/100 size model. We carried out a test using a nylon specimen in a centrifugal force field of 30 G and confirmed the operations of CENTURY5000-THM, control and measurement for 11 days. As the results, it was able to control the stress in the pressure vessel and measure the values of strain, temperature and pressure. And, as a result of scanning the small model of near-field including the metal overpack, bentonite buffer and rock by a medical X-rays CT scanner, the internal structure of the model was able to be evaluated when the metal artifact was reduced. From these results, the evaluation for a long term behavior of a disposal repository by the method of centrifugal model test became possible. (author)

[Peripheral facial nerve lesion induced long-term dendritic retraction in pyramidal cortico-facial neurons].

Science.gov (United States)

Urrego, Diana; Múnera, Alejandro; Troncoso, Julieta

2011-01-01

Little evidence is available concerning the morphological modifications of motor cortex neurons associated with peripheral nerve injuries, and the consequences of those injuries on post lesion functional recovery. Dendritic branching of cortico-facial neurons was characterized with respect to the effects of irreversible facial nerve injury. Twenty-four adult male rats were distributed into four groups: sham (no lesion surgery), and dendritic assessment at 1, 3 and 5 weeks post surgery. Eighteen lesion animals underwent surgical transection of the mandibular and buccal branches of the facial nerve. Dendritic branching was examined by contralateral primary motor cortex slices stained with the Golgi-Cox technique. Layer V pyramidal (cortico-facial) neurons from sham and injured animals were reconstructed and their dendritic branching was compared using Sholl analysis. Animals with facial nerve lesions displayed persistent vibrissal paralysis throughout the five week observation period. Compared with control animal neurons, cortico-facial pyramidal neurons of surgically injured animals displayed shrinkage of their dendritic branches at statistically significant levels. This shrinkage persisted for at least five weeks after facial nerve injury. Irreversible facial motoneuron axonal damage induced persistent dendritic arborization shrinkage in contralateral cortico-facial neurons. This morphological reorganization may be the physiological basis of functional sequelae observed in peripheral facial palsy patients.

Long Term Incentives for Residential Customers Using Dynamic Tariff

DEFF Research Database (Denmark)

Huang, Shaojun; Wu, Qiuwei; Nielsen, Arne Hejde

2015-01-01

This paper reviews several grid tariff schemes, including flat tariff, time-of-use, time-varying tariff, demand charge and dynamic tariff (DT), from the perspective of the long term incentives. The long term incentives can motivate the owners of flexible demands to change their energy consumption...... behavior in such a way that the power system operation issues, such as system balance and congestion, can be alleviated. From the comparison study, including analysis and case study, the DT scheme outperforms the other tariff schemes in terms of cost saving and network operation condition improving....

Reward signal in a recurrent circuit drives appetitive long-term memory formation.

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Ichinose, Toshiharu; Aso, Yoshinori; Yamagata, Nobuhiro; Abe, Ayako; Rubin, Gerald M; Tanimoto, Hiromu

2015-11-17

Dopamine signals reward in animal brains. A single presentation of a sugar reward to Drosophila activates distinct subsets of dopamine neurons that independently induce short- and long-term olfactory memories (STM and LTM, respectively). In this study, we show that a recurrent reward circuit underlies the formation and consolidation of LTM. This feedback circuit is composed of a single class of reward-signaling dopamine neurons (PAM-α1) projecting to a restricted region of the mushroom body (MB), and a specific MB output cell type, MBON-α1, whose dendrites arborize that same MB compartment. Both MBON-α1 and PAM-α1 neurons are required during the acquisition and consolidation of appetitive LTM. MBON-α1 additionally mediates the retrieval of LTM, which is dependent on the dopamine receptor signaling in the MB α/β neurons. Our results suggest that a reward signal transforms a nascent memory trace into a stable LTM using a feedback circuit at the cost of memory specificity.

A quantitative analysis of 2-D gels identifies proteins in which labeling is increased following long-term sensitization in Aplysia

International Nuclear Information System (INIS)

Castellucci, V.F.; Kennedy, T.E.; Kandel, E.R.; Goelet, P.

1988-01-01

Long-term memory for sensitization of the gill- and siphon-withdrawal reflex in Aplysia, produced by 4 days of training, is associated with increased synaptic efficacy of the connection between the sensory and motor neurons. This training is also accompanied by neuronal growth; there is an increase in the number of synaptic varicosities per sensory neuron and in the number of active zones. Such structural changes may be due to changes in the rates of synthesis of certain proteins. We have searched for proteins in which the rates of [ 35 S]methionine labeling are altered during the maintenance phase of long-term memory for sensitization by using computer-assisted quantitative 2-D gel analysis. This method has allowed us to detect 4 proteins in which labeling is altered after 4 days of sensitization training

Environmental radioactivity. Global transport, distribution and its long-term variation

International Nuclear Information System (INIS)

Hirose, Katsumi

2015-01-01

Fukushima Dai-ichi Nuclear Power Plant (F1NPP) accident, which occurred as a result of huge earthquake and resulting tsunami, had a severe impact on world communities as did Japanese, because of cause of serious radioactivity contamination in the environment. Long-term effects of radioactivity contamination from F1NPP are concerned. To assess the long-term environmental effects of the F1NPP accident, it is important to review the history of global radioactivity contamination, which started from Hiroshima and Nagasaki nuclear explosions in Aug. 1945. Radionuclides released in the environment as a result of atmospheric nuclear explosions, nuclear reactor accident and others are migrated between atmosphere, hydrosphere, biosphere and lithosphere according to natural processes. We describe long-term environmental behaviors of anthropogenic radionuclides derived from the atmospheric nuclear explosions and others, which is useful to predict the behaviors and fate of the F1NPP-derived radionuclides. (author)

Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states

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Allison eGraebner

2015-08-01

Full Text Available A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools have greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

Rape-related symptoms in adolescents: short- and long-term outcome after cognitive behavior group therapy.

Science.gov (United States)

Bicanic, Iva; de Roos, Carlijn; van Wesel, Floryt; Sinnema, Gerben; van de Putte, Elise

2014-01-01

Efficacy studies on treatment in adolescent victims of single rape are lacking, even though sexual victimization is most likely to occur during adolescence and despite the fact that adolescents are at risk to develop subsequent posttraumatic stress disorder. The aim of this prospective observational study was to evaluate the short- and long-term outcomes of a nine-session cognitive behavior group therapy (STEPS), including a parallel six-session parents' group on rape-related symptomatology in female adolescents (13-18 years). STEPS includes psychoeducation, exposure in sensu as well as in vivo, cognitive restructuring, and relapse prevention. Fifty-five female adolescents with mental health problems due to single rape, but without prior sexual trauma, received STEPS while their parents participated in a support group. Subjects were assessed on posttraumatic stress (PTS) and comorbid symptoms using self-report questionnaires prior to and directly after treatment, and at 6 and 12 months follow-up. Repeated measures analysis showed a significant and large decrease in symptoms of PTS, anxiety, depression, anger, dissociation, sexual concerns, and behavior problems directly after treatment, which maintained at 12 months follow-up. Time since trauma did not influence the results. Dropout during STEPS was 1.8%. The results potentially suggest that the positive treatment outcomes at short- and long-term may be caused by STEPS. The encouraging findings need confirmation in future controlled studies on the effectiveness of STEPS because it may be possible that the treatment works especially well for more chronic symptoms, while the less chronic part of the sample showed considerable improvement on its own.

Semi-automatic long-term acoustic surveying

DEFF Research Database (Denmark)

Andreassen, Tórur; Surlykke, Annemarie; Hallam, John

2014-01-01

Increasing concern about decline in biodiversity has created a demand for population surveys. Acoustic monitoring is an efficient non-invasive method, which may be deployed for surveys of animals as diverse as insects, birds, and bats. Long-term unmanned automatic monitoring may provide unique...... to determine bat behavior and correct for the bias toward loud bats inherent in acoustic surveying....

Long term adverse drug reaction to Efavirenz in a HIV infected ...

African Journals Online (AJOL)

There is only one published case of serious adverse reaction to Efavirenz in an adolescent after long-term use. The case of a male HIV Positive Nigerian patient aged 13 years. He presented with five-day history of Difficulty sleeping, abnormal dreams, inability to concentrate, restlessness, irrational behavior and long-term ...

Possibility of "superfast" consolidation of long-term memory.

Science.gov (United States)

Podolski IYa

1998-01-01

Two new behavioural tests in rats are described which demonstrate the fast consolidation of the long-term memory (LTM) in a dangerous natural situation (water escape). It is shown that after one-trial learning of the motor skill (jumping out of the water), long-term memory traces are retained without forgetting and are resistant to the blockade of M-cholinoreceptors by scopolamine (2 mg/kg) and of D1/D2 dopamine receptors by haloperidol (10 mg/kg) as well as electroconvulsive shock applied tank wall, learning of necessary motor skills, automatization and minimization of the skilled movements in 1.5-3.0 min, after 5 to 7 trials at two-second intervals (superfast learning) is demonstrated. It is suggested that the superfast consolidation of LTM (several minutes) is possible in life-threatening situations, the necessary time being 1-2 orders of magnitude less than it is generally accepted in the modern theories of memory. The proposed behavioural models may be helpful in investigation of some fundamental physiological and molecular mechanisms of stable neuronal interactions, as a basis for LTM consolidation.

Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory.

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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.

RNG105/caprin1, an RNA granule protein for dendritic mRNA localization, is essential for long-term memory formation.

Science.gov (United States)

Nakayama, Kei; Ohashi, Rie; Shinoda, Yo; Yamazaki, Maya; Abe, Manabu; Fujikawa, Akihiro; Shigenobu, Shuji; Futatsugi, Akira; Noda, Masaharu; Mikoshiba, Katsuhiko; Furuichi, Teiichi; Sakimura, Kenji; Shiina, Nobuyuki

2017-11-21

Local regulation of synaptic efficacy is thought to be important for proper networking of neurons and memory formation. Dysregulation of global translation influences long-term memory in mice, but the relevance of the regulation specific for local translation by RNA granules remains elusive. Here, we demonstrate roles of RNG105/caprin1 in long-term memory formation. RNG105 deletion in mice impaired synaptic strength and structural plasticity in hippocampal neurons. Furthermore, RNG105-deficient mice displayed unprecedentedly severe defects in long-term memory formation in spatial and contextual learning tasks. Genome-wide profiling of mRNA distribution in the hippocampus revealed an underlying mechanism: RNG105 deficiency impaired the asymmetric somato-dendritic localization of mRNAs. Particularly, RNG105 deficiency reduced the dendritic localization of mRNAs encoding regulators of AMPAR surface expression, which was consistent with attenuated homeostatic AMPAR scaling in dendrites and reduced synaptic strength. Thus, RNG105 has an essential role, as a key regulator of dendritic mRNA localization, in long-term memory formation.

Parental divorce: long-term effects on mental health, family relations and adult sexual behavior.

Science.gov (United States)

Jónsson, F H; Njardvik, U; Olafsdóttir, G; Grétarsson, S J

2000-06-01

Specific long term effects of parental divorce were examined in a sample of 179 Icelanders, 20 to 30 years of age. The participants answered the Borromean Family Index, the Affect Balance Scale and a number of questions on sexual behavior and attitudes towards marriage and divorce. Results showed that compared to adults whose parents remained married, those of divorced parents reported more negative emotional experiences at the time of the study and had looser family ties. They also had greater number of short love affairs, had their first love affair at a younger age, had a greater number of sexual partners, and were younger at the time of their first sexual intercourse than adults whose parents remained married.

MicroRNA-22 Gates Long-Term Heterosynaptic Plasticity in Aplysia through Presynaptic Regulation of CPEB and Downstream Targets

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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.

A phenomenological memristor model for short-term/long-term memory

International Nuclear Information System (INIS)

Chen, Ling; Li, Chuandong; Huang, Tingwen; Ahmad, Hafiz Gulfam; Chen, Yiran

2014-01-01

Memristor is considered to be a natural electrical synapse because of its distinct memory property and nanoscale. In recent years, more and more similar behaviors are observed between memristors and biological synapse, e.g., short-term memory (STM) and long-term memory (LTM). The traditional mathematical models are unable to capture the new emerging behaviors. In this article, an updated phenomenological model based on the model of the Hewlett–Packard (HP) Labs has been proposed to capture such new behaviors. The new dynamical memristor model with an improved ion diffusion term can emulate the synapse behavior with forgetting effect, and exhibit the transformation between the STM and the LTM. Further, this model can be used in building new type of neural networks with forgetting ability like biological systems, and it is verified by our experiment with Hopfield neural network. - Highlights: • We take the Fick diffusion and the Soret diffusion into account in the ion drift theory. • We develop a new model based on the old HP model. • The new model can describe the forgetting effect and the spike-rate-dependent property of memristor. • The new model can solve the boundary effect of all window functions discussed in [13]. • A new Hopfield neural network with the forgetting ability is built by the new memristor model

Leader neurons in population bursts of 2D living neural networks

International Nuclear Information System (INIS)

Eckmann, J-P; Zbinden, Cyrille; Jacobi, Shimshon; Moses, Elisha; Marom, Shimon

2008-01-01

Eytan and Marom (2006 J. Neurosci. 26 8465-76) recently showed that the spontaneous bursting activity of rat neuron cultures includes 'first-to-fire' cells that consistently fire earlier than others. Here, we analyze the behavior of these neurons in long-term recordings of spontaneous activity of rat hippocampal and rat cortical neuron cultures from three different laboratories. We identify precursor events that may either subside ('aborted bursts') or can lead to a full-blown burst ('pre-bursts'). We find that the activation in the pre-burst typically has a first neuron ('leader'), followed by a localized response in its neighborhood. Locality is diminished in the bursts themselves. The long-term dynamics of the leaders is relatively robust, evolving with a half-life of 23-34 h. Stimulation of the culture alters the leader distribution, but the distribution stabilizes within about 1 h. We show that the leaders carry information about the identity of the burst, as measured by the signature of the number of spikes per neuron in a burst. The number of spikes from leaders in the first few spikes of a precursor event is furthermore shown to be predictive with regard to the transition into a burst (pre-burst versus aborted burst). We conclude that the leaders play a role in the development of the bursts and conjecture that they are part of an underlying sub-network that is excited first and then acts as a nucleation center for the burst

Theoretical study on crystalline rock for evaluating of long-term behavior (Contract research)

International Nuclear Information System (INIS)

Ichikawa, Yasuaki; Seno, Yasuhiro; Sato, Toshinori; Nakama, Shigeo

2008-03-01

The Japan Atomic Energy Agency (JAEA) is working on the Project of Mizunami Underground Research Laboratory (MIU). The project aims at developing comprehensive techniques of geological investigation and of construction of deep underground space for a repository of HLW and/or TRU. This study contributes to an estimation of long-term stability of underground spaces. Rock materials commonly show time-dependent behavior such as creep and relaxation. The underground structures for geological disposal of radioactive wastes must keep stable not only during construction and operation but also after closing, and then the long-term stability of rock structures (over thousands of years) is essentially important for designing the structures. The true mechanism of time-dependent behavior of rock materials is not yet clearly understood, though the phenomena are widely known. This study aims at elucidating the scientific truth involved in the time-dependent behavior of rock showing creep and relaxation. We used samples of Toki granite and performed precise tests under laser microscope observation, and then developed theories representing the experimental results. These experimental and theoretical results will be served for the design and construction of the Phase III (Operation Phase) of the MIU Project. This is the report worked out in the fiscal year 2006. In this work we performed the following subjects: 1) Uniaxial and stress relaxation tests under observation of a confocal laser scanning microscope (CLSM) by using granite specimens of MIU. 2) Pressure dissolution experiment by using specimens of single crystal quartz and glass beads. 3) Development of the rate of pressure dissolution of quartz and a homogenization analysis for quartz dissolution. In Chapter 2 CLSM was used to acquire clear three-dimensional images of Mizunami granite specimens for uniaxial and stress relaxation tests, and observed the change of microscale structure including the mineral configuration under

Long-Term Mechanical Behavior of Nano Silica Sol Grouting

Science.gov (United States)

Zhang, Nong; Zhang, Chenghao; Qian, Deyu; Han, Changliang; Yang, Sen

2018-01-01

The longevity of grouting has a significant effect on the safe and sustainable operation of many engineering projects. A 500-day experiment was carried out to study the long-term mechanical behavior of nano silica sol grouting. The nano silica sol was activated with different proportions of a NaCl catalyst and cured under fluctuating temperature and humidity conditions. The mechanical parameters of the grout samples were tested using an electrohydraulic uniaxial compression tester and an improved Vicat instrument. Scanning electron microscope, X-ray diffraction, and ultrasonic velocity tests were carried out to analyze the strength change micro-mechanism. Tests showed that as the catalyst dosage in the grout mix is decreased, the curves on the graphs showing changes in the weight and geometric parameters of the samples over time could be divided into three stages, a shrinkage stage, a stable stage, and a second shrinkage stage. The catalyst improved the stability of the samples and reduced moisture loss. Temperature rise was also a driving force for moisture loss. Uniaxial compressive stress-strain curves for all of the samples were elastoplastic. The curves for uniaxial compression strength and secant modulus plotted against time could be divided into three stages. Sample brittleness increased with time and the brittleness index increased with higher catalyst dosages in the latter part of the curing time. Plastic strength-time curves exhibit allometric scaling. Curing conditions mainly affect the compactness, and then affect the strength. PMID:29337897

Long-Term Mechanical Behavior of Nano Silica Sol Grouting

Directory of Open Access Journals (Sweden)

Dongjiang Pan

2018-01-01

Full Text Available The longevity of grouting has a significant effect on the safe and sustainable operation of many engineering projects. A 500-day experiment was carried out to study the long-term mechanical behavior of nano silica sol grouting. The nano silica sol was activated with different proportions of a NaCl catalyst and cured under fluctuating temperature and humidity conditions. The mechanical parameters of the grout samples were tested using an electrohydraulic uniaxial compression tester and an improved Vicat instrument. Scanning electron microscope, X-ray diffraction, and ultrasonic velocity tests were carried out to analyze the strength change micro-mechanism. Tests showed that as the catalyst dosage in the grout mix is decreased, the curves on the graphs showing changes in the weight and geometric parameters of the samples over time could be divided into three stages, a shrinkage stage, a stable stage, and a second shrinkage stage. The catalyst improved the stability of the samples and reduced moisture loss. Temperature rise was also a driving force for moisture loss. Uniaxial compressive stress-strain curves for all of the samples were elastoplastic. The curves for uniaxial compression strength and secant modulus plotted against time could be divided into three stages. Sample brittleness increased with time and the brittleness index increased with higher catalyst dosages in the latter part of the curing time. Plastic strength-time curves exhibit allometric scaling. Curing conditions mainly affect the compactness, and then affect the strength.

Long term subsidence movements and behavior of subsidence-damaged structures

International Nuclear Information System (INIS)

Mahar, J.W.; Marino, G.G.

1999-01-01

Surface ground movement related to sag mine subsidence has been monitored above Illinois abandoned room and pillar coal workings for periods of more than 15 years. The long term movement related to a specific mine subsidence is typically small relative to the initial displacements but have caused crack and tilt damage in both repaired and unrepaired structures. Seasonal variations in ground surface elevations are superimposed on the downward movement related to mine subsidence. Thus it is necessary to measure long term subsidence movement at about the same time each year in order to minimize environmental factors. This paper presents long term monitoring data from five subsidence sags in central and southern Illinois. The abandoned coal mine workings are located at depths of 160 to 460 ft below the ground surface. measured residual mine subsidence ranges between 1.4 and 3.6 in. 4.4 to 15 years after mine failure. The magnitude of downward displacement is greater than settlement design values (1 in.) and are at rates (0.0004 to 0.0056 ft/month) that cause damage to structures. Most of the damage in unrepaired structures occurs along existing cracks and separations. In all five cases, the ground movements are continuing at residual rates. Sag subsidence movement in Illinois takes place for a minimum of five years after the damage is manifested at the ground surface. A classification of say development is provided based on the displacement-time data

Long-Term Behaviors of the OPC Concrete with Fly-ash and Type V Concrete Applied on Reactor Containment Building

International Nuclear Information System (INIS)

Yoon, Eui Sik; Lee, Hee Taik; Paek, Yong Lak; Park, Young Soo

2010-01-01

The prestressed concrete has been used extensively in the construction of Reactor Containment Buildings (RCBs) in Korea in order to strengthen the RCBs and at the same time, prevent the release of radiation due to the Design Basis Accident and Design Basis Earthquake. It is well known that the prestressed concrete loses its prestressing force over the age, and the shrinkage and creep of the concrete significantly contributes to these long term prestressing losses. In this study, an evaluations of long term behaviors of the concrete such as creep and shrinkage have been performed for two types of concretes : Ordinary Portland Cement containing fly-ash used for the Shin- Kori 1 and 2 NPP and Type V cement used for the Ul- Chin 5 and 6 NPP

Long-Term Behaviors of the OPC Concrete with Fly-ash and Type V Concrete Applied on Reactor Containment Building

Energy Technology Data Exchange (ETDEWEB)

Yoon, Eui Sik; Lee, Hee Taik; Paek, Yong Lak [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of); Park, Young Soo [Korea Hydro and Nuclear Power Co., Busan (Korea, Republic of)

2010-10-15

The prestressed concrete has been used extensively in the construction of Reactor Containment Buildings (RCBs) in Korea in order to strengthen the RCBs and at the same time, prevent the release of radiation due to the Design Basis Accident and Design Basis Earthquake. It is well known that the prestressed concrete loses its prestressing force over the age, and the shrinkage and creep of the concrete significantly contributes to these long term prestressing losses. In this study, an evaluations of long term behaviors of the concrete such as creep and shrinkage have been performed for two types of concretes : Ordinary Portland Cement containing fly-ash used for the Shin- Kori 1 and 2 NPP and Type V cement used for the Ul- Chin 5 and 6 NPP

Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice.

Science.gov (United States)

Cabral-Costa, J V; Andreotti, D Z; Mello, N P; Scavone, C; Camandola, S; Kawamoto, E M

2018-06-05

Phosphatase and tensin homolog (PTEN) is an important protein with key modulatory functions in cell growth and survival. PTEN is crucial during embryogenesis and plays a key role in the central nervous system (CNS), where it directly modulates neuronal development and synaptic plasticity. Loss of PTEN signaling function is associated with cognitive deficits and synaptic plasticity impairment. Accordingly, Pten mutations have a strong link with autism spectrum disorder. In this study, neuronal Pten haploinsufficient male mice were subjected to a long-term environmental intervention - intermittent fasting (IF) - and then evaluated for alterations in exploratory, anxiety and learning and memory behaviors. Although no significant effects on spatial memory were observed, mutant mice showed impaired contextual fear memory in the passive avoidance test - an outcome that was effectively rescued by IF. In this study, we demonstrated that IF modulation, in addition to its rescue of the memory deficit, was also required to uncover behavioral phenotypes otherwise hidden in this neuronal Pten haploinsufficiency model.

Drugs of abuse specifically sensitize noradrenergic and serotonergic neurons via a non-dopaminergic mechanism.

Science.gov (United States)

Lanteri, Christophe; Salomon, Lucas; Torrens, Yvette; Glowinski, Jacques; Tassin, Jean-Pol

2008-06-01

A challenge in drug dependence is to delineate long-term neurochemical modifications induced by drugs of abuse. Repeated d-amphetamine was recently shown to disrupt a mutual regulatory link between noradrenergic and serotonergic neurons, thus inducing long-term increased responses to d-amphetamine and para-chloroamphetamine, respectively. We show here that such a sensitization of noradrenergic and serotonergic neurons also occurs following repeated treatment with cocaine, morphine, or alcohol, three compounds belonging to main groups of addictive substances. In all cases, this sensitization is prevented by alpha 1b-adrenergic and 5-HT2A receptors blockade, indicating the critical role of these receptors on long-term effects of drugs of abuse. However, repeated treatments with two non-addictive antidepressants, venlafaxine, and clorimipramine, which nevertheless inhibit noradrenergic and serotonergic reuptake, do not induce noradrenergic and serotonergic neurons sensitization. Similarly, this sensitization does not occur following repeated treatments with a specific inhibitor of dopamine (DA) reuptake, GBR12783. Moreover, we show that the effects of SCH23390, a D1 receptor antagonist known to inhibit development of d-amphetamine behavioral sensitization, are due to its 5-HT2C receptor agonist property. SCH23390 blocks amphetamine-induced release of norepinephrine and RS102221, a 5-HT2C antagonist, can reverse this inhibition as well as inhibition of noradrenergic sensitization and development of behavioral sensitization induced by repeated d-amphetamine. We propose that noradrenergic/serotonergic uncoupling is a common neurochemical consequence of repeated consumption of drugs of abuse, unrelated with DA release. Our data also suggest that compounds able to restore the link between noradrenergic and serotonergic modulatory systems could represent important therapeutic targets for investigation.

Elamipretide (SS-31 Ameliorates Isoflurane-Induced Long-Term Impairments of Mitochondrial Morphogenesis and Cognition in Developing Rats

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Jian-Jun Yang

2017-04-01

Full Text Available Mitochondria are supposed to be involved in the early pathogenesis of general anesthesia (GA-induced neurotoxicity and long-term cognitive deficits in developing brains. However, effective pharmacologic agents targeted on mitochondria during GA exposure are lacking. This study explores the protective effects of mitochondrion-targeted antioxidant elamipretide (SS-31 on mitochondrial morphogenesis and cognition in developing rats exposed to isoflurane. Rat pups at postnatal day (PND 7 were exposed to 1.5% isoflurane for 6 h following intraperitoneal administration of elamipretide or vehicle with 30 min interval. The hippocampus was immediately removed for biochemical assays. Histopathological studies were conducted at PND 21, and behavioral tests were performed at PND 40 or 60. We found that early exposure to isoflurane caused remarkable reactive oxygen species (ROS accumulation, mitochondrial deformation and neuronal apoptosis in hippocampus. The injury occurrence ultimately gave rise to long-term cognitive deficits in developing rats. Interestingly, pretreatment with elamipretide not only provided protective effect against oxidative stress and mitochondrial damages, but also attenuated isoflurane-induced cognitive deficits. Our data support the notion that mitochondrial damage is an early and long lasting event of GA-induced injury and suggest that elamipretide might have clinically therapeutic benefits for pediatric patients undertaking GA.

Hypocretin/orexin neurons contribute to hippocampus-dependent social memory and synaptic plasticity in mice.

Science.gov (United States)

Yang, Liya; Zou, Bende; Xiong, Xiaoxing; Pascual, Conrado; Xie, James; Malik, Adam; Xie, Julian; Sakurai, Takeshi; Xie, Xinmin Simon

2013-03-20

Hypocretin/orexin (Hcrt)-producing neurons in the lateral hypothalamus project throughout the brain, including to the hippocampus, where Hcrt receptors are widely expressed. Hcrt neurons activate these targets to orchestrate global arousal state, wake-sleep architecture, energy homeostasis, stress adaptation, and reward behaviors. Recently, Hcrt has been implicated in cognitive functions and social interaction. In the present study, we tested the hypothesis that Hcrt neurons are critical to social interaction, particularly social memory, using neurobehavioral assessment and electrophysiological approaches. The validated "two-enclosure homecage test" devices and procedure were used to test sociability, preference for social novelty (social novelty), and recognition memory. A conventional direct contact social test was conducted to corroborate the findings. We found that adult orexin/ataxin-3-transgenic (AT) mice, in which Hcrt neurons degenerate by 3 months of age, displayed normal sociability and social novelty with respect to their wild-type littermates. However, AT mice displayed deficits in long-term social memory. Nasal administration of exogenous Hcrt-1 restored social memory to an extent in AT mice. Hippocampal slices taken from AT mice exhibited decreases in degree of paired-pulse facilitation and magnitude of long-term potentiation, despite displaying normal basal synaptic neurotransmission in the CA1 area compared to wild-type hippocampal slices. AT hippocampi had lower levels of phosphorylated cAMP response element-binding protein (pCREB), an activity-dependent transcription factor important for synaptic plasticity and long-term memory storage. Our studies demonstrate that Hcrt neurons play an important role in the consolidation of social recognition memory, at least in part through enhancements of hippocampal synaptic plasticity and cAMP response element-binding protein phosphorylation.

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

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Jun Il Kang

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

PKA Controls Calcium Influx into Motor Neurons during a Rhythmic Behavior

Science.gov (United States)

Wang, Han; Sieburth, Derek

2013-01-01

Cyclic adenosine monophosphate (cAMP) has been implicated in the execution of diverse rhythmic behaviors, but how cAMP functions in neurons to generate behavioral outputs remains unclear. During the defecation motor program in C. elegans, a peptide released from the pacemaker (the intestine) rhythmically excites the GABAergic neurons that control enteric muscle contractions by activating a G protein-coupled receptor (GPCR) signaling pathway that is dependent on cAMP. Here, we show that the C. elegans PKA catalytic subunit, KIN-1, is the sole cAMP target in this pathway and that PKA is essential for enteric muscle contractions. Genetic analysis using cell-specific expression of dominant negative or constitutively active PKA transgenes reveals that knockdown of PKA activity in the GABAergic neurons blocks enteric muscle contractions, whereas constitutive PKA activation restores enteric muscle contractions to mutants defective in the peptidergic signaling pathway. Using real-time, in vivo calcium imaging, we find that PKA activity in the GABAergic neurons is essential for the generation of synaptic calcium transients that drive GABA release. In addition, constitutively active PKA increases the duration of calcium transients and causes ectopic calcium transients that can trigger out-of-phase enteric muscle contractions. Finally, we show that the voltage-gated calcium channels UNC-2 and EGL-19, but not CCA-1 function downstream of PKA to promote enteric muscle contractions and rhythmic calcium influx in the GABAergic neurons. Thus, our results suggest that PKA activates neurons during a rhythmic behavior by promoting presynaptic calcium influx through specific voltage-gated calcium channels. PMID:24086161

PKA controls calcium influx into motor neurons during a rhythmic behavior.

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Han Wang

Full Text Available Cyclic adenosine monophosphate (cAMP has been implicated in the execution of diverse rhythmic behaviors, but how cAMP functions in neurons to generate behavioral outputs remains unclear. During the defecation motor program in C. elegans, a peptide released from the pacemaker (the intestine rhythmically excites the GABAergic neurons that control enteric muscle contractions by activating a G protein-coupled receptor (GPCR signaling pathway that is dependent on cAMP. Here, we show that the C. elegans PKA catalytic subunit, KIN-1, is the sole cAMP target in this pathway and that PKA is essential for enteric muscle contractions. Genetic analysis using cell-specific expression of dominant negative or constitutively active PKA transgenes reveals that knockdown of PKA activity in the GABAergic neurons blocks enteric muscle contractions, whereas constitutive PKA activation restores enteric muscle contractions to mutants defective in the peptidergic signaling pathway. Using real-time, in vivo calcium imaging, we find that PKA activity in the GABAergic neurons is essential for the generation of synaptic calcium transients that drive GABA release. In addition, constitutively active PKA increases the duration of calcium transients and causes ectopic calcium transients that can trigger out-of-phase enteric muscle contractions. Finally, we show that the voltage-gated calcium channels UNC-2 and EGL-19, but not CCA-1 function downstream of PKA to promote enteric muscle contractions and rhythmic calcium influx in the GABAergic neurons. Thus, our results suggest that PKA activates neurons during a rhythmic behavior by promoting presynaptic calcium influx through specific voltage-gated calcium channels.

Long-term exposure to noise impairs cortical sound processing and attention control.

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Kujala, Teija; Shtyrov, Yury; Winkler, Istvan; Saher, Marieke; Tervaniemi, Mari; Sallinen, Mikael; Teder-Sälejärvi, Wolfgang; Alho, Kimmo; Reinikainen, Kalevi; Näätänen, Risto

2004-11-01

Long-term exposure to noise impairs human health, causing pathological changes in the inner ear as well as other anatomical and physiological deficits. Numerous individuals are daily exposed to excessive noise. However, there is a lack of systematic research on the effects of noise on cortical function. Here we report data showing that long-term exposure to noise has a persistent effect on central auditory processing and leads to concurrent behavioral deficits. We found that speech-sound discrimination was impaired in noise-exposed individuals, as indicated by behavioral responses and the mismatch negativity brain response. Furthermore, irrelevant sounds increased the distractibility of the noise-exposed subjects, which was shown by increased interference in task performance and aberrant brain responses. These results demonstrate that long-term exposure to noise has long-lasting detrimental effects on central auditory processing and attention control.

Implicit attitudes towards smoking predict long-term relapse in abstinent smokers.

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Spruyt, Adriaan; Lemaigre, Valentine; Salhi, Bihiyga; Van Gucht, Dinska; Tibboel, Helen; Van Bockstaele, Bram; De Houwer, Jan; Van Meerbeeck, Jan; Nackaerts, Kristiaan

2015-07-01

It has previously been argued that implicit attitudes toward substance-related cues drive addictive behavior. Nevertheless, it remains an open question whether behavioral markers of implicit attitude activation can be used to predict long-term relapse. The main objective of this study was to examine the relationship between implicit attitudes toward smoking-related cues and long-term relapse in abstaining smokers. Implicit attitudes toward smoking-related cues were assessed by means of the Implicit Association Test (IAT) and the evaluative priming task (EPT). Both measures were completed by a group of smokers who volunteered to quit smoking (patient group) and a group of nonsmokers (control group). Participants in the patient group completed these measures twice: once prior to smoking cessation and once after smoking cessation. Relapse was assessed by means of short telephone survey, 6 months after completion of the second test session. EPT scores obtained prior to smoking cessation were related to long-term relapse and correlated with self-reported nicotine dependence as well as daily cigarette consumption. In contrast, none of the behavioral outcome measures were found to correlate with the IAT scores. These findings corroborate the idea that implicit attitudes toward substance-related cues are critically involved in long-term relapse. A potential explanation for the divergent findings obtained with the IAT and EPT is provided.

A study about the long-term stability of sedimentary rock

International Nuclear Information System (INIS)

Yoshino, Naoto; Miyanomae, Shun-ichi; Inoue, Hiroyuki; Nashimoto, Yutaka

2005-02-01

In this paper, following two issues were examined and estimated, (1) the influence of near field condition factor to the dynamical behavior of sedimentary soft rock, (2) the long term estimation of the dynamical behavior considering the condition of Horonobe area. As the study about the influence of near field condition factor to the dynamical behavior of sedimentary soft rock, the thermal factor was focused on and the laboratory tests using test pieces which were sampled in Horonobe area were carried out under the water temperature were 20 degrees and 80 degrees. As a result, the time dependence parameter in variable-compliance-type constitutive-equation could be obtained. And comparison between creep property under 20 degrees and 80 degrees was conducted. In addition, the general properties of sedimentary soft rock under several conditions were identified by the survey of the literature. And the way how to confirm the dynamical properties of sedimentary soft rock with in-situ test were presented. For the study on the short-term and long-term stability of rock surrounding buffer materials, numerical simulations were carried out assuming several conditions. The direction of disposal tunnels and the ratio of rock strength by initial stress were estimated to be the main factor affecting the short-term stability of rock. Time dependency of rock and the stiffness of buffer material were estimated to be the main factor affecting the long-term stability of rock. (author)

Rape-related symptoms in adolescents: short- and long-term outcome after cognitive behavior group therapy

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Iva Bicanic

2014-06-01

Full Text Available Background: Efficacy studies on treatment in adolescent victims of single rape are lacking, even though sexual victimization is most likely to occur during adolescence and despite the fact that adolescents are at risk to develop subsequent posttraumatic stress disorder. Aim: The aim of this prospective observational study was to evaluate the short- and long-term outcomes of a nine-session cognitive behavior group therapy (STEPS, including a parallel six-session parents’ group on rape-related symptomatology in female adolescents (13–18 years. STEPS includes psychoeducation, exposure in sensu as well as in vivo, cognitive restructuring, and relapse prevention. Methods: Fifty-five female adolescents with mental health problems due to single rape, but without prior sexual trauma, received STEPS while their parents participated in a support group. Subjects were assessed on posttraumatic stress (PTS and comorbid symptoms using self-report questionnaires prior to and directly after treatment, and at 6 and 12 months follow-up. Results: Repeated measures analysis showed a significant and large decrease in symptoms of PTS, anxiety, depression, anger, dissociation, sexual concerns, and behavior problems directly after treatment, which maintained at 12 months follow-up. Time since trauma did not influence the results. Dropout during STEPS was 1.8%. Conclusions: The results potentially suggest that the positive treatment outcomes at short- and long-term may be caused by STEPS. The encouraging findings need confirmation in future controlled studies on the effectiveness of STEPS because it may be possible that the treatment works especially well for more chronic symptoms, while the less chronic part of the sample showed considerable improvement on its own.

Audit of long-term and short-term liabilities

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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.

Long-Term Visual Training Increases Visual Acuity and Long-Term Monocular Deprivation Promotes Ocular Dominance Plasticity in Adult Standard Cage-Raised Mice.

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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.

Blast induces oxidative stress, inflammation, neuronal loss and subsequent short-term memory impairment in rats.

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Cho, H J; Sajja, V S S S; Vandevord, P J; Lee, Y W

2013-12-03

Molecular and cellular mechanisms of brain injury after exposure to blast overpressure (BOP) are not clearly known. The present study hypothesizes that pro-oxidative and pro-inflammatory pathways in the brain may be responsible for neuronal loss and behavioral deficits following BOP exposure. Male Sprague-Dawley rats were anesthetized and exposed to calibrated BOP of 129.23±3.01kPa while controls received only anesthesia. In situ dihydroethidium fluorescence staining revealed that BOP significantly increased the production of reactive oxygen species in the brain. In addition, real-time reverse transcriptase-polymerase chain reaction, immunofluorescence staining and enzyme-linked immunosorbent assay demonstrated a significant up-regulation of mRNA and protein expressions of pro-inflammatory mediators, such as interferon-γ and monocyte chemoattractant protein-1, in brains collected from BOP-exposed animals compared with the controls. Furthermore, immunoreactivity of neuronal nuclei in brains indicated that fewer neurons were present following BOP exposure. Moreover, novel object recognition paradigm showed a significant impairment in the short-term memory at 2weeks following BOP exposure. These results suggest that pro-oxidative and pro-inflammatory environments in the brain could play a potential role in BOP-induced neuronal loss and behavioral deficits. It may provide a foundation for defining a molecular and cellular basis of the pathophysiology of blast-induced neurotrauma (BINT). It will also contribute to the development of new therapeutic approaches selectively targeting these pathways, which have great potential in the diagnosis and therapy of BINT. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Long descending cervical propriospinal neurons differ from thoracic propriospinal neurons in response to low thoracic spinal injury

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Stelzner Dennis J

2010-11-01

Full Text Available Abstract Background Propriospinal neurons, with axonal projections intrinsic to the spinal cord, have shown a greater regenerative response than supraspinal neurons after axotomy due to spinal cord injury (SCI. Our previous work focused on the response of axotomized short thoracic propriospinal (TPS neurons following a low thoracic SCI (T9 spinal transection or moderate spinal contusion injury in the rat. The present investigation analyzes the intrinsic response of cervical propriospinal neurons having long descending axons which project into the lumbosacral enlargement, long descending propriospinal tract (LDPT axons. These neurons also were axotomized by T9 spinal injury in the same animals used in our previous study. Results Utilizing laser microdissection (LMD, qRT-PCR, and immunohistochemistry, we studied LDPT neurons (located in the C5-C6 spinal segments between 3-days, and 1-month following a low thoracic (T9 spinal cord injury. We examined the response of 89 genes related to growth factors, cell surface receptors, apoptosis, axonal regeneration, and neuroprotection/cell survival. We found a strong and significant down-regulation of ~25% of the genes analyzed early after injury (3-days post-injury with a sustained down-regulation in most instances. In the few genes that were up-regulated (Actb, Atf3, Frs2, Hspb1, Nrap, Stat1 post-axotomy, the expression for all but one was down-regulated by 2-weeks post-injury. We also compared the uninjured TPS control neurons to the uninjured LDPT neurons used in this experiment for phenotypic differences between these two subpopulations of propriospinal neurons. We found significant differences in expression in 37 of the 84 genes examined between these two subpopulations of propriospinal neurons with LDPT neurons exhibiting a significantly higher base line expression for all but 3 of these genes compared to TPS neurons. Conclusions Taken collectively these data indicate a broad overall down

Thermal stability of the French nuclear waste glass - long term behavior modeling

International Nuclear Information System (INIS)

Orlhac, X.

2000-01-01

The thermal stability of the French nuclear waste glass was investigated experimentally and by modeling to predict its long-term evolution at low temperature. The crystallization mechanisms were analyzed by studying devitrification in the supercooled liquid. Three main crystalline phases were characterized (CaMoO 4 , CeCO 2 , ZnCr 2 O 4 ). Their crystallisation was TO 4.24 wt%, due to the low concentration of the constituent elements. The nucleation and growth curves showed that platinoid elements catalysed nucleation but did not affect growth, which was governed by volume diffusion. The criteria of classic nucleation theory were applied to determine the thermodynamic and diffusional activation energies. Viscosity measurements illustrate the analogy between the activation energy of viscous flow and diffusion, indicating control of crystallization by viscous flow phenomena. The combined action of nucleation and growth was assessed by TTT plots, revealing a crystallization equilibrium line that enables the crystallized fractions to be predicted over the long term. The authors show that hetero-genetics catalyze the transformation without modifying the maximum crystallized fraction. A kinetic model was developed to describe devitrification in the glass based on the nucleation and growth curves alone. The authors show that the low-temperature growth exhibits scale behavior (between time and temperature) similar to thermo-rheological simplicity. The analogy between the resulting activation energy and that of the viscosity was used to model growth on the basis of viscosity. After validation with a simplified (BaO 2 SiO 2 ) glass, the model was applied to the containment glass. The result indicated that the glass remained completely vitreous after a cooling scenario with the one measured at the glass core. Under isothermal conditions, several million years would be required to reach the maximum theoretical crystallization fraction. (author)

Traumatic brain injury causes long-term behavioral changes related to region-specific increases of cerebral blood flow.

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Pöttker, Bruno; Stöber, Franziska; Hummel, Regina; Angenstein, Frank; Radyushkin, Konstantin; Goldschmidt, Jürgen; Schäfer, Michael K E

2017-12-01

Traumatic brain injury (TBI) is a leading cause of disability and death and survivors often suffer from long-lasting motor impairment, cognitive deficits, anxiety disorders and epilepsy. Few experimental studies have investigated long-term sequelae after TBI and relations between behavioral changes and neural activity patterns remain elusive. We examined these issues in a murine model of TBI combining histology, behavioral analyses and single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (CBF) as a proxy for neural activity. Adult C57Bl/6N mice were subjected to unilateral cortical impact injury and investigated at early (15-57 days after lesion, dal) and late (184-225 dal) post-traumatic time points. TBI caused pronounced tissue loss of the parietal cortex and subcortical structures and enduring neurological deficits. Marked perilesional astro- and microgliosis was found at 57 dal and declined at 225 dal. Motor and gait pattern deficits occurred at early time points after TBI and improved over the time. In contrast, impaired performance in the Morris water maze test and decreased anxiety-like behavior persisted together with an increased susceptibility to pentylenetetrazole-induced seizures suggesting alterations in neural activity patterns. Accordingly, SPECT imaging of CBF indicated asymmetric hemispheric baseline neural activity patterns. In the ipsilateral hemisphere, increased baseline neural activity was found in the amygdala. In the contralateral hemisphere, homotopic to the structural brain damage, the hippocampus and distinct cortex regions displayed increased baseline neural activity. Thus, regionally elevated CBF along with behavioral alterations indicate that increased neural activity is critically involved in the long-lasting consequences of TBI.

Numerical simulation for excavation and long-term behavior of large-scale cavern in soft rock

International Nuclear Information System (INIS)

Sawada, Masataka; Okada, Tetsuji

2010-01-01

Low-level radioactive waste is planned to be disposed at the depth of more than 50 m in Neogene tuff or tuffaceous sandstone. Generally there are few cracks in sedimentary soft rocks, thus it is considered to be easier to determine permeability of soft rocks than that of discontinuous rocks. On the other hand, sedimentary soft rocks show strong time-dependent behavior, and they are more sensitive to heat, groundwater, and their chemical effect. Numerical method for long-term behavior of underground facilities is necessary to their design and safety assessment. Numerical simulations for excavation of test cavern in disposal site are described in this report. Our creep model was applied to these simulations. Although it is able to reproduce the behavior of soft rock observed in laboratory creep test, simulation using parameters obtained from laboratory tests predicts much larger displacement than that of measurement. Simulation using parameters modified based on in-situ elastic wave measurement and back analysis reproduces measured displacements very well. Behavior of the surrounding rock mass during resaturation after setting of the waste and the engineered barrier system is also simulated. We have a plan to investigate chemical and mechanical interaction among soft rock, tunnel supports and engineered barriers, and to make their numerical models. (author)

Effects of Chronic Vitamin D3 Hormone Administration on Anxiety-Like Behavior in Adult Female Rats after Long-Term Ovariectomy

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Julia Fedotova

2017-01-01

Full Text Available The present preclinical study was created to determine the therapeutic effects of vitamin D hormone treatment as an adjunctive therapy alone or in a combination with low dose of 17β-estradiol (17β-E2 on anxiety-like behavior in female rats with long-term absence of estrogen. Accordingly, the aim of the current study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg subcutaneously, SC, once daily, for 14 days on the anxiety-like state after long-term ovariectomy in female rats. Twelve weeks postovariectomy, cholecalciferol was administered to ovariectomized (OVX rats and OVX rats treated with 17β-E2 (0.5 µg/rat SC, once daily, for 14 days. Anxiety-like behavior was assessed in the elevated plus maze (EPM and the light/dark test (LDT, and locomotor and grooming activities were tested in the open field test (OFT. Cholecalciferol at two doses of 1.0 and 2.5 mg/kg alone or in combination with 17β-E2 produced anxiolytic-like effects in OVX rats as evidenced in the EPM and the LDT, as well as increased grooming activity in the OFT. Our results indicate that cholecalciferol, at two doses of 1.0 and 2.5 mg/kg, has a profound anxiolytic-like effects in the experimental rat model of long-term estrogen deficiency.

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

OpenAIRE

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

2018-01-01

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

Delay-induced diversity of firing behavior and ordered chaotic firing in adaptive neuronal networks

International Nuclear Information System (INIS)

Gong Yubing; Wang Li; Xu Bo

2012-01-01

In this paper, we study the effect of time delay on the firing behavior and temporal coherence and synchronization in Newman–Watts thermosensitive neuron networks with adaptive coupling. At beginning, the firing exhibit disordered spiking in absence of time delay. As time delay is increased, the neurons exhibit diversity of firing behaviors including bursting with multiple spikes in a burst, spiking, bursting with four, three and two spikes, firing death, and bursting with increasing amplitude. The spiking is the most ordered, exhibiting coherence resonance (CR)-like behavior, and the firing synchronization becomes enhanced with the increase of time delay. As growth rate of coupling strength or network randomness increases, CR-like behavior shifts to smaller time delay and the synchronization of firing increases. These results show that time delay can induce diversity of firing behaviors in adaptive neuronal networks, and can order the chaotic firing by enhancing and optimizing the temporal coherence and enhancing the synchronization of firing. However, the phenomenon of firing death shows that time delay may inhibit the firing of adaptive neuronal networks. These findings provide new insight into the role of time delay in the firing activity of adaptive neuronal networks, and can help to better understand the complex firing phenomena in neural networks.

Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

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Leffa, Douglas Teixeira; Bellaver, Bruna; Salvi, Artur Alban; de Oliveira, Carla; Caumo, Wolnei; Grevet, Eugenio Horacio; Fregni, Felipe; Quincozes-Santos, André; Rohde, Luis Augusto; Torres, Iraci L S

2018-04-05

Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored. Copyright © 2018 Elsevier Inc. All rights reserved.

Preventive Intervention for Preschoolers at High Risk for Antisocial Behavior: Long-Term Effects on Child Physical Aggression and Parenting Practices

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Brotman, Laurie Miller; Gouley, Kathleen Kiely; Huang, Keng-Yen; Rosenfelt, Amanda; O'Neal, Colleen; Klein, Rachel G.; Shrout, Patrick

2008-01-01

This article presents long-term effects of a preventive intervention for young children at high risk for antisocial behavior. Ninety-two children (M age = 4 years) were randomly assigned to an 8-month family intervention or no-intervention control condition and assessed 4 times over a 24-month period. Intent-to-treat analyses revealed significant…

Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning

NARCIS (Netherlands)

Mansson, K.N.T.; Frick, A.; Boraxbekk, C.J.; Marquand, A.F.; Williams, S.C.; Carlbring, P.; Andersson, G.; Furmark, T.

2015-01-01

Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual's long-term clinical response therefore remains an important challenge.

Hippocampal long term memory: effect of the cholinergic system on local protein synthesis.

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Lana, Daniele; Cerbai, Francesca; Di Russo, Jacopo; Boscaro, Francesca; Giannetti, Ambra; Petkova-Kirova, Polina; Pugliese, Anna Maria; Giovannini, Maria Grazia

2013-11-01

The present study was aimed at establishing a link between the cholinergic system and the pathway of mTOR and its downstream effector p70S6K, likely actors in long term memory encoding. We performed in vivo behavioral experiments using the step down inhibitory avoidance test (IA) in adult Wistar rats to evaluate memory formation under different conditions, and immunohistochemistry on hippocampal slices to evaluate the level and the time-course of mTOR and p70S6K activation. We also examined the effect of RAPA, inhibitor of mTORC1 formation, and of the acetylcholine (ACh) muscarinic receptor antagonist scopolamine (SCOP) or ACh nicotinic receptor antagonist mecamylamine (MECA) on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition test was performed 30 min after i.c.v. injection of RAPA, a time sufficient for the drug to diffuse to CA1 pyramidal neurons, as demonstrated by MALDI-TOF-TOF imaging. Recall test was performed 1 h, 4 h or 24 h after acquisition. To confirm our results we performed in vitro experiments on live hippocampal slices: we evaluated whether stimulation of the cholinergic system with the cholinergic receptor agonist carbachol (CCh) activated the mTOR pathway and whether the administration of the above-mentioned antagonists together with CCh could revert this activation. We found that (1) mTOR and p70S6K activation in the hippocampus were involved in long term memory formation; (2) RAPA administration caused inhibition of mTOR activation at 1 h and 4 h and of p70S6K activation at 4 h, and long term memory impairment at 24 h after acquisition; (3) scopolamine treatment caused short but not long term memory impairment with an early increase of mTOR/p70S6K activation at 1 h followed by stabilization at longer times; (4) mecamylamine plus scopolamine treatment caused short term memory impairment at 1 h and 4 h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1 h and 4 h; (5

Long-term follow-up study and long-term care of childhood cancer survivors

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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.

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

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Maximilian Lenz

2015-01-01

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

Early exposure to volatile anesthetics impairs long-term associative learning and recognition memory.

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Bradley H Lee

Full Text Available Anesthetic exposure early in life affects neural development and long-term cognitive function, but our understanding of the types of memory that are altered is incomplete. Specific cognitive tests in rodents that isolate different memory processes provide a useful approach for gaining insight into this issue.Postnatal day 7 (P7 rats were exposed to either desflurane or isoflurane at 1 Minimum Alveolar Concentration for 4 h. Acute neuronal death was assessed 12 h later in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. In separate behavioral experiments, beginning at P48, subjects were evaluated in a series of object recognition tests relying on associative learning, as well as social recognition.Exposure to either anesthetic led to a significant increase in neuroapoptosis in each brain region. The extent of neuronal death did not differ between groups. Subjects were unaffected in simple tasks of novel object and object-location recognition. However, anesthetized animals from both groups were impaired in allocentric object-location memory and a more complex task requiring subjects to associate an object with its location and contextual setting. Isoflurane exposure led to additional impairment in object-context association and social memory.Isoflurane and desflurane exposure during development result in deficits in tasks relying on associative learning and recognition memory. Isoflurane may potentially cause worse impairment than desflurane.

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.

A New Approach to the Long-Term Activity Behavior of DM UMa

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Taş G.

2012-12-01

Full Text Available A long-term activity character of DM UMa (K0-1 IV-III, which is one of the most active members of the RS CVn type variables, is examined using the multicolor photometric observations which spread to the time interval between 1980 and 2009. In this work, we present a new approximation for the long-term light and color variation of DM UMa using data obtained by combining our own observations obtained in the Johnson broad-band U,B,V,R filters between the years 1997 and 2008 and data published in literature. Available light and color data were examined for the long-term and seasonal variations using PERIOD04 program. The period analysis of the V-band data reveals the period estimations of 51.2±2.8 years and 15.1±0.7 years superposed on it. The U-B, B-V and V-R colors do not show correlation with the longer period, but they show variations with a period similar to the shorter one, except for B-V color. The amplitude variation also does not exhibit any correlation with the V light and color curves. It is found that the movement of the spot minima phases in years also indicates the migration period of nearly 15 years, similar to the period derived from the analysis of the long-term photometric observations in V-band.

Repeated in vivo exposure of cocaine induces long-lasting synaptic plasticity in hypocretin/orexin-producing neurons in the lateral hypothalamus in mice.

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Rao, Yan; Mineur, Yann S; Gan, Geliang; Wang, Alex Hanxiang; Liu, Zhong-Wu; Wu, Xinyuan; Suyama, Shigetomo; de Lecea, Luis; Horvath, Tamas L; Picciotto, Marina R; Gao, Xiao-Bing

2013-04-01

Hypocretin (orexin), a neuropeptide synthesized exclusively in the perifornical/lateral hypothalamus, is critical for drug seeking and relapse, but it is not clear how the circuitry centred on hypocretin-producing neurons (hypocretin neurons) is modified by drugs of abuse and how changes in this circuit might alter behaviours related to drug addiction. In this study, we show that repeated, but not single, in vivo cocaine administration leads to a long-lasting, experience-dependent potentiation of glutamatergic synapses on hypocretin neurons in mice following a cocaine-conditioned place preference (CPP) protocol. The synaptic potentiation occurs postsynaptically and probably involves up-regulation of AMPA-type glutamate receptors on hypocretin neurons. Phosphorylation of cAMP response element-binding protein (CREB) is also significantly increased in hypocretin neurons in cocaine-treated animals, suggesting that CREB-mediated pathways may contribute to synaptic potentiation in these cells. Furthermore, the potentiation of synaptic efficacy in hypocretin neurons persists during cocaine withdrawal, but reverses to baseline levels after prolonged abstinence. Finally, the induction of long-term potentiation (LTP) triggered by a high-frequency stimulation is facilitated in hypocretin neurons in cocaine-treated mice, suggesting that long-lasting changes in synapses onto hypocretin neurons would probably be further potentiated by other stimuli (such as concurrent environmental cues) paired with the drug. In summary, we show here that hypocretin neurons undergo experience-dependent synaptic potentiation that is distinct from that reported in other reward systems, such as the ventral tegmental area, following exposure to cocaine. These findings support the idea that the hypocretin system is important for behavioural changes associated with cocaine administration in animals and humans.

Short and Long-Term Attentional Firing Rates Can Be Explained by ST-Neuron Dynamics

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Oscar J. Avella Gonzalez

2018-03-01

Full Text Available Attention modulates neural selectivity and optimizes the allocation of cortical resources during visual tasks. A large number of experimental studies in primates and humans provide ample evidence. As an underlying principle of visual attention, some theoretical models suggested the existence of a gain element that enhances contrast of the attended stimuli. In contrast, the Selective Tuning model of attention (ST proposes an attentional mechanism based on suppression of irrelevant signals. In this paper, we present an updated characterization of the ST-neuron proposed by the Selective Tuning model, and suggest that the inclusion of adaptation currents (Ih to ST-neurons may explain the temporal profiles of the firing rates recorded in single V4 cells during attentional tasks. Furthermore, using the model we show that the interaction between stimulus-selectivity of a neuron and attention shapes the profile of the firing rate, and is enough to explain its fast modulation and other discontinuities observed, when the neuron responds to a sudden switch of stimulus, or when one stimulus is added to another during a visual task.

Cell-based neurotrophin treatment supports long-term auditory neuron survival in the deaf guinea pig.

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Gillespie, Lisa N; Zanin, Mark P; Shepherd, Robert K

2015-01-28

The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the primary auditory neurons (ANs) of the cochlea. However, ANs degenerate in deafness; the preservation of a robust AN target population, in combination with advances in cochlear implant technology, may provide improved hearing outcomes for cochlear implant patients. The exogenous delivery of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 is well known to support AN survival in deafness, and cell-based therapies provide a potential clinically viable option for delivering neurotrophins into the deaf cochlea. This study utilized cells that were genetically modified to express BDNF and encapsulated in alginate microspheres, and investigated AN survival in the deaf guinea pig following (a) cell-based neurotrophin treatment in conjunction with chronic electrical stimulation from a cochlear implant, and (b) long-term cell-based neurotrophin delivery. In comparison to deafened controls, there was significantly greater AN survival following the cell-based neurotrophin treatment, and there were ongoing survival effects for at least six months. In addition, functional benefits were observed following cell-based neurotrophin treatment and chronic electrical stimulation, with a statistically significant decrease in electrically evoked auditory brainstem response thresholds observed during the experimental period. This study demonstrates that cell-based therapies, in conjunction with a cochlear implant, shows potential as a clinically transferable means of providing neurotrophin treatment to support AN survival in deafness. This technology also has the potential to deliver other therapeutic agents, and to be used in conjunction with other biomedical devices for the treatment of a variety of neurodegenerative conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of oxaliplatin on mouse myenteric neurons and colonic motility

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Wafai, Linah; Taher, Mohammadali; Jovanovska, Valentina; Bornstein, Joel C.; Dass, Crispin R.; Nurgali, Kulmira

2013-01-01

Oxaliplatin, an anti-cancer chemotherapeutic agent used for the treatment of colorectal cancer, commonly causes gastrointestinal side-effects such as constipation, diarrhoea, nausea, and vomiting. Damage to enteric neurons may underlie some of these gastrointestinal side-effects, as the enteric nervous system (ENS) controls functions of the bowel. In this study, neuronal loss and changes to the structure and immunoreactivity of myenteric neuronal nitric oxide synthase (nNOS) neurons were examined in colonic segments from mice following exposure to oxaliplatin ex vivo and following repeated intraperitoneal injections of oxaliplatin over 3 weeks in vivo, using immunohistochemistry and confocal microscopy. Significant morphological alterations and increases in the proportion of NOS-immunoreactive (IR) neurons were associated with both short-term oxaliplatin exposure and long-term oxaliplatin administration, confirming that oxaliplatin causes changes to the myenteric neurons. Long-term oxaliplatin administration induced substantial neuronal loss that was correlated with a reduction in both the frequency and propagation speed of colonic migrating motor complexes (CMMCs) in vitro. Similar changes probably produce some symptoms experienced by patients undergoing oxaliplatin treatment. PMID:23486839

Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning.

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Månsson, K N T; Frick, A; Boraxbekk, C-J; Marquand, A F; Williams, S C R; Carlbring, P; Andersson, G; Furmark, T

2015-03-17

Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual's long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52% (12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2-97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale-Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC-amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC-amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.

Implicit attitudes towards smoking predict long-term relapse in abstinent smokers

NARCIS (Netherlands)

Spruyt, A.; Lemaigre, V.; Salhi, B.; van Gucht, D.; Tibboel, H.; van Bockstaele, B.; de Houwer, J.; van Meerbeeck, J.; Nackaerts, K.

2015-01-01

Rationale: It has previously been argued that implicit attitudes toward substance-related cues drive addictive behavior. Nevertheless, it remains an open question whether behavioral markers of implicit attitude activation can be used to predict long-term relapse. Objectives: The main objective of

Behavioral cues to expand a pain model of the cognitively impaired elderly in long-term care

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Burfield AH

2012-07-01

Full Text Available Allison H Burfield,1 Thomas TH Wan,2 Mary Lou Sole,3 James W Cooper41School of Nursing, College of Health and Human Services, University of North Carolina-Charlotte, Charlotte, NC, 2Administration, and Medical Education, Doctoral Program in Public Affairs, College of Health and Public Affairs, 3College of Nursing, University of Central Florida, Orlando, FL, 4College of Pharmacy, University of Georgia, Athens, GA, USABackground: The purpose of this study was to determine the relationship between hypothesized pain behaviors in the elderly and a measurement model of pain derived from the Minimum Data Set-Resident Assessment Instrument (MDS-RAI 2.0 items.Methods: This work included a longitudinal cohort recruited from Medicare-certified long-term care facilities across the United States. MDS data were collected from 52,996 residents (mean age 83.7 years. Structural equation modeling was used to build a measurement model of pain to test correlations between indicators and the fit of the model by cognitive status. The model evaluates the theoretical constructs of pain to improve how pain is assessed and detected within cognitive levels.Results: Using pain frequency and intensity as the only indicators of pain, the overall prevalence of pain was 31.2%; however, analysis by cognitive status showed that 47.7% of the intact group was in pain, while only 18.2% of the severely, 29.4% of the moderately, and 39.6% of the mildly cognitively impaired groups were experiencing pain. This finding supports previous research indicating that pain is potentially under-reported in severely cognitively impaired elderly nursing home residents. With adjustments to the measurement model, a revised format containing affective, behavioral, and inferred pain indicates a better fit of the data to include these domains, as a more complete measure of the pain construct.Conclusion: Pain has a significant effect on quality of life and long-term health outcomes in nursing home

MicroRNA-22 Gates Long-Term Heterosynaptic Plasticity in Aplysia through Presynaptic Regulation of CPEB and Downstream Targets.

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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.

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

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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.

Long-Term Visual Training Increases Visual Acuity and Long-Term Monocular Deprivation Promotes Ocular Dominance Plasticity in Adult Standard Cage-Raised Mice

OpenAIRE

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 ...

Residual Fatigue Properties of Asphalt Pavement after Long-Term Field Service

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Peide Cui

2018-05-01

Full Text Available Asphalt pavement is widely used for expressways due to its advantages of flexibility, low cost, and easy maintenance. However, pavement failures, including cracking, raveling, and potholes, will appear after long-term service. This research evaluated the residual fatigue properties of asphalt pavement after long-term field service. Fatigue behavior of specimens with different pavement failure types, traffic load, service time, and layers were collected and characterized. Results indicate that after long-term field service, surface layer has a longer fatigue life under small stress levels, but shorter fatigue life under large stress levels. Longer service time results in greater sensitivity to loading stress, while heavier traffic results in shorter fatigue life. Surface and underneath layers present very close fatigue trend lines in some areas, indicating that the fatigue behavior of asphalt mixture in surface and underneath layers are aged to the same extent after eight to ten years of field service.

Contribution and limits of geochemical calculation codes to evaluate the long term behavior of nuclear waste glasses

International Nuclear Information System (INIS)

Fritz, B.; Crovisier, J.L.

1997-01-01

Geochemical models have been intensively developed by researchers since more than twenty five years in order to be able to better understand and/or predict the long term stability/instability of water-rock systems. These geochemical codes were ail built first on a thermodynamic approach deriving from the application of Mass Action Law. The resulting first generation of models allowed to detect or predict the possible mass transfers (thermodynamic models) between aqueous and mineral phases including irreversible dissolutions of primary minerals and/or precipitation near equilibrium of secondary mineral phases. The recent development of models based on combined thermodynamics and kinetics opens the field of Lime dependent reactions prediction. This is crucial if one thinks to combine geochemical and hydrological studies in the so-called coupled models for transport and reaction calculations. All these models are progressively applied to the prediction of long term behavior of mineral phases, and more specifically glasses. In order to succeed in chat specific extension of the models, but also the data bases, there is a great need for additional new data from experimental approaches and from natural analogues. The modelling approach appears than also very useful in order to interpret the results of experimental data and to relate them to long term data extracted from natural analogues. Specific functions for modelling solid solution phases mat' also be used for describing the products of glasses alterations. (authors)

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

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

2016-04-15

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

Depletion of Serotonin Selectively Impairs Short-Term Memory without Affecting Long-Term Memory in Odor Learning in the Terrestrial Slug "Limax Valentianus"

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Santa, Tomofumi; Kirino, Yutaka; Watanabe, Satoshi; Shirahata, Takaaki; Tsunoda, Makoto

2006-01-01

The terrestrial slug "Limax" is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC…

Long-term reliability of the visual EEG Poffenberger paradigm.

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Friedrich, Patrick; Ocklenburg, Sebastian; Mochalski, Lisa; Schlüter, Caroline; Güntürkün, Onur; Genc, Erhan

2017-07-14

The Poffenberger paradigm is a simple perception task that is used to estimate the speed of information transfer between the two hemispheres, the so-called interhemispheric transfer time (IHTT). Although the original paradigm is a behavioral task, it can be combined with electroencephalography (EEG) to assess the underlying neurophysiological processes during task execution. While older studies have supported the validity of both paradigms for investigating interhemispheric interactions, their long-term reliability has not been assessed systematically before. The present study aims to fill this gap by determining both internal consistency and long-term test-retest reliability of IHTTs produced by using the two different versions of the Poffenberger paradigm in a sample of 26 healthy subjects. The results show high reliability for the EEG Poffenberger paradigm. In contrast, reliability measures for the behavioral Poffenberger paradigm were low. Hence, our results indicate that electrophysiological measures of interhemispheric transfer are more reliable than behavioral measures; the later should be used with caution in research investigating inter-individual differences of neurocognitive measures. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuronal DNA Methylation Profiling of Blast-Related Traumatic Brain Injury.

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Haghighi, Fatemeh; Ge, Yongchao; Chen, Sean; Xin, Yurong; Umali, Michelle U; De Gasperi, Rita; Gama Sosa, Miguel A; Ahlers, Stephen T; Elder, Gregory A

2015-08-15

Long-term molecular changes in the brain resulting from blast exposure may be mediated by epigenetic changes, such as deoxyribonucleic acid (DNA) methylation, that regulate gene expression. Aberrant regulation of gene expression is associated with behavioral abnormalities, where DNA methylation bridges environmental signals to sustained changes in gene expression. We assessed DNA methylation changes in the brains of rats exposed to three 74.5 kPa blast overpressure events, conditions that have been associated with long-term anxiogenic manifestations weeks or months following the initial exposures. Rat frontal cortex eight months post-exposure was used for cell sorting of whole brain tissue into neurons and glia. We interrogated DNA methylation profiles in these cells using Expanded Reduced Representation Bisulfite Sequencing. We obtained data for millions of cytosines, showing distinct methylation profiles for neurons and glia and an increase in global methylation in neuronal versus glial cells (pDNA methylation perturbations in blast overpressure-exposed animals, compared with sham blast controls, within 458 and 379 genes in neurons and glia, respectively. Differentially methylated neuronal genes showed enrichment in cell death and survival and nervous system development and function, including genes involved in transforming growth factor β and nitric oxide signaling. Functional validation via gene expression analysis of 30 differentially methylated neuronal and glial genes showed a 1.2 fold change in gene expression of the serotonin N-acetyltransferase gene (Aanat) in blast animals (pDNA methylation induced in response to multiple blast overpressure exposures. In particular, increased methylation and decreased gene expression were observed in the Aanat gene, which is involved in converting serotonin to the circadian hormone melatonin and is implicated in sleep disturbance and depression associated with traumatic brain injury.

Long-Term Effects of Neurofeedback Treatment in Autism

Science.gov (United States)

Kouijzer, Mirjam E. J.; de Moor, Jan M. H.; Gerrits, Berrie J. L.; Buitelaar, Jan K.; van Schie, Hein T.

2009-01-01

Previously we demonstrated significant improvement of executive functions and social behavior in children with autism spectrum disorders (ASD) treated with 40 sessions of EEG neurofeedback in a nonrandomized waiting list control group design. In this paper we extend these findings by reporting the long-term results of neurofeedback treatment in…

In-Plant Fission Product Behavior in SGTR Accident with Long-Term SBO

Energy Technology Data Exchange (ETDEWEB)

Kim, Tae Woon; Han, Seok Jung; Ahn, Kwang Il [KAERI, Daejeon (Korea, Republic of)

2015-05-15

The off-site AC power was recovered in 9 days after the accident in the NPS. Therefore safety injection by fire pump truck with fresh water or seawater is only available in the Fukushima accident. However, safety injection by fire pump truck is not always effective due to the high pressure of RPV inside or leakages of alternative water injection flow paths. In the SBO situations in pressurized water reactor plant (PWR), turbine driven auxiliary feedwater (TD-AFW) pump can inject water to the secondary side of steam generator. However, turbine inlet steam flow control valve cannot work properly when loss of vital DC power occurs. Vital DC power is designed to be maintained during 4 or 8 hours in the SBO conditions. In this paper motor-driven and turbine driven AFW pumps are all assumed to be not working at time 0 sec as a worst case assumption. Iodine pool-scrubbing can occur in the secondary side of the faulted steam generator. However, iodine pool-scrubbing in the secondary side of the faulted steam generator is assumed not to be working, due to the assumption of the loss of DC battery for turbine inlet flow control valve. Iodine pool-scrubbing is one of the long-term research issues in safety assessment of nuclear power plant severe accident. PHEBUS FPT series and THAI experiment projects are typical projects on the resolving source term issues in severe accident of nuclear power plants. However, iodine retention by pool scrubbing is still a debating issue. In such containment bypass sequences, fission products can be released out to environment directly from RCS without retention or deposition in containment structures. SGTR is one of the hazardous accident scenarios in the typical PSA, because SGTR induces a large release amount of source term to environment directly. A key operation strategy was the isolation of the broken reactor coolant system loop from the intact loop. Typical core degradation in SGTR scenarios occurs with multiple failures of the isolation

A novel whole-cell mechanism for long-term memory enhancement.

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Iris Reuveni

Full Text Available Olfactory-discrimination learning was shown to induce a profound long-lasting enhancement in the strength of excitatory and inhibitory synapses of pyramidal neurons in the piriform cortex. Notably, such enhancement was mostly pronounced in a sub-group of neurons, entailing about a quarter of the cell population. Here we first show that the prominent enhancement in the subset of cells is due to a process in which all excitatory synapses doubled their strength and that this increase was mediated by a single process in which the AMPA channel conductance was doubled. Moreover, using a neuronal-network model, we show how such a multiplicative whole-cell synaptic strengthening in a sub-group of cells that form a memory pattern, sub-serves a profound selective enhancement of this memory. Network modeling further predicts that synaptic inhibition should be modified by complex learning in a manner that much resembles synaptic excitation. Indeed, in a subset of neurons all GABAA-receptors mediated inhibitory synapses also doubled their strength after learning. Like synaptic excitation, Synaptic inhibition is also enhanced by two-fold increase of the single channel conductance. These findings suggest that crucial learning induces a multiplicative increase in strength of all excitatory and inhibitory synapses in a subset of cells, and that such an increase can serve as a long-term whole-cell mechanism to profoundly enhance an existing Hebbian-type memory. This mechanism does not act as synaptic plasticity mechanism that underlies memory formation but rather enhances the response of already existing memory. This mechanism is cell-specific rather than synapse-specific; it modifies the channel conductance rather than the number of channels and thus has the potential to be readily induced and un-induced by whole-cell transduction mechanisms.

Short- and long-term antidepressant effects of ketamine in a rat chronic unpredictable stress model.

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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.

The long-term effects of stress and kappa opioid receptor activation on conditioned place aversion in male and female California mice.

Science.gov (United States)

Laman-Maharg, Abigail R; Copeland, Tiffany; Sanchez, Evelyn Ordoñes; Campi, Katharine L; Trainor, Brian C

2017-08-14

Psychosocial stress leads to the activation of kappa opioid receptors (KORs), which induce dysphoria and facilitate depression-like behaviors. However, less is known about the long-term effects of stress and KORs in females. We examined the long-term effects of social defeat stress on the aversive properties of KOR activation in male and female California mice (Peromyscus californicus) using a conditioned place aversion paradigm. Female California mice naïve to social defeat, formed a place aversion following treatment with 2.5mg/kg of the KOR agonist U50,488, but females exposed to defeat did not form a place aversion to this dose. This supports the finding by others that social defeat weakens the aversive properties of KOR agonists. In contrast, both control and stressed males formed an aversion to 10mg/kg of U50,488. We also examined EGR1 immunoreactivity, an indirect marker of neuronal activity, in the nucleus accumbens (NAc) and found that stress and treatment with 10mg/kg of U50,488 increased EGR1 immunoreactivity in the NAc core in females but reduced activation in males. The effects of stress and U50,488 on EGR1 were specific to the NAc, as we found no differences in the bed nucleus of the stria terminalis. In summary, our data indicate important sex differences in the long-term effects of stress and indicate the need for further study of the molecular mechanisms mediating the behavioral effects of KOR in both males and females. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

Han, Huili; Peng, Yan; Dong, Zhifang

2015-06-01

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

Study on effects of coupled phenomenon on long-term behavior for crystalline rock. FY2015 (Contract research)

International Nuclear Information System (INIS)

Ichikawa, Yasuaki; Kimoto, Kazushi; Matsui, Hiroya; Kuwabara, Kazumichi; Ozaki, Yusuke

2016-12-01

It is important to evaluate the stability of a repository for high-level radioactive waste not only during the design, construction and operation phases, but also during the post-closure period, for time frames likely exceeding several millennia or longer. The rock mass around the tunnels could be deformed through time in response to time dependent behavior such as creep and stress relaxation. On the other hand, it was revealed that the chemical reaction of groundwater in a rock had an influence on the long-term behavior. An evaluation of the microcracks to have an influence on rock mechanical and chemical coupled phenomena is the issue the past long-term behavior for rock study. In fiscal year 2015, using a laser Doppler vibrometer that extends a frequency band up to 20 MHz, and measuring the surface wave transmitted through the granite specimens were estimated group velocity. As a result, group velocity until 100 kHz ∼ 500 kHz, revealed that tends to decrease while vibrating. Estimation of the group velocity from the group delay, by using the spatially averaged waveform has improved estimated frequency band and reliability. For this reason, the estimation of the group velocity from the group delay has also been shown to be easier than estimated by the wave number - frequency spectrum. As a result obtained, in the case of the modeling by the viscoelastic theory of the granite and a microcrack nondestructiveness evaluation, it is thought that it is useful information in the future. In order to use the knowledge of this study, there is a need to clarify the correspondence between the microscopic properties of the medium such as a crack and crystal grain and the change of the group velocity. (author)

Long-lasting novelty-induced neuronal reverberation during slow-wave sleep in multiple forebrain areas.

Directory of Open Access Journals (Sweden)

Sidarta Ribeiro

2004-01-01

Full Text Available The discovery of experience-dependent brain reactivation during both slow-wave (SW and rapid eye-movement (REM sleep led to the notion that the consolidation of recently acquired memory traces requires neural replay during sleep. To date, however, several observations continue to undermine this hypothesis. To address some of these objections, we investigated the effects of a transient novel experience on the long-term evolution of ongoing neuronal activity in the rat forebrain. We observed that spatiotemporal patterns of neuronal ensemble activity originally produced by the tactile exploration of novel objects recurred for up to 48 h in the cerebral cortex, hippocampus, putamen, and thalamus. This novelty-induced recurrence was characterized by low but significant correlations values. Nearly identical results were found for neuronal activity sampled when animals were moving between objects without touching them. In contrast, negligible recurrence was observed for neuronal patterns obtained when animals explored a familiar environment. While the reverberation of past patterns of neuronal activity was strongest during SW sleep, waking was correlated with a decrease of neuronal reverberation. REM sleep showed more variable results across animals. In contrast with data from hippocampal place cells, we found no evidence of time compression or expansion of neuronal reverberation in any of the sampled forebrain areas. Our results indicate that persistent experience-dependent neuronal reverberation is a general property of multiple forebrain structures. It does not consist of an exact replay of previous activity, but instead it defines a mild and consistent bias towards salient neural ensemble firing patterns. These results are compatible with a slow and progressive process of memory consolidation, reflecting novelty-related neuronal ensemble relationships that seem to be context- rather than stimulus-specific. Based on our current and previous results

Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.

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Mieda, Michihiro; Okamoto, Hitoshi; Sakurai, Takeshi

2016-09-26

As the central pacemaker in mammals, the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is a heterogeneous structure consisting of multiple types of GABAergic neurons with distinct chemical identities [1, 2]. Although individual cells have a cellular clock driven by autoregulatory transcriptional/translational feedback loops of clock genes, interneuronal communication among SCN clock neurons is likely essential for the SCN to generate a highly robust, coherent circadian rhythm [1]. However, neuronal mechanisms that determine circadian period length remain unclear. The SCN is composed of two subdivisions: a ventral core region containing vasoactive intestinal peptide (VIP)-producing neurons and a dorsal shell region characterized by arginine vasopressin (AVP)-producing neurons. Here we examined whether AVP neurons act as pacemaker cells that regulate the circadian period of behavior rhythm in mice. The deletion of casein kinase 1 delta (CK1δ) specific to AVP neurons, which was expected to lengthen the period of cellular clocks [3-6], lengthened the free-running period of circadian behavior as well. Conversely, the overexpression of CK1δ specific to SCN AVP neurons shortened the free-running period. PER2::LUC imaging in slices confirmed that cellular circadian periods of the SCN shell were lengthened in mice without CK1δ in AVP neurons. Thus, AVP neurons may be an essential component of circadian pacemaker cells in the SCN. Remarkably, the alteration of the shell-core phase relationship in the SCN of these mice did not impair the generation per se of circadian behavior rhythm, thereby underscoring the robustness of the SCN network. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retrieval of long and short lists from long term memory: a functional magnetic resonance imaging study with human subjects.

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Zysset, S; Müller, K; Lehmann, C; Thöne-Otto, A I; von Cramon, D Y

2001-11-13

Previous studies have shown that reaction time in an item-recognition task with both short and long lists is a quadratic function of list length. This suggests that either different memory retrieval processes are implied for short and long lists or an adaptive process is involved. An event-related functional magnetic resonance imaging study with nine subjects and list lengths varying between 3 and 18 words was conducted to identify the underlying neuronal structures of retrieval from long and short lists. For the retrieval and processing of word-lists a single fronto-parietal network, including premotor, left prefrontal, left precuneal and left parietal regions, was activated. With increasing list length, no additional regions became involved in retrieving information from long-term memory, suggesting that not necessarily different, but highly adaptive retrieval processes are involved.

A small potassium current in AgRP/NPY neurons regulates feeding behavior and enery metabolism

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Neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons are dynamically regulated by energy status and coordinate appropriate feeding behavior to meet nutritional demands. However, intrinsic m...

[Long-term psychiatric hospitalizations].

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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

Long term effects of low doses of 56Fe ions on the brain and retina of the mouse: ultrastructural and behavioral studies

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Philpott, D. E.; Miquel, J.

1986-01-01

Eight month old male C57BL6 mice were exposed without anesthesia to whole-body irradiation in circular holders. The mice were tested for behavioral decrements after 0.5 and 50 rads of Fe particle irradiation at 6 and 12 months post irradiation to obtain long term results. A standard maze was used and the animals were timed for completion thereof. A string test also was administered to the mice, testing their ability to grasp and move along a string to safety. The results from animals exposed to 50 rads were significantly different from [correction of fron] control results to p = brain) and the retina were examined for ultrastructural changes. The ultrastructural changes were similar to those we found in our Cosmos 782, 936 and in our Argon experiments. The mouse data indicate that iron particles were able to induce long term changes in the central nervous system which lead to behavioral impairment.

Fractional-order leaky integrate-and-fire model with long-term memory and power law dynamics.

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Teka, Wondimu W; Upadhyay, Ranjit Kumar; Mondal, Argha

2017-09-01

Pyramidal neurons produce different spiking patterns to process information, communicate with each other and transform information. These spiking patterns have complex and multiple time scale dynamics that have been described with the fractional-order leaky integrate-and-Fire (FLIF) model. Models with fractional (non-integer) order differentiation that generalize power law dynamics can be used to describe complex temporal voltage dynamics. The main characteristic of FLIF model is that it depends on all past values of the voltage that causes long-term memory. The model produces spikes with high interspike interval variability and displays several spiking properties such as upward spike-frequency adaptation and long spike latency in response to a constant stimulus. We show that the subthreshold voltage and the firing rate of the fractional-order model make transitions from exponential to power law dynamics when the fractional order α decreases from 1 to smaller values. The firing rate displays different types of spike timing adaptation caused by changes on initial values. We also show that the voltage-memory trace and fractional coefficient are the causes of these different types of spiking properties. The voltage-memory trace that represents the long-term memory has a feedback regulatory mechanism and affects spiking activity. The results suggest that fractional-order models might be appropriate for understanding multiple time scale neuronal dynamics. Overall, a neuron with fractional dynamics displays history dependent activities that might be very useful and powerful for effective information processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prediction of long-term creep curves

International Nuclear Information System (INIS)

Oikawa, Hiroshi; Maruyama, Kouichi

1992-01-01

This paper aims at discussing how to predict long-term irradiation enhanced creep properties from short-term tests. The predictive method based on the θ concept was examined by using creep data of ferritic steels. The method was successful in predicting creep curves including the tertiary creep stage as well as rupture lifetimes. Some material constants involved in the method are insensitive to the irradiation environment, and their values obtained in thermal creep are applicable to irradiation enhanced creep. The creep mechanisms of most engineering materials definitely change at the athermal yield stress in the non-creep regime. One should be aware that short-term tests must be carried out at stresses lower than the athermal yield stress in order to predict the creep behavior of structural components correctly. (orig.)

Fasting launches CRTC to facilitate long-term memory formation in Drosophila.

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Hirano, Yukinori; Masuda, Tomoko; Naganos, Shintaro; Matsuno, Motomi; Ueno, Kohei; Miyashita, Tomoyuki; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-25

Canonical aversive long-term memory (LTM) formation in Drosophila requires multiple spaced trainings, whereas appetitive LTM can be formed after a single training. Appetitive LTM requires fasting prior to training, which increases motivation for food intake. However, we found that fasting facilitated LTM formation in general; aversive LTM formation also occurred after single-cycle training when mild fasting was applied before training. Both fasting-dependent LTM (fLTM) and spaced training-dependent LTM (spLTM) required protein synthesis and cyclic adenosine monophosphate response element-binding protein (CREB) activity. However, spLTM required CREB activity in two neural populations--mushroom body and DAL neurons--whereas fLTM required CREB activity only in mushroom body neurons. fLTM uses the CREB coactivator CRTC, whereas spLTM uses the coactivator CBP. Thus, flies use distinct LTM machinery depending on their hunger state.

Ketamine analgesia for inflammatory pain in neonatal rats: a factorial randomized trial examining long-term effects

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Bhutta Adnan T

2008-08-01

Full Text Available Abstract Background Neonatal rats exposed to repetitive inflammatory pain have altered behaviors in young adulthood, partly ameliorated by Ketamine analgesia. We examined the relationships between protein expression, neuronal survival and plasticity in the neonatal rat brain, and correlated these changes with adult cognitive behavior. Methods Using Western immunoblot techniques, homogenates of cortical tissue were analyzed from neonatal rats 18–20 hours following repeated exposure to 4% formalin injections (F, N = 9, Ketamine (K, 2.5 mg/kg × 2, N = 9, Ketamine prior to formalin (KF, N = 9, or undisturbed controls (C, N = 9. Brain tissues from another cohort of rat pups (F = 11, K = 12, KF = 10, C = 15 were used for cellular staining with Fos immunohistochemistry or FluoroJade-B (FJB, followed by cell counting in eleven cortical and three hippocampal areas. Long-term cognitive testing using a delayed non-match to sample (DNMS paradigm in the 8-arm radial maze was performed in adult rats receiving the same treatments (F = 20, K = 24, KF = 21, C = 27 in the neonatal period. Results Greater cell death occurred in F vs. C, K, KF in parietal and retrosplenial areas, vs. K, KF in piriform, temporal, and occipital areas, vs. C, K in frontal and hindlimb areas. In retrosplenial cortex, less Fos expression occurred in F vs. C, KF. Cell death correlated inversely with Fos expression in piriform, retrosplenial, and occipital areas, but only in F. Cortical expression of glial fibrillary acidic protein (GFAP was elevated in F, K and KF vs. C. No significant differences occurred in Caspase-3, Bax, and Bcl-2 expression between groups, but cellular changes in cortical areas were significantly correlated with protein expression patterns. Cluster analysis of the frequencies and durations of behaviors grouped them as exploratory, learning, preparatory, consumptive, and foraging behaviors. Neonatal inflammatory pain exposure reduced exploratory behaviors in adult

Semantic and phonological contributions to short-term repetition and long-term cued sentence recall.

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Meltzer, Jed A; Rose, Nathan S; Deschamps, Tiffany; Leigh, Rosie C; Panamsky, Lilia; Silberberg, Alexandra; Madani, Noushin; Links, Kira A

2016-02-01

The function of verbal short-term memory is supported not only by the phonological loop, but also by semantic resources that may operate on both short and long time scales. Elucidation of the neural underpinnings of these mechanisms requires effective behavioral manipulations that can selectively engage them. We developed a novel cued sentence recall paradigm to assess the effects of two factors on sentence recall accuracy at short-term and long-term stages. Participants initially repeated auditory sentences immediately following a 14-s retention period. After this task was complete, long-term memory for each sentence was probed by a two-word recall cue. The sentences were either concrete (high imageability) or abstract (low imageability), and the initial 14-s retention period was filled with either an undemanding finger-tapping task or a more engaging articulatory suppression task (Exp. 1, counting backward by threes; Exp. 2, repeating a four-syllable nonword). Recall was always better for the concrete sentences. Articulatory suppression reduced accuracy in short-term recall, especially for abstract sentences, but the sentences initially recalled following articulatory suppression were retained better at the subsequent cued-recall test, suggesting that the engagement of semantic mechanisms for short-term retention promoted encoding of the sentence meaning into long-term memory. These results provide a basis for using sentence imageability and subsequent memory performance as probes of semantic engagement in short-term memory for sentences.

Linking Neurons to Network Function and Behavior by Two-Photon Holographic Optogenetics and Volumetric Imaging.

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Dal Maschio, Marco; Donovan, Joseph C; Helmbrecht, Thomas O; Baier, Herwig

2017-05-17

We introduce a flexible method for high-resolution interrogation of circuit function, which combines simultaneous 3D two-photon stimulation of multiple targeted neurons, volumetric functional imaging, and quantitative behavioral tracking. This integrated approach was applied to dissect how an ensemble of premotor neurons in the larval zebrafish brain drives a basic motor program, the bending of the tail. We developed an iterative photostimulation strategy to identify minimal subsets of channelrhodopsin (ChR2)-expressing neurons that are sufficient to initiate tail movements. At the same time, the induced network activity was recorded by multiplane GCaMP6 imaging across the brain. From this dataset, we computationally identified activity patterns associated with distinct components of the elicited behavior and characterized the contributions of individual neurons. Using photoactivatable GFP (paGFP), we extended our protocol to visualize single functionally identified neurons and reconstruct their morphologies. Together, this toolkit enables linking behavior to circuit activity with unprecedented resolution. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Relocation and Individual and Environmental Factors on the Long-Term Stress Levels in Captive Chimpanzees (Pan troglodytes: Monitoring Hair Cortisol and Behaviors.

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Yumi Yamanashi

Full Text Available Understanding the factors associated with the long-term stress levels of captive animals is important from the view of animal welfare. In this study, we investigated the effects of relocation in addition to individual and environmental factors related to social management on long-term stress level in group-living captive chimpanzees by examining behaviors and hair cortisol (HC. Specifically, we conducted two studies. The first compared changes in HC levels before and after the relocation of 8 chimpanzees (Study 1 and the second examined the relationship between individual and environmental factors and individual HC levels in 58 chimpanzees living in Kumamoto Sanctuary (KS, Kyoto University (Study 2. We hypothesized that relocation, social situation, sex, and early rearing conditions, would affect the HC levels of captive chimpanzees. We cut arm hair from chimpanzees and extracted and assayed cortisol with an enzyme immunoassay. Aggressive behaviors were recorded ad libitum by keepers using a daily behavior monitoring sheet developed for this study. The results of Study 1 indicate that HC levels increased during the first year after relocation to the new environment and then decreased during the second year. We observed individual differences in reactions to relocation and hypothesized that social factors may mediate these changes. In Study 2, we found that the standardized rate of receiving aggression, rearing history, sex, and group formation had a significant influence on mean HC levels. Relocation status was not a significant factor, but mean HC level was positively correlated with the rate of receiving aggression. Mean HC levels were higher in males than in females, and the association between aggressive interactions and HC levels differed by sex. These results suggest that, although relocation can affect long-term stress level, individuals' experiences of aggression and sex may be more important contributors to long-term stress than

Long-Term Refugee Health: Health Behaviors and Outcomes of Cambodian Refugee and Immigrant Women

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Nelson-Peterman, Jerusha L.; Toof, Robin; Liang, Sidney L.; Grigg-Saito, Dorcas C.

2015-01-01

Refugees in the United States have high rates of chronic disease. Both long-term effects of the refugee experience and adjustment to the U.S. health environment may contribute. While there is significant research on health outcomes of newly resettled refugees and long-term mental health experiences of established refugees, there is currently…

Characterization, Long-Term Behavior Evaluation and Thermomechanical Properties of Untreated and Treated Flax Fiber-Reinforced Composites

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Amiri, Ali

In recent years there has been a resurgence of interest in the usage of natural fiber reinforced composites in more advanced structural applications. Consequently, the need for improving their mechanical properties as well as service life and long-term behavior modeling and predictions has arisen. In a step towards further development of these materials, in this study, two newly developed biobased resins, derived from soybean oil, methacrylated epoxidized sucrose soyate and double methacrylated epoxidized sucrose soyate are combined with untreated and alkaline treated flax fiber to produce novel biocomposites. Vinyl ester reinforced with flax fiber is used as control in addition to comparing properties of biobased composites against commercial pultruded composites. Effects of alkaline treatment of flax fiber as well as addition of 1% acrylic resin to vinyl ester and the two mentioned biobased resins on mechanical properties are studied. Properties are evaluated in short-term and also, after being exposed to accelerated weathering (i.e. UV and moisture). Moreover, long-term creep of these novel biobased composites and effect of fiber and matrix treatment on viscoelastic behavior is investigated using Time-temperature superposition (TTS) principle. Based on the results of this study, the TTS provides an accelerated method for evaluation of mechanical properties of biobased composites, and satisfactory master curves are achieved by use of this principle. Also, fiber and matrix treatments were effective in increasing mechanical properties of biobased composites in short-term, and treatments delayed the creep response and slowed the process of creep in composites under study in the steady state region. Overall, results of this study reveal the successful production of biocomposites having properties that meet or exceed those of conventional pultruded members while maintaining high biocontent. Composites using treated flax fiber and newly developed resins showed less

Long-term behavior of glass-ceramic zirconolite; Etude du comportement a long terme des vitrocristallins a base de zirconolite